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Biomedical subjects

T Yanagita

Publications and source records attributed to T Yanagita.

At least 19 recordsLinked to original sources
PubMed1992

Effects of an antitussive mixture and its constituents in rats discriminating methamphetamine from saline.

The discriminative effects of over-the-counter antitussive syrup containing dihydrocodeine (DHC), methylephedrine (MEP), caffeine (CAF), and chlorpheniramine (CPA) were compared with those of methamphetamine (MA) in a drug discrimination experiment using rats. Rats were trained to discriminate the effects of MA at 0.5 mg/kg SC and saline for food reinforcement under the fixed-ratio 10 schedule in a two-lever operant chamber situation. In substitution testing using a cumulative dose procedure by the subcutaneous route, DHC (4 and 8 mg/kg, expressed hereafter as referred to cumulative dose) or CPA (16-64 mg/kg) individually did not produce MA lever selection. On the other hand, MEP (128 mg/kg) and CAF (64 mg/kg) produced MA lever selection 41.5 and 57.2% of the time, respectively. The complete mixture (16 mg/kg DHC + 32 mg/kg MEP + 33.2 mg/kg CAF + 6.4 mg/kg CPA) produced MA level selection 65.8% of the time. The partial mixture containing only MEP + CAF at the above doses produced MA lever selection 95.6% of the time. Thus, the complete mixture only partially substituted for MA in rats while the partial mixture containing MEP and CAF completely substituted for MA.

Animals↗
PubMed1992

[Overview of the progress in drug dependence studies--mainly focussing on psychic dependence].

The technical term 'drug dependence' was officially adopted by WHO's Expert Committee on Addiction in 1964. Until this, to describe a state of dependence, terms such as 'poisoning', 'habit', 'ism', and 'addiction' had been used from time to time. Until the 1950's, investigators were mainly focussed on the phenomena of physical dependence. However, once the concept of psychic dependence had been introduced, behavioral and neuropharmacological studies on the modes of drug action that produce psychic dependence were activated and have progressed in the last two decades, and among the points clarified by these studies are the following: 1. The critical drug properties that produce psychic dependence are those of rewarding subjective and reinforcing effects of drugs but these effects are not the properties that produce physical dependence, although the development of physical dependence on particular drugs such as opiates may substantially enhance craving for the drugs. 2. The mesolimbic and mesocortical dopamine systems in the brain and also the N. Accumbens play a primary or at least a partial role in producing the subjective and reinforcing effects of major dependence-producing drugs such as cocaine, opiates, barbiturates, benzodiazepines, and ethanol. 3. Many drugs such as naltrexone, methadone, and some dopamine antagonists and serotonin reuptake inhibitors or antagonists were found to be effective in the pharmacotherapy of the dependence on opiates, cocaine, or ethanol.

Animals↗
PubMed1991

[Studies on the involvement of the nucleus accumbens in the discriminative effects of nicotine in rats].

The central mechanism mediating the discriminative effects of nicotine was studied using rats. Rats were trained to discriminate subcutaneously administered nicotine at 0.5 mg/kg from saline in a 2-lever operant chamber situation for food reinforcement. 1) Nicotine administered into the lateral ventricle at both 100 micrograms and 120 micrograms substituted for subcutaneously administered nicotine at 0.5 mg/kg. This result indicates that the discriminative effects of nicotine are mediated centrally. 2) Among the drugs, acetylcholine at 0.5-10 micrograms administered into the lateral ventricle and methamphetamine at 5-40 micrograms and dopamine at 1-10 micrograms administered into the nucleus accumbens, none substituted for subcutaneously administered nicotine. These results indicate that the discriminative effects of nicotine differ from those of the above drugs. 3) Nicotine at 100 micrograms administered into the nucleus accumbens almost completely substituted for subcutaneously administered nicotine. In addition, mecamylamine at 180 micrograms administered into the nucleus accumbens attenuated the discriminative effects of subcutaneously administered nicotine. These results suggest that nicotinic receptors in the nucleus accumbens may be involved in the discriminative effects of nicotine. However, further studies are needed, since the nucleus accumbens is regarded not to be a major site of action of nicotine for these effects because of its low susceptibility to nicotine and mecamylamine.

Acetylcholine↗
PubMed1991

Observation of the development of tolerance to and physical dependence on barbital by cortical evoked potential in rats.

To observe the dispositional and functional tolerance to and physical dependence on barbital, the influence of repeated administration of the drug on serum barbital levels, coordinative motion, body weight, and cortical evoked potential was assessed. Rats administered the first dose of barbital showed marked impairment of gross behavior and then loss of the righting reflex. While they were repeatedly treated with barbital for a 4-week period, the CNS depression became weaker and weaker, and loss of the righting reflex was no longer observed. Serum barbital levels after administration of barbital tended to decrease by the 28th day of repeated drug administration. Coordinative motion was markedly impaired after administration of the first dose, but gradually recovered during the repeated administration period. Barbital at 100 mg/kg, i.p., prolonged the latent time of the evoked potential in normal untreated rats but not in tolerant rats. During the withdrawal period, no particular change was observed in the animals' gross behavior. However, body weight loss and shortening of the latent time of the evoked potential were observed at 60 to 72 hours of withdrawal. These results suggest that cortical evoked potential can serve as a useful method for observing tolerance to and physical dependence on barbital.

Animals↗
PubMed1991

Smoking and health: a review prepared by the Smoking and Health Subcommittee of the Tobacco Industries Council, a council formed by the Minister of Finance of Japan.

Any definition of health is inevitably broad and contains various elements that may differ from one individual to another. Recent studies on the effects of smoking on physical and mental health have progressed remarkably and have great value in the fields of epidemiology, pathology, clinical medicine, and psychiatry. This report concludes that while smoking may have beneficial psychological effects on smokers, it may pose a risk to physical health.

Adolescent↗
PubMed1991

Cholesterol-lowering effect of Agemaki, a kind of shellfish, in mice.

Agemaki (Sinonovacula constricta) is an edible and popular shellfish in the western part of Japan. The present study demonstrated the effects of feeding Agemaki on cholesterol and triglyceride concentrations in mice plasma and liver. Mice were fed a diet containing 0.1% cholesterol and 0.1% Na-cholate for 1 week, and then a cholesterol-free diet or a cholesterol-enriched one for 2 weeks. To both diets, freeze-dried Agemaki was added at a 5% level. There was no statistically significant effect on the body-weight gain, food intake, and liver weight by feeding Agemaki in both dietary regimens. However, Agemaki significantly lowered the concentrations of plasma and liver cholesterol and also of plasma triglyceride in mice feeding on the cholesterol-rich diet. A similar tendency was also observed for the mice feeding on the cholesterol-free diet. The analysis of freeze-dried Agemaki revealed a relatively larger proportion of n-3 polyunsaturated fatty acids and plant sterols, which may possibly decrease plasma lipids. So far as we know, this is the first report showing hypolipidemic effect of Agemaki.

Animals↗
PubMed1991

New combined therapy of niceritrol and probucol on heterozygous familial hypercholesterolemia.

Seventeen patients with heterozygous familial hypercholesterolemia were sequentially treated with: a low cholesterol, fat restricted diet; diet and probucol (500 mg/day); and diet, probucol and niceritrol (1500 mg/day). Concentrations of plasma cholesterol decreased from 348 + 49 mg/dl on diet alone to 304 + 32 mg/dl, to 256 + 30 mg/dl on diet and probucol, and fell to 212 + 41 mg/dl on the combined regimen with niceritrol. Concentrations of LDL-cholesterol declined 13% on diet, and 26% on diet and probucol; the subsequent addition of niceritrol resulted in a 42% fall from the baseline. Plasma concentrations of apolipoprotein B fell 37% on the combined regimen with niceritrol. As a result, normal levels of cholesterol (less than 230 mg) were achieved in thirteen subjects treated with this new combination therapy. Moreover, atherogenic index improved with the addition of niceritrol. These results suggest even a small dose of niceritrol affords opportunity to maintain normal lipid profile in heterozygous familial hypercholesterolemia when given in combination with probucol.

Adult↗
PubMed1990

Comparative study of combination chemotherapy of ovarian cancer: cyclophosphamide, adriamycin and cisplatin versus 5-fluorouracil, cyclophosphamide and mitomycin C.

CAP, a multiple-drug combination therapy using cyclophosphamide (750 mg/m2), adriamycin (20-30 mg/m2) and cisplatin (50-75 mg/m2), was applied to 69 cases of epithelial ovarian cancer. The results of this therapy were compared with those of FAM (involving 5-fluorouracil, cyclophosphamide and mitomycin C) in 47 cases of the same cancer, retrospectively. The 5-year survival rate was 61.6% for cases treated with CAP and 56.3% for cases treated with FAM. All 9 patients at stage Ia treated with CAP are free of disease, however, 3 patients out of 13 at stage Ia treated with FAM experienced a recurrence of the disease and died. In stage III and IV cases with detectable lesions, a response was observed in 61.3% (19/31) treated with CAP and in 10.5% (2/19) treated with FAM.

Adolescent↗
PubMed1989

Effect of tetrahydroisoquinoline (TIQ), one of endogenous substances inducing parkinsonism, on isolated rat vas deferens.

1. The effect of tetrahydroisoquinoline (TIQ) was examined on isolated rat vas deferens. 2. TIQ shifted the concentration-response curve for norepinephrine towards lower concentrations: the pD2-value of norepinephrine in the presence of TIQ was significantly greater than in its absence. 3. Tyramine-induced contraction in the presence of TIQ decreased by a significant 35% more than in the absence of TIQ. 4. These results indicate that the pharmacological effect of TIQ is due to the inhibition of the neuronal uptake of catecholamines.

Animals↗
PubMed1988

Mode of potentiating action of cocaine in morphine analgesia.

The mechanism of antinociceptive interactions among morphine, cocaine and alcohol was studied in mice, guinea pigs and rabbits. In the tail-pressure test in mice, cocaine and alcohol alone showed almost no antinociceptive effects at doses up to 8 mg/kg, s.c., and 4 g/kg, respectively. Alcohol at 2 g/kg, i.g., also did not influence the effect of morphine, while cocaine at 4 mg/kg, s.c., significantly potentiated the antinociceptive effects of not only morphine but also pentazocine. In an analysis of serum and brain concentration levels of morphine in mice, when morphine and cocaine were simultaneously administered at 2 mg/kg, s.c., and 4 mg/kg, s.c., respectively, both serum and brain levels of morphine showed neither increase nor decrease in comparison with the levels in mice administered morphine alone. In myenteric plexus-longitudinal muscle preparations of isolated guinea pig ileum, 1 microM cocaine enhanced the agonistic effects of both pentazocine and ethylketocyclazocine. Furthermore, cocaine as well as ethylketocyclazocine showed naloxone-reversible agonistic effects in isolated rabbit vas deferens. These results indicate that cocaine may potentiate the antinociceptive effects of morphine and pentazocine by acting on the kappa-opioid receptors as an agonist.

Analgesia↗
PubMed1988

Effects of tizanidine in healthy volunteers: double-blind study compared with diazepam and a placebo.

Since an experiment in monkeys showed that tizanidine (DS 103-282), a centrally-acting muscle relaxant, has a certain amount of reinforcing property, a double-blind comparative study using questionnaires was carried out in 12 healthy volunteers to investigate the subjective effects of the drug as a measure of its psychic dependence potential using diazepam and a placebo. The dosages of tizanidine were 3 mg and 6 mg and that of diazepam was 10 mg. Neither the maximal clinical dosage of tizanidine (3 mg) nor twice that dosage (6 mg) induced any marked somatic or psychic symptoms compared with the placebo. On the other hand, diazepam 10 mg induced symptoms at a significantly higher incidence than the placebo and tizanidine; i.e., many of those given diazepam mentioned experiencing such symptoms of central nervous system depression as drowsiness and absent-mindedness. With diazepam the volunteers gave positive answers to some items which are regarded as direct parameters of psychic dependence; e.g., one noted that the drug effects were "desirable", two indicated a "euphoric feeling", and five noted a "drunken feeling". Influence on tapping, blood pressure, etc., were observed in the tizanidine 6 mg group in the same extent as in the diazepam group. The blood concentration of tizanidine 6 mg was about four times as high as tizanidine 3 mg. These results indicate that tizanidine is very unlikely to have psychic-dependence potential because of a lack of observable subjective effects and thus, it was concluded that there is little possibility of the drug being abused.

Adult↗
PubMed1987

Di(2-ethylhexyl)phthalate enhances hepatic phospholipid synthesis in rats.

The effects of di(2-ethylhexyl)phthalate, a typical peroxisomal proliferator, on the activities of key enzymes in the glycerophospholipid synthetic pathway and the incorporation of lipid precursors into liver lipids in vitro were studied periodically in rats. When di(2-ethylhexyl)phthalate was fed at the 1% level to rats, glycerol-3-phosphate acyltransferase activity increased 2-3-fold in liver homogenates and microsomes in 2-4 days. The specific activity of microsomal CTP:phosphocholine cytidylyltransferase increased by 1.5-fold, whereas the cytosolic activity was depressed. The microsomal CDPcholine:diacylglycerol cholinephosphotransferase specific activity decreased, whereas the activity in the homogenates increased, suggesting the proliferation of the hepatic endoplasmic reticulum in di(2-ethylhexyl)phthalate-treated rats. The incorporation of [1(3)-3H]glycerol or [1-14C]acetate into liver phospholipids in vitro increased in 2 days and stayed at a high level up to 12 days. The present study confirmed that di(2-ethylhexyl)phthalate induced an enhancement of phospholipid synthesis in the liver. The increase in hepatic phospholipid synthesis by this drug is presumably linked to the proliferation of peroxisomes and other intracellular membranes.

Acetates↗