Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002962 (angina)
 21,142 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Propranolol, available commercially as a racemic mixture, is a non-selective beta-adrenergic blocking agent used in the treatment of hypertension, angina pectoris and cardiac arrhythmias. We have developed and validated an RP-HPLC assay method for direct determination of R-(+)- and S-(-)-propranolol glucuronide in rat hepatic microsomes to investigate the enantioselectivity of propranolol glucuronidation metabolism. A baseline separation of propranolol glucuronide enantiomers was achieved on a 5 microm reversed-phase ODS column, with a mixture of phosphate buffer (pH 3.5, 0.067 mol/L) and methanol (55:45, v/v) as mobile phase. Ultraviolet detection was set at 220 nm, and p-nitrobenzoic acid was used as internal standard. The standard curve of assay for R-(+)- and S-(-)-propranolol glucuronide in spiked microsomal incubate showed good linearity throughout the concentration range from 0.50 to 20.0 micromol/L. The analytical method affords average recovery of 99.8 and 100.1% for R-(+)- and S-(-)-propranolol glucuronide, respectively. The method provides a high sensitivity and good precision for R-(+)- and S-(-)-propranolol glucuronide (RSD < 10%). The LOD was 0.15 micromol/L and the LOQ was 0.5 micromol/L (RSD < 8%, n = 5) for both R-(+)- and S-(-)-propranolol glucuronide. The method is simple, precise and accurate, and is suitable for quantifying the propranolol glucuronides enantiomers in rat hepatic microsomes.
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PMID:Direct determination of S-(-)- and R-(+)-propranolol glucuronide in rat hepatic microsomes by RP-HPLC. 1538 72

Cyclic nucleotides are important secondary messengers that control many physiologic processes, including smooth muscle contractility. Phosphodiesterases (PDEs) comprise of a superfamily of metallophosphydrolases that specifically cleave the 3',5'-cyclic phosphate moiety of cAMP and/or cGMP to produce the corresponding 5' nucleotide. Currently 21 PDE genes have been cloned and are classified into 11 families (1-11) according to their sequence of homology, biochemical and pharmacological properties. Phosphodiesterase type 5 (PDE5) is one of the members of the superfamily that specifically cleaves cyclic guanosine monophosphate (cGMP), a key intracellular secondary messenger. It is composed of 875 amino acids and was first identified in lungs, vascular and tracheal smooth muscle, and platelets. PDE5 is selectively inhibited by sildenafil, vardenafil and tadalafil, and less selectively by zaprinast and dipyridamole. PDE5 inhibitors have been reported to possess antiplatelet aggregation, weak cardiac inotropic effects and vascular relaxant properties. The tissue distribution of the PDE5 family is relatively restricted compared with other PDEs. Still, recent immunohistochemical and reverse transcriptase-polymerase chain reaction analysis have demonstrated the presence of anti-PDE5 antibodies and PDE5 transcripts in rat cerebellum, kidney, pancreas, aortic smooth muscle cells, heart, placenta, skeletal muscle, and, to a much lesser extent, in other regions of the brain, liver and lungs. Research in this field is intense, with a goal of identifying and developing new, selective PDE5 inhibitors that would be beneficial in a number of maladies, as well as angina, hypertension and erectile dysfunction (ED).
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PMID:Phosphodiesterase 5 enzyme and its inhibitors: update on pharmacological and therapeutical aspects. 1567 22

This article describes the relationship between CVD and CKD, the current state of knowledge regarding medical interventions, and underscores the importance of attending to both CVD and kidney disease aspects in each individual. The burden of cardiac disease in CKD patients is high with severe LVH, dilated cardiomyopathy and coronary artery disease occurring frequently. This predisposes to congestive heart failure, angina, myocardial infarction, and death. Multiple risk factors for cardiac disease exist and include hypertension, diabetes, smoking, anemia, abnormal calcium and phosphate metabolism, inflammation, and LVH. The efficacy of risk factor intervention has not been established in these populations, although there is good evidence for good blood pressure control, partial correction of anemia, treatment of dyslipidemia, cessation of tobacco use, correction of divalent abnormalities, and aspirin us. Appropriate use of ACE inhibitors, beta-blockers, and statins should be encouraged.
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PMID:Multiple risk factor intervention in chronic kidney disease: management of cardiac disease in chronic kidney disease patients. 1575 65

A 60-year-old Japanese man with myelodysplastic syndrome (MDS) and effort angina was referred to our clinic for treatment of MDS. The patient was transfusion-dependent and displayed coronary artery disease (CAD) with 99% obstruction of the left anterior descending coronary artery. Treatment comprised reduced-intensity hematopoietic stem cell transplantation with administration of fludarabine phosphate (180 mg/m(2)) and busulfan (8 mg/kg), followed by allogeneic peripheral blood stem cell transplantation from an HLA-matched sister. The regimen was well tolerated, and engraftment occurred rapidly without any therapy-related complications, including cardiovascular attack. Sex chromosome analysis by fluorescence in situ hybridization revealed complete donor chimerism on day 29 for bone marrow cells and on day 59 for peripheral blood leukocytes. The patient became transfusion-independent on posttransplantation day 8. As of 22 months postoperatively, he remains well, with 100% Karnofsky performance status, a limited type of chronic graft-versus-host disease, and no recurrence of disease. The clinical course of the patient suggests that this preparative regimen allows safe allogeneic stem cell transplantation for MDS patients with severe CAD.
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PMID:Successful reduced-intensity hematopoietic stem cell transplantation in myelodysplastic syndrome with severe coronary artery disease. 1651 35

Cardiac syndrome X (CSX), defined as typical exertional chest pain, a positive response to stress testing, and normal coronary arteriograms, encompasses different pathogenic subgroups. Both cardiac and non-cardiac mechanisms have been suggested to play a pathogenic role, and it has been shown that the syndrome is associated with myocardial ischaemia in at least a proportion of patients. Radionuclide myocardial perfusion defects, coronary sinus oxygen saturation abnormalities and pH changes, myocardial lactate production and stress-induced alterations of cardiac high energy phosphate have been reported in CSX patients, suggesting an ischaemic origin for their symptoms. Microvascular abnormalities often caused by endothelial dysfunction appear to be responsible for myocardial ischaemia in these patients. CSX is more prevalent in women than in men, and the majority of women with CSX are peri- or post-menopausal. Thus oestrogen deficiency has been suggested to have a pathogenic role in CSX. Additional factors such as abnormal pain perception may also contribute to the genesis of chest pain in patients with angina and normal coronary angiograms. The management of this syndrome is difficult because of the heterogeneity of pathogenic mechanisms and uncertainties as to its origin. This article discusses the problem of CSX in women, the potential pathogenic role of oestrogen deficiency, and practical clinical management.
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PMID:Cardiac syndrome X in women: the role of oestrogen deficiency. 1661 66

The present research work was aimed at development and optimization of alginate mucoadhesive microspheres of carvedilol for nasal delivery to avoid first pass metabolism and to improve the therapeutic efficacy in the treatment of hypertension and angina pectoris. The microspheres were prepared by a water-in-oil (w/o) emulsification technique. A 2(3) factorial design was employed with drug : polymer ratio, calcium chloride concentration and cross-linking time as independent variables while particle size of the microspheres and in vitro mucoadhesion were the dependent variables. Regression analysis was performed to identify the best formulation conditions. Particle size was analysed by dynamic laser light diffraction technique and found to be in the range of 26.36-54.32 microm, which is favourable for intranasal absorption. The shape and surface characteristics were determined by scanning electron microscopy (SEM) which depicted the spherical nature and nearly smooth surfaces of the microspheres. The percentage encapsulation efficiency was found to be in the range between 36.62-56.18. In vitro mucoadhesion was performed by adhesion number using sheep nasal mucosa and was observed in a range from 69.25-85.28. Differential scanning calorimetry and X-ray diffraction results indicated a molecular level dispersion of carvedilol in the microspheres. In vitro release studies in pH 6.2 phosphate buffer indicated non-Fickian or anomalous type of transport for the release of carvedilol from the microspheres.
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PMID:Development, optimization and in vitro evaluation of alginate mucoadhesive microspheres of carvedilol for nasal delivery. 1893 60

Fifty patients with stable angina who had undergone elective coronary angioplasty with stenting were examined. Myocardial microlesions diagnosed from the elevated levels of troponin (Tn) I and creatine phosphate kinase MB (CPK-MB) were detected in 48-54% of the patients; however, the content of Tn I exceeded the high reference level only in 18%. Tn I is a more specific method than CPK-MB in detecting myocardial microlesions during intracoronary intervention. The signs of myocardial microlesions were most commonly detected during intervention into the arteries with types B and C stenoses in case of complicated or technically difficult stent implantation.
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PMID:[Laboratory diagnosis of myocardial microlesions during coronary balloon angioplasty with stenting]. 2150 81

Effects of azelnidipine were examined and compared with those of amlodipine on stunned myocardium in dogs. The left anterior descending (LAD) coronary artery was ligated for 20 min and subsequently released for 60 min. A vehicle, azelnidipine (0.3 mg/kg), or amlodipine (0.3 or 1 mg/kg) was injected intravenously 20 min before LAD ligation. The heart rate increased after a depressor response in the presence of amlodipine, while it decreased despite a decrease in arterial pressures in the presence of azelnidipine. After reperfusion, the coronary flow (CF) significantly increased in the presence of azelnidipine, but did not change with amlodipine after reperfusion. A positive inotropic effect was observed after treatment with both calcium antagonists. Ischemia significantly decreased the percentage of segment shortening (%SS) in all groups. Treatment with both calcium antagonists significantly increased %SS after reperfusion, although high-energy phosphate levels did not improve in the presence of calcium antagonists 60 min after reperfusion. Mortality with azelnidipine was significantly lower than that with 0.3 mg/kg amlodipine immediately after reperfusion. In conclusion, improvement in myocardial stunning after pretreatment with azelnidipine is associated with an increase in CF after reperfusion. The negative chronotropic action may have contributed to decreased mortality due to reperfusion arrhythmias. Azelnidipine is more beneficial than amlodipine and may provide an additional advantage to patients with angina and hypertension.
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PMID:Comparative effects of azelnidipine and amlodipine on myocardial function and mortality after ischemia/reperfusion in dogs. 2159 38

Nicorandil is an original vasodilatator used to control angina by decreasing cardiac preload and afterload. Since 1997, many reports of single or multiple nicorandil-induced ulcerations have been published. To date, eight cases of nicorandil-induced fistula into adjacent organs have been described. The pathogeneses of nicorandil-induced ulceration and fistula into adjacent organs are not yet elucidated. The two main hepatic biotransformation pathways of nicorandil are denitration and reduction of the alkyl chain leading to nicotinamide and niconitic acid which merge into the endogenous pool of nicotinamide adenine dinucleotide/phosphate. This merging which is known as saturable, may contribute to a slow and abnormal distribution of nicotinamide and nicotinic acid out of the endogenous pool. Under these special conditions, providing these two molecules in situ, nicotinic acid associated with nicotinamide may ulcerate rather recent or maintained trauma. Ulcers and fistulae induced by nicorandil heal after withdrawal. Surgical intervention is unnecessary and inappropriate as it is ineffective and exacerbates morbidity. All practitioners should be correctly informed about these serious but preventable nicorandil side effects, which mostly occur in the elderly and fragile population. In the absence of corrective measures, withdrawal of this original and active drug should be considered.
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PMID:Nicorandil: from ulcer to fistula into adjacent organs. 2245 80

Perhexiline is a potent anti-anginal drug used for treatment of refractory angina and other forms of heart disease. It provides an oxygen sparing effect in the myocardium by creating a switch from fatty acid to glucose metabolism through partial inhibition of carnitine palmitoyltransferase 1 and 2. However, the precise molecular mechanisms underlying the cardioprotective effects elicited by perhexiline are not fully understood. The present study employed a combined proteomics, metabolomics and computational approach to characterise changes in murine hearts upon treatment with perhexiline. According to results based on difference in-gel electrophoresis, the most profound change in the cardiac proteome related to the activation of the pyruvate dehydrogenase complex. Metabolomic analysis by high-resolution nuclear magnetic resonance spectroscopy showed lower levels of total creatine and taurine in hearts of perhexiline-treated mice. Creatine and taurine levels were also significantly correlated in a cross-correlation analysis of all metabolites. Computational modelling suggested that far from inducing a simple shift from fatty acid to glucose oxidation, perhexiline may cause complex rebalancing of carbon and nucleotide phosphate fluxes, fuelled by increased lactate and amino acid uptake, to increase metabolic flexibility and to maintain cardiac output. This article is part of a Special Issue entitled "Focus on Cardiac Metabolism".
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PMID:Effects of perhexiline-induced fuel switch on the cardiac proteome and metabolome. 2327 91


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