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Background. Tesamorelin, a growth hormone—releasing hormone analogue, decreases visceral adipose tissue (VAT) by 15%—20% over 6—12 months in individuals with human immunodeficiency virus (HIV)—associated abdominal adiposity, but it is unknown whether VAT reduction is directly associated with endocrine and metabolic changes. Methods. In 2 phase III, randomized, double-blind studies, men and women with HIV-associated abdominal fat accumulation were randomly assigned (ratio, 2:1) to receive tesamorelin or placebo for 26 weeks. At week 26, patients initially receiving tesamorelin were randomly assigned to continue receiving tesamorelin or to receive placebo for an additional 26 weeks. In per-protocol analysis of 402 subjects initially randomly assigned to receive tesamorelin, those with ≥8% reduction in VAT were defined a priori as responders per the statistical analysis plan. Post hoc analyses were performed to assess differences between responders and nonresponders. Results. Compared with tesamorelin nonresponders, responders experienced greater mean (±SD) reduction in triglyceride levels (26 weeks: -0.6 ± 1.7 mmol/L vs -0.1 ± 1.2 mmol/L [P = .005]; 52 weeks: -0.8 ± 1.8 mmol/L vs 0.0 ± 1.1 mmol/L [P = .003]) and attenuated changes in fasting glucose levels (26 weeks: 1 ± 16 mg/dL vs 5 ± 14 mg/dL [P = .01]; 52 weeks: -1 ± 14 mg/dL vs 8 ± 17 mg/dL [P < .001]), hemoglobin A1c levels (26 weeks: 0.1 ± 0.3% vs 0.3 ± 0.4% [P < .001]; 52 weeks: 0.0 ± 0.3% vs 0.2 ± 0.5% [P = .003]), and other parameters of glucose homeostasis. Similar patterns were seen for adiponectin levels, with significant improvement in responders vs nonresponders. Changes in lipid levels and glucose homeostasis were significantly associated with percentage change in VAT. Conclusions. In contrast to nonresponders, HIV-infected patients receiving tesamorelin with ≥8% reduction in VAT have significantly improved triglyceride levels, adiponectin levels, and preservation of glucose homeostasis over 52 weeks of treatment. Clinicaltrials.gov Registration. NCT00123253, NCT00435136, NCT00608023.

Abstract Context Growth hormone (GH) and IGF-1 help regulate hepatic glucose and lipid metabolism, and reductions in these hormones may contribute to development of nonalcoholic fatty liver disease (NAFLD). Objective To assess relationships between hepatic expression of IGF1 and IGF-binding proteins (IGFBPs) and measures of glycemia and liver disease in adults with NAFLD. Secondarily to assess effects of GH-releasing hormone (GHRH) on circulating IGFBPs. Design Analysis of data from a randomized clinical trial of GHRH. Setting Two US academic medical centers. Participants Participants were 61 men and women 18 to 70 years of age with HIV-infection, ≥5% hepatic fat fraction, including 39 with RNA-Seq data from liver biopsy. Main Outcome Measures Hepatic steatosis, inflammation, and fibrosis by histopathology and measures of glucose homeostasis. Results Hepatic IGF1 mRNA was significantly lower in individuals with higher steatosis and NAFLD Activity Score (NAS) and was inversely related to glucose parameters, independent of circulating IGF-1. Among the IGFBPs, IGFBP2 and IGFBP4 were lower and IGFBP6 and IGFBP7 (also known as IGFBP-related protein 1) were higher with increasing steatosis. Hepatic IGFBP6 and IGFBP7 mRNA levels were positively associated with NAS. IGFBP7 mRNA increased with increasing fibrosis. Hepatic IGFBP1 mRNA was inversely associated with glycemia and insulin resistance, with opposite relationships present for IGFBP3 and IGFBP7. GHRH increased circulating IGFBP-1 and IGFBP-3, but decreased IGFBP-2 and IGFBP-6. Conclusions These data demonstrate novel relationships of IGF-1 and IGFBPs with NAFLD severity and glucose control, with divergent roles seen for different IGFBPs. Moreover, the data provide new information on the complex effects of GHRH on IGFBPs.

On February 7, News Corp's Fox Sports World remakes itself into an all-soccer-all-the-time channel. Fox Soccer Channel, which will have distribution in about 20 million homes, is aimed at those 18 million people in the US who participate in the sport and the fans who like to watch. promoters believe there was a hole in the market and the timing is right to launch a dedicated channel. The channel, which will be rebranded, with new logos, on-air graphics, music and schedule, will air games from around the world, devoting 80% of its schedule to game play. Cable is increasingly an important revenue source for Fox.

Traditional kid marketers, such as toy makers and snack conglomerates, are spending record amounts of money to reach young consumers. And auto marketers, retailers, hotel chains and tourism bureaus are leaping into the fray. Total spending on kid destinations such as Nickelodeon, Cartoon Network, Kids WB, and Fox's weekly Fox Box program block will eclipse $1 billion for the first time ever, several executives predict. That figure is up about 15% over last year. Advertisers such as the Build-A-Bear and JCPenney retail chains, hoteliers such as Holiday Inn and Embassy Suites, and the Cayman Islands tourism board are spending on Nickelodeon for the first time. Five auto manufacturers run ads on the cable network. Some advertisers want to speak directly to kids, not to the gatekeepers. Kids are being given more control of their own disposable income, and they are also getting brought into buying decisions as parents take them along on shopping trips.

3-Hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins) are widely prescribed. Statins may have important metabolic effects on insulin sensitivity and liver fat, but limited studies have assessed these effects by using euglycemic hyperinsulinemic clamp, stable isotopes, and 1H magnetic resonance spectroscopy (MRS) for liver fat quantification. To study the effects of pitavastatin on hepatic fat and insulin sensitivity. Six-month, double-blind, randomized, placebo-controlled trial. Academic clinical research center in Boston, Massachusetts. Overweight, insulin-resistant men aged 40 to 65 years who had not received statin therapy for ≥1 year. Pitavastatin 4 mg or placebo daily. The primary endpoints were changes in insulin sensitivity measured by euglycemic hyperinsulinemic clamp and liver fat measured by 1H MRS. Pitavastatin showed no effect on endogenous glucose production (ΔRa glucose 0.07 ± 0.07 vs 0.04 ± 0.07 mg/kg/min, pitavastatin vs placebo, P = 0.76) or insulin-stimulated glucose uptake during \"low dose\" (ΔM 0.1 ± 0.1 vs -0.3 ± 0.2 mg/kg/min, P = 0.11) and \"high dose\" (ΔM -0.5 ± 0.3 vs -0.7 ± 0.4 mg/kg/min, P = 0.70) euglycemic hyperinsulinemic clamps. There was also no effect of pitavastatin on fasting glucose, HbA1c, and 2-hour glucose after 75-g glucose challenge. There was also no change in liver fat fraction (-1 ± 1 vs -0 ± 1%, P = 0.56). Compared with placebo, pitavastatin did not affect hepatic or whole-body insulin sensitivity, and it did not reduce liver fat.

Abstract Context HIV-infected individuals demonstrate increased renin-angiotensin-aldosterone system activation in association with visceral adiposity, insulin resistance, and inflammation. A physiologically based treatment approach targeting mineralocorticoid receptor (MR) blockade may improve metabolic and inflammatory indices in HIV. Objective To investigate effects of eplerenone on insulin sensitivity, inflammatory indices, and other metabolic parameters in HIV. Design Six-month, double-blind, randomized, placebo-controlled trial. Setting Academic clinical research center. Participants HIV-infected individuals with increased waist circumference and abnormal glucose homeostasis. Intervention Eplerenone 50 mg or placebo daily. Outcome The primary end point was change in insulin sensitivity measured by the euglycemic-hyperinsulinemic clamp technique. Secondary end points included change in body composition and inflammatory markers. Results Forty-six individuals were randomized to eplerenone (n = 25) vs placebo (n = 21). Eplerenone did not improve insulin sensitivity [0.48 (−1.28 to 1.48) vs 0.43 (−1.95 to 2.55) mg/min/μIU/mL insulin; P = 0.71, eplerenone vs placebo] when measured by the gold standard euglycemic-hyperinsulinemic clamp technique. Intramyocellular lipids (P = 0.04), monocyte chemoattractant protein-1 (P = 0.04), and high-density lipoprotein (P = 0.04) improved among those randomized to eplerenone vs placebo. Trends toward decreases in interleukin-6 (P = 0.10) and high-sensitivity C-reactive protein (P = 0.10) were also seen with eplerenone vs placebo. Plasma renin activity and aldosterone levels increased in the eplerenone vs placebo-treated group, demonstrating expected physiology. MR antagonism with eplerenone was well tolerated among the HIV population, with no considerable changes in blood pressure or potassium. Conclusion MR blockade may improve selected metabolic and inflammatory indices in HIV-infected individuals. Further studies are necessary to understand the clinical potential of MR antagonism in HIV. Six months of eplerenone vs placebo has neutral effects on insulin sensitivity and improves metabolic (intramyocellular lipids and HDL) and inflammatory (MCP-1) indices among HIV-infected individuals.

NAFLD is a leading comorbidity in HIV with an exaggerated course compared to the general population. Tesamorelin has been demonstrated to reduce liver fat and prevent fibrosis progression in HIV-associated NAFLD. We further showed that tesamorelin downregulated hepatic gene sets involved in inflammation, tissue repair, and cell division. Nonetheless, effects of tesamorelin on individual plasma proteins pertaining to these pathways are not known. Leveraging our prior randomized-controlled trial and transcriptomic approach, we performed a focused assessment of 9 plasma proteins corresponding to top leading edge genes within differentially modulated gene sets. Tesamorelin led to significant reductions in vascular endothelial growth factor A (VEGFA, log 2 -fold change − 0.20 ± 0.35 vs. 0.05 ± 0.34, P  = 0.02), transforming growth factor beta 1 (TGFB1, − 0.35 ± 0.56 vs. − 0.05 ± 0.43, P  = 0.05), and macrophage colony stimulating factor 1 (CSF1, − 0.17 ± 0.21 vs. 0.02 ± 0.20, P  = 0.004) versus placebo. Among tesamorelin-treated participants, reductions in plasma VEGFA ( r  = 0.62, P  = 0.006) and CSF1 ( r  = 0.50, P  = 0.04) correlated with a decline in NAFLD activity score. Decreases in TGFB1 ( r  = 0.61, P  = 0.009) and CSF1 ( r  = 0.64, P  = 0.006) were associated with reduced gene-level fibrosis score. Tesamorelin suppressed key angiogenic, fibrogenic, and pro-inflammatory mediators. CSF1, a regulator of monocyte recruitment and activation, may serve as an innovative therapeutic target for NAFLD in HIV. Clinical Trials Registry Number: NCT02196831