Vascular effects of estrogen in type II diabetic postmenopausal women

AbstractOBJECTIVESWe assessed the effects of estrogen on vascular dilatory and other homeostatic functions potentially affected by nitric oxide (NO)-potentiating properties in type II diabetic postmenopausal women.BACKGROUNDThere is a higher cardiovascular risk in diabetic women than in nondiabetic women. This would suggest that women with diabetes do not have the cardioprotection associated with estrogen.METHODSWe administered placebo or conjugated equine estrogen, 0.625 mg/day for 8 weeks, to 20 type II diabetic postmenopausal women in a randomized, double-blinded, placebo-controlled, cross-over design.RESULTSCompared with placebo, estrogen tended to lower low-density lipoprotein (LDL) cholesterol levels by 15 ± 23% (p = 0.007) and increase high-density lipoprotein (HDL) cholesterol levels by 8 ± 16% (p = 0.034). Thus, the ratio of LDL to HDL cholesterol levels significantly decreased with estrogen, by 20 ± 24%, as compared with placebo (p = 0.001). Compared with placebo, estrogen tended to increase triglyceride levels by 16 ± 48% and lower glycosylated hemoglobin levels by 3 ± 13% (p = 0.295 and p = 0.199, respectively). However, estrogen did not significantly improve the percent flow-mediated dilatory response to hyperemia (17 ± 75% vs. placebo; p = 0.501). The statistical power to accept our observation was 81.5%. Compared with placebo, estrogen did not significantly change E-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1 or matrix metalloproteinase-9 levels. Compared with placebo, estrogen tended to decrease tissue factor antigen and increase tissue factor activity levels by 7 ± 46% and 5 ± 34%, respectively (p = 0.321 and p = 0.117, respectively) and lower plasminogen activator inhibitor-1 levels by 16 ± 31% (p = 0.043).CONCLUSIONSThe effects of estrogen on endothelial, vascular dilatory and other homeostatic functions were less apparent in type II diabetic postmenopausal women, despite the beneficial effects of estrogen on lipoprotein levels

Efficacy and safety of rapid intermittent correction compared with slow continuous correction with hypertonic saline in patients with moderately severe or severe symptomatic hyponatremia: study protocol for a randomized controlled trial (SALSA trial)

Abstract Background Hyponatremia is the most common electrolyte imbalance encountered in clinical practice, associated with increased mortality and length of hospital stay. However, no high-quality evidence regarding whether hypertonic saline is best administered as a continuous infusion or a bolus injection has been found to date. Therefore, in the current study, we will evaluate the efficacy and safety of rapid intermittent correction compared with slow continuous correction with hypertonic saline in patients with moderately severe or severe symptomatic hyponatremia. Methods/design This is a prospective, investigator-initiated, multicenter, open-label, randomized controlled study with two experimental therapy groups. A total of 178 patients with severe symptomatic hyponatremia will be enrolled and randomly assigned to receive either rapid intermittent bolus or slow continuous infusion management with hypertonic saline. The primary outcome is the incidence of overcorrection at any given period over 2 days. The secondary outcomes will include the efficacy and safety of two other approaches to the treatment of hyponatremia with 3% hypertonic saline. Discussion This is the first clinical trial to investigate the efficacy and safety of rapid intermittent correction compared with slow continuous correction with hypertonic saline in patients with moderately severe or severe hyponatremia. Trial registration ClinicalTrials.gov, identifier number: NCT02887469 . Registered on 1 August 2016

Android Fat Depot Is More Closely Associated with Metabolic Syndrome than Abdominal Visceral Fat in Elderly People

BACKGROUND: Fat accumulation in android compartments may confer increased metabolic risk. The incremental utility of measuring regional fat deposition in association with metabolic syndrome (MS) has not been well described particularly in an elderly population. METHODS AND FINDINGS: As part of the Korean Longitudinal Study on Health and Aging, which is a community-based cohort study of people aged more than 65 years, subjects (287 male, 75.9±8.6 years and 278 female, 76.0±8.8 years) with regional body composition data using Dual energy X-ray absorptiometry for android/gynoid area, computed tomography for visceral/subcutaneous adipose tissue (VAT/SAT), and cardiometabolic markers including adiponectin and high-sensitivity CRP were enrolled. We investigated the relationship between regional body composition and MS in multivariate regression models. Mean VAT and SAT area was 131.4±65.5 cm(2) and 126.9±55.2 cm(2) in men (P = 0.045) and 120.0±46.7 cm(2) and 211.8±65.9 cm(2) in women (P<0.01). Mean android and gynoid fat amount was 1.8±0.8 kg and 2.5±0.8 kg in men and 2.0±0.6 kg and 3.3±0.8 kg in women, respectively (both P<0.01). VAT area and android fat amount was strongly correlated with most metabolic risk factors compared to SAT or gynoid fat. Furthermore, android fat amount was significantly associated with clustering of MS components after adjustment for multiple parameters including age, gender, adiponectin, hsCRP, a surrogate marker of insulin resistance, whole body fat mass and VAT area. CONCLUSIONS: Our findings are consistent with the hypothesized role of android fat as a pathogenic fat depot in the MS. Measurement of android fat may provide a more complete understanding of metabolic risk associated with variations in fat distribution

Enhanced heat transfer is dependent on thickness of graphene films: the heat dissipation during boiling

Boiling heat transfer (BHT) is a particularly efficient heat transport method because of the latent heat associated with the process. However, the efficiency of BHT decreases significantly with increasing wall temperature when the critical heat flux (CHF) is reached. Graphene has received much recent research attention for applications in thermal engineering due to its large thermal conductivity. In this study, graphene films of various thicknesses were deposited on a heated surface, and enhancements of BHT and CHF were investigated via pool-boiling experiments. In contrast to the well-known surface effects, including improved wettability and liquid spreading due to micron-and nanometer-scale structures, nanometer-scale folded edges of graphene films provided a clue of BHT improvement and only the thermal conductivity of the graphene layer could explain the dependence of the CHF on the thickness. The large thermal conductivity of the graphene films inhibited the formation of hot spots, thereby increasing the CHF. Finally, the provided empirical model could be suitable for prediction of CHF.open111522Nsciescopu

Snake fang-inspired stamping patch for transdermal delivery of liquid formulations

A flexible microneedle patch that can transdermally deliver liquid-phase therapeutics would enable direct use of existing, approved drugs and vaccines, which are mostly in liquid form, without the need for additional drug solidification, efficacy verification, and subsequent approval. Specialized dissolving or coated microneedle patches that deliver reformulated, solidified therapeutics have made considerable advances; however, microneedles that can deliver liquid drugs and vaccines still remain elusive because of technical limitations. Here, we present a snake fang-inspired microneedle patch that can administer existing liquid formulations to patients in an ultrafast manner (&lt; 15 s). Rear-fanged snakes have an intriguing molar with a groove on the surface, which enables rapid and efficient infusion of venom or saliva into prey. Liquid delivery is based on surface tension and capillary action. The microneedle patch uses multiple open groove architectures that emulate the grooved fangs of rear-fanged snakes: Similar to snake fangs, the microneedles can rapidly and efficiently deliver diverse liquid-phase drugs and vaccines in seconds under capillary action with only gentle thumb pressure, without requiring a complex pumping system. Hydrodynamic simulations show that the snake fang-inspired open groove architectures enable rapid capillary force-driven delivery of liquid formulations with varied surface tensions and viscosities. We demonstrate that administration of ovalbumin and influenza virus with the snake fang-inspired microneedle patch induces robust antibody production and protective immune response in guinea pigs and mice