异烟肼的体外透皮实验研究

异烟肼在体外透皮吸收实验中,能透过离体兔皮,月桂氮酮能明显促进其透皮吸收,其中以5%浓度为最佳。     

异烟肼与利福平合用致肝毒性增加机制的研究概况

目的；综合抗结核药异烟肼与利福平合用时肝毒性增加机制的研究概况。方法：查询近年来国内外相关报道，综述和分析异烟肼代谢的机制，以及两药合用肝毒性与快慢乙酰化，肝药酶其他因素的关系。结果：临床研究及动物实验表明异烟肼与利福平二者合用时肝毒性增加有多种论述。结论：利福平可诱导肝药酶加速异烟肼代谢产生肝毒性物质。     

反相离子对高效液相色谱法测定人血清中异烟肼浓度

目的：建立一种快速简便的的反相离子对高效液相色谱法测定血清中异烟肼（ＩＮＨ）浓度。方法：用ＳｐｈｅｒｉｓｏｒｂＳｉＯ２（５μ，２５０ｍｍ×４６ｍｍ）色谱柱，以甲醇：２０ｍｍｏｌ／ＬＩＰＲ－Ｂ８＝１５∶８５（Ｖ∶Ｖ）为流动相，紫外检测器检测，波长２５４ｎｍ，烟酰胺（ＮＡ）为内标物。结果：在此色谱条件下，ＩＮＨ与ＮＡ的保留时间分别为７８１７ｍｉｎ和６８７２ｍｉｎ。在０５～２００μｇ／ｍｌ的浓度范围内，线性关系良好（ｒ＝０９９９５）。方法日内差异２１９％，日间差异４５１％，回收率９３３％，最低检测浓度５０ｎｇ／ｍｌ。结论：该法灵敏度高，特异性好，不需提取过程，大大减低了测定的工作量，对日常血药浓度监测和药代动力学工作的开展，具有极大的优越性。     

Effects of rifampicin and phenobarbital on the fate of isoniazid and hydrazine in vivo in rats

After the intraperitoneal (i.p.) administration of isoniazid (INH) to male Wistar rats, the liver and plasma levels of hydrazine (Hz) and acetylhydrazine (AcHz), which are hazardous metabolites of INH and well known as mutagens, carcinogens and hepatotoxins, were determined by gas chromatography-mass spectrometry (GC-MS). The levels of Hz in rifampicin (RMP)- or phenobarbital (PB)-pretreated groups were lower than those in the control group, while the amount of AcHz was scarcely altered. In each of the pretreated groups a pronounced increase in the oxidative elimination rate of Hz was observed. These results are of important toxicological significance in INH therapy with RMP, since an active intermediate of Hz seems to be a hepatotoxin.     

复方利福平胶囊的差示－三波长分光光度测定

分别采用差示－三波长分光光度法和单波长分光光度法测定复方利福平胶囊中的异烟肼及利福平。方法简便、准确。回收率和ＲＳＤ分别为９９．７９％、９９．３４％和０．５３％、０．６７％。     

Circling behavior elicited from the pedunculopontine nucleus: evidence for the involvement of hindbrain GABAergic projections

Unilateral microinjection of GABA agonists into the pedunculopontine nucleus (PPN) of the rat resulted in contraversive postural asymmetry and circling behavior; GABA antagonist caused ipsiversive asymmetry and circling when applied to the PPN. A hemitransection was placed immediately caudal to substania nigra (SN) and rostral to PPN in order to interrupt all connections between the PPN and ipsilateral forebrain nuclei. After hemitransection, microinjection of GABAergic drugs into the PPN on the hemitransected side produced postural asymmetry and circling identical to that observed in intact rats. The hemitransection resulted in a loss of glutamic acid decarboxylase activity in PPN (25%) not substantially greater than that observed in animals with unilateral destruction of SN, indicating that a major proportion of GABA terminals in PPN are derived from hindbrain sources. It appears that forebrain (that is, nigrotegmental) GABAergic projections are not essential for the GABA-mediated asymmetry elicited from PPN.     

Chelation in metal intoxication IX. Influence of amino and thiol chelators on excretion of manganese in poisoned rabbits

The effect of two polyamino-polycarboxylic acids, N-(2-hydroxyethyl) ethylenediamine triacetic acid (HEDTA) and diethylenetriamine penta-acetic acid (DTPA) and two thiol-chelating agents, sodium diethyldithiocarbamate (DDC). and dimercaptosuccinic acid (DMS) on the excretion of manganese (Mn) in rabbits given Mn i.p. was studied in order to investigate the affinity of this metal to N,O and S-containing compounds. HEDTA and DTPA were effective, and DDC and DMS were ineffective, in enhancing urinary and faecal excretions of Mn, indicating a greater binding capacity of Mn with chelators having N and O, than with those having S as electron donating centres.     

Effect of ascariasis and its treatment on drug absorption

Summary Ascariasis has been reported to impair the absorption of nutrients, vitamin A, and D-xylose, which is corrected on treatment. The effect of ascariasis and its treatment on the absorption of sulphadimidine and isoniazid has been investigated. There was no difference between drug absorption before and after the treatment or in comparison with a normal population.     

Protective effect of a 50% hydroalcoholic fruit extract of Emblica officinalis against anti-tuberculosis drugs induced liver toxicity

The present report showed the hepatoprotective property of a 50% hydroalcoholic extract of the fruits of Emblica officinalis (fruit) (EO-50) against antituberculosis (anti-TB) drugs-induced hepatic injury. The biochemical manifestations of hepatotoxicity induced by rifampicin (RIF), isoniazid (INH) and pyrazinamide (PZA), either given alone or in combination were evaluated. In vitro studies were done on suspension cultures of rat hepatocytes while sub-acute studies were carried out in rats. The hepatoprotective activity of EO-50 was found to be due to its membrane stabilizing, antioxidative and CYP 2E1 inhibitory effects.     

Eukaryotic arylamine N-acetyltransferase. Investigation of substrate specificity by high-throughput screening

Arylamine N-acetyltransferases (NAT; EC 2.3.1.5) catalyse the transfer of acetyl groups from acetylCoA to xenobiotics, including drugs and carcinogens. The enzyme is found extensively in both eukaryotes and prokaryotes, yet the endogenous roles of NATs are still unclear. In order to study the properties of eukaryotic NATs, high-throughput substrate and inhibitor screens have been developed using pure soluble recombinant Syrian hamster NAT2 (shNAT2) protein. The assay can be used with a wide range of compounds and was used to determine substrate specificity of shNAT2. We describe the expression and characterisation of shNAT2 and also purified recombinant human NAT1 and NAT2, including the use of the assay to explore the substrate specificities of each of the enzymes. Hamster NAT2 has similar substrate specificity to human NAT1, acetylating para-aminobenzoate but not arylhydrazine and hydralazine compounds. The overlapping but distinct substrate-specific activity profiles of human NAT1 and NAT2 were clearly observed from the screen. Naturally occurring compounds were tested as substrates or inhibitors of shNAT2 and succinylCoA was found to be a potent inhibitor of shNAT2.