结核分枝杆菌稳定L型变异的聚合酶链反应研究

目的：探讨结核分枝杆菌稳定L型变异的分子机制。方法：采用结核分枝杆菌聚合酶链反应(PCR)诊断试剂扩增结核分枝杆菌稳定L型纯培养物的染色体DNA，琼脂糖凝胶电泳、聚丙烯酰胺凝胶电泳(polyscrylamid gel electrophoresis，PAGE)薄层凝胶扫描分析。结果：结核分枝杆菌稳定L型比细菌型多一DNA条带。结论：结核分枝杆菌稳定L型的形成可能与基因突变有关，在特异性PCR反应中可形成与其亲代细菌型有差异的产物。     

In vitro/in vivo correlation of prolonged release dosage forms containing diltiazem HCl

Six preparations were considered: three multiple unit dosage forms (micropellets in capsules) (D, E and G) and one matrix tablet (B) were experimental prolonged release formulations, two non-disintegrating tablets (A and C) were commercial products. The in vitro dissolution behaviour of the differing formulations was investigated using the USP XXII paddle apparatus. The in vivo study was effected on a panel of 12 healthy volunteers. The two commercial tablets (A and C) showed mean dissolution time (MDT) of 1.34 and 1.44 h and t_d of 91 and 92 min, respectively; for prolonged release formulations (B, E, D, and G) MDT ranged between 2.28 and 4.23 h and t_d between 149 and 291 min. The mean residence time (MRT) was 8.68 and 6.47 h for tablets A and C, respectively; it ranged between 9.62 and 10.24 h for the multiple unit formulations E, D, and G and was 11.27 h for matrix B. Formulation B also showed the higher apparent elimination half-life t_1/2 (7.12 h), while apparent t_1/2 for all the other formulations were very similar, ranging between 5.04 and 5.28 h. High variability between the various formulations was found for C_max and AUC values, and no relationships could be established with the type of formulation. An in vitro/in vivo correlation was found for all the formulations examined on the basis of analogous parameters (MDT and MRT); (r = 0.83, p <0.05). In a few cases the Wagner-Nelson deconvolution method was applied to individual plasma level versus time curves and the corresponding absorption curves were obtained. In these cases the in vitro/in vivo correlation was tested on the basis of the comparison of the in vivo absorption curves with the in vitro dissolution profiles. This was accomplished using the ‘Levy's plot’ (per cent released versus per cent absorbed) approach and provided further support for the correlation found.     

羟甲基烟酰胺分散片的研制

目的：研制羟甲基烟酰胺分散片。方法：以崩解时间为指标。比较几种崩解剂的作用，以正交试验设计确立最佳处方，并与普通片进行体外溶出度比较。结果：崩解剂以低取代羟丙纤维素(L-HPC)效果最优，最佳处方崩解时间为78．9S，溶出速度远大于普通片。结论：所研制的羟甲基烟酰胺分散片溶出迅速。     

Liver microsomal cytochrome: P-450p and P-450h activity and blood corticosteroid levels of experimental animals exposed to physical factors

Laboratory of Experimental Therapy, Institute of Balneology, Ministry of Health of the Ukraine, Odessa. Department of Cell Physiology and Pathology, Institute of Clinical and Experimental Medicine, Siberian Branch, Academy of Medical Sciences, Novosibirsk. (Presented by Academician of the Academy of Medical Sciences V. Ya. Kaznacheev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 113, No. 5, pp. 498–500, May, 1992.     

Why homocysteine is a risk factor of neurodegenerative diseases mini review

The receptor-mediated effects of homocysteine and homocysteic acid on neurons and lymphocytes are described. Activation of glutamate receptors by these ligands was shown to induce an increase in intracellular calcium concentration and the level of active forms of oxygen in both types of cells. This increase may serve as a signal for activation of apoptosis. Metabotropic receptors of group III stimulated the excitotoxic effect of homocysteine and homocysteic acid, while those of group I and II prevented it. It is proposed that selective agonists/antagonists of these metabotropic receptors can be used for correction of neuronal and immune cell metabolism during hyperhomocysteinemia.     

心脏营养素-1治疗失神经骨骼肌萎缩过程中对正常肌肉组织的影响

目的 探讨应用心脏营养素-1(cardiotrophin-1,CT-1)治疗失神经骨骼肌萎缩的有效剂量和安全剂量,观察不同剂量的CT-1对正常骨骼肌、心肌和血管平滑肌的副作用.方法 取Swiss小鼠80只,随机分成8组,每组分别于胫神经切断术后连续腹腔注射重组小鼠CT-1(rmCT-1)40、60、80、100、120、140、160μg·kg-1·d-1,剩余1组腹腔注射等体积CT-1溶媒,28d后称量失神经侧腓肠肌、正常侧腓肠肌和心脏的湿重;测量胸主动脉平滑肌厚度;检测正常腓肠肌中α-actin和MHC Ⅱa以及心肌中β-MHC的表达、胸主动脉血管平滑肌细胞中α-actin的含量.结果 采用腹腔注射给药,当CT-1用量达到60μg·kg-1·d-1时,开始对失神经骨骼肌产生营养作用,并呈剂量依赖性增强,当给药剂量超过100 μg·kg-1·d-1后,出现对正常骨骼肌、心肌和血管平滑肌的影响.给药剂量达到120μg·kg-1·d-1时,开始促进心肌β-MHCmRNA的表达,增加正常心脏的湿重.当给药剂量达到140μg·kg-1·d-1时,开始促进正常骨骼肌α-actin和MHC Ⅱ amRNA的表达,以及骨骼肌湿重的增加,同时提高了主动脉血管平滑肌α-actin的含量,增加了血管平滑肌的厚度.结论 腹腔注射CT-1防治失神经骨骼肌萎缩的有效剂量为60 μg·kg-1·d-1,最高安全剂量为100 μg·kg-1·d-1.当给药剂量达到120 μg·kg-1·d-1时,开始出现心肌肥厚,当给药剂量达到140 μg·kg-1·d-1时,可导致正常骨骼肌的肥大和血管平滑肌的增厚.     

根据桂枝汤的效应消除半衰期和表观消除半衰期制订给药方案的探讨

为探讨药效法估测的效应消除半衰期和效量法估测的表观半衰期对合理制订给药方案的意义和作用,以桂枝汤解热和抗炎的药物动力学实验中所得的相应参数值设计了给药方案,观察了它们在提高药效上的作用。结果表明在给药总剂量相等、首次给药同时开始的情况下,以半衰期设计的给药方案组的药效均明显高于习惯的一次给药组;而以效应消除半衰期设计给药方案组药效增强率又高于以表观半衰期设计的方案组。提示效应消除半衰期比表观半衰期似更有实践意义。     

Moclobemide versus fluoxetine for a major depressive episode

The efficacy and tolerability of moclobemide (300–600 mg daily) and fluoxetine (20–40 mg daily) were compared in a 6-week, double-blind study of 65 inpatients and 34 outpatients suffering from major depressive episodes (DSM III-R). No statistically significant differences between the two treatment groups were noted regarding efficacy (HDRS, CGI) or safety (adverse events, laboratory examination, vital signs). Moclobemide (300–600 mg daily) and fluoxetine (20–40 mg daily) would thus appear to be comparable both in antidepressant efficacy and tolerability. Doubling the low dosage in non-responders after 3 weeks resulted in a statistically significant improvement of CGI in the moclobemide group by comparison with the fluoxetine group at study end, suggesting that 600 mg moclobemide/day can still improve the patient's condition, while 40 mg fluoxetine/day does not. Sexual dysfunction was reported in two patients taking fluoxetine.     

提高尿激酶原治疗急性心肌梗死疗效研究

尿激酶原是新一代特异性溶栓药。为进一步提高该药的安全性和有效性,本文从使用剂量、给药方案、与其他溶栓药伍用,及给药途径等方面提出了意见,供临床医生使用中参考。     

Different molecular forms of cholecystokinin and CCKB receptor binding in the rat brain after chronic antidepressant treatment

Cholecystokinin (CCK) is a neuropeptide recently implicated in affective disorders. This study aimed at measuring the levels of different molecular forms of CCK and the binding characteristics of CCK_B receptors in the rat brain after three weeks of treatment with four different antidepressants, imipramine, amitriptyline, desipramine, and citalopram (all at the dose of 10 mg/kg once per day i.p.). Chronic treatment with imipramine and desipramine had a significant immobility-reducing effect in the Porsolt‘s swim test. The effect of amitriptyline, albeit in the same direction, was not significant, and citalopram had no effect in this test. In the elevated plus-maze test of anxiety, all drugs tended to increase the number of open arm entries and the ratio open/total arm entries, but only the effects of imipramine were statistically significant. None of the treatments affected the total levels of CCK or the levels of CCK-8-sulphated, CCK-8-nonsulphated, CCK-5, or CCK-4 in the frontal cortex. There was no effect of the treatments on CCK_B receptor binding in the frontal cortex, hippocampus, or striatum. Imipramine and amitriptyline, however, increased the affinity of CCK_B receptor binding in the hypothalamus. Thus, no consistent effect of chronic antidepressant treatment on the CCK-ergic neurotransmission in the rats was found. Received: 4 June 1996 / Accepted: 26 August 1996