Detail of "10118-90-8"

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Formation of volatile nitrosamines by drug-nitrite interactions under physiological conditions

Formation of volatile nitrosamines by drug-nitrite interactions under physiological conditions. Sakai, Ayako; Inoue, Takiko; Tanimura, Akio (Div. Food Addit., Natl. Inst. Hyg. Sci., Tokyo 158, Japan). Gann, 75(3), 245-52 (English) 1984. CODEN: GANNA2. ISSN: 0016-450X. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 4, 18 Twenty-eight drugs, most of which are tertiary amines, were tested for the formation of volatile nitrosamines by reaction with NO2- under physiol.Several reagents with their cas registry numbers 621-64-7 and 932-83-2 are used here. conditions; the drugs (10mM) were incubated with NO2- (40mM) at pH 3.0, 37° for 1 and 4 h. The volatile nitrosamines formed were detd. by gas chromatog.-thermal energy anal. Of the 28 drugs, 24 formed measurable amts. of volatile nitrosamines that are known carcinogens. The yields of nitrosodimethylamine (NDMA) [62-75-9] from aminopyrine [58-15-1] (55-65%) and minocycline [10118-90-8] (11%) were higher than that from dimethylamine under the same conditions. There may be a pathway not involving the secondary amine (dimethylamine) as an intermediate in the formation of NDMA from minocycline as well as from aminopyrine. Tolazamide [1156-19-0] gave rise to nitrosopiperidine (NPIP) [100-75-4] in addn. to nitrosohexamethyleneimine (NHXI) [932-83-2], formation of which was expected from the chem. structure of tolazamide, and the yield of NPIP (2-7%) was higher than that of NHXI (0.2-1.2%). Ascorbic acid [50-81-7] (40mM) was effective in decreasing the formation of nitrosamines from drugs by reaction with NO2-, although the blocking effects varied between 88 and 100% depending on the drugs tested or on the nitrosamines formed. .

Minocycline reduces gingival collagenolytic activity during diabetes

Minocycline reduces gingival collagenolytic activity during diabetes. Preliminary observations and a proposed new mechanism of action. Golub, L. M.; Lee, H. M.; Lehrer, G.; Nemiroff, A.; McNamara, T. F.; Kaplan, R.; Ramamurthy, N. S. (Sch. Dent. Med., State Univ. New York, Stony Brook, NY, USA). J. Periodontal Res., 18(5), 516-26 (English) 1983. CODEN: JPDRAY. ISSN: 0022-3484. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 14 Diabetes increases gingival collagenase [9001-12-1] activity, an effect that may be mediated by endogenous tissue changes and exacerbated by an overgrowth of Gram-neg. organisms in the gingival crevice. In an attempt to reverse this collagenolytic abnormality, minocycline [10118-90-8] (a semi-synthetic tetracycline) was administered to diabetic rats and humans. Adult male conventional or germ-free rats were made diabetic with streptozotocin, and half of these animals were administered minocycline (20 mg/day) by tube feeding for 3-4 wk prior to sacrifice. The buccal gingiva, entire skins, and mandibles were dissected and tested for collagenolytic enzyme activity, collagen content and alveolar bone loss, resp. Minocycline (200 mg/day) was administered for 7 days to an insulin-dependent diabetic adolescent human and an adult nondiabetic human; the twin brother of the diabetic was treated with penicillin. Gingival fluid collagenase activity was measured (using [3H-methyl] collagen as substrate in a new microassay) in 8 periodontal pockets in each subject before and after antibiotic therapy. Examn. of collagenase digestion products by SDS-polyacrylamide gel electrophoresis and fluorog. was also carried out. In rats, minocycline treatment: (1) suppressed the abnormality elevated collagenolytic enzyme activity in gingiva of diabetic rats, even under germ-free conditions; (2) inhibited neutrophil collagenase activity in vitro, and effect that was reversed by the addn. of Ca2+ (penicillin-streptomycin had no effect on the activity of this enzyme); and (3) retarded the abnormal loss of skin collagen and alveolar bone in diabetic rats. In humans, minocycline therapy reduced the collagenase activity of gingival crevicular fluid, an effect not produced by penicillin. Apparently, tetracycline therapy inhibits tissue collagenolytic enzyme activity by a mechanism at least in part unrelated to its antibacterial efficacy. This mechanism may provide a new therapeutic approach for suppressing excessive collagen resorption which occurs during periodontal disease and which can occur during other pathol. conditions.