How does xenon produce anesthesia? A perspective from electrophysiological studies.
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Anesthetics, Inhalation↗
Biomedical subjects
S Morita
Publications and source records attributed to S Morita.
The effect of CYP2C19 and CYP2D6 genotypes on the metabolism of clomipramine in Japanese psychiatric patients.
In this study, the authors investigated the relationship between the metabolism of clomipramine (C) and the genotypes of cytochrome P450 (CYP) CYP2C19 and CYP2D6. Fifty-one Japanese patients (18 men and 33 women) were administered 10 to 250 mg/day of C by mouth and maintained on the same daily dose of C for at least 2 weeks to obtain steady-state concentrations. Plasma levels of C and its metabolites N-desmethylclomipramine (DC), 8-hydroxyclomipramine, and 8-hydroxy-N-desmethylclomipramine (HDC) were determined by high-performance liquid chromatography. The allele frequencies of CYP2C19*2, CYP2C19*3, CYP2D6*5, and CYP2D6*10 were 27.5%, 12.8%, 2.9%, and 43.1%, respectively. Subjects who were homozygous for mutated alleles of CYP2C19 showed approximately 75% higher concentrations of C corrected by dose and body weight compared with those who were homozygous for wild-type alleles. Also, subjects who were homozygous for mutated alleles of CYP2C19 showed an approximately 68% higher value of C/DC compared with those who were homozygous for wild-type alleles. No significant difference in the ratio of DC/HDC was observed between subjects who were homozygous for mutated alleles of CYP2D6 and those who were homozygous for wild-type alleles. These results suggest that genotyping CYP2C19 is useful for grossly predicting the risk of getting high plasma concentrations of C and the low individual capacity to demethylate C because there is marked interindividual variability within each genotype. However, the genotyping of CYP2D6 is not useful for predicting the individual capacity to hydroxylate DC.
Adolescent↗
Determination of exogenous melatonin and its 6-hydroxy metabolite in human plasma by liquid chromatography-mass spectrometry.
SUMMARY: Melatonin has recently garnered interest as a possible treatment for sleep disorders, and this has created a desire for appropriate pharmacokinetic studies. No method has yet been published that can measure the concentrations of both melatonin and its main metabolite, 6-hydroxymelatonin, in plasma or serum. Therefore, a liquid chromatography-mass spectrometry (LC/MS) method including enzymatic hydrolysis and one-step liquid-liquid extraction was developed for this purpose. The mean extraction recovery was 59% for melatonin and 42% for 6-hydroxymelatonin. The mean precision of the method as calculated from the interassay coefficient of variation of quality control samples at high and low concentrations was 18% for 6-hydroxymelatonin and 15% for melatonin. The inaccuracy was always less than 2%. The limit of detection was approximately 2 ng/mL for 6-hydroxymelatonin (signal/noise ratio = 4) and less than 2 ng/mL for melatonin (signal/noise ratio at 2 ng/mL = 10). The method was applied to the analysis of plasma from a healthy volunteer who had received a single oral dose of 25 mg melatonin.
Chromatography, Liquid↗
Importance of the cytochrome P450 2D6 genotype for the drug metabolic interaction between chlorpromazine and haloperidol.
The authors studied the interactive effects of the coadministration of haloperidol and chlorpromazine on plasma concentrations of haloperidol and reduced haloperidol. The subjects were 43 Japanese male schizophrenic inpatients who were concomitantly treated with chlorpromazine before or after monotherapy with haloperidol. Coadministration of chlorpromazine produced significant increases in the plasma concentrations of haloperidol (P < 0.01) and reduced haloperidol (P < 0.001) by an average of 28.5% +/- 83.3% and 160.8% +/- 288.9%, respectively. However, there were marked interindividual variations in the interactive effects of chlorpromazine. The authors analyzed the importance of five CYP2D6 genotypes, *1/ *1, *1/ *10, *10/ *10, *1/*5, and *5/*10 on the percentage of change in plasma concentrations of haloperidol and reduced haloperidol. Patients with the CYP2D6*5 allele (n = 4) showed a significantly smaller increase in plasma concentrations of haloperidol (P < 0.05) and a slightly smaller increase in those of reduced haloperidol (P = 0.074) in response to the coadministration of chlorpromazine compared than those with the CYP2D6*1/*1 genotype (n = 8). Those with the CYP2D6*1/*1 genotype (n = 8) showed a trend toward greater increases in plasma concentrations of haloperidol than those with other genotypes (P = 0.087).
Adult↗
Elevated interleukin-1beta in pericardial fluid of patients with ischemic heart disease.
BACKGROUND: Inflammatory cytokines may play an important role in the pathogenesis of atherosclerosis and heart failure. We have previously demonstrated that long-term treatment with interleukin (IL)-1beta in the coronary artery and myocardium promotes coronary arteriosclerosis and impairs cardiac function, respectively. The cytokines in pericardial fluid may reflect the extent of coronary atherosclerosis and may also directly promote the atherosclerotic process. This study was designed to examine the significance of cytokine concentrations in pericardial fluid of patients with cardiovascular disease. METHODS: We measured concentrations of 10 major cytokines in the pericardial fluid of 56 consecutive patients obtained during open heart surgery, 27 with ischemic heart disease (IHD group), 21 with valvular heart disease (VHD group) and eight with congenital heart disease (CHD group). RESULTS: The pericardial concentrations of IL-1beta (pg/ml) were significantly higher in the IHD group (60 +/- 15) than in the VHD (29 +/- 5) or the CHD group (26 +/- 4) (P < 0.05 both). There was no significant difference in pericardial concentrations of other cytokines among the three groups. In the IHD group, the IL-1beta concentrations were significantly elevated in patients who had undergone emergency operations or in those with unstable angina. CONCLUSIONS: These results suggest that pericardial concentrations of IL-1beta may reflect the extent of ischemic heart disease and that elevated IL-1beta concentrations in pericardial fluid may also directly promote the process of coronary atherosclerosis.
Adult↗
Determination of pyrimidine dimers in Escherichia coli and Cryptosporidium parvum during UV light inactivation, photoreactivation, and dark repair.
UV inactivation, photoreactivation, and dark repair of Escherichia coli and Cryptosporidium parvum were investigated with the endonuclease sensitive site (ESS) assay, which can determine UV-induced pyrimidine dimers in the genomic DNA of microorganisms. In a 99.9% inactivation of E. coli, high correlation was observed between the dose of UV irradiation and the number of pyrimidine dimers induced in the DNA of E. coli. The colony-forming ability of E. coli also correlated highly with the number of pyrimidine dimers in the DNA, indicating that the ESS assay is comparable to the method conventionally used to measure colony-forming ability. When E. coli were exposed to fluorescent light after a 99.9% inactivation by UV irradiation, UV-induced pyrimidine dimers in the DNA were continuously repaired and the colony-forming ability recovered gradually. When kept in darkness after the UV inactivation, however, E. coli showed neither repair of pyrimidine dimers nor recovery of colony-forming ability. When C. parvum were exposed to fluorescent light after UV inactivation, UV-induced pyrimidine dimers in the DNA were continuously repaired, while no recovery of animal infectivity was observed. When kept in darkness after UV inactivation, C. parvum also showed no recovery of infectivity in spite of the repair of pyrimidine dimers. It was suggested, therefore, that the infectivity of C. parvum would not recover either by photoreactivation or by dark repair even after the repair of pyrimidine dimers in the genomic DNA.
Animals↗
[Improvement of method to estimate guidance by pharmacists and trial to obtain standard pharmaceutical management and guidance services program].
The level of understanding of taking medicine was examined at the start and the end of medicine-taking guidance, based on the estimation by pharmacists and inpatients. Six items for the estimation, such as "the way of taking medicines" were evaluated using a five-grade system. The significant improvement was observed in all items, suggesting that inpatients' understanding is improved by the guidance. A markedly positive correlation was found between the estimation by inpatients and that by pharmacists (p < 0.001). This confirms the appropriateness of estimation by pharmacists. Inpatients whose estimation was significantly different from that by pharmacists (difference of two grades or more) were examined to identify clear and potential problems with taking medicine. The problems were classified into such seven categories as "types of medicine". For each item with differences in estimation (two grades or more), problems were biased in some specific categories. On the basis of such a bias, a flow chart was prepared to clarify problems. In addition, a standard pharmaceutical management and guidance services program was drafted, in which measures in observation, treatment and education against problems by pharmacists were described according to the frequency of occurrence. Information about the program available on the Internet enables its use by other hospitals.
Aged↗
Influence of cyclic variation of right ventricular volume on left ventricular mechanical parameters measured with conductance catheter.
The conductance catheter is widely used for the continuous measurement of the left ventricular (LV) pressure-volume loops. Cyclical change of the right ventricular (RV) volume may alter the parallel conductance volume, thereby affecting the LV mechanical parameters. Using 8 open-chest adult mongrel dogs, multiple LV pressure-volume loops were obtained by 2 methods: first with a vena cava occlusion (VCO) method, which involved RV volume alteration, and second with a right-heart-bypass (RHB) preparation, which decompressed the right ventricle completely. The slope of the end-systolic pressure-volume relation (Ees), the end-systolic volume associated with the end-systolic pressure of 100 mmHg (V100,es), stiffness constant (beta), and the end-diastolic volume associated with the end-diastolic pressure of 9 mmHg (V9,ed) were calculated from each loop. There was minimal influence from RV volume alteration on systolic-phase indices [Ees (VCO method, 6.37 +/- 1.91 mmHg/ml; RHB preparation, 6.60 +/- 1.66mmHg/ml; p=0.356), and V100,es (VCO method, 18.4 +/- 9.3ml; RHB preparation, 17.8 +/- 9.0 ml; p=0.681)], but there was a significant influence on diastolic-phase indices [beta (VCO method, 0.0599 +/- 0.0152; RHB preparation, 0.0839 +/- 0.0150; p=0.007), and V9,ed (VCO method, 35.6 +/- 11.3 ml; RHB preparation, 31.9 +/- 12.3 ml; p=0.001)]. The increase in the RV volume in the diastolic phase increased the parallel conductance volume, causing overestimation of the LV diastolic volume measured by the conductance catheter.
Animals↗
Conformational change in a single molecular species, beta3, of beta-conglycinin in acidic ethanol solution.
Several physicochemical experiments were done to obtain further information on the conformational changes occurring in beta-conglycinin in acidic-ethanol solution, using a single molecular species of this protein, beta3. By far-UV circular dichroism (CD), a transition from beta-sheet to alpha-helical structure was observed upon addition of acidic-ethanol, and the alpha-helix content was found to reach 76% in 70% ethanol (pH 2). From analyses of near-UV CD and difference absorption spectra, it was found that the tertiary structure of the beta3 species was significantly altered at ethanol concentrations between 10 and 20%. The profiles of binding of 1-anilinonaphthalene-8-sulfonic acid to the beta3 species during acidic-ethanol denaturation were indicative of the existence of intermediate conformers in the molten globule-like denaturation state. By measuring Fourier transform infrared spectra and estimating the Stokes radius by dynamic light scattering, the beta3 molecules were found to aggregate with an increase in ethanol concentration.
Anilino Naphthalenesulfonates↗
Prevention of pulmonary embolism by a foot sole pump.
We carried out a prospective, randomised study of 62 patients to determine the efficacy of a foot sole pump (the A-V Impulse System) for the prevention of pulmonary embolism (PE) after hip surgery. PE was assessed by pulmonary perfusion scintigraphy before and after operation. We defined a PE as any new scintigraphic defect which was larger than a bronchopulmonary segment. The incidence of PE was 55% in the control group and 21% in the treatment group. The foot sole pump significantly reduced the incidence of PE (p = 0.008) and we encountered no side-effects from its use.
Adolescent↗
Effects of absorbed components of saiboku-to on the release of leukotrienes from polymorphonuclear leukocytes of patients with bronchial asthma.
Previous studies confirmed the efficacy of the Chinese herbal remedy Saiboku-to in patients with steroid-dependent asthma. We studied 8 phenolic compounds, isolated from the urine of patients receiving Saiboku-to, with respect to their effects on leukotriene (LT) release by polymorphonuclear leukocytes (PMN) obtained from 6 patients with atopic asthma and 8 healthy subjects. The compounds (0.01-10 micrograms/ml) were incubated with Ca2+ ionophore (A23187)-stimulated PMN, and concentrations of leukotriene B4 (LTB4) and leukotriene C4 (LTC4) in the supernatant were measured by EIA. Each compound suppressed the release of LTB4 and LTC4 by PMN obtained from healthy and asthmatic subjects. In particular, baicalein and magnolol were 5-10 times more potent than azelastine, an antiallergic drug, and significantly suppressed LTC4 release by PMN obtained from asthmatic patients, as compared with healthy subjects. Suppression of LTC4 release by these compounds may play an important role in the clinical efficacy of Saiboku-to.
Adult↗
Bilateral massive pleural effusions caused by uremic pleuritis.
A 61-year-old man was started on hemodialysis in June 1998. Just after the commencement of dialysis, a chest X-ray film revealed bilateral pleural effusions. The effusions were hemorrhagic and exudative, and did not respond to dialysis. He was transferred to our university hospital on October 8,1998. Repeated thoracentesis demonstrated hemorrhagic and exudative characteristics without any diagnostic evidence. Pleural biopsies showed fibrosis and lymphocyte infiltration. The effusions were massive and did not respond to treatments including hemodialysis, repeatedly performed pleurodesis and the administration of antituberculous drugs. He died of respiratory failure on December 30, 1998. The autopsy confirmed bilateral fibrinous pleuritis without any underlying infections or malignancy. We diagnosed this case as uremic pleuritis from this clinical course and the autopsy findings. The clinical entity of uremic pleuritis was recognized as a complication of patients with hemodialysis in 1969. Uremic pleuritis generally responds to continued hemodialysis and the prognosis is usually good. However, some case reports demonstrated that surgical decortication is only indicated in cases with a severe clinical course. The clinical course of the present case was progressive and fatal. Uremic pleuritis is a serious complication of hemodialysis, which may lead to death.
Fatal Outcome↗
Painless thyroiditis induced by the cessation of betamethasone.
We describe the first reported case of painless thyroiditis induced by an abrupt cessation of betamethasone. A 53-year-old woman experienced transient thyrotoxicosis after the abrupt cessation of celestamine, a mixture of betamethasone and chlorpheniramine. Since neither TSH receptor- nor thyroid stimulating-antibodies were negative, and thyroid scintigram did not show the thyroid gland, she was diagnosed as having painless thyroiditis. Fourteen months after the onset of thyrotoxicosis, serum TSH was detectable without hypothyroidism. We speculate that reduction in betamethasone may be one of the triggers of painless thyroiditis.
Anti-Allergic Agents↗
[A case of stage IV gastric cancer with multiple liver metastases and carcinomatous ascites responding to TS-1 for six months before progression].
We report the case of a 72-year-old male with Stage IV gastric cancer accompanied by multiple liver metastases and carcinomatous ascites which responded to chemotherapy using TS-1. Treatment of the patient with daily oral administration of 120 mg TS-1 for 4 weeks resulted in complete regression of the liver metastases and ascites, as well as a 35% reduction in the size of the primary lesion. After 2 cycles, the primary tumor size was reduced to 55% and serum CA19-9 and CA125 levels were decreased to the normal ranges. This regimen was effective without any adverse effects, and improved the patient's QOL, for 6 months before progression of liver lesions. The patient received chemotherapy at our outpatient clinic for 10 months after the first treatment, after which he died of peritonitis carcinomatosa. The current case suggests that TS-1 may have a potent therapeutic efficacy in advanced gastric cancer patients.
Aged↗
The effect of temperature on the efficacy of ozonation for inactivating Cryptosporidium parvum oocysts.
Examination of the effects of water temperature on the inactivation of Cryptosporidium parvum oocysts with ozone, ozonation experiments were conducted in a semi-batch mode with a wide temperature range of 3-30 degrees C. Inactivation was assessed in terms of mice infectivity and in vitro excystation. The temperature dependency of the CT products by a reduction in infectivity of 2 log10 could be described successfully by the Arrhenius equation, 1/CT = 1.086 x 10(18)e-12520/K where CT is the integrated ozone concentration over the contact time (mg/min/L) and K is the Kelvin temperature of water. As for the reduction in viability assessed by the excystation assay, protocol B, the obtained regression equation, 1/CT = 1.802 x 10(18)e-12640/K, was almost identical to that observed for the infectivity. Thus, the CT products required for a 2 log10 reduction in both infectivity and viability increased by an average factor of 4.2 for every 10 degrees C decrease in water temperature. Additionally, our findings suggested that the viability, as determined by protocol B, could substitute for animal infectivity in evaluating the effects of environmental factors on the efficacy of ozonation.
Animals↗
High affinity binding of heparin by necrotic tumour cells neutralises anticoagulant activity--implications for cancer related thromboembolism and heparin therapy.
We have observed a striking neutralisation of the anticoagulant activity of unfractionated heparin in the presence of a pancreatic carcinoma cell line (MIA PaCa-2) due to binding of around 9 microg of heparin per 10(7) cells (apparent Kd, 30 nM). The loss of anticoagulant activity was less marked in the presence of low molecular weight forms of heparin. Binding to the cell blocked acceleration of the thrombin:antithrombin interaction by heparin. Neutralisation of heparin activity was also shown to occur in the presence of a number of other tumour cell lines. FACS analysis demonstrated that live cells did not bind heparin and high affinity binding only occurred to dead MIA PaCa-2 cells. Heparin binding proteins accumulating in cell medium were identified as histone and ribosomal proteins that will become exposed during necrosis. The release of these proteins from cells within the necrotic core of a tumour or from cells killed during chemotherapy may abrogate the heparan sulphate/antithrombin system and possibly contribute to the idiopathic thromboembolism often associated with cancer (Trousseau's syndrome). The findings also suggest a reason for the reported advantage of LMWH over UFH in treating venous thromboembolism in cancer patients and in improving patient survival.
Adsorption↗
[Effects of intraperitoneal injection of low-dose CDDP on 3 patients with ascites owing to peritonitis carcinomatosa of gastric and colorectal carcinoma].
Three patients received intraperitoneal chemotherapy of low-dose CDDP for carcinomatous ascites due to gastric and colorectal carcinoma. Intraperitoneal injection of CDDP (30-50 mg) was given and the patients underwent systemic chemotherapy. As a result, the QOL of all patients was improved. Adverse effects of Grade 1 were observed in 1 case (nausea). This intraperitoneal chemotherapy seems to be safe and effective for ascites due to peritonitis carcinomatosa.
Antineoplastic Agents↗
Metabolic gene polymorphism frequencies in control populations.
Using the International Project on Genetic Susceptibility to Environmental Carcinogens (GSEC) database containing information on over 15,000 control (noncancer) subjects, the allele and genotype frequencies for many of the more commonly studied metabolic genes (CYP1A1, CYP2E1, CYP2D6, GSTM1, GSTT1, NAT2, GSTP, and EPHX) in the human population were determined. Major and significant differences in these frequencies were observed between Caucasians (n = 12,525), Asians (n = 2,136), and Africans and African Americans (n = 996), and some, but much less, heterogeneity was observed within Caucasian populations from different countries. No differences in allele frequencies were seen by age, sex, or type of controls (hospital patients versus population controls). No examples of linkage disequilibrium between the different loci were detected based on comparison of observed and expected frequencies for combinations of specific alleles.
Black People↗