ABSTRACT
This study developed a population pharmacokinetic model for sodium tanshinone IIA sulfonate (STS) in healthy volunteers and coronary heart disease (CHD) patients in order to identify significant covariates for the pharmacokinetics of STS. Blood samples were obtained by intense sampling approach from 10 healthy volunteers and sparse sampling from 25 CHD patients, and a population pharmacokinetic analysis was performed by nonlinear mixed-effect modeling. The final model was evaluated by bootstrap and visual predictive check. A total of 230 plasma concentrations were included, 137 from healthy volunteers and 93 from CHD patients. It was a two-compartment model with first-order elimination. The typical value of the apparent clearance (CL) of STS in CHD patients with total bilirubin (TBIL) level of 10 μmol(L was 48.7 L(h with inter individual variability of 27.4%, whereas that in healthy volunteers with the same TBIL level was 63.1 L(h. Residual variability was described by a proportional error model and estimated at 5.2%. The CL of STS in CHD patients was lower than that in healthy volunteers and decreased when TBIL levels increased. The bootstrap and visual predictive check confirmed the stability and validity of the final model. These results suggested that STS dosage adjustment might be considered based on TBIL levels in CHD patients.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Bilirubin , Blood , Coronary Disease , Drug Therapy , Metabolism , Drugs, Chinese Herbal , Pharmacokinetics , Metabolic Clearance Rate , Models, Biological , Phenanthrenes , Blood , PharmacokineticsABSTRACT
Diabetic cardiomyopathy (DCM), a serious complication of diabetes mellitus, is associated with changes in myocardial structure and function. This study sought to explore the ability of insulin-like growth factor-1 (IGF-1) to modulate DCM and its related mechanisms. Twenty-four male Wistar rats were injected with streptozotocin (STZ, 60 mg/kg) to mimic diabetes mellitus. Myocardial fibrosis and apoptosis were evaluated by histopathologic analyses, and relevant proteins were analyzed by Western blotting. Inflammatory factors were assessed by ELISA. Markers of oxidative stress were tested by colorimetric analysis. Rats with DCM displayed decreased body weight, metabolic abnormalities, elevated apoptosis (as assessed by the bcl-2/bax ratio and TUNEL assays), increased fibrosis, increased markers of oxidative stress (MDA and SOD) and inflammatory factors (TNF-α and IL-1β), and decreased phosphorylation of Akt and glycogen synthase kinase (GSK-3β). IGF-1 treatment, however, attenuated the metabolic abnormalities and myocardial apoptosis, interstitial fibrosis, oxidative stress and inflammation seen in diabetic rats, while also increasing the phosphorylation levels of Akt and GSK-3β. These findings suggest that IGF-1 ameliorates the pathophysiological progress of DCM along with an activation of the Akt/GSK-3β signaling pathway. Our findings suggest that IGF-1 could be a potential therapeutic choice for controlling DCM.
Subject(s)
Animals , Humans , Male , Rats , Apoptosis , Blotting, Western , Body Weight , Diabetes Mellitus , Diabetic Cardiomyopathies , Enzyme-Linked Immunosorbent Assay , Fibrosis , Glycogen Synthase Kinases , In Situ Nick-End Labeling , Inflammation , Insulin-Like Growth Factor I , Oxidative Stress , Phosphorylation , Rats, Wistar , StreptozocinABSTRACT
To construct Fv antibodies against H5N1 Avian influenza virus hemagglutinin,extracted mRNA from B lymphoblastoid cell lines secreting anti-HA antibodies was used and the VH and VL genes were amplified by RT-PCR and linked together by splicing overlap extension (SOE) with (Gly4 Ser)3 linker. The recombinant plasmid was then transformed to E. coli BL21(DE3) and sequence analysis indicated the total length of scFv was 714 bp and the expression of Fv was validated by PAGE and Western blot.
Subject(s)
Animals , Mice , Antibodies , Genetics , Metabolism , Pharmacology , Birds , Cloning, Molecular , Escherichia coli , Genetics , Metabolism , Gene Expression Regulation , Hemagglutinins , Allergy and Immunology , Immunoglobulin Heavy Chains , Genetics , Immunoglobulin Light Chains , Genetics , Immunoglobulin Variable Region , Genetics , Metabolism , Influenza A Virus, H5N1 Subtype , Allergy and Immunology , Influenza in Birds , Virology , Mice, Inbred BALB C , Recombinant Fusion Proteins , Genetics , Metabolism , Pharmacology , Reverse Transcriptase Polymerase Chain Reaction , Viral Proteins , Allergy and ImmunologyABSTRACT
C57BL/6 mice were inoculated intranasally (50 microl) with serial 10-fold dilution of HAB/01 H5N1 virus. Three and five days later, three mice of each group were euthanized. Lung injury was assessed by observation of lung histopathology, virus titers and MCD50 were also measured. Our data showed that H5N1 viral infection in mice resulted in mainly epithelial injury and interstitial pneumonia, featuring significant weight loss, dramatically increased lung wet weight:body weight ratio, inflammatory cellular infiltration, alveolar and interstitial edema, hemorrhage in lungs with high virus titers, and MCD50 was 10(-6.5)/ 0.05 mL. These results suggested that a mouse model of H5N1 viral infection was successfully established which may benefit study of H5N1 avian influenza virus and pathogenic mechanism of host.
Subject(s)
Animals , Female , Humans , Mice , Brain , Pathology , Virology , Disease Models, Animal , Influenza A Virus, H5N1 Subtype , Virulence , Influenza, Human , Pathology , Virology , Liver , Pathology , Virology , Lung , Pathology , Virology , Mice, Inbred C57BL , Random Allocation , Spleen , Pathology , VirologyABSTRACT
<p><b>OBJECTIVE</b>To evaluate emergency prophylactic effects of the avian influenza virus immunized serum on experimentally infected mice.</p><p><b>METHODS</b>Serum HI antibody titers of 30 mice were detected at day 1 to 19 after being inoculated with 0.2 ml immune serum to estimate half life of immune serum. Ten mice clinical symptom was recorded to estimate the serum security after mice injected 1.5 ml immune serum. Seventy mice were randomly divided into 7 groups according to random number table and inoculated with 0.2 ml, 0.1 ml and 0.05 ml immune serum respectively via intraperitoneal injection on day 8, 4 and 1 prior to challenged with 10 LD(50) influenza virus intranasal. Mice were observed continually for 14 days to calculate the morbidity, mortality, average survival days and compare the lung index and viral titers in lung.</p><p><b>RESULTS</b>Serum HI antibody titers of mice which inoculated with 0.2 ml immune serum maintained 2(6) in 15 days after injection, but drawdown after day 17, the mice injected 1.5 ml immune serum were all alive and none onset. The survival rate of mice which injected 0.2 ml serum on the day 8, 4, 1 before challenge was 80%, 100% and 100%, and the average survival period was 13.1 days, 14.0 days and 14.0 days respectively. The survival rate of mice which injected 0.1 ml and 0.05 ml serum on day 1 before challenge was 100% and 50%, and the average survival days were 14.0 days and 11.7 days respectively. The mice lung index of experimental groups (0.0096 +/- 0.0033 - 0.0145 +/- 0.0060) was smaller than that of viral control group (0.0199 +/- 0.0025), with a statistical significance (P value 0.0022 - 0.0470, < 0.05). The viral titers in lung were significantly decreased by 2 titer as compared to the viral controls.</p><p><b>CONCLUSION</b>The avian influenza virus immunized serum might contain the emergency prophylactic effects and could be developed as an agent for possible human-avian influenza pandemic.</p>