慢性肾衰竭合并结核病在抗结核治疗中药动学的研究进展

在免疫功能低下患者中常常发生结核杆菌感染,如慢性肾衰竭。抗结核药物在肾功能不全患者中的药动学及剂量调整是非常重要的,在肾功能不全的患者中,尤其是透析患者应夏加重视。抗结核药物在透析一段时间后通常被透析清除一部分,需要随时调整剂量。然而,在肾衰竭的患者中对这些药物的剂量调节仍需进一步的药动学研究,特别是血液透析对于药动学的影响。     

Contact dermatitis to antituberculosis drugs

The literature has been reviewed for contact dermatitis occurring to antituberculosis agents. Of the 12 known drugs, 6 (isoniazid, rifampicin, ethambutol, para-aminosalicylic acid, streptomycin and kanamycin) have been documented by patch test to cause this type of dermatitis in certain individuals. Cross sensitization has been observed to contribute significantly to the allergic reactions noted from isoniazid, streptomycin, and kanamycin. Hyposensitization has also been discussed in this review.     

抗结核药物靶点的研究进展

摘要：由结核分枝杆菌(Mycobacterium tuberculosis,Mtb)感染引起的结核病(TB)是世界上最致命的感染性疾病之一。因抗 结核药物的泛用与滥用,细菌耐药问题日渐凸显。近几十年仅有2种抗结核新药上市,由于药物使用中的副作用及其耐药菌株 的出现,急需开展针对Mtb新靶点的药物研究。本文围绕近几年全球最新报道的抗结核药物靶点及其相关化合物进行综述并加 以系统总结,以期在一定程度上为新型抗结核药物的研发提供参考。     

一贯煎治疗抗结核药物性肝损害与还原型谷胱甘肽等效性随机平行对照研究

[目的]观察一贯煎治疗抗结核药物性肝损害与还原型谷胱甘肽等效性。[方法]使用随机平行对照方法,将118例住院患者按就诊先后顺序简单随机分为两组,常规抗结核,异烟肼0.3g/次,1次/d;利福平0.45g/次,1次/d;吡嗪酰胺0.5g/次,2次/d;乙胺丁醇0.75g/次,1次/d。对照组60例还原型谷胱甘肽1.2g/d。治疗组58例一贯煎(北沙参、麦冬、当归身、生地黄、甘杞子、香附、郁金),1剂/d,水煎200mL,早晚温服;大便秘结加栝蒌仁10g;腹胀,乏力加枳壳、陈皮各10g;食欲下降,恶心加茯苓、砂仁各10g。连续治疗4周为1疗程。观测临床症状、肝功能(谷草转氨酶-AST、血清丙氨酸氨基转移酶-ALT、总胆红素-TBIL)、不良反应。治疗1疗程,判定疗效。[结果]治疗组痊愈4例,显效33例,有效19例,无效4例,总有效率93.33%。对照组痊愈6例,显效36例,有效13例,无效3例,总有效率94.83%。临床疗效两组无显著差异(P0.05)。两组肝功能均有改善(P0.05),TBIL改善治疗组优于对照组(P0.05),ALT、AST改善两组无明显差异(P0.05)。[结论]一贯煎治疗抗结核药物性肝损害疗效显著,成本低廉,与还原型谷胱甘肽具有等效性,值得推广。     

含苯并咪唑片段结构的抗微生物药物研究新进展

含苯并咪唑片段结构的化合物在抗微生物领域研究开发较为活跃。本文结合近年来国内外文献简述了含苯并咪唑片段结构的化合物在抗菌、抗真菌、抗病毒、抗疟、抗结核等方面研究进展状况,着重强调了含苯并咪唑片段结构的抗微生物药物及其构效关系(SAR)的研发近况。随着研究的不断深入,有望成功开发出更多具有克服多药耐药性的高效低毒含苯并咪唑片段结构的抗微生物药物。     

Antituberculosis potential of some ethnobotanically selected Malaysian plants

Aim of the study

Many local plants are used in Malaysian traditional medicine to treat respiratory diseases including symptoms of tuberculosis. The aim of the study was to screen 78 plant extracts from 70 Malaysian plant species used in traditional medicine to treat respiratory diseases including symptoms of tuberculosis for activity against Mycobacterium tuberculosis H37Rv using a colorimetric microplate-based assay.

Materials and methods

Plant extracts were prepared by maceration in methanol (80%) and antituberculosis screening was carried out using Tetrazolium bromide microplate assay (TEMA) method to determine the minimum inhibitory concentration (MIC).

Results

Thirty-eight plant extracts from 36 plant species exhibited antituberculosis activity with MICs in the range of 1600-400 μg/ml. The leaf extract of Angiopteris evecta exhibited the highest activity with MIC of 400 μg/ml. Five other extracts, namely, Costus speciosus (stem and flower), Piper sarmentosum (whole plant), Pluchea indica (leaf), Pluchea indica (flower), and Tabernaemontana coronaria (leaf) exhibited antituberculosis activity, each with MIC of 800 μg/ml. To the best of our knowledge, this is the first report of in vitro high throughput screening of Malaysian medicinal plants for antituberculosis activity.

Conclusions

Antituberculosis activity of extracts of some plants justifies, to a certain extent their ethnomedicinal uses as remedies for symptoms of tuberculosis. These results also support the general view that, selecting the plants based on ethnobotanical criteria would enhance the probability of finding species with antituberculosis activity.     

Ag85B-卡介苗重组疫苗对结核病预防及治疗效果研究

目的评价Ag85B-卡介苗重组疫苗对结核病的预防及治疗效果。方法将小鼠随机分为6组,A、B、C为预防组,D、E、F为治疗组,A、D组为Ag85B-卡介苗重组疫苗免疫组,B、E组为BCG免疫组,C、F组为生理盐水对照组。通过研究各组小鼠在实验中的血清抗体水平、细胞免疫功能等指标以及体重变化、半数死亡时间、2个月死亡率、大体病变等,评价Ag85B-卡介苗重组疫苗在小鼠结核分枝杆菌感染的预防及治疗成效。结果在注射结核分枝杆菌后,各组小鼠体重平均增长明显减慢,C、F组增长最慢。A、B、D、E组与C、F组相比能延长半数死亡时间,降低一定时间内的死亡率。小鼠脏器大体病变各组之间无显著差别。A、B、D、E 4组小鼠,肺脏的结核分枝杆菌生长培养最低稀释度集中在105,肝脏、脾脏结核分枝杆菌生长培养最低稀释度集中在104。C、F组小鼠,肺脏结核分枝杆菌生长的培养最低稀释度集中在106,肝脏、脾脏结核分枝杆菌生长的培养最低稀释度集中在105。各组间的抗体检测及淋巴细胞增殖实验结果无显著差别。结论 Ag85B-卡介苗重组疫苗与卡介苗对于结核分枝杆菌感染的预防作用无显著区别,Ag85B-卡介苗重组疫苗和卡介苗对结核病无明显的治疗效果。     

Risk Factors of Hepatotoxicity During Anti-tuberculosis Treatment

Background

Antituberculosis treatment (ATT) induced hepato-toxicity is common, but risk factors predicting its development are poorly understood. The present study evaluates the clinical risk factors predicting the development of hepatotoxicity in Indian patients with tuberculosis on antituberculosis treatment.

Methods

Three groups of patients were studied at three service hospitals over a 3 year period from 2000-2002. Patients given ATT were followed up with monthly LFTs. Consecutive patients who developed Liver dysfunction (rise in SGPT > 5 times upper limit of normal) were studied, along with matched controls who did not. Markers for hepatitis B were also noted in these patients once in 6 months. A third group of patients who did not receive ATT but were HBsAg positive, were also similarly followed up. The possible association of age and sex of the patient, alcoholism, unrecognized chronic liver disease, hepatitis B virus carrier status and nutritional status with ATT-induced hepatitis was assessed. Statistical analysis was carried out by Chi square test/Fisher''s exact test using WHO provided software Epi Info 6. Sixty-nine patients with ATT-induced hepatotoxicity were prospectively studied. In addition 128 patients on anti-tuberculosis drugs without hepatotoxicity and 39 HBsAg carriers not on ATT were followed up for 1 year.

Results

Age, Sex, history of alcohol intake and BMI were not found to be related to development of hepatotoxicity. Presence of HBV infection or an underlying silent chronic liver disease were found to significantly increase the risk of development of ATT-induced hepatotoxicity. Continuation of ATT after development of jaundice was associated with a high fatality rate. It was possible to re-introduce isoniazid in 96% and rifampicin in 88% of patients with ATT induced hepatotoxicity.

Conclusion

ATT-induced hepatitis is common and is potentially fatal. It is likely to occur in those with underlying silent chronic liver disease, HBV infection and have been given ATT without a definite evidence of tuberculosis. Discontinuation of ATT leads to rapid recovery in most cases and drugs can safely be introduced after recovery in a majority of cases.Key Words: Antituberculosis treatment, hepatotoxicity, malnutrition     

警惕抗结核药物引起血液系统的异常

目的　观察抗结核药物对血液系统的影响。方法 回顾性分析1996年1月—2004年1月抗结核治疗中发生血液系统异常改变的115例的临床资料。结果 4812例结核病人抗结核治疗中发生血液系统异常改变115例(2.4%),以白细胞减少最常见(44.4%),其次是全血细胞减少(22.6%)及白细胞合并血小板减少(10.4%)。罕见有再生障碍性贫血、溶血性贫血、继发性骨髓纤维化。结论 几乎所有抗结核药物均可引起血液系统异常,以利福霉素类引起最常见,其次为吡嗪酰胺、异烟肼。既可引起血液系统中的一种有形成分改变,又可引起全血系统的异常,严重者引起死亡,应引起警惕。