These results identify the primary sources and inflammatory triggers for the enhancement of sST2 secretion and demonstrate a relationship between inflammation and the secretion of a bioactive member of the IL-1R family, both in vitro and in vivo.
Short-term intravenous dosing of liposomal curcumin appears to be safe up to a dose of 120 mg/m2. Changes in red blood cell morphology may represent a dose limiting sign of toxicity.
Objective: To stop smoking is commonly associated with significant weight gain, but the mechanisms for this are poorly understood. We assessed the effects of smoking cessation on body weight, insulin sensitivity, b-cell function, and appetite. Subjects and methods: Twenty-seven long-term smokers (nZ27; nine females/18 males, 28G1 years, 22.9G0.6 kg/m 2 )attending an ambulatory smoking cessation program in a community hospital in Vienna, Austria were examined at baseline (Visit A; still smoking) and after a minimum of 3 months of smoking abstinence (Visit B; nZ14); relapsed smokers were not followed up. Participants underwent 3-h oral glucose tolerance tests and body composition measurements at each study visit. Fasting (QUICKI) and dynamic (oral glucose insulin sensitivity (OGIS)) insulin sensitivity and b-cell secretion (insulinogenic index 140 (IGI40)) were calculated. Food intake was quantified with a free choice buffet. Fasting plasma concentrations of neuropeptide-Y (NPY), peptide-YY (PYY), glucagon-like peptide 1 (GLP1), leptin, ghrelin, and visfatin were measured. Results: After O3 months' smoking abstinence, body weight, and fat mass were increased (C4 and C22% respectively, P!0.05) and fasting insulin sensitivity deteriorated (QUICKI: post, 0.37G0.02 vs baseline, 0.41G0.2; P!0.05), while OGIS remained unchanged throughout. IGI40 increased by 31% after O3 months' smoking abstinence (P!0.01). Carbohydrate ingestion increased after stopping smoking (P!0.05). NPY fasting levels were increased after O3 months (P!0.05), PYY, GLP1, leptin, ghrelin, and visfatin were unchanged. Conclusion: Smoking cessation is associated with transient metabolic changes including increased b-cell secretion in response to glucose and fasting insulin resistance. These alterations may be associated with or contribute to the body weight gain after smoking cessation.
Our data confirm agonism of telmisartan, valsartan and lisinopril on PPARgamma. Pharmacokinetic differences may explain different potencies of PPARgamma stimulation by drugs acting on the renin-angiotensin system in clinical settings.
Developing effective therapies against chronic wound healing deficiencies is a global priority. Thus we evaluated the safety of two different doses of topically administered autologous APOSEC, the secretome of apoptotic peripheral blood mononuclear cells (PBMCs), in healthy male volunteers with artificial dermal wounds. Ten healthy men were enrolled in a single-center, randomized, double-blinded, placebo-controlled phase 1 trial. Two artificial wounds at the upper arm were generated using a 4-mm punch biopsy. Each participant was treated with both topically applied APOSEC and placebo in NuGel for 7 consecutive days. The volunteers were randomized into two groups: a low-dose group (A) receiving the supernatant of 12.5 × 106 PBMCs and a high-dose group (B) receiving an equivalent of 25 × 106 PBMCs resuspended in NuGel Hydrogel. Irradiated medium served as placebo. The primary outcome was the tolerability of the topical application of APOSEC. All adverse events were recorded until 17 days after the biopsy. Local tolerability assessment was measured on a 4-point scale. Secondary outcomes were wound closure and epithelization at day 7. No therapy-related serious adverse events occurred in any of the participants, and both low- and high-dose treatments were well tolerated. Wound closure was not affected by APOSEC therapy.
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