The inter-species differences of estradiol metabolism were investigated in human, Beagle dog and rat liver microsomes by comparing enzyme kinetics of parent drug and the formation of its major metabolites. The incubation systems of estradiol with liver microsomes of the three species were optimized in terms of estradiol concentration, microsomal protein content and incubation time. The concentrations of estradiol and its metabolites were measured by LC-MS/MS method. The t1/2, CLint, CLh, Km and Vmax of estradiol incubated with male human liver microsomes were 40.02 +/- 8.32 min, 41.39 +/- 6.57 mL x min(-1) x kg(-1), 13.81 +/- 12.36 mL x min(-1) x kg(-1), 26.8 +/- 6.99 micromol x L(-1) and 0.75 +/- 0.92 micromol x L(-1) x min(-1), respectively. The corresponding parameters of female human were 44.71 +/- 10.21 min, 29.85 +/- 8.97 mL x min(-1) x kg(-1), 0.01 +/- 0.68 mL x min(-1) x kg(-1), 44.2 +/- 7.73 micromol x L(-1) and 1.27 +/- 4.41 micromol x L(-1) x min(-1), that of male dog were 21 +/- 7.33 min, 165.53 +/- 29.33 mL x min(-1) xkg(-1), 26.01 +/- 8.39 mL x min(-1) x kg(-1), 19.5 +/- 7.34 micromol x L(-1) and 1.6 +/- 0.65 micromol x L(-1) x min(-1), that of female dog were 25.5 +/- 5.32 min, 135.11 +/- 42.34 mL x min(-1) x kg(-1), 0.24 +/- 3.18 mL x min(-1) x kg(-1), 8.33 +/- 6.32 micromol x L(-1) and 0.51 +/- 2.15 micromol x L(-1) x min(-1), that of male rat were 5.11 +/- 3.84 min, 485.63 +/- 36.52 mL x min(-1) x kg(-1), 49.57 +/- 15.29 mL x min(-1) x kg(-1), 62 +/- 13.74 micromol x L(-1) and 19.16 +/- 9.67 micromol x L(-1) x min(-1), and that of female rat were 7.0 +/- 3.69 min, 354.82 +/- 33.33 mL x min(-1) x kg(-1), 8.04 +/- 3.23 mL x min(-1) x kg(-1), 35.38 +/- 7.65 micromol x L(-1) and 8.39 +/- 4.91 micromol x L(-1) min(-1), respectively. There were nine metabolites detected from all the three species, but the relative amounts of the metabolites generated were different in three species. The results indicted that the major phase I metabolic pathway of estradiol was similar in the liver microsomes from all the three species. However, the inter-species differences were found in the view of relative amounts of the metabolites as well as the metabolic characteristics of estradiol in liver microsomal incubation.

AIM To study the chemical constituents from Buthus martensii Karsch.METHODS The dichloromethane and 70％ methanol fractions of B.martensii extract were isolated and purified by silica,ODS,Sephadex LH-20 and mid-pressure preparative column,then the structures of obtained compounds were identified by physiochemical properties and spectral data.RESULTS Nine compounds were isolated and identified as cholest4-en-3-one (1),cholesterol (2),uracil (3),1-stearyl-2-lyso-sn-glycero-3-phosphatidylcholine (4),glycerol (5),oleic acid (6),proline (7),alanine (8),leucine (9).CONCLUSION Compounds 1,4,5 are isolated from B.martensii for the first time.

Objective To observe the effect of circadian rhythm on hypnotic median effective dose( ED50) of ketamine. Methods Sixty mice were randomly divided into 4 groups which had 15 mice in each group. They were intraperitoneally injected with ketamine at different times of 2 Am,8 Am,2 Pm and 8 Pm, respectively. Righting reflex was recorded and the value of ED50 was measured with sequential experimental method. Results The hypnotic ED50 of ketamine at 2 Am was(54.57?0.82) mg/kg, with 95% confidence limit of ED50 38.06-78.22 mg/kg;ED50 was(49. 27?0. 12) mg/kg at 8 Am, with 95% confidence limit of ED50 40. 21-60. 37 mg/kg;ED50 at 2 Pm was (42.28?0.21) mg/kg, with 95% confidence limit 37.35 - 47 83 mg/kg;and ED50 at 8 Pm was(57.42?0.14) mg/kg, with 95% confidence limit 37.51-73 72 mg/kg,respectively. The ED50 were significant different at 2 Pm and 8 Pm. However, there were no significant difference in ED50 value among other groups. Conclusion The hypnotic effect of ketamine has circadian rhythm - dependent.

Objective To explore the immunophenotype of children with acute myeloid leukemia(AML) and its clinical significance.Methods Statistics was used to analyze the relationship between the immunophenotype of AML and their French-American-Britain(FAB) classification,complete remission (CR) in one month and 3-years event-free survival(EFS).Results CR rate was 71.6% and 3-years EFS rate was 50.8%. HLA-DR and CD34 absent mainly in M3, associated with higher CR and EFS rate. So did CD33 negative cases, especially in M2. CD13 positive was significantly predictive factor for achieving CR.Co-expression of lymphoid antigens and NK cell antigens(CD56) with M2 which correlated with lower CR and EFS rate.Conclusions The negative of HLA-DR, CD34, CD33,as well as CD13 positive, have relationship with good prognosis. Lymphoid antigens and CD56 are poor prognostic factors.

OBJECTIVETo explore the correlation of the gene polymorphisms of Toll-like receptor 2 ( TLR2) and TLR4 with the susceptibility and recurrence of condyloma acuminatum (CA).

METHODSUsing Snapshot, we detected the gene polymorphisms of TLR2 597(T/C), 1350(T/C), 15607(A/G), and 2258(G/A) and TLR4 896(A/G) and 1196(C/T) in the peripheral blood of 140 CA patients and 105 HPV-negative controls. We made comparisons between the CA patients and controls as well as between the cases of recurrent CA and those of non-recurrence at 6 months after treatment.

RESULTSThere were 72, 48, and 20 cases of genotype TT, TC, and CC of TLR2 597 (T/C), respectively, in the CA patients, as compared with 71, 31, and 3 cases in the controls. The gene frequency of mutant C was 31. 43% in the patients, significantly higher than 17.62% in the controls (χ2 = 12.04, P < 0.01), and it was 38.68% in the recurrent cases, remarkably higher than 27.01% in the non-recurrent cases (χ2 = 4.16, P < 0.05). There were 74, 49, and 17 cases of genotype TT, TC, and CC of TLR2 1350( T/C), respectively, in the CA patients, as compared with 73, 29, and 3 cases in the controls. The gene frequency of mutant C was 29. 64% in the patients, significantly higher than 16. 67% in the controls (χ2 =11.05, P < 0.01), and it was 36.79% in the recurrent cases, markedly higher than 25. 29% in the non-recurrent cases (χ2 = 4.18, P < 0.05). There were 44, 66, and 30 cases of genotype AA, AG, and GG of TLR2 15607(A/G), respectively, in the CA patients, as compared with 26, 58, and 21 cases in the controls. There was no significant difference in the gene frequencies of mutant G between the two groups (χ2 = 0.33, P > 0.05). No mutant genes of TLR2 2508 (G/A) or TLR4 896(A/G) and 1196(C/ T) were detected in either the CA patients or the controls. Linkage disequilibrium analysis showed a tight linkage between TLR2 597 (T/C) and 1350(T/C) (D' = 1, r2 = 0.93).

CONCLUSIONTLR2 597(T/C) is tightly linked to 1350(T/C), which is correlated with both the susceptibility and the recurrence of condyloma acuminatum.

Aged ; Case-Control Studies ; Condylomata Acuminata ; genetics ; Gene Frequency ; Genetic Linkage ; Genetic Predisposition to Disease ; Genotype ; Humans ; Polymorphism, Genetic ; Recurrence ; Toll-Like Receptor 2 ; genetics ; Toll-Like Receptor 4 ; genetics

Objective To detect the expression of urinary nuclear matrix protein 22(NMP22) and cytokeratin 20(CK20) mRNA in the monitoring of bladder tumor recurrence ,and to explore the clinical value of combined detection of urinary NMP22 and CK20 mRNA in the monitoring of bladder tumor recurrence .Methods Enzyme‐linked immunosorbent assay(ELISA) and nested reverse transcriptase polymerase chain reaction(Nested RT‐PCR) were used to detect the expression of NMP22 and CK20 mRNA in the u‐rine of 46 patients with recurrent bladder cancer tumor (recurrent group) ,66 patients without recurrent tumor (no‐recurrent group) and 40 healthy volunteers(control group) respectively .Results The expression of NMP22 and CK20 mRNA in the urine of control group were negative .There was statistically significant difference between the positive expression rate of NMP 22 and CK20 mRNA in the urines of the recurrent group[78 .3% (36/46) ,80 .4% (37/46))] and that of the no‐recurrent group[6 .1% (4/62) , 6 .1% (4/62)] and the control group respectively (P<0 .01) .There was no statistically significant difference between the no‐recur‐rent group and the control group(P>0 .05) .The expression level of NMP22 in recurrent tumor increased obviously along with the progression of the pathological grade and clinical classification of tumor (P<0 .05) .The positive rate of CK20 mRNA expression in the recurrent group increased obviously along with the increase of the tumor number (P<0 .05) .The sensitivity and specificity of NMP22 for monitoring bladder cancer recurrence were 78 .3% and 93 .9% ,of CK20 mRNA were 80 .4% and 93 .9% .Combined de‐tection of both sensitivity and specificity were 95 .7% and 92 .4% .Statistical significance was observed between combined sensitivi‐ty and that of single detection(P<0 .05) .No significant difference was observed between combined specificity and that of single de‐tection(P>0 .05) .Conclusion The positive expression of CK20 mRNA may also indicate tumor multiplicity .Combined detection of NM P22 and CK20 mRNA significantly increases the sensitivity and specificity in clinical detection .

AIM: To explore the role of NO in the induction of brain ischemic tolerance (BIT) by observing changes of NOS activity and NO_2-/NO_3- content following a transient cerebral ischemia. METHODS: The rat 4-vessel occluding brain ischemic model was used. 140 male Wistar rats were divided into sham, cerebral ischemic preconditioning (CIP), ischemic insult and CIP+ischemic insult groups. An occlusion of the 4 vessels for 3 min was normally used as CIP, and a relative long one for 10 min was used as ischemic insult. When CIP was followed by ischemic insult, the interval between them was 3 d. The CA1 region of the hippocampus of rats was dissected out at 0 h, 2 h, 16 h, 24 h, 36 h, 72 h and 7 d after the last time of ischemia to assay its NOS activity and NO_2-/NO_3- content. RESULTS: The NOS activity and NO_2-/NO_3- content began to increase at 16 h, peaked at 24 h and decreased to basal level at 36 h of reperfusion after CIP. The duration of the up-regulation of NOS activity and NO_2-/NO_3- content was much shorter than that of BIT, which usually takes place 1-7 d after CIP. The pattern of upregulation of the NOS activity and NO_2-/NO_3- content was similar to the CIP group, but the maximum (24 h) was much more than that in CIP group (P

Adolescent ; Bile Reflux ; etiology ; Child ; Child, Preschool ; Female ; Gastritis ; etiology ; Gastroscopy ; Helicobacter Infections ; complications ; diagnosis ; Helicobacter pylori ; Humans ; Male

Adenocarcinoma ; pathology ; Adenocarcinoma, Papillary ; pathology ; Aged, 80 and over ; Carcinoma, Renal Cell ; pathology ; Duodenal Neoplasms ; pathology ; Humans ; Kidney Neoplasms ; pathology ; Lung Neoplasms ; pathology ; Male ; Neoplasms, Multiple Primary ; pathology ; Sarcoma ; pathology ; Stomach Neoplasms ; pathology

BACKGROUND: Metabotropic glutamate receptor(mGluR) is G-protein coupled membrane receptors, which participate in various physiology or pathology process in brain, but how it induce brain ischemic tolerance(BIT)is unclear.OBJECTIVE: To study roles of mGluR2/3 and mGluR1/5 in the BIT induction.DESIGN: Randomized controlled study based on experimental animals.SETTING: Neurological department of provincial hospital and pathophysiological department of basic institute in a university.MATERIALS: The study was conducted at the Pathophysiological Department, Institute of Basic Medicine, Hebei Medical University from May 2002 to May 2003. Totally 64 healthy male SD rats were selected from the Experimental Animal Center of Hebei Medical University. Glial fibrillary acidic protein (GFAP) antibody, MTPG and(s)-4C3HPG were got from Sigma Company.INTERVENTIONS: 4 vessel occlusion(4VO) brain ischemic models in rats stained with thionine staining and GFAP immunohistochemistry staining. were used. Sixty-four rats, of which bilateral vertebral arteries were occluded permanently by electrocautery, were divided into the following 8groups: sham operation group, cerebral ischemic preconditioning(CIP)group, ischemic insult group; BIT group; MTPG + sham operation group;MTPG+BIT group; MTPG+ischemia group and(s) -4C3HPG+BIT coup. All the rats were killed 7 days after the operation or the final ischemic treatment. Cerebral sections were selected and stained with thionine staining and GFAP immunohistochemistry staining.MAIN OUTCOME MEASURE: The changes of the morphologic hippocampal pyramidal cell and GFAP expression of astrocyte.RESULTS: ① The 8 minutes ischemic insult increased the histological grade(HG) in CA1 area, decreased the pyramidal neuronal density(ND)and increased the expression of GFAP significantly( P ＜ 0.05) . ② The above changes were not observed in the BIT group, indicating that the CIP could protect pyramidal neurons against the 8-minute ischemic insult. ③The protective effects of the CIP were blocked by MTPG or(s)-4C3HPG, as manifested by significant increases in HG and decreases in ND in the groups of MTPG + BIT, MTPG + ischemia and(s)-4C3HPG + BIT( P ＜ 0.05).CONCLUSION: MTPG or (s) -4C3HPG could block the induction of BIT induced by CIP, but mGluR2/3 or mGluR1/5 could participate in the induction of BIT by which protect effect of mGluR is further induced.