Effect of hypoxia/reoxygenation on the cytokine-induced production of nitric oxide and superoxide anion in cultured osteoarthritic synoviocytes

SummaryObjectiveHypoxia/reoxygenation (H/R) is an important feature in the osteoarthritis (OA) physiopathology. Nitric oxide (NO) is a significant proinflammatory mediator in the inflamed synovium. The purpose of this study was to investigate the effects of H/R on inducible NO synthase (iNOS) activity and expression in OA synoviocytes. In addition we studied the relationship between nitrosative stress and NADPH oxidase (NOX) in such conditions.MethodsHuman cultured synoviocytes from OA patients were treated for 24 h with interleukin 1-β (IL-1β), tumour necrosis factor α (TNF-α) or neither; for the last 6 h, they were submitted to either normoxia or three periods of 1-h of hypoxia followed by 1-h of reoxygenation. NO metabolism (iNOS expression, nitrite and peroxynitrite measurements) was investigated. Furthermore, superoxide anion O2− production, NOX subunit expression and nitrosylation were also assessed.ResultsiNOS expression and nitrite (but not peroxynitrite) production were significantly increased under H/R conditions when compared with to normoxia (P < 0.05). H/R conditions decreased O2− production from ∼0.20 to ∼0.12 nmol min−1 mg proteins−1 (P < 0.05), while NOXs' subunit expression and p47-phox phosphorylation were increased. NOXs and p47-phox were dramatically nitrosylated under H/R conditions (P < 0.05 vs normoxia). Using NOS inhibitors under H/R conditions, p47-phox nitrosylation was prevented and O2− production was restored at normoxic levels (0.21 nmol min−1 mg of proteins−1).ConclusionsOur results provide evidence for an up-regulation of iNOS activity in OA synoviocytes under H/R conditions, associated to a down-regulation of NOX activity through nitrosylation. These findings highlight the importance of radical production to OA pathogenesis, and appraise the metabolic modifications of synovial cells under hypoxia

Lipocalin 2 as a potential systemic biomarker for central serous chorioretinopathy

No systemic biomarker of Central Serous Chorioretinopathy (CSCR) has been identified. Lipocalin 2 (LCN2 or NGAL), alone or complexed with MMP-9 (NGAL/MMP-9), is increased in several retinal disorders. Serum levels of LCN2 and NGAL/MMP-9 were measured in CSCR patients (n = 147) with chronic (n = 76) or acute/recurrent disease (n = 71) and in age- and sex-matched

Useulness of B Natriuretic Peptides and Procalcitonin in Emergency Medicine

Congestive heart failure (CHF) is the main cause of acute dyspnea in patients presented to an emergency department (ED), and it is associated with high morbidity and mortality. B-type natriuretic peptide (BNP) is a polypeptide, released by ventricular myocytes directly proportional to wall tension, for lowering renin-angiotensin-aldosterone activation. For diagnosing CHF, both BNP and the biologically inactive NT-proBNP have similar accuracy. Threshold values are higher in elderly population, and in patients with renal dysfunction. They might have also a prognostic value. Studies demonstrated that the use of BNP or NT-proBNP in dyspneic patients early in the ED reduced the time to discharge, total treatment cost. BNP and NT-proBNP should be available in every ED 24 hours a day, because literature strongly suggests the beneficial impact of an early appropriate diagnosis and treatment in dyspneic patients. Etiologic diagnosis of febrile patients who present to an ED is complex and sometimes difficult. However, new evidence showed that there are interventions (including early appropriate antibiotics), which could reduce mortality rate in patients with sepsis. For diagnosing sepsis, procalcitonin (PCT) is more accurate than C-reactive protein. Thus, because of its excellent specificity and positive predictive value, an elevated PCT concentration (higher than 0.5 ng/mL) indicates ongoing and potentially severe systemic infection, which needs early antibiotics (e.g. meningitis). In lower respiratory tract infections, CAP or COPD exacerbation, PCT guidance reduced total antibiotic exposure and/or antibiotic treatment duration