Colonic delivery of dexamethasone from a prodrug accelerates healing of colitis in rats without adrenal suppression

Dexamethasone-β-d-glucuronide, a colon-specific prodrug of dexamethasone, may be useful in the treatment of ulcerative colitis and Crohn's colitis. The aim of this study was to evaluate colonic delivery and efficacy of this prodrug in the rat. Distribution of dexamethasone in luminal contents and tissues of the gastrointestinal tract and in plasma was measured after oral administration of dexamethasone-β-d-glucuronide or free dexamethasone. Efficacy of the prodrug and free drug was tested in an acetic acid-induced rat colitis model. Healing of induced colitis was assessed by measuring net intestinal fluid absorption, colonic surface area of ulceration, histology, and myeloperoxidase activity. Glucocorticosteroid toxicity was evaluated with serum corticosterone and plasma adrenocorticotropic hormone levels. The drug delivery index (a measure of relative targeting efficiency) was 6.7 and 8.6 in the cecal and colonic mucosa, respectively. The prodrug was significantly more potent than free drug in improving net colonic fluid absorption while significantly reducing surface area of ulceration and histological grade in colitic rats. Treatment with free dexamethasone significantly reduced serum corticosterone levels to subnormal levels, and treatment with the prodrug maintained serum corticosterone and plasma adrenocorticotropic hormone levels near control levels. The prodrug dexamethasone-β-d-glucuronide delivers efficacious amounts of dexamethasone to the large intestine from lower doses than free dexamethasone.     

Attention‐network specific alterations of structural connectivity in the undamaged white matter in acute neglect

Visual neglect results from dysfunction within the spatial attention network. The structural connectivity in undamaged brain tissue in neglect has barely been investigated until now. In the present study, we explored the microstructural white matter characteristics of the contralesional hemisphere in relation to neglect severity and recovery in acute stroke patients. We compared age‐matched healthy subjects and three groups of acute stroke patients (9 ± 0.5 days after stroke): (i) patients with nonrecovered neglect (n = 12); (ii) patients with rapid recovery from initial neglect (within the first week post‐stroke, n = 7), (iii) stroke patients without neglect (n = 17). We analyzed the differences between groups in grey and white matter density and fractional anisotropy (FA) and used fiber tracking to identify the affected fibers. Patients with nonrecovered neglect differed from those with rapid recovery by FA‐reduction in the left inferior parietal lobe. Fibers passing through this region connect the left‐hemispheric analogues of the ventral attention system. Compared with healthy subjects, neglect patients with persisting neglect had FA‐reduction in the left superior parietal lobe, optic radiation, and left corpus callosum/cingulum. Fibers passing through these regions connect centers of the left dorsal attention system. FA‐reduction in the identified regions correlated with neglect severity. The study shows for the first time white matter changes within the spatial attention system remote from the lesion and correlating with the extent and persistence of neglect. The data support the concept of neglect as disintegration within the whole attention system and illustrate the dynamics of structural‐functional correlates in acute stroke. Hum Brain Mapp 35:4678–4692, 2014. © 2014 Wiley Periodicals, Inc .     

Temporal-controlled Release of Bovine Serum Albumin from Chitosan Nanoparticles: Effect on the Regulation of Alkaline Phosphatase Activity in Stem Cells from Apical Papilla

Introduction

The controlled delivery of bioactive molecules is crucial for the regulation of stem cell differentiation. In this study, we examined the effects of temporal-controlled release of bovine serum albumin (BSA) from chitosan nanoparticles (CSnp) to regulate the alkaline phosphatase activity (ALP) in stem cells from apical papilla (SCAP).

Methods

BSA-loaded CSnp were synthesized by 2 methods to achieve the variant temporal-controlled release: (1) the encapsulation technique (BSA-CSnpI) and (2) the adsorption technique (BSA-CSnpII). After characterization of the size, charge, and release kinetics, SCAP were cultured in the presence of these bioactive molecule–loaded nanoparticles. SCAP viability was analyzed at 1, 7, 14, 21, and 28 days, and ALP activity was analyzed every 7 days until 21 days to determine the effect of these bioactive molecule–releasing nanoparticles on the cytotoxicity and differentiation potential, respectively.

Results

BSA-CSnpI and BSA-CSnpII presented distinct in vitro release profiles of BSA in a time-controlled manner. Cell viability was significantly enhanced over time in the presence of BSA-CSnpI and BSA-CSnpII (P < .01), when compared with BSA nonloaded CSnp. ALP activity was significantly higher (P < .01) in the presence of BSA-CSnpI after 3 weeks than in BSA-CSnpII.

Conclusions

BSA-loaded CSnps were synthesized and characterized in this study. Based on the physical/chemical interaction of BSA with CSnp (encapsulation or surface adsorption), different time-controlled release profiles were observed that influenced the ALP activity of SCAP in vitro. This study highlighted the potential of temporal-controlled bioactive molecule release technology in the differentiation of stem cells in dentin pulp regeneration.     

耳尖放血联合药物治疗睑腺炎临症观察

目的观察耳尖放血配合药物治疗睑腺炎的临床疗效。方法选取2018年5月至2019年5月期间罗湖区中医院眼科门诊诊治的睑腺炎患者180例,随机分为两组,每组90例患者,两组均予局部热敷、左氧氟沙星滴眼液治疗,治疗组90例患者加用耳尖放血配合药物治疗,对比两组患者的治疗效果。结果治疗组的治疗总有效率为94.4%,显著高于对照组的77.8%,两组数据对比差异显著,两组治疗效果对比差异具有统计学意义(P<0.05)。结论耳尖放血配合药物治疗睑腺炎患者,可显著提高患者的治疗效果。     

从肝论治胸痹探要

从肝与心的生理联系、病因病机论述从肝论治胸痹。治宜疏肝与柔肝,疏之以刚克柔,柔之以柔克刚。用辛以助其条达之性,起到疏肝作用;用酸以抑其上逆之性,起到了柔肝的作用。     

浅谈从肝论治冠心病

冠心病属于中医"胸痹""心痛"的范畴,气机不畅是主要病机。肝与心在情志、五行、经络上相关联。现代医学认为抑郁和焦虑是冠心病的心理社会危险因素。因此,冠心病的治疗常从肝论治。     

茵芩清肝汤对酒精诱导的大鼠急性肝损伤保护作用的探讨

[目的]探讨茵芩清肝汤对酒精诱导的急性肝损伤的保护作用.[方法]将100只实验大鼠随机按处理不同分为5组(每组20只):茵芩清肝汤组、硫普罗宁组、水飞蓟宾胶囊组、模型对照组和空白对照组;观察茵芩清肝汤对模型大鼠血生化、肝脏病理学各指标的影响,并与其他各组进行比较.[结果]经酒精诱导,模型对照组大鼠肝指数明显增加、转氨酶明显上升,血清一氧化氮明显升高,谷胱甘肽-过氧化物酶明显降低.茵芩清肝汤组、硫普罗宁组、水飞蓟宾胶囊组较模型对照组大鼠肝组织损伤轻,茵芩清肝汤组肝脏指数明显降低,与模型对照组和水飞蓟宾胶囊组比较有显著性差异;茵芩清肝汤组能明显降低一氧化氮、提高谷胱甘肽-过氧化物酶活性,与模型对照组、硫普罗宁组比较差异有统计学意义;病理切片显示,茵芩清肝汤组大鼠肝索及肝血窦结构清晰,肝细胞仅为轻度或中度水肿.[结论]茵芩清肝汤能降低肝脏氧化应激和脂质过氧化的影响,改善肝脏病理变化,提示对酒精诱导的大鼠急性肝损伤具有保护作用.     

CT量化评分评估寰枢椎脱位及合并颅底凹陷症寰枢椎脱位复位难易程度的可行性研究

目的:探讨应用CT量化评分评估寰枢椎脱位(atantoaxial dislocatiion,AAD)及合并颅底凹陷症(basilar invagination,BI)的AAD复位难易程度的可行性,为手术决策提供指导.方法:2018年3月～2019年12月,对88例AAD(BI/AAD)患者入院后行颈椎CT扫描,依据定义...     

基于高通量测序中江丹参“发汗”过程中优势微生物群落与主要药效成分相关性研究

目的 探究中江丹参Salvia miltiorrhiza“发汗”过程中主要微生物群落及变化特征,以及优势微生物群落与主要药效成分之间的关系,以科学阐释传统“发汗”加工方式对中江丹参品质的影响。方法 采用高通量测序技术对“发汗”过程中江丹参的微生物多样性进行研究,结合化学品质分析,将优势微生物群落丰度与“发汗”丹参主要药效成分含量相关联,以期进一步判定“发汗”过程中影响中江丹参药材品质的主要微生物群落。结果 21个中江丹参“发汗”样品共检出221个真菌菌属,677个细菌菌属。“发汗”过程中始终存在的优势真菌有小戴卫霉属Davidiella、轮枝菌属Verticillium;优势细菌有绿菌门未归类菌属Chloroplast＿unclassified和根瘤菌属未归类菌属Mitochondria＿unclassified 2个未归类菌属,已知细菌有节细菌属Arthrobacter、链霉菌属Streptomyces等。同时,相关性研究表明,真菌小戴卫霉属与样品中紫草酸含量呈显著负相关;子囊菌门未归类霉属Ascomycota＿unclassified与丹参酮ⅡA含量呈显著正相关。细菌绿菌门未归类菌...