类风湿性关节炎药物治疗的进展

近年来,随着类风湿性关节炎发病机制及某些致炎因子的发现,出现了一系列新药。环氧合酶-Ⅱ特异性抑制剂与传统的非甾体类抗炎药相比具有疗效好、副作用小的优点;早期联合使用改变病情性抗风湿药在近期内有较好的临床疗效。此外重组可溶性肿瘤坏死因子受体融合蛋白 (etanercept)、人体抗肿瘤坏死因子-α单克隆抗体(adalimumab)和阿那白滞素(anakinra)等生物学治疗及中药治疗均显示了新的治疗前景。     

Brain uptake of α-[14C]methyl-para-tyrosine in the rat

The blood-brain permeabilities of L-[³H]tyrosine and the tyrosine hydroxylase (TH) inhibitor β-[¹⁴C]methyl-para-tyrosine ([¹⁴C]AMPT) were determined in rat striatum, a brain region rich in TH activity, and in other brain regions containing relatively little TH activity. In striatum, the unidirectional clearance rate (K₁) for L-[³H]tyrosine (6.2 ml hg- ^?1 min^?1) was significantly greater than the rates for L-[¹⁴C]AMPT (2.8 ml hg^?1 min^?1) and D-[¹⁴C]AMPT (0.8 ml hg^?1 min^?1). The apparent volume of distribution (V_f) for L-[¹⁴C]AMPT in striatum (72.5 ± 4.0 ml hg-¹) did not differ from the V_f in other brain regions. The homogeneous distribution of L-[¹⁴C]AMPT in rat brain indicates that labeled AMPT is unsuitable for the study of TH in vivo by quantitative autoradiography. © 1994 Wiley-Liss, Inc.     

A pilot study of bortezomib in Korean patients with relapsed or refractory myeloma

Recent clinical trials showed that bortezomib, a novel proteasome inhibitor, had therapeutic activity in multiple myeloma. However, there was no data about the feasibility of bortezomib in Korean patients. We performed a pilot study of bortezomib in patients with relapsed or refractory myeloma (1.3 mg/m2 twice weekly for 2 week in a 3-week cycle). Seven patients were enrolled. The median age of patients was 59 yr. All patients previously received VAD (vincristine, doxorubicin and dexamethasone) and thalidomide chemotherapy. Three patients previously received alkylator-containing chemotherapy and 4 patients, autologous stem cell transplantation. Bortezomib monotherapy resulted in 3 partial remissions (43%), 3 no changes (43%) and 1 progressive disease (14%). One patient who had no response to bortezomib monotherapy experienced partial remission after addition of dexamethasone to bortezomib. The most common serious toxicity was thrombocytopenia (grade 3/4, 10 of 20 cycles (50%)) and grade 3 peripheral neuropathy was developed in 2 of 20 cycles (10%). Drug-related adverse event led to discontinuation of bortezomib in 1 patient. There was no treatment related mortality. Overall, bortezomib seems to be effective and feasible. Conduction of larger clinical studies on Korean patients is necessary to characterize clinical efficacy and safety of bortezomib more precisely.     

Crystallisation of calcium oxalate dihydrate in normal urine in presence of sodium copper chlorophyllin

Summary A method is described for the growth of calcium oxalate dihydrate in normal urine. Soluble chlorophyllin, at a concentration of 20 g/ml inhibited the crystallisation and the growth kinetics of the dihydrate crystals. The inhibitory capacity of chlorophyllin was compared with previous results. Data obtained suggest that the food and drug colourant chlorophyllin might be useful in the treatment of calcium oxalate stone disease.     

β-内酰胺酶抑制剂研究进展

报道了4种β-内酰胺酶抑制剂(包括克拉维酸、舒巴坦、他唑巴坦以及BRL-42715)的特性、各抑制剂的复方制剂、作用 机制,以及这些酶抑制剂与不耐酶的β-内酰胺类抗生素联合应用后的协同作用,并对酶抑制剂抑酶作用进行了比较。     

The Catalytic Mechanism of Angiotensin Converting Enzyme

A detailed investigation of the catalytic mechanism of angiotensin converting enzyme was undertaken in order to establish a molecular basis for its mode of action. These studies include the characterization of the kinetic properties of the enzyme. In particular, a mechanism for the anion activation, a characteristic feature of angiotensin converting enzyme, has been established. The active site of the enzyme contains a catalytically essential zinc atom which appears to be directly involved in the hydrolytic step of catalysis. Further components of the active site are the carboxyl group of an aspartyl or glutamyl residue, tyrosyl, arginyl and lysyl residues. The latter one is involved in mediating the anion activation. These results have enabled us to compare the active site of angiotensin converting enzyme with those of two other zinc peptidases and, thereby, deduce a mechanism for its mode of action. These investigations have confirmed a hypothetical model of the active site of angiotensin converting enzyme which has served to construct potent inhibitors of the enzyme now being used as anti-hypertensive agents.     

III型分泌系统及其抑制剂的研究进展

细菌分泌系统的发现是近年来细菌致病机制研究的重点。致病菌为在宿主体内生存、繁殖、扩散，会分泌一些蛋白性质的毒性因子。目前认为革兰阴性致病菌在长期进化过程中形成入侵宿主细胞的特异性分泌系统共有5种类型(I~V型)，其中最显著的是细菌Ⅲ型分泌系统(type three secretion system, T3SS)，与细菌致病性密切相关。T3SS抑制剂的策略是细菌分泌毒力蛋白，阻止其对宿主细胞的侵染。本文对细菌T3SS的组成、T3SS抑制剂筛选系统、T3SS抑制剂以及作用机制等进行综述，为深入研究以T3SS为靶点的药物设计提供参考。