Absorption of Propranolol in Humans Following Oral,Jejunal, and Heal Administration

Pharmaceutical Research -     

Comparison of the Permeability Characteristics of a Human Colonic Epithelial (Caco-2) Cell Line to Colon of Rabbit,Monkey, and Dog Intestine and Human Drug Absorption

The in vitro permeabilities of Caco-2 monolayers and permeabilities in tissue sections from colon of monkey, rabbit, and dog were compared using a series of compounds. The selected compounds differed in their physicochemical properties, such as octanol/water partition coefficient, water solubility, and molecular weight. Their structure included steroids, carboxylic acids, xanthins, alcohols, and polyethylene glycols. A linear permeability relationship was established between Caco-2 and colon tissue from both rabbit and monkey. The results suggest that Caco-2 is twice as permeable as rabbit and five times as permeable as monkey colon. However, no clear relationship could be established between Caco-2 monolayers and dog colon permeability. A relationship between permeability in Caco-2 monolayers and human absorption was found. The results suggest that within certain limits, permeability of Caco-2 monolayers may be used as a predictive tool to estimate human drug absorption.     

Interactions between peripheral blood CD8 T lymphocytes and intestinal epithelial cells (iEC)

Intestinal intraepithelial lymphocytes (iIEL) are primarily CD8 cells and most of them have a CD28^? phenotype, the phenotype of effector cytotoxic T cells. We asked whether the predominance of CD8⁺ CD28^? T cells in the gut may result from peripheral blood T cells preferentially migrating to the iIEL compartment and adhering to iEC. Compared with CD4 cells, adhesion of resting CD8⁺ T cells to iEC cell lines was significantly higher. Adhesion could be blocked with a MoAb to gp180, a molecule expressed on iEC which is known to interact with CD8/lck. No significant difference in the level of adhesion was observed between CD8⁺ CD28⁺ and CD8⁺ CD28^? T cells. Thus CD8 cells may preferentially migrate to the iIEL compartment, but loss of CD28 expression could occur in situ after migration. Consistent with this hypothesis, the CD8⁺ CD28^? cells became enriched after co-culturing T cells with iEC cell lines and primary iEC. Induction of the CD8⁺ CD28^? phenotype in cord blood and adult T cells was observed in co-cultures with iEC and also with mitogens and superantigens. In the latter case, CD28 down-modulation was seen specifically in the Vβ subset targeted by the superantigen, indicating that loss of CD28 expression is a direct result of T cell receptor (TCR)-mediated stimulation. The combined results suggest that CD8⁺ CD28^? T cells are antigen experienced T cells, and that they may have a survival advantage in the presence of gut epithelial cells in vitro. This may contribute to the predominance of CD8⁺ CD28^? T cells in the iIEL compartment.     

小儿乙状结肠冗长症病理特点分析

目的 探讨小儿乙状结肠冗长症的病理特点，以提高对该症病理特点的认识。方法 分析我科1993～2002年间经手术治疗12例小儿乙状结肠冗长症的临床病理资料。结果 小儿乙状结肠冗长症病理特点与先天性巨结肠同源病相似。主要表现为乙状结肠肠壁肥厚，部分肌纤维变性。结肠黏膜萎缩，黏膜下充血水肿；肌间神经丛减少，均可见神经节细胞发育幼稚，且数量减少或体积变小，呈固缩或空泡变性。结论 小儿乙状结肠冗长症大多有肠神经元发育异常。     

实验小鼠肠道正常菌群

在动物肠道中栖息的细菌，构成了肠道正常菌群。实验动物的质量与肠道菌群的状态有着十分密切的联系，肠道菌群平衡状态在维持动物机体的生理状态、正常功能，以及抵抗外袭菌方面起着重要的作用。小鼠肠道中，每克肠内容物含有上亿个菌体，可分为10～15个属，上百个种。肠道正常菌群的主要菌属有双歧杆菌、拟杆菌(类杆菌)、肠球菌、乳杆菌、梭杆菌、真杆菌。不同品系的小鼠之间，各种菌的数量有所不同。本文简要介绍了近年来对小鼠肠道正常菌群的研究进展。     

褪黑素对结肠黏膜上皮细胞氧化应激的影响

目的 探讨褪黑素对大鼠结肠黏膜上皮细胞氧化应激的影响。方法 在分离培养正常大鼠结肠黏膜上皮细胞基础上，利用FeSO4 H2O2产生*OH攻击制备结肠黏膜细胞氧化损伤模型，同时预先加入褪黑素并观察损伤减轻程度。实验设正常对照组、模型对照组、5-氨基水杨酸给药组(0.1mmol／L)，褪黑素给药组(0．01、0．1、l.0mmol／L)。培养一定时间后，取上清测乳酸脱氢酶(LDH)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSHPx)、过氧化氢酶(CAT)、超氧化物歧化酶(SOD)、一氧化氮(NO)和黏液含量。结果 模型组大鼠结肠黏膜上皮细胞：MDA、LDH和NO水平增高，CAT、GSHPX、SOD和黏液含量减少。不同剂量褪黑素呈剂量依赖性的减少LDH释放，抑制MDA和NO的形成，恢复黏液、CAT、GSHPX及SOD水平。结论 褪黑素对大鼠结肠黏膜氧化损伤具有保护作用。     

Detailed Analysis of Mucosal Restoration of the Small Intestine After the Cavitary Two-Layer Cold Storage Method

Small bowel transplantation (SBT) is associated with a high incidence of infectious complications because of ischemia/reperfusion (I/R) mucosal injury concomitant with potent immunosuppression. In this study, we evaluated whether the cavitary two-layer method (cTLM) could reduce I/R injury and allow early mucosal restoration, particularly after prolonged preservation and transplantation. Canine heterotopic segmental SBT was performed immediately without preservation (group 1), after 24-h preservation in UW solution (group 2) or by the cTLM (group 3). The graft samples were taken 1 h after reperfusion and on days 1, 4 and 7. We assessed graft mucosa with detailed microscopic and electromicroscopic analyses. In Group 3, histological injury and cell apoptosis after transplantation were significantly alleviated and rapidly recovered to a similar level of group 1. The mucosal restoration was morphologically completed within 4 days. In contrast, in group 2, more pronounced mucosal injury and delayed recovery were noted. Crypt cell proliferation activity was well maintained in groups 1 and 3 throughout the experimental period. Our ultrastructural analysis suggested that mitochondrial integrity achieved by the cTLM was a basal mechanism under the prompt mucosal restoration. The cTLM could reduce I/R injury, facilitate mucosal regeneration and restore the nearly normal structure early after SBT.     

急诊左半结肠一期切除吻合术25例治疗体会

目的探讨急诊左半结肠切除一期肠吻合的可行性。方法腹腔探查完后，用布带结扎横结肠，游离肠系膜后，于预切除肠段的上端切开作肠外减压，挤压排空粪便，切除病变肠管，端端吻合，术后作肛管扩张，停留肛管引流，胃肠减压。结果全部病人预期痊愈出院，无发生吻合口漏和腹腔污染。结论该法有利于吻合口的愈合，增加左半结肠一期切除吻合的安全性，减少第2次手术痛苦，可推荐为左半结肠急诊切除一期吻合的良好方法。     

胃癌及肠化组织的微卫星不稳定性

目的 :探讨微卫星不稳定性 (MSI)在胃癌及肠化组织中的发生规律及其在胃癌发生过程中的作用。方法 :对 30例胃癌、4 0例肠上皮化生的石蜡标本分别提取病变及相应正常组织的DNA ,应用银染PCR SSCP技术检测 5个微卫星位点的不稳定性。结果 :胃癌组织MSI的发生率为2 3 3% ,胃窦癌MSI的发生率显著高于贲门癌 (P =0 0 4 4 )。肠化组织MSI发生率 2 0 % ,MSI全部出现在中度以上肠化组织中 (P =0 0 13) ,且更多见于女性 (P =0 0 4 4 )。结论 :MSI是胃癌多步骤发生过程中的早期分子事件 ,在胃癌的发生中可能具有重要作用。