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Biomedical subjects

M Inami

Publications and source records attributed to M Inami.

28 records · Page 2Linked to original sources
PubMed1980

Multi-institutional study on the teratogenicity and fetal toxicity of antiepileptic drugs: a report of a collaborative study group in Japan.

A multi-institutional collaborative study was conducted concerning the course of pregnancy and delivery and the incidence of abnormal infants delivered of epileptic women. Of 657 women receiving antiepileptic drugs, 73% delivered live infants, 14% had miscarriage or stillbirth, and 13% underwent induced abortion. In contrast to the above findings, 80% of 162 patients not receiving antiepileptic drugs delivered live infants and 4% had miscarriage or stillbirth. The latter outcome was significantly increased in the medicated patients. In this series, 63 (9.9%) of 638 live births were malformed, 55 (11.5%) being from medicated mothers and 3 (2.3%) from nonmedicated mothers. The incidence of fetal malformation in medicated mothers was thus five times as high as that in nonmedicated mothers. Cleft lip and/or palate and malformations involving the cardiovascular system were found frequently in the infants from medicated mothers. General background factors that might exert teratogenic effects on pregnant patients with epilepsy were studied, and the potential toxicity of antiepileptic drugs to the fetus was also analyzed. In this regard, consideration should be given to whether the patient has partial epileptic seizures, whether the patient herself exhibits any malformation, or whether her previous pregnancy resulted in an abnormal outcome. The incidence of fetal malformation was the highest (12.7%) in the medicated patients who had epileptic seizures during the pregnancy. It is presumed on the basis of the results of analysis of the data that a combination of more than three drugs and a daily dose greater than a certain minimal level is likely to produce malformed infants.

Abnormalities, Drug-Induced↗
PubMed1976

Action of enpiprazole on emotional behavior induced by hypothalamic stimulation in rats and cats.

Action of enpiprazole on emotional behavior elicited by hypothalamic stimulation in rats and cats was investigated and comparisons were made with effects of diazepam. Two behavioral patterns were elicited by stimulation of the postero-medial part of the hypothalamus in rats: a food-carrying response beginning with exploratory movement and an analogue of fear. Enpiprazole frequently changed the food-carrying response into food-taking response and occasionally analogues of fear into food-carrying and /or food-taking responses. Thresholds for these behaviors were also elevated. Diazepam showed the same effects on the thresholds as enpiprazole, having but little effect on the behavioral patterns. In cats, enpiprazole evelvated the thresholds for affective-defensive responses induced by hypothalamic stimulation in 6 of 8 cases, but lowered them in 2 cases. This suggests that enpiprazple has a 'biphasic effect' in the central nervous system. By contrast,diazepam consistently elevated thresholds. Comparing the action of enpiprazole with that of diazepam it can be presumed that the former is a different type of anxiolytic drug than the latter.

Animals↗
PubMedDate not supplied

Activation of lipoprotein lipase and inhibition of B16 melanoma-induced cachexia in mice by ponalrestat, an aldose reductase inhibitor.

Lipoprotein lipase (LPL) is a key regulatory enzyme responsible for the hydrolysis of triglyceride (TG)-rich lipoproteins. The reduction in LPL activity is observed in tumor bearing animals and cancer patients with cachectic symptoms, suggesting an involvement of LPL in inducing cancer cachexia. During a screening program for anti-cachectic agents we found that ponalrestat, an aldose reductase inhibitor, activates LPL activity. Ponalrestat increased the activity of LPL in adipose tissue in mice. The effect of ponalrestat on B16 melanoma-induced cachectic symptoms was next investigated in mice. The decrease in the weight of epididymal fat, carcass and whole body lipid was observed in mice following intraperitoneal inoculation of B16, compared to mice without the tumor inoculation. Treatment with ponalrestat resulted in the attenuation of the decrease in the tissue weight. The increase in the levels of TG and non-esterified fatty acid, and a decrease in the level of glucose in the blood, which was induced by the presence of tumor, were also restored to those of normal mice following ponalrestat treatment. The reduction in locomotor activity in tumor bearing mice was partially restored by the treatment with ponalrestat. Overall, this study demonstrated that ponalrestat, an aldose reductase inhibitor, possesses potent LPL activating activity and that the cachexia induced by B16 melanoma was alleviated by treatment with 'ponalrestat, suggesting that ponalrestat, a LPL activating agent, has a therapeutic potential for the treatment of cancer cachexia.

3T3 Cells↗
PubMedDate not supplied

Ponalrestat, an aldose reductase inhibitor, inhibits cachexia syndrome in nude mice bearing human melanomas G361 and SEKI.

Our recent study has demonstrated that ponalrestat, an aldose reductase inhibitor, activates lipoprotein lipase (LPL) activity in the adipose tissue and alleviates the cachectic symptoms induced by B16 melanoma in mice. In this study, the effect of ponalrestat on cachexia symptoms in nude mice bearing human melanomas G361 and SEKI was investigated because it has been suggested that the suppression of LPL has an important role in cachexia induction by these two melanomas in nude mice. Mice bearing G361 subcutaneously did not gain weight and became cachectic, associated with the tumor growth. Tumor growth was not affected by ponalrestat, nevertheless treatment with ponalrestat resulted in an amelioration of the reduction in the weight of body mass, epididymal fat, gastrocnemius muscle, carcass and whole body lipid induced by the presence of G361. A severe weight loss observed in nude mice bearing SEKI was also partially attenuated by ponalrestat treatment. Overall, this study showed that ponalrestat is effective in the attenuation of the cachectic symptoms induced by human melanomas G361 and SEKI in nude mice, suggesting that ponalrestat has a potential usefulness for the treatment of cancer cachexia.

Aldehyde Reductase↗
PubMedDate not supplied

Ponalrestat, an aldose reductase inhibitor, inhibits cachexia syndrome induced by colon26 adenocarcinoma in mice.

Our recent study has demonstrated that ponalrestat, an aldose reductase inhibitor, activates lipoprotein lipase activity and alleviates B16 melanoma-induced cachexia in mice. In this study, the effect of ponalrestat on murine adenocarcinoma colon26-induced cachexia was investigated in mice. Mice bearing colon26 subcutaneously lost weight and became cachectic, associated with the tumor growth. Although tumor growth was slightly stimulated when tumor bearing mice were treated with ponalrestat: nevertheless, the drug attenuated the reduction in the weight of body mass, epididymal fat, gastrocnemius muscle and carcass induced by colon26, as well as significantly prolonged the survival of the colon26 bearing mice. Ponalrestat inhibited the production of interleukin-1 (IL-1) from human monocytes stimulated by Lipopolysaccharide (LPS) in vitro, and also suppressed LPS-induced increase of IL-1 in the blood in mice. Overall, this study showed that ponalrestat suppresses IL-1 production both in vitro and in vivo, and inhibits the cachectic symptoms induced by colon26 adenocarcinoma in mice, suggesting that ponalrestat has a therapeutic potential for the treatment of cancer cachexia.

Adenocarcinoma↗
PubMedDate not supplied

Cachexia induction by EL-4 lymphoma in mice and possible involvement of impaired lipoprotein lipase activity.

Several lines of evidence have postulated that reduction in the activity of lipoprotein lipase (LPL) is involved in cachexia induction in cancer patients. Recently we have demonstrated that murine melanoma B16 has the ability to reduce the LPL activity and thereby induce cachexia symptoms in mice following intraperitoneal inoculation. In order to further investigate the relationship between LPL activity and cachectic syndrome, cachexia models other than melanoma B16 are required. However, there are few animal cachexia models in which LPL activity is involved in the induction of cachectic symptoms. In this study, cachectic symptoms and plasma LPL activity were investigated in mice bearing EL-4 mouse lymphoma. In EL-4 bearing mice the body weight including tumor weight in the abdominal cavity was rather higher than that of normal mice without tumor, whereas weights of carcass wet and gastrocnemius muscle were significantly decreased in EL-4 bearing mice. Elevated blood levels of triglyceride and non-esterified fatty acid were observed in mice bearing EL-4, associated with the impaired plasma LPL activity. Overall, this study indicated that EL-4 lymphoma in mice results in a severe cachexia which is possibly related to impaired LPL activity and also provided a useful cachexia model for understanding the role of LPL in the development of cancer cachexia.

Animals↗
PubMedDate not supplied

Effect of FR143430, a novel cytokine suppressive agent, on adenocarcinoma colon26-induced cachexia in mice.

Cancer cachexia, characterized by weight loss and progressive tissue wasting, has been postulated to be mediated by cytokines. In this study the effect of FR143430, (2-(4-fluorophenyl)-4, 5, 6, 7-tetrahydro-3-(4-pyridyl)pyrazolo[1, 5-a]pyrimidine monohydrochloride), an inhibitor of Interleukin-1 and Tumor necrosis factor-a (TNF- a), on adenocarcinoma colon26-induced cachexia was investigated in mice. Tumor growth was not affected. Nevertheless, treatment with FR143430 (0.1 to lmg) into the tumor resulted in the attenuation of the reduction in body weight, food intake, epididymal fat and carcass weight, the decrease in the circulating levels of triglyceride and glucose, and the increase in the circulating levels of total cholesterol, non esterified free fatty acid (NEFA) and total protein, which were induced by the presence of the tumor. However, oral treatment with FR143430 failed to show an inhibitory effect on cachexia induction. Overall, this study demonstrated that the cachexia induced by colon26 was alleviated by the injection of FR143430 into the tumor in sufficient quantity, without any effect on tumor growth, suggesting the potential utility of cytokine suppressive agents e for the treatment of cancer cachexia.

Animals↗