Citations

ABSTRACTIsoniazid (INH), a front-line antituberculosis agent, is activated by mycobacterial catalase-peroxidase KatG, converting INH into bactericidal reactive species. Here we investigated the requirements and the pathway of nitric oxide (NO˙) generation during oxidative activation of INH byMycobacterium tuberculosisKatG in vitro. We also provide in vivo evidence that INH-derived NO˙ can inhibit key mycobacterial respiratory enzymes, which may contribute to the overall antimycobacterial action of INH.

ABSTRACTIsonicotinic acid hydrazide (INH) is a frontline antituberculosis agent. Once taken up byMycobacterium tuberculosis, INH requires activation by the catalase-peroxidase KatG, converting INH from its prodrug form into a range of bactericidal reactive species. Here we used15N-labeled INH together with electron paramagnetic resonance spin trapping techniques to demonstrate that nitric oxide (NO˙) is generated from oxidation at the hydrazide nitrogens during the activation of INH byM. tuberculosisKatG. We also observed that a specific scavenger of NO˙ provided protection against the antimycobacterial activity of INH in bacterial culture. No significant increases in mycobacterial protein nitration were detected, suggesting that NO˙ and not peroxynitrite, a nitrating metabolite of NO·, is involved in antimycobacterial action. In conclusion, INH-derived NO·has biological activity, which directly contributes to the antimycobacterial action of INH.

Acute ulcers of the gastric mucosa are found in a large percentage of dogs and cats dying after adrenalectomy. These ulcers seem to develop during the moribund period. They are apparently peptic ulcers forming at the site of local hemorrhages in the gastric mucosa. They are true acute ulcers, usually penetrating to the muscularis mucosa with a total loss of epithelium. They develop in the absence of pancreatic secretion and bile. However, they appear to develop only in an acid medium.

Emboli made of paraffin and the animal's own blood were sent into the venous circulation of dogs. Death did not occur until the pulmonary circulation was practically occluded. The results were the same whether the blood pressure of the animal was normal or depressed by ether or disease and whether the procedure was carried out under ether or local anesthesia.

Acute gastric ulcers are found in a large percentage of animals dying from acute adrenal insufficiency. In dogs in which a portion of the jejunum had been transplanted some time previous to the removal of the adrenals, the gastric mucosa showed more marked changes than the transplanted jejunal mucosa. This tends to show that the gastric juice as the cause of the ulcer is but a secondary although necessary factor.

Purpose: A phase III, randomized, double-blind study was conducted by the North Central Cancer Treatment Group to determine the efficacy and toxicity of oral glutamine for the prevention of acute diarrhea in patients receiving pelvic radiation therapy (RT). Patients and Methods: All 129 patients enrolled from 14 institutions between February 1998 and October 1999 were eligible. Patients received 4 g of glutamine or placebo orally, twice a day, beginning with the first or second day of RT and continuing for 2 weeks after RT. During treatment, patients were assessed weekly for toxicity, and a bowel function questionnaire was administered. The primary measures of treatment efficacy were diarrhea levels measured by maximum grade of diarrhea, incidence of diarrhea, and average diarrhea score. After completion of RT, the bowel function questionnaire was administered weekly for 4 weeks and at 12 and 24 months. Toxicity was measured by National Cancer Institute common toxicity criteria. Results: The median age of patients was 69 years (range, 34 to 86 years). The two treatment arms were balanced with respect to all baseline factors. There were no significant differences in toxicity by treatment. Quality-of-life scores and the mean number of problems reported on the bowel function questionnaire were virtually identical for both treatment groups. The incidence of grade 3 or higher diarrhea was 20% for the glutamine arm and 19% for the placebo arm (P = .99). The maximum number of stools per day was 5.1 for the glutamine arm and 5.2 for the placebo arm (P = .99). Conclusion: There is no evidence of a beneficial effect of glutamine during pelvic RT.