Biomedical subjects

S L Huang

Publications and source records attributed to S L Huang.

At least 37 records · Page 2Linked to original sources

PubMed2001

Single plasma sampling to predict oral clearance of CYP3A probe midazolam.

AIM: To find out a single plasma sampling to estimate oral clearance of midazolam (MDZ) and CYP3A activity, and explore the pharmacokinetics of midazolam hydroxylation in Chinese subjects. METHODS: The pharmacokinetics of midazolam was assessed in ten healthy male individuals after an oral dose of 7.5 mg midazolam. RESULTS: A significant correlation (r = 0.7, P < 0.05, n = 10) was found between plasma MDZ clearance and the plasma ratio of 1'-hydroxymidazolam to midazolam, which was assessed at 1 h after MDZ intake in the volunteers. Pharmacokinetics parameters of midazolam were as follows: Cmax (191 +/- 17) nmol/L, tmax (1.01 +/- 0.14) h, t(1/2) (3.2 +/- 0.4) h, AUC(0-infinity) (681 +/- 43) nmol.h.L-1), Cl(oral) (0.54 +/- 0.04) L.h-1.kg-1, Ke (0.2415 +/- 0.0021) h-1, Kalpha (0.82 +/- 0.18) h-1. CONCLUSION: Single plasma sampling of 1 h after 7.5 mg oral MDZ intake can be used to predict the oral clearance of midazolam.

Administration, Oral↗

PubMed2001

Role of urbanization and air pollution in adolescent asthma: a mass screening in Taiwan.

BACKGROUND AND PURPOSE: The prevalence of asthma in school children in Taiwan is increasing. This study used mass screening among middle school children in Taiwan to determine the prevalence of asthma and related factors. METHODS: Data were collected from parents using a self-reported questionnaire and from children using the International Study of Asthma and Allergies in Childhood (ISAAC) video questionnaire. Six study teams conducted the survey nationwide in 1995-1996, with the assistance of middle school nurses and teachers. RESULTS: Among the 1,018,031 students at 795 middle schools who returned questionnaires, 8.5% had a history of asthma (ranging in prevalence from 4.2% to 13% in 25 areas). The prevalence of asthma was higher in boys than in girls (10.0% vs 7%) and was highest in more urbanized areas (11.2%), followed by moderately urbanized areas (7.4%) and less urbanized and rural areas (6.5%). Controlling for age, family smoking, family incense burning, and parental education level, multivariate logistic regression models indicated that children living in an area with heavy air pollution were more likely to have asthma than those in an area with no or light pollution (odds ratio, OR = 2.01 and 95% confidence interval, CI = 1.94-2.09 based on parental ranking of pollution level, or OR = 1.30 and 95% CI = 1.18-1.42 based on pollution level reported by the Environmental Protection Administration). CONCLUSIONS: Adolescent asthma in Taiwan is most prevalent in the most urbanized areas and decreases in prevalence in less urbanized areas. This study also found that higher parental education level and higher area air pollution were associated with higher adolescent asthma prevalence.

Adolescent↗

PubMed2001

[On cleanliness of hands in diminution of Ascaris lumbricoides infection in children].

OBJECTIVE: To study the relationship between cleanliness of children's hands and diminution of Ascaris lumbricoides infection. METHODS: Before the study all persons positive for ascaris eggs in the preliminary survey were treated with albendazole. Hand-washing habit before meal and after defecation was kept in children of experimental group, but not in the control group. Kato thick smear stool examination was done once every two months for one year to compare the new infection rates in children without ascaris infection in the two groups, and the reinfection rates in the cured negative cases were also compared between them in half a month after chemotherapy. RESULTS: All the new infection rates as well as reinfection rates of each reexamination in the experimental group were significantly lower than that of the control group (P < 0.001). Reexamination one year later showed that the ascaris infection rate of the experimental group was 35.2%, reducing by 48.5% as compared with 68.3% before the operation of the project; while ascaris infection rate of the control group was 73.7%, increasing by 78.0% as compared with 41.4% before the operation of the project. CONCLUSION: Washing hands with toilet soap to keep hands clean can significantly reduce ascaris infection rate.

Ascariasis↗

PubMed2000

Evaluation of stroke patients with the extended activities of daily living scale in Taiwan.

PURPOSE: This study examined the construct validity of the Nottingham Extended Activities of Daily Living scale (EADL) in stroke patients in Taiwan. METHODS: The EADL and the Barthel Index were administered via telephone interview. Minor revisions were made for the EADL to reflect cultural differences and the recommendations of two previous studies on the use of EADL. One hundred and fifty three stroke patients from the community participated in the study. RESULTS: Two items, 'make hot snack' and 'write letters', were deleted from the EADL because they appeared to be of little discriminative value. The results suggest that a changed hierarchical order was present among the domestic and leisure subscales. All of the subscales, then, fulfilled the Guttman scaling criteria (coefficient of reproducibility > 0.9, coefficient of scalability > 0.6). The scores of the revised EADL were significantly related to age and the Barthel Index scores (Spearman correlation coefficients = -0.41 and 0.69, respectively, p < 0.001). There was no significant difference between the overall scores of men and women (median = 10, 10, respectively, Mann-Whitney U test, p = 0.67). CONCLUSION: These data support the validity of the EADL with minor modifications in the evaluation of the functional performance in stroke patients in Taiwan and confirm it to be a useful outcome measure in stroke research.

Activities of Daily Living↗

PubMed2000

Cloning and characterization of a novel retinoid-inducible gene 1(RIG1) deriving from human gastric cancer cells.

Retinoids exert wide-spectrum anti-tumor activities, which are mediated via the induction of growth arrest, differentiation or apoptosis. To determine whether the effects of retinoids are mediated by specific gene activation or repression, SC-M1 CL23 gastric cancer cells, pretreated with either vehicle alone or all-trans retinoic acid (10 microM) for 1 day, were analyzed using the technique of differential display. A novel retinoid-inducible gene 1 (RIG1) was isolated. The full-length RIG1 cDNA contained 768 base pairs and encoded a protein of 164 amino acids with a molecular weight of 18 kDa. The RIG1 gene was ubiquitously expressed in normal tissue, and its expression was positively associated with cellular density. Nucleotide sequence analysis demonstrated that the RIG1 gene was similar to a recently-isolated TIG3 gene, and displayed 54% nucleotide sequence homology with a type II tumor suppressor gene H-REV-107-1. RIG1 cDNA, however, contained an extra 32 base pairs located at its 5' end and revealed three base pair differences for the remaining sequences leading to two amino acids substitution between the two encoded proteins. All-trans retinoic acid increased the level of RIG1 mRNA in a time- and concentration-dependent manner in SC-M1 CL23 gastric cancer cells. This was not observed for the H-REV-107-1 gene. The RIG1 regulation was related to cellular retinoid sensitivity. Both retinoic acid receptor alpha- and retinoic acid receptor gamma-selective agonists increased RIG1 mRNA level, and the retinoid x receptor-selective agonist potentiated this regulation. In conclusion, the cDNA of a novel retinoid-inducible gene RIG1 has been cloned. This gene is regulated by retinoic acid through the heterodimer of retinoic acid receptor and retinoid x receptor.

Amino Acid Sequence↗

PubMed2000

In vitro and in vivo suppression of growth of rat liver epithelial tumor cells by antisense oligonucleotide against protein kinase C-alpha.

BACKGROUND/AIMS: It has been hypothesized that liver stem cells may be activated and proliferate upon liver injury and may participate in the development of liver cancer. GP7TB, a rat liver epithelial tumor cell line, possesses characteristics of liver stem-like cells and can develop into a tumor in syngeneic Fischer 344 rat. We found that protein kinase C-alpha (PKC-alpha) is overexpressed in GP7TB cells. The importance of PKC-alpha for this liver tumor cell was elucidated. METHODS: Antisense oligonucleotide (ODN) was applied to suppress the production of PKC-alpha in GP7TB cells in vitro and in vivo. Cell viability was measured by acid phosphatase assay. The cellular levels of PKC-alpha and Bcl-2 were monitored by Western-blot analysis. Activation of nuclear factor NF-kappaB was analyzed by electrophoretic mobility shift assay. Cell cycle phase distribution was monitored by FACScan. Cell apoptosis was detected by TUNEL assay and histochemical staining of tumor tissue sections. The in vivo experiment was conducted by implanting tumor mass of GP7TB in the liver of F-344 rat and continuous delivery of the ODN by a mini-osmotic pump. RESULTS: Antisense ODN effectively suppressed the level of PKC-alpha that resulted in the decrease of Bcl-2 and nuclear NF-kappaB. The cumulative viable cells also decreased dramatically for the antisense-treated group. FACScan showed that the cells were arrested at early S-phase. These cells in turn went into apoptosis without completing a cell cycle. It was found that growth of the tumor was suppressed efficiently by antisense ODN. Cell apoptosis was found in the orthotopic tumor. The normal liver cells were not affected. CONCLUSIONS: A lethal effect of depressing the level of PKC-alpha in GP7TB cells and success in suppressing orthotopic tumor growth in vivo suggests that PKC-alpha antisense ODN would be a promising therapeutic agent for some liver cancers.

Acid Phosphatase↗

PubMed2000

Phenotypic polymorphism and gender-related differences of CYP1A2 activity in a Chinese population.

AIMS: To investigate the distribution characteristics of CYP1A2 in a Chinese population, and to examine gender-related differences in CYP1A2 activity. METHODS: Two hundred and twenty-nine healthy subjects, 120 men and 109 women, were enrolled in this study. CYP1A2 activity was measured by plasma paraxanthine/caffeine (1,7X/1,3,7X) ratio 6 h after administration of 300 mg caffeine. The concentrations of paraxanthine and caffeine in plasma were detected by h.p.l.c. RESULTS: A 16-fold variation of CYP1A2 activity (range 0. 09 to 1.46) was shown in this study. The coefficient of variation (CV %) of CYP1A2 activity was 62.9%. Non-normal distribution of CYP1A2 activity was indicated by the Shapiro-Wilk test (P<0.001). Probit plots of CYP1A2 activity revealed a bimodal distribution with breakpoint of 1,7X/1,3,7X ratio of 0.12. The percentage of poor metabolizers (PMs) was 5.24% (95% CI: 2.35% approximately 8.13%) in this Chinese population. Residual analysis of the data also supported bimodality (P<0.01). The CYP1A2 activity of men was higher than that of women (median: 0.33 vs 0.23, P<0.001). A probit plot of CYP1A2 activity in men was shifted to the left compared with that in women. Based on phenotype, the gender-related difference was observed in extensive metabolizers (EMs) (P<0.001), but not in PMs (P >0.1). In addition, there was no sex-related difference in the incidence of PMs (P >0.1). CONCLUSIONS: There is a phenotypic polymorphism in CYP1A2 activity in this Chinese population, and CYP1A2 activity is higher in men than that in women.

Adolescent↗

PubMed2000

Tumor necrosis factor gene polymorphism and septic shock in surgical infection.

OBJECTIVES: To evaluate the relationship of the genotype distribution of the tumor necrosis factor (TNF)-alpha polymorphism with regard to the plasma TNF-alpha concentration and the development of septic shock as well as mortality of infected patients in a surgical intensive care unit (SICU). DESIGN: A total of 112 postoperative critically ill infected patients were prospectively enrolled. SETTING: SICU of a tertiary university-affiliated medical center. PATIENTS: Patients who were consecutively admitted to the SICU because of surgical infection with sepsis. INTERVENTION: Blood sampling. MEASUREMENTS AND MAIN RESULTS: Blood sample was obtained 24 hrs after intensive care unit (ICU) admission or within 2 hrs after the onset of septic shock to determine the plasma TNF-alpha level and to analyze the genotype of the biallelic polymorphism of the TNF-alpha. RESULTS: The allele frequency of the TNF2 in our infected ICU patients was 12%. Forty-two (37.5%) patients admitted fulfilled the criteria of septic shock during their ICU stay. Patients carrying the TNF2 allele were not more likely to develop septic shock, nor did they have a higher mortality rate. In the patients with septic shock, those carrying the TNF2 allele had a significantly higher mortality rate than those with the homozygous TNF1 genotype (92% vs. 62%, p < .05). In those who developed septic shock, the TNF2 allele was significantly associated with higher TNF levels. CONCLUSION: In patients admitted to SICU with surgical infection, the frequency of TNF2 allele was higher than in the general population. SICU patients with TNF2 allele did not show a higher incidence of developing septic shock, nor was there a higher baseline TNF-alpha level after infection. However, once septic shock had developed, the mortality rate was higher in those patients carrying the TNF2 allele.

APACHE↗

PubMed2000

5-hydroxylation of omeprazole by human liver microsomal fractions from Chinese populations related to CYP2C19 gene dose and individual ethnicity.

It has been previously reported that omeprazole (OP) oxidation is mediated by CYP2C19 and CYP3A4 in human livers. In this study, we assessed their relative contributions with human liver microsomal fractions from Chinese populations that were genotyped by CYP2C19 and recruited from two ethnic groups, Han and Zhuang. The kinetics of 5-hydroxyomeprazole (5-OH-OP) formation was best described by the two-enzyme and single-enzyme Michaelis-Menten equations for liver microsomes from CYP2C19 extensive (EMs) and poor metabolizers, respectively. At a low substrate concentration that may be encountered in vivo, the monoclonal antibody to CYP2C8/9/19 strongly inhibited 5-OH-OP formation in EM microsomes, whereas troleandomycin (TAO) eliminated most of the formation at a high substrate concentration. In poor metabolizer microsomes, either TAO or anti-CYP3A4 could alone abolish 5-OH-OP formation. Furthermore, there were differences between homozygous and heterozygous EMs in the percentage of inhibition by TAO and the antibodies. At the low substrate concentration, OP 5-hydroxyaltion was correlated well with S-mephenytoin 4'-hydroxylation and CYP2C19 contents in liver microsomes of 34 Chinese individuals. Moreover, in these individuals, obviously genetic and somewhat ethnic differences in OP 5-hydroxylation were observed between different CYP2C19 genotypes (wt/wt > wt/m1 > m1/m1) and between Han and Zhuang (Han > Zhuang), respectively. The results indicate that CYP2C19 is a high-affinity enzyme for OP 5-hydroxylation by liver microsomes from Chinese individuals and that its contribution is CYP2C19 gene dependent and ethnically related. Similar studies indicate that OP sulfoxidation is mediated mainly by CYP3A4 and independent of CYP2C19 genotype status.

Adult↗

PubMed2000

Effect of PKC-zeta mediating Ang II-stimulated activation of CCDPK on rat cardiac fibroblast proliferation.

AIM: To investigate whether the effect of angiotensin (Ang) II or epidermal growth factor (EGF) on cardiac fibroblast proliferation involved in activation of extracellular signal-regulated kinase (ERK) 1/2 or Ca(2+)-calmodulin dependent protein kinase(CCDPK) mediated by protein kinase C (PKC)-zeta. METHODS: Relative activity of CCDPK was measured by Western blotting. DNA synthesis was assayed by [3H]thymidine incorporation. RESULTS: PDBU caused no decrease in Ang II- and 10% FCS-stimulated CCDPK activity and DNA synthesis. In contrary, 65% or 75% EGF- or tetradecanoylphorbol acetate (TDPA, formally called PMA)--stimulated CCDPK activity and 38% or 42% [3H]thymidine incorporation treated by PDBU were inhibited, respectively. Meanwhile 70% and 72% CCDPK activities induced by Ang II and EGF were inhibited by PD 98059, respectively. CONCLUSION: PKC-zeta mediated Ang II-induced activation of CCDPK and cardiac fibroblast proliferation.

Angiotensin II↗

PubMed2000

Antisense Ca(2+)-calmodulin dependent protein kinase oligonucleotide inhibits bFGF-induced proliferation of rat vascular smooth muscle cells.

AIM: To investigate the role of Ca(2+)-calmodulin dependent protein kinase (CCDPK) on basic fibroblast growth factor (bFGF)-induced vascular smooth muscle cell (VSMC) proliferation and the inhibitory effect of antisense CCDPK oligonucleotides (ODN). METHODS: Before being exposed to bFGF, cultured rat VSMC CCDPK activity was inhibited by pretreatment with either a phosphorothioate-protected 17-mer antisense CCDPK ODN-directed against the initiation of translation sites of the p42 and p44 CCDPK isoform or with CCDPK kinase inhibitor PD98059. All ODN were introduced into cells by liposomal transfection. DNA synthesis was measured by [3H]thymidine incorporation. P44- and p42-CCDPK protein expression and phosphorylation were measured by Western blot. RESULTS: PD98059 inhibited bFGF-induced phosphorylation of CCDPK and DNA synthesis. Antisense CCDPK ODN 0.2-0.8 mumol.L-1 reduced both p44- and p42-CCDPK expression and phosphorylation of CCDPK in a concentration-dependent manner and DNA synthesis induced by bFGF. Lipofectin alone or sense and random CCDPK ODN did not affect p44- and p42-CCDPK protein expression or bFGF-induced phosphorylation of CCDPK or DNA synthesis. CONCLUSION: bFGF-stimulated rat VSMC proliferation is mediated by CCDPK. The antisense CCDPK ODN can inhibit bFGF-induced VSMC proliferation through down-regulating p44- and p42-CCDPK level.

Animals↗

PubMed2000

Prevention of intima hyperplasia by mitogen-activated protein kinase antisense oligodeoxynucleotide.

AIM: To investigate the preventive effect of Ca(2+)-calmodulin dependent kinase (CCDPK) (formerly: mitogen-activated protein kinase or MAPK) antisense phosphorothioate oligodeoxynucleotide (ODN) on vascular smooth muscle cell (VSMC) proliferation in vitro and on intima hyperplasia after injury in vivo. METHODS: Liposomal transfection was used to introduce phosphorothioate-protected 17-mer antisense CCDPK ODN directed against the initiation of translation sites of the p42 and p44 CCDPK isoforms into cultured rat VSMC to deplete CCDPK and DNA synthesis induced by endothelin-1 (ET) or platelet derived growth factor (PDGF). A 17-mer sense and a random sequence CCDPK ODN were used as controls. CCDPK protein p44 and p42 levels were measured by Western blot. DNA synthesis was measured by [3H]thymidine incorporation. In in vivo study, rat balloon angioplasty was performed by a 2F Fogarty catheter. The antisense CCDPK ODN 200 micrograms was administered to the adventitial surface of the injured carotid artery by pluronic gel 30% (w/v) solution. Two weeks after vascular injury, carotid arteries were removed and cross sections were made and stained with hematoxylin/eosin for patho-histological examination. Fluorecein isothiocynate (FITC)-labeled and phosphorothioate-protected ODN was used to detect the uptake of ODN in vitro and in vivo. RESULTS: CCDPK antisense ODN (0.4 mumol.L-1) reduced p42/p44 protein expression and inhibited VSMC [3H]thymidine incorporation stimulated by ET and PDGF. Antisense CCDPK ODN treatment at 2 wk after injury resulted in a significant inhibition of intima hyperplasia, compared with untreated vessels. CONCLUSION: The p42/p44-CCDPK antisense ODN inhibits in vitro stimulated rat VSMC proliferation and in vivo injured arterial intima hyperplasia.

Animals↗

PubMed2000

Platelet-derived growth factor stimulated vascular smooth muscle cell proliferation and its molecular mechanism.

AIM: To study the molecular mechanism of platelet-derived growth factor (PDGF)-BB-stimulated vascular smooth muscle cell (VSMC) proliferation. METHODS: DNA synthesis was measured by [3H]thymidine incorporation. Phosphorylation of the 42- and 44-kDa Ca(2+)-calmodulin dependent protein kinase (CCDPK) was measured by Western blotting method. The expression of c-myc specific mRNA was detected by in situ hybridization. RESULTS: PDGF-BB (2 micrograms.L-1) induced DNA synthesis and activated CCDPK in a concentration-dependent manner and a induced a marked c-myc mRNA expression. Egtazic acid (EGTA, 5 mmol.L-1), genistein (400 mumol.L-1) or PD 98059 (50 mumol.L-1) reduced PDGF-BB (2 micrograms.L-1)-induced CCDPK activities and inhibited VSMC [3H]thymidine incorporation (P < 0.05). PD 98059 (50 mumol.L-1) also inhibited PDGF-BB (2 micrograms.L-1)-induced c-myc mRNA expression. CONCLUSION: PDGF stimulated VSMC proliferation by activation of p44/p42 CCDPK, which is mediated by Ca2+ and protein tyrosine kinase (PTK), and up-regulation of c-myc mRNA expression.

Animals↗

PubMed2000

Determination of procaterol in human plasma by gas chromatography/electron impact ionization mass spectrometry.

AIM: To improve a gas chromatography/electron impact ionization mass spectrometry (GC/MS) method for determining the concentration of procaterol in human plasma. METHODS: GC/MS was developed with capillary column. Samples were extracted by liquid phase before derivated. Imipramine was used as an internal standard. The injector and GC/MS interface temperatures were set at 280 degrees C and 250 degrees C, respectively. The carrier gas (helium) was 0.8 mL.min-1, and injections were made in the pulse-splitless mode. The MS source and MS Quad temperature were 230 degrees C and 150 degrees C, respectively. RESULTS: The detection limit of plasma procaterol was 5 ng.L-1. The assay was linear over the range of 10-10,000 ng.L-1 with correlation coefficient of 0.9987. The coefficients of variation were less than 10% for procaterol detection at high, medium and low concentration levels (n = 5). The average recovery of the assay was 99.1% +/- 1.3%. CONCLUSION: This assay was sensitive, precise, and accurate for evaluating the clinical pharmacokinetics of procaterol.

Bronchodilator Agents↗

PubMed2000

In vitro proguanil activation to cycloguanil is mediated by CYP2C19 and CYP3A4 in adult Chinese liver microsomes.

AIM: To identify the cytochrome P450 isoforms involved in proguanil (PG) activation to cycloguanil (CG) in Chinese liver microsomes. METHODS: The kinetics of the CG formation from PG was determined in the liver microsomes of 6 Chinese subjects. Selective chemical inhibitors to various cytochrome P450 isoforms were employed to conduct inhibition experiments. The relationship between the CG formation and S-mephenytoin 4'-hydroxylation was analyzed. RESULTS: The kinetic behaviors of CG formation were described well by a single-enzyme Michaelis-Menten equation in five livers. The apparent Km and Vmax were (82 +/- 47) mumol.L-1 and (8 +/- 6) pmol.min-1.mg-1 protein, respectively. However, the remaining one displayed a two-enzyme kinetic behavior. Inhibition experiments showed that troleandomycin (100 mumol.L-1) and diethyldithiocarbamate (100 mumol.L-1), as potent CYP3A4 and CYP2E1 inhibitors, respectively, reduced the formation rate of CG by 81.1% and 47.23%, while quinidine (10 mumol.L-1), furafylline (20 mumol.L-1), and sulfaphenazole (10 mumol.L-1), which were inhibitors towards CYP2D6, 1A2 and 2C9/10, respectively, did not display significant inhibition. At a low PG concentration of 5 mumol.L-1, the CG formation correlated well with S-mephenytoin 4'-hydroxylation (r = 0.805, P < 0.05). Nevertheless, when a high substrate concentration (500 mumol.L-1) was used, the correlation coefficient decreased (r = 0.581, P < 0.05). CONCLUSION: The present study indicates that CYP3A4 and CYP2C19 are involved in PG activation to CG in adult Chinese liver microsomes. CYP2C19 played an important role in the clearance of PG at a substrate concentration close to in vivo therapeutic concentrations, while CYP3A4 gradually made a dominant contribution with the increase of PG concentration.

Adult↗

PubMed2000

Probing CYP2C19 and CYP3A4 activities in Chinese liver microsomes by quantification of 5-hydroxyomeprazole and omeprazole sulphone.

AIM: To develop an analytical method for simultaneous quantification of 5-hydroxyomeprazole (5-OH-OP) and omeprazole sulfone (OPS), and explore whether omeprazole (OP) is an appropriate phenotypic probe for CYP2C19 and CYP3A4 in Chinese liver microsomes. METHODS: OP metabolism in vitro was conducted in Chinese liver microsomes, and the major metabolites 5-OH-OP and OPS were determined using high pressure liquid chromatography (HPLC). Monoclonal antibodies anti-CYP2C8/9/19 and anti-CYP3A4 were employed to conduct inhibition experiments. The protein contents of CYP2C19 and CYP3A4 were quantified using Western blot analysis and densitometric scanning. RESULTS: 5-OH-OP and OPS gave a baseline resolution in the HPLC analysis. The detection limits for both compounds were 0.01 nmol and the recovery (98%-102%) had good precision with relative standard deviation of < 9.5%. Both anti-CYP2C8/9/19 and anti-CYP3A4 had a significant inhibitory effect (P < 0.05) on the 5-OH-OP formation in a substrate concentration-dependent manner, and anti-CYP3A4 alone could almost abolish the formation of OPS (> 87%). At a substrate concentration of 2 mumol/L OP, good correlations were found between OP 5-hydroxylation and S-mephenytoin 4'-hydroxylation activities (r = 0.72, P < 0.01), OP 5-hydroxylation activities and CYP2C19 contents (r = 0.82, P < 0.01), and OP sulfoxidation activities and CYP3A4 contents (r = 0.78, P < 0.01) in Chinese liver microsomes. CONCLUSION: OP metabolism is mediated mainly by CYP2C19 and CYP3A4, and OP can be used to probe CYP2C19 and CYP3A4 activities in Chinese liver microsomes at appropriate substrate concentrations with the HPLC method presently developed.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2000

Comparison of appendectomy medical expense and clinical outcome between fee for service and prospective payment system.

Since the introduction of national health insurance on March 1st 1995 in Taiwan, another 9 items (including appendectomy) were introduced into the Taiwan/prospective payment system (T/PPS). The modified T/PPS was based on those complicated appendectomy cases with secondary diagnosis or second operation where a total fee over 37,500 New Taiwan (NT) dollars was paid by National Health Insurance Bureau (NHIB) according to the real cost. The T/PPS was implemented in October 1997 due to the continuously increasing financial burden of medical expenses on the NHIB. The purpose of this study is (1) to compare the length of stay (LOS) and total medical expense of appendectomy of fee for service (FFS) and T/PPS and (2) to compare the clinical outcome of wound healing after discharge of the two systems by telephone interview. Our study investigated 100 consecutive appendectomy cases under FFS payment system and 99 consecutive appendectomy cases under T/PPS. We retrospectively analyzed LOS, operation time, and hospital cost of different items through chart review and computer data. Our results revealed that the LOS and operation time of T/PPS were significantly shorter than those of FFS (both p < 0.01). The total hospital cost, fee for room service, treatment, pharmacy, examination and anesthesia in T/PPS were also significantly less than those in FFS (all p < 0.01, except for anesthesia p < 0.05). There existed positive correlation between total hospital cost and LOS, operation time, fee for room service, treatment, pharmacy, examination and anesthesia both for T/PPS and FFS. To evaluate the clinical outcome of appendectomy between T/PPS and FFS, we interviewed 73 T/PPS cases and 73 FFS cases by telephone and chart review. Our results revealed that there were no significant differences in frequencies of having painful incision, clear incision wound on the day of discharge, and removal of stitches at hospital (p all > 0.05). We concluded that compared to FFS, T/PPS can decrease LOS and total hospital cost of appendectomy, and T/PPS's clinical outcome of appendectomy in T/PPS showed no significant difference from that in FFS.

Adult↗

PubMed1999

Effect of the gene dosage of CgammaP2C19 on diazepam metabolism in Chinese subjects.

OBJECTIVE: To determine whether the gene dosage of CYP2C19 affects the metabolism of diazepam and desmethyldiazepam in healthy Chinese subjects. SUBJECTS AND METHODS: Eighteen unrelated adult men were recruited for the study from a total of 101 healthy Chinese volunteers who had been screened for CYP2C19 phenotype and genotype. All subjects received a single oral dose (5 mg) of diazepam, and the pharmacokinetics of diazepam and desmethyldiazepam were compared in six ml homozygotes (ml/ml), six ml heterozygotes (wt/ml), and six wild-type homozygotes (wt/wt). RESULTS: The plasma elimination half-life values of diazepam (84.0 +/- 13.7 hours) and desmethyldiazepam (176.0 +/- 28.9 hours) in subjects of ml/ml were significantly longer than those (62.9 +/- 9.8 hours for diazepam; 132.1 +/- 24.9 hours for desmethyldiazepam; both P < .01) in subjects of wt/ml or those (20.0 +/- 10.8 hours for diazepam; 99.2.+/- 21.7 hours for desmethyldiazepam; both P < .01) in subjects of wt/wt. A significant difference in the corresponding half-life values existed between the wt/ml and wt/wt subjects (P < .01). As expected, the slowest mean clearance of diazepam was observed in the ml/ml subjects (2.8 +/- 0.9 mL/min) and the fastest in the wt/wt subjects (19.5 +/- 9.8 mL/min), with the wt/ml heterozygotes having an intermediate value (7.2 +/- 2.6 mL/min). CONCLUSION: The presence of a single-nucleotide polymorphism (G681A) of the CYP2C19 gene cosegregates with the impaired metabolism of diazepam and desmethyldiazepam among Chinese subjects in a gene-dosage effect manner.

Adult↗