ABSTRACT
OBJECTIVES: The systemic inflammatory response syndrome (SIRS) after cardiac surgery with cardiopulmonary bypass (CPB) exacerbates organ dysfunction and increases postoperative mortality. The aim of this study was to reduce SIRS after CPB in a pig model by profoundly decreasing all blood defence factors (complement, coagulation and fibrinolytic and contact systems, leukocytes and thrombocytes) using preoperative aphaeresis. METHODS: Thirty-three pigs underwent 3 h of hypothermic CPB with 2 h of cardioplegic arrest, followed by 4 days of observation. One half of the sample underwent prebypass plasma-thrombo-leukocyte aphaeresis with the adjuvant leukofiltration. RESULTS: In the control group, there were classical signs of SIRS (tachycardia, tachypnea and leukocytosis) postoperatively. There was also myocardial ischaemia and the need for inotropic support in 90% of the control animals. Neutrophils showed an increase in superoxide anion production (P < 0.001), and surface neutral protease activity (P < 0.001) and blood endotoxin levels increased (P < 0.01) compared with preoperative levels. In contrast, in the aphaeretic group, there were no classical signs of SIRS; no myocardial ischaemia; minimum neutrophil production of the superoxide anion and protease activity were recorded (P < 0.001); and endotoxin levels were also decreased (P < 0.05) compared with the controls. In the control group, the haemodynamic problems associated with disconnecting from CPB correlated with the histologic findings in the myocardium (leukocyte endothelial adhesion and leukodiapedesis). CONCLUSIONS: Preoperative plasmathrombo-leukocyte aphaeresis significantly reduces the major symptoms of SIRS and organ dysfunction after 3 h of CPB without adverse effects, such as bleeding and infection, during the postoperative course.
Subject(s)
Blood Component Removal/methods , Cardiopulmonary Bypass/methods , Systemic Inflammatory Response Syndrome/prevention & control , Animals , Blood Platelets , Disease Models, Animal , Heart Arrest, Induced/methods , Hypothermia, Induced/methods , Leukapheresis/methods , Leukocytes/physiology , Myocardial Ischemia/etiology , Plasma , Plasmapheresis/methods , Preoperative Period , Swine , Swine, MiniatureABSTRACT
Xenograft models represent a promising tool to study the pathogenesis of hematological malignancies. To establish a reliable and appropriate in vivo model of aggressive human B-cell leukemia and lymphoma we xenotransplanted four p53-mutated cell lines and one ATM-mutated cell line into immunodeficient NOD/SCID IL2Rγ-null mice. The cell lines MEC-1, SU-DHL-4, JEKO-1, REC-1, and GRANTA-519 were transplanted intraperitoneally or subcutaneously and the engraftment was investigated using immunohistochemistry and flow cytometry. We found significant differences in engraftment efficiency. MEC-1, JEKO-1 and GRANTA-519 cell lines engrafted most efficiently, while SU-DHL-4 cells did not engraft at all. MEC-1 and GRANTA-519 massively infiltrated organs and the whole intraperitoneal cavity showing very aggressive growth. In addition, GRANTA-519 cells massively migrated to the bone marrow regardless of the transplantation route. The MEC-1 and GRANTA-519 cells can be especially recommended for in vivo study of p53-mutated chronic lymphocytic leukemia and ATM-mutated mantle cell lymphoma, respectively.
Subject(s)
Ataxia Telangiectasia Mutated Proteins/genetics , Interleukin Receptor Common gamma Subunit/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Lymphoma, Mantle-Cell/genetics , Lymphoma, Mantle-Cell/pathology , Mutation , Tumor Suppressor Protein p53/genetics , Animals , Biomarkers , Cell Line, Tumor , Disease Models, Animal , Female , Gene Knockout Techniques , Heterografts , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/metabolism , Male , Mice , Mice, Inbred NOD , Mice, Knockout , Mice, SCID , Transplantation, HeterologousABSTRACT
The aim of the present study is to assess aquatic ecosystem contamination using selected biochemical markers: cytochrome P450, ethoxyresorufin-O-deethylase (EROD), glutathione S-transferase (GST), tripeptide glutathione, vitellogenin, and 11-ketotestosterone in chub (Leuciscus cephalus L.). Seven locations on the Svitava and Svratka rivers (in the Brno conurbation, Czech Republic) were assessed. The results were compared with the levels of the most important inductors of these biomarkers: organic pollutants hexachlorocyclohexane (HCH), hexachlorobenzene (HCB), DDT and its metabolites, polychlorinated biphenyls, and polycyclic aromatic hydrocarbons in bottom sediment, fish muscle, and semipermeable membrane devices (SPMDs) and metals in sediment. The highest levels of pollutants were observed at sites situated downstream from Brno, especially at Modrice and Rajhradice. Significant positive correlations (p < 0.05) were found between EROD activity and HCH concentration in SPMDs, and also between GST and EROD activity with HCB concentration in muscle, after adjusting for age.
