Effectiveness and safety profiling of zolpidem and acupressure in CKD associated pruritus: An interventional study

Background:Chronic kidney disease (CKD)-associated pruritus (CKD-aP) contributes to poor quality of life, including reduced sleep quality and poor sleep quality is a source of patient stress and is linked to lower health-related quality of life. This study aimed to investigate the effectiveness of zolpidem 10 mg and acupressure therapy on foot acupoints to improve the sleep quality and overall quality of life among hemodialysis patients suffering from CKD-aP.Method:A multicenter, prospective, randomized, parallel-design, open label interventional study to estimate the effectiveness of zolpidem (10 mg) oral tablets versus acupressure on sleep quality and quality of life in patients with CKD-aP on hemodialysis. A total of 58 hemodialysis patients having sleep disturbance due to CKD-aP completed the entire 8-week follow-up. The patients were divided into a control (acupressure) group of 28 patients and an intervention (zolpidem) group of 30 patients.Results:A total of 58 patients having CKD-aP and sleep disturbance were recruited. In the control group there was a reduction in the PSQI score with a mean ± SD from 12.28 ± 3.59 to 9.25 ± 3.99, while in the intervention group the reduction in PSQI score with a mean ± SD was from 14.73 ± 4.14 to 10.03 ± 4.04 from baseline to endpoint. However, the EQ5D index score and EQ-visual analogue scale (VAS) at baseline for the control group with a mean ± SD was 0.49 ± 0.30 and 50.17 ± 8.65, respectively, while for the intervention group the values were 0.62 ± 0.26 and 47.17 ± 5.82, respectively. The mean EQ5D index score in the control group improved from 0.49 ± 0.30 to 0.53 ± 0.30, but in the intervention group there was no statistical improvement in mean EQ5D index score from 0.62 ± 0.26 to 0.62 ± 0.27 from baseline to week 8. The EQ 5D improved in both groups and the EQ-VAS score was 2.67 points higher at week 8 as compared to baseline in the control group, while in the intervention group the score was 3.33 points higher at week 8 as compared to baseline. Comparing with baseline, the PSQI scores were significantly reduced after week 4 and week 8 (P =  < .001). Furthermore, at the end of the study, the PSQI scores were significantly higher in the control as compared to the intervention group (P = .012).Conclusion:An improvement in sleep quality and quality of life among CKD-aP patients on hemodialysis has been observed in both the control and intervention groups. Zolpidem and acupressure safety profiling showed no severe adverse effect other that drowsiness, nausea and daytime sleeping already reported in literature of zolpidem.     

Enhancement of cellular uptake,transport and oral absorption of protease inhibitor saquinavir by nanocrystal formulation

Aim:

Saquinavir (SQV) is the first protease inhibitor for the treatment of HIV infection, but with poor solubility. The aim of this study was to prepare a colloidal nanocrystal suspension for improving the oral absorption of SQV.

Methods:

SQV nanocrystals were prepared using anti-solvent precipitation–high pressure homogenization method. The nanocrystals were characterized by a Zetasizer and transmission electron microscopy (TEM). Their dissolution, cellular uptake and transport across the human colorectal adenocarcinoma cell line (Caco-2) monolayer were investigated. Bioimaging of ex vivo intestinal sections of rats was conducted with confocal laser scanning microscopy. Pharmacokinetic analysis was performed in rats administered nanocrystal SQV suspension (50 mg/kg, ig), and the plasma SQV concentrations were measured with HPLC.

Results:

The SQV nanocrystals were approximately 200 nm in diameter, with a uniform size distribution. The nanocrystals had a rod-like shape under TEM. The dissolution, cellular uptake, and transport across a Caco-2 monolayer of the nanocrystal formulation were significantly improved compared to those of the coarse crystals. The ex vivo intestinal section study revealed that the fluorescently labeled nanocrystals were located in the lamina propria and the epithelium of the duodenum and jejunum. Pharmacokinetic study showed that the maximal plasma concentration (C_max) was 2.16-fold of that for coarse crystalline SQV suspension, whereas the area under the curve (AUC) of nanocrystal SQV suspension was 1.95-fold of that for coarse crystalline SQV suspension.

Conclusion:

The nanocrystal drug delivery system significantly improves the oral absorption of saquinavir.     

Study for cerebral central network mechanism of acupuncture stimulation quantity based on changes of cerebral functional connection of fMRI

Background:Ischemic stroke is a major chronic noninfectious disease that seriously endangers health. Acupuncture is effective for ischemic stroke and less adverse reactions. However, there is not enough clinical trial data and solid evidence could confirm how acupuncture work to cerebral functional connectivity changes, and whether the changes is related to the different stimulation quantity.Design:This is a multicenter, central-randomized, controlled, double-blind, noninferiority, 2 factors and 3 levels orthogonal clinical trial. A total of 100 participants with ischemic stroke aged from 40 to 80 were randomized into experimental group and control group, the experimental group was divided into 9 groups (A1-A9) according to different factors or levels, and each group have 10 participants. The whole study period is 17 days, including 1 week for baseline observation, 3 days treatment and observation, and 1 week follow-up. Primary outcome is the fMRI based on blood oxygenation level dependent. Secondary outcomes included National Institute of Health Stroke Scale, Modified Barthel Index, Brunnstrom stroke recovery, stroke Chinese medicine symptom. Clinical assessments will be evaluated at before and the 0 hour, 24 hours, 36 hours after treatment, and 1 week follow-up. The primary outcome of the postacupuncture effect were investigated by paired T-test, and the continuous outcome variables will be analyzed with univariate repetitive measurement deviation analysis. Adverse events will be noted and recorded for the safety evaluation.Conclusion:The purpose of this study was to evaluate the central mechanism of acupuncture stimulation quantity using time and frequency as control conditions. This study will provide reasonable stimulation parameters and strong mechanism evidence of cerebral central network for the use of acupuncture for ischemic stroke.CHICTR registration number:ChiCTR1900023169. Registered 15 May 2019.     

Combined spectroscopy methods and molecular simulations for the binding properties of trametinib to human serum albumin

Trametinib is a novel anticancer drug for treating metastatic cutaneous melanoma. The present study probed into the binding of trametinib to human serum albumin (HSA) through spectroscopy methods and molecular simulations. Trametinib could quench the fluorescence of HSA through static quenching which could be probed via fluorescence spectroscopy and time-resolved fluorescence. Thermodynamic parameters and docking results indicated that hydrogen bonds and van der Waals forces play crucial roles in this binding process, which exerts almost no effect on the HSA conformation under synchronous fluorescence, three-dimensional fluorescence, circular dichroism spectra, and molecular dynamics simulations. Site marker displacement experiments and molecular docking reveal that trametinib primarily binds to Sudlow site I of HSA. In addition, the trametinib–HSA interaction was hardly influenced by varying amino acid (glutamine, alanine, glycine, and valine) concentrations. This study can provide useful information for the pharmacokinetic properties of trametinib.

Probing the binding properties of trametinib to human serum albumin.     

EGCG对去势雌性大鼠骨量丢失的预防作用

目的:研究表没食子儿茶素没食子酸酯[(-)-epigallocatechin-3-gallate,EGCG]早期预防雌性去势大鼠骨量丢失的作用?方法:12周龄雌性Sprague-Dawley大鼠分为3组:A组,双侧卵巢切除去势术后第3天开始连续12周以10 mg/(kg?d) EGCG腹腔内注射;B组,仅接受双侧卵巢切除去势术,不接受EGCG干预;C组,假手术组,不接受EGCG干预?在实验终点时刻(24周龄)制作大鼠胫骨和股骨的离体标本用于micro-CT扫描,测量骨密度(BMD)和相关骨形态学参数:松质骨骨组织总量(total bone volume,TV)?骨量(bone volume,BV)?骨体积分数?平均骨小梁厚度?平均骨小梁数量和骨小梁分离度?皮质骨厚度和皮质骨骨体积分数;并对大鼠股骨远端骨组织进行HE染色?结果:根据micro-CT分析,A组大鼠的BMD和骨体积分数显著高于B组(P < 0.05)?A组松质骨分离度显著低于B组(P < 0.05)?其余骨形态学参数3组之间无统计学差异(P > 0.05)?骨组织学研究显示C组松质骨密度较A组和B组更加致密,A组松质骨密度则介于B组和C组之间?结论:EGCG在延缓雌性大鼠骨量丢失方面有积极作用,但是在年轻的雌性大鼠卵巢切除去势后以10 mg/(kg?d)的剂量预防性腹腔注射EGCG并不能完全恢复丢失的骨量?     

融水小型猪的实验动物化系列研究概述

融水小型猪的种源来自广西融水县,2012年被引到广东繁育并测定了基础数据,包括种质特性、繁殖性能、生长曲线、血液学指标、血生化指标、脏器系数、染色体分析。参照国家和地方有关实验动物标准,初步建立了融水小型猪微生物与寄生虫、环境与设施、饲料、病理学、遗传学等质量控制标准。融水小型猪能适应当地气候,繁殖良好,自然受孕率为88.3%,妊娠期平均112 d,初产平均胎产仔6.1头,经产平均产仔7.9头。融水小型猪体型小,雌雄成年体重(6月龄)分别为17.21±5.20 kg和16.35±5.23 kg,性情温顺,线粒体DNA分析表明融水小型猪比兰屿猪更为古老。通过标准化的饲养管理与质量控制,具有培育成实验用小型猪的基本条件。     

Validating the Psychometric Characteristics of the Perinatal Posttraumatic Stress Disorder Questionnaire (PPQ) in a Chinese Context

Background

Perinatal posttraumatic stress disorder (PPTSD) is a common stress-induced mental disorder worldwide. The Perinatal Posttraumatic Stress Disorder Questionnaire (PPQ) is an excellent questionnaire that measures the symptoms of PPTSD, but has not been translated into Chinese yet.

视网膜血管瘤样增生和湿性年龄相关性黄斑病变的鉴别

视网膜血管瘤样增生(retinal angiomatous proliferation,RAP)是湿性年龄相关性黄斑变性(age-related macular degeneration,AMD)的一种特殊类型,临床一般分三期,晚期有新生血管形成,但与起源于脉络膜的新生血管不同,多数学者认为RAP的新生血管起源于视网膜深层毛细血管网。目前对RAP和湿性AMD两者到底是同一种疾病的不同亚型还是独立的两种疾病还存在争议,由于两者的病程、预后及治疗存在差异,因此临床鉴别诊断十分重要。近年来,随着吲哚菁绿血管造影(indocyanine green angiography,ICGA)技术和新一代光学相干断层扫描(optical coherence tomography,OCT)技术的应用,对RAP和湿性AMD的鉴别取得了显著进步。本文就两者的临床表现、自然病程、治疗方法及预后等方面做一综述。     

Insulin sensitivity predicts glycemia after a protein load

Protein ingestion results in small but distinct changes in plasma glucose and insulin. We hypothesized that the glycemic and/or insulin response to protein might be related to the degree of insulin sensitivity. Our aim was to determine the relationships between insulin sensitivity (assessed by euglycemic-hyperinsulinemic clamp) and postprandial glucose, insulin, C-peptide, and glucagon responses to a 75-g protein meal and a 75-g glucose load. Sixteen lean healthy Caucasian subjects (mean +/- SD age, 25 +/- 6 years; body mass index [BMI], 23.1 +/- 1.7 kg/m2) participated in the study. After the protein meal, the mean plasma glucose declined gradually below fasting levels to a nadir of -0.36 +/- 0.46 mmol/L from 60 to 120 minutes, showing wide intraindividual variation. Insulin sensitivity (M value) was 1.1 to 3.9 mmol/L/m2 min in the subjects and correlated inversely with the plasma glucose response to the protein meal (r = -.58, P = .03), ie, the most insulin-sensitive subjects showed the greatest decline in plasma glucose. In contrast, there was no correlation between insulin sensitivity and the insulin or glucagon response to the protein load, or between the M value and the metabolic responses (glucose, insulin, C-peptide, and glucagon) to the glucose load. Our study suggests that the net effect of insulin and glucagon secretion on postprandial glucose levels after a protein meal might depend on the individual's degree of insulin sensitivity. Gluconeogenesis in the liver may be less susceptible to inhibition by insulin in the more highly resistant subjects, thereby counteracting a decline in plasma glucose.