Sexual dysfunction is more prevalent in obese than in normal-weight men. Meal replacements (MRs) are useful weight-loss strategies. We randomized obese (body mass index 27.5 kg m(-2), waist circumference (WC) 90 cm) Asian men (mean age 40.5 years, range 30-61) to a conventional reduced-fat diet (CD) (n=24) or MR-based plan (n=24) to reduce daily intake by 400 kcal for 12 weeks. There were significantly greater reductions in weight (4.2 ± 0.8 kg), WC (4.6 ± 0.7 cm), calorie and fat intake in the MR group, compared with the CD group (2.5 ± 0.4 kg, 2.6 ± 0.5 cm). Erectile function (International Index of Erectile Function 5-item score) improved comparably in the MR (3.4 ± 0.7 points) and CD (2.5 ± 0.5 points) groups, as did the Sexual Desire Inventory score (5.5 ± 2.3 vs 7.7 ± 2.1 points), quality of life (36-item Short Form survey score), plasma testosterone and endothelial function (Reactive Hyperemia Index). Subjects were switched to or continued CD for another 28 weeks. Weight, WC and erectile function were maintained at 40 weeks. MR induces greater reductions in weight and abdominal obesity than conventional diet, and comparable improvements in sexual and endothelial function, testosterone and quality of life.
ABSTRACT. Regulated on activation, normal T-cell expressed and secreted (RANTES) and stromal cell-derived factor 1 (SDF-1) are members of the CC-and CXC-chemokine families, respectively. Both genes have been postulated to be involved in the pathogenesis of systemic lupus erythematosus (SLE). We analyzed position 28 of the RANTES gene promoter region, as well as the SNP observed in the 3' UTR of the SDF-1 gene at position 801, in 130 patients presenting SLE at the Malaya University Medical Centre. Screening of 130 healthy volunteer controls using RFLP was also performed. RANTES-28 polymorphism analysis showed no significant (P = 0.3520) relationship, even though homozygous C/C was more frequent in SLE patients (OR = 1.4183) and heterozygous C/G was more frequent in healthy controls (OR = 0.7051). There were no significant (P = 0.2650) associations between A/A (OR = 0.783), G/G (OR = 1.5914) and G/A (OR = 0.8289) genotypes in the SDF-1 gene polymorphism with SLE. We conclude that there is no significant association of RANTES-28 and SDF-1 gene polymorphisms and occurrence of SLE in Malaysia.
High concentrations of estrogenic compounds can overstimulate estrogen receptors and potentially lead to breast, ovarian, and cervical cancers. Recently, a G-protein coupled estrogen receptor (GPER/GPR30) was discovered that has no structural similarity to the wellcharacterized, classical estrogen receptor ERα. The crystal structure of GPER has not yet been determined, and the ligand binding sites have not yet been experimentally identified. The recent explosion of GPCR crystal structures now allow homology modeling with unprecedented reliability. We create, validate, and describe a homology model for GPER. We describe and apply ConDock, the first hybrid scoring function to use information from protein surface conservation and ligand docking, to predict binding sites on GPER for four ligands, estradiol, G1, G15, and tamoxifen. ConDock is a simple product function of sequence conservation and binding energy scores. ConDock predicts that all four ligands bind to the same location on GPER, centered on L119, H307, and N310; this site is deeper in the receptor cleft than are ligand binding sites predicted by previous studies. We compare the sites predicted by ConDock and traditional methods analyzing surface geometry, surface conservation, and ligand chemical interactions. Incorporating sequence conservation information in ConDock avoids errors resulting from physics-based scoring functions and modeling.
Background: The aim of the current study was to determine whether a unique blueberry tea (BT) ameliorates insulin resistance by improving metabolic and vascular actions of insulin in skeletal muscle. Methods: Male Sprague Dawley rats were fed normal (4.8% fat wt/wt, ND) or high (22.6% fat wt/wt, HFD) fat diets for 4 weeks. A second group of HFD rats was provided BT (4.0% wt/vol) in the drinking water during the final 2 weeks. Animals were subjected to an intraperitoneal glucose tolerance test (1g glucose/kg IPGTT) or euglycaemic hyperinsulinaemic clamp (10mU/min/kg x 2hr). Results: HFD rats displayed significantly (p<0.05) higher plasma glucose levels at 15 and 30 mins following the IPGTT compared to ND, and this increase was completely abolished by BT treatment. Glucose infusion rate, muscle glucose uptake, and microvascular perfusion in muscle were significantly (p<0.05) impaired during clamps in HFD and all markedly improved (p<0.05) with BT treatment. Insulin-mediated changes in femoral artery blood flow were unaffected by HFD or BT treatment. Conclusions: We conclude that BT treatment ameliorates glucose intolerance and insulin resistance by restoring both metabolic and microvascular insulin sensitivity in high fat-fed rats. Therefore, BT consumption may have therapeutic implications for insulin resistance and type 2 diabetes.
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