Edyta Reichman-Warmusz

Biomolecular Mechanisms in Varicose Veins Development

Varicose veins (VVs) can be described as tortuous and dilated palpable veins, which are more than 3 mm in diameter. They are one of the clinical presentations of chronic venous disorders, which are a significant cause of morbidity. The prevalence of VVs has been estimated at 25-33% in women and 10-20% in men and is still increasing at an alarming rate. Family history, older age, female, pregnancy, obesity, standing occupations, and a history of deep venous thrombosis are the predominant risk factors. A great amount of factors are implicated in the pathogenesis of VVs, including changes in hydrostatic pressure, valvular incompetence, deep venous obstruction, ineffective function of calf muscle pump, biochemical and structural alterations of the vessel wall, extracellular matrix abnormalities, impaired balance between growth factors or cytokines, genetic alterations, and several other mechanisms. Nevertheless, the issue of pathogenesis in VVs is still not completely known, even if a great progress has been made in understanding their molecular basis. This kind of studies appears promising and should be encouraged, and perhaps the new insight in this matter may result in targeted therapy or possibly prevention.

Clinical Significance of Viral Genome Persistence in the Myocardium of Patients with Dilated Cardiomyopathy

Background: The impact of myocardial viral persistence on the clinical outcome of patients with dilated cardiomyopathy (DCM) is still open to question. Methods: Fifty-two patients with DCM were enrolled and followed for a median of 3.8 years with respect to death or heart transplantation. Studied patients were clinically stable for at least 6 months before hospitalization. They underwent coronary angiography and endomyocardial biopsy. Specimens were examined by histo- and immunohistochemistry, and the viral genomes of parvovirus B19, cytomegalovirus (CMV), Coxsackie B virus (CVB), and hepatitis B and C viruses were studied by real-time polymerase chain reaction. Results: Forty-two out of 52 patients were available for clinical follow-up. The viral genome was detected in the myocardium of 32 out of 42 patients. Among the viruses studied, CMV and CVB were the most frequently found. Nine out of 42 patients achieved the predefined study end point. No statistically significant correlation was found between the presence of a persistent viral genome and study end point. No statistically significant relationship between viral genomes studied and immunohistology results was detected. Conclusions: High prevalence of a viral genome in the myocardium of patients with DCM did not have an influence on their long-term clinical outcome.

The aberrant overexpression of vimentin is linked to a more aggressive status in tumours of the gastrointestinal tract

Vimentin is an intermediate filament protein normally expressed in cells of mesenchymal origin, e.g. myofibroblasts, chondrocytes, macrophages, and endothelial cells. The expression of vimentin, which has been thought of as the main mesenchymal marker, is also detected in tumour tissue. In tumours of the gastrointestinal tract vimentin expression is usually correlated with advanced stage of tumour, lymph node metastasis, and patient survival.

Inducible and Endothelial Nitric Synthetase Expression and Nitrotyrosine Accumulation in Iris Vasculature of Patients with Primary Open-Angle Glaucoma: A Pilot Study

Background The “double-faced” effect of nitric oxide (NO) is thought to play an important role in triggering and progression of glaucoma. Material/Methods Iris samples were obtained during iridectomy in 35 patients (mean age of 65.4±5.3 years) with diagnosed primary open-angle glaucoma (POAG). The controls were collected postmortem from 10 donors with a mean age of 62.2±1.9 years. Visual field defects were evaluated by perimetry. The Hodapp-Parrish-Anderson classification was used to divide patients into 3 visual field defect groups. The intraocular pressure was measured 3 times before surgery using applanation tonometry. The phenotype activity of nitric oxide synthase (NOS) isoenzymes (endothelial – eNOS and inducible – iNOS) and expression of nitrotyrosine in iris vasculature was assessed. Results Significant differences were found between glaucoma patients and the controls in eNOS and iNOS activity (Mann-Whitney test, U=35.5, Z=−2.037, p=0.04 and U=21, Z=2.69, p=0.007, respectively). In addition, the results showed an upregulation of nitrotyrosine in the capillary endothelial cells in the study group, which was associated with the duration of diagnosed glaucoma (R-Spearman of 0.33, p=0.0047) and visual field mean defect MD (R-Spearman of 0.29, p=0.019). Moreover, the activity of nitrotyrosine was significantly correlated with iNOS immunoreactivity (R-Spearman of 0.5, p=0.0001). However, the iNOS activity significantly varied among Hodapp-Parrish-Anderson groups (p=0.03). Conclusions Our observations confirmed the association between glaucomatous disturbances and upregulation of iNOS, together with increased nitrotyrosine storage.

von Willebrand factor in iris vasculature of glaucoma patients

Background Previous reports have indicated the role of endothelium disturbances, as expressed by von Willebrand factor (vWF) release, in pathophysiology of glaucoma. The objective of this study was to investigate the vWF expression in iris vasculature of patients with primary open-angle glaucoma (POAG). Material/Methods Immunohistochemistry of vWF expression was performed on cryostat sections of samples collected at the time of peripheral iridectomy and controls collected from dead donors. Results Twenty-seven Caucasians age 66.6±3.7 with 5.8±3.7-year history of treated PAOG and 10 controls age 62.2±1.92 with no history of glaucoma. The percentage of patients who presented normal and up-regulation of vWF phenotype expression differed statistically between examined and control groups: 48% versus 100% (p=0.035, chi-square test with Yates’ correction). Sex, age, glaucoma duration, and visual field quantitative indices had no impact on vWF expression. A significant correlation between mean pre-surgery intraocular pressure and vWF expression was found (Spearman r=0.42, p=0.03). Conclusions Considering the results, it may be suggested that vWF is actively involved in the pathophysiology of glaucoma.

Response to Dual Antiplatelet Therapy Does Not Impact Bleeding Risks in Patients Undergoing Oral Surgery after Acute Coronary Syndromes

Introduction: Oral surgery (OS) in patients on antecedent dual antiplatelet therapy (DAPT) may be associated with extra bleeding risks. Monitoring platelet activity in such patients may be beneficial for safety when performing OS. Objectives: The aim of this study was to assess whether platelet function during DAPT impacted the risk of bleeding following OS in patients with acute coronary syndromes (ACS). Patients and Methods: Patients who required OS on top of DAPT with aspirin and clopidogrel (n = 55) for invasively treated ACS were included. The control group (n = 33) consisted of patients who underwent OS with no antiplatelet agent. Platelet aggregation before OS was assessed with a Multiplate® analyzer. Bleeding during OS and at days 1, 3, 7 and 10 after surgery was serially evaluated. Results: All 88 patients completed the study. An incomplete response to aspirin or clopidogrel was observed in 43.6% of the patients. In 11% of the cases, an excessive response to clopidogrel was demonstrated. No excessive bleeding upon OS was exhibited in either group during the entire follow-up. Platelet aggregation values and the use of DAPT did not impact the performance of OS. Conclusion: Therapy with clopidogrel and aspirin after ACS does not seem to increase the risk of real-life bleeding following OS, regardless of the platelet activity response to DAPT.

Tissue hemostasis and chronic inflammation in colon biopsies of patients with inflammatory bowel disease.

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.

The relationship between late gadolinium enhancement imaging and myocardial biopsy in the evaluation of chronic heart failure patients with suspected myocarditis

Aim The aim of this study was to assess the relationship between late gadolinium-enhanced (LGE) cardiovascular magnetic resonance (CMR) and immunohistochemical markers of inflammation in patients with heart failure and a reduced ejection fraction (HFrEF). Material and methods Endomyocardial biopsy and CMR were performed in 38 consecutive patients (24 males, average age 43.2 ± 6.9 years, New York Heart Association [NYHA] class II) with HFrEF and suspected myocarditis. The immunohistochemical evaluation was done by the En-Vision system using DAKO monoclonal antibodies. The presence of > 14 infiltrating cells together with myocardial damage and ≥ 2 + up-regulation of HLA class II was considered diagnostic for myocarditis. The results of LGE were compared with the immunohistochemical markers of inflammation. All patients underwent coronary angiography. Results Twelve out of 38 (31.6%) patients met the immunohistological criteria for the diagnosis of myocarditis. Late gadolinium enhancement was present in 23 of 38 (60.5%) patients, mostly at the interventricular septum. No correlation was found between LGE and immunohistochemistry results (Kendalls tau; r = 0.21, p = 0.09). Conclusions Our study revealed no significant relationship between LGE cardiovascular magnetic resonance imaging and immunohistochemical markers of inflammation in patients with HFrEF.