Treatment of childhood brucellosis: results of a prospective trial on 113 children.

Treatment of childhood brucellosis is controversial and is currently dependent on inclusion of aminoglycoside antibiotics which are both costly and potentially toxic. Hence an alternate mode of therapy preferably dependent exclusively on oral agents is desirable because this decreases medical cost. In this study we prospectively treated 113 children with a combination of two oral agents, trimethoprim-sulfamethoxazole (10 to 12 mg/kg trimethoprim, 50 to 60 mg/kg sulfamethoxazole and rifampin 15 to 20 mg/kg in two divided doses for 6 weeks. The treatment was well-tolerated and all patients responded by defervescence of fever and resolution of all symptoms within 1 to 3 weeks. Relapse after 6 months occurred in four children all of whom responded to repeat therapy by the same agents. We conclude that the combination of trimethoprim-sulfamethoxazole and rifampin is both cost-effective and safe for the treatment of childhood brucellosis.

Effect of retinoic acid, butylated hydroxytoluene, propylgallate and selenium on 2-acetylaminofluorene induced hepatotoxicity.

Rats of the Sprague-Dawley strain were administered 2-acetylaminofluorene (2-AAF) in different diet regimens to ascertain the effect of retinoic acid(RA), butylated hydroxytoluene (BHT), propylgallate (PG), and selenium on induced hepatotoxicity. In the first study, groups of young male albino rats of the Sprague-Dawley strain were fed a diet containing 0.05% 2-AAF. Carcinogen was added to the diet for 3 weeks, omitted 1 week, added 2 weeks, omitted 2 weeks, added 3 weeks, and omitted for the final 4 weeks. Animals were terminated at the end of 15 weeks. Supplementation of the diet by 0.5% BHT, PG or 4 ppm selenium as sodium selenite in the drinking water either throughout the entire feeding period or only during the administration of the carcinogen-free diet greatly inhibited the hepatotoxicity of 2-AAF. In contrast, addition of 0.02% RA to the diet in the above feeding regimens enhanced the hepatotoxicity of 2-AAF. In the second study, male and female Sprague-Dawley rats were administered a diet containing 0.03% 2-AAF for 16 weeks or a diet containing 0.03% 2-AAF supplemented with 0.02% RA for the first 4 weeks and the last 6 weeks of the 16-week feeding period. Addition of the 0.02% RA to the diet enhanced the hepatotoxicity of 2-AAF, especially in the female rats.

Anti-oxidative effects of vitamin B2-butyrate on the cardiac mitochondrial disorders induced by adriamycin.

The combined use of CoQ10 with adriamycin has been recommended for reduction of the cardiotoxicity that occurs during cancer chemotherapy. Vitamin B2-butyrate was also investigated in order to determine anti-oxidative effects on adriamycin cardiotoxicity. This vitamin analysis prevented enhanced lipid peroxidation and rectified the respiratory disorders of heart mitochondria induced by adriamycin, however, the deficiency of the CoQ10-pool was not rectified. The combined approach of using CoQ10 for rectifying the deficiency of this component and of using B2-butyrate for reducing lipid peroxidation was indicated for adriamycin cancer chemotherapy.

Effect of retinoic acid, butylated hydroxytoluene, selenium and sorbic acid on azo-dye hepatocarcinogenesis.

Groups of male Sprague-Dawley rats were maintained on a basal diet containing 0.05% 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB) for 9 weeks. The diets of these groups were supplemented at certain stages of the study with retinoic acid, butylated hydroxytoluene (BHT), or sorbic acid. In other groups, selenium (as sodium selenite) was added to the drinking water. The study was terminated after 9 weeks and the livers evaluated for pre-cancerous changes and presence of tumors. 38/42 animals in the control groups given the diet containing the 3'-MeDAB developed liver tumors. Only 3/27 rats given the 3'-MeDAB regimen supplemented with retinoic acid had liver tumors. A similar reduction was obtained with BHT, while sorbic acid exerted no protective effect against hepatocarcinogenesis. Se supplementation afforded some protection if given throughout or during the early stages of azo-dye administration and a lesser effect if given during the later stages of dye feeding.

Effects of selenium and retinoic acid on the metabolism of N-acetylaminofluorene and N-hydroxyacetylamino-fluorene.

Male albino rats were given 4 ppm selenium (Se(as Na2SeO3) in the water, or 0.25% retinoic acid was added to the basal diet for 3 days. Control and treated animals were given 17 mg acetylaminofluorene (AAF)-9-14C or N-hydroxyacetylaminofluorene (NOHAAF)-9-14C/kg body wt. The administration of Se enhanced glucuronyl transferase activity by 100% and inhibited p-nitrophenol-sulfotransferase by 50%. Retinoic acid enhanced the glucuronyl transferase 37% and inhibited the p-nitrophenol-sulfotransferase by 50%. Pretreatment with Se lowered levels of both AAF and NOHAAF in liver tissue by 30%. Se administration lowered the binding of the labeled carcinogens, or metabolites thereof, to the liver DNA and tRNA.

Methylation of DNA in rat liver and intestine by dimethylnitrosamine and N-methylnitrosourea.

A chromatographic procedure for improved separation of deoxyribonucleosides and methylated deoxyribonucleosides is described. DNA was isolated from liver and small intestine of rats treated with [14C]dimethylnitrosamine ([14C]DMN) or N-[3H]methyl-N-nitrosourea ([3H]MNU), and the purified DNA was hydrolyzed enzymatically. The deoxyribonucleosides were chromatographed on an Aminex A-6 cation exchange column at 37 degrees C with 0.4 M ammonium formate, pH 4.5, as eluant. In addition to showing the presence of the expected alkylated products, N7-methyldeoxyguanosine (determined as N7-methylguanine) and O6-methyldeoxyguanosine, several other minor methylated products were found in liver and intestinal DNA of rats treated with DMN or MNU. Two of these products are believed to be N3-methylthymidine and O4-methylthymidine.

A phenylalanine transfer RNA azo dye complex in livers of rats fed diets containing 3'-methyl-4-dimethylaminoazobenzene.

A highly purified phenylalanine transfer RNA (tRNAPhe) was isolated from a normal rat liver and from livers of male and female rats fed a semisynthetic diet containing 0.06% 3'-methyl-4-dimethylaminoazobenzene for 3 weeks. Absorption spectral analysis on tRNAPhe from normal and carcinogen-fed rats indicated an unusual absorption above 335 nm by tRNAPhe isolated from the latter group. Ribonuclease T1 digestion followed by chromatography on diethylaminoethyl cellulose columns indicated the existence of a major peak of covalently bound oligonucleotide-azo complex. Microcrystalline cellulose thin-layer chromatography resolved the peak into one major and four minor components, all with similar absorption spectra. Enzymatic digestion of the major peak obtained from diethylaminoethyl cellulose chromatography to ribonucleosides, followed by chromatography on cellulose thin layer, resulted in one major and three minor components. A higher uridine:cytidine base ratio was also observed in the tRNAPhe isolated from the carcinogenfed animals. These findings suggest that certain transfer RNA's may be major targets for this azo carcinogen.