To investigate the effects of carbamazepine (CBZ) on the plasma concentrations of valproic acid (VPA) and its toxic metabolite 2-propyl-4-pentenoic acid (4-ene VPA) in epileptic patients, the plasma concentrations of VPA and 4-ene VPA were determined, and the effect of CBZ on pharmacokinetics of VPA was evaluated. All patients had been divided into two groups (VPA group, n = 87; and VPA+CBZ group, n = 19). As compared to VPA group, the combination of CBZ significantly (P < 0.01) decreased the trough concentration of VPA [VPA group, (69.5 +/- 28.8) microg x mL(-1); VPA+CBZ group, (46.3 +/- 25.6) microg x mL(-1)] and does-adjusted VPA trough concentration [VPA group, (4.89 +/- 2.21) microg x mL(-1) x mg(-1) x kg(-1); VPA+CBZ group, (3.14 +/- 1.74) microg x mL(-1) x mg(-1) x kg(-1)]. However, the addition of CBZ did not influence the concentration of 4-ene VPA. The present study revealed that coadministration of CBZ can reduce VPA plasma concentration and may impact VPA clinical effect, therefore therapeutic drug mornitoring of VPA should be used when combined use of CBZ and VPA.
Adolescent ; Adult ; Anticonvulsants ; blood ; pharmacokinetics ; therapeutic use ; Carbamazepine ; blood ; pharmacokinetics ; therapeutic use ; Drug Interactions ; Drug Therapy, Combination ; Epilepsy ; blood ; drug therapy ; Fatty Acids, Monounsaturated ; blood ; Female ; Humans ; Male ; Valproic Acid ; blood ; pharmacokinetics ; therapeutic use ; Young Adult

Objective To study the prevalence of mental disorders among the Chinese youths aged 15-34 years,in rural areas and to identify risk factors related to suicide.Methods A consecutive sampling strategy was used for suicidal cases in 16 randomly selected counties in Hunan,Liaoning,and Shandong provinces.Between 2005 and 2008,a total of 392 suicide cases were recruited with 416 community controls at the same age range,selected from the same areas one family member together with one close friend of each suicidal case were interviewed,using the psychological autopsy (PA) method.The same method with structured instruments was performed on the two informants for each control in the same community.SCID was used for the diagnosis of mental disease.Results 48.0％ of the suicides were diagnosed as having at least one mental disorder episode,in comparison with only 3.8％ among the controls.It was found that mental disorder was the most important risk factor for the Chinese young suicide cases in the rural areas.Conclusion As seen in the Western countries,mental disorder had also been the number one correlate on suicidal cases in China,with the difference as other social and psychological factors might have played relatively more important roles in China.

Objective To investigate the immunological pathogenesis of immune reconstitution inflammatory syndrome (IRIS) during highly active antiretroviral therapy( HAART), in this prospective cohort study we analyzed the lymphocyte subsets, lymphocyte activation, changes in regulatory T cells, and levels of Th1 and Th2 cytokines in both IRIS and non-IRIS groups. Methods Two hundred and thirty-eight AIDS patients received HAART and participated prospective research cohort for 24 weeks follow-up. Forty-seven IRIS cases and 191 non-IRIS cases were enrolled in the IRIS group or non-IRIS group respectively. Blood samples were collected in both groups at pre- and post-HAART 12 weeks, 24 weeks. Using flow cytometer to detect the immunophenotypes of lymphocyte subsets (CD4 + CD45RA+ CD62L+, CD8+ CD45RA+ CD62L+naive T cells; CD4+ CD45RO+, CD8+ CD45RO+ memory T cells), activated T lymphocytes (CD4+CD38 +, CD8 + CD38 + cells), and regulatory T cell ( CD4 + CD25 + Foxp3 + ). Blood samples collected at pre-and post-HAART4 weeks, 12 weeks, 24 weeks and used ELISA to detect IL-2, IFN-γ, IL-4, IL-10and IL-7 cytokine serum levels. Results The percentages of CD4 + and CD8 + naive T cells and mlemory T cells exhibited no significant differences at the baseline, 12 weeks, 24 weeks of HAART initiation between both groups, but CD4 + and CD8 + memory T cells were demonstrated a trend towards to increase while compared to baseline during HAART. The percentages of CD4 + and CD8 + activated T cells are significantly higher at the baseline while compared to normal control and demonstrated a downward trend, but between both groups showed no significant difference. The percentages of CD4 + regulatory T cell was lower in IRIS group than non-IRIS group at the baseline, 12 weeks, 24 weeks and the onset of IRIS. Th1 cytokines, IL-2 and IFN-γshowed an upward trend during HAART at the levels of IRIS group had significantly increased at 4 weeks and the onset of IRIS. Th2 cytokines, IL-4 and IL-10 showed a downward trend during HAART,and the levels of IL-10 in IRIS group had significantly decreased at 4 weeks and the onset of IRIS. IL-7 was higher than normal control at the baseline in two groups and showed a downward trend during HAART. The level of IL-7 was higher than non-IRIS group at all follow-up points. Conclusion Memory T cells appear rapid increase in the early stage of HAART and may play a significant role in the inflammatory response of IRIS. CD4 + and CD8 + naive T cells, memory T cells and activated T cells showed no significant difference between IRIS and non-IRIS group within 24 weeks after HAART started. There was a significant reduction in the frequency of regulatory T cells in IRIS group without obvious upward trend during HAART, suggesting that the immune suppression function of regulatory T cells in IRIS was impaired. IL-2 and IFN-γ significantly increased while IL-10 significantly decreased at 4 weeks post-HAART initiation and onset of IRIS in IRISgroup than non-IRIS group, suggested that IRIS was related to cytokines environment disorder. That is, a significant increase in inflammatory cytokines, while the relative lack of non-inflammatory cytokines. The level of IL-7 decreased gradually after HAART started, and it was higher in IRIS group when compared to non-IRIS group in the first 24 weeks after HAART started. Also IL-7 may play a role in the pathogenesis of IRIS.

Computer Graphics ; Computer-Assisted Instruction ; Forensic Pathology ; Humans ; Imaging, Three-Dimensional ; Pathology ; education ; Pathology, Clinical ; Specimen Handling ; methods

OBJECTIVETo study the changes in serum cortisol levels in adolescents with type 1 diabetes (T1DM) and elevated depressive symptoms.

METHODSTwenty-eight adolescents with T1DM and 31 healthy peers were assessed for depressive symptoms using a depression self-rating scale developed by the Epidemiological Survey Center. Selected subjects were classified into four groups: T1DM with elevated depressive symptoms group (n=15), T1DM without elevated depressive symptoms group (n=13), elevated depressive symptoms without T1DM group (n=15), and normal control group (n=16). Fasting blood samples were collected in the morning, and the levels of serum cortisol were compared among the four groups. The correlations of serum levels of cortisol and glycosylated hemoglobin A1c (HbA1c) with the score of depression self-rating scale were evaluated by Pearson correlation analysis.

RESULTSThe fasting serum cortisol levels in the 28 T1DM patients were significantly higher than in the 31 healthy peers (P<0.01). The fasting cortisol levels in the T1DM with elevated depressive symptoms group were significantly higher compared with those in the elevated depressive symptoms without T1DM group and normal control group (P<0.01). In adolescents with T1DM, serum HbA1c level was positively correlated with the score of depression self-rating scale (r=0.481, P=0.010).

CONCLUSIONSThe fasting serum cortisol levels in adolescents with T1DM and elevated depressive symptoms are significantly increased, suggesting that the patients with comorbidity of T1DM and depression develop dysfunction of the corticotropin-releasing hormone-adrenocorticotropic hormone-cortisol axis. The elevated depressive symptoms may be associated with a poor control of glucose metabolism.

Adolescent ; Adrenocorticotropic Hormone ; physiology ; Child ; Corticotropin-Releasing Hormone ; physiology ; Depression ; blood ; etiology ; Diabetes Mellitus, Type 1 ; blood ; Female ; Glucose ; metabolism ; Glycated Hemoglobin A ; analysis ; Humans ; Hydrocortisone ; blood ; Male

;Objective To investigate the influence of pharmacist inter-vention on patients′knowledge of anticoagulation therapy with warfarin . Methods Two hundred sixteen patients who were admitted to cardiovas-cular wards and were prescribed anticoagulation therapy with warfarin from October 2013 to August 2014 were included in the study .According to the ward they stayed , patients were divided into control group ( Cardiology ward No1.) and intervention group ( Cardiology ward No 2.) . In the control group , physicians and nurses introduced anticoagulation knowledge for the patients as usual , while intervention group received medication education and guidance on warfarin use by pharmacists .All patients of two groups filled out an assessment questionnaire about warfa-rin anticoagulation at discharge ( outpoint =13 ) .If any answer to the questions was wrong , pharmacists would educate them again .The score of the questionnaire were compared between the two groups . Results The intervention group enrolled 112 patients while the control group enrolled 104 patients. Scores of assessment questionnaire at discharge of the intervention group and the control group were (10.50 ±2.24) vs (8.08 ±2.61) respectively,with statistical difference ( P <0.05 ) .Conclusion Knowledge of warfarin therapy was much better in patients who received pharmacist intervention than patients who received usual care . Integrated management model with pharmacist interventions can improve patients′cognition in anticoagulation therapy with warfarin .

Adult rats chronic unpredictable stress model of depression (CUS) was adopted to elucidate the antidepressant pharmacological activity and related neurogenesis protective effect of the total flavonoids extract (licorice flavonoids, LF) from the Glycyrrhiza uralensis Fisch. cultivated locally in Ningxia. The rats were exposed to 9 kinds of unpredictable sequence of stressors and were given flavonoids (300 mg x kg(-1), 100 mg x kg(-1) and 30 mg x kg(-1)) for 28 days. The antidepressant effect was elucidated by open field test, forced swimming test and tail suspension test. The level of serum corticosterone was detected by radioimmunoassay. 5'-Bromo-2'-deoxyuridine (BrdU) labeling experiments was employed to study the neurogenesis protective activities. The flavonoids can increase the sum of line crosses and number of rears, and decrease the number of fecal boli produced in the open field test of the CUS rats. Also the flavonoids can decrease the immobility time in forced swim test as well as in the tail suspension test. In addition, the flavonoids (300 mg x kg(-1)) can decrease the serum corticosterone level of the CUS rats, and increase the number of the new born BrdU positive progenitor cells at the subgranular zone (SGZ) of dentate gyrus (DG) region in hippocampus. The results demonstrated that the total flavonoids extract from the cultivated Glycyrrhiza uralensis Fisch. could produce the anti-depressive effect on chronic unpredictable stress of depression model rats and its mechanism may be associated with its neurogenesis protective effect.
Animals ; Antidepressive Agents ; isolation & purification ; pharmacology ; Behavior, Animal ; drug effects ; Bromodeoxyuridine ; metabolism ; Corticosterone ; metabolism ; Depression ; metabolism ; physiopathology ; Flavonoids ; isolation & purification ; pharmacology ; Glycyrrhiza uralensis ; chemistry ; Hindlimb Suspension ; Hippocampus ; cytology ; metabolism ; Male ; Neurogenesis ; drug effects ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Stress, Psychological ; metabolism ; physiopathology ; Swimming

OBJECTIVETo suggest a chemical surface treatment for titanium and to initiate the formation of hydroxycarbonated apatite (HCA) on titanium surface during in vitro bioactivity tests in simulated body fluid (SBF).

METHODSTo improve the bone-bonding ability of Ti implants, commercially pure titanium (cpTi) by a simple chemical pre-treatment in orthophosphoric acid (H(3)PO(4)) with different density was activated, and then the phosphorylation specimens were soaked in SBF to investigate the function of biomineralization.

RESULTSThe scanning electron microscope (SEM) photographs showed that the surfaces of the pre-treated samples were characterized by a complex construction, which consisted of a mesh-like morphology matrix (a micro-roughened surface) and an uniform surface with different morphous of titanium dihydrogen orthophosphate [Ti(H(2)PO(4))(3)] crystal. After 14 days in SBF a homogeneous biomimetic apatite layer precipitated.

CONCLUSIONSThese data suggest that the treatment of titanium by acid etching in orthophosphoric acid is a suitable method to provide the titanium implant with bone-bonding ability.

Acid Etching, Dental ; methods ; Biomimetics ; Body Fluids ; Coated Materials, Biocompatible ; Dental Bonding ; Dental Implants ; Microscopy, Electron, Scanning ; Phosphoric Acids ; chemistry ; Phosphorylation ; Surface Properties ; Titanium ; chemistry

OBJECTIVETo construct a high metastatic potential human hepatocellular carcinoma (HCC) orthotopic transplantation model with palliative liver resection in nude mice.

METHODSA human HCC orthotopic nude mice model was established by administering a single inoculation of the highly metastatic MHCC97H tumor tissue (size 2 mm * 2 mm * 2 mm) into the left liver lobe. At day 14 post-inoculation, a random group of the mice received palliative liver resection; the unresected mice served as controls. Changes in expression levels of 113 genes with metastasis-related functions were evaluated in the residual HCC tissues. At day 35 post-resection, a random group of the mice were sacrificed by cervical dislocation and a comprehensive metastases examination was performed. The remaining mice were used to observe life span. All statistical analyses were performed by the SPSS v17.0 software, and significance was defined as P less than 0.05.

RESULTSThe nude mouse model of highly metastatic HCC with palliative liver resection was successfully established. Incidences of intrahepatic and abdominal metastases were higher in the palliative resected group (vs. unresected group: 11.7+/-4.7 vs. 6.3+/-2.8, t = -2.412, P less than 0.05 and 9.8+/-3.4 vs. 5.2+/-2.6, t = -2.641, P less than 0.05 respectively). In addition, the palliative resected group showed significantly enhanced pulmonary metastasis (vs. unresected group: 14.3+/-4.7 vs. 8.7+/-4.7, t = -2.348, P less than 0.05). Differential gene expression levels were found for MTSS1, TGFbl, SMAD2, IL-1b, and MMP7, and were situated in the central position of gene function net of residual HCC. The life-span of the palliative resected group was significantly longer than that of the unresected group (60.8+/-2.7 vs. 51.3+/-1.4 days, x2 = 12.850, P less than 0.01).

CONCLUSIONThe highly metastatic human HCC nude mouse model with palliative liver resection that was successfully constructed in this study represents a useful investigational tool to assess the biological characteristics of residual cancer and to screen therapeutic strategies.

Animals ; Carcinoma, Hepatocellular ; pathology ; surgery ; Disease Models, Animal ; Hepatectomy ; Humans ; Liver Neoplasms, Experimental ; pathology ; surgery ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Metastasis ; Neoplasm Transplantation ; Tumor Cells, Cultured

Objective In order to investigate etiology and molecular-epidemiological characteristics of enterovirus associated encephalitis (EAE) in Zhejiang,2008-2012.Method Cerebrospinal fluid and stool specimens were collected from suspected EAE patients,who were admitted to our hospitals.RD and Hep-2 cell lines were used to isolate enterovirus (EV).Serotypes of these EV isolates were identified through neutralization test by using serotype specific anti-sera.VP 1 genes of these isolates were sequenced,compared and used for the construction of phylogenetic tree.Results 127 (20.6％) human enterovirus (HEV) strains were isolated from 616 samples,which were collected from 610 patients.Serotypes of these EV isolates,including 60 coxsackievirus (CV),and 67 Echovirus (E) appeared to be CVA9,CVB1,CVB3-5,E3,E4,E6,E9,El4,E25 and E30,respectively.Predominant EV serotypes on EAE from 2008 to 2012 were seen as CVB3,CVB5,E6,E30 and E30,respectively.The full length of VP1 genes from different EV isolates was between 834 and 918 nucleotides.The VP1 gene similarities between these isolates and the reference strains were from 76.7％ to 85.0％ (nucleotides level) and 91.1％ to 97.9％ (amino acids level).The VP1 genes from E6 serotype isolates appeared most diverged,reaching 20.4％ (nucleotides level) attd 4.8％ (amino acids level).Based on the generated phylogenetic tree,all the EV isolates were fallen on the same branch of HEV-B,and the isolates in the same serotype formed one sub-branch,suggesting there existed geographical and temporal effects.E6 isolates diverged into two branchlets.Conclusion EVs from HEV-B were the etiologic agents for EAE in Zhejiang province from 2008 to 2012.All these EV isolates showed 12 serotypes,with predominant isolates varied every year.E30 was determined as the most dominant serotype while serotype E6 diverged into two sub-genetypes.