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Aims Several lines of evidence point to hypercoagulability as an important factor for heart failure (HF) pathogenesis. Methods We hypothesised that endothelial tissue factor (TF) expression reflects altered tissue haemostasis which is related to the severity of HF. Accordingly, we investigated TF expression in the biopsies of 60 patients with HF and 22 without HF. In addition, we assessed the relationship between endothelial TF expression and clinical markers of HF severity. Results The control subjects without HF presented absent or weak TF expression in few microvessels, while the endomyocardial biopsies of patients with HF, capillary vessels presented both weak and severe staining patterns by immunohistochemistry usually with regional distribution. This was collaborated by the immune electron microscopic study. The severe microvessel TF antigen expression was found in 11 (18.3%) patients with HF. The endothelial TF expression was inversely associated with left ventricular ejection fraction (r=-0.42, p=0.001) and positively with N-terminal brain natriuretic peptide (r=0.36, p<0.023), markers of HF severity. Conclusions Regional upregulation of the TF in the capillary endothelial cells suggests local myocardial thrombogenicity. Furthermore, the relationship between endothelial TF and HF severity would be keeping in line with the hypothesis that an altered tissue haemostasis is most profoundly expressed in patients with severe HF. Weak TF expression found in several microvessels of the biopsy specimens patients without HF pathology might be potentially related to a low basal level of activation of the clotting system in normal individuals. [ABSTRACT FROM AUTHOR]

Abstract: Inflammatory bowel disease (IBD) is characterized by a chronic inflammation accompanied by procoagulation settings. However, tissue hemostasis in IBD patients was only incidentally reported. Accordingly, the current study characterizes changes in tissue hemostasis components in a colon inflammatory setting. Serial cryostat sections of endoscopic mucosal biopsy specimens taken from 26 consecutive IBD patients diagnosed de novo and normal colon resection specimens taken from 6 patients were immunohistochemically stained with monoclonal anti-human tissue factor (TF), tissue factor pathway inhibitor (TFPI), thrombomodulin (TM), as well as CD3 and CD68 positive cells. The hemostatic components studied differed significantly from the control subjects. Up-regulation predominated in the case of TF while down-regulation was mainly found in TM and TFPI in IBD. In the control sections, TF was observed in a few fibroblast-shaped cells in the lamina propria, while in the majority of IBD sections, TF positively stained small microvessels, infiltrating mononuclear cells and fibroblast-shaped cells tightly surrounding the colon crypts. Thrombomodulin intensively stained the endothelium of the small capillary vessels in the control, whereas such staining mainly accompanied infiltrating mononuclear cells of the IBD subjects. Tissue factor pathway inhibitor positively stained the endothelium of the small capillary vessels in the control group, whereas in the IBD group endothelial cells presented only weak TFPI staining. The mean number of CD3-positive lymphocytes in IBD was 23.3±14.3, but the mean number of CD68-positive cells was 114.5±55.8. In the control sections, it was 4.1±2.4 and 39.6±17.9, respectively. There was no relationship between CD3 and CD68 (+) cells and the hemostasis markers studied. The results of the current study indicate a shift of tissue hemostasis toward the procoagulant state irrespective of the severity of inflammatory infiltration. In addition, TF distribution in the colon sections of IBD patients may indicate a role in the restoration of the barrier function in injured intestinal mucosa. [Copyright &y& Elsevier]

Background Psoriasis is a common autoimmune disease of unknown etiology. Recently, much attention has been paid to evidence that a local hypercoagulable state is an important contributing factor to the development of inflammatory skin diseases. Thus, the aim of this study was to characterize the local hemostasis in the affected skin of patients with psoriasis. Methods Skin biopsies of psoriatic plaques were obtained from 73 consecutive patients (48 M, 25 F, average age 45 years) with at least a one year history of the disease. The studied patients had not received any specific systemic treatment for at least 4 weeks before the biopsy was done. As a control, normal skin biopsies were obtained from 16 healthy subjects. For immunohistological study, the En-Vision method (DAKO EnVision Kit ®/Alkaline Phosphatase detection system), and monoclonal antibodies anti-tissue factor (TF), anti-thrombomodulin (TM) and anti-von Willebrand Factor (vWF) were used. All these molecules were assessed semi-quantitatively in the frozen sections. Results Clinically, the Body Surface Area index ranged between 1–90% and the Psoriasis Area Severity Index score ranged from 1.6 to 47. Immunohistochemistry revealed redistribution of TF antigens from the upper to lower layers of the epidermis as compared to the control. It was collaborated with the number of TF-positive cells in the psoriatic skin sections (78.3%) as compared with the healthy subjects (34.4%; P < 0.001). In addition, TF was uniformly and moderately expressed on capillary endothelial cells of the plaque sections in 43 out of 73 patients (58.9%). As far as the thrombomodulin is concerned, TM was clearly down-regulated and localized mainly in the upper layers of the psoriatic epidermis. It was collaborated with the number of TM positive cells in the psoriatic skin sections (38.9%) as compared with the healthy subjects (66.7%; P < 0.001). All capillary vessels found in the biopsy sections were positive for TM and vWF staining, with similar expression (≥2+) in both groups. In the current study, no relationship was found between the TF, TM and vWF expression and the PASI and BAS (NS). Conclusions A local procoagulable state found in psoriatic plaques suggests a significant role of local tissue hemostasis in pathogenesis of the disease. These findings indicate another potential target for a therapeutic approach in patients with psoriasis, although further research would help elucidate the exact mechanisms. [ABSTRACT FROM AUTHOR]

Introduction: It is generally accepted that mitochondria are a primary source of intracellular reactive oxygen species (ROS). Under physiological circumstances they are permanently formed as by-products of aerobic metabolism in the mitochondria. To counter the harmful effect of ROS, cells possess an antioxidant defence system to detoxify ROS and avert them from accumulation at high concentrations. Mitochondria-located manganese superoxide dismutase (MnSOD, SOD2) successfully converts superoxide to the less reactive hydrogen peroxide (H2O2). To the best of our knowledge, there are no available data regarding immunohistochemical expression of MnSOD in colorectal neoplastic tissues. Aim: To investigate the immunohistochemical expression status of MnSOD in colorectal premalignant and malignant lesions. Material and methods: This study was performed on resected specimens obtained from 126 patients who had undergone surgical resection for primary sporadic colorectal cancer, and from 114 patients who had undergone colonoscopy at the Municipal Hospital in Jaworzno (Poland). Paraffin-embedded, 4-µm-thick tissue sections were stained for rabbit polyclonal anti SOD2 antibody obtained from GeneTex (clone TF9-10-H10 from America Diagnostica). Results: Results of our study demonstrated that the development of colorectal cancer is connected with increased expression of MnSOD both in adenoma and adenocarcinoma stages. Samples of adenocarcinoma with G2 and G3 grade showed significantly higher levels of immunohistochemical expression of this antioxidant enzyme. Moreover, patients with the presence of lymphovascular invasion and higher degree of regional lymph node status have been also characterised by higher levels of MnSOD expression. The samples of adenoma have been characterised by higher levels of MnSOD expression in comparison to normal mucosa as well. Interestingly, there was no significant correlation between expression and histological type of adenoma. Conclusions: Development of colorectal cancer is connected with increased expression of MnSOD both in adenoma and adenocarcinoma stages. [ABSTRACT FROM AUTHOR]

Abstract: Vascular endothelial grow factor (VEGF) promotes angiogenesis by activating the specific receptors KDR and Flt-1. We investigate the expression of genes encoding VEGF and its receptors KDR and Flt- 1 by RT-QPCR reaction using Quanti Tect SYBR Green RT-PCR in patients with active and inactive ulcerative colitis (UC) and control subjects. The localization and level of VEGF protein and its receptors protein in intestinal tissue were estimated by immunohistochemistry. VEGF concentration in serum and plasma was determined by ELISA. We found a significant increase of VEGF gene expression and increase expression of genes encoding receptor Flt-1 in patients with active UC when compared with controls, but KDR was present in trace amount. VEGF and Flt-1 proteins were colocalized in enterocytes as well as in endothelium and muscularis layer of the intestine. The specific staining reaction for VEGF protein as well as for Flt-1 protein was significantly higher in active UC compared with controls. Serum level of VEGF was significantly higher in active UC patients as compared with inactive UC patients as well as with controls. The plasma VEGF level was found to be significantly higher in active UC patients as compared with controls. The increase of gene expression as well as protein level for VEGF and its receptor in UC – inflamed colon, and VEGF action via Flt-1 receptor may have a functional role in UC. Increased VEGF levels in both serum and plasma in active UC patients may reflect VEGF overexpression in intestinal inflammatory tissue. [ABSTRACT FROM AUTHOR]