OBJECTIVETo observe the effect of ketoconazole on the activity of cytochrome P450 (CYP) 1A2 and 3A4 in hepatic microsomes of healthy adults.

METHODSHuman hepatic microsomes obtained from healthy adults were randomly divided into control group and ketoconazole-treatment groups at different concentrations. After 15 min of culture, the substrates (testosterone for CYP3A4 and phenacetin for CYP1A2) were added and incubated for another 20 min. The metabolites (6-testosterone and acetaminophen) were then measured with high-performance liquid chromatography (HPLC) to assess the activities of CYP3A4 and 1A2.

RESULTSSignificant difference was found between the groups in the quantity of 6-testosterone and the relative activity of CYP3A4 (P<0.05). The IC(50) of ketoconazole for CYP3A4 was 0. 16 mg/L. Both the quantity of 6-testosterone and the relative activity of CYP3A4 were reduced gradually with the increment of ketoconazole concentration. Significant differences were found between the ketoconazole groups and the control group in both the quantity of acetaminophen and the relative activity of CYP1A2 (P<0.05). Ketoconazole at low doses reduced CYP1A2 activity and but increased the activities at high doses (P<0.05).

CONCLUSIONIn the range of maximum clinical blood concentration, ketoconazole can inhibit the activity of CYP3A4, but not that of CYP1A2, in the hepatic microsomes in healthy adults.

Adult ; Antifungal Agents ; pharmacology ; Cytochrome P-450 CYP1A2 ; metabolism ; Cytochrome P-450 CYP3A ; metabolism ; Dose-Response Relationship, Drug ; Female ; Humans ; Ketoconazole ; pharmacology ; Male ; Microsomes, Liver ; drug effects ; enzymology

OBJECTIVETo probe into the relationship between hypertension and hemodynamic score of cerebral vascular accumulative function by though studying the history of hypertension and level of blood pressure.

METHODSThe database of blood pressure and cerebral vascular hemodynamic indexes (CVHI) were from baseline data and measurement in a cohort. 18,512 participants who met the included criteria were enlisted in the study. The function scores were estimated using uniform methods according to CVHI. Participants were grouped by age, years of having hypertension and level of blood pressure. Differences of the function score between different groups were compared.

RESULTSThe function score in hypertension group was significantly lower than that of normal tension group, which decreased by 13.3 points. Within 5 years of hypertension history, the function score decreased as course of hypertension prolonged. The same trend was found between the score and level of both systolic and diastolic blood pressure. When systolic blood pressure elevated to 140 mmHg or diastolic blood pressure elevated to 95 mmHg, the function score was below 75 points.

CONCLUSIONThere were significant relationship between decrease of the function scores and medical history, course of hypertension as well as level of blood pressure.

Adult ; Age of Onset ; Aged ; Blood Pressure ; physiology ; Cerebrovascular Circulation ; physiology ; China ; epidemiology ; Cohort Studies ; Female ; Hemodynamics ; physiology ; Humans ; Hypertension ; epidemiology ; physiopathology ; Male ; Middle Aged

OBJECTIVETo investigate the effect of small hairpin interfering RNA (shRNA) in suppressing cytochrome P450 3A4 (CYP3A4) gene expression in CHL-3A4 cells.

METHODSThree shRNA expression vectors targeting CYP3A4 gene (CYP3A4 I, C YP3A4 II, and CYP3A4 III, respectively) were designed, synthesized and transfected into CHL-3A4 cells via liposomes. The inhibitory effect of shRNA on CYP 3A4 gene expression was detected by Western blotting and RT-PCR, and the effect of shRNA transfection in suppressing cyclophosphamide-induced cytotoxicity was measured using MTT assay.

RESULTSThe vector carrying CYP3A4 III shRNA significantly reduced the expression of CYP3A4 gene at both the mRNA (75%) and protein levels (80%) in CHL3A4 cells. The cytotoxicity of cyclophosphamide was markedly inhibited by CYP3A4 III-mediated suppression of CYP3A4 gene expression by 75% in CHL-3A4 cells.

CONCLUSIONThe vector-mediated RNA interference can suppress CYP3A4 gene expression in CHL-3A4 cells, and RNA interference technique provides a new means for studying cytochrome P450 gene function in mammalian cells.

Animals ; Cells, Cultured ; Cricetinae ; Cytochrome P-450 CYP3A ; genetics ; Fibroblasts ; cytology ; metabolism ; Humans ; Lung ; cytology ; RNA Interference ; RNA, Small Interfering ; genetics

OBJECTIVETo explore the expression of MICA/B in human esophageal cancer, and to analyze its correlation with clinicopathological features.

METHODSThe expression of MICA/B in 40 cases of esophagus carcinoma and corresponding normal esophageal mucosa tissues were examined by immunohistochemistry.

RESULTSThe positive rate of expression of MICA/B protein in the esophageal carcinoma was 75.0% (30/40), and that in the corresponding normal esophageal mucosa was 0 (0/40). Up-regulation of MICA/B expression was found in the esophageal carcinomas. The expression of MICA/B was related with histological grade of the esophageal carcinoma (P = 0.012).

CONCLUSIONMICA/B protein plays an important role in the esophageal carcinogenesis, and my become a useful molecular marker for the diagnosis of esophageal carcinoma.

Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; metabolism ; Esophageal Neoplasms ; diagnosis ; metabolism ; pathology ; Female ; Histocompatibility Antigens Class I ; metabolism ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Grading ; Up-Regulation

OBJECTIVETo present data from a baseline investigation on stroke-related cohort population in rural area of Shanghai.

METHODSA cross-sectional study was carried out in a cluster sampling population aged 40 years and over. General information and data on common risk factors in the population were gathered and cerebral vascular hemodynamic indexes were checked. Hemodynamic score was estimated according to single indexes by unified methods. 5335 persons who had met the inclusion criteria were enlisted in the study. Exposure level of risk factors, prevalence of stroke, and hemodynamic indexes were analyzed and distributional characteristics were described.

RESULTSExposure rate of hypertension, heart disease, diabetes, family history of hypertension, overweight or obesity in males were 31.74%, 6.09%, 1.16%, 3.22%, 17.64%, 29.68% and were 32.76%, 9.22%, 1.55%, 3.84%, 19.22%, 29.44% in female respectively. Standard prevalence of stroke was 1167.3/100000, which in male was significantly higher than that in female (P < 0.05). The change of cerebral vascular hemodynamic indexes was significantly associated with age. Hemodynamic score in 21.3% of the subjects was below 75 points.

CONCLUSIONSAmong population of 40 years old and over in rural areas, hypertension was the principal risk factor regarding the rate of stroke. Prevalence of stroke in males was significantly higher than that in females. Abnormal rate of hemodynamic score was about 20% in this population.

Adult ; Age Factors ; Aged ; Aged, 80 and over ; Brain ; blood supply ; China ; epidemiology ; Cohort Studies ; Cross-Sectional Studies ; Female ; Hemodynamics ; Humans ; Hypertension ; complications ; epidemiology ; Male ; Middle Aged ; Prevalence ; Risk Factors ; Rural Health ; Sampling Studies ; Sex Factors ; Stroke ; epidemiology ; physiopathology

OBJECTIVETo probe into changes of cerebral vascular hemodynamics indexes (CVHI) from normal population to different clinical stage before and after occurring of stroke.

METHODSParticipants were selected from 25,355 stroke cohort study population aged 35 years and over in Northeast of China and 55 acute stroke patients were selected from Fuzhou PLA General Hospital. CVHI indexes were checked during baseline investigation or within one week after acute stroke. Participant enlisted in the study were divided into following 5 groups, normal population, high risk population, individuals before stroke, acute stroke patients and convalescence stroke patients. Characteristics of CVHI indexes in different population were analyzed and compared.

RESULTSV(min) of cerebral vascular in previous defined 5 group participants were 11.39 +/- 3.27, 9.66 +/- 3.18, 6.71 +/- 3.30, 4.13 +/- 1.27, 6.78 +/- 3.09, respectively. V(mean) and V(max) were with the same decreasing trends as V(min). However, RV in 5 group participants were 62.35 +/- 21.11, 82.32 +/- 31.16, 122.72 +/- 52.73, 137.46 +/- 49.56 and 115.89 +/- 55.51, respectively. Zcv, WV, DR and CP were also with the same increasing trends as RV. Abnormal rate of CVHI score (< 75 points) from normal population to convalescence stroke patients were 13.3%, 34.7%, 74.1%, 100% and 66.7%, respectively.

CONCLUSIONFrom normal population to clinical stage of stroke, cerebral vascular velocity showed decreasing trends while other indexes, such as RV, Zcv, WV, DR and CP were increasing.

Brain ; blood supply ; Female ; Hemodynamics ; physiology ; Humans ; Male ; Stroke ; etiology ; physiopathology

OBJECTIVETo explore the indications of arthroscope for the treatment of knee osteoarthritis and investigate the correlation between knee osteoarthritis imaging and effects of arthroscope.

METHODSFrom 2005.8 to 2008.4, 86 patients with knee osteoarthritis underwent arthroscope examination and treatment. Among the patients, 44 patients were male, and 42 patients were female, ranging in age from 46 to 67 years, averaged 56.3 years. Arthrodial cartilage of knee was graded by ICRS MR, and by Kellgern Laqrence X-ray. All the patients were followed up, and the duration ranged from 12 to 30 months. The Lysholm score was evaluated at the follow-up time.

RESULTSAmong 86 knees in 86 cases, cartilage injury degree of knees was graded as follows: grade 4 in 30 cases, grade 3 in 22 cases, grade 2 in 20 cases, grade 1 in 12 cases, grade 0 in 2 cases, mean grade (2.77 +/- 1.138). Postoperative Lysholm score ranged from 59 to 100, averaged (95.17 +/- 7.556), Kendall's correlation coefficient was -0.089, P = 0.317. There was no correlations between cartilage injury degree and Lysholm score. X-ray of knees was graded as follows: grade 4 in 0 cases, grade 3 in 24 cases, grade 2 in 38 cases, grade 1 in 17 cases, grade 0 in 7 cases, mean grade was (2.13 +/- 0.67), the Kendall's correlation coefficient was -0.851 with negative correlations (P = 0.036) between postoperative Lysholm score and K/L grade.

CONCLUSIONThere is no correlation between the grade of knee cartilage injury confirmed by MRI (1.5T) and effects of arthroscopy, and the grade is not a gold standard as an operation indication in arthroscope procedure. The K/L grade in X-ray had important effects.

Aged ; Arthroscopes ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Osteoarthritis, Knee ; diagnostic imaging ; pathology ; Radiography

OBJECTIVETo study the reference range of cerebrovascular hemodynamics indexes (CVHI) in a sampling population.

METHODSFourteen thousand, four hundred and eighty participants without history of stroke or exposure to risk factors were screened from 26 cities in Northeast China, North China, East China, Northwest China, South China, and Southwest China in the prospective study on stroke intervention. CVHI were checked and 95% confidence intervals were calculated using normal distribution methods, which were grouped by age, sex, area, and check positions.

RESULTSCharacteristics of CVHI 95% confidence intervals showed that low limit of carotid blood velocity as V(max), V(min), V(mean) decreased, but upper limit of cerebral RV, Zcv, WV, DR and CP increased with the increase of age. However, Q(mean) and DP did not show significant trends of age difference. Low limit of Q(mean), V(max) and upper limit of RV, DR, CP and DP in males were higher than that in females while upper limit of WV and Zcv in females were higher than that in males. Left carotid low limit of Q(mean), V(mean), V(max), V(min), and upper limit of WV, Zcv and CP were higher than that of the right but upper limit of RV, DR and DP were lower than that of the right. There were no obvious differences between areas.

CONCLUSIONObvious differences of CVHI 95% confidence intervals ranges were found between age groups, sex, and checking positions, respectively, suggesting that the reference ranges of CVHI to be estimated by every subgroup.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Aging ; physiology ; Brain ; blood supply ; Child ; Child, Preschool ; Female ; Hemodynamics ; physiology ; Humans ; Male ; Middle Aged ; Reference Values

OBJECTIVETo establish a predicting model for stroke according to cerebral vascular hemodynamic indexes and major risk factors of stroke.

METHODSParticipants selected from a stroke cohort with 25,355 population in China. The first step was to carry out principal component analysis using CVHI. Logistic regression with principal component and main risk factors of stroke were then served as independent variables and stroke come on as dependent variables. The predictive model was established according to coefficient of regression and probability of each participant was also estimated. Finally, ROC curve was protracted and predictive efficacy was measured.

RESULTSThe accumulative contribution rates of four principal components were 58.1%, 79.4%, 88.4% and 94.6% respectively. Seven variables were being selected into the equation with the first to fourth principal component as history of hypertension, age and sex. Area under ROC curve was 0.855 and optimal cut-off point was probability over 0.05. Sensitivity, specificity and accuracy of stroke prediction were 80.7%, 78.5% and 78.5% respectively.

CONCLUSIONThe model established by principal component and regression could effectively predict the incidence of stroke coming on.

Brain ; blood supply ; Hemodynamics ; physiology ; Humans ; Logistic Models ; Models, Biological ; Principal Component Analysis ; Risk Factors ; Stroke ; etiology

OBJECTIVETo describe the distribution of cerebral vascular hemodynamic indexes (CVHI).

METHODSA number of 25,355 age 35 and over were selected in the Northeast China by cluster sampling. CVHI were checked during baseline survey and were followed to see the occurrence of stroke. Distribution of CVHI among non-stroke population, individuals prior to the onset of stroke and patients with stroke were described.

RESULTSThe CVHI accumulative score, V(mean), V(max) and V(min) were dramatically decreasing, but RV, Zcv, WV and DR were significantly increasing as age increased. V(max), RV and CP were significantly higher in males but WV was lower than that of females. The CVHI accumulative score, V(min) and RV were 95.0, 10.23 and 75.8 in non-stroke population, 51.25, 6.71 and 122.72 pre stroke group, and 55.0, 6.78 and 115.89 in patients with stroke respectively. There were significant differences among three groups after controlling of age and sex (P < 0.01).

CONCLUSIONVariance of CVHI was closely related to age, and there appeared a significant abnormal of CVHI before and after stroke.

Age Factors ; Aged ; Cluster Analysis ; Female ; Hemodynamics ; Humans ; Male ; Middle Aged ; Risk Factors ; Sex Factors ; Stroke ; physiopathology