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2,333,800 |
Calreticulin negatively regulates the surface expression of Cav1.3 L-type calcium channel.
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The neuroendocrine Cav1.3 L-type Ca channels have been recently found in the Human fetal heart and shown to play a vital role in Ca entry from the sarcolemma into the cell and in Ca homeostasis. Calreticulin, a Ca binding endoplasmic reticulum (ER) resident protein, has been recently shown to translocate to the cell surface where its role and function are just emerging. Here, we demonstrated a novel mechanism of Cav1.3 and calreticulin interaction resulting in downregulation of Cav1.3 channel densities in native Human fetal cardiac cells and Human Embryonic Kidney cell lines (tsA201).</AbstractText>Cell surface and cytoplasmic staining of calreticulin was demonstrated first in cultured human fetal cardiomyocytes (HFC), gestational age 18-24 weeks, using confocal microscopy thereby establishing that calreticulin is present at the cell surface in HFC. Co-immunoprecipitation from HFC using anti-Cav1.3 Ca channel antibody, and probing with anti-calreticulin antibody revealed a 46 kDa band corresponding to calreticulin suggesting that Cav1.3 Ca channel and calreticulin co-assemble in a macromolecular complex. Co-expression of Cav1.3 and calreticulin in tsA201 cells resulted in a decrease in surface expression of Cav1.3 Ca channels. These findings were consistent with the electrophysiological studies showing that co-transfection of Cav1.3 Ca channel and calreticulin resulted in 55% reduction of Cav1.3 Ca current densities recorded from tsA201 cells.</AbstractText>The results show the first evidence that calreticulin: (1) is localized outside the ER on the cell surface of HFC; (2) coimmunoprecipitates with Cav1.3 L-type Ca channel; (3) negatively regulates Cav1.3 surface expression thus resulting in decreased Cav1.3 Ca current densities. The data demonstrate a novel mechanism of modulation of Cav1.3 Ca channel by calreticulin, which may be involved in pathological settings such as autoimmune associated congenital heart block where Cav1.3 Ca channels are downregulated.</AbstractText>Published by Elsevier Inc.</CopyrightInformation>
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2,333,801 |
Elastic image registration to quantify 3-D regional myocardial deformation from volumetric ultrasound: experimental validation in an animal model.
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Although real-time 3-D echocardiography has the potential to allow more accurate assessment of global and regional ventricular dynamics compared with more traditional 2-D ultrasound examinations, it still requires rigorous testing and validation should it break through as a standard examination in routine clinical practice. However, only a limited number of studies have validated 3-D strain algorithms in an in vivo experimental setting. The aim of the present study, therefore, was to validate a registration-based strain estimation methodology in an animal model. Volumetric images were acquired in 14 open-chest sheep instrumented with ultrasonic microcrystals. Radial strain (ɛRR), longitudinal strain (ɛLL) and circumferential strain (ɛCC) were estimated during different stages: at rest, during reduced and increased cardiac inotropy induced by esmolol and dobutamine infusion, respectively, and during acute ischemia. Agreement between image-based and microcrystal-based strain estimates was evaluated by their linear correlation, indicating that all strain components could be estimated with acceptable accuracy (r = 0.69 for ɛRR, r = 0.64 for ɛLL and r = 0.62 for ɛCC). These findings are comparable to the performance of the current state-of-the-art commercial 3-D speckle tracking methods. Furthermore, shape of the strain curves, timing of peak values and location of dysfunctional regions were identified well. Whether 3-D elastic registration performs better than 3-D block matching-based methodologies still remains to be proven.
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2,333,802 |
Ultrasound guidance reduces the risk of local anesthetic systemic toxicity following peripheral nerve blockade.
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Local anesthetic systemic toxicity (LAST) is a potentially life-threatening complication of local anesthetic administration. In this article, the results of the Australian and New Zealand Registry of Regional Anaesthesia were analyzed to determine if ultrasound-guided peripheral nerve blockade (PNB) was associated with a reduced risk of LAST compared with techniques not utilizing ultrasound technology.</AbstractText>The period of study for this multicenter study involving 20 hospitals was from January 2007 through May 2012. The primary outcome was LAST comprising minor, major, and cardiac arrest (due to toxicity) events determined using standardized definitions. Multivariable logistic regression models and propensity score analyses were used to determine significant event predictors.</AbstractText>The study population comprised 20,021 patients who received 25,336 PNBs. There were 22 episodes of LAST, resulting in an incidence of LAST of 0.87 per 1000 PNBs (95% confidence interval, 0.54-1.3 per 1000). Ultrasound guidance was associated with a reduced incidence of local anesthetic toxicity. Site of injection, local anesthetic type, dose per weight, dose, and patient weight were all predictors of LAST.</AbstractText>This study provides the strongest evidence, to date, that ultrasound guidance may improve safety because it is associated with a reduced risk of LAST following PNB.</AbstractText>
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2,333,803 |
Safety and efficacy of a multi-electrode renal sympathetic denervation system in resistant hypertension: the EnligHTN I trial.
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Catheter-based renal artery sympathetic denervation has emerged as a novel therapy for treatment of patients with drug-resistant hypertension. Initial studies were performed using a single electrode radiofrequency catheter, but recent advances in catheter design have allowed the development of multi-electrode systems that can deliver lesions with a pre-determined pattern. This study was designed to evaluate the safety and efficacy of the EnligHTN(™) multi-electrode system.</AbstractText>We conducted the first-in-human, prospective, multi-centre, non-randomized study in 46 patients (67% male, mean age 60 years, and mean baseline office blood pressure 176/96 mmHg) with drug-resistant hypertension. The primary efficacy objective was change in office blood pressure from baseline to 6 months. Safety measures included all adverse events with a focus on the renal artery and other vascular complications and changes in renal function. Renal artery denervation, using the EnligHTN system significantly reduced the office blood pressure from baseline to 1, 3, and 6 months by -28/10, -27/10 and -26/10 mmHg, respectively (P < 0.0001). No acute renal artery injury or other serious vascular complications occurred. Small, non-clinically relevant, changes in average estimated glomerular filtration rate were reported from baseline (87 ± 19 mL/min/1.73 m2) to 6 months post-procedure (82 ± 20 mL/min/1.73 m2).</AbstractText>Renal sympathetic denervation, using the EnligHTN multi-electrode catheter results in a rapid and significant office blood pressure reduction that was sustained through 6 months. The EnligHTN system delivers a promising therapy for the treatment of drug-resistant hypertension.</AbstractText>
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2,333,804 |
Fat and carbohydrate metabolism during exercise in phosphoglucomutase type 1 deficiency.
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Phosphoglucomutase type 1 (PGM1) deficiency is a rare metabolic myopathy in which symptoms are provoked by exercise.</AbstractText>Because the metabolic block is proximal to the entry of glucose into the glycolytic pathway, we hypothesized that iv glucose could improve the exercise intolerance experienced by the patient.</AbstractText>This was an experimental intervention study.</AbstractText>The study was conducted in an exercise laboratory.</AbstractText>Subjects were a 37-year-old man with genetically and biochemically verified PGM1 deficiency and 6 healthy subjects.</AbstractText>Cycle ergometer, peak and submaximal exercise (70% of peak oxygen consumption), and exercise with an iv glucose infusion tests were performed.</AbstractText>Peak work capacity and substrate metabolism during submaximal exercise with and without an iv glucose infusion were measured.</AbstractText>Peak work capacity in the patient was normal, as were increases in plasma lactate during peak and submaximal exercise. However, the heart rate decreased 11 beats minute⁻¹, the peak work rate increased 12.5%, and exercise was rated as being easier with glucose infusion in the patient. These results were in contrast to those in the control group, in whom no improvements occurred. In addition, the patient tended to become hypoglycemic during submaximal exercise.</AbstractText>This report characterizes PGM1 deficiency as a mild metabolic myopathy that has dynamic exercise-related symptoms in common with McArdle disease but no second wind phenomenon, thus suggesting that the condition clinically resembles other partial enzymatic defects of glycolysis. However, with glucose infusion, the heart rate decreased 11 beats min⁻¹, the peak work rate increased 12.5%, and exercise was considered easier by the patient.</AbstractText>
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2,333,805 |
[Case of parturient who underwent resection of a spinal Tumor].
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Spinal tumors are rare in pregnancy, but they cause a serious problem in terms of continuing pregnancy. Here, we present a parturient with severe lumbago who underwent resection of a spinal tumor. A 42-year-old parturient at 26 weeks of gestation presented with acute onset of severe pain in the lumbar region and lower extremities. Magnetic resonance imaging revealed an intraspinal tumor from L4 to L5. Although sciatic nerve block and epidural anesthesia were performed to relieve the pain, their analgesic effects were insufficient. Since the continuation of pregnancy was difficult because of the severe pain, she was scheduled for the resection of the tumor under general anesthesia at 28 weeks gestation. Fetal heart monitoring was used to evaluate abnormal heart rate patterns in the operating room. In order to avoid a decrease in uteroplacental blood flow, the intraoperative systolic blood pressure was maintained at 100 mmHg or more and end-tidal carbon dioxide was maintained at 35-40 mmHg. She was placed on left lateral position to avoid aortocaval compression, and surgery was uneventfully completed. The pain was relieved after surgery, and the parturient could continue the pregnancy. She under- went cesarean section at 40 weeks of gestation, and gave birth to a healthy baby.
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2,333,806 |
Nox as a target for diabetic complications.
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Oxidative stress has been linked to the pathogenesis of the major complications of diabetes in the kidney, the heart, the eye or the vasculature. NADPH oxidases of the Nox family are a major source of ROS (reactive oxygen species) and are critical mediators of redox signalling in cells from different organs afflicted by the diabetic milieu. In the present review, we provide an overview of the current knowledge related to the understanding of the role of Nox in the processes that control cell injury induced by hyperglycaemia and other predominant factors enhanced in diabetes, including the renin-angiotensin system, TGF-β (transforming growth factor-β) and AGEs (advanced glycation end-products). These observations support a critical role for Nox homologues in diabetic complications and indicate that NADPH oxidases are an important therapeutic target. Therefore the design and development of small-molecule inhibitors that selectively block Nox oxidases appears to be a reasonable approach to prevent or retard the complications of diabetes in target organs. The bioefficacy of these agents in experimental animal models is also discussed in the present review.
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2,333,807 |
High gender -specific susceptibility to curare- a neuromuscular blocking agent.
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Curare, a selective skeletal muscle relaxant, has been used clinically to reduce shivering and as an anesthetic auxiliary in abdominal surgery. It is also widely used in animal experiments to block neuromuscular junction activity. Effective doses of curare diminish muscle contraction without affecting brain function, but at higher doses it is known to be lethal. However, the exact dose of curare initiating muscle relaxation vs. lethal effect has not been fully characterized in mice. In this study we carefully examined the dose-response for achieving muscle inactivity over lethality in both male and female mice (C57BL6/J). The most striking finding of this study is that female mice were highly susceptible to curare; both the ED₅₀ and LD₅₀ were at least 3-fold lower than male littermates. This study shows that gender-specific differences can be an important factor when administering skeletal muscle relaxants, particularly curare or other analogous agents targeted to the neuromuscular junction.
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2,333,808 |
Myeloid leukemia in a urine specimen: a case report and review of the literature.
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Urinary tract cytology has a long history of utilization for the diagnosis and follow-up of tumors involving the urothelial tract. As expected, the most common tumor encountered in exfoliative urine cytology is urothelial carcinoma. While the sensitivity of urinary tract cytology for the diagnosis of low-grade urothelial carcinomas is low, its sensitivity and accuracy for high grade urothelial carcinomas is much higher. However, nonurothelial malignancies, such as hematopoietic malignancies, can also be encountered in urine specimens. Leukemic cells in urine can be diagnosed readily by cytological examination in cases where more invasive procedures are difficult to perform. Additionally, cell block sections can be utilized to determine the immunocytochemical profile of the tumor cells to confirm the diagnosis. Herein we report a case of a 75-year-old man with a past medical history of acute myeloid leukemia (AML), who presented with congested heart failure and painless macroscopic hematuria. AML relapse was diagnosed. Cytological examination of the urine using a ThinPrep® smear, cytospin preparation, and immunohistochemical stains performed on the cell block sections were examined. Findings were consistent with leukemic cells of myeloid origin in the bladder washing specimen.
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2,333,809 |
Nanoscale distribution of ryanodine receptors and caveolin-3 in mouse ventricular myocytes: dilation of t-tubules near junctions.
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We conducted super-resolution light microscopy (LM) imaging of the distribution of ryanodine receptors (RyRs) and caveolin-3 (CAV3) in mouse ventricular myocytes. Quantitative analysis of data at the surface sarcolemma showed that 4.8% of RyR labeling colocalized with CAV3 whereas 3.5% of CAV3 was in areas with RyR labeling. These values increased to 9.2 and 9.0%, respectively, in the interior of myocytes where CAV3 was widely expressed in the t-system but reduced in regions associated with junctional couplings. Electron microscopic (EM) tomography independently showed only few couplings with caveolae and little evidence for caveolar shapes on the t-system. Unexpectedly, both super-resolution LM and three-dimensional EM data (including serial block-face scanning EM) revealed significant increases in local t-system diameters in many regions associated with junctions. We suggest that this regional specialization helps reduce ionic accumulation and depletion in t-system lumen during excitation-contraction coupling to ensure effective local Ca²⁺ release. Our data demonstrate that super-resolution LM and volume EM techniques complementarily enhance information on subcellular structure at the nanoscale.
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2,333,810 |
Effect of interscalene brachial plexus block on heart rate variability.
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Interscalene brachial plexus block (ISB) may be followed by cardiovascular instability. Until date, there is no clear picture available about the underlying mechanisms of ISB. In this study, we aimed to determine the changes in heart rate variability (HRV) parameters after ISB and the differences between right- and left-sided ISBs.</AbstractText>We prospectively studied 24 patients operated for shoulder surgery in sitting position and divided them into two respective groups: R (right-sided block = 14 pts) and L (left-sided block = 10 pts). HRV data were taken before and 30 min after the block. Ropivacaine without ephedrine was used for the ISB through an insulated block needle connected to a nerve stimulator. Statistical analysis implemented chi-square, Student's and t-paired tests. Skewed distributions were analyzed after logarithmic transformation.</AbstractText>All the studied patients had successful blocks. Horner's syndrome signs were observed in 33.3% of the patients (R = 5/14, L = 3/10; [P = 0.769]). There were no significant differences in pre-block HRV between the groups. The application of ISB had differential effect on HRV variables: R-blocks increased QRS and QTc durations and InPNN50, while a statistical decrease was seen in InLF. L-blocks did not show any significant changes. These changes indicate a reduced sympathetic and an increased parasympathetic influence on the heart's autonomic flow after R-block.</AbstractText>Based on the obtained results we conclude that ISB, possibly through extension of block to the ipsilateral stellate ganglion, alters the autonomic outflow to the central circulatory system in a way depending on the block's side.</AbstractText>
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2,333,811 |
Effect of retrobulbar nerve block on heart rate variability during enucleation in horses under general anesthesia.
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Analysis of any effect of retrobulbar block during ocular surgery on heart rate variability and oculocardiac reflex.</AbstractText>Prospective study.</AbstractText>Horses (n = 16) undergoing eye enucleation due to chronic ophthalmologic diseases.</AbstractText>Eye enucleation was performed under general anesthesia. The horses were randomly assigned to the first (inhalation anesthesia only, n = 10) or second group (inhalation and local retrobulbar anesthesia, n = 6). The retrobulbar block was performed using 12 mL of mepivacaine hydrochloride 2%. ECG data were taken by a Telemetric ECG before, during, and after surgery. Heart rate variability was analyzed in the time domain as mean heart rate, mean beat-to-beat interval duration, and standard deviation of continuous beat-to-beat intervals. The frequency domain analysis included the low- and high-frequency components of heart rate variability and the sympathovagal balance (low/high frequency). The low frequency represents mainly sympathetic influences on the heart, whereas high frequency is mediated by the parasympathetic tone.</AbstractText>All horses without a retrobulbar block showed a significant decrease in the heart rate during traction on the globe and pressure on the orbital fat pad for homoestasis (P = 0.04). Simultaneously, high-frequency power, as an indicator of vagal stimulation, increased significantly. High-frequency and low-frequency power in the retrobulbar block group increased in five horses, and heart rate decreased in only one horse. Both were not significant within the group, but there was a significant difference between both groups relating to the incidence of heart rate decrease occurring at globe traction.</AbstractText>Heart rate variability is a sensitive, non-invasive parameter to obtain sympathovagal stimulations during general anesthesia. The retrobulbar block can prevent heart rate decrease associated with initiation of the oculocardiac reflex.</AbstractText>© 2013 American College of Veterinary Ophthalmologists.</CopyrightInformation>
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2,333,812 |
Interfering amino terminal peptides and functional implications for heteromeric gap junction formation.
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Connexin43 (Cx43) is widely expressed in many different tissues of the human body. In cells of some organs, Cx43 is co-expressed with other connexins (Cx), including Cx46 and Cx50 in lens, Cx40 in atrium, Purkinje fibers, and the blood vessel wall, Cx45 in heart, and Cx37 in the ovary. Interactions with the co-expressed connexins may have profound functional implications. The abilities of Cx37, Cx45, Cx46, and Cx50 to function in heteromeric gap junction combinations with Cx43 are well documented. Different studies disagree regarding the ability of Cx43 and Cx40 to produce functional heteromeric gap junctions with each other. We review previous studies regarding the heteromeric interactions of Cx43. The possibility of negative functional interactions between the cytoplasmic pore-forming amino-terminal (NT) domains of these connexins was assessed using pentameric connexin sequence-specific NT domain [interfering NT (iNT)] peptides applied to cells expressing homomeric Cx40, Cx37, Cx45, Cx46, and Cx50 gap junctions. A Cx43 iNT peptide corresponding to amino acids 9-13 (Ac-KLLDK-NH2) specifically inhibited the electrical coupling of Cx40 gap junctions in a transjunctional voltage (V j)-dependent manner without affecting the function of homologous Cx37, Cx46, Cx50, and Cx45 gap junctions. A Cx40 iNT (Ac-EFLEE-OH) peptide counteracted the V j-dependent block of Cx40 gap junctions, whereas a similarly charged Cx50 iNT (Ac-EEVNE-OH) peptide did not, suggesting that these NT domain interactions are not solely based on electrostatics. These data are consistent with functional Cx43 heteromeric gap junction formation with Cx37, Cx45, Cx46, and Cx50 and suggest that Cx40 uniquely experiences functional suppressive interactions with a Cx43 NT domain sequence. These findings present unique functional implications about the heteromeric interactions between Cx43 and Cx40 that may influence cardiac conduction in atrial myocardium and the specialized conduction system.
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2,333,813 |
Outcome of pregnancy in Italian patients with primary Sjögren syndrome.
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To investigate pregnancy and fetal outcomes in patients with primary Sjögren syndrome (pSS).</AbstractText>An obstetric history of 36 women with established diagnosis of pSS at pregnancy was obtained from a multicenter cohort of 1075 patients. In a subgroup case-control analysis, 12 deliveries in patients with pSS were compared with 96 control deliveries.</AbstractText>Thirty-six women (31 with anti-SSA/Ro and/or anti-SSB/La antibodies) with an established diagnosis of pSS had 45 pregnancies with the delivery of 40 newborns. Two miscarriages, 2 fetal deaths, and 1 induced abortion were recorded. Mean age at the first pregnancy was 33.9 years; mean number of pregnancies was 1.25; 18/40 (45%) cesarean births were delivered; mean pregnancy length was 38.5 weeks (range 32-43), with 6 preterm deliveries. The mean Apgar score at 5 min was 8.9, mean birthweight was 2920 g (range 826-4060 g). Congenital heart block (CHB) occurred in 2/40 (5%) newborns. The reported rate of breastfeeding for at least 1 month was 60.5%. In 4/40 pregnancies (10%) a flare of disease activity was observed within a year from delivery. In the case-control subgroup analysis, 12 deliveries were compared with 96 controls and no significant differences were found.</AbstractText>Patients with pSS can have successful pregnancies, which might be followed by a mild relapse. CHB was the only cause of death for offspring of mothers with pSS.</AbstractText>
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2,333,814 |
Hemodynamic, ventilator, and ECG changes in pediatric patients undergoing extraction.
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Dental treatment induces pain anxiety and fear. This study was conducted to assess the changes in hemodynamic, ventilator, and electrocardiograph changes during extraction procedure among 12-15-year-old children and compare these changes with anxiety, fear, and pain.</AbstractText>A purposive sample of 60 patients selected based on inclusion and exclusion criteria underwent study procedure in the dental OPD of a medical college and hospital. The anxiety, fear, and pain were recorded by dental anxiety scale, dental fear scale, and visual analogue scale, respectively, before the start of the procedure. The systolic blood pressure, diastolic blood pressure, heart rate, oxygen saturation, and electrocardiogram changes were monitored during the extraction procedure. The recording was taken four times (preinjection phase, injection, extraction, and postextraction) and was analyzed.</AbstractText>At the preinjection phase the mean vales were systolic blood pressure (128 ± 11.2), diastolic blood pressure (85.7 ± 6.3), heart rate (79.7 ± 9.3), and oxygen saturation (97.9 ± 5.8). These values increased in injection phases and decreased in extraction phase and the least values were found after 10 min of procedure and this relation was significant for all parameters except oxygen saturation (P = 0.48, NS). ECG abnormalities were seen among 22 patients and were significant before and after injection of Local anesthetic (P = 0.0001, S).</AbstractText>Anxiety, fear, and pain have an effect on hemodynamic, ventilator, and cardiovascular parameters during the extraction procedure and hence behavioral management has to be emphasized among children in dental clinics.</AbstractText>
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2,333,815 |
The effects of dexmedetomidine added to spinal levobupivacaine for transurethral endoscopic surgery.
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Intrathecal α2 agonists prolong the duration of action of local anesthetics and reduce the required dose. Dexmedetomidine is an α2 receptor agonist and its α2/α1 selectivity is 8 times higher than that of clonidine.</AbstractText>In this study, we aimed to investigate the effect of adding dexmedetomidine to intrathecal levobupivacaine on the onset time and duration of motor and sensory blocks.</AbstractText>Randomized controlled study.</AbstractText>Patients were randomly assigned into two groups. Group L (n= 30) patients received 3 mL (15 mg) of 0.5% levobupivacaine +0.3 mL normal saline and Group LD (n= 30) patients received 3 mL (15 mg) of 0.5% levobupivacaine + 0.3 mL (3 μg) dexmedetomidine. Sensory block onset time, block reaching time to T10 dermatome, the most elevated dermatome level, two dermatome regression time, sensory block complete regression time as well as motor block onset time, reaching Bromage 3 and regressing to Bromage 0 were recorded.</AbstractText>Sensory and motor block onset times were shorter in Group LD than in Group L (p<0.001). The regression of the sensory block to S1 dermatome and Bromage 0 were longer in Group LD than Group L (p<0.001). The two dermatome regression time was longer in Group LD than Group L (p< 0.001). There were no statistically significant differences between groups in blood pressure and heart rate. There was no statistically significant difference between groups when adverse effects were compared.</AbstractText>We conclude that intrathecal dexmedetomidine addition to levobupivacaine for spinal anaesthesia shortens sensory and motor block onset time and prolongs block duration without any significant adverse effects.</AbstractText>
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2,333,816 |
Cardiac peroxisome proliferator-activated receptor δ (PPARδ) as a new target for increased contractility without altering heart rate.
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Agents having a positive inotropic effect on the heart are widely used for the treatment of heart failure. However, these agents have the side effect of altering heart rate. It has been established that peroxisome proliferator-activated receptor δ (PPARδ) is mediated in cardiac contraction, however the effect on heart rate is unknown. Thus, we used an agonist of PPARδ, GW0742, to investigate this issue in the present study.</AbstractText>We used isolated hearts in Langendorff apparatus and hemodynamic analysis in catheterized rats to measure the actions of GW0742 extra-vivo and in vivo. In diabetic rats with heart failure, GW0742 at a dose sufficient to activate PPARδ reversed cardiac contraction without changes in heart rate. In normal rats, PPARδ enhanced cardiac contractility and hemodynamic dP/dtmax significantly more than dobutamine. Both actions were diminished by GSK0660 at a dose enough to block PPARδ. However, GW0742 at the same dose failed to modify heart rate, although it did produce a mild increase in blood pressure. Detection of intracellular calcium level and Western blotting analysis showed that the intracellular calcium concentration and troponin I phosphorylation were both enhanced by GW0742.</AbstractText>Activation of PPARδ by GW0742 increases cardiac contractility but not heart rate. Thus, PPARδ may be a suitable target for the development of inotropic agents to treat heart failure without changing heart rate.</AbstractText>
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2,333,817 |
Adaptive Kaczmarz method for image reconstruction in electrical impedance tomography.
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We present an adaptive Kaczmarz method for solving the inverse problem in electrical impedance tomography and determining the conductivity distribution inside an object from electrical measurements made on the surface. To best characterize an unknown conductivity distribution and avoid inverting the Jacobian-related term J(T)J which could be expensive in terms of computation cost and memory in large-scale problems, we propose solving the inverse problem by applying the optimal current patterns for distinguishing the actual conductivity from the conductivity estimate between each iteration of the block Kaczmarz algorithm. With a novel subset scheme, the memory-efficient reconstruction algorithm which appropriately combines the optimal current pattern generation with the Kaczmarz method can produce more accurate and stable solutions adaptively as compared to traditional Kaczmarz- and Gauss-Newton-type methods. Choices of initial current pattern estimates are discussed in this paper. Several reconstruction image metrics are used to quantitatively evaluate the performance of the simulation results.
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2,333,818 |
Anesthetic efficacy of X-tip intraosseous injection using 2% lidocaine with 1:80,000 epinephrine in patients with irreversible pulpitis after inferior alveolar nerve block: A clinical study.
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The inferior alveolar nerve block (IAN) is the most frequently used mandibular injection technique for achieving local anesthesia in endodontics. Supplemental injections are essential to overcome failure of IAN block in patients with irreversible pulpitis.</AbstractText>To evaluate the anesthetic efficacy of X-tip intraosseous injection (2% lidocaine with 1:80,000 epinephrine) in patients with irreversible pulpitis in mandibular posterior teeth when conventional IAN block failed.</AbstractText>Thirty emergency patients diagnosed with irreversible pulpitis in a mandibular posterior tooth received an IAN block and experienced moderate to severe pain on endodontic access or initial instrumentation. The X-tip system was used to administer 1.8 ml of 2% lidocaine with 1:80,000 epinephrine. The success of X-tip intraosseous injection was defined as none or mild pain (Heft-Parker visual analogue scale ratings < 54 mm) on endodontic access or initial instrumentation.</AbstractText>Ninety-three percent of X-tip injections were successful and 7% were unsuccessful. Discomfort rating for X-tip perforation: 96.66% patients reported none or mild pain, whereas 3.34% reported moderate to severe pain. For discomfort rating during solution deposition, 74.99% patients reported none or mild pain and 24.92% reported moderate to severe pain. Ninety-six percent of the patients had subjective/objective increase in heart rate.</AbstractText>Supplemental X-tip intraosseous injection using 2% lignocaine with 1:80,000 epinephrine has a statistically significant influence in achieving pulpal anesthesia in patients with irreversible pulpitis.</AbstractText>
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2,333,819 |
Functional morphometric analysis in cellular behaviors: shape and size matter.
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Cellular morphogenesis in response to biophysical and topographical cues provides insights into cytoskeletal status, biointerface communications, and phenotypic adaptations in an incessant signaling feedback that governs cellular fate. Morphometric characterization is an important element in the study of the dynamic cellular behaviors, in their interactive response to environmental influence exerted by culture system. They collectively serve to reflect cellular proliferation, migration, and differentiation, which may serve as prognostic indices for clinical and pathological diagnosis. Various parameters are proposed to categorize morphological adaptations in relation to cellular function. In this review, the underlying principles, assumptions, and limitations of morphological characterizations are discussed. The significance, challenges, and implications of quantitative morphometric characterization of cell shapes and sizes in determining cellular functions are discussed.
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2,333,820 |
Glossopharyngeal neuralgia.
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In this review, the clinical characteristics, differentiating features from other forms of neuralgia, etiology and treatment options of glossopharyngeal neuralgia will be discussed.
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2,333,821 |
Consumers' estimation of calorie content at fast food restaurants: cross sectional observational study.
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To investigate estimation of calorie (energy) content of meals from fast food restaurants in adults, adolescents, and school age children.</AbstractText>Cross sectional study of repeated visits to fast food restaurant chains.</AbstractText>89 fast food restaurants in four cities in New England, United States: McDonald's, Burger King, Subway, Wendy's, KFC, Dunkin' Donuts.</AbstractText>1877 adults and 330 school age children visiting restaurants at dinnertime (evening meal) in 2010 and 2011; 1178 adolescents visiting restaurants after school or at lunchtime in 2010 and 2011.</AbstractText>Estimated calorie content of purchased meals.</AbstractText>Among adults, adolescents, and school age children, the mean actual calorie content of meals was 836 calories (SD 465), 756 calories (SD 455), and 733 calories (SD 359), respectively. A calorie is equivalent to 4.18 kJ. Compared with the actual figures, participants underestimated calorie content by means of 175 calories (95% confidence interval 145 to 205), 259 calories (227 to 291), and 175 calories (108 to 242), respectively. In multivariable linear regression models, underestimation of calorie content increased substantially as the actual meal calorie content increased. Adults and adolescents eating at Subway estimated 20% and 25% lower calorie content than McDonald's diners (relative change 0.80, 95% confidence interval 0.66 to 0.96; 0.75, 0.57 to 0.99).</AbstractText>People eating at fast food restaurants underestimate the calorie content of meals, especially large meals. Education of consumers through calorie menu labeling and other outreach efforts might reduce the large degree of underestimation.</AbstractText>
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2,333,822 |
Identification of novel small molecule inhibitors of adenovirus gene transfer using a high throughput screening approach.
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Due to many favourable attributes adenoviruses (Ads) are the most extensively used vectors for clinical gene therapy applications. However, following intravascular administration, the safety and efficacy of Ad vectors are hampered by the strong hepatic tropism and induction of a potent immune response. Such effects are determined by a range of complex interactions including those with neutralising antibodies, blood cells and factors, as well as binding to native cellular receptors (coxsackie adenovirus receptor (CAR), integrins). Once in the bloodstream, coagulation factor X (FX) has a pivotal role in determining Ad liver transduction and viral immune recognition. Due to difficulties in generating a vector devoid of multiple receptor binding motifs, we hypothesised that a small molecule inhibitor would be of value. Here, a pharmacological approach was implemented to block adenovirus transduction pathways. We developed a high throughput screening (HTS) platform to identify small molecule inhibitors of FX-mediated Ad5 gene transfer. Using an in vitro fluorescence and cell-based HTS, we evaluated 10,240 small molecules. Following sequential rounds of screening, three compounds, T5424837, T5550585 and T5660138 were identified that ablated FX-mediated Ad5 transduction with low micromolar potency. The candidate molecules possessed common structural features and formed part of the one pharmacophore model. Focused, mini-libraries were generated with structurally related molecules and in vitro screening revealed novel hits with similar or improved efficacy. The compounds did not interfere with Ad5:FX engagement but acted at a subsequent step by blocking efficient intracellular transport of the virus. In vivo, T5660138 and its closely related analogue T5660136 significantly reduced Ad5 liver transgene expression at 48 h post-intravenous administration of a high viral dose (1×10¹¹ vp/mouse). Therefore, this study identifies novel and potent small molecule inhibitors of the Ad5 transduction which may have applications in the Ad gene therapy setting.
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2,333,823 |
In silico assessment of drug safety in human heart applied to late sodium current blockers.
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Drug-induced action potential (AP) prolongation leading to Torsade de Pointes is a major concern for the development of anti-arrhythmic drugs. Nevertheless the development of improved anti-arrhythmic agents, some of which may block different channels, remains an important opportunity. Partial block of the late sodium current (I(NaL)) has emerged as a novel anti-arrhythmic mechanism. It can be effective in the settings of free radical challenge or hypoxia. In addition, this approach can attenuate pro-arrhythmic effects of blocking the rapid delayed rectifying K(+) current (I(Kr)). The main goal of our computational work was to develop an in-silico tool for preclinical anti-arrhythmic drug safety assessment, by illustrating the impact of I(Kr)/I(NaL) ratio of steady-state block of drug candidates on "torsadogenic" biomarkers. The O'Hara et al. AP model for human ventricular myocytes was used. Biomarkers for arrhythmic risk, i.e., AP duration, triangulation, reverse rate-dependence, transmural dispersion of repolarization and electrocardiogram QT intervals, were calculated using single myocyte and one-dimensional strand simulations. Predetermined amounts of block of I(NaL) and I(Kr) were evaluated. "Safety plots" were developed to illustrate the value of the specific biomarker for selected combinations of IC(50)s for I(Kr) and I(NaL) of potential drugs. The reference biomarkers at baseline changed depending on the "drug" specificity for these two ion channel targets. Ranolazine and GS967 (a novel potent inhibitor of I(NaL)) yielded a biomarker data set that is considered safe by standard regulatory criteria. This novel in-silico approach is useful for evaluating pro-arrhythmic potential of drugs and drug candidates in the human ventricle.
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2,333,824 |
The positive inotropic effect of pyruvate involves an increase in myofilament calcium sensitivity.
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Pyruvate is a metabolic fuel that is a potent inotropic agent. Despite its unique inotropic and antioxidant properties, the molecular mechanism of its inotropic mechanism is still largely unknown. To examine the inotropic effect of pyruvate in parallel with intracellular calcium handling under near physiological conditions, we measured pH, myofilament calcium sensitivity, developed force, and calcium transients in ultra thin rabbit heart trabeculae at 37 °C loaded iontophoretically with the calcium indicator bis-fura-2. By contrasting conditions of control versus sarcoplasmic reticulum block (with either cyclopiazonic acid and ryanodine or with thapsigargin) we were able to characterize and isolate the effects of pyruvate on sarcoplasmic reticulum calcium handling and developed force. A potassium contracture technique was subsequently utilized to assess the force-calcium relationship and thus the myofilament calcium sensitivity. Pyruvate consistently increased developed force whether or not the sarcoplasmic reticulum was blocked (16.8±3.5 to 24.5±5.1 vs. 6.9±2.6 to 12.5±4.4 mN/mm(2), non-blocked vs. blocked sarcoplasmic reticulum respectively, p<0.001, n = 9). Furthermore, the sensitizing effect of pyruvate on the myofilaments was demonstrated by potassium contractures (EC50 at baseline versus 20 minutes of pyruvate infusion (peak force development) was 701±94 vs. 445±65 nM, p<0.01, n = 6). This study is the first to demonstrate that a leftward shift in myofilament calcium sensitivity is an important mediator of the inotropic effect of pyruvate. This finding can have important implications for future development of therapeutic strategies in the management of heart failure.
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2,333,825 |
Unique X-linked familial FSGS with co-segregating heart block disorder is associated with a mutation in the NXF5 gene.
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Focal segmental glomerulosclerosis (FSGS) is the consequence of a disease process that attacks the kidney's filtering system, causing serious scarring. More than half of FSGS patients develop chronic kidney failure within 10 years, ultimately requiring dialysis or renal transplantation. There are currently several genes known to cause the hereditary forms of FSGS (ACTN4, TRPC6, CD2AP, INF2, MYO1E and NPHS2). This study involves a large, unique, multigenerational Australian pedigree in which FSGS co-segregates with progressive heart block with apparent X-linked recessive inheritance. Through a classical combined approach of linkage and haplotype analysis, we identified a 21.19 cM interval implicated on the X chromosome. We then used a whole exome sequencing approach to identify two mutated genes, NXF5 and ALG13, which are located within this linkage interval. The two mutations NXF5-R113W and ALG13-T141L segregated perfectly with the disease phenotype in the pedigree and were not found in a large healthy control cohort. Analysis using bioinformatics tools predicted the R113W mutation in the NXF5 gene to be deleterious and cellular studies support a role in the stability and localization of the protein suggesting a causative role of this mutation in these co-morbid disorders. Further studies are now required to determine the functional consequence of these novel mutations to development of FSGS and heart block in this pedigree and to determine whether these mutations have implications for more common forms of these diseases in the general population.
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2,333,826 |
Preventing congenital neonatal heart block in offspring of mothers with anti-SSA/Ro and SSB/La antibodies: a review of published literature and registered clinical trials.
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Offspring of women with anti-SSA/Ro-SSB/La antibodies are believed to be at risk for congenital heart block (CHB). Whether this risk can be reduced, and what constitutes standard of care treatment is, however, unclear. The objective of this review therefore was to determine whether currently proposed standard of care treatments to avoid CHB in offspring of mothers at risk are evidence-based. To do so, we conducted a review of the literature under appropriate keywords and phrases in Medline/PubMed and Google Scholar for the years 2000-2013. Reference lists were further reviewed, and relevant manuscripts were pulled. We also reviewed www.clinicaltrials.gov for registered studies. In the absence of randomized prospective clinical trials, a meta-analysis was not feasible. We, therefore, reviewed lower evidence level studies individually. Risk of CHB actually appears more closely associated with general autoimmunity than, specifically, with SSA/Ro-SSB/La antibodies. This and other observations raise questions whether CHB is caused by passively transferred maternal autoimmunity, as is currently widely believed. Observational studies suggest the possible effectiveness of intravenous gamma globulin (IV-Ig) and hydroxychloroquine (Plaquenil) in reducing CHB-risk. Evidence for both is, however, inconclusive, and studies are biased in favor of hydroxychloroquine and against IV-Ig. Based on the review of the literature, current evidence of effectiveness for any treatment has to be judged as insufficient. Among the available treatment options, some considerations favor IV-Ig over hydroxychloroquine or, alternatively, suggest treatment with IV-Ig periconceptionally and into early gestation, with hydroxychloroquine added or replacing IV-Ig at approximately 10weeks gestational age. Benefits for the utilization of steroid drugs are unclear. Since no treatment can be considered as established, prevention of CHB in offspring should be considered experimental, and performed under appropriate study conditions.
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2,333,827 |
Suppression of cardiac alternans by alternating-period-feedback stimulations.
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Alternans response, comprising a sequence of alternating long and short action potential durations in heart tissue, seen during rapid periodic pacing can lead to conduction block resulting in potentially fatal cardiac failure. A method of pacing with feedback control is proposed to reduce the alternans and therefore the probability of subsequent cardiac failure. The reduction is achieved by feedback control using small perturbations of constant magnitude to the original, alternans-generating pacing period T, viz., using sequences of two alternating periods of T+ΔT and T-ΔT, with ΔT<<T. Such a control scheme for alternans suppression is demonstrated experimentally in isolated whole heart experiments. This alternans suppression scheme is further confirmed and investigated in detail by simulations of ion-channel-based cardiac models both for a single cell and in one-dimensional spatially extended systems. The mechanism of the success of our method can be understood in terms of dynamics in phase space, viz., as the state of activity of the cell being confined within a narrow volume of phase space for the duration of control, resulting in extremely diminished variation in successive action potential durations. Our method is much more robust to noise than previous alternans reduction techniques based on fixed point stabilization and should thus be more efficient in terms of experimental implementation, which has implications for clinical treatment for arrhythmia.
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2,333,828 |
Perinatal bisphenol A exposure and adult glucose homeostasis: identifying critical windows of exposure.
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Bisphenol A (BPA) is a widespread endocrine-disrupting chemical used as the building block for polycarbonate plastics. Epidemiological evidence has correlated BPA exposure with higher risk of heart disease and type 2 diabetes. However, it remains unknown whether there are critical windows of susceptibility to BPA exposure on the development of dysglycemia. This study was an attempt to investigate the critical windows and the long-term consequences of perinatal exposure to BPA on glucose homeostasis. Pregnant mice were given either vehicle or BPA (100 µg/kg/day) at different time of perinatal stage: 1) on days 1-6 of pregnancy (P1-P6, preimplantation exposure); 2) from day 6 of pregnancy until postnatal day (PND) 0 (P6-PND0, fetal exposure); 3) from lactation until weaning (PND0-PND21, neonatal exposure); and 4) from day 6 of gestation until weaning (P6-PND21, fetal and neonatal exposure). At 3, 6 and 8 months of age, offspring in each group were challenged with glucose and insulin tolerance tests. Then islet morphometry and β-cell function were measured. The glucose homeostasis was impaired in P6-PND0 mice from 3 to 6 months of age, and this continued to 8 months in males, but not females. While in PND0-PND21 and P6-PND21 BPA-treated groups, only the 3-month-old male offspring developed glucose intolerance. Moreover, at the age of 3 months, perinatal exposure to BPA resulted in the increase of β-cell mass mainly due to the coordinate changes in cell replication, neogenesis, and apoptosis. The alterations of insulin secretion and insulin sensitivity, rather than β-cell mass, were consistent with the development of glucose intolerance. Our findings suggest that BPA may contribute to metabolic disorders relevant to glucose homeostasis and the effects of BPA were dose, sex, and time-dependent. Fetal development stage may be the critical window of susceptibility to BPA exposure.
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2,333,829 |
Population trends and variation in body mass index from 1971 to 2008 in the Framingham Heart Study Offspring Cohort.
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We examined body mass index (BMI) across place and time to determine the pattern of BMI mean and standard deviation trajectories.</AbstractText>We included participants in the Framingham Heart Study (FHS) Offspring Cohort over eight waves of follow-up, from 1971 to 2008. After exclusions, the final sample size was 4569 subjects with 28,625 observations. We used multi-level models to examine population means and variation at the individual and neighborhood (census tracts) levels across time with measured BMI as the outcome, controlling for individual demographics and behaviors and neighborhood poverty. Because neighborhoods accounted for limited BMI variance, we removed this level as a source of variation in final models. We examined sex-stratified models with all subjects and models stratified by sex and baseline weight classification.</AbstractText>Mean BMI increased from 24.0 kg/m(2) at Wave 1 to 27.7 at Wave 8 for women and from 26.6 kg/m(2) to 29.0 for men. In final models, BMI variation also increased from Waves 1 to 8, with the standard deviation increasing from 4.18 kg/m(2) to 6.15 for women and 3.31 kg/m(2) to 4.73 for men. BMI means increased in parallel across most baseline BMI weight classifications, except for more rapid increases through middle-age for obese women followed by declines in the last wave. BMI standard deviations also increased in parallel across baseline BMI classifications for women, with greater divergence of BMI variance for obese men compared to other weight classifications.</AbstractText>Over nearly 40 years, BMI mean and variation increased in parallel across most baseline weight classifications in our sample. Individual-level characteristics, especially baseline BMI, were the primary factors in rising BMI. These findings have important implications not only for understanding the sources of the obesity epidemic in the United States but also for the targeting of interventions to address the epidemic.</AbstractText>
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2,333,830 |
Prostaglandins and prostaglandin receptor antagonism in migraine.
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Human models of headache may contribute to understanding of prostaglandins' role in migraine pathogenesis. The current thesis investigated the migraine triggering effect of prostaglandin E2 (PGE2) in migraine patients without aura, the efficacy of a novel EP4 receptor antagonist, BGC20-1531, in prevention of PGE2-induced headache and the ability of prostaglandin F2α (PGF2α) to trigger headache without any vasodilatation in healthy volunteers. All studies were designed as double-blind, placebo-controlled, cross-over experiments, where PGE2/PGF2α or saline were infused over 20-25 min. In the study with EP4 receptor antagonist healthy volunteers were pre-treated with two different doses of BGC20-1531 or placebo followed by PGE2 infusion over 25 min. The headache data were collected during the whole study day, whereas the possible vascular changes were measured during the in-hospital phase of 1.5 h. The infusion of PGE2 caused the immediate migraine-like attacks and vasodilatation of the middle cerebral artery in migraine patients without aura. The highly specific and potent EP4 receptor antagonist, BGC20-1531, was not able to attenuate PGE2-induced headache and vasodilatation of both intra- and extra-cerebral arteries. The intravenous infusion of PGF2α did not induce headache or statistically significant vasoconstriction of cerebral arteries in healthy volunteers. Novel data on PGE2-provoked immediate migraine-like attacks suggest that PGE2 may be one of the important final products in the pathogenesis of migraine. The lack of efficacy of EP4 receptor antagonist suggests that a single receptor blockade is not sufficient to block PGE2 responses, hence EP2 receptor should be investigated as a potential drug target for the treatment of migraine. The absence of headache during the PGF2α infusion demonstrates that vasodilating properties are necessary for the induction of headache and migraine.
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2,333,831 |
Acute and subacute effects of the selective serotonin-noradrenaline reuptake inhibitor duloxetine on cardiac hERG channels.
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Duloxetine is a selective serotonin-noradrenaline reuptake inhibitor approved for treatment of major depressive disorder. So far, duloxetine has been found to be well tolerated and reported cardiac side effects were negligible. However, pharmacological effects on cardiac hERG channels have not been properly addressed yet. hERG channels were expressed in Xenopus oocytes and a human embryonic kidney (HEK) cell line. Currents were measured using voltage clamp and patch clamp techniques. Channel surface expression was quantified using Western blot analysis. We found that duloxetine inhibits heterologously expressed hERG channels in a concentration-dependent manner, yielding an IC50 of 142.8 μM in Xenopus oocytes. Inhibitory effects were even more pronounced when using a mammalian cell line resulting in a 34 or 59% current decrease by 10 or 30 μM duloxetine, respectively. Duloxetine did not affect channel activation or inactivation kinetics. However, channel deactivation was accelerated by duloxetine. We further showed that inhibition occurs in the open and inactivated, but not closed, states. There was no frequency dependence of block. However, effects of duloxetine were significantly attenuated when using the hERG pore mutants Y652A and F656A. Subacute effects of duloxetine on hERG channel expression were analyzed using the Western blot technique. We found that incubation with duloxetine results in a concentration-dependent decrease of channel surface expression. Whereas inhibitory effects of duloxetine seem negligible under therapeutically relevant concentrations, hERG block should be considered in cases of duloxetine overdose and when administering duloxetine to patients susceptible to drug-induced QT prolongation.
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2,333,832 |
Efficient transduction of human hematopoietic repopulating cells with a chimeric HIV1-based vector including SIV capsid.
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Innate immune factors, such as TRIM5α and cyclophilin A (CypA), act as a major restriction factor of retroviral infection among species. When HIV1 infects human cells, HIV1 capsid binds to human CypA to escape from human TRIM5α restriction. However, in rhesus cells, the mismatch between HIV1 capsid and rhesus CypA is recognized by rhesus TRIM5α to reduce HIV1 infectivity through proteasomal degradation. To circumvent this block, we previously developed a chimeric HIV1 vector (χHIV) that substituted HIV1 capsid with SIV capsid, and it significantly increased transduction efficiency for nonhuman primate cells. In this study, we evaluated whether the χHIV vector efficiently transduces human cells, and the transduction efficiency might increase by a CypA inhibitor (cyclosporine) and a proteasome inhibitor (MG132). The χHIV vector could transduce human CD34⁺ cells, as efficiently as the HIV1 vector, in vitro and in xenograft mice, even in the mismatch between SIV capsid and human CypA. Cyclosporine decreased transduction efficiency with the HIV1 vector, whereas it slightly increased transduction efficiency with the χHIV vector in human CD34⁺ cells. MG132 increased transduction efficiency with both χHIV and HIV1 vectors in the same manner. However, MG132 was toxic to human CD34⁺ cells at high concentrations, and both drugs had a small range of effective dosage. These findings demonstrate that both χHIV and HIV1 vectors have similar transduction efficiency for human hematopoietic repopulating cells, suggesting that the χHIV vector escapes from TRIM5α restriction, which is independent of human CypA.
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2,333,833 |
Peptides and peptide-derived molecules targeting the intracellular domains of Cx43: gap junctions versus hemichannels.
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About a decade ago, the molecular determinants controlling the opening and closing of Cx43 gap junction channels have been identified. Advanced biophysical approaches revealed a critical role for structural rearrangements in the cytoplasmic loop and dimerization of the C-terminal tail, resulting in binding of the C-terminal tail to the cytoplasmic loop and Cx43 gap junction channel closure during cellular acidosis. This has spurred the development of Cx43-mimetic peptides and peptidomimetics that interfere with these loop/tail interactions, thereby preventing the closure of Cx43 gap junctions, e.g. in the heart upon ischemia. Recently, we found that loop/tail interactions control Cx43-hemichannel activity but with an opposite effect. Binding of the C-terminal tail to the cytoplasmic loop is a requisite for the opening of Cx43 hemichannels in response to different stimuli, like decreased extracellular [Ca2+], increased intracellular [Ca2+], positive membrane potentials or ischemia. Strikingly, peptides that favor the open state of Cx43 gap junctions like the L2 peptide inhibit Cx43-hemichannel opening. These tools now provide unprecedented opportunities to selectively inhibit Cx43 hemichannels while maintaining Cx43 gap junction communication, impossible to achieve with siRNA or knockdown approaches both affecting gap junctions and hemichannels. These tools not only are very helpful to unravel the role of Cx43 hemichannels in complex biological systems, but also hold therapeutic potential to counteract excessive Cx43-hemichannel activity like in ischemia/reperfusion in the brain and the heart or to prevent Cx43 hemichannel-mediated gliotransmitter release in the basal amygdala during memory consolidation in response to emotional events. This article is part of the Special Issue Section entitled 'Current Pharmacology of Gap Junction Channels and Hemichannels'.
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2,333,834 |
Heart rate responses to temperature in free-swimming Pacific bluefin tuna (Thunnus orientalis).
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The bluefin tuna heart remains at ambient water temperature (Ta) but must supply blood to warm regions of the body served by countercurrent vascular heat exchangers. Despite this unusual physiology, inherent difficulties have precluded an understanding of the cardiovascular responses to Ta in free-swimming bluefin tunas. We measured the heart rate (f(H)) responses of two captive Pacific bluefin tunas (Thunnus orientalis; 9.7 and 13.3 kg) over a cumulative period of 40 days. Routine f(H) during fasting in the holding tank at a Ta of 20°C was 45.1±8.0 and 40.7±6.5 beats min(-1) for Tuna 1 and Tuna 2, respectively. f(H) decreased in each fish with a Q10 temperature coefficient of 2.6 (Tuna 1) and 3.1 (Tuna 2) as Ta in the tank was slowly decreased to 15°C (~0.4°C h(-1)), despite a gradual increase in swimming speed. The same thermal challenge during digestion revealed similar thermal dependence of f(H) and indicated that the rate of visceral cooling is not buffered by the heat increment of feeding. Acutely decreasing Ta from 20 to 10°C while Tuna 1 swam in a tunnel respirometer caused a progressive increase in tail-beat frequency and oxygen consumption rate (M(O2)). f(H) of this fish decreased with a Q10 of 2.7 as Ta decreased between 20 and 15°C, while further cooling to 10°C saw a general plateau in f(H) around 35 beats min(-1) with a Q10 of 1.3. A discussion of the relationships between f(H), and haemoglobin-oxygen binding sheds further light on how bluefin cardiorespiratory systems function in a changing thermal environment.
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2,333,835 |
Maternal and neonatal outcomes in pregnancies complicated by systemic lupus erythematosus: a population-based study.<Pagination><StartPage>323</StartPage><EndPage>328</EndPage><MedlinePgn>323-328</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/S1701-2163(15)30959-2</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S1701-2163(15)30959-2</ELocationID><Abstract><AbstractText Label="OBJECTIVE" NlmCategory="OBJECTIVE">To determine maternal and neonatal outcomes in pregnancies complicated by systemic lupus erythematosus (SLE).</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">In a retrospective cohort study using the Nova Scotia Atlee Perinatal Database, 97 pregnancies in women with SLE, with 99 live births, were compared with 211 355 pregnancies in women without SLE and their 214 115 babies. All were delivered in Nova Scotia between 1988 and 2008.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">In women with SLE, gestational age at birth and mean neonatal birth weight were lower (P < 0.001) than in women without SLE. On bivariate analysis, severe preeclampsia, Caesarean section, newborn resuscitation for > 3 minutes, respiratory distress syndrome, assisted ventilation, bronchopulmonary dysplasia, patent ductus arteriosus, mild to moderate intraventricular hemorrhage, retinopathy of prematurity, and congenital heart block in neonates were significantly more frequent in the women with SLE. Logistic regression analysis identified that having SLE increased the risks of Caesarean section (OR 1.8; 95% CI 1.1 to 2.8, P = 0.005), postpartum hemorrhage (OR 2.4; 95% CI 1.3 to 4.3, P = 0.003), need for blood transfusion (OR 6.9; 95% CI 2.7 to 17, P = 0.001), postpartum fever (OR 3.2; 95% CI 1.7 to 6.1, P = 0.032), small for gestational age babies (OR 1.7; 95% CI 1.005 to 2.9, P = 0.047), and gestational age ≤ 37 weeks (OR 2.1; 95% CI 1.3 to 3.4, P = 0.001). Neonatal death was not shown to be more common in women with SLE (RR 3.05; CI 0.43 to 21.44, P = 0.28).</AbstractText><AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">Mothers with SLE have an increased risk of Caesarean section, postpartum hemorrhage, and blood transfusion. They are more likely to deliver premature babies, smaller babies, and babies with congenital heart block.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Nili</LastName><ForeName>Firouzeh</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Department of Pediatrics, Tehran University of Medical Sciences, Tehran, Iran.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>McLeod</LastName><ForeName>Lynne</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Obstetrics and Gynecology, Dalhousie University, Halifax NS.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>O'Connell</LastName><ForeName>Colleen</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Perinatal Epidemiology Research Unit, Dalhousie University, Halifax NS.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sutton</LastName><ForeName>Evelyn</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine, Dalhousie University, Halifax NS.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>McMillan</LastName><ForeName>Douglas</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Department of Pediatrics, Dalhousie University, Halifax NS.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>J Obstet Gynaecol Can</MedlineTA><NlmUniqueID>101126664</NlmUniqueID><ISSNLinking>1701-2163</ISSNLinking></MedlineJournalInfo><SupplMeshList><SupplMeshName Type="Disease" UI="C535758">Congenital heart block</SupplMeshName></SupplMeshList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001724" MajorTopicYN="N">Birth Weight</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001803" MajorTopicYN="N">Blood Transfusion</DescriptorName><QualifierName UI="Q000706" MajorTopicYN="N">statistics & numerical data</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001997" MajorTopicYN="N">Bronchopulmonary Dysplasia</DescriptorName><QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002585" MajorTopicYN="N">Cesarean Section</DescriptorName><QualifierName UI="Q000706" MajorTopicYN="N">statistics & numerical data</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004374" MajorTopicYN="N">Ductus Arteriosus, Patent</DescriptorName><QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005865" MajorTopicYN="N">Gestational Age</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006327" MajorTopicYN="N">Heart Block</DescriptorName><QualifierName UI="Q000151" MajorTopicYN="N">congenital</QualifierName><QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007231" MajorTopicYN="N">Infant, Newborn</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007234" MajorTopicYN="N">Infant, Premature</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007235" MajorTopicYN="N">Infant, Premature, Diseases</DescriptorName><QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007236" MajorTopicYN="N">Infant, Small for Gestational Age</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008180" MajorTopicYN="N">Lupus Erythematosus, Systemic</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="Y">complications</QualifierName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009674" MajorTopicYN="N" Type="Geographic">Nova Scotia</DescriptorName><QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006473" MajorTopicYN="N">Postpartum Hemorrhage</DescriptorName><QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011225" MajorTopicYN="N">Pre-Eclampsia</DescriptorName><QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011247" MajorTopicYN="N">Pregnancy</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011248" MajorTopicYN="N">Pregnancy Complications</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="Y">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012127" MajorTopicYN="N">Respiratory Distress Syndrome, Newborn</DescriptorName><QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012178" MajorTopicYN="N">Retinopathy of Prematurity</DescriptorName><QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName></MeshHeading></MeshHeadingList><OtherAbstract Type="Publisher" Language="fre"><AbstractText>Objectif : Déterminer les issues maternelles et néonatales dans les cas de grossesse compliquée par le lupus érythémateux disséminé (LED). Méthodes : Dans le cadre d’une étude de cohorte rétrospective menée au moyen de la Nova Scotia Atlee Perinatal Database, 97 grossesses chez des femmes présentant le LED (ayant donné lieu à 99 naissances vivantes) ont été comparées à 211 355 grossesses chez des femmes ne présentant pas le LED (ayant donné lieu à 214 115 naissances vivantes). Toutes ces femmes ont accouché en Nouvelle-Écosse entre 1988 et 2008. Résultats : Chez les femmes présentant le LED, l’âge gestationnel à la naissance et le poids de naissance moyen étaient inférieurs (P < 0,001) à ceux qui ont été constatés chez les femmes ne présentant pas le LED. Dans le cadre de l’analyse bivariée, nous avons constaté que la prééclampsie grave, la césarienne, la réanimation néonatale menée pendant > 3 minutes, le syndrome de détresse respiratoire, la ventilation assistée, la dysplasie bronchopulmonaire, la persistance du canal artériel, l’hémorragie intraventriculaire allant de légère à modérée, la rétinopathie des prématurés et le bloc cardiaque congénital chez les nouveau-nés étaient considérablement plus fréquents chez les femmes présentant le LED. L’analyse par régression logistique a déterminé que le fait de présenter le LED entraînait une hausse des risques de césarienne (RC, 1,8; IC à 95 %, 1,1 - 2,8, P = 0,005), d’hémorragie postpartum (RC, 2,4; IC à 95 %, 1,3 - 4,3, P = 0,003), de voir une transfusion sanguine s’avérer nécessaire (RC, 6,9; IC à 95 %, 2,7 - 17, P = 0,001), de fièvre puerpérale (RC, 3,2; IC à 95 %, 1,7 - 6,1, P = 0,032), d’hypotrophie fœtale (RC, 1,7; IC à 95 %, 1,005 - 2,9, P = 0,047) et de constater un âge gestationnel ≤ 37 semaines (RC, 2,1; IC à 95 %, 1,3 - 3,4, P = 0,001). Il n’a pas été démontré que le décès néonatal était plus courant chez les femmes présentant le LED (RR, 3,05; IC 0,43 - 21,44, P = 0,28). Conclusion : Les mères présentant le LED sont exposées à un risque accru de césarienne, d’hémorragie postpartum et de transfusion sanguine. Elles sont plus susceptibles d’accoucher d’enfants prématurés, plus petits que la normale et présentant un bloc cardiaque congénital.</AbstractText></OtherAbstract><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">newborn</Keyword><Keyword MajorTopicYN="N">outcome</Keyword><Keyword MajorTopicYN="N">pregnancy</Keyword><Keyword MajorTopicYN="N">systemic lupus erythematosus</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2013</Year><Month>5</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2013</Year><Month>5</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2013</Year><Month>7</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">23660039</ArticleId><ArticleId IdType="doi">10.1016/S1701-2163(15)30959-2</ArticleId><ArticleId IdType="pii">S1701-2163(15)30959-2</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">23656914</PMID><DateRevised><Year>2019</Year><Month>11</Month><Day>20</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1558-2035</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2013</Year><Month>May</Month><Day>07</Day></PubDate></JournalIssue><Title>Journal of cardiovascular medicine (Hagerstown, Md.)</Title><ISOAbbreviation>J Cardiovasc Med (Hagerstown)</ISOAbbreviation></Journal>Left ventricular function and right ventricular pacing for isolated congenital heart block.
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Objectif : Déterminer les issues maternelles et néonatales dans les cas de grossesse compliquée par le lupus érythémateux disséminé (LED). Méthodes : Dans le cadre d’une étude de cohorte rétrospective menée au moyen de la Nova Scotia Atlee Perinatal Database, 97 grossesses chez des femmes présentant le LED (ayant donné lieu à 99 naissances vivantes) ont été comparées à 211 355 grossesses chez des femmes ne présentant pas le LED (ayant donné lieu à 214 115 naissances vivantes). Toutes ces femmes ont accouché en Nouvelle-Écosse entre 1988 et 2008. Résultats : Chez les femmes présentant le LED, l’âge gestationnel à la naissance et le poids de naissance moyen étaient inférieurs (P < 0,001) à ceux qui ont été constatés chez les femmes ne présentant pas le LED. Dans le cadre de l’analyse bivariée, nous avons constaté que la prééclampsie grave, la césarienne, la réanimation néonatale menée pendant > 3 minutes, le syndrome de détresse respiratoire, la ventilation assistée, la dysplasie bronchopulmonaire, la persistance du canal artériel, l’hémorragie intraventriculaire allant de légère à modérée, la rétinopathie des prématurés et le bloc cardiaque congénital chez les nouveau-nés étaient considérablement plus fréquents chez les femmes présentant le LED. L’analyse par régression logistique a déterminé que le fait de présenter le LED entraînait une hausse des risques de césarienne (RC, 1,8; IC à 95 %, 1,1 - 2,8, P = 0,005), d’hémorragie postpartum (RC, 2,4; IC à 95 %, 1,3 - 4,3, P = 0,003), de voir une transfusion sanguine s’avérer nécessaire (RC, 6,9; IC à 95 %, 2,7 - 17, P = 0,001), de fièvre puerpérale (RC, 3,2; IC à 95 %, 1,7 - 6,1, P = 0,032), d’hypotrophie fœtale (RC, 1,7; IC à 95 %, 1,005 - 2,9, P = 0,047) et de constater un âge gestationnel ≤ 37 semaines (RC, 2,1; IC à 95 %, 1,3 - 3,4, P = 0,001). Il n’a pas été démontré que le décès néonatal était plus courant chez les femmes présentant le LED (RR, 3,05; IC 0,43 - 21,44, P = 0,28). Conclusion : Les mères présentant le LED sont exposées à un risque accru de césarienne, d’hémorragie postpartum et de transfusion sanguine. Elles sont plus susceptibles d’accoucher d’enfants prématurés, plus petits que la normale et présentant un bloc cardiaque congénital.</OtherAbstract><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">newborn</Keyword><Keyword MajorTopicYN="N">outcome</Keyword><Keyword MajorTopicYN="N">pregnancy</Keyword><Keyword MajorTopicYN="N">systemic lupus erythematosus</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2013</Year><Month>5</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2013</Year><Month>5</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2013</Year><Month>7</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">23660039</ArticleId><ArticleId IdType="doi">10.1016/S1701-2163(15)30959-2</ArticleId><ArticleId IdType="pii">S1701-2163(15)30959-2</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">23656914</PMID><DateRevised><Year>2019</Year><Month>11</Month><Day>20</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1558-2035</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2013</Year><Month>May</Month><Day>07</Day></PubDate></JournalIssue><Title>Journal of cardiovascular medicine (Hagerstown, Md.)</Title><ISOAbbreviation>J Cardiovasc Med (Hagerstown)</ISOAbbreviation></Journal><ArticleTitle>Left ventricular function and right ventricular pacing for isolated congenital heart block.</ArticleTitle><Pagination><MedlinePgn/></Pagination><Abstract>BACKGROUND: Right ventricular pacing has been the treatment of choice in patients with congenital complete atrioventricular block (CAVB). However, the effect of chronic right ventricular pacing on left ventricular function in young patients is still controversial. AIM: The aim of the study was to assess the change in left ventricular systolic function in young patients (age ≤20 years) paced for isolated CAVB and to identify possible predictors of left ventricular systolic dysfunction. METHODS: We studied 55 young patients who underwent permanent right ventricular pacemaker implantation for CAVB in the absence of significant structural heart disease. We excluded patients affected by any condition known to affect left ventricular function. Echocardiographic data prior to and after pacemaker implantation were obtained. RESULTS: The mean age at the time of pacemaker implantation was 20 months, range 2.3-72 months. The mean duration of follow-up was 94.86 (range: 2-268 months). Chronic right ventricular pacing affected left ventricular shortening fraction (LVSF) significantly (pre = 37.8 ± 7.8 vs. post = 32.8 ± 5.5%, P = 0.0036). In 14 patients (25.4%), LVSF decreased by at least 7% (group A). The only parameter studied able to significantly discriminate the two groups was a better baseline LVSF in group A (baseline LVSF: 42.1 ± 5.2 vs. 32.2 ± 2.2%, P = 0.019; cut-off value >39%, P <0.0001; area under the curve = 0.887). CONCLUSION: Chronic right ventricular pacing in young patients without significant structural heart disease is responsible for a significant reduction in left ventricular systolic function, especially in patients with a good baseline LVSF. These patients need close follow-up not only for pacing parameters but also for left ventricular functional evaluation.
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2,333,836 |
Effects of cholesteryl ester transfer protein inhibitors on human lipoprotein metabolism: why have they failed in lowering coronary heart disease risk?
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To examine the recent advances in our knowledge of cholesteryl ester transfer protein (CETP) inhibitors, heart disease risk reduction, and human lipoprotein metabolism.</AbstractText>CETP inhibitors block the transfer of cholesteryl ester from HDLs to triglyceride-rich lipoproteins (TRLs), thereby raising HDL cholesterol and lowering TRL cholesterol, and in some cases LDL cholesterol. Two CETP inhibitors, dalcetrapib and torcetrapib, have been tested in large clinical trials in statin-treated coronary heart disease patients and have shown no clinical benefit compared to placebo. Anacetrapib and evacetrapib, two potent CETP inhibitors, are now being tested in large clinical trials. Torcetrapib has been shown to decrease the fractional catabolic rate (FCR) of HDL apolipoproteins (apo) A-I and A-II, enhance the FCR of TRL apoB-100 and apoE, and decrease TRL apoB-48 production, but has no significant effects on fecal cholesterol excretion in humans. Anacetrapib also delays the FCR of HDL apoA-I.</AbstractText>CETP inhibitors form a complex between themselves, CETP, and HDL particles, which may interfere with the many physiologic functions of HDL, including reverse cholesterol transport. Available data would suggest that CETP inhibitors will fail as lipid-altering medications to reduce coronary heart disease risk because of interference with normal human HDL metabolism.</AbstractText>
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2,333,837 |
Variability in high-throughput ion-channel screening data and consequences for cardiac safety assessment.
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Unwanted drug interactions with ionic currents in the heart can lead to an increased pro-arrhythmic risk to patients in the clinic. It is therefore a priority for safety pharmacology teams to detect block of cardiac ion channels, and new technologies have enabled the development of automated and high-throughput screening assays using cell lines. As a result of screening multiple ion-channels there is a need to integrate information, particularly for compounds affecting more than one current, and mathematical electrophysiology in-silico action potential models are beginning to be used for this.</AbstractText>We quantified the variability associated with concentration-effect curves fitted to recordings from high-throughput Molecular Devices IonWorks® Quattro™ screens when detecting block of I(Kr) (hERG), I(Na) (NaV1.5), I(CaL) (CaV1.2), I(Ks) (KCNQ1/minK) and I(to) (Kv4.3/KChIP2.2), and the Molecular Devices FLIPR® Tetra fluorescence screen for I(CaL) (CaV1.2), for control compounds used at AstraZeneca and GlaxoSmithKline. We examined how screening variability propagates through in-silico action potential models for whole cell electrical behaviour, and how confidence intervals on model predictions can be estimated with repeated simulations.</AbstractText>There are significant levels of variability associated with high-throughput ion channel electrophysiology screens. This variability is of a similar magnitude for different cardiac ion currents and different compounds. Uncertainty in the Hill coefficients of reported concentration-effect curves is particularly high. Depending on a compound's ion channel blocking profile, the uncertainty introduced into whole-cell predictions can become significant.</AbstractText>Our technique allows confidence intervals to be placed on computational model predictions that are based on high-throughput ion channel screens. This allows us to suggest when repeated screens should be performed to reduce uncertainty in a compound's action to acceptable levels, to allow a meaningful interpretation of the data.</AbstractText>Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.</CopyrightInformation>
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2,333,838 |
[Effect of electroacupuncture combined with cervical plexus block on stress responses in patients undergoing thyroid surgery].
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To observe the effect of electroacupuncture (EA) combined with cervical plexus block (CPB) on the stress response of patients undergoing thyroid surgery.</AbstractText>Forty thyroidectomy patients were randomly divided into sham EA plus CPB group (sham group) and EA+CPB group (20 cases in each group). For patients of the sham group, deep cervical plexus block (25% ropivacaine hydrochloride + 1% lidocaine hydrochloride) was performed first, followed by inserting acupuncture needles into bilateral Hegu (LI 4) and Neiguan (PC 6) separately without needle manipulation and then connecting the output wires of the EA therapeutic instrument to the handles of the acupuncture needles but without electric current output. For patients of the EA+CPB group, deep cervical plexus block was performed first followed by EA stimulation [10 Hz, (6 +/- 2) mA] of the bilateral LI 4 and PC 6 for 20 min. Systolic blood pressure (SBP), heart rate (HR) and breathing frequency were detected using a multipurpose monitor. Plasma adrenocorticotropic hormone (ACTH) and cortisol (Cor) contents were determined using chemiluminescence method, plasma epinephrine (E) level was detected by enzyme-linked immunosorbent assay, glucose (Glu) assayed by oxidase method, and plasma C-reactive protein (CRP) level detected using immumofluorescence technique.</AbstractText>(1) During surgery, the patients' SBP and HR of both sham and EA groups were increased significantly compared with their basic values (P < 0.05), but the levels of the increased SBP and HR of the EA group were obviously lower than those of the sham group (P < 0.05). (2) The levels of plasma ACTH during surgery and at the immediate time after surgery, Cor level at the immediate time after surgery, plasma E and Glu contents during surgery, at the immediate time and on day 1 after surgery, and plasma CRP at the immediate time, and on day 1 and 3 after surgery in the sham group were upregulated considerably (P < 0.05), while the levels of plasma ACTH, Cor, E, Glu and CRP in the above-mentioned time-points of the EA group were all remarkably lower than those of the sham group (P < 0.05).</AbstractText>EA combined with cervical plexus block significantly reduces peri-operative cardiovascular stress responses and inhibits abnormal increases of plasma stress hormones and inflammatory reaction in patients undergoing thyroid surgery.</AbstractText>
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2,333,839 |
Quantitative MUC5AC and MUC6 mucin estimations in gastric mucus by a least-squares minimization method.
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We have determined the molar proportions of the MUC5AC and MUC6 mucus glycoproteins (mucins) in mucus from the normal and pathological human gastric antrum using a least-squares minimization analysis applied to amino acid compositions. We noted that the content of MUC5AC mucin in mucus from individuals without gastroduodenal disease was very high, suggesting that the integrity and barrier properties of the adherent gastric mucus layer are normally maintained by building-block structures formed from this mucin alone. We observed that the molar content of MUC6 mucin doubled (without significance) in mucus from patients with duodenal ulcer, and increased five times (with high significance) in mucus from patients with gastric ulcer, when compared with that in mucus from individuals without gastroduodenal disease.
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2,333,840 |
Percutaneous autonomic neural modulation: a novel technique to treat cardiac arrhythmia.
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Ablation and anti-arrhythmic medications have shown promise but have been met with varying success and unwanted side effects such as myocardial injury, arrhythmias, and morbidity from invasive surgical intervention. The answer to improving efficacy of ablation may include modulation of the cardiac aspect of the autonomic nervous system. Our lab has developed a novel approach and device to navigate the oblique sinus and to use DC current and saline/alcohol irrigation to selectively stimulate and block the autonomic ganglia found on the epicardial side of the heart. This novel approach minimizes myocardial damage from thermal injury and provides a less invasive and targeted approach. For feasibility, proof-of-concept, and safety monitoring, we carried out canine studies to test this novel application. Our results suggest a safer and less invasive way of modulating arrhythmogenic substrate that may lead to improved treatment of AF in humans.
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2,333,841 |
Ion pumps as biological targets for decavanadate.
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The putative applications of poly-, oligo- and mono-oxometalates in biochemistry, biology, pharmacology and medicine are rapidly attracting interest. In particular, these compounds may act as potent ion pump inhibitors and have the potential to play a role in the treatment of e.g. ulcers, cancer and ischemic heart disease. However, the mechanism of action is not completely understood in most cases, and even remains largely unknown in other cases. In the present review we discuss the most recent insights into the interaction between mono- and polyoxometalate ions with ion pumps, with particular focus on the interaction of decavanadate with Ca(2+)-ATPase. We also compare the proposed mode of action with those of established ion pump inhibitors which are currently in therapeutic use. Of the 18 classes of compounds which are known to act as ion pump inhibitors, the complete mechanism of inhibition is only known for a handful. It has, however, been established that most ion pump inhibitors bind mainly to the E2 ion pump conformation within the membrane domain from the extracellular side and block the cation release. Polyoxometalates such as decavanadate, in contrast, interact with Ca(2+)-ATPase near the nucleotide binding site domain or at a pocket involving several cytoplasmic domains, and therefore need to cross through the membrane bilayer. In contrast to monomeric vanadate, which only binds to the E2 conformation, decavanadate binds to all protein conformations, i.e. E1, E1P, E2 and E2P. Moreover, the specific interaction of decavanadate with sarcoplasmic reticulum Ca(2+)-ATPase has been shown to be non-competitive with respect to ATP and induces protein cysteine oxidation with concomitant vanadium reduction which might explain the high inhibitory capacity of V10 (IC50 = 15 μM) which is quite similar to the majority of the established therapeutic drugs.
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2,333,842 |
A comparative study of hemodynamic changes between prone and supine emergence from anesthesia in lumbar disc surgery.
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Supine emergence from anesthesia in patients undergoing lumbar surgery in prone position leads to tachycardia, hypertension, coughing, laryngospasm and loss of monitoring as the patients are rolled back to supine position at the end of surgery. The prone extubation might facilitate a smoother emergence because the patients are not disturbed during emergence and secretions are drained away from patient's airway.</AbstractText>The patients were randomly allocated to one of the two groups of 30 each at conclusion of surgery. First group was extubated in prone position and second in supine position at conclusion of surgery. Supine group patients were rolled back and prone group patients were left undisturbed. Extubation was done after complete reversal of neuromuscular block. Heart rates (HR), mean arterial pressure (MAP) were noted at various points of time. Coughing, laryngospasm, vomiting, monitor disconnection if any were also noted.</AbstractText>During emergence from anesthesia heart rate was significantly more in group S than group P at all intervals (P < 0.001). Mean arterial pressure was significantly higher in the supine group at 2, 3, and 4 min compared to prone group (P = 0.003). Compared to supine patients, prone patients had fewer incidences of coughing (P = 0. 0004), laryngospasm, vomiting and monitor disconnection.</AbstractText>In healthy normotensive patients, emergence from anesthesia in the prone position is associated with minimal hemodynamic change, and fewer incidences of coughing, laryngospasm, and monitor disconnections.</AbstractText>
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2,333,843 |
Intraoperative conditions and quality of postoperative analgesia after adding dexmedetomidine to epidural bupivacaine and fentanyl in elective cesarean section using combined spinal-epidural anesthesia.
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This study was designed to evaluate the effect of adding dexmedetomidine to regular mixture of epidural drugs for pregnant women undergoing elective cesarean section with special emphasis on their sedative properties, ability to improve quality of intraoperative, postoperative analgesia, and neonatal outcome.</AbstractText>Fifty women of ASA physical status I or II at term pregnancy were enrolled randomly to receive plain bupivacaine plus fentanyl (BF Group) or plain bupivacaine plus mixture of fentanyl and dexmedetomidine (DBF Group). Incidence of hypotension, bradycardia, Apgar scores, intraoperative pain assessment, onset of postoperative pain, sedation scores, and side effects were recorded.</AbstractText>No difference in the times taken for block to reach T4 sensory level, to reach the highest level of sensory block, and interval between first neuraxial injection and onset of surgery between the groups was noted. Onset of postoperative pain was significantly delayed in the DBF group (P = 0.001), the need for supplementary fentanyl was significantly less in DBF group (P = 0.03), no significant difference was noted between both groups regarding neonatal Apgar scores as well as the incidence of hypotension, bradycardia, nausea, vomiting, and duration of motor blockade. DBF group had significantly less incidence of shivering (P = 0.03).</AbstractText>Adding dexmedetomidine to regular mixture of epidural anesthetics in women undergoing elective cesarean section improved intraoperative conditions and quality of postoperative analgesia without maternal or neonatal significant side effects.</AbstractText>
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2,333,844 |
The mechanistic action of carbon dioxide on a neural circuit and NMJ communication.
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Previous studies examining behavioral responses to CO(2) revealed that high [CO(2)] acts as a natural repellent in a concentration dependent manner for crayfish. Physiologically, CO(2) can rapidly block the autonomic responses in heart rate, as well as, inhibit an escape tail flip reflex in crayfish. Here, we demonstrate that the behavioral observations can be mechanistically explained by CO(2) blocking glutamate receptors at the neuromuscular junction and through inhibition of recruiting motor neurons within the CNS. The effects are not mimicked with a lower pH in the bathing solution. Since spontaneous and sensory-evoked activities in the sensory root and motor neurons are reduced by CO(2), this is an anesthetic effect. We propose this is due to blockage of electrical synapses, as well as, some of the central glutamatergic-drive. We used agonists and antagonists (glutamate, nicotine, domoic acid, cadmium, heptanol) to various synaptic inputs, which are possibly present in the ventral nerve cord (VNC). Results from these chemicals supported the idea that there is electrical as well as chemical drive within the circuit that can modulate intrinsic as well as sensory evoked activity in the motor neurons. We have documented that CO(2) has actions in the periphery as well as in the CNS, to account for the behavioral responses previously shown. Furthermore, we document that gap junctions as well as glutamatergic synapses are potential targets. This study also aids in the dissection of a neural circuitry within the VNC that drives spontaneous and sensory evoked activity of the superficial flexor motor neurons.
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2,333,845 |
Ginsenosides Have a Suppressive Effect on c-Fos Expression in Brain and Reduce Cardiovascular Responses Increased by Noxious Stimulation to the Rat Tooth.
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The purpose of this study is to investigate the antinociceptive effects of ginsenosides on toothache. c-Fos immunoreactive (IR) neurons were examined after noxious intrapulpal stimulation (NS) by intrapulpal injection of 2 M KCl into upper and lower incisor pulps exposed by bone cutter in Sprague Dawley rats. The number of Fos-IR neurons was increased in the trigeminal subnucleus caudalis (Vc) and the transitional region between Vc and subnucleus interpolaris (Vi) by NS to tooth. The intradental NS raised arterial blood pressure (BP) and heart rate (HR). The number of Fos-IR neurons was also enhanced in thalamic ventral posteromedial nucleus (VPMN) and centrolateral nucleus (CLN) by NS to tooth. The intradental NS increased the number of Fos-IR neurons in the nucleus tractus solitarius (NTS) and rostral ventrolateral medulla (RVLM), hypothalamic supraoptic nucleus (SON) and paraventricular nucleus (PVN), central cardiovascular regulation centers. Ginsenosides reduced the number of c-Fos-IR increased by NS to tooth in the trigeminal Vc and thalamic VPMN and CLN. Naloxone, an opioid antagonist, did not block the effect of ginsenoside on the number of Fos-IR neurons enhanced by NS to tooth in the trigeminal Vc and thalamic VPMN and CLN. Ginsenosides ameliorated arterial BP and HR raised by NS to tooth and reduced the number of Fos-IR neurons increased by NS to tooth in the NTS, RVLM, hypothalamic SON, and PVN. These results suggest that ginsenosides have an antinociceptive effect on toothache through non-opioid system and attenuates BP and HR increased by NS to tooth.
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2,333,846 |
Efficient and specific cardiac IK₁ inhibition by a new pentamidine analogue.
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In excitable cells, KIR2.x ion-channel-carried inward rectifier current (IK₁) is thought to set the negative and stable resting membrane potential, and contributes to action potential repolarization. Loss- or gain-of-function mutations correlate with cardiac arrhythmias and pathological remodelling affects normal KIR2.x protein levels. No specific IK1 inhibitor is currently available for in vivo use, which severely hampers studies on the precise role of IK1 in normal cardiac physiology and pathophysiology. The diamine antiprotozoal drug pentamidine (P) acutely inhibits IK₁ by plugging the cytoplasmic pore region of the channel. We aim to develop more efficient and specific IK₁ inhibitors based on the P structure.</AbstractText>We analysed seven pentamidine analogues (PA-1 to PA-7) for IK₁ blocking potency at 200 nM using inside-out patches from KIR2.1 expressing HEK-293 cells. PA-6 showed the highest potency and was tested further. PA-6 blocked KIR2.x currents of human and mouse with low IC₅₀ values (12-15 nM). Modelling indicated that PA-6 had less electrostatic but more lipophilic interactions with the cytoplasmic channel pore than P, resulting in a higher channel affinity for PA-6 (ΔG -44.1 kJ/Mol) than for P (ΔG -31.7 kJ/Mol). The involvement of acidic amino acid residues E224 and E299 in drug-channel interaction was confirmed experimentally. PA-6 did not affect INav1.5, ICa-L, IKv4.3, IKv11.1, and IKv7.1/minK currents at 200 nM. PA-6 inhibited the inward (50 nM 40%; 100 nM 59%; 200 nM 77%) and outward (50 nM 40%; 100 nM 76%; 200 nM 100%) components of IK₁ in isolated canine adult-ventricular cardiomyocytes (CMs). PA-6 prolonged action potential duration of CMs by 8 (n = 9), 26 (n = 5), and 34% (n = 11) at 50, 100, and 200 nM, respectively. Unlike P, PA-6 had no effect on KIR2.1 channel expression at concentrations from 0.1 to 3 μM. However, PA-6 at 10 μM increased KIR2.1 expression levels. Also, PA-6 did not affect the maturation of hERG, except when applied at 10 μM.</AbstractText>PA-6 has higher efficiency and specificity to KIR2.x-mediated current than P, lengthens action potential duration, and does not affect channel trafficking at concentrations relevant for complete IK₁ block.</AbstractText>
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2,333,847 |
Increased electrical nerve stimulation threshold of the sciatic nerve in patients with diabetic foot gangrene: a prospective parallel cohort study.
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Peripheral neuropathy may affect nerve conduction in patients with diabetes mellitus.</AbstractText>This study was designed to test the hypothesis that the electrical stimulation threshold for a motor response of the sciatic nerve is increased in patients suffering from diabetic foot gangrene compared to non-diabetic patients.</AbstractText>Prospective non-randomised trial with two parallel groups.</AbstractText>Two university-affiliated hospitals.</AbstractText>Patients scheduled for surgical treatment of diabetic foot gangrene (n = 30) and non-diabetic patients (n = 30) displaying no risk factors for neuropathy undergoing orthopaedic foot or ankle surgery.</AbstractText>The minimum current intensity required to elicit a typical motor response (dorsiflexion or eversion of the foot) at a pulse width of 0.1 ms and a stimulation frequency of 1 Hz when the needle tip was positioned under ultrasound control directly adjacent to the peroneal component of the sciatic nerve.</AbstractText>The non-diabetic patients were younger [64 (SD 12) vs. 74 (SD 7) years] and predominantly female (23 vs. 8). The geometric mean of the motor stimulation threshold was 0.26 [95% confidence interval (95% CI) 0.24 to 0.28] mA in non-diabetic and 1.9 (95% CI 1.6 to 2.2) mA in diabetic patients. The geometric mean of the electrical stimulation threshold was significantly (P < 0.001) increased by a factor of 7.2 (95% CI 6.1 to 8.4) in diabetic compared to non-diabetic patients.</AbstractText>The electrical stimulation threshold for a motor response of the sciatic nerve is increased by a factor of 7.2 in patients with diabetic foot gangrene, which might hamper nerve identification.</AbstractText>
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2,333,848 |
The role of 17-beta estradiol in ischemic preconditioning protection of the heart.
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The protective effects of 17-beta estradiol (E2) on cardiac tissue during ischemia/reperfusion (I/R) injury have not yet been fully elucidated.</AbstractText>To assess the protective effects of short- and long-term E2 treatments on cardiac tissue exposed to I/R, and to assess the effects of these treatments in combination with ischemic preconditioning (IPC) on cardiac protection from I/R injury.</AbstractText>SPRAGUE DAWLEY RATS WERE ASSIGNED TO THE FOLLOWING TREATMENT PROTOCOLS: control (no preconditioning); IPC (isolated hearts were subjected to two cycles of 5 min global ischemia followed by 10 min of reperfusion); E2 preconditioning (E2PC; isolated hearts were subjected to E2 pharmacological perfusion for 15 min); short-term in vivo E2 pretreatment for 3 h; long-term in vivo E2 pretreatment or withdrawal (ovariectomy followed by a six-week treatment with E2 or a placebo); combined IPC and E2PC; combined IPC and short- or long-term E2 pretreatments or withdrawal. All hearts were isolated and stabilized for at least 30 min before being subjected to 40 min of global ischemia followed by 30 min of reperfusion; left ventricular function and vascular hemodynamics were then assessed.</AbstractText>IPC, E2PC and short-term E2 pretreatment led to the recovery of left ventricle function and vascular hemodynamics. Long-term E2 and placebo treatments did not result in any protection compared with untreated controls. The combination of E2PC or short-term E2 treatments with IPC did not block the IPC protection or result in any additional protection to the heart. Long-term E2 treatment blocked IPC protection; however, placebo treatment did not.</AbstractText>Short-term treatment with E2 protected the heart against I/R injury through a pathway involving the regulation of tumour necrosis factor-alpha. The combination of short-term E2 treatment with IPC did not provide additional protection to the heart. Short-term E2 treatment may be a suitable alternative for classical estrogen replacement therapy.</AbstractText>
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2,333,849 |
Inhibitory effect of glybenclamide on mitochondrial chloride channels from rat heart.
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Glybenclamide is used as a pharmacological tool in studies of mitochondrial functions supposing its main role to block ATP-dependent potassium (KATP) channel. The aim of this study was to test whether glybenclamide might interact with the mitochondrial chloride channels. Mitochondrial membranes, isolated from rat heart muscle, were incorporated into lipid bilayer membrane and single chloride channel currents were measured in 250/50 mM KCl cis/trans solutions. The observed chloride channels (N=11) with mean conductance 120±14 pS were sensitive to glybenclamide, which decreased the open probability (IC50=129 μM) and affected the channel gating kinetics (IC50=12 μM) by perturbing its open state. It did not influence the channel conductance or reversal potential. These results indicate that glybenclamide interacts with chloride channels what should be taken into consideration, when glybenclamide is used as a specific inhibitor of KATP channels.
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2,333,850 |
CXC chemokine KC fails to induce neutrophil infiltration and neoangiogenesis in a mouse model of myocardial infarction.
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Chemokines and neutrophils, known as important players in the inflammatory cascade, also contribute to heart tissue recovery and scar formation after myocardial infarction (MI). The objective of this study was to determine the importance of ELR-containing CXC chemokine KC in neutrophil infiltration and neoangiogenesis, in a mouse model of chronic MI.</AbstractText>MI was induced in mice divided in four groups: control (untreated), anti-KC "later" (anti-KC antibody injections started 4 days after MI and then delivered every 72 hours for 3 weeks, to inhibit angiogenesis), anti-KC "earlier" (anti-KC antibody injections 1 day before and 1 day after MI, to block neutrophil infiltration), anti-KC (anti-KC antibody injections 1 day before and 1 day after MI, and then every 72 hours for 3 weeks). The efficiency of the anti-KC treatment was determined by the measurement of KC serum concentration and immunofluorescence staining, in each of the four groups. Surprisingly, we did not find any difference in neutrophil infiltration in the infarcted area between untreated and treated animals. Moreover, the heart function, infarct size, and neoangiogenesis were not different between the four groups. As expected, a comparable anti-CXCR2 treatment of mice before and after MI was able to significantly reduce neutrophil infiltration into the infarcted area and angiogenesis, but also to reduce the infarction size after long or "later" treatment.</AbstractText>The major finding of our study is that KC, a potent neutrophil chemoattractant and an established angiogenic factor, failed to interfere in the post-infarction inflammatory response, in wound healing and scar formation after MI. Therefore, these aspects need to be carefully taken into account when devising therapeutic strategies for myocardial infarction and ischemic cardiomyopathy.</AbstractText>Copyright © 2013 Elsevier Ltd. All rights reserved.</CopyrightInformation>
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2,333,851 |
[The comparison of epidural continuous infusion and epidural patient controlled bolus administration in labor analgesia].
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We aimed to compare the efficacies of patient controlled bolus administration and continuous infusion of low dose Fentanyl and Levobupivacaine combination by epidural catheter during vaginal labor on mother, baby and the duration of labor.</AbstractText>The 45 pregnant women involved in the study were divided randomly into two groups, Group HKEB (patient controlled epidural bolus) and Group SEI (continuous epidural infusion). Hemodynamic parameters and VAS values of the pregnant women, fetal heart rate, Apgar scores, duration of labor stages, types of delivery and side effects were recorded. Time to reach the T10 dermatome was determined. Motor block was evaluated with modified Bromage scale. Additional analgesic needs were followed up and total drug consumptions were compared.</AbstractText>Drug consumption was found to be significantly lower in HKEB administration (p<0.01).</AbstractText>Bolus administration of a basal dose that will keep the analgesia level constant and additional drugs administered upon patient requests will prevent pregnant women from experiencing a painful period, and will provide confidence and comfort to patients who need to ask for drugs according to their pain characteristics.</AbstractText>
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2,333,852 |
Artemisia copa aqueous extract as vasorelaxant and hypotensive agent.
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Artemisia copa Phil. (Asteraceae) is a medicinal plant commonly used in traditional medicine in Argentina.</AbstractText>The vasorelaxant and hypotensive activities of the aqueous extract of Artemisia copa have been investigated.</AbstractText>The in vitro effect of the extract and isolated compounds from Artemisia copa was investigated using isolated rat aortic rings. The acute effect caused by the intravenous (i.v.) infusion (0.1-300mg/kg) on blood pressure and heart rate was evaluated in spontaneous hypertensive rats. In addition, a phytochemical analysis of the extract was performed by HPLC.</AbstractText>Artemisia copa had a relaxant effect in endothelium-intact aortic rings that had been pre-contracted with 10(-7)M phenylephrine (Emax=96.7±1.3%, EC50=1.1mg/ml), 10(-5)M 5-hydroxytriptamine (Emax=96.7±3.5%, EC50=1.5mg/ml) and 80mM KCl (Emax=97.9± 4.4%, EC50=1.6mg/ml). In denuded aortic rings contracted by phenylephrine, a similar pattern was observed (Emax=92.7±6.5%, EC50=1.8mg/ml). l-NAME, indomethacin, tetraethylammonium and glibenclamide were not able to block the relaxation induced by the extract. Nevertheless, the pre-treatment with Artemisia copa attenuated the CaCl2-induced contraction in a concentration-dependent manner (Emax: 86% of inhibition for 3mg/ml and 52% de-inhibition for 1mg/ml). This pre-treatment also induced a significant attenuation of the norepinephrine-induced contraction in a concentration-dependent manner (Emax: 72.7% of inhibition for 3mg/ml and 27% de inhibition for 1mg/ml) in a Ca(2+) free medium. Upon analyzing the composition of the extract, the presence of p-coumaric acid, isovitexin, luteolin and chrysoeriol were found. Luteolin (CE50: 1.5μg/ml), chrysoeriol (CE50: 13.2μg/ml) and p-coumaric acid (CE50: 95.2μg/ml), isolated from the aqueous extract, caused dilatation of thoracic aortic rings pre-contracted with phenylephrine. Artemisia copa administered i.v. also induced a decrease in the mean arterial pressure but did not affect the heart rate in hypertensive rats.</AbstractText>The aqueous extract of Artemisia copa proved to have vasorelaxing and hypotensive effects through the inhibition of Ca(2+) influx via membranous calcium channels and intracellular stores. The presence of luteolin, chrysoeriol and p-coumaric acid found in this plant could be involved in this effect.</AbstractText>Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.</CopyrightInformation>
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2,333,853 |
Optimisation of embryonic and larval ECG measurement in zebrafish for quantifying the effect of QT prolonging drugs.
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Effective chemical compound toxicity screening is of paramount importance for safe cardiac drug development. Using mammals in preliminary screening for detection of cardiac dysfunction by electrocardiography (ECG) is costly and requires a large number of animals. Alternatively, zebrafish embryos can be used as the ECG waveform is similar to mammals, a minimal amount of chemical is necessary for drug testing, while embryos are abundant, inexpensive and represent replacement in animal research with reduced bioethical concerns. We demonstrate here the utility of pre-feeding stage zebrafish larvae in detection of cardiac dysfunction by electrocardiography. We have optimised an ECG recording system by addressing key parameters such as the form of immobilization, recording temperature, electrode positioning and developmental age. Furthermore, analysis of 3 days post fertilization (dpf) zebrafish embryos treated with known QT prolonging drugs such as terfenadine, verapamil and haloperidol led to reproducible detection of QT prolongation as previously shown for adult zebrafish. In addition, calculation of Z-factor scores revealed that the assay was sensitive and specific enough to detect large drug-induced changes in QTc intervals. Thus, the ECG recording system is a useful drug-screening tool to detect alteration to cardiac cycle components and secondary effects such as heart block and arrhythmias in zebrafish larvae before free feeding stage, and thus provides a suitable replacement for mammalian experimentation.
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2,333,854 |
Coronary endothelial dysfunction in patients with early coronary artery disease is associated with the increase in intravascular lipid core plaque.
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Endothelial dysfunction is considered to play a key role in the development of atherosclerosis. However, only a limited number of human imaging studies have been available to demonstrate this hypothesis. The present study used near-infrared spectroscopy (NIRS) to investigate whether coronary endothelial dysfunction is associated with the lipid core plaque (LCP) in patients with early coronary artery disease.</AbstractText>A total of 32 patients with chest pain who had diameter stenosis <30% were enrolled. All patients underwent coronary endothelial function assessment using intracoronary acetylcholine infusion and NIRS of the proximal left anterior descending artery. The lipid core burden index (LCBI), LCBI/L (LCBI divided by the length of scanned artery), maxLCBI4mm (maximum value of LCBI for any of the 4-mm segment) and block chemogram (yellow: probability of LCP presence >0.98, tan: 0.84 ≤ P ≤ 0.98, orange: 0.57 ≤ P ≤ 0.84, red: P < 0.57) were measured. The mean percentage of yellow, tan, and orange colour blocks in patients with epicardial endothelial dysfunction was significantly higher than in those with normal epicardial endothelial function (9.5 ± 11.4 vs. 3.1 ± 6.5%, P = 0.042). There was a significant correlation between LCBI (r = -0.460, P = 0.008), LCBI/L (r = -0.453, P = 0.009), and maxLCBI4mm (r = -0.431, P = 0.014) and the degree of epicardial endothelial function. However, there was no significant correlation between LCBI (r = -0.101, P = 0.58), LCBI/L (r = -0.099, P = 0.59), and maxLCBI4mm (r = -0.063, P = 0.73) and the degree of microvascular endothelial function.</AbstractText>Patients with early coronary artery disease and endothelial dysfunction had a higher lipid content in the vascular wall than patients with normal endothelial function. The result of the present study supports the hypothesis that endothelial dysfunction is associated with pathogenesis of early atherosclerosis.</AbstractText>
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2,333,855 |
Vitamin D toxicity presenting as hypercalcemia and complete heart block: An interesting case report.
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Vitamin D deficiency is widely prevalent across the globe. This has lead to widespread use of vitamin D supplements in populations. We present our experience of vitamin D toxicity in a subject resulting in hypercalcemia and CHB (Complete Heart Block). A 70-year-old female, known hypertensive for thirty five years and diabetic for seven years underwent total knee replacement (TKR) for osteoarthritis left knee in December 2010. For perioperative glycemic control, multiple subcutaneous injections of insulin were advised. Patient later presented with poor glycemic control, decreased appetite and constipation for last 1 month with history of episodes of transient loss of consciousness for 15 days and recurrent vomiting. Biochemical work-up showed hypercalcemia (Serum calcium 12.4 mg/dL). Sr. albumin, ALP, Sr. phosphorus and PTH levels were normal, thus suggesting PTH independent hypercalcemia. Strong suspicion led us to check vitamin D levels in dilution which were 2016 ng/mL, thus confirming vitamin D toxicity. Retrospective analysis of treatment history revealed patient receiving 4 injections of Architol (6 Lac units im) prior to presentation. Work-up for malignancy was negative, brain imaging and EEG were normal. Holter was suggestive of intermittent CHB. Patient was given hydration, injection calcitonin 100 I.U. subcutaneously, injection pamidronate 60 mg infusion, with serum calcium levels normalizing, with relief in constipation, vomiting and behavioral improvement. However, persistence of rhythm disturbances led to permanent pacemaker placement. The present case highlights the dangers of indiscriminate vitamin D usage, exposing patients to potentially life threatening complications.
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2,333,856 |
Mechanisms of [Ca2+]i elevation following P2X receptor activation in the guinea-pig small mesenteric artery myocytes.
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There is growing evidence suggesting involvement of L-type voltage-gated Ca2+ channels (VGCCs) in purinergic signaling mechanisms. However, detailed interplay between VGCCs and P2X receptors in intracellular Ca2+ mobilization is not well understood. This study examined relative contribution of the Ca2+ entry mechanisms and induced by this entry Ca2+ release from the intracellular stores engaged by activation of P2X receptors in smooth muscle cells (SMCs) from the guinea-pig small mesenteric arteries.</AbstractText>P2X receptors were stimulated by the brief local application of αβ-meATP and changes in [Ca2+]i were monitored in fluo-3 loaded SMCs using fast x-y confocal Ca2+ imaging. The effects of the block of L-type VGCCs and/or depletion of the intracellular Ca2+ stores on αβ-meATP-induced [Ca2+]i transients were analyzed.</AbstractText>Our analysis revealed that Ca2+ entry via L-type VGCCs is augmented by the Ca2+-induced Ca2+ release significantly more than Ca2+ entry via P2X receptors, even though net Ca2+ influxes provided by the two mechanisms are not significantly different.</AbstractText>Thus, arterial SMCs upon P2X receptor activation employ an effective mechanism of the Ca2+ signal amplification, the major component of which is the Ca2+ release from the SR activated by Ca2+ influx via L-type VGCCs. This signaling pathway is engaged by depolarization of the myocyte membrane resulting from activation of P2X receptors, which, being Ca2+ permeable, per se form less effective Ca2+ signaling pathway. This study, therefore, rescales potential targets for therapeutic intervention in purinergic control of vascular tone.</AbstractText>
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2,333,857 |
Effect of position changes after spinal anesthesia with low-dose bupivacaine in elderly patients: sensory block characteristics and hemodynamic changes.
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The purpose of this study is to compare the anesthetic characteristics in elderly patients who remain in sitting position for 2 min compared with patients that are placed in supine position after induction of spinal anesthesia.</AbstractText>Fifty-seven patients scheduled for transurethral surgery were randomized to assume supine position immediately after 6.5 mg hyperbaric bupivacaine were injected (L group) or to remain in the sitting position for 2 minutes before they also assumed the supine position (S group). Analgesic levels were assessed bilaterally, using pin-prick. Motor block was scored using a 12-point scale. The mean arterial pressure and heart rate were also recorded.</AbstractText>Sensory block levels were significantly lower at all time points for the L group. However, there were no significant differences in the degree of the motor block and hemodynamic changes between the two groups. However, in the L group, ephedrine or atropine were administered to three patients.</AbstractText>We concluded that performing a spinal anesthesia in sitting position was technically easier and induced less hypotension.</AbstractText>
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2,333,858 |
Cardiac ion channel trafficking defects and drugs.
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Fine control over the functional expression of cardiac ion channels is required to maintain normal action potential (AP) duration and QTc times. A growing number of drugs interfere with normal trafficking of ion channels to and from the plasma membrane, thereby altering the number of channels on the cell surface. Most drugs do this at clinically relevant concentrations, which may lead to potentially life-threatening cardiac arrhythmias. Recently, major progress has been made in the understanding of the subcellular mechanisms by which drugs affect the trafficking of ion channels, which is of great benefit for the development of ways to counteract these adverse drug effects. Pharmacological correction seems to be a promising approach to address the trafficking defects induced by several drugs. However, as pharmacological correction is hampered by concomitant direct channel block or unspecific effects, further studies are needed to improve its potential as a clinical therapy.
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2,333,859 |
Cardicola langeli sp. n. (Digenea: Aporocotylidae) from heart of sheepshead, Archosargus probatocephalus (Actinopterygii: Sparidae) in the Gulf of Mexico, with an updated list of hosts, infection sites and localities for Cardicola spp.
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Cardicola langeli n. sp. (Digenea: Aporocotylidae) infects the heart of sheepshead, Archosargus probatocephalus (Walbaum, 1792) (Perciformes: Sparidae) in the northern Gulf of Mexico off Horn Island (type locality), Mississippi, USA. The new species is described herein using light and scanning electron microscopy of adult specimens and can be most easily distinguished from the other 24 accepted species of Cardicola Short, 1953 by the combination of having (i) an ovovitelline duct that extends anteriad and that (ii) is posterior to the ootype, (iii) a male genital pore that is lateral to the oviducal seminal receptacle and (iv) a female genital pore lateral to the ootype. The new species is the only member of Cardicola so-far reported to have tegumental spines that are distally flattened and broad, rather than pointed. The new species generally resembles the two other species of Cardicola that infect sparids, i.e. Cardicola cardiocolum (Manter, 1947) (type species) from jolthead porgy, Calamus bajonado (Block et Schneider), in the Gulf of Mexico and Cardicola aurata Holzer, Montero, Repullés, Sitja-Bobadilla, Alvarez-Pellitero, Zarza et Raga, 2008, from gilthead seabream, Sparus aurata Linnaeus, in the Mediterranean Sea, by having a spheroid anterior sucker with concentric rows of minute spines anterior to the mouth and by having a similar general arrangement of the vitellarium, gonads and genitalia. However, it differs from them by having the combination of the aforementioned five features plus asymmetrical posterior caeca and a dextral posterior caecum that extends beyond the posterior margin of the ovary. Probable eggs of C. langeli n. sp. that contain a ciliated miracidium infect gill epithelium and are spheroid. An updated list of hosts, infection sites and geographic localities for the 25 accepted species of Cardicola is provided.
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2,333,860 |
Phenylephrine as a simulated intravascular epidural test dose in pediatrics: a pilot study.
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A test dose is used to detect intravascular injection during neuraxial block in pediatrics. Accidental intravascular epidural local anesthetic injection might be unrecognized in anesthetized children leading to potential life-threatening complications. In children, sevoflurane anesthesia blunts the hemodynamic response when intravascular cathecolamines are administered. No studies have explored the hemodynamics and the criteria for a positive test dose result following phenylephrine in sevoflurane anesthetized children.</AbstractText>Healthy children undergoing minor procedures were randomly assigned to receive intravenous placebo, or 5 μg∙kg(-1) phenylephrine (n = 11/group) during sevoflurane anesthesia. Hemodynamic response was assessed using electrocardiography, pulse oxymetry and non-invasive blood pressure monitoring for 5 min following drug administration in anesthetized patients.</AbstractText>All patients receiving phenylephrine showed a decreased heart rate (HR) but not all of them met the positive criterion for test dose response. Overall, at 1 min, patients receiving phenylephrine showed a 25% decrease in HR from the baseline while an increase in blood pressure was noticed in 54% of patients receiving phenylephrine.</AbstractText>Phenylephrine might be a future indicator of positive intravascular test dose. Further investigation is needed to find out the phenylephrine dose that elicits a reliable hemodynamic response and whether phenylephrine needs to be dose age-adjusted in order to appreciate relevant hemodynamic changes in children receiving neuraxial blocks undergoing general anesthesia.</AbstractText>© 2013 Blackwell Publishing Ltd.</CopyrightInformation>
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2,333,861 |
Assessment of maxillary and infraorbital nerve blockade for rhinoscopy in sevoflurane anesthetized dogs.
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To investigate the efficacy of maxillary and infraorbital nerve blocks for prevention of cardiovascular and qualitative responses to rhinoscopy, as well as response to skin clamping after assigned nerve block placement.</AbstractText>Randomized, blinded, placebo-controlled cross-over experimental study.</AbstractText>Eight random-source mixed breed dogs > 1 year old and weighing between 13 and 22 kg.</AbstractText>Within three anesthetic episodes, separated by at least 3 days, dogs were assigned to receive either 1 mL lidocaine 2% maxillary nerve block (ML); 0.5 mL lidocaine 2% infraorbital nerve block (IOL); or equal amounts of saline for maxillary or infraorbital nerve block combined as control treatment (S). Monitoring included temperature, respiratory rate, end-tidal CO2 , ECG, heart rate (HR), systolic, diastolic and mean arterial pressure (SAP, DAP, MAP). Posterior (pR) and anterior rhinoscopies (aR) were performed and scored. Differences from baseline for outcome parameters HR, SAP, DAP, MAP were analyzed using repeated-measures anova, and results reported as mean ± SD. Binary scores for rhinoscopy were analyzed using logistic regression, and odds ratio was reported.</AbstractText>Changes from baseline for HR and SAP were significant for all treatments, besides ML for pR. Difference in changes from baseline among treatments was statistically significant for HR during pR with ML < S, and for SAP, DAP and MAP in right and left aR with ML < S and IOL > ML, except for DAP in left aR with only IOL > ML. Analysis of the binary score showed that the probability of a response for S and IOL treatments was nearly triple that of the ML treatment. None of the dogs, regardless of the treatments applied, responded to skin clamping.</AbstractText>Cardiovascular parameters do not seem to reflect the occurrence of adverse reactions during rhinoscopy. The maxillary nerve block is superior to the infraorbital nerve block, as applied in this study, in preventing adverse reactions during posterior rhinoscopy.</AbstractText>© 2013 The Authors. Veterinary Anaesthesia and Analgesia © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.</CopyrightInformation>
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2,333,862 |
Cardiovascular Protective Effects of Adjunctive Alternative Medicine (Salvia miltiorrhiza and Pueraria lobata) in High-Risk Hypertension.
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Introduction. Hypertension in association with diabetes (DM), renal impairment (RI), and left ventricular hypertrophy (LVH) increases the risk of future cardiovascular events. We hypothesize, traditional herbal medicines Danshen and Gegen (D&G) have beneficial effects on atherogenesis in these high-risk hypertensive subjects. Subjects and Methods. 90 asymptomatic hypertensive subjects associated with LVH (63.3%), DM (62.2%), or RI (30%) were randomized to receive D&G herbal capsules 1 gm/day, 2 gm/day, or identical placebo capsules in double-blind and parallel fashion for 12 months. Brachial flow-mediated dilation (endothelium-dependent dilation, FMD) and carotid intima-media thickness (IMT) were measured by ultrasound. All data were analyzed using the Statistical Package for Social Sciences in Windows 16.0. Results. Their mean age was 55 ± 8 years, and 74.4% were male. After 12 months of adjunctive therapies and compared with baseline, there were no significant changes in blood pressure, heart rate, hematological, glucose, and creatinine profiles in both placebo and D&G groups. FMD improved significantly during D&G (P = 0.0001) and less so after placebo treatment (P = 0.001). There was a mild but significant decrease in carotid IMT after D&G (P < 0.001) but no significant changes after placebo. A trend of better improvement in FMD after higher versus lower D&G dosages was seen. D&G were well tolerated, with no significant adverse events or blood biochemistry changes. Conclusion. D&G adjunctive treatment was well tolerated and significantly improved atherogenesis in high-risk hypertensive patients, with potential in primary atherosclerosis prevention.
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2,333,863 |
The effect of oxygen administration on regional cerebral oxygen saturation after stellate ganglion block on the non-blocked side.
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Stellate ganglion block (SGB) causes sympathetic denervation of the head, neck, and upper extremities. In some studies, it has been reported that cerebral blood flow on the non-blocked side decreases after SGB, so when performing an SGB for pain management of the head, neck, and arm, the increased risk of cerebral ischemia should be considered.</AbstractText>To examine the influence of administration of oxygen via nasal cannula after SGB on regional cerebral oxygen saturation (rSO2) of the non-blocked and blocked sides using near-infrared spectroscopy (NIRS).</AbstractText>Prospective observational study.</AbstractText>Outpatient department for interventional pain management at Yonsei University College of Medicine, Seoul, Korea</AbstractText>Thirty-eight patients with disease entities in the head, neck, and upper extremity and 3 volunteers were studied. SGB was performed with 10 mL of 1% lidocaine using an anterior paratracheal approach at the C6 transverse process level. A successful block was determined based on the appearance of Horner syndrome at 15 minutes after SGB. Oxygen was supplied at a rate of 5 L/min via nasal cannula starting 15 minutes after SGB. rSO2, blood pressure (BP), and heart rate (HR) were obtained at 5-minute intervals for 30 minutes using NIRS, a non-invasive blood pressure manometer, an electrocardiogram, and a pulse oximetry.</AbstractText>On the non-blocked side, when compared to the baseline values, there were significant decreases in the rSO2 (P < 0.001) and after administration of oxygen, there were significant increases of the rSO2 compared to the rSO2 at 15 minutes (P < 0.001). The lowest rSO2 at 15 minutes on the non-blocked side recovered to greater than the baseline value 5 minutes after starting oxygen administration. On the blocked side, when compared to the baseline values, there were significant increases at all time points (P < 0.001) and after administration of oxygen there were significant increases compared to the rSO2 at 15 minutes (P < 0.001). The rSO2 on the blocked side and the non-blocked side were significantly different at 15 minutes (P = 0.015). After oxygen administration, there were no significant differences of rSO2 between the 2 sides.</AbstractText>This study is limited by its sample size and observational design. It is difficult to precisely define the importance of the effect of SGB and oxygen administration on rSO2 change as we did not examine how the intensity of the nerve block changed with the passage of time.</AbstractText>SGB leads to decreased cerebral blood flow of the non-blocked hemisphere, and oxygen administration seems to be a simple method to compensate for this response.</AbstractText>NCT01532713. IRB No.: 4-2011-0358.</AbstractText>
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2,333,864 |
Influence of an intra-articular lipopolysaccharide challenge on markers of inflammation and cartilage metabolism in young horses.
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Nineteen weanling Quarter Horses (225 to 380 kg) were used in a randomized complete block design to investigate the effects of intra-articular lipopolysaccharide (LPS) to induce acute joint inflammation in young horses. Horses were blocked by age, BW, and sex and were randomly assigned to 1 of 3 treatments for a 35-d experiment. Treatments included intra-articular injection of 0.25 ng (n = 7) or 0.50 ng (n = 6) of LPS obtained from Escherichia coli O55:B5 or sterile lactated Ringer's solution (n = 6; control) into the radial carpal joint. Synovial fluid was obtained at preinjection h 0 and 2, 6, 12, 24, 168, and 336 h postinjection and was analyzed for PGE2, carboxypeptide of type II collagen (CPII), and collagenase cleavage neopeptide (C2C) biomarkers via commercial ELISA kits. Rectal temperature (RT), heart rate (HR), respiratory rate (RR), and carpal circumference were recorded before each sample. Lameness scores on a 0 to 5 scale were conducted after arthrocentesis. Data were analyzed using PROC MIXED procedure of SAS. Linear and cubic effects were tested in the form of contrasts. Clinical assessment of HR, RR, and RT were not influenced by treatment (P ≤ 0.16). All horses exhibited increased lameness scores over time (P ≤ 0.01), and horses receiving LPS, regardless of dose, had greater recorded lameness scores at 12 and 24 h postinjection (P ≤ 0.05). Joint circumference increased (P ≤ 0.01) across treatments in response to repeated arthrocentesis. Mean synovial fluid PGE2 concentrations increased linearly with increasing levels of LPS administration (P ≤ 0.01). Additionally, regardless of treatment, PGE2 increased over time and peaked at 12 h postinjection (P ≤ 0.01) and remained elevated above baseline at 336 h postinduction. Synovial concentrations of anabolic CPII increased linearly (P ≤ 0.01) with increasing dosage of LPS and increased (P ≤ 0.01) over 24 h in all horses, beginning at 6 h and peaking at 24 h postinjection. Concentrations of C2C in synovial fluid were not influenced by treatment and decreased from 0 to 6 h and steadily increased to 24 h in all horses (P ≤ 0.01). These results indicate that intra-articular LPS induced intra-articular inflammation and collagen synthesis in young horses and that the response is dose dependent. The use of this model to induce predictable joint inflammation may provide insight to the efficacy of preventative strategies relating to joint disease in the young horse.
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2,333,865 |
Exercise intolerance in Glycogen Storage Disease Type III: weakness or energy deficiency?
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Myopathic symptoms in Glycogen Storage Disease Type IIIa (GSD IIIa) are generally ascribed to the muscle wasting that these patients suffer in adult life, but an inability to debranch glycogen likely also has an impact on muscle energy metabolism. We hypothesized that patients with GSD IIIa can experience exercise intolerance due to insufficient carbohydrate oxidation in skeletal muscle. Six patients aged 17-36-years were studied. We determined VO 2peak (peak oxygen consumption), the response to forearm exercise, and the metabolic and cardiovascular responses to cycle exercise at 70% of VO 2peak with either a saline or a glucose infusion. VO 2peak was below normal. Glucose improved the work capacity by lowering the heart rate, and increasing the peak work rate by 30% (108 W with glucose vs. 83 W with placebo, p=0.018). The block in muscle glycogenolytic capacity, combined with the liver involvement caused exercise intolerance with dynamic skeletal muscle symptoms (excessive fatigue and muscle pain), and hypoglycemia in 4 subjects. In this study we combined anaerobic and aerobic exercise to systematically study skeletal muscle metabolism and exercise tolerance in patients with GSD IIIa. Exercise capacity was significantly reduced, and our results indicate that this was due to a block in muscle glycogenolytic capacity. Our findings suggest that the general classification of GSD III as a glycogenosis characterized by fixed symptoms related to muscle wasting should be modified to include dynamic exercise-related symptoms of muscle fatigue. A proportion of the skeletal muscle symptoms in GSD IIIa, i.e. weakness and fatigue, may be related to insufficient energy production in muscle.
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2,333,866 |
Cervical sympathetic block regulates early systemic inflammatory response in severe trauma patients.<Pagination><StartPage>194</StartPage><EndPage>201</EndPage><MedlinePgn>194-201</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.12659/MSM.883833</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">This aim of this study was to investigate the effects of one-side cervical sympathetic block on early inflammatory response in severe trauma patients.</AbstractText><AbstractText Label="MATERIAL AND METHODS" NlmCategory="METHODS">Thirty severe trauma patients with injury severity score (ISS) of 16 to 25 were randomly divided into treatment and control groups (n=15 each). Patients in the treatment group underwent a right-side stellate ganglion block (SGB) using 8 mL 0.75% ropivacaine for 4 times, with the first injection within 12 hr of admission and the other 3 injections were 12 hr, 24 hr and 48 hr later. The same procedures were performed for the control group except that normal saline was injected instead of ropivacaine. Blood was collected before injection and at 6 hr, 24 hr, and 72 hr after the first SGB for serum interleukin (IL)-1beta, IL-4, IL-6, IL-10 and TNF-alpha measurement.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">The concentrations of IL-1beta, IL-6, and TNF-alpha between 24 hr to 72 hr after SGB were all significantly lower than those in the control group (all P values <0.01). However, there was no significant difference in the concentrations of anti-inflammatory IL-4 and IL-10 between treatment and control groups. There was no obvious impact of SGB on breathing and circulation except for a slower heart rate 10 to 50 min after injection (P<0.01).</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">SGB regulates early inflammatory response through inhibition of the proinflammatory cytokines IL-1beta, IL-6, and TNF-alpha during severe trauma. SGB has no impact on the levels of anti-inflammatory cytokines IL-4 and IL-10.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Ming-Hua</ForeName><Initials>MH</Initials><AffiliationInfo><Affiliation>Trauma Center of Southwest Hospital, Third Military Medical University, Chongqing, China. [email protected]</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tian</LastName><ForeName>Jun</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Su</LastName><ForeName>Yong-Ping</ForeName><Initials>YP</Initials></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Tao</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Xiang</LastName><ForeName>Qiang</ForeName><Initials>Q</Initials></Author><Author ValidYN="Y"><LastName>Wen</LastName><ForeName>Liang</ForeName><Initials>L</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><ArticleDate DateType="Electronic"><Year>2013</Year><Month>03</Month><Day>15</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Med Sci Monit</MedlineTA><NlmUniqueID>9609063</NlmUniqueID><ISSNLinking>1234-1010</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000577">Amides</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D016207">Cytokines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018836">Inflammation Mediators</NameOfSubstance></Chemical><Chemical><RegistryNumber>7IO5LYA57N</RegistryNumber><NameOfSubstance UI="D000077212">Ropivacaine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000577" MajorTopicYN="N">Amides</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001340" MajorTopicYN="Y">Autonomic Nerve Block</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016022" MajorTopicYN="N">Case-Control Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002574" MajorTopicYN="N">Cervical Vertebrae</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016207" MajorTopicYN="N">Cytokines</DescriptorName><QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007249" MajorTopicYN="N">Inflammation</DescriptorName><QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName><QualifierName UI="Q000150" MajorTopicYN="Y">complications</QualifierName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018836" MajorTopicYN="N">Inflammation Mediators</DescriptorName><QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012119" MajorTopicYN="N">Respiration</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000077212" MajorTopicYN="N">Ropivacaine</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013233" MajorTopicYN="N">Stellate Ganglion</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014947" MajorTopicYN="N">Wounds and Injuries</DescriptorName><QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName><QualifierName UI="Q000150" MajorTopicYN="Y">complications</QualifierName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName><QualifierName UI="Q000628" MajorTopicYN="Y">therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D055815" MajorTopicYN="N">Young Adult</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2013</Year><Month>3</Month><Day>16</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2013</Year><Month>3</Month><Day>16</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2013</Year><Month>6</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">23492458</ArticleId><ArticleId IdType="pmc">PMC3628790</ArticleId><ArticleId IdType="doi">10.12659/MSM.883833</ArticleId><ArticleId IdType="pii">883833</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Morris JA, Jr, Norris PR, Moore JH, et al. Genetic Variation in the Autonomic Nervous System Affects Mortality: A Study of 1,095 Trauma Patients. J Am Coll Surg. 2009;208(5):663–70.</Citation><ArticleIdList><ArticleId IdType="pubmed">19476811</ArticleId></ArticleIdList></Reference><Reference><Citation>Yang FL, Subeq YM, Lee CJ, et al. Rosiglitazone protects against severe hemorrhagic shock-induced organ damage in rats. Med Sci Monit. 2011;17(10):BR282–89.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3539481</ArticleId><ArticleId IdType="pubmed">21959602</ArticleId></ArticleIdList></Reference><Reference><Citation>Sikora JP, Kuzanski W, Andrzejewska E. Soluble cytokine receptors sTNFR I and sTNFR II, receptor antagonist IL-1ra, and anti-inflammatory cytokines IL-10 and IL-13 in the pathogenesis of systemic inflammatory response syndrome in the course of burns in children. Med Sci Monit. 2009;15(1):CR26–31.</Citation><ArticleIdList><ArticleId IdType="pubmed">19114968</ArticleId></ArticleIdList></Reference><Reference><Citation>Crockett A, Panickar A. Role of the sympathetic nervous system in pain. Anaesthesia & Intensive Care Medicine. 2010;12(2):50–54.</Citation></Reference><Reference><Citation>Lee C-C, Chuang C-C, Liou J-Y, et al. Successful management of contrast medium extravasation injury through stellate ganglion block and intra-arterial nitroglycerin. Acta Anaesthesiol Taiwan. 2011;49:116–18.</Citation><ArticleIdList><ArticleId IdType="pubmed">21982175</ArticleId></ArticleIdList></Reference><Reference><Citation>He J-Y, Jiang L-S, Dai L-Y. The roles of the sympathetic nervous system in osteoporotic diseases: A review of experimental and clinical studies. Ageing Research Reviews. 2011;10:253–63.</Citation><ArticleIdList><ArticleId IdType="pubmed">21262391</ArticleId></ArticleIdList></Reference><Reference><Citation>Nickel FT, Seifert F, Lanz S, et al. Mechanisms of neuropathic pain. Eur Neuropsychopharmacol. 2012;22:81–91.</Citation><ArticleIdList><ArticleId IdType="pubmed">21672666</ArticleId></ArticleIdList></Reference><Reference><Citation>Lu J, Shi Z, Su Y, et al. Effect of cervical sympathetic ganglia block on the mortality of mice with combined radiation and burn injury and its possible mechanism. Chin J Clin Rehabil. 2006;10(34):177–81.</Citation></Reference><Reference><Citation>Keel M, Trentz O. Pathophysiology of polytrauma. Injury. 2005;36(6):691–709.</Citation><ArticleIdList><ArticleId IdType="pubmed">15910820</ArticleId></ArticleIdList></Reference><Reference><Citation>Osuchowski MF, Welch K, Siddiqui J, Remick DG. Circulating cytokine/inhibitor profiles reshape the understanding of the SIRS/CARS continuum in sepsis and predict mortality. J Immunol. 2006;177(3):1967–74.</Citation><ArticleIdList><ArticleId IdType="pubmed">16849510</ArticleId></ArticleIdList></Reference><Reference><Citation>Lausevic Z, Lausevic M, Trbojevic-Stankovic J, et al. Predicting multiple organ failure in patients with severe trauma. Can J Surg. 2008;51(2):97–102.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2386337</ArticleId><ArticleId IdType="pubmed">18377749</ArticleId></ArticleIdList></Reference><Reference><Citation>Kin NW, Sanders VM. It takes nerve to tell T and B cells what to do. J Leukoc Biol. 2006;79(6):1093–104.</Citation><ArticleIdList><ArticleId IdType="pubmed">16531560</ArticleId></ArticleIdList></Reference><Reference><Citation>Mousa SA, Shaqura M, Brendl U, et al. Involvement of the peripheral sensory and sympathetic nervous system in the vascular endothelial expression of ICAM-1 and the recruitment of opioid-containing immune cells to inhibit inflammatory pain. Brain Behav Immun. 2010;24:1310–23.</Citation><ArticleIdList><ArticleId IdType="pubmed">20600813</ArticleId></ArticleIdList></Reference><Reference><Citation>Ley S, Weigert A, Brune B. Neuromediators in inflammation – a macrophage/nerve connection. Immunobiology. 2010;215:674–84.</Citation><ArticleIdList><ArticleId IdType="pubmed">20594610</ArticleId></ArticleIdList></Reference><Reference><Citation>Xu X, Wang P, Zou X, et al. The effects of sympathetic outflow on upregulation of vanilloid receptors TRPV1 in primary afferent neurons evoked by intradermal capsaicin. Exp Neurol. 2010;222:93–107.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2824038</ArticleId><ArticleId IdType="pubmed">20036240</ArticleId></ArticleIdList></Reference><Reference><Citation>Bellinger DL, Millar BA, Perez S, et al. Sympathetic modulation of immunity: Relevance to disease. Cell Immunol. 2008;252(1–2):27–56.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3551630</ArticleId><ArticleId IdType="pubmed">18308299</ArticleId></ArticleIdList></Reference><Reference><Citation>Pavlov VA, Ochani M, Gallowitsch-Puerta M, et al. Central muscarinic cholinergic regulation of the systemic inflammatory response during endotoxemia. Proc Natl Acad Sci USA. 2006;103(13):5219–23.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1405626</ArticleId><ArticleId IdType="pubmed">16549778</ArticleId></ArticleIdList></Reference><Reference><Citation>Tracey KJ. Physiology and immunology of the cholinergic antiinflammatory pathway. J Clin Invest. 2007;117(2):289–96.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1783813</ArticleId><ArticleId IdType="pubmed">17273548</ArticleId></ArticleIdList></Reference><Reference><Citation>Adachi M, Otsuki M, Akatsu M, Tase C. The effects of heat stimulation and cold stress on the rats with cervical sympathectomy. Masui. 2003;52(12):1293–99.</Citation><ArticleIdList><ArticleId IdType="pubmed">14733079</ArticleId></ArticleIdList></Reference><Reference><Citation>Quan SB, Liu JY, Wang QX, Yang G. Relationship between serum interleukin-6 level and stellate ganglion block in rabbit brain during ischemic-reperfusion period. Chin J Clin Rehabil. 2005;9(37):146.</Citation></Reference><Reference><Citation>Wang QX, Wang XY, Fu NA, et al. Stellate ganglion block inhibits formalin-induced nociceptive responses: mechanism of action. Eur J Anaesthesiol. 2005;22(12):913–18.</Citation><ArticleIdList><ArticleId IdType="pubmed">16318661</ArticleId></ArticleIdList></Reference><Reference><Citation>Chawda M, Hildebrand F, Pape H, Giannoudis P. Predicting outcome after multiple trauma: which scoring system? Injury. 2004;35(4):347–58.</Citation><ArticleIdList><ArticleId IdType="pubmed">15037369</ArticleId></ArticleIdList></Reference><Reference><Citation>Gebhard F, Pfetsch H, Steinbach G, et al. Is interleukin 6 an early marker of injury severity following major trauma in humans? Arch Surg. 2000;135(3):291–95.</Citation><ArticleIdList><ArticleId IdType="pubmed">10722030</ArticleId></ArticleIdList></Reference><Reference><Citation>Krinsley JS. Association between hyperglycemia and increased hospital mortality in a heterogeneous population of critically ill patients. Mayo Clin Proc. 2003;78(12):1471–78.</Citation><ArticleIdList><ArticleId IdType="pubmed">14661676</ArticleId></ArticleIdList></Reference><Reference><Citation>Tracey KJ. The inflammatory reflex. Nature. 2002;420(6917):853–59.</Citation><ArticleIdList><ArticleId IdType="pubmed">12490958</ArticleId></ArticleIdList></Reference><Reference><Citation>Downen M, Amaral TD, Hua LL, et al. Neuronal death in cytokine-activated primary human brain cell culture: role of tumor necrosis factor-alpha. Glia. 1999;28(2):114–27.</Citation><ArticleIdList><ArticleId IdType="pubmed">10533055</ArticleId></ArticleIdList></Reference><Reference><Citation>Ni Choileain N, Redmond HP. The immunological consequences of injury. Surgeon. 2006;4(1):23–31.</Citation><ArticleIdList><ArticleId IdType="pubmed">16459497</ArticleId></ArticleIdList></Reference><Reference><Citation>Windahl SH, Treuter E, Ford J, et al. The nuclear-receptor interacting protein (RIP) 140 binds to the human glucocorticoid receptor and modulates hormone-dependent transactivation. J Steroid Biochem Mol Biol. 1999;71(3–4):93–102.</Citation><ArticleIdList><ArticleId IdType="pubmed">10659697</ArticleId></ArticleIdList></Reference><Reference><Citation>Spielmann S, Kerner T, Ahlers O, et al. Early detection of increased tumour necrosis factor alpha (TNFalpha) and soluble TNF receptor protein plasma levels after trauma reveals associations with the clinical course. Acta Anaesthesiol Scand. 2001;45(3):364–70.</Citation><ArticleIdList><ArticleId IdType="pubmed">11207475</ArticleId></ArticleIdList></Reference><Reference><Citation>Savory JGA, Hsu B, Laquian IR, et al. Discrimination between NL1-and NL2-mediated nuclear localization of the glucocorticoid receptor. Mol Cell Biol. 1999;19(2):1025.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC116033</ArticleId><ArticleId IdType="pubmed">9891038</ArticleId></ArticleIdList></Reference><Reference><Citation>Mariathasan S, Monack DM. Inflammasome adaptors and sensors: intracellular regulators of infection and inflammation. Nat Rev Immunol. 2007;7(1):31–40.</Citation><ArticleIdList><ArticleId IdType="pubmed">17186029</ArticleId></ArticleIdList></Reference><Reference><Citation>Watanabe H, Gehrke S, Contassot E, et al. Danger signaling through the inflammasome acts as a master switch between tolerance and sensitization. J Immunol. 2008;180(9):5826–32.</Citation><ArticleIdList><ArticleId IdType="pubmed">18424701</ArticleId></ArticleIdList></Reference><Reference><Citation>Tschopp J, Martinon F, Burns K. NALPs: a novel protein family involved in inflammation. Nat Rev Mol Cell Biol. 2003;4(2):95–104.</Citation><ArticleIdList><ArticleId IdType="pubmed">12563287</ArticleId></ArticleIdList></Reference><Reference><Citation>Feldmann J, Prieur AM, Quartier P, et al. Chronic infantile neurological cutaneous and articular syndrome is caused by mutations in CIAS1, a gene highly expressed in polymorphonuclear cells and chondrocytes. Am J Hum Genet. 2002;71(1):198–203.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC384980</ArticleId><ArticleId IdType="pubmed">12032915</ArticleId></ArticleIdList></Reference><Reference><Citation>Parris WC, Lin S, Frist W., Jr Use of stellate ganglion blocks for chronic chest pain associated with primary pulmonary hypertension. Anesth Analg. 1988;67(10):993–95.</Citation><ArticleIdList><ArticleId IdType="pubmed">3421503</ArticleId></ArticleIdList></Reference><Reference><Citation>Hardy PA. Stellate ganglion block with bupivacaine. Minimum effective concentration of bupivacaine and the effect of added potassium. Anaesthesia. 1989;44(5):398–99.</Citation><ArticleIdList><ArticleId IdType="pubmed">2742100</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">23486416</PMID><DateCompleted><Year>2013</Year><Month>07</Month><Day>25</Day></DateCompleted><DateRevised><Year>2021</Year><Month>10</Month><Day>21</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1940-087X</ISSN><JournalIssue CitedMedium="Internet"><Issue>72</Issue><PubDate><Year>2013</Year><Month>Feb</Month><Day>26</Day></PubDate></JournalIssue><Title>Journal of visualized experiments : JoVE</Title><ISOAbbreviation>J Vis Exp</ISOAbbreviation></Journal>Catheter ablation in combination with left atrial appendage closure for atrial fibrillation.
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Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting millions of individuals worldwide. The rapid, irregular, and disordered electrical activity in the atria gives rise to palpitations, fatigue, dyspnea, chest pain and dizziness with or without syncope. Patients with AF have a five-fold higher risk of stroke. Oral anticoagulation (OAC) with warfarin is commonly used for stroke prevention in patients with AF and has been shown to reduce the risk of stroke by 64%. Warfarin therapy has several major disadvantages, however, including bleeding, non-tolerance, interactions with other medications and foods, non-compliance and a narrow therapeutic range. These issues, together with poor appreciation of the risk-benefit ratio, unawareness of guidelines, or absence of an OAC monitoring outpatient clinic may explain why only 30-60% of patients with AF are prescribed this drug. The problems associated with warfarin, combined with the limited efficacy and/or serious side effects associated with other medications used for AF, highlight the need for effective non-pharmacological approaches to treatment. One such approach is catheter ablation (CA), a procedure in which a radiofrequency electrical current is applied to regions of the heart to create small ablation lesions that electrically isolate potential AF triggers. CA is a well-established treatment for AF symptoms, that may also decrease the risk of stroke. Recent data showed a significant decrease in the relative risk of stroke and transient ischemic attack events among patients who underwent ablation compared with those undergoing antiarrhythmic drug therapy. Since the left atrial appendage (LAA) is the source of thrombi in more than 90% of patients with non-valvular atrial fibrillation, another approach to stroke prevention is to physically block clots from exiting the LAA. One method for occluding the LAA is via percutaneous placement of the WATCHMAN LAA closure device. The WATCHMAN device resembles a small parachute. It consists of a nitinol frame covered by fabric polyethyl terephthalate that prevents emboli, but not blood, from exiting during the healing process. Fixation anchors around the perimeter secure the device in the LAA (Figure 1). To date, the WATCHMAN is the only implanted percutaneous device for which a randomized clinical trial has been reported. In this study, implantation of the WATCHMAN was found to be at least as effective as warfarin in preventing stroke (all-causes) and death (all-causes). This device received the Conformité Européenne (CE) mark for use in the European Union for warfarin eligible patients and in those who have a contraindication to anticoagulation therapy. Given the proven effectiveness of CA to alleviate AF symptoms and the promising data with regard to reduction of thromboembolic events with both CA and WATCHMAN implantation, combining the two procedures is hoped to further reduce the incidence of stroke in high-risk patients while simultaneously relieving symptoms. The combined procedure may eventually enable patients to undergo implantation of the WATCHMAN device without subsequent warfarin treatment, since the CA procedure itself reduces thromboembolic events. This would present an avenue of treatment previously unavailable to patients ineligible for warfarin treatment because of recurrent bleeding or other warfarin-associated problems. The combined procedure is performed under general anesthesia with biplane fluoroscopy and TEE guidance. Catheter ablation is followed by implantation of the WATCHMAN LAA closure device. Data from a non-randomized trial with 10 patients demonstrates that this procedure can be safely performed in patients with a CHADS2 score of greater than 1. Further studies to examine the effectiveness of the combined procedure in reducing symptoms from AF and associated stroke are therefore warranted.
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2,333,867 |
Impact of subcutaneous infiltration of 0.5% bupivacaine on post-operative C-reactive protein serum titer after craniotomy surgery.
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Tissue injuries may provoke neuro-hormonal response which in turn may lead to release of inflammatory cytokines. We hypothesize that block of afferent sensory pathways by infiltration of 0.5% bupivacaine in the scalp may decrease neuro-hormonal response in the neurosurgical patient.</AbstractText>After obtaining informed consent, forty ASA physical statuses I, II, or III patients between the ages of 18 and 65 years were enrolled randomly into two equal groups to receive either 20 ml of 0.5% bupivacaine (group A) or 20 ml of 0.9% normal saline as a placebo (group B) in the site of pin insertion and scalp incision. As the primary outcome we checked serum C-reactive protein (CRP) levels before implementation of noxious stimulus, 24h, and 48h after the end of surgery to compare these values between groups. In addition, mean arterial pressure (MAP) and heart rate (HR) were checked at baseline (after the induction of anesthesia), one minute after pin fixation and 5, 10, and 15 minute after skin incision and the recorded values were compared between groups.</AbstractText>No significant difference was found between serum CRP levels of the two groups. Comparison of mean HR between groups shows no significant difference. The mean of MAP was significantly lower in the group A in comparison with the group B (p< 0.001).</AbstractText>The results of this study confirm that 0.5% bupivacaine scalp infiltration before skull-pin holder fixation and skin incision could not decrease post-operative C-reactive protein level.</AbstractText>
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2,333,868 |
High-frequency transcutaneous electrical nerve stimulation reduces pain and cardio-respiratory parameters in an animal model of acute pain: participation of peripheral serotonin.
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The objective of this study was to investigate the effect of high-frequency transcutaneous electrical nerve stimulation (HF-TENS) in antihyperalgesia, assessed through changes of sciatic nerve activity and its effects on cardiorespiratory parameters, using formalin-induced nociception in anesthetized rats. The animals were divided into formalin (FORM) and HF-TENS groups. All rats received injections of 5% formalin (50 μl, right hind-paw). The sciatic nerve activity and cardiopulmonary parameters (mean arterial pressure, heart rate, and respiratory frequency) were measured, and then the serum levels of serotonin (5-HT) were determined by an enzyme-linked immunosorbent assay kit. The formalin injection was able to increase the sciatic nerve activity, heart rate, and respiratory frequency. The treatment with HF-TENS significantly reduced the sciatic nerve activity and respiratory frequency 20 minutes after formalin injection and was able to increase serum 5-HT. Furthermore, when comparing the groups, reductions in the mean arterial pressure, heart rate, respiratory frequency, and sciatic nerve activity were shown at different times. Thus, we concluded that HF-TENS was capable of inducing analgesia, which was most likely related to increased serotonin release. Moreover, we demonstrated that TENS was able to block the adverse cardiovascular and respiratory changes induced by pain. Further neurophysiological studies are necessary to clarify the intrinsic mechanisms underlying HF-TENS-induced analgesia.
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2,333,869 |
Cerebral aqueduct block attenuates cardio-renal injuries in post-DOCA-NaCl-hypertensive Dahl R rats.
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The systemic and/or local effects of the hydrocephalic brain were investigated in DOCA-NaCl-hypertensive Dahl R rats induced by 250 mg kg(-1) DOCA in silicone and 1% saline water. After a 1-week recovery with 0.3% NaCl chow and tap water, one group had the aqueduct of Sylvius blocked with silicone and epoxy materials with a control sham group matching mean blood pressure (BP) and body weight. The 4-week-postsurgery BP on the 0.3% NaCl diet averaged 161±3.2 in the sham group and 146±2.3 mm Hg in the blocked group (P<0.0001). Both groups were then given an 8% NaCl diet and after 4 weeks, the sham group's BP was increased further with markedly increased mortality: 186 mm Hg vs. 154 mm Hg (P<0.0001); 12 sham rats died after 11 weeks, while all the blocked rats survived (P<0.0001). A transient change in plasma Na levels was observed in the blocked group after 48 h on the 8% NaCl diet. At 14 weeks, 0 sham rats survived, compared with 10 out of 16 blocked rats (P<0.0001). After 11 weeks on 8% NaCl, the average tail venous pressure in the sham group was significantly higher than that of the blocked rats (P<0.0001) indicating the end stage of renal and heart failure. The hearts and kidneys weighed significantly more in the sham vs. the blocked rats (P<0.0001 for both groups). These results indicate that the aqueduct block prevents post-DOCA hypertension and cardio-renal injuries, suggesting that centralized third ventricular brain signaling has a role in salt-genetic hypertension.
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2,333,870 |
Worsening Wenckebach after calcium gluconate injection: not uncommon but frequently missed diagnosis.
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The objective of the study is to demonstrate a common etiology of hyperkalemia and illustrate a potential iatrogenic errors in treatment.
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2,333,871 |
Episodic irregular tachycardia and AV block causing bradycardia: what is the mechanism?<Pagination><StartPage>834</StartPage><EndPage>836</EndPage><MedlinePgn>834-6</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1111/jce.12113</ELocationID><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Doppalapudi</LastName><ForeName>Harish</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. [email protected]</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yamada</LastName><ForeName>Takumi</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Osorio</LastName><ForeName>Jose</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Kay</LastName><ForeName>G Neal</ForeName><Initials>GN</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D002363">Case Reports</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2013</Year><Month>03</Month><Day>06</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Cardiovasc Electrophysiol</MedlineTA><NlmUniqueID>9010756</NlmUniqueID><ISSNLinking>1045-3873</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D054537" MajorTopicYN="N">Atrioventricular Block</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="Y">complications</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001919" MajorTopicYN="N">Bradycardia</DescriptorName><QualifierName UI="Q000209" MajorTopicYN="Y">etiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013610" MajorTopicYN="N">Tachycardia</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="Y">complications</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">conduction disturbances</Keyword><Keyword MajorTopicYN="N">dual AV nodal physiology</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2012</Year><Month>12</Month><Day>27</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2013</Year><Month>1</Month><Day>23</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2013</Year><Month>2</Month><Day>1</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2013</Year><Month>3</Month><Day>8</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2013</Year><Month>3</Month><Day>8</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2013</Year><Month>11</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">23464353</ArticleId><ArticleId IdType="doi">10.1111/jce.12113</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedBookArticle><BookDocument><PMID Version="1">23762958</PMID><ArticleIdList><ArticleId IdType="bookaccession">NBK143191</ArticleId></ArticleIdList><Book><Publisher><PublisherName>National Center for Biotechnology Information (US)</PublisherName><PublisherLocation>Bethesda (MD)</PublisherLocation></Publisher><BookTitle book="mlprobe">Probe Reports from the NIH Molecular Libraries Program</BookTitle><PubDate><Year>2010</Year></PubDate><BeginningDate><Year>2010</Year></BeginningDate><Medium>Internet</Medium></Book><ArticleTitle book="mlprobe" part="ml244">Potent Anti-Diabetic Actions of a Novel Non-Agonist PPARγ Ligand that Blocks Cdk5-Mediated Phosphorylation
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The incidence of diabetes is increasing rapidly as the percentage of the population ages and becomes more obese. According to the National Center for Health Statistics diabetes is now the sixth leading cause of death in the US. The biguanide metformin is typically the first-line medication used for treatment of type 2 diabetes mellitus (T2DM) as safety concerns over the use of the thiazolidinedione class [(TZD); rosiglitazone (Avandia) and pioglitazone (Actos) [1]] of insulin sensitizers has grown. This is unfortunate as TZDs have consistently shown robust efficacy for treatment of T2DM. TZDs target the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) and are classified as full agonists. While weight gain is associated with use of TZDs, the major safety concerns include edema, plasma volume expansion (PVE or hemodilution) which is likely linked to cardiomegaly and increased risk of congestive heart failure, and an increased risk of bone fractures. The latter risk is most troublesome as detection is typically only made when a patient suffers a fracture. Studies in animal models and in clinical trials have shown that indicators of weight gain and PVE, while not eliminated, can be minimized without loss of insulin sensitization by the use of modulators that are weak or partial agonists of PPARγ (e.g., minimal agonism of the receptor as compared to TZDs). Partial agonists have been referred to as selective PPARγ modulators or SPPARγMs and this class of ligand has been shown to have a different binding mode in the PPARγ ligand binding pocket (LBP) as compared to the full agonists [2]. Selective recruitment of transcriptional coactivators by partial agonists has also been demonstrated. A combination of different ligand binding mode and distinct coactivator recruitment profile may explain the change in gene expression patterns compared to that of full agonists [3]. While it is unclear if the bone fracture risk has been minimized with use of such agents, these studies clearly demonstrate that the anti-diabetic efficacy of partial agonists is uncoupled from their transcriptional activity but does correlate well with binding potency. Recently we have shown that many PPARγ-based drugs have a separate biochemical activity, blocking the obesity-linked phosphorylation of PPARγ by Cdk5. Due to their improved adverse event profile of partial agonists and the observation of separate biochemical activities of PPARγ ligands, we sought to develop compounds with high affinity binding to PPARγ but that lacked classical agonism and block the Cdk5-mediated phosphorylation in cultured adipocytes and in insulin-resistant mice. Here we describe one such compound, ML244, which has a unique mode of binding to PPARγ, has potent anti-diabetic activity while not causing the fluid retention and weight gain that are serious side effects of many of the PPARγ drugs. Unlike TZDs, ML244 does not interfere with bone formation in culture. These data illustrate that new classes of anti-diabetes drugs can be developed by specifically targeting the Cdk5-mediated phosphorylation of PPARγ.
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2,333,872 |
A comparison of the haemodynamic effects of lateral and sitting positions during induction of spinal anaesthesia for caesarean section.
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Hypotension during spinal anaesthesia occurs commonly in parturients. By influencing spread of local anaesthetic, maternal position may affect the speed of onset of sensory block and thus the haemodynamic effects. The aim of this study was to determine whether inducing spinal anaesthesia for caesarean section using plain bupivacaine in the lateral position would result in less hypotension compared with the sitting position.</AbstractText>One hundred American Society of Anesthesiologists physical status I and II patients undergoing elective caesarean section were randomised to receive spinal anaesthesia in the lateral position (Group L) or the sitting position (Group S). Using the L3-4 interspace, patients received intrathecal plain bupivacaine, 10mg or 12 mg according to their height, after which they were placed immediately in the supine position with left uterine displacement. Maternal blood pressure was measured every minute for 10 min, every three min for 20 min and 5-minutely thereafter. Hypotension was defined as a fall in systolic blood pressure >20% or a value <90 mmHg.</AbstractText>There was no difference in the lowest recorded systolic blood pressure in Group L (99.2±8.9 mmHg) compared with Group S (95.4±12.3 mmHg, P=0.081). However, the lowest recorded mean arterial pressure was greater in Group L (72.9±11.2 mmHg) than in Group S (68.2±9.6 mmHg; P=0.025). The incidence of hypotension was lower in Group L (17/50, 34%) than in Group S (28/50, 56%; P=0.027). Onset of hypotension was similar between groups.</AbstractText>Hypotension occurred less frequently when spinal anaesthesia for caesarean using plain bupivacaine was induced with patients in the lateral compared with the sitting position. Values for the lowest recorded mean arterial pressure were greater but values for the lowest recorded systolic blood pressure were similar for patients in the lateral position group.</AbstractText>Copyright © 2013 Elsevier Ltd. All rights reserved.</CopyrightInformation>
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2,333,873 |
Magnetic resonance imaging analysis of the spread of local anesthetic solution after ultrasound-guided lateral thoracic paravertebral blockade: a volunteer study.
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This study was designed to examine the spread of local anesthetic (LA) via magnetic resonance imaging after a standardized ultrasound-guided thoracic paravertebral blockade.</AbstractText>Ten volunteers were enrolled in the study. We performed ultrasound-guided single-shot paravertebral blocks with 20 ml mepivacaine 1% at the thoracic six level at both sides on two consecutive days. After each paravertebral blockade, a magnetic resonance imaging investigation was performed to investigate the three-dimensional spread of the LA. In addition, sensory spread of blockade was evaluated via pinprick testing.</AbstractText>The median (interquartile range) cranial and caudal distribution of the LA relative to the thoracic six puncture level was 1.0 (2.5) and 3.0 (0.75) [=4.0 vertebral levels] for the left and 0.5 (1.0) and 3.0 (0.75) [=3.5 vertebral levels] for the right side. Accordingly, the LA distributed more caudally than cranially. The median (interquartile range) number of sensory dermatomes which were affected by the thoracic paravertebral blockade was 9.8 (6.5) for the left and 10.7 (8.8) for the right side. The sensory distribution of thoracic paravertebral blockade was significantly larger compared with the spread of LA.</AbstractText>Although the spread of LA was reproducible, the anesthetic effect was unpredictable, even with a standardized ultrasound-guided technique in volunteers. While it can be assumed that approximately 4 vertebral levels are covered by 20 ml LA, the somatic distribution of the thoracic paravertebral blockade remains unpredictable. In a significant percentage, the LA distributes into the epidural space, prevertebral, or to the contralateral side.</AbstractText>
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2,333,874 |
The functional role of electrophysiological heterogeneity in the rabbit ventricle during rapid pacing and arrhythmias.
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Electrophysiological heterogeneity in action potential recordings from healthy intact hearts remains highly variable and, where present, is almost entirely abolished at fast pacing rates. Consequently, the functional importance of intrinsic action potential duration (APD) heterogeneity in healthy ventricles, and particularly its role during rapidly activating reentrant arrhythmias, remain poorly understood. By incorporating both transmural and apicobasal APD heterogeneity within a biventricular rabbit computational model and comparing with an equivalent homogeneous model, we directly investigated the functional importance of intrinsic APD heterogeneity under fast pacing and arrhythmogenic protocols. Although differences in APD were significantly modulated at the tissue level during pacing and further reduced as pacing frequency increased, small differences were still noticeable. Such differences were further marginally accentuated/attenuated via electrotonic effects relative to wavefront propagation directions. The remaining small levels of APD heterogeneity under the fastest pacing frequencies resulted in arrhythmia initiation via heterogeneous conduction block, in contrast to complete block in the homogeneous model. Such induction mechanisms were more evident during premature stimuli at slower paced rhythms where intrinsic heterogeneity remained to a greater degree. During sustained arrhythmias, however, intrinsic heterogeneity made little difference to overall reentrant behavior, either visually, or in terms of duration, metrics quantifying filament/phase singularity dynamics, and global electrocardiogram characteristics. These findings suggest that, despite being important during arrhythmia initiation, intrinsic electrophysiological heterogeneity plays little functional role during rapid pacing and sustained arrhythmia dynamics in the healthy ventricle and thus questions the need to incorporate such detail in computational models when simulating rapid arrhythmias.
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2,333,875 |
Infantile facioscapulohumeral muscular dystrophy revisited: Expansion of clinical phenotypes in patients with a very short EcoRI fragment.
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Contrary to the classical form, infantile facioscapulohumeral muscular dystrophy (FSHD) usually denotes a severe phenotype and is frequently associated with extramuscular involvements. To elucidate the genotype-phenotype correlation in this severe subgroup, we identified a cohort of nine patients with infantile FSHD who also carried a very short (10-13kb) EcoRI fragment. Their current age ranged from 8 to 33 years and age of onset ranged from 0.4 to 5 years. One patient even manifested his first FSHD-related symptoms at as early as 5 months of age, including inability to smile, poor response to call, and infantile spasms. To date, four patients were wheelchair-bound and six patients had asymmetric weakness. Sensorineural hearing loss and abnormal fundoscopic findings were observed in eight and all of patients respectively. Three with the smallest EcoRI fragments (10-11kb, with normal length being 50-300kb) had mental retardation. Two of these had epilepsy. Cardiac arrhythmias were found in five patients. Restrictive ventilatory defects were observed in seven patients, with one progressing to chronic respiratory failure. Two had swallowing difficulties; one of these required gastrostomy. We identified several rarely reported phenotypes in infantile FSHD, including cardiac arrhythmia, respiratory insufficiency, and swallowing difficulties. There seems to be a correlation between the severity of phenotype and the very short EcoRI fragment in the chromosome 4q35 region. We conclude that the high frequency of multi-organ involvements in this severe FSHD variant suggests the need for an early and multidisciplinary intervention.
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2,333,876 |
Characterization and mechanisms of action of novel NaV1.5 channel mutations associated with Brugada syndrome.
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Brugada syndrome is a heterogeneous heart rhythm disorder characterized by an atypical right bundle block pattern with ST-segment elevation and T-wave inversion in the right precordial leads. Loss-of-function mutations in SCN5A encoding the cardiac sodium channel Na(V)1.5 are associated with Brugada syndrome. We found novel mutations in SCN5A in 2 different families diagnosed with Brugada syndrome and investigated how those affected Na(V)1.5 channel function.</AbstractText>We performed genetic testing of the probands' genomic DNA. After site-directed mutagenesis and transfection, whole-cell currents were recorded for Na(V)1.5 wild type and mutants heterologously expressed in Chinese hamster ovary-K1 cells. Proband 1 had two novel Na(V)1.5 mutations: Na(V)1.5-R811H and Na(V)1.5-R620H. The Na(V)1.5-R811H mutation showed a significant loss of function in peak Na(+) current density and alteration of biophysical kinetic parameters (inactivation and recovery from inactivation), whereas Na(V)1.5-R620H had no significant effect on the current. Proband 2 had a novel Na(V)1.5-S1218I mutation. Na(V)1.5-S1218I had complete loss of function, and 1:1 expression of Na(V)1.5-wild type and Na(V)1.5-S1218I mimicking the heterozygous state revealed a 50% reduction in current compared with wild type, suggesting a functional haploinsufficiency in the patient.</AbstractText>Na(V)1.5-S1218I and R811H are novel loss-of-function mutations in the SCN5A gene causing Brugada syndrome.</AbstractText>
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2,333,877 |
MOG1 rescues defective trafficking of Na(v)1.5 mutations in Brugada syndrome and sick sinus syndrome.
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Loss-of-function mutations in Na(v)1.5 cause sodium channelopathies, including Brugada syndrome, dilated cardiomyopathy, and sick sinus syndrome; however, no effective therapy exists. MOG1 increases plasma membrane (PM) expression of Na(v)1.5 and sodium current (I(Na)) density, thus we hypothesize that MOG1 can serve as a therapeutic target for sodium channelopathies.</AbstractText>Knockdown of MOG1 expression using small interfering RNAs reduced Na(v)1.5 PM expression, decreased I(Na) densities by 2-fold in HEK/Na(v)1.5 cells and nearly abolished I(Na) in mouse cardiomyocytes. MOG1 did not affect Na(v)1.5 PM turnover. MOG1 small interfering RNAs caused retention of Na(v)1.5 in endoplasmic reticulum, disrupted the distribution of Na(v)1.5 into caveolin-3-enriched microdomains, and led to redistribution of Na(v)1.5 to noncaveolin-rich domains. MOG1 fully rescued the reduced PM expression and I(Na) densities by Na(v)1.5 trafficking-defective mutation D1275N associated with sick sinus syndrome/dilated cardiomyopathy/atrial arrhythmias. For Brugada syndrome mutation G1743R, MOG1 restored the impaired PM expression of the mutant protein and restored I(Na) in a heterozygous state (mixture of wild type and mutant Na(v)1.5) to a full level of a homozygous wild-type state.</AbstractText>Use of MOG1 to enhance Na(v)1.5 trafficking to PM may be a potential personalized therapeutic approach for some patients with Brugada syndrome, dilated cardiomyopathy, and sick sinus syndrome in the future.</AbstractText>
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2,333,878 |
Circadian expressions of cardiac ion channel genes in mouse might be associated with the central clock in the SCN but not the peripheral clock in the heart.
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Significant circadian variations exist in the frequency of cardiac arrhythmia, but few studies have examined the relation between cardiac ion channels genes and biological clocks. We investigated this relation using suprachiasmatic nuclei lesion (SCNX) and pharmacological autonomic nervous system block (ANSB) mice. Significant 24-h variations were observed in the expression of clock genes Per2, Bmal1, and Dbp and ion channel genes KCNA5, KCND2, KCHIP2, and KCNK3 in the control mice hearts. In the SCNX mice, all genes examined lost circadian rhythm. In the ANSB mice, the expressions of the three clock genes were dampened significantly but still had circadian rhythm, whereas the four ion channel gene expressions lost rhythm. Heart rate also lost circadian rhythm in both the SCNX and ANSB mice. These results suggest that some ion channel gene expressions might be regulated by the central clock in the SCN through the ANS but not the peripheral clock in the heart.
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2,333,879 |
Danshen mediates through estrogen receptors to activate Akt and inhibit apoptosis effect of Leu27IGF-II-induced IGF-II receptor signaling activation in cardiomyoblasts.
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Post-menopausal women show dramatically increased cardiovascular disease morbidity (CVD). Danshen is used widely in China for the treatment of cardiovascular disorders, including coronary heart disease. Danshen possesses lipid-soluble biologically active components with a structure similar to 17β-estrodiol (E2). This study assesses whether the cardio-protection exerted by Danshen is mediated through the ERs within H9c2 cardiomyoblast cells. Cardiomyoblast cells pretreated with Fulvestrant (ICI 182,780), an estrogen receptor antagonist was applied to investigate the estrogenic activity of Danshen. The Danshen extract preventive effects on Leu27IGF-II-induced IGF-IIR signaling activator and H9c2 cell apoptosis were identified using TUNEL assay, JC-1 staining and Western blot assay. We found that Danshen extract treatments significantly enhanced phosphorylated Akt through estrogen receptor activation to inhibit Leu27IGF-II-induced calcineurin activation and block H9c2 cell apoptosis. Danshen extracts suppressed the IGF-IIR signaling proteins, pro-apoptotic proteins and reversed the mitochondrial membrane instability induced by Leu27IGF-II. However, the cardioprotective properties of Danshen to inhibit Leu27IGF-II-induced cell apoptosis and promote cell survival were attenuated by applying ICI, which suggests that the Danshen cardioprotective effect is mediated through estrogen receptors. All our data indicated that Danshen exerts strong estrogenic activity which can be considered a novel selective estrogen receptor modulator (SERM) against IGF2R signaling that blocks cardiac apoptosis.
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2,333,880 |
Lipids in local anesthetic toxicity.
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With the advent of long-lasting local anesthetics, local and regional anesthesia gained considerable impetus and the use of these techniques has become increasingly widespread. New block techniques have been described and regional anesthesia is frequently associated with general anesthesia to provide postoperative analgesia. In contrast, large doses of local anesthetics are required with the risk of accidents due to inadvertent intravascular injection, which is a severe complication without a specific treatment until a few years ago. In 1998, the use of lipid emulsions was proposed in animals. Since 2006, many studies have demonstrated an interest in these solutions in cases of local anesthetic-induced toxicity with a decrease in morbidity and mortality. The aim of this review article was to research the methodology, reviewing mechanisms, interests, limitations and currently recommended treatment.</AbstractText>Some historical references on local anesthetics, articles published during the last 30 years in journals indexed in Medline and in two textbooks were reviewed. Articles on local anesthetic toxicity, lipid emulsion therapy, review articles on the topic and treatment adopted in diverse services and countries were selected, producing a summary.</AbstractText>It is no longer necessary to show the effectiveness and interest in lipid emulsion therapy for local anesthetic toxicity. Various specialty societies have already published their guidelines and advice about stocking these products in any setting in which local and regional anesthetic techniques are practiced.</AbstractText>
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2,333,881 |
The response of the composite variability index to a standardized noxious stimulus during propofol-remifentanil anesthesia.
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Recently the Composite Variability Index (CVI) was developed to quantify nociception. This index is derived from the standard deviations (s) of the Bispectral Index (sBIS) and the electromyogram (sEMG). The primary aim of our study was to compare CVI before and after a noxious stimulus. As secondary end points, we investigated the influence of remifentanil on the CVI and tested the ability of the CVI to indicate patient movement after a noxious stimulus under changing remifentanil concentrations. Furthermore, we measured the increase in CVI after a noxious stimulus in comparison to other clinical variables (BIS, sBIS, sEMG, heart rate [HR], and systolic blood pressure [BP(sys)]).</AbstractText>Twenty-four patients without a history of cardiac disease were investigated. Anesthesia was induced with propofol administered by target-controlled infusion. A standardized noxious electrical stimulus was applied (50 Hz, 70 mA, 30 seconds) to the ulnar nerve at increasing or decreasing remifentanil effect-compartment concentrations (Ce(remi)). Changes in baseline and poststimulus CVI, BIS, sBIS, sEMG, HR, and BP(sys) were investigated. Parameters' ability to indicate movement after a noxious stimulus was evaluated with the prediction probability (P(K)).</AbstractText>All investigated parameters (except BP(sys)) increased significantly after a noxious stimulus at 0, 1, 2, or 3 ng·mL(-1) Ce(remi). The association between poststimulus maximal parameters and movement were P(K) = 0.81 for HR, P(K) = 0.78 for sEMG, and P(K) = 0.72 for CVI (pairwise difference to CVI statistically nonsignificant). The association between ΔsEMG or ΔCVI (poststimulus value minus baseline value) and movement was significantly higher (P(K) = 0.76 and 0.75, respectively) compared with ΔHR (P(K) = 0.53) (P = 0.008 and P = 0.01, respectively). Receiver operating characteristic analysis revealed a threshold value for movement for ΔCVI of >0.39 (sensitivity of 0.71, specificity of 0.74) and for ΔsEMG of >0.31 (sensitivity of 0.68, specificity of 0.78).</AbstractText>In paralyzed patients, ΔsEMG and ΔCVI might help identify inadequately low levels of analgesia with an acceptable sensitivity and specificity. The impact of profound neuromuscular block on the CVI should be investigated in further studies.</AbstractText>
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2,333,882 |
Prolongation of PR interval is associated with endothelial dysfunction and activation of vascular repair in high-risk cardiovascular patients.
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Epidemiological studies showed that PR prolongation is associated with increased risk of adverse cardiovascular outcomes. We investigated the relations of PR interval with indices of vascular function and endothelial repair as the underlying mechanisms.</AbstractText>The study comprised 348 high-risk patients with prior coronary artery disease, ischemic stroke, and/or diabetes mellitus recruited from medical outpatient clinics and 150 healthy subjects without such a history. PR interval was considered prolonged if >200 ms, as determined from resting 12-lead electrocardiogram. Vascular function was assessed by brachial flow-meditated dilatation (FMD) using high-resolution ultrasound. Circulating CD133(+)/KDR(+) endothelial progenitor cell (EPC) levels were measured by flow cytometry.</AbstractText>Among healthy subjects, PR interval was inversely associated with FMD (R = -0.20, P = 0.015), but not with the level of circulating CD133(+)/KDR(+) EPC (R = 0.05, P = 0.58). Among high-risk cardiovascular patients, PR prolongation >200 ms was more common compared with healthy subjects (45/348 (13 %) versus 4/150 (3 %), P < 0.001). PR interval was associated inversely with FMD (R = -0.14, P = 0.01) and positively with circulating CD133(+)/KDR(+) EPC level (R = +0.14, P = 0.009). Circulating CD133(+)/KDR(+) EPC level was significantly increased in patients with PR prolongation >200 ms (0.87 ± 0.37 versus 0.68 ± 0.42 (log, ×10(-3)/ml), P = 0.005). Adjusted for potential confounders, increased PR interval remained independently associated with increased CD133(+)/KDR(+) EPC by +0.002 (95 % confidence interval (CI) 0.000 to 0.004 (log, ×10(-3)/ml), P = 0.011) and depressed FMD (B = -0.014 %, 95 % CI -0.027 to -0.002, P = 0.026).</AbstractText>PR prolongation is associated with endothelial dysfunction and evidence of endothelial repair activation in patients with high cardiovascular risk.</AbstractText>
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2,333,883 |
Changes in cerebral blood flow and vasoreactivity to CO2 measured by arterial spin labeling after 6days at 4350m.
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Changes in cerebral perfusion and CO2 cerebrovascular reactivity during and immediately after a sojourn at high altitude remain unclear but may be critical for acclimatization. The aim of the present study was to assess the effects of 6days at 4350m on cerebral perfusion and cerebrovascular reactivity (CVR) to CO2 by arterial spin labeling (ASL) magnetic resonance imaging at sea level and to compare it with transcranial Doppler (TCD) results at altitude. Eleven healthy male subjects, non-acclimatized to altitude, stayed for 6days at 4350m (Observatoire Vallot, massif du Mont-Blanc). Prior to the stay and within 6h after returning to sea level, subjects were investigated using pseudo-continuous ASL at 3T during a block-design inhalation paradigm to measure basal cerebral blood flow (CBF) and CO2 CVR. End-tidal CO2 (PetCO2), respiratory rate, heart rate and oxygen saturation were recorded during the exam. Subjects were also examined using TCD prior to and on day 5 of the stay at altitude to measure blood velocity in the middle cerebral artery (MCAv) and CO2 CVR. CO2 CVR was expressed as percent change in ASL CBF or TCD MCAv per mmHg change in PetCO2. PetCO2 was significantly decreased during and after altitude. Significant increases in TCD MCAv compared to before altitude measurements were observed on day 5 at altitude (+20.5±15.5%). Interestingly, ASL CBF remained increased in the MCA and anterior vascular territories (+22.0±24.1% and 20.5±20.3%, respectively) after altitude under normoxic conditions. TCD CVR tended to decrease on day 5 at 4350m (-12.3±54.5% in the MCA) while the ASL CVR was significantly decreased after altitude (-29.5±19.8% in the MCA). No correlation was observed between cerebral hemodynamic changes and symptoms of acute mountain sickness at high altitude. In conclusion, prolonged exposure to high altitude significantly increases blood flow during the altitude stay and within 6h after returning to sea level. Decreased CO2 CVR after prolonged altitude exposure was also observed using ASL. Changes in cerebral hemodynamics with altitude exposure probably involve other mechanisms than the vasodilatory effect of hypoxia only, since it persists under normoxia several hours following the descent.
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2,333,884 |
Comparison of motor-evoked potentials monitoring in response to transcranial electrical stimulation in subjects undergoing neurosurgery with partial vs no neuromuscular block.
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There have been no evidence-based comparisons of motor-evoked potential (MEP) monitoring with no and partial neuromuscular block (NMB). We compared the effects of different levels of NMB including no NMB on MEP parameters.</AbstractText>MEP-monitored 120 patients undergoing neurosurgery were enrolled. The patients were randomly allocated to four groups: Group A was to maintain two train-of-four (TOF) counts; Group B was to maintain a T(1)/Tc of 0.5; Group C was to maintain a T(2)/Tc of 0.5 (T(1,2), first or second twitch height of TOF; Tc, control twitch height); Group D did not maintain NMB. The mean MEP amplitude, coefficient of variation (CV), the incidence of spontaneous respiration or movement, the efficacy of MEP, and haemodynamic parameters were compared.</AbstractText>The median [inter-quartile range (IQR)] amplitudes of the left leg for Groups A, B, C, and D were 0.23 (0.15-0.57), 0.44 (0.19-0.79), 0.28 (0.15-0.75), and 0.75 (0.39-1.35) mV, respectively. The median (IQR) CVs of the left leg were 71.1 (56.9-88.8), 76.1 (54.2-93.1), 59.8 (48.6-95.6), and 25.2 (17.3-35.0), respectively. The differences between groups of the mean amplitudes of the left arm and both legs were statistically significant (Kruskal-Wallis test, P=0.011 for the left leg). For all limbs, the differences between groups of the CVs were significant (P<0.001, for the left leg). Other parameters were not different.</AbstractText>If NMB is used during MEP monitoring, a target T(2)/Tc of 0.5 is recommended. In terms of the MEP amplitude and variability, no NMB was more desirable than any level of partial NMB.</AbstractText>
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2,333,885 |
Aryl phosphate esters within a major PentaBDE replacement product induce cardiotoxicity in developing zebrafish embryos: potential role of the aryl hydrocarbon receptor.
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Firemaster 550 (FM550) is an additive flame retardant formulation of brominated and aryl phosphate ester (APE) components introduced as a major replacement product for the commercial polybrominated diphenyl ether mixture (known as PentaBDE) used primarily in polyurethane foam. However, little is known about the potential effects of FM550-based ingredients during early vertebrate development. Therefore, we first screened the developmental toxicity of each FM550 component using zebrafish as an animal model. Based on these initial screening assays, we found that exposure to the brominated components as high as 10µM resulted in no significant effects on embryonic survival or development, whereas exposure to triphenyl phosphate (TPP) or mono-substituted isopropylated triaryl phosphate (mono-ITP)-two APEs comprising almost 50% of FM550-resulted in targeted effects on cardiac looping and function during embryogenesis. As these cardiac abnormalities resembled aryl hydrocarbon receptor (AHR) agonist-induced phenotypes, we then exposed developing embryos to TPP or mono-ITP in the presence or absence of an AHR antagonist (CH223191) or AHR2-specific morpholino. Based on these studies, we found that CH223191 blocked heart malformations following exposure to mono-ITP but not TPP, whereas AHR2 knockdown failed to block the cardiotoxic effects of both components. Finally, using a cell-based human AHR reporter assay, we found that mono-ITP (but not TPP) exposure resulted in a significant increase in human AHR-driven luciferase activity at similar nominal concentrations as a potent reference AHR agonist (β-naphthoflavone). Overall, our findings suggest that two major APE components of FM550 induce severe cardiac abnormalities during early vertebrate development.
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2,333,886 |
Expression of coxsackievirus and adenovirus receptor (CAR)-Fc fusion protein in Pichia pastoris and characterization of its anti-coxsackievirus activity.
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Coxsackievirus and adenovirus receptors (CARs) are the common cellular receptors which mediate coxsackievirus or adenovirus infection. Receptor trap therapy, which uses soluble viral receptors to block the attachment and internalization of virus, has been developed for the inhibition of virus infection. In this study, we have constructed a pPIC3.5K/CAR-Fc expression plasmid for the economical and scale-up production of CAR-Fc fusion protein in Pichia pastoris. The coding sequence of the fusion protein was optimized according to the host codon usage bias. The amount of the CAR-Fc protein to total cell protein was up to 10% by 1% methanol induction for 96h and the purity was up to 96% after protein purification. Next, the virus pull-down assay demonstrated the binding activity of the CAR-Fc to coxsackievirus. The analyses of MTT assay, immunofluorescence staining and quantitative real-time PCR after virus neutralization assay revealed that CAR-Fc could significantly block coxsackievirus B3 infection in vitro. In coxsackievirus B3 infected mouse models, CAR-Fc treatment reduced mortality, myocardial edema, viral loads and inflammation, suggesting the significant virus blocking effect in vivo. Our results indicated that the P. pastoris expression system could be used to produce large quantities of bioactive CAR-Fc for further clinical purpose.
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2,333,887 |
Pediatric systems medicine: evaluating needs and opportunities using congenital heart block as a case study.
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Medicine and pediatrics are changing and health care is moving from being reactive to becoming preventive. Despite rapid developments of new technologies for molecular profiling and systems analysis of diseases, significant hurdles remain. Here, we use the clinical setting of congenital heart block (CHB) to uncover and illustrate key informatics challenges impeding the development of a systems medicine approach emphasizing the prevention and prediction of disease. We find that there is a paucity of useful bioinformatics tools enabling the integrative analysis of different databases of molecular information and clinical sources in a disease context such as CHB, contrasting with the current emphasis on developing bioinformatics tools for the analysis of individual data types. Moreover, informatics solutions for managing data, such as the Integrating Biology and the Bedside (i2b2) or Stanford Translational Research Integrated Database Environment, require serious software engineering support for the maintenance and import of data beyond the capabilities of clinicians working with CHB. Hence, there is an urgent unmet need for user-friendly tools facilitating the integrative analysis and management of omics data and clinical information. Pediatrics represents an untapped potential to execute such a systems medicine program in close collaboration with clinicians and families who are keen to do what is needed for their children to prevent and predict diseases and nurture wellness.
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2,333,888 |
Where are lifesaving automated external defibrillators located and how hard is it to find them in a large urban city?
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Automated external defibrillators (AEDs) are lifesaving, but little is known about where they are located or how to find them. We sought to locate AEDs in high employment areas of Philadelphia and characterize the process of door-to-door surveying to identify these devices.</AbstractText>Block groups representing approximately the top 3rd of total primary jobs in Philadelphia were identified using the US Census Local Employment Dynamics database. All buildings within these block groups were surveyed during regular working hours over six weeks during July-August 2011. Buildings were characterized as publically accessible or inaccessible. For accessible buildings, address, location type, and AED presence were collected. Total devices, location description and prior use were gathered in locations with AEDs. Process information (total people contacted, survey duration) was collected for all buildings.</AbstractText>Of 1420 buildings in 17 block groups, 949 (67%) were accessible, but most 834 (88%) did not have an AED. 283 AEDs were reported in 115 buildings (12%). 81 (29%) were validated through visualization and 68 (24%) through photo because employees often refused access. In buildings with AEDs, several employees (median 2; range 1-8) were contacted to ascertain information, which required several minutes (mean 4; range 1-55).</AbstractText>Door-to-door surveying is a feasible, but time-consuming method for identifying AEDs in high employment areas. Few buildings reported having AEDs and few permitted visualization, which raises concerns about AED access. To improve cardiac arrest outcomes, efforts are needed to improve the availability of AEDs, awareness of their location and access to them.</AbstractText>Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.</CopyrightInformation>
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2,333,889 |
Chemical and metabolomic screens identify novel biomarkers and antidotes for cyanide exposure.
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Exposure to cyanide causes a spectrum of cardiac, neurological, and metabolic dysfunctions that can be fatal. Improved cyanide antidotes are needed, but the ideal biological pathways to target are not known. To understand better the metabolic effects of cyanide and to discover novel cyanide antidotes, we developed a zebrafish model of cyanide exposure and scaled it for high-throughput chemical screening. In a screen of 3120 small molecules, we discovered 4 novel antidotes that block cyanide toxicity. The most potent antidote was riboflavin. Metabolomic profiling of cyanide-treated zebrafish revealed changes in bile acid and purine metabolism, most notably by an increase in inosine levels. Riboflavin normalizes many of the cyanide-induced neurological and metabolic perturbations in zebrafish. The metabolic effects of cyanide observed in zebrafish were conserved in a rabbit model of cyanide toxicity. Further, humans treated with nitroprusside, a drug that releases nitric oxide and cyanide ions, display increased circulating bile acids and inosine. In summary, riboflavin may be a novel treatment for cyanide toxicity and prophylactic measure during nitroprusside treatment, inosine may serve as a biomarker of cyanide exposure, and metabolites in the bile acid and purine metabolism pathways may shed light on the pathways critical to reversing cyanide toxicity.
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2,333,890 |
Newly developed urinary retention and motor weakness of lower extremities in a postherpetic neuralgia patient.
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During the early stage of postherpetic neuralgia, an epidural block on the affected segment is helpful in controlling pain and preventing progression to a chronic state. The main neurologic complication following an epidural block is cord compression symptom due to an epidural hematoma. When neurologic complications arise from an epidural block for the treatment of postherpetic neuralgia, it is important to determine whether the complications are due to the procedure or due to the herpes zoster itself. We report a case of a patient who was diagnosed with herpes zoster myelitis during treatment for postherpetic neuralgia. The patient complained of motor weakness in the lower extremities after receiving a thoracic epidural block six times. Although initially, we believed that the complications were due to the epidural block, it was ultimately determined to be from the herpes zoster myelitis.
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2,333,891 |
Obesity-related hypertension and the role of insulin and leptin in high-fat-fed rabbits.
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Feeding a high-fat diet (HFD) to rabbits results in increased blood pressure and renal sympathetic nerve activity (RSNA) and marked increases in plasma leptin and insulin. We determined the contribution of insulin and leptin signaling in the central nervous system to the increased blood pressure and RSNA during a HFD using specific antagonists. New Zealand White rabbits were implanted with an intracerebroventricular (ICV) catheter and RSNA electrode and placed on a normal or 13.5% HFD for 1 or 3 weeks. Blood pressure, heart rate, and RSNA were recorded before and for 90 minutes after ICV administration of a leptin antagonist (100 µg), insulin antagonist (0.5 U), or vehicle (50 µL) on separate days. Rabbits had higher blood pressure (+8%, +17%) and RSNA (+55%, +71%), at 1 and 3 weeks, respectively, of HFD compared with controls (n=7-11). ICV leptin antagonist reduced blood pressure by 9% and RSNA by 17% (P<0.001) after 3 weeks of HFD but had no effect at week 1. ICV administration of the insulin antagonist reduced blood pressure by ≈5% at both times (P<0.05) but there was no effect on RSNA. Leptin and insulin antagonist doses were confirmed to effectively block the pressor responses to ICV leptin and insulin, respectively. The elevation of blood pressure and RSNA induced by a HFD is predominantly mediated by central actions of leptin. Central actions of insulin contribute a smaller proportion of the hypertension but independently of RSNA.
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2,333,892 |
Psychometric testing of the Chinese Mandarin version of the Medical Outcomes Study Social Support Survey in patients with coronary heart disease in mainland China.
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To evaluate the psychometric properties of the Chinese Mandarin version of the Medical Outcomes Study Social Support Survey (MOS-SSS-CM) in patients with coronary heart disease (CHD) in mainland China.</AbstractText>Measurement performance of the MOS-SSS-CM was tested on a convenience sample of 200 Chinese patients with CHD in a University-affiliated hospital in Xi'an, P. R. China. To establish reliability of the instrument, 40 patients were retested 2 weeks later through telephone interview. The traditional Chinese version of the MOS-SSS was transformed into a simplified Chinese Mandarin version and administered to participants, together with Chinese Mandarin versions of the Short Form-36 item Health Survey (SF-36) and the Hospital Anxiety and Depression Scale (HADS).</AbstractText>The MOS-SSS-CM had acceptable internal consistency with Cronbach α coefficients of 0.91 for the overall scale and 0.71-0.84 for the four subscales. The high correlation (r = 0.56-0.87) between items and the remainder of the scale provides further evidence of internal consistency. The test-retest reliability was generally acceptable with intraclass correlation coefficients of 0.89 for the overall scale and 0.74-0.88 for the four subscales. There was acceptable concurrent validity with moderate significant correlations (r ≥ 0.3, p < 0.01) between the MOS-SSS-CM and the Chinese Mandarin version of the HADS. Confirmatory factor analysis supported a four-factor structure of the MOS-SSS-CM measuring the self-perceived adequacy of functional support of Chinese patients with CHD.</AbstractText>The MOS-SSS-CM is a valid and reliable measure for Chinese Mandarin-speaking patients with CHD.</AbstractText>
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2,333,893 |
The association between leisure time physical activity and coronary heart disease among men with different physical work demands: a prospective cohort study.
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The interplay of occupational and leisure time physical activity (LTPA) in affecting cardiovascular health is subject to debate. This study aimed to examine the independent and interacting associations of leisure time and occupational physical activity (OPA) with the incidence of coronary events within the BELSTRESS cohort. The study included 14,337 middle-aged men free from coronary heart disease at baseline. Standardized questionnaires and clinical examinations were used to assess socio-demographic factors, level of physical activity, job strain and classical coronary risk factors. The incidence of clinical coronary events was monitored during a mean follow-up time of 3.15 years. Results demonstrated overall a beneficial relation of LTPA and an adverse relation of physical work demands with cardiovascular health. However, an interaction effect between both physical activity types was observed, showing that men with high physical job demands who also engaged in physical activity during leisure time had an almost four times increased incidence of coronary events after adjusting for socio-demographic and classical coronary risk factors (HR 3.82; 95% CI 1.41-10.36). Stratified analyses revealed that moderate to high physical activity during leisure time was associated with a 60% reduced incidence rate of coronary events in men with low OPA (age adjusted HR 0.40; 95% CI 0.21-0.76), while this protective association was not observed in workers being exposed to high physical work demands (age adjusted HR 1.67; 95% CI 0.63-4.48). These findings suggest that recommendations regarding LTPA should be tailored according to the level of occupational physical activity.
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2,333,894 |
Pharmacokinetics and pharmacodynamic effects of tolazoline following intravenous administration to horses.
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Tolazoline is an α2-adrenergic receptor antagonist, used in veterinary medicine to antagonize the central nervous system depressant and cardiovascular effects of α2 receptor agonists. The pharmacokinetics and pharmacodynamic effects of tolazoline when administered subsequent to detomidine in the horse were recently reported, although the reversal of the sedative and cardiovascular effects following detomidine may not be complete. The current study therefore investigated the pharmacokinetics and pharmacodynamic effects of tolazoline when administered as a sole agent. Nine healthy adult horses were administered tolazoline (4mg/kgIV) and blood samples were collected at time 0 (prior to drug administration) and at various times up to 72h post drug administration. Plasma samples were analyzed using liquid chromatography-mass spectrometry and resulting data analyzed using compartmental analysis. Systemic clearance, steady state volume of distribution and terminal elimination half-life were 0.820±0.182L/h/kg, 1.68±0.379L/kg and 2.69±0.212h, respectively. Tolazoline administration had no effect on chin to ground distance, but the heart rate decreased (relative to baseline) and the percentage of atrial-ventricular block increased in all horses within 2min of administration. Packed cell volume and glucose concentrations were also increased throughout the sampling period. While not commonly used as a sole agent, caution is indicated whenever tolazoline is administered since the effects may be unpredictable.
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2,333,895 |
Conduction and block of inward rectifier K+ channels: predicted structure of a potent blocker of Kir2.1.
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Dysfunction of Kir2.1, thought to be the major component of inward currents, I(K1), in the heart, has been linked to various channelopathies, such as short Q-T syndrome. Unfortunately, currently no known blockers of Kir2.x channels exist. In contrast, Kir1.1b, predominantly expressed in the kidney, is potently blocked by an oxidation-resistant mutant of the honey bee toxin tertiapin (tertiapin-Q). Using various computational tools, we show that both channels are closed by a hydrophobic gating mechanism and inward rectification occurs in the absence of divalent cations and polyamines. We then demonstrate that tertiapin-Q binds to the external vestibule of Kir1.1b and Kir2.1 with K(d) values of 11.6 nM and 131 μM, respectively. We find that a single mutation of tertiapin-Q increases the binding affinity for Kir2.1 by 5 orders of magnitude (K(d) = 0.7 nM). This potent blocker of Kir2.1 may serve as a structural template from which potent compounds for the treatment of various diseases mediated by this channel subfamily, such as cardiac arrhythmia, can be developed.
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2,333,896 |
Differential effectiveness of tianeptine, clonidine and amitriptyline in blocking traumatic memory expression, anxiety and hypertension in an animal model of PTSD.
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Individuals exposed to life-threatening trauma are at risk for developing post-traumatic stress disorder (PTSD), a debilitating condition that involves persistent anxiety, intrusive memories and several physiological disturbances. Current pharmacotherapies for PTSD manage only a subset of these symptoms and typically have adverse side effects which limit their overall effectiveness. We evaluated the effectiveness of three different pharmacological agents to ameliorate a broad range of PTSD-like symptoms in our established predator-based animal model of PTSD. Adult male Sprague-Dawley rats were given 1-h cat exposures on two occasions that were separated by 10 days, in conjunction with chronic social instability. Beginning 24 h after the first cat exposure, rats received daily injections of amitriptyline, clonidine, tianeptine or vehicle. Three weeks after the second cat exposure, all rats underwent a battery of behavioral and physiological tests. The vehicle-treated, psychosocially stressed rats demonstrated a robust fear memory for the two cat exposures, as well as increased anxiety expressed on the elevated plus maze, an exaggerated startle response, elevated heart rate and blood pressure, reduced growth rate and increased adrenal gland weight, relative to the vehicle-treated, non-stressed (control) rats. Neither amitriptyline nor clonidine was effective at blocking the entire cluster of stress-induced sequelae, and each agent produced adverse side effects in control subjects. Only the antidepressant tianeptine completely blocked the effects of psychosocial stress on all of the physiological and behavioral measures that were examined. These findings illustrate the differential effectiveness of these three treatments to block components of PTSD-like symptoms in rats, and in particular, reveal the profile of tianeptine as the most effective of all three agents.
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2,333,897 |
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 unbooked 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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2,333,898 |
Medullary GABAergic mechanisms contribute to electroacupuncture modulation of cardiovascular depressor responses during gastric distention in rats.
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Electroacupuncture (EA) at P5-P6 acupoints overlying the median nerves typically reduces sympathoexcitatory blood pressure (BP) reflex responses in eucapnic rats. Gastric distention in hypercapnic acidotic rats, by activating both vagal and sympathetic afferents, decreases heart rate (HR) and BP through actions in the rostral ventrolateral medulla (rVLM) and nucleus ambiguus (NAmb), leading to sympathetic withdrawal and parasympathetic activation, respectively. A GABAA mechanism in the rVLM mediates the decreased sympathetic outflow. The present study investigated the hypothesis that EA modulates gastric distention-induced hemodynamic depressor and bradycardia responses through nuclei that process parasympathetic and sympathetic outflow. Anesthetized hypercapnic acidotic rats manifested repeatable decreases in BP and HR with gastric distention every 10 min. Bilateral EA at P5-P6 for 30 min reversed the hypotensive response from -26 ± 3 to -6 ± 1 mmHg and the bradycardia from -35 ± 11 to -10 ± 3 beats/min for a period that lasted more than 70 min. Immunohistochemistry and in situ hybridization to detect c-Fos protein and GAD 67 mRNA expression showed that GABAergic caudal ventral lateral medulla (cVLM) neurons were activated by EA. Glutamatergic antagonism of cVLM neurons with kynurenic acid reversed the actions of EA. Gabazine used to block GABAA receptors microinjected into the rVLM or cVLM reversed EA's action on both the reflex depressor and bradycardia responses. EA modulation of the decreased HR was inhibited by microinjection of gabazine into the NAmb. Thus, EA through GABAA receptor mechanisms in the rVLM, cVLM, and NAmb modulates gastric distention-induced reflex sympathoinhibition and vagal excitation.
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2,333,899 |
In vivo monitoring of cardiomyocyte proliferation to identify chemical modifiers of heart regeneration.
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Adult mammalian cardiomyocytes have little capacity to proliferate in response to injury, a deficiency that underlies the poor regenerative ability of human hearts after myocardial infarction. By contrast, zebrafish regenerate heart muscle after trauma by inducing proliferation of spared cardiomyocytes, providing a model for identifying manipulations that block or enhance these events. Although direct genetic or chemical screens of heart regeneration in adult zebrafish present several challenges, zebrafish embryos are ideal for high-throughput screening. Here, to visualize cardiomyocyte proliferation events in live zebrafish embryos, we generated transgenic zebrafish lines that employ fluorescent ubiquitylation-based cell cycle indicator (FUCCI) technology. We then performed a chemical screen and identified several small molecules that increase or reduce cardiomyocyte proliferation during heart development. These compounds act via Hedgehog, Insulin-like growth factor or Transforming growth factor β signaling pathways. Direct examination of heart regeneration after mechanical or genetic ablation injuries indicated that these pathways are activated in regenerating cardiomyocytes and that they can be pharmacologically manipulated to inhibit or enhance cardiomyocyte proliferation during adult heart regeneration. Our findings describe a new screening system that identifies molecules and pathways with the potential to modify heart regeneration.
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