胆碱能M受体拮抗剂：2α－（2＇，2＇－二取代基－2＇－羟基乙氧基）托品烷光学异构体合成

胆碱能Ｍ受体拮抗剂：２α－（２＇，２＇－二取代基－２＇－羟基乙氧基）托品烷光学异构体合成王林，恽榴红，张其楷（军事医学科学院毒物药物研究所，北京１００８５０）目前临床所用托品类抗胆碱药一般为３位取代托品酯类衍生物，这类药物作用较广泛，但选择性不高。Ａ...     

Mechanism of vascular smooth muscle cells activation by hydrogen peroxide: role of phospholipase C gamma.

BACKGROUND: Hydrogen peroxide (H2O2) formation is a critical factor in processes involving ischaemia/ reperfusion. However, the precise mechanism by which reactive oxygen species (ROS) induce vascular damage are insufficiently known. Specifically, activation of phospholipase C gamma (PLCgamma) is a probable candidate pathway involved in vascular smooth muscle cells (VSMC) activation by H2O2. METHODS: The activation of human venous VSMC was measured as cytosolic free calcium mobilization, shape change and protein phosphorylation, focusing on the role of tyrosine phosphorylation-activated PLCgamma. RESULTS: The exposure of VSMC to exogenous H2O2 caused a rapid increase in cytosolic free calcium concentration ([Ca2+]i), and induced a significant VSMC shape change. Both effects were dependent on a tyrosine kinase-mediated mechanism, as determined by the blockade of short-term treatment of VSMC with the protein tyrosine kinase inhibitor, genistein. Giving further support to the putative role of phospholipase C (PLC)-dependent pathways, the [Ca2+]i and VSMC shape change response were equally inhibited by the specific PLC blocker, 1-(6-((17-beta-methoxyestra-1,3,5(10)trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122). In addition, U73122 had a protective effect against the deleterious action (24 h) of H2O2 on non-confluent VSMC. As a further clarification of the specific pathway involved, the exposure to H2O2 significantly stimulated the tyrosine phosphorylation of PLCgamma with a concentration- and time-profile similar to that of [Ca(2+)](i) mobilization. CONCLUSIONS: The present study reveals that H(2)O(2) activates PLCgamma on VSMC through tyrosine phosphorylation and that this activation has a major role in rapid [Ca(2+)](i) mobilization, shape-changing actions and damage by H(2)O(2) in this type of cells. These findings have direct implications for understanding the mechanisms of the vascular actions of H(2)O(2) and may help to design pharmacologically protective strategies.     

Facilitating myasthenic syndrome and quadriceps myopathy

A patient presented with myasthenic syndrome apparently not related to any neoplasia. A peculiar myopathy characterized by absolute predominance (99.50%) and atrophy of type 2A muscle fibers was found in both quadriceps muscles. It is difficult to determine the relation between the myasthenic syndrome and the localized quadriceps myopathy for which a congenital nature is suggested.     

Primary segmental sclerosing cholangitis associated with Sj?gren's syndrome

We report the case of a patient with primary sclerosing cholangitis associated with Sj?gren's syndrome and Raynaud's phenomenon, an uncommon association. The presence of periportal lymph nodes with features similar to those described in autoimmune diseases suggests an immune pathogenesis of the disease. The localized and segmentary involvement of the common duct is also an uncommon finding. The pathogenetic and therapeutic aspects are discussed.     

Oral candidiasis as a clinical marker related to viral load, CD4 lymphocyte count and CD4 lymphocyte percentage in HIV-infected patients

BACKGROUND: High viral load is currently considered to be one of the main indicators of the progression of HIV-induced immunodepression, but few studies have analysed its relationship to the presence of oral candidiasis (OC). The aim of this cross-sectional study is to analyse the relationship between viral load, total CD4 lymphocyte count, and percentage of CD4 lymphocytes to the occurrence of OC. METHODS: The present cross-sectional study included 156 HIV-infected patients seen at a clinic for sexually transmitted diseases and HIV. We assessed the presence or absence of OC, and microbiological samples were obtained from the palatine mucosa and dorsal tongue for a smear stained with KOH (potassium hydroxide) and culture on Sabouraud's dextrose agar in all patients. Viral load was determined by quantification of viral RNA in peripheral blood with a minimum detectable level of 500 RNA copies/ml. CD4+ counts/CD4+ percentage were categorized as <200/<14%, 200-499/14-28%, and >500/>29%, and HIV viral loads were categorized as <500, 500-10,000, >10,000 copies/ml. RESULTS: Thirty-eight percent (37.8%) of the patients had OC. Patients with CD4+ lymphocyte counts below 200 x 10(6)/l and CD4+ percentages below 14% showed a significantly higher frequency of OC (57.9% and 48.0%, respectively). Patients with a viral load over 10,000 copies/ml also had OC more frequently (44.8%). In the multiple logistic regression analysis, OC showed a statistically significant association with high viral load [>10,000 vs <500, odds ratio (OR)=11.4], low percentage of CD4+ lymphocytes (<14% vs >28%, OR=5), and injection drug use (IDU vs heterosexual transmission, OR=10.2). In HIV-infected patients, high viral load was associated with more frequent OC, regardless of CD4+ lymphocyte level. CONCLUSIONS: These findings suggest that oral candidiasis could be a useful clinical marker of patients with high viral load. In view of these results, emphasis should be placed on the importance of systematic examination of the oral cavity in all medical follow-up examinations of HIV-infected patients.     

肾康宁片中黄芪甲苷的薄层扫描法测定

目的:建立肾康宁片中黄芪甲甙含量测定方法。方法:双波长薄层扫描法,经水饱和正丁醇液冷浸超声提取,再上D101大树脂纯化,以氯仿-甲醇-水(65:30:10)下层液为展开剂,检测波长为520nm,参比波长为700nm。结果:平均加样回收率为97.8％(RSD=1.4％,n=6),标准曲线r=0.9996。结论:方法结果可靠、操作简单,可作为肾康宁片的质量控制标准。     

压电频移中和萃取法测定微克量枸橼酸维静宁

用涂圈压电石英晶体频移一中和萃取法测定枸橼酸维静宁(咳必清),检出限0.02μg,在0.05～1.6μg范围内呈线性,相关系数0.999,变异系数为2.3%。与经典的中和萃取法相比,本法具有明显的优越性。