Influence of segmental body composition and adiposity hormones on resting metabolic rate and substrate utilization in overweight and obese adults.

PURPOSE: Low resting metabolic rate (RMR) and high carbohydrate reliance at rest are associated with weight gain, but are highly variable in obese individuals. This study determined the relationship of total and segmental body composition and adiposity hormones with RMR and respiratory exchange ratio (RER) in overweight and obese adults. METHODS: In 49 men (n = 23) and premenopausal women (n = 26) [mean ± SD; age = 35.0 ± 8.9 years; body mass index (BMI) = 33.6 ± 5.2 kg·m-2; percent body fat (%fat) = 40.0 ± 8.0%], RMR and RER were evaluated using indirect calorimetry. Total and segmental body composition [fat mass (FM), percent fat (%fat), lean mass (LM), visceral adipose tissue (VAT)] were estimated using dual-energy X-ray absorptiometry. Fasted blood and saliva samples were analyzed for insulin, leptin, estradiol, and cortisol. RESULTS: In men (M) and women (W), RMR significantly correlated (p < 0.05) with FM (M: R = 0.535; W: R = 0.784) and LM (M: R = 0.645; W: R = 0.867). Of the segmental measures, trunk LM (M: R = 0.593; W: R = 0.879; p < 0.05) and leg LM (M: R = 0.664; W: R = 0.821; p < 0.05) had the strongest correlations with RMR. In men, but not women, RER significantly correlated with FM (R = 0.449; p = 0.032), trunk FM (R = 0.501; p = 0.015), and VAT (R = 0.456; p = 0.029). In men, RMR positively correlated with cortisol (R = 0.430, p = 0.040) and estradiol (R = 0.649, p = 0.001) and RER positively correlated with insulin (R = 0.525, p = 0.010). In women, RMR positively correlated with insulin (R = 0.570, p = 0.006), but RER was not significantly correlated with hormones (p > 0.05). CONCLUSIONS: Segmental evaluation of body composition, specifically in the lower extremities and abdomen, may be an effective and efficient way to evaluate metabolic status. Sex-specific evaluations are also imperative.

Body Composition, Muscle Quality and Scoliosis in Female Collegiate Gymnasts: A Pilot Study.

Research has demonstrated an elevated prevalence of body weight concerns and scoliosis among female gymnasts. The purpose of the current pilot study was to evaluate the utility of ultrasonography and dual-energy X-ray absorptiometry (DXA) as practical imaging modalities to measure body composition and spinal curvature variables that may correlate with performance in female collegiate gymnasts (n=15). DXA was used to evaluate body composition and lateral spinal curvature, utilizing a modified Ferguson method. Echo intensity (EI) and cross-sectional area (CSA) of the vastus lateralis were determined from a panoramic cross-sectional ultrasound image. For returning athletes (n=9), performance scores from the previous season were averaged to quantify performance. The average performance score was correlated with lean mass of the arms (R=0.714; P=0.03) and right leg (R=0.680; P=0.04). Performance was not correlated with total mass, fat mass or body fat percentage (P>0.10). Scoliosis was identified in 3 of 15 scans (20%). Echo intensity and CSA of the vastus lateralis were inversely correlated with each other (R=-0.637, P=0.01), but not with other measures of body composition or performance. Results suggest that limb LBM may be a determinant of gymnastics performance, and DXA may provide important health and performance-related information for female collegiate gymnasts.

Low doses of the novel caspase-inhibitor GS-9450 leads to lower caspase-3 and -8 expression on peripheral CD4+ and CD8+ T-cells.

Chronic hepatitis C virus (HCV) infection is characterized by increased rates of apoptotic hepatocytes and activated caspases have been shown in HCV-infected patients. GS-9450, a novel caspase-inhibitor has demonstrated hepatoprotective activity in fibrosis/apoptosis animal models. This study evaluated the effects of GS-9450 on peripheral T-cell apoptosis in chronic HCV-infected patients. As sub study of the GS-US-227-0102, a double-blind, placebo-controlled phase 2a trial evaluating the safety and tolerability of GS-9450, apoptosis of peripheral CD4+ and CD8+ T-cells was measured using activated caspase-3, activated caspase-8 and CD95 (Fas). Blood samples were drawn at baseline, day 14 after therapy and at 5 weeks off-treatment follow-up in the first cohort of 10 mg. In contrast to the placebo-treated patients, GS-9450 caused a median of 46% decrease in ALT-values from baseline to day 14 in all treated patients (median of 118-64 U/l) rising again to a median of 140 U/l (19%) at 5 weeks off-treatment follow-up. In GS9450-treated patients, during treatment and follow-up, percentages of activated caspase-3+ and caspase-8 expression tended to decrease, in contrast to placebo-treated patients. Interestingly, compared to healthy controls, higher percentages of caspase-3 and caspase-8 positive CD4+ and CD8+ T-cells were demonstrated in HCV-infected patients at baseline. Decreased ALT-values were observed in all HCV-infected patients during treatment with low dose of the caspase-inhibitor GS-9450 accompanied by a lower expression of caspase-3 and -8 on peripheral T-cells. Furthermore, at baseline percentages of activated caspase-3, activated caspase-8 and CD95+ T-cells were higher in chronic HCV-infected patients compared to healthy controls.

Kinetics and mechanism of the hydrolysis of depsipeptides catalyzed by the beta-lactamase of Enterobacter cloacae P99.

The steady-state kinetics and mechanism of the hydrolysis and aminolysis of a series of acyclic depsipeptides, catalyzed by the class C beta-lactamase of Enterobacter cloacae P99, have been studied in order to more firmly establish the nature of the transition states involved. The class C beta-lactamase of Enterobacter cloacae P99 was employed. The depsipeptide substrates contained a constant acyl group, (phenylacetyl)glycyl, and chemically different leaving groups, m-carboxyphenoxide, m-carboxythiophenoxide, 3-carboxyl-4-nitrophenoxide, lactate, and thiolactate. Evaluation of the steady-state kinetic parameters and the effect of the alternative nucleophile methanol on these parameters and on the product distribution showed that deacylation was largely rate-determining to turnover of the aryl esters under conditions of substrate saturation, while acylation was rate-determining to the alkyl esters. The earlier conclusion [Govardhan & Pratt (1987) Biochemistry 26, 3385-3395] that acylation largely limited the turnover of the aryl esters was shown to be an artifact of phosphate buffer inhibition. The aminolysis of both the aryl the alkyl esters by D-phenylalanine was influenced by binding of the substrate at a second binding site on the acyl-enzyme intermediate. A study of inhibiton of the hydrolysis of (phenylacetyl)-glycyl-D-thiolactate by the aminolysis product (phenylacetyl)glycyl-D-phenylalanine indicated that the second binding site is also available for ligands to bind the free enzyme and to the noncovalent Michaelis complex with this substrate. It is likely that penicillin-recognizing enzymes in general, both beta-lactamases and DD-peptidases, possess an extended substrate-binding site into which a variety of small ligands may bind at any point along the reaction coordinate and, to a greater or lesser extent depending on circumstances, affect catalysis.

A method for interactive medical instruction utilizing the World Wide Web.

We describe the implementation of interactive medical teaching programs in radiology and histology which utilize the Internet's World Wide Web (WWW). The WWW standard hypertext interface allows for simple navigation between related documents but does not provide a method for student tracking or question queries. Electronic forms, a recent feature of the WWW, provide the means to present question documents to remote clients and track student performance. A feature of our approach is dynamic creation of HTML documents based upon interaction with database applications. The approach allows multiple simultaneous, yet asynchronous interactions by geographically dispersed students upon the same instructional database and is scalable, providing the capability for multiple image/document servers. The security of the database is assured given that it is not accessible through the Internet.