A large-scale synthesis of somatostatin for clinical use by a novel alternating solution/solid-phase procedure

A large-scale synthesis of somatostatin was developed. A stepwise C→N approach in solution was used, employing N(α)-t-butoxycarbonyl amino acid active esters. The scheme of semipermanent protection utilized 2-(methylsulfonyl)-ethoxycarbonyl for the -amino group of lysine; acetamidomethyl for the β-thiol groups of cysteine; the orange-colored 2-[4-(phenylazo)-phenylsulfonyl]-ethoxy group for the C-terminal carboxy group of cysteine. All condensations and N(α)-deprotections were carried out in homogeneous solution, while isolation and purification of peptides carrying the colored group was achieved by precipitation and washing of the solid products. Thus, the “alternating solution/solid-phase peptide synthesis” combines advantages of both the classical solution synthesis and the Merrifield solid-phase technique. The overall yield was 5%, or 16 g of somatostatin from 100 g of the novel amino acid derivative, N(α)-t-butoxycarbonyl-S-acetamidomethyl- -cysteine 2-[4-(phenylazo)-phenylsulfonyl]-ethyl ester. An improved method for the preparation of S-acetamidomethyl- -cysteine, free of thiazolidine carboxylic acid, is described.     

The Effect of Exercise on Visceral Adipose Tissue in Overweight Adults: A Systematic Review and Meta-Analysis

Excessive visceral adipose tissue appears to trigger a cascade of metabolic disturbances that seem to coexist with ectopic fat storage in muscle, liver, heart and the ß-cell. Therefore, the reduction of visceral adipose tissue potentially plays a pivotal role in the treatment of the metabolic syndrome. The purpose of this systematic review and meta-analysis is to describe the overall effect of exercise on visceral adipose tissue and to provide an overview of the effect of different exercise regimes, without caloric restriction, on visceral adipose tissue in obese persons. A systematic literature search was performed according to the PRISMA statement for reporting systematic reviews and meta-analyses. The initial search resulted in 87 articles after removing duplicates. After screening on title, abstract and full-text 15 articles (totalling 852 subjects) fulfilled the a priori inclusion criteria. The quality of each eligible study was assessed in duplicate with “The Critical Review Form for Quantitative Studies”. Using random-effects weights, the standardized mean difference (Hedge''s g) of the change in visceral adipose tissue was −0.497 with a 95% confidence interval of −0.655 to −0.340. The Z-value was −6.183 and the p-value (two tailed) was <0.001. A subgroup analysis was performed based on gender, type of training and intensity. Aerobic training of moderate or high intensity has the highest potential to reduce visceral adipose tissue in overweight males and females. These results suggest that an aerobic exercise program, without hypocaloric diet, can show beneficial effects to reduce visceral adipose tissue with more than 30 cm² (on CT analysis) in women and more than 40 cm² in men, even after 12 weeks.