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Biomedical subjects

Y Shiozaki

Publications and source records attributed to Y Shiozaki.

At least 37 records · Page 2Linked to original sources
PubMed1992

Establishment of the ethanol-induced place preference in rats.

Ethanol failed to induce a place preference in both 15 and 50 min conditioning schedules in free-feeding and in food deprived rats. Acetaldehyde, the primary metabolic product of ethanol, induced a weak place aversion, dose-dependently. Ethanol combined with pyrazole (an alcohol dehydrogenase inhibitor) significantly induced a place preference in rats (ethanol; 300 mg/kg, i.p., pyrazole; 100 mg/kg, i.p.) in a 50 min conditioning schedule. The ethanol (300 mg/kg) combined with pyrazole (100 mg/kg)-induced place preference was antagonized or reduced by 5-HT3 antagonists (MDL72222, ICS205-930). These results suggest that a blockade of ethanol metabolism is very important for development of the ethanol-induced place preference in rats, and that the ethanol-induced place preference may be mediated by the mesolimbic dopamine system through 5-HT3 receptors.

Animals↗
PubMed1992

Effects of calcium antagonists on the cocaine- and methamphetamine-induced conditioned place preference.

The effects of calcium antagonists (nifedipine, flunaridine and diltiazem) on the cocaine- and methamphetamine-induced place preference were examined. Calcium antagonists alone induced neither place preference nor place aversion. Nifedipine markedly antagonized and flunarizine and diltiazem reduced the cocaine-induced place preference. The methamphetamine-induced place preference was reduced by nifedipine and diltiazem, but not by flunarizine. These results suggest the possibility that the cocaine-induced place preference is strongly influenced by dihydropyridine sensitive calcium channels, whereas the methamphetamine-induced place preference is not.

Animals↗
PubMed1991

Potentiation of pentazocine conditioned place preference by tripelennamine in rats.

The effects of tripelennamine on place preference conditioning in rats with pentazocine were investigated. Pentazocine at a dose of 2 mg/kg (IP) slightly, but not significantly, induced a place preference. Concurrent dosing of pentazocine (2 mg/kg, IP) and tripelennamine (2.5 mg/kg, SC) significantly and prominently produced a place preference, although administration of tripelennamine (2.5 mg/kg, SC) alone did not. Chronic infusion of a dopamine D1 receptor antagonist, SCH23390 (1.0 mg/kg/day) during conditioning abolished the appetitive effect of pentazocine potentiated by the combination with tripelennamine. In conclusion, it is suggested that the dopaminergic system, especially at the D1 receptor, plays an important role in the potentiation effect of tripelennamine on the pentazocine-induced place preference.

Animals↗
PubMed1991

Prognosis of unresectable hepatocellular carcinoma: an evaluation based on multivariate analysis of 90 cases.

A multivariate analysis of data from 90 patients with unresectable hepatocellular carcinoma was performed using Cox's regression model to identify factors possibly affecting their prognoses. Thirty-one patients underwent arterial anticancer chemotherapy, and the remaining 59 patients received transcatheter arterial embolization with anticancer agents. Four of 27 variables tested for all the patients (i.e., encapsulation [p less than 0.05], gross appearance of hepatocellular carcinoma [p less than 0.01], clinical stage [p less than 0.01] and therapy [p less than 0.01]) were found to be prognostically significant. Five of 27 variables tested were prognostically significant for the transcatheter arterial embolization group; they were an extension rate of hepatocellular carcinoma (p less than 0.01), encapsulation (p less than 0.01), alpha-fetoprotein (p less than 0.01), prothrombin time (p less than 0.01) and serum sodium (p less than 0.01). Regression equations were used to describe a prognostic index. A prognostic index was defined as the regression equation derived from the results of a total of 90 patients; PI-1 = eY, where PI-1 = prognostic index 1 Y = 1.549 (gross appearance of hepatocellular carcinoma - 1.344) + 0.778 (encapsulation - 1.622) + 0.818 (clinical stage - 1.800) + 1.760 (therapy - 1.344) and prognostic index 2, the regression equation derived from the results of the transcatheter arterial embolization group of patients; PI-2 = eY, where PI-2 = prognostic index 2 Y = 1.210 (extension rate of hepatocellular carcinoma - 1.576) + 1.179 (encapsulation - 1.475) + 0.0001277 (alpha-fetoprotein - 1420.792) -0.039 (prothrombin time - 72.237) - 0.214 (serum sodium - 138.427).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

The carcinostatic effects of 1-(2-tetrahydrofuryl)-5-fluorouracil and uracil (UFT) on tongue carcinoma induced by 4-nitroquinoline 1-oxide (4NQO) in rats.

UFT is a carcinostatic agent used in adjuvant chemotherapy for head and neck cancer. In the present study. UFT was given orally to treat tongue carcinoma in rats induced by 4-nitroquinoline 1-oxide. The antitumor effects of UFT were studied macroscopically and histologically. In addition, the antitumor effects of UFT were evaluated in relationship to lesions of the clinical and, invasive types, and to there vascular structure. In clinical lesions, the antitumor effect of UFT was higher in extrovert tumor-mass lesions and lower in ulcerous lesions. With regard to vascular structure, the effect was higher in cases demonstrating irregular net-like patterns and branch-like patterns and lower in cases in which the pattern had been destroyed. There was a correlation between antitumor effect and invasive type. As invasive tendency the 3H-thymidine labeling index, and mitotic index increased, antitumor effect and degree of tumor cell degeneration decreased.

4-Nitroquinoline-1-oxide↗
PubMed1990

Depression of drug metabolizing activity in the human liver by interferon-alpha.

The depressant effect of interferon-alpha on drug metabolizing activity in the liver has been investigated in 12 patients with chronic active hepatitis B. 7-methoxy-coumarin (7-MC) O-demethylase and 7-ethoxycoumarin (7-EC) O-deethylase, in specimens obtained by liver biopsy, were measured before and after interferon treatment. 7-MC and 7-EC O-dealkylase activity were significantly reduced after interferon treatment, from 13.4 to 9.24 nmol.g-1 liver.min-1, and from 3.22 to 2.16 nmol.g-1 liver.min-1, respectively. The magnitude of the fall varied widely between individual patients. The study provides the first direct evidence that interferon-alpha can impair the activity of drug metabolizing enzymes in the human liver.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1990

Profiles of plasma amino acids in fasted patients with various liver diseases.

We examined the level of plasma amino acids, glucose, immunoreactive insulin (IRI) and immunoreactive glucagon (IRG) of patients in the fasted state with acute hepatitis in the actual acute stage (AHa), acute hepatitis in the convalescent stage (AHc), chronic active hepatitis (CAH), chronic persistent hepatitis (CPH) and liver cirrhosis (LC). In AHa patients, the plasma glucose (FPG), plasma alanine (Ala), tryptophan (Trp) and histidine (His) levels were significantly lower and plasma cystine (Cys) level significantly higher than the control levels. This however, was not the case in the other patients. The glutamic acid (Glu) concentration was significantly higher in AHa (p less than 0.02), CAH (p less than 0.001) and CPH (p less than 0.001) and the tyrosine (Tyr) concentration was significantly higher in AHa (p less than 0.02), CPH (p less than 0.001), CAH (p less than 0.001) and LC (p less than 0.001) than they were in the controls. The lysine (Lys) concentration was significantly raised in the AHa (p less than 0.02) and CPH (p less than 0.05) cases. The IRG level was significantly higher in AHa (p less than 0.001), in AHc (p less than 0.01) and LC (p less than 0.01). Valine (Val) showed a significant decrease in concentration in AHa (p less than 0.01) and LC (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Comparison of the effects of various inducers on 7-alkoxycoumarin O-dealkylase activities in liver microsomes.

The effects of six inducers and malotilate on 7-alkoxycoumarin O-dealkylase activities in rat liver microsomes were examined. Phenobarbital (PB) (100 mg/kg) was administered intraperitoneally to rats for 6 days; 3-methylcholanthrene (3-MC) (40 mg/kg), beta-naphthoflavone (beta-NF) (40 mg/kg), isosafrole (150 mg/kg) and polychlorinated biphenyls (PCB) (100 mg/kg) were administered intraperitoneally for 3 days; isoniazid (INH) (50 mg/kg) was administered intraperitoneally for 10 days; and malotilate (500 mg/kg) was administered orally for 3 days. The O-dealkylase activities toward 7-methoxycoumarin (7-MC), 7-ethoxycoumarin (7-EC) and 7-propoxycoumarin (7-PC) were examined 24 hr after the final administration of the drugs. The ratios of 7-EC O-deethylase and 7-PC O-depropylase to 7-MC O-demethylase activity in the control and six inducer-treated groups were compared. The ratios in the groups treated with the six compounds, each of which induces a different form(s) of cytochrome P-450 (P-450), were clearly different from each other. Therefore, the measurement of 7-alkoxycoumarin O-dealkylase activities should be extremely useful for the routine determination of the molecular species of P-450. On the other hand, the ratio in the malotilate-treated group was different from that in any other inducer-treated group, so that there might be a possibility that malotilate induced a form(s) of P-450 that is different from any of the already known species.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1989

[Relationships between ethanol-induced sleep and aspirin, indomethacin or PGE2 in inbred rats].

It is known that prostaglandin synthetase inhibitors (PGSI) inhibit ethanol (EtOH)-induced sleep in mice, and that EtOH increases production of prostaglandins (PGs). EtOH hypnosis and effects of prostaglandins on EtOH-induced sleeping in inbred rats were examined. The EtOH (3 g/kg, i.p.)-induced sleep time was significantly longer in Fischer 344 (F344) than in Lewis (LEW); blood EtOH concentrations (BAC) on awaking were significantly lower in F344 than in LEW. When aspirin (ASP) and indomethacin (IND) were given 15 and 30 min prior to EtOH administration, respectively, both strains significantly slept shorter than those receiving no PGSI. The BACs on awaking in both strains receiving PGSI were higher than those receiving no PGSI. When LEW and F344 rats were pretreated with PGE2 (0.05-0.5mg/kg, s.c.) 30 min prior to EtOH administration, either strain slept significantly shorter as compared with those receiving EtOH alone. The BACs on awaking were significantly higher in the animals receiving the combination of PGE2 and EtOH than those receiving EtOH alone. These results suggest that there is the strain difference between F344 and LEW in ethanol-induced sleep, and that PGs may, in part, play a role in EtOH-induced sleep in LEW and F344.

Animals↗
PubMed1989

[Ethanol-induced discriminative stimulus properties in inbred rats with reference to aspirin, indomethacin and desipramine].

It is known that ethanol (EtOH) possesses discriminative stimulus (DS) effects, but there has been no report on the effects of aspirin, indomethacin and desipramine on the DS properties of EtOH. Lewis (LEW) and Fischer 344 (F344) rats weighing approximately 80% of free-fed animals were used. In the training process, EtOH (600 and 1200 mg/kg) or saline was administered i.p. once a day 5 min prior to beginning of the session according to the following sequence: EtOH-EtOH-saline-saline, under a fixed ratio ten (FR10) schedule. Discriminative test was performed in each animal after the discriminative response had achieved both the two criteria: (1) First Food Pellet (FFP) was below 12 responses and (2) the correct response rate was above 80%. There was no difference in session number to get to the criteria in the discrimination process between LEW and F344. Pentobarbital (PBA) well generalized to EtOH in both strains. The EtOH dose for 50% correct responses (FD50) was lower in F344 than in LEW. However, the ED50 for PBA was lower in LEW than in F344. There may be differences in sensitivity to EtOH and PBA. Dose response curve was not affected by pretreatment with aspirin, indomethacin and desipramine. These results suggest that aspirin, indomethacin and desipramine may not markedly affect in EtOH discriminative stimulus effects in LEW and F344 rats.

Animals↗
PubMed1987

Effect of malotilate (diisopropyl 1,3-dithiol-2-ylidenemalonate) on drug metabolizing activity in rat liver microsomes.

The effect of malotilate (diisopropyl 1,3-dithiol-2-ylidenemalonate) on drug metabolizing activity in rat liver microsomes was examined. Malotilate (500 mg/kg/day) was administered orally to rats for 3 days. The contents of cytochrome P-450 (P-450) and cytochrome b5 (b5), the activity of NADPH-cytochrome c reductase, and the metabolization of aniline, aminopyrine, benzo(a)pyrene (B(a)P) and 7-ethoxycoumarin (7-EC) in the microsomal fraction were examined 24 hr after the final administration of malotilate. The content of b5 and the activity of NADPH-cytochrome c reductase were increased by the malotilate treatment, but the content of P-450 was not significantly affected. 7-EC O-deethylation was markedly and aminopyrine N-demethylation was moderately enhanced; in contrast, aniline hydroxylation was significantly and B(a)P hydroxylation was slightly reduced. Such different effects of malotilate among the four substrate-metabolizing activities may be due mainly to the increase in the content of b5, which participates in the transport of the second electron required for P-450 function to various extents. It is also possible that malotilate affects the population of P-450 subtypes, each having a different substrate specificity and a different affinity for b5.

Aminopyrine↗
PubMed1987

Changes in plasma amino acids during the oral glucose tolerance test in hepatic diseases.

We have measured the plasma concentration of neutral amino acids before and after an oral glucose tolerance test (100 g) in patients with liver cirrhosis (LC), chronic active hepatitis (CAH), chronic persistent hepatitis (CPH), acute hepatitis in the acute stage (AHa) and acute hepatitis in the convalescent stage (AHc) and normal controls. The ratio of the concentration of an amino acid to the sum of those of the other neutral amino acids that compete during transport through the blood brain barrier (BBB), which was reported to correlate well with the brain level of the amino acid, was compared in patients with various liver diseases. The ratios of Trp (Trp/Tyr + Phe + Ile + Leu + Val), Tyr, Phe, and Val increased after glucose loading in all subjects, except Tyr in normal controls, which slightly decreased. On the other hand, Ile and Leu ratios decreased (Trp; tryptophan, Tyr; tyrosine, Phe; phenylalanine, Ile; isoleucine, Leu; leucine, Val; valine). LC showed a characteristic pattern; the ratios of Trp and Tyr were highest among all diseases at 3 hours after glucose loading, and those of Ile, Leu and Val were lowest. We assumed that delta an amino acid ratio = the amino acid ratio at 3 hrs after glucose loading minus the amino acid ratio at 0 hr. In LC, delta Trp ratio and delta Tyr ratio were highest, while delta Val ratio was lowest. The delta Phe ratios in AHa and AHc were significantly higher than those in healthy controls. From these results, the uptake of Trp and Tyr might be supposed to be highest and that of Val was lowest in LC, after glucose loading.

Adult↗
PubMed1986

Drug metabolizing activity in rats with chronic liver injury induced by carbon tetrachloride: relationship with the content of hydroxyproline in the liver.

The drug metabolizing activity of rat liver during long-term administration of carbon tetrachloride (CCl4), and its relationship with the content of hydroxyproline (Hyp) in the liver were examined. The contents of cytochrome P-450 (P-450) and cytochrome b5 (b5) and the metabolization of aniline, aminopyrine, 7-ethoxycoumarin (7-EC) and benzo(a)pyrene (B(a)P) in the microsomal fraction were examined five days after the final administration of CCl4. The contents of P-450 and b5 and the activity to metabolize the four substrates were gradually reduced as the Hyp content in the liver increased. However, aminopyrine N-demethylation and B(a)P hydroxylation, particularly the latter, was more reduced than aniline hydroxylation and 7-EC O-deethylation in the early stage of hepatic fibrosis. Such differences may be due mainly to the different P-450 subtypes affected by CCl4.

Animals↗