Long-term calorie restriction, but not endurance exercise, lowers core body temperature in humans

Reduction of body temperature has been proposed to contribute to the increased lifespan in calorie restricted animals and mice overexpressing the uncoupling protein-2 in hypocretin neurons. However, nothing is known regarding the long-term effects of calorie restriction (CR) with adequate nutrition on body temperature in humans. In this study, 24-hour core body temperature was measured every minute by using ingested telemetric capsules in 24 men and women (mean age 53.7±9.4 yrs) consuming a CR diet for an average of 6 years, 24 age- and sex-matched sedentary (WD) and 24 body fat-matched exercise-trained (EX) volunteers, who were eating Western diets. The CR and EX groups were significantly leaner than the WD group. Energy intake was lower in the CR group (1769±348 kcal/d) than in the WD (2302±668 kcal/d) and EX (2798±760 kcal/d) groups (P<0.0001). Mean 24-hour, day-time and night-time core body temperatures were all significantly lower in the CR group than in the WD and EX groups (P≤0.01). Long-term CR with adequate nutrition in lean and weight-stable healthy humans is associated with a sustained reduction in core body temperature, similar to that found in CR rodents and monkeys. This adaptation is likely due to CR itself, rather than to leanness, and may be involved in slowing the rate of aging

Serum Albumin Is Inversely Associated With Portal Vein Thrombosis in Cirrhosis

We analyzed whether serum albumin is independently associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) and if a biologic plausibility exists. This study was divided into three parts. In part 1 (retrospective analysis), 753 consecutive patients with LC with ultrasound-detected PVT were retrospectively analyzed. In part 2, 112 patients with LC and 56 matched controls were entered in the cross-sectional study. In part 3, 5 patients with cirrhosis were entered in the in vivo study and 4 healthy subjects (HSs) were entered in the in vitro study to explore if albumin may affect platelet activation by modulating oxidative stress. In the 753 patients with LC, the prevalence of PVT was 16.7%; logistic analysis showed that only age (odds ratio [OR], 1.024; P = 0.012) and serum albumin (OR, -0.422; P = 0.0001) significantly predicted patients with PVT. Analyzing the 112 patients with LC and controls, soluble clusters of differentiation (CD)40-ligand (P = 0.0238), soluble Nox2-derived peptide (sNox2-dp; P &lt; 0.0001), and urinary excretion of isoprostanes (P = 0.0078) were higher in patients with LC. In LC, albumin was correlated with sCD4OL (Spearman's rank correlation coefficient [r(s)], -0.33; P &lt; 0.001), sNox2-dp (r(s), -0.57; P &lt; 0.0001), and urinary excretion of isoprostanes (r(s), -0.48; P &lt; 0.0001) levels. The in vivo study showed a progressive decrease in platelet aggregation, sNox2-dp, and urinary 8-iso prostaglandin F2 alpha-III formation 2 hours and 3 days after albumin infusion. Finally, platelet aggregation, sNox2-dp, and isoprostane formation significantly decreased in platelets from HSs incubated with scalar concentrations of albumin. Conclusion: Low serum albumin in LC is associated with PVT, suggesting that albumin could be a modulator of the hemostatic system through interference with mechanisms regulating platelet activation

Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D

Early and long-term clinical outcomes of bilio-intestinal diversion in morbidly obese patients

To evaluate the early and long-term postoperative results of malabsorptive surgery in morbidly obese patients. Between 2000 and 2007, 102 morbidly obese patients were referred to the Department of Surgery "Pietro Valdoni", "Sapienza" University of Rome, Policlinico "Umberto IA degrees", Rome, Italy for malabsorptive surgery. All patients underwent derivative biliodigestive surgery after they had been reviewed by a team of surgeons, physicians, dieticians, and psychologists. There were no intra-operative complications, but two patients suffered postoperative pulmonary embolisms, which resolved with medical treatment. The mean postoperative hospital stay was 7 days, with no early or late mortality. Maximum weight loss was reached 12-24 months after surgery, while the mean percentage excess weight loss at 3-5 years ranged from 45 to 64 %. Specific postoperative complications in the first 2 years after surgery were abdominal abscess (n = 2), gastroduodenal reflux (n = 4), and incisional hernia (n = 6). Diabetes resolved in 98 % of the diabetic patients within a few weeks after surgery and blood pressure normalised in 86.4 % of those who had had hypertension preoperatively. Obstructive sleep apnoea and obesity hypoventilation syndrome also improved significantly in 92 % of the patients. Morbidly obese patients can undergo biliodigestive surgery safely with good long-term weight loss and quality of life expectancy

Effects of long-term calorie restriction on serum sex hormones concentration in men

Calorie restriction (CR) slows aging and consistently reduces circulating sex hormones in laboratory animals. However, nothing is known regarding the long-term effects of CR with adequate nutrition on serum sex-hormone concentration in lean healthy humans. In this study, we measured body composition, and serum total testosterone, total 17-beta-estradiol, sex hormone-binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEA-S) concentrations in 24 men (mean age 51.5 +/- 13 years), who had been practicing CR with adequate nutrition for an average of 7.4 +/- 4.5 years, in 24 age- and body fat-matched endurance runners (EX), and 24 age-matched sedentary controls eating Western diets (WD). We found that both the CR and EX volunteers had significantly lower body fat than the WD volunteers (total body fat, 8.7 +/- 4.2%; 10.5 +/- 4.4%; 23.2 +/- 6.1%, respectively; P = 0.0001). Serum total testosterone and the free androgen index were significantly lower, and SHBG was higher in the CR group than in the EX and WD groups (P < or = 0.001). Serum 17beta-estradiol and the estradiol:SHBG ratio were both significantly lower in the CR and EX groups than in the WD group (P < or = 0.005). Serum DHEA-S concentrations were not different between the three groups. These findings demonstrate that, as in long-lived CR rodents, long-term severe CR reduces serum total and free testosterone and increases SHBG concentrations in humans, independently of adiposity. More studies are needed to understand the role of this CR-mediated reduction in sex hormones in modulating the pathogenesis of age-associated chronic diseases such as cancer and the aging process itself

Long-term effects of calorie restriction on serum sex-hormone concentrations in men

Calorie restriction (CR) slows aging and consistently reduces circulating sex hormones in laboratory animals. However, nothing is known regarding the long-term effects of CR with adequate nutrition on serum sex-hormone concentration in lean healthy humans. In this study, we measured body composition, and serum total testosterone, total 17-beta-estradiol, sex hormone-binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEA-S) concentrations in 24 men (mean age 51.5 +/- 13 years), who had been practicing CR with adequate nutrition for an average of 7.4 +/- 4.5 years, in 24 age-and body fat-matched endurance runners (EX), and 24 age-matched sedentary controls eating Western diets (WD). We found that both the CR and EX volunteers had significantly lower body fat than the WD volunteers (total body fat, 8.7 +/- 4.2%; 10.5 +/- 4.4%; 23.2 +/- 6.1%, respectively; P = 0.0001). Serum total testosterone and the free androgen index were significantly lower, and SHBG was higher in the CR group than in the EX and WD groups (P <= 0.001). Serum 17 beta-estradiol and the estradiol: SHBG ratio were both significantly lower in the CR and EX groups than in the WD group (P <= 0.005). Serum DHEA-S concentrations were not different between the three groups. These findings demonstrate that, as in long-lived CR rodents, long-term severe CR reduces serum total and free testosterone and increases SHBG concentrations in humans, independently of adiposity. More studies are needed to understand the role of this CR-mediated reduction in sex hormones in modulating the pathogenesis of age-associated chronic diseases such as cancer and the aging process itself