Mustafa Calis

Increased advanced oxidation protein products in Behcet's disease: a new activity marker?

Background  Behçets disease (BD) is a chronic inflammatory disease with unknown pathogenesis. As various functions of neutrophils in peripheral blood, such as chemotaxis, phagocytosis and generation of reactive oxygen species (ROS) increase in BD, ROS‐mediated oxidative stress related to neutrophil activation may have an important role in the pathogenesis of BD.

Expert opinion and key recommendations for the physical therapy and rehabilitation of patients with ankylosing spondylitis

Aim:  Physiotherapy is an integral part of the management of ankylosing spondylitis (AS) and there is a need for recommendations which focus on the rehabilitation of patients with AS. We aimed to develop recommendations for the physical therapy and rehabilitation of patients with AS based on the evidence and expertise.

The pathophysiological significance of red blood cell nitric oxide concentrations in inflammatory Behcet's disease.

Nitric oxide (NO) is a free oxygen radical with powerful vasodilator properties studied in many tissues. It is produced by NO synthases in endothelial cells upon stimulation by various agents like cytokines and tumor necrosis factor. The end-products of NO are nitrite and nitrate. Their levels are used biochemically to determine NO synthase activity. Evidence is accumulating for the role of NO in the pathophysiology of inflammatory Behcet’s disease (BD). Indeed, we first demonstrated that serum NO production is increased in active BD, suggesting a possible new activity marker. More recently, we have reported that pro-inflammatory cytokines, inducers of NO, and lipid peroxidation are increased and associated with decreased antioxidant enzyme activities in BD. Our findings were then supported by four independent investigations, one of which was from the present group. 7 Moreover, aqueous humor NO levels were found to be increased in uveitic BD patients. Furthermore, Salvarani et al . have recently shown that the GluAsp298 polymorphism of endothelial NO synthase gene is associated with BD susceptibility. Therefore, to support our previous studies, this report further investigated for the first time NO levels in red blood cells of BD patients compared with age-matched and sex-matched healthy control volunteers. A total of 20 patients with BD (16 men, four women), with a mean age of 33.4 years, and 15 healthy control subjects (12 men, three women), with a mean age of 32.1 years, were enrolled in this study. Patients with BD had to fulfil the International Study Group criteria for the diagnosis of BD. Fasting whole-blood samples were taken from BD patients and control subjects by venipuncture from an antecubital peripheral vein into heparinised plain tubes to prepare the erythrocyte sediment. The buffy coat on the erythrocyte sediment was carefully separated. The erythrocyte sediment was subsequently washed three times with 10-fold volumes of 0.9% sodium chloride solution to remove the plasma remnants. Following this, the erythrocyte sediment was treated with four-fold volumes of ice-cold deionised water to obtain hemolysate. NO is a labile compound and has a brief half-life, and therefore its detection as the native NO molecule is difficult. It is rapidly converted to the stable end-products nitrate (NO3 ) and nitrite (NO2 ) in typical oxygenated aqueous solutions and tissues. Thus, erythrocyte total nitrite levels were measured as an index of NO production. For total nitrite detection, lysate was treated with copperised cadmium in glycine buffer at pH 9.7 (2.5 /3.0 g of cadmium granules for a 4 ml reaction mixture) to reduce NO3 to NO2 . Measurement of total nitrite was based on the Griess reaction, in which a chromofore with a strong absorbance at 540 nm is formed by the reaction of nitrite with a mixture of sulphanilamide and N -(1Letter

Tumour necrosis factor alpha, lipid peroxidation and NO* are increased and associated with decreased free-radical scavenging enzymes in patients with Weill-Marchesani syndrome.

AIM: Weill-Marchesani syndrome (WMS) is a rare systemic disorder with both autosomal recessive and dominant inheritances. Accumulation of reactive oxygen species such as O2*-, H2O2 and OH* causes lipid peroxidation (LPO), whereas antioxidant enzymes (superoxide dismutase (SOD), glutathione peroxidase (GSHPx)) mediate defence against oxidative stress. Excess tumour necrosis factor (TNF)-alpha and NO* react with O2*- and cause further antioxidant depletion with an increase in mutation frequency by H2O2. This study investigated the levels of SOD, GSHPx, catalase (CAT), TNF-alpha, NO and LPO in patients with WMS. METHODS: A group of 10 WMS patients (four males, six females; age, 26.5+/-19.0 years) and 10 age-matched and sex-matched controls (five males, five females; age, 27.3+/-18.2 years) were included. Serum TNF-alpha levels were determined by a spectrophotometer technique using immulite chemiluminescent immunometric assay. Malondialdehyde (MDA) was determined in plasma; CAT in red blood cells (RBCs), and SOD and GSHPx in both plasma and RBCs. Total serum NO* levels were evaluated by Griess reaction. RESULTS: Mean levels of TNF-alpha (8.3+/-0.6 pg/ml) in WMS patients were significantly (p<0.001) higher than controls (4.3+/-0.2 pg/ml). Plasma MDA levels in patients and controls were 5.4+/-0.8 and 1.8+/-0.6 micromol/l, respectively, and the difference was significant (p=0.0002). SOD and GSHPx activities were significantly lower in both RBCs and plasma of WMS than in controls (RBC-SOD, 3981.9+/-626.6 versus 5261.6+/-523.0 U/g haemoglobin (Hb), p=0.0005; plasma-SOD, 529.4+/-49.3 versus 713.4+/-55.7 U/g protein, p=0.0002; RBC-GSHPx, 682.7+/-42.0 versus 756.5+/-47.6 U/g Hb, p=0.0011; plasma-GSHPx, 107.3+/-15.0 versus 131.4+/-19.7 U/g protein, p=0.0113). In addition, serum NO (NO*-2 + NO*-3) levels were also significantly (p = 0.0002) increased in WMS patients (54.4+/-5.7 versus 26.9+/-6.7 micromol/l). RBC-CAT levels were similar between groups (125.6+/-21.3 versus 131.0+/-21.5 k/g Hb, p = 0.8798). CONCLUSIONS: The elevated LPO, TNF-alpha and NO* with decreased antioxidant enzyme activities indicated impaired antioxidative defence mechanisms with an oxidative injury and cell toxicity in WMS patients. The use of multiple antioxidants and free radical scavengers might be helpful in this genetic disorder.

Acrodysostosis associated with hypercalcemia.

An 18-year-old man was admitted to the clinic complaining of deterioration in the function of his hands and feet. The clinical examination revealed that his movements were clumsy and that he had disproportionally short limbs. In addition, he also had facial abnormalities of frontal bossing, hypertelorism, maxillary hypoplasia, broad low nasal bridge, short upturned nose with anteverted nostrils and triangular mouth. All extremities appeared short with stubby fingers and toes and with broad hands and wrinkling of the dorsal skin. Chromosomal analysis showed a normal (46, XY) karyotype. X-ray studies revealed broad, short metacarpals and phalanges with cone-shaped epiphyses and brachycdactyly and a diagnosis of peripheral dysostosis was confirmed by the characteristic radiographic appearance of the hands. Serum calcium and alkaline phosphatase levels were high, parathormone (PTH) was low, but 25 (OH) Vitamin D, albumin, and 24 hour urine calcium levels were in the normal range. Based on these findings, a diagnosis of acrodysostosis associated with hypercalcemia was made. To the best of our knowledge, this represents the first description of this syndrome.

Influence of patient training on persistence, compliance, and tolerability of different dosing frequency regimens of bisphosphonate therapy: An observational study in Turkish patients with postmenopausal osteoporosis

Objective In our study, we aimed to evaluate the influence of training on compliance and persistence with bisphosphonate treatment given on a weekly vs. monthly basis in postmenopausal osteoporosis patients. Methods A total of 979 patients with postmenopausal osteoporosis (mean age: 63.2 ± 7.2 years) were included in this national, multicenter, prospective non-interventional observational cohort registry study. Patients were randomized into training (n = 492, 50.3%, mean age: 63.4 ± 7.2 years) and control (n = 487, 49.7%, mean age: 63.0 ± 7.1 years) groups. Patients in each intervention group were given weekly (44.9% and 44.6% for training and control subjects, respectively) or monthly (55.1% and 55.4%, respectively) bisphosphonate regimens. After the initial visit, patients were followed up at three-month intervals throughout 12 months of treatment for evaluation of persistence, compliance and adverse events. Results On average, 79.4% of the patients were persistent with the treatment with a mean of 350.4 days of duration during the 12-month follow-up period. The mean compliance in the compliant and fully compliant group remained at an average of 86.6%. No significant difference was detected between the training and control groups in terms of compliance and persistence. Significantly longer persistence (360.0 ± 89.0 vs. 345.0 ± 108.0 days; p = 0.035), higher percentage of persistent patients (83.4% vs. 74.2%; p = 0.012) and higher compliance rates (88.8% vs. 83.3%; p = 0.002) were noted in monthly regimen patients in comparison to those given weekly regimen. Conclusion Our findings revealed remarkably high rates for persistence and compliance with bisphosphonate treatment in postmenopausal osteoporosis, with no impact of training on compliance and persistence rates. Longer persistence and better compliance rates were achieved with the monthly bisphosphonate regimen when compared to the weekly regimen.

AB0711 Natriuretic Peptide Levels and the Correlation of Oxidative Stress in Patients with Ankylosing Spondylitis

Background Recently, studies are focused on finding the relation between Natriuretric Peptide and the immune system. Objectives The aim of the present study is assessing the role of serum levels of natriuretic peptides and the correlation of oxidative stress in patients with ankylosing spondylitis Methods This study has been carried out in patients with ankylosing spondylitis (AS). 45 patients with AS and 20 healthy controls were enrolled. Serum levels of pro atrial natriuretic peptide (proANP), brain natriuretic peptide (BNP), N terminal pro C type natriuretic peptide (NTproCNP) who were from natriuretic peptide (NP) family and myeloperoxidase (MPO) activity, serum levels of total lipid hydroperoxides (LHP), neopterin, total oxidant status (TOS), total antioxidant status (TAOS), tumour necrosis factor alpha (TNF-α), advanced oxidation protein products (AOPP) and thiol levels were assayed. Results There was no significant difference in neopterin, TNF-α, TOS, TAOS, proANP and NTproCNP concentration between patients with AS and healthy controls. ESR, CRP, AOPP, MPO, LHP and BNP levels were significantly higher in patients with AS than in controls. Thiol, albumin levels were significantly lower in patients with AS than in controls. There was statistically significant difference between acut phase response markers, ESR and CRP levels of active group and inactive group. AOPP and MPO levels were significantly higher in active group than in inactive group and control group. LHP and thiol levels were statistically significant different in active and inactive group than in control group. NTproCNP, AOPP and LHP levels were significantly higher in patients who were active status than in remission status. Thiol, albumin levels were significantly lower in patients who were active status than in remission status. Serum AOPP levels correlated with BASDAI and BASFI scores, CRP and ESR levels in patients with AS. Conclusions These results indicate that serum AOPP and proANP levels may reflect clinical activity of disease and may be helpful for monitoring patients with AS. The higher levels of MPO activity showed us enhanced production of ROS by activated neutrophils play a role in the pathogenesis of AS patients. It is thought that NPs related to the oxidative stres in patients with AS and may play an important role of the pathogenesis. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1064