ABSTRACT
Objective: To study the long-term (iv for 30 days) toxic effect of recombinant batroxobin (rBAT) on Macaca mulatta. Methods: Twenty-four Macaca mulatta (12 male and 12 female) were randomly divided into 4 groups according to their body weights (n=6): rBAT treatment groups (1.5, 5.0, 15.0 kU/kg of rBAT once daily for 30 consecutive days through iv injection) and acetate buffer treatment group (as control). Half of the animals in each group were sacrificed at the end of medication and the rest were sacrificed after another 15 days' recovery. The general symptoms, the hematological, chemical parameters, urinalysis values, ECG results, bone marrow findings, pathologic changes and the antibody detection were observed or performed in all groups. Results: On d15 and d30, the blood samples of each group were collected at 30 min and 24 h after iv injection. Compared with control group or with d0 data of each corresponding group, the fibrinogen (Fib) was significantly decreased 30 min after iv injection of rBAT, and the decrease was in a dose-dependent manner. Fib returned to the normal level 24 h after iv injection. Histopathological examination showed congestion and slight edema of liver and kidney cells in each group, probably due to latent infection of the animals. On d30, there was local inflammatory reaction in the injection sites of some animals in each group, but none was found on d45. Non-neutralizing antibodies to rBAT were continuously detected from d15 to d45. Conclusion: rBAT has pharma cological and toxicological effects on hematology system of Macaca mulatta. It can dose-dependently decrease Fib. The target organ of rBAT is the hematology system and the effect of rBAT is reversible. The safety dose of rBAT for Macaca mulatta is 1.5 kU/ kg. Attention should be given when rBAT is used clinically.
ABSTRACT
In our previous work we reported that HIV Tat and 6 cysteine rich peptides of Tat induce tumor necrosis factor-related apoptosis-induced ligand (TRAIL) in human monocytes (Yang et al., 2003). Here our results showed that HIV Tat and Tat cysteine rich peptide increase CCR5 expression in human monocytes, and this activity is inhibited by rabbit anti-Tat. Boiled Tat does not increase CCR5 expression in monocytes. These results provide insight into a new mechanism by which HIV Tat plays a key role in the pathogenesis of HIV-1 infection.
Subject(s)
Humans , Amino Acid Sequence , Cells, Cultured , Cysteine , Chemistry , Dose-Response Relationship, Drug , Extracellular Fluid , Chemistry , Gene Expression Regulation , Physiology , Gene Products, tat , Chemistry , Pharmacology , Molecular Sequence Data , Monocytes , Metabolism , Peptides , ChemistryABSTRACT
<p><b>OBJECTIVE</b>To investigate the influence of lipopolysaccharide (LPS) on macrophages expressing TNF-alpha related apoptosis induced-ligand (TRAIL) and its relation to apoptosis of HepG2 cell line.</p><p><b>METHODS</b>Membrane-bound TRAIL (mTRAIL) was measured by flow cytometry; soluble TRAIL in supernatant was detected by enzyme-linked immunoabsorbent sandwich assay (ELISA); cytotoxicity of TRAIL to HepG2 cell line was measured by chromium release assay, and apoptosis of HepG2 cell was confirmed by Annexin V staining.</p><p><b>RESULTS</b>LPS only slightly increased membrane-bound TRAIL expression of macrophages. On the other hand, soluble TRAIL in the supernatant was increased with LPS stimulation, and the optimal concentration of LPS was 100 ng/ml (sTRAIL value 67.40 ng/ml+/-5.08 ng/ml). The soluble TRAIL in the supernatant was cytotoxic to HepG2 cells, and this activity can be blocked by TRAIL neutralizing antibodies.</p><p><b>CONCLUSION</b>LPS increases the expression of soluble TRAIL in macrophages, and soluble TRAIL is toxic to HepG2 cells. All of our results indicate that TRAIL may play an important role in the pathogenesis of viral hepatitis.</p>
Subject(s)
Humans , Apoptosis , Carcinoma, Hepatocellular , Pathology , Enzyme-Linked Immunosorbent Assay , Lipopolysaccharides , Pharmacology , Liver Neoplasms , Pathology , Macrophages , Metabolism , TNF-Related Apoptosis-Inducing Ligand , Genetics , Pharmacology , Tumor Cells, CulturedABSTRACT
<p><b>OBJECTIVE</b>To study the effects of HIV Tat protein on CCR5 expression of monocytes and HIV infection in monocytes.</p><p><b>METHODS</b>Membrane expression of CCR5 on monocytes was analyzed by flow cytometry. Stimulated with HIV Tat protein, monocytes were infected with monocyte-tropic HIV(Ba-L) and HIV gag p24 level in the supernatant was measured by ELISA methods.</p><p><b>RESULTS</b>HIV Tat protein increased CCR5 expression in human monocytes,which was inhibited by rabbit anti-Tat polyclonal antibody. Tat protein also increased p24 level after monocyte-tropic HIV-1(Ba-L) infected monocytes.</p><p><b>CONCLUSION</b>Tat increases CCR5 expression and HIV-1 infection in monocytes, which indicates that HIV Tat might be a key protein in HIV-1 infection.</p>
Subject(s)
Humans , Flow Cytometry , Gene Products, tat , Pharmacology , HIV , HIV Infections , Metabolism , Monocytes , Metabolism , Receptors, CCR5 , Genetics , tat Gene Products, Human Immunodeficiency VirusABSTRACT
Objective:To investigate the long-term toxicity of recombinant human interleukin-11(rhIL-11) in cynomolgus. Methods: Eighteen cynomolgus were randomized into 4 groups: control group(2/sex), low dose group(2/sex), medium dose group(2/sex)， and high dose group(3/sex). The drug groups were sc adminstered 0.1, 0.3 and 1.0 mg/kg of rhIL-11 for 90 days with a 30-day recovery period. The clinical signs were observed, electrocardiogram, hematological, biochemical, urinary and immunological parameters were measured, organ masses were weighed, bone marrow and pathological histology were observed. Results: The food consumption, body mass of the drug groups were decreased, the body temperature was increased transiently. One of the low dose group showed restricted movements and tremors. One of the high dose group vomited and another died. Reduced red blood cell(RBC) count, hemoglobin(Hb) concentration, hematocrit(Hct), mean corpuscular volume(MCV), mean corpuscular hemoglobin(MCH), and mean corpuscular hemoglobin concentration(MCHC), dose-related increase of platelet(Plat) counts were present in drug groups. Biochemical examinations revealed dose-related decreases in serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), lactate dehydrogenase(LDH), total proteins(TP) and albumin(Alb) increases in serum alkaline phosphatase(ALP) levels. Positive antibody responses were seen and circulatory immune complex(CIC) was significantly increased in all drug groups. Hypertropy of marrow megakaryocyocytes was noted in the medium and high dose groups. The heart and liver masses were slightly increased in all treatment groups. Treatment-related microscopic findings included dose-related degeneration in the liver and the kidney. The adverse effects were reversed by the end of the recovery period. Conclusion: The target organs and systems are blood, liver, kidney, immmue system and bone marrow. The toxicity injuries were reversible and the no-toxic-effect level is 0.1 mg/kg.
ABSTRACT
Objective:To investigate the long-term toxicity of recombinant human interleukin-11(rhIL-11) in cynomolgus. Methods: Eighteen cynomolgus were randomized into 4 groups: control group(2/sex), low dose group(2/sex), medium dose group(2/sex)， and high dose group(3/sex). The drug groups were sc adminstered 0.1, 0.3 and 1.0 mg/kg of rhIL-11 for 90 days with a 30-day recovery period. The clinical signs were observed, electrocardiogram, hematological, biochemical, urinary and immunological parameters were measured, organ masses were weighed, bone marrow and pathological histology were observed. Results: The food consumption, body mass of the drug groups were decreased, the body temperature was increased transiently. One of the low dose group showed restricted movements and tremors. One of the high dose group vomited and another died. Reduced red blood cell(RBC) count, hemoglobin(Hb) concentration, hematocrit(Hct), mean corpuscular volume(MCV), mean corpuscular hemoglobin(MCH), and mean corpuscular hemoglobin concentration(MCHC), dose-related increase of platelet(Plat) counts were present in drug groups. Biochemical examinations revealed dose-related decreases in serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), lactate dehydrogenase(LDH), total proteins(TP) and albumin(Alb) increases in serum alkaline phosphatase(ALP) levels. Positive antibody responses were seen and circulatory immune complex(CIC) was significantly increased in all drug groups. Hypertropy of marrow megakaryocyocytes was noted in the medium and high dose groups. The heart and liver masses were slightly increased in all treatment groups. Treatment-related microscopic findings included dose-related degeneration in the liver and the kidney. The adverse effects were reversed by the end of the recovery period. Conclusion: The target organs and systems are blood, liver, kidney, immmue system and bone marrow. The toxicity injuries were reversible and the no-toxic-effect level is 0.1 mg/kg.