ABSTRACT
AIM: To study the influence of the COX inhibitor--lornoxicam (LX)--on Toll-like receptor (TLR)-mediated production of proinflammatory and anti-inflammatory cytokines by peripheral blood mononuclear cells (PBMC) from healthy subjects and patients with acute pancreatitis (AP) in vitro. MATERIALS AND METHODS: Cytokine production by PBMC of healthy donors was stimulated by TLR1/2 ligand peptidoglycan (PG) and TLR4 ligand lypopolysaccharide (LPS) in presence of LX. Levels of cyotokines (IL-1beta, IL-6, IL-8, IL-10, IL-12, and TNFalpha) were measured by ELISA. Group of patients with acute pancreatitis of toxic etiology included 11 subjects: patients from main group received combined therapy supplemented with NSAID from the oxicam class--LX; patients who received only standard basic treatment formed comparison group. RESULTS: It was found that in vitro LX inhibits production of both proinflammatory and anti-inflammatory cytokines by PBMC of healthy subjects mediated by ligands of TLR1/2 and TLR4. Maximal inhibitory effect of LX was observed when cytokine production was induced through TLR1/2. Patients with AP demonstrated increased production of TNFalpha induced by TLR1/2 and TLR4 ligands. CONCLUSION: LX inhibits TLR-mediated production of both proinflammatory (IL-1, IL-6, IL-8, IL-12, TNFalpha) and anti-inflammatory (IL-10) cytokinesby PBMC of healthy subjects in vitro. Treatment with LX in patients with AP results in diminished effector function of TLR1/2 and TLR4 already during 1st day of the illness and normalization of these indices by 6th day.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Cyclooxygenase Inhibitors/administration & dosage , Cytokines/antagonists & inhibitors , Leukocytes, Mononuclear/drug effects , Pancreatitis, Acute Necrotizing/immunology , Piroxicam/analogs & derivatives , Toll-Like Receptors/antagonists & inhibitors , Adult , Cells, Cultured , Cytokines/biosynthesis , Down-Regulation/drug effects , Enzyme-Linked Immunosorbent Assay , Humans , Injections, Intravenous , Leukocytes, Mononuclear/immunology , Pancreatitis, Acute Necrotizing/drug therapy , Piroxicam/administration & dosage , Toll-Like Receptors/biosynthesis , Tumor Necrosis Factor-alpha/analysis , Tumor Necrosis Factor-alpha/biosynthesisSubject(s)
Analgesia/methods , Analgesics, Opioid/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , First Aid , Pain/drug therapy , Piroxicam/analogs & derivatives , Transportation of Patients , Wounds and Injuries , Adult , Drug Therapy, Combination , Humans , Piroxicam/administration & dosage , Promedol/administration & dosageABSTRACT
Inhibitory activity of fibrin-collagen substance (FCS) impregnated by various antibacterial agents against various microorganisms was investigated. It was demonstrated that antibacterials bind well with FCS, providing its sufficient antibacterial activity. Determination of growth-inhibition zones showed that antibacterial agents diffuse into medium well and demonstrated the same activity as discs with antibiotics. For clinical practice it is recommended to use for impregnation the following drugs: gentamycin, meropenem, cefriaxone and ciprofloxacin.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Collagen , Fibrin , Administration, Topical , Colony Count, Microbial , Drug Carriers , Enterococcus/drug effects , Escherichia coli/drug effects , Klebsiella oxytoca/drug effects , Proteus vulgaris/drug effects , Pseudomonas aeruginosa/drug effects , Staphylococcus aureus/drug effectsABSTRACT
The experiments with AKR mice, that are carriers of the T-cell leukemia virus showed their higher radiosensitivity as compared to (CBA x C57Bl)F1 mice in respect of survival and hemopoietic status. The regular patterns observed are presumed to result from lower ability of AKR mice to repair radiation damage and provide resistance to infections.
Subject(s)
Carrier State/virology , Hematopoietic System/radiation effects , Leukemia Virus, Murine , Leukemia, Experimental/virology , Retroviridae Infections/virology , Tumor Virus Infections/virology , Animals , Carrier State/congenital , Dose-Response Relationship, Radiation , Female , Gamma Rays , Leukemia, Experimental/congenital , Male , Mice , Mice, Inbred AKR , Mice, Inbred C57BL , Mice, Inbred CBA , Radiation Tolerance , Retroviridae Infections/congenital , Species Specificity , Tumor Virus Infections/congenitalABSTRACT
In experiments with three species of animals (mice, rabbits, monkeys) irradiated with sublethal and lethal doses of gamma-irradiation, it was observed, that leukinferon used in 4 hours or 10 days after provided antiradiation therapeutical effect. When lethal dose was used (mice) the survival of animals was significantly increased. The preparation decreased depression of the functional activity of leukocytes as it was observed with IFH-alpha and gamma-production. Pestoring this function was accelerated. Phenomena pancytopenia and thrombocytopenia induced by radiation were decreased. Therapeutical effect was explained with capacity of the preparation to defence the hemopoietic organs from the radiation and to stimulate hematopoiesis. So, spleen weights and quantity of cells into bone marrow were higher in experimental group in comparison with control at any observation. CFUs were also higher (with optimal dose of preparation). Stimulation of the restoring processes was confirmed also by more intensive increasing of the reticulocyte quantities in the circulation of experimental monkeys within 20 days. Then their level became more close in both groups. The preparation stimulated also differentiation of immune effectors: immature neutrophils were absent in the circulation of experimental monkeys. Production of IFN-gamma (which is function of T-lymphocytes) was restored more fast. As a result, immunoreactivity of monkeys in experimental group was more complete and restored faster: the growth of the automicroflora on the skin surface became to increase 7 days later and was restrained. Leukinferon hindered the development of acute radiation sickness symptoms.
Subject(s)
Adjuvants, Immunologic/therapeutic use , Cytokines/therapeutic use , Interferon Type I/therapeutic use , Radiation Injuries, Experimental/prevention & control , Radiation-Protective Agents , Acute Disease , Adjuvants, Immunologic/administration & dosage , Animals , Blood Cell Count , Bone Marrow/drug effects , Bone Marrow/radiation effects , Cytokines/administration & dosage , Drug Combinations , Haplorhini , Hematopoiesis/drug effects , Hematopoiesis/radiation effects , Interferon Type I/administration & dosage , Interferon-alpha/immunology , Interferon-gamma/immunology , Mice , Rabbits , Radiation Dosage , Radiation Injuries, Experimental/blood , Radiation Injuries, Experimental/immunology , Skin/microbiology , Spleen/drug effects , Spleen/radiation effects , T-Lymphocytes/immunology , Time FactorsABSTRACT
A model for secondary postradiation immunodeficiency of mice has been used to compare immunocorrective activities of some new immunomodulators (arbidol, cagocel, myelopid, proleukinferon and fragmine) administered at late times (2-3 months) after exposure to a nonlethal radiation dose (4.0 Gy). The highest immunocorrective effect has been shown with fragmine and proleukinferon.
