OBJECTIVE:To study the effects of Tibetan medicine Zuotai on the activities of cytochrome oxidase (CYP1A2) and drug metabolism enzyme N-acetyltransferase 2(NAT2)in rats. METHODS:70 SD rats were equally randomized into a normal control (normal saline) group,the groups of single administration of low,middle and high-dose (1.2,3.8 and 12 mg/kg) Zuotai and the groups of multiple administrations thereof(once daily for 12 consecutive days). The rats were given drugs ig. caffeine(25 mg/kg)was given ig to the rats in the normal control group and the groups of single administration on the 2nd day,and to those in the groups of multiple administrations on the 13th day. 5 h later,their urine was collected and added with vitamin C based on 10 mg/ml. High performance liquid chromatography (HPLC) was adopted to determine the cafeine metabolites contents of 5-acetami-do-6-formamido-3-methyl-uric acid(AFMU),1-methylxanthine(1X),1-methyl-uric acid(1U)and 1,7-dimethyl uric acid(17U) in rats’urine,and the activities of CYP1A2 and NAT2 were reflected through (AFMU+1X+1U)/17U and AFMU/(AFMU+1X+1U). RESULTS:Compared with normal control group,the(AFMU+1X+1U)/17U and AFMU/(AFMU+1X+1U)in rats were de-creased,namely the activities of CYP1A2 and NAT2 were lower in the groups of single administration of middle-dose Zuotai and multiple administrations of middle and high-dose Zuotai than in the normal control group. There was statistical difference (P<0.05). CONCLUSIONS:Zuotai can obviously inhibit the activities of CYP1A2 and NAT2 in rats.

Poly(ADP-ribose) polymerase-1 (PARP-1) has emerged as a promising anticancer drug target due to its key role in the DNA repair process. It can polymerize ADP-ribose units on its substrate proteins which are involved in the regulation of DNA repair. In this work, a novel series of para-substituted 1-benzyl-quinazoline-2, 4 (1H, 3H)-diones was designed and synthesized, and the inhibitory activities against PARP-1 of compounds 7a-7e, 8a-8f, 9a-9c and 10a-10c were evaluated. Of all the tested compounds, nine compounds displayed inhibitory activities with IC50 values ranging from 4.6 to 39.2 micromol x L(-1). In order to predict the binding modes of the potent molecules, molecular docking was performed using CDOCKER algorithm, and that will facilitate to further develop more potent PARP-1 inhibitors with a quinazolinedione scaffold.

Objective To compare the hemodynamic responses to orotracheal intubation during emergency operation with the proseal laryngeal mask airway and endotracheal Intubation.Methods Fifty six patients who were ASA GRADE Ⅰ-Ⅱ before onset undergoing orotracheal intubation were randomly dirideed into either without laryngoscope direct proseal laryngeal mask intubation(PLMA) group or direct laryngoscope endotracheal intubation(TT) group.SBP、DBP、HR and SpO2 were recorded before,durring and 5 minutes after intubation.Intubation time and first attempt insertion success rate were recordeddso.All patients were followed up postoperatively for adverse effects like sore throat or hoarseness.Results In intubation time、first attempt insertion success rate and adverse effects like sore throat or hoarseness,PLMA group was 96.43%,(19.7?5.7)s and 7.1%,TT group was 100%,(27.9?11.3)s and 39.29%.Intubation time was significantly shorter and adverse effects like sore throat or hoarseness were lower in the PLMA group than TT group(P

Objective To investigate the prevalence of nutritional risk,undemutrition,overweight/obesi-ty,and apphcation of nutrition support in departments of neurology in 3 metropolitan hospitals in Beijing. Methods Adult patients in the departments of neurology from 3 metropolitan hospitals in Beijing were consecutively en-rolled from March 2005 to March 2006.Nutritional Risk Screening 2002(NRS2002)score≥3 was defined a8 nu-tritian risk,while body mass index(BMI)<18.5 ks/m2 as undemutrition.NRS2002 was performed on the next morning of admission and nutritional support evaluation was performed on the 14th day of admission or discharge day.The relationship between nutrition risk and nutrition support was analyzed.Results A total of 753 patients were enrolled.NRS2002 scoring results were obtained in 461 patients.The prevalence of undemutrition was 4.2%and nutritional risk Was 21.2%.Among them 292 cases in undemutrition category were estimated by semm albu-min<30g/L without accurate BML If the cases without accurate BMl were excluded,the prevalence of undemutri-tion was 5.4%and nutritional risk Was 10.8%.Twenty-three patients(14.4%)with NRS2002≥3 received nutrition support.Thirteen patients(2.2%)with NRS2002<3 received nutrition support.The average PN:EN ratio Wag 1:2.Conclusions A large proportion of inpatients were at nutritional risk or undemutrition in the de-partments of neurology in metropolitan hospitals in Beijing.The application of nutrition support Wag somehow inap-propriate in these patients.Evidence-based guidelines are required to improve this situation

OBJECTIVE: To observe the expression of discs large homolog 4 (DLG4) protein in hippocampus, amygdala and frontal cortex of rats and evaluate postsynaptic density in heroin dependence. METHODS: The rat heroin dependent model was established by increasing intraperitoneal injection of heroin. DLG4 proteins in hippocampus, amygdala and frontal cortex of heroin dependent 9, 18, 36 days rats were detected with immunohistochemical staining and compared with that in the control group. RESULTS: DLG4 proteins in hippocampus, amygdala and frontal cortex were gradually reduced with extension of heroin dependent time. CONCLUSION Heroin dependence can affect postsynaptic density of hippocampus, amygdala and frontal cortex. The changes become more apparent with extension of heroin dependence time.
Amygdala/metabolism* ; Animals ; Disks Large Homolog 4 Protein ; Frontal Lobe/metabolism* ; Heroin/pharmacology* ; Heroin Dependence ; Hippocampus/metabolism* ; Injections, Intraperitoneal ; Intracellular Signaling Peptides and Proteins/metabolism* ; Membrane Proteins/metabolism* ; Rats

Objective To investigate the effects of δ-opioid receptor agonist DADLE (D-Ala2-D-Leu5-enkephalin) on the hemodynamics and oxygen metabolism in rats with sepsis. Methods Eighty healthy male SD rats were randomly divided into 4 groups ( n = 20 each) : sham operation group (group S), sepsis group (group SEP) ,DADLE, group and DADLE2, group. Sepsis was induced by cecum ligation and puncture (CLP) in SEP, DADLE,and DADLE2 groups. In DADLE1 and DADLE2 groups, 0.5 mg/ml DADLE 10 mg/kg was injected intraperitoneally (IP) 0.5 h before CLP and immediately after CLP respectively. Mean arterial pressure (MAP), left ventricular systolic pressure (LVSP) and ± dp/dtmax were recorded at 0, 2, 4 and 6 h after CLP (T1-4). Blood samples from left common carotid artery and right external jugular vein were collected at T4 for blood gas analysis. The cardiac index (CI), O2 delivery (DO2), O2 consumption (VO2) and O2 extraction rate (ERO2) were calculated.Results Compared with group S, MAP and LVSP were significantly increased at T2, while decreased at T3,4, and ± dp/dtmax was significantly increased in group SEP, MAP was significantly increased at T2, while decreased at T3,4, LVSP was significantly increased at T2,3, while decreased at T4 , and ± dp/dtmax was significantly increased in DADLE, and DADLE2 groups, and CI, DO2 and VO2 were significantly decreased and ERO2 was increased in SEP, DADLE, and DADLE2 groups (P＜0.05). Compared with group SEP, MAP, LVSP and ± dp/dtmax at T3,4 and CI, DO2 and VO2 were significantly increased, while ERO2 was significantly decreased in DADLE1 and DADLE2 groups (P ＜ 0.05). There was no significant difference in the parameters mentioned above between DADLE1 and DADLE2 groups ( P ＞ 0.05). Conclusion δ-opioid receptor agonist DADLE can obviously improve the hemodynamics and oxygen metabolism in septic rats.

Objective To compare the effect of using ambroxol hydrochloride combined with co-xuanju capsule,co-xuanju capsule and ambroxol hydroehloride in the treatment of semen liquefaction.Methods Sixty semen liquefaction patients were divided randomly into three groups.Clinical trials involving 20 who received ambroxol hydrochloride+co-xuanju capsule(group A),20 co-xuanju capsule(group B) and 20 ambroxol hydrochloride(group C),were carried out for 3 months.The changes of semen liquefaction time and semen quality were measured and assayed before and after treatment Results Compared withpretherapy,various parameters in the semen quality and semen liquefaction time after treatment all had a significantly difference in every group,and the patients of semen liquefaction time less than 60 minutes were 17 in group A,11 in group B and 14 in group C respectively.The results of semen liquefaction time andsemen quality in group A were significandy higher than the other groups(P<0.05),but the results between group B and group C had no significant difference.Conclusion The combination of ambroxol hydrochlorideand co-xuanju capsule can eridently improve the semen liquefaction time and semen quality and is an effective method in treating male infertility.

Objective To prepare the phmaceutical reference materials of total lactones extract from ginkgo leaf for quantitative analysis.Methods A HPLC determination method was developed to investigate the uniformity and stability of the reference extract of ginkgo leaf total lactones using with bilobalide, ginkgolide A, ginkgolide B and ginkgolide C as the indexes.Three laboratories participated in the collaborative calibration test.Results The four components in reference extract had good uniformity and stability with RSD less than 2.0%;the marked values of the four components had been determined through statistical data analysis which provided by assigned traceability values.The values of bilobalide, ginkgolide A, ginkgolide B, and ginkgolide C were 39.54%, 29.03%, 15.96% and 11.69%, respectively.Conclusion The reference extract of ginkgo leaf total lactones can be prepared for quality control in future quantitative analysis.

Objective To investigate current situation of prescription of traditional Chinese medicine (TCM) for acute stroke patients.Methods From June 2008 to October 2010,with simple cluster sampling,48 centers were randomly assigned to the intervention group receiving a standardized treatment strategy,and the usual care group without specific recommendations for treatment.No specific recommendations or restrictions of TCM were proposed for both groups.Consecutive hospitalized patients with acute ischemic stroke were recruited in this study.Clinical data and treatment strategy (including TCM) were recorded by trained investigators.The prescription of TCM three months prior to admission and at discharge was recorded and analyzed.The chi-square test was used for analysis of qualitative data.Results Totally 3 664 patients were included in the analysis (1 709 patients in standard care group and 1 955 patients in the usual care group) with male to female ratio 2∶ 1.The difference of distribution of age,sex and education level between the two groups was not statistically significant.One hundred and eighty-seven patients (5.10％) had taken TCM three months prior to admission,81.28％ of them only taking one type of TCM,without significant difference between the two groups.The percentage of patients taking TCM at discharge was significantly increased to 30.65％ for all the patients with higher percentage (38.16％) in the usual care group than that in the standard care group (22.06％).The percentage of using more than one type of TCM was also higher in the usual care group (x2 =141.43,P ＜ 0.01).Totally,112 types of TCM were prescribed at discharge.Conclusions Nearly one third of hospitalized patients with acute stroke were prescribed TCM at discharge,with mostly monotherapy and a great variety.

Poly(ADP-ribose) polymerase-1 (PARP-1) has emerged as a promising anticancer drug target due to its key role in the DNA repair process. It can polymerize ADP-ribose units on its substrate proteins which are involved in the regulation of DNA repair. In this work, a novel series of para-substituted 1-benzyl-quinazoline-2, 4 (1H, 3H)-diones was designed and synthesized, and the inhibitory activities against PARP-1 of compounds 7a-7e, 8a-8f, 9a-9c and 10a-10c were evaluated. Of all the tested compounds, nine compounds displayed inhibitory activities with IC50 values ranging from 4.6 to 39.2 micromol x L(-1). In order to predict the binding modes of the potent molecules, molecular docking was performed using CDOCKER algorithm, and that will facilitate to further develop more potent PARP-1 inhibitors with a quinazolinedione scaffold.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Drug Design ; Enzyme Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Molecular Docking Simulation ; Molecular Structure ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerases ; Quinazolinones ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship