Potentiation of ethanol narcosis by dopamine- and l-DOPA-based isoquinolines.

The isoquinolines, salsolinol and 3-carboxysalsolinol, prolong ethanol-induced narcosis in mice. Pretreatment with carbidopa increases the effect of 3-carboxysalsolinol but not of salsolinol. These results suggest that ethanol sleeping-time potentiation by l-LOPA may involve a partial conversion to the isoquinoline in vivo. A central depressant action of salsolinol or the 3-carboxy analogue is suggested.     

Antitumor activity of the Isodon diterpenoids: structural requirements for the activity.

A significant antitumor activity of oridonin (1) and lasiokaurin (2), the kaurene-type diterpenoids of Isodon species, was shown by their i.p. injection to the test mice inoculated by Ehrlich ascites carcinoma. Enmein (8), compounds 9 and 3 were also active under larger dose. Subsequently, the relationship between their chemical structure and antitumor activity was investigated, and the activity of oridonin (1) and lasiokaurin (2) was rationalized in terms of their structural feature.     

Different effects of synthetic delta 9-tetrahydrocannabinol and cannabis extract on steroid metabolism in male rats

Repeated oral administration of cannabis extract as well as synthetic delta9-tetrahydrocannabinol to male rats produced significant changes in excretion of androgenic steroids and their metabolites as detectable in blood and urine. Cannabis extracts were found to be significantly more active than the mixtures containing same amounts of synthetic cannabinoids.     

Administration of D-alanine did not cause increase of D-amino acid oxidase activity in mice.

D-amino acid oxidase (DAAO) activity was not altered in the liver and kidney by oral administration of D-alanine to adult mice. The enzyme was apparently not induced by the enteric microflora either, since the enzyme activity in the liver and kidney of germ-free mice was not different from that of specific-pathogen-free mice. The times of appearance of DAAO activity and of free D-amino acids in the kidney were elucidated using suckling mice. DAAO activity started to increase 7 days after birth, and reached almost the adult level by 28 days. The content of free neutral D-amino acids also increased with age, in a similar fashion. A possible conclusion is that the enzyme activity normally increases during this period, to eliminate the free D-amino acids which have increased with age in the suckling mice. Consequently, the administration of D-alanine had no further effect in increasing enzyme activity.     

Increase in pituitary melanocyte-stimulating hormone activity of genetically obese (ob/ob) mice

Summary Melanocyte-stimulating hormone (MSH) activity was measured in the pituitaries of genetically obese and lean control mice using the frog skin bioassay. Obese mice pituitaries demonstrated very significantly elevated levels of biologically active MSH when compared to their lean littermates. These results support the hypothesis that the elevated levels of pituitary hormones found in obese mice possess true biological activity.     

Search for sex-dependent and gestation-induced changes in choline and ethanolamine phosphorylating activities.

Choline kinase and ethanolamine kinase of liver, brain and kidney had nearly the same activity in 4-month-old male and virgin female mice. Ethanolamine kinase activity was almost doubled in the liver and brain of mice in advanced pregnancy compared with the virgin, while choline kinase activity was unaltered.     

Comparative studies on the trichomonacidal activity of 5-nitroimidazole-derivatives in mice infected s.c. or intravaginally with T. vaginalis.

The trichomonacidal efficacy of metronidazole, tinidazole, nimorazole and ornidazole was studied in mice infected s.c., or for comparison purposes intravaginally. In both test systems, the drugs revealed nearly the same order of efficacy, whereby the compounds showed a marked decrease of activity when analyzed in s.c. infected mice.     

Search for sex-dependent and gestation-induced changes in choline and ethanolamine phosphorylating activities

Summary Choline kinase and ethanolamine kinase of liver, brain and kidney had nearly the same activity in 4-monthold male and virgin female mice. Ethanolamine kinase activity was almost doubled in the liver and brain of mice in advanced pregnancy compared with the virgin, while choline kinase activity was unaltered.Acknowledgment. The author records his sincere thanks to Prof. P. S. Krishnan and Prof. G. G. Sanwal for their valuable suggestions.     

Dependence on age of methamphetamine-produced changes in thermoregulation and metabolism.

In contrast to juvenile mice, old mice treated with methamphetamine are unable to adequately mobilize their carbohydrate reserves. They cannot increase their overall metabolism and become hypothermic, while juvenile mice react with increased calorigenesis and hyperthermia.     

The (Na+ + K+)-ATPase activity in brain of Quaking mice.

The (Na+ 4 K+)- and Mg2+-dependent ATPase distribution in several brain areas has been investigated in Quaking mutant mice characterized by myelin deficiency. A marked decrease of (Na+ + K+)-ATPase activity has been found in limbic structures, hypothalamus and cerebellum. The Mg2+-dependent activity did not change. A possible involvement of the impairment of the (Na+ + K+)-ATPase activity in the seizure susceptibility of this mice is discussed.     

Reduction of serum X-prolyl dipeptidyl-aminopeptidase activity in tumour-bearing mice and reversal of reduced enzyme activity by lentinan, an anti-tumour polysaccharide.

Serum X-prolyl dipeptidyl-aminopeptidase activity which had been shown to be depressed in cancer patients was clearly reduced in mice with Ehrlich carcinoma and Sarcoma 180, and slightly reduced in mice with methylcholanthrene-induced sarcomas. The reduced enzyme activity was completely reversed during tumour regression of sarcoma 180 by administration of lentinan, which causes regression of sarcoma 180.     

Involvement of D-amino acid oxidase in elimination of D-serine in mouse brain.

The physiological role of D-amino acid oxidase (EC 1. 4. 3. 3) in mouse brain is described. The presence of D-enantiomers of neutral common amino acids was surveyed in the brain. D-serine was shown to be present at high concentration only in regions where the enzyme activity was low. In normal mice whose D-amino acid oxidase activity was much higher in the cerebellum than in the cerebrum, free D-serine content was apparently lower in the cerebellum than in the cerebrum. In mice of a mutant strain lacking D-amino acid-oxidase activity, the free D-serine level was remarkably high both in the cerebrum and cerebellum. The results suggest that the enzyme is involved in the elimination of free D-serine in the cerebellum.     

The fasciolicidal activity of a halogenated benzenesulfonanilide.

Halogenated benzenesulfonanilides have potent fasciolicidal activity. The efficacy of 1 such compound in mice, sheep, and cattle is reported.     

Protection by chlorpromazine against lethality and renal toxicity of cisplatin in mice.

The effect of chlorpromazine on acute lethal toxicity and nephrotoxicity induced by cisplatin was studied in mice. Chlorpromazine given (i.p.) 1 h before cisplatin greatly reduced lethal and renal toxicities of cisplatin. Chlorpromazine did not reduce the antitumor activity of cisplatin against Sarcoma 180 in ddY mice or EL-4 Leukemia in C57BL/6J mice.     

Renal glucose utilization in genetically diabetic microangiopathy.

Glucose uptake into kidney tissue is not influenced by the development of glomerulosclerosis in KK mice. Glucosyltransferase activity remains at a normal level even at an age having a highest incidence of serious development of glomerulosclerosis. The observation suggests that biosynthesis of basement membrane reflected by its glucosyltransferase activity does not accelerate in genetically transmitted microangiopathy.     

Cellular and molecular mechanism of low-turnover osteopenia in the klotho-deficient mouse

The mouse homozygous for a disruption of the klotho locus (KL-/- or klotho mouse) exhibited multiple pathological conditions resembling human aging. We observed osteopenia in KL-/- mice with a low bone turnover, in which the decrease in bone formation exceeded the decrease in bone resorption and resulted in net bone loss. This pathophysiology resembles closely that of senile osteoporosis in humans. Osteoblastic cells from KL-/- mice proliferated normally in vitro; however, they showed much lower alkaline phosphatase activity and mineralized matrix formation than those from control mice. Cultured osteoclastic cells from KL-/- mice had normal resorbing activity and survival rate, but the differentiation of osteoclastic cells from their precursors was significantly disturbed: in the co-culture of osteoblastic cells and osteoclast precursor cells, the formation of tartrate-resistant acid phosphatase-positive multinucleated osteoclastic cells was extremely poor only when osteoclast precursor cells originated from KL-/- mice independently of the origin of the osteoblastic cells. In addition, we found that osteoprotegerin a secreted factor which inhibits osteoclastogenesis, was up-regulated in KL-/- mice. We conclude that a defect in klotho gene expression leads to the independent impairment of osteoblast and osteoclast differentiation, which can be a cause of low-turnover osteoporosis.     

Lecithin-cholesterol acyltransferase activity in carbohydrate-induced hypertriglyceridemia in mice. An immunofluorescent method for identification of isolated thyrotropic cells

Summary Feeding to mice of both basal as well as high sucrose diet led to increased levels of plasma triglycerides, which was associated with increased lecithin-cholesterol acyltransferase activity. Although males had significantly higher LCAT activity than females in all the dietary groups, sex difference in the plasma triglycerides was observed in high sucrose group only. Increase in plasma triglycerides in experimental groups was associated with an increase in LCAT activity.     

Tumor promoting constituent ofEuphorbia serrata L. latex

Summary Euphorbia serrata latex has initially ingenol-3-palmitate, which by action of silica gel is converted to ingenol-20-palmitate. The former is responsible for the irritant and cocarcinogenic activity of the latex on mouse ear and on mice back skin.     

Administration of D-alanine did not cause increase of D-amino acid oxidase activity in mice

D-amino acid oxidase (DAAO) activity was not altered in the liver and kidney by oral administration of D-alanine to adult mice. The enzyme was apparently not induced by the enteric microflora either, since the enzyme activity in the liver and kidney of germ-free mice was not different from that of specific-pathogen-free mice. The times of appearance of DAAO activity and of free D-amino acids in the kidney were elucidated using suckling mice. DAAO activity started to increase 7 days after birth, and reached almost the adult level by 28 days. The content of free neutral D-amino acids also increased with age, in a similar fashion. A possible conclusion is that the enzyme activity normally increases during this period, to eliminate the free D-amino acids which have increased with age in the suckling mice. Consequently, the administration of D-alanine had no further effect in increasing enzyme activity.     

Preferential excretion of glycated albumin in C57BL-Ks-J mice: effects of diabetes.

Urinary excretion of glycated albumin was quantitated in genetically hyperglycemic mice (C57BL-Ks-J, db/db mice), a model for non-insulin-dependent diabetes mellitus, and compared with their non-diabetic littermates. The data indicated a preferential excretion of glycated albumin in non-diabetic mice. This phenomenon of 'editing' of glycated albumin is decreased significantly in diabetic mice. Quantitative measurements of overall excretion of glycated albumin suggested that the loss of editing in diabetic mice is due to the dilution of glycated albumin by the unmodified albumin which is excreted in large amounts in diabetic mice. Therefore, the loss of editing observed in this model resembled the one we characterized in insulin-dependent diabetic humans and a streptozotocin-diabetic rat model.