Studies on fibrin gel structure

Fibrin gel formation is the final result of interaction between multiple plasma proteins; as a result of activation, fibrinogen is converted to fibrin and crosslinking of fibrin occurs by activated factor XIII, which stabilises the formed clot. Fibrin gel networks were studied in purified fibrinogen systems and in plasma samples from patients with cardiovascular complications and healthy individuals, using light-scattering, turbidity, liquid permeation and confocal 3D microscopy techniques. The results showed that the porosity of fibrin gels formed in recalcified plasma are within a wide range of thrombin concentrations determined by the rate of fibrinogen activation. The initial network creates a scaffold into which subsequently activated fibrinogen molecules are deposited. Changes in thrombin concentration that occur during gelation do not qualitatively alter the scaffold. Zinc ions have profound effects on the fibrin polymerisation process and final gel structure. Increasing zinc concentrations decreased the clotting time but increased the porosity of the gels. Zinc ions in any concentrations, cannot substitute for calcium ions in factor XIIIa induced crosslinking of fibrin. Glu1- and Lys78-plasminogen have positive effects on fibrin gelation. The effect of Lys78- plasminogen on the gel porosity is much stronger than that of Glu1- plasminogen, and this effect was inhibited by the fibrinolytic inhibitor e-aminocaproic acid (EACA). Antithrombin (AT) depleted plasma was used to investigate the influence of variation in the AT level on thrombin generation and fibrin formation. The fibrin gel structure was positively related to the AT concentrations, and the initial rate of thrombin-antithrombin complex formation decreased with increasing AT concentration. Tighter and more space-filling fibrin gels are formed in plasma samples from young survivors of myocardial infarction than in those from matched healthy controls. In the patient group, fibrin gel characteristics were inversely correlated to the plasma levels of plasminogen activator inhibitor-l (PAI-l), the main physiological inhibitor of the endogenous fibrinolytic enzyme system. We investigated the effect of acetylsalicylic acid (ASA) on gel structure and fibrinolytic potential in patients with stable angina pectoris during and after ASA treatment and in untreated healthy controls. During ASA treatment the permeability, i.e. porosity, was increased and the clot Iysis time was reduced. One and two weeks after ASA withdrawal, the gel porosity was decreased and longer clot lysis times were observed. The findings in the patients may have important implications for our understanding of the pathogenesis of atherosclerosis and coronary heart disease

Survivin expression in canine spontaneous cutaneous and subcutaneous tumors and its prognostic importance

Aim: The present study was carried out to know the expression level of survivin, an inhibitor of apoptosis protein with an objective to determine its prognostic importance in cutaneous and subcutaneous tissue tumors of dogs. Materials and Methods: Forty cases of canine cutaneous and subcutaneous tissue tumors on histopathological examination revealed various round cell, epithelial, and mesenchymal cell tumors. Survivin gene expression was detected in all tumors tested by TaqMan real-time polymerase chain reaction assay by comparative cycle threshold method. Results: The mean survivin gene expression value of benign tumors was 0.94±0.63 folds and that of malignant tumors was 18.87±5.30 folds. Postsurgical follow up of 30 malignant tumor cases revealed death in 8, recurrence in 7, and neoplastic free alive status in 15 dogs with mean survivin fold difference values of 48.49±12.39, 14.63±6.37, and 5.034±2.27, respectively. The mean survivin gene expression value was significantly higher in malignant (30 cases, 18.87±5.30) compared to benign tumors (10 cases, 0.94±0.63), and it varied between various postsurgical follow-up groups (p<0.05). Survival analysis, using survivin gene expression median cutoff value of 3.74 in 30 malignant tumors, was performed to predict probable survival period in malignant cutaneous and subcutaneous tumors of dogs. Conclusion: Results of the present study indicated that the expression of survivin in canine cutaneous and subcutaneous tumors has prognostic value, and survivin expression greater than median cutoff value of 3.74 has a poor prognosis