I Fresko

Istanbul University, İstanbul, Istanbul, Turkey

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Publications (64)208.72 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Detailed information on patient recruitment and study settings is an important component of reports of randomized controlled trials (RCTs). We had the impression that many RCTs published in rheumatology journals lacked this information. This study was undertaken to systemically survey this matter in 6 leading journals. A hand search was conducted for RCTs published in 2011 and 2012 in Arthritis & Rheumatism, Annals of the Rheumatic Diseases, Rheumatology (Oxford), Arthritis Care & Research, The Journal of Rheumatology, and Clinical and Experimental Rheumatology. Using the Consolidated Standards of Reporting Trials (CONSORT) guidelines, 2 observers evaluated the articles for the inclusion of patient eligibility criteria, including method of recruitment; study health care settings; geographic location; and, among multicenter studies, a discussion of possible effects of intercenter differences on outcomes. Among 118 articles, an informative account of the method of recruitment was available in 36 (30.5%). Information about the study health care setting was found in 56 (47.5%). Patient socioeconomic profile was available in 11 (9.3%), patient education level in 10 (8.4%), and patient race in 48 (40.7%). Among 76 multicenter studies, the potential effects of possible intercenter differences on outcome were discussed in 13 (17.1%). There were no important differences between the 3 journals that emphasized the use of CONSORT in their author guidelines and the remaining 3 journals. Adequate information on patient recruitment, the trial setting, and a discussion of possible multicenter design effects on outcomes are lacking in the majority of RCT reports in rheumatology. This affects the validity of these reports and calls for closer attention of authors, journals, and reviewers.
    Arthritis & rheumatology (Hoboken, N.J.). 05/2014; 66(5):1395-1399.
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    ABSTRACT: Behçet's syndrome (BS) is a systemic inflammatory disorder with unknown etiology. Features of both innate and adaptive immunity have been claimed in the pathogenesis of BS. To test the possible dysregulation of the NLRP3/cryopyrin (Nod-like receptor with a pyrin domain 3) inflammasome, as a result of mutation(s), we performed single-strand conformation polymorphism analyses and/or sequencing of all the coding regions and intron-exon boundaries of NLRP3/cryopyrin and ASC (apoptosis-associated speck-like protein containing CARD) genes from Turkish BS patients and healthy controls. At the same time, we determined pro-inflammatory cytokine secretion profiles of peripheral blood cells in response to LPS treatment using ELISA. BS patients with vascular involvement showed significantly increased levels of TNF-α release at 2-, 4- and 8-h post-treatment and significantly increased IL-1β levels were detected at 2h (P = 0.005) and 4h (P = 0.025) (n = 10). We identified four mutations in the NLRP3/cryopyrin gene, V200M (n = 3/104) and T195M (n = 1/104), in BS patients but none in control samples. No mutations were detected in the ASC gene. The effect of these NLRP3/cryopyrin mutants on ASC speck assembly and IL-1β secretion was tested and the V200M mutant was shown to induce IL-1β secretion. Thus, it is likely that certain mutations in NLRP3/cryopyrin in combination with yet unknown other factors may contribute to the pro-inflammatory cytokine profiles in BS patients.
    International Immunology 10/2013; · 3.14 Impact Factor
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    ABSTRACT: Behçet's syndrome (BS) is a systemic inflammatory disorder with unknown etiology. Features of both innate and adaptive immunity have been claimed in the pathogenesis of BS. To test the possible dysregulation of the NLRP3/cryopyrin (Nod-like receptor with a pyrin domain 3)inflammasome, as a result of mutation(s), we performed single-strand conformation polymorphism analyses and/ or sequencing of all the coding regions and intron–exon boundaries of NLRP3/cryopyrin and ASC (apoptosis-associated speck-like protein containing CARD) genes from Turkish BS patients and healthy controls. At the same time, we determined pro-inflammatory cytokine secretion profiles of peripheral blood cells in response to LPS treatment using ELISA. BS patients with vascular involvement showed significantly increased levels of TNF-α release at 2-, 4-and 8-h post-treatment and significantly increased IL-1β levels were detected at 2 h (P=0.005) and 4 h (P=0.025) (n=10). We identified four mutations in the NLRP3/cryopyrin gene, V200M (n=3/104) and T195M (n=1/104), in BS patients but none in control samples. No mutations were detected in the ASC gene. The effect of these NLRP3/cryopyrin mutants on ASC speck assembly and IL-1β secretion was tested and the V200M mutant was shown to induce IL-1β secretion. Thus, it is likely that certain mutations in NLRP3/cryopyrin in combination with yet unknown other factors may contribute to the pro-inflammatory cytokine profiles in BS patients.
  • Indian Journal of Rheumatology 09/2013; 6(3):S14.
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    ABSTRACT: Takayasu arteritis is a rare inflammatory disease of large arteries. The etiology of Takayasu arteritis remains poorly understood, but genetic contribution to the disease pathogenesis is supported by the genetic association with HLA-B(∗)52. We genotyped ∼200,000 genetic variants in two ethnically divergent Takayasu arteritis cohorts from Turkey and North America by using a custom-designed genotyping platform (Immunochip). Additional genetic variants and the classical HLA alleles were imputed and analyzed. We identified and confirmed two independent susceptibility loci within the HLA region (r(2) < 0.2): HLA-B/MICA (rs12524487, OR = 3.29, p = 5.57 × 10(-16)) and HLA-DQB1/HLA-DRB1 (rs113452171, OR = 2.34, p = 3.74 × 10(-9); and rs189754752, OR = 2.47, p = 4.22 × 10(-9)). In addition, we identified and confirmed a genetic association between Takayasu arteritis and the FCGR2A/FCGR3A locus on chromosome 1 (rs10919543, OR = 1.81, p = 5.89 × 10(-12)). The risk allele in this locus results in increased mRNA expression of FCGR2A. We also established the genetic association between IL12B and Takayasu arteritis (rs56167332, OR = 1.54, p = 2.18 × 10(-8)).
    The American Journal of Human Genetics 07/2013; · 11.20 Impact Factor
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    ABSTRACT: Behçet's disease usually begins with cutaneous manifestations, such as recurrent aphthous stomatitis, genital ulcers, erythema nodosum-like lesions, papulopustular findings, and pathergy phenomenon. Recurrent aphthous stomatitis is generally the first sign, and other findings may develop in the course of the disease. There is no specific diagnostic available for Behçet's disease. It is most prevalent among patients along the ancient Silk Road. The high frequency of HLA-B51 among a wide range of ethnic populations favors the role of genetic factors. Behçet's disease usually appears in the third to fourth decade of life, and is rarely seen in children and adults over 50 years of age. It affects both genders equally, but the course of the disease is more severe in men. Eye involvement leading to loss of vision, plus vascular, articular, and central nervous system involvement are more commonly observed among men. Behçet's disease is a systemic inflammatory disorder. A complex genetic background, coupled with innate and adaptive immune system activation, causes the diverse clinical manifestations that characterize the clinical picture.
    Clinics in dermatology 01/2013; 32(3):435-42. · 3.11 Impact Factor
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    ABSTRACT: A similar disease severity among men and women in Brasil, a high frequency of gastrointestinal involvement in China, Japan and USA, a low frequency of pathergy positivity in Japan and USA underline the ethnic variations reported in recent studies. Polymorphisms pertaining both to innate and adaptive immunity in genome wide association studies, clusters in phenotype, and new mechanisms for emerging therapeutic implications have been reported. A Th17 dominance seems to be likely with the exception of gastrointestinal involvement. Infliximab, interferon-alpha and cyclosporine-A may be showing their beneficial effects also by affecting the Th17 cells. The clinical course and outcome of isolated pulmonary artery thrombosis is similar to pulmonary artery aneurysms. Parenchymal lesions (nodules, consolidations, cavities and ground glass lesions) are common in patients with pulmonary involvement. Pericarditis is a frequent cardiac manifestation in France. Treatment of BS became more intensive than before. Immunosuppressives and corticosteroids seem to prevent relapses of venous thrombosis. Studies are needed to understand the role of anticoagulants. Interferon alpha-2a appears to be effective at lower dosage, which brings the advantage of decreased cost and increased tolerability. Switching between anti-TNF agents, when needed, is possible. Interleukin-1 and interleukin-6 are new promising targets.
    Clinical and experimental rheumatology 09/2012; · 2.66 Impact Factor
  • Izzet Fresko
    Clinical and experimental rheumatology 09/2012; · 2.66 Impact Factor
  • Aksel Siva, Izzet Fresko
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    ABSTRACT: – •Clinical and imaging data suggest that Behçet’s disease (BD) can present with a variety of neurologic complications, which may be subclassified into two forms. One is attributable to small venous inflammatory disease with focal or multifocal central nervous system involvement and is seen in the majority of patients. It is designated Central Nervous System-Neuro-Behcet syndrome (CNS-NBS). The other form is due to cerebral venous sinus thrombosis and has limited symptoms and a better prognosis. It is very uncommon for these two types of involvement to occur in the same individual. It is very likely that the two major forms have different pathogeneses. – •Patients with small vein inflammation should be considered for aggressive treatment. A substantial number of patients in this group will have a relapsing-remitting course; for some, this will evolve into a secondary progressive course. A few patients from this group will have progressive CNS dysfunction from the onset. – •Acute attacks of CNS-NBS are treated with either oral prednisone (1 mg/kg/d up to 4 weeks or until improvement is observed) or high-dose intravenous methylprednisolone (IVMP), 1 g/d for 5 to 7 days. After either treatment, an oral tapering dose of glucocorticoids should be given over 2 to 3 months to avoid early relapses. Some patients may require the long-term use of low maintenance doses of glucocorticoids to prevent exacerbations. – •Immunosuppressive agents (eg, azathioprine, cyclosporine A, cyclophosphamide, and chlorambucil), given either alone or in different combinations (eg, azathioprine with cyclosporine) for the long-term treatment of various systemic manifestations of BD, have not been shown to prevent the development of the neurologic complications of the disease, reduce its exacerbations, or stop its progression. – •Immunomodulatory treatments such as interferon alfa and thalidomide have been shown to be effective in treating some of the systemic manifestations of BD, but there is no information on their effects on the development and progression of CNS-NBS. – •Cerebral venous sinus thrombosis in BD is treated with either intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin given together with a short course of glucocorticoids. Evidence of benefit from this treatment, however, is weak.
    Current Treatment Options in Neurology 04/2012; 2(5):435-447. · 1.94 Impact Factor
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    ABSTRACT: Immunosuppressives are frequently stopped in patients with granulomatosis with polyangiitis (GPA) (Wegener's granulomatosis) who develop end-stage renal disease. This is done because of the high frequency of infections reported among dialysis patients under immunosuppressives and the former impression that GPA patients no longer experience relapses after the development of end-stage renal disease. We present here a 22-year-old male patient with GPA who had gastrointestinal, genitourinary and respiratory system involvement. The patient died because of a gastrointestinal disease activation that occurred after immunosuppressives were stopped at the initiation of dialysis. The decision to stop immunosuppressives while starting dialysis should be made on an individual basis in patients with GPA, and the risks and benefits should be carefully evaluated.
    Clinical and experimental rheumatology 02/2012; 30(1 Suppl 70):S104-6. · 2.66 Impact Factor
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    ABSTRACT: Takayasu's arteritis (TA) is a chronic arterial inflammation of unknown etiology involving mainly the aorta and its major branches. Based on the associations of programmed death-1 (PD-1) protein encoding gene (PDCD1) with connective tissue diseases and vasculitides, PDCD1 polymorphisms are studied for susceptibility to TA in this study. The study group is made up of TA patients (n=229) fulfilling the 1990 ACR classification criteria and compared to 193 healthy controls (HC). PD-1.3, PD-1.5 and PD-1.6 single nucleotide polymorphisms of PDCD1 gene are genotyped by polymerase chain reaction and restriction analysis (PCR-RFLP). The distribution of PD-1.5 polymorphism in TA patients and HC revealed a similar presence of TT genotype in patients and controls (13.3% vs. 11.4%). PD-1.3 and PD-1.6 were less polymorphic and did not differ between the groups. Rare AA genotype of PD-1.3 (1.4% vs. 1.0%) and AG genotype of PD-1.6 was again similarly (22.4% vs. 19.2%) present in TA and HC. PD-1.3, 1.5 and 1.6 polymorphisms of PDCD1 gene, which were shown to be associated with various autoimmune disorders and vasculitides, are not associated with a susceptibility to TA in Turkish population.
    Clinical and experimental rheumatology 01/2012; 30(1 Suppl 70):S11-4. · 2.66 Impact Factor
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    ABSTRACT: Determination of oxidant stress in plasma of rheumatoid arthritis (RA) and primary osteoarthritis (POA) patients is important in understanding the pathogenesis of these diseases. In this study, we examined the relationship between oxidant stress and inflammation by measuring protein carbonyl content, thiol levels and plasma protein fractions as the oxidation markers and erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) tests as inflammation markers. Protein carbonyls content was higher in RA and POA patients, as compared to controls (p<0.0001), while the plasma thiol levels in both groups of patients were significantly lower than controls (p<0.0001). Increased levels of proteins under 40 kDa molecular mass were detected in the RA and POA patients compared to that of controls (p<0.0001) both in HPLC and SDS-PAGE analysis. Total protein concentration in plasma of RA patients was higher than the controls (p<0.001), while in POA patients was lower than that of controls (p<0.001). ESR and CRP levels were higher in both the patient groups than the normal group (p<0.001). These results suggested that alterations in the oxidant stress markers could be the cause of inflammation in these diseases. Thus, while working for RA/POA treatment strategies, consideration of the relationship between oxidant stress and inflammation would be worth evaluating.
    Indian journal of biochemistry & biophysics 12/2010; 47(6):353-8. · 1.03 Impact Factor
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    ABSTRACT: Case reports on monozygotic (MZ) twins with Behçet's syndrome (BS) have been few and we are not aware of formal twin studies. We sought the frequency of MZ and dizygotic (DZ) twin births in BS and compared it to a healthy population sample from the same geography. We also looked for the concordance rate among the MZ and DZ twins. 1705 (1039M/666F) patients attending a dedicated BS outpatient clinic and 7761 (3848M/3913F) medical school students were asked about having a MZ or DZ twin sibling. MZ and DZ twins thus identified among both patients and controls were individually seen at the clinic. In addition, HLA, DNA microsatellite markers and blood groups were typed to further confirm twin- ship. All twins were contacted 8 years later for new emergence of disease. There were 14 (0.82%) patients with BS and 120 (1.55%) controls who had a twin sibling (p=0.022). Of these, 8 (0.47%) patients with BS and 92 (1.19%) controls had a DZ twin sibling (p=0.009). MZ twin frequency was similar between BS patients (6/1705; 0.35%) and control population (28/7761; 0.36%). The pairwise concordance rate for BS was 2/6 (95% CI: -0.21-0.88) for MZ and 1/8 (95% CI: -0.17-0.42) for DZ twins (p=0.538). Genetic effects accounted for 41% of the phenotypic variance for BS among twins. After 8 years of follow-up, 4 of 6 MZ and 6 of 7 DZ twin pairs were still discordant. The frequency of MZ twin births in BS is not different than that in the general population while the DZ twins were seen less frequently among the BS patients. The concordances for BS were higher in MZ compared with DZ twins, suggesting genetic predisposition. On the other hand, the persistence of discordance after 8 years of follow up among the remaining MZ twins demands further research to understand non- genetic factors in causation of BS.
    Clinical and experimental rheumatology 01/2010; 28(4 Suppl 60):S62-6. · 2.66 Impact Factor
  • Izzet Fresko, Hasan Yazici
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    ABSTRACT: Behçet's disease (BD) is a multisytemic vasculitis characterized by oral and genital ulceration, other skin lesions, uveitis and manifestations affecting the blood vessels, CNS and gastrointestinal system. It is rare in the Western world but is frequent in the Middle and Far East. The aim of this review is to discuss treatment strategies in BD. These might vary between simple reassurance and a combination of immunosuppressives. A systematic literature search was done using the Cochrane and Medline databases in June 2008. The EULAR recommendations for the management of BD were also taken into account. The last two decades have witnessed considerable improvement in eye disease and musculoskeletal involvement. However, the treatment of thrombophlebitis, CNS, and gastrointestinal manifestations remains problematic.
    Expert Opinion on Pharmacotherapy 01/2009; 9(18):3211-9. · 2.86 Impact Factor
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    ABSTRACT: We had the impression and preliminary evidence that atherosclerosis was not much increased in Behçet's syndrome (BS). Thus, we evaluated the presence of subclinical atherosclerosis in a sizeable group of patients with BS both with major organ involvement and mucocutaneous disease along with diseased and healthy controls. We studied 239 (162 M/ 77 F; mean age: 40.7+/-7.0) patients with BS. Seventy-two (32 M/ 40 F) had only mucocutaneous and/or joint disease and 167 (130 M/ 37 F) had major organ involvement. Also 100 (24 M/ 76 F; mean age: 44.7+/-7.1) patients with rheumatoid arthritis (RA), 74 (58 M/ 16 F; mean age: 39.4+/-7.0) patients with ankylosing spondylitis (AS) and 156 (83 M/ 73 F; mean age: 39.2+/-6.6) healthy controls (HC) were studied as the control groups. We used B-mode USG to assess the frequency of plaques and intima-media thickness (IMT) in the carotid and femoral arteries. Traditional atherosclerotic risk factors were also evaluated. Men and women were analyzed separately. The frequency of plaques and the mean IMT in the carotid and femoral arteries were similar between patients with BS, AS and HC and also between the 2 subgroups of BS, among both men and women. Only men with RA were found to have significantly increased frequency of carotid artery plaques after adjustment for atherosclerotic risk factors. Increased atherosclerosis is not a prominent feature of BS, even among those patients with major organ involvement.
    Seminars in Arthritis and Rheumatism 09/2008; 38(1):1-12. · 3.81 Impact Factor
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    ABSTRACT: Takayasu's arteritis (TA) is a chronic, rare granulomatous panarteritis of unknown aetiology involving mainly the aorta and its major branches. In this study, genetic susceptibility to TA has been investigated by screening the functional single nucleotide polymorphism (SNP) of PTPN22 gene encoding the lymphoid-specific protein tyrosine phosphatase. Totally, 181 patients with TA and 177 healthy controls are genotyped by PCR-RFLP method for the SNP rs2476601 (A/G) of PTPN22 gene. Polymorphic region was amplified by PCR and digested with Xcm I enzyme. Detected frequencies of heterozygous genotype (AG) were 5.1% (9/177) in control group and 3.8% (7/181) in TA group (P = 0.61, odds ratio: 0.75, 95% CI: 0.3, 2.0). No association with angiographic type, vascular involvement or prognosis of TA was observed either. The distribution of PTPN22 polymorphism did not reveal any association with TA in Turkey.
    Rheumatology (Oxford, England) 06/2008; 47(5):634-5. · 4.24 Impact Factor
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    ABSTRACT: Behçet's syndrome is characterized by clusters of disease expression, one of which is the coexistence of acne and arthritis. The aim of this study was to test the hypothesis that enthesopathy is increased in this cluster, having features reminiscent of acne-associated arthritis. The study group comprised 35 patients with Behçet's syndrome who had acne and arthritis (BS-AA), 38 patients with Behçet's syndrome who did not have arthritis (BS-WA), 37 patients with ankylosing spondylitis (AS), 25 patients with rheumatoid arthritis (RA), and 25 healthy control subjects. Five entheseal sites (the superior and inferior poles of the patella, the tibial tuberosity, and the superior and inferior poles of the calcaneus) on both lower extremities were examined by 2 independent observers, using ultrasonography. A previously validated composite score was calculated for each patient. The numbers of entheseal sites giving a positive power Doppler signal in each group were also compared. Patients with AS had the highest enthesopathy score (mean +/- SD 4.1 +/- 2.4; F [4df] = 8.43, P < 0.001) followed by BS-AA patients (3.0 +/- 1.9; F [3df] = 3.63, P = 0.015). The mean +/- SD enthesopathy scores among the remaining 3 groups were similar (for BS-WA, 1.8 +/- 1.4; for RA, 2.2 +/- 1.6; for healthy controls, 2.0 +/- 1.5 [F (2df) = 0.65, P = 0.53]). Power Doppler scores were highest for the BS-AA group (mean +/- SD 3.0 +/- 1.5; F [4df] = 15.54, P < 0.001) followed by the AS group (2.7 +/- 1.8; F [3df] = 14.38, P < 0.001), the RA group (2.6 +/- 1.8; F [2df] = 13.88, P < 0.001), the BS-WA group (1.2 +/- 1.3; F [1df] = 4.48, P = 0.038), and the control group (0.5 +/- 1.1). There was 87% agreement between the 2 observers (kappa = 0.55, intraclass correlation coefficient 0.71). The increased presence of enthesopathy among BS-AA patients compared with that among BS-WA patients further supports the hypothesis that patients with Behçet's syndrome who also have arthritis and acne form a distinct cluster.
    Arthritis & Rheumatology 05/2008; 58(5):1539-45. · 7.48 Impact Factor
  • Clinical and experimental rheumatology 01/2008; 26 (Suppulement 50):S103-6. · 2.66 Impact Factor
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    ABSTRACT: To investigate the role of shared epitope (SE) alleles in the short-term clinical response to leflunomide for the treatment of active RA. In an open-label, multi-centre study of 16-weeks duration, 93 patients (82% female) fulfilling ARA 1987 RA criteria were treated with leflunomide (100 mg loading dose for 3 days, then 20 mg/day as the maintenance dose). The primary efficacy criterion was the response status according to the European League Against Rheumatism (EULAR) response criteria using Disease Activity Score-28 (DAS28) activity measure. SE determinations have been undertaken by polymerase chain reaction and sequence-specific oligonucleotide genotyping methods. The mean (s.d.) Disease Activity Score-28 (DAS28) was 5.1 (1.3) before the treatment, which was significantly decreased after 16 weeks [3.0 (1.1), P < 0.001]. According to the EULAR response criteria, 55 patients (59.1%) were classified as good responders. SE was positive in 51 (54.8%) of the patients, with 13 (13.9%) having SE homozygosity or carrying any two SE alleles. Among SE-positive patients, 68.6% (35/51) were good responders, compared with 47.6% (20/42) in SE negatives (P = 0.04). No difference was present according to SE hetero- or homozygosity (68.4 vs 69.2%). RF was also present significantly more frequently in the SE-positive group compared with negatives (78.4 vs 57.1%, P = 0.03). However, no significant difference was observed in the prevalence of RF positivity in patients with a good clinical response (72.7 vs 63.2%, P = 0.32). The results suggest that HLA-DRB1 SE presence may favourably affect the outcome of leflunomide monotherapy in an unselected group of RA patients with an active disease and naive to leflunomide.
    Rheumatology (Oxford, England) 12/2007; 46(12):1842-4. · 4.24 Impact Factor
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    ABSTRACT: Accumulation of oxidized proteins and impaired antioxidant system have been shown to be associated with arthritis. Serum sialic acid (SA) is known as a parameter of inflammation. In the present study, to explore the potential role of SA in arthritis, we measured serum SA levels, plasma protein oxidation, and antioxidant status in patients with primary osteoarthritis (POA) and inactive rheumatoid arthritis (RA). Inactive RA (iRA) was defined upon the American College of Rheumatology criteria for clinical remission of RA. A total of 40 patients (20 POA patients, including 4 male subjects, and 20 iRA female patients) and 20 healthy female subjects were included in this study. SA, antioxidants, and protein oxidation levels were determined spectrophotometrically in serum or plasma samples. Serum SA levels were significantly increased in POA (3.34 +/- 0.37 mM, p < 0.0001) and iRA (3.11 +/- 0.47 mM, p < 0.05), compared with healthy controls (2.41 +/- 0.16 mM). Plasma total antioxidant activity, plasma superoxide dismutase activity and serum reduced glutathione levels were significantly decreased in patients with POA and those with iRA, whereas plasma carbonyl content and serum total protein were increased in those patients. Moreover, plasma total thiol levels were significantly increased in iRA and decreased in POA. Thus, increased SA and protein oxidation levels are associated with the decreased antioxidant levels in POA and iRA patients. These results suggest that SA may be considered as a potent defense molecule against oxidative damage in arthritis. Antioxidant therapy may halt or ameliorate the progression of arthritis.
    The Tohoku Journal of Experimental Medicine 11/2007; 213(3):241-8. · 1.37 Impact Factor

Publication Stats

1k Citations
208.72 Total Impact Points

Institutions

  • 1998–2014
    • Istanbul University
      • • Department of Family Medicine (Cerrahpasa Faculty of Medicine)
      • • Department of Physiology
      • • Department of Basic Sciences
      İstanbul, Istanbul, Turkey
  • 2010
    • Haydarpasa Numune Research and Teaching Hospital
      İstanbul, Istanbul, Turkey
  • 1993
    • Nisa Hospital, Turkey
      İstanbul, Istanbul, Turkey