Short-term physical inactivity impairs vascular function.

BACKGROUND: Sedentarism, also termed physical inactivity, is an independent risk factor for cardiovascular diseases. Mechanisms thought to be involved include insulin resistance, dyslipidemia, hypertension, and increased inflammation. It is unknown whether changes in vascular and endothelial function also contribute to this excess risk. We hypothesized that short-term exposure to inactivity would lead to endothelial dysfunction, arterial stiffening, and increased vascular inflammation. METHODS: Five healthy subjects (four men and one woman) underwent 5 d of bed rest (BR) to simulate inactivity. Measurements of vascular function (flow-mediated vasodilation to evaluate endothelial function; applanation tonometry to assess arterial resistance), inflammation, and metabolism were made before BR, daily during BR, and 2 d after BR recovery period. Subjects maintained an isocaloric diet throughout. RESULTS: BR led to significant decreases in brachial artery and femoral artery flow-mediated vasodilation (brachial: 11 ± 3% pre-BR versus 9 ± 2% end-BR, P = 0.04; femoral: 4 ± 1% versus 2 ± 1%, P = 0.04). The central augmentation index increased with BR (-4 ± 9% versus 5 ± 11%, P = 0.03). Diastolic blood pressure increased (58 ± 7 mm Hg versus 62 ± 7 mm Hg, P = 0.02), whereas neither systolic blood pressure nor heart rate changed. 15-Hydroxyeicosatetraenoic acid, an arachidonic acid metabolite, increased but the other inflammatory and metabolic biomarkers were unchanged. CONCLUSIONS: Our findings show that acute exposure to sedentarism results in decreased endothelial function, arterial stiffening, increased diastolic blood pressure, and an increase in 15-hydroxyeicosatetraenoic acid. We speculate that inactivity promotes a vascular "deconditioning" state characterized by impaired endothelial function, leading to arterial stiffness and increased arterial tone. Although physiologically significant, the underlying mechanisms and clinical relevance of these findings need to be further explored.

3-Methoxybutan-2-one as a sustainable bio-based alternative to chlorinated solvents.

Methylation of acetoin with dimethyl carbonate was performed in a sustainable one-step process, with improved process mass intensity (PMI) and atom economy compared to previously published methods. The resulting product, 3-methoxybutan-2-one (MO) was successfully evaluated as a bio-based solvent, while both Kamlet-Taft solvatochromic parameters and Hansen solubility parameters demonstrate its potential viability in the substitution of chlorinated solvents. MO exhibited a low peroxide forming potential and a negative Ames mutagenicity test and was successfully used as a solvent in a Friedel-Crafts acylation (79% yield compared to 77% in dichloromethane) and for N-alkylations. MO is a renewable oxygenated solvent, with the potential ability to substitute carcinogenic halogenated solvents in some applications.

Moderate statin treatment reduces prebeta-1 high-density lipoprotein levels in dyslipidemic patients.

BACKGROUND: Elevated plasma levels of prebeta-1 high-density lipoprotein (HDL), the principal acceptor of cholesterol effluxed from macrophages, are associated with increased risk of atherosclerotic coronary heart disease and myocardial infarction. OBJECTIVE: The objective of the study was to assess the effects on prebeta-1 HDL levels of 6-week moderate-dose statin treatment. METHODS: We studied 101 patients (mean age 52.7 years; 53.5% female; 63 with primary hypercholesterolemia; 38 with combined hyperlipidemia) before and after treatment with statins. Mean atorvastatin potency equivalence was 23.6 mg/d. Prebeta-1 HDL plasma levels were measured by immunofixation of agarose gels using anti-apolipoprotein A-1 antibody. RESULTS: We observed a 42.0% reduction of low-density lipoprotein cholesterol (181 ± 56 vs 105 mg/dL, P < .001). Triglyceride (TG) levels decreased by 22.3% (157 vs 122 mg/dL, P < .001), HDL cholesterol levels remained similar (56.0 vs 57.1, P = NS). Levels of prebeta-1 HDL were significantly reduced by 17.9% after statin treatment (mean 11.4 vs 9.4 mg apoA-1/dL, P < .001). The magnitude of this decrease was similar with each of 3 statins (atorvastatin, simvastatin, and rosuvastatin). The decrease in prebeta-1 HDL was strongly associated with the decline in TG, but not with the decline in low-density lipoprotein cholesterol. CONCLUSIONS: The association of high prebeta-1 HDL with coronary heart disease identifies it as an inferential measure of the rate of cholesterol efflux from the artery wall. Our observations demonstrate a reduction of prebeta-1 HDL with statin therapy, partially reflecting the reduced TGs, and probably reflecting a direct beneficial impact on cholesterol efflux.

The ends of a continuum: genetic and temperature-dependent sex determination in reptiles.

Two prevailing paradigms explain the diversity of sex-determining modes in reptiles. Many researchers, particularly those who study reptiles, consider genetic and environmental sex-determining mechanisms to be fundamentally different, and that one can be demonstrated experimentally to the exclusion of the other. Other researchers, principally those who take a broader taxonomic perspective, argue that no clear boundaries exist between them. Indeed, we argue that genetic and environmental sex determination in reptiles should be seen as a continuum of states represented by species whose sex is determined primarily by genotype, species where genetic and environmental mechanisms coexist and interact in lesser or greater measure to bring about sex phenotypes, and species where sex is determined primarily by environment. To do otherwise limits the scope of investigations into the transition between the two and reduces opportunities to use studies of reptiles to advance understanding of vertebrate sex determination generally.