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To investigate whether accelerated blood clearance (ABC) phenomenon could be induced after repeated injection of mitoxantrone thermosensitive liposomes, LC-MS/MS and enzyme linked immunosorbent assay (ELISA) were used to measure the concentration of mitoxantrone and the anti-polyethylene glycol (PEG) IgM levels in rat plasma, separately. The drug was rapidly cleared away after the second administration. The anti-PEG IgM was detected after the first dose which was neutralized quickly after the second dose. It is proved that repeated administration of mitoxantrone thermosensitive liposomes in rat caused the ABC phenomenon.
Animals ; Antineoplastic Agents ; administration & dosage ; blood ; pharmacokinetics ; Chromatography, High Pressure Liquid ; Immunoglobulin M ; blood ; Liposomes ; administration & dosage ; blood ; pharmacokinetics ; Male ; Metabolic Clearance Rate ; Mitoxantrone ; administration & dosage ; blood ; pharmacokinetics ; Polyethylene Glycols ; administration & dosage ; chemistry ; pharmacokinetics ; Rats ; Rats, Wistar ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry

In order to determine the challenge dose of pigeon paramyxovirus type 1 (PPMV-1) inactivated vaccine (S-1 strain). The virus titer of PPMV-1 E5 allantoic fluid (Chuansha strain) was determined using SPF chicken embryos in this research. After inoculating 30-day-old and 120-day-old pigeons with low-HI antibody against PPMV-1 (HI antibody < or =2) with different doses of PPMV-1 (Chuansha strain), the clinical symptoms and histopathological lesions of the challenged pigeons were examined. The results showed that the minimal lethal dose (MLD) of PPMV-1 (Chuansha strain) was 102.5 ELD50, so we determined that 10(5.5) ELD50, which was 1000 times the MLD, could be taken as the challenge dose in the vaccine efficacy test for PPMV-1 inactivated vaccine (S-1 strain).
Animals ; Antibodies, Viral ; immunology ; Bird Diseases ; immunology ; mortality ; virology ; Chick Embryo ; Columbidae ; immunology ; virology ; Newcastle Disease ; immunology ; mortality ; virology ; Newcastle disease virus ; immunology ; pathogenicity ; Phylogeny ; Viral Vaccines ; immunology ; Virulence

Objective To evaluate the efficacy and safety of infliximab plus methotrexate combination therpy in Chinese with rheumatoid arthritis patients.Methods This was a double-blind placebo-controlled phaseⅢclinical trial,173 patients who had active rheumatoid arthritis were randomised to placebo(n=86)or infliximab(n=87)group on a background of a stable dosage of methotrexate.Patients were assessed at weeks 0,2,6,14 and 18.Results At week 2,the American College of Rheumatology(20)response criteria,which represent a 20% improvement from baseline,the same results with swollen joint count,tender joint count,du- ration of morning stiffness,VAS score,CRP,ESR were achieved in 52.9% of patients,compared with 14.0% of patients receiving placebo plus methotrexate.A 20% improvement was achieved in 75.9% of infliximab plus methotrexate at week 18,compared with 48.8% of patients on placebo plus methotrexate(P=0.0003).A 50% improvement was achieved in 43.7% of infliximab plus methotrexate at week 18,compared with 25.6% of pa- tients on placebo plus methotrexate(P=0.011).Infliximab was well-tolerated;withdrawals for adverse events as well as the occurrence of serious adverse events or serious infections were similar to those in the placebo group.There was only one case of tuberculosis in the treatment group.Conclusion Treatment with infliximab plus methotrexate is more effective than methotrexate alone in patients with active rheumatoid arthritis.It has rapid onset of effect and the efficacy is persistent.

Objective To evaluate the efficacy and safety of PES14LF polyethersulfone highflux dialyzer on maintenance hemodialysis(MHD)patients. Methods A total of 72 MHD patients from two hospitals in Shanghai were enrolled in a randomized parallel controlled study.Conventional hemodialysis was performed for 4 h with PES14LF dialyzer in trial group and with German F6 dialyzer in control group.For each patient the study lasted one week.The clearances of urea,creatinine and phosphate were calculated.Adverse event and adverse reaction were recorded.Results There were no significant difierences of urea and creatinine clearance and reduction ratio between trial and control group.The phosphate clearance in trial group was significantly higher than that in control group[(144.57±27.83)ml/min vs(117.15±22.77)ml/min,P＜0.051.There was no significant difference of phosphate reduction ratio between trial and control group.The efficiency of urea clearance and urea reduction ratio achieved clinic effective target in two groups and no significant differences in above indexes between two groups were found. Conclusion PES14LF dialyzer is effective and safe for clinical application.

OBJECTIVETo investigate the inhibitory effects of OMT on TGF-β1-induced CFBs proliferation, and then explore the mechanism.

METHODThe experiment was randomly divided into 6 groups as following: control group (serum free DMEM), model group (20 μg x L(-1) TGF-β1), OMT low dose group (1.89 x 10(-4) mol x L(-1) + 20 μg x L(-1) TGF-β1), OMT medium dose group (3.78 x 10(-4) mol x L(-1) + 20 μg x L(-1) TGF-β1), OMT high dose group (7.56 x 10(-4) mol x L(-1) + 20 μg x L(-1) TGF-β1), SB203580 group (p38MAPK blocking agent, 1 x 10(-5) mol x L(-1) + 20 μg x L(-1) TGF-β1). Vimentin of CFBs was identified by immunocytochemical methods, α-SMA of myFBs as well. Inhibitory effects of OMT on CFBs proliferation was detected by the MTT assay. Picric acid Sirius red staining was analyzed collagen type I and collagen type III deposition. Western blot was determined the expression of p38MAPK, p-p38MAPK, collagen type I and collagen type III.

RESULTMTT results showed that OMT significantly inhibited CFBs proliferation induced by TGF-β1 (P < 0.01) α-SMA immunocytochemical experiments suggested that OMT could protect against the CFBs proliferation. OMT could significantly decrease the deposition of collagen type I and collagen type III by Western bloting and picric acid Sirius red staining. Western blot results showed that TGF-β1 enhanced p38MAPK phosphorylation, however OMT attenuated the phosphorylation of p38MAPK induced by TGF-β1 (P < 0.01).

CONCLUSIONOMT can inhibit the CFBs proliferation induced by TGF-β1, and its mechanism may be involved in inhibiting p38MAPK phosphorylation.

Alkaloids ; pharmacology ; Animals ; Cell Proliferation ; drug effects ; Collagen ; metabolism ; Down-Regulation ; Female ; Fibroblasts ; drug effects ; Heart ; drug effects ; In Vitro Techniques ; Male ; Phosphorylation ; Quinolizines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; antagonists & inhibitors ; p38 Mitogen-Activated Protein Kinases ; antagonists & inhibitors ; metabolism

Adolescent ; Adult ; Aged ; China ; epidemiology ; Female ; Genes, Viral ; Genotype ; Hepacivirus ; genetics ; Hepatitis C, Chronic ; epidemiology ; Humans ; Male ; Middle Aged ; Young Adult

Objective To discuss the active role of health education on control of diabetes mdlitus and prevention of its complications.Methods 96 cases of hospitalized patients with diabetes mellitus were randomly divided into the control group and the observation group with 48 patients in each group from June 2009 to June 2010.The control group received conventional diabetes treatment and distribution of health education brochures,based on this,the observation group was given health education,including cognitive,nutrition,behavioral intervention.The general prevention condition of diabetes and its complications as well as the education effect were compared before the education and six months after education.Results The fasting blood glucose,2-hour postprandial blood glucose,glycosylated hemoglobin,body mass index and incidence of complications were greatly improved in the observation group than those of the control group.Conclusions Strengthening health education can improve self-care ability of patients,effectively improve the overall control level of diabetes,reduce acute and chronic complications,disability,death rate.

OBJECTIVETo study the effect of PGC-1alpha in human liver carcinogenesis, and explore the regulatory role of PGC-1alpha in the development of liver cancer.

METHODSThe changes of PGC-1alpha mRNA level in normal human liver tissues and human liver tumors was examined by quantitative RT-PCR. PGC-1alpha mRNA level was interfered by siRNA in human liver cell line L02 in vitro, and their morphological changes were observed by pathology with HE staining. The ultrastructure of cells was observed by electron microscopy. In addition, the gene expression pattern of decreasing PGC-1alpha in L02 cells and liver tumor tissue was compared by human genome 70-mer oligonucleotide microarray analysis.

RESULTSPGC-1alpha expression was weaker in the malignant liver tumors compared with that in normal liver tissues. When PGC-1alpha expression was suppressed in human liver L02 cells, the cells became smaller with enlarged nuclei, and myelin figures were observed in mitochondria by electron microscopy, similar with the ultrastructure of liver cancer cells. Microarray analysis showed that the decrease of PGC-1alpha in L02 cells induced up-regulation of some oncogenes and adhesive genes, and down-regulation of a number of tumor suppressor genes and cell proliferation suppressor genes. The changes of decreasing expression pattern of PGC-1alpha gene in L02 cells were similar to those in human liver cancer tissue.

CONCLUSIONThe results of the present study show that PGC-1alpha is down-regulated in liver cancers and is involved in the malignant transformation in human normal liver cells in vitro, suggesting an important regulatory role of PGC-1alpha in the development of liver cancer.

Adult ; Carcinoma, Hepatocellular ; metabolism ; pathology ; ultrastructure ; Cell Line, Tumor ; Cell Transformation, Neoplastic ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Heat-Shock Proteins ; genetics ; metabolism ; Humans ; Liver ; metabolism ; pathology ; Liver Neoplasms ; metabolism ; pathology ; ultrastructure ; Male ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; RNA Interference ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; Transcription Factors ; genetics ; metabolism

Objective A resistin binding peptide (RBP) was selected by phage display in our previous work. Studies had shown that RBP could antagonize the role of resistin on the lipid metabolism and endocrine function of adipose tissue, but whether RBP affects the insulin secretion of pancreatic cells is still unknown. The aim of this study is to assess the effect of RBP on basal insulin secretion in RINm5F insulinoma cells. Methods The cell viability was measured by 3-[4,5-dimethyhhiazol-2-yl]-2,5-diphenyltetra-zolium bromide (MTT) cytotoxicity assay. The supernatants were assayed for insulin content by enzyme linked immunosorbent assay (ELISA). Reverse transcriptase-PCR assay and Western blotting were used to determine the expression of glucose transporter 2 (GLUT2) involved in insulin secretion. Cytosolic Ca2+, the trigger of insulin exocytosis, was analyzed with the fluorescent probe FURA-3/AM. Results RBP did no effect on the cell viability with a concentration of 10-8-10-12mol/L of 2 hours intervention. But it stimulated basal insulin secretion of RINm5F cells, accompanied by up-regulated increased expression of GLUT2 and elevated concentration of cytosolic Ca2+. Conclusion RBP could stimulate basal insulin secretion without affecting the cell viability.