K21. The mean t1/2(?) was (2.7?0.4) h, Vd was about 11.18 L?kg-1.The C-T profile conformed to two compartment open model. The plasma Dau concentration-time curves showed a double-peak phenomenon in all dosages of all dogswhen dauricine was given by intragastric was.The tpeak(1) was (0.8?0.6) ～(1.2?0.5) h,tpeak(2) was (5.2?3.2) ～(6.5?1.9)h,Cmax(2) 0.05) and the AUC was increased in proportion.The drug is eliminated non-linearly when the dosage is above 50 mg?kg-1, the parameters t1/2(el),CL, AUC/X0 shows great difference (P

Aim The relative bioavailability of domestic ibudilast sustained release capsules in healthy volunteers was observed.Methods A single oral dose of 20 mg of imported and domestic ibudilast sustained release capsules and 10 mg of ibudilast raw material was separately given to 12 healthy volunteers in a randomized crossover study. Ibudilast concentration in plasma was determined by HPLC method.Results The Cmax were (54.9?9.7),(60.7?9.1) and (62.2?11.5) ?g?L-1; the tmax were (3.8?0.8),(3.9?0.8) and (1.8?0.3) h;the t1/2(ke) were (1.5?1.4),(12.1?1.0) and (3.5?0.5) h,and the AUC(0～t) were (618.1?57.7),(588.1?66.6) and (233.0?46.4) ?g?h?L-1 in imported capsule group, domestic capsule group and raw material group respectively. The relative bioavailability of domestic sustained release capsules of ibudilast is (95.6?11.0)%. Conclusion The results of statistical analysis demonstrate that the imported and domestic sustained capsules have significant character of significantly sustained release and are bioequivalent.

Adolescent ; Bacteria ; isolation & purification ; Child ; Child, Preschool ; Humans ; Infant ; Infant, Newborn ; Respiratory Tract Infections ; microbiology

Objective To observe whether the expression of interferon-regulatory factor genes are re- lated to systemic lupus erythematosus (SLE).Methods The clinical data of 45 SLE patients and 37 normal controls were collected.Total RNA of peripheral blood was extracted and transcripted into cDNA.Sybr green dye based real-time quantitative PCR method was used to compare the expression (indicated as-??Ct value) of IRFI,IRF4,IRF8 in patients with SLE and those in the controls.Results The levels of IRF1,IRF4 and IRF8 mRNA were-3.90?0.19,-8.04?0.25 and 3.60?0.15 respectively in normal controls.In SLE patients, IRF4 mRNA expression was -8.82?0.18,higher than that in normal (P=0.011).But IRF8 mRNA expression was 3.09?0.13,lower than that in normal (P=0.012).Conclusion Abnormal IRF mRNA expression is found in the peripheral blood of SLE patients.IRFs may play roles in the pathogenesis of SLE by affecting the differen- tiation of Th cells.

OBJECTIVETo study the changes of HBV markers and HBV DNA and the perioperative factors influencing them after orthotopic liver transplantation (OLT).

METHODSA retrospective study was undertaken. Data was collected from 97 patients in the First Affiliated Hospital of Sun Yat-sen University from March 1999 to October 2003. Patients were investigated on the 7-14, 14-30, 30-90, 90-180, 180-360 and 360- days after OLT. All the patients who received OLT were serum HBV positive before their operations.

RESULTSKinetic expressions of HBV serum marker and HBV DNA were established. A few patient's HBeAg was negative (8%) before their operation. Within 7 day following surgery, no patient was HBeAg positive. However, the rate of HBeAg positive increased on the 90-180 day following surgery. The postoperation time of taking lamivudine was different between patients with HBeAg seroconversion and of those without (U = 88.5). Peaks occurred within 14 d of HBsAg negative and 14-30 d of anti-HBs positive after operation. Then they decreased and minimized at 90-180 day after liver transplantation. Patients who suffered more bleeding during the operation were more likely to be anti-HBs positive (3800ml vs. 3000ml, U = 8193.0) and HBsAg negative in serum within 2 week (5200ml vs. 4200ml, U = 1648.5) after OLT. While patient's who received more blood transfusion (1000ml vs. 1600ml, U = 9796.0) during operation were not likely to be anti-HBs positive in serum after surgery. Furthermore, the time of infusing HBIg did not affect the state of anti-HBs (U = 1252.5). At the same time, there were no correlations between the change of HBsAg in serum and in the method of operation (chi2 = 0.042). During this process, presentation of anti-HBc changed a little.

CONCLUSIONThe advantages brought on by operative factors become blunt 7-14 d following OLT. More attention should be taken to avoid reinfection of HBV 90-180 day after OLT. Tyrosine-methionine-aspartic acid-aspartic acid (YMDD) mutation of HBV is more likely to occur when taking lamivudine longer. Then, HBV DNA should be monitored and a liver biopsy should be scheduled regularly after OLT.

Adult ; DNA, Viral ; blood ; Female ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; isolation & purification ; Hepatitis B, Chronic ; complications ; surgery ; Humans ; Liver Cirrhosis ; surgery ; virology ; Liver Transplantation ; Male ; Middle Aged ; Postoperative Period ; Retrospective Studies

Osteoclasts and osteoblasts are not exist alone,while communicating with each other through direct contact, diffusible paracrine factors and cell-bone matrix interaction. Co-culture system of osteoblast with osteoclast,including direct co-culture and indirect co-culture. It should be according to the ratio of osteoclasts and osteoblasts under the pathology, choosing the same species. Compared with lonely culture of osteoblasts or osteoclasts,co-culture system is much closer to the microenvironment in vivo. It benefits to explain the interactions between osteoblasts and osteoclasts, exploring molecular communication in bone diseases. It was mainly used to investigate the pharmacological mechanism of herbal and western medicine in bone remodeling. Some osteoporosis drugs (such as epimedium,sanchi, fructus psoraleae, ranelate strontium) not only promoted osteoblastic bone formation, but also inhibited osteoclastic bone resorption in the system,so as to balance bone homeostasis. At the same time,it has been used to study medical physics and assess biomedical materials in recent years. Considerably,the co-cultrue system will be used to study the subchondral bone remodeling and its pharmacological mechanism of herbal and western medicine in osteoarthritis.
Animals ; Bone Remodeling ; Cell Communication ; Coculture Techniques ; Humans ; Osteoblasts ; cytology ; Osteoclasts ; cytology

An anti-alpha-synuclein (alpha-SYN) monoclonal antibody produced in our laboratory was used to investigate the effect of repeated acute hypoxic treatments on the expression of alpha-SYN in the mouse cerebral cortex. Western blot analysis showed that the expression levels of alpha-SYN in the cortex changed accordingly upon hypoxic exposure times, as that the alpha-synuclein level significantly increased after the first hypoxic exposure and then dropped down to the background level after the fourth hypoxic exposure. Immunohistochemical staining revealed that the alpha-SYN-immunopositive substance was localized not only in the nerve endings, but also within the nuclei of some neurons. The cell density of the neurons with alpha-SYN immunopositive nuclei was increased significantly after the first hypoxic exposure but returned back to control levels after the fourth hypoxic exposure. Our results indicate that both of the alpha-SYN expression level in the brain and the number of the neurons with alpha-SYN positive nuclei are affected by the repeated acute hypoxic treatments and that this modification is hypoxic time-dependent. The mechanism and the physiological significance underlying these changes need to be further investigated.
Animals ; Brain ; blood supply ; Brain Ischemia ; metabolism ; Cerebral Cortex ; metabolism ; Ischemic Preconditioning ; Mice ; Mice, Inbred BALB C ; Nerve Tissue Proteins ; biosynthesis ; genetics ; Neurons ; metabolism ; Phosphoproteins ; biosynthesis ; genetics ; Random Allocation ; Synucleins ; alpha-Synuclein

Objective To observe the effect of stanozolol(ST) on long bone growth and maturation of pubertal female rats treated with gonadotropin releasing hormone agonist(GnRHa).Methods At 3 weeks of age,42 female Sprague-Dawley rats(brood) were divided into 7 groups(ST dosage groups,as 5 000 ?g/100 g group,200 ?g/100 g group,100 ?g/100 g group,50 ?g/100 g group,25 ?g/100 g group,solvent control group and blank control group)(n=6).Forty-eight female rats were divided into 8 groups(ST therapeutic duration)(n=6).Rats received 2.5 mg/kg im slow-released GnRHa(triptorelin,as 2 d group,3 d group,5 d group,7 d group,10 d group,13 d group,soluent control group and blank control group) which was repeated every 2 weeks for 2 times,3 days after the 2nd GnRHa(D1),ST dosage groups were subcutaneously administrated ST at the various dosage daily(D1-D13).ST therapeutic duration groups were subcutaneously administrated ST at the dosage of 100 ?g/100 g daily for different duration.All the rats were killed on the D14.On the day of sacrifice,body weight,body length and left tibial length were measured,plasma were taken for determining insulin-like growth factor-1(IGF-1),right tibia were fixed,demineralized and processed for paraffin-embedding.Paraff sections were HE stained for growth plate measurements.proliferating cell nuclear antigen(PCNA) on growth plate was analyzed with immunohistochemistry staining and image.Results 1.In the 5 000 ?g/100 g ST dosage group,the weight,Height and tibial length exceeded than those of the other dosage and control groups(Pa

OBJECTIVETo explore the effect of ITF2357, a novel histone deacetylase (HDAC) inhibitor, on the growth, differentiation and apoptosis of acute myeloid leukemic (AML) cells and its mechanism.

METHODSAML cell lines kasumi-1 cells as a model for AML1-ETO positive, and THP1 cells for AML1-ETO negative, the leukemic cells proliferation was analyzed by MTT assay, expression of myeloid-specific differentiation antigen and cell cycle by flow cytometry, cell apoptosis by annexin V staining and flow cytometry. AML1-ETO, acetyl-histone, and caspase protein was analyzed by Western blot.

RESULTS0.5 µmol/L ITF2357 treatment significantly inhibited kasumi-1 cells proliferation, with the 48 h half inhibitory concentration (IC(50)) of 0.1 µmol/L. The initial inhibitory concentration of THP1 cell line was 5 µmol/L. ITF 2357 induced apoptosis of kasumi-1 cells in a time- and dose-dependent manner. A dose-dependent increase in early apoptosis occurred at 24 hours treatment and in late apoptosis at 48 hours treatment by ITF2357. Early apoptosis cells increased from (1.44 ± 1.52)% to (24.51 ± 5.79)%. Late apoptosis cells increased from (2.37 ± 2.8)% to (63.66 ± 1.56)%. ITF2357 induced AML1-ETO degradation by caspase-dependent pathway. 0.25 µmol/L ITF2357 induced a time- and dose-dependent increase in expression of myeloid cell surface protein CD13 and CD15. 5 µmol/L ITF2357 blocked the cells at G(0)/G(1) phase, G(0)/G(1) cells increased from (39.69 ± 6.56)% to (79.2 ± 6.51)% and s-phase cells declined from (60.12 ± 3.29)% to (18.97 ± 6.62)%. Kasumi-1 cells incubated with 0.5 µmol/L of ITF2357, AML1-ETO protein began to decrease at 24 hours and could hardly be detected at 96 hours. ITF2357 induced AML1/ETO degradation through a caspase-dependent mechanism. At the same time, acetylated H3 and H4 increased.

CONCLUSIONLow-dose HDAC inhibitor ITF2357 can effectively inhibit the AML cells proliferation, especially for AML1-ETO positive AML cells. It inhibits Kasumi-1 cells proliferation degradation of AML1-ETO protein expression, blocks the cells at G(0)/G(1) phase, and induces apoptosis and differentiation of the cells.

Acetylation ; Apoptosis ; drug effects ; Cell Differentiation ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Histone Deacetylase Inhibitors ; pharmacology ; Histones ; metabolism ; Humans ; Hydroxamic Acids ; pharmacology ; Oncogene Proteins, Fusion ; metabolism

This study was aimed to analyze hemoglobin F (HbF) level and single nucleotide polymorphisms at rs11886868 locus of BCL11A gene in β-thalassemia patients, and to explore correlation between them. 89 mild β-thalassemia patients with known mutations were registered, and HbF levels were determined by capillary electrophoresis. Genomic DNA was extracted from peripheral leukocytes, fragment including rs11886868 locus in BCL11A gene was amplified by PCR, and polymorphism was determined by DNA sequencing. The results showed that 2 polymorphisms including C and T were found at rs11886868 locus in BCL11A gene among 89 mild β-thalassemia patients. HbF levels in red blood cells were (4.47 ± 3.42)% and (2.79 ± 2.21)% for β-thalassemia patients carrying C/C and C/T haplotypes, respectively. There was difference between 2 haplotype groups. It is concluded that the C and T polymorphisms are found at rs11886868 locus in the BCL11A gene for β-thalassemia patients. C polymorphism may be related to high HbF expression in red blood cells.
Adolescent ; Adult ; Carrier Proteins ; genetics ; Child ; Female ; Fetal Hemoglobin ; metabolism ; Haplotypes ; Humans ; Male ; Middle Aged ; Nuclear Proteins ; genetics ; Polymorphism, Single Nucleotide ; Young Adult ; beta-Thalassemia ; blood ; genetics