Effects of insulin on maltase and N-acetyl-beta-D-glucosaminidase (NAG) activities of serum and kidney in experimental diabetic rats

The activities of lysosomal maltase in the serum, urine and kidney were determined in rats with diabetes induced by streptozotocin (STZ, 75 mg/kg, i.p.) and compared with the changes in N-acetyl-beta-D-glucosaminidase (NAG) activity. Moreover, effects of insulin on maltase and NAG activities of the serum, urine and kidney in diabetic rats were studied. The following results were obtained: 1) The serum maltase activity within 24 hr after administration of STZ was influenced by insulin secretion. 2) Significant increases in blood urea nitrogen (BUN) levels were observed from the 3rd week after a single administration of STZ. The serum insulin level significantly decreased at 3 weeks after treatment of STZ. In this time, maltase activity in the serum rapidly increased, while the enzyme activity in the kidney decreased considerably. On the other hand, the changes in NAG activities in the serum, urine and kidney after administering STZ were almost similar to those in maltase activities. 3) There were positive relationships between maltase and NAG activities in the serum and urine in diabetic rats, respectively. 4) When lente insulin (2U) was subcutaneously injected once daily for 20 days from 24 hr after administration of STZ, NAG activities in the serum and kidney approached to the control levels. However, maltase activities in the group treated with insulin were significantly higher in the serum and kidney than those in the control group.     

Electrophysiological actions of N-(2,6-dimethylphenyl)-8-pyrrolizidine-acetamide hydrochloride hemihydrate (SUN 1165), a new antiarrhythmic agent

The electrophysiological actions of SUN 1165 on isolated guinea pig atrial and papillary muscles, canine Purkinje fibers, and rabbit sinoatrial node were studied using standard microelectrode techniques. SUN 1165 in low (10(-7) g/ml) concentration had little effect on any of the action potential parameters measured. Intermediate (10(-6) g/ml) concentration of the compound shortened the duration of action potential of canine Purkinje fibers and increased ratio of the effective refractory period to the duration of action potential at 90% repolarization in guinea pig atrial muscles. At high (10(-5) g/ml) concentration, the compound reduced the maximum rate of rise of phase 0 in guinea pig atrial, papillary muscles, and canine Purkinje fibers, though the change in the latter was not statistically significant, and also decreased the action potential amplitude in guinea pig atrial muscles and canine Purkinje fibers. At all concentrations (10(-7)-10(-5) g/ml) tested, the compound exerted little effect both on spontaneous action potentials in rabbit sinoatrial node cells and on Ca2+-mediated slow responses in partially depolarized guinea pig papillary muscles. These results indicate that SUN 1165 may selectively inhibit cardiac sodium channels and is likely to be of value in correcting not only ventricular but also supraventricular tachyarrhythmias.     

Myrocin C, a new diterpene antitumor antibiotic from Myrothecium verrucaria. I. Taxonomy of the producing strain, fermentation, isolation and biological properties

A new diterpene antitumor antibiotic, myrocin C, has been isolated from the culture filtrate of a soil fungus, Myrothecium verrucaria strain No. 55. The antibiotic was effective against Gram-positive bacteria, fungi and yeasts, and prolonged the life span of mice bearing Ehrlich ascites carcinoma.     

Liver transplantation in children. Blood transfusion and metabolic disorders

Metabolic disorders during hepatic transplantation can be partly induced by blood transfusion. A retrospective survey of perioperative biological data recorded in patients under 18 years of age having liver transplantation was performed. Blood transfusion was also studied. For this evaluation, patients were divided in a paediatric group I (n = 20; mean age: 3.7 years) and an adolescent group II (n = 11; mean age: 14.3 years). Blood transfusion was significantly (p less than 0.05) more important in group I (302 +/- 286 ml X kg-1) than in group II (148.5 +/- 156 ml X kg-1). Autotransfusion of washed red cells was performed in six patients, allowing a mean 17 +/- 7% saving in blood transfusion. Severe hypernatraemia over 152 mmol X l-1 due to blood transfusion was observed only in five patients in group I. Hyperglycaemia increasing till the revascularization of the new liver was constant in both groups, but significantly more pronounced in group II. Cardiac arrest occurred twice in group I at initial revascularization. In group I, children with biliary atresia were not significantly different from the others for the duration of operation and the volume of blood transfusion; however the latter was more abundant. Conversely, in group II, the duration of operation was longer (p less than 0.05) in patients with previous abdominal surgery than in others. Finally the paediatric group differs from the adolescent group by obvious differences in anaesthesia and intensive care and specifically in hepatic transplantation by larger volume of blood transfusion leading to severe hypernatraemia. In further studies, adolescents should be distinct from the paediatric group and included in the adult group.     

Antitumor activity of orally administered streptococcal preparation, OK-432 on murine solid tumors and its absorption from the gut

OK-432 is an immunopotentiator which is normally administered by injection. In the present study, the antitumor activity of orally administered OK-432 on various solid tumors and the absorption of OK-432 from the gut were studied. Orally administered OK-432 inhibited the growth of Meth-A and BAMC-1 fibrosarcomas which had been subcutaneously transplanted in BALB/c mice. Autoradiograms of mice which had been administered 14C-labelled OK-432 orally demonstrated the absorption of OK-432 from the gut, and about 6% of orally administered OK-432 was absorbed 24 hrs after its administration. Moreover, an immunofluorescent study using an anti-OK-432 antibody revealed specific fluorescence in the mesenteric lymph node of mice which had been orally administered with OK-432. These results suggest that oral administration of OK-432 may be a beneficial immunotherapy.     

In vivo activity and metabolic fate of 2-(2,3,3-triiodoallyl)tetrazole (ME1401), a novel antifungal agent

2-(2,3,3-Triiodoallyl)tetrazole (ME1401), a novel antifungal agent, showed therapeutic effectiveness in topical treatment of experimental dermal infections with Trichophyton mentagrophytes and Candida albicans in guinea-pigs. Addition of diethyl sebacate to the ME1401 preparations increased its in vivo antifungal activity and its penetration into the skin. When the estimation of efficacy of treatment with active formulations was made on the basis of skin lesion and the rate of negative skin cultures in comparison with those for infected, untreated or placebo-treated controls, the in vivo activity of 0.5% ethanol tincture or gel of ME1401 was comparable to that of reference antimycotic drugs such as clotrimazole, haloprogin and others. Pharmacokinetic studies in the experimental animals demonstrated that ME1401 was unstable in vivo, being readily converted to an active metabolite 2-(3-iodopropargyl)tetrazole (CN144) first and then to 2-propargyltetrazole (CN151). CN144 showed potent in vitro and in vivo antifungal activities, while the in vitro activity of CN151 was negligible.     

Ontogeny of gamma-melanocyte-stimulating hormone in the brain and hypophysis of the rat: an immunohistochemical analysis

The ontogeny of gamma-melanocyte stimulating hormone (gamma-MSH)-like immunoreactive (gamma-MSHI) structures in the brain and hypophysis was investigated in the rat by means of indirect immunofluorescence. gamma-MSHI neurons in the arcuate nucleus appeared at Day 13 of gestation, in the anterior hypophysis at Day 16, in the intermediate lobe at Day 18, and in the nucleus commissuralis after birth. gamma-MSHI fibers first appeared at Day 15 of gestation in the hypothalamic area and extended dorsally to reach the surface of the diencephalon. At Day 16 of gestation, another gamma-MSHI fiber bundle was found that ran laterally along the ventral surface of the diencephalon. At Day 19, immunoreactive fibers first appeared in the forebrain, diencephalon, midbrain and upper pons, and thereafter they increased in number, reaching a maximum at postnatal Day 15. gamma-MSHI fibers in the lower pons and medulla oblongata first appeared after birth. They also increased in number with age and reached a maximum at postnatal Day 15. The present ontogenetical study has demonstrated the different times of first appearance of each of the 3 major gamma-MSHI structures-containing cell groups in the brain, i.e., the arcuate nucleus, hypophysis and nucleus commissuralis. These findings may reflect the different functions of 3 groups of cells.