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

Objective: Hypoxia/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.

High DNA oxidative damage in systemic sclerosis.

Objective: Several lines of evidence suggest that the generation of reactive oxygen species (ROS) is of major importance in the pathogenesis of SSc. Protein and lipid damage have previously been demonstrated, but scarce data are available on oxidative damage to DNA. In patients with SSc, we evaluated levels of 8-hydroxy-2'-deoxyguanosine (8-oxodG), the main validated biomarker of endogenous oxidative damage to DNA, compared to levels of F2-isoprostane, a product of free radical-mediated peroxidation of arachidonic acid.

[Evaluation of analytical and diagnostic performances of the anti-cyclic citrullinated peptides (anti-CCP) automated assay on Elecsys analyzer].

Anti-cyclic citrullinated peptides (anti-CCP) are highly characteristics of rheumatoid arthritis (RA). Since 2006, anti-CCP assays have been included in both French and European recommendations. We have evaluated the analytical and clinical performances of the anti-CCP assay on the Elecsys analyzer (Roche Diagnostics).

Assessment of the nitrosylation process.

Purpose Of Review: To understand the principles and limits of the methodologies used for the measurement of S-nitrosylated proteins.

Recent Findings: Among methods for studying protein S-nitrosylation, chemoluminescence and biotin switch assay have rapidly gained popularity. However, recent findings have attempted to highlight potential pitfalls for these methods.

B-type natriuretic peptides for the diagnosis of congestive heart failure in dyspneic oldest-old patients.

Objectives: To evaluate the accuracy of B-type natriuretic peptide (BNP) and amino-terminal pro-brain natriuretic peptide (NT-proBNP) for the diagnosis of congestive heart failure (CHF) in dyspneic patients aged >or=85 years admitted to the Emergency Department (ED), and to define threshold values in this oldest-old population.

Design And Methods: This study involved 210 oldest-old patients, and 360 patients aged from 65 to 84 years (<85 years), admitted to the ED for dyspnea.

Results: Median BNP and NT-proBNP levels were significantly higher in CHF oldest-old patients (p<0.

N-Terminal pro B-type natriuretic peptide testing for short-term prognosis in breathless older adults.

Background: Amino-terminal pro-brain natriuretic peptide (NT-proBNP) is useful for the triage of patients with dyspnea. Our aim was to determine whether NT-proBNP levels could predict in-hospital outcome in breathless elderly patients.

Methods: At admission, NT-proBNP plasma concentrations were determined in 324 dyspneic patients aged 75 years and older.

High N-terminal pro-brain natriuretic peptide levels and low diffusing capacity for carbon monoxide as independent predictors of the occurrence of precapillary pulmonary arterial hypertension in patients with systemic sclerosis.

Objective: To evaluate predictors of pulmonary arterial hypertension (PAH) in a prospective cohort of patients with systemic sclerosis (SSc).

Methods: Routine clinical assessments as well as measurements of the diffusing capacity for carbon monoxide/alveolar volume (DLCO/VA) ratio and N-terminal pro-brain natriuretic peptide (NT-proBNP) level were performed in a prospective cohort of 101 SSc patients who did not have PAH or severe comorbidities. After a planned 36-month followup, we evaluated the predictive value of these parameters for the development of precapillary PAH, as demonstrated by cardiac catheterization, disease progression, and death.

Glucose transport in fibroblasts is unaffected by polyamines.

Objective: Wound healing is characterized by a net increase in glucose utilization in wound tissues. The mediators involved in this process remain largely unknown. Because polyamines are known to stimulate d-glucose uptake in brush-border membrane vesicles, we investigated whether or not they stimulated sugar uptake in confluent cultured fibroblasts.

Implication of cytosolic phospholipase A2 (cPLA2) in the regulation of human synoviocyte NADPH oxidase (Nox2) activity.

NADPH oxidase Nox2 is involved in the production of superoxide by rheumatoid synovial cells, constitutively and after pro-inflammatory cytokine treatment. The aims of the study were to evaluate the capacity of these cells to produce the superoxide anion in response to arachidonic acid (AA), and to study the involvement of cytosolic phospholipase A(2) (cPLA(2)) in the cytokine regulation of Nox2. Superoxide production was quantified in synovial cells obtained from six patients with rheumatoid arthritis (RA) and six with osteoarthritis (OA), stimulated with (i) AA, and (ii) PLA(2) inhibitors prior to IL-1beta or TNF-alpha treatment.

Impairment of thioredoxin reductase activity by oxidative stress in human rheumatoid synoviocytes.

The thioredoxin/thioredoxin reductase system is strongly induced in patients with rheumatoid arthritis (RA). We have investigated the impact on TR activity of doses of superoxide anion generated by the hypoxanthine (HX)/xanthine oxidase (XO) system and by hydrogen peroxide, H(2)O(2), for various times and compared the findings with synoviocytes obtained from osteoarthritis (OA) patients. At baseline, TR activity in RA cells was significantly higher than in OA cells (2.

Expression and extracellular release of Trx80, the truncated form of thioredoxin, by TNF-alpha- and IL-1beta-stimulated human synoviocytes from patients with rheumatoid arthritis.

Thioredoxin (Trx) plays several important roles, through changes to sulfhydryl reactions and protein interactions, in controlling cellular signalling processes in RA (rheumatoid arthritis). Trx80, the 10 kDa C-terminal truncated form of Trx, is a potent mitogenic cytokine and is involved in the Th1 response. In the present study, we have investigated the ability of synoviocytes from five RA patients to induce Trx80 after ex vivo stimulation by the pro-inflammatory cytokines IL-1beta (interleukin-1beta) and TNF-alpha (tumour necrosis factor-alpha) or by H(2)O(2).

[The N-terminal pro-brain natriuretic peptide (NT-proBNP) assay with the Stratus CS analyzer].

Background: NT-proBNP is an efficient biomarker for the evaluation, management and prognosis of patients with heart failure.

Methods: We evaluated the analytical performance of the NT-proBNP immunoenzymatic assay with the Stratus CS semi-automated analyzer in two hospital laboratories. The characteristics assessed included imprecision, functional sensitivity, linearity/recovery, interferences study, high-dose hook effect and a comparison of Acute Care(TM) pPBNP (on Stratus)CS) versus PBNP (on Dimension HM) results on patient heparinized plasma samples.

Superoxide production and NADPH oxidase expression in human rheumatoid synovial cells: regulation by interleukin-1beta and tumour necrosis factor-alpha.

Objectives: to evaluate the rheumatoid synovial cell capacity to produce superoxide anion in response to interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha), and to study the NADPH oxidase involvement in this production.

Material And Methods: Synovial cells obtained from 7 rheumatoid arthritis (RA), 5 osteoarthritic (OA) patients, and dermal fibroblasts, were stimulated (i) with IL-1beta and TNF-alpha, or (ii) with specific oxidase activators and inhibitors, before studying superoxide production; we also studied NADPH oxidase mRNAs and protein expression, and p47-phox phosphorylation.

Results: Constitutive superoxide production by RA cells was increased in comparison to OA cells and dermal fibroblasts, and was stimulated by PMA and ionomycin.

Lack of association between three vascular endothelial growth factor gene polymorphisms and systemic sclerosis: results from a multicenter EUSTAR study of European Caucasian patients.

Introduction: Systemic sclerosis (SSc) is characterised by disturbed vessel morphology and an overproduction of vascular endothelial growth factor (VEGF). The VEGF gene located on chromosome 6p21.3 has several polymorphisms.

Serum protein oxidation in patients with rheumatoid arthritis and effects of infliximab therapy.

Objective: To examine protein oxidation in rheumatoid arthritis (RA) and evaluate its evolution after infliximab therapy in a subgroup of patients.

Methods: Seventy-one consecutive patients with RA were included. Among them, 30 patients refractory to conventional therapy were treated with infliximab.

High redox thioredoxin but low thioredoxin reductase activities in the serum of patients with rheumatoid arthritis.

Background: Thioredoxin (Trx)/thioredoxin reductase (TrxR) is a redox-active system induced by oxidative stress. We investigated its status as a function of RA disease activity.

Methods: 64 consecutive RA patients and 27 healthy subjects were enrolled in the study.

Effects of repeated infliximab therapy on serum lipid profile in patients with refractory rheumatoid arthritis.

Background: Patients with rheumatoid arthritis (RA) frequently display an atherogenic lipid profile which has been linked with inflammation. Tumor necrosis factor-alpha (TNF-alpha), a pivotal pro-inflammatory cytokine in RA may be involved in the development of the disturbed lipid metabolism. We investigated whether infliximab, an anti-TNF-alpha therapy, may modify the lipid profile.

Influence of renal function on N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients admitted for dyspnoea in the Emergency Department: comparison with brain natriuretic peptide (BNP).

Background: Renal dysfunction influences the optimum brain natriuretic peptide (BNP) threshold for a diagnosis of cardiac-related dyspnoea, but this has not been demonstrated for N-terminal pro-brain natriuretic peptide (NT-proBNP). We studied the influence of renal function on NT proBNP and BNP concentrations in dyspnoeic patients admitted by night to the Emergency Department (ED).

Methods: NT-proBNP, BNP, and creatinine levels were measured in blood samples collected routinely from 381 patients; estimated glomerular filtration rate (eGFR) was calculated.

Increased plasma soluble CD40 ligand concentrations in systemic sclerosis and association with pulmonary arterial hypertension and digital ulcers.

Background: Increased expression of CD40L has been reported on activated CD4+ T lymphocytes in systemic sclerosis. CD40L can be expressed in soluble form (sCD40L).

Objective: To compare sCD40L concentrations in patients with systemic sclerosis and healthy controls.

Nifedipine protects against overproduction of superoxide anion by monocytes from patients with systemic sclerosis.

We have reported previously that dihydropyridine-type calcium-channel antagonists (DTCCA) such as nifedipine decrease plasma markers of oxidative stress damage in systemic sclerosis (SSc). To clarify the cellular basis of these beneficial effects, we investigated the effects in vivo and in vitro of nifedipine on superoxide anion (O2*-) production by peripheral blood monocytes. We compared 10 healthy controls with 12 patients with SSc, first after interruption of treatment with DTCCA and second after 2 weeks of treatment with nifedipine (60 mg/day).

Lack of association of eNOS (G894T) and p22phox NADPH oxidase subunit (C242T) polymorphisms with systemic sclerosis in a cohort of French Caucasian patients.

Objective: To assess the influence of endothelial nitric oxide synthase (eNOS) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase polymorphisms on the susceptibility of patients to and clinical expression of systemic sclerosis (SSc).

Methods: Seventy-seven French Caucasian patients with SSc were studied. Patients and ethnically matched controls (n=49) were genotyped, by restriction enzyme digestion of polymerase chain reaction (PCR) products, for G894T polymorphism in exon 7 of the eNOS gene and for C242T polymorphism of the gene encoding the p22(phox) NADPH oxidase subunit.

Nifedipine decreases sVCAM-1 concentrations and oxidative stress in systemic sclerosis but does not affect the concentrations of vascular endothelial growth factor or its soluble receptor 1.

Microvascular injury, oxidative stress, and impaired angiogenesis are prominent features of systemic sclerosis (SSc). We compared serum markers of these phenomena at baseline and after treatment with nifedipine in SSc patients. Forty successive SSc patients were compared with 20 matched healthy subjects.

Acute and sustained effects of dihydropyridine-type calcium channel antagonists on oxidative stress in systemic sclerosis.

Purpose: To evaluate the potential antioxidant properties of dihydropyridine calcium channel antagonists in systemic sclerosis.

Methods: Forty-two patients with systemic sclerosis were included (mean [+/- SD] age, 54 +/- 12 years; mean disease duration, 8 +/- 7 years). Plasma markers of oxidative stress (carbonyl residues, advanced oxidation protein products, malondialdehyde, nitrosothiols, and total thiol groups) were determined 72 hours after the discontinuation of usual dihydropyridine treatment (with either nifedipine or nicardipine), shortly after reinitiation of treatment, and 9 to 12 months later (long-term treatment) in 19 of the patients.

Increased pasma S-nitrosothiol concentrations predict cardiovascular outcomes among patients with end-stage renal disease: a prospective study.

The plasma concentrations of S-nitrosothiols, which are circulating nitric oxide metabolites with potential biologic activity, are increased among patients undergoing chronic hemodialysis (HD). However, the ability of S-nitrosothiols to release nitric oxide at physiologically relevant sites may be reduced among HD patients, because of impaired availability and/or activity of factors involved in S-nitrosothiol breakdown. The resultant lack of S-nitrosothiol bioavailability could contribute to the high cardiovascular risk for such patients.