Anti-aging effects of anti-lipolytic drugs

Genetic disruption of insulin and insulin-like signaling pathways may extend lifespan. Hyperinsulinemia and insulin resistance may accelerate aging. The hypothesis was tested that a once-a-week life-long inhibition of insulin secretion by the administration of anti-lipolytic drugs might have anti-aging effects. Groups of 3-month-old male Sprague-Dawley rats were (a) given standard laboratory food ad libitum (AL); (b) fed AL 6 days and fasted 1 day every week (FW); (c) fed AL every other day (EOD), (d) fed like FW and given Acipimox (50 mg/kg b.w.) on the day of fasting (FWA) by the gastric tube. The AL, FW and EOD groups received saline intragastrically. Treatment with ACIPIMOX transiently decreased plasma free fatty acids, glucose and insulin and increased valine plasma levels, and had no long-term effect on food consumption and body weight. By age 6, 12 and 24 months subgroups were taken and the age-related changes in liver dolichol and autophagic proteolysis--which are correlated with life-expectancy--were measured. Liver dolichol levels increased and autophagic proteolysis decreased in mature and older AL rats; EOD and FWA fully counteracted these changes; FW rats had significant but smaller beneficial effects. It is concluded that life-long weekly-repeated transient inhibition of insulin secretion by antilipolytic drugs may have an anti-aging effect, additive to the anti-aging effect of a milder caloric restriction. Speculation is that transiently lower plasma insulin levels might stimulate the anti-aging cell-repair mechanism autophagy, which has longer lasting effects on cell housekeeping.     

Anti-aging therapy through fitness enhancement

Physical exercise is proposed as a highly effective means of treating and preventing the main causes of morbidity and mortality – most of which are associated with aging – in industrialized countries. Low physical fitness is an important risk factor for cardiovascular and all-causes morbidity and mortality; indeed, it is even a predictor of these problems. When properly measured, the assessment of physical fitness can be a highly valuable indicator of health and life expectancy and, therefore, should be performed routinely in the clinical setting. Individually adapted training programs could be prescribed based on fitness assessment results and an adequate knowledge of patient lifestyle and daily physical activity. Such training programs would allow people to develop their maximum physical potential, improve their physical and mental health, and attenuate the negative consequences of aging.     

卒中的急救——从"时间是大脑"到"生理是大脑"

卒中诊疗研究的历史充满了积极进取和消极悲观两种态度的抗争。40年前，当神经科或内科急诊夜班医师遇见突发一侧偏瘫的患者时，他们不需要匆忙去给患者作检查，因为那时对该病的认识为“当卒中发生的时候，它已经结束了”。1995年，《新英格兰杂志》发表了组织型纤溶酶原激活剂（t-PA）可用于3h以内脑梗死治疗的研究结果后，对脑梗死的治疗进入了一个“时间是大脑“的新时代。许多医院建立起了“绿色通道”，各种媒体也开始宣传脑梗死患者早期到医院溶栓的重要性。今天，尽管研究者仍频繁地引用1996年被美国食品药品监督管理局（FDA）批准的美国国立神经病和卒中研究所（NINDS）试验结果，但令人遗憾的是：在美国仅有3％～8％的卒中患者可以得到溶栓治疗，t-PA没有显著改善公众健康。重要原因在于：在急性卒中组织管理的效率因素外，3h的时间窗确实过于狭窄，即使在发达国家，多数患者仍不能及时到达医院，并在时间窗内完成治疗。     

Increased CK-MB release is a "trade-off" for optimal stent implantation: an intravascular ultrasound study

OBJECTIVES: We sought to determine the impact of aggressive stent expansion on creatine kinase-MB isoenzyme (CK-MB) release and clinical restenosis. BACKGROUND: Elevation of CK-MB after percutaneous coronary interventions has been associated with late mortality. METHODS: We identified 989 consecutive patients who underwent intravascular ultrasound-guided stenting of 1,015 coronary lesions. Patients were divided into three groups according to stent expansion, defined as the ratio of final lumen over the reference lumen cross-sectional areas: Group 1 (ratio <70%, n = 117 patients with 126 lesions); Group 2 (ratio 70% to 100%, n = 551 patients with 562 lesions); Group 3 (ratio >100%, n = 321 patients with 327 lesions). RESULTS: The peak CK-MB values increased significantly with increasing stent expansion: CK-MB = 3 to 5x normal occurred 16%, 18%, and 25% in Groups 1, 2, and 3, respectively, p = 0.02; CK-MB >5 times normal occurred 9%, 13%, and 16% respectively, p = 0.02. Conversely, at one year follow-up there was a stepwise decrease in target lesion revascularization (11% vs. 19% and 17%, respectively, p = 0.04) and major adverse cardiac events with increasing stent expansion. In addition, there was a trend toward lower mortality in Group 3 (9% vs. 4.4% vs. 4.0%, p = 0.07). CONCLUSIONS: Intravascular ultrasound-guided stent overexpansion (final lumen greater than reference lumen cross-sectional area) is accompanied by a higher periprocedural CK-MB release but a lower target lesion revascularization and a trend toward lower mortality at one year. Increased periprocedural CK-MB release appears as a trade-off for optimal stent implantation and lower clinical restenosis.