European journal of clinical investigation
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Eur. J. Clin. Invest. · Sep 2006
ReviewDual ET(A)/ET(B) vs. selective ET(A) endothelin receptor antagonism in patients with pulmonary hypertension.
Since the identification of endothelin as a key mediator in the pathogenesis of several diseases, including pulmonary arterial hypertension (PAH), the pharmacologic control of the activated endothelin system with endothelin receptor antagonists (ETRA) has been a major therapeutic achievement for the treatment of patients with PAH. To date, dual ET(A)/ET(B) and selective ET(A) receptor antagonists have clinically been evaluated. To answer the question of whether selective or dual ETRA is preferable in patients with PAH, experimental and clinical data with relevance to the pulmonary circulation are reviewed in this article. ⋯ On the contrary, there is clear evidence that endothelial ET(B) receptors continue to mediate vasodilation, vasoprotection and ET-1 clearance despite the pathology associated with pulmonary hypertension. More difficult to assess is the net effect of these mechanisms in patients to be treated with ETRA. When considering the available data from controlled clinical trials, nonselectivity does not appear to carry a relevant clinical benefit for the treatment of patients with PAH when compared with selective ET(A) receptor antagonism.
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Eur. J. Clin. Invest. · Sep 2006
The importance of independent risk-factors for long-term mortality prediction after cardiac surgery.
The purpose of the present study was to determine independent predictors for long-term mortality after cardiac surgery. The European System for Cardiac Operative Risk Evaluation (EuroSCORE) was developed to score in-hospital mortality and recent studies have shown its ability to predict long-term mortality as well. We compared forecasts based on EuroSCORE with other models based on independent predictors. ⋯ In the four models, the odds of death in the highest-risk quartile was 8.4-, 8.5-, 9.4- and 15.6-fold higher, respectively, than the odds of death in the lowest-risk quartile (P < 0.0001 for all). EuroSCORE is a good predictor of long-term mortality after cardiac surgery. We developed and validated a model using selected preoperative, intra-operative and post-operative variables that has better discriminatory ability.
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Eur. J. Clin. Invest. · Sep 2006
Bosentan for the treatment of pulmonary arterial hypertension associated with congenital heart defects.
Bosentan is an effective first-line therapy in New York Heart Association (NYHA) III patients with idiopathic pulmonary arterial hypertension (PAH). Pre-clinical data support the rationale for the potential benefit of bosentan in PAH associated with congenital heart disease (CHD). ⋯ Bosentan improves exercise capacity, functional class and haemodynamics in most patients with PAH-associated CHD, without serious side-effects, suggesting bosentan may be an important treatment option for these patients.
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Eur. J. Clin. Invest. · Sep 2006
Adipocyte fatty acid binding protein in a Caucasian population: a new marker of metabolic syndrome?
Adipocyte fatty acid binding protein (A-FABP) has been suggested as playing an important role in the pathogenesis of metabolic syndrome. The aim of this study was to evaluate serum A-FABP as a marker of metabolic syndrome and to assess its predictive accuracy in a Caucasian population. Anthropometric and serum analyses were performed for body mass index (BMI), waist circumference, A-FABP, insulin, triglycerides, total cholesterol, high-density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c), uric acid, and glucose on 67 non-obese, healthy subjects and 71 subjects with metabolic syndrome. ⋯ The A-FABP serum level correlated with fasting levels of insulin (r = 0.34; P < 0.01), glucose (r = 0.21; P = 0.01), triglycerides (r = 0.4; P < 0.01), BMI (r = 0.57; P < 0.01) and waist circumference (r = 0.51; P < 0.01), but negatively with HDL-c (r = -0.23; P < 0.01) and Quicki (r = -0.32; P < 0.01). The relationship was defined between serum A-FABP level and metabolic syndrome diagnosis with 40% sensitivity and 99% specificity at A-FABP level 16.4 microg L(-1). Serum A-FABP level might be an independent marker of metabolic syndrome in a Caucasian population.
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Eur. J. Clin. Invest. · Sep 2006
In vivo and mechanistic evidence of nuclear receptor CAR induction by artemisinin.
Artemisinin (a sesquiterpene lactone endoperoxide) has become important in multi-drug treatment of malaria. There is evidence that artemisinin induces drug metabolism which could result in drug-drug interactions. The objective of this study was to characterize the inductive properties of artemisinin on drug-metabolizing cytochrome P450 (CYP450) enzymes. ⋯ The results demonstrate that the drug exerts its effects on drug metabolism via the CAR receptor that results in up-regulation of genes such as the Cyp2b. The weaker up-regulation of CYP2A5 might also be CAR-dependent or alternatively, a consequence of artemisinin toxicity. The results of this study are of importance when predicting potential drug-drug interactions in multi-drug therapies with artemisinin.