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2,333,700 |
Effect of dexmedetomidine on sevoflurane requirements and emergence agitation in children undergoing ambulatory surgery.
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Dexmedetomidine, a potent selective α2-adrenergic agonist, produces sedation and analgesia. This study was conducted to assess the effect of dexmedetomidine infusion on sevoflurane requirements, recovery profiles, and emergence agitation in children undergoing ambulatory surgery.</AbstractText>Forty children undergoing ambulatory hernioplasty or orchiopexy were randomized into two groups. The dexmedetomidine group (Group D, n=20) received dexmedetomidine 1 μg/kg, followed by 0.1 μg/kg/h until the end of surgery, whereas the saline group (Group S, n=20) received volume-matched normal saline. Sevoflurane was used for induction and maintenance of anesthesia and caudal block was performed in all children. End-tidal sevoflurane concentration (ET-sevo), the incidence of emergence agitation, pain scores, and sedation scores were recorded. Hemodynamic changes and other adverse effects were assessed in the perioperative period.</AbstractText>ET-sevo of Group D was significantly reduced in 23.8-67% compared to Group S during surgery. The incidence of emergence agitation was lower in Group D than in Group S (5% vs. 55%, p=0.001). Postoperative pain was comparable, and discharge time was not different between the groups. Mean arterial pressure and heart rate were significantly lower in Group D during surgery.</AbstractText>Intraoperative infusion of dexmedetomidine reduced sevoflurane requirements and decreased emergence agitation without delaying discharge in children undergoing ambulatory surgery. However, caution should be taken in regard to bradycardia and hypotension.</AbstractText>
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2,333,701 |
Ginkgo biloba extract reducing myocardium cells apoptosis by regulating apoptotic related proteins expression in myocardium tissues.
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The Bax, cyt-c and caspase-3 proteins play an important role in regulating the myocardial apoptosis. Although very little is known about the specific signal pathways modulated by Ginkgo biloba extract (GBE), it seems advisable to suppose that GBE-induced antiapoptotic effect might be attributed to the regulation of the expression of these proteins. Our aim was to investigate whether GBE could attenuate ischemia/reperfusion-induced apoptosis in cardiac myocytes and its potential mechanisms. In the myocardium ischemia reperfusion (IR) rat model, treatment of GBE (400 mg/kg) significantly decreased the cardiomyocyte cell apoptosis and myocardium infarction. Immunohistochemical analysis showed that GBE significantly inhibited I/R-induced increase of myocardial Bax, caspase-3, and cyt-c proteins expression. Western blot analysis confirmed results of immunohistochemical analysis. It is most likely that multiple pathways are involved in IR-induced apoptosis in rat myocardium cells. Therefore, these results demonstrate that GBE exhibits significant protective effect against myocardial I/R injury in rat heart, which is related to down-regulate Bax, cyt-c and caspase-3. Bcl-2 overexpression might prevent IR-induced apoptosis by inhibiting cytochrome c release from the mitochondria and block activation of caspase-3.
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2,333,702 |
Myocardial necrosis depth prediction during extracellular photosensitization reaction of talaporfin sodium by defined index using fluorescence measurement.
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An application of photodynamic therapy for myocardial ablation, which would induce myocardial electrical conduction block, is proposed. For the proposed application, an extracellular photosensitization reaction (PR) is performed while photosensitizer is distributed in myocardial interstitial space by employing a short drug-light interval. Because the myocardial necrosis depth must be accurately controlled to prevent surrounding tissue injury during the myocardial ablation procedure, the necrosis depth during PR needs to be predicted. The purpose of this study is to investigate the availability of predicting PR-induced myocardial necrosis depth (d(nec)) using a defined fluorescence-fall amount (FA), which is the calculated result of fluorescence intensity decrease from the start of the PR multiplied by irradiation duration and corresponds to photosensitizer consumption amount under an assumption that the photosensitizer consumption rate is faster than the photosensitizer supply rate. The correlation between FA and d nec was experimentally investigated in vivo using an open-chested canine heart model with 2.5 and 5.0 mg/kg of talaporfin sodium at an irradiance of 5-20 W/cm(2) for 5-20 s. The fluorescence measurement was performed at a wavelength of 710 nm during the PR to derive FA. One week after the PR, a uniform necrosis depth was measured histopathologically as d(mnec). A logarithmic correlation between d(mnec) and FA was confirmed with R(2) = 0.69-0.80 and a d(mnec) range of 0.2-7.1 mm. The defined FA might be useful for predicting d nec for the extracellular PR in myocardium when using talaporfin sodium.
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2,333,703 |
Dexmedetomidine added to ropivacaine extends the duration of interscalene brachial plexus blocks for elective shoulder surgery when compared with ropivacaine alone: a single-center, prospective, triple-blind, randomized controlled trial.
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Research suggests that the addition of dexmedetomidine to local anesthetics can prolong peripheral nerve blocks; however, clinical safety data are limited, and interscalene blocks have not been studied. The present study was designed to test the hypothesis that dexmedetomidine added to ropivacaine would safely enhance the duration of analgesia without adverse effects when compared with ropivacaine alone.</AbstractText>We conducted a single-center, prospective, randomized, triple-blind, controlled trial of 62 patients undergoing elective shoulder surgery under general anesthesia with an interscalene block. Patients underwent ultrasound-guided interscalene blocks using either 12 mL of 0.5% ropivacaine or 0.5% ropivacaine plus 150-µg dexmedetomidine. The primary outcomes were self-reported duration of the nerve block and safety assessment (adverse effects and neurological sequelae). Data were analyzed in a blinded fashion.</AbstractText>The median duration of the nerve block was 18 hours (95% confidence interval, 18-20) in the dexmedetomidine group and 14 hours (95% confidence interval, 14-16) in the ropivacaine group (P = 0.0001). Dexmedetomidine also lowered pain scores for the first 14 hours postoperatively and significantly hastened the time to sensory (P = 0.04) and motor (P = 0.002) block onset. Dexmedetomidine lowered heart rate but blood pressures were stable. Plasma levels of ropivacaine were not different between groups, and plasma dexmedetomidine levels were relatively low. There were no adverse events or neurological sequelae.</AbstractText>Dexmedetomidine added to ropivacaine for interscalene blocks increased the duration of the nerve block and improved postoperative pain. These additional efficacy and safety data should encourage further study of peripheral perineural dexmedetomidine in humans.</AbstractText>
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2,333,704 |
[Neonatal lupus: a fetal-maternal immunisation model?].
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Neonatal lupus is due to passive fetal transfer of maternal anti-SSA/Ro and anti-SSB/La antibodies. The clinical spectrum includes transient skin lesions, hematologic and hepatic disorders, and neurological manifestations. Congenital heart block (CHB) is the main complication, occurring in the absence of severe cardiac malformation. The presence of anti-SSA/Ro antibodies is necessary but not sufficient to provoke CHB. The prevalence of CHB in newborns of anti-SSA/Ro-positive women ranges from 1% to 2%, and the estimated risk of recurrence is 10% to 17%. Mothers of newborns with CHB may be asymptomatic or have systemic lupus erythematosus or Sjogren's syndrome. The first pathophysiological step is the translocation of intracellular SSA/Ro-SSB/La antigens to the surface of apoptotic cardiomyocytes, where they can be bound by anti-SSA/Ro antibodies. These antibody-coated apoptotic cardiocytes are then phagocytosed by macrophages, that in turn secrete proinflammatory cytokines such as TNF and TGFbeta. This inflammatory cascade results in major alterations of the fibroblast phenotype, ultimately leading to fibrosis of the conducting system. While non-cardiac lesions are transient, CHB is permanent and is associated with significant morbidity (a pacemaker must be implanted in two-thirds of cases) and mortality (estimated at 16-19%).
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2,333,705 |
Two-ventricle repair for complex congenital heart defects palliated towards single-ventricle repair.
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Complex congenital heart defects that present earlier in life are sometimes channelled towards single-ventricle repair, because of anatomical or logistic challenges involved in two-ventricle correction. Given the long-term functional and survival advantage, we have been consciously exploring the feasibility of a biventricular repair in these patients when they present later for Fontan completion.</AbstractText>Since June 2009, 71 patients were referred for staged completion of the Fontan procedure. Following detailed evaluation that included three-dimensional echocardiography and magnetic resonance imaging, 10 patients (Group 1-median age 6 years) were identified and later underwent complex biventricular repair with takedown of Glenn shunt, while completion of extracardiac Fontan repair was done in 61 patients (Group 2-median age 7 years).</AbstractText>Two-ventricle repair was accomplished in all the 10 Group 1 patients. One patient developed complete heart block requiring permanent pacemaker insertion. Late patch dehiscence occurred in another (awaiting repair). At a median follow-up of 15 months, there was no mortality among the Group 1 patients and all except for 1 patient were symptom free. There were 2 early deaths (3.3%) in the Group 2 patients.</AbstractText>Two-ventricular repair, although surgically challenging, should be considered in all patients with two functional ventricles who come for Fontan completion. Comprehensive preoperative imaging and meticulous planning helps in identifying suitable candidates.</AbstractText>
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2,333,706 |
Impact of anaesthetic drugs and adjuvants on ECG markers of torsadogenicity.
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Drug-induced prolongation of cardiac repolarization may trigger malignant ventricular arrhythmias, such as torsade de pointes. The duration of QT interval, QT corrected for heart rate (QTc), JT interval, QT dispersion (QTd), QT variability index, and transmular dispersion of repolarization (TDR) are ECG markers of torsadogenicity. All volatiles, especially isoflurane and desflurane, have been found to prolong QTc and QTcd, while sevoflurane has probably no effects on TDR. Among i.v. anaesthetics, propofol seems superior due to its minimal effects on QTc and TDR; moreover, a decrease in QTc and QTcd has been demonstrated in many studies. Regarding opioids, fentanyl, alfentanil, and remifentanil produce no effects on QTc, while sufentanil, at high doses, may induce QT prolongation. Succinylcholine, but not the non-depolarizing neuromuscular blockers, produces QTc prolongation which can be attenuated by opioids and β-blockers. Reversal of neuromuscular block with anticholinesterase-anticholinergic combinations has been associated with significant QTc prolongation, while such an effect has not been demonstrated for sugammadex, even at high doses. Local anaesthetics have probably no intrinsic action on duration of repolarization; nevertheless, an extensive subarachnoid sympathetic block may increase the duration of QTc. On the contrary, thoracic epidural anaesthesia has been associated with a decrease in both QTc and TDR. Among adjuvants, midazolam seems to have no effect on QTc and TDR, while commonly used antiemetics, such as droperidol, domperidone, and most 5-HT3 antagonists, produce significant QT prolongation. The effects of anaesthetic drugs and techniques on electrocardiographic torsadogenic markers should be considered in the perioperative management of patients with preexisting repolarization abnormalities.
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2,333,707 |
Spinal anesthesia with hyperbaric bupivacaine: a comparison of hypertensive and normotensive patients.
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Hypotension is the most common problem with spinal anesthesia. This prospective study aimed to compare normotensive and hypertensive patients with respect to the hemodynamic effects of spinal anesthesia performed with hyperbaric bupivacaine.</AbstractText>Sixty patients who were scheduled to undergo various elective operations under spinal anesthesia were included into the study. The patients were separated into 2 groups: hypertensive patients constituted Group H (n=30) and normotensive patients constituted Group N (n=30). After fluid loading, spinal anesthesia was performed with 3.5 ml 0.5% hyperbaric bupivacaine. Demographic characteristics and incidence of hypotension and bradycardia were compared. Systolic (SBP), diastolic (DBP), and mean blood pressures (MBP) and heart rate (HR) were also compared before and after spinal anesthesia.</AbstractText>There was no significant difference between the groups with respect to demographic characteristics, maximal height of sensory block, incidences of hypotension and bradycardia, and the amount of fluids infused (p>0.05). In the hypertensive patient group, the SBP, DBP, and MBP values were significantly higher than in the normotensive patient group at all measurement times (p<0.05). Comparison within the groups did not reveal any significant differences in either group compared to the basal values (p>0.05). There were no significant differences in HR between or within groups (p>0.05).</AbstractText>There was no significant difference between normotensive and hypertensive patients in the incidences of hypotension caused by spinal anesthesia with 0.5% hyperbaric bupivacaine.</AbstractText>
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2,333,708 |
Oxyntomodulin increases intrinsic heart rate through the glucagon receptor.
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Two hormones from the gastrointestinal tract, glucagon and oxyntomodulin (OXM), vigorously elevate the intrinsic heart rate (IHR) of mice. We have previously shown that OXM influences murine heart rate (HR) independent of the glucagon-like peptide 1 (GLP-1) receptor. Here, we demonstrate using radiotelemetry in mice deficient in the glucagon receptor (Gcgr -/-) that both OXM and glucagon require the glucagon receptor for their chronotropic effects on the heart. Furthermore, we found that other hormones associated with hunger and satiety (ghrelin, leptin, and PYY3-36) had no effect on IHR, while cholecystokinin moderately elevated the IHR. Finally, the resting HR of Gcgr -/- mice was higher than in control mice (Gcgr +/+ and Gcgr +/-) at thermal neutral temperature (30°C). Using atropine, we demonstrated that Gcgr -/- mice have diminished parasympathetic (PNS) influence of the heart at this temperature. Gcgr -/- mice displayed a normal bradycardia as compared to controls in response to administration of either methacholine (to activate the muscarinic acetylcholine receptor) or methoxamine (to activate the baroreflex through agonism of the α1 adrenergic receptor agonist) suggesting that vagal pathways are intact in the Gcgr -/- mice. As OXM is an agonist of the GLP-1 receptor and Gcgr with antidiabetic activity, we suggest OXM may be an alternative to glucagon in the treatment of overdose of beta-blockers to elevate HR in clinical conditions.
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2,333,709 |
Hypoxia-induced epigenetic modifications are associated with cardiac tissue fibrosis and the development of a myofibroblast-like phenotype.
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Ischemia caused by coronary artery disease and myocardial infarction leads to aberrant ventricular remodeling and cardiac fibrosis. This occurs partly through accumulation of gene expression changes in resident fibroblasts, resulting in an overactive fibrotic phenotype. Long-term adaptation to a hypoxic insult is likely to require significant modification of chromatin structure in order to maintain the fibrotic phenotype. Epigenetic changes may play an important role in modulating hypoxia-induced fibrosis within the heart. Therefore, the aim of the study was to investigate the potential pro-fibrotic impact of hypoxia on cardiac fibroblasts and determine whether alterations in DNA methylation could play a role in this process. This study found that within human cardiac tissue, the degree of hypoxia was associated with increased expression of collagen 1 and alpha-smooth muscle actin (ASMA). In addition, human cardiac fibroblast cells exposed to prolonged 1% hypoxia resulted in a pro-fibrotic state. These hypoxia-induced pro-fibrotic changes were associated with global DNA hypermethylation and increased expression of the DNA methyltransferase (DNMT) enzymes DNMT1 and DNMT3B. Expression of these methylating enzymes was shown to be regulated by hypoxia-inducible factor (HIF)-1α. Using siRNA to block DNMT3B expression significantly reduced collagen 1 and ASMA expression. In addition, application of the DNMT inhibitor 5-aza-2'-deoxycytidine suppressed the pro-fibrotic effects of TGFβ. Epigenetic modifications and changes in the epigenetic machinery identified in cardiac fibroblasts during prolonged hypoxia may contribute to the pro-fibrotic nature of the ischemic milieu. Targeting up-regulated expression of DNMTs in ischemic heart disease may prove to be a valuable therapeutic approach.
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2,333,710 |
Neonatal lupus erythematosis: a five-year case review.
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Neonatal lupus erythematosus is an infrequent disease seen in newborns. It is caused by transplacental maternal autoantibody passage. Cutaneous involvement and congenital heart block (CHB) are the most common affections, although it may involve multiple organs like the liver, lungs, blood, nervous or digestive systems. This article present a review of the four cases diagnosed in the past five years in a Neonatal Unit, which shows the different clinical spectrum which can develop around this disease (CHB, multisystemic affection and two cutaneous cases), different autoantibodies (specially anti-SSA) with an early negativization during the first year of life and the possibility of future collagen vascular disease as occurred in one case.
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2,333,711 |
Compound loss of muscleblind-like function in myotonic dystrophy.
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Myotonic dystrophy (DM) is a multi-systemic disease that impacts cardiac and skeletal muscle as well as the central nervous system (CNS). DM is unusual because it is an RNA-mediated disorder due to the expression of toxic microsatellite expansion RNAs that alter the activities of RNA processing factors, including the muscleblind-like (MBNL) proteins. While these mutant RNAs inhibit MBNL1 splicing activity in heart and skeletal muscles, Mbnl1 knockout mice fail to recapitulate the full-range of DM symptoms in these tissues. Here, we generate mouse Mbnl compound knockouts to test the hypothesis that Mbnl2 functionally compensates for Mbnl1 loss. Although Mbnl1(-/-) ; Mbnl2(-/-) double knockouts (DKOs) are embryonic lethal, Mbnl1(-/-) ; Mbnl2(+/-) mice are viable but develop cardinal features of DM muscle disease including reduced lifespan, heart conduction block, severe myotonia and progressive skeletal muscle weakness. Mbnl2 protein levels are elevated in Mbnl1(-/-) knockouts where Mbnl2 targets Mbnl1-regulated exons. These findings support the hypothesis that compound loss of MBNL function is a critical event in DM pathogenesis and provide novel mouse models to investigate additional pathways disrupted in this RNA-mediated disease.
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2,333,712 |
Estimating the decline in excess risk of cerebrovascular disease following quitting smoking--a systematic review based on the negative exponential model.
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We attempted to quantify the decline in stroke risk following quitting using the negative exponential model, with methodology previously employed for IHD. We identified 22 blocks of RRs (from 13 studies) comparing current smokers, former smokers (by time quit) and never smokers. Corresponding pseudo-numbers of cases and controls/at risk formed the data for model-fitting. We tried to estimate the half-life (H, time since quit when the excess risk becomes half that for a continuing smoker) for each block. The method failed to converge or produced very variable estimates of H in nine blocks with a current smoker RR <1.40. Rejecting these, and combining blocks by amount smoked in one study where problems arose in model-fitting, the final analyses used 11 blocks. Goodness-of-fit was adequate for each block, the combined estimate of H being 4.78(95%CI 2.17-10.50) years. However, considerable heterogeneity existed, unexplained by any factor studied, with the random-effects estimate 3.08(1.32-7.16). Sensitivity analyses allowing for reverse causation or differing assumed times for the final quitting period gave similar results. The estimates of H are similar for stroke and IHD, and the individual estimates similarly heterogeneous. Fitting the model is harder for stroke, due to its weaker association with smoking.
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2,333,713 |
Chitosan oligosaccharides block LPS-induced O-GlcNAcylation of NF-κB and endothelial inflammatory response.
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It is known that chitosan oligosaccharides (COS) suppress LPS-induced vascular endothelial inflammatory response by mechanism involving NF-κB blockade. It remains unknown how COS inhibit NF-κB. We provided evidence both in cultured endothelial cells and mouse model supporting a new mechanism. Regardless of the endothelial cell types, the LPS-induced NF-κB-dependent inflammatory gene expression was suppressed by COS, which was associated with reduced NF-κB nucleus translocation. LPS enhanced O-GlcNAc modification of NF-κB/p65 and activated NF-κB pathway, which could be prevented either by siRNA knockdown of O-GlcNAc transferase (OGT) or pretreatment with COS. Inhibition of either mitogen-activated protein kinase or superoxide generation abolishes LPS-induced NF-κB O-GlcNAcylation. Consistently, aortic tissues from LPS-treated mice presented enhanced NF-κB/p65 O-GlcNAcylation in association with upregulated gene expression of inflammatory cytokines in vascular tissues; however, pre-administration of COS prevented these responses. In conclusion, COS decreased OGT-dependent O-GlcNAcylation of NF-κB and thereby attenuated LPS-induced vascular endothelial inflammatory response.
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2,333,714 |
Continuous bilateral TAP block in patient with prior abdominal surgery.
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We present as an option for epidural analgesia and intravenous opioid infusion a clinical case of transversus abdominis plane (TAP) block, with bilateral placement of catheter for postoperative analgesia after exploratory laparotomy performed in a patient with previous abdominal surgery and heart, kidney and liver failure.
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2,333,715 |
The influence of interscalene block technique on adverse hemodynamic events.
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A hemodynamic event such as hypertension after interscalene block (ISB) is a complication that is often overlooked. The irregular spread of local anesthetic would cause a blockade of carotid sinus baroreceptors leading to the adverse event. The purpose of the present study is to compare ultrasound and neurostimulation technique in preventing hypertension after ISB.</AbstractText>Thirty patients without hypertension history who underwent arthroscopic shoulder surgery for a rotator cuff tear were enrolled. After preoperative administration of the State Trait Anxiety Inventory questionnaire, patients were allocated to receive ultrasound-guided ISB with 20 ml levobupivacaine-HCl 0.5 % (group US) and 40 ml levobupivacaine-HCl 0.5 % with neurostimulation (group NS). The need for antihypertensive drug was recorded. Block onset sensory and motor times were assessed. Systolic and diastolic blood pressures, and heart rate and pulse oximetry (SpO2), were evaluated before the block as well as 2, 5, 10, 15, 20, and 30 min after.</AbstractText>No differences in patient characteristics and anxiety were found in the two groups. Block onset times were similar. At 15 min after block placement, group NS showed significantly higher systolic and diastolic blood pressures compared to group US. No differences in heart rate and SpO2 were found between the two groups. Three patients of group NS required urapidil administration because of hypertension.</AbstractText>Ultrasound-guided ISB permits the use of a low volume of local anesthetic and seems to reduce the incidence of hypertension.</AbstractText>
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2,333,716 |
Review: the enigmatic role of endoglin in the placenta.
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The cellular expression, structure and function of endoglin, and its implication in several vascular disorders remain enigmatic, even 30 years after its discovery. Endoglin (CD105) is a homodimeric glycoprotein (180 kDa) constitutively expressed in the vascular endothelium. It is essential for cardiovascular development and mutations in the ENG gene lead to Hereditary Hemorrhagic Telangiectasia, a disorder characterized by arteriovenous malformations. Endoglin is also expressed in the syncytiotrophoblast throughout pregnancy, but transiently upregulated in the extravillous trophoblast of anchoring villi. Endoglin modulates responses to several TGF-β superfamily ligands and is essential for the negative regulation by TGF-β isoforms 1 and 3 of extravillous trophoblast differentiation. Membrane endoglin binds endothelial NO synthase and regulates its activation and vasomotor tone. There is also a circulating soluble form of endoglin (sEng; 65 kDa); its levels in the serum of women with preeclampsia are increased and correlated with disease severity. The exact sequence of sEng is still unresolved and the proposed mechanism of release from the syncytium by metalloproteases would not yield the expected size protein. The nature of the ligand sequestered by sEng is also an enigma. sEng is said to block the effects of TGF-β on NO-mediated vasorelaxation. However, sEng alone cannot scavenge these ligands for which it has very low affinity. sEng binds with high affinity to BMP9, which stimulates secretion from endothelial cells of the vascoconstrictor endothelin-1, also implicated in endothelial cell stabilization. It remains to be determined if scavenging of circulating BMP9 by sEng is important in preeclampsia and regulation of hypertension.
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2,333,717 |
Variant at 9p21 rs1333049 is associated with age of onset of coronary artery disease in a Western Indian population: a case control association study.
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The 9p21 chromosomal region has been associated with coronary artery disease (CAD) in many genome wide association studies (GWAS). To date no information exists regarding the rs1333039 SNP which showed the strongest association in the WTCCC GWAS with CAD risk in the Indian population. The present study attempts to replicate the findings in the Indian population. Genotyping for rs1333049 was done in 229 cases and 151 controls by allele-specific real-time assay. A higher frequency of the risk allele rs1333049C was seen in cases (0·60) as compared with controls (0·49), which associated with CAD risk both in univariate (OR = 1·564, 95%CI = 1·154-2·119, P = 0·003) and multivariate analysis (OR = 2·460, 95%CI = 1·139-5·314, P = 0·022). Increased frequency of the risk allele was seen in younger individuals with CAD where 40% individuals in the age group 30-55 years had the CC genotype as compared with 29 and 24·5% in the age group 56-65 years and > 65 years, respectively (CC versus GG, P = 0·045). Higher incidence of the CC genotype was seen in MI patients, but missed significance when compared with controls (OR = 1·361, 95%CI = 0·954-1·942, P = 0·084). In conclusion, the rs1333049 variant is significantly associated with CAD risk and also with age of onset in the Western Indian population. However there are differences in the haplotype structure of this SNP with the neighbouring rs10757278 SNP, these differences emphasize the importance of genotyping all risk variants at this locus which could underlie the differences in risk susceptibility to CAD across populations.
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2,333,718 |
Motion-compensated compressed sensing for dynamic contrast-enhanced MRI using regional spatiotemporal sparsity and region tracking: block low-rank sparsity with motion-guidance (BLOSM).
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Dynamic contrast-enhanced MRI of the heart is well-suited for acceleration with compressed sensing (CS) due to its spatiotemporal sparsity; however, respiratory motion can degrade sparsity and lead to image artifacts. We sought to develop a motion-compensated CS method for this application.</AbstractText>A new method, Block LOw-rank Sparsity with Motion-guidance (BLOSM), was developed to accelerate first-pass cardiac MRI, even in the presence of respiratory motion. This method divides the images into regions, tracks the regions through time, and applies matrix low-rank sparsity to the tracked regions. BLOSM was evaluated using computer simulations and first-pass cardiac datasets from human subjects. Using rate-4 undersampling, BLOSM was compared with other CS methods such as k-t SLR that uses matrix low-rank sparsity applied to the whole image dataset, with and without motion tracking, and to k-t FOCUSS with motion estimation and compensation that uses spatial and temporal-frequency sparsity.</AbstractText>BLOSM was qualitatively shown to reduce respiratory artifact compared with other methods. Quantitatively, using root mean squared error and the structural similarity index, BLOSM was superior to other methods.</AbstractText>BLOSM, which exploits regional low-rank structure and uses region tracking for motion compensation, provides improved image quality for CS-accelerated first-pass cardiac MRI.</AbstractText>Copyright © 2013 Wiley Periodicals, Inc.</CopyrightInformation>
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2,333,719 |
Managing lupus patients during pregnancy.
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Systemic lupus erythematosus (SLE) is an auto-immune disease, primarily affecting young females. Pregnancy in a woman with SLE remains a high-risk situation with higher maternal and foetal mortality and morbidity. Although live births are achieved in majority of the pregnancies, active disease and major organ involvement can negatively affect the outcomes. A higher risk of foetal loss, pre-term birth, intra-uterine growth restriction (IUGR) and neonatal lupus syndromes (NLSs) are major foetal issues. Mothers are faced with disease flares, pre-eclampsia and other complications. Disease flares during SLE pregnancy pose the unique issue of recognition and differentiation between physiologic changes and disease state. Similarly, pre-eclampsia and lupus nephritis may lead to diagnostic confusion. Treatment choices during pregnancy are limited to a few safe drugs, further restricting the options. Refractory pregnancy loss associated with anti-phospholipid antibodies (aPLs) and complete heart block associated with anti-Ro antibodies remain unresolved issues. A multidisciplinary approach, with close monitoring, is essential for optimal outcomes.
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2,333,720 |
Spatial profiles of electrical mismatch determine vulnerability to conduction failure across a host-donor cell interface.
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Electrophysiological mismatch between host cardiomyocytes and donor cells can directly affect the electrical safety of cardiac cell therapies; however, the ability to study host-donor interactions at the microscopic scale in situ is severely limited. We systematically explored how action potential (AP) differences between cardiomyocytes and other excitable cells modulate vulnerability to conduction failure in vitro.</AbstractText>AP propagation was optically mapped at 75 μm resolution in micropatterned strands (n=152) in which host neonatal rat ventricular myocytes (AP duration=153.2±2.3 ms, conduction velocity=22.3±0.3 cm/s) seamlessly interfaced with genetically engineered excitable donor cells expressing inward rectifier potassium (Kir2.1) and cardiac sodium (Na(v)1.5) channels with either weak (conduction velocity=3.1±0.1 cm/s) or strong (conduction velocity=22.1±0.4 cm/s) electrical coupling. Selective prolongation of engineered donor cell AP duration (31.9-139.1 ms) by low-dose BaCl2 generated a wide range of host-donor repolarization time (RT) profiles with maximum gradients (∇RT(max)) of 5.5 to 257 ms/mm. During programmed stimulation of donor cells, the vulnerable time window for conduction block across the host-donor interface most strongly correlated with ∇RT(max). Compared with well-coupled donor cells, the interface composed of poorly coupled cells significantly shortened the RT profile width by 19.7% and increased ∇RT(max) and vulnerable time window by 22.2% and 19%, respectively. Flattening the RT profile by perfusion of 50 μmol/L BaCl2 eliminated coupling-induced differences in vulnerability to block.</AbstractText>Our results quantify how the degree of electrical mismatch across a cardiomyocyte-donor cell interface affects vulnerability to conduction block, with important implications for the design of safe cardiac cell and gene therapies.</AbstractText>
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2,333,721 |
Comparison of spread of subarachnoid sensory block and incidence of hypotension in early and late second trimester of pregnancy.
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Obstetric or non-obstetric surgery can be performed in pregnant women during the second trimester. We evaluated maximal sensory block level (MSBL), and other sensory block characteristics after spinal anesthesia in early and late second trimester pregnant women.</AbstractText>Forty-four pregnant women scheduled for cervical cerclage under spinal anesthesia in the early second trimester (Group E) or in the late second trimester (Group L) were enrolled in this study. Spinal anesthesia was performed at the L3/4 and 7 mg of 0.5% hyperbaric bupivacaine was injected into the subarachnoid space. Hemodynamic variables, incidence of nausea/vomiting, ephedrine dose, and sensory block were recorded every 2.5 min during the first 15 min and 20 min after the injection. The MSBL, the time at which MSBL was achieved, and the time to the two-segment regression of the sensory level were also recorded.</AbstractText>The maximum number of segments blocked was significantly greater in the Group L than in the Group E. The incidence of nausea/vomiting and hypotension, and dose of administrated ephedrine were significantly higher in the Group L than in the Group E. The mean arterial pressure during the 15 min after subarachnoid injection was significantly lower compared to the baseline value in the Group L.</AbstractText>The MSBL of spinal anesthesia with hyperbaric bupivacaine 7 mg were T9 in the early and T5 in the late second trimester groups. Pregnant women in the late second trimester exhibited increased incidence of hypotension and need for ephedrine than women in the early second trimester.</AbstractText>
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2,333,722 |
Heart rate variability as a predictor of hypotension after spinal anesthesia in hypertensive patients.
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Hypotension is a common phenomenon after spinal anesthesia in hypertensive patients. We investigated whether heart rate variability could predict the occurrence of hypotension after spinal anesthesia in hypertensive patients.</AbstractText>Forty-one patients undergoing spinal anesthesia were included. Heart rate variability was measured at five different time points such as before fluid loading (baseline), after fluid loading as well as 5 min, 15 min and 30 min after spinal anesthesia. Fluid loading was performed using 5 ml/kg of a crystalloid solution. Baseline total power and low to high frequency ratio (LF/HF) in predicting hypotension after spinal anesthesia were analyzed by calculating the area under the receiver operating characteristic curves (AUC).</AbstractText>Moderate hypotension, defined as a decrease of mean arterial pressure to below 20-30% of the baseline, occurred in 13 patients and severe hypotension, defined as a decrease of mean arterial pressure greater than 30% below the baseline, occurred in 7 patients. LF/HF ratiosand total powers did not significantly change after spinal anesthesia. AUCs of LF/HF ratio for predicting moderate hypotension was 0.685 (P = 0.074), severe hypotension was 0.579 (P = 0.560) and moderate or severe hypotension was 0.652 (P = 0.101), respectively. AUCs of total power for predicting moderate hypotension was 0.571 (P = 0.490), severe hypotension was 0.672 (P = 0.351) and moderate or severe hypotension was 0.509 (P = 0.924), respectively.</AbstractText>Heart rate variability is not a reliable predictor of hypotension after spinal block in hypertensive patients whose sympathetic activity is already depressed.</AbstractText>
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2,333,723 |
Non-uniform dispersion of the source-sink relationship alters wavefront curvature.
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The distribution of cellular source-sink relationships plays an important role in cardiac propagation. It can lead to conduction slowing and block as well as wave fractionation. It is of great interest to unravel the mechanisms underlying evolution in wavefront geometry. Our goal is to investigate the role of the source-sink relationship on wavefront geometry using computer simulations. We analyzed the role of variability in the microscopic source-sink relationship in driving changes in wavefront geometry. The electrophysiological activity of a homogeneous isotropic tissue was simulated using the ten Tusscher and Panfilov 2006 action potential model and the source-sink relationship was characterized using an improved version of the Romero et al. safety factor formulation (SFm2). Our simulations reveal that non-uniform dispersion of the cellular source-sink relationship (dispersion along the wavefront) leads to alterations in curvature. To better understand the role of the source-sink relationship in the process of wave formation, the electrophysiological activity at the initiation of excitation waves in a 1D strand was examined and the source-sink relationship was characterized using the two recently updated safety factor formulations: the SFm2 and the Boyle-Vigmond (SFVB) definitions. The electrophysiological activity at the initiation of excitation waves was intimately related to the SFm2 profiles, while the SFVB led to several counterintuitive observations. Importantly, with the SFm2 characterization, a critical source-sink relationship for initiation of excitation waves was identified, which was independent of the size of the electrode of excitation, membrane excitability, or tissue conductivity. In conclusion, our work suggests that non-uniform dispersion of the source-sink relationship alters wavefront curvature and a critical source-sink relationship profile separates wave expansion from collapse. Our study reinforces the idea that the safety factor represents a powerful tool to study the mechanisms of cardiac propagation in silico, providing a better understanding of cardiac arrhythmias and their therapy.
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2,333,724 |
New drug therapies interfering with the renin-angiotensin-aldosterone system for resistant hypertension.
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There is a persistent need for the development of new antihypertensive drugs, because the control of blood pressure is still not achievable in a significant proportion of hypertensive patients. Since the approval in 2007 of aliskiren, no other new antihypertensive based on new mechanism(s) of action have been approved. In fact, the development of promising novel drugs has been stopped for safety, efficacy or marketing reasons. Despite these difficulties, the pipeline is not dry and different new antihypertensive strategies targeting the renin-angiotensin-aldosterone pathway, are in clinical development stage. The dual angiotensin II receptor-neprilysin inhibitor LCZ696, a single molecule synthetized by cocrystallisation of valsartan and the neprilysin inhibitor prodrug AHU377 is in development for resistant hypertension and for heart failure. Daglutril is a dual neprylisin-endothelin converting enzyme inhibitor which was shown to decrease BP in patients with type 2 diabetic nephropathy. Aldosterone synthase inhibitors and the third and fourth generation non-steroidal dihydropyridine based mineralocorticoid receptors blockers are new ways to target the multiple noxious effects of aldosterone in the kidney, vessels and heart. Centrally acting aminopeptidase A inhibitors block brain angiotensin III formation, one of the main effector peptides of the brain renin angiotensin system. However, a long time will be still necessary to evaluate extensively the efficacy and safety of these new approaches. In the mean time, using appropriate and personalized daily doses of available drugs, decreasing physician inertia, improving treatment adherence, improving access to healthcare and reducing treatment costs remain major objectives to reduce the incidence of resistant hypertension.
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2,333,725 |
Mechanical strength of sutured block copolymers films for load bearing medical applications.
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The mechanical behavior of three styrenic thermoplastic block copolymer elastomers with applied surgical sutures was studied by uniaxial tensile testing. The materials exhibited oriented cylindrical microstructure. Distinct macroscopic deformation mechanisms have been observed upon stretching of samples with vertical and horizontal orientation. Deformation progressed along the axis of the suture in samples with parallel orientation (P), while it in case of normal orientation (N) the whole sample responded to the applied force. Also the analysis of the stress-strain curves showed a significant difference between samples P and N. Greater stress at break was observed for samples P, while samples N showed the capability to tolerate higher strain. The influence of morphology on the tear-out shape has been also observed. The thread made a vertical tear out in samples P while for samples N ripping off the bottom was observed.
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2,333,726 |
Astilbin protects diabetic rat heart against ischemia-reperfusion injury via blockade of HMGB1-dependent NF-κB signaling pathway.
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Astilbin, a flavonoid compound was isolated from the rhizome of Smilax china L. In this study, we investigated the anti-myocardial ischemia and reperfusion (I/R) injury effect of Astilbin on diabetic rats in vivo and elucidated the potential mechanism in vitro. The results showed that Astilbin significantly attenuated hypoxia-induced cell injury in a concentration-dependent manner. Treatment of H9c2 cells with Astilbin at 15 μM blocked nuclear factor kappaB (NF-κB) phosphorylation by blocking High-mobility group box protein 1 (HMGB1) expression. Treatment of diabetic rats with Astilbin by intravenous injection (i.v.) at a single dose of 50 mg/kg protected the rats from myocardial I/R injury as indicated by decreasing infarct volume, improving hemodynamics and reducing myocardial damage, and also lowered serum levels of pro-inflammatory factors, reduced HMGB1 and phosphorylated NF-κB expression in ischemic myocardial tissue from diabetic rats. Additionally, treatment of diabetic rats with Astilbin at dose of 50 mg/kg by i.v. for continuous 14 days attenuated cardiac remodeling in the model myocardial I/R injury. These protective effects suggested that Astilbin might be due to block of the myocardial inflammatory cascade via the HMGB1-dependent NF-κB signaling pathway.
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2,333,727 |
Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease.
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Although inhibitors of the renin-angiotensin-aldosterone system can slow the progression of diabetic kidney disease, the residual risk is high. Whether nuclear 1 factor (erythroid-derived 2)-related factor 2 activators further reduce this risk is unknown.</AbstractText>We randomly assigned 2185 patients with type 2 diabetes mellitus and stage 4 chronic kidney disease (estimated glomerular filtration rate [GFR], 15 to <30 ml per minute per 1.73 m(2) of body-surface area) to bardoxolone methyl, at a daily dose of 20 mg, or placebo. The primary composite outcome was end-stage renal disease (ESRD) or death from cardiovascular causes.</AbstractText>The sponsor and the steering committee terminated the trial on the recommendation of the independent data and safety monitoring committee; the median follow-up was 9 months. A total of 69 of 1088 patients (6%) randomly assigned to bardoxolone methyl and 69 of 1097 (6%) randomly assigned to placebo had a primary composite outcome (hazard ratio in the bardoxolone methyl group vs. the placebo group, 0.98; 95% confidence interval [CI], 0.70 to 1.37; P=0.92). In the bardoxolone methyl group, ESRD developed in 43 patients, and 27 patients died from cardiovascular causes; in the placebo group, ESRD developed in 51 patients, and 19 patients died from cardiovascular causes. A total of 96 patients in the bardoxolone methyl group were hospitalized for heart failure or died from heart failure, as compared with 55 in the placebo group (hazard ratio, 1.83; 95% CI, 1.32 to 2.55; P<0.001). Estimated GFR, blood pressure, and the urinary albumin-to-creatinine ratio increased significantly and body weight decreased significantly in the bardoxolone methyl group, as compared with the placebo group.</AbstractText>Among patients with type 2 diabetes mellitus and stage 4 chronic kidney disease, bardoxolone methyl did not reduce the risk of ESRD or death from cardiovascular causes. A higher rate of cardiovascular events with bardoxolone methyl than with placebo prompted termination of the trial. (Funded by Reata Pharmaceuticals; BEACON ClinicalTrials.gov number, NCT01351675.).</AbstractText>
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2,333,728 |
[Sick sinus syndrome possibly due to lopinavir-ritonavir: report of two cases].
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We describe herein two cases of sick sinus syndrome possibly due to lopinavir-ritonavir in HIV-infected individuals. The heart rate dropped to 30 to 40 beats per minute in both cases, but patients remained asymptomatic and recovered promptly after discontinuation of lopinavir-ritonavir. The time until onset varied; one patient developed bradyarrhythmia 9 days after the initial dose, and another 4 hours after. Since lopinavir-ritonavir is a frequently used antiretroviral agent, clinicians must be aware of this potentially lethal adverse effect.
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2,333,729 |
Estimating medically fragile population in storm surge zones: a geographic information system application.
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To develop a simple, cost-effective method for determining the size and geographic distribution of medically fragile (MF) individuals at risk from tropical storm surges for use by emergency management planners.</AbstractText>The study used Geographic Information System (GIS) spatially referenced layers based on secondary data sources from both state and federal levels.</AbstractText>The study setting included the eastern North Carolina coastal counties that would be affected by tropical storm surges.</AbstractText>The initial MF population was extrapolated from national estimates for five conditions and then applied to US Census block population. These conditions included insulin dependent diabetes, chronic obstructive pulmonary disease, congestive heart failure, end stage renal disease, and patients receiving long-term oxygen treatment.</AbstractText>The main outcome of this study was a series of local and regional maps that portrayed the geographic distribution and estimated counts of potentially at-risk MF population from a tropical storm surge scenario.</AbstractText>Maps depicting the geographic distribution and potential numbers of MF individuals are important information for planning and preparedness in emergency management and potentially engaging the public.</AbstractText>
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2,333,730 |
Corticosteroid treatment normalizes QTc prolongation and improves heart block in an elderly patient with anti-Ro-positive systemic lupus erythematosus.
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Systemic lupus erythematosus (SLE) is a multisystemic disease which potentially involves various organs including the skin, joints, kidneys, liver, hematopoetic system, and serous membranes. It is rarely seen in elderly males. The most common cardiovascular involvement type is pericarditis. Anti-Ro antibodies may be associated with neonatal lupus which causes heart blocks. Recent literature indicates that anti-Ro antibodies may be associated with various rhythm and conduction disturbances in the adulthood. The most common finding associated with anti-Ro antibodies is prolonged corrected QT (QTc) interval. Herein, we present an elderly male patient with anti-Ro-positive SLE associated with prolonged QTc interval and AV blocks that significantly improved after corticosteroid treatment.
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2,333,731 |
Prevention and treatment of postmenopausal osteoporosis.
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In the beginning, that is from the 1960's, when a link between menopause and osteoporosis was first identified; estrogen treatment was the standard for preventing bone loss, however there was no fracture data, even though it was thought to be effective. This continued until the Women's Health Initiative (WHI) study in 2001 that published data on 6 years of treatment with hormone therapy that showed an increase in heart attacks and breast cancer. Even though the risks were small, 1 per 1500 users annually, patients were worried and there was a large drop off in estrogen use. In later analyses the WHI study showed that estrogen reduced fractures and actually prevented heart attacks in the 50-60 year age group. Estrogen alone appeared to be safer to use than estrogen+the progestin medroxyprogesterone acetate and actually reduced breast cancer. At the same time other drugs were being developed for bone that belong to the bisphosphonate group and the first generation of compounds showed moderate potency on bone resorption. The second and third generation compounds were much more potent and in a series of large trials were shown to reduce fractures. For the last 15 years the treatment of osteoporosis belonged to the bisphosphonate compounds, most of which reduce fracture rates by 50 percent. With the exception of gastrointestinal irritation the drugs are well tolerated and highly effective. The sophistication of the delivery systems now allow treatment that can be given daily, weekly, monthly and annually either orally or intravenously. Bone remodeling is a dynamic process that repairs microfractures and replaces old bone with new bone. In the last 10 years there has been a remarkable understanding of bone biology so that new therapies can be specifically designed on a biological basis. The realization that RANKL was the final cytokine involved in the resorption process and that marrow cells produced a natural antagonist called Osteoprotegerin (OPG) quickly led to two lines of therapy. First OPG was used as a therapy to block RANKL was initially successful but later antibodies against OPG developed and this line of treatment had to be discontinued. The next step was to develop a monoclonal antibody against RANKL and this proved to be highly effective in blocking bone resorption. It led to development of a drug Denosumab that successfully reduces fractures and is now one of the therapeutic options for osteoporosis treatment. On the anabolic side bone biology research showed that osteocytes produces sclerostin an inhibitor of the anabolic WNT signaling pathway. Recent development of a monoclonal antibody against sclerostin has shown remarkable anabolic activity in bone showing large increases in bone density and fracture trials are now underway. The newer treatments for osteoporosis are likely to be based on our understanding of bone biology and the design of new highly specific compounds with fewer side effects. This review summarizes the diagnosis of postmenopausal osteoporosis and various available non-pharmacological and pharmacological therapies available for its management. This article is part of a Special Issue entitled 'Menopause'.
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2,333,732 |
Ultrasound-guided pudendal nerve block in cats undergoing perineal urethrostomy: a prospective, randomised, investigator-blind, placebo-controlled clinical trial.
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The objective of this study was to evaluate the clinical usefulness, in terms of analgesic efficacy and safety, of ultrasound-guided pudendal nerve block performed with bupivacaine in cats undergoing perineal urethrostomy. Eighteen client-owned male cats scheduled for perineal urethrostomy were enrolled in the study and assigned to one of two treatment groups. The pudendal nerve block was performed under general anaesthesia, as described elsewhere, with 0.3 ml/kg of either saline (group C) or 0.5% bupivacaine (group B) - the total injection volume being split equally between the two sites of injection (left and right). Intra-operatively, assessment of nociception was based on the rescue analgesics requirement, as well as on the evaluation of changes in physiological parameters in comparison with the baseline values. Postoperative pain assessment was performed using three different pain scales at recovery and then 1, 2 and 3 h after recovery. Cats in group B showed lower heart rates and required fewer analgesics during surgery than group C. Postoperatively, group B had lower pain scores and needed less rescue buprenorphine than group C. Iatrogenic block-related complications were not observed. In conclusion, the ultrasound-guided pudendal nerve block can be considered clinically useful in feline medicine as it provides reliable analgesia in cats undergoing perineal urethrostomy.
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2,333,733 |
Effect of poloxamer 407 administration on the serum lipids profile, anxiety level and protease activity in the heart and liver of mice.
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Chronic administration of the poloxamer 407 (P-407), a block copolymer, to elevate serum lipids in mice is a well-established mouse model of hyperlipidemia and atherosclerosis. We tested the hypothesis that the activity of several types of proteases in heart and liver tissue is changed in the early stages of atherosclerosis development. Additionally, we evaluated whether increased serum lipids would induce anxiety in mice, as determined by using a 'plus-maze' test. The mice were administered P-407 by intraperitoneal injection twice a week for one month. P-407 administration to mice resulted in a marked increase in total serum cholesterol, atherogenic non-HDL-cholesterol, and especially in total triglycerides, and it also increased anxiety. Morphological changes observed in P-407-treated mice included contractile type changes in cardiomyocytes and foamy macrophages in liver. A significant increase of cysteine proteases cathepsin B and cathepsin L (at 24 h) and aspartate protease cathepsin D (at both 24 h and 5 days) was determined in heart tissue following P-407 administration. However, no changes were noted in heart matrix metalloproteinase activity. The activity of cysteine and aspartate proteases was significantly increased in liver at both 24 hours and 5 days after P-407 administration. In conclusion, administration of P-407 to mice for one month resulted in increased anxiety, and more importantly, there was an increase in the activity of heart and liver proteases secondary to sustained dyslipidemia. It is suggested that heart and liver cysteine and aspartate proteases may represent potential therapeutic targets in the early stages of atherosclerosis.
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2,333,734 |
Effects of a nurse-based case management compared to usual care among aged patients with myocardial infarction: results from the randomized controlled KORINNA study.
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Transition from hospital to home is a critical period for older persons with acute myocardial infarction (AMI). Home-based secondary prevention programs led by nurses have been proposed to facilitate the patients' adjustment to AMI after discharge. The objective of this study was to evaluate the effects of a nurse-based case management for elderly patients discharged after an AMI from a tertiary care hospital.</AbstractText>In a single-centre randomized two-armed parallel group trial of patients aged 65 years and older hospitalized with an AMI between September 2008 and May 2010 in the Hospital of Augsburg, Germany, patients were randomly assigned to a case management or a control group receiving usual care. The case-management intervention consisted of a nurse-based follow-up for one year including home visits and telephone calls. Key elements of the intervention were to detect problems or risks and to give advice regarding a wide range of aspects of disease management (e.g. nutrition, medication). Primary study endpoint was time to first unplanned readmission or death. Block randomization per telephone call to a biostatistical center, where the randomization list was kept, was performed. Persons who assessed one-year outcomes and validated readmission data were blinded. Statistical analysis was based on the intention-to-treat approach and included Cox Proportional Hazards models.</AbstractText>Three hundred forty patients were allocated to receive case-management (n=168) or usual care (n=172). The analysis is based on 329 patients (intervention group: n=161; control group: n=168). Of these, 62% were men, mean age was 75.4 years, and 47.1% had at least either diabetes or chronic heart failure as a major comorbidity. The mean follow-up time for the intervention group was 273.6 days, and for the control group it was 320.6 days. During one year, in the intervention group there were 57 first unplanned readmissions and 5 deaths, while the control group had 75 first unplanned readmissions and 3 deaths. With respect to the endpoint there was no significant effect of the case management program after one year (Hazard Ratio 1.01, 95% confidence interval 0.72-1.41). This was also the case among subgroups according to sex, diabetes, living alone, and comorbidities.</AbstractText>A nurse-based management among elderly patients with AMI had no significant influence on the rate of first unplanned readmissions or death during a one-year follow-up. A possible long-term influence should be investigated by further studies.</AbstractText>ISRCTN02893746.</AbstractText>
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2,333,735 |
The effects of subarachnoid administration of hyperbaric solutions of bupivacaine or ropivacaine in xylazine-sedated calves undergoing surgery.
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The aim of this study was to compare the effects of subarachnoid administration of hyperbaric solutions of bupivacaine or ropivacaine in xylazine-sedated calves undergoing surgery. Subarachnoid anaesthesia was performed with either 20 mg of hyperbaric bupivacaine (bupivacaine group (BG), n=10) or 30 mg of hyperbaric ropivacaine (ropivacaine group (RG), n=10) into the lumbar dural space of 20 calves in a randomised, prospective clinical trial. Systolic (SBP), diastolic (DBP) and mean (MBP) blood pressure, heart rate (HR), respiratory rate, rectal temperature were recorded after sedation (time 0), and up to 120 minutes after injection. Onset, duration and magnitude of sensory block (scale 1-4) were determined using the pin-prick test throughout surgery. Data were analysed using analysis of variance and non-parametric tests (P<0.05). Bodyweight, age, duration of surgery, SBP, DBP, MBP, HR were not significantly different between groups. Onset of anaesthesia (mean±sd; BG, 5±1 minutes; RG, 7±1 minutes) and duration of anaesthesia (mean±sd; BG, 153±32 minutes; RG, 86±12 minutes) were significantly different between groups. Analgesic scores were significantly higher than baseline from 5 to 120 min, and from 7 to 85 min in BG and RG, respectively. Subarachnoid administration of hyperbaric solutions of bupivacaine produced faster onset and longer duration of anaesthesia than ropivacaine.
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2,333,736 |
Brain delivery of proteins via their fatty acid and block copolymer modifications.
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It is well known that hydrophobic small molecules penetrate cell membranes better than hydrophilic molecules. Amphiphilic molecules that dissolve both in lipid and aqueous phases are best suited for membrane transport. Transport of biomacromolecules across physiological barriers, e.g. the blood-brain barrier, is greatly complicated by the unique structure and function of such barriers. Two decades ago we adopted a simple philosophy that to increase protein delivery to the brain one needs to modify this protein with hydrophobic moieties. With this general idea we began modifying proteins (antibodies, enzymes, hormones, etc.) with either hydrophobic fatty acid residues or amphiphilic block copolymer moieties, such as poy(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (pluronics or poloxamers) and more recently, poly(2-oxasolines). This simple approach has resulted in impressive successes in CNS drug delivery. We present a retrospective overview of these works initiated in the Soviet Union in 1980s, and then continued in the United States and other countries. Notably some of the early findings were later corroborated by brain pharmacokinetic data. Industrial development of several drug candidates employing these strategies has followed. Overall modification by hydrophobic fatty acids residues or amphiphilic block copolymers represents a promising and relatively safe strategy to deliver proteins to the brain.
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2,333,737 |
A multi-endpoint in vivo larval zebrafish (Danio rerio) model for the assessment of integrated cardiovascular function.
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Despite effective in vitro preclinical strategies to identify cardiovascular (CV) liabilities, there remains a need for early functional assessment prior to complex in vivo mammalian models. The larval zebrafish (Danio rerio, Zf) has been suggested for this role: previous data suggest that cardiac electrophysiology and vascular ultrastructure are comparable with mammals, and also indicate responsiveness of individual Zf CV system endpoints to some functional modulators. Little information is, however, available regarding integrated functional CV responses to drug treatment. Consequently, we developed a novel larval Zf model capable of simultaneous quantification of chronotropic, inotropic and arrhythmic effects, alongside measures of blood flow and vessel diameter.</AbstractText>Non-invasive video analysis of the heart and dorsal aorta of anaesthetized and agarose-embedded larval ZF was used to measure multiple cardiovascular endpoints, simultaneously, following treatment with a range of functional modulators of CV physiology.</AbstractText>Changes in atrial and ventricular beat frequencies were detected in response to acute treatment with cardio-stimulants (adrenaline and theophylline), and negative chrono/inotropes (cisapride, haloperidol, terfenadine and verapamil). Arrhythmias were also observed including terfenadine-induced 2:1 atrial-ventricular (A-V) block, a previously proposed hERG surrogate measure. Significant increases in blood flow were detected in response to adrenaline and theophylline exposure; and decreases after cisapride, haloperidol, terfenadine, and verapamil treatment. Using dorsal aorta (DA) blood flow and ventricular beat rate, surrogate stoke volumes were also calculated for all compounds.</AbstractText>These data support the use of this approach for CV function studies. Moreover the throughput and compound requirements (approximately 3 compounds/person effort/week and <10 mg) make our approach potentially suitable for higher throughput drug safety and efficacy applications, pending further assessment of ZF-mammalian pharmacological comparability.</AbstractText>© 2013.</CopyrightInformation>
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2,333,738 |
Cutaneous manifestations of neonatal lupus: a case report.
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Neonatal Lupus Erythematosus (NLE) is a rare disease associated with placental transport of maternal anti-Ro/La and/or anti-U1RNP antibodies into the fetal circulation and characterized by cardiac, cutaneous, hematologic and hepatic manifestations. The most serious complication of NLE is complete heart block and cardiomyopathy. The maternal connective tissue disorder has been systemic lupus erythematosus (SLE) or Sjögren syndrome in most cases, however approximately 50% of mothers are asymptomatic at the time of diagnosis, testing positive only against Ro and/ or U1RNP auto-antibodies. We describe a case of neonatal lupus erythematosus and review the clinical and laboratory manifestations of this rare disease.
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2,333,739 |
Analgesic and motor effects of a high-volume intercoccygeal epidural injection of 0.125% or 0.0625% bupivacaine in adult cows.
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The objectives of this study were to determine the analgesic and motor effects of a high-volume intercoccygeal epidural injection of bupivacaine at 2 concentrations in cows. A prospective, randomized, blinded, crossover trial was conducted on 6 adult cows. An indwelling epidural catheter was placed in the first intercoccygeal space and advanced 10 cm cranially. All the cows received 3 treatments with a washout period of 48 h: saline (control), 0.125% bupivacaine (high dose), or 0.0625% bupivacaine (low dose), at a final volume of 0.15 mL per kilogram of body weight, infused manually into the epidural space over a period of 15 min. The anal and tail tone and motor deficits of the pelvic limbs were evaluated in 5 of the cows with use of a numerical rating scale and a visual analogue scale (VAS). Sensory block was assessed in 4 of the cows by the response to needle pricks in different regions with the use of a VAS. Measurements were obtained before and at different time points after injection, up to 360 min. Analysis of variance for repeated measures and post-hoc Tukey's and Dunnett's tests were used. Differences were considered significant when the P-value was ≤ 0.05. One cow became recumbent 6 h after injection. Anal and tail tones were significantly decreased and motor deficits of the pelvic limbs were significantly increased after bupivacaine treatment compared with control treatment. The overall mean VASpain scores ± standard deviation were 66 ± 8 after control treatment, 52 ± 5 after low-dose bupivacaine treatment, and 43 ± 5 after high-dose bupivacaine treatment. The pain scores were significantly lower in caudal regions up to the saphenous nerve after high-dose bupivacaine treatment compared with control treatment and significantly lower in the anus, vulva, and tail after low-dose bupivacaine treatment compared with control treatment. Thus, analgesia with moderate motor deficits of the pelvic limbs may be obtained with 0.125% bupivacaine administered epidurally.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Rioja</LastName><ForeName>Eva</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, Ontario.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rubio-Martínez</LastName><ForeName>Luis M</ForeName><Initials>LM</Initials></Author><Author ValidYN="Y"><LastName>Monteith</LastName><ForeName>Gabrielle</ForeName><Initials>G</Initials></Author><Author ValidYN="Y"><LastName>Kerr</LastName><ForeName>Carolyn L</ForeName><Initials>CL</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016449">Randomized Controlled Trial</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Canada</Country><MedlineTA>Can J Vet Res</MedlineTA><NlmUniqueID>8607793</NlmUniqueID><ISSNLinking>0830-9000</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000779">Anesthetics, Local</NameOfSubstance></Chemical><Chemical><RegistryNumber>Y8335394RO</RegistryNumber><NameOfSubstance UI="D002045">Bupivacaine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D015360" MajorTopicYN="N">Analgesia, Epidural</DescriptorName><QualifierName UI="Q000592" MajorTopicYN="N">standards</QualifierName><QualifierName UI="Q000662" MajorTopicYN="Y">veterinary</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000779" MajorTopicYN="N">Anesthetics, Local</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001794" MajorTopicYN="N">Blood Pressure</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002045" MajorTopicYN="N">Bupivacaine</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002417" MajorTopicYN="N">Cattle</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018592" MajorTopicYN="N">Cross-Over Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004311" MajorTopicYN="N">Double-Blind Method</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006339" MajorTopicYN="N">Heart Rate</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007268" MajorTopicYN="N">Injections, Epidural</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="N">methods</QualifierName><QualifierName UI="Q000592" MajorTopicYN="N">standards</QualifierName><QualifierName UI="Q000662" MajorTopicYN="Y">veterinary</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010147" MajorTopicYN="N">Pain Measurement</DescriptorName><QualifierName UI="Q000662" MajorTopicYN="N">veterinary</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010865" MajorTopicYN="N">Pilot Projects</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011446" MajorTopicYN="N">Prospective Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D056152" MajorTopicYN="N">Respiratory Rate</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014741" MajorTopicYN="N">Video Recording</DescriptorName></MeshHeading></MeshHeadingList><OtherAbstract Type="Publisher" Language="fre">Les objectifs de la présente étude étaient de déterminer chez la vache les effets analgésiques et moteurs d’une injection épidurale inter-coccygienne d’un volume important de bupivacaïne à deux concentrations. Une étude croisée prospective, randomisée, et à l’aveugle a été réalisée chez 6 vaches adultes. Un cathéter épidural à demeure a été placé dans le premier espace inter-coccygien et avancé cranialement de 10 cm. Toutes les vaches ont reçu 3 traitements avec une période d’évacuation de 48 h : saline (témoin), 0,125 % de bupivacaïne (dose élevée) ou 0,0625 % de bupivacaïne (faible dose), à un volume final de 0,15 mL par kilo de poids corporel, infusé manuellement dans l’espace épidural sur une période de 15 min. Le tonus anal et de la queue ainsi que les déficits moteurs des membres pelviens ont été évalués chez 5 des vaches au moyen d’une échelle numérique de pointage et une échelle analogue visuelle (VAS). Le bloc sensitif a été évalué chez 4 des vaches par la réponse à des piqûres d’aiguille dans différentes régions avec l’utilisation d’une VAS. Les mesures ont été obtenues avant et à différents temps après l’injection, jusqu’à 360 min. Une analyse de variance pour mesures répétées et les tests post-hoc de Tukey et de Dunnett ont été utilisés. Les différences étaient considérées significatives lorsque la valeur de P était ≤ 0,05. Une vache est demeurée couchée 6 h après l’injection. Le tonus anal et de la queue était réduit de manière significative et les déficits moteurs des membres pelviens étaient significativement augmentés après le traitement à la bupivacaïne comparativement au traitement témoin avec la saline. Dans l’ensemble les scores moyens ± l’écart-type de VASdouleur étaient 66 ± 8 après le traitement témoin, 52 ± 5 après le traitement à faible dose de bupivacaïne, et 43 ± 5 après le traitement avec la dose élevée de bupivacaïne. Les scores de douleur étaient significativement plus faibles dans les régions caudales jusqu’au nerf saphène après le traitement avec les doses élevées de bupivacaïne comparativement au traitement témoin et significativement plus faibles au niveau de l’anus, la vulve et la queue après le traitement avec les faibles doses de bupivacaïne comparativement au traitement témoin. Ainsi, une analgésie avec des déficits moteurs modérés des membres pelviens peut être obtenue avec de la bupivacaïne à 0,125 % administrée par voie épidurale.(Traduit par Docteur Serge Messier).
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2,333,740 |
Evolvable rough-block-based neural network and its biomedical application to hypoglycemia detection system.
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This paper focuses on the hybridization technology using rough sets concepts and neural computing for decision and classification purposes. Based on the rough set properties, the lower region and boundary region are defined to partition the input signal to a consistent (predictable) part and an inconsistent (random) part. In this way, the neural network is designed to deal only with the boundary region, which mainly consists of an inconsistent part of applied input signal causing inaccurate modeling of the data set. Owing to different characteristics of neural network (NN) applications, the same structure of conventional NN might not give the optimal solution. Based on the knowledge of application in this paper, a block-based neural network (BBNN) is selected as a suitable classifier due to its ability to evolve internal structures and adaptability in dynamic environments. This architecture will systematically incorporate the characteristics of application to the structure of hybrid rough-block-based neural network (R-BBNN). A global training algorithm, hybrid particle swarm optimization with wavelet mutation is introduced for parameter optimization of proposed R-BBNN. The performance of the proposed R-BBNN algorithm was evaluated by an application to the field of medical diagnosis using real hypoglycemia episodes in patients with Type 1 diabetes mellitus. The performance of the proposed hybrid system has been compared with some of the existing neural networks. The comparison results indicated that the proposed method has improved classification performance and results in early convergence of the network.
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2,333,741 |
The biology of PCSK9 from the endoplasmic reticulum to lysosomes: new and emerging therapeutics to control low-density lipoprotein cholesterol.
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Proprotein convertase subtilisin/kexin type 9 (PCSK9) directly binds to the epidermal growth factor-like repeat A domain of low-density lipoprotein receptor and induces its degradation, thereby controlling circulating low-density lipoprotein cholesterol (LDL-C) concentration. Heterozygous loss-of-function mutations in PCSK9 can decrease the incidence of coronary heart disease by up to 88%, owing to lifelong reduction of LDL-C. Moreover, two subjects with PCSK9 loss-of-function mutations on both alleles, resulting in a total absence of functional PCSK9, were found to have extremely low circulating LDL-C levels without other apparent abnormalities. Accordingly, PCSK9 could represent a safe and effective pharmacological target to increase clearance of LDL-C and to reduce the risk of coronary heart disease. Recent clinical trials using anti-PCSK9 monoclonal antibodies that block the PCSK9:low-density lipoprotein receptor interaction were shown to considerably reduce LDL-C levels by up to 65% when given alone and by up to 72% in patients already receiving statin therapy. In this review, we will discuss how major scientific breakthroughs in PCSK9 cell biology have led to the development of new and forthcoming LDL-C-lowering pharmacological agents.
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2,333,742 |
Ultrasound-guided rectus sheath block for pyloromyotomy in infants: a retrospective analysis of a case series.
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To analyze the applicability of US-guided rectus sheath block and to find out the efficacy of analgesia provided using this method without the need for opioids in conventional Hypertrophic pyloric stenosis (HPS) surgery in infants.</AbstractText>This study describes the provision of intra- as well as postoperative analgesia by the use of an ultrasound-guided rectus sheath block in infants undergoing conventional HPS surgery under general anesthesia.</AbstractText><AbstractText Label="METHODS/MATERIALS" NlmCategory="METHODS">The anesthetic protocols of 26 infants undergoing HPS surgery were reviewed retrospectively.</AbstractText>The weight of the infants ranged from 2.6 to 4.6 kg. The rectus sheath block was regarded as successful in all patients as there was no heart rate increase upon surgical skin incision in any of the patients. Two out of 26 (7.6%) babies needed additional intraoperative rescue analgesia and were administered fentanyl at 20 and 40 min after skin incision. Two more (a total of 4; 15.3%) babies required postoperative analgesia and were administered tramadol droplets and liquid ibuprofen at 15, 120 and 150 min postoperatively. Duration of surgery was significantly longer in those two patients who required intraoperative rescue analgesia (Wilcoxon-Mann-Whitney test: P < 0.05). These were also the only two patients who received one intra- and one postoperative dose of opioid each (7.6%).</AbstractText>US-guided rectus sheath block seems to be a simple and quick method for the provision of intra- and postoperative analgesia in infants undergoing conventional HPS surgery.</AbstractText>© 2013 John Wiley & Sons Ltd.</CopyrightInformation>
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2,333,743 |
Anxiolytic effects of vestipitant in a sub-group of healthy volunteers known to be sensitive to CO2 challenge.
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The pharmacological properties of two NK1 antagonists were studied in comparison with a benzodiazepine during a 7% CO2 challenge in a population of healthy volunteers selected for a high sensitivity to the challenge. In total, 19 healthy subjects, pre-screened for their responsiveness to the 7% CO2 test, took part in the randomised, double-blind, cross-over, incomplete block design study. After receiving treatment or placebo, the volunteers were subjected to three 7% CO2 challenges each for a time of 20 min. The treatment consisted of the administration of the following three active drugs: a single dose of benzodiazepine alprazolam (0.75 mg) and a single dose of the NK1 antagonists vestipitant (GW597599) (15 mg) and vofopitant (GR205171) (25 mg). Anxiety during the challenge was evaluated with Visual Analogue Scale-Anxiety (VAS-A) and with Panic Symptom List (PSL III-R). Respiratory parameters, heart rate and skin conductance were also recorded. Compared with placebo, vestipitant showed a significant reduction (p<0.05) in anxiety assessed on the VAS-A scale (ΔVAS-A%) while alprazolam significantly (p<0.01) attenuated the PSL III-R total score. Vofopitant did not show any anxiolytic effect. In the comparison analysis between placebo and drugs, none of the respiratory and other physiological parameters showed a statistically significant difference.
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2,333,744 |
5-HT stimulation of heart rate in Drosophila does not act through cAMP as revealed by pharmacogenetics.
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The fruit fly, Drosophila melanogaster, is a good experimental organism to study the underlying mechanism of heart rate (HR) regulation. It is already known that many neuromodulators (serotonin, dopamine, octopamine, acetylcholine) change the HR in Drosophila melanogaster larvae. In this study, we investigated the role of cAMP-PKA signaling pathway in HR regulation and 5-HT positive chronotropic action. In order to obtain insight into the 5-HT mechanism of action in larvae cardiomyocytes, genetic and pharmacological approaches were used. We used transgenic flies that expressed the hM4Di receptor [designer receptors exclusively activated by designer drugs (DREADDs)] as one tool. Our previous results showed that activation of hM4Di receptors (modified muscarinic acetylcholine receptors) decreases or arrests the heart from beating. In this study, it was hypothesized that the positive chronotropic effect of serotonin [5-hydroxytryptamine (5-HT)] are mediated by serotonin receptors coupled to the adenylyl cyclase pathway and downstream cAMP and PKA activity. Activation of hM4Di by clozapine-N-oxide (CNO) was predicted to block the effects of serotonin by inhibiting adenylyl cyclase activity through Gαi pathway activation. Interestingly, we found here that manipulation of adenylyl cyclase activity and cAMP levels had no significant effect on HR. The ability of hM4Di receptor activation to slow or stop the heart is therefore likely mediated by activation of GIRK channels to produce hyperpolarization of cardiomyocytes, and not through inhibition of adenylyl cyclase.
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2,333,745 |
Molecularly designed architectures--the metalloligand way.
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Designed materials offer noteworthy applications which are often architecture dependent. Despite knowing such a fact, one of the major challenges faced by the scientific community is to find ways to predict and, if possible, control the resultant architecture of a network. If such an exercise is fruitful, it creates enormous opportunities to synthesize exotic materials with tailor-made applications. Any network is composed of individual molecules and the transition from a single molecule to a network can be achieved through several routes taking advantage of synthetic chemistry. There exists a molecular building block at the heart of such a transition which mediates such a process from a single molecule to a network. Although a large number of building blocks have created assorted materials, utilization of a well-defined coordination complex as the building block (i.e., metalloligand) is unique for the construction of a designed architecture. A coordination complex as the building block offers structural rigidity that places the auxiliary functional groups to a pre-organized conformation. Such auxiliary functional groups could then coordinate a secondary metal ion or be involved in the self-assembly via weak interactions, such as hydrogen bonds. This review focuses on the recent progress achieved through assorted molecular building blocks towards generating ordered networks. Broadly, two classes of metalloligands will be discussed: those offering hydrogen bond sensitive functional groups and those tendering coordination bond responsive groups. Nevertheless, the result is the construction of networks of a highly-ordered nature in both cases. The present review is expected to provide new strategies for constructing functional materials through metalloligands for challenging and practical applications.
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2,333,746 |
Exxon Valdez to Deepwater Horizon: comparable toxicity of both crude oils to fish early life stages.
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The 2010 Deepwater Horizon disaster in the Gulf of Mexico was the largest oil spill in United States history. Crude oils are highly toxic to developing fish embryos, and many pelagic fish species were spawning in the northern Gulf in the months before containment of the damaged Mississippi Canyon 252 (MC252) wellhead (April-July). The largest prior U.S. spill was the 1989 grounding of the Exxon Valdez that released 11 million gallons of Alaska North Slope crude oil (ANSCO) into Prince William Sound. Numerous studies in the aftermath of the Exxon Valdez spill defined a conventional crude oil injury phenotype in fish early life stages, mediated primarily by toxicity to the developing heart. To determine whether this type of injury extends to fishes exposed to crude oil from the Deepwater Horizon - MC252 incident, we used zebrafish to compare the embryotoxicity of ANSCO alongside unweathered and weathered MC252 oil. We also developed a standardized protocol for generating dispersed oil water-accommodated fractions containing microdroplets of crude oil in the size range of those detected in subsurface plumes in the Gulf. We show here that MC252 oil and ANSCO cause similar cardiotoxicity and photo-induced toxicity in zebrafish embryos. Morphological defects and patterns of cytochrome P450 induction were largely indistinguishable and generally correlated with polycyclic aromatic compound (PAC) composition of each oil type. Analyses of embryos exposed during different developmental windows provided additional insight into mechanisms of crude oil cardiotoxicity. These findings indicate that the impacts of MC252 crude oil on fish embryos and larvae are consistent with the canonical ANSCO cardiac injury phenotype. For those marine fish species that spawned in the northern Gulf of Mexico during and after the Deepwater Horizon incident, the established literature can therefore inform the assessment of natural resource injury in the form of potential year-class losses.
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2,333,747 |
A Comparison of the Effects of Esmolol and Dexmedetomidine on the Clinical Course and Cost for Controlled Hypotensive Anaesthesia.
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To compare the effects of esmolol (β-blocker) and dexmedetomidine (α-2-agonist) on patients' clinical course and cost of application of controlled hypotension during middle-ear surgery.</AbstractText>Fifty ASA I-II patients scheduled for tympanomastoidectomy were enrolled in the study and were randomized into two groups. Bispectral Index (BIS) and neuromuscular monitoring (TOF GUARD-SX) were applied to all patients. In group E (n=25), 0.5 mg kg(-1) min(-1) esmolol was infused over 1 min before induction and titrated over a range of 10-200 μg kg(-1) min(-1); in group D (n=25), 0.5 μg kg(-1) dexmedetomidine was infused over 10 minutes before induction, and then titrated over a range of 0.2-0.7 μg kg(-1) hr(-1) to maintain mean arterial pressure (MAP) between 55 and 65 mmHg and BIS 40-50 after induction. In both groups, 0.25 μg kg(-1) min(-1) remifentanil infusion was used for anaesthesia maintenance. Maintaining end-tidal CO2 (EtCO2) at 35-40, using 1 MAC sevoflurane in 50% O2-air mixture, mechanical ventilation was started. The effects of both agents on hemodynamic conditions [(heart rate (HR), mean arterial pressure (MAP)], neuromuscular blockage [onset of action (OA), duration of clinical action (DCA), recovery index (RI)], amount of bleeding, surgeon satisfaction, and total dexmedetomidine and esmolol doses used during the intervention were recorded and costs were compared between the groups.</AbstractText>No significant difference was present in hemodynamic conditions, bleeding scores or surgeon satisfaction between groups. Although OA was similar in both groups, DCA and RI were significantly higher in group D. Cost was significantly higher with esmolol than dexmedetomidine.</AbstractText>We conclude that although both agents are feasible in inducing hypotensive anaesthesia, while neuromuscular block time prolonged by using dexmedetomidine, higher costs were observed with esmolol.</AbstractText>
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2,333,748 |
Sustained elevation of systemic oxidative stress and inflammation in exacerbation and remission of asthma.
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Oxidative stress has been implicated in the pathogenesis of asthma. We aimed at investigating the biomarkers of oxidative stress, inflammation, and tissue damage in patients with asthma in acute exacerbation and remission. We recruited 18 asthmatics admitted to hospital with acute exacerbation and 18 healthy nonsmoking controls matched for age. We evaluated plasma levels of 8-isoprostane, C-reactive protein (CRP) and total matrix metalloproteinase- (MMP-) 9 by ELISA, and MMP-9 activity by zymographic analysis. Plasma levels of 8-isoprostane and CRP were significantly elevated in acute exacerbation and decreased in remission but remained significantly higher compared to healthy controls. The activities of pro-MMP-9 were also significantly higher in acute exacerbation and decreased in remission but remained significantly higher compared to healthy controls in parallel to plasma levels of total MMP-9. These data suggest that overproduction of MMP-9 along with highly elevated levels of oxidative stress and inflammation is implicated in asthma exacerbation and that measurements of these biomarkers can be a valid index in its management.
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2,333,749 |
[Effect of stellate ganglion block on cardiomyocyte apoptosis and expression of Bcl-2/Bax protein in spontaneously hypertensive rats].
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To investigate the relationship between apoptosis of myocardial cells in spontaneously hypertensive rats (SHRs) and the expressions of Bcl-2 and Bax protein, and the protective effect of stellate ganglion block on apoptosis of myocardial cells.</AbstractText>A total of 32 ten-week-old male SHRs were assigned randomly into 4 groups: a left stellate ganglion block group (group LS), a right stellate ganglion block group (group RS), a captopril group (group D) and a control group (group C). The arterial systolic blood pressure was measured by ALC-NIBP system. After 10 weeks, all rats were anaesthetized by 3% pentobarbital sodium, cardiomyocyte apoptosis index of left ventricle was assessed by TUNEL, and the localization of myocardium Bcl-2, Bax was investigated by immunohistochemistry.</AbstractText>Compared with group LS and C, the apoptotic index decreased (P<0.05). SHR myocardial expression of Bcl-2 significantly increased (P<0.05), Bax expression significantly decreased (P<0.05) and Bcl-2/Bax was significantly higher (P<0. 05) in group RS.</AbstractText>Bcl-2 and Bax play an important role in the apoptosis of myocardial cells in SHRs. Right stellate ganglion block can reduce the apoptosis of myocardial cells and reverse the reconstruction of the left ventricle in SHRs via regulation of apoptosis-related gene proteins.</AbstractText>
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2,333,750 |
Characterization of fluoride-tolerant halophilic Bacillus flexus NM25 (HQ875778) isolated from fluoride-affected soil in Birbhum District, West Bengal, India.
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A new Gram-positive, nonpigmented, rod-shaped fluoride-tolerant bacterial strain, NM25, was isolated from waterlogged muddy field soil collected from the fluoride endemic area of Rampurhat II block (average fluoride in water, 4.7 mg/l, and in soil, 1.5 mg/kg) in Birbhum District, West Bengal, India. The study was undertaken to characterize the fluoride-tolerant bacterial isolate, to determine its role in bioaccumulation of fluoride, and to analyze the water and soil quality of the bacterial environment. The isolate was positive for catalase, lipase, urease, protease, oxidase, and H2S production, but negative for indole production, nitrate reduction, and Vogues-Proskauer test. The organisms were sensitive to recommended doses of ofloxacin, kanamycin, rifampicin, levofloxacin, vancomycin, gatifloxacin, gentamicin, doxycycline, streptomycin, and nalidixic acid but resistant to ampicillin. Based on the phenotypic characteristics, 16S rRNA gene sequence, and phylogenetic analysis, the bacterial isolate NM25 was identified as Bacillus flexus. The G+C content of the 16S rDNA was 53.14 mol%. This strain tolerated up to 20% (w/v) NaCl in nutrient agar medium and was grown at the pH range 4-12. It reduced fluoride concentration up to 67.45% and tolerated more than 1,500 ppm of fluoride in brain-heart infusion agar medium.
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2,333,751 |
Cardiac myocyte diversity and a fibroblast network in the junctional region of the zebrafish heart revealed by transmission and serial block-face scanning electron microscopy.
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The zebrafish has emerged as an important model of heart development and regeneration. While the structural characteristics of the developing and adult zebrafish ventricle have been previously studied, little attention has been paid to the nature of the interface between the compact and spongy myocardium. Here we describe how these two distinct layers are structurally and functionally integrated. We demonstrate by transmission electron microscopy that this interface is complex and composed primarily of a junctional region occupied by collagen, as well as a population of fibroblasts that form a highly complex network. We also describe a continuum of uniquely flattened transitional cardiac myocytes that form a circumferential plate upon which the radially-oriented luminal trabeculae are anchored. In addition, we have uncovered within the transitional ring a subpopulation of markedly electron dense cardiac myocytes. At discrete intervals the transitional cardiac myocytes form contact bridges across the junctional space that are stabilized through localized desmosomes and fascia adherentes junctions with adjacent compact cardiac myocytes. Finally using serial block-face scanning electron microscopy, segmentation and volume reconstruction, we confirm the three-dimensional nature of the junctional region as well as the presence of the sheet-like fibroblast network. These ultrastructural studies demonstrate the previously unrecognized complexity with which the compact and spongy layers are structurally integrated, and provide a new basis for understanding development and regeneration in the zebrafish heart.
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2,333,752 |
Effects of post-resuscitation administration with sodium hydrosulfide on cardiac recovery in hypoxia-reoxygenated newborn piglets.
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Hydrogen sulfide may protect multiple organ systems against ischemic-reperfusion injuries. It is unknown if treatment with sodium hydrosulfide (NaHS, a hydrogen sulfide donor) will improve myocardial function and minimize oxidative stress in hypoxic-reoxygenated newborn piglets. Mixed breed piglets (1-5 day, 1.5-2.5 kg) were anesthetized and acutely instrumented for the measurement of systemic, pulmonary and regional (carotid, superior mesenteric and renal) hemodynamics and blood gas parameters. The piglets were induced with normocapnic alveolar hypoxia (10-15% oxygen, 2h) followed by reoxygenation with 100% (1h) then 21% oxygen (3h). At 10 min of reoxygenation, either NaHS (10mg/kg, 5 ml) or saline (5 ml) was administered intravenously for 30 min (5 min bolus followed by 25 min of continuous infusion) in a blinded, block-randomized fashion (n = 7/group). Plasma lactate and troponin I levels and tissue markers of myocardial oxidative stress were also determined. Two hours hypoxia caused cardiogenic shock (45 ± 3% of respective normoxic baseline), reduced regional perfusion with metabolic acidosis (pH 6.94 ± 0.02). NaHS infusion significantly improved recovery of cardiac index (84 ± 3% vs. 72 ± 5% in controls), systemic oxygen delivery (84 ± 3% vs. 72 ± 5% in controls) and systemic oxygen consumption (102 ± 5% vs. 84 ± 6% in controls) at 4h of reoxygenation. NaHS had no significant effect on systemic and pulmonary blood pressures, regional blood flows, plasma lactate and troponin I levels. The myocardial glutathionine ratio was reduced in piglets treated with NaHS (vs. controls, P<0.05). Post-resuscitation administration of NaHS improves cardiac function and systemic perfusion and attenuates myocardial oxidative stress in newborn piglets following hypoxia-reoxygenation.
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2,333,753 |
Three-dimensional reconstruction of cardiac sarcoplasmic reticulum reveals a continuous network linking transverse-tubules: this organization is perturbed in heart failure.
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The organization of the transverse-tubular (t-t) system and relationship to the sarcoplasmic reticulum (SR) underpins cardiac excitation-contraction coupling. The architecture of the SR, and relationship with the t-ts, is not well characterized at the whole-cell level. Furthermore, little is known regarding changes to SR ultrastructure in heart failure.</AbstractText>The aim of this study was to unravel interspecies differences and commonalities between the relationship of SR and t-t networks within cardiac myocytes, as well as the modifications that occur in heart failure, using a novel high-resolution 3-dimensional (3D) imaging technique.</AbstractText>Using serial block face imaging coupled with scanning electron microscopy and image analysis, we have generated 3D reconstructions of whole cardiomyocytes from sheep and rat left ventricle, revealing that the SR forms a continuous network linking t-ts throughout the cell in both species. In sheep, but not rat, the SR has an intimate relationship with the sarcolemma forming junctional domains. 3D reconstructions also reveal details of the sheep t-t system. Using a model of tachypacing-induced heart failure, we show that there are populations of swollen and collapsed t-ts, patches of SR tangling, and disorder with rearrangement of the mitochondria.</AbstractText>We provide the first high-resolution 3D structure of the SR network showing that it forms a cell-wide communication pipeline facilitating Ca(2+) diffusion, buffering, and synchronicity. The distribution of the SR within the cell is related to interspecies differences in excitation-contraction coupling, and we report the first detailed analysis of SR remodeling as a result of heart failure.</AbstractText>
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2,333,754 |
Targeting gp130 to prevent inflammation and promote insulin action.
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Obesity and type 2 diabetes are now the most prevalent metabolic diseases in the Western world and the development of new strategies to treat these metabolic diseases is most warranted. Obesity results in a state of chronic low-grade inflammation in metabolically active tissues such as the liver, adipose tissue, brain and skeletal muscle. Work in our laboratory has focussed on the role of the cytokine interleukin-6 (IL)-6 and other IL-6-like cytokines that signal through the gp130 receptor complex. We have focussed on the role of blocking IL-6 trans-signalling to prevent inflammation on the one hand, and activating membrane-bound signalling to promote insulin sensitivity on the other hand. Since the cloning of the IL-6 gene nearly 30  years ago, a pattern has emerged associating IL-6 with a number of diseases associated with inflammation including rheumatoid arthritis (RA), Crohn's disease and several cancers. Accordingly, tocilizumab, an IL-6 receptor-inhibiting monoclonal antibody, is now useful for the treatment of RA. However, this may not be the most optimal strategy to block inflammation associated with IL-6 and may result in unwanted side effects that, paradoxically, could actually promote metabolic disease.
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2,333,755 |
The diuretic torasemide does not prevent aldosterone-mediated mineralocorticoid receptor activation in cardiomyocytes.
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Aldosterone binds to the mineralocorticoid receptor (MR) and exerts pleiotropic effects beyond enhancing renal sodium reabsorption. Excessive mineralocorticoid signaling is deleterious during the evolution of cardiac failure, as evidenced by the benefits provided by adding MR antagonists (MRA) to standard care in humans. In animal models of cardiovascular diseases, MRA reduce cardiac fibrosis. Interestingly diuretics such as torasemide also appear efficient to improve cardiovascular morbidity and mortality, through several mechanisms. Among them, it has been suggested that torasemide could block aldosterone binding to the MR. To evaluate whether torasemide acts as a MRA in cardiomyocytes, we compared its effects with a classic MRA such as spironolactone. We monitored ligand-induced nuclear translocation of MR-GFP and MR transactivation activity in the cardiac-like cell line H9C2 using a reporter gene assay and known endogenous aldosterone-regulated cardiac genes. Torasemide did not modify MR nuclear translocation. Aldosterone-induced MR transactivation activity was reduced by the MRA spironolactone, not by torasemide. Spironolactone blocked the induction by aldosterone of endogenous MR-responsive genes (Sgk-1, PAI-1, Orosomucoid-1, Rgs-2, Serpina-3, Tenascin-X), while torasemide was ineffective. These results show that torasemide is not an MR antagonist; its association with MRA in heart failure may however be beneficial, through actions on complementary pathways.
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2,333,756 |
ATP-sensitive potassium currents from channels formed by Kir6 and a modified cardiac mitochondrial SUR2 variant.
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Cardiac ATP-sensitive potassium channels (KATP) are found in both the sarcoplasmic reticulum (sarcKATP) and the inner membrane of mitochondria (mitoKATP). SarcKATP are composed of a pore containing subunit Kir6.2 and a regulatory sulfonylurea receptor subunit (SUR2), but the composition of mitoKATP remains unclear. An unusual intra-exonic splice variant of SUR2 (SUR2A-55) was previously identified in mitochondria of mammalian heart and brain, and by analogy with sarcKATP we proposed SUR2A-55 as a candidate regulatory subunit of mitoKATP. Although SUR2A-55 lacks the first nucleotide binding domain (NBD) and 2 transmembrane domains (TMD), it has a hybrid TMD and retains the second NBD. It resembles a hemi-ABC transporter suggesting it could multimerize to function as a regulatory subunit. A putative mitochondrial targeting signal in the N-terminal domain of SUR2A-55 was removed by truncation and when co-expressed with Kir6.1 and Kir6.2 it targeted to the plasma membrane and yielded KATP currents. Single channel conductance, mean open time, and burst open time of SUR2A-55 based KATP was similar to the full-length SUR2A based KATP. However, the SUR2A-55 KATP were 70-fold less sensitive to block by ATP, and twice as resistant to intracellular Ca (2+) inhibition compared with the SUR2A KATP, and were markedly insensitive to KATP drugs, pinacidil, diazoxide, and glybenclamide. These results suggest that the SUR2A-55 based channels would tend to be open under physiological conditions and in ischemia, and could account for cardiac and mitochondrial phenotypes protective for ischemia.
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2,333,757 |
The role of dopamine D2, but not D3 or D4, receptor subtypes, in quinpirole-induced inhibition of the cardioaccelerator sympathetic outflow in pithed rats.
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Quinpirole (a dopamine D2-like receptor agonist) inhibits the cardioaccelerator sympathetic outflow in pithed rats by sympathoinhibitory D2-like receptors. The present study was designed to identify pharmacologically the specific D2-like receptor subtypes (i.e. D2 , D3 and D4) involved in this sympathoinhibition by quinpirole.</AbstractText>One hundred fourteen male Wistar rats were pithed, artificially ventilated with room air and prepared for either preganglionic spinal (C7-T1) stimulation of the cardioaccelerator sympathetic outflow (n = 102) or i.v. bolus injections of exogenous noradrenaline (n = 12). This approach resulted in frequency-dependent and dose-dependent tachycardic responses, respectively, as previously reported by our group.</AbstractText>I.v. continuous infusions of quinpirole (0.1-10 μg kg(-1)  min(-1)), but not of saline (0.02 mL min(-1)), dose-dependently inhibited the sympathetically induced tachycardic responses. Moreover, the cardiac sympathoinhibition induced by 3 μg kg(-1)  min(-1) quinpirole (which failed to affect the tachycardic responses to i.v. noradrenaline) was: (i) unchanged after i.v. injections of the antagonists SB-277011-A (D3 ; 100-300 μg kg(-1)) or L-745,870 (D4 ; 30-100 μg kg(-1)); and (ii) markedly blocked and abolished by, respectively, 100 and 300 μg kg(-1) of the D2 preferring receptor subtype antagonist L-741,626. These doses of antagonists, which did not affect per se the sympathetically induced tachycardic responses, were high enough to completely block their respective receptors.</AbstractText>The cardiac sympathoinhibition induced by 3 μg kg(-1)  min(-1) quinpirole involves the dopamine D2 receptor subtype, with no evidence for the involvement of the D3 or D4 subtypes. This provides new evidence for understanding the modulation of the cardioaccelerator sympathetic outflow.</AbstractText>© 2013 The British Pharmacological Society.</CopyrightInformation>
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2,333,758 |
Cryo-EM structures of the actin:tropomyosin filament reveal the mechanism for the transition from C- to M-state.
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Tropomyosin (Tm) is a key factor in the molecular mechanisms that regulate the binding of myosin motors to actin filaments (F-Actins) in most eukaryotic cells. This regulation is achieved by the azimuthal repositioning of Tm along the actin (Ac):Tm:troponin (Tn) thin filament to block or expose myosin binding sites on Ac. In striated muscle, including involuntary cardiac muscle, Tm regulates muscle contraction by coupling Ca(2+) binding to Tn with myosin binding to the thin filament. In smooth muscle, the switch is the posttranslational modification of the myosin. Depending on the activation state of Tn and the binding state of myosin, Tm can occupy the blocked, closed, or open position on Ac. Using native cryogenic 3DEM (three-dimensional electron microscopy), we have directly resolved and visualized cardiac and gizzard muscle Tm on filamentous Ac in the position that corresponds to the closed state. From the 8-Å-resolution structure of the reconstituted Ac:Tm filament formed with gizzard-derived Tm, we discuss two possible mechanisms for the transition from closed to open state and describe the role Tm plays in blocking myosin tight binding in the closed-state position.
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2,333,759 |
Tracheal intubation in intellectually disabled patients: clinical usefulness of remifentanil and sevoflurane without a muscle relaxant.
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To compare two remifentanil doses (1 µg/kg and 2 µg/kg) in order to determine the preferred dose in intellectually disabled patients undergoing day care dental surgery under sevoflurane-induced general anaesthesia.</AbstractText>Patients were randomly assigned to receive either 1 µg/kg (group 1) or 2 µg/kg (group 2) remifentanil; both groups received 8% sevoflurane anaesthesia induction. All other conditions were identical in both groups. Heart rate (HR), mean arterial pressure (MAP) and intubation conditions were assessed.</AbstractText>A total of 27/30 (90.0%) patients in group 1 and 29/30 patients (96.7%) in group 2 had acceptable intubation conditions. Remifentanil administration resulted in significant reductions in HR compared with baseline levels, in both groups. There were no significant between-group differences in HR at any timepoint. MAP decreased significantly compared with baseline in group 2 only.</AbstractText>Successful tracheal intubation in intellectually disabled patients can be accomplished with a combination of 1 µg/kg or 2 µg/kg remifentanil and 8% sevoflurane anaesthesia induction, without the requirement for neuromuscular blocking drugs.</AbstractText>
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2,333,760 |
Slow delayed rectifier potassium current blockade contributes importantly to drug-induced long QT syndrome.
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Drug-induced long QT syndrome is generally ascribed to inhibition of the cardiac rapid delayed rectifier potassium current (IKr). Effects on the slow delayed rectifier potassium current (IKs) are less recognized. Triggered by a patient who carried the K422T mutation in KCNQ1 (encoding the α-subunit of the IKs channel), who presented with excessive QT prolongation and high serum levels of norfluoxetine, we investigated the effects of fluoxetine and its metabolite norfluoxetine on IKs.</AbstractText>ECG data from mutation carriers and noncarriers revealed that the K422T mutation per se had mild clinical effects. Patch clamp studies, performed on HEK293 cells, showed that heterozygously expressed K422T KCNQ1/KCNE1 channels had a positive shift in voltage dependence of activation and an increase in deactivation rate. Fluoxetine and its metabolite norfluoxetine both inhibited KCNQ1/KCNE1 current, with norfluoxetine being the most potent. Moreover, norfluoxetine increased activation and deactivation rates. Computer simulations of the effects of norfluoxetine on IKs and IKr demonstrated significant action potential prolongation, to which IKs block contributed importantly. Although the effects of the mutation per se were small, additional IKs blockade by norfluoxetine resulted in more prominent QTc prolongation in mutation carriers than in noncarriers, demonstrating synergistic effects of innate and drug-induced IKs blockade on QTc prolongation.</AbstractText>IKs blockade contributes importantly to drug-induced long QT syndrome, especially when repolarization reserve is reduced. Drug safety tests might have to include screening for IKs blockade.</AbstractText>
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2,333,761 |
Sjögren's syndrome associated with antiphospholipid syndrome and fetal myocardial echogenicity: case report.
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Sjögren's syndrome is a rare systemic autoimmune disorder associated with pregnancy (0.3-0.6%). The typical occurrence of anti-Ro/SSA and anti-La/SSB autoantibodies in the maternal serum can modify the perinatal outcome: neonatal lupus and congenital heart block are the most common fetal complications.</AbstractText>we report a case of pregnancy complicated by a secondary form of SS associated with antiphospholipid syndrome and fetal myocardial echogenicity.</AbstractText>in conclusion, increased attention must be paid to pregnancies associated with autoimmune disorders, since careful ultrasonographic and clinical monitoring and preventive treatment with corticosteroids could minimize severe and common fetal complications.</AbstractText>
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2,333,762 |
Coffee consumption and cardiovascular health: getting to the heart of the matter.
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As coffee-consumption is a widespread tradition, its possible impact on health has been of considerable interest. This review examines the effects of coffee on cardiovascular risk, outlines underlying biological mechanisms, and discusses implications for public health. In the past, coffee was often viewed as a cardiovascular risk-factor. However, in meta-analyses of recent well-controlled prospective epidemiologic studies, coffee-consumption was not associated with risk of coronary heart disease and weakly associated with a lower risk of stroke and heart failure. Also, available evidence largely suggests that coffee-consumption is not associated with a higher risk of fatal cardiovascular events. In randomized trials coffee-consumption resulted in small increases in blood pressure. Unfiltered coffee increased circulating LDL cholesterol and triglycerides concentrations, but filtered coffee had no substantial effects on blood lipids. In summary, for most healthy people, moderate coffee consumption is unlikely to adversely affect cardiovascular health. Future work should prioritize understanding the effects of coffee in at-risk populations.
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2,333,763 |
Effect of supplementation of low dose intravenous dexmedetomidine on characteristics of spinal anaesthesia with hyperbaric bupivacaine.
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Intravenous (IV) dexmedetomidine with excellent sedative properties has been shown to reduce analgesic requirements during general anaesthesia. A study was conducted to assess the effects of IV dexmedetomidine on sensory, motor, haemodynamic parameters and sedation during subarachnoid block (SAB).</AbstractText>A total of 50 patients undergoing infraumbilical and lower limb surgeries under SAB were selected. Group D received IV dexmedetomidine 0.5 mcg/kg bolus over 10 min prior to SAB, followed by an infusion of 0.5 mcg/kg/h for the duration of the surgery. Group C received similar volume of normal saline infusion. Time for the onset of sensory and motor blockade, cephalad level of analgesia and duration of analgesia were noted. Sedation scores using Ramsay Sedation Score (RSS) and haemodynamic parameters were assessed.</AbstractText>Demographic parameters, duration and type of surgery were comparable. Onset of sensory block was 66±44.14 s in Group D compared with 129.6±102.4 s in Group C. The time for two segment regression was 111.52±30.9 min in Group D and 53.6±18.22 min in Group C and duration of analgesia was 222.8±123.4 min in Group D and 138.36±21.62 min in Group C. The duration of motor blockade was prolonged in Group D compared with Group C. There was clinically and statistically significant decrease in heart rate and blood pressures in Group D. The mean intraoperative RSS was higher in Group D.</AbstractText>Administration of IV dexmedetomidine during SAB hastens the onset of sensory block and prolongs the duration of sensory and motor block with satisfactory arousable sedation.</AbstractText>
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2,333,764 |
An unusual case of anomalous origin of the right coronary artery and hepatic focal nodular hyperplasia.
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Anomalous origin of the right coronary artery (ARCA) and focal nodular hyperplasia (FNH) are frequently reported in association with congenital heart abnormalities but not with each other. We propose that both conditions may share common origins in a maladative hyperplastic response to differential vascular flow due to developmental arterial malformations or aberrant Notch signalling during simultaneous gut and cardiac vasculorigenesis.
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2,333,765 |
Anesthesia management with single injection paravertebral block for aorta coarctation in infant.
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Thoracotomy causes severe pain in the postoperative period. Perioperative thoracic paravertebral block reduces pain score and may improve outcome after pediatric cardiac surgery. This prospective study was designed for the efficacy and duration of a single level, single injection ultrasound-guided thoracic paravertebral block (TPVB) for fifteen infants undergoing aortic coarctation repair.</AbstractText>After approval of the ethical committee and the relatives of the patients, 15 infants who had undergone thoracotomy were enrolled in the study. The patients received 0.5 ml·kg(-1) a bolus 0.25% bupivacaine with epinephrine 1 : 200 000 at T5-6 level after standard general anesthesia induction. Anesthesia depth with Index of Consciousness (IOC) and tissue oxygen saturation with cerebral (rSO2-C) and somatic thoracodorsal (rSO2-S) were monitored. Intraoperative hemodynamic and postoperative hemodynamic and pain scores were evaluated for 24 h after surgery. Face, Legs, Activity, Cry, Consolability (FLACC) score was utilized to measure postoperative pain in the intensive care unit. Rescue 0.05 mg·kg(-1) IV morphine was applied to patients in whom FLACC was >3.</AbstractText>The median age of the patients was 4.5 (1-11) months, and the median intraoperative endtidal isoflurane concentration was 0.6% (0.3-0.8). The amount of remifentanil used intraoperatively was 4.5 (2.5-14) μg·kg(-) (1) ·h(-1). Intraoperative heart rate and blood pressure values significantly decreased compared with values detected at 5th, 10th, and 15th min after TPVB application, after incision prior and after cross-clamp (P < 0.01). The median time of first dose of morphine application after block was 320 (185-430) min. The median morphine consumption in 24 h was 0.16 (0.09-0.4) mg·kg(-1). The median length of postoperative intensive care unit and in-hospital stay times was 23 (1-67) h and 4 (1-10) days, respectively.</AbstractText>We believe that TPVB, as part of a balanced anesthetic and analgesic regime, provides effective pain relief in patients undergoing aortic coarctation repair.</AbstractText>© 2013 John Wiley & Sons Ltd.</CopyrightInformation>
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2,333,766 |
Addition of dexmedetomidine to ropivacaine improves cervical plexus block.
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To investigate the sensory block onset time, duration time, and side effects of adding dexmedetomidine to ropivacaine for cervical plexus block.</AbstractText>Forty American Society of Anesthesiologists (ASA) Class I or II adult patients who were scheduled to undergo thyroid surgery were randomly allocated to the following groups to receive cervical plexus block: 30 mL of 0.375% ropivacaine combined with 1 μg kg(-1) of dexmedetomidine; 30 mL of 0.375% ropivacaine combined with saline (control). The sensory block onset time, duration of analgesia, mean arterial pressure (MAP), heart rate (HR), and the incidences of side effects, such as hypotension, bradycardia, and hypoxemia were recorded.</AbstractText>The addition of dexmedetomidine to ropivacaine (Group D) shortened the sensory block onset time compared with the ropivacaine group (Group C) (95% confidence interval [CI] 4.18-5.26; p < 0.05). The duration of analgesia of cervical plexus block in Group D was significantly longer than that in Group C (95% CI 295.96-311.12; p < 0.05). The Ramsay sedation score at 5, 10, 20, 40, 60, 90, and 120 minutes after local anesthetic administration in Group D was significantly higher than that in Group C (p < 0.05). MAP level and HR level in Group D were significantly lower than that in Group C (p < 0.05).</AbstractText>The addition of 1 μg kg(-1) dexmedetomidine to ropivacaine for cervical plexus block could shorten the sensory block onset time and extend the duration of analgesia, and increased the quality of analgesia, with the patients being sedated and arousable.</AbstractText>Copyright © 2013. Published by Elsevier B.V.</CopyrightInformation>
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2,333,767 |
The role of pre-junctional D2 -like receptors mediating quinpirole-induced inhibition of the vasodepressor sensory CGRPergic out-flow in pithed rats.
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Calcitonin gene-related peptide (CGRP) released from perivascular sensory nerves plays a role in the regulation of vascular tone. Indeed, electrical stimulation of the perivascular sensory out-flow in pithed rats produces vasodepressor responses, which are mainly mediated by CGRP release. This study investigated the potential role of dopamine D1 -like and D2 -like receptors in the inhibition of these vasodepressor responses. For this purpose, male Wistar pithed rats (pre-treated i.v. with 25 mg/kg gallamine and 2 mg/kg min. hexamethonium) received i.v. continuous infusions of methoxamine (20 μg/kg min.) followed by physiological saline (0.02 ml/min.), the D1 -like receptor agonist SKF-38393 (0.1-1 μg/kg min.) or the D2 -like receptor agonist quinpirole (0.03-10 μg/kg min.). Under these conditions, electrical stimulation (0.56-5.6 Hz; 50 V and 2 ms) of the thoracic spinal cord (T9 -T12 ) resulted in frequency-dependent vasodepressor responses which were (i) unchanged during the infusions of saline or SKF-38393 and (ii) inhibited during the infusions of quinpirole (except at 0.03 μg/kg min.). Moreover, the inhibition induced by 0.1 μg/kg min. quinpirole (which failed to inhibit the vasodepressor responses elicited by i.v. bolus injections of exogenous α-CGRP; 0.1-1 μg/kg) was (i) unaltered after i.v. treatment with 1 ml/kg of either saline or 5% ascorbic acid and (ii) abolished after 300 μg/kg (i.v.) of the D2 -like receptor antagonists haloperidol or raclopride. These doses of antagonists (enough to completely block D2 -like receptors) essentially failed to modify per se the electrically induced vasodepressor responses. In conclusion, our results suggest that quinpirole-induced inhibition of the vasodepressor sensory CGRPergic out-flow is mainly mediated by pre-junctional D2 -like receptors.
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2,333,768 |
Short communication: a comparison of 2 nonsteroidal antiinflammatory drugs following the first stage of a 2-stage fistulation surgery in dry dairy cows.
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Postoperative pain and its management following fistulation surgery in cattle are poorly understood. The purpose of this study was to compare 2 nonsteroidal antiinflammatory drugs (NSAID) as potential postoperative pain management treatments following the first stage of a 2-stage fistulation surgery. A randomized complete block design trial was conducted in dry Holstein cows (n=10) following fistulation surgery. Ketoprofen (3mg/kg of body weight i.m.) was administered on the day of surgery and 24 h later, whereas meloxicam (0.5 mg/kg of body weight s.c.) was administered once only on the day of surgery. Outcomes evaluated at 0, 2, 9, 24, 26, and 33 h postsurgery were heart rate, respiration rate, rectal temperature, and infrared temperature around the surgical site. Outcomes evaluated on the day of surgery and d 1 following surgery and compared with the average for the 4d before surgery were lying activity (total lying time, total time spent lying on the left side, and percentage of time lying on the left side) and feed intake. A difference was observed in dry matter intake on d 1 but this effect was not different on d 0 compared with presurgical averages. A difference was observed in time spent lying on the left side and a difference was observed in heart rate following the first stage of fistulation surgery compared with presurgical averages. The infrared temperature readings around the surgical site were significantly greater in the hours following surgery compared with presurgical averages. The respiration rate increased over time after 24h postsurgery compared with presurgical values. Although it was clear that the surgery is painful, the drug effects were more difficult to explain. On d 0 and 1, the meloxicam-treated cows ate 3 kg more but spent 101 min/d less time lying on their left side compared with ketoprofen-treated cows. The first stage of a 2-stage fistulation surgery was considered painful based on changes in heart rate, respiration rate, infrared temperature readings, dry matter intake, and time spent lying on the left side. It is clear that left flank surgery is painful and that NSAID can improve outcomes associated with that pain, but we cannot make recommendations as to which NSAID to choose based on these results.
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2,333,769 |
Involvement of the FoxO3a pathway in the ischemia/reperfusion injury of cardiac microvascular endothelial cells.
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FoxO3a, a member of the forkhead transcription factors, has been demonstrated to be involved in myocardial ischemia/reperfusion (I/R) injury. Cardiac microvascular endothelial cells (CMECs) are some of the predominant cells damaged immediately after myocardial I/R injury. Despite the importance of injured CMECs in an ischemic heart, little is known about the involvement of FoxO3a in regulating CMECs injury. Thus, we used rat CMECs following simulated I/R to examine FoxO3a activation and signaling in relation to survival, the cell cycle and apoptosis in CMECs. We found that Akt negatively regulates activation of the FoxO3a pathway by phosphorylating FoxO3a in CMECs as demonstrated with an Akt inhibitor and activator. Upon I/R injury, the FoxO3a pathway was significantly activated in CMECs, which was accompanied by Akt deactivation. In parallel, the I/R of CMECs induced G1-phase arrest through p27(Kip1) up-regulation and significant activation of caspase-3. Accordingly, inhibition of the FoxO3a pathway by IGF-1, an Akt activator, could significantly block the I/R-enhanced activation of p27(Kip1) and caspase-3 in CMECs. Collectively, our results indicate that the FoxO3a pathway is involved in the I/R injury of CMECs at least in part through the regulation of cell cycle arrest and apoptosis, suggesting that the FoxO3a pathway may be a novel therapeutic target that protects against microvascular endothelial damage in ischemic hearts.
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2,333,770 |
Linagliptin for patients aged 70 years or older with type 2 diabetes inadequately controlled with common antidiabetes treatments: a randomised, double-blind, placebo-controlled trial.
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A substantial proportion of patients with type 2 diabetes are elderly (≥65 years) but this group has been largely excluded from clinical studies of glucose-lowering drugs. We aimed to assess the effectiveness of linagliptin, a dipeptidyl peptidase-4 inhibitor, in elderly patients with type 2 diabetes.</AbstractText>In this randomised, double-blind, parallel-group, multinational phase 3 study, patients aged 70 years or older with type 2 diabetes, glycated haemoglobin A1c (HbA1c) of 7·0% or more, receiving metformin, sulfonylureas, or basal insulin, or combinations of these drugs, were randomised (by computer-generated randomisation sequence, concealed with a voice-response system, stratified by HbA1c level [<8·5% vs ≥8·5%] and insulin use [yes vs no], block size four) in a 2:1 ratio to once-daily oral treatment with linagliptin 5 mg or matching placebo for 24 weeks. Investigators and participants were masked to assignment throughout the study. The primary endpoint was change in HbA1c from baseline to week 24. This trial is registered with ClinicalTrials.gov, number NCT01084005.</AbstractText>241 community-living outpatients were randomised (162 linagliptin, 79 placebo). Mean age was 74·9 years (SD 4·3). Mean HbA1c was 7·8% (SD 0·8). At week 24, placebo-adjusted mean change in HbA1c with linagliptin was -0·64% (95% CI -0·81 to -0·48, p<0·0001). Overall safety and tolerability were much the same between the linagliptin and placebo groups; 75·9% of patients in both groups had an adverse event (linagliptin n=123, placebo n=60). No deaths occurred. Serious adverse events occurred in 8·6% (14) of patients in the linagliptin group and 6·3% (five) patients in the placebo group; none were deemed related to study drug. Hypoglycaemia was the most common adverse event in both groups, but did not differ between groups (24·1% [39] in the linagliptin group, 16·5% [13] in the placebo group; odds ratio 1·58, 95% CI 0·78-3·78, p=0·2083).</AbstractText>In elderly patients with type 2 diabetes linagliptin was efficacious in lowering glucose with a safety profile similar to placebo. These findings could inform treatment decisions for achieving individualised glycaemic goals with minimal risk in this important population of patients.</AbstractText>Boehringer Ingelheim.</AbstractText>Copyright © 2013 Elsevier Ltd. All rights reserved.</CopyrightInformation>
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2,333,771 |
Effects of pain mitigation and method of castration on behavior and feedlot performance in cull beef bulls.
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The objectives of this study were to evaluate the effects of castration method (banding vs. surgical) and use of analgesia on behavior and feedlot performance in cull bulls. Angus, Hereford, and Angus-crossbred bulls (n = 20; initial BW = 384 ± 59.3 kg; 336 ± 20.1 d old) were housed in feedlot pens equipped with the ability to measure individual daily feed intake. A balanced randomized block design using a 2 × 2 factorial arrangement of treatments was used. A multimodal analgesia (MMA) protocol was used and consisted of sutcutaneous ketamine stun containing butorphanol (0.01 mg/kg BW), xylazine (0.02 mg/kg BW), ketamine (0.04 mg/kg BW), and a local 2% lidocaine hydrochloride anesthetic block of the spermatic cords (10 mL/cord) and scrotum (10 mL) on d 0. Flunixin meglumine (1.2 mg/kg) was administered intravenously on d 0, 1, 2, and 3 to MMA cattle. Cattle were stratified to treatments based on breed, BW, age, and a temperament score. Treatments included 1) band castration without analgesia (BND), 2) band castration with analgesia (BND-MMA), 3) surgical castration without analgesia (SURG), and 4) surgical castration with analgesia (SURG-MMA). All castrations were performed on d 0. Chute exit velocity (EV) and time in chute (TIC) were collected on d -9, 0, 1, 2, and 13. Willingness-to-enter-chute (WTE) score, rectal temperature (TEMP), heart rate (HR), and respiration (RESP) were collected on d 0, 1, 2, 3, and 13. Cattle were weighed on d -9 and 13 while feeding behaviors were collected continuously for 57 d precastration and 28 d postcastration. There was a tendency (P < 0.09) for ADG to be greater in cattle receiving analgesia. Both SURG treatments exhibited elevated TEMP on d 1 (P < 0.001) and 2 (P < 0.05) compared to BND treatments. Postcastration DMI was greater (P = 0.02) in MMA treatments compared with nonmedicated treatments throughout the trial. Meal duration was greater (P < 0.05) in BND than SURG castrates during the first week postcastration. Results suggest that pain mitigation reduces the impact of castration on ADG and DMI.
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2,333,772 |
Lipid rescue reverses the bupivacaine-induced block of the fast Na+ current (INa) in cardiomyocytes of the rat left ventricle.
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Cardiovascular resuscitation upon intoxication with lipophilic ion channel-blocking agents has proven most difficult. Recently, favorable results have been reported when lipid rescue therapy is performed, i.e., the infusion of a triglyceride-rich lipid emulsion during resuscitation. However, the mechanism of action is poorly understood.</AbstractText>The authors investigate the effects of a clinically used lipid emulsion (Lipovenös® MCT 20%; Fresenius Kabi AG, Bad Homburg, Germany) on the block of the fast Na current (INa) induced by the lipophilic local anesthetic bupivacaine in adult rat left ventricular myocytes by using the whole cell patch clamp technique.</AbstractText>Bupivacaine at 10 µm decreased INa by 54% (-19.3 ± 1.9 pApF vs. -42.3 ± 4.3 pApF; n = 17; P < 0.001; VPip = -40 mV, 1 Hz). Addition of 10% lipid emulsion in the presence of bupivacaine produced a 37% increase in INa (-26.4 ± 2.8 pApF; n = 17; P < 0.001 vs. bupivacaine alone). To test whether these results could be explained by a reduction in the free bupivacaine concentration by the lipid (lipid-sink effect), the authors removed the lipid phase from the bupivacaine-lipid mixture by ultracentrifugation. Also, the resulting water phase led to an increase in INa (+19%; n = 17; P < 0.001 vs. bupivacaine), demonstrating that part of the bupivacaine had been removed during ultracentrifugation. The substantially less lipophilic mepivacaine (40 µm) reduced INa by 27% (n = 24; P < 0.001). The mepivacaine-lipid mixture caused a significant increase in INa (+17%; n = 24; P < 0.001). For mepivacaine, only a small lipid-sink effect could be demonstrated (+8%; n = 23; P < 0.01), reflecting its poor lipid solubility.</AbstractText>The authors demonstrate lipid rescue on the single-cell level and provide evidence for a lipid-sink mechanism.</AbstractText>
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2,333,773 |
Hypertensive retinopathy and risk of stroke.
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Although assessment of hypertensive retinopathy signs has been recommended for determining end-organ damage and stratifying vascular risk in persons with hypertension, its value remains unclear. In this study, we examine whether hypertensive retinopathy predicts the long-term risk of stroke in those with hypertension. A total of 2907 participants with hypertension aged 50 to 73 years at the 1993 to 1995 examination, who had gradable retinal photographs, no history of diabetes mellitus, stroke, and coronary heart disease at baseline and data on incident stroke, were included from the Atherosclerosis Risk in Communities (ARIC) Study. Retinal photographs were assessed for hypertensive retinopathy signs and classified as none, mild, and moderate/severe. Incident events of any stroke, cerebral infarction, and hemorrhagic stroke were identified and validated. After a mean follow-up period of 13.0 years, 165 persons developed incident stroke (146 cerebral infarctions and 15 hemorrhagic strokes). After adjusting for age, sex, blood pressure, and other risk factors, persons with moderate hypertensive retinopathy were more likely to have stroke (moderate versus no retinopathy: multivariable hazard ratios, 2.37 [95% confidence interval, 1.39-4.02]). In participants with hypertension on medication with good control of blood pressure, hypertensive retinopathy was related to an increased risk of cerebral infarction (mild retinopathy: hazard ratio, 1.96 [95% confidence interval, 1.09-3.55]; and moderate retinopathy: hazard ratio, 2.98 [95% confidence interval, 1.01-8.83]). Hypertensive retinopathy predicts the long-term risk of stroke, independent of blood pressure, even in treated patients with hypertension with good hypertension control. Retinal photographic assessment of hypertensive retinopathy signs may be useful for assessment of stroke risk.
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2,333,774 |
In vivo arrhythmogenicity of the marine biotoxin azaspiracid-2 in rats.
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Azaspiracids (AZAs) are marine biotoxins produced by the dinoflagellate Azadinium spinosum that accumulate in several shellfish species. Azaspiracid poisoning episodes have been described in humans due to ingestion of AZA-contaminated seafood. Therefore, the contents of AZA-1, AZA-2 and AZA-3, the best-known analogs of the group, in shellfish destined to human consumption have been regulated by food safety authorities of many countries to protect human health. In vivo and in vitro toxicological studies have described effects of AZAs at different cellular levels and on several organs, however, AZA target remains unknown. Very recently, AZAs have been demonstrated to block the hERG cardiac potassium channel. In this study, we explored the potential cardiotoxicity of AZA-2 in vivo. The effects of AZA-2 on rat electrocardiogram (ECG) and cardiac biomarkers were evaluated for cardiotoxicity signs besides corroborating the hERG-blocking activity of AZA-2. Our results demonstrated that AZA-2 does not induce QT interval prolongation on rat ECGs in vivo, in spite of being an in vitro blocker of the hERG cardiac potassium channel. However, AZA-2 alters the heart electrical activity causing prolongation of PR intervals and the appearance of arrhythmias. More studies will be needed to clarify the mechanism by which AZA-2 causes these ECG alterations; however, the potential cardiotoxicity of AZAs demonstrated in this in vivo study should be taken into consideration when evaluating the possible threat that these toxins pose to human health, mainly for individuals with pre-existing cardiovascular disease when regulated toxin limits are exceeded.
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2,333,775 |
Pre-conditioning with synthetic CpG-oligonucleotides attenuates myocardial ischemia/reperfusion injury via IL-10 up-regulation.
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The aim of the study was to investigate whether pre-conditioning with CpG-oligodeoxynucleotides (CpG-ODN) may change cardiac ischemia/reperfusion (I/R)-dependent inflammation and modulates infarct size and cardiac performance. WT and TLR9-deficient mice were pre-treated with 1668-, 1612- and H154-thioate or D-Gal as control. Priming with 1668-thioate significantly induced inflammatory mediators in the serum and a concomitant increase of immune cells in the blood and spleen of WT mice. Furthermore, it induced myocardial pattern recognition receptors and pro-inflammatory cytokines peaking 2 h after priming and a continuous increase of IL-10. 16 h after pre-conditioning, myocardial ischemia was induced for 1 h. Infarct size determined after 24 h of I/R was reduced by 75 % due to pre-conditioning with 1668-thioate but not in the other groups. During reperfusion, cytokine expression in 1668-thioate primed mice increased further with IL-10 exceeding the other mediators by far. These changes were observed neither in animals pre-treated with 1612- or H154-thioate nor in TLR9-deficient mice. The 1668-thioate-dependent increase of IL-10 was further supported by results of a micro-array analysis 3 h after begin of reperfusion. Block of IL-10 signaling increased I/R size and prevented influence of priming. In the group pre-treated with 1668-thioate, cardiac function was preserved 24 h, 14 days and 28 days after I/R, whereas animals without pre-conditioning exhibited impaired heart function 24 h and 14 days after I/R. The excessive 1668-thioate-dependent IL-10 up-regulation during pre-conditioning and after I/R seems to be the key factor for reducing infarct size and improving cardiac function. This is in agreement with the finding that IL-10 block prevents cardioprotection by pre-conditioning.
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2,333,776 |
Cardiac arrest following spinal anaesthesia for Caesarean section: a case report.
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Spinal anaesthesia is regarded safe for caesarean section. Serious complications resulting from spinal anaesthesia such as cardiac arrest are often times considered rare. This is a case of a 27 year old un-booked gravida1 who was scheduled for emergency caesarean section on account of cephalo-pelvic disproportion (CPD) with associated history of prolonged labour. The patient was preloaded with normal saline one hour before subarachnoid block (SAB) was established and suffered a cardiac arrest immediately after establishing SAB. She was successfully resuscitated using chest compressions, adrenaline and oxygen and a live baby was delivered during cardiopulmonary resuscitation (CPR). The patient developed seizures in the immediate postoperative period. She was treated with an anti-epileptic drug and was also mechanically ventilated. She also developed features of puerperal psychosis and was managed with anti-psychotics. The patient was on admission in the intensive care unit for four days and she made quick recovery with no apparent residual damage.
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2,333,777 |
The effect of low concentrations versus high concentrations of local anesthetics for labour analgesia on obstetric and anesthetic outcomes: a meta-analysis.
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The influence that different concentrations of labour epidural local anesthetic have on assisted vaginal delivery (AVD) and many obstetric outcomes and side effects is uncertain. The purpose of this meta-analysis was to determine whether local anesthetics utilized at low concentrations (LCs) during labour are associated with a decreased incidence of AVD when compared with high concentrations (HCs).</AbstractText>We searched PubMed, Ovid EMBASE, Ovid MEDLINE, CINAHL, Scopus, clinicaltrials.gov, and Cochrane databases for randomized controlled trials of labouring patients that compared LCs (defined as ≤ 0.1% epidural bupivacaine or ≤ 0.17% ropivacaine) of epidural local anesthetic with HCs for maintenance of analgesia. The primary outcome was AVD and secondary outcomes included Cesarean delivery, duration of labour, analgesia, side effects (nausea and vomiting, motor block, hypotension, pruritus, and urinary retention), and neonatal outcomes. The odds ratios (OR) or weighted mean differences (WMD) and 95% confidence intervals (CI) were calculated using random effects modelling. An OR < 1 or a WMD < 0 favoured LCs.</AbstractText>Eleven studies met our criteria (eight bupivacaine and three ropivacaine studies), providing 1,145 patients in the LCs group and 852 patients in the HCs group for analysis of the primary outcome. Low concentrations were associated with a reduction in the incidence of AVD (OR = 0.70; 95% CI 0.56 to 0.86; P < 0.001). There was no difference in the incidence of Cesarean delivery (OR 1.05; 95% CI 0.82 to 1.33; P = 0.7). The LCs group had less motor block (OR 3.9; 95% CI 1.59 to 9.55; P = 0.003), greater ambulation (OR 2.8; 95% CI 1.1 to 7.14; P = 0.03), less urinary retention (OR 0.42; 95% CI 0.23 to 0.73; P = 0.002), and a shorter second stage of labour (WMD -14.03; 95% CI -27.52 to -0.55; P = 0.04) compared with the HCs group. There were no differences between groups in pain scores, maternal nausea and vomiting, hypotension, fetal heart rate abnormalities, five-minute Apgar scores, and need for neonatal resuscitation. One-minute Apgar scores < 7 favoured the HCs group (OR 1.53; 95% CI 1.07 to 2.21; P = 0.02), and there was more pruritus in the LCs group (OR 3.36; 95% CI 1.00 to 11.31; P = 0.05).</AbstractText>When compared with HCs of local anesthetics, the use of LCs for labour epidural analgesia reduces the incidence of AVD. This may be due to a reduction in the amount of local anesthetic used and the subsequent decrease in motor blockade. We therefore recommend the use of LCs of local anesthetics for epidural analgesia to optimize obstetric outcome.</AbstractText>
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2,333,778 |
Tmem88a mediates GATA-dependent specification of cardiomyocyte progenitors by restricting WNT signaling.
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Biphasic control of WNT signaling is essential during cardiogenesis, but how the pathway switches from promoting cardiac mesoderm to restricting cardiomyocyte progenitor fate is unknown. We identified genes expressed in lateral mesoderm that are dysregulated in zebrafish when both gata5 and gata6 are depleted, causing a block to cardiomyocyte specification. This screen identified tmem88a, which is expressed in the early cardiac progenitor field and was previously implicated in WNT modulation by overexpression studies. Depletion of tmem88a results in a profound cardiomyopathy, secondary to impaired cardiomyocyte specification. In tmem88a morphants, activation of the WNT pathway exacerbates the cardiomyocyte deficiency, whereas WNT inhibition rescues progenitor cells and cardiogenesis. We conclude that specification of cardiac fate downstream of gata5/6 involves activation of the tmem88a gene to constrain WNT signaling and expand the number of cardiac progenitors. Tmem88a is a novel component of the regulatory mechanism controlling the second phase of biphasic WNT activity essential for embryonic cardiogenesis.
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2,333,779 |
Predictors of herbal medicine in patients with coronary artery disease in Jordan.
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To explore the relation between herbal use and 14 independent variables among cardiac patients.</AbstractText>The cross-sectional study was conducted through face-to-face interviews of 690 consecutive patients visiting the outpatient department at the Queen Alia Heart Institute from June 1, 2008 to June 1, 2009. Data were collected using a specially-designed questionnaire. Univariate analysis was carried out to explore the relation between herbal use and 14 pre-determined risk factors. Categorical data between the two groups (herb users, nonusers) were studied using paired two-tailed Fischer's exact test. Variables were expressed as absolute numbers and percentages. Multivariate logistic regression analysis of significant univariate predictors of herbal use was then performed using the block entry method.</AbstractText>There were 471 (68.26%) men and 219 (31.73%) women in the study population. Of the total, there were 97 (14.1%) subjects using herbs: 77 (79.4%) men, 20 (20.6%) women (p = 0.01). Other factors of statistically significance included history of smoking (p = 0.008), urban residence (p = 0.005), duration of coronary artery disease < 5 years (p = 0.03), impaired left ventricular function (p = 0.002), lower educational level (p = 0.02). Multivariate logistic regression analysis predicted herbal use in all univariate predictors except for the duration of coronary artery disease (p = 0.053).</AbstractText>Specific and appropriate awareness and educational programmes need to be initiated with target audience in mind to optimise safety and efficacy of consumed herbs and to ensure an affordable healthcare system.</AbstractText>
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2,333,780 |
Ionic mechanisms limiting cardiac repolarization reserve in humans compared to dogs.
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The species-specific determinants of repolarization are poorly understood. This study compared the contribution of various currents to cardiac repolarization in canine and human ventricle. Conventional microelectrode, whole-cell patch-clamp, molecular biological and mathematical modelling techniques were used. Selective IKr block (50-100 nmol l(-1) dofetilide) lengthened AP duration at 90% of repolarization (APD90) >3-fold more in human than dog, suggesting smaller repolarization reserve in humans. Selective IK1 block (10 μmol l(-1) BaCl2) and IKs block (1 μmol l(-1) HMR-1556) increased APD90 more in canine than human right ventricular papillary muscle. Ion current measurements in isolated cardiomyocytes showed that IK1 and IKs densities were 3- and 4.5-fold larger in dogs than humans, respectively. IKr density and kinetics were similar in human versus dog. ICa and Ito were respectively ~30% larger and ~29% smaller in human, and Na(+)-Ca(2+) exchange current was comparable. Cardiac mRNA levels for the main IK1 ion channel subunit Kir2.1 and the IKs accessory subunit minK were significantly lower, but mRNA expression of ERG and KvLQT1 (IKr and IKs α-subunits) were not significantly different, in human versus dog. Immunostaining suggested lower Kir2.1 and minK, and higher KvLQT1 protein expression in human versus canine cardiomyocytes. IK1 and IKs inhibition increased the APD-prolonging effect of IKr block more in dog (by 56% and 49%, respectively) than human (34 and 16%), indicating that both currents contribute to increased repolarization reserve in the dog. A mathematical model incorporating observed human-canine ion current differences confirmed the role of IK1 and IKs in repolarization reserve differences. Thus, humans show greater repolarization-delaying effects of IKr block than dogs, because of lower repolarization reserve contributions from IK1 and IKs, emphasizing species-specific determinants of repolarization and the limitations of animal models for human disease.
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2,333,781 |
The importance of needle echogenity in ultrasound guided axillary brachial plexus block: a randomized controlled clinical study.
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In this study we aimed to compare the echogenic needles and the nerve stimulation addition to non-echogenic needles in ultrasound guided axillary brachial plexus block for upper extremity surgery.</AbstractText>90 patients were enrolled to the study. The patients were allocated into three groups randomly: Group E (n=30): ultrasound guided axillary block using echogenic needle, Group N (n=30): ultrasound guided axillary block using non-echogenic needle, Group NS (n=30): ultrasound guided axillary block using non-echogenic needle with nerve stimulator assistance. Duration of block procedure, mean arterial pressure, heart rate, pulse-oximetry, onset time of sensory and motor block, duration of sensory and motor block, time to first analgesic use, total need for analgesics, postoperative pain scores, patient and surgeon satisfaction scores were recorded.</AbstractText>Duration of block procedure values were lower in group E and NS, sensory and motor block durations, were significantly lower in group N. Sensorial and motor block onset time values were found lower in group NS but higher in group N. Patient and surgeon satisfaction scores were found lower in group N.</AbstractText>We conclude that ultrasound guided axillary block may be performed successfully using both echogenic needles and nerve stimulation assisted non-echogenic needles.</AbstractText>
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2,333,782 |
Induction position for spinal anaesthesia: sitting versus lateral position.
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To compare the effect of induction position on block characteristics (sensory and motor nerves) and haemodynamic stability in elderly patients with isobaric bupivacaine. Patient comfort was also looked at.</AbstractText>The randomized single blinded study was conducted at the Aga Khan University Hospital, Karachi, from September 2007 to August 2008. A total of 70 patients aged >60 years of both genders were included. Spinal anaesthesia was performed either in sitting or lateral position according to random allocation. Assessments of sensory, motor block and heart rate, systolic and diastolic blood pressure were recorded for 20 minutes. SPSS 16 was used for statistical analysis.</AbstractText>There was no significant difference for haemodynamic variables heart rate, systolic and diastolic blood pressure. The onset of anaesthesia was faster in the sitting group (4.5 minutes vs 5.4 minutes). The motor block characteristics were similar in both the groups. The majority of patients who reported 'very comfortable' for induction position belonged to the lateral group.</AbstractText>Both sitting and lateral positions have similar effects on sensory and motor blockade and haemodynamic stability. However, patients generally found lateral position very comfortable.</AbstractText>
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2,333,783 |
Motor Weakness after Caudal Epidural Injection Using the Air-acceptance Test.
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Air injected into the epidural space may spread along the nerves of the paravertebral space. Depending on the location of the air, neurologic complications such as multiradicular syndrome, lumbar root compression, and even paraplegia may occur. However, cases of motor weakness caused by air bubbles after caudal epidural injection are rare. A 44-year-old female patient received a caudal epidural injection after an air-acceptance test. Four hours later, she complained of motor weakness in the right lower extremity and numbness of the S1 dermatome. Magnetic resonance imaging showed no anomalies other than an air bubble measuring 13 mm in length and 0.337 ml in volume positioned near the right S1 root. Her symptoms completely regressed within 48 hours.
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2,333,784 |
Cardiovascular control and time domain Granger causality: insights from selective autonomic blockade.
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We studied causal relations among heart period (HP), systolic arterial pressure (SAP) and respiration (R) according to the definition of Granger causality in the time domain. Autonomic pharmacological challenges were used to alter the complexity of cardiovascular control. Atropine (AT), propranolol and clonidine (CL) were administered to block muscarinic receptors, β-adrenergic receptors and centrally sympathetic outflow, respectively. We found that: (i) at baseline, HP and SAP interacted in a closed loop with a dominant causal direction from HP to SAP; (ii) pharmacological blockades did not alter the bidirectional closed-loop interactions between HP and SAP, but AT reduced the dominance of the causal direction from HP to SAP; (iii) at baseline, bidirectional interactions between HP and R were frequently found; (iv) the closed-loop relation between HP and R was unmodified by the administration of drugs; (v) at baseline, unidirectional interactions from R to SAP were often found; and (vi) while AT induced frequently an uncoupling between R and SAP, CL favoured bidirectional interactions. These results prove that time domain measures of Granger causality can contribute to the description of cardiovascular control by suggesting the temporal direction of the interactions and by separating different causality schemes (e.g. closed loop versus unidirectional relations).
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2,333,785 |
Expression of lymphocyte coding genes in peripheral blood and lymphocyte infiltration in cardiac tissues influenced by cyclosporin A in heterotopic heart transplantation model in rats.
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To systematically compare the expression of coding genes with pathological changes of transplanted cardiac tissue and peripheral blood lymphocytes in an allo-heterotopic rat cardiac transplant model. Using SD rats as donors and Wistar rats as recipients, animals were divided into two groups, control and cyclosporine A intervention plus heart transplant groups. After transplant at 1, 3, 7, 10 and 12d, we assessed the ability of lymphocytes to infiltrate into cardiac tissues and levels of leukocyte coding genes in peripheral blood. Histopathological changes were monitored in cardiac tissue to determine the level of transplant rejection.</AbstractText>(1) 24h after transplant peripheral blood lymphocytes' transcription and expression were temporarily reduced. (2) CD4(+) and CD8(+) lymphocytes infiltrate into cardiac tissue and Grade 1R pathological changes were observed 3d-7d after heart transplant. (3)Cyclosporine A was not able to completely block heart transplant rejection.(4) Although cyclosporine A was not able to effectively suppress CD4(+) T cell gene expression, it did suppress CD8(+) T cell gene transcription. (5) Cyclosporine A did not effectively reduce the rapid infiltration of CD4(+) or CD8(+) infiltration in 3d, but significantly reduced the degree of CD4(+) T cell infiltration in cardiac tissues between 3 and 7d. (6) Differential display (DD-PCR): Graft control group: there were differences in 2,3-bisphosphoglycerate, ribosomal protein S25, 12S ribosomal, gig18, MHC-III and ATPase H(+), which occurred 24h before CD4/CD8 surface protein expression. Cyclosporine A group: there were differences in thrombospondin-1, TCR, 2,3-bisphosphoglycerate, sodium channel beta-1, gig18 and TCR. In the cyclosporine A group 2,3-bisphosphoglycerate positive expression was observed 24h after the control group, which indicates that cyclosporine A slowed down the 2,3-bisphosphoglycerate transcription rate in peripheral lymphocytes and delayed its expression time. Cyclosporine A also suppressed gig18 transcription in peripheral lymphocytes. After 24h, sodium channel beta-1 was positively expressed in the cyclosporine A group. The relationship between molecular surface receptor expression and coding genes in cardiac tissue and peripheral blood after transplant indicates that early detection of acute rejection and anti-rejection drugs' curative effect can be assessed.</AbstractText>© 2013 Elsevier B.V. All rights reserved.</CopyrightInformation>
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2,333,786 |
Effects of anxiety on the execution of police arrest and self-defense skills.
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We investigated the effects of anxiety on the execution of police officers' arrest and self-defense skills. Police officers (n=13) performed three tasks in which they kicked, blocked, or restrained an opponent who attacked them with a rubber knife (low anxiety, LA) or a shock knife (high anxiety, HA) in a within-subject design. We analyzed performance (on a 5-point Likert scale), movement times, posture, and movement velocity and acceleration. Results revealed that performance was worse in the HA compared to the LA condition. Furthermore, analysis of full-body movement showed that under increased anxiety, police officers' performance contained characteristics of avoidance behavior, such as faster reactions (to reduce the time being exposed to the threat), leaning further backward (kick), and ducking down (block). In line with recent theoretical developments, it appears that under increased anxiety, police officers were less able to inhibit stimulus-driven processing (fear of getting hit) and enforce goal-directed processing (perform the skill as well as possible) leading to avoidance behavior and a decrease in performance.
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2,333,787 |
Autologous biological pacing function with adrenergic-responsiveness in porcine of complete heart block.
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To assess the efficacy of autologous biological pacing function by autograft of gene-transferred mesenchymal stem cells in a porcine model of complete heart block.</AbstractText>Fourteen healthy young male pigs were randomized into active group (n=8) and control group (n=6). Porcine MSCs were transfected with Ad.HCN4 or Ad.Null. The pacemaker function of transfected MSCs was studied by whole-cell patch clamp. The CHB model of porcine was created with transthoracic ablation technique and the transfected MSCs were autografted into the free wall of right ventricle. The pacing function was studied by ECG and ambulatory Holter recording weekly. The adrenergic responsiveness was evaluated by the variation of heart rate after isoprenaline infusion or food provision following an overnight fasting. HCN4-MSCs expressed a robust time-dependent inward current (If) and the current density of If was 4.3±0.6 pA/pF at -105 mV. In week 2 after autograft, the heart rate of active group became significantly higher than control (53±5 bpm vs. 38±4 bpm, P<0.05) and the percent of pacing beats in active group was higher than control (69±10% vs. 28±8%, P<0.05). By infusion of isoprenaline, the heart rate was increased significantly in both groups. However, there was a significant increase of heart rate when presenting food for active group (P<0.05) while not in control.</AbstractText>Our findings demonstrated that autografted HCN4-MSCs could increase the heart rate by providing an adrenergic-responsive biological pacing function, indicating a promising approach without immunological or ethical issues for the treatment of complete heart block.</AbstractText>Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.</CopyrightInformation>
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2,333,788 |
The effectiveness of patient-controlled epidural analgesia with ropivacaine 0.165% with fentanyl 2.0 miroc g/ml or levobupivacaine 0.125% with fentanyl 2.0 micro g/ml as a method of postoperative analgesia after major orthopaedic surgery.
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This prospective randomized single-blinded study was conducted to determine whether there were differences in consumption, demand dosing and postoperative analgesia quality between PCEA using ropivacaine and levobupivacaine. Seventy patients with ASA classification I and II aged 18 to 80 years old scheduled for elective total knee replacement or total hip replacement were studied. All patients received CSE and then were randomly allocated to receive either ropivacaine 0.165% (Group A) or levobupivacaine 0.125% (Group B) both added with fentanyl 2.0 mcro g/ml via epidural route. PCEA regime was offered for 48 hours with additional standard orthopaedic practice of oral analgesia (etoricoxib 120 mg OD and paracetamol 1.0 gm QID) on the second postoperative day. Basal infusion of PCEA was at 3.0 ml/hour and discontinued after 24 hours following started of PCEA. The consumption of local anaesthetics used within the first 24 hours (basal + demand) and 48 hours (total basal + total demand) were recorded. The VAS pain score, sedation score, side effects and vital signs (blood pressure, heart rate and respiratory rate) were also recorded every four hours for 48 hours. This study showed that the total volume of drug used was significantly higher in Group A (163.31+/- 29.01 ml) than Group B (142.69 +/- 30.93ml) (p<0. 01). The mean dose of Group A for the first 48 hours after surgery was 251.43 +/- 70.02mg and was significantly greater than the mean dose of Group B (178.91 +/-42.33 mg) (p<0.01). The numbers of PCEA boluses delivered (D) and PCEA attempts (A) were higher in the Group A (22.37 +/-7.32 and 27.66 +/- 9.12) in contrast to Group B (17.63 +/- 7.71 and 24.40 +/- 11.51) but the differences were not statistically significant. The ratio D/A showed significantly higher in Group A (0.83 +/- 0.13) than Group B (0.74 +/- 0.15) (p<0. 02). The VAS pain score was similar for both groups. One patient in Group B had vomiting and there was no sedation, hypotension, pruritus or motor block recorded in both groups. In conclusion this study showed that both PCEA using ropivacaine 0.165% with fentanyl 2.0 micro g/ml and levobupivacaine 0.125% with fentanyl 2.0 micro g/ml provided effective postoperative analgesia within the first 48 hours of major lower limb orthopaedic surgery despite clinically significant dose difference. There was no hypotension, pruritus, sedation or motor block recorded in both groups.
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2,333,789 |
Changes in intraocular pressures during laparoscopy: a comparison of propofol total intravenous anesthesia to desflurane-thiopental anesthesia.
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The aim of the study was to examine intraocular pressure (IOP) changes during laparoscopic cholecystectomy performed under either desflurane-thiopental anesthesia or propofol total intravenous anesthesia (TIVA). 36 patients who will undergo elective laparoscopic cholecystectomy were enrolled in the study. The patients were randomly divided into one of two groups: desflurane (Group D, n=18) or propofol (Group P, n=18). All patients received fentanyl 2 micro/kg IV, and then breathed 100% oxygen for 3 minutes prior to induction of anesthesia. Anesthesia was induced by using thiopental 5 mg/kg IV in Group D and 2 mg/kg IV propofol in group P. Neuromuscular block was achieved with rocuronium 0.6 mg/kg IV. Anesthesia was maintained with desflurane 3-6% in group D and propofol infusion 5-10 mg/kg/h in group P. Desflurane and propofol concentrations were adjusted to maintain mean arterial pressure witihin 20% of the preinduction value. During anaesthesia, fractionated doses of fentanyl 0.5-1 micro g /kg IV and maintenance doses of muscle relaxants were used. In both groups, the the mixture 60% nitrous oxide and 40% oxygen was administered used. Arterial pressure, heart rate, ETCO2, SpO2 and IOP were recorded at the predefined time points. Creation of pneumoperitoneum resulted in a significant increase in IOP which remained elevated throughout the operation in both groups. Also, we recorded a similar IOP changes with both techniques except at five minutes after pneumoperitoneum in 15 degrees reverse Trendelenburg position during desflurane-thiopental anesthesia. In c6nclusion, desflurane-thiopental anesthesia maintains the IOP at least at similar levels compared to propofol TIVA anesthesia.
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2,333,790 |
Targeting non-small cell lung cancer cells by dual inhibition of the insulin receptor and the insulin-like growth factor-1 receptor.
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Phase III trials of the anti-insulin-like growth factor-1 receptor (IGF1R) antibody figitumumab in non-small cell lung cancer (NSCLC) patients have been discontinued owing to lack of survival benefit. We investigated whether inhibition of the highly homologous insulin receptor (IR) in addition to the IGF1R would be more effective than inhibition of the IGF1R alone at preventing the proliferation of NSCLC cells. Signalling through IGF1R and IR in the NSCLC cell lines A549 and Hcc193 was stimulated by a combination of IGF1, IGF2 and insulin. It was inhibited by antibodies that block ligand binding, αIR3 (IGF1R) and IR47-9 (IR), and by the ATP-competitive small molecule tyrosine kinase inhibitors AZ12253801 and NVPAWD742 which inhibit both IGF1R and IR tyrosine kinases. The effect of inhibitors was determined by an anchorage-independent proliferation assay and by analysis of Akt phosphorylation. In Hcc193 cells the reduction in cell proliferation and Akt phosphorylation due to anti-IGF1R antibody was enhanced by antibody-mediated inhibition of the IR whereas in A549 cells, with a relatively low IR:IGF1R expression ratio, it was not. In each cell line proliferation and Akt phosphorylation were more effectively inhibited by AZ12253801 and NVPAWD742 than by combined αIR3 and IR47-9. When the IGF1R alone is inhibited, unencumbered signalling through the IR can contribute to continued NSCLC cell proliferation. We conclude that small molecule inhibitors targeting both the IR and IGF1R more effectively reduce NSCLC cell proliferation in a manner independent of the IR:IGF1R expression ratio, providing a therapeutic rationale for the treatment of this disease.
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2,333,791 |
Ventricular premature contractions associated with iloperidone.
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Typical and atypical antipsychotic drugs are known to block potassium repolarization channels, prolong the QTc interval, and thereby predispose to ventricular tachyarrhythmias. We report a young male schizophrenic patient who experienced clinically significant and symptomatically distressing ventricular premature contractions (VPCs) in close temporal relation with iloperidone (8-16 mg/day) treatment; there had been no VPCs with prior exposure to risperidone, trihexyphenidyl, and olanzapine, nor with subsequent exposure to asenapine. We hypothesize that the VPCs may have been triggered by an alpha 2c receptor blockade-mediated cardiostimulatory action associated with iloperidone.
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2,333,792 |
The bile acid receptor TGR5 does not interact with β-arrestins or traffic to endosomes but transmits sustained signals from plasma membrane rafts.
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TGR5 is a G protein-coupled receptor that mediates bile acid (BA) effects on energy balance, inflammation, digestion, and sensation. The mechanisms and spatiotemporal control of TGR5 signaling are poorly understood. We investigated TGR5 signaling and trafficking in transfected HEK293 cells and colonocytes (NCM460) that endogenously express TGR5. BAs (deoxycholic acid (DCA), taurolithocholic acid) and the selective agonists oleanolic acid and 3-(2-chlorophenyl)-N-(4-chlorophenyl)-N, 5-dimethylisoxazole-4-carboxamide stimulated cAMP formation but did not induce TGR5 endocytosis or recruitment of β-arrestins, as assessed by confocal microscopy. DCA, taurolithocholic acid, and oleanolic acid did not stimulate TGR5 association with β-arrestin 1/2 or G protein-coupled receptor kinase (GRK) 2/5/6, as determined by bioluminescence resonance energy transfer. 3-(2-chlorophenyl)-N-(4-chlorophenyl)-N, 5-dimethylisoxazole-4-carboxamide stimulated a low level of TGR5 interaction with β-arrestin 2 and GRK2. DCA induced cAMP formation at the plasma membrane and cytosol, as determined using exchange factor directly regulated by cAMP (Epac2)-based reporters, but cAMP signals did not desensitize. AG1478, an inhibitor of epidermal growth factor receptor tyrosine kinase, the metalloprotease inhibitor batimastat, and methyl-β-cyclodextrin and filipin, which block lipid raft formation, prevented DCA stimulation of ERK1/2. Bioluminescence resonance energy transfer analysis revealed TGR5 and EGFR interactions that were blocked by disruption of lipid rafts. DCA stimulated TGR5 redistribution to plasma membrane microdomains, as localized by immunogold electron microscopy. Thus, TGR5 does not interact with β-arrestins, desensitize, or traffic to endosomes. TGR5 signals from plasma membrane rafts that facilitate EGFR interaction and transactivation. An understanding of the spatiotemporal control of TGR5 signaling provides insights into the actions of BAs and therapeutic TGR5 agonists/antagonists.
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2,333,793 |
Mammalian cardiac regeneration after fetal myocardial infarction requires cardiac progenitor cell recruitment.
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In contrast to the adult, fetal sheep consistently regenerate functional myocardium after myocardial infarction. We hypothesize that this regeneration is due to the recruitment of cardiac progenitor cells to the infarct by stromal-derived factor-1α (SDF-1α) and that its competitive inhibition will block the regenerative fetal response.</AbstractText>A 20% apical infarct was created in adult and fetal sheep by selective permanent coronary artery ligation. Lentiviral overexpression of mutant SDF-1α competitively inhibited SDF-1α in fetal infarcts. Echocardiography was performed to assess left ventricular function and infarct size. Cardiac progenitor cell recruitment and proliferation was assessed in fetal infarcts at 1 month by immunohistochemistry for nkx2.5 and 5-bromo-2-deoxyuridine.</AbstractText>Competitive inhibition of SDF-1α converted the regenerative fetal response into a reparative response, similar to the adult. SDF-inhibited fetal infarcts demonstrated significant infarct expansion by echocardiography (p < 0.001) and a significant decrease in the number of nkx2.5+ cells repopulating the infarct (p < 0.001).</AbstractText>The fetal regenerative response to myocardial infarction requires the recruitment of cardiac progenitor cells and is dependent on SDF1α. This novel model of mammalian cardiac regeneration after myocardial infarction provides a powerful tool to better understand cardiac progenitor cell biology and to develop strategies to cardiac regeneration in the adult.</AbstractText>Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.</CopyrightInformation>
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2,333,794 |
Referral to palliative care in COPD and other chronic diseases: a population-based study.
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To describe how patients with COPD, heart failure, dementia and cancer differ in frequency and timing of referral to palliative care services.</AbstractText>We performed a population-based study with the Sentinel Network of General Practitioners in Belgium. Of 2405 registered deaths respectively 5%, 4% and 28% were identified as from COPD, heart failure or cancer and 14% were diagnosed with severe dementia. GPs reported use and timing of palliative care services and treatment goals in the final three months of life.</AbstractText>Patients with COPD (20%) were less likely than those with heart failure (34%), severe dementia (37%) or cancer (60%) to be referred to palliative care services (p < 0.001). The median days between referral and death was respectively 10, 12, 14 and 20. Patients with COPD who were not referred more often received treatment with a curative or life-prolonging goal and less often with a palliative or comfort goal than did the other patients who were not referred.</AbstractText>Patients with COPD are underserved in terms of palliative care compared to those with other chronic life-limiting diseases. Awareness of palliative care as an option for patients with COPD needs to increase in palliative care services, physicians and the general public.</AbstractText>Copyright © 2013 Elsevier Ltd. All rights reserved.</CopyrightInformation>
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2,333,795 |
Brachial plexus block using lidocaine/epinephrine or lidocaine/xylazine in fat-tailed sheep.
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This blinded, randomized experimental study was designed to evaluate the analgesic effects of adding epinephrine or xylazine to lidocaine solution for brachial plexus block (BPB) in sheep. Nine healthy, fat-tailed female lambs (26.6 ± 1.5 kg) were randomly allocated into three groups: lidocaine 2%, 5 mg kg(-1) (LID, n = 6), lidocaine (5 mg kg(-1)) with epinephrine 5 µg mL(-1) (LIDEP, n = 6) or lidocaine (5 mg kg(-1)) with xylazine 0.05 mg kg(-1) (LIDXY, n = 6). Each animal was tested twice. The sheep received a total volume of 0.25 mL kg(-1) for BPB. A nerve stimulator was used to locate the nerves of the brachial plexus. Onset and duration of analgesia of the forelimb were evaluated using superficial and deep pin prick and pinching of skin with a hemostat clamp. Heart and respiratory rates, and rectal temperature were recorded before and at predetermined intervals following the completion of the block. Brachial administration of LID, LIDEP or LIDXY produced forelimb analgesia within 11.3, 11.0 and 7.0 minutes, respectively. The mean duration of analgesia was 100.0 min in LID and 133.2 min in LIDEP group. The mean duration of analgesia in LIDXY group (186.8 min) was significantly longer compared with LID group. In LIDEP group a significant increase in heart rate occurred 5 min after drug administration. Heart rate decreased from 35 to 80 min in sheep received LIDXY. In conclusion, the addition of xylazine to lidocaine solution for BBP provided a prolonged duration of action without any adverse effects in fat-tailed sheep.
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2,333,796 |
Surgical Placement of Permanent Epicardial Pacing Systems in Very Low-Birth Weight Premature Neonates: A Review of Data From the Pediatric Cardiac Care Consortium (PCCC).
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Few studies have characterized the surgical outcomes following epicardial pacemaker placement in very low-birth weight infants with congenital complete heart block. This study was undertaken to review the surgical experience with this patient population based on data from a large multi-institutional registry.</AbstractText>The Pediatric Cardiac Care Consortium (PCCC) multi-institutional database was retrospectively reviewed to identify premature, low-birth weight neonates that underwent surgical placement of an epicardial pacing system for heart block. We reviewed 179 patients with birth weights less than 1.5 kg that underwent a major operative procedure. Of these, 10 patients underwent surgical placement of an epicardial pacing system for heart block. Patients had heart block in otherwise structurally normal hearts (n = 6) or heart block associated with complex structural congenital cardiac anomalies (n = 4).</AbstractText>There were no deaths directly related to the surgical placement of the epicardial pacing system. There were no immediate complications with either lead or generator placement. One generator pocket was revised three months following placement. Survival to discharge was 60%. The four deaths occurred at a mean of 11 days (range 1-45 days) following the procedure.</AbstractText>Neonates born with prematurity and congenital heart block represent a challenging subset of patients with significant mortality. Generator pocket breakdown and infection have been considered barriers to optimal short- and long-term outcomes. Among cases in the PCCC, there were no deaths or major complications that could be attributed to permanent epicardial pacemaker placement. These data suggest that an aggressive surgical strategy may be justified.</AbstractText>
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2,333,797 |
Pharmacological studies on Myrica rubra Sieb et zucc. Effects on the cardiovascular system and platelets.
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The effects of 50% Drink of Myrica rubra (MRD) on the cardiovascular system of the rat and on the platelets aggregation of rats and guinea pigs were studied.</AbstractText>Different groups of male Wistar rats were treated either with 50% Myrica rubra drink as drinking vehicle (4 weeks) or water. The animals were then prepared for the measurement of arterial blood pressure and heart rate, ECG, sensitivity of the baroreceptors, platelets' aggregation, blood clotting time and cardiac parasympathetic ganglia. The mechanism of action of any induced effect was elucidated using different receptor blockers.</AbstractText>Treatment induced a significant decrease in the arterial blood pressure and heart rate on Wistar rats, but no significant changes in the ECG were observed. Pretreatment of rats with MRD 10 or 20 ml/kg (i. p.) significantly suppressed vagal electrical stimulation to the heart and nicotine-induced bradycardia, via decreasing phenylephrine-induced rise in the arterial blood pressure and the reflexly-induced bradycardia. It significantly suppressed the Baroreceptor Sensitivity Index (BSI). The treatment also significantly suppressed ADP-induced platelets aggregation in rats and arachidonic acid-induced aggregation in guinea pigs.All these actions seemed to be mediated by the MRD constituents such as proanthocyanidins, polyphenols and flavonoids. The decreases in the heart rate and BSI were probably caused by an inherent ability to block the parasympathetic ganglia.</AbstractText>The results of this study regarding the effects of MRD actions on the cardiovascular system and platelets qualify the drink to be classified as a functional food.</AbstractText>© Georg Thieme Verlag KG Stuttgart · New York.</CopyrightInformation>
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2,333,798 |
Q-site inhibitor induced ROS production of mitochondrial complex II is attenuated by TCA cycle dicarboxylates.
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The impact of complex II (succinate:ubiquinone oxidoreductase) on the mitochondrial production of reactive oxygen species (ROS) has been underestimated for a long time. However, recent studies with intact mitochondria revealed that complex II can be a significant source of ROS. Using submitochondrial particles from bovine heart mitochondria as a system that allows the precise setting of substrate concentrations we could show that mammalian complex II produces ROS at subsaturating succinate concentrations in the presence of Q-site inhibitors like atpenin A5 or when a further downstream block of the respiratory chain occurred. Upon inhibition of the ubiquinone reductase activity, complex II produced about 75% hydrogen peroxide and 25% superoxide. ROS generation was attenuated by all dicarboxylates that are known to bind competitively to the substrate binding site of complex II, suggesting that the oxygen radicals are mainly generated by the unoccupied flavin site. Importantly, the ROS production induced by the Q-site inhibitor atpenin A5 was largely unaffected by the redox state of the Q pool and the activity of other respiratory chain complexes. Hence, complex II has to be considered as an independent source of mitochondrial ROS in physiology and pathophysiology.
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2,333,799 |
Late-onset advanced heart block due to vagal nerve stimulation.
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Vagal nerve stimulation (VNS) is widely accepted as an effective and safe therapy for refractory seizure disorders. Significant cardiac complications, such as complete heart block or symptomatic bradycardia, are extremely rare. We present a case report of a 40-year-old man with drug-resistant epilepsy, treated with VNS, who developed the late-onset (12 months after implant), stimulation-related, symptomatic advanced heart block that was initially misinterpreted for a new type of seizure. The patient was otherwise free from other stimulation-related side effects. To our knowledge, this is the first case report of late-onset advanced heart block due to VNS.
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