Pharmacogenetics of CYP2C subfamily in a Japanese population.
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Aryl Hydrocarbon Hydroxylases↗
Biomedical subjects
S Higuchi
Publications and source records attributed to S Higuchi.
[Nurses' knowledge of alcohol-related problems and their treatment: a comparison of nurses in general hospital and alcoholism treatment units].
Nurses have the most contact with patients in the clinical settings, and they play an important role in the guidance and education of patients. Nurses' basic knowledge of alcohol-related problems greatly influences early discovery of and early intervention against alcohol-related problems in general units (GU). In a study undertaken mainly to understand the status of nurses' knowledge in GU, a survey was performed to compare the knowledge and attitude of nurses working in GU and those with working in units specializing in the treatment of alcoholism (AU). For reference, we used the results of separate surveys performed previously on the general population. The results showed that, compared with nurses in AU, nurses in GU (1) were more tolerant of drinking, but (2) were more stigmatic concerning alcoholism, and (3) had little knowledge concerning alcohol-related problems. Nurses in GU tended to have less knowledge about alcohol-related problems than the general population. Moreover, the knowledge of nurses in AU could not be considered sufficient. This study suggested the need for basic education concerning alcohol-related problems and their treatment aimed at nurses.
Adult↗
Pharmacokinetics and plasma protein binding of tamsulosin hydrochloride in rats, dogs, and humans.
The pharmacokinetics of tamsulosin hydrochloride, a selective alpha1-adrenoceptor antagonist, was investigated after single iv and oral dosing to rats and dogs, and oral dosing to healthy male volunteers. After iv dosing, plasma tamsulosin concentrations declined in an apparent biexponential manner with terminal half-lives of 0.32 hr in rats and 1.13 hr in dogs. Values for total blood clearance (CLB) were 6.57 l/hr/kg in rats and 1.61 l/hr/kg in dogs, suggesting "hepatic blood flow-limited" and "intermediate flow-dependent" clearance, respectively. After oral dosing, tamsulosin was rapidly absorbed and reached maximum levels within 1 hr in rats and dogs, and at 1.0-1.8 hr in humans. Values for oral clearance (CLoral) in rats, dogs, and humans were 34.5-113.6, 3.01-3. 99, and 0.031-0.041 l/hr/kg, respectively, showing wide variation among these species. The absolute bioavailability (F) increased with dose in rats (from 6.9% at 1 mg/kg to 22.8% at 10 mg/kg), but was almost constant in dogs (29.7-42.0% over the 0.3-3 mg/kg dose range). The plasma protein binding of 14C-tamsulosin in humans was much higher (98.9-99.1%) than that in rats and dogs (79.0-80.6% and 90. 2-90.3%, respectively). The ratio of blood to plasma concentrations (RB) value in rats, dogs, and humans decreased in this order (1.2, 0. 72, and 0.53, respectively), corresponding to the decrease in plasma unbound fraction (fu) in these species. These results imply that the large interspecies difference in CLoral is attributable to a difference not only in hepatic metabolism but also in protein binding among these species.
Administration, Oral↗
Vasorelaxant and negative inotropic effects of gallopamil and LU49700, a metabolite of gallopamil, on isolated rat aorta and guinea-pig ventricular myocardium.
The effects of LU49700 (CAS 116759-60-5), the main metabolite of gallopamil (CAS 16662-47-8) on the mechanical response of isolated rat aortic and guinea-pig ventricular papillary muscle preparations were compared with those of gallopamil. Gallopamil and LU49700 inhibited the 64 mmol/l KCl-induced contraction of rat aorta in a concentration-dependent manner. The vasorelaxant potency of LU49700 was 244 times weaker than that of gallopamil. Gallopamil and LU49700 produced concentration-dependent negative inotropic effects on isolated right ventricular papillary muscles. The negative inotropic potency of LU49700 was 418 times weaker than that of gallopamil. These findings indicate that LU49700 has a weaker cardiovascular depressant potency than gallopamil. Therefore, LU49700 may not mediate the effects of gallopamil for treating subjects with cardiovascular diseases.
Animals↗
Chronopharmacology of granulocyte colony-stimulating factor in mice.
The role of the sensitivity of bone marrow cells to, and the pharmacokinetics of granulocyte colony-stimulating factor (G-CSF) on the rhythm of leukocyte-increasing effect was investigated in ICR male mice housed under a standardized light-dark cycle (lights on at 0700, off at 1900). A significant circadian rhythm was demonstrated for leukocyte counts at 24 hr after G-CSF (250 microg/kg, s.c.) injection at six different circadian times (P < .01). The leukocyte counts of mice given G-CSF at 0500, 0900, 1300 or 1700 were significantly higher than those of mice given G-CSF at 2100 (P < .01, respectively). The rhythmic pattern resembled overall the rhythm occurring after saline injection. In the comparison between leukocyte counts after G-CSF injection at 0700 and 1900, the time when leukocyte counts are equal in nondrugged state, the leukocyte counts at 24 hr after G-CSF (250 microg/kg, i.v.) injection were approximately 50% higher in mice injected with the drug at 0700 than at 1900 (P < .01). Bone marrow cultures obtained at two times of day resulted in different numbers of myeloid colonies even when treated with the same concentrations of G-CSF in vitro. The colony-forming activity of G-CSF was significantly more potent at 0700 than at 1900 (P < .01). The plasma G-CSF concentrations after G-CSF (250 or 5 microg/kg, i.v.) injection were significantly higher in mice receiving injections with the drug at 0700 than at 1900 (P < .05, respectively). The area under the curve and mean residence time were significantly larger in mice injected with the drug at 0700 than at 1900 (P < .01, P < .05, respectively). Our suggests that the rhythm of G-CSF activity is caused by that of the sensitivity of bone marrow cells to, and the pharmacokinetics of the drug.
Animals↗
Clinical characteristics and disease course of alcoholics with inactive aldehyde dehydrogenase-2.
Inactive aldehyde dehydrogenase-2 (ALDH2) is known as a genetic negative risk factor for the development of alcoholism. In alcoholics with inactive ALDH2, unidentified factors that overcome the adverse reactions of high blood acetaldehyde concentration after drinking may increase such persons' susceptibility to alcoholism. Comparison of clinical characteristics, including sociofamilial backgrounds and psychopathologies, failed to show significant differences between alcoholics with inactive ALDH2 (inactive group) and those with active ALDH2 (active group). Examination of the temporal profile of disease development showed that the inactive group experienced each stage or event in the history of drinking and alcoholism 1 to 5 years later in life than the active group; however, not all comparisons reached statistically significant levels. Although preliminary, these results suggest that an inactive ALDH2-mediated delay in the occurrence of alcohol-related problems seems to contribute to the suppression of alcoholism development.
Acetaldehyde↗
[A case of fulminant myocarditis treated by ABIOMED BVS 5000 biventricular support].
Reported is a case of acute fulminant myocarditis with profound circulatory compromise. The patient was supported with biventricular assist devices (BVS 5000 ; ABIOMED Inc., Danvers, Mass.). The patient had remarkable recovery of ventricular function, which allowed for the removal of the device after 269 hours of support and the recovery to the normal quality of life. This case shows the success of mechanical support to treat potentially fatal disease process.
Adult↗
Short-term follow-up after endoscopic mucosectomy of early esophageal cancer and aldehyde dehydrogenase-2 genotype in Japanese alcoholics.
The risk of the future development of primary esophageal cancer after endoscopic esophageal mucosal resection of esophageal cancer is not known; hence, there are no established guidelines for follow-up surveillance programs. Simultaneous occurrence of multiple cancers associated with esophageal cancer is common among heavy drinkers who have the inactive form of aldehyde dehydrogenase-2 (ALDH2) as a risk factor. Thirty-four Japanese male alcoholics with intraepithelial or mucosal squamous cell carcinoma in the esophagus were treated by endoscopic esophageal mucosal resection, followed by endoscopy and esophageal iodine staining, to find the additional development of primary esophageal cancer. Primary esophageal squamous cell carcinoma was detected in nine patients (26.5%) at 3-21 months after the first cancer diagnosis. Cancer occurred more frequently in patients with inactive ALDH2 than it did in those with active ALDH2 [42.1% (8 of 19) versus 6.7% (1 of 15), P = 0.047], and it occurred more frequently in those with multiple esophageal cancers than it did in those without them [60.0% (6 of 10) versus 12.5% (3 of 24), P = 0.009]. Kaplan-Meier estimates of the proportions of patients with additional primary esophageal cancers showed that patients with inactive ALDH2 (P = 0.024) or multiple esophageal cancers (P = 0.007) had a significantly increased likelihood of the development of additional cancer. Close follow-up examinations using endoscopy and iodine staining are needed for such high-risk patients.
Adult↗
Effect of pibutidine hydrochloride on nitric oxide production in rat gastric mucosa.
This study examined the effect of pibutidine hydrochloride, a novel histamine H2 receptor antagonist (IT-066), on nitric oxide (NO) production in gastric mucosa by measuring nitrite and nitrate contents. IT-066 (0.3-3 mg/kg, p.o.) and NO donors, sodium nitroprusside (0.3 mg/kg, s.c.) and NOR3 (0.1 mg/kg, s.c.), increased the NO contents in gastric mucosa. Cimetidine (100 mg/kg, p.o.), ranitidine (30 mg/kg, p.o.) and famotidine (10 mg/kg, p.o.) did not significantly affect the NO production. Pretreatment with NG-nitro-L-arginine methyl ester (3 mg/kg, i.v.), a NO synthase inhibitor, decreased the level of IT-066 (3 mg/kg, p.o.)-stimulated NO production. These results suggest that IT-066 stimulated gastric mucosal NO production, and that endogenous NO may be implicated in the pharmacological effect of IT-066.
Animals↗
Serotonin transporter gene regulatory region polymorphism and anxiety-related traits in the Japanese.
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Adolescent↗
Monoamine oxidase genes polymorphisms and mood disorder.
We investigated a genetic association between mood disorders (bipolar and unipolar) and the alleles of monoamine oxidase (MAO) A and B (MAOA and MAOB). One hundred and twelve unrelated Japanese patients (60 bipolar, 52 unipolar) and 100 controls were genotyped for three markers of MAOA and for one marker of MAOB. No statistically significant difference in the distribution of the alleles existed between cases and controls. Therefore, our results did not support the involvement of the alleles at MAOA and MAOB in the etiology of mood disorder.
Adult↗
Association between dopamine D4 receptor (D4DR) exon III polymorphism and novelty seeking in Japanese subjects.
This study was designed to assess the association between novelty seeking and D4DR gene polymorphism in the Japanese population. The 48 bp repeat polymorphism in the third exon of the dopamine D4 receptor gene of 153 normal female students was correlated with personality feature results from the Japanese version of Cloninger's Temperament and Character Inventory. The Novelty Seeking subscale of Exploratory Excitability had a significant association with long alleles of the polymorphic exon III repeat sequence of D4DR. Our results suggest that there is an association between long alleles of the polymorphic exon III repeat sequence of D4DR and the personality traits of the Novelty Seeking subscale of Exploratory Excitability, regardless of racial differences in the frequencies of D4DR exon III repeat polymorphism.
Adolescent↗
Purification and characterization of a cytochrome P450 from liver microsomes of Xenopus laevis.
A new cytochrome P450 (P450) has been purified to near homogeneity from Xenopus laevis liver microsomes. Two steps of column chromatographies (n-octylamino Sepharose 4B and Mono Q) and fast protein liquid chromatofocusing were performed consecutively, and the final preparation containing 19 nmol P450/mg protein gave a single band of 52 kDa on SDS-PAGE at an isoelectric point of 6.7. This enzyme had a common feature of microsomal P450s in NH2-terminal region, and some of the internal sequences were similar to the corresponding sequences of reported P450s. The purified Xenopus P450 cross-reacted with antibodies against CYP2B1, rat CYP2E1, and CYP2C13, but not with rat CYP1A1, CYP3A2, or CYP4A1. Upon reconstitution with rat NADPH-cytochrome P450 reductase and phospholipid, the Xenopus P450 catalyzed aniline hydroxylation and N-nitrosodimethylamine N-demethylation. Cytochrome b5 enhanced these reactions. This P450 did not catalyze the hydroxylation of either hexobarbital or testosterone. Thus, the catalytic activities of this P450 were comparable with those of mammalian CYP2E1. Expression of this P450 was observed in liver, kidney, lung, and testis, and the level was highest in kidney. Tissue specificity of expression was the same in both male and female frogs.
Amino Acid Sequence↗
Regional cerebral glucose utilization is modulated by the dosage of apolipoprotein E type 4 allele and alpha1-antichymotrypsin type A allele in Alzheimer's disease.
Twenty Alzheimer's disease (AD) patients with defined apolipoprotein E (APOE), alpha1-antichymotrypsin (ACT) and presenilin-1 (PS-1) intronic genotypes were examined to quantify the regional cerebral metabolic rate of glucose (rCMRglc) using positron emission tomography (PET) and 18F-2-fluoro-2-deoxy-D-glucose (FDG). The frontal rCMRglc was significantly increased in patients with the APOE epsilon4 allele in a dose-dependent fashion. In contrast, the temporo-parietal rCMRglc was significantly reduced in ACT type A allele (ACT*A) carriers compared with those in non-ACT*A carriers. The PS-1 type 1 intronic allele had no significant effects on rCMRglc in any cerebral region. These results suggest that both the APOE and ACT genes may play a distinct role in the progression of AD as monitored by imaging studies of cerebral glucose utilization.
Aged↗
Highly sensitive method for the determination of tamsulosin hydrochloride in human plasma dialysate, plasma and urine by high-performance liquid chromatography-electrospray tandem mass spectrometry.
A highly sensitive method for the determination of tamsulosin hydrochloride, a structurally new type of sulphamoile derivative, in human plasma dialysate, plasma and urine has been developed by using liquid chromatography-electrospray tandem mass spectrometry (LC-MS-MS). Plasma dialysate, plasma and urine samples were extracted by brief liquid-phase extraction and analyzed using an HPLC system coupled to a mass spectrometer via an electrospray ionization interface. Selected reaction monitoring was used for the detection of tamsulosin and its internal standard. This method was validated in the concentration range 10-1000 pg/ml in plasma dialysate, 0.5-50 ng/ml in plasma, and 1-100 ng/ml in urine with sufficient specificity, accuracy and precision. The in vivo protein binding study demonstrated that the unbound tamsulosin in human plasma obtained by the equilibrium dialysis after 0.4-mg oral dosing was measurable. In addition, the percentage of unbound tamsulosin in an in vitro study (0.71-0.91%) obtained by using spiked 14C-labelled tamsulosin was slightly larger than that of the in vivo study (0.68-0.86%), indicating that the unbound concentration calculated by the product of the plasma concentration and the in vitro unbound fraction (fu) was unfavorably overestimated. These results suggest that the combination of LC-MS-MS and equilibrium dialysis method has enough sensitivity to determine the unbound concentration in clinical use and gives the concentration more exactly than the in vitro fu.
Adrenergic alpha-Antagonists↗
Herpes simplex virus and risk of Alzheimer's disease.
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Aged↗
Cloning and sequence analysis of a Bothrops jararaca cDNA encoding a precursor of seven bradykinin-potentiating peptides and a C-type natriuretic peptide.
A 1.8-kb cDNA clone was isolated from a Bothrops jararaca venom gland cDNA library that encodes a 256-aa precursor for bradykinin-potentiating peptides (angiotensin-converting enzyme inhibitors) and a C-type natriuretic peptide (CNP). The seven bradykinin-potentiating peptides are aligned tandemly after the hydrophobic signal peptide sequence, followed by a putative intervening sequence and a CNP at the C terminus. Northern blot analysis indicated the predominant expression of a 1.8-kb mRNA in the venom glands as well as in the spleen and the brain. Two lower intensity mRNA bands of 3.5 kb and 5.7 kb also hybridized to the cDNA clone. Radioimmunoassay for the CNP was performed using the antiserum against rat CNP. The presence of CNP immunoreactivity was detected in the low molecular weight fraction of the Bothrops jararaca venom.
Amino Acid Sequence↗
H-aggregation of Methyl Orange at the Interface between the Water Phase and Oil Phase in a Water-in-Oil Microemulsion
Methyl orange dissolved in a water-in-oil microemulsion was examined by UV-VIS absorption spectroscopy and differential scanning calorimetry (DSC). Methyl orange showed two temperature-dependent peaks at 416 and 354 nm in the microemulsion. The former was attributed to a methyl orange monomer, and the latter to aggregates of the dye in the parallel orientation (H-aggregates) at the interface between the water phase and the oil phase in the microemulsion. The position of methyl orange in the microemulsion was verified by DSC analysis.
Journal Article↗