Sex difference in the O-dealkylation activity of 7-hydroxycoumarin O-alkyl derivatives in liver microsomes of rats

Sex differences in the O-dealkylation activities of O-alkyl derivatives of 7-hydroxycoumarin were compared using liver microsomes from male and female rats. The sex difference (male>female) in the O-depropylation activity was found to be greater than the sex differences in O-demethylation and O-deethylation activities. The magnitude of sex difference seen in the O-depropylation activity was diminished after pretreatment of rats with spironolactone, phenobarbital, isosafrole or 3-methylcholanthrene. The latter two inducers were much more effective than the former in enhancing the activity. The sex differences in the O-dealkylation activities were also seen when the activities were measured in the presence of cumene hydroperoxide instead of NADPH. The sex difference of the O-depropylation activity remained essentially unchanged by the fortification of male and female microsomes with purified NADPH-cytochrome c (P-450) reductase. The difference was also seen when reconstituted with cyto- chrome P-450 partially purified from both male and female rats by means of ω-amino-n-octyl Sepharose 4B and hydroxylapatite columns. The addition of 7,8-benzoflavone to the incubation mixture resulted in the increased magnitude of sex difference in the O-depropylation activity.From these results, we confirm that one or more cytochrome P-450 species other than a cytochrome P-450 species sensitive to 7,8-benzoflavone are present in male microsomes in higher amounts than in female microsomes.     

Pathological changes associated with topical chemotherapy of adriamycin for bladder cancer

Since the study of intravesical instillation of thio-TEPA by Jones and Swinney, the method of topical chemotherapy with several anti-cancer drugs for superficial bladder tumors have been reported and it is now an established method of anti-bladder cancer treatment. Adriamycin is one of the most common topical agents against bladder tumor today. We studied the histopathological changes associated with the topical treatment in 26 cases of bladder cancer, all in which either TUR-Bt or cystectomy (partial or radical) had been performed after intravesical instillation of adriamycin. Transurethral biopsies of bladder tumor were done before the chemotherapy, and these findings were histopathologically compared with those of the surgical specimens. In 3 of the 26 cases, the tumors disappeared completely. In the other 23 cases, the main changes were: 1) cellular atrophy of tumor, 2) exfoliation, 3) interstitial hyalinous degeneration, 4) hemorrhage, and 5) dystrophic calcification. These changes are nonspecific of adriamycin, which seems to act as a toxic substance despite its potential activity to inhibit RNA replication.     

Clinical use of gentamicin in the field of surgery (author's transl)]

Gentamicin (GM) was intramuscularly administered to 24 patients with various infections (including 1 for prophylaxis of a postoperative infection) in the dose of 40 mg X 2/day for 4-26 days. In children, the maximum daily dose was 3.4 mg/kg and the minimum was 1.2 mg/kg (mean: 2-3 mg/kg). The results obtained are as follows: 1) Clinical efficacy of GM was excellent in 2, good in 9, fair in 4, null in 4 and indeterminate in 5, out of 24 cases. The effective rate was 57.9% (11/19). 2) In 21 strains isolated in 13 cases out of 24, efficacy of GM was good in 10, fair in 5, null in 3 and indeterminate in 3. The effective rate was 55.6% (10/18). 3) No significant side effect was observed in this clinical study.     

Pharmacological studies on oxatomide: (4) Effect on the histamine release from isolated rat peritoneal exudate cells (PEC) and lung slices

The present study was carried out to evaluate the inhibitory effect of oxatomide and disodium cromoglycate (DSCG) on the histamine release from rat PEC and lung slices induced by antigen-antibody reaction, concanavalin A, compound 48/80 and A-23187. Oxatomide in the range of 1 microM to 10 microM inhibited the allergic histamine release from rat PEC and lung slices induced by antigen-antibody reaction in the presence of phosphatidyl-L-serine (PS). Although the inhibitory action of oxatomide was significant even at a concentration of 1 microM, the action did not increase with an increase in concentration of the drug. DSCG showed a concentration-dependent inhibition on the allergic histamine release from rat PEC and lung slices in the range of 10 microM to 100 microM. The histamine release from rat PEC induced by the combined treatment of concanavalin A and PS was inhibited by oxatomide (0.1 to 10 microM) and DSCG (10 to 100 microM). Oxatomide (up to 10 microM) showed no effect on the histamine release induced by compound 48/80, while DSCG in the range of 10 microM to 100 microM showed a concentration dependent inhibition of the release. Oxatomide at a concentration of 10 microM showed a significant inhibition on the histamine release induced by the calcium ionophore A-23187. On the other hand, DSCG had no effect on this reaction. Oxatomide at high concentrations did not stimulate the histamine release by itself.     

Fluid and fibrosis in the human middle ear

Temporal bones from 12 cases of adult otitis media with effusion were studied for the process of fibrosis. There were three types of fibrotic courses, including total replacement of fluid and complete obliteration of middle ear spaces. Thus, the author concluded that effusion, tissue proliferation, fibrosis, and adhesions of the tympanic membrane are sequential findings of otitis media with effusion.