Drug discovery and development is an expensive process with a high attrition rate. Cytochrome P450 (CYP) induction and inhibition mediated drug-drug interaction of drug candidates serves as one of the reasons for such attrition. Consequently a great effort is paid to identify those compounds that influence pharmacokinetic parameters of other drugs, which may lead to drug-drug interactions. CYP plays a central role in metabolism and biosynthesis of a wide range of exogenous and endogenous compounds. CYP induction mediated drug-drug interactions may result in an increased metabolic clearance for coadministrated drugs, and subsequently affect their effectiveness and safety. Assessment of CYP induction potential for drug candidates has become an integral part of new drug discovery and development. This article reviews the current understanding on CYP induction mediated drug-drug interaction and its clinical implications, along with the in vitro and in vivo methodologies for assessment of the induction potential of new drug candidates.

Animals ; Cell Survival ; Cells, Cultured ; GTP-Binding Proteins ; metabolism ; Isoproterenol ; adverse effects ; Myocytes, Cardiac ; cytology ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic, beta-2 ; metabolism

Objective:To investigate the value of magnetic resonance cholangiopancreatography(MRCP)in the diagnosis of pancreas divisum by comparing with endoscopic retrograde cholangiopancreatography(ERCP).Methods:The MRCP and ERCP images of 8 patients with pancreas divisum were retrospectively analyzed.The diagnostic accuracy and findings by MRCP were compared with those by ERCP.Results:MRCP had a diagnostic accuracy of 87.5%(7/8)based on the result of ERCP.ERCP displayed the dominant dorsal pancreatic ducts in all 8 cases and ventral pancreatic ducts in 6 cases;MRCP also displayed the dominant dorsal pancreatic ducts in all 8 cases,but the ventral pancreatic ducts only in 3 cases.Conclusion:As a non-invasive technique,MRCP has important clinical value in the diagnosis of pancreas divisum.

BACKGROUND:C2 transpedicle screw fixation for Hangman fractures has been paid more attention due to reliability and no loss of physiological function.However,there are lacks of biomechanical evidences for indication treatment because the fixation is single segmental.OBJECTIVE:To investigate the biomechanical stability of C2 transpedicle screw fixation for Hangman fractures.DESIGN,TIME and SEITING:This was a contrast study which was performed at the General Key Laboratory of Biomechanics,First Military Medical University of Chinese PLA from May to August 2004.MATERIALS:AO-universal titanium alloy transpedicle screw of 18 25 mm in length and 3.5 mm in diameter was adopted in this study.Six fresh C1-C4 cervical vetebrae samples were ordiually made into type Ⅰ,ⅡA,and Ⅱ Hangman fracture models.METHODS:After transpedicle screw fixation.Hangman fracture models were measured by non-destroyed style with spinal anterior flexion/posterior extension,left/right lateral curvature,and left/right axial direction.Loading/unlonding circulation was performed three times during each testing.Kinematics indicators were measured on the 3rd circulation.MAIN OUTCOME MEASURES:Spinal motor images at zero load and maximal load were obtained with laser photoscanning(0.1% in precision),and the corresponding systematic software was adopted to calculate 3D range of movement.RESULTS:The relative stability of type Ⅰ Hangman fracture models after C2 transpedicle screw fixation was 100.62%(inflexion),96.91%(posterior extension),99.19%(lateral curvature),and 97.12%(rotation)as compared to control group (P＞0.05).The relative stability of type Ⅱ Hangman fracture models after C2 transpedicle screw fixation was 47.84%(inflexion),21.29%(posterior extension),65.98%(lateral curvature),and 41.69%(rotation)as compared to control group (P＜0.05).CONCLUSION:Biochemical evaluation suggests that type Ⅰ and Ⅱ A Hangman fractures do fit for C2 transpedicle screw fixation,and the fixation may generate well physiological fixation or stability.However,stability of type Ⅱ Hangman fracture is poor,so it is not suitably adopted single transpedicle screw fixation.

Objective To probe the effects of nuclear factor kappa B (NF-?B) on cell apoptosis and left ventricular segmental function in acute ischemia repeffusion in dogs.Method Twenty-four dogs were randomly divided into three groups:without left anterior artery (lAD) ligation group (C group),LAD was occluded 30 min following reperfusion 120 minutes in isehemical reperfusion group (IR group),and dogs were administered with PDTC before LAD ligation in ischemical reperfusion plus pyorrole dithitocarbamate group (PDTC group).The left ventricular segmental function was detected by echo cardiography using strain rate anlysis software.EF measured by Simpson's method.Cardiac myocyte apoptosis numbers were determined by terminal deoxynudeotidy transferease-mediated biotinylated deoxyuridine triphosphate nick end labeling (TUNEL).lmmunohistochemistry and western-blot anylysis of NF-?B protein expression.Results NF-?B was obviously expression on injury myocardium of IR group,and increased significantly in contrast to control group (P0.05)Conclusions NF-?B might play an important role in acute myocardial ischemia reperfusion.PDTC reduces myocardial iscbemia/repeffasion injury by preventing expression of factor NF-?B.

OBJECTIVETo determine the genetic diversity of Eucommia ulmoides.

METHOD260 samples of 20 populations were analyzed through radom amplified polymorphic DHA (RAPD).

RESULTTotal polymorphic loci percentage was 96.36 and the average was 38.92. 110 bands were produced with 10 random primers and 106 were polymorphic. Nei's gene diversity (H) was 0.246 1, Shannon's Information index(I) was 0.386 8, Gst was 0.424 4, indicating that 42.44% of the genetic variation was distributed among populations and 57.65% within populations.

CONCLUSIONThe genetic variation was relatively high in E. ulmoides, so the genetic diversity conservation principle should mainly focus on protection of the populations.

China ; Conservation of Natural Resources ; DNA, Plant ; genetics ; Eucommiaceae ; classification ; genetics ; Genetics, Population ; Phylogeny ; Plants, Medicinal ; genetics ; Polymorphism, Genetic ; Random Amplified Polymorphic DNA Technique

AIMTo investigate the role of overexpression of beta2-adrenoceptor on contraction in cardiac myocytes isolated from failure hearts of rats and primarily analyses its mechanisms.

METHODSPrimarily cultured cardiac myocytes were infected with adenovirus containing the sequence for human beta2-adrenoceptors. The expression of beta2-adrenoceptors was tested by Western blot. The contraction amplitudes induced by isoprenaline stimulation were measured.

RESULTSOverexpression of beta2-adrenoceptor increased the content in failure cardiac myocytes. The contraction amplitudes in failure cardiac myocytes were lower than that in the control (P < 0.01). Overexpression of beta2 adrenoceptor improved the contraction of failure cardiac myocytes (P < 0.01, Failure+ Adv.Beta2 group vs. Failure group). Selective beta2-adrenoceptor antagonist ICI 118,551 partially reversed the effects (P < 0.05, Failure+ Adv.beta2 + ICI group vs Failure + Adv.beta2 group), but the contraction amplitudes in this Failure +/- Adv.beta2 + ICI 118,551 group were still higher than that in only heart failure group (P < 0.05). Selective beta1 adrenoceptor antagonist CGP20712A completely inhibited the effects of overexpression of beta2 adrenoceptor on contraction amplitude in failure cardiac myocytes.

CONCLUSIONOverexpression of beta2-adrenoceptors improves the contraction of cardiac myocytes isolated from failure hearts of rats. The effect is related to beta1-adrenoceptor.

Adenoviridae ; genetics ; Adrenergic beta-Antagonists ; pharmacology ; Animals ; Cells, Cultured ; Heart Failure ; metabolism ; physiopathology ; Humans ; Imidazoles ; pharmacology ; Isoproterenol ; pharmacology ; Male ; Myocardial Contraction ; Myocytes, Cardiac ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic, beta-2 ; genetics ; metabolism

Objective To unveil the changes of endemic fluorosis in order to provide the scientific basis for making countermeasure. Methods Seven villages was selected as monitoring points in Qianan County of Jilin Province where drinking water was improved or was going tobe improved. Dental fluorosis was surveyed with Dean method and for urine fluoride content was tested using fluoride ion-selective electrode analysis in 8 - 12 years old children. Clinical skeletal fluorosis was detected in all residents of aged 16 and over in the beginning of the monitor and every 3 years. X-ray films were taken in those over 16 years old at the beginning of the monitor and every 5 years. Results Detectable rate of dental fluorosis was decreased compared with before(Weizi: 11.3% to 2.2%, Danzi: 16.3% to 12.1%, Houqi: 53.7% to 37.5%, Houju: 38.6% to 33.3%), and severity was declining, for example, in Dongnanjing, rate of being moderate was dropping from 11.3% to 7.8%, severe rate from 2.8% to 0;in Houqi: moderate rate from 16.7% to 0, severe rate from 1.9% to 0;in Houju, moderate rate from 1.4% to 0,severe rate from 1.4% to 0. However, detectable rate of dental fluorosis rose in Dabin from 61.7% to 70.0% and in Dongbin-donju from 52.7% to 71.1% due to increased fluorides in drinking water. Urine fluorides content in 8 - 12 years old children was decreased to normal level(1.5 mg/L) in most of monitoring spots, but in Dabin it still remained at a high level, being 4.03 and 4.57 mg/L before and after respectively. Detectable rate clinical skeletal fluorosis was between 11.1% - 25.7% among those aged 16 and over in 7 monitoring point in 1991 - 2006, however it increased year after year in Dabin (15.9%, 21.6% and 25.7% in 1991, 1993 and 1995). Positive X-ray rate for skeletal fluorosis was decreased from 54.9% to 24.0% in Dabin, from 40.7% to 23.5% in Dongbin-donju and from 28.6% to 20.4% in Dangnanjing. Conclusions Endemic fluorosis has been controlled attributed to improved drinking water and decreased fluorides content in drinking water. Combined methods are needed to decrease to the intake of fluorides to control the diseases.

OBJECTIVETo review the recent development of functional MRI application in epilepsy.

DATA SOURCESBoth Chinese and English language literatures were researched using MEDLINE/CD ROM (1996 - 2005) and the Chinese Biomedical Literature Disk (1996 - 2005).

STUDY SELECTIONPublished articles about functional MRI application and epilepsy were selected.

DATA EXTRACTIONData were mainly extracted from 38 articles which are listed in the reference section of this review.

RESULTSfMRI can be used to localize seizure foci through detecting these cerebral hemodynamic changes produced by epileptiform discharges. EEG-triggered fMRI, which has higher spatial and temporal resolution, helps to detect the spatiotemporal pattern of spike origin and propagation, and define localization of the epileptogenic focus. fMRI is also useful in language and memory cognitive function assessment and presurgical assessment of refractory epilepsy. Atypically distributed cognitive function areas can be detected by fMRI, because of cortical language and memory areas reorganization during long-term epileptic activity in patients with epilepsy.

CONCLUSIONSfMRI technique plays a very important role in cognitive function and presurgical assessment of patients with epilepsy. It is meaningful for understanding pathogenesis of epilepsy.

Cognition ; Epilepsy ; diagnosis ; pathology ; psychology ; Humans ; Magnetic Resonance Imaging ; methods

OBJECTIVETo investigate the association of non-bacterial respiratory pathogens with asthmatic diseases in children, and the clinical significance of total serum IgE levels and peripheral eosinophil count in infection with non-bacterial respiratory pathogens.

METHODSIndirect immunofluorescence assay was used to detect IgM antibodies against nine types of non-bacterial respiratory pathogens in the sera of 490 children with asthmatic diseases between September 2010 and September 2011. Pathogens were analyzed and total serum IgE levels and peripheral eosinophil count were measured in IgM-positive cases.

RESULTSOf the 490 children with asthmatic diseases, 47.6% (233 cases) were positive with IgM antibodies against non-bacterial respiratory pathogens, the most common being Mycoplasma pneumoniae (MP) (25.3%), followed by adenovirus (ADV) (8.9%) and influenza B virus (Flu B) (8.8%). Thirty-six cases suffered from co-infection of two or more non-bacterial pathogens, mainly comprising MP and other pathogens (94%). There were significant differences in the total detection rate of IgM antibodies among all age groups (0-30 days: 50.0%; 1-6 months: 67.3%; 0.5-1 year: 33.1%; 1-3 years: 57.3%; 3-8.9 years: 61.7%). The positive rate of IgM antibodies against respiratory pathogens was highest in children with bronchial asthma, followed by children with asthmatic bronchitis, and it was lowest in children with bronchiolitis. IgM-positive children had significantly decreased blood eosinophils and significantly increased total serum IgE levels.

CONCLUSIONSThe main non-bacterial respiratory pathogens include MP, ADV and Flu B in children with asthmatic diseases, and co-infection of MP and other non-bacterial pathogens is common. Infants aged 1 to 6 months have a higher infection rate than other age groups. Monitoring the changes in total serum IgE levels and peripheral eosinophil count has great significance for the clinical diagnosis and treatment of asthmatic diseases in children.

Adenoviridae Infections ; diagnosis ; Age Factors ; Antibodies, Viral ; blood ; Asthma ; etiology ; microbiology ; virology ; Child ; Child, Preschool ; Eosinophils ; Female ; Fluorescent Antibody Technique, Indirect ; Humans ; Immunoglobulin E ; blood ; Immunoglobulin M ; blood ; Infant ; Infant, Newborn ; Male ; Pneumonia, Mycoplasma ; diagnosis