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ID PMID Title PublicationDate abstract
22240069 [Multicystic lung revealing a Sjogren's syndrome]. 2012 Aug The Sjogren's syndrome is a chronic inflammatory autoimmune disease that affects primarily the exocrine glands, but can affect other organs particularly the lungs. Cystic lung disease is very significant but exceptionally recounted in the literature. We report the case of a patient, 54 years old, whose disease was discovered incidentally after a routine chest radiograph. The diagnosis of cystic lung revealing a primary Sjogren's syndrome was held before a group of radio-clinical, immunological and histological arguments. Through our observation, the diagnosis of Sjogren's syndrome should be included in the list of diagnoses to raise in a multicystic lung.
22153586 Successful outcome of two pregnancies in patients with adult-onset Still's disease treated 2011 Nov Adult onset Still's disease (AOSD) is an uncommon, systemic, inflammatory disorder of unknown etiology, characterised by spiking fevers, skin rash, and arthritis. Treatment consists of glucocorticosteroids and immunosuppressive drugs. Over the last few years it has become increasingly evident that treatment with the IL-1 receptor antagonist (IL-1RA) anakinra is highly effective even in patients with intractable disease. So far, there are scant data available on the effects of anakinra in pregnancy. We report two patients with AOSD who successfully gave birth while treated with anakinra during pregnancy.
22888423 Proinflammatory soluble interleukin-15 receptor alpha is increased in rheumatoid arthritis 2012 Rheumatoid arthritis (RA) is an autoimmune and inflammatory disease in which many cytokines have been implicated. In particular, IL-15 is a cytokine involved in the inflammatory processes and bone loss. The aim of this study was to investigate the existence in synovial fluid of soluble IL-15Rα, a private receptor subunit for IL-15 which may act as an enhancer of IL-15-induced proinflammatory cytokines. Soluble IL-15Rα was quantified by a newly developed enzyme-linked immunosorbent assay (ELISA) in samples of synovial fluid from patients with RA and osteoarthritis (OA). The levels of IL-15Rα were significantly increased in RA patients compared to OA patients. Also, we studied the presence of membrane-bound IL-15 in cells from synovial fluids, another element necessary to induce pro-inflammatory cytokines through reverse signaling. Interestingly, we found high levels of IL-6 related to high levels of IL-15Rα in RA but not in OA. Thus, our results evidenced presence of IL-15Rα in synovial fluids and suggested that its pro-inflammatory effect could be related to induction of IL-6.
22345789 Disseminated granuloma annulare: a cutaneous adverse effect of anti-tnf agents. 2011 Nov Tumor necrosis factor-alpha (TNF-α) inhibitors, such as etanercept, infliximab, and adalimumab, bind to TNF-α and thereby act as anti-inflammatory agents. This group of drugs has been approved for the treatment of rheumatoid arthritis, psoriatic arthritis, moderate to severe plaque psoriasis, ankylosing spodylitis, Crohn disease, and juvenile idiopathic arthritis. We describe a 56-year-old woman who developed an erythematous pruritic rash on both arms-diagnosed as granuloma annulare by skin biopsy-approximately 22 months after initiating adalimumab for treatment of rheumatoid arthritis. On stopping adalimumab there was total clearance of the skin lesions, but a similar rash developed again when her treatment was switched to another anti-TNF agent (etanercept). This clinical observation supports a link between TNF inhibition and the development of granuloma annulare.
23429967 Massage therapy for lyme disease symptoms: a prospective case study. 2012 INTRODUCTION: To study the effects of massage therapy (MT) on Lyme disease (LD) symptoms and affect. METHODS: A 21-year-old female college student previously diagnosed with LD was recruited for a prospective case study that incorporated alternating periods of treatment and nontreatment across 65 days. Her self-reported symptoms of pain, fatigue, and impairment of concentration were assessed by means of a daily diary with corresponding visual analog scales. Immediate effects of MT on affect were assessed by completion of the Positive and Negative Affect Scales before and after each treatment session. RESULTS: LD symptoms decreased during treatment periods and increased during nontreatment periods. Positive affect was increased at every MT session. CONCLUSIONS: MT is a promising treatment for the symptoms pain, fatigue, and impaired concentration associated with LD. In addition, MT reliably increased positive affect. Massage therapists should consider using light-to-medium pressure MT for treatment of persons who present with a similar pattern of LD symptoms, and further research with this population is warranted.
22369699 Local delivery of AAV2-CTLA4IgG decreases sialadenitis and improves gland function in the 2012 Feb 27 INTRODUCTION: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a key negative costimulatory molecule that displays a wide range of anti-inflammatory properties and is currently approved to treat rheumatoid arthritis as a recombinant fusion protein (CTLA4IgG). To better understand the role of CTLA4IgG in primary Sjögren's syndrome (pSS), we generated a recombinant adeno-associated virus vector serotype 2 (AAV2) expressing a chimera of mouse CTLA-4 fused with a human immunoglobulin (AAV2-CTLA4IgG) and observed the effect of this molecule in C57BL/6.NOD-Aec1Aec2 mice, an animal model of pSS. METHODS: A recombinant adeno-associated virus-2 (AAV-2) vector was constructed encoding a CTLA4IgG fusion protein. The AAV2-CTLA4IgG vector and an AAV2 control vector encoding beta galactosidase (LacZ) were administered by retrograde cannulation of the submandibular glands of C57BL/6.NOD-Aec1Aec2 mice. Protein expression was measured by ELISA and salivary glands were assessed for inflammation and activity. RESULTS: Recombinant CTLA4IgG blocked B7 expression on macrophages in vitro. In vivo, localized expression of CTLA4IgG in the salivary glands of C57BL/6.NOD-Aec1Aec2 mice inhibited the loss of salivary gland activity and decreased T and B cell infiltration as well as dendritic cells and macrophages in the glands compared with control mice. In addition a decrease in several proinflammatory cytokines and an increase in transforming growth factor beta-1 (TGF-β1) expression were also observed. CONCLUSIONS: These data suggest expression of CTLA4IgG in the salivary gland can decrease the inflammation and improve the xerostomia reported in these mice.
22781207 Combined pulmonary fibrosis and emphysema in connective tissue disease. 2012 Sep PURPOSE OF REVIEW: This review discusses combined pulmonary fibrosis and emphysema (CPFE) in the setting of connective tissue disease. RECENT FINDINGS: CPFE is a recently identified syndrome in smokers or ex-smokers characterized by dyspnea often severe, preserved lung volumes, severely impaired gas exchanges, and an increased risk of pulmonary hypertension associated with a dismal prognosis, and possibly lung cancer. It may be encountered in the setting of connective tissue diseases, especially rheumatoid arthritis and systemic sclerosis, with generally similar features as 'idiopathic' (tobacco-related) CPFE. The diagnosis is based on the presence of both emphysema predominating in the upper lobes and frequently paraseptal, and interstitial abnormalities suggesting pulmonary fibrosis in the lower lung zones with velcro crackles at auscultation. Pathologic radiological correlations are difficult owing to various pathology and difficulties in identifying honeycombing at chest high-resolution computed tomography in the setting of coexistent emphysema. Tobacco smoking is associated with an increased risk of developing most of the individual components of the syndrome (i.e. emphysema, pulmonary fibrosis, pulmonary hypertension, rheumatoid arthritis, and pulmonary fibrosis among patients with rheumatoid arthritis). CPFE impacts modalities of follow-up for pulmonary function and detection of pulmonary hypertension especially in systemic sclerosis. SUMMARY: The syndrome of CPFE is a distinct pulmonary manifestation in the spectrum of lung diseases associated with connective tissue diseases, especially in smokers or ex-smokers.
22566958 Inflammation and bone destruction in arthritis: synergistic activity of immune and mesench 2012 Rheumatoid arthritis (RA) is an immune-mediated disease of the joints that is characterized by chronic inflammation and synovial hyperplasia that eventually lead to cartilage and bone destruction. Synovial fibroblasts are mesenchymal cells recognized as a key cell population in RA due to their hyperproliferative and hypersensitive properties in the inflammatory milieu and hyperproduction of both inflammatory cytokines and matrix-degrading enzymes. On the immune cell side, a wealth of evidence has shown that CD4(+)T-cells, especially IL-17 producing helper T (Th17) cells, play a prominent role, particularly in the initiation of systemic immune response in RA. However, it is still unclear how the local chronic inflammation in the joint is elicited by a systemic immune response. Recent studies have shed light on the importance of the interaction between immune and mesenchymal cells in joints including synovial fibroblasts. In particular, mesenchymal cells contribute to the Th17-mediated chronic inflammation in RA by promoting the migration of Th17 cells to the inflamed site and then the homeostatic proliferation and concomitant increase in IL-17 production. In addition, recent progress in osteoimmunology has provided new insight into the pathogenesis of the bone destruction which takes place in RA. Th17-related cytokines have been shown to enhance osteoclastogenesis, mainly via synovial fibroblasts. Thus, mesenchymal cells are a determinant of the development of RA that links the systemic immune response and the local disorder in the joints. In addition, the interaction of immune and mesenchymal cells plays a key role in both the chronic inflammation and bone destruction seen in RA. Elucidation of the precise events involved in this interaction will lead to a better understanding of the mechanisms by which chronic inflammation and bone destruction in joint results from a systemic immune response, and also will help provide a molecular basis for novel therapeutic strategies to treat RA.
22709487 The ubiquitin proteasome system and efficacy of proteasome inhibitors in diseases. 2012 Jun In eukaryotes the ubiquitin proteasome pathway plays an important role in cellular homeostasis and also it exerts a critical role in regulating a wide variety of cellular pathways, including cell growth and proliferation, apoptosis, DNA repair, transcription and immune response. Defects in these pathways have been implicated in a number of human pathologies. Inhibition of the ubiquitin proteasome pathway by proteasome inhibitors may be a rational therapeutic approach for various diseases, such as cancer and inflammatory diseases. Many of the critical cytokine and chemokine mediators of the progression of rheumatoid arthritis are regulated by nuclear factor kappa B (NF-κB). In peptidoglycan/polysaccharide-induced polyarthritis, proteasome inhibitors limit the overall inflammation, reduce NF-κB activation, decrease cellular adhesion molecule expression, inhibit nitric oxide synthase, attenuate circulating levels of proinflammatory cytokine interleukin-6 and reduce the arthritis index and swelling in the joints of the animals. Since proteasome inhibitors exhibit anti-inflammatory and anti proliferative effects, diseases characterized by both of these processes such as rheumatoid arthritis might also represent clinical opportunities for such drugs. The regulation of the proteasomal complex by proteasome inhibitors also has implications and potential benefits for the treatment of rheumatoid arthritis. This review summarizes the ubiquitin proteasome pathway, the structure of 26S proteasomes and types of proteasome inhibitors, with their actions, and clinical applications of proteasome inhibitors in various diseases.
22870176 The relationship of metabolic syndrome with disease activity and the functional status in 2012 Aug BACKGROUND: The aim of this study is to investigate the frequency of metabolic syndrome (MS) in patients with rheumatoid arthritis (RA) and to determine the relationship between the clinical and laboratory parameters of RA and the components of the metabolic syndrome (MS). METHODS: Fifty-four patients with RA and 52 healthy individuals were enrolled in this study. The diagnosis of rheumatoid arthritis was based on the American College of Rheumatology criteria and the diagnosis of the metabolic syndrome was made according to the criteria set out in the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI). The functional status and disease activity were also recorded in patients with RA. RESULTS: MS was diagnosed in 42.6% of the patients with RA and in 9.6% of the healthy controls. The systolic and diastolic blood pressure values were observed to be significantly higher in the patients with RA in comparison to the controls. Also, the frequency of MS was higher in the inferior functional group in relation to the higher functional group. A positive correlation was observed between the DAS28 scores and hypertension in patients with RA. CONCLUSIONS: In this study, MS was more frequently detected in the patients with RA compared to the control group. Also, an inferior functional status in RA was also found to be associated with the presence of MS. Thus, the presence of MS in patients with RA may be associated with a higher cardiovascular risk.
31644034 Leflunomide. 2012 Leflunomide is an immunomodulatory agent used in the therapy of rheumatoid arthritis and psoriatic arthritis. Leflunomide therapy is associated with frequent elevations in serum aminotransferase levels and with rare instances of clinically apparent acute liver injury which can be severe and even fatal.
23204896 Increased prevalence of subclinical atherosclerosis in rheumatoid arthritis patients of In 2012 Spring BACKGROUND: Studies have shown that rheumatoid arthritis (RA) patients are two to five times more likely to develop premature cardiovascular disease, thus shortening their life expectancy by five to 10 years. This risk has risen to approximately 12.6% in the urban population and 7.4% in the rural population of India. The Framingham risk score (FRS) identifies patients at increased cardiovascular risk and helps determine the need for preventive interventions. An investigation of the patients' coronary arteries and coronary artery calcification (CAC) - a measure of atherosclerotic plaque - has been found to be a strong predictor of cardiovascular disease. OBJECTIVE: To identify important biological markers for easy and non-invasive identification of cardiovascular disease in RA patients, and to investigate whether there is a relationship between the FRS and coronary artery atherosclerosis in RA patients. METHODS: The present study included 43 established RA patients and 50 healthy individuals (controls). Traditional and nontraditional risk factors were studied and compared with the control group. Insulin resistance was assessed using the homeostasis model of assessment of insulin resistance (HOMA-IR) and the homeostasis model of assessment of beta cell function. The FRS and the 10-year cardiovascular risk were compared between RA patients and controls. The presence of CAC was determined using electron-beam computed tomography, and the association between the FRS and CAC was examined. RESULTS: Significant differences in body mass index, waist circumference, rheumatoid factors (immunoglobulin [Ig]G, IgM and IgA) and inflammatory markers - C-reactive protein and erythrocyte sedimentation rate - were noted. There was significant correlation between HOMA-IR and body mass index, hypertension and C-reactive protein, but no correlation was seen with the homeostasis model of assessment of beta cell function. Significant differences were observed in the nontraditional biomarkers in RA patients, thus supporting their importance. Calcium deposition was observed in only seven RA patients. CONCLUSIONS: RA patients with increased C-reactive protein levels and erythrocyte sedimentation rates showed an increase in serum insulin levels and significant differences in HOMA-IR, thus indicating insulin resistance, which could lead to underlying progression of artherosclerosis. Significant differences were observed in the nontraditional risk factors, which could be chosen as biomarkers for endothelial dysfunction. There was a significant correlation between calcium score and the FRS in seven patients, suggestive of an underlying risk of atherosclerosis.
22194709 Gene Expression Profile of T-cell Receptors in the Synovium, Peripheral Blood, and Thymus 2011 Oct BACKGROUND: Current management strategies attempt to diagnose rheumatoid arthritis (RA) at an early stage. Transcription profiling is applied in the search for biomarkers for detecting early-stage disease. Even though gene profiling has been reported using several animal models of RA, most studies were performed after the development of active arthritis, and conducted only on the peripheral blood and joint. Therefore, we investigated gene expression during the initial phase of collagen-induced arthritis (CIA) before the arthritic features developed in the thymus in addition to the peripheral blood and synovium. METHODS: For gene expression analysis using cDNA microarray technology, samples of thymus, blood, and synovium were collected from CIA, rats immunized only with type II collagen (Cll), rats immunized only with adjuvant, and unimmunized rats on days 4 and 9 after the first immunization. Arrays were scanned with an Illumina bead array. RESULTS: Of the 21,910 genes in the array, 1,243 genes were differentially expressed at least 2-fold change in various organs of CIA compared to controls. Among the 1,243 genes, 8 encode T-cell receptors (TCRs), including CD3ζ, CD3δ, CD3ε, CD8α, and CD8β genes, which were down-regulated in CIA. The synovium was the organ in which the genes were differentially expressed between CIA and control group, and no difference were found in the thymus and blood. Further, we determined that the differential expression was affected by adjuvant more than Cll. The differential expression of genes as revealed by real-time RT-PCR, was in agreement with the microarray data. CONCLUSION: This study provides evidence that the genes encoding TCRs including CD3ζ, CD3δ, CD3ε, CD8α, and CD8β genes were down-regulated during the initial phase of CIA in the synovium of CIA. In addition, adjuvant played a greater role in the down-regulation of the CD3 complex compared to CII. Therefore, the down-regulation of TCR gene expression occurred dominantly by adjuvant could be involved in the pathogenesis of the early stage at CIA.
27683395 The Role of IL-33 in the Inflammation Process of Asthma and Atherosclerosis. 2011 Oct Interleukin-33 (IL-33) is a newly found cytokine of the interleukin-1 (IL-1) family. It's mainly expressed by epithelial and endothelial cells. This expression is upregulated by pro-inflammatory stimulation, thus has an important role in inflammatory responses, such as hypersensitive diseases (asthma), autoimmune diseases (rheumatoid arthritis), cardiovascular diseases (heart failure) and neurodegenerative diseases (Alzheimer). Several studies explored the complicated mechanism of IL-33 action in asthma and atherosclerosis, as this IL is significantly increased in these pathologies, and suggested its potential use in the therapeutic procedures.
22965242 The biological activity of auranofin: implications for novel treatment of diseases. 2012 Dec More than 30 years ago, auranofin was developed for the treatment of rheumatoid arthritis as a substitution for the injectable gold compounds aurothiomalate and aurothioglucose. Both the ease of oral administration over intramuscular injections and more potent anti-inflammatory effects in vitro made auranofin seem like an excellent substitute for the traditional injectable gold compounds. Despite efficacy in the treatment of both rheumatoid arthritis and psoriasis, currently, auranofin is seldom used as a treatment for patients with rheumatoid arthritis as more novel anti-rheumatic medications have become available. Despite the decline in its clinical applications, research on auranofin has continued as it shows promise in the treatment of several different diseases. In recent years, advances in technology have allowed researchers to use molecular techniques to identify novel mechanisms of action of auranofin. Additionally, researchers are discovering potential new applications of auranofin. Dual inhibition of inflammatory pathways and thiol redox enzymes by auranofin makes it a new candidate for cancer therapy and treating microbial infections. This review will summarize recently obtained data on the mechanisms of action of auranofin, and potential new applications of auranofin in the treatment of various diseases, including several types of leukaemia, carcinomas, and parasitic, bacterial, and viral infections.
22007257 Treatment of rheumatoid arthritis with marine and botanical oils: influence on serum lipid 2011 The gap in mortality between patients with rheumatoid arthritis (RA) and the general population (1.5-3.0 fold risk) is increasing. This disparity is attributable mainly to cardiovascular disease (CVD), as the CVD risk is comparable to patients with diabetes mellitus. The purpose of this study is to determine whether borage seed oil rich in gamma-linolenic acid, fish oil rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), or the combination of both oils are useful treatments for dyslipidemia in patients with RA. We randomized patients into a double blind, 18 month trial. Mixed effects models were used to compare trends over time in serum lipids. No significant differences were observed between the three groups: All three treatment groups exhibited similar meaningful improvement in the lipid profile at 9 and 18 months. When all groups were combined, these treatments significantly reduced total and LDL-cholesterol and triglycerides, increased HDL-cholesterol, and improved the atherogenic index. All improvements observed at 9 months persisted at 18 months (P < 0.001 verses baseline). Conclusion. Marine and botanical oils may be useful treatment for rheumatoid arthritis patients who are at increased risk for cardiovascular disease compared to the general population.
23206275 Surface modification of poly (l-lactic acid) microspheres for site-specific delivery of ke 2013 Apr The purpose of this research was to investigate the potential of surface modified Poly (l-lactic acid) (PLA) microspheres as a carrier for site-specific delivery of anti-inflammatory drug, ketoprofen, for the treatment of rheumatoid arthritis. Microspheres were prepared by solvent evaporation method using 20% w/w PLA in methylene chloride and 100 mL of a 2.5% poly vinyl alcohol (PVA) solution. Formulations were optimized for several processing parameters like drug to polymer ratio, stirring rate and volume of preparation medium etc. The surface of PLA microspheres was modified with gelatin to impart fibronectin recognition. The microspheres were characterized by surface morphology, size distribution, encapsulation efficiency, and by in vitro drug release studies. The prepared microspheres were light yellow, discrete, and spherical. Formulation with optimum drug to polymer ratio exhibited smallest vesicle size (43.02), high drug encapsulation efficiency (81.11) and better process yield (83.45). The release of drug was extended up to 24 h with Higuchi pattern of drug release. The in vivo results showed that the gelatin modified formulation reduced paw edema at greater extent than pure drug and PLA microspheres and it could be a promising carrier system for controlled and site-specific delivery of ketoprofen with possible clinical applications.
22396899 Telomere dysfunction, autoimmunity and aging. 2011 Dec Immune aging is associated with loss of critical immune functions, such as host protection from infection and malignancy. Unexpectedly, immunosenescence also renders the host susceptible to inflammation, which may translate into tissue-damaging disease as the senescent immune system loses its ability to maximize inflammatory protection while minimizing inflammatory injury. On the other hand, chronic inflammation associated with immune-mediated disease represents a profound stress factor for the immune system, affecting cellular turn-over, replication and exhaustion. Immune cell longevity is tightly connected to the functional integrity of telomeres which are regulated by cell multiplication, exposure to oxidative stress and DNA repair mechanisms. Lymphocytes are amongst the few cell types that can actively elongate telomeres through the action of telomerase. In patients with the autoimmune disease rheumatoid arthritis (RA), telomerase deficiency is associated with prematurity of immune aging. Patients with RA have other defects in DNA repair mechanisms, including the kinase Ataxia telangiectasia mutated (ATM), critically involved in the repair of DNA double strand breaks. ATM deficiency in RA shortens lymphocyte survival. Dynamics of telomeric length and structure are beginning to be understood and have distinct patterns in different autoimmune diseases, suggesting a multitude of molecular mechanisms defining the interface between chronic immune stimulation and progressive aging of the immune system.
22870479 'Old drugs for new applications': can orthopedic research benefit from this strategy? 2011 Aug New drug exploration is difficult in a clinical setting and the development of new drugs may be costly and time consuming. With further research into the pathological mechanisms and etiology of diseases as well as the rapid development of biological techniques, many 'old drugs' that have been applied in clinics may have new therapeutic functions which may shed light on clinical management. Based on this, we have investigated the 'old drugs for new applications' strategy in pharmacology which may be less expensive and more efficient in the clinical setting. In this paper we have explored and illustrated the potential applications of 'old drugs' for the treatment of orthopedic diseases, especially in arthritis and osteoporosis therapy.
22734944 Clinical follow-up study of adult-onset Still's disease. 2012 Nov Eighteen patients with adult-onset Still's disease have been followed up for 3-22 years in our department. Initial manifestations were fever with skin rash in 14 patients, fever, skin rash and sore throat in two, skin rash in one and arthralgia in one. During the follow-up period, typical skin rash was seen in all patients, of them five patients (29%) revealed atypical skin rash simultaneously. Atypical rash included persistent erythema with pigmentation in two, persistent plaques and papules with linear erythema in two and edema of the eyelids mimicking dermatomyositis in one. Persistent papules and plaques revealed histologically characteristic features, such as dyskeratotic keratinocyte and liquefaction degeneration as well as a sparse superficial dermal infiltrate containing scattered neutrophils. In patients of chronic articular type and polycyclic systemic type, atypical skin rash, lymphadenopathy and hyperferritinemia were noted to be significantly higher than those of monocyclic type. These factors might be prognostic factors of adult-onset Still's disease in our study.