Thrombosis in vasculitis: from pathogenesis to treatment

In recent years, the relationship between inflammation and thrombosis has been deeply investigated and it is now clear that immune and coagulation systems are functionally interconnected. Inflammation-induced thrombosis is by now considered a feature not only of autoimmune rheumatic diseases, but also of systemic vasculitides such as Behçet’s syndrome, ANCA-associated vasculitis or giant cells arteritis, especially during active disease. These findings have important consequences in terms of management and treatment. Indeed, Behçet’syndrome requires immunosuppressive agents for vascular involvement rather than anticoagulation or antiplatelet therapy, and it is conceivable that also in ANCA-associated vasculitis or large vessel-vasculitis an aggressive anti-inflammatory treatment during active disease could reduce the risk of thrombotic events in early stages. In this review we discuss thrombosis in vasculitides, especially in Behçet’s syndrome, ANCA-associated vasculitis and large-vessel vasculitis, and provide pathogenetic and clinical clues for the different specialists involved in the care of these patients

Incidence of cerebral ischemic events in patients with atrial septal aneurysm

Atrial septal aneurysm (ASA) is a localized saccular deformity, generally at the level of fossa ovalis, which protrudes to the right or left atrium, or both. A possible relationship between ASA and cerebral ischemic events have been suggested in retrospective and case-control studies. The purpose of this study was to determine the embolic potential of ASA by following-up patients with this abnormality. Of the 2319 consecutive patients undergoing transesophageal echocardiogaphy (TEE) for various indications, we identified 65 (2.8%) patients with ASA. Forty-four of these who were in sinus rhythm and were contactable were followed-up prospectively for 2.3 years. Their mean age was 43.8 years. During the follow-up of 101.6 patient-years, one patient had a transient ischemic attack (TIA), whereas none of the patients suffered a stroke or other systemic thromboembolism. The patient who had the TIA had primary pulmonary hypertension, enlargement of the right heart chambers and a bidirectional and very mobile ASA, and an intact interatrial septum. She had no history of a previous cerebrovascular accident. As a result, the yearly incidence of a cerebral ischemic event was about 1% in our hospital based cohort. We conclude that ASA found on TEE may be associated with TIA and embolic stroke, but the risk seems to be low

Investigation of in vivo effect of florfenicol on metabolic-antioxidantenzymes’ activities on Morkaraman normal and lactating sheep

AbstractFlorfenicol is a broad-spectrum, primarily bacteriostatic, antibiotic with a range of activity including many gram-negative and gram-positive organisms. This study was carried out to determine the in vivo effect of florfenicol on the paraoxonase (PON), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities on Morkaraman normal and lactating sheep. For these studies, three normal and three lactating sheep groups (55–60kg) were selected for each of intramuscular administration for 24h of florfenicol (30mg/kg). Three normal and three lactating sheep groups were included in the study for a control group, which were not subjected to drug administration. For florfenicol, the mean of the hemolysate paraoxonase, glutathione peroxidase, superoxide dismutase, catalase activities and milk paraoxonase, catalase, lactoperoxidase, superoxide dismutase activity was determined and compared to the control group. According to the research results, while PON1 and CAT enzymes were activated, SOD and GPX enzymes were inhibited by florfenicol in both normal and lactating Morkaraman sheep. While florfenicol did not change milk PON1 and SOD activities, it significantly inhibited milk CAT and LPO enzyme activities

In silico molecular docking and ADME studies of 1,3,4-thiadiazole derivatives in relation to in vitro PON1 activity

Background: Paraoxonase 1 (PON1) is a paraoxonase, arylesterase and lactonase associated with protection of lipoproteins and cell membranes against oxidative modification. Objective: Based on antioxidative properties of PON1 and significance of 1,3,4-thiadiazoles in pharmaceutical chemistry, herein we aimed to evaluate the potentials of 1,3,4-thiadiazole derivatives as PON1 activators. Methods: 2-[[5-(2,4-Difluoro/dichlorophenylamino)-1,3,4-thiadiazol-2-yl]thio]acetophenone derivatives (1-18) were in vitro evaluated for their activator effects on PON1 which was purified using ammonium sulfate precipitation (60-80%) and DEAE-Sephadex anion exchange chromatography. Molecular docking studies were performed for the detection of affinities of all compounds to the active site of PON1. Moreover, Absorption, Distribution, Metabolism and Excretion (ADME) properties of all compounds were also in silico predicted. In silico molecular docking and ADME studies were carried out according to modules of Schrodinger’s Maestro molecular modeling package. Results: All compounds, particularly compounds 10, 13 and 17, were determined as promising PON1 activators and apart from compound 1, all of them were detected in the active site of PON1. Besides, ADME results indicated that all compounds were potential orally bioavailable drug-like molecules. Conclusion: PON1 activators, compounds 10, 13 and 17 stand out as potential drug candidates for further antioxidant studies and these compounds can be investigated for their therapeutic effects in many disorders such as atherosclerosis, diabetes mellitus, obesity, chronic liver inflammation and many more. © 2019 Bentham Science Publishers