Subject(s)
Cytomegalovirus Infections/complications , Kidney Transplantation , Lymphohistiocytosis, Hemophagocytic/etiology , Postoperative Complications/etiology , Antigens, Viral/blood , Antiviral Agents/therapeutic use , Combined Modality Therapy , Cyclosporine/administration & dosage , Cyclosporine/therapeutic use , Cytomegalovirus/immunology , Cytomegalovirus/isolation & purification , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/therapy , False Negative Reactions , Fatal Outcome , Ganciclovir/therapeutic use , Humans , Immunocompromised Host , Immunoglobulins, Intravenous/therapeutic use , Male , Methylprednisolone/therapeutic use , Middle Aged , Multiple Organ Failure/etiologyABSTRACT
OBJECTIVE: To evaluate the effect of low molecular weight heparin on plasma xanthine oxidase concentrations and lung inflammatory response during acute pancreatitis. DESIGN: Randomized, controlled trial. SETTING: Experimental laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: Acute pancreatitis was induced by intraductal administration of 5% sodium taurocholate. Low molecular weight heparin (0, 30, 90, or 300 units/kg) was administered immediately after induction of pancreatitis. MEASUREMENTS AND MAIN RESULTS: Lipase and xanthine oxidase plasma concentrations were measured 3 hrs after pancreatitis induction. Expression of P-selectin messenger RNA and myeloperoxidase activity as a marker of neutrophil infiltration were determined in the lung. An increase in xanthine oxidase plasma concentrations was observed during pancreatitis. Administration of heparin also increased plasma xanthine oxidase activity in both control and pancreatitis animals. Measures of xanthine oxidase present in the endothelial surface indicate that during pancreatitis, the enzyme is released from the gastrointestinal endothelium. By contrast, heparin mobilizes xanthine oxidase from almost all organs evaluated. Neutrophil infiltration was increased in the lung during pancreatitis. Heparin administration further increased, in a dose-dependent manner, myeloperoxidase activity and P-selectin expression in the lung in animals with pancreatitis. By contrast, in control animals, heparin had no effect on myeloperoxidase activity and did not induce P-selectin up-regulation. CONCLUSION: During acute pancreatitis, heparin administration might mobilize xanthine oxidase attached to endothelial cells, originating a free radical-generating system in the circulation that would trigger an inflammatory response in the lung.
Subject(s)
Heparin, Low-Molecular-Weight/pharmacology , Pancreatitis/complications , Pneumonia/etiology , Xanthine Oxidase/drug effects , Acute Disease , Animals , Male , Pancreatitis/blood , Random Allocation , Rats , Rats, Wistar , Xanthine Oxidase/bloodABSTRACT
To study the relevance of the terminal alpha,beta-unsaturated gamma-methyl-gamma-lactone moiety of the antitumoral acetogenins of Annonaceae for potent mitochondrial complex I inhibition, we have prepared a series of semisynthetic acetogenins with modifications only in this part of the molecule, from the natural rolliniastatin-1 (1) and cherimolin-1 (2). Some of the hydroxylated derivatives (1b, 1d and 1e) in addition to two infrequent natural beta-hydroxy gamma-methyl gamma-lactone acetogenins, laherradurin (3) and itrabin (4), are more potent complex I inhibitors than any other known compounds.
