Objective T o analyse the m etabolic changes in urine of rats w ith brodifacoum intoxication, and to reveal the m olecular m echanism of brodifacoum-induced toxicity on rats. Methods B y establish-ing a brodifacoum poisoning rats m odel, the urine m etabolic profiling data of rats w ere acquired using high performance liquid chromatography-timeofflightmassspectrometry (HPLC-TOF-M S).The orthogo-nal partial least squares analysis-discrim ination analysis (O PLS-D A ) w as applied for the m ultivariate statistics and the discovery of differential m etabolites closely related to toxicity of brodifacoum . Results O PLS-D A score plot show ed that the urinary m etabolic at different tim e points before and after drug adm inistration had good sim ilarity w ithin tim e period and presented clustering phenom enon. C om paring the urine sam ples of rats before drug adm inistration w ith w hich after drug adm inistration, tw enty-tw o m etabolites related to brodifacoum-induced toxicity w ere selected. Conclusion T he toxic effect of brodi-facoum w orked by disturbing the m etabolic pathw ays in rats such as tricarboxylic cycle, glycolysis, sphin-golipid m etabolism and tryptophan m etabolism , and the toxicity of brodifacoum is characterized of accu-m ulation effect. The m etabonom ic m ethod based on urine H PLC-TO F-M S can provide a novel insight into the study on m olecular m echanism of brodifacoum-induced toxicity.

A sensitive LC-MS/MS method to determine cocaine and its major metabolite benzoylecgonine in guinea pig's hair has been established. About 20 mg of decontaminated hair sample was hydrolyzed with 0.1 mol·L-1 HCl at 50 ℃ overnight, in the presence of cocaine-d3 and benzoylecgonine-d8 used as internal standards, and then extracted with dichlormethane. The analysis was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Positive electrospray ionization (ESI+) and multiple reactions monitoring (MRM) mode were used. The limit of detection (LOD) for cocaine and benzoylecgonine was 1 pg·mg-1. The calibration curves of extracted standards were linear over the range from 5 pg·mg-1 to 250 pg·mg-1 (r2≥0.999 7). The method was validated and applied to the analysis of guinea pig's hair after a single dose administration of cocaine hydrochloride. Cocaine and benzoylecgonine were not only detected, but also quantified in guinea pigs hair.

Objective To explore the changes of plasma brain natriuretic peptide(BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP)of sepsis combined with myocardial injury in newborns.Methods According to neonatal sepsis treatment program,45 cases of sepsis newborns in NICU of the Second Hospital in Lanzhou University from Jul.2007 to Jun.2008 were collected.According to the myocardial injury diagnostic criteria,45 cases neonatal sepsis were divided into myocardial injury group(n=22) and non-myocardial injury group(n=23).Myocardial injury group was also divided into congenital heart disease group and non-congenital heart disease group accor-ding to echocardiography.At the same time,30 healthy newborns were collected as healthy control group.Every newborns were tested the level of plasma BNP,NT-proBNP,creatine kinase-MB(CK-MB) and cardiac-troponin I (cTnI).Results There were significant difference between myocardial injury group,non-myocardial injury group and healthy control group in the levels of plasma BNP,NT-proBNP,CK-MB and cTnI,those in congenital heart disease group were higher than those in non-myocardial injury group and the healthy control group(Pa0.05).Conclusions BNP and NT-proBNP can be early used to diagnose myocardial injury and heart failure of neonatal sepsis associated with CK-MB and cTnI.In NICU,infants with sepsis should normally test BNP and NT-proBNP in order to early diagnose myocardial injury of neonatal sepsis.

Adult ; Air Pollutants ; adverse effects ; Humans ; Male ; Military Medicine ; Monitoring, Physiologic ; Noise, Occupational ; adverse effects

The construction of teaching team is a very important part of quality project of higher education in China. The objective of team construction is to renew the teaching content, to develop the teaching resource, to facilitate the study on methodology and exchange of experience, to strengthen echelon construc- tion and to improve on teaching quality. The Microbiology Curricula Team of Wuhan University is one of the first authorized teaching teams of Hubei Province in 2007. It became one of the first national-level teaching teams in the field of microbiology in 2008. This paper focuses on the feature and the train of thought of the construction and development of the team.

OBJECTIVETo study the effects of specific immunotherapy with standardized house dust mite extract on the lung function and immunologic markers in children with asthma.

METHODSThirty-two children with mild to moderate asthma who were allergic to house dust mite were assigned to two groups: an immunotherapy group that received subcutaneous specific immunotherapy with standardized house dust mite extract beside glucocorticoids treatment (n=15) and a control group that received glucocorticoids treatment alone (n=17). Lung function was determined before treatment and 3, 6, 12, 18 and 24 months after treatment. The frequency of asthma attacks was observed before treatment and 12 and 24 months after treatment. Serum immunological markers, including total IgE, specific IgE and specific IgG4 against house dust mite (Dermatophagoides pteronyssinus, Der P), ECP, IL-10, IL-4, and IFN-γ, were measured before treatment and 12 and 24 months after treatment.

RESULTSThe parameters of lung function were kept at the normal level or near normal level after treatment in the immunotherapy group. Compared with before treatment, the percentage of patients without asthma attacks increased significantly after treatment in the immunotherapy group (P<0.05) and increased more significantly with a prolonged treatment time (P<0.05). The level of serum sIgG4 against Der P increased significantly throughout the period of the immunotherapy treatment compared with before treatment (P<0.01). There were no significant differences in the levels of serum total IgE, sIgE against Der P, ECP, IL-10, IL-4 and IFN-γ before and after treatment in the immunotherapy group. There were no significant differences in all the parameters measured before and after treatment in the control group.

CONCLUSIONSSubcutaneous specific immunotherapy with standardized house dust mite extract for two years decreases the frequency of asthma attacks and the lung functions are kept in a normal level in children with asthma. The role of the specific immunotherapy may attribute to the increased level of serum sIgG4 against Der P.

Animals ; Asthma ; immunology ; physiopathology ; therapy ; Child ; Child, Preschool ; Desensitization, Immunologic ; Eosinophil Cationic Protein ; blood ; Female ; Humans ; Interleukin-10 ; blood ; Interleukin-4 ; blood ; Lung ; physiopathology ; Male ; Pyroglyphidae ; immunology

OBJECTIVE: To establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for detection of mexiletine by liquid chromatography tandem mass spectrometry. METHODS: After simple protein precipitation of the blood sample with acetonitrile, the organic solvent layer diluted with LC mobile solvent was separated by Allure PFP Propyl column, confirmed and quantified by MS/MS in the multi-reaction monitoring (MRM) mode via positive electrospray ionization. RESULTS: Mexiletine and naloxone (internal standard) got ideal resolution under the selected analytical condition. The correlation coeficient of linear calibration curve was over 0.9999 within the mexiletine concentration range 0.02-10 microg/mL. The relative standard deviations were under 10% for intra-day and under 15% for inter-day, and the detection limit was 0.01 microg/mL. CONCLUSION The established LC-MS/MS method is simple, rapid, sensitive, unaffected by matrix effect and appropriate for detection of mexiletine in blood in the field of therapeutic drug monitoring and forensic toxicology.
Anti-Arrhythmia Agents/chemistry* ; Forensic Medicine ; Humans ; Mexiletine/poisoning* ; Molecular Structure ; Naloxone/chemistry* ; Reproducibility of Results ; Sensitivity and Specificity ; Spectrometry, Mass, Electrospray Ionization/methods* ; Tandem Mass Spectrometry/methods*

To investigate the effects of telmisartan on steatohepatitis (NASH) in rats by activating peroxisome proliferator-activated receptor gamma (r). Thirty male SD rats were randomized into normal control group, NASH control group and telmisartan prevention group. Normal control group was given standard food and the other two groups were given high fat diet for 16 weeks to induce NASH. Prevention group was given telmisartan (5 mg.kg-1.d-1) for 4 weeks by intragastric adminstration after 12 weeks. At the end of the 16th week, all the rats were sacrificed. Pathological changes of liver were observed by optical microscopy. Serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), fasting blood glucose(FBG), fasting insulin(FINS), HOMA-IR(homeostasis model assessment insulin resistance), Serum TNF-a and adiponectin were detected and analyzed.Western blot and RT-PCR were used to detect PPARr expression in hepatic tissues on protein and mRNA levels. (1) Rats were successfully modeled. The liver tissue samples were divided into 4 degrees (F0 - 4) based on total fatty degeneration of liver cells.There was one rat reached F3 and nine rats reached F4 in NASH group, one rat reached F1, six rats reached F2 and three rats reached F3 in prevention group. Inflammatory activity scores of hepatic tissues in the model group were 2.67+/-0.25, while that in the control group was 0 (U=15 and P is less than to 0.01), in the prevention group were 2.67+/-0.25 and 1.36+/-0.12 (U=24 and P is less than to 0.05 ). (2) The levels of serum ALT, AST, FBG, FINS, TNFa and HOMA-IR in the model group were increased than those in the control group( the vaules of q were 13.130, 6.472, 6.909, 26.619, 14.591 and 49.683 respectively, P less than 0.01). The levels of serum ALT, FINS, FBG, TNFa and HOMA-IR in the prevention group were decreased as compared to the model group (the vaules of q were 7.024, 4.145, 14.829, 13.195 and 31.991 respectively, P less than 0.01 ). (3) The serum adiponectin, PPARrmRNA and protein in liver tissues of the model group were lower than those in the control group (q values were 10.696, 8.679 and 16.762 respectively, P is less than to 0.05).The data in the prevention group were higher as compared to the model group(q values were 3.879,3.079,6.400, P is less than to 0.05 respectively). HOMA-IR was positively correlated with the expression of TNFa but negatively correlated with the expression of adiponectin (r = 0.927, P is less than to 0.01; r = -0.891, P is less than to 0.01, respectively). Telmisartan may has preventive effect on rats with steatohepatitis (NASH) by a mechanism of activating peroxisome proliferator-activated receptor r.
Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Fatty Liver ; Insulin Resistance ; Non-alcoholic Fatty Liver Disease ; Rats ; Rats, Sprague-Dawley

A sensitive LC-MS/MS method to determine cocaine and its major metabolite benzoylecgonine in guinea pig' s hair has been established. About 20 mg of decontaminated hair sample was hydrolyzed with 0. 1 mol x L(-1) HCl at 50 degrees C overnight, in the presence of cocaine-d3 and benzoylecgonine-d8 used as internal standards, and then extracted with dichlormethane. The analysis was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Positive electrospray ionization (ESI +) and multiple reactions monitoring (MRM) mode were used. The limit of detection (LOD) for cocaine and benzoylecgonine was 1 pg x mg(-1). The calibration curves of extracted standards were linear over the range from 5 pg x mg(-1) to 250 pg x mg(-1) (r2 > or = 0.9997). The method was validated and applied to the analysis of guinea pig's hair after a single dose administration of cocaine hydrochloride. Cocaine and benzoylecgonine were not only detected, but also quantified in guinea pigs hair.
Animals ; Chromatography, High Pressure Liquid ; Cocaine ; administration & dosage ; analogs & derivatives ; analysis ; metabolism ; Guinea Pigs ; Hair ; chemistry ; metabolism ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry

Objective Tostudyrecentclinicalefficacyandadversereactionsofpemetrexedincombi-nationwithcisplatininthetreatmentofadvancedbreastcancer.Methods Usingenvelopesandrandomlythe patients were dividing into treatment group and control group.The treatment group with 1 8 cases of advanced breast cancer were treated with pemetrexed and cisplatin while in the control group ,23 cases advanced breast cancer patients were treated with gemcitabine and cisplatin with 21 days as a cycle.The efficacy and adverse re-actions were determined according to the WHO on Response Evaluation Criteria in Solid Tumors therapy and chemotherapytoxicityevaluationcriteria.Results Tumorcontrolrateinthetreatmentgroupwas83.3%(1 5/1 8),while in the control group was 78.3%(1 8/23 ),and the difference was not statistically significant (χ2 =0.000 94,P>0.05);while the adverse reactions differenced between the treatment group and the con-trol group were statistically significant(bone marrow suppression χ2 =9.23;fatigue χ2 =4.96;nausea and vomi-tingχ2=4.98;diarrheaχ2=4.45;skinrashχ2=5.03,P<0.05).Conclusion Pemetrexedcombinedwith cisplatin in patients with advanced breast cancer has a good effect,and the adverse reaction is low.