The suppressive effect of dipyridamole on the proteinuria of aminonucleoside nebhrosis and protamine-induced proteinuria, was investigated. Male Wistar rats were given puromycin aminonucleoside (80 mg/kg s.c.) or protamine sulfate (20 mg/kg i.v.), and the urine was collected in metabolic cages. The content of proteins in the urine was determined by using a continuous gradient microgel electrophoresis procedure. Dipyridamole (20 mg/kg p.o.) suppressed the excretion of albumin and proteins larger than albumin (HMP) in aminonucleoside nephrosis. But the excertion of proteins smaller than albumin (LMP) was not affected by dipyridamole. Dipyridamole also suppressed the excertion of HMP in protamine-induced proteinuria, though the excretion of albumin and LMP was not affected. Puromycin aminonucleoside and protamine sulfate were known to cause renal glomerular epithelial changes referred to as "fusion" of foot processes. Since dipyridamole was effective in suppressing the both types of proteinuria, this drug was considered to improve the damaged renal glomerular barrier for plasma proteins.
The interaction of zinc and other metal such as lead, mercury (II), cadmium, silver (II) on the activity of erythrocyte δ-aminolevulinic acid dehydratase (ALA-D) was investigated in vitro. At the concentrations ranging from 0.01 to 1.0 mmol/l, lead, mercury (II), cadmium and silver (II) strikingly inhibited the erythrocyte ALA-D activity. The in vitro addition of zinc having an activating effect for the erythrocyte ALA-D, was observed to eliminate the lead-induced inhibition of the erythrocyte ALA-D activity. And the degree of the elimination seemed to depend on the molar ratio (Zn/Pb) of both metal concentrations in the ALA-D assay. However, the inhibition of erythrocyte ALA-D activity caused by mercury (II), cadmium and silver (II) was not removed by the in vitro addition of zinc.
When liver fragments from eleven-day chick embryos were maintained on Eagle's minimal essential medium by the established method of organ culture, they developed ultrastructural features similar to liver cells in vivo, except that they had small amounts of smooth endoplasmic reticulum and little glycogen. The cultured liver cells synthesized DNA, RNA and protein. The addition of aflatoxin B1 to the medium inhibited the synthesis of nucleic acid. Aflatoxin B1 also produced the segregation of granular and fibrillar components in nucleoli and the disarrangement of ribosomes attached to endoplasmic reticulum. Since these results were consistent with the known effects of the toxin in animals, we concluded that organ culture of chick embryo liver could be a useful technique for other studies.
Rats of various ages were treated orally or intraperitoneally with potassium aspartate. The dose required to induce hypothalamic lesion varied considerably by the age of animals and route of administration. Additional experiment, in which the animals were orally treated three times a day with potassium aspartate in dose levels between the maximum safety dose and minimum lesion-producing dose in the preceding single dose study, revealed no hypothalamic lesion at all in any animals of each age group. In this condition, the maximum safety dose was 3-5 times as large as that in single dosage administration experiment. Regarding the safety evaluation of potassium aspartate preparations, brief discussions on some points in extrapolation of the results of the present experimental study to the clinical use were made.
Carteolol was administered orally by gastric intubation at 3, 15, 75 or 150mg/kg/day to ICR-JCL mice of both sexes prior to mating and to females during early stage of pregnancy to determine its effects on the entire reproductive process and fetal development. Following results were obtained: 1) The decrease of spontaneous motor activity was observed in all treatment groups, and some animals in the 75 mg/kg and 150 mg/kg groups pressed the chest or abdomen against the cage wall. 2) The incidence of early resorptions in the 75 mg/kg and 150 mg/kg groups was significantly higher than that in controls. 3) The ossification of the talus and calcaneus was significantly retarded in the 75 mg/kg and 150 mg/kg groups. The maximum non-effective dose on fertility and reproduction for carteolol was estimated to be 15 mg/kg/day, although the incidence of early resorptions was slightly elevated with this dose.
Carteolol was orally administered to mice once a day at doses of 3, 30 and 150 mg/kg/day during the perinatal and lactation periods and evaluated on its adverse effects on pregnant animals and their offspring. No appreciably abnormal findings related to the drug administration were revealed. Therefore, it was concluded that carteolol have no serious toxic potential on parturition and lactation by mother animals, no adverse effects on growth and development, and behavioral and reproductive performance of offspring and no carcinogenic action through placental and milk transfer.