New bis-aminomercaptotriazoles and bis-triazolothiadiazoles as possible anticancer agents

A series of bis-phenoxyacetic acids 2 were prepared starting from corresponding unsubstituted/substituted 1,4-quinols 1. The fusion of bis-phenoxyacetic acids 2 with thiocarbohydrazide gave the corresponding bis-[4-amino-5-mercapto-1,2,4-triazol-3-yl-methyleneoxy]phenylenes (3) in a one pot reaction. The reaction of bis-triazoles 3 with various reagents afforded N-bridged heterocycles 4-6 in good yields. The newly synthesised compounds were screened for their anticancer activity against a panel of 60 cell lines derived from seven cancer types namely, lung, colon, melanoma, renal, ovarian, CNS and leukemia. Some of the tested compounds showed promising anticancer properties.     

Hemodialysis vascular access dysfunction from basic biology to clinical intervention

Hemodialysis vascular access dysfunction is a major cause of morbidity and hospitalization in the hemodialysis population at a cost of over 1 billion dollars per annum. Venous stenosis and thrombosis as a result of venous neointimal hyperplasia are the major causes of hemodialysis vascular access dysfunction. Despite the magnitude of the clinical problem, there are currently no effective therapies for this condition. We believe that this could be because of an inadequate understanding of the pathogenesis of this condition. At a histological level, venous neointimal hyperplasia (both in human specimens and in a pig model) is characterized by the presence of smooth muscle cells/myofibroblasts, microvessel formation (angiogenesis), and the accumulation of extracellular matrix components, all of which could be potential targets for therapeutic intervention. In particular, polytetrafluoroethylene dialysis access grafts could be the ideal clinical model for testing out novel local therapies to block neointimal hyperplasia. The current review describes the lesion of venous neointimal hyperplasia in human samples and in a pig model and suggests possible future directions for the development of effective local therapies for this condition.     

膦甲酸钠治疗疱疹病毒相关性进展性卒中26例

1临床资料我院神经内科200112/200203应用膦甲酸钠(PFA,foscarnetsodium)治疗进展性卒中(progressivestroke,PS)患者26例.男12例,女14例,年龄35～70(平均57±14)岁.总病程19～72d.有高血压病史19例,有短暂性脑缺血发作病史11例,有脑梗死病史3例,有冠心病病史1例.标准符合1995年第四届全国脑血管病会议脑梗死诊断标准[1],并经脑CT或MRI证实为脑梗死;发病后1wk内病情逐步或阶梯样加重,临床常规治疗不能阻止病情进展,按1995年第四届全国脑血管病会议神经功能缺损评分标准[2]评分增加2分(包括2分)以上.采用金标免疫斑点法检测患者血清中人巨…     

阿卡波糖和二甲双胍治疗糖耐量异常合并代谢综合征的比较

目的:观察阿卡波糖和二甲双胍治疗对糖耐量异常合并代谢综合征的影响.方法:糖耐量异常并代谢综合征患者48例,分为2组,分别给予阿卡波糖50～100 mg,3次/d,即阿卡波糖组;或给予盐酸二甲双胍片250～500mg,3次/d,即二甲双胍组;疗程均为3 mo.结果:阿卡波糖组能显著控制餐后血糖,疗效优于二甲双胍,且具有调节血脂的作用,故可治疗2型糖尿病,改善代谢综合征,预防心血管疾病的发生.     

Ingested IFN-alpha: results of a pilot study in relapsing-remitting MS

OBJECTIVE: To investigate whether ingested human recombinant interferon-alpha2a (IFN-alpha2a) was safe and whether treatment reduces the number of gadolinium-enhanced lesions on serial MRI in patients with active relapsing-remitting MS (RRMS). METHODS: Entry criteria included clinically definite RRMS and one or more gadolinium-enhanced lesions on a screening MRI. RESULTS: Of 80 patients screened, 33 were eligible and 30 patients were enrolled for treatment. Patients were randomized (10 per group) to placebo, 10,000 or 30,000 IU IFN-alpha2a ingested on alternate days for 9 months. They were examined clinically and with monthly cerebral MRI. Sample size projections were based on the assumption of a parenteral IFN-like effect, a 90% reduction of enhancing lesions evident within 1 month of the initiation of treatment in the active treatment groups sustained during the 9-month study as the primary outcome variable. RESULTS: There was no significant effect on enhancing lesions. However, post hoc analysis suggested a possible treatment effect in the 10,000 IU group. By direct monthly comparison of placebo and 10,000 IU group in treatment month 5, there were 73% (p < 0.05) fewer enhancements in the 10,000 IU group than in the placebo group. There was a decrease of tumor necrosis factor-alpha protein secretion at months 4 and 5. Relapses and adverse events were not different among the treatment groups. Ingested IFN-alpha2a did not induce systemic anti-IFN-alpha antibodies. CONCLUSIONS: This trial showed no benefit based on the primary outcome measure. Because changes were detected in immune response and post hoc analysis suggested that a smaller dose could have an effect, IFN-alpha may deserve further study.     

Case report: A patient with primary biliary cirrhosis and autoimmune haemolytic anaemia

Diseases of an autoimmune nature are well recognized in association with primary biliary cirrhosis. Although autoimmune thyroiditis and many rheumatological conditions are well described in primary biliary cirrhosis, autoimmune haematological diseases have been less well reported. We report on a 66 year old North American Indian man with coincident primary biliary cirrhosis and warm antibody haemolytic anaemia. This case report supports the suggestion of an association between autoimmune haemolytic anaemia and primary biliary cirrhosis.     

Catheter-induced cystitis: evaluation by cystosonography

The bladders of 23 patients with indwelling catheters were examined by ultrasound and cystoscopy. Twelve of the 23 showed changes consistent with bullous cystitis, a catheter-induced reaction of the bladder mucosa that may simulate a bladder tumor on intravenous urography and sonography. The changes seen included a thickened mucosa that was smooth in the early stages, becoming redundant and polypoid in later stages. The mucosa was usually hypoechoic and the lesions were localized on the posterior wall or were diffuse and more severe, depending on the length of catheterization. It is concluded that the sonographic findings in the appropriate clinical setting are suggestive of this entity. Although cystoscopy is not often indicated, cystoscopic findings are diagnostic and biopsy is, therefore, unnecessary.