Propionyl-L-carnitine: a new compound in the metabolic approach to the treatment of effort angina.

The effects of propionyl-L-carnitine on exercise tolerance of 12 patients with stable exertional angina were assessed in a double-blind, placebo-controlled, cross-over protocol using serial exercise tests. Compared to placebo, propionyl-L-carnitine significantly increased total work from 514 +/- 199 to 600 +/- 209 W (P less than 0.05) (17%) and prolonged exercise time and time to ischemic threshold from 515 +/- 115 to 565 +/- 109 sec (P less than 0.05) (10%) and from 375 +/- 102 to 427 +/- 93 sec (P less than 0.01) (14%), respectively. ST segment depression at the highest common work level was significantly reduced from 0.19 +/- 0.08 to 0.15 +/- 0.08 mV (P less than 0.05) (21%). No significant changes in heart rate, systolic blood pressure, and rate-pressure product at rest, at the highest common work level, on appearance of the ischemic threshold, or at peak exercise were observed after propionyl-L-carnitine treatment. No side effects were observed under propionyl-L-carnitine treatment. This study shows that propionyl-L-carnitine can significantly improve exercise tolerance in patients with stable angina. Our data seem to confirm that propionyl-L-carnitine most likely exerts its protective action via the metabolic pathway.     

血糖波动:糖尿病治疗的新靶点

糖尿病的"血糖代谢紊乱"包括三要素:空腹、餐后血糖升高和血糖波动特征异常.血糖急性波动通过活化氧化应激、内皮功能紊乱、激活凝血系统和炎性反应过程参与糖尿病慢性并发症的进展.因此,控制血糖波动应该是糖尿病治疗策略的一个重要内容,其中胰高血糖素样肽-1(GLP-1)受体激动剂、二肽基肽酶(DPP)-IV抑制剂和超短效胰岛素类似物具有广阔的治疗应用前景.     

If you try to stop smoking,should we pay for it? The cost–utility of reimbursing smoking cessation support in the Netherlands

Background Smoking cessation can be encouraged by reimbursing the costs of smoking cessation support (SCS). The short‐term efficiency of reimbursement has been evaluated previously. However, a thorough estimate of the long‐term cost–utility is lacking. Objectives To evaluate long‐term effects of reimbursement of SCS. Methods Results from a randomized controlled trial were extrapolated to long‐term outcomes in terms of health care costs and (quality adjusted) life years (QALY) gained, using the Chronic Disease Model. Our first scenario was no reimbursement. In a second scenario, the short‐term cessation rates from the trial were extrapolated directly. Sensitivity analyses were based on the trial's confidence intervals. In the third scenario the additional use of SCS as found in the trial was combined with cessation rates from international meta‐analyses. Results Intervention costs per QALY gained compared to the reference scenario were approximately €1200 extrapolating the trial effects directly, and €4200 when combining the trial's use of SCS with the cessation rates from the literature. Taking all health care effects into account, even costs in life years gained, resulted in an estimated incremental cost–utility of €4500 and €7400, respectively. In both scenarios costs per QALY remained below €16 000 in sensitivity analyses using a life‐time horizon. Conclusions Extrapolating the higher use of SCS due to reimbursement led to more successful quitters and a gain in life years and QALYs. Accounting for overheads, administration costs and the costs of SCS, these health gains could be obtained at relatively low cost, even when including costs in life years gained. Hence, reimbursement of SCS seems to be cost‐effective from a health care perspective.     

Lipin:治疗胰岛素抵抗的新靶点

脂素基因(LPIN)是新近发现的双向调控身体脂肪的一个基因家族,至少包括LPIN1,LPIN2,LPIN3 3个成员.其蛋白产物称为脂素(lipin).该蛋白家族在不同组织发挥相似的功能,主要有两个作用:一是作为磷脂酸磷酸酶(PAP)1发挥甘油三酯、磷脂合成作用,二是作为转录协同刺激因子联系肝过氧化物酶体增殖物活化受体(PPAR)γ协同刺激因子1α(PGC1α)和PPARα,进而调节脂肪酸氧化基因的表达,因而在脂质合成和基因表达方面有双重作用,影响着糖脂代谢.该基因变异可能与胰岛素抵抗、肥胖、2型糖尿病及代谢综合征相关.Lipin可能为胰岛素抵抗、肥胖、糖尿病及其相关代谢异常提供新的治疗靶点.     

Vasopressin: a new target for the treatment of heart failure

Background

Arginine vasopressin is a peptide hormone that modulates a number of processes implicated in the pathogenesis of heart failure. Numerous vasopressin antagonists are currently under development for the treatment of this syndrome.

Methods

Preclinical and clinical data describing the effects of vasopressin and the vasopressin antagonists on both normal physiology and heart failure were reviewed.

Results

Through activation of V_1a and V₂ receptors, vasopressin regulates various physiological processes including body fluid regulation, vascular tone regulation, and cardiovascular contractility. Vasopressin synthesis is significantly and chronically elevated in patients with heart failure despite the volume overload and reductions in plasma osmolality often observed in these patients. Vasopressin also appears to adversely effect hemodynamics and cardiac remodeling, while potentiating the effects of norepinephrine and angiotensin II. The selective V₂ and dual V_1a/V₂ receptor antagonists tolvaptan and conivaptan, respectively, substantially increase free water excretion and plasma osmolality, reduce body weight, improve symptoms of congestion, and moderately increase serum sodium concentrations in patients with heart failure who present with symptoms of fluid overload. Tolvaptan effectively normalizes serum sodium concentrations in hyponatremic heart failure patients. Conivaptan significantly reduces pulmonary capillary wedge pressure without affecting systemic vascular resistance or cardiac output. The clinical significance of V_1a receptor antagonism requires further investigation.

Conclusions

Current preclinical and clinical findings with the vasopressin antagonists appear promising, however further evaluation in phase III clinical trials is necessary to define the role of vasopressin antagonism in the treatment of heart failure.     

Urotensin II: a new pharmacologic target in the treatment of cardiovascular disease

Urotensin II was first identified over 30 years ago as a potent vasoconstrictor, and the identification of its receptor in the heart, lungs, blood vessels, and brain have made it a potential target for human pharmacotherapy. Current research would suggest that urotensin II plays a major role in the pathophysiology of various cardiovascular disease entities. This article discusses the biologic effects of urotensin under normal and pathophysiologic conditions, and reviews the research experiences with synthetic urotensin blockers in the treatment of various cardiovascular illnesses.     

Now you see me,now you don't: The case of a vanishing outflow gradient in a patient with hypertrophic cardiomyopathy

Cardiogenic shock is well described in hypertrophic cardiomyopathy (HCM) as acute hemodynamic collapse can develop in the setting of acute worsening of left ventricular outflow tract (LVOT) obstruction. We present the case of a 60‐year‐old man with drug refractory LVOT obstruction due to hypertrophic cardiomyopathy. On the evening prior to planned alcohol septal ablation, the patient presented in cardiogenic shock. Interestingly, his previously recorded LVOT gradients of 50 mm Hg at rest and 118 mm Hg at peak exercise were absent. With recovery of left ventricular function, significant left ventricular outflow obstruction returned. The patient then underwent successful septal reduction therapy. © 2016 Wiley Periodicals, Inc.     

Beneficial effect of diltiazem, a new antianginal drug, on angina pectoris at rest.

The effect of oral administration of diltiazem, a new 1,5-benzothiazepine derivative, on the frequency of anginal attack at rest was studied in 8 patients. Our own experience showed that diltiazem gave excellent results in patients with ST elevation (variant type) but its effect was insufficient in the patients whose ST segment was depressed during the attack.