OBJECTIVE:To study the pharmacokinetics of oral single dose adefovir dipivoxil(ADV) tablet in Chinese healthy volunteers.METHODS:The study was a randomized,open,three-way crossover study.Twelve healthy volunteers were randomly assigned to receive single oral dose of 5 mg(Group A),10mg(Group B) or 30 mg(Group C) ADV tablets in three weeks.The plasma concentrations of ADV were determined by LC/MS/MS method.The pharmacokinetic parameters were computed.RESULTS:The main pharmacokinetic parameters in Group A,B and C were as follows:Cmax were(11.4? 3.7),(25.4? 8.2) and(76.3? 23.0) ng? mL-1;tmax were(1.69? 1.41),(0.90? 0.56) and(0.94? 0.50) h;AUC0～ t were(102.7? 51.7),(235.0? 82.3) and(715.4? 267.6) ng? h.mL-1;AUC0～ ∞ were(168.7? 30.7),(266.2? 83.7) and(741.5? 273.9) ng? h? mL-1,respectively.CONCLUSION:ADV tablets had a rapid absorption in healthy volunteers and the Cmax and AUC of adefovir tablets were directly correlated to doses.It is safe for healthy volunteers to take ADV tablets at a dose of 5～30mg.

To investigate the effects of Yiguanjian Decoction, a compound traditional Chinese herbal medicine, on rats with cirrhosis based on the method of differential proteomics.

Objective: To investigate the effects of Yiguanjian Decoction, a compound traditional Chinese herbal medicine, on collagen metabolism of hepatic tissues in rats with carbon tetrachloride (CCl(4))-induced liver fibrosis. Methods: Liver fibrosis was induced in rats by intraperitoneal injection of 50% CCl(4)-olive oil solution at a dose of 1 mL/kg body weight, twice per week for 9 consecutive weeks. Six rats were sacrificed for dynamic observation at the end of the 3rd and 6th week respectively, and the other rats were divided into 9-week untreated group and Yiguanjian Decoction group which was given Yiguanjian Decoction intragastrically in the subsequent 3-week modeling period. Another 6 rats were used as normal group. Rats in the normal group and 9-week untreated group were treated with distilled water. At the end of the 9th week, all rats were sacrificed, and their blood serum and liver tissue were collected for measuring hepatic histology and expressions of α-smooth muscle actin (α-SMA), tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, matrix metalloproteinase (MMP)-13, MMP-14, collagen type I (Col I), and activities of MMP-2 and -9. Results: Compared with the normal group, collagen fiber deposition, expressions of α-SMA, Col I, TIMP-1, TIMP-2, MMP-13 and MMP-14 and activities of MMP-2 and -9 in the liver tissues gradually increased in the untreated group (P<0.05, P<0.01). These changes were significantly suppressed by Yiguanjian Decoction. Conclusion: Yiguanjian Decoction exerts inhibition on formation of CCl(4)-induced cirrhosis in rats. The therapeutic mechanism may be related to inhibiting hepatic stellate cell activation, collagen secretion, and promoting collagen fiber degradation.

Appropriate selection and measurement of lead biomarkers of exposure are critically important for health care management purposes, public health decision making, and primary prevention synthesis. Lead is one of the neurotoxicants that seems to be involved in the etiology of psychologies. Biomarkers are generally classified into three groups: biomarkers of exposure, effect, and susceptibility.The main body compartments that store lead are the blood, soft tissues, and bone; the half-life of lead in these tissues is measured in weeks for blood, months for soft tissues, and years for bone. Within the brain, lead-induced damage in the prefrontal cerebral cortex, hippocampus, and cerebellum can lead to a variety of neurological disorders, such as brain damage, mental retardation, behavioral problems, nerve damage, and possibly Alzheimer's disease, Parkinsons disease, and schizophrenia. This paper presents an overview of biomarkers of lead exposure and discusses the neurotoxic effects of lead with regard to children and adults.
Alzheimer Disease ; chemically induced ; metabolism ; pathology ; physiopathology ; psychology ; Animals ; Behavior ; drug effects ; Biomarkers ; metabolism ; Brain ; metabolism ; pathology ; physiopathology ; Brain Diseases ; chemically induced ; pathology ; physiopathology ; Environmental Exposure ; adverse effects ; Humans ; Lead ; pharmacokinetics ; toxicity ; Lead Poisoning ; etiology ; metabolism ; pathology ; physiopathology ; psychology ; Neurotoxicity Syndromes ; etiology ; metabolism ; pathology ; physiopathology ; psychology ; Parkinson Disease, Secondary ; chemically induced ; metabolism ; pathology ; physiopathology ; psychology ; Schizophrenia ; chemically induced ; metabolism ; pathology ; physiopathology

Apoptosis ; drug effects ; Cell Division ; drug effects ; Esophageal Neoplasms ; pathology ; Humans ; Selenomethionine ; pharmacology ; Tumor Cells, Cultured

Objective To explore the correlation between-173G/C gene polymorphism of macrophage migration inhibitory factor(MIF) and Henoch-Schonlein purpura(HSP),Henoch-Schonlein purpura nephritis(HSPN) in children in Jiangxi Province.Methods One hundred and thirty-one ethnic Han children with HSP were enrolled,including 80 children with concurrent nephritis(HSPN group) and 51 children without nephritis(HSP without nephritis group).One hundred and five healthy children were used as the healthy control group.Germline DNA was extracted from peripheral blood by Promega blood genomic DNA kit.Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) was used for genotyping the-173G/C polymorphism of MIF.Genotype distribution and allele frequencies were obtained by direct counting.Statistical analysis was performed by using SPSS 11.5 software.Allele and genotype distribution were compared by using the chi-square test.The relative risk of allele was described by odds ratios(OR) and 95% confidence intervals(95%CI).Results Three genotypes(GG,GC,CC) were detected in MIF-173 G/C.GG,GC genotypes were detected in HSP without nephritis and healthy control group.GG,GC and CC genotypes were detected in HSPN group.Mutant genotype(37.5%) and C allele frequency(20.0%) in HSPN group were significantly higher than those in healthy control group(20.0% and 10.0%,respectively)(?2=6.964,7.400,Pa

Objective To examine the composition and distribution of animal reservoir of plague in Quanzhou city, Fujian province, and so as to accumulate basic data for making the plague prevention and control measures. Methods Rodents were captured by cages in six monitoring spots of Quanzhou city between 2000 and 2009. Then rodents and flea species were identified. Rats liver and spleen homogenates were detected of plague F1 antigen by reverse indirect hemagglutination test (RIHA); rats serum were detected of plague F1 antibody by indirect hemagglutination test (IHA). ResultsA total of 26 264 rodents were captured between 2000 and 2009.Rattus norvegicus and Rattus flavipectus were dominant species, which were accounted for 45.97％ (12 074/26 264)and 32.01％(8407/26 264), respectively. The account of Rattus flavipectus captured between 2005 and 2009 was (26.99 ± 2.46)％ and (37.03 ± 3.79)％ between 2000 and 2004. The difference was statistically significant (t =4.97, P ＜ 0.05). Total rodent densities was (6.86 ± 1.44)％, including(5.36 ± 1.83)％ in mountains and (6.81 ±1.66)％ in coastal areas, respectively, and the difference was not statistically significant(t =1.01, P ＞ 0.05). Total flea index and flea infection rate of rodents were 1.39 ± 0.34 and (35.90 ± 5.34)％, respectively. Xenopsylla Cheopis index was 1.20 and free flea index was 0.009. Flea infection rate was (32.36 ± 0.96)％ between 2005 and 2009, which was lower than (39.44 ± 0.39)％ between 2000 and 2004(t =2.76, P ＜ 0.05). ConclusionsThe major rodent species found in Quanzhou city is Rattus norvegicus. Xenopsylla Cheopis is the dominant flea species.Spreading of plague among Rattus is not found.

OBJECTIVETo develop a novel gene delivery vector TAT-PEI-beta-CyD.

METHODSbeta-cyclodextrin (beta-CyD) was linked by low molecular weight (PEI 600) via 1, 1-carbonyldiimidazole (CDI), and TAT peptide (RRRQRRKKRC) was coupled to PEI 600 by [N-succinimidy-3-(2-pyridyldithio) propionate, SPDP]. The copolymer was characterized by (1)H-NMR and FT-IR. Physiochemical characteristics of TAT-PEI-beta-CyD/DNA complexes were tested by agarose gel electrophoresis and particle size measurements. Cell viability and transfection efficiency were evaluated in A293 and B16 cells using PEI 25 kDa as a control.

RESULTTAT peptide was successfully coupled to PEI-beta-CyD. The result of gel electrophoresis showed that the TAT-PEI-beta-CyD was able to condense DNA efficiently at N/P ratio of 4. The particle size of TAT-PEI-beta-CyD/DNA complexes was around 100 nm. The cytotoxicity of TAT-PEI-beta-CyD was lower than that of PEI 25 kDa. The transfection efficiency of TAT-PEI-beta-CyD was higher than that of PEI 25 kDa in A293 and B16 cells at N/P ratio of 30.

CONCLUSIONThe novel vector TAT-PEI-beta-CyD has been developed successfully with low cytotoxicity and high transfection efficiency.

Cell Line ; Gene Transfer Techniques ; Genetic Therapy ; methods ; Humans ; Peptide Fragments ; chemistry ; Polyethyleneimine ; chemistry ; beta-Cyclodextrins ; chemistry ; tat Gene Products, Human Immunodeficiency Virus ; chemistry

OBJECTIVETo develop a novel non-viral gene delivery vector based on polyethylenimine and beta-cyclodextrin targeting to Her-2 receptor (MC10-PEI-beta-CyD).

METHODSThe PEI-beta-CyD was synthesized by low molecular weight polyethylenimine (PEI, Mw 600) cross-linked beta-cyclodextrin (beta-CyD) via N, N-carbonyldiimidazole (CDI). The chemical linker[N-succinimidy-3-(2-pyridyldithio) propionate, SPDP] was used to bind peptide MC10 (MARAKEGGGC) to PEI-beta-CyD to form the vector MC10-PEI-beta-CyD. The (1)H-NMR was used to confirm the structure of vector. The DNA condensing ability,and the particle size of MC10-PEI-beta-CyD/DNA complexes were demonstrated by gel retardation assay and electron microscope observation (TEM). Cell viability was tested by MTT assay. The transfection efficiency was determined on cultured SKOV-3, A549 and MCF-7 cells.

RESULTMC10 was linked onto PEI-beta-CyD successfully. The vector was able to condense DNA at N/P ratio of 5 and particle size was about (170 +/-35)nm. The vector showed low cytotoxicity and high transfection efficiency in cultured SKOV-3, A549 and MCF-7 cells.

CONCLUSIONA novel non-viral vector MC10-PEI-beta-CyD with low cytotoxicity and high transfection efficiency has been successfully synthesized.

Cell Line ; Gene Targeting ; Gene Transfer Techniques ; Genetic Vectors ; Humans ; Peptides ; chemistry ; Polyethyleneimine ; chemistry ; pharmacology ; Receptor, ErbB-2 ; genetics ; beta-Cyclodextrins ; chemistry

OBJECTIVETo construct a drug carrier and gene vector PEG-PEI-Pt.

METHODSPolyethyleneglycol (PEG) was coupled to polyethylenimine (PEI 600) and platinum tetrachloride; PEG-PEI-Pt complex was formed in ethanol. The complex was characterized by XRD, UV-VIS and FT-IR and the DNA condensation was tested by electrophoretic mobility shift assay. The cell viability was evaluated by MTT assay in Hela, B16, A293 and COS-7 cells and in vitro transfection efficiency was measured in A293 and B16 cells.

RESULTThe structure of PEG-PEI-Pt was characterized by XRD, UV-VIS and FT-IR. PEG-PEI-Pt complex was able to bind DNA at N/P weight ratio of 0.4:1; the complex showed cytotoxicity on Hela and B16 cells. The complex had higher transfection efficiency in A293 and B16 cells than PEI 600.

CONCLUSIONA novel drug carrier and gene vector PEG-PEI-Pt was constructed successfully.

Cell Line ; Drug Carriers ; chemical synthesis ; Gene Transfer Techniques ; Genetic Therapy ; methods ; Humans ; Platinum Compounds ; chemistry ; Polyethylene Glycols ; chemistry ; Polyethyleneimine ; chemistry ; Transfection