Mechanistic insights of the controlled release capacity of polar functional group in transdermal drug delivery system: the relationship of hydrogen bonding strength and controlled release capacity

BackgroundHydrogen bonding interaction was considered to play a critical role in controlling drug release from transdermal patch. However, the quantitative evaluation of hydrogen bonding strength between drug and polar functional group was rarely reported, and the relationship between hydrogen bonding strength and controlled release capacity of pressure sensitive adhesive (PSA) was not well understood. The present study shed light on this relationship.MethodsAcrylate PSAs with amide group were synthesized by a free radical-initiated solution polymerization. Six drugs, i.e., etodolac, ketoprofen, gemfibrozil, zolmitriptan, propranolol and lidocaine, were selected as model drugs. In vitro drug release and skin permeation experiments and in vivo pharmacokinetic experiment were performed. Partial correlation analysis, fourier-transform infrared spectroscopy and molecular simulation were conducted to provide molecular details of drug-PSA interactions. Mechanical test, rheology study, and modulated differential scanning calorimetry study were performed to scrutinize the free volume and molecular mobility of PSAs.ResultsRelease rate of all six drugs from amide PSAs decreased with the increase of amide group concentrations; however, only zolmitriptan and propranolol showed decreased skin permeation rate. It was found that drug release was controlled by amide group through hydrogen bonding, and controlled release extent was positively correlated with hydrogen bonding strength.ConclusionFrom these results, we concluded that drugs with strong hydrogen bond forming ability and high skin permeation were suitable to use amide PSAs to regulate their release rate from patch.     

Pro-caspase-3 is constitutively expressed in luteinized granulosa cells from women undergoing controlled ovarian stimulation for in vitro fertilization

Apoptosis regulation in luteinized granulosa cells (LGC) during assisted reproduction procedures is still controversial. Caspase-3 is a major apoptosis mediator encoded by CASP3 and formed through cleavage of its precursor pro-caspase-3. The aim of this study was to investigate the expression patterns of pro-caspase-3 (mRNA and protein) and cleaved caspase-3 in human LGC. Thirty-five women undergoing controlled ovarian stimulation for in vitro fertilization were prospectively enrolled in the study. LGC were isolated from follicular fluid during oocyte pickup and evaluated by immunocytochemistry for pro-caspase-3 and cleaved caspase-3, and by real-time PCR for CASP3 mRNA expression. We found a positive staining of pro-caspase-3 in 77 % of the LGC (95 % confidence interval [CI] 60%–84%), whereas cleaved caspase-3 was found in only 4% of the cells (95 % CI 3%–6%). The abundance of cells expressing pro-caspase-3 was independent from CASP3 mRNA levels (r = 0.24, p = 0.255) and did not correlate with the amount of cleaved caspase-3 (r = -0.24, p = 0.186). Multivariable logistic regression showed that pro-caspase-3 positivity was not influenced by clinical characteristics such as age, cause or length of infertility, antral follicle count or hormonal drugs used to induce ovulation. These findings suggest that pro-caspase-3 is constitutively expressed in LGC, allowing quick cleavage into active caspase-3 and apoptosis triggering whenever needed in the course of gonadotropin-induced follicular development.     

Marks caused by the scavenging activity of Necrobia rufipes (Coleoptera: Cleridae) under laboratory conditions

Insects are an important group involved in carrion consumption and are thus of forensic interest. In the laboratory we studied the taphonomic marks that Necrobia rufipes (Cleridae) can produce. Pig trotters were exposed to adult beetles at 21 ± 3 °C and 12:12 h day/night cycle. We made observations and took photographs every 4–5 days for 12 months. Marks were noted after a month. We found scratches, pits, holes, and tunnels in several kinds of tissue such as integumental, connective and muscular. This work contributes preliminary data of significant application in biology, ecology, anthropology and forensics. Until now, no study has provided taphonomic information with N. rufipes.     

Prevention of unhealthy weight in children by promoting physical activity using a socio-ecological approach: What can we learn from intervention studies?

AimOur objectives was to identify the characteristics of interventions likely to successfully prevent overweight in youngsters by promoting physical activity (PA), with special focus on dimensions of the socio-ecological model of behaviour and health, and unresolved issues.MethodsThis was a systematic review of population-based interventions either promoting PA or limiting sedentary behaviour in children with measure of weight status as an endpoint. The efficacy of studies was evaluated according to the levels of PA determinants in the socio-ecological model (individual, interpersonal, institutional environment, community) targeted by the interventions.ResultsA total of 54 studies met our inclusion criteria, most of them published within the last 5 years and targeting children aged 6–12 years. Twenty-three interventions targeted individual and/or interpersonal PA determinants only; 26 targeted determinants at three or four levels with at least one environment component at the institutional level; and five were multilevel community-based interventions. Our review indicated that programmes targeting PA determinants at the different levels of the socio-ecological model, including the social and organizational/built environments, had the greatest potential for preventing obesity in youngsters. Targeting various facets of PA, including everyday PA, might represent another key element for program efficacy on weight status.ConclusionData regarding the efficacy of comprehensive PA interventions that simultaneously address individual attitudes and skills, the social context, and the environment, to prevent overweight in children are encouraging. Further studies are needed to evaluate the maintenance of the effects and whether such strategies apply to young children and older adolescents, and to different cultural contexts.     

生长激素在短方案促排卵治疗中的临床应用

目的探寻生长激素对体外受精一胚胎移植中应用GnRHa短方案促排卵患者的临床价值。方法选择2010年1月至2011年5月我中心IVF—ET治疗中接受GnRHa短方案促排卵的276名患者共299个周期,72个周期有添加生长激素设为研究组,227个周期未添加生长激素设为对照组。分析比较两组一般情况、治疗情况及临床结局。结果研究组Gn用药天数略低于对照组,但Gn平均用量稍高于对照组,差异有统计学意义。两组之间获卵数、成熟卵子数、受精率、取消周期率、妊娠率均无显著性差异。活产率方面,对照组显著高于对照组。结论对于卵巢储备功能降低患者应用Gn—RHa短方案,添加生长激素虽不能改善其妊娠率,但能显著提高活产率。     

Metabolic syndrome in hypertensive patients:An unholy alliance

For many years, it has been recognized that hypertension tends to cluster with various anthropometric and metabolic abnormalities including abdominal obesity, elevated triglycerides, reduced high-density lipoprotein cholesterol, glucose intolerance, insulin resistance and hyperuricemia. This constellation of various conditions has been transformed from a pathophysiological concept to a clinical entity, which has been defined metabolic syndrome(MetS). The consequences of the MetS have been difficult to assess without commonly accepted criteria to diagnose it. For this reason, on 2009 the International Diabetes Federation, the American Heart Association and other scientific organizations proposed a unified MetS definition. The incidence of the MetS has been increasing worldwide in parallel with an increase in overweight and obesity. The epidemic proportion reached by the MetS represents a major public health challenge, because several lines of evidence showed that the MetS, even without type 2 diabetes, confers an increased risk of cardiovascular morbidity and mortality in different populations including also hypertensive patients. It is likely that the enhanced cardiovascular risk associated with MetS in patients with high blood pressure may be largely mediated through an increased prevalence of preclinical cardiovascular and renal changes, such as left ventricular hypertrophy, early carotid atherosclerosis, impaired aortic elasticity, hypertensive retinopathy and microalbuminuria. Indeed, many reports support this notion, showing that hypertensive patients with MetS exhibit, more often than those without it, these early signs of end organ damage, most of which are recognized as significant independent predictors of adverse cardiovascular outcomes.     

选择性激光熔化技术在口腔医学中的应用

选择性激光熔化（Selective laser melting,SLM）技术是一种快速成型技术,它以其制作方便、快捷、产品组织结构密度高、精度高、避免传统加工方式原材料浪费等优点,被逐渐运用于各个行业。然而,在口腔医学中的应用还报道较少,主要集中在冠桥修复、可摘局部义齿支架、骨替代物及生物植片等方面。本文介绍了SLM技术的原理,分类以及在口腔医学中的应用特点和前景。