Rheumatology (Sunnyvale, Calif.)最新文献

{"title":"The Relationship of Pulse Pressure and Bone Mineral Density in Adult USA Population: Analysis of the National Health and Nutritional Examination Survey.","authors":"Isabel M McFarlane,&nbsp;Tai Ho Shin,&nbsp;Manjeet Bhamra,&nbsp;Milena Rodriguez Alvarez,&nbsp;Su Zhaz Leon,&nbsp;David J Ozeri,&nbsp;Carla Saladini,&nbsp;Yair Saperstein,&nbsp;Latoya Freeman,&nbsp;Muhammad A Khan,&nbsp;Perry Wengrofsky,&nbsp;Nwakile Ojike,&nbsp;Moro O Salifu","doi":"10.4172/2161-1149.1000240","DOIUrl":"https://doi.org/10.4172/2161-1149.1000240","url":null,"abstract":"<p><strong>Background/purpose: </strong>Accumulating evidence indicates a relationship between Cardiovascular Disease (CVD) and osteoporosis. Hypertension, a known risk factor for CVD is also associated with low Bone Mineral Density (BMD). We hypothesize that Pulse Pressure (PP); a CVD risk factor is associated with BMD.</p><p><strong>Methods: </strong>Data from two consecutive cycles of National Health and Nutritional Examination Survey (NHANES) from 2009-2010 and 2011-2012. Point estimates of demographic variables were calculated using descriptive methods. Study participants were divided into 4 groups based on quartile distribution of PP. Multivariate linear regression analysis was performed to assess the relationship between BMD and PP.</p><p><strong>Results: </strong>A total of 8,179 NHANES participants were included in the study (Tables 1-3). The cohort's mean age (± SE) was 53.3 years 0.19, mean BMI (± SE) 29.6 kg/m² ± 0.07. PP was significantly higher with increased age, among Blacks (57.4 ± 0.52) and Hispanics (57.5 ± 0.19) compared to whites (53.9 ± 0.29), and for men (57.2 ± 0.16) when compared to women (54.1 ± 0.17), p<0.05. After adjusting for age, sex, race, menopause, body mass index, family history of osteoporosis, PP was associated with femoral neck BMD, β=-0.0005, p<0.05 but was not significantly associated with lumbar spine BMD, β=-0.0002, p=0.07.</p><p><strong>Conclusion: </strong>Our results support the hypothesis that wide PP is associated with low BMD. This negative association was demonstrated at the femoral neck where bone loss and osteoporotic fractures occur at a more advanced stage, further supporting the relationship between atherosclerosis and osteoporosis risk. These findings have the potential for identifying high osteoporotic risk patients among those with wide pulse pressure, providing further indications for bone mineral density testing among these elderly frail patients. Further research is needed to investigate the mechanisms behind the relationship between PP and BMD.</p>","PeriodicalId":74735,"journal":{"name":"Rheumatology (Sunnyvale, Calif.)","volume":"8 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4172/2161-1149.1000240","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10541011","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":"Tacrolimus-Induced Remission in Drug Resistant Inflammatory Myopathy: A Case Series.","authors":"Karina Rotella,&nbsp;Milena Rodriguez Alvarez,&nbsp;Yair Saperstein,&nbsp;Manjeet S Bhamra,&nbsp;Su Zhaz Leon,&nbsp;Alekznder Feoktiztov,&nbsp;Isabel M McFarlane","doi":"10.4172/2161-1149.1000238","DOIUrl":"https://doi.org/10.4172/2161-1149.1000238","url":null,"abstract":"<p><p>Idiopathic inflammatory myopathies are rare autoimmune disorders characterized by proximal muscle weakness, elevation of muscle enzymes, abnormal electromyogram and imaging studies revealing areas of edema and inflammation. Initial approach to inflammatory myopathies includes steroids and immunosuppressive agents, with most individuals responding satisfactorily to therapy. However, treatment-refractory myopathies prompts clinicians to use second line agents to achieve remission. In this case series, we describe three patients with refractory idiopathic inflammatory myopathies who were treated with tacrolimus (TAC) added to mycophenolate mofetil (MMF) and steroid therapy, who achieved clinical and biochemical remission.</p>","PeriodicalId":74735,"journal":{"name":"Rheumatology (Sunnyvale, Calif.)","volume":"8 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4172/2161-1149.1000238","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10541008","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":"Gastrointestinal Manifestations of Systemic Sclerosis.","authors":"Isabel M McFarlane,&nbsp;Manjeet S Bhamra,&nbsp;Alexandra Kreps,&nbsp;Sadat Iqbal,&nbsp;Firas Al-Ani,&nbsp;Carla Saladini-Aponte,&nbsp;Christon Grant,&nbsp;Soberjot Singh,&nbsp;Khalid Awwal,&nbsp;Kristaq Koci,&nbsp;Yair Saperstein,&nbsp;Fray M Arroyo-Mercado,&nbsp;Derek B Laskar,&nbsp;Purna Atluri","doi":"10.4172/2161-1149.1000235","DOIUrl":"https://doi.org/10.4172/2161-1149.1000235","url":null,"abstract":"<p><p>Systemic sclerosis (SSc) is a rare autoimmune disease characterized by fibroproliferative alterations of the microvasculature leading to fibrosis and loss of function of the skin and internal organs. Gastrointestinal manifestations of SSc are the most commonly encountered complications of the disease affecting nearly 90% of the SSc population. Among these complications, the esophagus and the anorectum are the most commonly affected. However, this devastating disorder does not spare any part of the gastrointestinal tract (GIT), and includes the oral cavity, esophagus, stomach, small and large bowels as well as the liver and pancreas. In this review, we present the current understanding of the pathophysiologic mechanisms of SSc including vasculopathy, endothelial to mesenchymal transformation as well as the autoimmune pathogenetic pathways. We also discuss the clinical presentation and diagnosis of each part of the GIT affected by SSc. Finally, we highlight the latest developments in the management of this disease, addressing the severe malnutrition that affects this vulnerable patient population and ways to assess and improve the nutritional status of the patients.</p>","PeriodicalId":74735,"journal":{"name":"Rheumatology (Sunnyvale, Calif.)","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4172/2161-1149.1000235","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36353123","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}

{"title":"Prevalence and Clinical Characteristics of Rheumatoid Arthritis in an Inner City Population with Sickle Cell Disease.","authors":"Isabel M McFarlane,&nbsp;David J Ozeri,&nbsp;Joshy Pathiparampil,&nbsp;Randolph Sanchez,&nbsp;Justin Levinson,&nbsp;Odeth Barrett-Campbell,&nbsp;Carla Saladini-Aponte,&nbsp;Beatrix Boisette,&nbsp;Moro Salifu","doi":"10.4172/2329-8731.1000218","DOIUrl":"https://doi.org/10.4172/2329-8731.1000218","url":null,"abstract":"<p><strong>Objectives: </strong>Rheumatoid arthritis (RA) has been rarely reported in association with sickle cell disease (SCD). Our study aimed to estimate the prevalence of RA in SCD population and to describe the clinical characteristics of RA associated with SCD.</p><p><strong>Methods: </strong>Retrospective chart review of SCD and RA patients followed at 2 large urban hospitals. Seven RA/SCD patients were identified and compared to age and sex matched cohort of SCD only and of RA only group. All patients were Black.</p><p><strong>Results: </strong>There were 739 SCD cases, seven (0.94%) met ACR criteria for RA (SCD-RA), 411 cases were RA only group. Mean age was significantly higher in SCD-RA compared to the entire population of SCD and RA (41.7 ± 3.9 (± SEM) <i>vs</i>. 33.26 ± 0.47, <i>vs</i>. 61.39 ± 0.79, p<0.01). SCD-RA patients had lower hemoglobin (g/dl) when compared to the age and sex matched SCD or RA only patients (7.4 ± 0.49 <i>vs.</i> 8.3 ± 0.60 <i>vs</i>. 11 ± 0.59, p <0.01) respectively. There were no significant differences in laboratory and treatment approach between SCD-RA and RA only groups, except for the radiographic evidence of periarticular osteopenia and greater difficulty in the activities of daily living (ADL) among SCD-RA cohort, compared to the age and sex matched RA cohort (p=0.01).</p><p><strong>Conclusion: </strong>In contrast to older reports, the prevalence of RA among SCD patients in our study (0.94%) was similar to that reported in the general population (0.5-1%) and was to be associated with difficulty in ADL and periarticular osteopenia. Since RA manifests at an older age, our reported prevalence is likely explainable by improved survival of SCD patients due to enhanced medical care and the advent of hydroxyurea as a major therapeutic breakthrough for SCD.</p>","PeriodicalId":74735,"journal":{"name":"Rheumatology (Sunnyvale, Calif.)","volume":"7 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4172/2329-8731.1000218","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35442262","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}

{"title":"Rheumatoid Arthritis in Sickle-Cell Population: Pathophysiologic Insights, Clinical Evaluation and Management.","authors":"Isabel M McFarlane,&nbsp;David J Ozeri,&nbsp;Yair Saperstein,&nbsp;Milena Rodriguez Alvarez,&nbsp;Su Zhaz Leon,&nbsp;Kristaq Koci,&nbsp;Sophia Francis,&nbsp;Soberjot Singh,&nbsp;Moro Salifu","doi":"10.4172/2161-1149.1000225","DOIUrl":"https://doi.org/10.4172/2161-1149.1000225","url":null,"abstract":"<p><p>The advent of hydroxyurea and advanced medical care, including immunizations has led to improved survival among patients with Sickle Cell Disease (SCD). This prolonged survival however, introduces a chronic inflammatory disorder, Rheumatoid Arthritis (RA), which presents at a relatively older age and is rarely reported among SCD patients. In this review, we highlight the epidemiological association of SCD-RA and discuss the underlying common pathogenetic mechanisms, such as endothelial dysfunction, the role of inflammatory cytokines and oxidative stress. We also point to the difficulties in ascertaining the clinical diagnosis of RA in SCD patients. Finally, we provide rationale for therapeutic options available for RA and the challenges in the management of these patients with agents that are known to increase the risk of infection and immunosuppression such as steroids, disease modifying anti-rheumatic drugs and biologics.</p>","PeriodicalId":74735,"journal":{"name":"Rheumatology (Sunnyvale, Calif.)","volume":"7 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4172/2161-1149.1000225","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35772370","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}

{"title":"Development of a Composite Outcome Measure for Systemic Sclerosis Related Interstitial Lung Disease.","authors":"Elizabeth R Volkmann,&nbsp;Donald P Tashkin,&nbsp;Ning Li,&nbsp;Daniel E Furst,&nbsp;Philip J Clements,&nbsp;Robert M Elashoff","doi":"10.4172/2161-1149.1000154","DOIUrl":"https://doi.org/10.4172/2161-1149.1000154","url":null,"abstract":"<p><strong>Objective: </strong>While systemic sclerosis-related interstitial lung disease (SSc-ILD) trials predominantly use forced vital capacity (FVC) as the primary outcome, combining individual outcomes may lead to a more comprehensive measure of treatment response and minimize the risk of type 1 error. The present analysis aimed to develop a composite outcome measure to assess treatment response in SSc-ILD patients.</p><p><strong>Methods: </strong>We used data from the Scleroderma Lung Study I (SLS-I) to create the composite outcome measure. SLS I was a multi-institutional, double-blind clinical trial, in which 158 patients with SSc-ILD were randomized to receive either oral cyclophosphamide (CYC) (titrated to 2.0 mg/kg once daily) or matching placebo for one year. To select the variables for inclusion in the composite outcome, we first performed a univariate analysis using all of the outcome variables measured in SLS I. We subsequently combined the variables with significant treatment effects (p<0.05) in a principal component analysis (PCA) to assess the difference between treatment groups. These variables included the FVC% predicted, computer-based score for quantitative lung fibrosis in the zone of maximum fibrosis (QLF-ZM) from thoracic high-resolution computer tomography (HRCT) scans, transitional dyspnea index (TDI), and the Health Assessment Questionnaire-Disability Index (HAQ-DI) at 12 months.</p><p><strong>Results: </strong>Of the 158 patients, 82 had complete outcome data and were included in this analysis. There were no significant differences in baseline characteristics between the 82 patients included in this analysis and the remaining 76 patients. The regression model with the first principal component for FVC% predicted, QLF-ZM, TDI and HAQ-DI as the composite outcome demonstrated a significant treatment effect favoring cyclophosphamide (Estimate 0.7 [SE 0.2]; p=0.005). Eliminating FVC% predicted from the composite outcome model did not change the overall treatment effect (Estimate 0.8 [SE 0.2]; p=0.004).</p><p><strong>Conclusion: </strong>The CYC treatment effect observed from using the composite outcome of FVC% predicted, QLF-ZM, TDI and HAQ-DI was stronger than the effect observed using FVC% predicted alone. These findings suggest that combining patient-reported outcomes with structural and physiologic outcomes into a single outcome may serve as a more robust measure of treatment response compared with FVC alone in SSc-ILD trials.</p>","PeriodicalId":74735,"journal":{"name":"Rheumatology (Sunnyvale, Calif.)","volume":"5 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4172/2161-1149.1000154","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35363272","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}

{"title":"Identification of α1-Antitrypsin as a Potential Candidate for Internal Control for Human Synovial Fluid in Western Blot","authors":"Shaowei Wang, Jingming Zhou, Xiaochun Wei, Pengcui Li, Kai Li, Dongming Wang, Fangyuan Wei, Jianzhong Zhang, Lei Wei","doi":"10.4172/2161-1149.S6-006","DOIUrl":"https://doi.org/10.4172/2161-1149.S6-006","url":null,"abstract":"Western blot of synovial fluid has been widely used for osteoarthritis (OA) research and diagnosis, but there is no ideal loading control for this purpose. Although β-actin is extensively used as loading control in western blot, it is not suitable for synovial fluid because it is not required in synovial fluid as a cytoskeletal protein. A good loading control for synovial fluid in OA studies should have unchanged content in synovial fluids from normal and OA groups, because synovial fluid protein content can vary with changes in synovial vascular permeability with OA onset. In this study, we explore the potential of using α1-antitripsin (A1AT) as loading control for OA synovial fluid in western blot. A1AT level is elevated in inflammatory conditions such as rheumatoid arthritis (RA). Unlike RA, OA is a non-inflammation disease, which does not induce A1AT. In this study, we identified A1AT as an abundant component of synovial fluid by Mass Spectrometry and confirmed that the level of A1AT is relative constant between human OA and normal synovial fluid by western blot and ELISA. Hence, we proposed that A1AT may be a good loading control for western blot in human OA synovial fluid studies provided that pathological conditions such as RA or A1AT deficiency associated liver or lung diseases are excluded.","PeriodicalId":74735,"journal":{"name":"Rheumatology (Sunnyvale, Calif.)","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80799916","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":"Beyond the Glands: An in-Depth Perspective of Neurological Manifestations in Sjögren's Syndrome.","authors":"Alexandria Voigt,&nbsp;Sukesh Sukumaran,&nbsp;Cuong Q Nguyen","doi":"10.4172/2161-1149.S4-010","DOIUrl":"https://doi.org/10.4172/2161-1149.S4-010","url":null,"abstract":"<p><p>Primary Sjögren's Syndrome (pSjS) is an autoimmune disease characterized by sicca (xerophthalmia or xerostomia) symptoms, anti-SS-A (Ro) or anti-SS-B (La) autoantibodies, and lymphocytic infiltrates in the exocrine glands. Disease incidence is estimated to be 0.1-3% of the general population with 0.4-3.1 million individuals in the US with women being nine times more likely to be afflicted with SjS than men. The frequency continues to rise accompanied with the multi-factorial etiology making it a challenging disease to manage and treat. Treatment of this disease remains problematic due to the lack of therapeutic treatments relying on replacement therapies such as artificial saliva and eye lubricants or immunosuppressive agents. To further complicate the management of the disease, there are number of multi-systemic manifestations specifically peripheral neuropathy associated with later stage of disease onset. Increasingly, there is mounting evidence that suggests the involvement of central nervous system. It remains to be determined the underlying cause and effect of the dysregulated immune response and the neuropathy associated with SjS. In this review, we provided an in-depth look at key neurological dysfunctions documented to occur in pSjS. Specifically, we discussed the prevalence, symptomology, and current treatments.</p>","PeriodicalId":74735,"journal":{"name":"Rheumatology (Sunnyvale, Calif.)","volume":"2014 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4172/2161-1149.S4-010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33966350","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}

{"title":"Aortic Atherosclerosis in Systemic Lupus Erythematosus.","authors":"Paola C Roldan,&nbsp;Michelle Ratliff,&nbsp;Richard Snider,&nbsp;Leonardo Macias,&nbsp;Rodrigo Rodriguez,&nbsp;Wilmer Sibbitt,&nbsp;Carlos A Roldan","doi":"10.4172/2161-1149.S5-006","DOIUrl":"https://doi.org/10.4172/2161-1149.S5-006","url":null,"abstract":"<p><p>Aortic atherosclerosis (AoA) defined as <i>intima-media thickening or plaques</i> and aortic stiffness (AoS) also considered an atherosclerotic process and defined as <i>decreased vessel distensibility</i> (higher pulse pressure to achieve similar degree of vessel distension) are common in patients with SLE. Immune-mediated inflammation, thrombogenesis, traditional atherogenic factors, and therapy-related metabolic abnormalities are the main pathogenic factors of AoA and AoS. Pathology of AoA and AoS suggests an initial subclinical endothelialitis or vasculitis, which is exacerbated by thrombogenesis and atherogenic factors and ultimately resulting in AoA and AoS. Computed tomography (CT) for detection of arterial wall calcifications and arterial tonometry for detection of increased arterial pulse wave velocity are the most common diagnostic methods for detecting AoA and AoS, respectively. MRI may become a more applicable and accurate technique than CT. Although transesophageal echocardiography accurately detects earlier and advanced stages of AoA and AoS, it is semi-invasive and cannot be used as a screening method. Although imaging techniques demonstrate highly variable prevalence rates, on average about one third of adult SLE patients may have AoA or AoS. Age at SLE diagnosis; SLE duration; activity and damage; corticosteroid therapy; metabolic syndrome; chronic kidney disease; and mitral annular calcification are common independent predictors of AoA and AoS. Also, AoA and AoS are highly associated with carotid and coronary atherosclerosis. Earlier stages of AoA and AoS are usually subclinical. However, earlier stages of disease may be causally related or contribute to peripheral or cerebral embolism, pre-hypertension and hypertension, and increased left ventricular afterload resulting in left ventricular hypertrophy and diastolic dysfunction. Later stages of disease predisposes to visceral ischemia, aortic aneurysms and aortic dissection. Even earlier stages of AoA and AoS have been associated with increased cardiovascular and cerebrovascular morbidity and mortality of SLE patients. Aggressive non-steroidal immunosuppressive therapy and non-pharmacologic and pharmacologic interventions for control of atherogenic risk factors may prevent the development or progression of AoA and AoS and may decrease cardiovascular and cerebrovascular morbidity and mortality in SLE.</p>","PeriodicalId":74735,"journal":{"name":"Rheumatology (Sunnyvale, Calif.)","volume":"Suppl 5 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4172/2161-1149.S5-006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32979615","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}

{"title":"Monosodium Urate and Tumor Necrosis Factor-α Increase Apoptosis in Human Chondrocyte Cultures.","authors":"Charles J Malemud,&nbsp;Yan Sun,&nbsp;Eric Pearlman,&nbsp;Nell M Ginley,&nbsp;Amad Awadallah,&nbsp;Bradley A Wisler,&nbsp;James E Dennis","doi":"10.4172/2161-1149.1000113","DOIUrl":"https://doi.org/10.4172/2161-1149.1000113","url":null,"abstract":"<p><p>Monosodium urate and tumor necrosis factor-α, are two potent mediators of separate inflammatory response pathways in arthritic joints where inflammation may be accompanied by the loss of chondrocyte vitality via apoptosis. To address this possibility <i>in vitro</i>, chondrocyte cultures were employed to determine the extent to which monosodium urate and recombinant TNF-α altered the frequency of apoptotic chondrocytes. Apoptosis as a function of the activation of p38 kinase, C-Jun-terminal kinase, signal transducer and activator of transcription-3 and/or the activity of xanthine oxidase was also studied. Using normal human chondrocytes, monosodium urate or recombinant tumor necrosis factor-α increased the frequency of apoptosis and activity of xanthine oxidase. However, the xanthine oxidase-specific inhibitor, febuxostat, failed to blunt this response. Monosodium urate, tumor necrosis factor-α or the Janus kinase inhibitor, AG-490, increased the frequency of apoptotic nuclei in macroaggregate pellet cultures initiated from juvenile human chondrocytes, but not in pellet cultures derived from mesenchymal stem cells. In OA chondrocytes, activation of p38, C-Jun-NH₂-kinase and signal transducer and activator of transcription-3 preceded apoptosis. Activation of signal transducer and activator of transcription-3 also was seen in pellet cultures initiated from juvenile chondrocytes and MSCs incubated with MSU, recombinant tumor necrosis factor-α or febuxostat, but apoptosis was increased only in the pellet cultures derived from juvenile chondrocytes. Although AG-490 or the combination of AG-490 and febuxostat inhibited signal transducer and activator of transcription-3 activation, apoptosis was unaffected. These results showed that recombinant tumor necrosis factor-α, monosodium urate and AG-490 increased apoptosis in normal human chondrocytes, OA chondrocytes and human juvenile chondrocyte pellet cultures, but not in chondrocyte pellet cultures initiated from MSCs. The increased frequency of apoptotic chondrocytes in response to recombinant tumor necrosis factor-α or monosodium urate was not dependent on either activation of STAT3 or the activity of XO.</p>","PeriodicalId":74735,"journal":{"name":"Rheumatology (Sunnyvale, Calif.)","volume":"2 ","pages":"113"},"PeriodicalIF":0.0,"publicationDate":"2012-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/37/43/nihms529418.PMC3959644.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32200678","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}