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Biomedical subjects

M Takashima

Publications and source records attributed to M Takashima.

At least 145 records · Page 8Linked to original sources
PubMed1983

Behavioral sensitization and relative hyperresponsiveness of striatal and limbic dopaminergic neurons after repeated methamphetamine treatment.

Rats were used in a study of the effects of repeated methamphetamine treatment on stereotyped behavior and striatal and limbic dopamine metabolism in response to challenge with the drug or other dopamine agonists. Repeated administration of d-methamphetamine (6 mg/kg per day for 3-14 days) produced long-term behavioral sensitization (augmented response to a challenge injection) not only to the compound (at 44-89 days after drug withdrawal) but also to apomorphine and nomifensine. Even a single injection of d-methamphetamine (6 mg/kg) enhanced the behavioral response to the drug. A challenge dose of d-methamphetamine (2 mg/kg) markedly increased dopamine turnover (lower dopamine and higher 3,4-dihydroxyphenylacetic acid levels, higher ratios of 3,4-dihydroxyphenylacetic acid over dopamine) in the striatum and mesolimbic area of the sensitized animals on day 15 of withdrawal from treatment repeated for 14 days with the drug (6 mg/kg per day). These findings demonstrate that behavioral sensitization induced by methamphetamine is accompanied by increased central dopaminergic transmission.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1983

[High dosage haloperidol reduces cataleptic response with increased noradrenaline metabolism in the rat brain areas].

The neurochemical background of clinical experiences that the patients receiving high dosage haloperidol showed no extrapyramidal side effects was investigated by using rats. Haloperidol at doses of 1, 2.5, 5, 7.5 and 10 mg/kg, ip caused a dose-dependent decrease in the duration of catalepsy. Haloperidol at a dose of 10 mg/kg induced catalepsy lasting only 20% of that by 1 mg/kg. Haloperidol decreased noradrenaline content in the frontal cortex and thalamus in a dose-dependent manner while 3-methoxy-4-hydroxyphenylglycol content showed a dose-dependent increase in the same brain areas. Thus, there is an inverse relationship between the duration of catalepsy and the ratio of 3-methoxy-4-hydroxyphenylglycol to noradrenaline in the frontal cortex or thalamus. In contrast, haloperidol caused a dose-dependent decrease in homovanillic acid and 3, 4-dihydroxyphenylacetic acid content in the striatum and mesolimbic area. These results indicate that noradrenergic hyperfunction in the frontal cortex or thalamus induced by high dosage haloperidol may reduce cataleptogenic effect of the drug via indirect stimulation of dopaminoceptive neuron in the striatum or mesolimbic area.

Animals↗
PubMed1982

Dopamine metabolism increases in post-mortem schizophrenic basal ganglia.

The dopamine-rich regions of post-mortem brains from 6 schizophrenics and 7 controls were analyzed. There were no significant changes in dopamine concentrations in basal ganglia and nucleus accumbens of schizophrenics compared with controls. Schizophrenic basal ganglia (putamen and caudate) showed significantly higher levels of homovanillic acid, and tyrosine hydroxylase activity. Among the schizophrenic patients, markedly high activity of tyrosine hydroxylase was measured in a patient diagnosed as catatonic type. He had not taken antipsychotic drugs for 3 months prior to death. In his relatives, three other schizophrenics were found to the second degree. A remarkable low level of dopamine and a high level of homovanillic acid measured indicate this case would have had an increased turnover rate of dopamine in the dopaminergic nerve terminals. Among the schizophrenic patients, there might be one group whose enzyme activity of dopamine synthesis in the brain is exceptionally high.

Adult↗
PubMed1982

Metal contents in duodenal aspirates of normal subjects during pancreozymin-secretin test.

The calcium, magnesium, zinc, copper and manganese concentrations in the duodenal aspirates obtained during pancreozymin-secretin tests were measured in 16 normal subjects. Total outputs of calcium, magnesium, zinc, copper and manganese during the 70 minute period (10 minutes after pancreozymin injection and 60 minutes after secretin injection) were 4.91 +/- 3.47 mg, 1.88 +/- 0.96 mg, 180 +/- 42 micrograms, 162 +/- 104 micrograms and 16.9 +/- 14.2 micrograms (mean +/- S.D.), respectively. The concentrations of metals were the highest in P fraction (during 10 minutes after pancreozymin injection) and the lowest is S3 fraction (during the 20-40 minute period after secretin injection). Although calcium, magnesium, copper and manganese concentrations varied widely from case to case especially in P fraction, zinc concentration exhibited comparatively small variation in every fraction. Magnesium, copper and manganese concentrations exhibited significant correlations with icterus indices of the aspirates. Zinc and magnesium concentrations correlated with amylase activity and magnesium concentration exhibited an inverse relation to bicarbonate concentration. Most metal concentrations correlated well each other, but there were no correlations between zinc and calcium and between zinc and manganese concentrations. Zinc seemed to be excreted mainly with pancreatic juice and copper and manganese mainly with bile.

Adult↗
PubMed1982

Absorption, excretion and tissue distribution of silver sulphadiazine.

It was clarified that the absorption of silver sulphadiazine cream, a widely-used topical agent against Pseudomonas infection after burns, through both superficial and deep dermal burn surfaces as well as the normal skin, was negligible, but that its absorption increased when the blister was removed. After absorption, the silver sulphadiazine was dissociated into two portions. The sulphadiazine portion was excreted into the urine quickly and the silver portion, on the contrary, remained at a certain level in the body for a long time. Our results given some suggestions about the indications for silver sulphadiazine cream. The cream seems to be inadequate for treating second-degree burns but may be useful for the treatment of third- or fourth-degree burns.

Administration, Topical↗
PubMed1981

Enhancement of haloperidol-induced increase in rat striatal or mesolimbic 3,4-dihydroxyphenylacetic acid and homovanillic acid by pretreatment with chronic methamphetamine.

After a drug-free period of 1 week following 2 weeks of haloperidol treatment, the increased response of striatal 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) to a challenge dose of haloperidol was significantly reduced. Tolerance to this effect was not, however, seen in the mesolimbic system. Pretreatment of the rats with methamphetamine (MAP) for 8 days prior to chronic haloperidol significantly enhanced the DOPAC and HVA increase produced by the challenge with haloperidol in both brain areas. The reduced response of striatal DOPAC or HVA after chronic haloperidol was prevented by pretreatment with MAP. The data suggest that the long-term dopamine receptor stimulation induced by MAP may antagonize the tolerance produced by chronic haloperidol treatment.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1981

A short-term in vitro assay for promoter substances using human lymphoblastoid cells latently infected with Epstein-Barr virus.

We designed a short-term in vitro assay for detecting tumor promoters, utilizing the activation of Epstein-Barr virus (EBV) expression in EBV genome-carrying human lymphoblastoid cells. This system is composed of EBV-non-producer Raji cells as the indicator, n-butyrate as the EBV-inducer, and the test substance. After addition of the latter 2 components to the culture medium, the cells are cultivated for 48 h at 37 degrees C and the ratio of EBV early antigen (EA)-expressing cells was assessed using immunofluorescence. This assay system allows for a rapid detection of the activity of the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and its related compounds and also of the Euphorbiaceae plant extracts containing such active principles. Among several microbial products tested, teleocidin, an indole-alkaloid produced by a Streptomyces species, was also detected and had an activity level comparable to that of TPA. Other promoters, such as anthralin, phenol, Tween 60 and 80 and the carcinogenic ("initiator") substances including benzopyrene, did not react with the system. The test is simple to perform, reproducible and should be applicable for mass-screening of promoter substances in the environment.

Carcinogens↗
PubMed1981

Synthesis and neuroleptic activity of benzamides. Cis-N-(1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-(methylamino)benzamide and related compounds.

Three series of benzamides of N,N-disubstituted ethylenediamines (linear alkane-1,2-diamines), 1-substituted 2-(aminomethyl)pyrrolidines, and 1-substituted 3-aminopyrrolidines (cyclic alkane-1,2-diamines) were designed and synthesized as potential neuroleptics. All target compounds were evaluated for their inhibitory effects on apomorphine-induced stereotyped behavior in rats, and a good correlation between structure and activity was found throughout the series. In the linear series (analogues of metoclopramide), introduction of a benzyl group on the terminal nitrogen, rather than an ethyl group, and a methyl group on the p-amino group of metoclopramide both enhanced the activity. The resulting N-[2-(N-benzyl-N-methylamino)ethyl]-5-chloro-2-methoxy-4-(methylamino) benzamide(23) was about 15 times more active than metoclopramide. In the cyclic series, particularly among the benzamides of 1-benzyl-3-aminopyrrolidine, most of the compounds tested were more active than the corresponding linear benzamides. cis-N-(1-Benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-(methylamino) benzamide (YM-09151-2, 55) was the most active among all of the compounds tested, being 13 and 408 times more potent than haloperidol and metoclopramide, respectively. Moreover, compound 55 exhibited a fairly high ratio of antistereotypic activity to cataleptogenicity compared with haloperidol and metoclopramide. It is expected that compound 55 may be used as a potent drug with few side effects in the treatment of psychosis.

Animals↗
PubMed1980

Human operator dynamics in manual tracking systems with auditory input.

Response characteristics of human operators in manual pursuit tracking with auditory input are investigated. The human operator hears in his left ear a sound whose frequency varies in proportion to an external random signal. At the same time, he hears in his right ear another sound whose frequency varies in proportion to the angle of a control lever of a potentiometer. The operator controls the angle of the lever so that the frequencies, of the sounds in both ears remain as close as possible. The dynamics of the human operator is studied by assuming a "man-machine system" whose input is the external signal and whose output is the voltage of the potentiometer. A learning identification method proposed by one of the authors is used to calculate the weighting function of the man-machine system, which is displayed on a CRT screen in renal time. During the tracking task, the skin potential activity (SPA) is measured as an index of arousal of the operator.

Arousal↗
PubMed1980

Hyperglycemic effect of hydralazine in rats.

The effect of hydralazine in the alteration of blood sugar, tissue glycogen and blood cAMP levels in rats were investigated. Hydralazine was found to increase blood sugar level in intact rats when administered i.p. On the other hand, this hyperglycemia was partially blocked either by the treatment of intact rats with propranolol, beta-adrenergic blocker, or by adrenalectomy. Hydralazine treatment increased blood cAMP level, leading to the hyperglycemia, because pretreatment with phentolamine partially blocked the hydralazine-induced hyperglycemia.

Adrenal Glands↗