thromboplastin and Peritoneal-Diseases

Endometriosis is a major cause of chronic pain, infertility, medical and surgical interventions, and health care expenditures. Tissue factor (TF), the primary initiator of coagulation and a modulator of angiogenesis, is not normally expressed by the endothelium; however, prior studies have demonstrated that both blood vessels in solid tumors and choroidal tissue in macular degeneration express endothelial TF. The present study describes the anomalous expression of TF by endothelial cells in endometriotic lesions. The immunoconjugate molecule (Icon), which binds with high affinity and specificity to this aberrant endothelial TF, has been shown to induce a cytolytic immune response that eradicates tumor and choroidal blood vessels. Using an athymic mouse model of endometriosis, we now report that Icon largely destroys endometriotic implants by vascular disruption without apparent toxicity, reduced fertility, or subsequent teratogenic effects. Unlike antiangiogenic treatments that can only target developing angiogenesis, Icon eliminates pre-existing pathological vessels. Thus, Icon could serve as a novel, nontoxic, fertility-preserving, and effective treatment for endometriosis.

Topics: Adult; Animals; CHO Cells; Cricetinae; Cricetulus; Drug Delivery Systems; Endometriosis; Endothelium, Vascular; Female; Humans; Immunoconjugates; Immunoglobulin Fc Fragments; Immunotherapy; Mice; Mice, Nude; Middle Aged; Neovascularization, Pathologic; Peritoneal Diseases; Thromboplastin; Transplantation, Heterologous

Peritoneal adhesions are the most common complication of the abdominal surgery. Normal saline is frequently used to rinse the peritoneal cavity during abdominal surgery, although there is no well-established data describing effect of such procedure on the process of formation of peritoneal adhesions.. Effect of 0.9% NaCl solution on viability, oxidative stress, and fibrinolytic activity of human peritoneal mesothelial cells maintained in in vitro culture was evaluated.. Exposure of mesothelial cells to 0.9% NaCl induces oxidative stress, derangement of their structure with subsequent increased release of tissue factor (+75%) and plasminogen activator inhibitor-1 (+19%), and simultaneous suppression of tissue plasminogen activator release (-39%). In effect, ration tissue plasminogen activator/plasminogen activator inhibitor-1 was reduced in 0.9% NaCl-treated cells by 50%. Pretreatment of cells with precursor of glutathione synthesis: L-2-oxothiazolidine-4-carboxylic acid prevented these changes.. Oxidative stress in the peritoneal mesothelium caused by 0.9% NaCl activates their procoagulant activity and impairs fibrinolytic properties of these cells. These effects disqualify 0.9% NaCl as rinsing solution during abdominal surgery.

Topics: Cells, Cultured; Contraindications; Epithelial Cells; Fibrinolysis; Glutathione; Humans; Omentum; Osmolar Concentration; Oxidative Stress; Peritoneal Cavity; Peritoneal Diseases; Pyrrolidonecarboxylic Acid; Reactive Oxygen Species; Sodium Chloride; Solutions; Therapeutic Irrigation; Thiazolidines; Thromboplastin; Tissue Adhesions