[Effect of MHS-G, an amino acids granule, on hepatic encephalopathy in portacaval anastomosis rats].

Using portacaval anastomosis (PCA) rats as a model with or without injection of ammonium acetate, we investigated the effects of MHS-G on the abnormalities of electroencephalogram (EEG) and brain amines metabolism in comparison with those of SF-1008C, a commercial nutritional preparation for hepatic failure. MHS-G (0.68 g/kg, p.o.) clearly improved both the abnormalities of EEG (such as reduction of amplitude, increasing delta wave distribution and decreasing beta wave distribution) and brain amines metabolism (such as increasing of Trp and DOPAC content) after injection of ammonium acetate. Moreover, MHS-G significantly increased branched chain amino acid concentrations and decreased aromatic amino acid concentrations in plasma and brain in comparison with water, and it significantly decreased the ammonia level in plasma in comparison with water and SF-1008C. These results suggest that MHS-G has a positive effect on abnormalities of EEG and amino acids metabolism in the plasma and brain of PCA rats.

Serogrouping of oral Streptococcus intermedius.

Employing twenty fresh oral isolates of Streptococcus intermedius, studies were carried out to characterize serological relations among the isolates and also between the isolates and the strains of bacterial species closely related to S. intermedius. The Rantz-Randall extracts from the cells were used as antigens. The anti-rabbit serum raised against S. intermedius ATCC 27335T reacted with the cell extracts from only three strains of the isolates, which were designated serogroup I strains. The other isolates were classified into four serogroups, I, III, IV, and V, which specifically reacted with the cell extracts from the homologous serogroup strains. However, the serogroup II antiserum formed in immunodiffusion a common precipitin line between the extracts from the cells of serogroups II and I. The serogroups I, III, IV, and V antisera reacted with none of the extracts from the bacterial cells closely related to S. intermedius, which included Streptococcus anginosus ATCC 33397T, Streptococcus constellatus ATCC 27823T, three NCTC strains of "Streptococcus milleri," and three ATCC strains of Streptococcus MG. The precipitin line formed by the homologous reaction of the serogroup II antiserum was found to be a reaction of identity with that formed by the extract from "S. milleri" NCTC 10708. Conversely, the antiserum against NCTC 10708 strain did not react with the cell extracts of serogroup II.

[Intravenous chronic toxicity of lentinan in rats: 6-month treatment and 3-month recovery (author's transl)].

Chronic toxicity of lentinan was studied in male and female JCL : SD rats. Lentinan was given intravenously into tail vein. Dosage levels employed were 0 (5% mannitol), 0.01, 0.1, 1 (with or without dextran), and 10 mg/kg/day for 6 months in a volume of 1 ml/100 g body weight. After 6 months, the treatment was discontinued and a recovery study was performed for 3 months. Rats receiving 10 mg/kg had redness and necrosis of the tail, the treatment was stopped at week 5, and the rats were sacrificed. Rats receiving 1 mg/kg showed redness of the ear, tail, and scrotum, which was remarkable in the 2nd and 3rd months. Body weight gains were not adversely affected. Laboratory examinations revealed an increase in leukocyte count, decreases in differential eosinophil count and platelet count, and an increase in serum beta-globulin level in drug-treated rats. At autopsy after 6 months, rats from the drug-treated groups had pulmonary hemorrhage and enlargements of the spleen and mesenteric lymph nodes. Histologic changes attributable to treatment included (1) activation of reticulo-endothelial system such as small epithelioid cell nodule in the liver, spleen, and mesenteric lymph nodes, and mobilization of Kupffer cells; (2) arteritis in various organs, especially notable in the spleen, testis, and epididymis ; (3) hemorrhage in the lung; and (4) hypospermatogenesis. All these changes described above had a propensity to recover. The maximum no effect level was estimated to be less than 0.01 mg/kg in the present study in male and female rats.

[Chronic toxicity test of 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone (M73101) in beagle dogs (author's transl)].

Male and female dogs, aged 17--21 months, were administered orall M 73101 (0, 60, 120 and 240 mg/kg/day), a new analgesic and antiinflammatory drug, for 27 weeks, and following recovery test was carried out for 5 weeks. Dead animals were not found throughout the experimental period. Body weight gain, and food and water consumption were not affected due to M 73101 administration. Except for a slight increase of vomitting in the highest dose, there were no abnormal symptoms. Biochemical examination showed the slight increase in serum alkaline phosphatase activity and free cholesterol level. Pathological examination revealed a dose-dependent increase of liver weight and hypertrophy of hepatocytes due to proliferation of smooth endoplasmic reticulum. In addition, mitochondria became irregularly large in the highest dose. There were no abnormal findings in the gastro-intestinal tracts except for an erosion of gastric mucosa, which was noted in a female dog treated 240 mg/kg/day of M 73101. From these results, it was suggested that the maximum non-toxic dose was 60 mg/kg/day or less, and the greatest safety dose was 120 mg/kg/day in beagle dogs.

[Subacute toxicity test of AMI-U-II, a new amino acid solution for renal failure (author's transl)].

Subacute toxicity test of AMI-U-II was carried out using male and female JCL:SD rats. The animals were given intravenously AMI-U-II (80, 40 and 20ml/kg) or reference solution (80 and 40ml/kg) for five weeks. Tachypnea, depression of spontaneous activity, blepharoptosis and edema of face were observed in rats treated with AMI-U-II or reference solution at highest dose. Food consumptions and gaining body weight were slightly reduced in male of these animals, but water intakes were increased in both sexes. Autopsies of the animals which died during five weeks showed pulmonary congestion and/or edema, ascites and pleural effusion. Microscopically, hydropic degeneration of liver cells and dilation of renal tubules and Bowman's capsules were shown. It seems likely that most of these findings were caused by hypervolumic administration of amino acid solution.