E. Tchetina, G. Markova, A. Poole, D. Zukor, J. Antoniou, S. Makarov, A. N. Kuzin
{"title":"Deferoxamine Suppresses Collagen Cleavage and Protease, Cytokine, and COL10A1 Expression and Upregulates AMPK and Krebs Cycle Genes in Human Osteoarthritic Cartilage","authors":"E. Tchetina, G. Markova, A. Poole, D. Zukor, J. Antoniou, S. Makarov, A. N. Kuzin","doi":"10.1155/2016/6432867","DOIUrl":"https://doi.org/10.1155/2016/6432867","url":null,"abstract":"This study reports the effects of the iron chelator deferoxamine (DFO) on collagen cleavage, inflammation, and chondrocyte hypertrophy in relation to energy metabolism-related gene expression in osteoarthritic (OA) articular cartilage. Full-depth explants of human OA knee articular cartilage from arthroplasty were cultured with exogenous DFO (1–50 μM). Type II collagen cleavage and phospho-adenosine monophosphate-activated protein kinase (pAMPK) concentrations were measured using ELISAs. Gene expression studies employed real-time PCR and included AMPK analyses in PBMCs. In OA explants collagen cleavage was frequently downregulated by 10–50 μM DFO. PCR analysis of 7 OA patient cartilages revealed that 10 μM DFO suppressed expression of MMP-1, MMP-13, IL-1β, and TNFα and a marker of chondrocyte hypertrophy, COL10A1. No changes were observed in the expression of glycolysis-related genes. In contrast, expressions of genes associated with the mitochondrial Krebs cycle (TCA), AMPK, HIF1α, and COL2A1 were upregulated. AMPK gene expression was reduced in OA cartilage and increased in PBMCs from the same patients compared to healthy controls. Our studies demonstrate that DFO is capable of suppressing excessive collagenase-mediated type II collagen cleavage in OA cartilage and reversing phenotypic changes. The concomitant upregulation of proanabolic TCA-related gene expressions points to a potential for availability of energy generating substrates required for matrix repair by end-stage OA chondrocytes. This might normally be prevented by high whole-body energy requirements indicated by elevated AMPK expression in PBMCs of OA patients.","PeriodicalId":51715,"journal":{"name":"International Journal of Rheumatology","volume":"2016 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2016-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2016/6432867","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64478841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Risk of Malignant Neoplasm in Patients with Incident Rheumatoid Arthritis 1980–2007 in relation to a Comparator Cohort: A Population-Based Study","authors":"Shafay Raheel, C. Crowson, K. Wright, E. Matteson","doi":"10.1155/2016/4609486","DOIUrl":"https://doi.org/10.1155/2016/4609486","url":null,"abstract":"Objective. To determine whether the incidence of malignancy is increased in patients with rheumatoid arthritis (RA) compared to a matched comparison cohort and to identify risk for any individual malignancy in RA. Methods. A cohort of 813 Olmsted County, Minnesota, residents who first fulfilled 1987 ACR criteria for RA in 1980–2007 was previously identified by medical record review. Medical records of 813 RA cases and a comparison cohort of age and sex matched Olmsted County residents without RA were evaluated retrospectively for cancer occurrence. Patients in both cohorts were followed until death, migration from Olmsted County, or 12/31/2014. Results. The RA and non-RA cohorts (mean age at incidence/index date: 55.9 [SD: 15.7] years; 68.4% females in both cohorts) were followed on average of 14.1 (SD: 7.7) and 14.9 (SD: 8.1) years, respectively. Prior to RA incidence/index date, 52 RA patients and 66 non-RA subjects had malignancies excluding NMSC (p = 0.21). During follow-up, significantly more malignancies occurred in patients with RA (n = 143) than in comparator subjects (n = 118; hazard ratio: 1.32; p = 0.027). Inclusion of NMSC obviated this difference. Conclusion. After excluding NMSC, there was a small to moderately increased risk of malignancies in patients with RA. Cancer surveillance is imperative in all patients with RA.","PeriodicalId":51715,"journal":{"name":"International Journal of Rheumatology","volume":"2016 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2016-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2016/4609486","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64388393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Makoto Tanaka, H. Yamada, S. Nishikawa, H. Mori, Y. Ochi, N. Horai, Minqi Li, N. Amizuka
{"title":"Joint Degradation in a Monkey Model of Collagen-Induced Arthritis: Role of Cathepsin K Based on Biochemical Markers and Histological Evaluation","authors":"Makoto Tanaka, H. Yamada, S. Nishikawa, H. Mori, Y. Ochi, N. Horai, Minqi Li, N. Amizuka","doi":"10.1155/2016/8938916","DOIUrl":"https://doi.org/10.1155/2016/8938916","url":null,"abstract":"The role of cathepsin K in joint degradation in a model of collagen-induced arthritis (CIA) in cynomolgus monkey was examined using biochemical markers and histology. Joint swelling, urinary C-telopeptide of type II collagen (CTX-II), deoxypyridinoline (DPD), and N- and C-telopeptides of type I collagen (NTX and CTX-I, resp.) were analyzed. Immunohistochemistry of type II collagen, cathepsin K, and CTX-II were performed using joints. Joint swelling reached peak on day 42 and continued at this level. The CTX-II level peaked on day 28 and declined thereafter, while CTX-I, NTX, and DPD reached plateau on day 43. Joint swelling was positively correlated with CTX-II increases on days 20 and 42/43, with increases in CTX-I and NTX/Cr on days 42/43 and 84, and with DPD increases throughout the study period. Intense cathepsin K staining was observed in osteoclasts and in articular cartilage and synovial tissue in arthritic joints. CTX-II was present in the superficial layer of articular cartilage in CIA monkeys. Evidence from biochemical markers suggests that matrix degradation in the CIA model starts with degradation of cartilage, rather than bone resorption. Cathepsin K expressed in osteoclasts, articular cartilage, and synovial tissue may contribute to degradation of cartilage.","PeriodicalId":51715,"journal":{"name":"International Journal of Rheumatology","volume":"2016 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2016-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2016/8938916","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64590889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G E M Reeves, N Collins, P Hayes, J Knapp, M Squance, H Tran, B Bastian
{"title":"SAPHIRE: Stress and Pulmonary Hypertension in Rheumatoid Evaluation-A Prevalence Study.","authors":"G E M Reeves, N Collins, P Hayes, J Knapp, M Squance, H Tran, B Bastian","doi":"10.1155/2016/4564531","DOIUrl":"10.1155/2016/4564531","url":null,"abstract":"<p><p>Pulmonary artery hypertension (PAH) is a disorder of elevated resistance in the pulmonary arterial vessels, reflected by elevation of measured pulmonary artery pressure (PAP), and presenting with breathlessness and, if untreated, progressing to right heart failure and death. The heightened prevalence of PAH in populations with underlying systemic autoimmune conditions, particularly scleroderma and its variants, is well recognised, consistent with the proposed autoimmune contribution to PAH pathogenesis, along with disordered thrombotic, inflammatory, and mitogenic factors. Rheumatoid arthritis (RA) is one of a group of systemic autoimmune conditions featuring inflammatory symmetrical erosive polyarthropathy as its hallmark. This study explored the prevalence of PAH in a population of unselected individuals with RA, using exercise echocardiography (EchoCG). The high prevalence of EchoCG-derived elevation of PAP (EDEPP) in this population (14%) suggests that, like other autoimmune conditions, RA may be a risk factor for PAH. Patients with RA may therefore represent another population for whom PAH screening with noninvasive tools such as EchoCG may be justified. </p>","PeriodicalId":51715,"journal":{"name":"International Journal of Rheumatology","volume":"2016 ","pages":"4564531"},"PeriodicalIF":2.3,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34397847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M Y Pervakova, V L Emanuel, O N Titova, S V Lapin, V I Mazurov, I B Belyaeva, A L Chudinov, T V Blinova, E A Surkova
{"title":"The Diagnostic Value of Alpha-1-Antitrypsin Phenotype in Patients with Granulomatosis with Polyangiitis.","authors":"M Y Pervakova, V L Emanuel, O N Titova, S V Lapin, V I Mazurov, I B Belyaeva, A L Chudinov, T V Blinova, E A Surkova","doi":"10.1155/2016/7831410","DOIUrl":"https://doi.org/10.1155/2016/7831410","url":null,"abstract":"<p><p>The deficiency of alpha-1 protease inhibitor, or alpha-1-antitrypsin (A1AT), predisposes to chronic lung diseases and extrapulmonary pathology. Besides classical manifestations, such as pulmonary emphysema and liver disease, alpha-1-antitrypsin deficiency (A1ATD) is also known to be associated with granulomatosis with polyangiitis (GPA or Wegener's granulomatosis). The aim of our study was to evaluate the frequency of allelic isoforms of A1AT and their clinical significance among GPA patients. Detailed clinical information, including Birmingham Vasculitis Activity Score (BVAS), incidence of lung involvement, anti-proteinase 3 (PR3) antibodies concentrations, and other laboratory data were collected in 38 GPA patients. We also studied serum samples obtained from 46 healthy donors. In all collected samples A1AT phenotyping by isoelectrofocusing (IEF) and turbidimetric A1AT measurement were performed. Abnormal A1AT variants were found in 18.4% (7/38) of cases: 1 ZZ, 4 MZ, 2 MF, and only 1 MZ in control group (2%). The mean A1AT concentration in samples with atypical A1AT phenotypes was significantly lower (P = 0.0038) than in normal A1AT phenotype. We found that patients with abnormal A1AT phenotypes had significantly higher vasculitis activity (BVAS) as well as anti-PR3 antibodies concentration. We conclude that A1AT deficiency should be considered in all patients with GPA. </p>","PeriodicalId":51715,"journal":{"name":"International Journal of Rheumatology","volume":"2016 ","pages":"7831410"},"PeriodicalIF":2.3,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2016/7831410","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34441319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohammed Alsuwaidi, Margit Dollinger, Martin Fleck, Boris Ehrenstein
{"title":"The Reliability of a Novel Automated System for ANA Immunofluorescence Analysis in Daily Clinical Practice.","authors":"Mohammed Alsuwaidi, Margit Dollinger, Martin Fleck, Boris Ehrenstein","doi":"10.1155/2016/6019268","DOIUrl":"https://doi.org/10.1155/2016/6019268","url":null,"abstract":"<p><p>Automated interpretation (AI) systems for antinuclear antibody (ANA) analysis have been introduced based on assessment of indirect immunofluorescence (IIF) patterns. The diagnostic performance of a novel automated IIF reading system was compared with visual interpretation (VI) of IIF in daily clinical practice to evaluate the reduction of workload. ANA-IIF tests of consecutive serum samples from patients with suspected connective tissue disease were carried out using HEp-2 cells according to routine clinical care. AI was performed using a visual analyser (Zenit G-Sight, Menarini, Germany). Agreement rates between ANA results by AI and VI were calculated. Of the 336 samples investigated, VI yielded 205 (61%) negative, 42 (13%) ambiguous, and 89 (26%) positive results, whereas 82 (24%) were determined to be negative, 176 (52%) ambiguous, and 78 (24%) positive by AI. AI displayed a diagnostic accuracy of 175/336 samples (52%) with a kappa coefficient of 0.34 compared to VI being the gold standard. Solely relying on AI, with VI only performed for all ambiguous samples by AI, would have missed 1 of 89 (1%) positive results by VI and misclassified 2 of 205 (1%) negative results by VI as positive. The use of AI in daily clinical practice resulted only in a moderate reduction of the VI workload (82 of 336 samples: 24%). </p>","PeriodicalId":51715,"journal":{"name":"International Journal of Rheumatology","volume":"2016 ","pages":"6019268"},"PeriodicalIF":2.3,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2016/6019268","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34534881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chuan-Yin Sun, Yan Shen, Xiao-Wei Chen, Yu-Cheng Yan, Feng-Xia Wu, Ming Dai, Ting Li, Cheng-De Yang
{"title":"Erratum to \"The Characteristics and Significance of Locally Infiltrating B Cells in Lupus Nephritis and Their Association with Local BAFF Expression\".","authors":"Chuan-Yin Sun, Yan Shen, Xiao-Wei Chen, Yu-Cheng Yan, Feng-Xia Wu, Ming Dai, Ting Li, Cheng-De Yang","doi":"10.1155/2016/7513892","DOIUrl":"https://doi.org/10.1155/2016/7513892","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1155/2013/954292.]. </p>","PeriodicalId":51715,"journal":{"name":"International Journal of Rheumatology","volume":"2016 ","pages":"7513892"},"PeriodicalIF":2.3,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2016/7513892","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34731295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fawad Aslam, Salman J Bandeali, Cynthia Crowson, Mahboob Alam
{"title":"Cardiac Function and Diastolic Dysfunction in Behcet's Disease: A Systematic Review and Meta-Analysis.","authors":"Fawad Aslam, Salman J Bandeali, Cynthia Crowson, Mahboob Alam","doi":"10.1155/2016/9837184","DOIUrl":"https://doi.org/10.1155/2016/9837184","url":null,"abstract":"<p><p>Background. Cardiovascular involvement in Behcet's disease (BD) is reported and has variable manifestations. It is not clear if diastolic dysfunction (DD) is increased in BD. Our objective was to evaluate the existing literature to determine if cardiac dysfunction, particularly DD, was more prevalent in these patients. Methods. A systematic review and meta-analysis of the available studies analyzing the echocardiographic findings in BD was conducted using a random-effects model. Mean differences were used to calculate the effect sizes of the echocardiographic parameters of interest. Results. A total of 22 studies with 1624 subjects were included in the analysis. Patients with BD had statistically significantly larger mean left atrial dimension (0.08, p = 0.0008), greater aortic diameter (0.16, p = 0.02), significantly reduced ejection fraction (-1.08, p < 0.0001), significantly prolonged mitral deceleration time (14.20, p < 0.0001), lower E/A ratio (-0.24, p = 0.05), and increased isovolumetric relaxation time (7.29, p < 0.00001). Conclusion. DD is increased in patients with BD by the presence of several echocardiographic parameters favoring DD as compared to controls. The meta-analysis also identified that LA dimension is increased in BD patients. EF has also been found to be lower in BD patients. Aortic diameter was also increased in BD patients as compared to controls. </p>","PeriodicalId":51715,"journal":{"name":"International Journal of Rheumatology","volume":"2016 ","pages":"9837184"},"PeriodicalIF":2.3,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2016/9837184","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34534882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aurélien Dinh, Maxime Jean, Frédérique Bouchand, Benjamin Davido, Alexis Descatha, Clara Duran, Guillaume Gras, Christian Perronne, Denis Mulleman, Jérôme Salomon, Louis Bernard
{"title":"Impact of Anti-Inflammatory Drugs on Pyogenic Vertebral Osteomyelitis: A Prospective Cohort Study.","authors":"Aurélien Dinh, Maxime Jean, Frédérique Bouchand, Benjamin Davido, Alexis Descatha, Clara Duran, Guillaume Gras, Christian Perronne, Denis Mulleman, Jérôme Salomon, Louis Bernard","doi":"10.1155/2016/9345467","DOIUrl":"10.1155/2016/9345467","url":null,"abstract":"<p><p><i>Objective</i>. Pyogenic vertebral osteomyelitis (PVO) are frequently misdiagnosed and patients often receive anti-inflammatory drugs for their back pain. We studied the impact of these medications. <i>Methods</i>. We performed a prospective study enrolling patients with PVO and categorized them depending on their drugs intake. Then, we compared diagnosis delay, clinical presentation at hospitalization, incidence of complications, and cure rate. <i>Results</i>. In total, 79 patients were included. Multivariate analysis found no correlation between anti-inflammatory drug intake and diagnosis delay, clinical presentation, complications, or outcome. <i>Conclusion</i>. Anti-inflammatory drugs intake does not affect diagnostic delay, severity at diagnosis, or complications of PVO.</p>","PeriodicalId":51715,"journal":{"name":"International Journal of Rheumatology","volume":"2016 1","pages":"9345467"},"PeriodicalIF":2.3,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2016/9345467","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64610132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kaspar Tootsi, Jaak Kals, Mihkel Zilmer, Kaido Paapstel, Aare Märtson
{"title":"Severity of Osteoarthritis Is Associated with Increased Arterial Stiffness.","authors":"Kaspar Tootsi, Jaak Kals, Mihkel Zilmer, Kaido Paapstel, Aare Märtson","doi":"10.1155/2016/6402963","DOIUrl":"https://doi.org/10.1155/2016/6402963","url":null,"abstract":"<p><p>Objective. Osteoarthritis (OA) is associated with increased cardiovascular comorbidity and mortality. Evidence is lacking about whether arterial stiffness is involved in OA. The objective of our study was to find out associations between OA, arterial stiffness, and adipokines. Design. Seventy end-stage knee and hip OA patients (age 62 ± 7 years) and 70 asymptomatic controls (age 60 ± 7 years) were investigated using the applanation tonometry to determine their parameters of arterial stiffness. Serum adiponectin, leptin, and matrix metalloproteinase 3 (MMP-3) levels were determined using the ELISA method. Correlation between variables was determined using Spearman's rho. Multiple regression analysis with a stepwise selection procedure was employed. Results. Radiographic OA grade was positively associated with increased carotid-femoral pulse wave velocity (cf-PWV) (r = 0.272, p = 0.023). We found that OA grade was also associated with leptin and MMP-3 levels (rho = -0.246, p = 0.040 and rho = 0.235, p = 0.050, resp.). In addition, serum adiponectin level was positively associated with augmentation index and inversely with large artery elasticity index (rho = 0.293, p = 0.006 and rho = -0.249, p = 0.003, resp.). Conclusions. Our results suggest that OA severity is independently associated with increased arterial stiffness and is correlated with expression of adipokines. Thus, increased arterial stiffness and adipokines might play an important role in elevated cardiovascular risk in end-stage OA. </p>","PeriodicalId":51715,"journal":{"name":"International Journal of Rheumatology","volume":"2016 ","pages":"6402963"},"PeriodicalIF":2.3,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2016/6402963","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34624832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}