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ID PMID Title PublicationDate abstract
30356424 Endobronchial Watanabe Spigots for Treatment of Pyopneumothorax due to Nontuberculous Myco 2018 Nontuberculous mycobacterial lung disease sometimes causes pneumothorax and empyema, which are often intractable because of patients' background factors. Biological products used in the treatment of rheumatoid arthritis have caused the problem of an increase in infection rates as a side effect, one of which is nontuberculous mycobacteriosis (NTM). On the basis of past experience, we report the case of a patient who had a history of undergoing treatment with biological products against rheumatoid arthritis. The patient was treated for NTM-induced pyopneumothorax by endoscopic bronchial occlusion therapy using endobronchial Watanabe spigots.
30593897 Fatty acids uptake and oxidation are increased in the liver of rats with adjuvant-induced 2019 Mar 1 Severe rheumatoid cachexia is associated with pronounced loss of muscle and fat mass in patients with advanced rheumatoid arthritis. This condition is associated with dyslipidemia and predisposition to cardiovascular diseases. Circulating levels of triglycerides (TG) and free fatty acids (FFA) have not yet been consistently defined in severe arthritis. Similarly, the metabolism of these lipids in the arthritic liver has not yet been clarified. Aiming at filling these gaps this study presents a characterization of the circulating lipid profile and of the fatty acids uptake and metabolism in perfused livers of rats with adjuvant-induced arthritis. The levels of TG and total cholesterol were reduced in both serum (10-20%) and liver (20-35%) of arthritic rats. The levels of circulating FFA were 40% higher in arthritic rats, possibly in consequence of cytokine-induced adipose tissue lipolysis. Hepatic uptake and oxidation of palmitic and oleic acids was higher in arthritic livers. The phenomenon results possibly from a more oxidized state of the arthritic liver. Indeed, NADPH/NADP(+) and NADH/NAD(+) ratios were 30% lower in arthritic livers, which additionally presented higher activities of the citric acid cycle driven by both endogenous and exogenous FFA. The lower levels of circulating and hepatic TG possibly are caused by an increased oxidation associated to a reduced synthesis of fatty acids in arthritic livers. These results reveal that the lipid hepatic metabolism in arthritic rats presents a strong catabolic tendency, a condition that should contribute to the marked cachexia described for arthritic rats and possibly for the severe rheumatoid arthritis.
30687331 Treatment Effects of the Second-Generation Tyrosine Kinase Inhibitor Dasatinib on Autoimmu 2018 Rheumatoid arthritis (RA) is a multifactorial autoimmune disease that primarily manifests as persistent synovitis and progressive joint destruction. Imatinib exhibited a therapeutic effect in murine collagen-induced arthritis (CIA) via selective inhibition tyrosine kinases. The second-generation tyrosine kinase inhibitor dasatinib exhibits more durable hematological and cytogenetic effects and more potency compared to imatinib. However, the effect of dasatinib on CIA is poorly understood. The present study investigated the treatment effect of dasatinib on autoimmune arthritis. We demonstrated that dasatinib alleviated arthritis symptoms and histopathological destruction in CIA mice. Dasatinib treatment inhibited the production of proinflammatory cytokines including IL-1β, TNF-α, and IL-6, and promoted the production of the anti-inflammatory cytokine IL-10. Dasatinib treatment also suppressed the expression of anti-mouse CII antibodies including total IgG, IgG1, IgG2, and IgG2b, in CIA mice. We further demonstrated that dasatinib inhibited the migration and proliferation of fibroblast-like synoviocytes (FLS) from RA patients and promoted FLS apoptosis. The mRNA expression of MMP13, VEGF, FGF, and DKK1 was down-regulated in FLS treated with dasatinib. Our findings suggest that dasatinib exhibited treatment effects on CIA mice and that FLS are an important target cell of dasatinib treatment in autoimmune arthritis.
30647481 The importance of ultrasound examination in early arthritis. 2018 OBJECTIVES: To assess the importance of ultrasound (US) examination of joints in hands and feet in patients with early arthritis and perform comparative analysis of the diagnostic value of US examination for 8, 12 and 52 selected joints. MATERIAL AND METHODS: 123 patients (87 women, 36 men) with arthritis lasting less than 12 months, naive to disease-modifying anti-rheumatic drugs and glucocorticosteroids. Necessary differential diagnostics was performed for each patient. After the preliminary analysis, 72 patients met the classification criteria for rheumatoid arthritis (RA) according to ACR/EULAR of 2010, and undifferentiated arthritis (UA) was diagnosed in 51 patients. UA patients were followed up after 6 and 12 months, and verification of the initial diagnosis yielded the following groups of patients: patients meeting classification criteria for RA, patients with maintained diagnosis of UA, patients in remission, and patients with other diagnoses. Ultrasound examination was performed considering the volume of joint effusion (JE), synovial membrane hypertrophy (GS), and synovial membrane hyperaemia assessed by power Doppler (PD). Results were assessed using the semi-qualitative scale. Coefficients being the sum of US scores for the assessment of JE, GS and PD for 52 and 12 joints in hands and feet, and 8 joints in hands were determined for the purpose of the study. RESULTS: In patients meeting classification criteria for RA during the initial assessment the US examination yielded significantly higher PD-52I, PD-12I and PD-8I coefficients. In UA patients who were diagnosed with RA after 12 months, the GS-8I coefficient was significantly higher. CONCLUSIONS: Ultrasonography is a valuable tool in diagnostics of early arthritis. The GS assessment has prognostic value for UA patients. The assessment of 8 or 12 selected joints is often sufficient for the diagnostics of patients with early arthritis.
28833755 Tacrolimus regulates endoplasmic reticulum stress-mediated osteoclastogenesis and inflamma 2018 Apr Tacrolimus is an immunosuppressive drug that inhibits the release of inflammatory cytokines involved in rheumatoid arthritis development by blocking T cell activation. "Endoplasmic reticulum stress," an imbalance between protein folding load and capacity leading to the accumulation of unfolded proteins in the endoplasmic reticulum lumen, has been implicated in rheumatoid arthritis and other inflammatory and metabolic diseases. We aimed to investigate the effect of tacrolimus on endoplasmic reticulum stress-mediated osteoclastogenesis and inflammation and elucidate the underlying mechanisms. In vitro studies were performed using mouse bone marrow cells that were cultured with or without interleukin-1β, thapsigargin, or tacrolimus to induce osteoclast differentiation. A mouse model of arthritis was established by immunizing mice with bovine type II collagen. Tacrolimus was orally administered to mice from day 20 to 45 following the initial immunization, and histopathological changes and expression of specific biomarkers of endoplasmic reticulum stress-mediated inflammatory signaling pathways were examined. In vitro, tacrolimus inhibited receptor activator of nuclear factor-κB ligand-mediated osteoclast formation augmented by interleukin-1β, thapsigargin, or both. Furthermore, tacrolimus inhibited glucose-regulated protein (GRP78), protein kinase R-like endoplasmic reticulum kinase, inositol-requiring enzyme 1 (IRE 1), and activating transcription factor 6 (ATF6) augmented by interleukin-1β, thapsigargin, or both. Tacrolimus significantly ameliorated osteolysis and endoplasmic reticulum stress intensity in mice. Simultaneously, it reduced inflammatory cell infiltration, osteoclastogenesis, and inflammatory responses by inhibiting GRP78, IRE 1, and ATF6. These findings suggest that tacrolimus exhibits an anti-inflammation effect in rheumatoid arthritis and might inhibit joint damage progression by inhibiting endoplasmic reticulum stress.
30568519 Treatment persistence of subcutaneous TNF inhibitors among Australian patients with immune 2018 INTRODUCTION: To describe the persistence of treatment with subcutaneous tumor necrosis factor inhibitors (TNFi) adalimumab, etanercept, and golimumab in immune-mediated rheumatic disease (rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis) by treatment sequence (first-line treatment, second-line or further lines of treatment). METHODS: A retrospective cohort analysis was conducted using the Australian Commonwealth Department of Human Services Pharmaceutical Benefits Scheme 10% sample data from January 1, 2010, to June 30, 2016. Pharmaceutical Benefits Scheme indications were used to identify patient prescriptions for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. A patient was considered persistent until a 3-month gap period where a prescription was not dispensed. The 3-month gap interval was chosen because only 1% of all discontinuations occurred beyond this 3-month period. RESULTS: Data from 2,612 first-line patients were included. Treatment discontinuation among first-line patients treated with etanercept or adalimumab was not significantly different from those treated with golimumab (HR 1.10, 95% CI 0.95-1.28, P=0.22; HR 1.06, 95% CI 0.93-1.22, P=0.39; respectively). Among the 1,276 patients in the second-line cohort (etanercept=41%, adalimumab=41%, golimumab=18%) discontinuation was significantly higher for patients on etanercept compared with golimumab (HR 1.24, 95% CI 1.03-1.50, P=0.03); but not for adalimumab compared with golimumab (HR 1.11, 95% CI 0.91-1.34, P=0.31). In the third-line setting, treatment persistence with etanercept was longer than golimumab (HR 0.75, 95% CI 0.59-0.96, P=0.02), but there was no difference between golimumab and adalimumab. Similar findings occurred in the propensity score matched population. CONCLUSION: Our study shows there is variance in real-world persistence to TNFi in patients with immune-mediated rheumatic disease by line of therapy, with the time on therapy decreasing by line. Australian persistence has been reported at lower overall rates than international evidence.
29511028 'Deep Koebner' phenomenon of the flexor tendon-associated accessory pulleys as a novel fac 2018 Jun OBJECTIVES: Skin and joint involvement in psoriasis (PsO) and psoriatic arthritis (PsA) are thought to relate to the so-called Koebner response. Given that dactylitis is non-randomly distributed in the digits, this study tested the hypothesis that the accessory pulleys linked to the flexor tendons were thickened in PsA and thus exhibited koebnerisation. METHODS: Ninety-six subjects (27 PsA, 27 rheumatoid arthritis (RA), 23 PsO and 19 healthy controls (HCs)) were enrolled. The A1, A2 and A4 pulley thickness was measured using a high-resolution probe (22 MHz). All patients were in remission or low disease activity with current dactylitis being excluded. RESULTS: Within 864 pulleys investigated, patients with PsA had thicker pulleys in every digit compared with both RA (P<0.001 and P=0.003) and HCs (P<0.001). RA and PsO groups had some pulleys in some digits thicker than HCs whereas some others were comparable. The second digit A1 pulley thickness was higher in patients with PsA with previous dactylitis (P=0.020). More pulleys were thickened in the PsA group (165/243, 68%) than RA (41/243, 17%; P<0.001) and HCs (13/171, 7.6%; P<0.001). CONCLUSIONS: In established PsA, the accessory pulleys are thickened compared with RA, PsO or HCs and especially in subjects with a history of dactylitis. These findings implicate the involvement of pulleys in PsA-related tenosynovitis and dactylitis supporting the idea of deep koebnerisation in dactylitis and sites of high physical stress.
30679969 Cardiovascular effects of methotrexate in immune-mediated inflammatory diseases. 2019 Feb The cardiovascular effects of disease-modifying antirheumatic drugs and particularly of methotrexate (MTX) are complex and frequently incorrectly understood, which might lead to the unjustified discontinuation of this treatment. MTX, 'the gold standard' and first line treatment in rheumatoid arthritis, psoriatic arthritis, and other immune-mediated inflammatory diseases, has been proven to decrease inflammation, improve cardiovascular risk factors, and reduce mortality. This is supported by both the mechanism of action, as well as a body of clinical data evidence. MTX's cardiovascular effects, although incompletely understood, are explained by its antiproliferative, immunosuppressive, anti-inflammatory, and antiatherogenic effects. Several clinical trials have shown that MTX is associated with improved endothelial function, slower atherosclerosis progression, decreased risk of major cardiovascular adverse events, and benefits on survival. Given its systemic cardiovascular effects, MTX could be regarded as an important therapeutic agent not only to control disease activity in rheumatic diseases, but also to reduce cardiovascular risk and mortality.
30205019 Effect of Polarization and Chronic Inflammation on Macrophage Expression of Heparan Sulfat 2019 Jan Heparan sulfate (HS) proteoglycans on immune cells have the ability to bind to and regulate the bioactivity more than 400 bioactive protein ligands, including many chemokines, cytokines, and growth factors. This makes them important regulators of the phenotype and behavior of immune cells. Here we review how HS biosynthesis in macrophages is regulated during polarization and in chronic inflammatory diseases such as rheumatoid arthritis, atherosclerosis, asthma, chronic obstructive pulmonary disease and obesity, by analyzing published micro-array data and mechanistic studies in this area. We describe that macrophage expression of many HS biosynthesis and core proteins is strongly regulated by macrophage polarization, and that these expression patterns are recapitulated in chronic inflammation. Such changes in HS biosynthetic enzyme expression are likely to have a significant impact on the phenotype of macrophages in chronic inflammatory diseases by altering their interactions with chemokines, cytokines, and growth factors.
29543042 Nintedanib reduces pulmonary fibrosis in a model of rheumatoid arthritis-associated inters 2018 Jun 1 Rheumatoid arthritis (RA)-associated interstitial lung disease (RA-ILD) develops in ~20% of patients with RA. SKG mice, which are genetically prone to development of autoimmune arthritis, develop a pulmonary interstitial pneumonia that resembles human cellular and fibrotic nonspecific interstitial pneumonia. Nintedanib, a tyrosine kinase inhibitor approved for treatment of idiopathic pulmonary fibrosis, has been shown to reduce the decline in lung function. Therefore, we investigated the effect of nintedanib on development of pulmonary fibrosis and joint disease in female SKG mice with arthritis induced by intraperitoneal injection of zymosan (5 mg). Nintedanib (60 mg·kg(-1)·day(-1) via oral gavage) was started 5 or 10 wk after injection of zymosan. Arthritis and lung fibrosis outcome measures were assessed after 6 wk of treatment with nintedanib. A significant reduction in lung collagen levels, determined by measuring hydroxyproline levels and staining for collagen, was observed after 6 wk in nintedanib-treated mice with established arthritis and lung disease. Early intervention with nintedanib significantly reduced development of arthritis based on joint assessment and high-resolution μ-CT. This study impacts the RA and ILD fields by facilitating identification of a therapeutic treatment that may improve both diseases. As this model replicates the characteristics of RA-ILD, the results may be translatable to the human disease.
29875735 Rheumatic Disease: Protease-Activated Receptor-2 in Synovial Joint Pathobiology. 2018 Protease-activated receptor-2 (PAR2) is one member of a small family of transmembrane, G-protein-coupled receptors. These receptors are activated via cleavage of their N terminus by serine proteases (e.g., tryptase), unveiling an N terminus tethered ligand which binds to the second extracellular loop of the receptor. Increasing evidence has emerged identifying key pathophysiological roles for PAR2 in both rheumatoid arthritis (RA) and osteoarthritis (OA). Importantly, this includes both pro-inflammatory and destructive roles. For example, in murine models of RA, the associated synovitis, cartilage degradation, and subsequent bone erosion are all significantly reduced in the absence of PAR2. Similarly, in experimental models of OA, PAR2 disruption confers protection against cartilage degradation, subchondral bone osteosclerosis, and osteophyte formation. This review focuses on the role of PAR2 in rheumatic disease and its potential as an important therapeutic target for treating pain and joint degradation.
30584274 Curcumin alleviates rheumatoid arthritis-induced inflammation and synovial hyperplasia by 2018 PURPOSE: Rheumatoid arthritis (RA) is a chronic, progressive autoimmune disease characterized by aggressive and symmetric polyarthritis. Mammalian target of rapamycin (mTOR) was reported to be a new target for RA therapy and its inhibitor rapamycin can significantly reduce the invasive force of fibroblast-like synoviocytes. Here, we determined the effect of curcumin to alleviate inflammation and synovial hyperplasia for the therapy of RA. MATERIALS AND METHODS: Collagen-induced arthritis (CIA) was developed in Wistar rats and used as a model resembling RA in humans. Rats were treated with curcumin (200 mg/kg) and the mTOR inhibitor rapamycin (2.5 mg/kg) daily for 3 weeks. Effects of the treatment on local joint, peripheral blood, and synovial hyperplasia in the pathogenesis of CIA were analyzed. RESULTS: Curcumin and rapamycin significantly inhibited the redness and swelling of ankles and joints in RA rats. Curcumin inhibited the CIA-induced mTOR pathway and the RA-induced infiltration of inflammatory cells into the synovium. Curcumin and rapamycin treatment inhibited the increased levels of proinflammatory cytokines including IL-1β, TNF-α, MMP-1, and MMP-3 in CIA rats. CONCLUSION: Our findings show that curcumin alleviates CIA-induced inflammation, synovial hyperplasia, and the other main features involved in the pathogenesis of CIA via the mTOR pathway. These results provide evidence for the anti-arthritic properties of curcumin and corroborate its potential use for the treatment of RA.
29669300 GZMB gene silencing confers protection against synovial tissue hyperplasia and articular c 2018 Jul INTRODUCTION: Rheumatoid arthritis (RA) represents the most commonly occurring inflammatory type of arthritis and is a major cause of disability. Reports have placed emphasis on the potential of, granzyme B (GZMB) as a potentially valuable prognostic marker in early RA, the mechanism of which still remains largely unclear. Thus, the aim of the current study was to investigate the effects GZMB gene silencing influences synovial tissue hyperplasia and articular cartilage tissue injury of RA through the regulation of the MAPK signaling pathway. METHODS: Following the successful establishment of the collagen-induced animal model of RA in rats, a five-grade scoring method was applied to evaluate the swelling degree measurement of the rats for model identification. The various rat responses to GZMB shRNA and U-46619 (activator of the MAPK signaling pathway) were subsequently detected. The general status of rats was observed and recorded, with their weight and ankle diameter kept accurate record of. ELISA was employed to detect the levels of inflammatory cytokines, while RT-qPCR and Western blotting techniques were applied to determine the expressions of GZMB and pathway-related genes and proteins. RESULTS: GZMB gene silencing was observed to aid in the maintenance of rat weight increases, while acting to reduce the degree of ankle swelling, while hypertrophy of the synovial tissue and the injury of the articular cartilage tissue were not obvious. GZMB gene silencing was shown to decrease inflammatory cytokine levels, as well as decreased bcl-2, Cyclin D1, VEGF and bFGF while increasing caspase 3. Notably, GZMB gene silencing suppressed the activation of the MAPK signaling pathway by reducing the phosphorylation extent of ERK and MEK. CONCLUSION: Taken together, the key findings of the present study ultimately suggest that GZMB gene silencing acts to inhibit MAPK signaling pathway through regulating the expressions of inflammatory factors, factors correlated with apoptosis (bcl-2 and caspase), as well as factors associated with angiogenesis (VEGF and bFGF), thus relieving synovial tissue hyperplasia and articular cartilage tissue injury brought about by RA. The GZMB gene could well be a new therapeutic target for RA treatment.
29416576 Association of SIRT-1 Gene Polymorphism and Vitamin D Level in Egyptian Patients With Rheu 2018 Mar BACKGROUND: We investigated SIRT-1 genetic variant and its association with vitamin D level in Egyptian patients with rheumatoid arthritis (RA). METHODS: Seventy Egyptian subjects were enrolled in our study and divided into two groups: RA group (n = 50 patients) and healthy control group (n = 20 subjects). Five milliliter blood sample was withdrawn from each subject followed by laboratory investigation and DNA extraction for SIRT-1 gene polymorphism assessment (rs7895833 A>G, rs7069102 C>G and rs2273773 C>T) and vitamin D level expression. RESULTS: There was statistically significant difference between rheumatoid cases and controls with regard to vitamin D level with 88% of cases showing insufficient vitamin D versus all controls showing sufficient level. SIRT-1 different SNPs rs2273773, rs7895833and rs7069102 genotype frequencies were statistically significant in RA compared to control group (P = 0.001). There was no statistically significant difference between different genotypes of rs2273773, rs7895833 and rs7069102 with regard to vitamin D level. CONCLUSION: We concluded that there is a strong association between SIRT-1 polymorphism genotyping and RA. Vitamin D level was insufficient in Egyptian patients with RA.
29973350 Overdiagnosis and overtreatment in rheumatology: a little caution is in order. 2018 Oct Overdiagnosis is a term coined by experts in cancer screening to point to indolent cancers detected by screening that would have never led to manifest health problems. Overdiagnosis leads to unnecessary medical care (overtreatment), anxiety and cost. In rheumatology overdiagnosis and overtreatment are hardly discussed but likely present. This viewpoint examines how our prevailing views on the management of inflammatory rheumatic diseases may relate to overdiagnosis and overtreatment. Six paradigms of modern rheumatology will be discussed: early diagnosis, intensive treatment, remission, prognosis and risk stratification, evidence-based rheumatology, and precision medicine. It is concluded that, in spite of the enormous progress that they have brought, all paradigms bear the intrinsic dangers of overdiagnosis and overtreatment. So a little caution is in order.
29997611 Kruppel-Like Factor 4 Positively Regulates Autoimmune Arthritis in Mouse Models and Rheuma 2018 Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes mild to severe joint inflammation. During RA pathogenesis, fibroblast-like synoviocytes (FLS) acquire a tumor-like phenotype and mediate cartilage destruction both directly and indirectly by producing proinflammatory cytokines and matrix metalloproteinases (MMPs). Kruppel-like factor (KLF) 4, a member of the KLF family, plays significant roles in cell survival, proliferation, and differentiation. A recent study reported increased expression of KLF4 in synovial tissue from RA patients. However, its precise role in RA in different models, including mouse autoimmune disease models, remains unclear. In this study, we examined the role of KLF4 during development of autoimmune arthritis in mouse models. To do this, we used KLF4 knockout mice rendered by ribonucleic acid (RNA)-guided endonuclease (RGEN) and performed collagen antibody-induced arthritis (CAIA). We found that deletion of KLF4 reduces inflammation induced by CAIA. In addition, we assessed collagen-induced arthritis (CIA) in control mice and KLF4-overexpressing mice generated by a minicircle vector treatment. Severity of CIA in mice overexpressing KLF4 was greater than that in mice injected with control vector. Finally, we verified the inflammatory roles of KLF4 in CIA by treating Kenpaullone which is used as KLF4 inhibitor. Next, we focused on human/mouse FLS to discover the cellular process involved in RA pathogenesis including proliferation, apoptosis, and inflammation including MMPs. In FLS, KLF4 upregulated expression of mRNA encoding proinflammatory cytokines interleukin (IL)-1β and IL-6. KLF4 also regulated expression of matrix metallopeptidase 13 in the synovium. We found that blockade of KLF4 in FLS increased apoptosis and suppressed proliferation followed by downregulation of antiapoptotic factor BCL2. Our results indicate that KLF4 plays a crucial role in pathogenesis of inflammatory arthritis in vivo, by regulating apoptosis, MMP expression, and cytokine expression by FLS. Thus, KLF4 might be a novel transcription factor for generating RA by modulating cellular process of FLS.
29540097 Crocin exerts anti-inflammatory and anti-arthritic effects on type II collagen-induced art 2018 Dec CONTEXT: Rheumatoid arthritis (RA) is a common systemic auto-immune disease, which is characterized by chronic and symmetry synovial inflammation. Crocin has been reported to exhibit anti-inflammatory effects in animal models. OBJECTIVE: This study investigates the anti-inflammatory and anti-arthritic effects of crocin on type II collagen-induced arthritis (CIA) in Wistar rats. MATERIALS AND METHODS: The CIA rat model was established and randomly divided into five groups with or without crocin treatment (10, 20 or 40 mg/kg), which was started on day 21 after arthritis induction and persisted for 36 days. The symptoms and molecular mechanisms of CIA and crocin-treated CIA rats were compared and investigated. RESULTS: CIA rats presented severe RA symptoms, including high arthritis score, paw swelling, joint inflammation, bone erosion, chondrocyte death, cartilage destruction, enhanced expressions of matrix metalloproteinase (MMP) and pro-inflammatory cytokines. However, crocin could mitigate these symptoms. Crocin (40 mg/kg) exhibited the most efficient therapeutic function on CIA rats: the histological scores of joint inflammation, bone erosion, chondrocyte death, cartilage surface erosion, and bone erosion of CIA rats receiving 40 mg/kg crocin treatment were comparable to the normal rats. MMP-1, -3 and -13 protein expression levels of CIA rats with 40 mg/kg crocin treatment were decreased to levels similar to normal rats. Moreover, crocin could also inhibit the expression of TNF-α, IL-17, IL-6 and CXCL8 in serum and ankle tissues of CIA rats. CONCLUSIONS: In summary, crocin exhibits therapeutic potential for RA, by mitigating the symptoms and inhibiting the pro-inflammatory factor expression.
30048923 Methotrexate prodrugs sensitive to reactive oxygen species for the improved treatment of r 2018 Aug 5 Methotrexate (MTX) is the standard of care in the treatment of rheumatoid arthritis (RA), a common autoimmune disease that is characterized by chronic inflammation in the synovial membrane of joints. Unfortunately, MTX suffers from high discontinuation rates due to a large variability in efficacy and, in particular, adverse effects. As inflammation is associated with elevated levels of reactive oxygen species (ROS) like H(2)O(2), we propose to improve treatment through site-selective delivery of MTX to inflammatory tissue by use of a H(2)O(2) sensitive MTX prodrug. To establish proof proof-of-concept, two novel H(2)O(2) sensitive, thiazolidinone-based MTX prodrugs were synthesized and evaluated for this purpose. MTX-γ-thiazolidinone (MTX-γ-TZ) exhibited the most promising properties - good to high chemical and metabolic stability, excellent aqueous solubility, while being activated when subjected to patho-physiological concentrations of H(2)O(2). In vivo, MTX-γ-TZ exhibited comparable efficacy to MTX in a murine collagen type II-induced arthritis (CIA) model while treated mice showed indications of reduced toxicity as their body weight decreased less towards the end of the study, compared to the MTX-treated group.
30332943 From Molecular Mechanism to the Etiology of Sjogren Syndrome. 2018 Sjogren's Syndrome (SS) is a chronic, female overwhelming fundamental issue of an immune system rheumatic sickness that influences the whole body. It is described by lymphocytic invasion of the exocrine viz. salivary and lacrimal glands and by surprising B-cell hyperactivity. Keratoconjunctivitis sicca (dry eye) and Stomatitis sicca (oral dryness) are the primary visual appearances of SS. The primary SS is recognized from secondary SS which happens as a piece of other immune system maladies. The secondary SS exists together particularly with fundamental lupus erythematosus (15- 36%), rheumatoid joint inflammation (20- 32%) and also restricted and progressive systemic sclerosis (11- 24%), less as often as possible with different sclerosis and immune system hepatitis and thyreoiditis. We assess changes in salivary epidermal growth factor (EGF) intensity and estimate the relationship between salivary EGF levels and the seriousness of intraoral symptoms in SS individuals. The outcomes demonstrated that the salivary EGF levels diminished with the movement of SS, and this crumbling in salivation quality and additionally, hyposalivation could imagine a vital constituent in the pathogenesis of refractory intraoral indication in SS suffering patients. A strong relationship between particular alleles of the MHC and SS improvement has been recommended. The primary hereditary examination on SS revealed a relationship amongst SS and HLA-DR3 in SS population. Subsequent reports featured the relationship amongst SS and the HLA-D locus, with a diverse distribution between primary SS and secondary SS. The motivation behind this manuscript is to give a concise survey on the molecular mechanism, effects of infectious agents and genetic factors in the etiology of Sjogren's Syndrome. Such effects are discussed independently.
29124434 Effect of prednisone treatment for 30 and 90 days on bone metabolism in collagen-induced 2018 Nov Glucocorticoids (GCs) are often prescribed to treat rheumatoid arthritis (RA) in the long term, but there is still controversy in the administration of GCs, mainly because of the adverse reactions such as osteoporosis. Numerous studies have demonstrated that osteoporosis could be induced by GCs in normal rats. However, few experiments have focused on whether osteoporosis could be induced or aggravated by GCs in collagen induced arthritis (CIA) rats. We have investigated bone changes in CIA rats treated with prednisone at 4.5 mg/kg/day for 30 and 90 days by bone histomorphometry, bone mineral density (BMD), micro-CT, biomechanical test, and enzyme-linked immunosorbant assay. We found that high bone turnover osteoporosis was shown in CIA rats. Prednisone treatment for 30 and 90 days improved articular structure and decelerated the degeneration of the femur in CIA rats, but did not improve BMD and bone biomechanics. We conclude that osteoporosis was not aggravated in CIA rats treated with prednisone for 30 and 90 days. On the contrary, prednisone treatment for 30 and 90 days could prevent bone loss of the femur in CIA rats. There was a negative effect on bone metabolism in CIA rats treated with prednisone for 90 days.