The cytochrome P450 (CYP) 3A subfamily is estimated to participate in the biotransformation of 50% of the currently prescribed drugs. Four members of the CYP3A subfamily have been identified in humans: CYP3A4, CYP3A5, CYP3A7, and CYP3A43. Initial data suggested that CYP3A5 accounts for only a small proportion of the total hepatic CYP3A in about 20% of samples, but it was later revealed that CYP3A5 represents more than 50% of the total CYP3A amount in some individuals. Several genetic variants have been described for the CYP3A5 gene, of which the CYP3A5*3 allele (gA6986G), the most common form and leading to the loss of CYP3A5 activity, has been extensively investigated in the aspect of pharmacokinetics and disease risk. This review summarized the molecular characteristics of the CYP3A5 gene, and discusses the association of the CYP3A5*3 polymorphism with disease risks such as cancer and hypertension, along with its role in the pharmacokinetics of CYP3A substrates.
Alleles ; Biotransformation ; Cytochrome P-450 CYP3A ; Cytochrome P-450 Enzyme System ; Humans ; Hypertension ; Pharmacogenetics ; Pharmacokinetics

No abstract available.
Arthrogryposis* ; Humans ; Siblings*

The authors reviewed 3145 pediatric patients who visited the emergecy room in this hospital during 3yrs period from Jan. 1989 to Dec. 1991. 1) Among the patients visiting the emergency room, the patients under 15 years of age were 26.4% (3145) of total emergency patients (11930). 2) yearly distribution of patients were decreased 17% between 1989 and 1991. 3) Monthly distribution of visits showed higher incidence in June and July. The male to female ratio was 1.5:1. 4) Weekly distribution of visits showed higher incidence on Sunday and Saturday, relatively. 5) Most popular time of visiting the emergency room was between 8:00 PM to 12:00 PM during which time 29.5% of all pediatric patient were seen. 6) Distribution of age showed peak incidence between 6 and 12 years of age (30.9%). 7) 65.18% of total emergency room isits were pediatric patients. 8) Distribution of cases was as follows: Respiratory disease 37%, accident, GI disease in turn listed respectively in ecreasing order of freqency. 9) The admission rate through emergency was 8.5% of total pediatric emergency patients. 10) 82.3% of total emergency visits had medical insurance coverage, 7% had no insurance and 10.7% were on medical aid program.
Emergencies* ; Emergency Service, Hospital* ; Female ; Humans ; Incidence ; Insurance ; Insurance Coverage ; Male

PURPOSE: This study aimed to investigate the clinical significance of serum alanine aminotransferase (ALT) levels in children with nonalcoholic fatty liver disease (NAFLD) and the effect of lifestyle intervention on NAFLD. METHODS: The clinical data of 86 children diagnosed with NAFLD were reviewed retrospectively. Forty-six patients belonged to the elevated ALT group and 40 to the normal ALT group. The clinical parameters of patients with NAFLD were also compared based on the status of ALT levels after lifestyle intervention. RESULTS: Patients with elevated ALT had significantly higher body mass index (BMI) scores than those with normal ALT (P<0.05). Of all the patients with elevated ALT, 89% exhibited moderate or severe degree of fatty change in the liver on ultrasonographic examination, whereas most patients with normal ALT exhibited mild or moderate degree changes. Liver biopsy was performed in 15 children with elevated ALT and all showed mild histological changes. Of all patients with elevated ALT, 49% achieved normal ALT levels after lifestyle intervention. Those with more severe histological changes tended to have continuously increasing ALT levels. There was no correlation between the normalization of posttreatment ALT level and BMI, as well as ultrasonographic findings at diagnosis. CONCLUSION: ALT elevation in NAFLD is highly associated with higher BMI scores and more severe degree of fatty changes on ultrasonographic examination. Lifestyle intervention can significantly improve ALT in children with NAFLD. The degree of histologic changes appears to be a predictor of the treatment response to NAFLD.
Alanine Transaminase* ; Alanine* ; Biopsy ; Body Mass Index ; Child* ; Diagnosis ; Humans ; Life Style* ; Liver ; Non-alcoholic Fatty Liver Disease* ; Retrospective Studies

BACKGROUND: Sulfonylurea drugs have been used for many decades as one of the main families of drugs for the treatment of type 2 diabetes mellitus. Even though there are many opportunities to medicate sulfonylurea drugs concomitantly with many other drugs, and furthermore there have been several case reports on drug interactions with sulfonylurea drugs, there has been no clear demonstration revealing the mechanisms that cause these interactions. We therefore evaluated inhibitory potential of sulfonylurea drugs, including glibenclamide, glipizide and gliclazide, on the cytochrome P450 (CYP)-catalyzing enzymes using human liver microsomes. METHODS: The inhibitory effects of glibenclamide, glipizide and gliclazide, on the CYP-catalyzing reaction, were evaluated for CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 using human liver microsomes, and probe drugs for each. RESULTS: Glibenclamide showed relative potent inhibitory effects on the CYP2C9- and CYP3A4-catallyzed reaction (IC50; 11.3 ( microM and 59.0 ( microM). The other CYP isoforms tested showed only weak inhibitory effects by due to glibenclamide (IC50 > 112 ( microM). Glipizide showed potent inhibitory effect on CYP3A4-catalyzed reaction only (IC50; 11.2 ( microM), and weak, or no, inhibitory effects on each on the other CYP isoforms tested (IC50 > 276 ( microM). CONCLUSION: The sulfonylurea drugs showed inhibitory potential on the CYP-catalyzing reaction in human liver microsomes. The results obtained in the present study provide insights into the potential of the drug interaction to ward drugs co-administered with sulfonylureas. It will be necessary to take into consideration the control of blood glucose, as well as therapeutic drug monitoring, to reduced toxicities when sulfonylurea drugs are co-administered with drugs of a narrow therapeutic range, or with severe dose-dependent toxicities.
Blood Glucose ; Cytochrome P-450 CYP1A2 ; Cytochrome P-450 CYP2D6 ; Cytochrome P-450 Enzyme System ; Cytochromes* ; Diabetes Mellitus, Type 2 ; Drug Interactions ; Drug Monitoring ; Gliclazide ; Glipizide ; Glyburide ; Humans* ; Liver* ; Microsomes, Liver* ; Protein Isoforms

PURPOSE: To assess the reproducibility of circumpapillary retinal nerve fiber layer (cpRNFL) thickness measurement (measurement agreement) and its color-coded classification (classification agreement) by Cirrus spectral domain optical coherence tomography (OCT) in pseudophakic eyes. METHODS: Two-hundred five participants having glaucoma or glaucoma suspected eyes underwent two repeated Cirrus OCT scans to measure cpRNFL thickness (optic disc cube 200 x 200). After classifying participants into three different groups according to their lens status (clear media, cataract, and pseudophakic), values of intra-class coefficient (ICC), coefficient of variance, and test-retest variability were compared between groups for average retinal nerve fiber layer (RNFL) thicknesses and that corresponding to four quadrant maps. Linear weighted kappa coefficients were calculated as indicators of agreement of color code classification in each group. RESULTS: ICC values were all excellent (generally defined as 0.75 to 1.00) for the average and quadrant RNFL thicknesses in all three groups. ICC values of the clear media group tended to be higher than those in the cataract and pseudophakic groups for all quadrants and average thickness. Especially in the superior and nasal quadrants, the ICC value of the cataract group was significantly lower than that of the clear media and pseudophakic groups. For average RNFL thickness, classification agreement (kappa) in three groups did not show a statistically significant difference. For quadrant maps, classification agreement (kappa) in the clear media group was higher than those in the other two groups. CONCLUSIONS: Agreement of cpRNFL measurement and its color code classification between two repeated Cirrus OCT scans in pseudophakic eyes was as good as that in eyes with clear crystalline lens. More studies are required to ascertain the effect of lens status on the reproducibility of Cirrus OCT according to different stages of glaucoma patients.
Aged ; Cataract/complications ; Cataract Extraction ; Female ; Glaucoma/complications/*pathology ; Humans ; Lens, Crystalline/cytology/pathology ; Male ; Middle Aged ; Nerve Fibers/pathology ; Optic Disk/pathology ; Pseudophakia/complications ; Reproducibility of Results ; Retinal Ganglion Cells/*pathology ; Tomography, Optical Coherence/*methods/*standards

No abstract available.
Erythrocyte Membrane* ; Erythrocytes* ; Hydroxyl Radical* ; Lipid Peroxidation* ; Macrophages, Alveolar* ; Mineral Fibers*

Ultrasonographic Doppler techniques have improved greatly over the years, allowing more sophisticated evaluation of breast tumor vascularity. Superb microvascular imaging (SMI) and contrast-enhanced ultrasound (CEUS) with second-generation contrast agents are two representative up-to-date techniques. SMI is a sensitive Doppler technique that adopts an intelligent filter system to separate low-flow signals from artifacts. With the development of second-generation contrast agents, CEUS has also emerged as a useful Doppler technique for evaluating tumor microcirculation. Both techniques can improve the diagnostic performance of gray-scale ultrasonography by providing vascular information useful not only for the morphologic assessment of microvessels, but also for the quantitative analysis of perfusion. In this review, we explain the imaging principles and previous research underlying these two vascular techniques, and describe our clinical experiences.
Artifacts ; Breast Neoplasms* ; Breast* ; Contrast Media ; Microcirculation ; Microvessels ; Perfusion ; Ultrasonography* ; Ultrasonography, Doppler

Microvascular ultrasound (US) techniques are advanced Doppler techniques that provide high sensitivity and spatial resolution for detailed visualization of low-flow vessels. Microvascular US imaging can be applied to breast lesion evaluation with or without US contrast agents. Microvascular US imaging without a contrast agent uses a sophisticated wall filtering system to selectively obtain low-flow Doppler signals from overlapped artifacts. Microvascular US imaging with secondgeneration contrast agents amplifies flow signals and makes them last longer, which facilitates hemodynamic evaluation of breast lesions. In this review article, we will introduce various microvascular US techniques, explain their clinical applications in breast cancer diagnosis and radiologic-histopathologic correlation, and provide a summary of a recent radiogenomic study using microvascular US.

Microvascular ultrasound (US) techniques are advanced Doppler techniques that provide high sensitivity and spatial resolution for detailed visualization of low-flow vessels. Microvascular US imaging can be applied to breast lesion evaluation with or without US contrast agents. Microvascular US imaging without a contrast agent uses a sophisticated wall filtering system to selectively obtain low-flow Doppler signals from overlapped artifacts. Microvascular US imaging with secondgeneration contrast agents amplifies flow signals and makes them last longer, which facilitates hemodynamic evaluation of breast lesions. In this review article, we will introduce various microvascular US techniques, explain their clinical applications in breast cancer diagnosis and radiologic-histopathologic correlation, and provide a summary of a recent radiogenomic study using microvascular US.