Mechanism of testicular atrophy induced by di-n-butyl phthalate in rats. Part 1

Repeated oral doses of di-n-butyl phthalate (DBP) to male rats caused a decrease in testicular fructose and glucose and a sloughing of the germ cells on the first day of treatment. On day 2, more severe sloughing was seen and was accompanied by decreases in testicular iron and zinc levels and increases in the level of inositol and cholesterols. The sloughing was followed by atrophy, accompanied by dissociation of the germ cells from the Sertoli cells and reduction of triglycerides, cholesterols and phospholipids containing choline and ethanolamine residues in the testis.     

Effects of Panax ginseng extract on the benzo(a)pyrene metabolizing enzyme system

Ethanol extract of Panax ginseng C. A. Meyer, which has been used for centuries as a tonic in Asian countries, exhibited a selective induction of epoxide hydratase and cytosolic glutathione transferase activity without the concurrent induction of aryl hydrocarbon hydroxylase activity. Thus, Panax ginseng appears to have the potential to alter the metabolic patterns of benzo(a)pyrene and its reactive metabolites.     

A case of leiomyosarcoma of the prostate

A 50-year-old man with the symptom of anal pain was treated by pelvic exenteration, ileal conduit diversion and artificial anus. The pathologic diagnosis was leiomyosarcoma of the prostate. At 5 months post-operatively, the patient had no evidence of metastasis or recurrence.     

Pharmacokinetics of isosorbide dinitrate and its mononitrate metabolites after intravenous infusion

Plasma concentrations of isosorbide dinitrate (ISDN) and its two active metabolites 2-isosorbide mononitrate (2-ISMN) and 5-isosorbide mononitrate (5-ISMN) have been measured during and for 6 hr after intravenous infusion at a rate of 2.5 mg/hr during 1.75 hr in six cardiac patients, by a capillary gas chromatographic method. Data were analyzed by simultaneous modeling of the observed kinetics of the three compounds. Two or three phases were detected on the postinfusion ISDN concentration-time curves. ISDN concentrations declined with a mean terminal half-life of 2.81 hr +/- 0.7 SD. The mean systemic clearance of ISDN (2.9 L/min +/- 0.7 SD) and its mean total volume of distribution (259 L +/- 48 SD) were relatively high. Plasma 5-ISMN concentrations were 5- to 6-fold greater than those of 2-ISMN during the whole observation period. Maximum levels of 2-ISMN (6.7 ng/ml +/- 0.9 SD) and of 5-ISMN (27 ng/ml +/- 6 SD) occurred within a few minutes after the end of infusion. The mean half-lives of 2-ISMN (1.59 hr +/- 0.19 SD) and of 5-ISMN (3.78 hr +/- 0.79 SD) estimated by the model were smaller than those calculated by a model-independent method (2.95 hr +/- 0.41 SD and 5.98 hr +/- 2.22, respectively), but were in good agreement with those reported in the literature following separate administration of both metabolites to man. This study shows how such modeling can distinguish between metabolite formation and elimination processes and allow the determination of metabolite half-lives after administration of the precursor drug.     

Immunotherapy for lung cancer by streptococcal preparation OK-432

To evaluate the clinical efficacy of OK-432 immunotherapy, patients admitted between 1975 and 1982 were randomized into two groups: An immunochemotherapy (IM-C) group and a chemotherapy (control) group. For each group, a fixed chemotherapy was administered using a combination of three drugs. The survival rates of cases with non-small cell carcinoma were evaluated at the end of 1987. One hundred and fifty-seven cases in the IM-C group and 148 in the control group were eligible for evaluation of long-term survival rates. Statistically significant improvement of the survival rates in the IM-G group were noted in the following items: All cases, resected cases, non-resected cases, resected stage I + II cases, resected stage III cases, completely resected cases, incompletely resected cases, and cases with epidermoid carcinoma. However, in comparison of adenocarcinoma there was no significant difference between the two groups. SU-polysaccharide skin test and natural killer activity were the best immunological parameters during the OK-432 therapy. To intensify the effects of immunotherapy, a possibility of regional immunotherapy was studied following some experimental works. Regional infusion of LAK cells (induced by incubation of patient's lymphocytes with rIL-2) through bronchial artery after regional infusion of OK-432 and chemotherapeutics showed favorable effect for advanced lung cancer. Future prospect of these regional adoptive immunotherapy was discussed.     

Isozyme variation in Simulium (Edwardsellum) damnosum s.l. (Diptera: Simuliidae) from Kenya

Isozyme variation of the Simulium damnosum sibling species complex was studied by cellulose acetate electrophoresis (CAE) from four Kenyan river systems. Two enzymes, PGM and HK, were diagnostic and differentiated the larvae collected in Western and Nyanza provinces from the larvae collected at Mt. Kenya. Allele frequency differences of the enzyme PGI allowed about 75% separation of the geographically distinct populations.     

Metabolic fate of 125I-labeled batroxobin in rats and dogs

125I-Labeled batroxobin was prepared and following its intravenous and subcutaneous administrations to rats and dogs, the blood radioactivity was determined. In the both species following the intravenous injections, the decrease in radioactivity was biexponential. Following subcutaneous administration, radioactivity became maximal at 6h and decreased in a manner similar to that of the beta-phase of the intravenous injection. The blood concentration of fibrinogen in dogs was also determined. After the intravenous injection, fibrinogen became undetectable 1h later, and appeared again in the blood at 24h. After the subcutaneous injection, the decrease was not so rapid. Fibrinogen resumed its original levels at 7 day after the administration in both the routes. Radioactivity after the both injections was excreted generally in the urine in about the same amounts. The total urinary and fecal excretions in rats and dogs were 80 and 95%, respectively. The distribution of radioactivity in the tissues was examined by counting technique and whole-body autoradiography. Radioactivity predominantly accumulated in the thyroid and stomach and could also be found in the kidneys and liver in fair amounts. The distribution patterns of radioactivity for both the routes of administrations and also for male and pregnant rats were basically the same. In fetus rats, a slight distribution was noted. From the results of gel filtration chromatography and trichloroacetic acid fractionation, [125I] batroxobin was metabolized soon after the administration to afford low molecular substances such as 125I-ion in the plasma and urine.