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2,334,100 |
Second malignant neoplasms and cardiovascular disease following radiotherapy.
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Second malignant neoplasms (SMNs) and cardiovascular disease (CVD) are among the most serious and life-threatening late adverse effects experienced by the growing number of cancer survivors worldwide and are due in part to radiotherapy. The National Council on Radiation Protection and Measurements (NCRP) convened an expert scientific committee to critically and comprehensively review associations between radiotherapy and SMNs and CVD, taking into account radiobiology; genomics; treatment (ie, radiotherapy with or without chemotherapy and other therapies); type of radiation; and quantitative considerations (ie, dose-response relationships). Major conclusions of the NCRP include: 1) the relevance of older technologies for current risk assessment when organ-specific absorbed dose and the appropriate relative biological effectiveness are taken into account and 2) the identification of critical research needs with regard to newer radiation modalities, dose-response relationships, and genetic susceptibility. Recommendation for research priorities and infrastructural requirements include 1) long-term large-scale follow-up of extant cancer survivors and prospectively treated patients to characterize risks of SMNs and CVD in terms of radiation dose and type; 2) biological sample collection to integrate epidemiological studies with molecular and genetic evaluations; 3) investigation of interactions between radiotherapy and other potential confounding factors, such as age, sex, race, tobacco and alcohol use, dietary intake, energy balance, and other cofactors, as well as genetic susceptibility; 4) focusing on adolescent and young adult cancer survivors, given the sparse research in this population; and 5) construction of comprehensive risk prediction models for SMNs and CVD to permit the development of follow-up guidelines and prevention and intervention strategies.
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2,334,101 |
Clonidine does not improve quality of ropivacaine axillary brachial plexus block in children.
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The addition of clonidine to peripheral nerve blocks is controversial in children.</AbstractText>The aim of our study was to evaluate the effect of clonidine added to ropivacaine in pediatric axillary brachial plexus block (ABPB).</AbstractText>Children aged 1-6 years, scheduled to undergo forearm or hand surgery, were recruited into this prospective, double-blind controlled trial. Patients were randomly allocated to receive an ABPB either with ropivacaine 0.2% 0.4 ml · kg(-1) plus saline in 1 ml (RS) or ropivacaine 0.2% 0.4 ml · kg(-1) plus clonidine 1 μg · kg(-1) in 1 ml (RC). Primary endpoints were quality of postoperative analgesia as assessed by pain scores and total 24-h postoperative analgesia requirements. Secondary outcomes were time to first analgesia request and duration of motor blockade.</AbstractText>Sixty patients were recruited (n = 30 per group) into the study. Pain scores were comparable throughout the first 24 h between the two groups. Ten children in the (RS) and six in (RC) groups required supplementary analgesia during the first 24 h (P = 0.24). Children who required further analgesia did so after 288 ± 94 min in the (RS) and 437 ± 204 min in the (RC) group (P = 0.06). There was no difference in the duration of motor block [186 ± 71 and 154 ± 56 min, P = 0.12 for (RS) and (RC), respectively].</AbstractText>Ropivacaine (0.2% 0.4 ml · kg(-1) ) for ABPB provides sufficient postoperative analgesia in children scheduled for forearm or hand surgery. The addition of clonidine to ABPB does not improve overall postoperative analgesia but may increase the time to first analgesia request.</AbstractText>© 2012 Blackwell Publishing Ltd.</CopyrightInformation>
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2,334,102 |
Prognostic values of clockwise and counterclockwise rotation for cardiovascular mortality in Japanese subjects: a 24-year follow-up of the National Integrated Project for Prospective Observation of Noncommunicable Disease and Its Trends in the Aged, 1980-2004 (NIPPON DATA80).
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Although clockwise rotation and counterclockwise rotation are distinct findings of the ECG, their prognostic significance is rarely studied.</AbstractText>We studied prognostic values of clockwise and counterclockwise rotation on total, cardiovascular disease (CVD), and subtype mortality using the National Integrated Project for Prospective Observation of Noncommunicable Disease and Its Trends in the Aged, 1980-2004 (NIPPON DATA80) database with a 24-year follow-up. At baseline in 1980, data were collected on study participants aged ≥30 years from randomly selected areas in Japan. We followed 9067 participants (44% men; mean age, 51 years). During the 24-year follow-up, mortality was as follows: 2581 total, 887 CVD, 179 coronary heart disease, 173 heart failure, and 411 stroke. The multivariate-adjusted hazard ratio (HR) with the use of the Cox model including biochemical and other ECG variables revealed that clockwise rotation was significantly positively associated with heart failure in men and women combined (HR=1.79; 95% confidence interval [CI], 1.13-2.83; P=0.013), CVD in men and in men and women combined (HR=1.49; 95% CI, 1.12-1.98; P=0.007 in men; HR=1.28; 95% CI, 1.02-1.59; P=0.030 in combined), and total mortality in men and in men and women combined (HR=1.19; 95% CI, 1.00-1.49; P=0.0496 in men; HR=1.15; 95% CI, 1.00-1.32; P=0.045 in combined). Counterclockwise rotation was significantly inversely associated stroke in men and women combined (HR=0.77; 95% CI, 0.62-0.96; P=0.017), CVD in men and in men and women combined (HR=0.74; 95% CI, 0.59-0.94; P=0.011 in men; HR=0.81; 95% CI, 0.70-0.94; P=0.006 in combined), and total mortality in women (HR=0.87; 95% CI, 0.77-0.98; P=0.023).</AbstractText>We found a significant positive association of clockwise rotation and a significant inverse association of counterclockwise rotation with CVD mortality in men and in men and women combined, independent of confounding factors including other ECG changes.</AbstractText>
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2,334,103 |
Dynamic variations of P-wave duration in a patient with acute decompensated congestive heart failure.
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Interatrial block is an abnormally delayed atrial activation, characterized at ECG by prolonged P-wave duration (more than 110 ms), irrespective of morphology. We report the case of a patient with acute decompensated severe congestive heart failure, that at hospital admission showed a prolonged P-wave, which reverted after diuretic therapy. The dynamic change of the atrial P-wave correlates with clinical evolution and serum level modification of B-type natriuretic peptide.
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2,334,104 |
Pros and cons for C4d as a biomarker.
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The introduction of C4d in daily clinical practice in the late nineties aroused an ever-increasing interest in the role of antibody-mediated mechanisms in allograft rejection. As a marker of classical complement activation, C4d made it possible to visualize the direct link between anti-donor antibodies and tissue injury at sites of antibody binding in a graft. With the expanding use of C4d worldwide several limitations of C4d were identified. For instance, in ABO-incompatible transplantations C4d is present in the majority of grafts but this seems to point at 'graft accommodation' rather than antibody-mediated rejection. C4d is now increasingly recognized as a potential biomarker in other fields where antibodies can cause tissue damage, such as systemic autoimmune diseases and pregnancy. In all these fields, C4d holds promise to detect patients at risk for the consequences of antibody-mediated disease. Moreover, the emergence of new therapeutics that block complement activation makes C4d a marker with potential to identify patients who may possibly benefit from these drugs. This review provides an overview of the past, present, and future perspectives of C4d as a biomarker, focusing on its use in solid organ transplantation and discussing its possible new roles in autoimmunity and pregnancy.
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2,334,105 |
Curvature-Dependent Excitation Propagation in Cultured Cardiac Tissue.
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The geometry of excitation wave front may play an important role on the propagation block and spiral wave formation. The wave front which is bent over the critical value due to interaction with the obstacles may partially cease to propagate and appearing wave breaks evolve into rotating waves or reentry. This scenario may explain how reentry spontaneously originates in a heart. We studied highly curved excitation wave fronts in the cardiac tissue culture and found that in the conditions of normal, non-inhibited excitability the curvature effects do not play essential role in the propagation. Neither narrow isthmuses nor sharp corners of the obstacles, being classical objects for production of extremely curved wave front, affect non-inhibited wave propagation. The curvature-related phenomena of the propagation block and wave detachment from the obstacle boundary were observed only after partial suppression of the sodium channels with Lidocaine. Computer simulations confirmed the experimental observations. The explanation of the observed phenomena refers to the fact that the heart tissue is made of finite size cells so that curvature radii smaller than the cardiomyocyte size loses sense, and in non-inhibited tissue the single cell is capable to transmit excitation to its neighbors.
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2,334,106 |
Medical therapy is best for atherosclerotic renal artery stenosis: Arguments for.
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Atherosclerotic renal artery stenosis (ARAS) is a common condition that causes hypertension and reduction in the glomerular filtration rate and is an independent risk factor for death. Despite high technical success, the clinical benefit of renal artery (RA) angioplasty with stenting in ARAS remains doubtful. The published randomized clinical trials provide no support for the notion that renal angioplasty with stenting significantly improves blood pressure, preserves renal function, or reduces episodes of congestive heart failure in patients with ARAS. RA stenting is associated with procedure-related morbidity and mortality. Agents to block the renin-angiotensin-aldosterone system improve outcome and should be a part of a multifaceted medical regimen in ARAS. Medical therapy effectively controls atherosclerotic renovascular disease at all levels of vasculature and hence is the best therapy for ARAS.
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2,334,107 |
Penile block for paediatric urological surgery: A comparative evaluation with general anaesthesia.
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Peri-operative pain relief in children can be provided by conventional general anaesthesia or by regional nerve blocks. The present study was carried out to evaluate and compare the effectiveness of penile block for penile surgery with the standard technique of general anaesthesia (GA) of short duration of less than two hours, and also to evaluate the postoperative pain relief obtained by penile block.</AbstractText>The study was carried out in the department of Anaesthesiology and Intensive care of our hospital, on 60 children in the age group of 1-10 years, belonging to American Society of Anesthesiologists (ASA) grades I and II, and divided randomly into two groups: Group B and group G, comprising of 30 patients each. Group B children received a penile block whereas group G children underwent a standard general anaesthetic procedure. Baseline, intra-operative and post-operative heart rate (HR), electrocardiogram (ECG), non-invasive blood pressure (NIBP) (systolic and diastolic) and pulse oximeter oxygen saturation (SpO(2)) were recorded at regular intervals. The duration of post-operative pain relief, time to rescue analgesia and time to first feed were also evaluated and recorded. Statistical analysis was carried out using statistical package for social sciences (SPSS) 11 version for windows and employing analysis of variance (ANOVA), unpaired student t test, Chi-square test and Mann Whitney U test for various parameters. Value of P<0.05 was considered as significant and P<0.0001 as highly significant.</AbstractText>The demographic characteristics were comparable in both the groups. Heart rate, systolic blood pressure, diastolic blood pressure and pulse oximetry showed remarkable differences at various time intervals during intra-operative and post-operative period, which were statistically significant on comparison (P<0.05 and P<0.0001). Post-operative pain relief, time to first rescue analgesia and time to first feed also showed statistically significant differences.</AbstractText>Penile block is very effective when used along with light sedation for distal penile surgeries of less than 2 hours duration as compared to standard GA as reflected by more stable haemodynamics in peri-operative period, excellent pain relief extending up to 6-8 hrs postoperatively and absence of any significant complications or side effects.</AbstractText>
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2,334,108 |
Associations of processed meat and unprocessed red meat intake with incident diabetes: the Strong Heart Family Study.
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Fifty percent of American Indians (AIs) develop diabetes by age 55 y. Whether processed meat is associated with the risk of diabetes in AIs, a rural population with a high intake of processed meat (eg, canned meats in general, referred to as "spam") and a high rate of diabetes, is unknown.</AbstractText>We examined the associations of usual intake of processed meat with incident diabetes in AIs.</AbstractText>This prospective cohort study included AI participants from the Strong Heart Family Study who were free of diabetes and cardiovascular disease at baseline and who participated in a 5-y follow-up examination (n = 2001). Dietary intake was ascertained by using a Block food-frequency questionnaire at baseline. Incident diabetes was defined on the basis of 2003 American Diabetes Association criteria. Generalized estimating equations were used to examine the associations of dietary intake with incident diabetes.</AbstractText>We identified 243 incident cases of diabetes. In a comparison of upper and lower quartiles, intake of processed meat was associated with a higher risk of incident diabetes (OR: 1.63; 95% CI: 1.21, 2.63), after adjustment for potential confounders. The relation was particularly strong for spam (OR for the comparison of upper and lower quartiles: 2.06; 95% CI: 1.30, 3.27). Intake of unprocessed red meat was not associated with incident diabetes (OR for the comparison of upper and lower quartiles: 0.90; 95% CI: 0.59, 1.37).</AbstractText>The consumption of processed meat, such as spam, but not unprocessed red meat, was associated with higher risk of diabetes in AIs, a rural population at high risk of diabetes and with limited access to healthy foods.</AbstractText>
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2,334,109 |
[Rocuronium vs vecuronium for neuromuscular block during transsternal thymectomy in the patient with myasthenia gravis].
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Myasthenia gravis is an autoimmune disease marked by high titers of immunoglobulin G antibodies, which accelerate destruction of cholinergic receptors and interfere with neuromuscular transmission. This study aimed to determine whether neuromuscular function under a rocuronium block is different from function under a vecuronium block patients with myasthenia gravis and to describe extubation conditions in the operating room or the intensive care unit.</AbstractText>Randomized, single-blind clinical trial enrolling patients with myasthenia gravis type IIa and IIb according to the classification of Osserman. The patients were randomized to groups receiving a vecuronium or rocuronium block. We recorded arterial oxygen saturation, capnogram, heart rate, noninvasive blood pressure, electrocardiogram, and neuromuscular function by accelerometry. During surgery 25% of the total dose of the neuromuscular blocking agent was administered. Maintenance was with a continuous infusion of propofol and fentanyl. All patients were extubated according to clinical criteria, confirmed by train-of-four ratio (T4/T1).</AbstractText>The mean (SD) time elapsed before recovery of 25% of neuromuscular function was 53.1 (1.9) min in the rocuronium group and 56.2 (0.8) min in the vecuronium group (P = .01). Time elapsed before recovery of 90% of function was 71.3 (2.7) min in the rocuronium group and 96.3 (1.2) min in the vecuronium group (P = .001). Twenty-eight of the 30 patients in the rocuronium group (93.3%) were extubated with recovery of 89.1% (0.5%) of twitch response and a T4/T1 ratio of 0.83. The difference between groups was statistically significant (P = .01). In no case was it necessary to administer a maintenance dose or reverse the block.</AbstractText>The rocuronium block had a better profile than the vecuronium block in this study. With this blocking agent we were able to circumvent respiratory depression, with its immediate consequences, and thus meet the main clinical criterion when anesthetizing patients with myasthenia gravis.</AbstractText>
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2,334,110 |
Venous flow dynamics during spinal block in normotensive and hypertensive elderly patients: a duplex ultrasonographic study.
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Spinal block induces hyperkinetic change in lower extremity blood flow. We compared the venous flow dynamic responses to spinal block in normotensive and hypertensive elderly patients.</AbstractText>Following spinal block using 10 mg 0.5% (w/v) bupivacaine, we measured changes in blood pressure, heart rate, and venous flow dynamics of the popliteal vein by duplex ultrasonography in 20 normotensive (NBP group) and 18 hypertensive (HIBP group) patients.</AbstractText>Spinal block caused significant decreases in blood pressure in both groups; similar rates of hypotension were observed. At baseline, peak velocity, time-averaged maximum velocity, and time-averaged mean velocity were higher in the HIBP than in the NBP group. During spinal block, peak velocity increased in both groups, and the between-group differences were no longer significant. At baseline, volume flow in the two groups was similar and increased by 141.5% in the NBP and 131.7% in the HIBP group during spinal block.</AbstractText>Blood pressure and flow dynamics in the popliteal vein showed similar changes during spinal anaesthesia in elderly patients taking antihypertensive medication and normotensive patients, despite differences in baseline values.</AbstractText>© 2012 The Authors. Acta Anaesthesiologica Scandinavica © 2012 The Acta Anaesthesiologica Scandinavica Foundation.</CopyrightInformation>
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2,334,111 |
Block based neural network for hypoglycemia detection.
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In this paper, evolvable block based neural network (BBNN) is presented for detection of hypoglycemia episodes. The structure of BBNN consists of a two-dimensional (2D) array of fundamental blocks with four variable input-output nodes and weight connections. Depending on the structure settings, each block can have one of four different internal configurations. To provide early detection of hypoglycemia episodes, the physiological parameters such as heart rate (HR) and corrected QT interval (QTc) of electrocardiogram (ECG) signal are used as the inputs of BBNN. The overall structure and weights of BBNN are optimized by an evolutionary algorithm called hybrid particle swarm optimization with wavelet mutation (HPSOWM). The optimized structures and weights of BBNN are capable to compensate large variations of ECG patterns caused by individual and temporal difference since a fixed structure classifiers are easy to fail to trace ECG signals with large variations. The ECG data of 15 patients are organized into a training set, a testing set and a validation set, each of which has randomly selected 5 patients. The simulation results shows that the proposed algorithm, BBNN with HPSOWM can successfully detect the hypoglycemic episodes in T1DM in term of testing sensitivity (76.74%) and test specificity (50.91%).
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2,334,112 |
HRV analysis in local anesthesia using Continuous Wavelet Transform (CWT).
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Spectral analysis of Heart Rate Variability (HRV) is used for the assessment of cardiovascular autonomic control. In this study Continuous Wavelet Transform (CWT) has been used to evaluate the effect of local anesthesia on HRV parameters in a group of fourteen patients undergoing axillary brachial plexus block. A new method which takes signal characteristics into account has been presented for the estimation of the variable boundaries associated with the low and the high frequency band of the HRV signal. The variable boundary method might be useful in cases when the power related to respiration component extends beyond the traditionally excepted range of the high frequency band (0.15-0.4 Hz). The statistical analysis (non-parametric Wilcoxon signed rank test) showed that the LF/HF ratio decreased within an hour of the application of the brachial plexus block compared to the values fifteen minutes prior to the application of the block. These changes were observed in thirteen of the fourteen patients included in this study.
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2,334,113 |
Interactions between cardiac fibrosis spatial pattern and ionic remodeling on electrical wave propagation.
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Cardiac fibrosis is an important form of pathological tissue remodeling. Fibrosis can electrically-uncouple neighboring excitable cardiomyocytes thus acting as an obstacle to electrical propagation. In this study, we investigated the effects of fibrosis spatial pattern on electrical propagation in control, decreased maximum sodium conductance, and increased intracellular resistivity conditions. Simulations were performed with a monodomain approach and a realistic canine ionic model. We found that the propagation failure is highly dependent on the spatial pattern of fibrosis for all conditions studied with maximum sensitivity for patterns with combination of small and large clusters. However, the effect is particularly sensitive to reduced sodium current condition where conduction block occurred at lower fibrosis density.
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2,334,114 |
Study of neurovascular and autonomic response in a divided attention test by means of EEG, ECG and NIRS signals.
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We evaluated neurovascular and autonomic response to a Divided Attention task within a group of 16 healthy subjects, by means of Electroencephalography, Electrocardiography, functional Near Infrared Spectroscopy techniques, acquired simultaneously. We exctracted Alpha (8-13,5 Hz) and Beta (13,5-30 Hz) power rhythms with a spectral autoregressive residual model, and inter-beat-interval (RR series) and separated superficial (extracortical) and depth NIRS contribution. Cross Correlation Function at different time lags was then calculated between each signal and the task, modeled as a square wave and among couples of signals, in order to evaluate the sequence of activation of the different physiological districts involved and the common information shared. Results showed the presence of a cascade of responses and a strong influence by the block task on each signal, representative of the neurovascular coupling elicited by the cognitive cerebral activation.
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2,334,115 |
Mice expressing a human K(ATP) channel mutation have altered channel ATP sensitivity but no cardiac abnormalities.
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<AbstractText Label="AIMS/HYPOTHESIS" NlmCategory="OBJECTIVE">Patients with severe gain-of-function mutations in the Kir6.2 subunit of the ATP-sensitive potassium (K(ATP)) channel, have neonatal diabetes, muscle hypotonia and mental and motor developmental delay-a condition known as iDEND syndrome. However, despite the fact that Kir6.2 forms the pore of the cardiac K(ATP) channel, patients show no obvious cardiac symptoms. The aim of this project was to use a mouse model of iDEND syndrome to determine whether iDEND mutations affect cardiac function and cardiac K(ATP) channel ATP sensitivity.</AbstractText>We performed patch-clamp and in vivo cine-MRI studies on mice in which the most common iDEND mutation (Kir6.2-V59M) was targeted to cardiac muscle using Cre-lox technology (m-V59M mice).</AbstractText>Patch-clamp studies of isolated cardiac myocytes revealed a markedly reduced K(ATP) channel sensitivity to MgATP inhibition in m-V59M mice (IC(50) 62 μmol/l compared with 13 μmol/l for littermate controls). In vivo cine-MRI revealed there were no gross morphological differences and no differences in heart rate, end diastolic volume, end systolic volume, stroke volume, ejection fraction, cardiac output or wall thickening between m-V59M and control hearts, either under resting conditions or under dobutamine stress.</AbstractText><AbstractText Label="CONCLUSIONS/INTERPRETATION" NlmCategory="CONCLUSIONS">The common iDEND mutation Kir6.2-V59M decreases ATP block of cardiac K(ATP) channels but was without obvious effect on heart function, suggesting that metabolic changes fail to open the mutated channel to an extent that affects function (at least in the absence of ischaemia). This may have implications for the choice of sulfonylurea used to treat neonatal diabetes.</AbstractText>
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2,334,116 |
Anesthetic and analgesic effects in patients undergoing a lumbar laminectomy of spinal, epidural or a combined spinal-epidural block with the addition of morphine.
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This study was designed to evaluate the anesthetic, analgesic and side effects of spinal, epidural and combined spinal-epidural anesthesia with the addition of morphine for lumbar laminectomy. A total of 66 patients undergoing lumbar laminectomy were included in the present study of whom 64 completed the study. Patients were randomly divided into three groups: (i) spinal anesthesia - the SA group; (ii) epidural anesthesia - the EA group; and (iii) combined spinal-epidural anesthesia - the CA group. Demographical data, surgical times and peak sensory levels of groups were similar. Heart rate, mean arterial pressure, and peripheral oxygen saturation did not differ between the three groups. No differences were observed intraoperatively in Ramsey sedation scale (RSS) scores between the groups, but postoperatively, although RSS scores were similar for the EA and CA groups, they were significantly lower for the SA group. The postoperative visual analogue scale pain scores were higher in the SA group compared to the EA and the CA groups except for the second postoperative hour. Time-to-use of the first patient controlled analgesia was similar for all groups. The total consumption of morphine over the 24-hour study period was significantly higher in the SA group compared to the EA and the CA groups. Postoperative nausea and vomiting frequencies were higher in SA group, but pruritus frequency was lower than the EA and the CA groups. In conclusion, although spinal, epidural, and combined spinal-epidural anesthesia are adequate and effective for lumbar laminectomies, epidural and combined spinal-epidural anesthesia techniques are more effective than spinal anesthesia for postoperative analgesia and sedation with lesser side effects.
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2,334,117 |
Comparing caudal and penile nerve blockade using bupivacaine in hypospadias repair surgeries in children.
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Caudal anaesthesia is recommended for most surgical procedures of the lower part of the body, mainly below the umbilicus. It has been well established that a dorsal penile nerve block immediately after surgery decreases postoperative pain in children undergoing hypospadias repair. This study aimed to compare caudal or penile nerve block using bupivacaine in postoperative pain control in hypospadias repair in children.</AbstractText>After local ethical committee approval and obtaining informed parental consent, 85 American society of Anesthesiologists status I and II patients, aged 6 months to 6 years old, undergoing hypospadias repair, were prospectively enrolled in this study. The patients were randomly divided into the following two groups: Caudal block was performed in 44 and penile block was performed in 41 patients. Cardiorespiratory systems data, analgesic requirement and complications were compared between the groups.</AbstractText>There were statistically significant haemodynamic (blood pressure and heart rate) alteration during operation in each group (P<0.01). The haemodynamic parameters were stable during operation in successful blocks in both groups. Caudal block success rate is 97.7%, whereas in penile block is 92.6%. Nineteen of 43 patients (44%) in caudal group and 29 of 41 patients (70%) in penile group received analgesia in the postoperative period and this difference was significant between the two groups (P = 0.025).</AbstractText>Without ultrasonography and with blind block, with anatomic landmarks only, the caudal block success rate is high and if there is no contraindication for caudal block, it is the best choice in children under 6 years old (or 25 kg) for hypospadias repair.</AbstractText>
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2,334,118 |
Control of pain through epidural block and incidence of cardiac dysrhythmias in postoperative period of thoracic and major abdominal surgical procedures: a comparative study.
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Upper abdomen and thorax surgeries cause intense pain. Some of postoperative pain main complications are cardiocirculatory complications. The objective of this study was to test the hypothesis that postoperative analgesia with employment of local anesthetics plus spinal opioids may reduce the incidence of cardiovascular complications in postoperative period of patients in these conditions, comparing with classical methods of postoperative analgesia, opioids and NSAIDs, administered upon patient's demand.</AbstractText>Eighty adult patients, ASA I and II, without ECG alterations, were allocated into two groups of 40: Group A, patients under general anesthesia with propofol, cisatracurium and isoflurane, associated with epidural anesthesia with catheter and control of postoperative analgesia with bupivacaine and epidural morphine; and Group B, patients under general anesthesia with the same drugs and doses of A, plus postoperative analgesia carried out with NSAIDs and intravenous morphine at the end of surgery and in regular intervals. In both groups Holter was applied for 24 hours. Pain evaluation was carried out through visual analog scale.</AbstractText>In pain evaluation, an evident predominance of 0 score (p<0.001) was observed in Group A and there was also reduction of blood pressure levels in postoperative period in a more accentuated way. Ventricular and supraventricular dysrhythmias were five times more frequent in Group B (p=0.00001), in which a tendency to a higher frequency of ventricular extrasystoles in age>50 years (22.2% versus 0.0%. p=0.26) was also detected. No significative difference of heart rate among groups (p>0.05) was observed.</AbstractText>The best quality of analgesia in postoperative period, carried out in Group A, reduced the incidence of cardiovascular complications.</AbstractText>Copyright © 2012 Elsevier Editora Ltda. All rights reserved.</CopyrightInformation>
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2,334,119 |
The role of non-covalent interactions in anticancer drug loading and kinetic stability of polymeric micelles.
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A new series of acid- and urea-functionalized polycarbonate block copolymers were synthesized via organocatalytic living ring-opening polymerization using methoxy poly(ethylene glycol) (PEG) as a macroinitiator to form micelles as drug delivery carriers. The micelles were characterized for critical micelle concentration, particle size and size distribution, kinetic stability and loading capacity for a model anticancer drug, doxorubicin (DOX) having an amine group. The acid/urea groups were placed in block forms (i.e. acid as the middle block or the end block) or randomly distributed in the polycarbonate block to investigate molecular structure effect. The micelles formed from the polymers in both random and block forms provided high drug loading capacity due to strong ionic interaction between the acid in the polymer and the amine in DOX. However, the polymers with acid and urea groups placed in the block forms formed micelles with wider size distribution (two size populations), and their DOX-loaded micelles were less stable. The number of acid/urea groups in the random form was further varied from 5 to 8, 13 and 19 to study its effects on self-assembly behaviors and DOX loading. An increased number of acid/urea groups yielded DOX-loaded micelles with smaller size and enhanced kinetic stability because of improved inter-molecular polycarbonate-polycarbonate (urea-urea and urea-acid) hydrogen-bonding and polycarbonate-DOX (acid-amine) ionic interactions. However, when the number of acid/urea groups was 13 or higher, micelles aggregated in a serum-containing medium, and freeze-dried DOX-loaded micelles were unable to re-disperse in an aqueous solution. Among all the polymers synthesized in this study, 1b with 8 acid/urea groups in the random form had the optimum properties. In vitro release studies showed that DOX release from 1b micelles was sustained over 7 h without significant initial burst release. MTT assays demonstrated that the polymer was not toxic towards HepG2 and HEK293 cells. Importantly, DOX-loaded micelles were potent against HepG2 cells with IC(50) of 0.26 mg/L, comparable to that of free DOX (IC(50): 0.20 mg/L). In addition, DOX-loaded 1b micelles yielded lower DOX content in the heart tissue of the tested mice as compared to free DOX formulation after i.v. injection. These findings signify that 1b micelles may be a promising carrier for delivery of anticancer drugs that contain amine groups.
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2,334,120 |
Promoter polymorphism G-6A, which modulates angiotensinogen gene expression, is associated with non-familial sick sinus syndrome.
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It is well known that familial sick sinus syndrome (SSS) is caused by functional alterations of ion channels and gap junction. Limited information is available on the mechanism of age-related non-familial SSS. Although evidence shows a close link between arrhythmia and the renin-angiotensin system (RAS), it remains to be determined whether the RAS is involved in the pathogenesis of non-familial SSS.</AbstractText>In this study, 113 patients with documented non-familial SSS and 125 controls were screened for angiotensinogen (AGT) and gap junction protein-connexin 40 (Cx40) promoter polymorphisms by gene sequencing, followed by an association study. A luciferase assay was used to determine the transcriptional activity of the promoter polymorphism. The interaction between nuclear factors and the promoter polymorphism was characterized by an electrophoretic mobility shift assay (EMSA).</AbstractText>Association study showed the Cx40 -44/+71 polymorphisms are not associated with non-familial SSS; however, it indicated that four polymorphic sites at positions -6, -20, -152, and -217 in the AGT promoter are linked to non-familial SSS. Compared to controls, SSS patients had a lower frequency of the G-6A AA genotype (OR 2.88, 95% CI 1.58-5.22, P = 0.001) and a higher frequency of the G allele at -6 position (OR 2.65, 95% CI 1.54-4.57, P = 0.0003). EMSA and luciferase assays confirmed that nucleotide G at position -6 modulates the binding affinity with nuclear factors and yields a lower transcriptional activity than nucleotide A (P<0.01).</AbstractText>G-6A polymorphism, which modulates the transcriptional activity of the AGT promoter, may contribute to non-familial SSS susceptibility.</AbstractText>
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2,334,121 |
Impact of collection and storage of lung tumor tissue on whole genome expression profiling.
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Gene expression profiling could assist in revealing biomarkers of lung cancer prognosis and progression. The handling of biological samples may strongly influence global gene expression, a fact that has not been addressed in many studies. We sought to investigate the changes in gene expression that may occur as a result of sample processing time and conditions. Using Illumina Human WG-6 arrays, we quantified gene expression in lung carcinoma samples from six patients obtained at chest opening before and immediately after lung resection with storage in RNAlater [T1a((CO)) and T1b((LR))], after receipt of the sample for histopathology, placed in RNAlater [T2a((HP))]; snap frozen [T2b((HP.SF))]; or snap frozen and stored for 1 week [T2c((HP.SFA))], as well as formalin-fixed, paraffin-embedded (FFPE) block samples. Sampling immediately after resection closely represented the tissue obtained in situ, with only 1% of genes differing more than twofold [T1a((CO)) versus T1b((LR))]. Delaying tissue harvest for an average of 30 minutes from the operating theater had a significant impact on gene expression, with approximately 25% of genes differing between T1a((CO)) and T2a((HP)). Many genes previously identified as lung cancer biomarkers were altered during this period. Examination of FFPE specimens showed minimal correlation with fresh samples. This study shows that tissue collection immediately after lung resection with conservation in RNAlater is an optimal strategy for gene expression profiling.
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2,334,122 |
Structural studies on bovine heart cytochrome c oxidase.
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Among the X-ray structures of bovine heart cytochrome c oxidase (CcO), reported thus far, the highest resolution is 1.8Å. CcO includes 13 different protein subunits, 7 species of phospholipids, 7 species of triglycerides, 4 redox-active metal sites (Cu(A), heme a (Fe(a)), Cu(B), heme a(3) (Fe(a3))) and 3 redox-inactive metal sites (Mg(2+), Zn(2+) and Na(+)). The effects of various O(2) analogs on the X-ray structure suggest that O(2) molecules are transiently trapped at the Cu(B) site before binding to Fe(a3)(2+) to provide O(2)(-). This provides three possible electron transfer pathways from Cu(B), Fe(a3) and Tyr244 via a water molecule. These pathways facilitate non-sequential 3 electron reduction of the bound O(2)(-) to break the OO bond without releasing active oxygen species. Bovine heart CcO has a proton conducting pathway that includes a hydrogen-bond network and a water-channel which, in tandem, connect the positive side phase with the negative side phase. The hydrogen-bond network forms two additional hydrogen-bonds with the formyl and propionate groups of heme a. Thus, upon oxidation of heme a, the positive charge created on Fe(a) is readily delocalized to the heme peripheral groups to drive proton-transport through the hydrogen-bond network. A peptide bond in the hydrogen-bond network and a redox-coupled conformational change in the water channel are expected to effectively block reverse proton transfer through the H-pathway. These functions of the pathway have been confirmed by site-directed mutagenesis of bovine CcO expressed in HeLa cells.
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2,334,123 |
cAMP and Epac in the regulation of tissue fibrosis.
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Fibrosis, the result of excess deposition of extracellular matrix (ECM), in particular collagen, leads to scarring and loss of function in tissues that include the heart, lung, kidney and liver. The second messenger cAMP can inhibit the formation and extent of ECM during this late phase of inflammation, but the mechanisms for these actions of cAMP and of agents that elevate tissue cAMP levels are not well understood. In this article, we review the fibrotic process and focus on two recently recognized aspects of actions of cAMP and its effector Epac (Exchange protein activated by cAMP): (a) blunting of epithelial-mesenchymal transformation (EMT) and (b) down-regulation of Epac expression by profibrotic agents (e.g. TGF-β, angiotensin II), which may promote tissue fibrosis by decreasing Epac-mediated antifibrotic actions. Pharmacological approaches that raise cAMP or blunt the decrease in Epac expression by profibrotic agents may thus be strategies to block or perhaps reverse tissue fibrosis. LINKED ARTICLES This article is part of a themed section on Novel cAMP Signalling Paradigms. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.166.issue-2.
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2,334,124 |
Escape-echo bigeminy.
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Escape-capture bigeminy is a well-known arrhythmia characterized by group beating of a junctional beat followed by a conducted sinus beat. We report a variant of this arrangement where a junctional beat gives rise to a retrograde P wave, which is then conducted back to the ventricles producing a hitherto undescribed combination (escape-echo bigeminy) resembling escape-capture bigeminy. The clinical significance of escape-echo bigeminy appears similar to that of classic escape-capture bigeminy.
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2,334,125 |
Modelling tissue electrophysiology with multiple cell types: applications of the extended bidomain framework.
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The bidomain framework has been extensively used to model tissue electrophysiology in a variety of applications. One limitation of the bidomain model is that it describes the activity of only one cell type interacting with the extracellular space. If more than one cell type contributes to the tissue electrophysiology, then the bidomain model is not sufficient. Recently, evidence has suggested that this is the case for at least two important applications: cardiac and gastrointestinal tissue electrophysiology. In the heart, fibroblasts ubiquitously interact with myocytes and are believed to play an important role in the organ electrophysiology. Along the GI tract, interstitial cells of Cajal (ICC) generate electrical waves that are passed on to surrounding smooth muscle cells (SMC), which are interconnected with the ICC and with each other. Because of the contribution of more than one cell type to the overall organ electrophysiology, investigators in different fields have independently proposed similar extensions of the bidomain model to incorporate multiple cell types and tested it on simplified geometries. In this paper, we provide a general derivation of such an extended bidomain framework applicable to any tissue and provide a generic and efficient implementation applicable to any geometry. Proof-of-concept results of tissue electrophysiology on realistic 3D organ geometries using the extended bidomain framework are presented for the heart and the stomach.
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2,334,126 |
A Comparison between Sedative Effect of Propofol-Fentanyl and Propofol-Midazolam Combinations in Microlaryngeal Surgeries.
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Considering the growing trend of laryngeal surgeries and the need to protect the airway during and after surgery, among several therapeutic regimens to induce sedation, two regimens of propofol-fentanyl and propofol-midazolam were compared in microlaryngeal surgeries. Forty ASA I-II class patients undergoing microlaryngeal surgeries and referring routinely for postoperative visits were randomly recruited into two groups. For all the patients, 0.5 mg/Kg of propofol was used as bolus and then, 50 mcg/Kg/min of the drug was infused intravenously. For one group, 0.03 mg/Kg bolus of midazolam and for the other group, 2 mcg/Kg bolus of fentanyl was administered in combination with propofol. Ramsay system was used in order to evaluate the effect of the two drugs in inducing sedation. The need for additional dose, blood pressure, heart rate, arterial blood oxygen saturation, and also recovery time and adverse effects such as nausea/vomiting and recalling intra-operative memories, were assessed. The patients in the two groups were not statistically different regarding the number of patients, age, sex, preoperative vital signs, the need for additional doses of propofol, systolic blood pressure and mean systolic blood pressure during laryngoscopy. However, mean systolic blood pressure 1 min after removal of laryngoscope returned faster to the baseline in midazolam group (p < 0.01). Mean heart rate returned sooner to the baseline in fentanyl group following removal of stimulation. Besides, heart rate showed a more reduction following administration of fentanyl (p < 0.02). Mean arterial blood oxygen saturation during laryngoscopy significantly decreased in fentanyl group (p < 0.05) compared to the other group. The time it took to achieve a full consciousness was shorter in midazolam group (p < 0.01). Nausea/vomiting was significantly more prevalent in fentanyl group while the patients in midazolam group apparently experienced more of amnesia, comparatively (p < 0.01). Inducing laryngeal block and local anesthesia using propofol-midazolam regimen is not only associated with a more rapid recovery and less recalling of unpleasant memories, but also better in preventing reduction of arterial oxygen saturation during laryngoscopy compared with propofol-fentanyl regimen.
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2,334,127 |
The effects of vibration during maximal graded cycling exercise: a pilot study.
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Whole Body Vibration training is studied and used in different areas, related to sport performance and rehabilitation. However, few studies have investigated the effects of Vibration (Vib) exposure on aerobic performance through the application of this concept to cycling exercise. A specifically designed vibrating cycloergometer, the powerBIKE(™), was used to compare the effects of Vib cycling exercise and normal cycling on different physiological parameters during maximal graded exercise test. Twelve recreationally active male adults (25 ± 4.8 yrs; 181.33 ± 5.47 cm; 80.66 ± 11.91 kg) performed two maximal incremental cycling tests with and without Vib in a block-randomized order. The protocol consisted of a 4 min warm up at 70 rev·min(-1) followed by incremental steps of 3 min each. Cycling cadence was increased at each step by 10 rev·min(-1) until participants reached their volitional exhaustion. Respiratory gases (VO2, VCO2), Heart Rate, Blood Lactate and RPE were collected during the test. Paired t-tests and Cor-relation Coefficients were used for statistical analysis. A significantly greater (P<0.05) response in the VO2, HR, BLa and RPE was observed during the Vib trial compare to normal cycling. No significant differences were found in the maximal aerobic power (Vib 34.32 ± 9.70 ml·kg(-1)·min(-1); no Vib 40.11 ± 9.49 ml·kg(-1)·min(-1)). Adding Vib to cycling exercise seems eliciting a quicker energetic demand during maximal exercise. However, mechanical limitations of the vibrating prototype could have affected the final outcomes. Future studies with more comparative setting are recommended to deeply appraise this concept.
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2,334,128 |
Congenital complete heart block in a 71-year old.
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A case of a 71-year-old male with congenital complete heart block is discussed. Patient remained asymptomatic with stable electrocardiograms.
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2,334,129 |
[The selection of best anesthesiological technique for hip fracture surgery in older high-risk patients].
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Hip fracture is a pathological condition, more common in older age, i.e. in people over 65 years. The prevalence of this disorder is continuously increasing, simultaneously with higher age limit. In evaluation of risk for operation and anesthesia, older age itself represents higher risk and calls for special attention. In selection of anesthesiological technique, it is more usual to apply neuroaxial block or peripheral nerve block, which is more advantageous over general anesthesia.</AbstractText>A female, 80-year old, patient B.D. was admitted to hospital for hip fracture, with the diagnosis of the right, lateral, basicervical femoral fracture. On admission, heart decompensation (decompensated dilated myocardiopathy), pulmonary edema and the left lateral pleural effusion were established. Due to high risk (ASA III) of intraoperative and postoperative complications, it was decided to apply combined peripheral nerve block. Using the neurostimulators, 3-in-1 block, lumbosacral block and sciatic nerve block were applied. During the operation, the patient was sedated by Propofol and had spontaneous respiration through the laryngeal mask. Intra- and postoperatively, the patient's hemodynamics was stable.</AbstractText>Peripheral nerve blocks are safe and effective anesthesiological technique, which may reduce the mortality in patients with the hip fracture and maintain the hemodynamic stability, both during and after the surgical intervention.</AbstractText>
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2,334,130 |
Activation of growth hormone releasing hormone (GHRH) receptor stimulates cardiac reverse remodeling after myocardial infarction (MI).
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Both cardiac myocytes and cardiac stem cells (CSCs) express the receptor of growth hormone releasing hormone (GHRH), activation of which improves injury responses after myocardial infarction (MI). Here we show that a GHRH-agonist (GHRH-A; JI-38) reverses ventricular remodeling and enhances functional recovery in the setting of chronic MI. This response is mediated entirely by activation of GHRH receptor (GHRHR), as demonstrated by the use of a highly selective GHRH antagonist (MIA-602). One month after MI, animals were randomly assigned to receive: placebo, GHRH-A (JI-38), rat recombinant GH, MIA-602, or a combination of GHRH-A and MIA-602, for a 4-wk period. We assessed cardiac performance and hemodynamics by using echocardiography and micromanometry derived pressure-volume loops. Morphometric measurements were carried out to determine MI size and capillary density, and the expression of GHRHR was assessed by immunofluorescence and quantitative RT-PCR. GHRH-A markedly improved cardiac function as shown by echocardiographic and hemodynamic parameters. MI size was substantially reduced, whereas myocyte and nonmyocyte mitosis was markedly increased by GHRH-A. These effects occurred without increases in circulating levels of growth hormone and insulin-like growth factor I and were, at least partially, nullified by GHRH antagonism, confirming a receptor-mediated mechanism. GHRH-A stimulated CSCs proliferation ex vivo, in a manner offset by MIA-602. Collectively, our findings reveal the importance of the GHRH signaling pathway within the heart. Therapy with GHRH-A although initiated 1 mo after MI substantially improved cardiac performance and reduced infarct size, suggesting a regenerative process. Therefore, activation of GHRHR provides a unique therapeutic approach to reverse remodeling after MI.
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2,334,131 |
Fetal outcome in autoimmune diseases.
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The impact on fetal outcome in women with autoimmune diseases is a result of a several conditions. Fetal success depends on early immunological changes in the mother, which rely in modifications of the innate and adaptative immune system, inducing tolerance to the semi-allogenic fetus. Others crucial factors are maternal disease activity, severity of organ damage, circulating antibodies, and drug treatment. Although fetal outcome is becoming better still it has a worse prognosis in comparison with healthy women. Diseases like antiphospholipid syndrome, systemic lupus erythematosus and vasculitis have the higher risk while rheumatoid arthritis and spondiloarthopaties the least. In the majority of the diseases the risk of poor fetal outcome directly correlates with the activity of disease. While there are no pathognomonic autoantibodies for fetal outcome, antiphospholipid and anti-thyroid antibodies have been implicated in unsuccessful pregnancies and anti-Ro and, to a lesser extent, anti-La antibodies may result in neonatal lupus syndrome congenital heart block. There is increasingly the hope that fetal outcome will be good if the disease is well controlled prior to pregnancy, and with a specialized interdisciplinary support.
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2,334,132 |
Relative contribution of cyclooxygenases, epoxyeicosatrienoic acids, and pH to the cerebral blood flow response to vibrissal stimulation.
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The increase in cerebral blood flow (CBF) during neuronal activation can be only partially attenuated by individual inhibitors of epoxyeicosatrienoic acids (EETs), cyclooxgenase-2, group I metabotropic glutamate receptors (mGluR), neuronal nitric oxide synthase (nNOS), N-methyl-D-aspartate receptors, or adenosine receptors. Some studies that used a high concentration (500 μM) of the cyclooxygenase-1 inhibitor SC-560 have implicated cyclooxygenase-1 in gliovascular coupling in certain model systems in the mouse. Here, we found that increasing the concentration of SC-560 from 25 μM to 500 μM over whisker barrel cortex in anesthetized rats attenuated the CBF response to whisker stimulation. However, exogenous prostaglandin E(2) restored the response in the presence of 500 μM SC-560 but not in the presence of a cyclooxygenase-2 inhibitor, thereby suggesting a limited permissive role for cyclooxygenase-1. Furthermore, inhibition of the CBF response to whisker stimulation by an EET antagonist persisted in the presence of SC-560 or a cyclooxygenase-2 inhibitor, thereby indicating that the EET-dependent component of vasodilation did not require cyclooxygenase-1 or -2 activity. With combined inhibition of cyclooxygenase-1 and -2, mGluR, nNOS, EETs, N-methyl-D-aspartate receptors, and adenosine 2B receptors, the CBF response was reduced by 60%. We postulated that the inability to completely block the CBF response was due to tissue acidosis resulting from impaired clearance of metabolically produced CO2. We tested this idea by increasing the concentration of superfused bicarbonate from 25 to 60 mM and found a markedly reduced CBF response to hypercapnia. However, increasing bicarbonate had no effect on the initial or steady-state CBF response to whisker stimulation with or without combined inhibition. We conclude that the residual response after inhibition of several known vasodilatory mechanisms is not due to acidosis arising from impaired CO2 clearance when the CBF response is reduced. An unidentified mechanism apparently is responsible for the rapid, residual cortical vasodilation during vibrissal stimulation.
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2,334,133 |
Increased vulnerability of human ventricle to re-entrant excitation in hERG-linked variant 1 short QT syndrome.
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The short QT syndrome (SQTS) is a genetically heterogeneous condition characterized by abbreviated QT intervals and an increased susceptibility to arrhythmia and sudden death. This simulation study identifies arrhythmogenic mechanisms in the rapid-delayed rectifier K(+) current (I(Kr))-linked SQT1 variant of the SQTS. Markov chain (MC) models were found to be superior to Hodgkin-Huxley (HH) models in reproducing experimental data regarding effects of the N588K mutation on KCNH2-encoded hERG. These ionic channel models were then incorporated into human ventricular action potential (AP) models and into 1D and 2D idealised and realistic transmural ventricular tissue simulations and into a 3D anatomical model. In single cell models, the N588K mutation abbreviated ventricular cell AP duration at 90% repolarization (APD(90)) and decreased the maximal transmural voltage heterogeneity (δV) during APs. This resulted in decreased transmural heterogeneity of APD(90) and of the effective refractory period (ERP): effects that are anticipated to be anti-arrhythmic rather than pro-arrhythmic. However, with consideration of transmural heterogeneity of I(Kr) density in the intact tissue model based on the ten Tusscher-Noble-Noble-Panfilov ventricular model, not only did the N588K mutation lead to QT-shortening and increases in T-wave amplitude, but δV was found to be augmented in some local regions of ventricle tissue, resulting in increased tissue vulnerability for uni-directional conduction block and predisposing to formation of re-entrant excitation waves. In 2D and 3D tissue models, the N588K mutation facilitated and maintained re-entrant excitation waves due to the reduced substrate size necessary for sustaining re-entry. Thus, in SQT1 the N588K-hERG mutation facilitates initiation and maintenance of ventricular re-entry, increasing the lifespan of re-entrant spiral waves and the stability of scroll waves in 3D tissue.
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2,334,134 |
Verapamil as an antiarrhythmic agent in congestive heart failure: hopping from rabbit to human?
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Repolarization-dependent cardiac arrhythmias only arise in hearts facing multiple 'challenges' affecting its so-called repolarization reserve. Congestive heart failure (CHF) is one such challenge frequently observed in humans and is accompanied by altered calcium handling within the contractile heart cell. This raises the question as to whether or not the well-known calcium channel antagonist verapamil acts as an antiarrhythmic drug in this setting, as seen in arrhythmia models without CHF. According to the study of Milberg et al. in this issue of BJP, the answer is yes. The results of this study, using a rabbit CHF model, raise important questions. First, given that the model combines CHF with a number of other interventions that predispose towards arrhythmia, will similar conclusions be reached in a setting where CHF is a more prominent proarrhythmic challenge; second, what is the extent to which other effects of calcium channel block would limit the clinical viability of this pharmacological approach in CHF? In vivo studies in large animal CHF models are now required to further explore this interesting, but complex, approach to the treatment of arrhythmia. LINKED ARTICLE This article is a commentary on Milberg et al., pp. 557-568 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476-5381.2011.01721.x.
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2,334,135 |
A comparative study of duration of postoperative analgesia between epidural bupivacaine and epidural clonidine plus bupivacaine in lumbar laminectomy surgery under general anaesthesia.
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A randomised prospective double-blind placebo controlled study was undertaken in 60 patients of ASA-I and II, scheduled for lumbar laminectomy under general anaesthesia using thiopentone, fentanyl, artracurium, N2O/O2 and isoflurane. After obtaining written Informed consent from all patients, they were randomly allocated to two equal groups ie, group A (n = 30) and group B (n = 30). Group A patients received clonidine 0.5 ml (75 microg) plus 5 ml 0.25% bupivacaine and group B patients received 5 ml 0.25% bupivacaine plus 0.5 ml of normal saline (NS) as a control through epidural route placed by the surgeon at the closure of the surgery. All the vital parameters were recorded at the time of epidural catheter placement and administering drugs and at 10 minutes interval thereafter till the patients were reversed with neostigmine and glycopyrrolate and then in the postanaesthetic care unit (PACU) at 15 minutes interval till the end of the study. All patients received injection diclofenac 75 mg IM as soon as they complained of pain or when the VAS score became > or = 4cm. The study ended when patients received injection diclofenac 75 mg IM as rescue analgesic. Any feature of motor block, sedation score and event of urinary retention were recorded in the PACU. Duration of postoperative analgesia was taken as the primary outcome and measured from the time of regaining full consciousness following surgery till receiving first injection of rescue analgesic in the PACU. Duration of postoperative analgesia was (546.36 +/- 11.55 minutes) in group A compared to (240.15 +/- 07.32 minutes) in group B. No clinically significant difference was found in heart rate, blood pressure, respiratory rate, oxygen saturation and motor blockade. Sedation score was slightly higher in group A, which was not significant. So small dose of clonidine (75 microg) as an adjuvant to 5 ml 0.25% bupivacaine in epidural route following lumbar laminectomy significantly prolonged postoperative analgesia and improved patient satisfaction without any clinically significant adverse reaction.
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2,334,136 |
In vivo delivery of nucleic acids via glycopolymer vehicles affords therapeutic infarct size reduction in vivo.
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Using a new class of nontoxic and degradable glycopolymer-based vehicles termed poly(glycoamidoamine)s, we demonstrate virus-like delivery efficacy of oligodeoxynucleotide (ODN) decoys to cardiomyoblasts (H9c2), primary cardiomyocytes, and the mouse heart. These glycopolymers bind and compact ODN decoys into nanoparticle complexes that are internalized by the cell membrane and mediate nuclear uptake of DNA in 90+% of cultured primary cardiomyocytes and 87% of the mouse myocardium. Experimental results reveal that decoys delivered via these glycopolymers block the activation of the transcription factor NF-κB, a major contributor to ischemia/reperfusion injury. Decoy complexes formed with glycopolymer T4 significantly blocked downstream gene expression of Cox-2 and limited myocardial infarction in vivo, phenocopying a transgenic mouse model. These promising delivery vehicles may facilitate high-throughput genetic approaches in animal models. Additionally, the low toxicity, biodegradation, and outstanding delivery efficacy suggest that these nanomedicines may be clinically applicable for gene regulatory therapy.
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2,334,137 |
[Effects of 15 mcg intrathecal clonidine added to bupivacaine and sufentanil for labor analgesia].
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For the combined spinal epidural analgesia for labour, 30 mcg of subarachnoid clonidine has proved its effectiveness to extend the analgesia, but increased severe hemodynamic effects.</AbstractText>To assess the effectiveness and the safety of 15 mcg intra thecal clonidine for labour analgesia.</AbstractText>Four months, prospective, randomised, simple blind Study, including ASA I or II women, with mono foetal pregnancy. Patients were randomised in 2 groups: SB Group received intra thecal isobaric bupivacaine 2.5 mg and sufentanil 5 mcg and SBC Group received 15 mcg clonidine added to the same doses of bupivacaïne and sufentanil. Epidural analgesia was used when VAS is more than 30. Studied parameters were: delay of installation, duration of analgesia, VAS score, hemodynamic parameters and the incidence of maternal and neonatal side effects.</AbstractText>Sixty pregnant women were included (27 in SBC Group and 33 in SB group). The duration of initial analgesia was significantly longer in the SBC group (145 ± 43 min) compared with the SB group (98 ± 28 min). The delay of analgesia, sensory level and motor block level were similar. There was neither significant increase of the low incidence of blood pressure nor of the ephedrine consumption. The abnormalities of fetal heart rate, the mode of delivery and the incidence of side effects were also similar.</AbstractText>The addition of 15 mcg intra thecal clonidine to the bupivacaine and the sufentanil during combined spinal epidural analgesia for obstetrical labour results in extended significantly duration of analgesia without increasing side effects.</AbstractText>
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2,334,138 |
Latent Epstein-Barr virus can inhibit apoptosis in B cells by blocking the induction of NOXA expression.
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Latent Epstein-Barr virus (EBV) has been shown to protect Burkitt's lymphoma-derived B cells from apoptosis induced by agents that cause damage to DNA, in the context of mutant p53. This protection requires expression of the latency-associated nuclear proteins EBNA3A and EBNA3C and correlates with their ability to cooperate in the repression of the gene encoding the pro-apoptotic, BH3-only protein BIM. Here we confirm that latent EBV in B cells also inhibits apoptosis induced by two other agents--ionomycin and staurosporine--and show that these act by a distinct pathway that involves a p53-independent increase in expression of another pro-apoptotic, BH3-only protein, NOXA. Analyses employing a variety of B cells infected with naturally occurring EBV or B95.8 EBV-BAC recombinant mutants indicated that the block to NOXA induction does not depend on the well-characterized viral latency-associated genes (EBNAs 1, 2, 3A, 3B, 3C, the LMPs or the EBERs) or expression of BIM. Regulation of NOXA was shown to be at least partly at the level of mRNA and the requirement for NOXA to induce cell death in this context was demonstrated by NOXA-specific shRNA-mediated depletion experiments. Although recombinant EBV with a deletion removing the BHRF1 locus--that encodes the BCL2-homologue BHRF1 and three microRNAs--partially abrogates protection against ionomycin and staurosporine, the deletion has no effect on the EBV-mediated block to NOXA accumulation.
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2,334,139 |
Misleading ECG recordings.
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Misleading electrocardiogram recordings are not uncommon, and can lead to misdiagnosis. This article highlights two examples and discusses the strategies to recognise them.
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2,334,140 |
Inhibition of microRNA-17 improves lung and heart function in experimental pulmonary hypertension.
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MicroRNAs (miRs) control various cellular processes in tissue homeostasis and disease by regulating gene expression on the posttranscriptional level. Recently, it was demonstrated that the expression of miR-21 and members of the miR-17-92 cluster was significantly altered in experimental pulmonary hypertension (PH).</AbstractText>To evaluate the therapeutic efficacy and antiremodeling potential of miR inhibitors in the pathogenesis of PH.</AbstractText>We first tested the effects of miR inhibitors (antagomirs), which were specifically designed to block miR-17 (A-17), miR-21 (A-21), and miR-92a (A-92a) in chronic hypoxia-induced PH in mice and A-17 in monocrotaline-induced PH in rats. Moreover, biological function of miR-17 was analyzed in cultured pulmonary artery smooth muscle cells.</AbstractText>In the PH mouse model, A-17 and A-21 reduced right ventricular systolic pressure, and all antagomirs decreased pulmonary arterial muscularization. However, only A-17 reduced hypoxia-induced right ventricular hypertrophy and improved pulmonary artery acceleration time. In the monocrotaline-induced PH rat model, A-17 treatment significantly decreased right ventricular systolic pressure and total pulmonary vascular resistance index, increased pulmonary artery acceleration time, normalized cardiac output, and decreased pulmonary vascular remodeling. Among the tested miR-17 targets, the cyclin-dependent kinase inhibitor 1A (p21) was up-regulated in lungs undergoing A-17 treatment. Likewise, in human pulmonary artery smooth muscle cells, A-17 increased p21. Overexpression of miR-17 significantly reduced p21 expression and increased proliferation of smooth muscle cells.</AbstractText>Our data demonstrate that A-17 improves heart and lung function in experimental PH by interfering with lung vascular and right ventricular remodeling. The beneficial effects may be related to the up-regulation of p21. Thus, inhibition of miR-17 may represent a novel therapeutic concept to ameliorate disease state in PH.</AbstractText>
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2,334,141 |
Quantitative comparison of cardiac ventricular myocyte electrophysiology and response to drugs in human and nonhuman species.
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Explanations for arrhythmia mechanisms at the cellular level are usually based on experiments in nonhuman myocytes. However, subtle electrophysiological differences between species may lead to different rhythmic or arrhythmic cellular behaviors and drug response given the nonlinear and highly interactive cellular system. Using detailed and quantitatively accurate mathematical models for human, dog, and guinea pig ventricular action potentials (APs), we simulated and compared cell electrophysiology mechanisms and response to drugs. Under basal conditions (absence of β-adrenergic stimulation), Na(+)/K(+)-ATPase changes secondary to Na(+) accumulation determined AP rate dependence for human and dog but not for guinea pig where slow delayed rectifier current (I(Ks)) was the major rate-dependent current. AP prolongation with reduction of rapid delayed rectifier current (I(Kr)) and I(Ks) (due to mutations or drugs) showed strong species dependence in simulations, as in experiments. For humans, AP prolongation was 80% following I(Kr) block. It was 30% for dog and 20% for guinea pig. Under basal conditions, I(Ks) block was of no consequence for human and dog, but for guinea pig, AP prolongation after I(Ks) block was severe. However, with β-adrenergic stimulation, I(Ks) played an important role in all species, particularly in AP shortening at fast rate. Quantitative comparison of AP repolarization, rate-dependence mechanisms, and drug response in human, dog, and guinea pig revealed major species differences (e.g., susceptibility to arrhythmogenic early afterdepolarizations). Extrapolation from animal to human electrophysiology and drug response requires great caution.
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2,334,142 |
Ro52 autoantibody-positive women's experience of being pregnant and giving birth to a child with congenital heart block.
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congenital heart block may develop in the fetus of women with Ro/SSA autoantibodies. The aim of this study was to investigate how women expecting a child with congenital heart block (CHB) experienced their pregnancy and post-partum period.</AbstractText><AbstractText Label="DESIGN, SETTING AND PARTICIPANTS" NlmCategory="METHODS">women giving birth to a child with CHB in Sweden during 2000-2009 were identified in a population-based manner and individually interviewed post-pregnancy using a semi-structured interview guide. The interviews (n=21) were audiotaped, transcribed verbatim and analysed by qualitative content analysis.</AbstractText>three categories emerged from the responses: learning, suspense and facing. Learning contained both learning about the child's heart block, but frequently also about autoantibody-positivity and a potential rheumatic diagnosis in the mother (16/21). The medical procedures and information differed considerably depending on the area of residence and who was encountered in the health-care system. In many cases, ignorance about this rare condition caused a delay in treatment and surveillance. Suspense described the women's struggle to cope with the feeling of guilt and that the child had a serious heart condition and might not survive the pregnancy. Facing included the post-partum period, leaving the hospital and adjusting to everyday life. The women had tended to put their pregnancies 'on hold', and some described that they needed prolonged time to bond with their newborn child.</AbstractText>increased awareness and knowledge of CHB are needed to provide adequate care. Offering psychological support by a health-care professional to facilitate early bonding with the child should be considered.</AbstractText>there is a need for structured programs for surveillance of the pregnancies. Such programme should implement guidelines for the involved personnel in the chain of care and make relevant information accessible for the women and families.</AbstractText>Copyright © 2011 Elsevier Ltd. All rights reserved.</CopyrightInformation>
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2,334,143 |
The effect of the intravenous phenylephrine on the level of spinal anesthesia.
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Spinal anesthesia causes hypotension and bradycardia due to sympathetic nerve block and it is difficult to predict the level of sensory block and the duration of blockade. Recent studies have reported that intravenous phenylephrine can reduce the rostral spread of spinal anesthesia in pregnant women. We think a phenylephrine infusion will be useful for maintaining the baseline blood pressure by reducing the rostral spread of spinal anesthesia during the elective surgery of non-obstetric patients.</AbstractText>SIXTY PATIENTS WHO WERE UNDERGOING UROLOGIC SURGERY WERE RANDOMIZED INTO TWO GROUPS: Group C (the control group without phenylephrine) and Group P (with the addition of phenylephrine). After a bolus infusion of 50 µg phenylephrine following the spinal injection, phenylephrine was continuously infused at the rate of 200 µg/hr. We compared the dermatomal spreads of spinal anesthesia, the hemodynamic parameters (blood pressure, heart rate) and the incidences of hypotension between the two groups.</AbstractText>At 20 minutes, the level of the upper dermatome blocked against cold sensation was a median of T8 (interquartile range: T8-T10) for the phenylephrine group, as compared with T4 (interquartile range: T4-T6) for the control group (P < 0.001).</AbstractText>Intravenous phenylephrine can decrease the rostral spread of spinal anesthesia during urologic surgery.</AbstractText>
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2,334,144 |
Addition of intrathecal Dexamethasone to Bupivacaine for spinal anesthesia in orthopedic surgery.
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Spinal anesthesia has the advantage that profound nerve block can be produced in a large part of the body by the relatively simple injection of a small amount of local anesthetic. Intrathecal local anesthetics have limited duration. Different additives have been used to prolong spinal anesthesia. The effect of corticosteroids in prolonging the analgesic effects of local anesthetics in peripheral nerves is well documented. The purpose of this investigation was to determine whether the addition of dexamethasone to intrathecal bupivacaine would prolong the duration of sensory analgesia or not.</AbstractText>We conducted a randomized, prospective, double-blind, case-control, clinical trial. A total of 50 patients were scheduled for orthopedic surgery under spinal anesthesia. The patients were randomly allocated to receive 15 mg hyperbaric bupivacaine 0.5% with 2 cc normal saline (control group) or 15 mg hyperbaric bupivacaine 0.5% plus 8 mg dexamethasone (case group) intrathecally. The patients were evaluated for quality, quantity, and duration of block; blood pressure, heart rate, nausea, and vomiting or other complications.</AbstractText>There were no signification differences in demographic data, sensory level, and onset time of the sensory block between two groups. Sensory block duration in the case group was 119±10.69 minutes and in the control group was 89.44±8.37 minutes which was significantly higher in the case group (P<0.001). The duration of analgesia was 401.92±72.44 minutes in the case group; whereas it was 202±43.67 minutes in the control group (P<0.001). The frequency of complications was not different between two groups.</AbstractText>This study has shown that the addition of intrathecal dexamethasone to bupivacaine significantly improved the duration of sensory block in spinal anesthesia without any changes in onset time and complications.</AbstractText>
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2,334,145 |
Novel biodegradable, biomimetic and functionalised polymer scaffolds to prevent expansion of post-infarct left ventricular remodelling.
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Over the past decade, a large number of strategies and technologies have been developed to reduce heart failure progression. Among these, cardiac tissue engineering is one of the most promising. Aim of this study is to develop a 3D scaffold to treat cardiac failure. A new three-block copolymer, obtained from δ-valerolactone and polyoxyethylene, was synthesised under high vacuum without catalyst. Copolymer/gelatine blends were microfabricated to obtain a ECM-like geometry. Structures were studied under morphological, mechanical, degradation and biological aspects. To prevent left ventricular remodelling, constructs were biofunctionalises with molecularly imprinted nanoparticles towards the matrix metalloproteinase MMP-9. Results showed that materials are able to reproduce the ECM structure with high resolution, mechanical properties were in the order of MPa similar to those of the native myocardium and cell viability was verified. Nanoparticles showed the capability to rebind MMP-9 (specific rebinding 18.67) and to be permanently immobilised on the scaffold surface.
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2,334,146 |
Side effects and complications of intraosseous anesthesia and conventional oral anesthesia.
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To analyze the side effects and complications following intraosseous anesthesia (IA), comparing them with those of the conventional oral anesthesia techniques.</AbstractText>A simple-blind, prospective clinical study was carried out. Each patient underwent two anesthetic techniques: conventional (local infiltration and locoregional anesthetic block) and intraosseous, for respective dental operations. In order to allow comparison of IA versus conventional anesthesia, the two operations were similar and affected the same two teeth in opposite quadrants. Heart rate was recorded in all cases before injection of the anesthetic solution and again 30 seconds after injection. The complications observed after anesthetic administration were recorded.</AbstractText>A total of 200 oral anesthetic procedures were carried out in 100 patients. Both IA and conventional anesthesia resulted in a significant increase in heart rate, though the increase was greater with the latter technique. Incidents were infrequent with either anesthetic technique, with no significant differences between them. Regarding the complications, there were significant differences in pain at the injection site, with more intense pain in the case of IA (x2=3.532, p=0.030, Φ2=0.02), while the limitation of oral aperture was more pronounced with conventional anesthesia (x2=5.128, p<0.05, Φ2=0.014). Post-anesthetic biting showed no significant differences (x2=4.082, p=0.121, Φ2=0.009).</AbstractText>Both anesthetic techniques significantly increased heart rate, and IA caused comparatively more pain at the injection site, while limited oral aperture was more frequent with conventional anesthesia. Post-anesthetic biting showed no significant differences between the two techniques.</AbstractText>
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2,334,147 |
Sympathetic nerve stimulation induces local endothelial Ca2+ signals to oppose vasoconstriction of mouse mesenteric arteries.
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It is generally accepted that the endothelium regulates vascular tone independent of the activity of the sympathetic nervous system. Here, we tested the hypothesis that the activation of sympathetic nerves engages the endothelium to oppose vasoconstriction. Local inositol 1,4,5-trisphosphate (IP(3))-mediated Ca(2+) signals ("pulsars") in or near endothelial projections to vascular smooth muscle (VSM) were measured in an en face mouse mesenteric artery preparation. Electrical field stimulation of sympathetic nerves induced an increase in endothelial cell (EC) Ca(2+) pulsars, recruiting new pulsar sites without affecting activity at existing sites. This increase in Ca(2+) pulsars was blocked by bath application of the α-adrenergic receptor antagonist prazosin or by TTX but was unaffected by directly picospritzing the α-adrenergic receptor agonist phenylephrine onto the vascular endothelium, indicating that nerve-derived norepinephrine acted through α-adrenergic receptors on smooth muscle cells. Moreover, EC Ca(2+) signaling was not blocked by inhibitors of purinergic receptors, ryanodine receptors, or voltage-dependent Ca(2+) channels, suggesting a role for IP(3), rather than Ca(2+), in VSM-to-endothelium communication. Block of intermediate-conductance Ca(2+)-sensitive K(+) channels, which have been shown to colocalize with IP(3) receptors in endothelial projections to VSM, enhanced nerve-evoked constriction. Collectively, our results support the concept of a transcellular negative feedback module whereby sympathetic nerve stimulation elevates EC Ca(2+) signals to oppose vasoconstriction.
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2,334,148 |
Gliosis in the mouse hippocampus without neuronal death after systemic administration of high dosage of tetanus toxin.
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Tetanus toxin (TeT), an exotoxin, has been studied to cause tetanus in mammalian brains, and it can block the release of some neurotransmitters and affect seizure propagation. In the present study, we investigated neuronal damage/death and glial changes in the mouse hippocampus after systemic administration (intraperitoneal injection) of TeT 10 and 100 ng/kg. In both the 10 and 100 ng/kg TeT-treated groups, no neuronal death occurred in any subregions of the mouse hippocampus until 24 h post-treatment; however, there were changes in glia in the hippocampus depending on time course and dosage. The morphology of GFAP-immunoreactive astrocytes and Iba-1-immunoreactive microglia was apparently changed in the 100 ng/kg TeT treated-group compared to the 10 ng/kg TeT treated-group. In the 100 ng/kg TeT treated-group, they were increased in size and their immunoreactivity was distinctively increased from 12 h post-treatment. We also found that their protein levels were increased in the hippocampus at 12 h post-treatment of 100 ng/kg TeT. In conclusion, these results indicate that the systemic administration of 100 ng/kg TeT induced a distinctive microglia changes in the mouse hippocampus without any neuronal death/damage.
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2,334,149 |
Prenatal diagnosis and outcome of fetuses with double-inlet left ventricle.
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The aim of this study is to characterize the in utero presentation of the subtype of double-inlet left ventricle (DILV), a rare congenital heart disease, and assess the postnatal outcome. We retrospectively studied fetuses diagnosed prenatally with DILV between 2007 and 2011. We reviewed the prenatal and postnatal echocardiograms, clinical presentations, karyotypes, and the postnatal outcomes. There were eight fetuses diagnosed with DILV with L-transposition of the great vessels (S, L, L). Mean gestational age at diagnosis was 24.7 weeks. Of these, four fetuses (50%) had pulmonary atresia. One fetus (12.5%) also had tricuspid atresia and coarctation of the aorta and died at 17 months of age. Complete heart block and long QT syndrome was present in one fetus (12.5%), who died shortly after birth. There were no extracardiac or karyotypic abnormalities. Six (75%) infants are alive and doing well. Double-inlet left ventricle with varied presentation can be accurately diagnosed prenatally. The outcome of fetuses is good in the absence of associated rhythm abnormalities with surgically staged procedures leading to a Fontan circulation.
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2,334,150 |
Elevation of the antifibrotic peptide N-acetyl-seryl-aspartyl-lysyl-proline: a blood pressure-independent beneficial effect of angiotensin I-converting enzyme inhibitors.
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Blockade of the renin-angiotensin system (RAS) is well recognized as an essential therapy in hypertensive, heart, and kidney diseases. There are several classes of drugs that block the RAS; these drugs are known to exhibit antifibrotic action. An analysis of the molecular mechanisms of action for these drugs can reveal potential differences in their antifibrotic roles. In this review, we discuss the antifibrotic action of RAS blockade with an emphasis on the potential importance of angiotensin I-converting enzyme (ACE) inhibition associated with the antifibrotic peptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP).
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2,334,151 |
Endothelin-2, the forgotten isoform: emerging role in the cardiovascular system, ovarian development, immunology and cancer.
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Endothelin-2 [ET-2; also known as vasoactive intestinal contractor (VIC), in rodents] differs from endothelin-1 (ET-1) by only two amino acids, and unlike the third isoform, endothelin-3 (ET-3), it has the same affinity as ET-1 for both ET(A) and ET(B) receptors. It is often assumed that ET-2 would mimic the actions of the more abundant ET-1 and current pharmacological interventions used to inhibit the ET system would also block the actions of ET-2. These assumptions have focused research on ET-1 with ET-2 studied in much less detail. Recent research suggests that our understanding of the ET family requires re-evaluation. Although ET-2 is very similar in structure as well as pharmacology to ET-1, and may co-exist in the same tissue compartments, there is converging evidence for an important and distinct ET-2 pathway. Specifically is has been demonstrated that ET-2 has a key role in ovarian physiology, with ET-2-mediated contraction proposed as a final signal facilitating ovulation. Furthermore, ET-2 may also have a pathophysiological role in heart failure, immunology and cancer. Comparison of ET-2 versus ET-1 mRNA expression suggests this may be accomplished at the level of gene expression but differences may also exist in peptide synthesis by enzymes such as endothelin converting enzymes (ECEs) and chymase, which may allow the two pathways to be distinguished pharmacologically and become separate drug targets. LINKED ARTICLES This article is part of a themed section on Endothelin. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.168.issue-1.
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2,334,152 |
The analgesic effect of dexketoprofen when added to lidocaine for intravenous regional anaesthesia: a prospective, randomized, placebo-controlled study.
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This prospective, randomized, placebo-controlled study evaluated the effects of dexketoprofen as an adjunct to lidocaine in intravenous regional anaesthesia (IVRA) or as a supplemental intravenous (i.v.) analgesic. Patients scheduled for elective hand or forearm soft-tissue surgery were randomly divided into three groups. All 45 patients received 0.5% lidocaine as IVRA. Dexketoprofen was given either i.v. or added into the IVRA solution and the control group received an equal volume of saline both i.v. and as part of the IVRA. The times of sensory and motor block onset, recovery time and postoperative analgesic consumption were recorded. Compared with controls, the addition of dexketoprofen to the IVRA solution resulted in more rapid onset of sensory and motor block, longer recovery time, decreased intra- and postoperative pain scores and decreased paracetamol use. It is concluded that coadministration of dexketoprofen with lidocaine in IVRA improves anaesthetic block and decreases postoperative analgesic requirements.
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2,334,153 |
Comparison of bupivacaine femoral and sciatic nerve block versus bupivacaine and morphine epidural for stifle surgery in dogs.
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To evaluate the efficacy of combined femoral and sciatic nerve blocks as an alternative to epidural anesthesia and analgesia in dogs undergoing stifle surgery under general anesthesia.</AbstractText>Prospective, blinded, randomized, clinical comparison.</AbstractText>Twenty dogs weighing 37 ± 11 (mean ± SD) kg, aged 3 (1-8) [median (minimum-maximum)] years undergoing elective unilateral tibial-plateau leveling osteotomy.</AbstractText>Dogs were assigned randomly to receive either epidural anesthesia (bupivacaine 0.5%, 0.5 mg kg(-1) + morphine 0.1%, 0.1 mg kg(-1), in 0.2 mL kg(-1); EPID) or femoral and sciatic nerve blocks (Bupivacaine 0.5%, 0.1 mL kg(-1), was administered at each site; F + S) guided by electrolocation. All patients received a standard general anesthesia technique. Pain and sedation were scored (on scales of 0-10 and 0-3, respectively) pre-operatively, at extubation, and at 1, 4 and then every 4 hours thereafter up to 24 hours. Postoperatively, hydromorphone was administered to any patient with a pain score of >5 or whenever the blinded caregiver determined that more hydromorphone was necessary. Intraoperative heart rate (HR), mean arterial pressure (MAP), end tidal isoflurane (FE'ISO), body temperature, post-operative pain scores, time to first hydromorphone dose after surgery, time to first feeding, time to first drinking, time to first urination, time to first ambulation (walk on a lead) and cumulative dose of hydromorphone were recorded.</AbstractText>Intra-operatively, FE'ISO and MAP were significantly lower in the EPID group (p = 0.05 and p = 0.04, respectively). Postoperatively, the cumulative hydromorphone consumption (p = 0.04) and the incidence of urinary retention (p = 0.03) were higher in the EPID group.</AbstractText>F + S is a practical alternative to EPID that produces less urine retention and reduces opioid consumption in the 24 hours after surgery. EPID might be associated with a lower isoflurane requirement and lower systemic blood pressure.</AbstractText>© 2011 The Authors. Veterinary Anaesthesia and Analgesia. © 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.</CopyrightInformation>
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2,334,154 |
New mechanism of spiral wave initiation in a reaction-diffusion-mechanics system.
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Spiral wave initiation in the heart muscle is a mechanism for the onset of dangerous cardiac arrhythmias. A standard protocol for spiral wave initiation is the application of a stimulus in the refractory tail of a propagating excitation wave, a region that we call the "classical vulnerable zone." Previous studies of vulnerability to spiral wave initiation did not take the influence of deformation into account, which has been shown to have a substantial effect on the excitation process of cardiomyocytes via the mechano-electrical feedback phenomenon. In this work we study the effect of deformation on the vulnerability of excitable media in a discrete reaction-diffusion-mechanics (dRDM) model. The dRDM model combines FitzHugh-Nagumo type equations for cardiac excitation with a discrete mechanical description of a finite-elastic isotropic material (Seth material) to model cardiac excitation-contraction coupling and stretch activated depolarizing current. We show that deformation alters the "classical," and forms a new vulnerable zone at longer coupling intervals. This mechanically caused vulnerable zone results in a new mechanism of spiral wave initiation, where unidirectional conduction block and rotation directions of the consequently initiated spiral waves are opposite compared to the mechanism of spiral wave initiation due to the "classical vulnerable zone." We show that this new mechanism of spiral wave initiation can naturally occur in situations that involve wave fronts with curvature, and discuss its relation to supernormal excitability of cardiac tissue. The concept of mechanically induced vulnerability may lead to a better understanding about the onset of dangerous heart arrhythmias via mechano-electrical feedback.
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2,334,155 |
Reduction in spinal-induced hypotension with ondansetron in parturients undergoing caesarean section: a double-blind randomised, placebo-controlled study.
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Subarachnoid block is the preferred method of anaesthesia for caesarean section, but is associated with hypotension and bradycardia, which may be deleterious to both parturient and baby. Animal studies suggest that in the presence of decreased blood volume, 5-HT may be an important factor inducing the Bezold Jarisch reflex via 5-HT3 receptors located in intracardiac vagal nerve endings. In this study, we evaluated the effect of ondansetron, as a 5-HT3 receptor antagonist, on the haemodynamic response following subarachnoid block in parturients undergoing elective caesarean section.</AbstractText>Fifty-two parturients scheduled for elective caesarean section were randomly allocated into two groups. Before induction of spinal anaesthesia Group O (n=26) received intravenous ondansetron 4 mg; Group S (n=26) received normal saline. Blood pressure, heart rate and vasopressor requirements were assessed.</AbstractText>Decreases in mean arterial pressure were significantly lower in Group O than Group S from 14 min until 35 min. Patients in Group O required significantly less vasopressor (P=0.009) and had significantly lower incidences of nausea and vomiting (P=0.049).</AbstractText>Ondansetron 4 mg, given intravenously 5 min before subarachnoid block reduced hypotension and vasopressor use in parturients undergoing elective caesarean section.</AbstractText>Copyright © 2011 Elsevier Ltd. All rights reserved.</CopyrightInformation>
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2,334,156 |
Arrhythmias following spinal anesthesia for cesarean delivery - Is Wenckebach common?
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Arrhythmias in pregnancy are common and may cause concern for the well-being of both mother and fetus. Generally, no previous history of heart disease is elicited and majority of the arrhythmias are benign. Bradycardia is commonly seen following subarachnoid block for cesarean section. However, the incidence of subsequent heart block is low. This case report highlights the occurrence of perioperative arrhythmias following sympathetic blockade in pregnant patients and their early detection by vigilant monitoring.
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2,334,157 |
Effects of moderate exercise on VLDL₁ and Intralipid kinetics in overweight/obese middle-aged men.
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Prior moderate exercise reduces plasma triglyceride (TG)-rich lipoprotein concentrations, mainly in the large very low-density lipoprotein (VLDL₁) fraction, but the mechanism responsible is unclear. We investigated the effects of brisk walking on TG-rich lipoprotein kinetics using a novel method. Twelve overweight/obese middle-aged men underwent two kinetic studies, involving infusion of Intralipid to block VLDL₁ catabolism, in random order. On the afternoon prior to infusion, subjects either walked on a treadmill for 2 h at ∼50% maximal oxygen uptake or performed no exercise. Multiple blood samples were taken during and after infusion for separation of Intralipid (S(f) 400) and VLDL₁ (S(f) 60-400). VLDL₁-TG and -apoB production rates were calculated from their linear rises during infusion; fractional catabolic rates (FCR) were calculated by dividing linear rises by fasting concentrations. Intralipid-TG FCR was determined from the postinfusion exponential decay. Exercise reduced fasting VLDL₁-TG concentration by 30% (P = 0.007) and increased TG enrichment of VLDL₁ particles [30% decrease in cholesteryl ester (CE)/TG ratio (P = 0.007); 26% increase in TG/apoB ratio (P = 0.059)]. Exercise also increased VLDL₁-TG, VLDL₁-apoB, and Intralipid-TG FCRs by 82, 146, and 43%, respectively (all P < 0.05), but had no significant effect on VLDL₁-TG or -apoB production rates. The exercise-induced increase in VLDL₁-apoB FCR correlated strongly with the exercise-induced changes in VLDL₁ CE/TG (r = -0.659, r = 0.020) and TG/apoB (r = 0.785, P = 0.002) ratios. Thus, exercise-induced reductions in VLDL₁ concentrations are mediated by increased catabolism, rather than reduced production, which may be facilitated by compositional changes to VLDL₁ particles that increase their affinity for clearance from the circulation.
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2,334,158 |
[Evaluation of safety and anesthetic effect for ultrasound-guided cervical plexus block].
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To observe the influences upon the degree of diaphragmatic excursion during deep cervical plexus block at the third cervical vertebra (C3) and compare the safety and anesthetic effect of modified cervical plexus block by ultrasonic guidance and blocking of cervical plexus at one point.</AbstractText>Part I: 30 patients of ASA (American society of anesthesiologists) I-II scheduled for thyroid surgery were selected for bilateral cervical plexus block at C3 and bilateral skin nerve branches via ultrasonic guidance. Diaphragmatic excursion was recorded. Part II: 80 patients of ASAI-II scheduled for thyroid surgery were randomly divided into 2 groups: experimental group (Group U) and control group (Group C). In Group U, modified cervical plexus block was used to fix both sides of C3 and skin nerve branches. The anesthetic mixture with 2% lidocaine and 0.75% ropivacaine was injected. And anesthetic effects and complications were detected. In control group, traditional one-point method for blocking cervical plexus was employed.</AbstractText>High-frequency Doppler sonography could clearly visualize important neck structures and precisely guide the injection of mixture to the transverse process of C3. Diaphragmatic excursion decreased significantly at 15 and 30 min post-blocking (P < 0.05). And no paralysis of diaphragmatic muscle occurred. Hoverer 3 cases had partial diaphragmatic paralysis. Both blood pressure and heart rate increased significantly post-blocking in both groups (P < 0.05 or 0.01). In comparison with Group C, the range of blood pressure was notably lower at 10 and 20 min in Group U. And heart rate was notably lower at 5, 10, 20 and 30 min (P < 0.05 or 0.01). Furthermore the onset time of skin nerve branches was significantly shorter in Group U (P < 0.01). And the anesthetic effect score was better than that in Group C (P < 0.01). The incidence of complications, such as hoarseness, was significantly lower in Group U (12 cases in Group C but none in Group U, P < 0.01) and Horner's syndrome (2 cases in Group C). The number of cases requiring hypotensor and heart rate control drug was significantly smaller in Group U than that in Group C (P < 0.01).</AbstractText>The improving effect of ultrasound-guided cervical plexus block upon the degree of diaphragmatic movement is within the compensatory range of body. In comparison with the traditional one-point blocking of cervical plexus, the modified cervical plexus block with ultrasonic guidance offers better anesthetic effects, fewer complications and convenient anesthetic localization. Thus it may be clinically applicable.</AbstractText>
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2,334,159 |
Volume kinetics of acetated Ringer's solution during experimental spinal anaesthesia.
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General anaesthesia lowers the clearance of crystalloid fluid, but the volume kinetics of such fluid throughout the duration of spinal anaesthesia has not been studied.</AbstractText>Ten female volunteers (mean age 29 years) received an intravenous infusion of 25 ml/kg of acetated Ringer's solution with and without spinal anaesthesia. A volume kinetic model was fitted to serial measurements of the haemoglobin concentration over 240 min based on arterial, cubital vein, and femoral vein blood. The measured urine flow was compared to the model-predicted elimination.</AbstractText>The arterial pressure remained stable, although the block reached to Th3-Th5 in half of the volunteers. There were no differences in fluid kinetics between the spinal anaesthesia and the control experiments. The administered volume was well confined to the kinetic system, which consisted of two communicating fluid spaces that were 2.8 l and approximately 7 l in size at baseline. The arteriovenous difference in plasma dilution remained positive for 30 min post-infusion in those having analgesia reaching to Th3-Th5, which differed significantly from low-level analgesia (Th12-L2, P < 0.03) when venous plasma was sampled from the leg. The urinary excretion averaged 1.13 l and 1.01 l for the spinal and control experiments, respectively. Volume kinetics predicted the urinary excretion at 5- to 10-min intervals with an overall bias of 52 ml.</AbstractText>Acetated Ringer's solution showed the same kinetics during experimental spinal anaesthesia as when the fluid was infused alone. Hence, spinal anaesthesia is not associated with the reduced fluid clearance reported for general anaesthesia.</AbstractText>© 2011 The Authors Acta Anaesthesiologica Scandinavica © 2011 The Acta Anaesthesiologica Scandinavica Foundation.</CopyrightInformation>
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2,334,160 |
Impedance-based detection of beating rhythm and proarrhythmic effects of compounds on stem cell-derived cardiomyocytes.
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The xCELLigence real time cell analyzer Cardio system offers a new system for real-time cell analysis that measures impedance-based signals in a label-free noninvasive manner. The aim of this study was to test whether impedance readings are a useful tool to detect compound effects on beating frequency (beats per minute, bpm) and arrhythmias of human induced pluripotent stem cell- and a mouse embryonic stem cell-derived cardiomyocyte line (hiPSC-CM and mESC-CM, respectively). Baseline values for control wells were 45±3 and 179±6 bpm, respectively (n=6). Correspondingly, isoproterenol increased beating frequency by 77% and 71%, whereas carbachol decreased frequency by 11% and 100% (stopped in 5/6 mESC-CM wells). E-4031 decreased beating rate and caused arrhythmias in both cell types, however, more pronounced in the human iPSC-CMs. Amlodipine inhibited contractions in both models, and T-type calcium channel block strongly reduced beating rate and eventually stopped beating in mESC-CM but caused a smaller effect in hiPSC-CM. The results of this initial study show that, under the right conditions, the beating frequency of a monolayer of cells can be stably recorded over several days. Additionally, the system detects changes in beating frequency and amplitude caused by added reference compounds. This assay system has the potential to enable medium-throughput screening, but for implementation into routine daily work, extended validation, testing of additional batches of cardiomyocytes, and further assay optimization (e.g., frequency of media exchange, growth matrix, seeding density, age of cells after plating, and temperature control) will be needed.
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2,334,161 |
Mathematical modeling mechanisms of arrhythmias in transgenic mouse heart overexpressing TNF-α.
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Transgenic mice overexpressing tumor necrosis factor-α (TNF-α mice) possess many of the features of human heart failure, such as dilated cardiomyopathy, impaired Ca(2+) handling, arrhythmias, and decreased survival. Although TNF-α mice have been studied extensively with a number of experimental methods, the mechanisms of heart failure are not completely understood. We created a mathematical model that reproduced experimentally observed changes in the action potential (AP) and Ca(2+) handling of isolated TNF-α mice ventricular myocytes. To study the contribution of the differences in ion currents, AP, Ca(2+) handling, and intercellular coupling to the development of arrhythmias in TNF-α mice, we further created several multicellular model tissues with combinations of wild-type (WT)/reduced gap junction conductance, WT/prolonged AP, and WT/decreased Na(+) current (I(Na)) amplitude. All model tissues were examined for susceptibility to Ca(2+) alternans, AP propagation block, and reentry. Our modeling results demonstrated that, similar to experimental data in TNF-α mice, Ca(2+) alternans in TNF-α tissues developed at longer basic cycle lengths. The greater susceptibility to Ca(2+) alternans was attributed to the prolonged AP, resulting in larger inactivation of I(Na), and to the decreased SR Ca(2+) uptake and corresponding smaller SR Ca(2+) load. Simulations demonstrated that AP prolongation induces an increased susceptibility to AP propagation block. Programmed stimulation of the model tissues with a premature impulse showed that reduced gap junction conduction increased the vulnerable window for initiation reentry, supporting the idea that reduced intercellular coupling is the major factor for reentrant arrhythmias in TNF-α mice.
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2,334,162 |
Rosuvastatin blocks hERG current and prolongs cardiac repolarization.
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Blocking of the potassium current I(Kr) [human ether-a-go-go related gene (hERG)] is generally associated with an increased risk of long QT syndrome (LQTS). The 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor, rosuvastatin, is a methanesulfonamide derivative, which shows structural similarities with several I(Kr) blockers. Hence, we assessed the effects of rosuvastatin on cardiac repolarization by using in vitro, ex vivo, and in vivo models. Patch clamp experiments on hERG-transfected human embryonic kidney (HEK) 293 cells established the potency of rosuvastatin to block hERG [half maximal inhibitory concentration (IC(50) ) = 195 nM]. We showed in isolated guinea pig hearts that 195 nM rosuvastatin prolonged (basic cycle length of 250 ms; p < 0.05) the monophasic action potential duration at 90% repolarization (MAPD(90) ) by 11 ± 1 ms. Finally, rosuvastatin (10 mg/kg, intraperitoneal) prolonged corrected QT interval (QTc) in conscious and unrestrained guinea pigs from 201 ± 1 to 210 ± 2 ms (p < 0.05). Thus, rosuvastatin blocks I(Kr) and prolongs cardiac repolarization. In additional experiments, we also show that hERG blockade in HEK 293 cells was modulated by coexpression of efflux [breast cancer resistance protein (BCRP), multidrug resistance gene (MDR1)] and influx [organic anion transporting polypeptide (OATP) 2B1] transporters involved in the disposition and cardiac distribution of the drug. Genetic polymorphisms observed for BCRP, MDR1, and OATP2B1, and IC(50) determined for hERG blocking lead us to propose that some patients may be at risk of rosuvastatin-induced LQTS.
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2,334,163 |
Differential hemodynamic effects of levosimendan in a porcine model of neonatal hypoxia-reoxygenation.
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Neonatal asphyxia can be complicated by myocardial dysfunction with secondary alterations in pulmonary and regional hemodynamics. Levosimendan is a calcium-sensitizing inotrope that may support cardiac output, but little is known regarding its differential hemodynamic effects in asphyxiated neonates.</AbstractText>Mixed breed piglets (1-4 days old, weight 1.6-2.3 kg) were acutely instrumented. Normocapnic alveolar hypoxia (10-15% oxygen) was induced for 2 h, followed by reoxygenation with 100% (1 h) and then 21% oxygen (3 h). At 2 h of reoxygenation, after volume loading (Ringer's lactate 10 ml/kg), either levosimendan (0.1 or 0.2 μg/kg/min) or D(5)W (placebo) was infused for 2 h in a blinded, block-randomized fashion (n = 7-8/group). The systemic, pulmonary and regional (carotid, superior mesenteric and renal) hemodynamics were compared.</AbstractText>At 0.1 and 0.2 μg/kg/min, levosimendan significantly increased cardiac output (121 and 123% of pretreatment, respectively) and heart rate, and decreased systemic vascular resistance without causing hypotension. Pulmonary arterial pressure and estimated pulmonary vascular resistance were significantly increased from pretreatment baseline in 0.1 but not 0.2 μg/kg/min levosimendan. Levosimendan infusion had no effects on regional hemodynamics. Myocardial efficiency but not oxygen consumption increased with 0.1 μg/kg/min levosimendan without significant effects on plasma troponin and myocardial lactate levels.</AbstractText>In newborn piglets following hypoxia-reoxygenation injury, levosimendan improves cardiac output but has no marked effects in carotid, superior mesenteric and renal perfusion. It appears that various doses of levosimendan increase the cardiac output through different mechanisms. Further investigations are needed to examine the effectiveness of levosimendan as a cardiovascular supportive therapy either alone or in conjunction with other inotropes in asphyxiated neonates.</AbstractText>Copyright © 2011 S. Karger AG, Basel.</CopyrightInformation>
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2,334,164 |
Comparison of epidural tramadol-ropivacaine and fentanyl-ropivacaine for labor analgesia: a prospective randomized study.
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To test the hypothesis that 5 mg/mL tramadol is superior to 3 ?g/mL fentanyl when combined with 0.125% ropivacaine in parturients undergoing labor during epidural analgesia.</AbstractText>Sixty-one parturients undergoing labor selected for delivery with epidural analgesia were randomized into two groups: Group tramadol (0.125% ropivacaine plus tramadol 5 mg/mL) and Group fentanyl (0.125% ropivacaine plus fentanyl 3 ug/mL). Hemodynamics, rate of cesarean delivery, sensory block level, Bromage motor scale scores, instrument-assisted delivery, oxytocin use, visual analog scale (VAS) scores, Apgar scores, umbilical cord artery gas analysis, and maternal side-effects including nausea, vomiting, pruritus, urinary retention, shivering, hypotension, and respiratory depression were recorded.</AbstractText>The two groups had no significant differences with respect to maternal hemodynamics, neonatal heart rate, VAS scores, rate of cesarean delivery, sensory block level, Bromage motor scale scores, instrument-assisted delivery, oxytocin use, hypotension, nausea, vomiting, and respiratory depression (p > 0.05). The incidence of pruritus, shivering, and urinary retention were more commonly observed in Group fentanyl despite there was no significant difference between the two groups. Umbilical artery pH was significantly lower while PCO(2) was higher in Group fentanyl than Group tramadol (p = 0.003 and p = 0.026, respectively). Birth-weight, umbilical artery PO(2) and base deficit, and Apgar scores at 1 and 5 min were comparable between the two groups (p > 0.05).</AbstractText>Our observations suggest that tramadol seems to be a safe alternative to fentanyl for labor analgesia due to its similar analgesic efficacy.</AbstractText>
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2,334,165 |
Suturing of penetrating wounds to the heart in the nineteenth century: the beginnings of heart surgery.
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The beginnings of cardiac surgery go back to the 19th century. This article describes the history of the first attempts to operate on the heart. In 1882, Dr Block from Danzig, and in 1895, Simplicio Del Vecchio, published reports of animal experiments showing that the suturing of heart wounds is possible. After unsuccessful attempts by Axel Cappelen in Norway and Guido Farina in Italy, it was Ludwig Rehn of Germany who first sutured a laceration of the right ventricle of a human heart. Shortly afterward, Antonio Parrozzani successfully sutured a stab wound of the left ventricle. Following cardiac surgery back to its very beginnings, it is striking that the first attempts in the 19th century to repair the injured heart were regarded with great skepticism, and that heart suturing only slowly became an established method of treatment. Once the concept of cardiac surgery had become accepted, however, many kinds of operations were developed, paving the way for an explosion in the number of cardiac operations, as we well know, in the century that followed.
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2,334,166 |
Comparison of intranasal methamphetamine and d-amphetamine self-administration by humans.
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There are no studies directly comparing self-administration of methamphetamine and d-amphetamine by humans. This study compared intranasal methamphetamine- and d-amphetamine self-administration and characterized the mood, performance and physiological effects produced by the drugs.</AbstractText>A randomized, double-blind, placebo-controlled, cross-over study.</AbstractText>An out-patient research unit at the New York State Psychiatric Institute.</AbstractText>Male recreational methamphetamine users (n = 13).</AbstractText>Five 2-day blocks of sessions were conducted. On the first day of each block, participants 'sampled' a single methamphetamine or d-amphetamine dose (0, 12, 50 mg/70 kg) and a monetary reinforcer ($5 or $20). Amphetamine plasma levels, cardiovascular, mood, and psychomotor performance effects were assessed before drug administration and repeatedly thereafter. On the second day of each block, participants chose between the sampled reinforcers (drug or money).</AbstractText>There were no significant differences between the drugs on the majority of measures. Under the $5 condition, both amphetamines increased self-administration dose-dependently, with 41% drug choices overall. Under the $20 condition, only 17% drug options were selected. Both drugs increased cardiovascular activity and 'positive' mood, although methamphetamine produced more prominent effects on some measures (e.g. heart rate and ratings of 'high').</AbstractText>Methamphetamine and d-amphetamines appear to produce a similar dose-related profile of effects in humans, which supports their equivalence for abuse potential.</AbstractText>© 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.</CopyrightInformation>
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2,334,167 |
Mild hyperkalemia and low eGFR a tedious recipe for cardiac disaster in the elderly: an unusual reversible cause of syncope and heart block.
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Hyperkalemia affects the myocardial tissue producing electrocardiographic abnormalities, such as prolongation of the P-R interval, tall peaked T waves, a reduction in the amplitude and an increase in the duration of P wave, and atrial and ventricular arrhythmias, including variable degree heart blocks. Elderly patients are particularly predisposed to developing hyperkalemia and the associated abnormalities due to an age-related reduction in glomerular filtration rate and pre-existing medical problems. Therefore, the impact of aging on potassium homeostasis must be taken into consideration, and preventive measures, such as early recognition of possible hyperkalemia in the geriatric population treated with certain medications or supplements must be investigated. The threshold for cardiac arrhythmias in the elderly can be lower than the general population. We report 3 unusual cases of mild hyperkalemia in elderly patients presenting with hypotension, syncope and variable degree heart blocks which resolved spontaneously with the correction of hyperkalemia.
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2,334,168 |
[Ephedrine vs. phenylephrine by intravenous bolus and continuous infusion to prevent hypotension secondary to spinal anesthesia during cesarean section: a randomized comparative trial].
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Subarachnoid spinal anesthesia for cesarean section is associated with a high incidence of hypotension, which can require the use of vasoconstrictors. The aim of this trial was to compare ephedrine to phenylephrine for the prevention of secondary hypotension and to assess the adverse effects on both mother and newborn.</AbstractText>Eighty patients undergoing elective or emergency cesarean section, in the absence of uterine activity or fetal risk, were randomized to receive prophylaxis with ephedrine or phenylephrine immediately after the spinal block. Patients in the ephedrine group received an intravenous bolus of 0.1 mg/kg plus continuous infusion at a rate of 0.5 mg/kg/h; patients in the phenylephrine group received an intravenous bolus of 1.5 microg/kg plus a continuous infusion at 1.5 microg/kg/min. Infusion was maintained until umbilical cord clamping. We recorded maternal blood pressure, heart rate, nausea and vomiting, dizziness, bradycardia, hypotension, hypertension, fetal Apgar index, and umbilical cord blood parameters (pH, PCO2, and HCO3).</AbstractText>The overall incidence of hypotension was 11.2%, with no significant between-group differences (ephedrine group, 11.4%; phenylephrine group, 11.1%). The incidences of hypertension and bradycardia were higher in the phenylephrine group (27.8% and 2.3%, respectively) than in the ephedrine group (25% and 0%, respectively). Umbilical cord blood parameters and Apgar scores were similar. After suspension of continuous infusion, an episode of hypotension was detected in 22.5% of the patients (72.2% of these patients were in the phenylephrine group and 27.8% were in the ephedrine group).</AbstractText>At the doses of ephedrine and phenylephrine administered in this trial, the ability of these drugs to prevent hypotension during cesarean section proved to be similar. Higher incidences of adverse events (hypertension and bradycardia) were observed in the phenylephrine group. No differences were observed in neonatal effects.</AbstractText>
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2,334,169 |
Effect of a telemonitoring-facilitated collaboration between general practitioner and heart failure clinic on mortality and rehospitalization rates in severe heart failure: the TEMA-HF 1 (TElemonitoring in the MAnagement of Heart Failure) study.
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Chronic heart failure (CHF) patients are frequently rehospitalized within 6 months after an episode of fluid retention. Rehospitalizations are preventable, but this requires an extensive organization of the healthcare system. In this study, we tested whether intensive follow-up of patients through a telemonitoring-facilitated collaboration between general practitioners (GPs) and a heart failure clinic could reduce mortality and rehospitalization rate.</AbstractText>One hunderd and sixty CHF patients [mean age 76 ± 10 years, 104 males, mean left ventricular ejection fraction (LVEF) 35 ± 15%] were block randomized by sealed envelopes and assigned to 6 months of intense follow-up facilitated by telemonitoring (TM) or usual care (UC). The TM group measured body weight, blood pressure, and heart rate on a daily basis with electronic devices that transferred the data automatically to an online database. Email alerts were sent to the GP and heart failure clinic to intervene when pre-defined limits were exceeded. All-cause mortality was significantly lower in the TM group as compared with the UC group (5% vs. 17.5%, P = 0.01). The total number of follow-up days lost to hospitalization, dialysis, or death was significantly lower in the TM group as compared with the UC group (13 vs. 30 days, P = 0.02). The number of hospitalizations for heart failure per patient showed a trend (0.24 vs. 0.42 hospitalizations/patient, P = 0.06) in favour of TM.</AbstractText>Telemonitoring-facilitated collaboration between GPs and a heart failure clinic reduces mortality and number of days lost to hospitalization, death, or dialysis in CHF patients. These findings need confirmation in a large trial.</AbstractText>
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2,334,170 |
Influence of pH on Ca²⁺ current and its control of electrical and Ca²⁺ signaling in ventricular myocytes.
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Modulation of L-type Ca(2+) current (I(Ca,L)) by H(+) ions in cardiac myocytes is controversial, with widely discrepant responses reported. The pH sensitivity of I(Ca,L) was investigated (whole cell voltage clamp) while measuring intracellular Ca(2+) (Ca(2+)(i)) or pH(i) (epifluorescence microscopy) in rabbit and guinea pig ventricular myocytes. Selectively reducing extracellular or intracellular pH (pH(o) 6.5 and pH(i) 6.7) had opposite effects on I(Ca,L) gating, shifting the steady-state activation and inactivation curves to the right and left, respectively, along the voltage axis. At low pH(o), this decreased I(Ca,L), whereas at low pH(i), it increased I(Ca,L) at clamp potentials negative to 0 mV, although the current decreased at more positive potentials. When Ca(2+)(i) was buffered with BAPTA, the stimulatory effect of low pH(i) was even more marked, with essentially no inhibition. We conclude that extracellular H(+) ions inhibit whereas intracellular H(+) ions can stimulate I(Ca,L). Low pH(i) and pH(o) effects on I(Ca,L) were additive, tending to cancel when appropriately combined. They persisted after inhibition of calmodulin kinase II (with KN-93). Effects are consistent with H(+) ion screening of fixed negative charge at the sarcolemma, with additional channel block by H(+)(o) and Ca(2+)(i). Action potential duration (APD) was also strongly H(+) sensitive, being shortened by low pH(o), but lengthened by low pH(i), caused mainly by H(+)-induced changes in late Ca(2+) entry through the L-type Ca(2+) channel. Kinetic analyses of pH-sensitive channel gating, when combined with whole cell modeling, successfully predicted the APD changes, plus many of the accompanying changes in Ca(2+) signaling. We conclude that the pH(i)-versus-pH(o) control of I(Ca,L) will exert a major influence on electrical and Ca(2+)-dependent signaling during acid-base disturbances in the heart.
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2,334,171 |
Transmitochondrial mice as models for mitochondrial DNA-based diseases.
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Mitochondrial genome (mtDNA) mutations and the resultant mitochondrial respiratory abnormalities are associated with a wide variety of disorders, such as mitochondrial diseases, neurodegenerative diseases, diabetes, and cancer, as well as aging. Generation of model animals carrying mutant mtDNAs is important for understanding the pathophysiological mechanisms of the mtDNA-based diseases. We have succeeded in generating three kinds of mice with pathogenic mutant mtDNAs, named "mito-mice," by the introduction of mitochondria carrying pathogenic mutant mtDNAs into mouse zygotes and mouse embryonic stem (ES) cells. In the case of mito-mice possessing the heteroplasmic state of wild-type mtDNA and pathogenic mtDNA with a large-scale deletion (ΔmtDNA, mito-miceΔ), a high load of ΔmtDNA induced mitochondrial respiration defects in various tissues, resulting in mitochondrial disease phenotypes, such as low body weight, lactic acidosis, ischemia, myopathy, heart block, deafness, male infertility, long-term memory defects, and renal failure. In this review, we summarize generation and clinical phenotypes of three types of mito-mice and we introduce several treatment trials for mitochondrial diseases using mito-miceΔ.
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2,334,172 |
The effects of paeoniflorin monomer of a Chinese herb on cardiac ion channels.
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Because of the potential proarrhythmic effect of current antiarrhythmic drugs, it is still desirable to find safer antiarrhythmic drugs worldwide. Paeoniflorin is one of the Chinese herb monomers that have different effects on many ion channels. The present study aimed to determine the effects of paeoniflorin on cardiac ion channels.</AbstractText>Whole-cell patch-clamp technique was used to record ion channel currents. L-type calcium current (I(Ca-L)), inward rectifier potassium current (I(K1)), and transient outward potassium current (I(to1)) were studied in rat ventricular myocytes and sodium current (I(Na)), slow delayed rectifier current (I(Ks)), and HERG current (I(Kr)) were investigated in transfected human embryonic kidney 293 cells.</AbstractText>One hundred µmol/L paeoniflorin reduced the peak I(Ca-L) by 40.29% at the test potential of +10 mV (from (-9.78 ± 0.52) pA/pF to (-5.84 ± 0.89) pA/pF, n = 5, P = 0.028). The steady-state activation curve was shifted to more positive potential in the presence of the drug. The half activation potentials were (-11.22 ± 0.27) mV vs. (-5.95 ± 0.84) mV (n = 5, P = 0.007), respectively. However, the steady-state inactivation and the time course of recovery from inactivation were not changed. One hundred µmol/L paeoniflorin completely inhibited the peak I(Na) and the effect was reversible. Moreover, paeoniflorin inhibited the I(K1) by 30.13% at the test potential of -100 mV (from -25.26 ± 8.21) pA/pF to (-17.65 ± 6.52) pA/pF, n = 6, P = 0.015) without effects on the reversal potential and the rectification property. By contrast, 100 µmol/L paeoniflorin had no effects on I(to1), I(Ks) or I(Kr) channels.</AbstractText>The study demonstrated that paeoniflorin blocked I(Ca-L), I(Na), and I(K1) without affecting I(to1), I(Ks), or I(Kr). The multi-channel block effect may account for its antiarrhythmic effects with less proarrhythmic potential.</AbstractText>
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2,334,173 |
Cognitive reserve moderates the association between heart failure and cognitive impairment.
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Cognitive impairment in persons with heart failure is common. Theories of cognitive reserve suggest that premorbid factors, such as intellectual ability, may provide a buffer against cognitive impairment due to neuropathological insult. No study has examined the influence of cognitive reserve on cognitive functioning in older adults with heart failure.</AbstractText>This study examined whether cognitive reserve moderates the relationship between heart failure severity and cognitive function.</AbstractText>A total of 157 persons with heart failure (69.26 ± 9.26 years; 39% female) completed neuropsychological testing and a brief fitness assessment. Cognitive reserve was operationalized using estimated premorbid intellect on the American National Adult Reading Test (AMNART).</AbstractText>A moderation analysis was performed using hierarchical regression models for each cognitive domain. An interaction term between the AMNART and 2-Minute Step Test was created and entered into the final block of the model, with demographic, psychosocial, and heart failure severity entered in the previous blocks. The interaction term was significant for attention, t(155) = -2.54, p = .012, executive function, t(155) = -3.30, p = .001, and language, t(155) = -2.83, p = .005, domains.</AbstractText>The current findings suggest that cognitive reserve moderates the association between heart failure severity and cognitive function in multiple cognitive domains. Further work is needed to clarify the mechanisms by which cognitive reserve attenuates cognitive impairment in this population.</AbstractText>
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2,334,174 |
Enhancing effects of salicylate on quinidine-induced block of human wild type and LQT3 related mutant cardiac Na+ channels.
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It is unknown whether salicylate enhances the action of antiarrhythmic agents on human Na+ channels with state dependency and tissue specificity. We therefore investigated effects of salicylate on quinidine-induced block of human cardiac and skeletal muscle Na+ channels. Human cardiac wild-type (hH1), LQT3-related mutant (ΔKPQ), and skeletal muscle (hSkM1) Na+ channel α subunits were expressed in COS7 cells. Effects of salicylate on quinidine-induced tonic and use-dependent block of Na+ channel currents were examined by the whole-cell patch-clamp technique. Salicylate enhanced the quinidine-induced tonic and use-dependent block of both hH1 and hSkM1 currents at a holding potential (HP) of -100 mV but not at -140 mV. Salicylate decreased the IC50 value for the quinidine-induced tonic block of hH1 at an HP of -100 mV, and produced a negative shift in the steady-state inactivation curve of hH1 in the presence of quinidine. According to the modulated receptor theory, it is probable that salicylate decreases the dissociation constant for quinidine binding to inactivated-state channels. Furthermore, salicylate significantly enhanced the quinidine-induced tonic and use-dependent block of the peak and steady-state ΔKPQ channel currents. The results suggest that salicylate enhances quinidine-induced block of Na+ channels via increasing the affinity of quinidine to inactivated state channels.
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2,334,175 |
The metabolic and toxicological considerations for mTOR inhibitors in the treatment of hepatocarcinoma.
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Hepatocellular carcinoma (HCC) is a major health problem worldwide. Several molecular pathways involved in HCC growth and progression have recently been identified. Rapamycin analogs are able to inhibit one of the most active oncogenic molecular pathways in HCC cells: the mammalian target of rapamycin (mTOR) pathway.</AbstractText>In this review, the authors analyze the principal molecular features of the mTOR pathway and the use of rapamycin analogs in the treatment of hepatocarcinoma. The article also looks at the reoccurrence of HCC following liver transplantation as well as after the treatment of de novo neoplasms. Finally, the authors discuss the advantage of using a combined HCC pharmacological therapy to obtain a synergistic effect on tumor mass.</AbstractText>Among the available options for the treatment of advanced-stage HCC, mTOR pathway inhibitors show great promise. Once these agents have their safety and efficacy confirmed, in the treatment of liver disease, their use should be considered in patients affected by HCC. This should especially be the case for those who have had liver transplants or suffered with de novo tumors. Moreover, the authors believe that mTOR inhibitors could be used in a combined pharmacological approach to improve HCC molecular-targeted therapy by producing a multiple-level block of tumor intracellular signaling.</AbstractText>
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2,334,176 |
Irrigated-tip vs. conventional-tip catheters for primary ablation of posteroseptal and right free-wall accessory pathways: a prospective randomized study.
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The use of irrigated-tip catheters enables elimination of almost all accessory pathways (APs) resistant to standard radiofrequency ablation (RFA). However, efficacy of irrigation catheter technology in the initial AP ablation has not been studied systematically yet.</AbstractText>We tested whether the externally irrigated-tip catheters are more effective than the conventional-tip catheters for initial RFA of the posteroseptal and right free-wall APs, i.e., where application of the conventional RFA is expected to have a lower success rate.</AbstractText>Fifty consecutive patients (39 +/- 12 years, 32 males), who were subjected to primary catheter-ablation of the posteroseptal or right free-wall AP were randomly assigned to RFA with an externally irrigated-tip catheter (group I, n = 25; 45 degrees C/40 W outside the coronary sinus (CS) and 45 degrees C/30 W inside the CS) or a conventional-tip catheter (group C, n = 25; 60 degrees C/60 W outside and 55 degrees C/35 W inside the CS).</AbstractText>No significant difference was identified between groups I and C with respect to acute success rate (88% vs. 96%), number of radiofrequency applications (6.8 +/- 4.7 vs. 6.1 +/- 4.3), RFA time (373 +/- 242 sec vs 365 +/- 241 sec), energy (11,022 +/- 7833 J vs. 12,870 +/- 11,414 J), fluoroscopy time (669 +/- 443 sec vs. 789 +/- 578 sec) and recurrence rate (18.2% vs. 16.7%). The only complication was encountered in group I, manifested as AV-block I-II degree after elimination of the right posteroseptal AP.</AbstractText>Irrigated-tip catheters are not more efficient than conventional catheters in initial RFA of the posteroseptal and right free-wall APs. Therefore, the use of irrigated-tip catheters is justifiable only for ablation of the APs resistant to previously attempted conventional RFA.</AbstractText>
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2,334,177 |
Nox4-derived reactive oxygen species mediate cardiomyocyte injury in early type 1 diabetes.
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Oxidative stress contributes to diabetic cardiomyopathy. This study explored the role of the NADPH oxidase Nox4 as a source of reactive oxygen species (ROS) involved in the development of diabetic cardiomyopathy. Phosphorothioated antisense (AS) or sense (S) oligonucleotides for Nox4 were administered for 2 wk to rats made diabetic by streptozotocin. NADPH oxidase activity, ROS generation, and the expression of Nox4, but Nox1 or Nox2, were increased in left ventricular tissue of the diabetic rats. Expression of molecular markers of hypertrophy and myofibrosis including fibronectin, collagen, α-smooth muscle actin, and β-myosin heavy chain were also increased. These parameters were attenuated by the administration of AS but not S Nox4. Moreover, the impairment of contractility observed in diabetic rats was prevented in AS- but not S-treated animals. Exposure of cultured cardiac myocytes to 25 mM glucose [high glucose (HG)] increased NADPH oxidase activity, the expression of Nox4, and molecular markers of cardiac injury. These effects of HG were prevented in cells infected with adenoviral vector containing a dominant negative form of Nox4. This study provides strong evidence that Nox4 is an important source of ROS in the left ventricle and that Nox4-derived ROS contribute to cardiomyopathy at early stages of type 1 diabetes.
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2,334,178 |
[Assessment of renal function, iatrogenic hyperkalemia and acute renal dysfunction in cardiology. Contrast-induced nephropathy].
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Renal impairment influences the prognosis of patients with cardiovascular disease and increases cardiovascular risk. Renal dysfunction is a marker of lesions in other parts of the vascular tree and detection facilitates early identification of individuals at high risk of cardiovascular events. In patients with cardiovascular disease, renal function is assessed by measuring albuminuria in a spot urine sample and by estimating the glomerular filtration rate using creatinine-derived predictive formulas or equations. We recommend the Chronic Kidney Disease Epidemiology Collaboration or the Modification of Diet in Renal Disease formulas. The Cockcroft-Gault formula is a possible alternative. The administration of drugs that block the angiotensin-renin system can, on occasion, be associated with acute renal dysfunction or hyperkalemia. We need to know when risk of these complications exists so as to provide the best possible treatment: prevention. Given the growing number of diagnostic and therapeutic procedures in the field of cardiology that use intravenous contrast media, contrast-induced nephrotoxicity represents a significant problem. We should identify the risk factors and patients at greatest risk, and prevent it from appearing.
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2,334,179 |
Substrate oxidation and cardiac performance during exercise in disorders of long chain fatty acid oxidation.
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The use of long-chain fatty acids (LCFAs) for energy is inhibited in inherited disorders of long-chain fatty acid oxidation (FAO). Increased energy demands during exercise can lead to cardiomyopathy and rhabdomyolysis. Medium-chain triglycerides (MCTs) bypass the block in long-chain FAO and may provide an alternative energy substrate to exercising muscle.</AbstractText>To determine the influence of isocaloric MCT versus carbohydrate (CHO) supplementation prior to exercise on substrate oxidation and cardiac workload in participants with carnitine palmitoyltransferase 2 (CPT2), very long-chain acyl-CoA dehydrogenase (VLCAD) and long-chain 3-hydroxyacyl CoA dehydrogenase (LCHAD) deficiencies.</AbstractText>Eleven subjects completed two 45-minute, moderate intensity, treadmill exercise studies in a randomized crossover design. An isocaloric oral dose of CHO or MCT-oil was administered prior to exercise; hemodynamic and metabolic indices were assessed during exertion.</AbstractText>When exercise was pretreated with MCT, respiratory exchange ratio (RER), steady state heart rate and generation of glycolytic intermediates significantly decreased while circulating ketone bodies significantly increased.</AbstractText>MCT supplementation prior to exercise increases the oxidation of medium chain fats, decreases the oxidation of glucose and acutely lowers cardiac workload during exercise for the same amount of work performed when compared with CHO pre-supplementation. We propose that MCT may expand the usable energy supply, particularly in the form of ketone bodies, and improve the oxidative capacity of the heart in this population.</AbstractText>Copyright © 2011 Elsevier Inc. All rights reserved.</CopyrightInformation>
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2,334,180 |
Preventing Staphylococcus aureus sepsis through the inhibition of its agglutination in blood.
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Staphylococcus aureus infection is a frequent cause of sepsis in humans, a disease associated with high mortality and without specific intervention. When suspended in human or animal plasma, staphylococci are known to agglutinate, however the bacterial factors responsible for agglutination and their possible contribution to disease pathogenesis have not yet been revealed. Using a mouse model for S. aureus sepsis, we report here that staphylococcal agglutination in blood was associated with a lethal outcome of this disease. Three secreted products of staphylococci--coagulase (Coa), von Willebrand factor binding protein (vWbp) and clumping factor (ClfA)--were required for agglutination. Coa and vWbp activate prothrombin to cleave fibrinogen, whereas ClfA allowed staphylococci to associate with the resulting fibrin cables. All three virulence genes promoted the formation of thromboembolic lesions in heart tissues. S. aureus agglutination could be disrupted and the lethal outcome of sepsis could be prevented by combining dabigatran-etexilate treatment, which blocked Coa and vWbp activity, with antibodies specific for ClfA. Together these results suggest that the combined administration of direct thrombin inhibitors and ClfA-antibodies that block S. aureus agglutination with fibrin may be useful for the prevention of staphylococcal sepsis in humans.
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2,334,181 |
Crucial role of a shared extracellular loop in apamin sensitivity and maintenance of pore shape of small-conductance calcium-activated potassium (SK) channels.
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Activation of small-conductance calcium (Ca(2+))-dependent potassium (K(Ca)2) channels (herein called "SK") produces membrane hyperpolarization to regulate membrane excitability. Three subtypes (SK1-3) have been cloned and are distributed throughout the nervous system, smooth muscle, and heart. It is difficult to discern the physiological role of individual channel subtypes as most blockers or enhancers do not discriminate between subtypes. The archetypical blocker apamin displays some selectivity between SK channel subtypes, with SK2 being the most sensitive, followed by SK3 and then SK1. Sensitivity of SK1 is species specific, with the human isoform being blocked by the toxin, whereas the rat is not. Mutation studies have identified residues within the outer pore that suggest apamin blocks by an allosteric mechanism. Apamin also uses a residue within the S3-S4 extracellular loop to produce a high-sensitivity block. We have identified that a 3-amino acid motif within this loop regulates the shape of the channel pore. This motif is required for binding and block by apamin, suggesting that a change in pore shape underlies allosteric block. This motif is absent in rat SK1, explaining why it is insensitive to block by apamin. The overlapping distribution of SK channel subtype expression suggests that native heteromeric channels may be common. We show that the S3-S4 loop of one subunit overlaps the outer pore of the adjacent subunit, with apamin interacting with both regions. This arrangement provides a unique binding site for each combination of SK subunits within a coassembled channel that may be targeted to produce blockers specific for heteromeric SK channels.
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2,334,182 |
Subcellular heterogeneity of ryanodine receptor properties in ventricular myocytes with low T-tubule density.
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In ventricular myocytes of large mammals, not all ryanodine receptor (RyR) clusters are associated with T-tubules (TTs); this fraction increases with cellular remodeling after myocardial infarction (MI).</AbstractText>To characterize RyR functional properties in relation to TT proximity, at baseline and after MI.</AbstractText>Myocytes were isolated from left ventricle of healthy pigs (CTRL) or from the area adjacent to a myocardial infarction (MI). Ca(2+) transients were measured under whole-cell voltage clamp during confocal linescan imaging (fluo-3) and segmented according to proximity of TTs (sites of early Ca(2+) release, F>F(50) within 20 ms) or their absence (delayed areas). Spontaneous Ca(2+) release events during diastole, Ca(2+) sparks, reflecting RyR activity and properties, were subsequently assigned to either category.</AbstractText>In CTRL, spark frequency was higher in proximity of TTs, but spark duration was significantly shorter. Block of Na(+)/Ca(2+) exchanger (NCX) prolonged spark duration selectively near TTs, while block of Ca(2+) influx via Ca(2+) channels did not affect sparks properties. In MI, total spark mass was increased in line with higher SR Ca(2+) content. Extremely long sparks (>47.6 ms) occurred more frequently. The fraction of near-TT sparks was reduced; frequency increased mainly in delayed sites. Increased duration was seen in near-TT sparks only; Ca(2+) removal by NCX at the membrane was significantly lower in MI.</AbstractText>TT proximity modulates RyR cluster properties resulting in intracellular heterogeneity of diastolic spark activity. Remodeling in the area adjacent to MI differentially affects these RyR subpopulations. Reduction of the number of sparks near TTs and reduced local NCX removal limit cellular Ca(2+) loss and raise SR Ca(2+) content, but may promote Ca(2+) waves.</AbstractText>
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2,334,183 |
Echocardiographic diagnosis and prognosis of fetal left ventricular noncompaction.
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Left ventricular noncompaction (LVNC) has rarely been described in the fetus.</AbstractText>The presence of associated congenital heart disease and rhythm disturbance was identified and the presence of heart failure was assessed using the cardiovascular profile score in all fetuses with LVNC presenting from January 1999 to July 2010. The left ventricle was divided into 12 segments-four segments each at the base, midpapillary, and apical regions-in the short-axis view to calculate the noncompaction/compaction ratio for each segment.</AbstractText>Of 24 fetuses with LVNC included in the study, 22 had significant congenital heart disease, and 15 had complete heart block. Of the 16 patients with adequate follow-up and not electively terminated, 12 (81%) died or progressed to heart transplantation. The average noncompaction/compaction ratios were 2.02 in patients who died or underwent heart transplantation and 1.67 in survivors (P = .2034). Fifty-seven of 93 measured segments (61%) of the left ventricle in the patients who died or underwent heart transplantation had noncompaction/compaction ratios ≥ 2 compared with five of 17 measured segments (29%) in survivors (P = .0837). The average cardiovascular profile score was 6. The apical region had greater involvement of noncompaction than the midpapillary and basal regions, with ratios of 2.27, 2.14, and 1.10, respectively (P = .00035).</AbstractText>Fetuses with LVNC have a poor prognosis that may be related to associated congenital heart disease, increased segmental involvement of noncompaction, and complete heart block and can be predicted by the cardiovascular profile score.</AbstractText>Copyright © 2012 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.</CopyrightInformation>
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2,334,184 |
Binding of anti-SSA antibodies to apoptotic fetal cardiocytes stimulates urokinase plasminogen activator (uPA)/uPA receptor-dependent activation of TGF-β and potentiates fibrosis.
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In congenital heart block (CHB), binding of maternal anti-SSA/Ro Abs to fetal apoptotic cardiocytes impairs their removal by healthy cardiocytes and increases urokinase plasminogen activator (uPA)/uPA receptor (uPAR)-dependent plasmin activation. Because the uPA/uPAR system plays a role in TGF-β activation, we evaluated whether anti-Ro binding to apoptotic cardiocytes enhances plasmin-mediated activation of TGF-β, thereby promoting a profibrosing phenotype. Supernatants from cocultures of healthy cardiocytes and apoptotic cardiocytes bound by IgG from a mother whose child had CHB (apoptotic-CHB-IgG [apo-CHB-IgG]) exhibited significantly increased levels of active TGF-β compared with supernatants from cocultures of healthy cardiocytes and apoptotic cardiocytes preincubated with IgG from a healthy donor. Treatment of the culture medium with anti-TGF-β Ab or TGF-β inhibitor (SB431542) abrogated the luciferase response, thereby confirming TGF-β dependency. Increased uPA levels and activity were present in supernatants generated from cocultures of healthy cardiocytes and apo-CHB-IgG cardiocytes compared with healthy cardiocytes and apoptotic cardiocytes preincubated with IgG from a healthy donor, respectively. Treatment of apo-CHB-IgG cardiocytes with anti-uPAR or anti-uPA Abs or plasmin inhibitor aprotinin prior to coculturing with healthy cardiocytes attenuated TGF-β activation. Supernatants derived from cocultures of healthy cardiocytes and apo-CHB-IgG cardiocytes promoted Smad2 phosphorylation and fibroblast transdifferentiation, as evidenced by increased smooth muscle actin and collagen expression, which decreased when fibroblasts were treated with supernatants from cocultures pretreated with uPAR Abs. These data suggested that binding of anti-Ro Abs to apoptotic cardiocytes triggers TGF-β activation, by virtue of increasing uPAR-dependent uPA activity, thus initiating and amplifying a cascade of events that promotes myofibroblast transdifferentiation and scar.
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2,334,185 |
Chronic phase of Chagas disease: why should it be treated? A comprehensive review.
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The pathogenesis and evolutive pattern of Chagas disease suggests that the chronic phase should be more widely treated in order to (i) eliminate Trypanosoma cruzi and prevent new inflammatory foci and the extension of tissue lesions, (ii) promote tissue regeneration to prevent fibrosis, (iii) reverse existing fibrosis, (iv) prevent cardiomyopathy, megaoesophagus and megacolon and (v) reduce or eliminate cardiac block and arrhythmia. All cases of the indeterminate chronic form of Chagas disease without contraindications due to other concomitant diseases or pregnancy should be treated and not only cases involving children or recently infected cases. Patients with chronic Chagas cardiomyopathy grade II of the New York Heart Association classification should be treated with specific chemotherapy and grade III can be treated according to medical-patient decisions. We are proposing the following new strategies for chemotherapeutic treatment of the chronic phase of Chagas disease: (i) repeated short-term treatments for 30 consecutive days and interval of 30-60 days for six months to one year and (ii) combinations of drugs with different mechanisms of action, such as benznidazole + nifurtimox, benznidazole or nifurtimox + allopurinol or triazole antifungal agents, inhibition of sterol synthesis.
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2,334,186 |
Cardiac specific effects of thyroid hormone analogues.
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There is significant interest in development of thyroid hormone analogues to harness specific properties as therapeutic agents for a variety of clinical indications including obesity, hypercholesterolemia, heart failure, and thyrotoxicosis. To date, most analogues have been designed to target liver specific effects, which can promote weight loss and lipid lowering through either tissue specific uptake or thyroid hormone receptor (TR) β isoform selectivity at the same time minimizing the unwanted cardiac and bone effects. We have developed a molecular biomarker assay to study the induction of the transcription of the cardiac specific α-myosin heavy chain (MHC) gene as a more sensitive and specific measure of thyroid hormone action on cardiac myocytes. We tested 5 TRβ and 1 TRα selective agonists as well as 2 putative TR antagonists in our α-MHC hnRNA assay. Using reverse transcription and polymerase chain reaction, we measured the induction of the α-MHC primary transcript in response to administration of drug. The TRα and only 2 of the TRβ agonists were highly active, when compared to the effect of T3, at the level of the cardiac myocyte. In addition, our data suggests that the reason that the antagonist NH-3 is not able to block the T3-mediated induction of α-MHC is that it does not get transported into the cardiac myocyte. Our data suggest that this assay will be useful in preclinical studies of the potential cardiac specific effects of thyroid hormone analogues and that predictions of function based on structure are not necessarily accurate or complete.
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2,334,187 |
The cardiogenic niche as a fundamental building block of engineered myocardium.
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Cardiac muscle engineering is evolving rapidly, aiming at the provision of innovative models for drug development and therapeutic myocardium. The progress in this field will depend crucially on the proper exploitation of stem cell technologies. Understanding the processes governing stem cell differentiation towards a desired phenotype and subsequent maturation in an organotypic manner will be key to ultimately providing realistic tissue models or therapeutics. Cardiogenesis is controlled by milieu factors that collectively constitute a so-called cardiogenic niche. The components of the cardiogenic niche are not yet fully defined but include paracrine factors and instructive extracellular matrix. Both are provided by supportive stromal cells under strict spatial and temporal control. Detailed knowledge on the exact composition and functionality of the dynamic cardiogenic niche during development will likely be instrumental to further advance cardiac muscle engineering. This review will discuss the concept of myocardial tissue engineering from the stem cell/developmental biology perspective and put forward the hypothesis of the cardiogenic niche as a fundamental building block of tissue-engineered myocardium.
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2,334,188 |
MERRF and Kearns-Sayre overlap syndrome due to the mitochondrial DNA m.3291T>C mutation.
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A 48-year-old man presented with a complex phenotype of myoclonus epilepsy with ragged-red fibers (MERRF) syndrome and Kearns-Sayre syndrome (KSS), which included progressive myoclonus epilepsy, cerebellar ataxia, hearing loss, myopathic weakness, ophthalmoparesis, pigmentary retinopathy, bifascicular heart block, and ragged-red fibers. The m.3291T>C mutation in the tRNA(Leu(UUR)) gene was found with 92% heteroplasmy in muscle. This mutation has been reported with MELAS, myopathy, and deafness with cognitive impairment. This is the first description with a MERRF/KSS syndrome.
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2,334,189 |
Severe cardiovascular depression in a cat following a mandibular nerve block with bupivacaine.
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A 12 year old cat was presented for anaesthesia to remove a mandibular squamous cell carcinoma. After intramuscular premedication with dexmedetomidine and methadone, anaesthesia was induced with alfaxalone, administered intravenously (IV) to effect, and maintained with isoflurane vaporized in oxygen, following oro-tracheal intubation. Approximately 5 minutes after performing a mandibular nerve block with 1.16 mg kg(-1) of bupivacaine, the cat developed severe cardiovascular depression. Anaesthetic delivery was discontinued and cardiopulmonary resuscitation instituted. Drug administration consisted of atropine (0.02 mg kg(-1) IV, repeated three times), followed by atipamezole (0.08 mg kg(-1) IV). Dobutamine was subsequently administered (1 μg kg(-1) minute(-1) IV) until cardiovascular performance was considered satisfactory. During recovery from anaesthesia the cat exhibited seizure-like activity, which was controlled by a variable rate infusion of propofol. The cat made an uneventful recovery following discontinuation of propofol infusion, without residual neurological signs, and the surgical procedure was postponed.</AbstractText>This clinical report describes successful management of cardiovascular and neurological complications following a mandibular nerve block with bupivacaine in a cat. Although treatment was successful, the role played by the drugs administered during resuscitation remains uncertain.</AbstractText>© 2011 The Authors. Veterinary Anaesthesia and Analgesia. © 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.</CopyrightInformation>
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2,334,190 |
Greasing the wheels of managing overweight and obesity with omega-3 fatty acids.
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The epidemic of overweight and obesity around the world and in the US is a major public health challenge, with 1.5 billion overweight and obese adults worldwide, and 68% of US adults and 31% of US children and adolescents overweight or obese. Obesity leads to serious health consequences, including an increased risk of type 2 diabetes mellitus and heart disease. Current preventive and medical treatments include lifestyle modification, medication, and bariatric surgery in extreme cases; however, they are either not very efficacious or are very expensive. Obesity is a complex condition involving the dysregulation of several organ systems and molecular pathways, including adipose tissue, the pancreas, the gastrointestinal tract, and the CNS. The role of the CNS in obesity is receiving more attention as obesity rates rise and treatments continue to fail. While the role of the hypothalamus in regulation of appetite and food intake has long been recognized, the roles of the CNS reward systems are beginning to be examined as the role of environmental influences on energy balance are explored. Omega-3 polyunsaturated fatty acids are essential nutrients that play a beneficial role in several disease processes due to their anti-inflammatory effects, modulation of lipids, and effects on the CNS. Omega-3 fatty acids, specifically EPA and DHA, have shown promising preliminary results in animal and human studies in the prevention and treatment of obesity. Given their effects on many of the pathways involved in obesity, and specifically in the endocannabinoid and mesocorticolimbic pathways, we hypothesize that EPA and DHA supplementation in populations can reduce the reward associated with food, thereby reduce appetite and food intake, and ultimately contribute to the prevention or reduction of obesity. If these fatty acids do harbor such potential, their supplementation in many parts of the world may hold great promise in reducing the global burden of obesity.
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2,334,191 |
New kids on the block: the emerging role of apolipoproteins in the pathogenesis and treatment of asthma.
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New treatments are needed for patients with severe asthma. We hypothesized that a clinically relevant experimental model of house dust mite (HDM)-induced murine asthma could be used to discover new pathways that regulate disease severity. In HDM-challenged mice, genome-wide expression profiling of the asthmatic lung transcriptome identified apolipoprotein E (apoE) as a steroid-unresponsive gene with persistently upregulated expression despite dexamethasone treatment. ApoE and low-density lipoprotein receptor (LDLR) knockout mice were used to demonstrate that apoE, which is produced by lung macrophages, functions in a paracrine fashion by binding to LDLRs expressed on ciliated airway epithelial cells, to negatively modulate airway hyperreactivity, mucin gene expression, and goblet cell hyperplasia. Furthermore, administration of an apoE mimetic peptide, which corresponded to the LDLR-binding domain of apoE, prevented the induction of airway inflammation, airway hyperreactivity, and goblet cell hyperplasia in HDM-challenged apoE knockout mice. This suggests that therapeutic strategies that activate the apoE-LDLR pathway, such as apoE mimetic peptides, may represent a novel treatment approach for patients with asthma. Similarly, we showed that administration of a 5A apolipoprotein A-I mimetic peptide attenuated the induction of HDM-mediated asthma in mice. These preclinical data suggest that apoE and apoA-I mimetic peptides might be developed into alternative treatments for patients with severe asthma. Future clinical trials will be required to determine whether inhaled apolipoprotein E or apolipoprotein A-I mimetic peptides are effective for the treatment of severe asthma, including patients with phenotypes that lack effective therapeutic options.
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2,334,192 |
Effects of sitting up for five minutes versus immediately lying down after spinal anesthesia for Cesarean delivery on fluid and ephedrine requirement; a randomized trial.
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Patient position after spinal anesthesia has had variable effects on blood pressure and ephedrine requirements. The aim of this study was to determine the effects that sitting the patient up for five minutes after spinal anesthesia would have on intraoperative fluid and ephedrine requirements.</AbstractText>The study included 120 women at term gestation who were scheduled for Cesarean delivery under spinal anesthesia. After anesthetic administration, the women were randomized either to sit up for five minutes then lie down (Group S) or to lie down immediately (Group L) to a tilted supine position. A blinded observer recorded sensory block level, systolic blood pressure, heart rate, ephedrine and fluid requirements, adverse events, and time to motor recovery (modified Bromage score of 2).</AbstractText>Group S had a lower intraoperative sensory block height than Group L [T4 (1) vs T2 (1), respectively; P < 0.001]; Group S also required less ephedrine (8% vs 47%, respectively; P < 0.001), received less fluid [709 (59) mL vs 789 (90) mL, respectively; P < 0.001], and experienced less nausea and vomiting (5% vs 22%, respectively; P = 0.014) and shortness of breath (3% vs 28%, respectively; P < 0.001) intraoperatively. In Group S, the odds of requiring ephedrine were 0.09 compared with 0.89 in Group L (odds ratio 0.10). There were no differences in systolic blood pressure (P = 0.127) or heart rate (P = 0.831) over time between groups. Time to a modified Bromage score of 2 was longer in Group S than in Group L [101 (15) min vs 88 (14) min, respectively; P < 0.001].</AbstractText>Sitting the patient up for five minutes rather than laying the patient down immediately after spinal anesthesia for Cesarean delivery decreased intraoperative sensory block height, ephedrine and fluid requirements, and intraoperative nausea, vomiting, and shortness of breath without affecting systolic blood pressure or the success of the anesthetic. However, the method resulted in delayed postoperative motor recovery.</AbstractText>
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2,334,193 |
Single level paravertebral versus caudal block in paediatric inguinal surgery.
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Paravertebral block (PVB) has been used for postoperative analgesia in children since 1992. There are no prospective randomised studies comparing the use of PVB versus caudal block (CB) for outpatient inguinal hernia repair surgery. The hypothesis of this study is that a single level, single injection PVB can provide a longer duration of analgesia and less requirement for supplemental analgesia than single shot CB for children undergoing inguinal surgery. Seventy children, aged three to seven, American Society of Anesthesiologists score I to II, having unilateral inguinal surgery were enrolled in the study. The patients were divided into two randomised groups. In group PVB, a single shot of 0.2 ml/kg levobupivacaine was administered via the lumbar paravertebral route and in group CB, patients were given 1 ml/kg levobupivacaine caudally. Sevoflurane concentration was evaluated after induction and recorded during incision, sac traction and closure. Face, legs, activity, cry and consolability (FLACC) scores, heart rate, blood pressure and SpO2 were evaluated postoperatively. Only four (11.4%) patients in the PVB group needed rescue analgesic drugs compared to 12 (34.3%) patients in the CB group (P = 0.044). Patients were given tramadol as rescue analgesia in the first four postoperative hours. No other supplemental analgesic drug was given apart from tramadol. FLACC scores were the same in the both groups. Parental satisfaction was significantly higher in the PVB group compared to the CB group (74.3 vs 40%, P = 0.01). This study has demonstrated that a single level single injection paravertebral block provides superior intraoperative and postoperative analgesia when compared to a caudal block for unilateral inguinal hernia repair.
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2,334,194 |
Effect of cleistanthin A and B on adrenergic and cholinergic receptors.
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The aim was to study the in vitro and in silico interactions of cleistanthin A and B on the adrenergic and cholinergic receptors using isolated animal tissues and bioinformatics tools.</AbstractText>The alpha adrenergic receptor activities of cleistanthin A and B were studied in vitro using a guinea pig vas deferens preparation. The beta adrenergic receptor activities of cleistanthin A and B on an isolated rat heart were studied in vitro using a modified Langendorff apparatus. The effects of cleistanthin A and B on the nicotinic and muscarinic cholinergic receptors were studied in vitro using rabbit vas deferens and rabbit jejunum, respectively. All the drug responses were recorded using a data acquisition system through a variable force transducer. The receptor-ligand interactions of cleistanthin A and B with adrenergic and cholinergic receptor proteins were determined using the ArgusLab molecular modeling and drug docking program.</AbstractText>Cleistanthin A and B significantly inhibited the actions of the alpha adrenergic receptor and the nicotinic cholinergic receptor. Cleistanthin A and B shifted the dose-response curve to the right with an increased EC(50) value of phenylephrine and acetylcholine. Both cleistanthin A and B did not have any significant effect on the beta adrenergic and muscarinic cholinergic receptors.</AbstractText>Cleistanthin A and B block the alpha adrenergic and nicotinic cholinergic receptors, but these compounds do not interact at all with the beta adrenergic and muscarinic cholinergic receptors.</AbstractText>
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2,334,195 |
A human ventricular cell model for investigation of cardiac arrhythmias under hyperkalaemic conditions.
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In this study, several modifications were introduced to a recently proposed human ventricular action potential (AP) model so as to render it suitable for the study of ventricular arrhythmias. These modifications were driven by new sets of experimental data available from the literature and the analysis of several well-established cellular arrhythmic risk biomarkers, namely AP duration at 90 per cent repolarization (APD(90)), AP triangulation, calcium dynamics, restitution properties, APD(90) adaptation to abrupt heart rate changes, and rate dependence of intracellular sodium and calcium concentrations. The proposed methodology represents a novel framework for the development of cardiac cell models. Five stimulation protocols were applied to the original model and the ventricular AP model developed here to compute the described arrhythmic risk biomarkers. In addition, those models were tested in a one-dimensional fibre in which hyperkalaemia was simulated by increasing the extracellular potassium concentration, [K(+)](o). The effective refractory period (ERP), conduction velocity (CV) and the occurrence of APD alternans were investigated. Results show that modifications improved model behaviour as verified by: (i) AP triangulation well within experimental limits (the difference between APD at 50 and 90 per cent repolarization being 78.1 ms); (ii) APD(90) rate adaptation dynamics characterized by fast and slow time constants within physiological ranges (10.1 and 105.9 s); and (iii) maximum S1S2 restitution slope in accordance with experimental data (S(S1S2)=1.0). In simulated tissues under hyperkalaemic conditions, APD(90) progressively shortened with the degree of hyperkalaemia, whereas ERP increased once a threshold in [K(+)](o) was reached ([K(+)](o)≈6 mM). CV decreased with [K(+)](o), and conduction was blocked for [K(+)](o)>10.4 mM. APD(90) alternans were observed for [K(+)](o)>9.8 mM. Those results adequately reproduce experimental observations. This study demonstrated the value of basing the development of AP models on the computation of arrhythmic risk biomarkers, as opposed to joining together independently derived ion channel descriptions to produce a whole-cell AP model, with the new framework providing a better picture of the model performance under a variety of stimulation conditions. On top of replicating experimental data at single-cell level, the model developed here was able to predict the occurrence of APD(90) alternans and areas of conduction block associated with high [K(+)](o) in tissue, which is of relevance for the investigation of the arrhythmogenic substrate in ischaemic hearts.
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2,334,196 |
Proximity to food establishments and body mass index in the Framingham Heart Study offspring cohort over 30 years.
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Existing evidence linking residential proximity to food establishments with body mass index (BMI; weight (kg)/height (m)(2)) has been inconclusive. In this study, the authors assessed the relation between BMI and proximity to food establishments over a 30-year period among 3,113 subjects in the Framingham Heart Study Offspring Cohort living in 4 Massachusetts towns during 1971-2001. The authors used novel data that included repeated measures of BMI and accounted for residential mobility and the appearance and disappearance of food establishments. They calculated proximity to food establishments as the driving distance between each subject's residence and nearby food establishments, divided into 6 categories. The authors used cross-classified linear mixed models to account for time-varying attributes of individuals and residential neighborhoods. Each 1-km increase in distance to the closest fast-food restaurant was associated with a 0.11-unit decrease in BMI (95% credible interval: -0.20, -0.04). In sex-stratified analyses, this association was present only for women. Other aspects of the food environment were either inconsistently associated or not at all associated with BMI. Contrary to much prior research, the authors did not find a consistent relation between access to fast-food restaurants and individual BMI, necessitating a reevaluation of policy discussions on the anticipated impact of the food environment on weight gain.
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2,334,197 |
Unilateral stellate ganglion block produces bidirectional changes in tissue oxygen tension of the mental nerve in rabbits.
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The purpose of this study was to investigate changes in the tissue oxygen tension (PO(2)) of the mental nerve bilaterally before and after unilateral stellate ganglion block (SGB).</AbstractText>Nine male Japan white rabbits were used. Anesthesia was maintained by a continuous infusion of propofol under mechanical ventilation with room air. For the SGB, the tip of a 26-gauge needle was placed on the left transverse process of the cervical vertebra; 0.2 mL of 1% lidocaine solution was injected. Data were recorded immediately before SGB and when the maximal change in PO(2) after SGB was observed. Observed variables were heart rate, blood pressure, common carotid arterial blood flow, tongue mucosal blood flow, left PO(2), and right PO(2).</AbstractText>PO(2) showed maximal changes 7.9 ± 2.0 minutes after SGB. No changes were observed in heart rate and blood pressure after SGB. Common carotid arterial blood flow, tongue mucosal blood flow, and left PO(2) were increased by 106.4% ± 39.8%, 36.2% ± 35.2%, and 38.7% ± 19.8%, respectively, after SGB. In contrast, right PO(2) was decreased by 29.8% ± 7.4% after SGB.</AbstractText>These results suggest that unilateral SGB produces bidirectional changes in the PO(2) of the mental nerve and that SGB decreases the PO(2) of the mental nerve on the contralateral side.</AbstractText>Copyright © 2012 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.</CopyrightInformation>
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2,334,198 |
Epidural anesthesia and post-operative analgesia for bilateral inguinal mesh hernioplasty: Comparison of equipotent doses of ropivacaine and bupivacaine.
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Ropivacaine is a long-acting amide local anesthetic, which is structurally very similar to bupivacaine but produces less motor block and less cardiac and central nervous system toxicity. It is also about 40% less potent than bupivacaine. Our double blind study was designed to compare the clinical efficacy of the equipotent doses of ropivacaine 0.75% and bupivacaine 0.5% for epidural anesthesia and ropivacaine 0.2% and bupivacaine 0.125% for post-operative analgesia in patients undergoing bilateral mesh hernioplasty.</AbstractText>Sixty-one patients were randomized to receive 15 ml of 0.75% ropivacaine or 0.5% bupivacaine. Sensory and motor block characteristics were compared. Changes in heart rate, mean arterial blood pressure, and adverse effects were noted. For post-operative analgesia, 0.2% ropivacaine and 0.125% bupivacaine were given as continuous epidural infusion. Analgesia using VAS scores, motor block, volume of local anesthetic used and patient satisfaction was assessed.</AbstractText>There was no significant variation in the sensory block profile. A greater intensity of motor block was achieved with bupivacaine in the beginning but by 30 minutes the difference was not significant. Duration of motor block was similar in the two groups. Visual analog scale scores were similar in both groups during the post-operative period, with a similar motor block profile. No major side effects were noted in any group.</AbstractText>The equipotent doses of ropivacaine and bupivacaine provided good quality epidural anesthesia and post-operative analgesia.</AbstractText>
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2,334,199 |
The evaluation of upper leg traction in lateral position for pediatric caudal block.
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A well-functioning caudal block is an excellent adjunct to general anesthesia, but misplaced injection results in poor analgesia as well as possibility of serious morbidity. Therefore, the purpose of this study was to evaluate the effectiveness of leg traction on success rate of caudal block in lateral position in children.</AbstractText>Two hundred children, age 2 months to 6 years, ASA I and II, who underwent lower abdominal surgeries were randomized in prospective controlled clinical trial study in two groups. After induction of General anesthesia, the caudal block was performed in the lateral position with upper leg traction (L-T-) or with the standard position (S-P) (leg flexed 90°). Hemodynamicchanges, movement of lower extremity in response to surgical stimulus were evaluated.</AbstractText>There was no significant difference in caudal block's success rate between two groups at first attempt (P=0.25). In group (S-P) the procedure was successful in 60% of cases at first attempt, 25% at second,10% at third attempt and 5% failure of caudal block, whereas in the first group it was 75%, 20%, 1% and 4% of cases respectively. There were no significant differences in heart rate and blood pressure changes between two groups (P>0.05).</AbstractText>The success rate of pediatric caudal block in upper leg traction did not differ from that of the standard position.</AbstractText>
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