Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The American Heart Association meeting reported the results of several clinical trials of particular interest to those who care for patients with heart failure. Omega-3 fatty acids were associated with a trend to increased recurrence of ventricular arrhythmias but not mortality in patients with an implantable debrillator. The ACTIV in CHF study provides more evidence of a therapeutic role for arginine vasopressin antagonists in the treatment of heart failure. The VALIANT study provides further evidence to suggest that a combination of angiotensin receptor antagonist and ACE inhibitor does not reduce mortality but may reduce morbidity in post-MI patients with heart failure or major LV systolic dysfunction. A study of autologous bone marrow cell transplantation into myocardial scar give gave encouraging results. SPORTIF V showed ximelagation to be as effective as warfarin but with improved safety. ORBIT and PAD showed public access defibrillators saved lives but questioned their cost effectiveness. DEFINITE supported a role for ICDs in patients with non-ischemic cardiomyopathy, although cost-effectiveness remains in doubt.
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PMID:Clinical trials update from the American Heart Association meeting: Omega-3 fatty acids and arrhythmia risk in patients with an implantable defibrillator, ACTIV in CHF, VALIANT, the Hanover autologous bone marrow transplantation study, SPORTIF V, ORBIT and PAD and DEFINITE. 1501 26

PAD has been overlooked in many epidemiologic studies evaluating cardiovascular risk associated with renal disease. Conversely, CKD has not been evaluated as a potential risk factor in epidemiologic studies of PAD. PAD, however,seems to be more prevalent among patients with even moderate CKD than in the general population and is most common among chronic dialysis patients, one third or more of whom have a low ABI. Patients with CKD also seem to be at increased risk for developing claudication and for requiring surgical intervention for lower extremity PAD. Furthermore, even moderate CKD seems to be a risk factor for postoperative death and complications after both lower extremity amputation and revascularization procedures. Conversely, even asymptomatic PAD seems to be a risk factor for death among dialysis patients. In the general population, statins, antiplatelet agents (particularly clopidogrel), antihypertensive agents, and ACE inhibitors all have a proven benefit in reducing cardiovascular events in patients with PAD and in some instances may also reduce PAD events. Available evidence suggests that patients with CKD also experience cardio-vascular risk reduction with statin and ACE-inhibitor therapy, but these therapies have not been shown to reduce PAD events specifically in patients with CKD. Further studies are needed to identify interventions that can specifically reduce the incidence of PAD complications in patientswith CKD. Although it is clear that mortality and complication rates after both lower extremity amputation and revascularization are increased in patients with even moderate CKD, currently available observational studies do not provide clear guidance for surgical decision making in CKD patients with limb-threatening ischemia. Further studies are needed to evaluate the risksand benefits of amputation over revascularizationamong patients with CKD and to investigatereasons for the high mortality associated with these procedures in this patient group. Further studies are also needed to measure the impact of CKD on care processes for PAD with the goal of identifying target areas for improvement.
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PMID:Management of peripheral arterial disease in chronic kidney disease. 1608 74

Dramatic progresses have occurred during the past 10 years in the field of cardiovascular secondary prevention. Many randomized trials have established the efficacy of statins, antiplatelet agents, beta-blockers and ACE inhibitors for reducing cardiovascular mortality, myocardial infarction and stroke in patients with coronary heart disease. Since 2002, American and European guidelines have emphasized the importance of optimal utilization of those four main therapeutic classes. Nevertheless, drugs prescription registries conducted in France since 1995 revealed a persistent gap between evidence based medicine and clinical practice, only a minority of patient received an optimal treatment. Some factors associated with lower rate prescription have been identified: elderly patients, female gender, missing of LDL-cholesterol measurement, history of peripheral artery disease or stroke, and finally the difficulty of observance. At this time, optimization of management of these patients require a systematic measurement of LDL-cholestererol level for all patients with CAD, PAD or history of stroke, a larger prescription of statins in female patients and in elderly particularly for secondary prevention. Increasing observance which is the main challenge could involved the utilization of fixed drugs associations.
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PMID:[Changes in the prescription of cardiovascular prevention drugs in France between 1995 and 2003: factors influencing the gap between evidence base medicine and clinical practice]. 1641 49

Arterial hypertension must also be consistently treated in patients with PAD. Current guidelines and recommendations have to be considered, although in some patients the walk performance may be affected temporary by blood pressure dropping. In PAD, ideal antihypertensives are ACE inhibitors, AT1 receptor antagonists, calcium channel blockers and also alpha receptor blockers in combination. Beta receptor blockers-indicated in coronary heart disease-do not influence pain-free walking distance (PFWD) in patients with PAD. Diuretics should only be given in low dosage and in combination with other antihypertensive drugs in order to avoid a decrease of blood flow ability with clinical events.
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PMID:[Risk adapted therapy in vascular diseases: antihypertensive treatment in peripheral arterial disease]. 1641 58

Peripheral artery disease is a global disease. When present, the occurrence of cardiovascular events and death rises. Patients suffering from peripheral artery disease belong to the high CV risk category. Based on the prevention recommendations when PAD is present, treatments with and without medicine are equally necessary. A change in life-style, blood pressure reduction, diabetes mellitus treatment, reaching the target cholesterol values, treatments with ACE inhibitor, statin and thrombocyte inhibitor all lower the occurrence of CV events. The early identification of the Doppler index can help in the early diagnosis of atherothrombosis.
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PMID:[Cardiovascular prevention with peripheral artery disease]. 1761 Nov 80

A role of ACE I/D polymorphism in the pathogenesis of abdominal aortic aneurysm (AAA) has been demonstrated, possibly due to the effect of angiotensin II on vascular tissue remodelling. Angiotensin II exerts profibrogenic effects through the local induction of TGF-beta. Dysregulated TGF-beta signalling may result from mutations in TGFBR1 and TGFBR2 genes, thus resulting in degenerative changes in the vessel wall. We performed a case-control study in order to investigate the role of TGFBR1 9A6A polymorphism as predisposing factor to AAA per se, and in the presence of ACE DD and AT1R 1166 CC genotypes in 201 AAA patients (mean age+/-S.D., 71.5+/-6.9) referred to the Unit of Vascular Surgery of the University of Florence, compared with 252 healthy controls (mean age+/-S.D., 70.6+/-8.6). A significant difference in genotype distribution and allele frequency between patients and controls was found for ACE, but not for AT1R and TGFBR1 polymorphisms. At univariate analysis a significant association between ACE DD, but not AT1R CC and TGFBR1 6A allele, and the susceptibility to the disease was found [ACE DD OR=1.86 (95% CI 1.26-2.76), p=0.002]. After adjustment for age, gender, traditional cardiovascular risk factors, and CAD, PAD and CVD, ACE DD genotype still affected the susceptibility to AAA [OR=2.13 (95% CI 1.06-4.28), p=0.03], and the contemporary presence of ACE DD genotype and TGFBR1 6A allele, increased the predisposition to the disease [OR=5.09 (95% CI 1.44-18.02), p=0.01]. This study, which demonstrates an interaction between ACE and TGFBR1 genes in predisposing to AAA, may provide further information on the mechanisms contributing to AAA susceptibility, and offer a topic for future larger studies.
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PMID:ACE and TGFBR1 genes interact in influencing the susceptibility to abdominal aortic aneurysm. 1855 62

Screening for asymptomatic peripheral artery disease (aPAD) with the ankle-brachial index (ABI) test is hypothesized to reduce disease progression and cardiovascular (CV) events by identifying individuals who may benefit from early initiation of medical therapy. Using a Markov model, we evaluated the cost effectiveness of initiating medical therapy (e.g. statin and ACE-inhibitor) after a positive ankle-brachial index (ABI) screen in 65-year-old patients. We modeled progression to symptomatic PAD (sPAD) and CV events with and without ABI screening, evaluating differences in costs and quality-adjusted life years (QALYs). The cost of the ABI test, physician visit, new medication, CV events, and interventions for sPAD were incorporated in the model. We performed sensitivity analysis on model variables with uncertainty. Our model found an incremental cost of US $338 and an incremental QALY of 0.00380 with one-time ABI screening, resulting in an incremental cost-effectiveness ratio (ICER) of $88,758/QALY over a 35-year period. The variables with the largest effects in the ICER were aPAD disease prevalence, cost of monthly medication after a positive screen and 2-year medication adherence rates. Screening high-risk populations, such as tobacco users, where the prevalence of PAD may be 2.5 times higher, decreases the ICER to $24,092/QALY. Our analysis indicates the cost effectiveness of one-time screening for aPAD depends on prevalence, medication costs, and adherence to therapies for CV disease risk reduction. Screening in higher-risk populations under favorable assumptions about medication adherence results in the most favorable cost effectiveness, but limitations in the primary data preclude definitive assessment of cost effectiveness.
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PMID:Cost-effectiveness analysis of asymptomatic peripheral artery disease screening with the ABI test. 2934 48

Pyranose dehydrogenases (PDHs; EC 1.1.99.29; AA3_2) demonstrate ability to oxidize diverse carbohydrates. Previous studies of these enzymes have also uncovered substrate-dependent regioselectivity, along with potential to introduce more than one carbonyl into carbohydrate substrates. Enzymatic oxidation of carbohydrates facilitates their further derivatization or polymerization into bio-based chemicals and materials with higher value; accordingly, PDHs that show activity on xylooligosaccharides could offer a viable approach to extract higher value from hemicelluloses that are typically fragmented during biomass processing. In this study, AbPDH1 from Agaricus bisporus and AmPDH1 from Leucoagaricus meleagris were tested using linear xylooligosaccharides, along with xylooligosaccharides substituted with either arabinofuranosyl or 4-O-(methyl)glucopyranosyluronic acid residues with degree of polymerization of two to five. Reaction products were characterized by HPAEC-PAD to follow substrate depletion, UPLC-MS-ELSD to quantify the multiple oxidation products, and ESI-MSⁿ to reveal oxidized positions. A versatile method based on product reduction using sodium borodeuteride, and applicable to carbohydrate oxidoreductases in general, was established to facilitate the identification and quantification of oxidized products. AbPDH1 activity toward the tested xylooligosaccharides was generally higher than that measured for AmPDH1. In both cases, activity values decreased with increasing length of the xylooligosaccharide and when using acidic rather than neutral substrates; however, AbPDH1 fully oxidized all linear xylooligosaccharides, and 60-100% of all substituted xylooligosaccharides, after 24 h under the tested reaction conditions. Oxidation of linear xylooligosaccharides mostly led to double oxidized products, whereas single oxidized products dominated in reactions containing substituted xylooligosaccharides. Notably, oxidation of specific secondary hydroxyls vs. the reducing end C-1 depended on both the enzyme and the substrate. For all substrates, however, oxidation by both AbPDH1 and AmPDH1 was clearly restricted to the reducing and non-reducing xylopyranosyl residues, where increasing the length of the xylooligosaccharide did not lead to detectable oxidation of internal xylopyranosyl substituents. This detailed analysis of AbPDH1 and AmPDH1 action on diverse xylooligosaccharides reveals an opportunity to synthesize bifunctional molecules directly from hemicellulose fragments, and to enrich for specific products through appropriate PDH selection.
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PMID:Quantitative Comparison of Pyranose Dehydrogenase Action on Diverse Xylooligosaccharides. 3204 37

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