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Biomedical subjects

S Kaneko

Publications and source records attributed to S Kaneko.

At least 235 records · Page 13Linked to original sources
PubMed1999

Characteristics and risk factors of acute dystonia in schizophrenic patients treated with nemonapride, a selective dopamine antagonist.

The occurrence of acute dystonia was prospectively monitored in 39 schizophrenic patients (18 male and 21 female) treated with 9 to 27 mg/day of nemonapride, a selective dopamine antagonist, and the relationship of acute dystonia with characteristics of patients and plasma concentrations of the drug and prolactin was investigated. Twenty (51.3%) of 39 patients had dystonic reactions, the onsets of which occurred within 3 days after the initiation of treatment in 90% of dystonic patients. The incidence of acute dystonia was significantly higher in male than in female patients (77.8% vs. 28.6%, p < 0.05). Younger male patients (< or = 30 years) especially had an extremely high incidence of this side effect (91.7%). A positive correlation between prolactin response after 1 week of treatment and dystonia rating scores was found in male (Spearman rank correlation: r(s) = 0.606,p < 0.01) but not in female patients (r(s) = -0.378,p = not significant). These results suggest that young male patients have the highest risk of neuroleptic-induced dystonia. Prolactin response after 1 week of treatment as an index of dopamine blockade may reflect vulnerability to the development of acute dystonia at least in male patients treated with nemonapride.

Acute Disease↗
PubMed1999

Effects of itraconazole on the steady-state plasma concentrations of haloperidol and its reduced metabolite in schizophrenic patients: in vivo evidence of the involvement of CYP3A4 for haloperidol metabolism.

The effects of itraconazole, a potent inhibitor of cytochrome P450 (CYP) 3A4, on the steady-state plasma concentrations of haloperidol and reduced haloperidol were examined in schizophrenic patients. Thirteen schizophrenic patients treated with haloperidol 12 or 24 mg/day received 200 mg/day of itraconazole for 7 days. Plasma concentrations of haloperidol and reduced haloperidol were measured by high-performance liquid chromatography together with clinical assessment by the Brief Psychiatric Rating Scale (BPRS) and the Udvalg for Kliniske Undersogelser side effect rating scale just before and during itraconazole treatment and 1 week after its discontinuation. Plasma concentrations of haloperidol and reduced haloperidol during the itraconazole treatment (16.9 +/- 11.2 and 6.1 +/- 6.6 ng/mL, respectively) were significantly (p < 0.01) higher than those observed before itraconazole treatment (13.0 +/- 7.9 and 4.9 +/- 5.1 ng/mL) or 1 week after its discontinuation (13.5 +/- 8.2 and 4.9 +/- 5.0 ng/mL). No change was found in clinical symptoms assessed by BPRS, whereas neurologic side effects were significantly (p < 0.05) increased during itraconazole coadministration. The elevated plasma concentrations of haloperidol and reduced haloperidol during itraconazole coadministration were likely due to the inhibitory effects of itraconazole on the metabolism of haloperidol and reduced haloperidol. Thus, this study may provide in vivo evidence of involvement of CYP3A4 in the metabolism of haloperidol and possibly in that of reduced haloperidol. Deterioration of neurologic side effects during itraconazole treatment may result from the increased plasma concentrations of haloperidol and reduced haloperidol during itraconazole treatment.

Adult↗
PubMed1999

Lack of significant pharmacokinetic interaction between haloperidol and grapefruit juice.

The effects of repeated ingestion of grapefruit juice, an inhibitor of cytochrome P4503A4 (CYP3A4), on the steady-state plasma concentrations of haloperidol and reduced haloperidol were examined. Twelve schizophrenic inpatients receiving haloperidol 12 mg/day, ingested grapefruit juice 600 ml/day for 7 days. Blood samples were collected before and during grapefruit juice coadministration and 1 week after its discontinuation together with an assessment of clinical status. Plasma drug concentrations were measured using high-performance liquid chromatography. Clinical status for each patient was assessed by the Brief Psychiatric Rating Scale (BPRS) and the UKU side-effect rating scale (UKU). Plasma concentrations of haloperidol and reduced haloperidol during grapefruit juice coadministration (9.0 +/- 3.0 and 2.6 +/- 1.4 ng/ml, respectively) were not significantly different from those before grapefruit juice coadministration (9.1 +/- 2.8 and 2.6 +/- 1.5 ng/ml) or those 1 week after its discontinuation (8.8 +/- 2.7 and 2.6 +/- 1.3 ng/ml). There was no change in the scores of BPRS or UKU during the study period. The present results shows that grapefruit juice does not affect the plasma concentrations of haloperidol and reduced haloperidol or clinical status in patients receiving haloperidol.

Adult↗
PubMed1999

Effects of carbamazepine coadministration on plasma concentrations of the enantiomers of mianserin and of its metabolites.

Concentrations of the enantiomers of unconjugated and of total (unconjugated plus conjugated) mianserin, desmethylmianserin and 8-hydroxymianserin were measured in 12 patients before and after the introduction of carbamazepine. The dose of mianserin was 60 mg/d, carbamazepine was coadministered at 400 mg/d for 4 weeks, and blood samples were taken at weekly intervals after the introduction of carbamazepine. Each week, carbamazepine significantly decreased plasma concentrations of unconjugated and total (S)-mianserin (the more potent enantiomer) and of unconjugated and total (R)-mianserin. On average, plasma concentrations of unconjugated and total (S)-mianserin and of unconjugated and total (R)-mianserin were 55%, 56%, 66%, and 55%, respectively, of the corresponding values before introduction of carbamazepine. These results strongly suggest the involvement of CYP3A4, the major CYP enzyme induced by carbamazepine, in the metabolism of both enantiomers of mianserin. A strong decrease in the concentrations of (S)-8-hydroxymianserin was also measured (on average, the concentrations were 69% of the corresponding values before carbamazepine introduction). Conversely, plasma concentrations of unconjugated and of total (S)-desmethylmianserin, (R)-desmethylmianserin, and (R)-8-hydroxymianserin were only slightly modified by carbamazepine. From a clinical point of view, as a therapeutic window for (S)-mianserin has been recently suggested, the dose of racemic mianserin for a patient whose (S)-mianserin concentrations have been stabilized within this therapeutic window would need to be approximately doubled if carbamazepine, at 400 mg/d, is introduced as a comedication.

Adult↗
PubMed1999

No pharmacokinetic but pharmacodynamic interactions between cisapride and bromperidol or haloperidol.

Pharmacokinetic and pharmacodynamic interactions between the gastrokinetic drug cisapride and the antipsychotic drugs bromperidol and haloperidol were studied in 29 schizophrenic inpatients. Fourteen patients were taking bromperidol (12-24 mg/d), and 15 were taking haloperidol (12-36 mg/d). Cisapride 10 mg/d was coadministered for 1 week, and blood sampling was performed before cisapride treatment, 1 week after starting cisapride treatment, and I week after stopping cisapride treatment. On the same days as the blood sampling, psychotic symptoms and side effects were evaluated using the Brief Psychiatric Rating Scale (BPRS) and the Udvalg for Kliniske Undersøgelser (UKU) side effect rating scale (UKU), respectively. Plasma concentrations of bromperidol, haloperidol, and their reduced metabolites were measured by high-performance liquid chromatography. The mean BPRS scores after adding cisapride were significantly higher than those before cisapride (p<0.01) and after stopping cisapride (p<0.001) in the haloperidol group in this uncontrolled study. A similar tendency was observed in the bromperidol group, although it did not reach statistical significance (p = 0.08). Cisapride coadministration caused no significant changes in the mean plasma concentrations of bromperidol, haloperidol, and their reduced metabolites or in the mean UKU score. The present study suggests that there is no significant pharmacokinetic interaction between cisapride and bromperidol or haloperidol, but cisapride appears to deteriorate psychotic symptoms by a pharmacodynamic interaction in schizophrenic patients treated with haloperidol.

Antipsychotic Agents↗
PubMed1999

Zinc accumulation in adriamycin-induced cardiomyopathy in rats: effects of melatonin, a cardioprotective antioxidant.

We have recently reported that melatonin protects against adriamycin-induced cardiomyopathy whose pathogenesis may involve free radicals and lipid peroxidation. Melatonin has also been shown to affect zinc turnover. Since zinc may act as an antioxidant, we investigated the role of zinc in the pathogenesis of adriamycin-induced cardiomyopathy as well as in the treatment of melatonin against this disorder. Sprague-Dawley rats were given adriamycin (cumulative dose, 15 mg/kg); melatonin (cumulative dose, 84 mg/kg); adriamycin plus melatonin; adriamycin plus probucol, another antioxidant (cumulative dose, 90 mg/kg); or vehicle alone, according to previously-used regimens. Cardioprotective effects of both antioxidants (melatonin and probucol) were confirmed by the parameters of fractional shortening, heart weight, heart/body weight ratio, ascites volume, and mortality. Adriamycin increased both the myocardial and plasma levels of thiobarbituric acid reactive substances (TBARS) and myocardial zinc levels, and decreased plasma zinc levels. The significant negative correlation observed between the myocardial and plasma zinc levels (r = 0.73, P < 0.01) among the samples of adriamycin-treated and control rats suggested an internal redistribution of zinc. Melatonin and probucol were equally effective in inhibiting the increase in myocardial TBARS as well as zinc levels, suggesting that myocardial zinc accumulation might be a protective response against adriamycin-induced oxidative stress. Melatonin also inhibited the adriamycin-induced decrease in plasma zinc levels; probucol was not as effective in doing so. In addition to melatonin's antioxidative effect, it may have the effect of maintaining the plasma zinc levels.

Animals↗
PubMed1999

Serum levels of soluble Fas and disease activity in patients with IgA nephropathy.

Using a sandwich ELISA, we studied 48 patients with IgA nephropathy and 10 patients with diffuse mesangial proliferative glomerulonephritis without IgA deposition (non-IgA PGN) to determine if levels of serum soluble Fas (s-Fas) might reflect the disease activity. The levels of serum s-Fas in patients with the advanced stage of IgA nephropathy were significantly higher than those in patients with the mild stage of the disease, in non-IgA PGN or in healthy controls. The results showed that advanced stage IgA nephropathy patients who showed heavy proteinuria and the presence of urinary casts revealed high levels of serum s-Fas. It was thus suggested that the measurement of serum s-Fas is useful in evaluating the degree of renal injury in patients with IgA nephropathy.

Adolescent↗
PubMed1999

[Effects of propiverine hydrochloride (propiverine) on isolated rat and dog urinary bladder].

Propiverine is a drug for the treatment of incontinence and pollakiuria. The effects of propiverine on isolated rat and dog urinary bladder were investigated. At doses of 10(-6)-3 x 10(-5) M, propiverine caused both a rightward shift and inhibition of the maximum response in the acetylcholine (ACh) dose-response curve. The pA2 values for rat and dog urinary bladder were 5.97 and 6.62, respectively. At doses of 10(-5)-10(-5) M, propiverine also dose-dependently inhibited KCl (100 mM)-induced contractions. The IC50 values for rat and dog urinary bladder were 3.9 x 10(-6) M and 3.8 x 10(-6) M, respectively. The pA2 value and the IC50 value of terodiline for rat urinary bladder were 6.08 and 6.6 x 10(-6) M, respectively. In contrast, the pA2 value and the IC50 value of oxybutynin for rat urinary bladder were 7.69 and 4.5 x 10(-6) M, respectively, suggesting that oxybutynin exerts an anti-muscarinic effect at doses at which no discernible anti-KCl effect was observed, whereas propiverine and terodiline exerted both effects at the same doses. The inhibitory effect of drugs on the contraction induced by electrical field stimulation was tested. At a dose of 10(-7) g/ml, tetrodotoxin inhibited the contraction of rat and dog urinary bladder by 76.6% and 92.6%, respectively. Propiverine and verapamil dose-dependently inhibited the contractile response induced by electrical field stimulation at doses of 10(-5) M or more and 3 x 10(-6) M or more, respectively. At these concentrations, a marked anti-KCl effect of the drugs on smooth muscle was observed. On the other hand, atropine caused no inhibition of the contractile response in rat urinary bladder at a dose of 3 x 10(-5) M, and it inhibited the contraction in dog urinary bladder by 14.9% at a dose of 10(-5) M. These findings suggest that although propiverine exhibits both anti-muscarinic and anti-KCl effects in isolated rat and dog urinary bladder, the inhibitory effects of propiverine on the atropine-resistant part of contraction may be mainly due to its anti-KCl effect.

Acetylcholine↗
PubMed1999

[Effects of propiverine hydrochloride (propiverine) on the muscarinic receptor binding affinity in guinea pig tissues and on salivation in conscious dogs].

Propiverine is a drug for the treatment of incontinence and pollakiuria. Such micturitional disorders are principally caused by a hyperactive bladder. The effects of propiverine, its active metabolite, 1-methyl-4-piperidyl benzilate N-oxide (DPr-P-4 (N-->O)), oxybutynin and terodiline on muscarinic receptors in guinea pig urinary bladder, salivary glands, cerebral cortex, ileal longitudinal muscle and heart were compared. Both propiverine and DPr-P-4 (N-->O) competitively inhibited specific binding of 3H-quinuclidinyl benzilate (3H-QNB) to membrane fractions of these tissues. Oxybutynin, terodiline, pirenzepine and atropine also competitively inhibited the binding of 3H-QNB. The order of these drugs in terms of their affinity for muscarinic receptors was as follows: atropine > oxybutynin > pirenzepine, DPr-P-4 (N-->O), terodiline > propiverine. Propiverine and DPr-P-4 (N-->O) had no selectivity for muscarinic receptors in these tissues, the same as atropine. In contrast, pirenzepine, a M1-selective drug, had 10.1 times greater affinity for muscarinic receptors in the cerebral cortex than in urinary bladder, and the affinity of oxybutynin for muscarinic receptors in salivary glands and in cerebral cortex was 10.9 times and 13.9 times higher, respectively, than in urinary bladder. The affinity of terodiline for muscarinic receptors in the cerebral cortex was 4.4 times higher than in urinary bladder. In this study, the effect of propiverine and oxybutynin on pilocarpine (1 mg/kg, s.c.)-induced salivation in conscious dogs was also compared. Propiverine (5 mg/kg, i.v.) had no effect on pilocarpine-induced salivation, whereas oxybutynin (0.1 mg-0.5 mg/kg, i.v.) inhibited it significantly and dose-dependently. The ID50 values (95% confidence limits) for propiverine and oxybutynin during the 20 min after intravenous administration were 6.88 mg/kg (4.71-15.67) and 0.154 mg/kg (0.115-0.205), respectively. These findings suggest that although propiverine, its active metabolite DPr-P-4 (N-->O), oxybutynin and terodiline competitively inhibit the binding of 3H-QNB to muscarinic receptors, the affinity of these drugs for the muscarinic receptors of these tissues is very different and that propiverine has less effect on salivation than oxybutynin.

Animals↗
PubMed1999

[Factors regulating survival and death of midbrain dopamine neurons].

We utilized organotypic midbrain slice cultures for the assessment of survival and degeneration of dopaminergic neurons in the substantia nigra. Application of N-methyl-D-aspartate (NMDA) to midbrain slice cultures for 24 h caused a concentration-dependent decrease in the number of surviving dopaminergic neurons visualized by tyrosine hydroxylase immunohistochemistry. Simultaneous application of (-)-deprenyl significantly attenuated the cytotoxic effect of NMDA. Because pretreatment with (-)-deprenyl failed to reduce NMDA toxicity, it is suggested that the neuroprotective effect of (-)-deprenyl is not mediated by its irreversible inhibitory action on monoamine oxidase B. We also prepared co-cultures of midbrain and striatal slices to investigate whether the presence of target tissue influences toxic actions of several drugs on dopaminergic neurons. Co-cultured dopaminergic neurons formed dense innervation to the striatal tissue. Dopaminergic neurons in midbrain--striatum co-cultures were more resistant to the cytotoxic actions of NMDA and a nitric oxide donor NOC-18, than the same neuronal population in single midbrain cultures. On the other hand, the toxicity of 1-methyl-4 phenylpyridinium ion or buthionine-[S,R]-sulfoximine was more prominent in midbrain--striatum co-cultures than that in single midbrain cultures. Organotypic slice cultures appeared to be a useful system for evaluation of dopaminergic neuronal death under experimental conditions relevant to physiological/pathophysiological situations.

1-Methyl-4-phenylpyridinium↗
PubMed1999

Receptor-mediated modulation of voltage-dependent Ca2+ channels via heterotrimeric G-proteins in neurons.

The activity of voltage-dependent Ca2+ channels is highly regulated by neurotransmitter receptors coupled to heterotrimeric G-proteins. In the expression studies using cloned Ca2+ channel subunits, it has been clarified that the main mechanism of the inhibition of N-type channel current is mediated directly by G-protein betagamma subunits in a membrane-delimited and voltage-sensitive manner. In addition, recent studies have also clarified that N-type channels are modulated by several G-protein alpha subunits in different ways. Among them, G(alpha o) mediates a voltage-resistant inhibition of N-type current by neurotransmitters. This type of inhibition is more apparent in the case of P/Q-type channels in both native cells and expression systems. Moreover, other G-protein subunits, such as G(alpha q) and G(alpha s), also seem to regulate N-type channels in a membrane-delimited manner. The fine tunings of Ca2+ channel activity by intracellular proteins have physiological and pathological meanings in the regulation of Ca2+ influx into excitable cells by neurotransmitters and pharmacological implications as novel drug targets for controlling Ca2+ influx.

Animals↗
PubMed1999

Purification and characterization of recombinant Mortierella vinacea alpha-galactosidases I and II expressed in Saccharomyces cerevisiae.

The cDNAs coding for Mortierella vinacea alpha-galactosidases I and II were expressed in Saccharomyces cerevisiae under the control of the yeast GAL10 promoter. The recombinant enzymes purified to homogeneity from the culture filtrate were glycosylated, and had properties identical to those of the native enzymes except for improving the heat stability of alpha-galactosidase II and decreasing the specific activities of both enzymes.

Bacterial Proteins↗
PubMed1999

Adrenal insufficiency due to metastatic hepatocellular carcinoma.

A 73-year-old man with general malaise and nausea following a common cold diagnosed by a local physician was found to have multiple hepatocellular carcinomas with enlarged bilateral adrenal glands, combined with adrenal insufficiency. Hydrocortisone replacement improved the symptoms and laboratory findings. Autopsy findings revealed that each adrenal gland was completely replaced by the tumor measuring 11 cm in diameter, and no adrenal tissue was recognized. Histologically, the adrenal tumors, as well as the liver tumors, were moderately differentiated Edmondson type II hepatocellular carcinomas. This is a second report of adrenal insufficiency due to hepatocellular carcinoma as a primary site of metastatic adrenal tumor.

Adrenal Gland Neoplasms↗
PubMed1999

Setting up an automated system for evaluation of bone age.

The "Tanner-Whitehouse 2" method is the most popular in evaluating skeletal maturation, but this method has some inherent weak points. We therefore developed the new system to automatically evaluate the skeletal maturation of Japanese children by means of a personal computer. The subjects of this study were 318 healthy Japanese boys and 199 girls ranging from 2 to 15 years of age. The bone age was calculated by multiple regression analysis with parameters for the epiphysis and metaphysis. Successful automatic evaluation was about 80-90% on each phalanx. There was a significant correlation between chronological age and the ratio of epiphyseal width to metaphyseal width. The system developed in this study was useful for evaluating the skeletal maturation.

Adolescent↗
PubMed1999

Human glutathione S-transferase P1 polymorphism and susceptibility to smoking related epithelial cancer; oral, lung, gastric, colorectal and urothelial cancer.

The A/G polymorphism at nucleotide 313 in the glutathione S-transferase P1-1 (GSTP1) gene was examined in patients with different types of smoking-related cancers (oral, lung, gastric, colorectal and urothelial cancers) and healthy control individuals. This polymorphism results in an amino acid substitution from isoleucine to valine at residue 105, which reduces catalytic activity of the enzyme. In control individuals, 23.8% of individuals had GSTP1 AG or GG genotype. This rose to 37.3% [n = 83, odds ratio = 1.93 (1.05-3.58), P = 0.035] in oral cancer patients. No increase in the frequency of the GSTP1 AG or GG genotype was obtained in lung, gastric, colorectal or urothelial cancers in this Japanese population. After grouping by smoking status, no consistent difference was observed between smoking patients and corresponding control individuals for the frequency of the GSTP1 A/G polymorphism for any cancer. However, a moderate risk (odds ratio = 2.78; 95% confidence interval 1.06-7.51) was associated with this polymorphism in the non-smoking group of oral cancer patients. The results suggest the GSTP1 polymorphism at nucleotide 313 may be associated with susceptibility to oral squamous cell carcinoma in the Japanese population.

Base Sequence↗