Synthesis and evaluation of novel 2-[(1,2,4-triazol-3-yl)thio]acetamide derivatives as potential serum paraoxonase-1 (PON1) activators

Coronary artery disease and low-density lipoprotein (LDL) levels in the blood have long been known to be associated with peripheral vascular diseases. Paraoxonase-1 (PON1) enzyme is related to serum levels of high-density lipoprotein (HDL) and protects LDL from oxidation which may result in development of microvascular disease in diabetes. The enzyme has a major role in the prevention of atherosclerosis besides antioxidant properties. Additionally, PON1 is important in the detoxification of organophosphate insecticides from the body. In this study, we aimed to synthesize highly active new compounds which can be a drug candidate and evaluate their effects on PON1 activity. Nine novel triazole compounds bearing thioacetamide moiety (5a-i) were synthesized and their in vitro PON1 activity was investigated. The PON1 enzyme was purified from human serum using ammonium sulfate precipitation method. Also, it was further purified using Sepharose 4B-L-tyrosine- 1-naphthylamine affinity chromatography. Among the synthesized triazole compounds, 5b, 5c, 5f and 5h have been determined to increase PON1 activity, remarkably. Compounds 5b, 5c, 5f and 5h bearing 5-nitrothiazole, benzothiazole, 6-ethoxybenzothiazole and 6-florobenzothiazole moieties could be considered to proceed in vivo investigations which is a further stage for a drug candidate. © 2017, Marmara University. All rights reserved

Cerebral Venous Sinus Thrombosis as a Rare Complication of Systemic Lupus Erythematosus: Subgroup Analysis of the VENOST Study

Aim: Systemic lupus erythematosus (SLE) is an unusual risk factor for cerebral venous sinus thrombosis (CVST). As few CVST patients with SLE have been reported, little is known regarding its frequency as an underlying etiology, clinical characteristics, or long-term outcome. We evaluated a large cohort of CVST patients with SLE in a multicenter study of cerebral venous thrombosis, the VENOST study, and their clinical characteristics. Material and Method: Among the 1144 CVST patients in the VENOST cohort, patients diagnosed with SLE were studied. Their demographic and clinical characteristics, etiological risk factors, venous involvement status, and outcomes were recorded. Results: In total, 15 (1.31%) of 1144 CVST patients had SLE. The mean age of these patients was 39.9 ± 12.1 years and 13 (86.7%) were female. Presenting symptoms included headache (73.3%), visual field defects (40.0%), and altered consciousness (26.7%). The main sinuses involved were the transverse (60.0%), sagittal (40.0%), and sigmoid (20.0%) sinuses. Parenchymal involvement was not seen in 73.3% of the patients. On the modified Rankin scale, 92.9% of the patients scored 0-1 at the 1-month follow-up and 90.9% scored 0-1 at the 1-year follow-up. Conclusions: SLE was found in 1.31% of the CVST patients, most frequently in young women. Headache was the most common symptom and the CVST onset was chronic in the majority of cases. The patient outcomes were favorable. CVST should be suspected in SLE patients, even in those with isolated chronic headache symptoms with or without other neurological findings. © 2019 Elsevier Inc

Risk assessment and survival of patients with pulmonary hypertension: Multicenter experience in Turkey.

OBJECTIVE: Risk stratification continues to evolve in pulmonary arterial hypertension (PAH). Our aim was to further confirm the risk assessment strategy in our cohort and to determine the most reliable model. METHODS: We enrolled incident patients with idiopathic PAH (IPAH), heritable, drug-induced, congenital heart disease (CHD), connective tissue diseases (CTD) subsets, and chronic thromboembolic pulmonary hypertension (CTEPH) from January 2008 to February 2018. Data from the baseline and subsequent follow-ups within 1 year of diagnosis were included. An abbreviated risk assessment strategy was applied using the following variables: functional class (FC), 6-minute walk distance (6 MWD), N-terminal pro-brain natriuretic peptide (NT-proBNP) or BNP, right atrial (RA) area, pericardial effusion, the mean RA pressure, cardiac index, and mixed venous oxygen saturation. Three different methods were applied to categorize patients. RESULTS: A total of 189 subjects (46+-17 years, 23% male) were included. Sixty-one patients had died. The survival differed significantly between the risk groups both at diagnosis and during the follow-up. Patients with a low-risk profile had a better survival rate. An abbreviated risk assessment tool predicted mortality at early follow-up in the entire group and CHD, CTD subsets, and CTEPH, separately. An overall mortality among risk categories was significantly different according to each categorization method. The most reliable model comprised FC, 6 MWD, NT pro-BNP/BNP, and the RA area at the follow-up. CONCLUSION: The abbreviated risk assessment tool may be valid for the PAH subsets and CTEPH. Echocardiographic variables do matter. A model comprising FC, 6 MWD, NT pro-BNP/BNP, and the RA area at the follow-up could be useful for better prognostication