Effect of bioamines on the cellular differentiation of Hartmannella culbertsoni

Epinephrine, 5-hydroxytryptamine, dopamine and tyramine induce axenic encystation of the free living amoeba Hartmannella culbertsoni. Cycloheximide inhibits encystation of amoeba mediated by the amines. The amines uniformly stimulate 3 to 4-fold the ability of the cells to synthesize cyclic 3′,5′-adenosine monophosphate from adenosine triphosphate formed in situ. Epinephrine[¹⁴C] is bound to membranes of the amoeba (K_mof binding = 6.5 mM epinephrine). When amoebae are exposed to epinephrine, tyramine, dopamine or cAMP in a non-nutrient medium for 6 hr protein kinase activity is stimulated as evident from increased incorporation of ³²P into cellular proteins.     

Action of theophylline and imidazole on dog submaxillary secretion

The effects of close arterial infusions of theophylline and imidazole were studied by measuring salivary flow rates and electrolyte concentrations in the retroperfused, pilocarpine-stimulated submaxillary gland of the dog.     

Action of methylxanthines and imidazole on the contractility of the terminal ileum of the guinea pig

Methylxanthines (aminophylline and caffeine) and imidazole, substances with an opposite action on phosphodiesterase (PDE), were found to contract the terminal ileum and to potentiate nerve-mediated responses — contractions elicited by electrical stimulation (ES) at 3 Hz and 30 Hz. Imidazole-induced contractions which were partly reduced by atropine, potentiated both responses to ES to about the same extent, and enhanced contractility of the preparation to histamine and potassium. The action of imidazole on the terminal ileum could be related to its influence on PDE in the smooth muscle.The effects of aminophylline and caffeine were found to be more complex, possibly involving some mechanisms other than inhibition of PDE. They produced atropine-sensitive contractions of the terminal ileum, which were potentiated by physostigmine and strongly depressed by hemicholinium. In the presence of atropine, they potentiated ES-induced contractions, particularly those elicited by ES at 30 Hz, which are thought to be of adrenergic orig origin. Both actions appeared to be due to presynaptic effects—activation of cholinergic and adrenergic neurons in the intestinal wall, possibly by enhanced influx of calcium, and facilitated release of acetylcholine and noradrenaline. Aminophylline, in concentrations which potentiated nerve-mediated contractions elicited by ES, did not affect direct smooth muscle-contracting action of drugs. Higher concentrations of aminophylline, above 0.1 mM, were found to inhibit histamine- and noradrenaline-induced contractions presumbly due to inhibition of PDE in the smooth muscle and subsequent elevation of cAMP levels.     

Non-specific vaginitis: diagnostic features and response to imidazole therapy (metronidazole, ornidazole)

Detailed quantitative aerobic, anaerobic, fungal and mycoplasma flora was obtained for 43 women presenting with complaints of vaginal discharge and malodour. Clinical response was associated with eradication of the abnormal anaerobic flora, despite persistence of G vaginalis in nine (26%). Topical imidazole therapy appeared to have some advantage over oral therapy. Gram stains of vaginal swabs were found to be the most useful laboratory investigation.     

Studies of the imidazole series.

Conclusions The bromination of 2-alkyl-4(5)-nitro-, 1,2-dialkyl-4-nitro-, and 1,2-dialkyl-5-nitroimidazoles was studied and at the same time a simple method was devised for obtaining 2-alkyl-4(5)-nitro-5(4)-bromo- and 1,2-dialkyl-4-nitro-5-bromoimidazoles. 1,2-Dialkyl-5-nitroimidazoles cannot be brominated. 1,2-Dialkyl-4-bromo-5-nitroimidazoles can be obtained by alkylation of 2-alkyl-4(5)-nitro-5(4)-bromoimidazoles by dialkyl sulfates.Translated from Khimiko-Farmatsevticheskii Zhurnal, No. 10, pp. 22–25, October, 1968.     

Formulation effects on the mechanical properties of metronidazole tablets.

The individual and interaction effects of nature of binder (N), concentration of binder (C) and the physical form of the formulation (P) on the tensile strengths (T--a measure of the bond strength of tablets) and the brittle fracture index values (BFI--a measure of the lamination tendency of tablets) of metronidazole tablets have been studied using a 2(3) factorial experimental design in each case. Changing binder concentration from a 'low' to a 'high' level increased T and reduced the BFI of the tablets. Methylcellulose 20 exhibited stronger binding effect and greater ability to reduce the lamination tendency of the tablets than polyvinylpyrrolidone of molecular weight 44,000. Granular formulations produced tablets with lower T values but also with lower BFI values than tablets produced from powdered formulations. The ranking of these individual effects on tensile strength was P greater than C greater than N while the ranking for the BFI was P greater than N greater than C. For the interaction effects, the ranking for tensile strength was P-N much greater than N-C greater than P-C while the ranking for the BFI was N-C much greater than P-C greater than P-N.     

Evaluation of the anticholinesterase activity of metronidazole and misonidazole.

Contrary to an earlier report that metronidazole exhibited anticholinesterase activity on isolated organ preparations, a direct spectrophotometric assay was unable to demonstrate any significant inhibition of either true or pseudocholinesterase activity in the presence of this drug. The related nitroimidazole, misonidazole, was also found to be inactive when tested in this system. This report demonstrates that the clinical neurotoxicity of these two compounds cannot be attributed to any direct effect on the cholinesterase enzymes.     

Tinidazole and metronidazole in the treatment of intestinal amoebiasis.

Sixty adult patients with symptomatic intestinal amoebiasis and with Entamoeba histolytica present in stools were allocated at random to treatment with tinidazole or metronidazole, both administered in a dose of 2 g once daily for 3 consecutive days. The treatment period was extended in patients with stools positive for Entamoeba histolytica on the day following the last treatment day. Fifty-six patients, 29 on tinidazole and 27 on metronidazole, completed the trial as per the protocol. Twenty-eight patients (96.5%) on tinidazole and 15 (55.5%) on metronidazole were cured. Parasitological cure with partial relief of symptoms was obtained in 1 (3.5%) and 5 (18.5%) patients on tinidazole and metronidazole, respectively. Seven patients (26%) on metronidazole were treatment failures. Treatment had to be extended beyond 3 day in 53% of patients (8/15) on metronidazole as opposed to 11% (3/28) on tinidazole (p less than 0.01). The total number of side-effects, their severity, and the types were more in the metronidazole group. No toxic effects due to either drug were recorded. Tinidazole provided significantly higher cure rates than metronidazole in the treatment of symptomatic intestinal amoebiasis (p less than 0.01), and was better tolerated than metronidazole.     

取代咪唑酮合成工艺研究

目的:优化取代咪唑酮类化合物的合成工艺.方法:采用正交设计法,重点考察反应溶剂,投料比例及温度对收率的影响.结果:投料比例对收率的影响最为显著.结论:使收率由低于10%提高到42.5%,使得更加符合工业生产的要求.     

Cytogenetic study of metronidazole and three metronidazole analogues in cultured human lymphocytes with and without metabolic activation.

Metronidazole (MTZ) and other nitroimidazole derivatives have been extensively used to treat infections caused by protozoa and anaerobic bacteria. However, the need for new derivatives with similar therapeutic activity but lower toxicity to human beings prevails. On this purpose, three metronidazole analogues were synthesized, namely: 1-(p-methylphenacyl)-2-methyl-4-nitro imidazole (CPMe), 1-(p-methoxyphenacyl)-2-methyl-4-nitroimidazole (CPMeO), and 1-(p-fluorphenacyl)-2-methyl-4-nitroimidazole (CPF), which at low concentrations (0.5-2 microg/ml) showed a higher activity against Entamoeba histolytica than MTZ (3-6 microg/ml). The aim of this work was to investigate the cytogenetic effect of the three MTZ analogues on human lymphocyte cultures with and without metabolic activation in vitro, using the sister chromatid exchange test (SCE), comparatively with MTZ. The effect of the compounds on the cell proliferation kinetics (CPK) measured by the replication index (RI) and the cytotoxic effect in the mitotic index (MI) was evaluated as well. The SCE frequencies with and without S9 metabolic activation in treated and control lymphocytes showed no significant statistical differences. However when metabolic activation was involved a significant increase in the amount of third division metaphases provoked the CPK increased significantly with all the tested compounds. The RI showed similar behaviour, except for compound CPF.     

Release and diffusional modeling of metronidazole lipid matrices.

In this study, the first aim was to investigate the swelling and relaxation properties of lipid matrix on diffusional exponent (n). The second aim was to determine the desired release profile of metronidazole lipid matrix tablets. We prepared metronidazole lipid matrix granules using Carnauba wax, Beeswax, Stearic acid, Cutina HR, Precirol ATO 5, and Compritol ATO 888 by hot fusion method and pressed the tablets of these granules. In vitro release test was performed using a standard USP dissolution apparatus I (basket method) with a stirring rate of 100 rpm at 37 degrees C in 900 ml of 0.1 N hydrochloric acid, adjusted to pH 1.2, as medium for the formulations' screening. Hardness, diameter-height ratio, friability, and swelling ratio were determined. Target release profile of metronidazole was also drawn. Stearic acid showed the highest and Carnauba wax showed the lowest release rates in all formulations used. Swelling ratios were calculated after the dissolution of tablets as 9.24%, 6.03%, 1.74%, and 1.07% for Cutina HR, Beeswax, Precirol ATO 5, and Compritol ATO 888, respectively. There was erosion in Stearic acid, but neither erosion nor swelling in Carnauba wax, was detected. According to the power law analysis, the diffusion mechanism was expressed as pure Fickian for Stearic acid and Carnauba wax and the coupling of Fickian and relaxation contributions for other Cutina HR, Beeswax, Compritol ATO 888, and Precirol ATO 5 tablets. It was found that Beeswax (kd=2.13) has a very close drug release rate with the target profile (kt=1.95). Our results suggested that swelling and relaxation properties of lipid matrices should be examined together for a correct evaluation on drug diffusion mechanism of insoluble matrices.     

HPLC法同时测定甲硝唑含漱液中甲硝唑和羟苯乙酯含量

目的建立同时测定甲硝唑含漱液中甲硝唑和羟苯乙酯含量的方法。方法高效液相色谱法,选用phenomenex-C18（4.6×250mm,5μm）柱,以乙腈∶水（25∶75）为流动相,检测波长为255nm。结果甲硝唑和羟苯乙酯的回归方程分别为：Y=1.3892×10^4X-1.068226×10^4（r=0.9999,n=9）和Y=1.092077×10^5X-2.022870×10^4（r=0.9999,n=9）;线性范围分别为2.7-270.8μg.mL^-1和0.2-53.0μg.mL^-1;平均回收率分别为104.5%和98.3%。结论所用方法简便快速,结果准确可靠,可作为甲硝唑含漱液的质量控制方法。     

四苯硼钠法测定甲硝唑葡萄糖注射液中甲硝唑的含量

为了消除《中国药典》法测定甲硝唑葡萄糖注射中葡萄糖分解产物5－HMF对测定甲硝唑的含量的影响,采用四苯硼钠法测定甲硝唑葡萄糖注射液中甲硝唑的含量。求得该法的平均回收率98．95,RDS为0．4％,表明该法简便,可靠,能消除5－HMF的干扰,检测无需特殊条件。     

甲硝唑明胶海绵阴道栓剂的实验研究

本文介绍了甲硝唑明胶海绵阴道栓剂的制备和质量控制。经与以聚乙二醇为基质的甲硝唑栓剂和以聚醚型聚氨酯泡沫塑料为材料的甲硝唑阴道海绵栓剂比较，表明该剂型具有长效、安全、使用方便的特点。此外，该剂型经体内释放试验，证明体内外释药相关。