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We investigated the effects of ketoconazole (KCZ) and fluconazole (FCZ) on rat liver microsomal nevirapine (NVP) metabolism in vitro and on NVP plasma profiles in vivo in order to determine whether the in vivo drug interactions could be predicted quantitatively from the in vitro data. The Ki values of KCZ and FCZ for NVP 12-hydroxylation were 1.59 microm and 11.5 microM, respectively, indicating that KCZ inhibited this activity more strongly than FCZ in vitro. In contrast, FCZ orally pre-administered at 20 mg/kg to rats increased the area under the plasma concentration-time curve (AUC) of NVP 7.4-fold, whereas KCZ increased it 2.1-fold, compared to the vehicle. We next investigated the inhibitory potency and unbound concentrations of KCZ and FCZ in microsomal mixtures with or without rat albumin. In the presence of albumin, the inhibition by KCZ was greatly decreased. Further, the unbound fraction of KCZ was decreased dramatically to around 3%, whereas more than 90% of FCZ remained in unbound form. When the increase in the AUC for NVP was calculated based on the concentrations of unbound inhibitors in the portal vein, good agreement with the observed in vivo values was obtained. | The objective of this study was to investigate the effect of oral administration of antiretroviral drugs (indinavir, ritonavir, atazanavir, efavirenz and nevirapine) on the pharmacodynamics of gliclazide in rats (normal and diabetic) and rabbits with respect to glucose–insulin homeostasis to evaluate the safety and effectiveness of the combinations. Blood samples were collected at regular time intervals in rats from retro orbital puncture and by marginal ear vein puncture in rabbits. All the blood samples were analyzed for blood glucose by glucose oxidase–peroxidase method and insulin by a radio immuno assay method. The insulin resistance index and β-cell function were determined by a homeostasis model assessment. Indinavir and ritonavir alone had significant impact on glucose–insulin homeostasis in animal models among the antiretroviral drugs used in our study. In combination, indinavir and efavirenz significantly reduced the activity of gliclazide, while ritonavir and atazanavir significantly increased the activity of gliclazide. However, nevirapine had no significant effect on the activity of gliclazide. From this study we conclude that glucose–insulin homeostasis disorders associated with antiretroviral drugs are not class-specific, but are drug-specific. So care should be taken when indinavir, ritonavir, atazanavir and efavirenz are prescribed for diabetic patients. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,800 |
Background Cognitive deficits are present in a large majority of Bipolar Disorder (BD) patients and known to be a marker of bad prognosis. Because, these deficits encompass several domains and no specific medical treatment seems to be effective, it is important to better understand the mechanisms underlying cognitive deterioration. As Toxoplasma gondii is known to induce the synthesis of pro-inflammatory cytokines such as IL-6, we will explore here the possible role of T. gondii in the cognitive decline observed in BD. Methods 42 euthymic BD patients and 36 controls were assessed for episodic verbal memory using the CVLT and for working memory and verbal ability using the WAIS III. Patients and controls were also screened for seropositivity to T. gondii and evaluated for the levels of IL-6 transcripts. Results The seropositivity for T. gondii was significantly higher in BD patients as compared to controls ( p =0.005). The cognitive deterioration index (DI) was higher in BD patients ( p =5.10 −6 ) and correlated to high IL-6 mRNA expression only among those infected by T. gondii (rho=0.43, p =0.01). Among deteriorated patients (defined by scores above 0.10 according to Weschler׳s definition), the IL-6 mRNA expression was twice greater ( p =0.01). Limitations Our results are to be interpreted with caution because of our small sample size and the cross-sectional design. Conclusions A long-term exposure to inflammation, measured here with IL-6 mRNA expression in T. gondii infected BD may alter cognitive functioning. IL-6 could thus be a useful predictive marker of cognitive deterioration in BD and may help to design personalized treatment. | Bipolar disorder (BD) is strongly associated with immune dysfunction. Replicated epidemiological studies have demonstrated that BD has high rates of inflammatory medical comorbidities, including autoimmune disorders, chronic infections, cardiovascular disease and metabolic disorders. Cytokine studies have demonstrated that BD is associated with chronic low-grade inflammation with further increases in pro-inflammatory cytokine levels during mood episodes. Several mechanisms have been identified to explain the bidirectional relationship between BD and immune dysfunction. Key mechanisms include cytokine-induced monoamine changes, increased oxidative stress, pathological microglial over-activation, hypothalamic-pituitary-adrenal (HPA) axis over-activation, alterations of the microbiome-gut-brain axis and sleep-related immune changes. The inflammatory-mood pathway presents several potential novel targets in the treatment of BD. Several proof-of-concept clinical trials have shown a positive effect of anti-inflammatory agents in the treatment of BD; however, further research is needed to determine the clinical utility of these treatments. Immune dysfunction is likely to only play a role in a subset of BD patients and as such, future clinical trials should also strive to identify which specific group(s) of BD patients may benefit from anti-inflammatory treatments. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,801 |
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by abdominal pain and bowel dysfunction in the absence of structural abnormality. Diagnosis can be challenging and often leads to extensive medical tests, non-effective therapeutic modalities, and reduced quality of life (QOL). Identifying factors associated with dysfunction have the potential to enhance outcomes. Participants with IBS (n = 41) and healthy volunteers (n = 74) were recruited into this cross-sectional, descriptive, natural history protocol at the National Institute of Health, Clinical Center. Demographic characteristics were self-reported. QOL was assessed with the Irritable Bowel Syndrome Quality of Life (IBS-QOL) questionnaire. Statistical analysis included descriptive statistics, factorial ANOVA, and multiple regression. Individuals with IBS reported lower QOL scores across all QOL-subscales compared to healthy controls. Normal-weight women and overweight men with IBS reported the greatest QOL impairment. Body fat percent had confounding effects on the relationship between IBS and QOL. The disparity between QOL scores in participants with IBS by both gender and weight groups may reflect different social pressures perceived by normal and overweight women and men. These findings enhance the recognition of the disparities in patients with chronic symptoms and thereby lead to personalized assessment and interventions to improve their QOL. | Sex and gender effects in irritable bowel syndrome (IBS) have been reported in epidemiological, physiological, and clinical treatment studies. The potential role of gonadal hormones is discussed based on the female predominance in IBS and the correlation between IBS symptoms and hormonal status. Several different models have been proposed to examine the role of sex hormones in gastrointestinal (GI) function, including changes in GI symptoms during the menstrual cycle and differences in symptom expression in pre- and post-menopausal women as well as changes during pregnancy, hormonal treatment, or after ovariectomy. Gonadal hormones, in particular estrogens, can significantly modulate various clinical manifestations of IBS, including alterations in GI motility and visceral hypersensitivity. Additionally, sex differences in the stress response of the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system are considered to be contributing factors in the pathogenesis of functional bowel disorders. The modulatory effects of estrogens on visceral pain may result from interactions with numerous neurotransmitters at different levels of the brain-gut axis, with a pivotal role of estrogens' interactions with the serotonin and corticotropin-releasing factor (CRF) signaling systems. Estrogens can also modulate neuroimmune interactions triggered by stress via the brain-gut axis. Sex differences in the biological actions, pharmacokinetics, and treatment efficacy of serotonergic medications clearly suggest sex differences in pain pathways that have to be taken into consideration in therapeutic interventions. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,802 |
Platelet survival time and platelet adhesiveness and aggregation were examined in 16 patients with prosthetic mitral valves. Subsequently, nine patients were treated with sulfinpyrazone in doses of 400 mg and 800 mg/day, and the studies were repeated after a treatment period of 5 to 8 weeks. 51 Chromium survival time was shortened in 15 of 16 patients, and the mean value for the entire group was 5.49 ± 0.23 days (normal, 6.73 ± 0.21 days; P P P | The decision to initiate long-term anticoagulant therapy in a patient with valvular heart disease is frequently difficult because of the many variables that influence the risks of thromboembolism and of bleeding in a given individual. The patient's age, the specific valve lesion, the heart rhythm, the duration of the valve disease, a history of thromboembolism, patient attitude and life-style, associated diseases, and medications all must be considered. Because the state of such variables may change with time, a proper decision at one time in a patient's life may be inappropriate at another time. In some instances, the literature on a given subject is sparse or contains conflicting data that further confound the issue. Since the database for these guidelines is constantly being modified, particularly as a consequence of new randomized clinical trials, the clinician would do well to review his decision at frequent intervals. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,803 |
Single-dose pharmacokinetics of azlocillin, cefoperazone and ceftazidime were studied in 17 patients with cystic fibrosis (CF). All patients had broncho-pulmonary infections caused by Pseudomonas aeruginosa. Three groups of five, six, and six patients were treated with azlocillin, cefoperazone, or ceftazidime, respectively. The size of the single dose was 133 mg/kg for azlocillin, 66.7 mg/kg for ceftazidime and 66.7 mg/kg for cefoperazone. The clearance values for the three antibiotics calculated from the single-dose data were, on the average, higher than the values previously reported for normal subjects. After the first dose, the patients received a repeated-dose treatment with the same antibiotic. During the first 5 days of therapy, a complement postural drainage of sputum was obtained four times a day for each patient. Cefoperazone could be measured in 47 (39.2%) of the 120 sputum samples assayed while ceftazidime was shown to be present in all 120 sputum samples examined. Azlocillin was not detected in any of the 100 sputum samples assayed. | Despite the promising activity of ceftazidime against Pseudomonas aeruginosa and Burkholderia cepacia, there has not yet been a study that directly compared the pharmacokinetics (PK) of ceftazidime in cystic fibrosis (CF) patients and healthy volunteers by population PK methodology. We assessed the population PK and PK/pharmacodynamic (PD) breakpoints of ceftazidime in CF patients and healthy volunteers. Eight CF patients (total body weight [WT] [average +/- standard deviation] = 42.9 +/- 18.4 kg) and seven healthy volunteers (WT = 66.2 +/- 4.9 kg) received 2 g ceftazidime as a 5-min intravenous infusion. High-performance liquid chromatography (HPLC) was used for drug analysis, and NONMEM (results reported), S-ADAPT, and NPAG were used for parametric and nonparametric population PK modeling. We considered linear and allometric body size models to scale clearance and volume of distribution. Monte Carlo simulations were based on a target time of non-protein-bound plasma concentration of ceftazidime above MIC of > or =65%, which represents near-maximal killing. Unscaled total clearance was 19% lower in CF patients, and volume of distribution was 36% lower. Total clearance was 7.82 liters/h for CF patients and 6.68 liters/h for healthy volunteers with 53 kg fat-free mass. Allometric scaling by fat-free mass reduced the between-subject variability by 32% for clearance and by 18 to 26% for volume of both peripheral compartments compared to linear scaling by WT. A 30-min ceftazidime infusion of 2 g/70 kg WT every 8 h (q8h) achieved robust (> or =90%) probabilities of target attainment (PTAs) for MICs of < or =1 mg/liter in CF patients and < or =3 mg/liter in healthy volunteers. Alternative modes of administration achieved robust PTAs up to markedly higher MICs of < or =8 to 12 mg/liter in CF patients for 5-h infusions of 2 g/70 kg WT q8h and < or =12 mg/liter for continuous infusion of 6 g/70 kg WT daily. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,804 |
It is undeniable that most patients with advanced ovarian cancer derive benefit from primary cytoreductive surgery, with relief of symptoms, prolonged survival, improved quality of life, and establishment of a definitive diagnosis. Several questions, however, remain unanswered, including the relative effects of surgical intervention and tumor biology and the benefit of ultraradical debulking with or without technologic advances, such as the CUSA or laser therapy. Future studies will likely clarify many issues, including the therapeutic index of neoadjuvant chemotherapy and interval debulking compared with standard treatment and the impact of debulking within homogeneous cohorts of patients (i.e., stage IIIc) with similar host factors. | Interstitial photodynamic therapy (PDT) using the pegylated photosensitizer PEG-m-THPC was evaluated as a minimally-invasive procedure to selectively debulk unrespectable pelvic ovarian cancer (NuTu-19) in immunocompetent rats. To assess tumour selectivity, PEG-m-THPC at dosages of 0.3, 3.0 and 30 mg kg–1 body weight was administered intravenously to 30 rats 4 weeks following tumour induction. Eight days later laser light at 652 nm and optical doses ranging from 100 to 900 J cm–1 diffuser-length was delivered by an interstitial cylindrical diffusing fibre inserted blindly into the pelvis. Three days following light application, the volume of necrosis was measured and the damage to pelvic organs was assessed histologically on cross sections. For analysis of survival, 20 tumour-bearing rats received PDT using drug doses of 3 or 9 mg kg–1 body weight and an optical dose of 900 J cm–1 diffuser-length, whereas ten untreated tumour-bearing rats served as controls. The histological assessment of PDT induced necrosis showed a non-linear dose–response for both the photosensitizer dose and the optical dose. The lowest drug dose activated with the highest optical dose did not induce more necrosis than seen in tumour-bearing control animals. The same optical dose induced necrosis of 17 mm in diameter using 30 mg kg–1 and 11 mm using 3 mg kg–1 photosensitizer. The optical threshold for induction of significant necrosis was between 100 and 300 J cm–1 diffuser-length for 30 mg kg–1 and between 300 and 500 J cm–1 for 3 mg kg–1 PEG-m-THPC. Significant damage to normal pelvic organs was only seen if 30 mg kg–1 photosensitizer was activated with optical doses of 700 J cm–1 or more. In the survival study, all treated animals survived PDT for at least 2 weeks and the intestinal and urinary tract remained functional. No clinical signs of blood vessel or nerve injury were observed. Mean overall survival of untreated tumour-bearing rats was 25.0 ± 4.5 days compared to 38.4 ± 3.8 days and 40.0 ± 3.6 days for rats treated with 3 mg kg–1 or 9 mg kg–1 PEG-m-THPC mediated PDT respectively (P < 0.05). We conclude that PEG-m-THPC mediated PDT has a favourable therapeutic window and that this minimally-invasive procedure can reduce pelvic cancer bulks effectively and selectively. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,805 |
Interaction of tumor cells with the vascular wall is required for metastasis from the bloodstream. The precise interaction among metastatic cells, circulating platelets, the vessel wall, and physiological flow conditions remains to be determined. In this study, we investigated the interaction of shear on metastatic cell lines adherent to lipopolysaccharide (LPS)-treated endothelium. Tumor cells were perfused over LPS-treated human umbilical vein endothelial cells (HUVECs) at incremental venous shear rates from 50 to 800 s(-1). At a venous shear rate of 400 s(-1), 3% of adherent tumor cells formed pseudopodia under shear, a process we termed shear-induced activation. Because platelets promote tumor dissemination, we then investigated the effect of pretreating tumor cells with platelet releasate collected from activated platelet concentrate. We found that in the presence of platelet releasate, the number of tumor cells adhering to HUVECs increased and tumor "activation" occurred at a significantly lower shear rate of 50 s(-1). This was inhibited with acetylsalicylic acid. Depletion of fibronectin or vitronectin from the platelet releasate resulted in significantly less adhesion at higher venous shear rates of 600 and 800 s(-1). The integrin alphavbeta3 has been shown to mediate cell adhesion primarily through vitronectin and fibronectin proteins. Inhibition of alphavbeta3, followed by the addition of platelet releasate to the tumor cells, resulted in significantly less adhesion at higher venous shear rates of 600 and 800 s(-1). Collectively, our data suggest that alphavbeta3 promotes the metastatic phenotype of tumor cells through interactions with the secreted platelet proteins vitronectin and fibronectin under venous shear conditions. | Epithelial ovarian cancer (EOC) is usually discovered after extensive metastasis have developed in the peritoneal cavity. The ovarian surface is exposed to peritoneal fluid pressures and shear forces due to the continuous peristaltic motions of the gastro-intestinal system, creating a mechanical micro-environment for the cells. An in vitro experimental model was developed to expose EOC cells to steady fluid flow induced wall shear stresses (WSS). The EOC cells were cultured from OVCAR-3 cell line on denuded amniotic membranes in special wells. Wall shear stresses of 0.5, 1.0 and 1.5 dyne/cm2 were applied on the surface of the cells under conditions that mimic the physiological environment, followed by fluorescent stains of actin and β-tubulin fibers. The cytoskeleton response to WSS included cell elongation, stress fibers formation and generation of microtubules. More cytoskeletal components were produced by the cells and arranged in a denser and more organized structure within the cytoplasm. This suggests that WSS may have a significant role in the mechanical regulation of EOC peritoneal spreading. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,806 |
A comparative study was performed on the pharmacology and biochemistry of venoms from three subspecies of Lachesis muta (L. m. stenophrys, L. m. muta and L. m. rhombeata) from Brazil, Colombia and Costa Rica. All venoms induced lethal, hemorrhagic, edema-forming, myotoxic, coagulant and defibrinating effects, showing also proteolytic and indirect hemolytic activities. The venoms of L. m. stenophrys from Costa Rica and L. m. muta from Cascalheira, Brazil, had the highest lethal and hemorrhagic activities and the venom of L. m. rhombeata showed the highest coagulant activity, whereas no significant differences were observed in myotoxic and edema-forming activities at most of the time intervals studied. In addition, venoms showed similar electrophoretic patterns on SDS-polyacrylamide gel electrophoresis. In conclusion, despite quantitative differences in toxic and enzymatic activities, together with subtle variations in electrophoretic patterns, our results indicate that experimental envenomation by these venoms induce a qualitatively similar pathophysiological profile. | Envenomation by the bushmaster snake Lachesis muta muta is considered severe, characterized by local effects including necrosis, the main cause of permanent disability. However, cellular mechanisms related to cell death and tissue destruction, triggered by snake venoms, are poorly explored. The purpose of this study was to investigate the cytotoxic effect caused by L. m. muta venom in normal human keratinocytes and to identify the cellular processes involved in in cellulo envenomation. In order to investigate venom effect on different cell types, Alamar Blue assay was performed to quantify levels of cellular metabolism as a readout of cell viability. Apoptosis, necrosis and changes in mitochondrial membrane potential were evaluated by flow cytometry, while induction of autophagy was assessed by expression of GFP-LC3 and analyzed using fluorescence microscopy. The cytotoxic potential of the venom is shown by reduced cell viability in a concentration-dependent manner. It was also observed the sequential appearance of cells undergoing autophagy (by 6 hours), apoptosis and necrosis (12 and 24 hours). Morphologically, incubation with L. m. muta venom led to a significant cellular retraction and formation of cellular aggregates. These results indicate that L. m. muta venom is cytotoxic to normal human keratinocytes and other cell lines, and this toxicity involves the integration of distinct modes of cell death. Autophagy as a cell death mechanism, in addition to apoptosis and necrosis, can help to unravel cellular pathways and mechanisms triggered by the venom. Understanding the mechanisms that underlie cellular damage and tissue destruction will be useful in the development of alternative therapies against snakebites. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,807 |
Hydrogen peroxide (H2O2) is known to be involved in drug-induced and ischemic proximal tubular damage. The purpose of this study was to elucidate the effects of hydrogen peroxide on organic anion transport mediated by human organic anion transporters 1 and 3 (hOAT1 and hOAT3), which are localized at the basolateral side of the proximal tubule. For this purpose, we established and utilized the second segment of the proximal tubule cells from mice stably expressing hOAT1 or hOAT3 (S2 hOAT1 or S2 hOAT3, respectively). H2O2 induced a dose- and a time-dependent decrease in organic anion transport mediated by hOAT1 and hOAT3. Kinetic analysis revealed that H2O2 decreased the Vmax, but not Km of organic anion transport both in S2 hOAT1 and S2 hOAT3. The effects of gentamicin, known to induce proximal tubular damage via the production of H2O2, on the organic anion transporters were also examined. Gentamicin induced a significant decrease in organic anion transport in S2 hOAT1 but not S2 hOAT3. H2O2-induced decrease in organic anion transport was significantly inhibited by pretreatment with pyruvate as well as catalase, whereas the gentamicin-induced decrease was significantly inhibited by pretreatment with pyruvate but not with catalase. In conclusion, these results suggest that H2O2, which is produced during tubular injuries, downregulates organic anion transport mediated by both hOAT1 and hOAT3, leading to further modulation of pathophysiology. | Lansoprazole, a proton pump inhibitor, potently inhibits human organic anion transporter, hOAT3 (SLC22A8). Lansoprazole has an asymmetric atom in its structure and is clinically administered as a racemic mixture of (R)-and (S)-enantiomers. However, little is known about the stereoselective inhibitory potencies of lansoprazole against hOAT3 and its homolog, hOAT1. In the present study, the stereoselective inhibitory effect of lansoprazole was evaluated using hOAT1-and hOAT3-expressing cultured cells. hOAT1 and hOAT3 transported [14C]p-aminohippurate and [3H]estrone-3-sulfate (ES) with Michaelis-Menten constants of 29.8 ± 4.0 and 30.1 ± 9.0 µmol/L respectively. Lansoprazole enantiomers inhibited hOAT1- and hOAT3-mediated transport of each substrate in a concentration-dependent manner. The IC50 value of (S)-lansoprazole against hOAT3-mediated transport of [3H]ES (0.61 ± 0.08 µmol/L) was significantly lower than that of (R)-lansoprazole (1.75 ± 0.31 µmol/L). In contrast, stereoselectivity was not demonstrated for the inhibition of hOAT1. Furthermore, (S)-lansoprazole inhibited hOAT3-mediated transport of pemetrexed and methotrexate (hOAT3 substrates) more strongly than the corresponding (R)-lansoprazole. This study is the first to demonstrate that the stereoselective inhibitory potency of (S)-lansoprazole against hOAT3 is greater than that of (R)-lansoprazole. The present findings provide novel information about the drug interactions associated with lansoprazole. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,808 |
3,5,3'-Triiodo-L-thyronine (L-T3)-binding sites from rat and human red cells were characterized as to their distribution between the two surfaces of the membrane. Analysis of L-T3 binding to sealed right-side-out and inside-out vesicles from erythrocyte membrane revealed that high affinity L-T3-binding sites are located on the external side in rat erythrocytes and on the internal side in human red cells. These results were further confirmed by preincubation of intact red cells with p-chloromercuribenzoate, a slowly permeant reagent that interacts reversibly with SH groups of proteins. Following this treatment only the SH groups of L-T3 sites from rat erythrocytes were found to be blocked. Scatchard analysis of the binding data for rat right-side-out and human inside-out vesicles showed high affinity sites with Kd values of 0.2 x 10(-10) and 2 x 10(-10) M, respectively. The results suggest that the orientation of L-T3-binding sites in the erythrocyte membrane is species-dependent. | The effect of thyroid hormones on the steady-state fluorescence polarization and on the release of the liposomal content was analyzed in liposomes composed of egg phosphatidylcholine and egg phosphatidyl choline:cholesterol in different molar ratios. Depending on liposome cholesterol composition, a dual effect of triiodothyronine was found. The fluorescence polarization of 1,6 diphenyl 1,3,5 hexatriene or 1-(4-trimethylaminophenyl) 6 phenyl-1, 3, 5 hexatriene decreased by the addition of the hormone when cholesterol content was in the range from 0 to 30 moles %, while it increased with cholesterol from 30 to 50 moles %. In the release experiments, the effect of triiodothyronine was also biphasic; the leakage was the highest at 0% and 50% and the lowest at 30 moles % of cholesterol. On the contrary, thyroxine was without effect on liposomes containing cholesterol from 30 to 50 mol %. This fact correlated with a lower incorporation of thyroxine, compared with that of triiodothyronine in liposomes containing up to 30 moles % of cholesterol. The fact that the above differential incorporation of thyroid hormones was also observed at physiological concentration and that most of the mammalian membrane cells have more than 25 moles % of cholesterol have for physiological implications to the observations reported here. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,809 |
To investigate the functional relationship between astrocytes and Ca2+-ATPase of cerebral capillary endothelial cells (capillary Ca2+-ATPase), cold lesions were produced and the cytochemical reaction (CR) for Ca2+-ATPase activity and morphological changes of astrocytes were chronologically studied. Under normal conditions, CR for capillary Ca2+-ATPase activity was mild. However, at 20 min after the operation, astrocytic end-feet embracing the capillaries were swollen, and CR was moderate. Deposits of slightly coarsened reaction product (RP) appeared and accumulated on the abluminal surface. CR became stronger as edema fluid accumulated. At 4, 7 and 15 days, detachment of the astrocytic processes from the capillary wall was observed and in the uncovered capillaries, CR was intense, especially on the abluminal surface. It could be thus possible that the enzyme was related to the blood-brain barrier (BBB). At 2 months, reactive astrocytes has recovered lesionresistant capillaries. CR was mild and its associated deposits were coarser, the number decreasing on both surfaces. The nature and localization of the deposits of RP in the scar were different from those under normal conditions, possibly due to the functional differences between normal and reactive astrocytes in the BBB. CR was mild in association with astrocytes embracing the capillary wall and was intense without astrocytes. Therefore, it might be possible that astrocytes exerted certain effects on capillary Ca2+-ATPase activity in relation to BBB function. | The histo- and cytochemical localization of Ca++-ATPase activity in the adenohypophysis of the guinea pig was studied utilizing a newly developed method (Ando et al. 1981). An intense reaction was observed in the wall of the blood vessels and between non-secretory cells (stellate cells) and endocrine cells of the pars distalis. Under the electron microscope the Ca++-ATPase reaction product was located extracellularly in relation to the plasmalemma of the stellate cells. This reaction was dependent on Ca++ and the substrate, ATP, and reduced by the addition of 0,1 mM quercetin to the standard incubation medium. Preheating of the sections before incubation completely inhibited the enzyme activity. When Mg++ in different concentrations were substituted for Ca++ in the incubation medium the reaction was always reduced. Both Ca++ and Mg++ in the incubation medium also reduced the reaction. The plasmalemma of the endocrine cells contains no demonstrable amount of Ca++-ATPase activity. The function of the Ca++-ATPase activity is discussed in relation to the regulation of the extracellular Ca++ concentration which seems to be important with respect not only to the secretory process of the endocrine cells but also to the metabolism of the adenohypophysis. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,810 |
In a physiological medium the resting membrane potential of synaptosomes from guinea-pig cerebral cortex, estimated from rhodamine 6G fluorescence measurements, was nearly -50mV. This agreed with calculations using the Goldman-Hodgkin-Katz equation. With external [Ca2+] less than or equal to 3 mM veratridine depolarisation (to -30 mV) was accompanied by increases in intrasynaptosomal free calcium concentrations (monitored by entrapped quin2) and parallel increases in total acetylcholine release. With external [Ca2+] greater than 3 mM both intrasynaptosomal free calcium concentrations and transmitter release were paradoxically reduced, providing further evidence for a close correlation between the two events. To support an explanation of these findings based on divalent cation screening of membrane surface charge (increasing the voltage gradient within the membrane and closing voltage-inactivated channels) surface potential measurements were made on synaptic lipid liposomes by using a fluorescent surface-bound pH indicator. These experiments provided evidence for the presence of screenable surface charge on synaptosomes, and it was further shown in depolarised synaptosomes themselves that total external [Ca2+ + Mg2+], and not [Ca2+] alone, set the observed peak in intrasynaptosomal free calcium. | The molecular mechanisms involved in veratridine-induced chromaffin cell death have been explored. ::: ::: ::: ::: ::: We have found that exposure to veratridine (30 μM, 1 h) produces a delayed cellular death that reaches 55% of the cells 24 h after veratridine exposure. This death has the features of apoptosis as DNA fragmentation can be observed. ::: ::: ::: ::: ::: Calcium ions play an important role in veratridine-induced chromaffin cell death because the cell permeant Ca2+ chelator BAPTA-AM and extracellular Ca2+ removal completely prevented veratridine-induced toxicity. ::: ::: ::: ::: ::: Following veratridine treatment, there is a decrease in mitochondrial function and an increase in superoxide anion production. Veratridine-induced increase in superoxide production was blocked by tetrodotoxin (TTX; 10 μM), extracellular Ca2+ removal and the mitochondrial permeability transition pore blocker cyclosporine A (10 μM). ::: ::: ::: ::: ::: Veratridine-induced death was prevented by different antioxidant treatments including catalase (100 IU ml−1), N-acetyl cysteine (100 μM), allopurinol (100 μM) or vitamin E (50 μM). ::: ::: ::: ::: ::: Veratridine-induced DNA fragmentation was prevented by TTX (10 μM). ::: ::: ::: ::: ::: Veratridine produced a time-dependent increase in caspase activity that was prevented by Ca2+ removal and TTX (10 μM). In addition, calpain and caspases inhibitors partially prevented veratridine-induced death. ::: ::: ::: ::: ::: These results indicate that chromaffin cells share with neurons the molecular machinery involved in apoptotic death and might be considered a good model to study neuronal death during neurodegeneration. ::: ::: ::: ::: ::: ::: ::: British Journal of Pharmacology (2000) 130, 1496–1504; doi:10.1038/sj.bjp.0703451 | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,811 |
Alterations in the glutathione system and impairment in energy metabolism have both been implicated in the loss of dopamine neurons in Parkinson's disease. This study examined the importance of cellular glutathione and the involvement of oxidative stress in the loss of mesencephalic dopamine and GABA neurons due to inhibition of energy metabolism with malonate, the reversible, competitive inhibitor of succinate dehydrogenase. Consistent with previous findings, exposure to malonate for 24 h followed by 48 h of recovery caused a dose-dependent loss of the dopamine population with little effect on the GABA population. Toxicity was assessed by simultaneous measurement of the high-affinity uptake of [3H]dopamine and [14C]GABA. Total glutathione content in rat mesencephalic cultures was decreased by 65% with a 24-h pretreatment with 10 microM buthionine sulfoxamine. This reduction in glutathione level greatly potentiated damage to both the dopamine and GABA populations and removed the differential susceptibility between the two populations in response to malonate. These findings point to a role for oxidative stress occurring during energy impairment by malonate. Consistent with this, several spin-trapping agents, alpha-phenyl-tert-butyl nitrone and two cyclic nitrones, MDL 101,002 and MDL 102,832, completely prevented malonate-induced damage to the dopamine neurons in the absence of buthionine sulfoxamine. The spin-trapping agents also completely prevented toxicity to both the dopamine and GABA populations when cultures were exposed to malonate after pretreatment with buthionine sulfoxamine to reduce glutathione levels. Counts of tyrosine hydroxylase-positive neurons verified enhancement of cell loss by buthionine sulfoxamine plus malonate and protection against cell loss by the spin-trapping agents. NMDA receptors have also been shown to play a role in malonate-induced dopamine cell loss and are associated with the generation of free radicals. Consistent with this, toxicity to the dopamine neurons due to a 1-h exposure to 50 microM glutamate was attenuated by the nitrone spin traps. These findings provide evidence for an oxidative challenge occurring during inhibition of energy metabolism by malonate and show that glutathione is an important neuroprotectant for midbrain neurons during situations when energy metabolism is impaired. | © 2012 Kanunnikova et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Use of CoA Biosynthesis Modulators and Selenoprotein Model Substance in Correction of Brain Ischemic and Reperfusion Injuries | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,812 |
Acetaminophen (APAP) hepatotoxicity has been related to several cases of hepatitis, cirrhosis, and hepatic transplant. As APAP hepatotoxicity is related to reactive oxygen species (ROS) formation and excessive oxidative stress, natural antioxidant compounds have been tested as an alternative therapy to diminish the hepatic dysfunction induced by APAP. Taraxacum officinale Weber (Family Asteraceae), commonly known as dandelion, is used for medicinal purposes because of its choleretic, diuretic, antioxidant, anti-inflammatory, and hepatoprotective properties. This study evaluated the hepatoprotective activity of T. officinale leaf extract against APAP-induced hepatotoxicity. T. officinale was able to decrease thiobarbituric acid-reactive substance levels induced by 200 mg/kg APAP (p.o.), as well as prevent the decrease in sulfhydryl levels caused by APAP treatment. Furthermore, histopathological alterations, as well as the increased levels of serum aspartate and alanine aminotransferases caused by APAP, were prevented by T. officinale (0.1 and 0.5 mg/mL). In addition, T. officinale extract also demonstrated antioxidant activity in vitro, as well as scavenger activity against 2,2-diphenyl-1-picrylhydrazyl and nitric oxide radicals. Our results clearly demonstrate the hepatoprotective effect of T. officinale against the toxicity induced by APAP. The possible mechanisms involved include its scavenger activities against ROS and reactive nitrogen species, which are attributed to the content of phenolic compounds in the extract. | Creatine has been reported to exert beneficial effects in several neurodegenerative diseases in which glutamatergic excitotoxicity and oxidative stress play an etiological role. The purpose of this study was to investigate the protective effects of creatine, as compared to the N-Methyl- d -Aspartate (NMDA) receptor antagonist dizocilpine (MK-801), against glutamate or hydrogen peroxide (H 2 O 2 )-induced injury in human neuroblastoma SH-SY5Y cells. Exposure of cells to glutamate (60–80 mM) or H 2 O 2 (200–300 μM) for 24 h decreased cellular viability and increased dichlorofluorescein (DCF) fluorescence (indicative of increased reactive oxygen species, ROS) and nitric oxide (NO) production (assessed by mono-nitrogen oxides, NOx, levels). Creatine (1–10 mM) or MK-801 (0.1–10 μM) reduced glutamate- and H 2 O 2 -induced toxicity. The protective effect of creatine against glutamate-induced toxicity involves its antioxidant effect, since creatine, similar to MK-801, prevented the increase on DCF fluorescence induced by glutamate or H 2 O 2 . Furthermore, creatine or MK-801 blocked glutamate- and H 2 O 2 -induced increases in NOx levels. In another set of experiments, the repeated, but not acute, administration of creatine (300 mg/kg, po ) in mice prevented the decreases on cellular viability and mitochondrial membrane potential (assessed by tetramethylrhodamine ethyl ester, TMRE, probe) of hippocampal slices incubated with glutamate (10 mM). Creatine concentration-dependent decreased the amount of nitrite formed in the reaction of oxygen with NO produced from sodium nitroprusside solution, suggesting that its protective effect against glutamate or H 2 O 2 -induced toxicity might be due to its scavenger activity. Overall, the results suggest that creatine may be useful as adjuvant therapy for neurodegenerative disease treatments. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,813 |
α-Quartz dust of respirable size—on inhalation—deposits in the lung, where it may remain for long duration and be a risk factor in the development of silicosis and (with increasing weight of evidence) lung cancer in humans. The risk assessment for these end points is fundamentally based on those properties of α-quartz that allow it to persist over time in the lung. For individual samples of respirable α-quartz it is likely that the specific toxicity of the α-quartz in the sample is related to this residence time, which, in turn, will be a function of its crystallinity because of the latter's potential influence on α-quartz's cytotoxicity and solubility. Current X-ray powder diffraction technology allows for the routine assessment of diffraction line broadening by measuring the full-width-at-half-maximum (FWHM) of a diffraction line. The FWHM for any accessible α-quartz diffraction line in a sample can then be used to directly assess Murata and Norman's Crystallinity Index for the α-quartz. This method gre... | Nanotechnology has enabled the discovery of a multitude of novel materials exhibiting unique physicochemical (PChem) properties compared to their bulk analogues. These properties have led to a rapidly increasing range of commercial applications; this, however, may come at a cost, if an association to long-term health and environmental risks is discovered or even just perceived. Many nanomaterials (NMs) have not yet had their potential adverse biological effects fully assessed, due to costs and time constraints associated with the experimental assessment, frequently involving animals. Here, the available NM libraries are analyzed for their suitability for integration with novel nanoinformatics approaches and for the development of NM specific Integrated Approaches to Testing and Assessment (IATA) for human and environmental risk assessment, all within the NanoSolveIT cloud-platform. These established and well-characterized NM libraries (e.g. NanoMILE, NanoSolutions, NANoREG, NanoFASE, caLIBRAte, NanoTEST and the Nanomaterial Registry (>2000 NMs)) contain physicochemical characterization data as well as data for several relevant biological endpoints, assessed in part using harmonized Organisation for Economic Co-operation and Development (OECD) methods and test guidelines. Integration of such extensive NM information sources with the latest nanoinformatics methods will allow NanoSolveIT to model the relationships between NM structure (morphology), properties and their adverse effects and to predict the effects of other NMs for which less data is available. The project specifically addresses the needs of regulatory agencies and industry to effectively and rapidly evaluate the exposure, NM hazard and risk from nanomaterials and nano-enabled products, enabling implementation of computational 'safe-by-design' approaches to facilitate NM commercialization. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,814 |
The purpose of this research was to prepare and evaluate floating drug delivery system of Lamivudine. Floating matrix tablets of Lamivudine were developed to prolong gastric residence time and increase its bioavailability. Rapid gastrointestinal transit could result in incomplete drug release from the drug delivery system above the absorption zone leading to diminished efficacy of the administered dose. The tablets were prepared by direct compression technique, using polymers such as hydroxyl propyl methyl cellulose (HPMC E15), Ethyl cellulose and Xanthan gum combination and other standard excipients. Sodium bicarbonate was incorporated as a gas-generating agent. The effects of different concentrations of HPMC, EC and Xanthan gum on drug release profile and floating properties were investigated. Comparable release profiles between the commercial product and the designed system were obtained. The model fitting showed that the optimized formulation F2 formulations followed Korsmeyer and Peppas model, which had a higher value of correlation coefficient (r). While tablet hardness had little or no effect on the release kinetics and was found to be a determining factor with regards to the buoyancy of the tablets. | Nicardipine hydrochloride, a calcium channel blocker with significant vasodilating and antihypertensive activities, was formulated in this work as sustained release floating capsules. A hydrocolloid of high viscosity grade was used for the floating systems. The inclusion of sodium bicarbonate to allow evolution of CO2 to aid buoyancy was studied. Polymers that retard drug release were included as coprecipitates with the drug and/or as additives in the formulated capsules. Both simple powder mixing of the ingredients and granule preparation via wet granulation were used. Seven capsule formulae were prepared. The prepared capsules were evaluated in vitro by testing drug dissolution, floating time and the kinetics of drug release. In vitro evaluation of a commercially available conventional 20 mg capsule of nicardipine hydrochloride, "Micard", was carried out for comparison. The hydrocolloid used succeeded in effecting capsule buoyancy. Floating time increased with increasing the proportion of the hydrocolloid. Inclusion of sodium bicarbonate increased buoyancy. All of the seven floating capsule formulae prepared proved efficient in controlling drug release. The sustained release floating capsule formulation of choice was evaluated in vivo in comparison to "Micard" capsules using rabbits. Reversed phase HPLC with UV detection was used for drug determination in rabbit plasma. Plasma concentration time curves revealed a longer drug duration for administration in the sustained release formula than the conventional "Micard" capsule being 16 h in the former versus 8 h for the latter. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,815 |
Chronic heart failure is debilitating, often fatal, expensive to treat and common. In most patients it is a late consequence of myocardial infarction (MI). The intracellular signals following infarction that lead to diminished contractility, apoptosis, fibrosis and ultimately heart failure are not fully understood but probably involve p38-mitogen activated protein kinases (p38), a family of serine/threonine kinases which, when activated, cause cardiomyocyte contractile dysfunction and death. Pharmacological inhibitors of p38 suppress inflammation and are undergoing clinical trials in rheumatoid arthritis, Chrohn's disease, psoriasis and surgery-induced tissue injury. In this review, we discuss the mechanisms, circumstances and consequences of p38 activation in the heart. The purpose is to evaluate p38 inhibition as a potential therapy for ischaemic heart disease. | Emerging evidence indicates the pronounced role of inflammasome activation linked to reactive oxygen species (ROS) in the sterile inflammatory response triggered by ischemia/reperfusion (I/R) injury. Ethyl pyruvate (EP) is an antioxidant and conveys myocardial protection against I/R injury, while the exact mechanisms remain elusive. We aimed to investigate the effect of EP on myocardial I/R injury through mechanisms related to ROS and inflammasome regulation. The rats were randomly assigned to four groups: (1) sham, (2) I/R-control (IRC), (3) EP-pretreatment | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,816 |
Anti-apoptotic Bcl-2 localizes in the membranes of mitochondria and endoplasmic reticulum (ER) and resists a broad range of apoptotic stimuli. However, the precise function of Bcl-2 in ER is still unclear. We herein examined the anti-apoptotic potencies of Bcl-2 in mitochondria and ER in vitro. The mitochondria isolated from HeLa cells, which have little or practically no Bcl-2, were apoptosis-competent. That is, membrane-bound Bax was activated and cytochrome c was released when the isolated mitochondria were incubated at 35 °C. Cytochrome c release from the apoptosis-competent mitochondria was suppressed by co-incubation with the mitochondria with overexpressed Bcl-2 (Bcl-2 mitochondria), suggesting that Bcl-2 anchored in one mitochondrion can suppress cytochrome c release from another mitochondrion. Similar results were obtained when microsomes with overexpressed Bcl-2 (Bcl-2 microsomes) were co-incubated with apoptosis-competent mitochondria. A quantitative titration analysis showed that Bcl-2 in the ER suppresses cytochrome c release as efficiently as that in the mitochondria. An immunoprecipitation assay showed that Bcl-2 in both mitochondria and ER binds to Bax at almost the same degree. However, in the presence of tBid, co-incubation of apoptosis-competent mitochondria with Bcl-2 microsomes, but not with Bcl-2 mitochondria, diminished the Bax-binding to Bcl-2 significantly, suggesting that Bcl-2 in ER is readily inactivated by tBid. Co-incubation assay further confirmed that Bcl-2 in the ER, but not Bcl-2 in the mitochondria, is potentially inactivated by tBid. Our quantitative in vitro studies indicate that Bcl-2 in mitochondria and ER are similarly potent in inhibiting Bax-associated apoptosis of other mitochondria, but are regulated by tBid differently. | Two important questions on the molecular mechanism of the B cell CLL/lymphoma 2 (BCL2) proteins involve the interaction network between pro- and antiapoptotic members and the role of their translocation to the mitochondrial membrane during apoptosis. We used fluorescence correlation spectroscopy to quantify the molecular interactions of BH3-interacting domain death agonist (BID) and its truncated form tBID with the B cell lymphoma extra-large protein truncated at the C terminus (BCL(XL)DeltaCt) in solution and in membranes, and we found that (i) only the active form tBID binds to BCL(XL)DeltaCt and (ii) that the membrane strongly promotes binding between them. Particularly, a BH3 peptide from BID disrupts the tBID-BCL(XL) complex in solution, but only partially in lipid bilayers. These data indicate that tBID-BCL(XL) interactions in solution and lipid membranes are distinct, and they support a model in which BCL(XL) inhibition of tBID takes place predominantly at the membrane. Our findings imply an active role of the membrane in modulating the interactions between BCL2 proteins that has so far been underestimated. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,817 |
SGTB (Small glutamine-rich tetratricopeptide repeat (TPR)-containing, β) plays a critical role in protein-protein interactions. The interaction between SGTB and heat shock cognate protein (Hsc70)/heat shock protein (Hsp70) has aroused much attention in recent years. The present study was designed to elucidate dynamic changes in SGTB expression and distribution in the cerebral cortex in a lipopolysaccharide (LPS)-induced neuroinflammation rat model. It was found that SGTB expression was increased significantly in apoptotic neurons after LPS injection. The result of our in vitro study suggested that SGTB up-regulation might be associated with neuronal apoptosis after H2O2 challenge. In addition, silencing of SGTB in cultured PC12 (Pheochromocytoma) by siRNA indicated that SGTB was required for neuronal apoptosis induced by oxidative stress. Our finding about the cellular signal pathway may provide a new strategy against neuronal apoptosis in neuroinflammation in CNS. | Background ::: Giant cell arteritis (GCA) is the most common form of vasculitis affecting elderly people. It is one of the few true ophthalmic emergencies but symptoms and signs are variable thereby making it a challenging disease to diagnose. A temporal artery biopsy is the gold standard to confirm GCA, but there are currently no specific biochemical markers to aid diagnosis. We aimed to identify a less invasive method to confirm the diagnosis of GCA, as well as to ascertain clinically relevant predictive biomarkers by studying the transcriptome of purified peripheral CD4+ and CD8+ T lymphocytes in patients with GCA. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,818 |
We previously reported that the lower activity of mevalonate pyrophosphate decarboxylase (MPD) was caused by the reduced amount of this enzyme in stroke-prone spontaneously hypertensive rat (SHRSP) by immunoblot analysis using 20,000 x g supernatant containing cytosol and microsomes. A recent study showed that at least three different subcellular compartments, including peroxisomes, are involved in cholesterol synthesis. In this study, we examined the subcellular distribution of 45- and 37-kDa MPD in the liver of SHRSP and compared normotensive Wistar Kyoto rat (WKY) and SHRSP. 45-kDa MPD was detected in the cytosol and peroxisomes of SHRSP, while 37-kDa MPD was detected in the cytosol of SHRSP, but not in the peroxisomes. The relative enrichment of 45-kDa MPD in peroxisomes was lower than that of LDH, suggesting the possibility that 45-kDa MPD of SHRSP did not exist in the peroxisomes. Also, 45-kDa MPD was decreased in the crude extract containing 1% Triton X-100, cytosol and peroxisomes of SHRSP, and 37-kDa MPD was decreased in the crude extract containing 1% Triton X-100 and cytosol of SHRSP, as compared with WKY. These data indicate that the cholesterol synthesis in the liver of SHRSP by the reduced amount of MPD is significantly reduced. | Strokes are preceded by oxidative stress and inflammation, two processes linked to atherosclerosis and hypertension. Statins have been widely employed to control atherosclerosis; however, there could be neurological implications to its use—including cognitive impairment. Thus,we aimed to determine whether alpha-tocopherol is capable of reversing the neurological side effects of statins and enhancing its anti-inflammatory properties. To assess these effects, 15-week-old stroke-prone spontaneously hypertensive rats (SHRSPs) were divided into four groups (n = 6, each): alpha-tocopherol (AT), lovastatin (LoV), alpha-tocopherol + lovastatin (AT + LoV), and control (C).We administered 120 IU of alpha-tocopherol diluted in 0.1 ml of coconut oil,whereas the dose of lovastatin was administered at a ratio of 1 mg/kg of rat body weight. The control group received 0.1 ml coconut oil. All animals received the treatments via orogastric gavage.We assessed body weight, diuresis, food and water intake, oxidative stress (malondialdehyde levels), the total cellular injury marker (lactate dehydrogenase), short and long-term memory, cognition, and histopathological changes in the hippocampus. The results demonstrated that lovastatin treatment did not negatively affect the memory of our animal model. In fact, the animals treated with AT and LoV showed improvement in memory and cognition. Additionally, both treatments decrease lactate dehydrogenase and oxidative stress levels. Furthermore, our study also demonstrated hippocampal tissue preservation in the treated groups. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,819 |
Living organisms are continually exposed to free radicals and other reactive oxygen species as a result of metabolizing oxygen and other redox-active compounds. Excessive production can result in biological damage, whereas in other situation, specific oxidants are generated as a host defense mechanism or as a cell signal that activates gene expression and metabolic responses. This article provides an overview of the specific reactive oxygen species that are generated biologically, how and where they arise, and their chemical reactivity with biological molecules. ::: ::: ::: Keywords: ::: ::: biological generation of reactive oxygen species; ::: biological reactivity of reactive oxygen species; ::: oxygen radicals; ::: superoxide; ::: hydrogen peroxide; ::: oxidative stress; ::: redox regulation | Purine 5′,8-cyclo-2′-deoxynucleosides (cPu) are tandem-type lesions observed among the DNA purine modifications and identified in mammalian cellular DNA in vivo. These lesions can be present in two diasteroisomeric forms, 5′R and 5′S, for each 2′-deoxyadenosine and 2′-deoxyguanosine moiety. They are generated exclusively by hydroxyl radical attack to 2′-deoxyribose units generating C5′ radicals, followed by cyclization with the C8 position of the purine base. This review describes the main recent achievements in the preparation of the cPu molecular library for analytical and DNA synthesis applications for the studies of the enzymatic recognition and repair mechanisms, their impact on transcription and genetic instability, quantitative determination of the levels of lesions in various types of cells and animal model systems, and relationships between the levels of lesions and human health, disease, and aging, as well as the defining of the detection limits and quantification protocols. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,820 |
Adlay bran free phenolic extract has been previously demonstrated to possess potent xanthine oxidase (XOD) inhibitory activity. The aims of this study were to characterize the free phenolic profile of adlay bran and investigate the structure-activity relationship, underlying mechanism and interaction of phenolic acids as XOD inhibitors. A total of twenty phenolics including ten phenolic acids, two coumarins, two phenolic aldedhyes and six flavonoids were identified in a phenolic compound-guided separation by UPLC-QTOF-MS/MS. Adlay bran free phenolic extract possessed strong XOD inhibitory activity related to hydroxycinnamic acids with methoxyl groups. The hydrogen bonding and hydrophobic interactions were the main forces in the binding of adlay phenolics to XOD. Sinapic acid, identified in adlay bran for the first time, possessed strong XOD inhibitory activity in a mixed non-competitive manner, and synergistic effects with other adlay phenolic acids at low concentrations, and would be a promising agent for preventing and treating hyperuricemia. | Adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) contains various phytonutrients for treating many diseases in Asia. To investigate whether orally administered adlay bran oil (ABO) can cause drug interactions, the effects of ABO on the pharmacokinetics of five cytochrome P450 (CYP) probe drugs were evaluated. Rats were given a single oral dose (2.5 mL/kg BW) of ABO 1 h before administration of a drug cocktail either orally or intravenously, and blood was collected at various time points. A single oral dose of ABO administration did not affect the pharmacokinetics of five probe drugs when given as a drug cocktail intravenously. However, ABO increased plasma theophylline (+28.4%), dextromethorphan (+48.7%), and diltiazem (+46.7%) when co-administered an oral drug cocktail. After 7 days of feeding with an ABO-containing diet, plasma concentrations of theophylline (+45.4%) and chlorzoxazone (+53.6%) were increased after the oral administration of the drug cocktail. The major CYP enzyme activities in the liver and intestinal tract were not affected by ABO treatment. Results from this study indicate that a single oral dose or short-term administration of ABO may increase plasma drug concentrations when ABO is given concomitantly with drugs. ABO is likely to enhance intestinal drug absorption. Therefore, caution is needed to avoid food–drug interactions between ABO and co-administered drugs. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,821 |
Plasma samples from patients with chancroid diagnosed both on clinical and microbiological grounds were assessed for their ability to inhibit mitogen-induced proliferation of human lymphocytes from healthy donors. All serum samples analysed suppressed phytohaemagglutinin A (PHA) blastogenic response. A significant difference in the observed extent was seen when serum samples from patients with and without associated lymphadenopathy were compared (P < 0.05). Using an interleukin-2 (IL-2)-dependent cell line it could be demonstrated that the addition of patients' plasma to cultured cells markedly depressed mitogen-induced IL-2 synthesis. Results presented suggest that cell-mediated mechanisms play a role in the pathogenesis of infection due to Haemophilus ducreyi. | Recent studies undertaken in southern Africa and elsewhere indicate that many short or single dose treatments are available to treat chancroid. Erythromycin 500 mg three times a day for five days, ciprofloxacin 500 mg, sulphamethopyrazine 800 mg and trimethoprim 1000 mg or sulphametrole 3200 mg and trimethoprim 640 mg as single oral doses, or ceftriaxone 250 mg as a single intramuscular injection are all effective in treating the disease. The widespread use of these regimens largely depends on the accuracy of diagnosis, susceptibilities of local Haemophilus ducreyi isolates to antimicrobials, and financial considerations. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,822 |
Activation of the sympathetic neurons and release of adrenomedullary catecholamines are the principal early reflex responses to hemorrhage. These are initiated by arterial baro- and chemoreceptors, from other cardiopulmonary receptors, and by intracerebral receptors responding to ischemia. A principal gateway for integrating the autonomic responses are a small collection of neurons in a region of the rostral ventrolateral medulla (RVL), containing a cluster of neurons of the C1 adrenergic cell group, the C1 area. Neurons in the C1 area of RVL project exclusively to autonomic nuclei of the spinal cord, are tonically active, and fire with a rhythm linked to the cardiac cycle. They are essential for maintaining resting discharge of sympathetic nerves and, consequently, arterial pressure (AP) and heart rate. They also are critical for reflex changes in AP in the baro- and chemoreceptor, somato-sympathetic (pain), and cerebral ischemic reflexes. Neurons of the C1 area are under tonic excitatory and inhibitory control by pathways from other autonomic centers. They are controlled by a range of neurotransmitters including, gamma aminobutyric acid (GABA), acetylcholine, catecholamines, enkephalin, and several neuropeptides. They also serve as a site of action for the hypotensive actions of several clinically important neurotransmitters. The C1-area of RVL may play a critical role in the autonomic responses to hemorrhage and may be an important target for drugs seeking to treat hemorrhagic shock. | Stimulation of cutaneous and muscle afferents induces several cardiovascular adjustments such as hypertension, tachycardia, and muscle vasodilation. Although previous studies have demonstrated that the rostral ventrolateral medulla (RVL) mediates sympathoexcitation and pressor responses to sciatic nerve stimulation (SNS), whether it also mediates blood flow adjustments remains unclear. Therefore, in the present study, we examined the role of the RVL in the vasodilation induced by SNS and the possible neurotransmitters involved. In Urethane-anesthetized, paralyzed, and artificially ventilated rats, SNS (square pulses, 1 ms, 20 Hz, 800--1200 microA, 10 s) produced increases in blood pressure, heart rate, blood flow, and vascular conductance of the stimulated limb. Unilateral microinjection of kainic acid (2 nmol/100 nl) into the RVL contralateral to the stimulated limb abolished cardiovascular adjustments to SNS. Unilateral microinjections of kynurenic acid (2 nmol/100 nl) selectively abolished the pressor response to SNS, whereas bicuculline (400 pmol/100 nl) abolished the increases in blood flow without changing the pressor response. These results suggest that glutamatergic synapses within the RVL mediate pressor responses, whereas GABAergic synapses may mediate the vasodilation to SNS. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,823 |
Copper and zinc percutaneous absorptions were assessed in vitro using sliced human skin and both petrolatum and hydrophilic gels as vehicles. Applied quantities were largely in excess for the duration of the experiment (72 h). The absorption of sulphates and chlorides was compared. The cumulated amount recovered in receptor fluid was below 50 micrograms/cm2. The apparent permeability constant values kept in the range of 10(-6) cm h-1, except for ZnCl2 in gel vehicle (2.9 10(-5) cm h-1). With the exception of CuCl2 in gel vehicle, chlorides gave higher absorption rates than sulphates. This can be related to the higher octanol-water partition coefficient of chlorides. Storage within the epidermis was found to be equal to or greater than, and within the dermis equal to or lower than the 72 hour cumulative amount in receptor fluid. No difference was found in this respect between copper an d zinc. This work confirms the poor absorption of electrolytes through normal human skin, whatever the vehicle used. | Zinc is one of the most important microelements in human body. It is a constituent of a great number of enzymes. It influences on many metabolic processes and provides proper functioning of all body as well as the skin. Zinc protects from free radicals and UV radiation, regulates keratinization and fibroblast proliferation. Zinc is also involved in melanogenesis, fatty acids and vitamin A and E metabolism. Topically applied zinc fastens wound healing, regulates sebum secretion, and exhibits antiseptic and antibacterial activity. Zinc compounds are cosmetic ingredients of frequent use. They can be found in nearly every type of cosmetic products exhibiting a wide range of properties. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,824 |
Publisher Summary The membrane-free cytosol of pig brain contains glycolipid transfer protein (GL-TP) that stimulates the transfer of various glycosphingolipids and glyceroglycolipids among membranes in vitro. The protein has been purified to homogeneity from this source. The GL-TP from pig brain functions as a specific carrier of glycolipids most likely by forming a 1 : 1 molecular complex. Under conditions where one of the membranes lacks glycolipids, GL-TP has been found to catalyze a net transfer reaction. The chapter describes the purification of GL-TP from pig brain. GL-TP has also been partially purified from rat brain and several cell lines of rat, mouse, and human origin. Antisera raised against pig GL-TP in rabbits are cross-reactive with rat, mouse, and human GL-TP. | Glycolipid transfer protein (GL-TP), a nonglycosylated protein with a molecular weight of 22,000 K, has been purified from pig brain. The protein transfers, by a carrier mechanism, glycolipids with a beta-glucosyl or beta-galactosyl residue directly linked to either ceramide or diacylglycerol. GL-TP appears to be present in most animal cells, and evidence has been obtained which indicates that it is a cytoplasmic protein. Little is known about the function of GL-TP. Current evidence indicates that glycosphingolipid glycosylation occurs at the luminal side of the Golgi apparatus, except for the glucosylation of ceramide, which has been shown to occur at the cytoplasmic side of the Golgi or endoplasmic membrane. It appears most likely that GL-TP participates in the intracellular traffic of glucosylceramide. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,825 |
Aims: Ofloxacin is used as anti-microbial agent. Due to its high solubility in gastric pH, a floating drug delivery system was selected to improve the bioavailability and therapeutic efficacy of the drug. Settings and Design: The purpose of the study was to prepare and evaluate effervescent floating tablets of ofloxacin to prolong its gastric residence and increase bioavailability. Materials and Methods: Drug, semi-synthetic and natural polymers, such as HPMC K4M, Guar gum, Xanthan gum and Chitosan, were used. Sodium bicarbonate and citric acid were used as gas-generating agents and tablet compression was done by direct compression. The prepared tablets were characterized and were evaluated for in vitro floating behavior, swelling index, in vitro drug release studies and release kinetics. Results: Formulation F6 containing xanthan gum and chitosan in a 1:1 ratio attained sustained release for 12 h and drug release observed was about 76.7%. Swelling index was in the range 62.17 ± 1.49% to 194.02 ± 1.05%. Floating lag time was observed in the range 4.11-6.26 min. Conclusion: The in vitro results showed better drug release conditions, supported by follow-up in vivo studies, suggesting that this formulation is advantageous over the current marketed formulation, through increased gastric residence and bioavailability. | Objectives: The purpose of the work was to develop gastro retentive floating tablets of Dicloxacillin sodium using different ratios of HPMC K 100M, Xanthan gum, Guar gum. Sodium bicarbonate is used as a gas generating agent. Dicloxacillin sodium is used to treat a wide variety of bacterial infections and has a half-life of about 2 hr. Methods: Gastro retentive floating tablets containing 270 mg of dicloxacillin sodium were prepared by wet granulation method employing different ratios of polymers. Results: The formulated tablets were evaluated for precompression parameters and were in the acceptable limits. Post-compression parameters such as weight variation, hardness, friability, swelling index, floating lag time and total floating time were also evaluated. The formulation F3 with HPMC K 100M showed 98.87% of drug release at the end of 12 hr, maintained integrity of tablets and have an optimum floating lag time of 90±0.14 sec and total floating time of 12 hr. The optimized formulation F3 was fitted to various kinetic models and the results showed that F3 formulation followed Zero order kinetics with an R2 value of 0.993. The mechanism of drug release from F3 formulation was non-fickian diffusion. Conclusion: The study concluded that, among all the developed formulations, F3 formulation floated up to 12 hr with maximum drug release and can be considered as promising formulation. Key words: Dicloxacillin sodium, Floating tablets, HPMC K100M, Swelling index, Buoyancy. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,826 |
Clostridioides difficile is the major pathogen causing diarrhea following antibiotic treatment. It is considered to be a strictly anaerobic bacterium, however, previous studies have shown a certain and strain-dependent oxygen tolerance. In this study, the model strain C. difficile 630Δerm was shifted to micro-aerobiosis and was found to stay growing to the same extent as anaerobically growing cells with only few changes in the metabolite pattern. However, an extensive change in gene expression was determined by RNA-Seq. The most striking adaptation strategies involve a change in the reductive fermentation pathways of the amino acids proline, glycine and leucine. But also a far-reaching restructuring in the carbohydrate metabolism was detected with changes in the phosphotransferase system (PTS) facilitated uptake of sugars and a repression of enzymes of glycolysis and butyrate fermentation. Furthermore, a temporary induction in the synthesis of cofactor riboflavin was detected possibly due to an increased demand for flavin mononucleotid (FMN) and flavin adenine dinucleotide (FAD) in redox reactions. However, biosynthesis of the cofactors thiamin pyrophosphate and cobalamin were repressed deducing oxidation-prone enzymes and intermediates in these pathways. Micro-aerobically shocked cells were characterized by an increased demand for cysteine and a thiol redox proteomics approach revealed a dramatic increase in the oxidative state of cysteine in more than 800 peptides after 15 min of micro-aerobic shock. This provides not only a catalogue of oxidation-prone cysteine residues in the C. difficile proteome but also puts the amino acid cysteine into a key position in the oxidative stress response. Our study suggests that tolerance of C. difficile towards O2 is based on a complex and far-reaching adjustment of global gene expression which leads to only a slight change in phenotype. | We define multiple mechanisms by which commensals protect against or worsen Clostridioides difficile infection. Using a systems-level approach we show how two species of Clostridia with distinct metabolic capabilities modulate the pathogen’s virulence to impact host survival. Gnotobiotic mice colonized with the amino acid fermenter Clostridium bifermentans survived infection, while colonization with the butyrate-producer, Clostridium sardiniense, more rapidly succumbed. Systematic in vivo analyses revealed how each commensal altered the pathogen’s carbon source metabolism, cellular machinery, stress responses, and toxin production. Protective effects were replicated in infected conventional mice receiving C. bifermentans as an oral bacteriotherapeutic that prevented lethal infection. Leveraging a systematic and organism-level approach to host-commensal-pathogen interactions in vivo, we lay the groundwork for mechanistically-informed therapies to treat and prevent this disease. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,827 |
Near-infrared (NIR) spectroscopy was applied to rat liver allografts for assessing nitric oxide (NO) synthesis and tissue oxygenation as a means of monitoring the rejection response following liver transplantation. Orthotopic liver transplantation was performed in rats, which were assigned to three groups as follows: group 1, a syngeneic combination (lewis to Lewis); group 2, an allogeneic combination (ACI to Lewis); and group 3, an allogeneic combination treated with 15-deoxyspergualin. NIR spectroscopy was performed on the grafts in recipients, and the relative changes in nitrosyl-Hb (NO bound to erythrocyte hemoglobin), oxy-Hb, and oxidized cytochrome oxidase (Cyt.aa3) were obtained. The level of nitrosyl-Hb was significantly elevated from postoperative day (POD) 3 in group 2 compared with that in group 1, which remained constant (P < 0.05). In group 3, the elevation was significantly suppressed. These data indicate that the alloimmune response is associated with a dramatic change in NO synthesis in grafted livers. In a separate experiment, NO synthesis was also increased after long cold preservation (24 hr) in syngeneic liver transplants. However, the increase was transient and subsided on POD 3. Levels of oxy-Hb and oxidized Cyt.aa3 in group 2 were significantly decreased when parenchymal disorder was confirmed histologically (POD 6 and 8), compared with those in group 1, which remained constant (P < 0.05). In group 3, both of these levels showed improvement. Thus, our NIR spectroscopy technique was shown to be capable of assessing simultaneously both the immune response and the degree of immune-induced destruction of allograft tissue following liver transplantation through monitoring of NO synthesis and tissue oxygenation. | The nitric oxide radical (NO•) is an important mediator of both physiological and pathophysiological processes. NO• is produced by nitric oxide synthase (NOS; EC 1.14.13.39), an enzyme that exists in three isoforms encoded by distinct genes (1)(2). All isoforms of NOS catalyze the conversion of l-arginine into citrulline and NO•. In this reaction, which requires oxygen and NADPH, a guanidino-nitrogen atom of l-arginine is incorporated into NO•. Neuronal NOS (type I, nNOS) and endothelial (type III, eNOS) are Ca2+- and calmodulin-dependent constitutive NOS isoforms. nNOS has a function in neurotransmission. NO• produced by eNOS is identical to endothelium-derived relaxing factor and is the principal signal for relaxation of vascular smooth muscle cells. In addition, NO• produced by the endothelium has antithrombotic actions. Thus, eNOS and nNOS isoforms have important functions under normal conditions. They are present intracellularly, are rapidly activated by intracellular Ca2+ fluxes, and produce small quantities of NO•. ::: ::: Inducible NOS (iNOS, type II) is not expressed under normal conditions. iNOS is induced by cytokines and (or) endotoxin during inflammatory and infectious processes and produces abundant amounts of NO• for extended periods. iNOS can be induced in many cell types, including hepatocytes, macrophages, neutrophils, smooth muscle cells, and chondrocytes. Induction of iNOS requires de novo protein synthesis. NO• produced by iNOS has antimicrobial activity and may be involved in killing tumor cells. As such, it is part of the nonspecific host defense system. Increased expression of iNOS has been demonstrated in a wide range of disorders, including sepsis, asthma, rheumatoid arthritis, atherosclerotic lesions, tuberculosis, inflammatory bowel disease, Helicobacter pylori-induced gastritis, allograft rejection, Alzheimer disease, and multiple sclerosis (3)(4)(5)(6)(7)(8)(9 … | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,828 |
A calibration-based technique for real-time measurement of pyruvate polarization by partial integral analysis of the doublet from the neighbouring J-coupled carbon is presented. In vitro calibration data relating the C2 and C1 asymmetries to the instantaneous C1 and C2 polarizations, respectively, were acquired in blood. The feasibility of using the in vitro calibration data to determine the instantaneous in vivo C1 and C2 polarizations was demonstrated in the analysis of rat kidney and pig heart spectral data. An approach for incorporating this technique into in vivo protocols is proposed. Copyright © 2013 John Wiley & Sons, Ltd. | The phenomenon of nuclear magnetic resonance (NMR) involves placing magnetically active nuclear spins embedded in a gas, liquid or solid phase in a constant, large and uniform magnetic field, causing a splitting of magnetic energy levels.Energy can be absorbed by these spins from a resonant radiofrequency (RF) field causing transitions between these levels. Immediately following this absorption, the spins start to exchange this energy among themselves and also pass it on to other degrees of freedom, that is, the spins start to relax. Relaxation is central to the NMR phenomenon as a necessary prerequisite for its detection. It is also used as a probe for obtaining information on the local environment of the spins and about the dynamics of the molecules in which the spins are embedded. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,829 |
To examine the cellular mechanisms of H+ transfer in rabbit papillary collecting duct (PCD), the 5,5-[14C]dimethyloxazolidine-2,4-dione-derived cell pH (pHi), the [3H]triphenylmethylphosphonium-derived membrane potential (Em), the lumen-to-cell Na+ concentration gradient [( Na+]o/[Na+]i), and cell potassium and chloride concentrations were studied at 37 degrees C in separated PCD from rabbits pretreated with deoxycorticosterone acetate. The variations in cell pH values were used as an index of changes in H+ secretion. Under standard conditions pHi was 7.30 +/- 0.04, [Na+]o/[Na+]i was 2.46 +/- 0.43, Em was 78 +/- 7 mV (cell negative), [K+]i was 105 +/- 10 mM, and [Cl-]i was 33 +/- 6 mM; the value of pHi thus remained higher than expected if H+ ions were passively distributed (6.13). Acetazolamide, 10(-4) M, alkalinized the cells. When [Na+]o/[Na+]i was reduced (low-Na+ medium or 10(-3) M ouabain), the cells did not acidify, suggesting that net H+ secretion did not decrease; also, pHi was not linked to the variations in the transmembrane chloride concentration gradients. When the cells were depolarized (low-Na+ medium), they became more alkaline; when the cells were hyperpolarized (10(-4) M amiloride), they became more acid; minor change in Em (ouabain) was associated with no change in pHi. It is concluded that: 1) H+ is actively secreted into the lumen; 2) active H+ secretion may not be secondary, via electroneutral Na+:H+ countertransport or HCl cotransport, but probably occurs via a primary H+ pump; 3) variations in Em probably affect pHi by acting on both the active H+ transport system and passive movements of HCO-3 (or its equivalent). | Paired micropuncture experiments were carried out in plasma-replete volume-expanded rats to examine the acute effects of 1-desamino-8-D-arginine vasopressin (dDAVP) on urinary acidification and tubular handling of bicarbonate and chloride. No effect was detected on the fractional absorption of water, total CO2, and chloride at end-proximal and early distal sites of superficial nephrons in intact animals; dDAVP, however, inhibited the fractional absorption of total CO2 in Henle's loop while stimulating that of chloride in thyroparathyroidectomized (TPTX) somatostatin-infused rats. In the distal tubule accessible to micropuncture, net total CO2 secretion was observed during hypotonic volume expansion, which reversed to net total CO2 absorption during dDAVP infusion in intact Wistar rats. Marked stimulation of urinary acidification occurred in all animals as attested by a fall in urine pH and bicarbonate excretion. Net acid excretion almost doubled in intact rats. We conclude that (a) antidiuretic hormone (ADH) inhibits fractional bicarbonate absorption in the thick ascending limb while stimulating that of chloride at least in TPTX somatostatin-infused rats, and (b) ADH stimulates proton secretion (or inhibits bicarbonate secretion) in the distal tubule and cortical collecting ducts, which leads to enhanced urinary acidification. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,830 |
The movement of fluid and solutes across biological membranes facilitates the transport of nutrients for living organisms and maintains the fluid and osmotic pressures in biological systems. Understanding the pressure balances across membranes is crucial for studying fluid and electrolyte homeostasis in living systems, and is an area of active research. In this study, a set of enhanced Kedem-Katchalsky (KK) equations is proposed to describe fluxes of water and solutes across biological membranes, and is applied to analyze the relationship between fluid and osmotic pressures, accounting for active transport mechanisms that propel substances against their concentration gradients and for fixed charges that alter ionic distributions in separated environments. The equilibrium analysis demonstrates that the proposed theory recovers the Donnan osmotic pressure and can predict the correct fluid pressure difference across membranes, a result which cannot be achieved by existing KK theories due to the neglect of fixed charges. The steady-state analysis on active membranes suggests a new pressure mechanism which balances the fluid pressure together with the osmotic pressure. The source of this pressure arises from active ionic fluxes and from interactions between solvent and solutes in membrane transport. We apply the proposed theory to study the transendothelial fluid pressure in the in vivo cornea, which is a crucial factor maintaining the hydration and transparency of the tissue. The results show the importance of the proposed pressure mechanism in mediating stromal fluid pressure and provide a new interpretation of the pressure modulation mechanism in the in vivo cornea. | Current models for protrusive motility in animal cells focus on cytoskeleton-based mechanisms, where localized protrusion is driven by local regulation of actin biochemistry. In plants and fungi, protrusion is driven primarily by hydrostatic pressure. For hydrostatic pressure to drive localized protrusion in animal cells, it would have to be locally regulated, but current models treating cytoplasm as an incompressible viscoelastic continuum or viscous liquid require that hydrostatic pressure equilibrates essentially instantaneously over the whole cell. Here, we use cell blebs as reporters of local pressure in the cytoplasm. When we locally perfuse blebbing cells with cortex-relaxing drugs to dissipate pressure on one side, blebbing continues on the untreated side, implying non-equilibration of pressure on scales of approximately 10 microm and 10 s. We can account for localization of pressure by considering the cytoplasm as a contractile, elastic network infiltrated by cytosol. Motion of the fluid relative to the network generates spatially heterogeneous transients in the pressure field, and can be described in the framework of poroelasticity. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,831 |
CONTEXT AND OBJECTIVE ::: Red grape seed extract (RGSE) contains oligomeric proanthocyanidin complexes as a class of flavonoids. These compounds are potent antioxidants and exert many health-promoting effects. This study aimed to determine the effects of RGSE on serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein AI (apo-AI) levels and paraoxonase (PON) activity in patients with mild to moderate hyperlipidemia (MMH). ::: ::: ::: DESIGN AND SETTINGS ::: A randomized double-blind placebo-controlled clinical trial was conducted at Shahid-Modarres Hospital (Tehran, Iran) and Tabriz University of Medical Sciences. Seventy MMH patients were randomly assigned to receive treatment (200 mg/day of RGSE) or placebo for eight weeks. ::: ::: ::: RESULTS ::: Significant elevation in serum levels of apo-AI (P = 0.001), HDL-C (P = 0.001) and PON activity (P = 0.001) and marked decreases in concentrations of TC (P = 0.015), TG (P = 0.011) and LDL-C (P = 0.014) were found in the cases. PON activity was significantly correlated with apo-AI (r = 0.270; P < 0.01) and HDL-C (r = 0.45; P < 0.001). Significant differences between the RGSE and control groups (before and after treatment) for TC (P = 0.001), TG (P = 0.001), PON (P = 0.03), apo-AI (P = 0.001) and LDL-C (P = 0.002) were seen. ::: ::: ::: CONCLUSION ::: It is possible that RGSE increases PON activity mostly through increasing HDL-C and apo-AI levels in MMH patients. It may thus have potential beneficial effects in preventing oxidative stress and atherosclerosis in these patients. | Oxidative stress and inflammatory responses sustained for a long period of time cause many diseases. A proinflammatory cytokine, tumor necrosis factor α (TNF-α), plays a pivotal role in the pathogenesis of chronic and autoimmune diseases. The present review, supplemented by hitherto unpublished data of the authors and their coworkers, shows that the intake of polyphenols contained in natural sources, such as hydroxytyrosol, tyrosol, oleuropein (olives), naringin and hesperidin (Citrus fruits), resveratrol, procyanidins or oligomeric procyanidin (grapes or grape seed extracts), (-)-epigallocatechin gallate (green tea) and quercetin (grapes, green tea) etc., are able to modulate chronic inflammatory diseases, such as type 2 diabetes, rheumatoid arthritis, inflammatory bowel disease, and affect the formation and interaction of advanced glycation end products with their respective receptors. Furthermore, potent activities of fermented grape marc, prepared as a fine lyophilized powder from fresh skin and seeds of a Japanese grape strain (Koshu) and then fermented with Lactobacillus plantarum, are described. Finally, the bioavailability of representative polyphenols will be discussed. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,832 |
Kosteletzkya virginica (L.) Presl., a dicotyledonous halophyte native to brackish tidal marshes, was grown on nutrient solution containing 0. 85, 170 or 255 mol m-3 NaCl, and the effects of external salinity on shoot growth and ion content of individual leaves were studied in successive harvests. Growth was stimulated by 85 mol m-3 NaCl and was progressively reduced at the two higher salinities. Growth suppression at high salinity resulted principally from decreased leaf production and area, not from accelerated leaf death. As is characteristic of halophytic dicots. K. virginica accumulated inorganic ions in its leaves, particularly Na+ and K+. However, the Na+ concentration of individual leaves did not increase with time, but remained constant or even declined, seeming to be well-coordinated with changes in water content. A striking feature of the ion composition of salinized plants was the development of a dramatic gradient in sodium content, with Na+ partitioned away from the most actively growing leaves. Salt-treated plants exhibited a strong potassium affinity, with foliar K+ levels higher in salinized plants than unsalinized plants after an initial decrease. These results suggest that selective uptake and transport, foliar compartmentation of Na+ and K+ in opposite directions along the shoot axis, and the regulation of leaf salt loads over time to prevent build-up of toxic concentrations are whole-plant features which enable K. virginica to establish favourable K+-Na+ relations under saline conditions. | Data regarding NaCl impact on halophyte plant species exposed to a polymetallic contamination remain scarce. Seedlings of the salt marsh species Kosteletzkya pentacarpos were simultaneously exposed to cadmium (10 μM) and zinc (100 μM) in the absence or presence of 50 mM NaCl. Heavy metal exposure reduced plant growth and increased Cd and Zn concentrations in all organs. Cd and Zn accumulation reduced net photosynthesis in relation to stomatal closure, decreased in chlorophyll concentration and alteration in chlorophyll fluorescence-related parameters. Salinity reduced Cd and Zn bioaccumulation and translocation, with a higher impact on Cd than Zn. It mitigated the deleterious impact of heavy metals on photosynthetic parameters. NaCl reduced the heavy metal-induced oxidative stress assessed by malondialdehyde, carbonyl, and H2O2 concentration. Subcellular distribution revealed that Cd mainly accumulated in the cell walls, but NaCl increased it in the cytosol fraction in the leaf and in the metal-rich granule fraction in the roots. It had no impact on Zn subcellular distribution. The additional NaCl contributed to a higher sequestration of Cd on phytochelatins and stimulated glutathione synthesis. The positive impact of NaCl on K. pentacarpos response to polymetallic pollution made this species a promising candidate for revegetation of heavy metal-contaminated salt areas. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,833 |
The renal microvasculature is an important component in the regulation of kidney function. Recent studies suggest that oxygen radicals can contribute to the modulation of renal cortical and medullary microvascular function under normal conditions as well as in pathophysiological conditions such as diabetes mellitus and hypertension. This review focuses on studies that indicate oxygen radicals can cause renal vasoconstriction, mediate the vasoconstriction of other agonists, and modulate nitric oxide-dependent actions in the normal kidney. Hypertension and diabetes mellitus are associated with oxidative stress. Recent investigations suggest that oxygen radicals may contribute to the enhanced renal vascular tone, increased sensitivity to vasoconstrictors, impaired endothelium-dependent vasodilation, and enhanced tubuloglomerular feedback found in these pathophysiological conditions. | A chemical amplification positive resist composition comprising a polymeric mixture of a polyhydroxystyrene derivative having a Mw of 1000-500,000 and a copolymer of hydroxystyrene and (meth)acrylate having a Mw of 1000-500,000, as a base resin, has improved dry etching resistance, high sensitivity, high resolution, and process adaptability, and is suppressed in the slimming of pattern films after development with aqueous base. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,834 |
The aim of the investigation was to study a possibility to prevent the effects of geomagnetic storms (GMS) on cardiovascular patients. The subjects were patients with stage II to III essential hypertension and functional class II to III coronary artery disease, who were divided into three groups. Patients in group I received basic pharmacotherapy; patients in group II were treated with basic medications plus vitamin E; patients in group III received basic medications plus melatonin (melaxen). Vitamin E and melaxen were administered during a calm period, three days before a GMS, on the day of a GMS, and during three subsequent days. Besides clinico-instrumental examination, the patients were questioned for a range of clinical data. The results of the study substantiate the use of melatonin as a measure to prevent the influence of GMS. | A controversial body of literature demonstrates associations of geomagnetic storms (GMS) with numerous cardiovascular, psychiatric and behavioural outcomes. Various melatonin hypotheses of GMS have suggested that temporal variation in the geomagnetic field (GMF) may be acting as an additional zeitgeber (a temporal synchronizer) for circadian rhythms, with GMS somehow interfering with the hypothesized system. The cryptochrome genes are known primarily as key components of the circadian pacemaker, ultimately involved in controlling the expression of the hormone melatonin. Cryptochrome is identified as a clear candidate for mediating the effect of GMS on humans, demonstrating the prior existence of several crucial pieces of evidence. A distinct scientific literature demonstrates the widespread use of geomagnetic information for navigation across a range of taxa. One mechanism of magnetoreception is thought to involve a light-dependent retinal molecular system mediated by cryptochrome, acting in a distinct functionality to its established role as a circadian oscillator. There is evidence suggesting that such a magnetosense--or at least the vestiges of it--may exist in humans. This paper argues that cryptochrome is not acting as secondary geomagnetic zeitgeber to influence melatonin synthesis. Instead, it is hypothesized that the cryptochrome compass system is mediating stress responses more broadly across the hypothalamic-pituitary-adrenal (HPA) axis (including alterations to circadian behaviour) in response to changes in the GMF. Two conceptual models are outlined for the existence of such responses--the first as a generalized migrational/dispersal strategy, the second as a stress response to unexpected signals to the magnetosense. It is therefore proposed that GMS lead to disorientation of hormonal systems in animals and humans, thus explaining the effects of GMS on human health and behaviour. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,835 |
OBJECTIVES: To determine how the use of essential oils (OE) Lavender and Geranium change the perception of anxiety, and to compare their effectiveness in treating anxiety. METHODS: The sample included students from the first year of nursing school who were randomized into three groups: two groups received OE (in a gel polymer-based) and the other received a placebo (essence of Rose). A previously validated scale was used to assess anxiety. It was administered before the end of 30 and 60 days of use of aromatic gels. RESULTS: The group using Lavender exhibited a reduction of -11.80 in mean scores on the anxiety scale, but this was not statistically significant. CONCLUSION: Although not statistically significant, there was greater efficacy of Lavender EO in reducing anxiety. | Background: Most anxiety complaints are treated with pharmacological measures involving barbiturates and benzodiazepines, in which they may end up causing tolerance and pharmacological dependence. Integrative approaches such as aromatherapy are used in addition to medications to improve sleep quality and reduce anxiety. Thus, PinetoninTM, a phytocomplex obtained from a blend of essential oils aims to aid in the symptoms of stress and anxiety. Methods: The cytotoxicity of PinetoninTM was evaluated MTT assay using fibroblasts and astrocytes showed reduction in the cell viability only at high concentrations. Evaluation of intracellular calcium and determination of residual glutamate in the supernatant of astrocyte cultures showed agonist action of dihydroxyphenylglycine (DHPG) increasing linearly the concentration of intracellular calcium and the glutamate levels in the supernatants of the cultures. On the other hand, cultures of astrocytes treated with PinetoninTM showed residual glutamate levels in the supernatants reducing proportionally, as well as, intracellular calcium reduction. The determination of salivary cortisol showed a significant reduction in salivary cortisol levels in the group that received PinetoninTM. The evaluation of the electroencephalogram in patients treated with PinetoninTM had a significant increase (P < 0.05) in the frequency (Hz) of the alpha and beta waves. Results: A reduction in dose-dependent cell viability was observed when compared to cultures of PinetoninTM treated fibroblasts with control culture. When PinetoninTM and linole are administered in astrocytic cells, there was a reduction of the intracellular concentration of Ca2+ against a control group treated with DHPG agonist. The evaluation of salivary cortisol demonstrated a reduction when the patient group was treated with PinetoninTM by purchasing the results against the group of patients treated with saline. Reinforcing the relaxed state of that group, alpha waves have been increased and reductions in beta waves. Conclusion: The results obtained after intranasal administration of PinetoninTM suggest that this phytocomplex can help reduce the symptoms of stress and the better quality of life. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,836 |
Niuhuang Jiedu tablet (NHJDT) is a realgar-containing traditional Chinese medicine. A direct inductively coupled plasma-mass spectrometry (ICP-MS) method for the simultaneous determination of 20 trace elements (Mg, K, Ca, Na, Fe, As, Zn, Sr, Ba, Cu, Mn, Ni, Pb, V, Cr, Se, Co, Mo, Cd, Hg) in NHJDT, as well as in water, gastric fluid and intestinal fluid was established. Meanwhile, a high performance liquid chromatography–inductively coupled plasma-mass spectrometry (HPLC–ICP-MS) method was developed for the determination of arsenite (As III ), arsenate (As V ), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and for the identification of arsenobetaine (AsB) and arsenocholine (AsC) in these extracts. Both methods were fully validated in the respect of linearity, sensitivity, precision, stability and accuracy. The reliability of the ICP-MS method was further evaluated using a certified standard reference material prepared from dried tomato leaves (NIST, SRM 1572a). The analysis showed that some manufacturers formulated lower amount of realgar than required in the Chinese Pharmacopoeia (ChP) in their preparations. In addition, almost same extraction profiles for total As and inorganic As were found in water and in gastrointestinal fluids, while higher extraction rates for other 19 elements were observed in gastrointestinal fluids. Our findings show that the toxicities of Hg, Cu, Cd and Pb in NHJDP are low, while the real As toxicity in NHJDT should be deeply investigated. | Niuhuang Jiedu Tablet (NJT) is a classical formula in treating acute tonsillitis, pharyngitis, and so on. In the formula, significant level of Realgar as a potentially toxic element is contained. Our previous experiments revealed that it was less toxic for combined Realgar in NJT. However, the active fraction of this prescription with toxicity alleviation effect on Realgar was still obscure. NJT was divided into five different polar fractions (NJT-PET, NJT-25, NJT-50, NJT-75, and NJT-95), and we explored the toxicity alleviation effect on Realgar. Based on 1H NMR spectra of urine and serum from rats, PCA and PLS-DA were performed to identify different metabolic profiles. Liver and kidney histopathology examinations and serum clinical chemistry analysis were also performed. With pattern recognition analysis of metabolites in urine and serum, Realgar group showed a clear separation from control group, while the metabolic profiles of NJT-PET, NJT-25, NJT-50, and NJT-95 groups were similar to Realgar group, and the metabolic profiles of NJT and NJT-75 groups were very close to control group. Statistics results were confirmed by the histopathological examination and biochemical assay. The present work indicated that 75% EtOH fraction of NJT was the most valid fraction with the toxicity alleviation effect on Realgar. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,837 |
The primary ocular and dermal irritations of four quaternary ammonium compounds, namely cetylpyridinium chloride (CPC), stearylphenylethyldimethylammonium tosylate (SPDAT), dimethyldistearylammonium bisulfate (DDABS) and tri(N-butyl)benzylammonium 4-hydroxynapththalene-1-sulfonate (TBAHNS), were studied. Both CPC and SPDAT were extremely or severely irritating to the eyes of the test animals, whereas DDABS and TBAHNS were mildly or minimally irritating. Both CPC and SPDAT were also severely or extremely irritating to the skin of the test animals, while DDABS and TBAHNS were non-irritating. These quaternary ammonium compounds have little similarity in chemical structure and possess different solubilities. CPC is very soluble in both lipid and water; SPDAT is very soluble in lipid but only slightly soluble in water; and DDABS and TBAHNS are poorly soluble in either lipid or water. The irritancy of these compounds is likely to be related to their solubility, in addition to the cationic characteristics. It appears that not all quaternary ammonium compounds in this study are irritants. Those that are not soluble are not expected to be absorbed in eye/skin tissues and thus irritation reactions will not take place. The use of in vitro alternatives should be considered when assessing the ocular and dermal irritancy potential of water- and lipid-soluble quaternary ammonium compounds. | BACKGROUND ::: Resistance toward quaternary ammonium compounds (QACs) is widespread among a diverse range of microorganisms and is facilitated by several mechanisms such as biofilm formation. ::: ::: ::: OBJECTIVES ::: In this study, the effects of benzalkonium chloride on planktonic growth and biofilm formation by some field isolates of animal bacterial pathogens were investigated. ::: ::: ::: MATERIALS AND METHODS ::: Forty clinical isolates of Escherichia coli, Salmonella serotypes, Staphylococcus aureus and Streptococcus agalactiae (10 isolates of each) were examined for effects of benzalkonium chloride on biofilm formation and planktonic growth using microtiter plates. For all the examined strains in the presence of benzalkonium chloride, biofilm development and planktonic growth were affected at the same concentrations of disinfectant. ::: ::: ::: RESULTS ::: The means of strains growth increase after the minimal inhibitory concentration (MIC) were significant in all the bacteria (except for E. coli in 1/32 and S. agalactiae in of 1/8 MIC). Biofilm formation increased with decrease of antiseptics concentration; a significant increase was found in all the samples. The most turbidity related to S. aureus and the least to Salmonella. ::: ::: ::: CONCLUSIONS ::: Bacterial resistance against quaternary ammonium compounds is increasing which can increase the bacterial biofilm formation. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,838 |
An acid-buffering bioadhesive vaginal tablet was developed for the treatment of genitourinary tract infections. From the bioadhesion experiment and release studies it was found that polycarbophil and sodium carboxymethylcellulose is a good combination for an acid-buffering bioadhesive vaginal tablet. Sodium monocitrate was used as a buffering agent to provide acidic pH (4.4), which is an attribute of a healthy vagina. The effervescent mixture (citric acid and sodium bicarbonate) along with a superdisintegrant (Ac-Di-sol) was used to enhance the swellability of the bioadhesive tablet. The drugs clotrimazole (antifungal) and metronidazole (antiprotozoal as well as an antibacterial) were used in the formulation along with Lactobacillus acidophilus spores to treat mixed vaginal infections. From the ex vivo retention study it was found that the bioadhesive polymers hold the tablet for more than 24 hours inside the vaginal tube. The hardness of the acid-buffering bioadhesive vaginal tablet was optimized, at 4 to 5 kg hardness the swelling was found to be good and the cumulative release profile of the developed tablet was matched with a marketed conventional tablet (Infa-V). The in vitro spreadability of the swelled tablet was comparable to the marketed gel. In the in vitro antimicrobial study it was found that the acid-buffering bioadhesive tablet produces better antimicrobial action than marketed intravaginal drug delivery systems (Infa-V, Candid-V and Canesten 1). | In this study, a bioadhesive dosage form of eoconazole nitrate for vaginal delivery was designed using a combination of bioadhesive polymers: Carbopol 941 p and sodium carboxymethylcellulose or methylcellulose in different ratios. The bioadhesive strength was evaluated by measuring the force required to detach the tablet from sheep vaginal mucosal membrane. It was found that the bioadhesive force was directly proportional to Carbopol 941 p content in the different formulae. The formulae were tested for their swelling behavior using agar gel plate method. The results showed that formulae containing a combination of Carbopol 941 p and sodium carboxymethylcellulose had greater swelling index than those containing a combination of Carbopol 941 p and methylcellulose. In vitro drug release study showed that the release of eoconazole nitrate from Formulae containing sodium carboxymethylcellulose was faster than its release from those containing methylcellulose.The dissolution profiles of the formula containing Carbopol 941 p alone and those conaining various combinations of Carbopol 941 p and methylcellulose could be considered similar since their calculated similarity factor values were >50. Formula F3 composed of CP/NaCMC in a ratio 1:1 showed moderate swelling, good bioadhesion and retardation of drug release. Thus, it may be considered a good candidate for vaginal bioadhesive dosage forms. ::: Key words: Bioadhesive, econazole nitrate, vaginal tablet | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,839 |
1. The ability of Purkinje cells to rapidly buffer depolarization-evoked intracellular calcium changes (delta [Ca2+]i) was estimated by titrating the endogenous buffer against incremental concentrations of the Ca(2+)-sensitive dye fura-2. 2. In cells from 15-day-old rats, pulse-evoked delta [Ca2+]i were stable during the loading with 0.5 mM fura-2 through the patch pipette. In cells from 6-day-old rats, delta [Ca2+]i decreased by approximately 50% during equivalent experiments. This decrease was not related to changes in Ca2+ influx, since the integral of the Ca2+ currents remained constant throughout the recording. 3. Experiments with high fura-2 concentrations (1.75-3.5 mM) were performed in order to obtain for each cell the curve relating delta [Ca2+]i to fura-2 concentration. From this relationship, values for the Ca2+ binding ratio (the ratio of buffer-bound Ca2+ changes over free Ca2+ changes) were calculated. 4. In Purkinje cells from 15-day-old rats, the Ca2+ binding ratio was approximately 2000, an order of magnitude larger than that of other neurones and neuroendocrine cells studied to date. This Ca2+ binding ratio was significantly smaller (approximately 900) in Purkinje cells from 6-day-old rats. 5. We propose that the large Ca2+ binding ratio of Purkinje cells is related to the presence of large concentrations of Ca2+ binding proteins and that these cells regulate their ability to handle Ca2+ loads during development through changes in the concentration of Ca2+ binding proteins. | Calcium-binding proteins such as calretinin are abundantly expressed in distinctive patterns in the CNS, but their physiological function remains poorly understood. Calretinin is expressed in cerebellar granule cells, which provide the major excitatory input to Purkinje cells through parallel fibers. Calretinin-deficient mice exhibit dramatic alterations in motor coordination and Purkinje cell firing recorded in vivo through unknown mechanisms. In the present study, we used patch-clamp recording techniques in acute slice preparation to investigate the effect of a null mutation of the calretinin gene on the intrinsic electroresponsiveness of cerebellar granule cells at a mature developmental stage. Calretinin-deficient granule cells exhibit faster action potentials and generate repetitive spike discharge showing an enhanced frequency increase with injected currents. These alterations disappear when 0.15 mm of the exogenous fast-calcium buffer BAPTA is infused in the cytosol to restore the calcium-buffering capacity. A proposed mathematical model demonstrates that the observed alterations of granule cell excitability can be explained by a decreased cytosolic calcium-buffering capacity resulting from the absence of calretinin. This result suggests that calcium-binding proteins modulate intrinsic neuronal excitability and may therefore play a role in information processing in the CNS. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,840 |
Van der Waals (vdW) volumes ( V w,x ) of 117 molecular fragments ( X ) have been calculated by numerical integration of the van der Waals envelope using the hard-sphere approximation, standard geometries, and effective atomic van der Waals radii which were determined by comparison of their effects on the predicted sterically allowed conformations of peptides with observed crystal structures. vdW volume fragmental constants give accurate estimates of molecular, vdW volume as sum of approximate V w,x s. | A pattern recognition quantitative structure-activity relationship (QSAR) study has been performed to determine the molecular features of carbamate anticonvulsants which influence biological activity. Although carbamates, such as felbamate, have been used to treat epilepsy, their mechanisms of efficacy and toxicity are not completely understood. Quantum and classical mechanics calculations have been exploited to describe 46 carbamate drugs. Employing a principal component analysis and multiple linear regression calculations, five crucial structural descriptors were identified which directly relate to the bioactivity of the carbamate family. With the resulting mathematical model, the biological activity of carbamate analogues can be predicted with 85-90% accuracy. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,841 |
The effects of Leuconostoc mesenteroides strain NTM048 and type strain JCM6124T on the murine immune system were characterized. Although the bacterial cells and exopolysaccharides of each strain induced immunoglobulin A production in Peyer’s patch cells, the effects of NTM048 were more potent than those of JCM6124T. Oral administration of the cells of each strain increased the fecal immunoglobulin A content in NTM048-treated mice, but not in JCM6124T-treated mice. A flow cytometric analysis showed that the CD4+ T-cell populations in the mouse spleens tended to increase in the NTM048 group. These results suggest that immunomodulating ability is characteristic of strain NTM048. | The spleen is the main filter for blood-borne pathogens and antigens, as well as a key organ for iron metabolism and erythrocyte homeostasis. Also, immune and hematopoietic functions have been recently unveiled for the mouse spleen, suggesting additional roles for this secondary lymphoid organ. Here we discuss the integration of the spleen in the regulation of immune responses locally and in the whole body and present the relevance of findings for our understanding of inflammatory and degenerative diseases and their treatments. We consider whether equivalent activities in humans are known, as well as initial therapeutic attempts to target the spleen for modulating innate and adaptive immunity. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,842 |
To investigate which fixative is most suitable for the preservation of cochlear hair cells three main groups of fixatives were used: 1. 3% glutar aldehyde in various buffers (osmolality altered). 2. Glutar aldehyde/paraform aldehyde combination (ad modum Karnovsky). 3. Osmic acid solutions (OsO4) in veronal acetate buffer according to Rhodin (1954). The 2% osmic acid fixative (350--370mosm/kg) resulted in an excellent ultrastructural preservation; an acceptable result was obtained with a 3% glutar aldehyde fixative in 0.1 M sodium phosphate buffer, 600--700 mosm/kg and the Karnovsky's fixative. | This report contains graphs that relate molarity with pH and osmolality (as measured by freezing point depression) for 5 buffer systems that are commonly used in preparing fixatives for electron microscopy, namely: cacodylate-HCl, s-collidine-HCl, Millonig's phosphate, Sorensen's phosphate, and veronal-acetate-HCl. In addition, osmolality is shown as a function of concentration for glutaraldehyde, OsO4, NaCl, glucose, sucrose, and CaCl2. These data provide simple guides for the design of buffered fixatives of any desired pH and tonicity. Osmolality cannot generally be calculated accurately from theory because of the partial ionization and aggregation of the concentrated solutions used. Commercially available glutaraldehyde often contains impurities which may increase its osmolality. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,843 |
BACKGROUND ::: The current progress in pharmaceutical nanotechnology field has been exploited in the design of functionalized radiolabelled nanoparticles that are able to deliver radionuclides in a selective manner to improve the outcome of diagnosis and treatment. Silica nanoparticles (SNPs) have been widely developed for biomedical applications due to their high versatility, excellent functional properties and low cost production, with the possibility to control different topological parameters relevant for multidisciplinary applications. ::: ::: ::: PURPOSE ::: The aim of the present study was to characterize and evaluate both in vitro, by microscopy techniques, and in vivo, by scintigraphic imaging, the biodistribution of silica nanostructures derivatives (Cy5.5 conjugated SNPs and (99m)Tc radiolabelled SNPs) to be applied as radiotracers in biomedicine. ::: ::: ::: METHODS ::: SNPs were synthesized by hydrolysis and condensation of silicon alkoxides, followed by surface functionalization with amino groups available for fluorescent dye and radiolabelling possibility. ::: ::: ::: RESULTS ::: Our data showed the particles size distribution (200-350 nm), the surface charge (negative for bare and fluorescent SNPs and positive for amino SNPs), polydispersity index (broad distribution), the qualitative composition and the toxicity assessments (safe material) that made the obtained SNPs candidates for in vitro/in vivo studies. A high uptake of fluorescent SNPs in all the investigated organs was evidenced by confocal microscopy. The (99m)Tc radiolabelled SNPs biodistribution was quantified in the range of 12-100% counts/g organ using the scintigraphic images. ::: ::: ::: CONCLUSIONS ::: The obtained results reveal improved properties, namely, reduced toxicity with a low level of side effects, an improved biodistribution, high labelling efficiency and stability of the radiolabelled SNPs with potential to be applied in biomedical science, particularly in nuclear medicine as a radiotracer. | Ketoprofen (Ket) was intercalated into layered double hydroxides (ZnAlLDH and MgAlLDH) using the ionic exchange method. The drug intercalation was confirmed by X-ray diffraction (XRD) and FTIR spectroscopy. Ket release from the inorganic matrix was studied at pH 7.4 in continuous regime with a flow rate of 0.5 and respectively 1.0 ml/min. The kinetical data were interpreted using the Ritger and Peppas model. The data prove that the release kinetics and mechanism depend on the eluent flow rate. Quantification of gastric tolerance shows that the ulcerogenic effect of the intercalated drug is lower than the one of the raw Ket. The antinociceptive effect of both formulations was studied by the hot-plate method performed on mice. The MgAlLDH_Ket formulation shows a tendency towards a stronger antinociceptive effect than its ZnAlLDH_Ket counterpart during the 210 min recorded period. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,844 |
Eicosanoids play an important role in the evaluation of pro-inflammatory responses and in the safety and toxicity of novel therapeutic agents. This work describes a high-throughput UFLCMS/MS method for the analysis of three urinary prostanoid biomarkers of pro-inflammatory responses, tetranor PGEm, 6-keto PGF(1alpha) and 2,3-dinor-6-keto PFG(1alpha). Nine male volunteers of various age and fitness level participated in this study. Six provided pre- and post-exercise samples and three provided intraday samples. Tetranor PGEm and 6-keto PGF(1alpha) increased significantly in patients after exercise (p<0.017 and p<0.029). In individual patient sets, tetranor PGEm levels increased from 1.5- to 6-fold pre- vs. post-exercise, levels of 6-keto PGF(1alpha) increased more dramatically from 2- to 55-fold pre- vs. post-exercise. The prostanoid 2,3-dinor-6-keto PGF(1alpha) remained unchanged post-exercise. Data was normalized to urinary creatinine concentration, which increased approximately 40% post-exercise. | The ω-6 and ω-3 polyunsaturated fatty acids (PUFAs) such as arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) are the precursors of various bioactive lipid mediators including prostaglandins, thromboxanes, leukotrienes, hydroxyeicosatetraenoic acid, isoprostanes, lipoxins, and resolvins (Rvs). These lipid mediators play important roles in various physiological and pathological processes. The quantitative determination of PUFA metabolites seems necessary for disease research and for developing biomarkers. However, there is a paucity of analytical methods for the quantification of ω-6 and ω-3 PUFA metabolites—the specialized pro-resolving mediators (SPMs) present in the human urine. We developed a method for the quantification of ω-6 and ω-3 PUFA metabolites present in human urine using ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS). The developed method shows good linearity, with a correlation coefficient >0.99 for all of the analytes. The validation results indicate that our method is adequately reliable, accurate, and precise. The method was successfully used to examine urine samples obtained from 43 healthy volunteers. We could identify 20 PUFA metabolites, and this is the first report of the quantitative determination of RvD1, 17(R)-RvD1, 11-dehydro thromboxane B3, RvE2, and 5(S)-HETE in human urine. The urinary 8-iso PGF(2α) and PGE2 levels were significantly higher in the men smokers than in the men nonsmokers (p < 0.05). In this study, we developed an accurate, precise, and novel analytical method for estimating the ω-6 and ω-3 PUFA metabolites, and this is the first report that the SPMs derived from EPA and DHA are present in human urine. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,845 |
In these studies we have compared the relative amounts and isoforms of tropomyosin in capillary and postcapillary venule pericytes, endothelial cells, and vascular smooth muscle cells in four rat microvascular beds: heart, diaphragm, pancreas, and the intestinal mucosa. The results, obtained by in situ immunoperoxidase localization, indicate that (a) tropomyosin is present in capillary and postcapillary venule pericytes in relatively high concentration; (b) the tropomyosin content of pericytes appears to be somewhat lower than in vascular smooth muscle cells but higher than in endothelia and other vessel-associated cells; and (c) pericytes, unlike endothelia and other nonmuscle cells, contain detectable levels of tropomyosin immunologically related to the smooth muscle isoform. These results and our previous findings concerning the presence of a cyclic GMP-dependent protein kinase (Joyce, N., P. DeCamilli, and J. Boyles, 1984, Microvasc. Res. 28:206-219) in pericytes demonstrate that these cells contain significant amounts of at least two proteins important for contraction regulation. Taken together, the evidence suggests that pericytes are contractile elements related to vascular smooth muscle cells, possibly involved, as are the latter, in the regulation of blood flow through the microvasculature. | PURPOSE ::: Pericytes are contractile cells outside the endothelial lining of capillaries. The study investigated whether nitric oxide, known to cause relaxation of vascular smooth muscle cells, also relaxes pericytes. ::: ::: ::: METHODS ::: Cultured bovine pericytes were exposed to a nitric oxide donor, sodium nitroprusside, and to 8-bromoguanosine 3':5'-cyclic monophosphate (8-bromo cGMP) in the presence and in the absence of methylene blue, an inhibitor of guanylate cyclase. Relaxation was assessed by counting the loss of wrinkles induced by pericytes when they are cultured on thin sheets of silicone. Intracellular cyclic guanosine monophosphate (cGMP) was measured by radioimmunoassay. ::: ::: ::: RESULTS ::: Pericytes relaxed to sodium nitroprusside (3 x 10(-8) to 10(-4) M) in a concentration-dependent manner (ED50: 10(-6) M). The maximal response was characterized by the loss of almost all the wrinkles. The half-maximal relaxation was strongly inhibited by methylene blue (3 x 10(-7) M). Sodium nitroprusside (3 x 10(-6) M) caused a 14-fold increase in the intracellular concentration of cGMP, an effect inhibited by methylene blue (3 x 10(-7) M). The cGMP analogue, 8-bromo-cGMP (10(-5) and 3 x 10(-5) M) strongly relaxed the cells in a concentration-dependent manner, but the relaxation was not reduced by methylene blue (3 x 10(-7) M). ::: ::: ::: CONCLUSIONS ::: Sodium nitroprusside, which releases nitric oxide, strongly relaxes pericytes through an increase of cGMP. Therefore, the presence of the endothelium-derived relaxing factor nitric oxide in the microcirculation can modulate the tone of pericytes, and it thus has the potential to influence blood flow in capillaries. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,846 |
The bidirectional effects of vanadyl on the oxygen affinity of hemoglobin depend on the mole ratio of vanadyl to Hb(R). In low R, the vanadyl ion increases Hb's oxygen affinity due to DPG hydrolysis. The lowered oxygen affinity in higher R is mainly due to the reactive-oxygen-species, probably superoxide, induced oxidation of Fe(II)-Hb to Fe(III)-Hb. The conformation change due to vanadyl binding contribute also to the lowered oxygen binding, but is monotonously decreasing with increasing of R values. | Low Temperature Matrix Isolation - Electron Paramagnetic Resonance (LTMI-EPR) Spectroscopy was utilized to identify the species of iron oxide nanoparticles generated during the oxidative pyrolysis of 1-methylnaphthalene (1-MN). The otherwise gas-phase reactions of 1--MN were impacted by a polypropylenimine tetra-hexacontaamine dendrimer complexed with iron (III) nitrate nonahydrate diluted in air under atmospheric conditions. The EPR fine structure of Fe (III)2O3 nanoparticles clusters, characterized by g-factors of 2.00, 2.28, 3.76 and 4.37 were detected on a cold finger maintained at 77 K after accumulation over a multitude of experiments. Additionally, a high valence Fe (IV) paramagnetic intermediate and superoxide anion-radicals, O2 (•-) adsorbed on nanoparticle surfaces in the form of Fe (IV) --- O2 (•-) were detected from the quenching area of Zone 1 in the gas-phase. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,847 |
It was found that the inhibitory effect of resorcinol is less pronounced if it is added in a later stage of the Briggs−Rauscher reaction, which indicates that an accumulating intermediate—most probably iodomalonic acid—can suppress the inhibition. In fact, when iodomalonic acid was added to the reaction mixture, the inhibitory period was shortened considerably even at micromolar levels of the iodomalonic acid concentration. Moreover, iodomalonic acid can accelerate the rate of the reaction when applied in the same low concentrations, suggesting that it can be an autocatalytic intermediate of the Briggs−Rauscher reaction. | The influence of adrenaline on two iodate based oscillating chemical reactions, the Bray–Liebhafsky (BL) and Briggs–Rauscher (BR) reactions was investigated. It was observed that the addition of adrenaline has different effects on the examined systems. Its addition to the BR system significantly changes the dynamics, while in the BL system, the presence of adrenaline does not show any effect. In order to find out the cause of such a different response of two similar oscillators, UV/VIS spectroscopy was used. Results obtained from recorded UV/VIS spectra indicated that, from all investigated stable reaction species, adrenaline interacts only with potassium iodate and iodine, which are present in both oscillating reactions. Because of this, the different response of the oscillators cannot be ascribed to the reactions between adrenaline and common iodine (stable and unstable) components. As a result, the considerable response of the BR system to adrenaline may be related to the reactions between adrenaline (or its oxidation products) and non-common derivatives of malonic acid or manganese intermediate species. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,848 |
Flavonoids from Phyllostachys pubescens shoot were extracted by methods of water,ethanol backflow and ultrasonic wave extractions.The optimum extraction condition was obtained by single factor analy-sis and orthogonal test.The results showed that the yield of flavonoids was 0.706% by water extraction under the conditions of 60℃,1∶30 solid-liquid ratio,pH 9.0 and 1.5 h.The order of the factors which affected water ex-traction was soild-liquid ratio extraction temperature extraction time pH.The yield of flavonoids was 1.063% by the method of ethanol backflow under the conditions of 1∶40 solid-liquid ratio,60℃,70% ethanol and 2.0 h.The order of the factors which affected the ethanol backflow extraction was soild-liquid ratio extrac-tion temperature extraction time volume fraction of ethanol solution.The yield of flavonoids was 0.797% by methods of ultrasonic wave under the conditions of 1∶40 solid-liquid ratio,50℃,70% ethanol and 30 min.The order of the factors which affected the ultrasonic wave extraction was soild-liquid ratio extraction temperature extraction time volume fraction of ethanol solution. | This paper introduces the research progress related to the antioxidant activity of bamboo leaf flavonoid (EOB-f) and its pharmacological activity of heart and cerebral vessels. The paper studied what role EOB-f played in the diagnosis of heart and cerebral vessels, based on the in vitro, in vivo and animal model as well as the pharmacological research experiment. 1) The in vitro and in vivo experiments indicated that EOB-f has the function of anti-reactive-oxide species, anti-aging and anti-fatigue; 2) The research of animal model indicated that EOB-f can significantly decrease the triglyceride (TG) content in serum, significantly increase high density lipoprotein cholesterol (HDL-C) content in serum, regulate blood lipids and reduce the risk of atherosclerosis; 3) The pharmacological study showed that EOB-f has the effect to resist the whole animal anoxia, can effectively dilate coronary vessels, increase coronary flow, increase myocardial contractility, obviously improve myocardial ischemia and diminish the myocardial infarction scope, inhibit the coagulation process and reduce platelet aggregation, and has certain protective effect on cerebral ischemia. EOB-f has the potential to develop as the natural drug and functional foods for prevention of cardiovascular and cerebrovascular diseases. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,849 |
Little is known about the stereochemistry of sulfation of chiral phenolic drugs. In this study we examined several in vitro approaches to this question, using (+)-, (-)-, or (+/-)-terbutaline as the substrate and the rat liver cytosol as the phenolsulfotransferase enzyme source. The cosubstrate PAPS was either generated by the cytosol from inorganic sulfate and ATP or added to the cytosol. The intact sulfate conjugates formed were determined by HPLC. Using the PAPS generating system, which is best suited for the production of relatively large quantities of sulfate conjugates, with the individual enantiomers as substrates, (T)-terbutaline was conjugated to a much greater extent than (-)-terbutaline; the (+)/(-)-enantiomer ratio was 7.3 +/- 0.3 (mean +/- SE). When (+/-)-terbutaline was the substrate and chiral derivatization was employed to separate the sulfate enantiomers formed, a similar (+)/(-)-enantiomer ratio of 7.9 +/- 0.2 was obtained. With PAP35S added to the cytosol, an approach best suited for kinetic studies, the substrate concentration dependence of sulfation could be determined. The Km app for this reaction was identical for (+)- and (-)-terbutaline. However, the Vmax app was 8.1 +/- 0.4 times greater for (+)-terbutaline. This study for the first time shows enantioselectivity in sulfation of a chiral phenolic drug. The experimental approaches used should be valuable for human studies of stereoselective sulfation of terbutaline and other chiral drugs. | Since the early 1980s the usefulness of dietary beta-agonists to improve the efficiency of feed utilization and(or) to enhance carcass leanness in livestock species has been well documented. Less well documented are the pharmacokinetic properties, biotransformation pathways, and tissue residue profiles of beta-agonists used to enhance leanness in experimentally or illegally treated animals. Pharmacokinetic data for clenbuterol, cimaterol, fenoterol, L-644,969, ractopamine, salbutamol, and terbutaline have been published but biotransformation and tissue residue studies for these compounds in livestock species are sparse. In general, beta-agonists having halogenated aromatic ring systems are metabolized by oxidative and conjugative pathways and have long plasma half-lives, whereas beta-agonists having hydroxylated aromatic rings are metabolized solely by conjugation and have relatively short plasma half-lives. Beta-Agonists having high oral bioavailabilities, long plasma half-lives, and relatively slow rates of elimination have high oral potencies in humans. Residues of such illegally used compounds in edible tissues of livestock represent a genuine risk to consumers. Conversely, beta-agonists having low oral bioavailabilities, short plasma half-lives, and rapid rates of elimination have low oral potencies in humans. Residues of such compounds in edible tissues of properly treated animals would not likely represent a credible risk to consumers of such products. The reviewed data indicate that the development of a safe and effective beta-agonist for use in livestock is possible. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,850 |
Objective:Borneol and menthol are both main active substances of Qingyan Drop Pills.To establish a method for simultaneous determination of borneol and menthol in plasma of rats after ig administration of Qingyang Drop Pills by gas chromatography.Methods:The blood sample was carried out by liquid-liquid extraction (LLE) with an internal standard solution in naphthalene.Borneol and menthol were determined by means of flame ionization detection (FID).Results:The pharmacokinetic parameters were estimated by a compartmental method using the DAS software program (Version 1.0).The standard curves were linear over a wide concentration rang of 2.5-50.0 ng/μL (r=0.996 3),8.7-62.2 ng/μL (r=0.999 4) for both borneol and menthol in plasma,respectively.The limit of quantification (LOQ) of borneol and menthol in plasma was 2.4 and 5.0 ng/μL,respectively.Conclusion:This validated assay method has been successfully applied to a pharmacokinetic study of borneol and menthol in plasma of rats after ig administration of Qingyan Drop Pills.The pharmacokinetic parameters provide some information for clinical administration of Qingyan Drop Pills. | A gas chromatography mass spectrometry (GC-MS) method has been developed and fully validated for the simultaneous determination of natural borneol (NB) and its metabolite, camphor, in rat plasma. Following a single liquid-liquid extraction, the analytes were separated using an HP-5MS capillary column (0.25 mm×30 m×0.25 μm) and analyzed by MS in the selected ion monitoring mode. Selected ion monitor (m/z) of borneol, camphor and internal standard was 95, 95 and 128, respectively. Linearity, accuracy, precision and extraction recovery of the analytes were all satisfactory. The method was successfully applied to pharmacokinetic studies of NB after oral administration to Wistar rats. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,851 |
Integrins are type I heterodimeric (alpha/beta) cell adhesion molecules. They trigger cell-signaling by recruiting cytosolic molecules to their cytoplasmic tails. Integrin alpha cytoplasmic tail contributes towards integrin function specificity, an important feature of integrins having different alpha subunits but sharing the same beta subunit. Herein, we show that the src family kinase Hck co-capped selectively with leukocyte integrin alpha(M)beta(2) but not alpha(L)beta(2) or alpha(X)beta(2). This was disrupted when the alpha(M) cytoplasmic tail was substituted with that of alpha(L) or alpha(X). Co-capping was recovered by alpha(L) or alpha(X) cytoplasmic tail truncation or forced separation of the alpha and beta cytoplasmic tails via salt-bridge disruption. | CD18; Cell surface adhesion glycoprotein LFA1/CR3/P150,959 beta subunit precursor); Cell surface adhesion glycoproteins LFA-1/CR3/p150,95 subunit beta; Complement receptor C3 beta-subunit; Complement receptor C3 subunit beta; Integrin beta chain, beta 2; Integrin beta-2; Integrin, beta 2 (complement component 3 receptor 3 and 4 subunit); ITGB2; LAD; LCAMB; Leukocyte cell adhesion molecule CD18; Leukocyte-associated antigens CD18/11A, CD18/11B, CD18/11C; LFA-1; MAC-1; MF17; MFI7 | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,852 |
The 5' untranslated sequence (5' UTS) of the platelet-derived growth factor B (PDGF B/c-sis) mRNA is GC rich, includes AUGs upstream of the translation initiation site, and inhibits translation of downstream heterologous and autologous coding sequences. Its primary sequence has been remarkably conserved through evolution. In this study, we identified two additional PDGF B/c-sis mRNAs expressed in endothelial cells. These were shown by Northern, primer extension, and nuclease protection analyses to differ in extent of 5' untranslated first exon sequence. The predominant of these 5' truncated transcripts was 2.8kb, extended 15nt upstream of the translation start site and was markedly stabilized by cycloheximide and anisomycin, but not puromycin or pactamycin. Cycloheximide increased the half-life of this mRNA approximately 7 fold, without affecting stability of the full length mRNA. Cycloheximide withdrawal caused its abrupt destabilization. The 2.8kb PDGF B/c-sis mRNA lacks translation inhibitory 5' UTS, encodes the same PDGF B protein, appears initiated from within first exon genomic sequences, and is degraded through a process that is sensitive to translation arrest and distinct from that degrading the 3.8kb PDGF B/c-sis mRNA. | Platelet-derived growth factor (PDGF) is a major mitogen for connective tissue cells and certain other cell types. It is a dimeric molecule consisting of disulfide-bonded, structurally similar A- and B-polypeptide chains, which combine to homo- and heterodimers. The PDGF isoforms exert their cellular effects by binding to and activating two structurally related protein tyrosine kinase receptors, denoted the alpha-receptor and the beta-receptor. Activation of PDGF receptors leads to stimulation of cell growth, but also to changes in cell shape and motility; PDGF induces reorganization of the actin filament system and stimulates chemotaxis, i.e., a directed cell movement toward a gradient of PDGF. In vivo, PDGF has important roles during the embryonic development as well as during wound healing. Moreover, overactivity of PDGF has been implicated in several pathological conditions. The sis oncogene of simian sarcoma virus (SSV) is related to the B-chain of PDGF, and SSV transformation involves autocrine stimulation by a PDGF-like molecule. Similarly, overproduction of PDGF may be involved in autocrine and paracrine growth stimulation of human tumors. Overactivity of PDGF has, in addition, been implicated in nonmalignant conditions characterized by an increased cell proliferation, such as atherosclerosis and fibrotic conditions. This review discusses structural and functional properties of PDGF and PDGF receptors, the mechanism whereby PDGF exerts its cellular effects, and the role of PDGF in normal and diseased tissues. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,853 |
BackgroundWounds are increasingly important in our aging societies. Pathologies such as diabetes predispose patients to chronic wounds that can cause pain, infection, and amputation. The vacuum assisted closure device shows remarkable outcomes in wound healing. Its mechanism of action is unclear despite several hypotheses advanced. We previously hypothesized that micromechanical forces can heal wounds. To understand better the biological response of soft tissue to forces, rat ears in vivo were stretched and their gene expression patterns over time obtained. The absolute enrichment (AE) algorithm that obtains a combined up and down regulated picture of the expression analysis was implemented.ResultsWith the use of AE, the hypoxia gene set was the most important at a highly significant level. A co-expression network analysis showed that important co-regulated members of the hypoxia pathway include a glucose transporter (slc2a8), heme oxygenase, and nitric oxide synthase2 among others.ConclusionIt appears that the hypoxia pathway may be an important modulator of response of soft tissue to forces. This finding gives us insights not only into the underlying biology, but also into clinical interventions that could be designed to mimic within wounded tissue the effects of forces without all the negative effects that forces themselves create. | BackgroundAmyotrophic Lateral Sclerosis (ALS) is a lethal disorder characterized by progressive degeneration of motor neurons in the brain and spinal cord. Diagnosis is mainly based on clinical symptoms, and there is currently no therapy to stop the disease or slow its progression. Since access to spinal cord tissue is not possible at disease onset, we investigated changes in gene expression profiles in whole blood of ALS patients.ResultsOur transcriptional study showed dramatic changes in blood of ALS patients; 2,300 probes (9.4%) showed significant differential expression in a discovery dataset consisting of 30 ALS patients and 30 healthy controls. Weighted gene co-expression network analysis (WGCNA) was used to find disease-related networks (modules) and disease related hub genes. Two large co-expression modules were found to be associated with ALS. Our findings were replicated in a second (30 patients and 30 controls) and third dataset (63 patients and 63 controls), thereby demonstrating a highly significant and consistent association of two large co-expression modules with ALS disease status. Ingenuity Pathway Analysis of the ALS related module genes implicates enrichment of functional categories related to genetic disorders, neurodegeneration of the nervous system and inflammatory disease. The ALS related modules contain a number of candidate genes possibly involved in pathogenesis of ALS.ConclusionThis first large-scale blood gene expression study in ALS observed distinct patterns between cases and controls which may provide opportunities for biomarker development as well as new insights into the molecular mechanisms of the disease. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,854 |
Mitochondria-produced reactive oxygen species (ROS) are thought to contribute to cell death caused by a multitude of pathological conditions. The molecular sites of mitochondrial ROS production are not well established but are generally thought to be located in complex I and complex III of the electron transport chain. We measured H 2 O 2 production, respiration, and NADPH reduction level in rat brain mitochondria oxidizing a variety of respiratory substrates. Under conditions of maximum respiration induced with either ADP or carbonyl cyanide p -trifluoromethoxyphenylhydrazone,α-ketoglutarate supported the highest rate of H 2 O 2 production. In the absence of ADP or in the presence of rotenone, H 2 O 2 production rates correlated with the reduction level of mitochondrial NADPH with various substrates, with the exception of α-ketoglutarate. Isolated mitochondrial α-ketoglutarate dehydrogenase (KGDHC) and pyruvate dehydrogenase (PDHC) complexes produced superoxide and H 2 O 2 . NAD + inhibited ROS production by the isolated enzymes and by permeabilized mitochondria. We also measured H 2 O 2 production by brain mitochondria isolated from heterozygous knock-out mice deficient in dihydrolipoyl dehydrogenase (Dld). Although this enzyme is a part of both KGDHC and PDHC, there was greater impairment of KGDHC activity in Dld-deficient mitochondria. These mitochondria also produced significantly less H 2 O 2 than mitochondria isolated from their littermate wild-type mice. The data strongly indicate that KGDHC is a primary site of ROS production in normally functioning mitochondria. | Protein oxidative or redox modifications induced by reactive oxygen species (ROS) or reactive nitrogen species (RNS) not only can impair protein function, but also can regulate and expand protein function under a variety of stressful conditions. Protein oxidative modifications can generally be classified into two categories: irreversible oxidation and reversible oxidation. While irreversible oxidation usually leads to protein aggregation and degradation, reversible oxidation that usually occurs on protein cysteine residues can often serve as an "on and off" switch that regulates protein function and redox signaling pathways upon stress challenges. In the context of ischemic tolerance, including preconditioning and postconditioning, increasing evidence has indicated that reversible cysteine redox modifications such as S-sulfonation, S-nitrosylation, S-glutathionylation, and disulfide bond formation can serve as a cellular defense mechanism against tissue ischemic injury. In this review, I highlight evidence of cysteine redox modifications as protective measures in ischemic injury, demonstrating that protein redox modifications can serve as a therapeutic target for attenuating tissue ischemic injury. Prospectively, more oxidatively modified proteins will need to be identified that can play protective roles in tissue ischemic injury, in particular, when the oxidative modifications of such identified proteins can be enhanced by pharmacological agents or drugs that are available or to be developed. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,855 |
Ethnopharmacological relevance Blechnum orientale Linn. ( B. orientale ) is a fern traditionally used by the natives as a poultice to treat wounds, boils, ulcers, blisters, abscesses, and sores on the skin. Aim of the study To investigate the wound healing ability of a concentrated extract of B. orientale in a hydrogel formulation in healing diabetic ulcer wounds. Materials and methods The water extract from the leaves of B. orientale was separated from the crude methanolic extract and subjected to flash column chromatography techniques to produce concentrated fractions. These fractions were tested for phytochemical composition, tannin content, antioxidative and antibacterial activity. The bioactive fraction was formulated into a sodium carboxymethylcellulose hydrogel. The extract-loaded hydrogels were then characterized and tested on excision ulcer wounds of streptozotocin-induced diabetic rats. Wound size was measured for 14 days. Histopathological studies were conducted on the healed wound tissues to observe for epithelisation, fibroblast proliferation and angiogenesis. All possible mean values were subjected to statistical analysis using One-way ANOVA and post-hoc with Tukey’s T-test ( P Results One fraction exhibited strong antioxidative and antibacterial activity. The fraction was also highly saturated with tannins, particularly condensed tannins. Fraction W5–1 exhibited stronger antioxidant activity compared to three standards (α-Tocopherol, BHT and Trolox-C). Antibacterial activity was also present, and notably bactericidal towards Methicillin-resistant Staphylococcus aureus (MRSA) at 0.25 mg/ml. The extract-loaded hydrogels exhibited shear-thinning properties, with high moisture retention ability. The bioactive fraction at 4% w/w was shown to be able to close diabetic wounds by Day 12 on average. Other groups, including controls, only exhibited wound closure by Day 14 (or not at all). Histopathological studies had also shown that extract-treated wounds exhibited re-epithelisation, higher fibroblast proliferation, collagen synthesis, and angiogenesis. Conclusion The ethnopharmacological effects of using B. orientale as a topical treatment for external wounds was validated and was also significantly effective in treating diabetic ulcer wounds. Thus, B. orientale extract hydrogel may be presented as a potential treatment for diabetic ulcer wounds. | CONTEXT: A wound is defined as a loss or breaking of cellular, anatomical, or functional continuity of living tissues. Diabetes may delay the process of wound healing leading to development of chronic wounds. Healing impairment of diabetic wounds presents serious clinical problems for both diabetic patients and physicians worldwide. AIMS: This study aims to validate the use of Leptadenia hastata in the treatment of diabetic and nondiabetic wounds. SETTINGS AND DESIGN: Diabetes mellitus was induced in twenty Albino rats using a single injection of streptozotocin (50 mg/kg i.p.). The rats were divided into four groups (III–VI) consisting of five rats each. In addition, ten nondiabetic rats were grouped into I and II. SUBJECTS AND METHODS: Full-thickness excision wounds extending to the subcutaneous tissue were made on the mid-dorsal region, and rats in Group III–VI had their wounds treated with olive oil, 100 mg/kg of extract, 200 mg/kg of extract, and procaine penicillin, respectively. Rats in Groups I and II received olive oil and 200 mg/kg of extract, respectively, for 28 days. Wound areas were calculated, and histological sections of the wound area were analyzed. STATISTICAL ANALYSIS USED: Data were statistically analyzed using GraphPad InStat software using one-way analysis of variance and expressed as mean ± standard error of mean and percentage followed by Bonferroni multiple comparisons test. RESULTS: Analysis of wound area in all groups revealed that the extract promoted wound healing in the diabetic rats by significantly (P CONCLUSIONS: The extract enhanced diabetic wound healing by reducing inflammation, increasing wound contraction and epithelialization. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,856 |
Le traitement combine par injection intralesionnelle de OK432 suivie de l'administration intraperitoneale de lentinane et de lipopolysaccharide bacterien a entraine la regression presque complete de la tumeur solide MH134. Ces 3 substances ont ete necessaires pour obtenir une activite antitumorale maximale. Les souris chez lesquelles la tumeur a regresse par suite du traitement presentent une augmentation de la reaction d'hypersensibilite tardive contre la tumeur et une resistance a l'epreuve de provocation par le MH134 mais ne possedent pas d'anticorps cytolytiques dans leur serum | Changes of serum proteins have recently received much attention in studies of immunomodulators. In this work, changes of serum proteins, especially LB, were studied by gel electrophoresis of sera after administration of 23 immunomodulators or antitumor agents. Fourteen of the 23 compounds increased the concentration of LB in the serum of normal ddY mice when injected once ip. Six compounds caused a very rapid (day 1) increase of LB, and 8 agents caused a slow increase (day 4 approximately day 10). On the basis of the results, these compounds were classified into type I (causing a rapid increase in LB; i.e., lipopolysaccharide, dextran sulfate and poly (I)-poly(C), type II (causing a slow increase in LB; i.g., lentinan, TAK and PS-K), and type O (causing no increase in LB; e.g., levamisole and bestatin). The antitumor activities of these three types of compounds in combination with lipopolysaccharide (type I) or lentinan (type II) were studied in an Ehrlich carcinoma-ddY mouse system. The results suggested that different types of compounds frequently showed synergistic antitumor activities. Typing of immuno-modulators and the antitumor activities of combinations of these compounds are discussed. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | fra_Latn | 22,857 |
The effects of phorbol esters on contractions of detrusor strips isolated from mouse urinary bladder were studied. β-Phorbol-12,13-dibutyrate (β-PDBu, 10 nM) significantly enhances both the neurogenic and myogenic detrusor contractions to a similar extent. By contrast, an inactive isoform of protein kinase C (PKC) stimulation, α- phorbol-12,13-dibutyrate (100 nM) has no such enhancing effect on the muscle contraction. The effect of β-PDBu was dependent on the extracellular Ca2+ concentration. Nifedipine (0.3 µM, a L-type Ca2+ channel blocker), staurosporine (1 µM) and bisindolylmaleimide I ( µM, a selective PKC inhibitor) but not ω-conotoxin GVIA (an N-type Ca2+ channel blocker) abolished the enhancing effect of β-PDBu. In other words, β-PDBu failed to augment the nifedipine-insensitive component of the muscle contraction. Moreover, β-PDBu not only enhances the muscle response induced by exogenous agonists (acetylcholine or ATP) and KCl but also increases the resting tone of detrusor muscle, an effect which is also inhibited by nifedipine and bisindolylmaleimide I. From these findings, it is concluded that the enhancing effect of β-PDBu is due to activation of the L-type Ca2+ channel through phosphorylation by protein kinase C. This allows more Ca2+ influx from the extracellular medium, leading to an increase in the contractions of the mouse detrusor muscle. | Isolated perfused rabbit ear arteries contract when treated with 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of the calcium-activated, phospholipid-dependent protein kinase or C-kinase. Under conditions where the calcium concentration in the perfusate is 1.5 mM and the potassium concentration is 4.8 mM, there is a latent period of 70 +/- 19 min (mean +/- S.E.M., n = 10) between TPA addition and the onset of the contractile response. Once initiated, the contractile response is progressive and sustained. When perfusion conditions are altered in such a way as to modify calcium flux across the plasma membrane (i.e., raising the extracellular calcium concentration to 2.5 mM Ca++, raising the extracellular potassium concentration to 10 mM, and/or preincubating the tissues in media containing 100 nM Bay K 8644, a potent calcium channel agonist), the latency period between TPA addition and initiation of the contractile response is significantly reduced (2.5 mM Ca++, 37 +/- 7 min; 10 mM K+ and 2.5 mM Ca++, 11 +/- 3 min; 100 nM Bay K 8644 and 1.5 mM Ca++, 20 +/- 7 min; 100 nM Bay K 8644 and 2.5 mM Ca2+, 8.5 +/- 1.7 min; 10 mM K+ and 100 nM Bay K 8644, 11 +/- 5 min). Likewise, the combination of 2.5 mM calcium, 100 nM Bay K 8644, and 3.3 microM ouabain results in a contractile response 4.5 +/- 2.0 min after TPA addition (means +/- S.E.M., n = 4). Control tissues (absence of TPA addition) run simultaneously show no contractile responses to the various Ca++ flux regulators even after 90 min of incubation.(ABSTRACT TRUNCATED AT 250 WORDS) | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,858 |
The “outer sphere” association of Co(NH 3 ) 6 +3 with acid mucopolysaccharides of connective tissue has been investigated by a spectrophotometric procedure. The data fit a linear form of the LANGMUIR adsorption isotherm and allow calculation of parameters characterizing the binding affinity and the number of binding sites. A similar equation, based upon competition between trivalent cation and Na + for binding sites, was derived and accounts approximately for the dependence of association on Na + concentration. The method distinguishes specific site-binding, or ion-pair formation, from non-localized retention of microions in the potential field of the macroion. It is suggested that the binding affinities depend largely on electrostatic interactions between neighboring charged groups on the polyion. In this manner, the high affinities of heparin preparations may be accounted for, and differences between isomeric chondroitin sulfates related to structural differences between the respective repeating disaccharide periods. | A dissection procedure has been devised to permit zonal analysis of the epiphyseal plate of fetal calf leg bones. Samples of whole and washed tissue from the various zones were analyzed for their content of electrolyte and organic constituents, as well as for density, ash and moisture. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,859 |
Membrane channels provide routes for the rapid, passive movement of solutes across plasma and intracellular membranes. It is generally assumed that the major physiological role of membrane channels is to transport inorganic ions for processes such as transepithelial salt absorption and secretion, cell volume regulation, signal transduction, and control of membrane electrical properties. Increasing evidence indicates, however, that channels play an important role in organic solute transport in a wide variety of cell types and organisms. Some of the major physiological roles of organic solute channels include uptake of nutrients, excretion of metabolic waste products, volume-regulatory organic osmolyte transport, and control of mitochondrial metabolism. This article reviews the functions and characteristics of channels that participate in the transport and regulation of both charged and electroneutral organic solutes. | Swelling of cells in the nervous system is frequently associated with pathological states such as cerebral ischemia. The major cell type that swells in gray matter appears to be the astrocyte, although swelling of neuronal dendrites also occurs. Such swelling probably affects function by reducing the volume of the extracellular space. In addition the properties of the swollen cells themselves are altered, such as the swelling-induced release of excitatory amino acids, which are likely to be deleterious. Recent work has shown that these effects, linked to astrocytic swelling, may be involved in pathological states such as cerebral ischemia and trauma. Increased understanding of such swelling in the CNS will thus be of great importance in understanding mechanisms of brain damage and may provide specific sites for therapeutic intervention. NEUROSCIENTIST 6:14-25, 2000 | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,860 |
The Cl- secretory response of colonic cells to Ca(2+)-mediated agonists is transient despite a sustained elevation of intracellular Ca2+. We evaluated the effects of second messengers proposed to limit Ca(2+)-mediated Cl- secretion on the basolateral membrane, Ca(2+)-dependent K+ channel (Kca) in colonic secretory cells, T84. Neither protein kinase C (PKC) nor inositol tetrakisphosphate (1,3,4,5 or 3,4,5,6 form) affected Kca in excised inside-out patches. In contrast, arachidonic acid (AA; 3 microM) potently inhibited Kca, reducing NP0, the product of number of channels and channel open probability, by 95%. The apparent inhibition constant for this AA effect was 425 nM. AA inhibited Kca in the presence of both indomethacin and nordihydroguaiaretic acid, blockers of the cyclooxygenase and lipoxygenase pathways. In the presence of albumin, the effect of AA on Kca was reversed. A similar effect of AA was observed on Kca during outside-out recording. We determined also the effect of the cis-unsaturated fatty acid linoleate, the trans-unsaturated fatty acid elaidate, and the saturated fatty acid myristate. At 3 microM, all of these fatty acids inhibited Kca, reducing NP0 by 72-86%. Finally, the effect of the cytosolic phospholipase A2 inhibitor arachidonyltrifluoromethyl ketone (AACOCF3) on the carbachol-induced short-circuit current (Isc) response was determined. In the presence of AACOCF3, the peak carbachol-induced Isc response was increased approximately 2.5-fold. Our results suggest that AA generation induced by Ca(2+)-mediated agonists may contribute to the dissociation observed between the rise in intracellular Ca2+ evoked by these agonists and the associated Cl- secretory response. | We investigated adenosine (Ado) activation of the cystic fibrosis transmembrane conductance regulator (CFTR) in vitro and in vivo. A(2B) Ado receptors were identified in Calu-3, IB-3-1, COS-7, and primary human airway cells. Ado elevated cAMP in Calu-3, IB-3-1, and COS-7 cells and activated protein kinase A-dependent halide efflux in Calu-3 cells. Ado promoted arachidonic acid release from Calu-3 cells, and phospholipase A(2) (PLA(2)) inhibition blocked Ado-activated halide efflux in Calu-3 and COS-7 cells expressing CFTR. Forskolin- and beta(2)-adrenergic receptor-stimulated efflux were not affected by the same treatment. Cytoplasmic PLA(2) (cPLA(2)) was identified in Calu-3, IB-3-1, and COS-7 cells, but cPLA(2) inhibition did not affect Ado-stimulated cAMP concentrations. In cftr(+) and cftr(-/-) mice, Ado stimulated nasal Cl(-) secretion that was CFTR dependent and sensitive to A(2) receptor and PLA(2) blockade. In COS-7 cells transiently expressing DeltaF508 CFTR, Ado activated halide efflux. Ado also activated G551D CFTR-dependent halide efflux when combined with arachidonic acid and phosphodiesterase inhibition. In conclusion, PLA(2) and protein kinase A both contribute to A(2) receptor activation of CFTR, and components of this signaling pathway can augment wild-type and mutant CFTR activity. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,861 |
The major route of tumor spread is through the bloodstream. Once in circulation, the tumor cells aggregate in clumps with platelets, which enhances the tumor cell survival. The tumor emboli will then adhere to the endothelium and by the release of proteases extravasation of the cells will occur. One of the platelet-secreted proteins is thrombospondin-1. In this article, thrombospondin-1 will be described as a modulator of angiogenesis through its role in regulating endothelial cell apoptosis, protease expression, and vascular endothelial growth factor expression. We hope to convey the idea that activity of thrombospondin-1 in tumor progression is dependent upon its interaction with several host- and tumor-associated proteins. | Objective— Thrombospondin-1 (TSP1) is described as a positive regulator of vascular smooth muscle growth in cell culture. However, insight into the in vivo effects of TSP1 on smooth muscle cell (SMC) function is lacking. Methods and Results— We analyzed wild-type (WT) and TSP1-deficient (Tsp1−/−) mice in a carotid artery ligation model, in which neointimal lesions form without overt mechanical damage to the endothelium. On ligation, the expression of TSP1 increased strongly in the matrix of neointima and adventitia. In the early phase after ligation (day 3 to 7), activation, proliferation, and migration of medial SMCs were delayed and impaired in Tsp1−/− mice, in parallel with defective upregulation of metalloproteinase (MMP)-2 activity. As a result, Tsp1−/− arteries developed smaller neointimal lesions, a thicker media but comparably attenuated patency as in WT arteries, 28 days after ligation. Furthermore, medial and neointimal SMCs in Tsp1−/− mice produced more collagen, more osteopontin, and displayed... | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,862 |
Objective: To evaluate the role of surfactant in the mechanism and treatment of acute lung injury caused by inhalation of fabric protector. Design: Prospective, randomized study. Setting: University laboratory. Interventions: In vitro experiment: a porcine surfactant suspension (10 mg · ml−1) was exposed to a fabric protector aerosolized with an ultrasonic nebulizer for 1 min. Minimum surface tension (γ min) was sequentially measured using pulsating bubble equipment. Animal experiment: 14 adult rats were anesthetized with pentobarbital and mechanically ventilated with pure oxygen. Then, all rats inhaled fabric protector aerosolized with the nebulizer for five breaths. Three hours after inhalation, the rats were randomly assigned to two groups: a surfactant group (n = 7), in which surfactant (100 mg · kg−1) was replaced, and a control group (n = 7), in which no substance was given. Measurements and results: In vitro experiment: exposure to fabric protector aerosol increased the mean γ min of the surfactant from 1.7 to 19.2 mN · m−1 (n = 5, p < 0.05). Animal experiment: the mean partial pressure of oxygen in arterial blood (PaO2) in all rats decreased from 62.8 to 17.1 kPa at 3 h after inhalation. The PaO2 in the surfactant group increased to 49.8 ± 11.1 (SD) kPa at 30 min after surfactant replacement (p < 0.05), while the PaO2 in the control group remained below 20 kPa. Conclusions: Impairment of surfactant is a factor involved in the development of acute lung injury caused by inhalation of fabric protector. Surfactant replacement may be therapeutic for such injuries. | With a pulsating bubble surfactometer we assessed the ability of various agents, fibrinogen, human serum, albumin, and a 55,000-dalton serum protein, to interfere with the surface activity of Surfactant TA. From a highest final protein concentration of 4 mg/ml the potential inhibitors were diluted down to 0.125 mg/ml in six steps, and each concentration was evaluated together with two final phospholipid concentrations, 6.25 and 1.25 mg/ml, of the surfactant preparation. The strongest inhibiting action was exerted by fibrinogen, followed by human serum and the 55,000-dalton serum protein; the weakest inhibitor was albumin. Bilirubin, when added in an amount of 1.73 mg/100 ml dissolved in human serum, significantly (P less than 0.001) augmented the inhibition over that exerted by human serum alone. Adsorption rate, as reflected in the mean value of surface tension 2 and 10 s after creation of a bubble, not pulsating, was seriously affected by each of the protein-containing inhibitors in concentrations exceeding 1 mg/ml. Surface tension was raised significantly when the pulsating bubble was at maximal and minimal size. The effect was dose dependent. At maximal size it showed no tendency to disappear during the 10-min recording, but at minimal bubble size the inhibition gradually diminished. We conclude that proteins present in the airways may seriously interfere with the activity of Surfactant TA. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,863 |
Objective:To investigate the mechanism of acute Sodium ammonium dimethyl 2 propano 1.3 dithiosulfate monohydrate(SCD) poison and the protective antidotal effects of 2.3 Dimercaptopropane 1 sulfonate sodium(Na DMPS) on Succinate dehydrogenase(SDH) activities in mice.Methods:The mice were randomly divided into three groups: Control group, SCD group, (Na DMPS) group. The activities of Succinate dehydrogenase(SDH) in mitochondria of liver and myocardium and Lactic dehydrogenase(LDH) activities in plasma of three groups were determined.Results:SDH decreased significantly (P0.05) and LDH increased remarkably (P0.001) in SCD group compared with those of control group. SDH enhanced obviously (P0.05) and LDH reduced notably (P0.001) in (Na DMPS + SCD) group than those of SCD group.Conclusion:SCD could inhibit the activities of SDH of mitochondria consequently suppressing cell respiration in mice. Na DMPS could antagonize significantly the inhibiting effects of SCD on the activities of SDH. This antagonistic actions play an important role in preventing and curing SCD poison. | Sodium dimercaptopropane sulfonate is used in place of dimercaprol in the treatment of poisoning by heaving metals and metalloids as a well-known specific antidote. It is claimed to be less toxic. In early stage, the pharmacologists and clinical doctors in Wenzhou Medical College found this drug as antidote against non-metallic pesticides as nereistoxin insecticides, Chlordimeform, bactercide 402, and tetramine. We did a lot of animal experiments and clinical trials to confirm that this antagonist possesses a strong antidotal effect. Now it is widely used in China. Great break through has been made not only in the theory but also in its practice. Furthermore, the combination use of this antidote and central anticonvulsant as diazepam indicated synergistic antidotal effect, which is probably the best utilization in the treatment of acute poisoning by tetramine. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,864 |
Rabbit tracheal epithelial (RbTE) cells in culture undergo terminal squamous differentiation characterized by enhanced transglutaminase activity, synthesis of specific keratins, and the formation of cross-linked envelopes. The expression of each of these markers of differentiation occurs spontaneously after the cells reach confluency, but this expression can be inhibited by the inclusion of retinoids in the extracellular medium. In the current work, we demonstrate that radioactive sulfate incorporation into the organic phase of a CHCl3/CH3OH (2:1) extract of RbTE cells increases 50- to 100-fold upon differentiation and that this accumulation can be completely blocked by the inclusion of retinoic acid in the culture medium. By the techniques of specific metabolic radiolabeling, thin layer chromatography, gas chromatography-mass spectrometry, and fast atom bombardment-mass spectrometry, the sulfated amphiphile was shown to be cholesterol 3-sulfate. Cholesterol sulfate accumulation begins 1 to 2 days after the RbTE cells reach the stationary phase of growth which is the same time that other differentiated functions begin to be expressed. The inhibition of accumulation by retinoic acid is concentration-dependent and half-maximal at 5 X 10(-11) M. The relative efficacy of a series of synthetic retinoids in inhibiting cholesterol sulfate accumulation correlated with their binding to the cellular retinoic acid-binding protein. These data taken together indicate that cholesterol sulfate is a marker of squamous differentiation in RbTE cells in culture. Possible biochemical mechanisms of the regulation of cholesterol sulfate levels during differentiation are discussed. | Theoretical inferences, based on biophysical, biochemical, and biosemiotic considerations, are related here to the pathogenesis of cardiovascular disease, diabetes, and other degenerative conditions. We suggest that the "daytime" job of endothelial nitric oxide synthase (eNOS), when sunlight is available, is to catalyze sulfate production. There is a striking alignment between cell types that produce either cholesterol sulfate or sulfated polysaccharides and those that contain eNOS. The signaling gas, nitric oxide, a well- known product of eNOS, produces pathological effects not shared by hydrogen sulfide, a sulfur-based signaling gas. We propose that sulfate plays an essential role in HDL-A1 cholesterol trafficking and in sulfation of heparan sulfate proteoglycans (HSPGs), both critical to lysosomal recycling (or disposal) of cellular debris. HSPGs are also crucial in glucose metabolism, protecting against diabetes, and in maintaining blood colloidal suspension and capillary flow, through systems dependent on water-structuring properties of sulfate, an anionic kosmotrope. When sunlight exposure is insufficient, lipids accumulate in the atheroma in order to supply cholesterol and sulfate to the heart, using a | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,865 |
Vinculin binds to multiple focal adhesion and cytoskeletal proteins and has been implicated in transmitting mechanical forces between the actin cytoskeleton and integrins or cadherins. It remains unclear to what extent the mechano- coupling function of vinculin also involves signaling mechanisms. We report the effect of vinculin and its head and tail domains on force transfer across cell adhesions and the generation of contractile forces. The creep modulus and the adhesion forces of F9 mouse embryonic carcinoma cells (wild-type), vinculin knock-out cells (vinculin � /� ), and vinculin � /� cells expressing either the vinculin head domain, tail domain, or full-length vinculin (rescue) were measured using magnetic tweezers on fibronectin-coated super-paramagnetic beads. Forces of up to 10 nN were applied to the beads. Vinculin � /� cells and tail cells showed a slightly higher incidence of bead detachment at large forces. Compared to wild-type, cell stiffness was reduced in vinculin � /� and head cells and was restored in tail and rescue cells. In all cell lines, the cell stiffness increased by a factor of 1.3 for each doubling in force. The power-law exponent of the creep modulus was force-independent and did not differ between cell lines. Importantly, cell tractions due to contractile forces were suppressed markedly in vinculin � /� and head cells, whereas tail cells generated tractions similar to the wild-type and rescue cells. These data demonstrate that vinculin contributes to the mechanical stability under large external forces by regulating contractile stress generation. Furthermore, the regulatory function resides in the tail domain of vinculin containing the paxillin-binding site. | The three-dimensional intracellular network formed by the filamentous polymers comprising the cytoskeletal affects the way cells sense their extracellular environment and respond to stimuli. Because the cytoskeleton is viscoelastic, it provides a continuous mechanical coupling throughout the cell that changes as the cytoskeleton remodels. Such mechanical effects, based on network formation, can influence ion channel activity at the plasma membrane of cells and may conduct mechanical stresses from the cell membrane to internal organelles. As a result, both rapid responses such as changes in intracellular Ca2+ and slower responses such as gene transcription or the onset of apoptosis can be elicited or modulated by mechanical perturbations. In addition to mechanical features, the cytoskeleton also provides a large negatively charged surface on which many signaling molecules including protein and lipid kinases, phospholipases, and GTPases localize in response to activation of specific transmembrane receptors. The resulting spatial localization and concomitant change in enzymatic activity can alter the magnitude and limit the range of intracellular signaling events. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,866 |
The kinetics of sulfate uptake were studied in basolateral membrane vesicles from rat renal cortex. Sulfate uptake exhibits a DIDS-sensitive, saturable component, and a DIDS-insensitive component, which does not saturate in the tested sulfate concentration range (up to 10 mM). Intravesicular (= trans) sulfate strongly stimulates sulfate uptake by increasing Jmax and--to a lesser degree--by decreasing apparent Km. The marked dependence of Jmax on trans-sulfate indicates that the transport system operates as an anion exchanger. Half-maximal sulfate uptake occurs at 0.08-0.14 mmol/l extravesicular sulfate. Half-maximal trans-stimulation is observed at 11 mmol/l intravesicular sulfate indicating that the sulfate transporter is highly asymmetric. Lowering extravesicular pH stimulates sulfate uptake, suggesting that external protons are essential for sulfate uptake. This stimulation is mainly due to a decrease in Km. An inside positive membrane potential stimulates sulfate uptake at pHout = 8.8, but not at pHout = 6.4. These results are compatible with electrogenic sulfate transport at higher and electroneutral 2H+ -SO4(2-) cotransport at lower pH. | The fluorescence enhancement of 4,4′-dibenzamido-2,2′-disulfonic stilbene (DBDS) upon binding to membranes was used to examine proximal tubule stilbene binding sites. Equilibrium binding studies of DBDS to renal brush border (BBMV) and basolateral membrane vesicles (BLMV) were performed using a fluorescence enhancement technique developed for red blood cells (A.S. Verkman, J.A. Dix and A.K. Solomon,J. Gen. Physiol.81:421–449, 1983). In the absence of transportable anions, DBDS bound reversibly to a single class of sites on BLMV isolated from rabbit (K d =3.8 μm) and rat (3.2 μm); 100 μm dihydro-4,4′-diisothiocyano-2,2′-disulfonic stilbene (H2DIDS) blocked >95% of binding. H2DIDS inhibitable DBDS binding was not detected using rat or rabbit BBMV. In rabbit BLMV, DBDSK d doubled with 10mm SO4, 50mm HCO3 and 100mm Cl, but was not altered by Na or pH (6–8). In stopped-flow experiments the exponential time constant for DBDS binding slowed with SO4, HCO3 and Cl, but was unaffected by Na. These results are consistent with competitive binding of DBDS and anions at an anion transport site. To relate DBDS binding data to anion transport inhibition we used35SO4 uptake to characterize several modes of rabbit BLM anion transport: H/SO4 and Na/SO4 cotransport, and Cl/SO4 countertransport. Each transport process was electroneutral and was inhibited by H2DIDS, furosemide, probenecid, chlorothiazide and DBDS. The apparentK t 's for DBDS (3–20 μm) were similar toK d for DBDS binding. These studies define a class of anion transport sites on the proximal tubule basolateral membrane measureable optically by a fluorescent stilbene. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,867 |
An 80 kJ electrothermal gun facility was assembled at Kumamoto University in order to investigate the dependence of capillary discharges on ambient pressure. The observation of capillary discharges using an image converter camera shows that early phenomena of the discharges vary with ambient pressure. At a pressure of one atmosphere, discharges begin to occur near the radial center of the capillary. On the other hand, at a lower pressure of about 1 Pa, discharges occur near the insulator surface of the capillary. Plasma parameters, such as electron density, electron temperature, and the species of the plasma and neutral gas, are measured by spectroscopic techniques. The electron density at low pressure is more than 10/sup 17/ cm/sup -3/ at a current of only about 1 kA because of severe wall ablation by the surface discharge. At high pressure, the electron density is quite low for electron currents less than 2 kA. For currents greater than 2 kA, the electron density is over 10/sup 18/ cm/sup -3/ at both pressures. The temperature estimated from a Boltzmann plot is in the range of 0.6 eV to 0.7 eV at low pressure. | Cold plasma discharges have been shown to have medically-relevant thera- peutic effects when applied to living tissues, including blood coagulation and wound healing; thus, plasma treatment of infl amed tissues in ulcerative colitis disease may be an effective ap- proach to reduce adverse consequences if not cure the disease. Here we discuss results of the fi rst experimental study of cold plasma treatment of ulcerative colitis in a mouse model. As a plasma source, a cold spark discharge has been used. The results show that plasma treatment of experimental model of ulcerative colitis in mice has some benefi cial effects by suppressing the progression of the disease while no damage to colon tissues is observed; and these effects are comparable to standard therapy. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,868 |
Introduction Small-cell lung cancer (SCLC) is a highly vascularized tumor. ASA404 is a tumor vascular disrupting agent. This is the first trial to report the effects of combining chemotherapy with ASA404 in SCLC. Methods Patients with untreated metastatic SCLC were treated with carboplatin (area under curve, 6) plus paclitaxel (175 mg/m2) plus ASA404 (1800 mg/m2) on day 1 every 21 days for up to 6 cycles. The primary endpoint was the progression-free survival (PFS) rate at 24 weeks. Results Median age was 61 years; 53% were women, 41% had weight loss; and 96% had a performance status of 0-1. Twelve patients completed all 6 cycles, and most adverse events were related to chemotherapy. Median PFS and time to progression were 7.0 months (95% CI, 5.7-9.4 months) and 7.5 months (95% CI, 5.7-9.4 months), respectively. The progression-free survival (PFS) rate at 24 weeks was 41% (95% CI, 18%-65%). The overall response rate was 94%. The median overall survival time was 14.2 months (95% CI, 8.2-16.0 months) and 1-year survival was 57%. The median follow-up time was 17.7 months. Due to negative results with ASA404 in non–small-cell lung cancer trials, the trial was stopped prematurely after 17 of 56 planned patients were being accrued. Conclusions This is the first report of a clinical trial with a vascular disrupting agent in SCLC. No unexpected toxicity was observed. PFS was not prolonged with carboplatin and paclitaxel plus ASA404. | Xanthone derivatives have been described as compounds with a privileged scaffold exhibiting diverse biological/pharmacological activities, what directed the interest to pursue the development of these derivatives into drug candidates. Nevertheless, to achieve this purpose it is crucial to study their pharmacokinetics and toxicity (PK/tox) properties as decision endpoints to continue or interrupt the development investment. This review aims to expose the most relevant analytical methods used in the physicochemical and PK/tox studies in order to detect, quantify, and identify different bioactive xanthones. Analyzing the main results from in vitro and in vivo systems towards ADME properties such as solubility, lipophilicity, pKa, chemical and metabolic stability, permeability, transporters modulation, and plasma protein binding, it is possible to uncover some threats governing the PK properties and to understand the bioavailability and drugability of xanthone derivatives. The last section of this review focuses on a case-study of the development of the drug candidate DMXAA, which has reached clinical trials, to provide the paths and the importance of PK/tox parameters of this scaffold. The data assembled in this review intends to guide for tackling issues in the design of potential lead compounds and drug candidates with a xanthone scaffold. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,869 |
Triterpene saponins (saponosides) are found in a variety of higher plants and display a wide range of pharmacological activities, including expectorant, anti-inflamatory, vasoprotective, gastroprotective and antimicrobial properties. Recently, a potential anticancer activity of saponins has been suggested by their cytotoxic, cytostatic, pro-apoptotic and anti-invasive effects. At high concentrations (more than 100 µM) saponins exert cytotoxic and haemolytic effects via permeabilization of the cell membranes. Noteworthy, the inhibition of cancer cell proliferation, the induction of apoptosis and attenuation of cell invasiveness is observed in the presence of low saponin concentrations. Saponins might affect the expression of genes associated with malignancy. These alterations are directly related to the invasive phenotype of cancer cells and depend on "cellular context". It illustrates the relationships between the action of saponins, and the momentary genomic/proteomic status of cancer cells. Here, we discuss the hallmarks of anti-cancer activity of saponins with the particular emphasis on anti-invasive effect of diverse groups of saponins that have been investigated in relation to tumor therapy. | Ginsenoside Rd is a protopanaxadiol-type ginsenoside found in ginseng and is the active ingredient in several Oriental herbal medicines. We investigated the effects of ginsenoside Rd on tumor invasion and metastasis in the human hepatocellular carcinoma HepG2 and its possible mechanism of action. HepG2 cells were treated with ginsenoside Rd at different concentrations. Scratch wound and Boyden chamber assays were used to determine the effects of ginsenoside Rd on the migration and invasiveness of HepG2 cells, respectively. The molecular mechanisms by which ginsenoside Rd inhibited the invasion and migration of HepG2 cells were investigated by RT-PCR, Western blotting, gelatin zymography, promoter assay, and treatment with inhibitors of MAPK signaling. Immunofluorescence analysis was conducted to evaluate the effect of ginsenoside Rd on focal adhesion formation in HepG2 cells. Treatment with ginsenoside Rd dose- and time-dependently inhibited the migration and invasion of HepG2 cells. It achieved this by reducing the expression of MMP-1, MMP-2, and MMP-7, by blocking MAPK signaling by inhibiting the phosphorylation of ERK and p38 MAPK, by inhibition of AP-1 activation, and by inducing focal adhesion formation and modulating vinculin localization and expression. Treatment of HepG2 cells with ginsenoside Rd significantly inhibited metastasis, most likely by blocking MMP activation and MAPK signaling pathways involved in cancer cell migration. These findings may be useful for the development of novel chemotherapeutic agents for the treatment of malignant cancers. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,870 |
The capacity of extracts from toxigenic and non-toxigenic ruminant strains of Fusobacterium necrophorum to protect against challenge with homologous and heterologous bacteria was examined in mice. The numbers of F. necrophorum which were infective or lethal for mice increased 5- to 8-fold in animals which had been previously inoculated with complete Freund's adjuvant (FCA). Although preparations containing lipopolysaccharide (LPS) and outer membrane proteins (OMP) from several strains gave protection against a non-toxigenic strain (FnB-3), they did not significantly immunize mice against a challenge infection with a toxigenic bovine strain, FnB-1. Only material which had been prepared by gel filtration of 18-h liquid culture supernates of toxigenic F. necrophorum elicited significant immunity against homologous challenge with FnB-1. This preparation contained LPS and the majority of the leucotoxic activity. However, passive protection was not afforded to mice inoculated with bovine or rabbit sera which possessed high neutralization titres against the leucocidin. | Bacterial exotoxins may contribute to the pathogenic potential of micro-organisms through interactions with cells of the host defence system as well as by directly damaging host tissue. The present studies were designed to explore mechanisms of interaction between bovine granulocytes and the leucotoxin produced by Pasteurella haemolytica, a major cause of bovine respiratory disease. Leucotoxin-containing supernatant from P. haemolytica A1 caused rapid cell death in isolated bovine granulocytes that was close to half-maximal by 5 min and nearly 90% complete after 30 min at 37 degrees C. Maintaining granulocytes at ice-water temperature markedly attenuated or prevented the toxic effect; furthermore, if exposed to supernatants at ice-water temperature and then washed, most cells remained viable even after rewarming to room temperature. However, even a very brief exposure (about 5 s) at 37 degrees C led to extensive cell death even after immediate cold dilution and washing. Granule enzymes such as arylsulphatase were released far more slowly than cytosol contents. Leucotoxin purified by column chromatography showed temperature dependence and divergence between cytosol and granule marker release similar to those observed with the crude supernatant preparation. These findings indicate that irreversible interaction between P. haemolytica leucotoxin and bovine granulocytes is initiated very rapidly at 37 degrees C but markedly impeded at low temperature, while granule enzyme release follows cytosol marker release over a much longer period. The results suggest either a requirement for target cell metabolic activity to initiate toxin effects or a temperature-dependent receptor conformation, with granule enzyme release following as a secondary consequence of granulocyte death. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,871 |
Structure-activity relationships are presented for some representative compounds from a novel series of potent inhibitors of lipid peroxidation. The compounds are indenoindole derivatives with oxidation potentials in organic solvents of between 0.2 and 1.5 V. Two of these compounds, cis-5,5a,6,10b-tetrahydro-9-methoxy-7-methylindeno[2,1-b]indole (H 290/51) with an oxidation potential of 0.32 V and cis-4b,5,9b,10- tetrahydro-8-methoxy-6-methylindeno[1,2-b]indole (H 290/30) with an oxidation potential of 0.30 V, have been tested more extensively and compared with reference compounds in several pharmacological models of lipid peroxidation. The inhibitory potencies (pIC50) of the compounds in respect to Fe/Ascorbate-induced production of thiobarbituric acid-reactive substances (TBARS) in a suspension of purified soybean lecithin were calculated. These data are 8.2 for H 290/51; 8.0 for H 290/30; 5.6 for vitamin E; and 6.6 for butylated hydroxytoluene (BHT). In isolated rat renal tissue subjected to hypoxia and reoxygenation, the potency for inhibition of TBARS formation is 6.9 for H 290/51, 6.9 for H 290/30, and <5 for vitamin E. In oxidative modification of low-density lipoproteins (LDL) induced by mouse peritoneal macrophages, the corresponding pIC50 values for TBARS inhibition for each compound are: 8.7, 8.3, <5, and 6.9, respectively. It is concluded that the synthetic indenoindoles are potent antioxidants. The results suggest that indenoindoles such as H 290/51 and H 290/30 could be useful as therapeutic agents in pathophysiological situations where lipid peroxidation plays an important role. | In this research, two types of sulfated polysaccharide derivatives were successfully synthesized. Their antioxidant activities were investigated by employing various established in vitro systems. In addition, the degree of sulfation was evaluated using ion-chromatography and IR spectra. The results verify that, when employing scavenging superoxide radical tests, both the sulfation of acid Auricularia auricular polysaccharides (SAAAP) and the sulfation of neutral Auricularia auricular polysaccharides (SNAAP) derivatives possessed considerable antioxidant activity and had a more powerful antioxidant competence than that of the native non-sulfated polysaccharides (AAAP and NAAP). On the other hand, AAAP and NAAP exhibited stronger activity on scavenging both the hydroxyl radical and lipid peroxidation. Available data obtained with in vitro measurements indicates that the sulfated groups of AAAP and NAAP played an important role on antioxidant activity. In sum, the research demonstrates that the antioxidant activity of sulfated polysaccharide derivatives in vitro has a potential significance for seeking new natural antioxidant protective agents. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,872 |
Bioactive gel-glasses, such as the silver-doped Ag-S70C30 glass, can be used to modify the inflammatory response in a local body compartment such as in acne lesions and in nonhealing dermal wounds. In this study, the cytotoxicity of soluble silver, calcium and silica ions on human epidermal keratinocytes was investigated by measurements of mitochondrial activity (MTT assay) and neutral red dye uptake (NR assay). Ag-S70C30 extracts were prepared by soaking glass powder in complete culture medium at concentrations of 1 mg/ml and 2 mg/ml (mg of glass powder per ml of culture medium). Silver concentrations for both concentrations of approximately 1 ppm were detected by inductive coupled plasma analysis (ICP). No negative effect on the cell viability was measured for an initial gel-glass concentration of 1 mg/ml and for the two shortest extraction times at a concentration of 2 mg/ml. Based on the results from MTT/ NR assays, a pH rise of approximately one unit had no negative effect on the NHEK-A cell viability. This preliminary study on keratinocyte viability merits future investigations on silver bioglass as a novel antimicrobial wound healing agent. | During the 1960s and 1970s, a first generation of materials was specially developed for use inside the human body. These developments became the basis for the field of biomaterials. The devices made from biomaterials are called prostheses. Professor Bill Bonfield was one of the first to recognize the importance of understanding the mechanical properties of tissues, especially bone, in order to achieve reliable skeletal prostheses. His research was one of the pioneering efforts to understand the interaction of biomaterials with living tissues. The goal of all early biomaterials was to 'achieve a suitable combination of physical properties to match those of the replaced tissue with a minimal toxic response in the host'. By 1980, there were more than 50 implanted prostheses in clinical use made from 40 different materials. At that time, more than three million prosthetic parts were being implanted in patients worldwide each year. A common feature of most of the 40 materials was biological 'inertness'. Almost all materials used in the body were single-phase materials. Most implant materials were adaptations of already existing commercial materials with higher levels of purity to eliminate release of toxic by-products and minimize corrosion. This article is a tribute to Bill Bonfield's pioneering efforts in the field of bone biomechanics, biomaterials and interdisciplinary research. It is also a brief summary of the evolution of bioactive materials and the opportunities for tailoring the composition, texture and surface chemistry of them to meet five important challenges for the twenty-first century. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,873 |
Nickel-based alloys have been in use since the 1930s; however, there are concerns regarding the release of metal ions (Be+2, Cr+6, Cr+3, Ni+2, Mo+6) from these alloys into surrounding tissues. Therefore, the objective of this study was to determine the cellular location and accumulation of ions using atomic absorption spectroscopy and correlate location with the cytotoxic, morphologic, and ultrastructural evaluations reported previously. Human gingival fibroblasts were exposed to the metal ions for 72 h. Controlled atomic absorption spectroscopy studies were used to determine the intracellular location of these ions reported as parts per million metal ions per milligram protein. Enzymatic markers were shown to correspond to the appropriate fraction indicating success in fractionation of the gingival fibroblasts. These results correspond with the cytotoxic, morphologic, and ultrastructural alterations reported previously for fibroblasts exposed to these ions. The highest concentration of beryllium ions occurred in the low-density molecule fraction, where lipofuscin granules were found, which has been shown to contain metal ions. The highest concentrations of hexavalent chromium ions occurred in the plasma membrane and nuclear fractions followed by the mitochondria fraction, which is supported by the ions’ ability to oxidize to trivalent chromium accumulating at the membrane as well as the alterations in nuclear and mitochondrial function. For trivalent chromium, the highest concentrations occurred in the low-density molecule and the plasma membrane fractions, which correlates with the ions’ inability to readily cross membranes. The highest concentration of molybdenum ions occurred in the plasma membrane fraction correlating with alterations in membrane morphology and increased numbers of myelin figures. The highest concentration of nickel ions was associated with the cytosol fraction where lipid droplets seen in the transmission electron micrographs were located. The current study demonstrates that a successful subcellular fractionation was obtained on gingival fibroblasts and that the location of metallic ions within the fractions correlated with cellular alterations reported previously. © 2001 Wiley Periodicals, Inc. J Biomed Mater Res 59: 466–472, 2002 | The long-term effects of metal-on-metal arthroplasty are currently under scrutiny because of the potential biological effects of metal wear debris. This review summarises data describing the release, dissemination, uptake, biological activity, and potential toxicity of metal wear debris released from alloys currently used in modern orthopaedics. The introduction of risk assessment for the evaluation of metal alloys and their use in arthroplasty patients is discussed and this should include potential harmful effects on immunity, reproduction, the kidney, developmental toxicity, the nervous system and carcinogenesis. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,874 |
BACKGROUND ::: Over the years, numerous studies have been conducted to find a storage medium with favorable properties to preserve the avulsed teeth. Oral Rehydration Solution (ORS) is a simple oral solution containing glucose and electrolytes. In addition to physiologic PH and osmolality, it has other important properties such as availability and inexpensiveness, storing potential in different conditions and places, and long lifetime. This study was carried out to more precisely investigate the storage of cells in this substance in different concentrations and in longer times, and to evaluate the programmed cell death or apoptosis as well as cell viability. ::: ::: ::: MATERIAL AND METHODS ::: The cultured PDL cells of this experimental study were exposed to three concentrations of 25%, 50%, and 100% ORS in comparison with Hanks Balanced Salt Solution (HBSS) and tap water. They were then analyzed by Tetrazolium Salt-based Colorimetric (MTT) Assay in 2-, 6-, 12-, 24-, and 48-h periods and by Apoptosis Assay in 12-, 24-, and 48-h time periods. Data were analyzed by spss software using anova and Post hoc (Duncan) tests. P ≤ 0.05 was considered significant. ::: ::: ::: RESULTS ::: Overall, the maximum viable cells and minimum apoptotic cells were reported after the cells' exposure to ORS (100%). Also, the minimum level of viable cells was observed in ORS (25%) group and the highest level of apoptotic cells was observed in 25% and 50% ORS groups. ::: ::: ::: CONCLUSION ::: ORS preserved more viable cells and induced fewer apoptotic cells in comparison with HBSS. | BACKGROUND/AIMS ::: The best treatment for an avulsed tooth is immediate replantation. If this is not possible, a proper transport medium is required for the maintenance of viability of the periodontal ligament cells (PDL). The aim was to systematically review the efficacy of different storage media used for the survival of PDL cells of avulsed teeth in the in vitro setting. ::: ::: ::: METHODS ::: The search strategy was based on the MeSH keywords in PubMed/MEDLINE: "Transport media for avulsed teeth," "Storage media for avulsed teeth," "Knocked out teeth," "Tooth avulsion," "Biological transport of avulsed tooth," "Cell survival of avulsed tooth," "Cell viability of avulsed tooth," "Tooth replantation," and "Periodontal ligament in avulsed teeth." The "AND" and "OR" Boolean operators were applied to combine keywords. Each study was evaluated for eight criteria, including use of human PDL, in vitro cell culture models, the number of passages, types of storage media, percentages of surviving PDL cells, pH and osmolality of storage media, and the type of test used to asses PDL viability. ::: ::: ::: RESULTS ::: In 15 selected studies, nine storage media (HBSS, tap water, DMEM, milk, saliva, 10% and 20% propolis, Gatorade, and Viaspan) were analyzed at six time points. For storage up to 2 hours, HBSS, DMEM, milk, 10% propolis, 20% propolis, and Viaspan conserved more than 80% of PDL viability. For storage at 24 hours, Viaspan showed best cell survival at 88.4%, followed by DMEM (70.9%) and 10% propolis (68.3%). Milk and HBSS showed similar PDL survival at 24 hours (57.2% and 57.3%, respectively). ::: ::: ::: CONCLUSIONS ::: Milk remains the most convenient, cheapest, and readily available solution in most situations while also being capable of keeping PDL cells alive. Further studies are required to evaluate the efficacy of more commonly found storage media besides milk. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,875 |
Recently we have demonstrated that, besides V gamma 5+ gamma/delta TcR+ T cells (V gamma 5+ gamma/delta T cells), V gamma 5- gamma/delta TcR+ T cells (V gamma 5- gamma/delta T cells) are also present in murine skin. In the present study, to characterize the functional differences between these two different cutaneous gamma/delta T cells we examined the expression pattern of E-cadherin and its two integrins. After co-culturing of Ly-5+ epidermal cells and migrating cells from organ-cultured murine skin with cutaneous stromal cells, we could expand V gamma 5+ gamma/delta T cells and V gamma 5- gamma/delta T cells, respectively. Flow cytometry demonstrated that cultured V gamma 5+ gamma/delta T cells expressed E-cadherin, but V gamma 5- gamma/delta T cells did not. This difference in E-cadherin expression was also observed in freshly isolated V gamma 5+ and V gamma 5- gamma/delta T cells. On the other hand, both V gamma 5+ and V gamma 5- gamma/delta T cells expressed the alpha chain of the vitronectin receptor, but did not express the alpha 4 integrin. Of these two cutaneous gamma/delta T cells, only V gamma 5+ gamma/delta T cells adhered to murine keratinocyte cell line, PAM 212 cells. Unexpectedly, however, the adhesion of E-cadherin-expressing V gamma 5+ gamma/delta T cells to PAM 212 cells was not inhibited by anti-E-cadherin antibody, which effectively abrogated the adhesion of Langerhans cells to PAM 212 cells. These distinct phenotypic and functional characteristics in the sub-sets of cutaneous gamma/delta T cells may suggest that they reside in different locations in the skin to play different functional roles in skin immunophysiology. | Epithelial tissues line the body providing the body with a protective barrier from the external environment. Maintenance of these epithelial barrier tissues critically relies on the presence of a functional resident T cell population. In some tissues, the resident T cell population is exclusively comprised of gamma delta T cells, while in others gamma delta T cells are found together with, alpha beta T cells and other lymphocyte populations. Epithelial resident gamma delta T cells function not only in the maintenance of the epithelium, but are also central to the repair process following damage from environmental and pathogenic insults. Key to their function is the crosstalk between gamma delta T cells and neighboring epithelial cells. This crosstalk relies on multiple receptor-ligand interactions through both the T cell receptor and accessory molecules leading to temporal and spatial regulation of cytokine, chemokine, growth factor and extracellular matrix protein production. As antigens that activate epithelial gamma delta T cells are largely unknown and many classical costimulatory molecules and coreceptors are not used by these cells, efforts have focused on identification of novel coreceptors and ligands that mediate pivotal interactions between gamma delta T cells and their neighbors. In this review, we discuss recent advances in the understanding of functions for these coreceptors and their ligands in epithelial maintenance and repair processes. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,876 |
A particular challenge for nanotoxicology is the evaluation of the biological fate and toxicity of nanomaterials that dissolve in aqueous fluids. Zinc oxide nanomaterials are of particular concern because dissolution leads to release of the toxic divalent zinc ion. Although zinc ions have been implicated in ZnO cytotoxicity, direct identification of the chemical form of zinc taken up by cells exposed to ZnO nanoparticles, and its intracellular fate, has not yet been achieved. We combined high resolution X-ray spectromicroscopy and high elemental sensitivity X-ray microprobe analyses to determine the fate of ZnO and less soluble iron-doped ZnO nanoparticles following exposure to cultures of human bronchial epithelial cells, BEAS-2B. We complemented two-dimensional X-ray imaging methods with atomic force microscopy of cell surfaces to distinguish between nanoparticles that were transported inside the cells from those that adhered to the cell exterior. The data suggest cellular uptake of ZnO nanoparticles is a mechanism of zinc accumulation in cells. Following uptake, ZnO nanoparticles dissolved completely generating intracellular Zn(2+) complexed by molecular ligands. These results corroborate a model for ZnO nanoparticle toxicity that is based on nanoparticle uptake followed by intracellular dissolution. | Comparative hazard identification of nanomaterials (NMs) can aid in the prioritisation for further toxicity testing. Here, we assessed the acute lung, systemic and liver responses in C57BL/6N mice for three NMs to provide a hazard ranking. A silver (Ag), non-functionalised zinc oxide (ZnO) and a triethoxycaprylylsilane functionalised ZnO NM suspended in water with 2% mouse serum were examined 24 hours following a single intratracheal instillation (I.T.). An acute pulmonary inflammation was noted (marked by a polymorphonuclear neutrophil influx) with cell damage (LDH and total protein) in broncho-alveolar lavage fluid (BALF) after administration of both non-functionalised and functionalised ZnO. The latter also induced systemic inflammation measured as an increase in blood neutrophils and a decrease in blood lymphocytes. Exposure to Ag NM was not accompanied by pulmonary inflammation or cytotoxicity, or by systemic inflammation. A decrease in glutathione levels was demonstrated in the liver following exposure to high doses of all three nanomaterials irrespective of any noticeable inflammatory or cytotoxic effects in the lung. By applying benchmark dose (BMD) modeling statistics to compare potencies of the NMs, we rank functionalised ZnO ranked the highest based on the largest number of affected endpoints, as well as the strongest responses observed after 24 hours. The non-functionalised ZnO NM gave an almost similar response, whereas Ag NM did not cause an acute response at similar doses. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,877 |
Predicting enzymatic behavior in silico is an integral part of our efforts to understand biology. Hundreds of millions of compounds lie in targeted in silico libraries waiting for their metabolic potential to be discovered. In silico "enzymes" capable of accurately determining whether compounds can inhibit or react is often the missing piece in this endeavor. This problem has now been solved for the cytosolic sulfotransferases (SULTs). SULTs regulate the bioactivities of thousands of compounds--endogenous metabolites, drugs and other xenobiotics--by transferring the sulfuryl moiety (SO3) from 3'-phosphoadenosine 5'-phosphosulfate to the hydroxyls and primary amines of these acceptors. SULT1A1 and 2A1 catalyze the majority of sulfation that occurs during human Phase II metabolism. Here, recent insights into the structure and dynamics of SULT binding and reactivity are incorporated into in silico models of 1A1 and 2A1 that are used to identify substrates and inhibitors in a structurally diverse set of 1,455 high value compounds: the FDA-approved small molecule drugs. The SULT1A1 models predict 76 substrates. Of these, 53 were known substrates. Of the remaining 23, 21 were tested, and all were sulfated. The SULT2A1 models predict 22 substrates, 14 of which are known substrates. Of the remaining 8, 4 were tested, and all are substrates. The models proved to be 100% accurate in identifying substrates and made no false predictions at Kd thresholds of 100 μM. In total, 23 "new" drug substrates were identified, and new linkages to drug inhibitors are predicted. It now appears to be possible to accurately predict Phase II sulfonation in silico. | Human cytosolic sulfotransferase 2A1 (SULT2A1) is an important phase II metabolic enzyme. The detection of SULT2A1 is helpful for the functional characterization of SULT2A1 and diagnosis of its related diseases. However, due to the overlapping substrate specificity among members of the sulfotransferase family, it is difficult to develop a probe substrate for selective detection of SULT2A1. In the present study, through characterization of the sulfation of series of bufadienolides, arenobufagin (AB) was proved as a potential probe substrate for SULT2A1 with high sensitivity and specificity. Subsequently, the sulfation of AB was characterized by experimental and molecular docking studies. The sulfate-conjugated metabolite was identified as AB-3-sulfate. The sulfation of AB displayed a high selectivity for SULT2A1 which was confirmed by in vitro reaction phenotyping assays. The sulfation of AB by human liver cytosols and recombinant SULT2A1 both obeyed Michaelis-Menten kinetics, with similar kinetic parameters. Molecular docking was performed to understand the interaction between AB and SULT2A1, in which the lack of interaction with Met-137 and Tyr-238 of SULT2A1 made it possible to eliminate substrate inhibition of AB sulfation. Finally, the probe was successfully used to determine the activity of SULT2A1 and its isoenzymes in tissue preparations of human and laboratory animals. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,878 |
Gap junctions establish direct pathways for cell-to-cell communication through the assembly of twelve connexin subunits that form intercellular channels connecting neighbouring cells. Co-assembly of different connexin isoforms produces channels with unique properties and enables communication across cell types. Here we used single-particle cryo-electron microscopy to investigate the structural basis of connexin co-assembly in native lens gap junction channels composed of connexin 46 and connexin 50 (Cx46/50). We provide the first comparative analysis to connexin 26 (Cx26), which—together with computational studies—elucidates key energetic features governing gap junction permselectivity. Cx46/50 adopts an open-state conformation that is distinct from the Cx26 crystal structure, yet it appears to be stabilized by a conserved set of hydrophobic anchoring residues. ‘Hot spots’ of genetic mutations linked to hereditary cataract formation map to the core structural–functional elements identified in Cx46/50, suggesting explanations for many of the disease-causing effects.Cryo-electron microscopy structures of connexin channels composed of connexin 46 and connexin 50 in an open-state reveal features that govern permselectivity and the location of mutated residues linked to herediatry cataracts. | Recent applications of mass spectrometry (MS) to study membrane protein complexes are yielding valuable insights into the binding of lipids and their structural and functional roles. To date, most native MS experiments with membrane proteins are based on detergent solubilization. Many insights into the structure and function of membrane proteins have been obtained using detergents; however, these can promote local lipid rearrangement and can cause fluctuations in the oligomeric state of protein complexes. To overcome these problems, we developed a method that does not use detergents or other chemicals. Here we report a detailed protocol that enables direct ejection of protein complexes from membranes for analysis by native MS. Briefly, lipid vesicles are prepared directly from membranes of different sources and subjected to sonication pulses. The resulting destabilized vesicles are concentrated, introduced into a mass spectrometer and ionized. The mass of the observed protein complexes is determined and this information, in conjunction with 'omics'-based strategies, is used to determine subunit stoichiometry as well as cofactor and lipid binding. Within this protocol, we expand the applications of the method to include peripheral membrane proteins of the S-layer and amyloid protein export machineries overexpressed in membranes from which the most abundant components have been removed. The described experimental procedure takes approximately 3 d from preparation to MS. The time required for data analysis depends on the complexity of the protein assemblies embedded in the membrane under investigation. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,879 |
Respiratory syncytial virus is the most common cause of severe lower respiratory disease in infants and young children. Its importance as a pathogen in the elderly and in the immunocompromised is becoming more clearly understood. RSV infection in infancy may lead to chronic lung disease ion later life. Newer forms of therapy are needed. This review will discuss the status of many types of compounds that interfere with RSV infection, including antibodies, inosine-5'-monophosphate dehydrogenase (IMPDH) inhibitors, fusion inhibitors, entry inhibitors, anti-sense RNA inhibitors, and nucleoprotein inhibitors. | Respiratory syncytial virus (RSV) is a common cause of seasonal respiratory viral infection in patients who have undergone hematopoietic stem cell transplantation. RSV usually presents as an upper respiratory tract infection in this patient population but may progress rapidly to lower respiratory tract infection. Available therapies that have been used for the treatment of RSV infections are limited to ribavirin, intravenous immunoglobulin, and palivizumab. The use of aerosolized ribavirin, alone or in combination with either palivizumab or intravenous immunoglobulin, remains controversial. In this comprehensive review, we present and discuss the available literature on management of RSV infections in adult hematopoietic stem cell transplantation recipients with a focus on therapeutic modalities and outcomes. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,880 |
Lasalocid (X537A) produces selective swelling of the Golgi cisternae and inhibits glycosaminoglycan synthesis [40]. 6-Diazo-5-oxo- l -norleucine (DON) inhibits glycosaminoglycan synthesis and produces vacuolation in cardiac cells [41]. In this study, we found that the vacuolation of the Golgi apparatus by X537A was inhibited by metabolic inhibitors or d -glucosamine, but not by Na-free solutions or by ouabain. In cardiac cell cultures, X537A vacuolated muscle cells before fibroblasts, while DON vacuolated the cells in reverse order. DON did not produce vacuolation in cultured vascular smooth muscle cells, and in cultured cardiac cells the vacuolation was peripheral and not due to swelling of the Golgi cisternae. X537A did not produce detectable changes in the K, Na, Mg or Ca content of cultured guinea pig aortic cells. Pre-treatment of cultured aortic cells for up to 72 h with X537A alone or in combination with DON did not reduce the number of lectin-binding sites/cell when labelling was done at 4 °C. DON alone or with X537A inhibited the increased labelling observed at 37 °C. We conclude that: (1) the swelling of the Golgi cisternae by X537A is due to accumulation of organic osmotically active solutes and not to a passive accumulation of ions with water; (2) lectin-binding sites of the surface membrane are probably glycosylated at some site other than the Golgi apparatus, although alternative interpretations cannot be unequivocally ruled out. | Granulosa cells, isolated by collagenase digestion from the mature ovarian follicle of laying hens, were incubated in the presence of two ionophores, lasalocid (X537A) and ionomycin, to determine their effects on basal and stimulated steroidogenesis, as well as their effects on various cell parameters including DNA, RNA, and protein synthesis. Both ionophores caused a dose-dependent inhibition of agonist-promoted progesterone production and, in the presence of calcium, a small but significant increase in basal output of progesterone. Whereas the conversion of pregnenolone to progesterone was unaffected by the ionophores, the activity of cholesterol side-chain cleavage enzyme was inhibited in a dose-related manner. Both ionophores decreased cellular levels of ATP and inhibited the incorporation of radioactively-labeled precursors into DNA, RNA, and proteins. Morphologically, ionophore-treated cells showed swelling of the rough endoplasmic reticulum. Similar morphological changes were also observed in cells treated with oligomycin, a known metabolic inhibitor. These results suggest that the ionophores lasalocid and ionomycin impair release of energy and thereby exert the principal cause of the inhibited steroidogenic response by granulosa cells to a variety of agonists. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,881 |
Oxidative stress has been considered as a major cause of cellular injuries in a variety of clinical abnormalities. One of the plausible ways to prevent the reactive oxygen species (ROS)-mediated cellular injury is dietary or pharmaceutical augmentation of endogenous antioxidant defense capacity. In this study, we investigated the protective actions of citrus flavanones naringin and nobiletin against the cytotoxicity induced by exposure to hydrogen peroxide (H(2)O(2)) (150μM, 3h) in PC12 cells. The results showed that naringin and nobiletin inhibited the decrease of cell viability (MTT reduction), prevented membrane damage (LDH release), scavenged ROS formation, reduced caspase-3 activity, and attenuated the decrease of mitochondrial membrane potential (MMP), respectively, in H(2)O(2)-induced PC12 cells. Meanwhile, naringin and nobiletin increased superoxide dismutase (SOD) and glutathione (GSH) activity, while decreased malondialdehyde (MDA), the production of lipid peroxidation, in H(2)O(2)-induced PC12 cells. In addition, the percentage of cells undergoing H(2)O(2)-induced apoptosis was decreased in the presence of naringin and nobiletin. These results first demonstrate that naringin and nobiletin, even at physiological concentrations, have neuroprotective effects against H(2)O(2)-induced cytotoxicity in PC12 cells. All the above results suggest that these dietary antioxidants are potential candidates for use in the intervention for neurodegenerative diseases. | Carbon nanotubes (CNTs) were extensively explored for their beneficial use in nervous system tissue engineering. However, an important concern regarding the use of CNTs is their toxicity during the interaction between cells and the nano particles. The rat pheochromocytoma cell line (PC12) was co-cultured with three types of single-walled carbon nanotubes (SWNTs), purified raw SWNTs (C), hydroxyl purified SWNTs (C-OH) and carboxyl purified SWNTs (C-COOH) at 25 µg/mL and 100 µg/ml. The experimental results revealed that SWNTs at the concentration below 100 µg/mL did not affect the cell viability. Notably, powerful antioxidant system in nerous system tissue is able to counteract with the toxicity of CNTs, which is characterized by the prominently enhanced expression of main antioxidant enzymes (catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione-S-transferase (GST)). Therefore, we believe that CNTs can be good candidates for the fabrication of biomedical scaffolds for the nerve tissue repair. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,882 |
S1P5 is one of 5 receptors for sphingosine-1-phosphate and is highly expressed on endothelial cells within the blood-brain barrier, where it maintains barrier integrity in in vitro models (J. Neuroinflamm. 2012, 9, 133). Little more is known about the effects of S1P5 modulation due to the absence of tool molecules with suitable selectivity and drug-like properties. We recently reported that molecule A-971432 (Harris, 2010) (29 in this paper) is highly efficacious in reversing lipid accumulation and age-related cognitive decline in rats (Van der Kam , , AAIC 2014). Herein we describe the development of a series of selective S1P5 agonists that led to the identification of compound 29, which is highly selective for S1P5 and has excellent plasma and CNS exposure after oral dosing in preclinical species. To further support its suitability for in vivo studies of S1P5 biology, we extensively characterized 29, including confirmation of its selectivity in pharmacodynamic assays of S1P1 and S1P3 function in rats. In addition, we found that 29 improves blood-brain barrier integrity in an in vitro model and reverses age-related cognitive decline in mice. These results suggest that S1P5 agonism is an innovative approach with potential benefit in neurodegenerative disorders involving lipid imbalance and/or compromised blood-brain barrier such as Alzheimer's disease or multiple sclerosis. | Somatosensation encompasses a wide range of sensations including pain, itch, touch, and temperature and is essential for the detection of environmental stimuli, ultimately allowing an organism to e... | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,883 |
An inductively coupled plasma mass spectrometer (ICP-MS) coupled with ultrasonic nebulization was used as a liquid chromatographic detector for the determination of tin compounds. Inorganic tin, trimethyltin, triethyltin, tripropyltin, tributyltin, and triphenyltin were separated by reversed phase liquid chromatography. The separation was complete in less than 6 min. Detection limits were in the range of 2.8–16 pg Sn for various tin species. The relative standard deviation of the peak areas for five injections of 50 μg 1−1 organotin mixture was in the range of 6–9%. This method has been applied to determine various tin species in harbour sediment reference sample PACS-1 and harbour water sample. | A novel and portable strategy based on fluorescence polarization immunoassay (FPIA) using quantum dots (QDs) was described in this study for simple, rapid, and sensitive detection of carcinoembryonic antigen (CEA). Under optimal conditions, the sensor has a wide dynamic range (from 0.5 ng/mL to 200 ng/mL) and a good correlation. The limit of detection (LOD) is 0.21 ng/mL (S/N = 3). The sensor has been applied for detection of carcinoembryonic antigen in 10 human serum samples with the range of recovery from 92.1 % to 103.6 %. Furthermore, bioconjugation of the core-shell QDs with streptavidin (SA) has been successfully applied in immunofluorescent imaging of the human hepatocellular carcinoma (HEPG2) cell line. The experimental results demonstrated the successful application of QDs-based fluorescence polarization immunoassay for detection of target proteins of biomedical importance. This strategy shows great promise for clinical diagnoses and basic discovery with high sensitivity, good specificity, simple procedures and short analysis time. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,884 |
There is a potential for widespread occupational exposure to jet fuel among military and civilian personnel. Urinary metabolites of naphthalene have been suggested for use as short-term biomarkers of exposure to jet fuel (jet propulsion fuel 8 (JP8)). In this study, urinary biomarkers of JP8 were evaluated among US Air Force personnel. Personnel (n=24) were divided a priori into high, moderate, and low exposure groups. Pre- and post-shift urine samples were collected from each worker over three workdays and analyzed for metabolites of naphthalene (1- and 2-naphthol). Questionnaires and breathing-zone naphthalene samples were collected from each worker during the same workdays. Linear mixed-effects models were used to evaluate the exposure data. Post-shift levels of 1- and 2-naphthol varied significantly by a priori exposure group (levels in high group>moderate group>low group), and breathing-zone naphthalene was a significant predictor of post-shift levels of 1- and 2-naphthol, indicating that for every unit increase in breathing-zone naphthalene, there was an increase in naphthol levels. These results indicate that post-shift levels of urinary 1- and 2-naphthol reflect JP8 exposure during the work-shift and may be useful surrogates of JP8 exposure. Among the high exposed workers, significant job-related predictors of post-shift levels of 1- and 2-naphthol included entering the fuel tank, repairing leaks, direct skin contact with JP8, and not wearing gloves during the work-shift. The job-related predictors of 1- and 2-naphthol emphasize the importance of reducing inhalation and dermal exposure through the use of personal protective equipment while working in an environment with JP8. | OBJECTIVE ::: To evaluate the association between inhalation exposure to jet propulsion fuel 8 (JP-8) and urinary metabolites among US Air Force (USAF) personnel, and investigate the role of glutathione S-transferase polymorphisms. ::: ::: ::: METHODS ::: Personal air samples were collected from 37 full-time USAF personnel during 4 consecutive workdays and analyzed for JP-8 constituents and total hydrocarbons. Pre- and postshift urine samples were collected each day and analyzed for polycyclic aromatic hydrocarbon urinary metabolites. ::: ::: ::: RESULTS ::: Work shift exposure to total hydrocarbons was significantly associated with postshift urinary 1-naphthol (β = 0.17; P = <0.0001), 2-naphthol (β = 0.09; P = 0.005), and 2-hydroxyfluorene concentrations (β = 0.08; P = 0.006), and a significant gene-environment interaction was observed with glutathione S-transferase mu-1. ::: ::: ::: CONCLUSIONS ::: USAF personnel experience inhalation exposure to JP-8, which is associated with absorption of JP-8 constituents while performing typical job-related tasks, and in our data the glutathione S-transferase mu-1 polymorphism was associated with differential metabolism of naphthalene. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,885 |
1. Changes in protein fluorescence have been utilized in determining the stoicheiometry and dissociation constants of the complexes of diphtheria toxin with NADH2, NAD, NADPH2 and NADP. 2. The binding stoicheiometry is 2moles of NADH2 and 1mole of NADPH2/mole of diphtheria toxin. The binding sites for NADH2 appear to be equivalent and independent. 3. The toxin shows a higher affinity for the reduced than for the oxidized forms of the nucleotides. 4. Dissociation constants at 0·01I, pH7 and 25° are 0·7×10−6m for NADH2 and 0·45×10−6m for NADPH2. Dissociation constants increase with increasing ionic strength, indicating that the binding is mainly electrostatic. 5. Bound NADH2 and NADPH2 may be activated to fluoresce by the transfer of energy from the excited aromatic amino acids of the toxin. Activation and emission spectra of bound and free nucleotides are compared. 6. Since NAD and NADH2 are cofactors specifically required for the inhibition of protein synthesis by diphtheria toxin, the possible role of toxin–nucleotide complexes is discussed in this regard. | The effects of diphtheria toxin on cell-free protein synthesis in a bacterial system, and preparations obtained from animals that were sensitive and resistant to toxin were examined. In the presence of nicotinamide adenine dinucleotide (NAD), toxin inhibited the incorporation of amino acids by endogenous and synthetic polynucleotides in both rat liver and guinea pig liver cell-free systems that were exposed to 6 Lf units per ml of toxin. A cell-free system derived from Streptococcus faecalis was resistant to high concentrations of toxin. Dialyzed toxin-antitoxin floccules that are formed in the presence of NAD and the 105,000 x g supernatant fluid from rat liver contain NAD. Such floccules are also active in protein synthesis in the absence of added transferase I or II. An operational model presents the view that the intoxication complex is formed at the ribosomal level and occurs in two steps. First, the toxin molecule binds to transferase II and alters its stereospecific relationship to transferase I, but it does not result in an inactive complex. Second, the stereospecific alteration in transferase I, but it does not result in an inactive complex. Second, the stereospecific alteration in transferase II caused by the binding of diphtheria toxin allows NAD to bridge between transferase I and II, which then results in an inactivated complex. The sensitivity of the cell-free system derived from the normally resistant rat implies that in some cells the cell membrane serves as a permeability barrier to the toxin molecule. The resistance of bacterial cell-free protein synthesizing systems to diphtheria toxin may reflect basic differences between transferase enzymes from bacterial and mammalian sources. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,886 |
Blood-brain barrier (BBB) has long been known to impede the delivery of therapeutic and diagnostic agents into the central nervous system. Although ultrasound with microbubbles has been shown to disrupt the BBB, we presently examine another ultrasound-induced mechanism for opening of the BBB: ultrasound induction of spreading depression. In this process, local physical changes induced by the ultrasound pressure field, increase regional [K+]o concentration to the point of depolarization, thus initiating an oscillation process known as auto-waves or Leao spreading depression that propagates through the nerve tissue causing reversible depression of spontaneous neuronal activity. Cortical spreading depression (CSD) was induced in the brain of 18 rats by focused ultrasound (FUS) exposure (frequency: 4.89 MHz) through both the skull window (n=13) and the intact skull (n=5). CSD was also induced by application of 4 muL of 2%KCl to the cortex (n=10). Electrical activity of the cerebral cortex (ECoG) was recorded by using implanted electrodes. Occurrence of the CSD was verified through the depression of the ECoG high-frequency activity in a gamma band (>20 Hz). Five to seven CSD's were initiated in each animal at the first day (electrode implantation) and induced repeatedly 1-7 days later. The CSD induced by both FUS and KCl was associated with BBB disruption detected by a leakage of trypan blue IV injected 18-20 hours after the last induced CSD. This result suggests that the FUS-induced spreading depression can be used for non-invasive BBB disruption in targeted locations. This disruption may be useful for targeted drug delivery in the brain. | Antibody-based anticancer agents are promising chemotherapeutic agents. Among these agents, Herceptin (trastuzumab), a humanized anti-human epidermal growth factor receptor 2 (HER2/c-erbB2) monoclonal antibody, has been used successfully in patients with breast cancer. However, in patients with brain metastasis, the blood–brain barrier limits its use, and a different delivery method is needed to treat these patients. Here, we report that Herceptin can be delivered locally and noninvasively into the mouse central nervous system through the blood–brain barrier under image guidance by using an MRI-guided focused ultrasound blood–brain barrier disruption technique. The amount of Herceptin delivered to the target tissue was correlated with the extent of the MRI-monitored barrier opening, making it possible to estimate indirectly the amount of Herceptin delivered. Histological changes attributable to this procedure were minimal. This method may represent a powerful technique for the delivery of macromolecular agents such as antibodies to treat patients with diseases of the central nervous system. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,887 |
Microinjection of cholinergic and adenosinergic agonists into the medial pontine reticular formation of rats produces long lasting increases in the time spent in rapid eye movement sleep. Several G-protein-coupled muscarinic and adenosinergic receptors share a common action of inhibition of adenylyl cyclase and inhibition of cyclic adenosine monophosphate. Inhibition of cyclic adenosine monophosphate has been implicated in the mechanism of rapid eye movement sleep induction in the cat. We sought to determine whether a direct inhibitor of adenylyl cyclase microinjected into the rat reticular formation at sites where muscarinic and adenosinergic agonists are effective in producing long lasting elevations in rapid eye movement sleep also result in similar effects on the sleep/wake cycle. The caudal, oral pontine reticular formation was unilaterally infused with 60 nl volumes of carbachol (0.1-1.1mM) and N(6)-cyclohexyladenosine (0.1mM) each within 1h of lights on. Sites effective for significantly elevating rapid eye movement sleep for the 8h following microinjection of both receptor agonists were additionally injected with the adenylyl cyclase inhibitor, SQ22,536 (0.1M). Pontine injections of SQ22,536 resulted in significant mean increases in rapid eye movement sleep time and rapid eye movement sleep period frequency at all of these sites. As with the receptor agonists, SQ22,536 did not alter latency to rapid eye movement sleep onset. Rapid eye movement sleep amounts were observed to be significantly elevated by SQ22,536 at two days, but not at four days, following a single microinjection. These data implicate inhibition of cyclic adenosine monophosphate in the pons of the rat as a mechanism involved in the long-term modulation of rapid eye movement sleep. This mechanism may underlie the homeostatic regulation exhibited by this sleep-state. | In the last century much progress has been made in unraveling the mechanisms underlying sleep, shifting the paradigm of thought from sleep being a passive “off” state to one that is actively promoted by a complex neural network. The primarily wake-active monoaminergic and cholinergic systems are balanced by the sleep-promoting systems through a pair of flip-flop switches used to regulate the transitions between wake and sleep, as well as between non rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. Multiple systems external to the main switches serve to moderate sleep wake behavior: hypocretin and melanin concentrating hormone (MCH) in the lateral hypothalamic area; environmental circadian signals transduced through the suprachiasmatic nucleus (SCN); and a homeostatic drive, promoting sleep through somnogen accumulation. Despite gains in understanding of the neurocircuitry of sleep, many of the functions of sleep are just beginning to be elucidated. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,888 |
Monoclonal antibodies (mAb) reactive against complement components involved in the classical activation pathway were applied in an indirect immunoperoxidase technique for the histological study of normal and diseased human renal tissues. Prominent staining with antibodies against the C4d fragment was seen in all glomeruli and some renal arteriolar walls. The C4d staining was mesangial with light microscopy, whereas the subendothelial site of the glomerular basement membrane (GBM) also appeared to be positive in immunoelectron microscopy. In similar localization, albeit with distinctly weaker intensity, IgM and C4 binding protein (C4bp) were detected. In kidney biopsies from patients with various types of glomerulonephritis, C4d reactive antibodies stained the glomerular structures in a strong, diffuse or granular pattern in contrast to the more segmental distribution and weaker staining intensity in normal kidney specimens. Increased amounts of C4d, occasionally also of C4b, were paralleled in diseased kidney tissues by distinct deposits of IgM and/or IgG in the presence of C4bp. This study suggests that the C4d fragment in normal human glomeruli is indicative of a continuous, local complement activation via the classical pathway induced by the physiological deposition of IgM-containing immune complexes. | Treatment of the third component of human complement (C3) with methylamine results in a loss of hemolytic function and the appearance of a thiol group. Studies with [14C]methylamine have indicatd a stoichiometric and covalent reaction with the native protein. Hydrazine-inactivated C3 and C3b prepared with bovine trypsin were unreactive with [14C]-methylamine. Alkylation experiments with [1-14C]iodoacetamide have further established a 1:1 correspondence between methylamine incorporation and expression of the reactive thiol. Autoradiographic analyses of [14C]methylamine-treated C3 and methylamine-inactivated [1-14C]carboxyamidomethylated C3 after NaDodSO4/polyacrylamide gel electrophoresis have shown a specific incorporation of each radiolabel into the alpha polypeptide chain. [14C]Methylamine-treated C3 was immobilized on Sepharose 4B by reaction of the protein thiol with a mixed disulfide. Digestion with bovine trypsin in 4 M urea released 96% of the bound absorbance (at 280 nm) units; the radiolabel remained associated with the Sepharose beads. Peptide material labeled with 14C was eluted with dithiothreitol, carboxymethylated with [3H]iodoacetic acid, and chromatographed on Sephadex G-75. On Edman degradation S-[3H]carboxymethylcysteine was released at step 9 and gamma-glutamyl[14C]-methylamide was released at step 12. We interpret these data to indicate the presence of an internal thiolester bond in native C3. In addition, evidence is presented for an identical reactive site in alpha 2-macroglobulin. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,889 |
OBJECTIVE ::: The present study demonstrated the antifungal potential of the chemically characterized essential oil (EO) of Laurus nobilis L. (bay laurel) against Candida spp. biofilm adhesion and formation, and further established its mode of action on C. albicans. ::: ::: ::: METHODS ::: L. nobilis EO was obtained and tested for its minimum inhibitory and fungicidal concentrations (MIC/MFC) against Candida spp., as well as for interaction with cell wall biosynthesis and membrane ionic permeability. Then we evaluated its effects on the adhesion, formation, and reduction of 48hC. albicans biofilms. The EO phytochemical profile was determined by gas chromatography coupled to mass spectrometry (GC/MS). ::: ::: ::: RESULTS ::: The MIC and MFC values of the EO ranged from (250 to 500) μg/mL. The MIC values increased in the presence of sorbitol (osmotic protector) and ergosterol, which indicates that the EO may affect cell wall biosynthesis and membrane ionic permeability, respectively. At 2 MIC the EO disrupted initial adhesion of C. albicans biofilms (p<0.05) and affected biofilm formation with no difference compared to nystatin (p>0.05). When applied for 1min, every 8h, for 24h and 48h, the EO reduced the amount of C. albicans mature biofilm with no difference in relation to nystatin (p>0.05). The phytochemical analysis identified isoeugenol as the major compound (53.49%) in the sample. ::: ::: ::: CONCLUSIONS ::: L. nobilis EO has antifungal activity probably due to monoterpenes and sesquiterpenes in its composition. This EO may affect cell wall biosynthesis and membrane permeability, and showed deleterious effects against C. albicans biofilms. | Candida albicans is the most common fungal pathogen causing serious diseases, while there are only a paucity of antifungal drugs. Therefore, the present study was performed to investigate the antifungal effects of saponin extract from rhizomes of Dioscorea panthaica Prain et Burk (Huangshanyao Saponin extract, HSE) against C. albicans. HSE inhibits the planktonic growth and biofilm formation and development of C. albicans. 16–64 μg/mL of HSE could inhibit adhesion to polystyrene surfaces, transition from yeast to filamentous growth, and production of secreted phospholipase and could also induce endogenous reactive oxygen species (ROS) production and disrupt cell membrane in planktonic cells. Inhibitory activities against extracellular exopolysaccharide (EPS) production and ROS production in preformed biofilms could be inhibited by 64–256 μg/mL of HSE. Cytotoxicity against human Chang’s liver cells is low, with a half maximal inhibitory concentration (IC50) of about 256 μg/mL. In sum, our study suggested that HSE might be used as a potential antifungal therapeutic against C. albicans. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,890 |
Lipid hydroperoxides are formed in vivo through free radical pathways from the action of reactive oxygen species on polyunsaturated fatty acids. They are also formed as specific products of lipoxygenases and cyclooxygenases. Homolytic decomposition of lipid hydroperoxides to the α,β-unsaturated aldehyde genotoxins, 4-oxo-2-nonenal, 4,5-epoxy-2( E )-decenal, and 4-hydroxy-2-nonenal occurs through two quite distinct pathways. One pathway involves a complex rearrangement of the alkoxy radical derived from the lipid hydroperoxide and the other pathway involves the intermediate formation of another potential genotoxin, 4-hydroperoxy-2-nonenal. 4,5-Epoxy-2( E )-decenal forms the unsubstituted etheno-2-deoxyadenosine adduct with DNA, a mutagenic lesion which has been observed in human tissue DNA samples. Several new ethano- and etheno-DNA-adducts have been identified from the reaction of 4-oxo-2-nonenal with DNA. 4-Hydroxy-2-nonenal forms propano adducts with 2′-deoxyguanosine. It can also up-regulate cyclooxygenase-2 expression. As cyclooxygenase-2 converts linoleic acid into lipid hydroperoxides, this provides a potential mechanism for increased production of genotoxic bifunctional electrophiles. Malondialdehyde (β-hydroxy-acrolein), another genotoxic bifunctional electrophile, is formed during homolytic decomposition of lipid hydroperoxides that contain more than two double bonds. Other sources of malondialdehyde include, hydroxyl radical-mediated decomposition of the 2′-deoxyribose DNA backbone and formation as a side-product during the biosynthesis of thromboxane A 2 . Malondialdehyde reacts with DNA to form primarily a propano adduct with 2′-deoxyguanosine (M 1 G-dR). Significant advances in the characterization and analysis of lipid hydroperoxide-derived endogenous DNA-adducts have been made over the last decade so that dosimetry studies of human populations are now possible. Such studies will help elucidate the role of lipid hydroperoxide-derived endogenous DNA as mediators of cancer, cardiovascular disease, and neurodegeneration, the three most prevalent diseases of aging. | Ulmus davidiana Nakai (UDN) has been used for a long time to cure inflammation in oriental medicine. To evaluate the cytoprotective effects of the UDN glycoprotein, we measured cytotoxicity, the level of intracellular reactive oxygen species (ROS), activity of nuclear factor-kappaB (NF-kappaB), nitric oxide (NO) production, and thiobarbituric acid-reactive substances (TBARS) formation in 12-O-tetradecanoylphorbol 13-acetate (TPA)-treated BNL CL.2 cells. In TPA-treated BNL CL.2 cells, the results showed that UDN glycoprotein has dose-dependent blocking activities against TPA-induced cytotoxicity and NF-kappaB activation. In cytotoxic-related events, UDN glycoprotein (200 microg/ml) has an inhibitory effect on intracellular ROS production, NO production, and TBARS formation, without any toxic effects in the BNL CL.2 cells. These results suggest that UDN glycoprotein has cytoprotective abilities against TPA-induced oxidative cell injury. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,891 |
Previous studies in the biotin-deficient rat have shown that brain biotin concentrations and the activity of biotin-dependent carboxylases are relatively preserved in the face of biotin starvation and systemic biotin deficiency. These data suggested the existence of a concentration mechanism for biotin in brain, and the present studies were undertaken to further characterize brain biotin transport. We presently show that rat cerebrospinal fluid biotin concentrations are 2.5 times higher than serum concentrations, consistent with the existence of a concentrative mechanism for biotin. Further, we demonstrate uptake of 3H-biotin into rat brain from blood at physiologic biotin concentrations, using single pass clearance measurements of a brain uptake index. The calculated brain uptake indices for biotin, and the inhibition kinetics, are consistent with the possible existence of a low affinity mediated uptake mechanism. The results have implications for the pathophysiology of human biotin-responsive multiple carboxylase deficiency. | Many studies have been written on vitamin supplementation, fatty acid, and dementia, but results are still under debate, and no definite conclusion has yet been drawn. Nevertheless, a significant amount of lab evidence confirms that vitamins of the B group are tightly related to gene control for endothelium protection, act as antioxidants, play a co-enzymatic role in the most critical biochemical reactions inside the brain, and cooperate with many other elements, such as choline, for the synthesis of polyunsaturated phosphatidylcholine, through S-adenosyl-methionine (SAM) methyl donation. B-vitamins have anti-inflammatory properties and act in protective roles against neurodegenerative mechanisms, for example, through modulation of the glutamate currents and a reduction of the calcium currents. In addition, they also have extraordinary antioxidant properties. However, laboratory data are far from clinical practice. Many studies have tried to apply these results in everyday clinical activity, but results have been discouraging and far from a possible resolution of the associated mysteries, like those represented by Alzheimer’s disease (AD) or small vessel disease dementia. Above all, two significant problems emerge from the research: No consensus exists on general diagnostic criteria—MCI or AD? Which diagnostic criteria should be applied for small vessel disease-related dementia? In addition, no general schema exists for determining a possible correct time of implementation to have effective results. Here we present an up-to-date review of the literature on such topics, shedding some light on the possible interaction of vitamins and phosphatidylcholine, and their role in brain metabolism and catabolism. Further studies should take into account all of these questions, with well-designed and world-homogeneous trials. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,892 |
Erratum to: Characterization of a citrate-negative mutant of Leuconostoc mesenteroides subsp. mesenteroides: metabolic and plasmidic properties | Comparison of the parental strain of the Leuconostoc mesenteroides subsp. mesenteroides (19D) and its citrate-negative mutant, which has lost a 22-kb plasmid, has confirmed the energetic role of citrate. Fermentation balance analysis showed that citrate led to a change in heterolactic fermentation from glucose. High levels of enzyme activity in both mutant and parental strains were found for NADH oxidase, lactate dehydrogenase, acetate kinase, alcohol dehydrogenase, diacetyl reductase and acetoin reductase, although NADH oxidase, alcohol dehydrogenase, diacetyl reductase and acetoin reductase were partly repressed by citrate. All these enzymes studied were not plasmid linked. In the parental strain, citrate lyase was induced by citrate. No citrate lyase activity was found in the citrate-negative mutant grown in presence of citrate, but this does not provide evidence that citrate lyase is linked to the 22-kb plasmid. | Neurokinin A, neurokinin B and substance P caused concentration-related contractions of rabbit isolated aorta with pD2 values of 8.1, 6.9, and 6.0, respectively. [D-Pro2, D-Trp7, 9]-substance P, a competitive tachykinin antagonist, had pA2 values of 5.3 against neurokinin A, 5.1 against neurokinin B and 5.2 against substance P indicating that tachykinin receptors mediated responses to the agonists. [pGlu5,MePhe8,-MeGly9]-substance P 5 - 11 (DiMe-C7), senktide and septide did not contract the aorta. It is concluded that of the known tachykinin receptors smooth muscle of the rabbit isolated aorta contains only the NK-2 type. | eng_Latn | 22,893 |
OBJECTIVE ::: To determine the role of rhinoscopic evaluation and repeated serologic testing in assessing the success rate of intranasally administered clotrimazole for treatment of dogs with nasal aspergillosis. ::: ::: ::: DESIGN ::: Prospective case series. ::: ::: ::: ANIMALS ::: 23 dogs with nasal aspergillosis. ::: ::: ::: PROCEDURES ::: Dogs with nasal aspergillosis were treated with an intranasal infusion of 1% clotrimazole solution. Response to treatment was assessed with repeated rhinoscopic evaluation, with histologic examination and fungal culture when available. Results of repeated serologic testing for aspergillosis were monitored throughout the treatment course. ::: ::: ::: RESULTS ::: 11 of the 23 (48%) dogs had no rhinoscopic evidence of disease after the first treatment. Three of 7 dogs were free of disease after the second treatment, and 1 of 3 dogs was free after the third treatment. Presence or absence of nasal discharge and results of repeated serologic testing were not consistent with disease status. Overall, the efficacy of intranasally administered clotrimazole for treatment of nasal aspergillosis could be confirmed in 15 of 17 dogs. Delayed recurrence or reinfection was confirmed in 3 of 15 dogs. When recurrences were taken into account, the success rate was 67% (12/15 dogs). ::: ::: ::: CONCLUSIONS AND CLINICAL RELEVANCE ::: Clinical signs were not predictive of disease state, and follow-up rhinoscopy is recommended to assess response to treatment. The success rate of intranasally administered clotrimazole was similar to rates in previous reports; however, the number of dogs with recurrent disease was relatively high. Monitoring of the results of serologic testing is not recommended for use in determining response to treatment. | OBJECTIVES ::: To determine the safety and efficacy of posaconazole and terbinafine for the treatment of naturally occurring sino-nasal aspergillosis in dogs refractory to conventional topical and systemic treatment. ::: ::: ::: MATERIALS AND METHODS ::: Ten client-owned dogs with sino-nasal aspergillosis and not responsive to conventional treatments were prospectively enrolled to receive a dose of 5 mg/kg posaconazole orally every 12 hours for six months. All dogs were concurrently treated with doses of 30 mg/kg terbinafine orally every 12 hours and 5 mg/kg doxycycline orally every 12 hours for 6 to 18 months. ::: ::: ::: RESULTS ::: All 10 enrolled dogs completed the study. The treatment response was defined as complete clinical remission (n=7) or partial clinical remission (n=3). Two dogs relapsed after cessation of combination therapy. All dogs lived more than one year after starting combination therapy and eight dogs are alive at the time of writing. No clinically relevant adverse reactions or increases in hepatic enzyme activity occurred during the combination therapy. ::: ::: ::: CLINICAL SIGNIFICANCE ::: The results of this study suggest that this combination therapy appears safe and well-tolerated for the treatment of refractory sino-nasal aspergillosis in dogs. Long-term survival is possible with prolonged treatment, but relapse is possible. Larger prospective studies are warranted to further evaluate these preliminary findings. | We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero. | eng_Latn | 22,894 |
Nasal Immunity, Rhinitis, and Rhinosinusitis | Chapter 9 Infectious diseases of the ear, nose, throat, and bronchus | Allergic Rhinitis: Natural History. A Twenty Years Follow up Study | eng_Latn | 22,895 |
Sinus irrigation is the traditional treatment for chronic maxillary sinusitis. Functional endoscopic sinus surgery (FESS) restores aeration and allows secretions to be removed from an infected sinus. This study compares the efficacy of sinus irrigation with that of sinus irrigation followed by FESS in 89 patients. We measured the effects by way of sinus radiographs, nasendoscopic findings, and patient complaints. When we analyzed the data in terms of intent to treat, we found significantly favorable results for sinus irrigation followed by FESS at the end point, though only for loss of smell and purulent rhinitis. Treatment consisting of sinus irrigation alone prevented surgery in 58% of all patients for 1 year. Both treatment methods were combined with a 10-day course of loracarbef, which might have contributed to the outcome. We conclude that a good option for treatment of chronic maxillary sinusitis seems to be sinus irrigation in combination with a broad-spectrum antibiotic followed by FESS. | Our endoscopic endonasal surgery, under the guidance of rigid endoscopes, aims at the primary focuses in the anterior ethmoid, clearing stenotic clefts and infected ethmoidal cells of diseased mucosa. The maxillary ostium is enlarged into the anterior nasal fontanelle to provide drainage and ventilation. There is no need for any fenestration into the inferior nasal meatus. Once the ethmoidal focus is cleared, the dependent larger sinuses usually heal without having been touched--even if their mucosal pathologies seemed almost irreversible. The endoscopic procedure, which except in children is carried out under local and surface anesthesia, is described in detail. Excellent results with this method, developed by Messerklinger, indicate that there is seldom need for a Caldwell-Luc operation as the state-of-the-art procedure in chronic recurring sinusitis. | Berzelius failed to make use of Faraday's electrochemical laws in his laborious determination of equivalent weights. | eng_Latn | 22,896 |
Niridazole in dracontiasis: A controlled study | Abstract A double-blind trial with niridazole has conclusively shown the value of the drug in the treatment of dracontiasis. The therapeutic efficacy was evident from the rapidity with which healing occurred in more than 90% of the patients in the niridazole group. Although minor side effects were seen in a large number of patients, the acceptability of the drug was fairly high. | Objective To discuss the key point of diagnosis and treatment of non=invasive fungal naso sinusitis with naso-endoscopy.Methods The clinical materials of 47 cases of such patient were analyzed retrospectively.Results There were 45 cases cured after 6 months to 5 year follow-up according to Haikou standard.There was a relapsed in short time who was changed dressing with endoscopy.And a case was re-operated one and half year after first time.Conclusion The micro-invasive operation could remove the fungus tissue in sinus and reconstruct ventilation.The local use of corticosteroid could change the sinus environment so that to prevent the relapse. | eng_Latn | 22,897 |
HLA frequencies in less common arthropathies. | There was no increased incidence of HLA-B27 in patients suffering from rubella arthropathy, when compared to both the Westminster controls and a group of patients with arthritis secondary to dysentery who nearly all possessed this allele. | Treatment for chronic inflammatory conditions in children should take into account the specific pathophysiological and clinical processes underlying these disorders. These guidelines provide a framework for both the medical and surgical treatment of chronic inflammatory diseases such as otitis media, allergic rhinitis and chronic rhinosinusitis, chronic inflammation of tonsils and adenoids, and laryngitis. In addition, the role of vaccinations and immunomodulatory therapies is discussed. Whenever possible, the evidence levels for specific treatments comply with the Oxford Levels of Evidence. | eng_Latn | 22,898 |
Clinical Observation on Non-invasive Fungal Naso Sinusitis Treated with Naso-endoscopy | Objective To discuss the key point of diagnosis and treatment of non=invasive fungal naso sinusitis with naso-endoscopy.Methods The clinical materials of 47 cases of such patient were analyzed retrospectively.Results There were 45 cases cured after 6 months to 5 year follow-up according to Haikou standard.There was a relapsed in short time who was changed dressing with endoscopy.And a case was re-operated one and half year after first time.Conclusion The micro-invasive operation could remove the fungus tissue in sinus and reconstruct ventilation.The local use of corticosteroid could change the sinus environment so that to prevent the relapse. | In order to adapt requirements of pathogenic micro-organisms in sea foods safety testing,this article describes the detection methods and techniques of pathogenic microorganisms in sea foods,including traditional media,enzyme-linked immunology,molecular biology techniques.at the same time,Sum up detection techniques microbiological safety of food applications. | eng_Latn | 22,899 |
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