Intestinal permeability of mitragynine in rats using in situ absorption model

The intestinal permeability of mitragynine was investigated in situ using a single pass intestinal perfusion (SPIP) absorption model, in small intestine of rat using mitragynine in the absence/presence of the permeability markers, P-gp and/or CYP3A4 inhibitors. Mitragynine demonstrated high intestinal permeability (P_eff of 1.11 × 10^?4 cm/s) that is in the range of highly permeable drugs such as propranolol (P_eff of 1.27 × 10^?4 cm/s) indicating that it readily crosses the intestine. The addition of azithromycin (P-glycoprotein inhibitor) and ciprofloxacin (CYP3A4 inhibitor) or combination of both has no effect on intestinal permeability of mitragynine across the rat small intestine.     

“药妆品”全球监管情况以及对我国的启示

目的：梳理全球范围内"药妆品"监管情况，并对我国政府监管和行业发展提出建议。方法：选取化妆品生产和消费的主要国家或地区作为研究对象，如欧盟、美国、日本、韩国、加拿大等。通过对我国以及上述国家或地区的化妆品定义、相关产品分类、是否承认"药妆品"等情况进行研究比对，对其中容易造成错误理解的概念进行阐释，结合近年来相关问题的监管手段及监管趋势进行分析，总结出适合我国国情的监管建议。结果：通过研究比对，"药妆品"概念不符合大多数国家或地区关于"化妆品"的定义及相关法规要求，监管部门对此持相对谨慎态度，并采取了多种监管手段。结论："药妆品"在全球范围内基本不具有合法地位，我国监管部门应继续保持打击力度，加强上市后监督检查；同时，进一步规范产品分类和功效宣称，积极引导整个行业长期健康发展。     

Biopharmaceutics classification and intestinal absorption of chikusetsusaponin IVa

The objective of this study was to investigate the absorption behavior of chikusetsusaponin IVa (CHS‐IVa) in the rat intestine using single‐pass intestinal perfusion (SPIP) and to classify CHS‐IVa into the biopharmaceutics classification system (BCS). The equilibrium solubility of CHS‐IVa was determined by the shaker method. The absorption mechanism of CHS‐IVa in the intestine was studied by comparing the P_eff of different concentrations of CHS‐IVa. The intestinal site dependence of CHS‐IVa absorption was studied by comparing the P_eff of the same concentration of CHS‐IVa in different intestinal segments. The relationship between CHS‐IVa and intestinal efflux protein was studied by perfusion with an efflux protein inhibitor. The permeability of CHS‐IVa was investigated by comparing the P_eff of CHS‐IVa and the reported value. The solubility of CHS‐IVa over the pH range 1.0–7.5 was 14.4 ± 0.29 to 16.9 ± 0.34 mg/ml. The P_eff of CHS‐IVa in the duodenum was 1.76 × 10^?3 to 2.00 × 10^?3 cm/min. The P_eff of CHS‐IVa in the jejunum was 1.26 × 10^?3 to 1.39 × 10^?3 cm/min. The P_eff of CHS‐IVa in the ileum was 1.25 × 10^?3 to 1.31 × 10^?3 cm/min. The P_eff of CHS‐IVa in the colon was 1.02 × 10^?3 to 1.08 × 10^?3 cm/min. There was no statistical difference of the P_eff in the four segments at different CHS‐IVa concentrations. The P_eff of CHS‐IVa (0.07, 0.7 and 7.0 mg/ml) were all notably smaller than the reported P_eff (3.00 × 10^?3 cm/min) in the jejunum. The P_eff of CHS‐IVa was not influenced by verapamil (P‐gp inhibitor), indomethacin (MRP inhibitor) and pantoprazole (BCRP inhibitor). CHS‐IVa was classified as high solubility, low permeability and BCS III. The main absorptive tracts were the upper intestinal tracts and the rank order of intestinal permeability was duodenum > jejunum ≈ ileum > colon. The transport mechanism of CHS‐IVa in all intestinal segments might be primarily passive transport. CHS‐IVa was not a substrate of P‐gp, MRP and BCRP.     

药物性肝损伤生物标志物

生物标志物是源于机体器官、组织、细胞、亚细胞器中的标志性和(或)功能性分子,可以标记器官、组织、细胞及亚细胞结构或功能的改变。药物性肝损伤(DILI)一般会临床表型几乎涉及所有急慢性肝脏疾病,其发生发展过程的动态监控一直是基础和应用药理学研究领域面临的巨大挑战。除了传统的ALT,ASP,AST等指标外,目前许多新型生物分子作为生物标志物被报道,组学技术的发展也为DILI检测提供了更多的生物标志物分子,本文综述了导致肝损伤的药物类型,并对肝损伤的生物标志物进行综述,为DILI的研究提供选择和指导。     

Various classes of removable partial dentures: A study of prevalence among patients attending a dental and educational institute in Riyadh,Saudi Arabia

PurposeKnowledge about the most prevalent types of Kennedy classifications is of great value and will enlighten dental students, dental technicians, and practitioners regarding the treatment needs of their patients, ultimately leading to better treatment outcomes. The aim was to determine the prevalence of various Kennedy classifications among patients attending clinics at the College of Dentistry at King Saud bin Abdulaziz University for Health Sciences and King Abdulaziz Dental Center, National Guard Health Affairs, who were seeking treatment for partial edentulism.MethodsAn observational cross-sectional study was conducted by visualizing cast models for partially edentulous patients. Kennedy classification, age, gender, and treatment design were recorded from the lab request sheets that were attached to the casts in the labs at both the College of Dentistry at King Saud bin Abdulaziz University for Health Sciences and King Abdulaziz Dental Center, National Guard Health Affairs. The statistical analyses were performed with SPSS version 20.0 utilizing frequency and Pearson’s and Spearman’s correlation tests.ResultsKennedy Class I (45.0%) was the most prevalent pattern in both dental arches, followed by Class III (26.2%). Next was Class II (23.3%), while Class IV was the least prevalent (5.4%).ConclusionKennedy Class I was the most noted classification in our patient population. As age increases, there is an increased tendency toward Class I and II.     

Kienböck's disease: pathophysiology,classification and treatment of this insidious condition

Kienböck's disease is the result of avascular necrosis of the lunate. Whilst no causal aetiology has been identified, several factors have been found to show an association with the condition. These include anatomical aspects such as lunate morphology; wrist biomechanics and vascular supply patterns, which in combination with external influences such as repetitive trauma, maybe a potential cause of the condition. Diagnosis and assessment of severity has historically been made using plain radiographs to stage the condition, however other assessment modalities such as magnetic resonance imaging and direct visualization with wrist arthroscopy have been advocated. Lichtman has sought to amalgamate these diagnostic techniques into a new comprehensive staging tool with the aim of better standardizing and guiding treatment. Whilst no single treatment has been proven to improve the natural outcome of the disease, current recognized treatments, in general, aim to protect the compromised lunate in the early stage of the condition, whilst in the later stages the focus shifts to procedures that either bypass, fuse or excise the affected peri-lunate articulations.     

Do adolescents with cerebral palsy agree with their caregivers on their participation and quality of life?

Background

It is important to determine the quality of life (QoL) and level of participation in children with Cerebral Palsy (CP). Previous research has used reports from adolescents or caregivers, but there is no evidence that caregivers' reports accurately reflect the experiences of the adolescents they are interested in.