| |||
Blockers
Kinds of Blockers Terms modified by Blockers Selected AbstractsEFFECT OF COMBINATION THERAPY (ANG II ANTAGONIST, VALSARTAN AND A CALCIUM CHANNEL BLOCKER) IN A HYPERTENSIVE MODEL OF DIABETIC NEPHROPATHYNEPHROLOGY, Issue 3 2000Allen Tj Davis Bj [source] Protective Effect of HOE642, a Selective Blocker of Na+ -H+ Exchange, Against the Development of Rigor Contracture in Rat Ventricular MyocytesEXPERIMENTAL PHYSIOLOGY, Issue 1 2000Marisol Ruiz-Meana The objective of this study was to investigate the effect of Na+ -H+ exchange (NHE) and HCO3, -Na+ symport inhibition on the development of rigor contracture. Freshly isolated adult rat cardiomyocytes were subjected to 60 min metabolic inhibition (MI) and 5 min re-energization (Rx). The effects of perfusion of HCO3, or HCO3, -free buffer with or without the NHE inhibitor HOE642 (7 ,M) were investigated during MI and Rx. In HCO3, -free conditions, HOE642 reduced the percentage of cells developing rigor during MI from 79 ± 1% to 40 ± 4% (P < 0.001) without modifying the time at which rigor appeared. This resulted in a 30% reduction of hypercontracture during Rx (P < 0.01). The presence of HCO3, abolished the protective effect of HOE642 against rigor. Cells that had developed rigor underwent hypercontracture during Rx independently of treatment allocation. Ratiofluorescence measurement demonstrated that the rise in cytosolic Ca2+ (fura-2) occurred only after the onset of rigor, and was not influenced by HOE642. NHE inhibition did not modify Na+ rise (SBFI) during MI, but exaggerated the initial fall of intracellular pH (BCEFC). In conclusion, HOE642 has a protective effect against rigor during energy deprivation, but only when HCO3, -dependent transporters are inhibited. This effect is independent of changes in cytosolic Na+ or Ca2+ concentrations. [source] Angiotensin Receptor Blocker Use May Decrease the Incidence and Progression of Alzheimer's Disease and Dementia in Older Men but the Strength of the Evidence Is QuestionableJOURNAL OF CLINICAL HYPERTENSION, Issue 6 2010Michael J. Bloch MD First page of article [source] Can an Angiotensin Receptor Blocker Be Used in a Patient in Whom Angioedema Developed With an Angiotensin-Converting Enzyme Inhibitor?JOURNAL OF CLINICAL HYPERTENSION, Issue 12 2008Debbie L. Cohen MD No abstract is available for this article. [source] What Should the Physician Do When Creatinine Increases After Starting an Angiotensin-Converting Enzyme Inhibitor or an Angiotensin Receptor Blocker?JOURNAL OF CLINICAL HYPERTENSION, Issue 10 2008Debbie L. Cohen MD No abstract is available for this article. [source] N-type Calcium Channel Blocker for Pain TreatmentPAIN MEDICINE, Issue 2 2010Jianren Mao MD No abstract is available for this article. [source] Medizinische Chemie der ,1 -Blocker.PHARMAZIE IN UNSERER ZEIT (PHARMUZ), Issue 4 2008Bei Bluthochdruck nicht mehr erste Wahl Adrenerge ,1 -Rezeptor-Antagonisten mit Chinazolin- und Arylpiperazin-Grundstrukur wurden aufgrund ihrer vasodilatierenden Wirkungen in der Vergangenheit häufig als Antihypertensiva eingesetzt. Heute spielen sie in diesem Indikationsbereich nur mehr eine untergeordnete Bedeutung. In der glatten Muskulatur der Prostata und des Blasenhalses führt die Blockade der ,1 -Rezeptoren zu einer Steigerung des Urinflusses und zu einer Abnahme des Restharnvolumens, weshalb ,1 -Rezeptor-Antagonisten neben den 5,-Reduktasehemmern als Mittel der Wahl bei der Behandlung von Miktionsstörungen beim benignen Prostatasyndrom gelten. [source] Pharmakoökonomische Überlegungen zu Beta-Blockern: Wirtschaftliche Therapie-AspektePHARMAZIE IN UNSERER ZEIT (PHARMUZ), Issue 6 2004Björn Lemmer Prof. Dr. med Dr. h.c. Der GKV-Arzneimittelumsatz im Jahre 2002 betrug 22,7 Mrd. Euro, dabei war ein Anstieg von 6,5 % gegenüber dem Vorjahr festzustellen. Unter den 20 führenden Indikationsgruppen, die etwa 77 % der gesamten Verordnungen und 70 % des Umsatzvolumens ausmachen, lag an Stelle 2 die Gruppe der ,-Adrenozeptor-Antagonisten/Calcium-Kanal-Blocker/Angiotensin-Rezeptor-Antagonisten [1a]. Damit stellen diese kardiovaskulär wirksamen Pharmaka einen bedeutsamen Anteil an den Arzneimittelkosten dar. An dieser Stelle soll auf die Gruppe der ,-Adrenozeptor-Antagonisten (,-Blocker) näher eingegangen werden. [source] KC 12291: An Atypical Sodium Channel Blocker with Myocardial Antiischemic PropertiesCARDIOVASCULAR THERAPEUTICS, Issue 1 2004Gareth W. John ABSTRACT KC 12291 was designed as a voltage-gated sodium channel (VGSC) blocker with cardioprotective properties. KC 12291 has moderate inhibitory effects on peak (or rapid) Na+ current, and markedly reduces sustained (or slowly or non-inactivating) Na+ current. This distinguishes KC 12291 from conventional VGSC blockers such as local anesthetics or antiarrhythmics, which have little or no cardioprotective properties. Since VGSCs represent the main pathway for ischemic Na+ loading by failing to inactivate fully, KC 12291 exerts pronounced antiischemic activity principally by reducing the amplitude of sustained Na+ current. In isolated atria and Langendorff-perfused hearts, KC 12291 inhibits diastolic contracture, renowned for its resistance to pharmacological inhibition, reduces ischemic Na+ loading and preserves cardiac energy status. KC 12291 exerts oral antiischemic activity in vivo in the absence of major hemodynamic effects. Cardiac VGSC blockers such as KC 12291, which block cardiac VGSCs in atypical fashion by effectively inhibiting the sustained component of Na+ current, represent, therefore, promising potential antiischemic and cardioprotective drugs. [source] Clinical and Hemodynamic Effects of Nesiritide (B-Type Natriuretic Peptide) in Patients With Decompensated Heart Failure Receiving , BlockersCONGESTIVE HEART FAILURE, Issue 2 2005William T. Abraham MD The use of , blockers in congestive heart failure presents a therapeutic challenge for patients with acute episodes of decompensation. Such patients may be less responsive to positive inotropic agents, whereas the beneficial effects of nesiritide, which are not dependent on the ,-adrenergic receptor signal-transduction pathway, may be preserved. This analysis of the Vasodilation in the Management of Acute CHF trial evaluated the safety and efficacy of nesiritide in decompensated congestive heart failure patients receiving , blockers. The Vasodilation in the Management of Acute CHF trial was a multicenter, randomized, controlled evaluation of nesiritide in 489 hospitalized patients with decompensated congestive heart failure. One hundred twenty-three patients were on chronic ,-blocker therapy at enrollment (31 randomized to placebo, 50 to nesiritide, and 42 to nitroglycerin). Primary end points included pulmonary capillary wedge pressure and dyspnea evaluation at 3 hours. Patients receiving nesiritide, but not IV nitroglycerin, had significantly reduced pulmonary capillary wedge pressure vs. placebo at 3 hours regardless of ,-blocker use. The use of , blockers did not alter the beneficial effects of nesiritide on systemic blood pressure, heart rate, or dyspnea evaluation. In nesiritide-treated subjects, safety profiles were similar regardless of ,-blocker use. Thus, the clinical and hemodynamic benefits and safety of nesiritide are preserved in decompensated congestive heart failure patients receiving chronic , blockade. [source] Role of ß Blockers in Congestive Heart FailureCONGESTIVE HEART FAILURE, Issue 6 2000MPhil, Nazim Uddin Azam Khan MD Prolonged activation of the adrenergic nervous system has adverse consequences on the cardiovascular system in patients with congestive heart failure. , adrenergic receptor,blocker therapy modifies these deleterious effects. , blockers have been shown to improve myocardial function and survival when used in conjunction with conventional treatment with diuretics, angiotensinconverting enzyme inhibitors, and digoxin. , blocker therapy in mild-to-moderate heart failure should not be delayed because it causes some reversal of both neurohormonal compensatory mechanisms and the deletorious myocardial remodeling process. This paper reviews the beneficial effects of , adrenergic receptor-blocker therapy on the pathophysiology, symptoms, left ventricular function, morbidity, and mortality in patients with congestive heart failure. [source] Antiepileptic Effect of Gap-junction Blockers in a Rat Model of Refractory Focal Cortical EpilepsyEPILEPSIA, Issue 7 2006Karen E. Nilsen Summary:,Purpose: Epilepsy is the most common serious neurologic disease, and current treatments are ineffective for ,30% of patients. Gap junctions have been implicated in seizure generation and propagation, and as such, may represent a novel therapeutic target but have been little investigated in vivo. We set out to assess the efficacy and tolerability of gap-junction blockers delivered to the seizure focus in a well-characterized model of refractory cortical epilepsy in rats. Methods: A chronic epilepsy focus was induced in the cortex of rats by using tetanus toxin, and subsequent studies were conducted in freely moving unanesthetized animals with frequent spontaneous seizures, as we previously described. Carbenoxolone, meclofenamic acid, and saline were applied directly to the seizure focus. EEG, electromyogram (EMG), and behavioral parameters were measured for ,1 h before drug infusion and for ,3 h afterward. No ill effects were observed. Results: An immediate and marked reduction in percentage of seizure time was seen in rats receiving carbenoxolone (baseline, 69.4%± 7.0% (SEM); maximum effect, 9.3%± 3.5%, p ,0.001) and meclofenamic acid (baseline, 58.3%± 3.7%; maximum effect, 0.92%± 0.92%, p < 0.001). No effect was seen after saline infusion. Conclusions: Gap-junction blockers applied focally are effective at suppressing seizures and, as such, represent a potential new treatment for epilepsy. Development of focal treatment strategies is essential in this regard. [source] Mechanisms of ATP action on motor nerve terminals at the frog neuromuscular junctionEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2005S. Grishin Abstract We have shown previously that ATP inhibits transmitter release at the neuromuscular junction through the action on metabotropic P2Y receptors coupled to specific second messenger cascades. In the present study we recorded K+ or Ca2+ currents in motor nerve endings or blocked K+ or Ca2+ channels in order to explore the nature of downstream presynaptic effectors. Endplate currents were presynaptically depressed by ATP. Blockers of Ca2+ -activated K+ -channels, such as iberiotoxin, apamin or tetraethylammonium, did not change the depressant action of ATP. By contrast, K+ channel blocker 4-aminopyridine (4-AP) and raised extracellular Ca2+ attenuated the effect of ATP. However, these effects of 4-AP and high Ca2+ were reversed by Mg2+, suggesting Ca2+ -dependence of the ATP action. Ba2+ promoted the depressant action of ATP as did glibenclamide, a blocker of ATP-sensitive K+ channels, or mild depolarization produced by 7.5 mm K+. None of the K+ channel blockers affected the depressant action of adenosine. Focal recording revealed that neither ATP nor adenosine affected the fast K+ currents of the motor nerve endings. However, unlike adenosine, ATP or UTP, an agonist of P2Y receptors, reversibly reduced the presynaptic Ca2+ -current. This effect was abolished by suramin, an antagonist of P2 receptors. Depressant effect of ATP on the endplate and Ca2+ -currents was mimicked by arachidonate, which precluded the action of ATP. ATP reduced acetylcholine release triggered by ionomycin or sucrose, suggesting inhibition of release machinery. Thus, the presynaptic depressant action of ATP is mediated by inhibition of Ca2+ channels and by mechanism acting downstream of Ca2+ entry. [source] Enantioselective Synthesis of , -Blockers via Hydrolytic Kinetic Resolution of Terminal Oxiranes by Using Bimetallic Chiral {{2,2,-[Cyclohexane-1,2-diylbis(nitrilomethylidyne)]bis[phenolato]}(2,)}cobalt ([Co(salen)])-Type ComplexesHELVETICA CHIMICA ACTA, Issue 2 2008Rahul Abstract The synthesis of chirally pure , -blockers was successfully achieved via hydrolytic kinetic resolution of butyl (±)-4-(oxiran-2-ylmethoxy)benzeneacetate ((±)- 1) and (±)-4-(oxiran-2-ylmethoxy)benzeneacetonitrile ((±)- 2) in the presence of bimetallic chiral [Co(salen)]-type complexes. The newly synthesized bimetallic chiral [Co(salen)]-type complexes exhibited excellent enantioselectivities of up to >98% ee in good yields (Tables,1,3). [source] Addressing Gaps in Our Knowledge of the Angiotensin Receptor Blockers: Report of a RoundtableJOURNAL OF CLINICAL HYPERTENSION, Issue 2009Michael A. Weber MD Editor in Chief First page of article [source] ,-Blockers in Hypertension: Truths and Half-TruthsJOURNAL OF CLINICAL HYPERTENSION, Issue 7 2008C. Venkata S. Ram MD First page of article [source] A Cost-Effectiveness Analysis of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Diabetic NephropathyJOURNAL OF CLINICAL HYPERTENSION, Issue 10 2007Panagiotis C. Stafylas MD The aim of this study was to estimate the cost-effectiveness of renin-angiotensin-aldosterone system blockers in patients with diabetic nephropathy. A cost-effectiveness analysis was performed based on a meta-analysis of studies investigating the effect of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) as part of a treatment regimen on the incidence of end-stage renal disease (ESRD) in patients with diabetic nephropathy. The primary outcome was the cost to prevent 1 patient from developing ESRD. Cost analysis was performed from a third-party payer perspective in 2006 US dollars. As part of a treatment regimen, ARBs significantly reduced the incidence of ESRD and doubling of serum creatinine concentration (P<.05) but not total mortality. The cost to prevent 1 patient from developing ESRD was $31,729 (95% confidence interval, $19,443,$85,442; P<.01), $189,190 (P=.13) and $51,585 (P=.068) for patients receiving ARBs, ACE inhibitors, or either of them, respectively. This study demonstrates that blocking the RAAS, which delays the progression to ESRD, appears to be cost-effective. The current analysis favors ARBs in terms of cost-effectiveness. [source] Pharmacologic and Therapeutic Considerations in Hypertension Therapy With Calcium Channel Blockers: Focus on VerapamilJOURNAL OF CLINICAL HYPERTENSION, Issue 2 2007Domenic A. Sica MD In the past 2 decades, calcium channel blockers have emerged as important and useful agents for treating hypertension. The safety of this drug class has been vigorously debated for some time, and it has only been in the past few years that such debate has been quieted by favorable outcomes data with these compounds. Calcium channel blockers are a heterogeneous group of compounds as alike as they are dissimilar. Calcium channel blockers can be separated into dihydropyridine and nondihydropyridine subclasses, with representatives of the latter being verapamil and diltiazem. A lengthy treatment experience exists for verapamil, a compound that has progressed from an immediate-release to a sustained-release and, more recently, a delayed/sustained-release formulation designated for administration at bedtime. This latter formulation synchronizes drug delivery with the early morning rise in blood pressure, which is a particularly attractive feature when viewed in the context of the distinctive pharmacokinetic and pharmacodynamic features of verapamil. [source] Pharmacotherapy Review: Calcium Channel BlockersJOURNAL OF CLINICAL HYPERTENSION, Issue 1 2006Domenic A. Sica MD As a drug class, calcium channel blockers encompass a heterogeneous group of compounds with distinctive structures and pharmacologic characteristics. These agents are widely used in the treatment of hypertension, chronic coronary ischemia, and/or supraventricular arrhythmias. Much of the early debate alluding to increased cardiovascular risk associated with calcium channel blocker use has been silenced by an array of outcomes trials that show these drugs to be both safe and effective in reducing hard cardiovascular end points. The most common side effects associated with calcium channel blockers are vasodilatory in nature and include a non-volume-dependent form of peripheral edema, flushing, and headache. Despite the sometimes discomforting side effects seen with calcium channel blocker therapy, their robust blood pressure-lowering effect makes them an important component of most multidrug regimens used for blood pressure control. [source] Systolic Hypertension; a Blockers and Prostatism; Are , Blockers Still Indicated; Diabetes, Obesity, and Hypertension,Comments on the JCH ContentsJOURNAL OF CLINICAL HYPERTENSION, Issue 4 2001Marvin Moser MD Editor in Chief No abstract is available for this article. [source] Ophthalmically Administered , Blockers and Their Cardiopulmonary EffectsJOURNAL OF CLINICAL HYPERTENSION, Issue 3 2001Domenic A. Sica MD Early clinical studies revealed that timolol and other topical , blockers were effective in reducing intra-ocular pressure, without the side effects associated with other antiglaucoma agents. However, because persons with cardiovascular or respiratory diseases were generally excluded from many of these early studies, the risk of serious cardiovascular and respiratory side effects was seriously underestimated. Once these drugs were made available to the general population, reports of systemic side effects began to proliferate. Very quickly, adverse effects from topical , blockade became "old news." Despite this recognition, many treating physicians remained unaware of the potential for systemic , blockade from topically applied , blockers. A significant portion of a topically administered dose of a , blocker can be absorbed and thereby affect systemic , blockade. Sensitivity to systemic , blockade can be quite dramatic in certain highly susceptible patients, particularly those with either cardiac or pulmonary abnormalities. Careful review of patients' medications will generally lessen, but not completely eliminate, the risk of undesired complications attributable to topical P blockade. [source] Inhibition of neural activity depletes orexin from rat hypothalamic slice cultureJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2010Shotaro Michinaga Abstract Orexins (hypocretins) are neuropeptides produced by a small population of hypothalamic neurons whose dysregulation may lead to narcolepsy, a neurological disorder characterized by disorganization of sleep and wakefulness. Excessive stimulation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors causes preferential loss of orexin neurons in the hypothalamus, whereas an adequate level of neuronal excitatory activities is generally known to be important for the maintenance of central neurons. By examining the effect of manipulation of neural activity, we found that 24,72 hr application of tetrodotoxin (TTX) caused a substantial decrease in the number of orexin-immunoreactive neurons, but not of melanin-concentrating hormone-immunoreactive neurons, in hypothalamic slice culture. Similar results were obtained when neural activity was arrested by added extracellular Mg2+. Reduction of orexin expression by TTX and Mg2+ was also observed at mRNA level. The decrease of orexin-immunoreactive neurons was attributable to depletion of orexin, because it was reversible after washout of TTX or elevated extracellular Mg2+ and was not associated with induction of cell death. Blockers of voltage-dependent Ca2+ channels as well as of NMDA receptors also induced a significant and selective decrease of orexin-immunoreactive neurons. Moreover, TTX-induced decrease of orexin immunoreactivity was largely abrogated by concurrent application of a moderate concentration of NMDA. These results suggest that Ca2+ entry associated with nontoxic levels of spontaneous activity of glutamatergic inputs plays an important role in the maintenance of orexin neurons in a tissue culture model. © 2009 Wiley-Liss, Inc. [source] Review article: anti-fibrotic agents for the treatment of Crohn's disease , lessons learnt from other diseasesALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2010H. SZABÒ Summary Background, The current therapies for Crohn's disease (CD) are mainly focused on blockade of inflammation. Fibrosis remains one of the major complications of CD often leading to surgery, affecting patients' quality-of-life. Aim, To summarize the published data regarding the potential anti-fibrotic role of drugs commonly used in CD and the most effective anti-fibrotic drugs used in other diseases evaluating their potential use to treat intestinal fibrosis in CD. Methods, A literature search was performed in the PubMed, Medline, Cochrane and EMBASE databases, considering in vitro, animal and human studies on fibrosis in inflammatory bowel disease and other similar chronic pathologies. Results, Treatment of fibrosis in CD is limited to surgery or endoscopic dilatation, although some of the drugs currently used may have anti-fibrotic activity. In other diseases, anti-fibrotic agents are already used or are in preclinical or clinical trials. ACE inhibitors, Angiotensin Receptor Blockers, and HMG-CoA inhibitors merit further investigation in CD because of their role in preventing fibrosis in cardiovascular and renal diseases. Conclusions, Anti-fibrotic drugs are under evaluation or already used in clinical practice in other chronic inflammatory diseases. In CD, there is a great need for investigation into agents that may prevent, reduce or reverse intestinal fibrosis. Aliment Pharmacol Ther,31, 189,201 [source] ,-Blockers protect against spontaneous bacterial peritonitis in cirrhotic patients: a meta-analysisLIVER INTERNATIONAL, Issue 8 2009Marco Senzolo Abstract Introduction: Bacterial infections have been hypothetized to be a trigger of variceal bleeding in cirrhotic patients and ,-blockers may have a protective effect by decreasing bacterial translocation, reducing portal pressure. The aim of our study was to evaluate the possible role of ,-blockers in preventing spontaneous bacterial peritonitis (SBP) in patients with liver cirrhosis and ascites. Materials and Methods: Extensive search of the literature including randomized controlled trial (RCT) and non-RCT of primary and secondary prophylaxis for variceal bleeding in cirrhotics using ,-blockers were evaluated. We performed a meta-analysis using the occurrence of SBP as endpoint in all the studies, using the random effect model. Results: Three RCT and three retrospective studies in which ,-blockers were evaluated against no treatment for the prevention of SBP in ascitic cirrhotics were included. There was a statistically significant difference of 12.1%, P<0.001 in favour of propranolol in preventing SBP, which was confirmed by sensitivity analysis evaluating only RCTs (7.8% difference). The effect was still present when haemodynamic responders were compared with non-responders. Conclusions: This analysis suggests a role of ,-blockers in preventing SBP in ascitic cirrhotics, independent of haemodynamic response. Further formal RCTs are needed to confirm this finding. [source] Conversion to Silodosin in Men on Conventional ,1 -Blockers for Symptomatic Benign Prostatic HyperplasiaLUTS, Issue 1 2010Masahiko TANAKA Objectives:,1 -blockers have commonly been used as first-line medical therapy for symptomatic benign prostatic hyperplasia (BPH). Recently, a highly selective ,1A -adrenoceptor antagonist, silodosin, was developed in Japan. We examined the efficacy and safety of conversion from conventional ,1 -blockers to silodosin in men with BPH. Methods: Conversion to silodosin was proposed to consecutive patients on conventional ,1 -blockers for symptomatic BPH for at least 6 months. The effects of conversion were examined by the International Prostate Symptom Score, quality of life index, overactive bladder symptom score, peak flow rate, residual urine volume, and adverse events at 12 weeks. The efficacy of silodosin was also evaluated by patients' impression. Results: Eighty-one men underwent conversion, for the most part because of dissatisfaction with the efficacy of their current treatment in improving nocturia or weak stream. The International Prostate Symptom Score total score significantly improved from 12.7 ± 5.9 at baseline to 10.6 ± 5.4 at 4 weeks (P < 0.001) and 10.9 ± 5.8 at 12 weeks (P < 0.01). The progress was mostly due to improvement in voiding symptoms, although reduction of storage symptoms was also significant. The quality of life index also significantly decreased with conversion to silodosin. Efficacy as judged by patients' impression was 76% (37/49) at 12 weeks of treatment. None of the overactive bladder symptom score, peak flow rate, and residual urine volume exhibited significant change. No serious adverse events were observed during the study period. Conclusion: Conversion to silodosin may be beneficial in men who are dissatisfied with conventional ,1 -blockers for BPH, and be particularly useful in improving voiding symptoms. [source] Topical Application of Calcium Channel Blockers to Reduce the Progression of Experimentally Induced Myringosclerosis and TympanosclerosisTHE LARYNGOSCOPE, Issue 4 2008Adin Selcuk MD Abstract Objectives: This study aimed to evaluate the ability of topically applied calcium channel blockers (diltiazem) to reduce the progression of experimentally induced myringosclerosis and tympanosclerosis. Study Design: Animal model. Experimental prospective study. Methods: The study included 25 adult albino guinea pigs that were bilaterally myringotomized and inoculated with a suspension of Streptococcus pneumonia type 3. The right ears were treated with topical application of diltiazem, and the untreated left ears served as the control group. Otomicroscopy and remyringotomy were conducted every week. One animal was sacrificed after 1 week and the remaining at the end of 6 weeks. Temporal bones were dissected, and tympanic bullae were analyzed with light microscopy. Results: The untreated control ears showed evidence of extensive myringosclerosis on otomicroscopy, and the ears treated with calcium channel blockers did as well although to a lesser degree. Under light microscopy, the lamina propria of both tympanic membranes and middle ear mucosae of the control group exhibited thicker (P < .1 and P < .05, respectively) and larger (P < .01 and P < .01, respectively) sclerotic tissue in comparison with the treatment group. Conclusion: The results suggest that calcium channel blockers had an influence in the prevention of tympanosclerosis. [source] GP IIb-IIIa Receptor Blockers Minimize Vascular and Perivascular Damage in the Hippocampus after Cardiopulmonary Bypass ManagementANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 2005S. Arnhold Brain injury remains a significant and potentially devastating outcome of cardiopulmonary bypass (CPB) under circulatory arrest. These outcomes caused by a microvasculature embolization are associated with increased mortality, longer hospital stays and increased use of intermediate or long term care facilities. The administration of heparin in heart surgery during deep hypothermic cardiopulmonary bypass is the basic prophylactic strategy for reducing or even preventing, microvasculature embolization. Unfortunately, an incidence of neuropsychological impairments (NPI) is found in as many as 25 % of the survivors. As it is suspected that these impairments are correlated with morphological alterations, in our study we use the GP IIb-IIIa receptor blocker Eptifibatide for the inhibition of platelet aggregation, in order to look for a reduction of tissue damage compared to the standard treatment. Two groups of 11 piglets (mean body weight of 15±5 kg) underwent 10-minute normothermic bypass, 40-minute cooling on cardiopulmonary bypass, 60-minutes deep hypothermic circulatory arrest (DHCA) at 15°C, and 40-minute rewarming to 37°C. Group 1 was treated only with unfractionated heparin (UFH), whereas Group 2 was medicated with Eptifibatide, in addition to the UFH-treatment group 1. After rewarming, all animals underwent bilateral carotid perfusion with 4% paraformaldehyde. Histological investigations of semi thin sections reveal a marked decrease of hippocampal alterations by using the GP IIb-IIIa receptor blocker in addition to standard UFH treatment. We detect a reduction of degenerative areas in perivascular (vessels with 10,30 ,m in diameter) tissue. These semi-quantitative data are confirmed by ultrastructural findings. [source] ,-Blockers masking catecholamine release in ischemic stroke,ANNALS OF NEUROLOGY, Issue 3 2009Weekitt Kittisupamongkol MD No abstract is available for this article. [source] Sodium Channel Blockers Enhance the Temporal QT Interval Variability in the Right Precordial Leads in Brugada SyndromeANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 1 2008Tetsuzou Kanemori M.D. Background: Temporal QT interval variability is associated with sudden cardiac death. The purpose of this study was to evaluate temporal QT interval variability in Brugada syndrome (BS). Methods: We measured QT and RR intervals in precordial leads (V1,V6) based on 12-beat resting ECG recordings from 16 BS patients (B group) with spontaneous ST elevation in right precordial leads (V1,V2) and from 10 patients with normal hearts (C group). We measured the response in B group before and after administration of pilsicainide (1 mg/kg). The standard deviation (QT-SD, RR-SD) of the time domain and total frequency power (QT-TP, RR-TP) were calculated for all precordial leads, and the latter was to analyze the frequency domain. Results: The right precordial leads in BS exhibited an additional and prominent ST elevation (coved-type) after pilsicainide administration. Both QT-SD and QT-TP values were significantly more increased in B, than in C (5.1 ± 1.2 vs 3.6 ± 0.2 and 23.4 ± 2.9 vs 12.3 ± 1.7 msec2, P < 0.01, respectively) and after pilsicainide administration in B. (5.1 ± 0.4 vs 3.9 ± 0.3, 25.8 ± 3.4 vs 16.3 ± 2.6 msec2, P < 0.01, respectively) However, QT-SD and QT-TP did not significantly change in any of other leads (V3,V6) and RR-SD and RR-TP were similar for both groups, as well as after intravenous pilsicainide administration in B. Conclusions: The temporal QT interval variability was identified in BS. Moreover, sodium channel blocker induced temporal fluctuation in QT interval and it may possibly provide a substrate for ventricular arrhythmia in BS patients. [source] Indoloquinolizidine Derivatives as Novel and Potent Apoptosis Inducers and Cell-Cycle BlockersCHEMBIOCHEM, Issue 3 2008Frank Wehner Prof. Abstract A collection of approximately 11,000 natural-product derived and inspired compounds was screened for potential apoptosis inducers in the human tumour cell lines HepG2 (liver), HeLa (cervix) and MCF-7 (breast) by means of MTT and ATP-luminescence assays, automated cell counting, caspase 3/7 assay as well as by fluorescence activated cell sorting (FACS) analysis. A group of seven indoloquinolizidine derivatives was identified that exhibited IC50 values for cell proliferation as low as 2 ,mol,L,1, with no major necrosis of cells detectable. At the same time, an increase in the rate of apoptosis of up to 600,% relative to the reference level was observed. FACS analysis indicated that these effects are related to an arrest of cells in the G2M phase of the cell cycle. [source] |