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ID PMID Title PublicationDate abstract
33672659 Circulating Free DNA and Its Emerging Role in Autoimmune Diseases. 2021 Feb 20 Liquid biopsies can be used to analyse tissue-derived information, including cell-free DNA (cfDNA), circulating rare cells, and circulating extracellular vesicles in the blood or other bodily fluids, representing a new way to guide therapeutic decisions in cancer. Among the new challenges of liquid biopsy, we found clinical application in nontumour pathologies, including autoimmune diseases. Since the discovery of the presence of high levels of cfDNA in patients with systemic lupus erythaematosus (SLE) in the 1960s, cfDNA research in autoimmune diseases has mainly focused on the overall quantification of cfDNA and its association with disease activity. However, with technological advancements and the increasing understanding of the role of DNA sensing receptors in inflammation and autoimmunity, interest in cfDNA and autoimmune diseases has not expanded until recently. In this review, we provide an overview of the basic biology of cfDNA in the context of autoimmune diseases as a biomarker of disease activity, progression, and prediction of the treatment response. We discuss and integrate available information about these important aspects.
33523662 Confident Identification of Citrullination and Carbamylation Assisted by Peptide Retention 2021 Mar 5 The chromatographic behavior of peptides carrying citrulline and homocitrulline residues in proteomic two-dimensional (2D) liquid chromatography-mass spectrometry (LC-MS) experiments has been investigated. The primary goal of this study was to determine the chromatographic conditions that allow differentiating between arginine citrullination and deamidation of asparagine based on retention data, improving the confidence of MS-based identifications. Carbamylation was used as a reference point due to a high degree of similarity between modification products and anticipated changes in chromatographic behavior. We applied 2D LC-MS/MS (a high-pH-low-pH reversed phase (RP), hydrophilic interaction liquid chromatography (HILIC)-low-pH RP, and strong cation exchange (SCX)-low-pH RP) to acquire retention data for modified-nonmodified peptide pairs in the four separation modes. Modifications of a standard protein mixture were induced enzymatically (PAD-2) or chemically (urea) for citrullination and carbamylation, respectively. Deamidation occurs spontaneously. Similar retention shifts were observed for all three modifications in a high-pH RP (decrease) and a low-pH RP (increase), thus limiting the applicability of this 2D LC combination. HILIC on bare silica and strong cation exchange separations have been probed to amplify the effect of charge loss upon citrullination, with SCX demonstrating the most differentiating power: the elimination of basic residues upon citrullination/carbamylation results in an ∼58 mM KCl retention decrease, while retention of deamidated products decreases slightly.
33976699 Tofacitinib for the Treatment of Severe Interstitial Lung Disease Related to Rheumatoid Ar 2021 Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by chronic symmetrical erosive synovitis and extra-articular manifestations, including interstitial lung disease (ILD), whose treatment is nowadays challenging due to high infectious risk and possible pulmonary iatrogenic toxicity. Janus kinase inhibitors, namely, tofacitinib, baricitinib, and upadacitinib, are the latest drug class for the treatment of RA with a good safety profile. We present the case of a patient with RA-ILD successfully treated with tofacitinib. A 52-year-old man was referred to our multidisciplinary clinic for rheumatic and pulmonary diseases for an active erosive seropositive RA and progressive ILD. Previous treatments were GC, hydroxychloroquine, methotrexate, etanercept, withdrawn after ILD detection, and tocilizumab, discontinued due to relapsing infections. After our evaluation, we proposed rituximab in addition to low-dose GC and hydroxychloroquine, ineffective on joint involvement. Therefore, we proposed tofacitinib which allowed us to control joint involvement, stabilize ILD improving respiratory symptoms, and manage the frequent infectious episodes that occurred initially. The short half-life and rapid-acting of tofacitinib are two helpful characteristics regarding this aspect. Despite limited data from randomized trials and real-life, tofacitinib could represent a safe therapeutic option for RA-ILD patients. Longitudinal studies are required to confirm this encouraging report.
35118101 Single Cell RNA Sequencing in Autoimmune Inflammatory Rheumatic Diseases: Current Applicat 2021 Single cell RNA sequencing (scRNA-seq) represents a new large scale and high throughput technique allowing analysis of the whole transcriptome at the resolution of an individual cell. It has emerged as an imperative method in life science research, uncovering complex cellular networks and providing indices that will eventually lead to the development of more targeted and personalized therapies. The importance of scRNA-seq has been particularly highlighted through the analysis of complex biological systems, in which cellular heterogeneity is a key aspect, such as the immune system. Autoimmune inflammatory rheumatic diseases represent a group of disorders, associated with a dysregulated immune system and high patient heterogeneity in both pathophysiological and clinical aspects. This complicates the complete understanding of underlying pathological mechanisms, associated with limited therapeutic options available and their long-term inefficiency and even toxicity. There is an unmet need to investigate, in depth, the cellular and molecular mechanisms driving the pathogenesis of rheumatic diseases and drug resistance, identify novel therapeutic targets, as well as make a step forward in using stratified and informed therapeutic decisions, which could now be achieved with the use of single cell approaches. This review summarizes the current use of scRNA-seq in studying different rheumatic diseases, based on recent findings from published in vitro, in vivo, and clinical studies, as well as discusses the potential implementation of scRNA-seq in the development of precision medicine in rheumatology.
35002280 Qing-Luo-Yin Alleviated Experimental Arthritis in Rats by Disrupting Immune Feedback Betwe 2021 BACKGROUND: Qing-Luo-Yin (QLY) is an anti-rheumatic herbal formula. Despite the well-investigated therapeutic efficacy of QLY, its immune regulatory properties are largely unknown. CD4(+) T cells and monocytes are two key parameters in rheumatoid arthritis (RA). This study investigated the changes in these cells in QLY-treated RA animal models. MATERIALS AND METHODS: RA models were induced in male SD rats and were orally treated with QLY. Dynamic metabolic changes in collagen-induced arthritis (CIA) rats were monitored by (1)H NMR approach. The immunity profiles of CIA and adjuvant-induced arthritis (AIA) rats were evaluated using immunohistochemical, PCR, ELISA, cytokine chip, flow cytometry, and immunofluorescence experiments. The bioactive components in QLY were identified by bioinformatic-guided LC-MS analyses. The compounds with high abundance in QLY decoction and easily absorbed were taken as key anti-rheumatic components and used to treat blood-derived immune cells using in vitro experiments. RESULTS: The results indicated that QLY decreased Th17 cells frequency and T cells-released IL-6, IL-17 and GM-CSF in CIA rats, which was attributed to the impaired lymphocyte maturation and altered differentiation. QLY inhibited lactic acid production and inflammatory polarization in the monocytes during the peak period of AIA and CIA. AIA monocytes elicited significant increase in Th17 cells counts, IL-6 and IL-1β secretion in co-cultured splenocytes, which was abrogated by QLY. QLY-containing serum suppressed the phosphorylation of JNK and p65 in AIA lymphocyte-stimulated normal monocytes and consequently inhibited iNOS and IL-1β expression as well as IL-6 and IL-1β production. Matrine, sinomenine and sophocarpine were identified as major bioactive compounds in QLY. These identified compounds effectively inhibited the development of inflammatory T cells using concentrations detected in QLY-treated rats. At higher concentrations (20-fold increase), the chemical stimuli significantly suppressed the production of IL-1β in AIA monocytes by inhibiting JNK and p65 pathways. CONCLUSION: By targeting inflammatory T cells and monocytes as well as disrupting their interplay, QLY improved immune environment in RA models especially during the active stages of disease.
34919889 Tofacitinib enhances interferon-γ-induced expression of major histocompatibility complex 2022 Jan 15 Tofacitinib is the first selective Janus kinase (JAK) 1/3 inhibitor approved for the treatment of rheumatoid arthritis and has been demonstrated to exhibit its efficacy through suppression of lymphocyte activation. Although macrophages are critically involved in the pathogenesis of rheumatoid arthritis, little is known about the influence of tofacitinib on macrophage activation especially expression of major histocompatibility complex class II (MHC II) and co-stimulatory molecule CD86. In the present study, we examined the effect of tofacitinib on the expression of MHC II and CD86 in RAW264.7 murine macrophages. Interferon (IFN)-γ induces the cell surface expression of MHC II and CD86. The treatment of tofacitinib at 0.5 μM significantly upregulated IFN-γ-induced expression of MHC II, while decreased the expression of CD86. Hence the population of CD86(-) MHC II(+) cells that induced by tofacitinib at 0.5 μM in the presence of IFN-γ were approximately three times larger than that of IFN-γ alone. Consistent with the surface expression, tofacitinib enhanced IFN-γ-induced mRNA expression of MHC II, and contrarily, decreased that of CD86. Similarly, tofacitinib increased the mRNA expression of MHC II transactivator (CIITA), especially CIITA type I, which is a key regulator of MHC II gene transcription. These findings suggested that tofacitinib enhanced IFNγ-induced MHC II expression by transcriptional regulation through induction of CIITA in macrophages and raise the possibility that a novel action of tofacitinib.
34887866 SIRT1: A Potential Therapeutic Target in Autoimmune Diseases. 2021 The morbidity and mortality of autoimmune diseases (Ads) have been increasing worldwide, and the identification of novel therapeutic strategies for prevention and treatment is urgently needed. Sirtuin 1 (SIRT1), a member of the class III family of nicotinamide adenine dinucleotide (NAD(+))-dependent histone deacetylases, has been reported to participate in the progression of several diseases. SIRT1 also regulates inflammation, oxidative stress, mitochondrial function, immune responses, cellular differentiation, proliferation and metabolism, and its altered functions are likely involved in Ads. Several inhibitors and activators have been shown to affect the development of Ads. SIRT1 may represent a novel therapeutic target in these diseases, and small molecules or natural products that modulate the functions of SIRT1 are potential therapeutic agents. In the present review, we summarize current studies of the biological functions of SIRT1 and its role in the pathogenesis and treatment of Ads.
34596038 Effects of multimodal rheumatologic complex treatment in patients with rheumatoid arthriti 2021 Sep 28 OBJECTIVES: To prospectively evaluate the effects of multimodal rheumatologic complex treatment (MRCT), a special concept of in-patient physical treatment (PT), in patients with rheumatoid arthritis (RA). METHODS: RA patients receiving a 16-day MRCT were eligible. MRCT was delivered to participants in 64 PT sessions of various modalities with a minimum of 1.400 Minutes of treatment. The primary outcome was the change in pain levels measured on a numeric rating scale (0-10) between baseline and discharge. Secondary outcomes were assessments of i) disease activity, ii) functional disabilities, iii) serum cytokine levels, iv) analgesic usage, v) patient global health and vi) patient's satisfaction with their therapeutic response to MRCT from baseline to discharge and over a 12-week follow-up. RESULTS: 53 RA patients completed the study and were analysed. Pain levels were reduced significantly and clinically meaningfully (mean ± standard error: -2.1 ± 0.3, p<0.001). Effects of MRCT lasted up to 12 weeks after discharge. After MRCT and during the 12-week follow-up use of analgesics was reduced compared to baseline. Regression analyses revealed no influencing factors on change in pain levels. Patient global health assessment remained improved throughout the entire follow-up period. No MRCT-related side effects were recorded. CONCLUSIONS: MRCT as a multimodal treatment concept with a strong emphasis on PT reduces pain significantly and in a clinically meaningful manner allowing for reduced analgesic usage.
34511040 Cluster analysis identifies unmet healthcare needs among patients with rheumatoid arthriti 2021 Sep 13 OBJECTIVE: To identify the patterns of healthcare resource utilization and unmet needs of persistent disease activity, pain, and physical disability in rheumatoid arthritis (RA) by cluster analysis. METHOD: Patients attending the Jyväskylä Central Hospital rheumatology unit, Finland, were, from 2007, prospectively enrolled in a clinical database. We identified all RA patients in 2010-2014 and combined their individual-level data with well-recorded administrative data on all public healthcare contacts in fiscal year 2014. We ran agglomerative hierarchical clustering (Ward's method), with 28-joint Disease Activity Score with three variables, Health Assessment Questionnaire index, pain (visual analogue scale 0-100), and total annual health service-related direct costs (€) as clustering variables. RESULTS: Complete-case analysis of 939 patients derived four clusters. Cluster C1 (remission and low costs, 550 patients) comprised relatively young patients with low costs, low disease activity, and minimal disability. C2 (chronic pain, disability, and fatigue, 269 patients) included those with the highest pain and fatigue levels, and disability was fairly common. C3 (inflammation, 97 patients) had rather high mean costs and the highest average disease activity, but lower average levels of pain and less disability than C2, highlighting the impact of effective treatment. C4 (comorbidities and high costs, 23 patients) was characterized by exceptionally high costs incurred by comorbidities. CONCLUSIONS: The majority of RA patients had favourable outcomes and low costs. However, a large group of patients was distinguished by chronic pain, disability, and fatigue not unambiguously linked to disease activity. The highest healthcare costs were linked to high disease activity or comorbidities.
34532317 Synovial Fluid of Patient With Rheumatoid Arthritis Enhanced Osmotic Sensitivity Through t 2021 Rheumatoid arthritis (RA) is an autoimmune disease that causes inflammation of the synovial membrane ultimately leading to permanent damage in the affected joints. For this study, synovial fluids from 16 patients diagnosed with either RA or osteoarthritis (OA) were used to examine volume regulation and cooperative water channels, both of which are involved in the cytotoxic edema identified in RA-fibroblast-like synoviocytes (FLS). The osmolarity and inflammatory cytokine interleukin (IL)-6 of synovial fluids from RA patients were mildly enhanced compared to that from OA patients. RA-FLS demonstrated the enhanced property of regulatory volume increase in response to IL-6 and synovial fluids from RA patients. Although there was no difference in the protein expression of the volume-associated protein sodium-potassium-chloride cotransporter1 (NKCC1), its activity was increased by treatment with IL-6. Membrane localization of NKCC1 was also increased by IL-6 treatment. Additionally, both the protein and membrane expressions of aquaporin-1 were increased in RA-FLS by IL-6 stimulation. The IL-6-mediated enhanced osmotic sensitivity of RA-FLS likely involves NKCC1 and aquaporin-1, which mainly constitute the volume-associated ion transporter and water channel elements. These results suggest that RA-FLS provide enhanced electrolytes and concomitant water movement through NKCC1 and aquaporin-1, thereby inducing cellular swelling ultimately resulting in cytotoxic edema. Attenuation of cytotoxic edema and verification of its related mechanism will provide novel therapeutic approaches to RA treatment within the scope of cytotoxic edema.
34363746 Adherence to Weight-Based Dosing Guidelines in Patients Receiving Hydroxychloroquine for S 2021 Oct OBJECTIVE: Hydroxychloroquine (HCQ) is commonly prescribed for the treatment of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and other rheumatic diseases. To limit retinal toxicity, the 2016 American Academy of Ophthalmology (AAO) guidelines recommended limiting the HCQ dose to 5 mg/kg/day or less. Our objective was to develop a quality improvement program to improve adherence to these guidelines. METHODS: We performed a retrospective analysis of 801 adult patients receiving HCQ for SLE and RA in a single academic rheumatology practice. In 2018, we calculated weight-based doses of HCQ at two time points at least 6 months apart. We surveyed provider opinions regarding the 2016 AAO guidelines and implemented a quality improvement intervention during which dosing data were shared with all prescribers (individually and in aggregate) and nurse-aided decision support was provided for HCQ refill requests. One year after the initial analysis and intervention, we again assessed weight-based doses of HCQ for the 674 patients still taking HCQ. RESULTS: At both measured time points during 2018, 22.8% of patients received doses greater than 5 mg/kg/day. For 60% of those patients, the dose of HCQ was reduced to 5 mg/kg/day or less by the study end. Between the second time point in 2018 and the postintervention time point in 2019, there was a statistically significant increase in the proportion of patients receiving of dose of 5 mg/kg/day or less (from 74% to 87%; P < 0.0001). CONCLUSION: We observed a significant increase in adherence with current AAO guidelines for weight-based HCQ dosing after providing feedback to providers regarding their prescribing data and reviewing weight-based dosing prior to refilling prescriptions.
34121740 What is the impact of thyroidectomy on autoimmune features associated with Hashimoto's thy 2021 Jun BACKGROUND: Hashimoto's thyroiditis (HT) is one of the commonest endocrine disorders, globally. Often, HT presents a protean range of associated autoimmune features (AAI) such as vitiligo, rheumatoid arthritis, pernicious anemia, skin allergy/atopy, thrombocytopenia, Addison's disease, type 1 diabetes, celiac disease, eosinophilia, etc., The usual treatment of HT is symptomatic with no curative option. In this context, we report our experience on the impact of surgical thyroidectomy on remission of AAI in HT. AIMS: To report our experience on the impact of surgical thyroidectomy on remission of AAI in patients with HT. MATERIAL AND METHODS: This is a retrospective study conducted in the Endocrine Surgery department of a tertiary care hospital. A total of 61 patients with HT and various AAI combinations were included in this study. All the clinicoinvestigative and operative data were systematically analyzed. The most frequent indication for surgery was nodular goiter followed by associated malignancy, persistent goiter, and painful thyroiditis. Others were cosmetic/pressure symptoms and not AAI per se. The mean follow-up after surgery was 55.6 ± 11.8 months. RESULTS: The gender ratio was 5.8:1 in favor of women and the mean age was 41.5 ± 5.4 years. The mean preoperative and postoperative serum anti-thyroperoxidase antibody (Anti-TPO Ab) levels were 339 ± 98.2 and 58.75 ± 25 IU/L at the last follow-up visit. A total of 60% AAI manifestations had resolution or significant alleviation. The major improvements in AAI were skin allergy, eosinophilia, rheumatoid arthritis, vitiligo, thrombocytopenia, celiac disease symptomatic episodes; but, type 1 diabetes and Addison's disease showed static response. CONCLUSIONS: Surgical total thyroidectomy and anti-TPO Ab-related autoimmunity appear to play a beneficial role and definitive role in the remission of AAI in HT.
33777549 Abatacept-Induced Panniculitis With Necrobiosis Lipoidica-Like Features in a Patient With 2021 Feb 20 We present a 57-year-old female with a past medical history of rheumatoid arthritis, hypertension, and hypothyroidism who presented with poorly demarcated, nonblanching, painful, erythematous nodules on the bilateral lower legs for two weeks. The patient recently switched from infliximab to abatacept infusions, and skin eruptions presented 53 days from her initial abatacept infusion. A 5 mm punch biopsy of the left anterior upper leg in the zone of involvement showed a deep dermal granulomatous infiltrate with associated eosinophils and a vaguely horizontally palisaded pattern with necrobiosis. The granulomatous inflammation extended into the subcutaneous septae with a widening of the septae, edema, and lipomembranous fat necrosis. The patient was started on naproxen 500 mg PO BID and halobetasol propionate 0.05% lotion BID. Concomitantly, she was started on a four-day course of oral prednisone 10 mg PO daily and restarted infliximab infusions on the third day of prednisone treatment. At her initial infliximab infusions, she received one dose of solumedrol 40 mg and diphenhydramine 50 mg. The eruption resolved 21 days after the initial presentation. The present case is unique from the nine other cutaneous eruptions described after initiating abatacept therapy. Less than 10 cases of cutaneous panniculitides have been reported as adverse reactions to abatacept, with the most common reactions associated with oral contraceptives, nonsteroidal anti-inflammatory drugs, antibiotics, and leukotriene modifying agents. This case underscores the variety of histological findings in drug-induced panniculitis, highlighting the possibility of a drug reaction in a patient with rheumatological disease presenting with panniculitis.
33770833 CYP2D6 and CYP3A4 variants influence the risk and outcome of COVID-19 infection among rheu 2021 Mar 26 OBJECTIVES: Hydroxychloroquine (HCQ) has been used as an off label for the management of coronavirus disease (Covid-19) infection with other drugs. However, different genetic variants can affect the metabolism of HCQ leading to inter-individual differences in its efficacy. In this study, we investigated the effects of variants in CYP2D6, CYP3A4 and CYP3A5 on the risk of Covid-19 infection among patients receiving HCQ for controlling rheumatoid arthritis (RA). METHODS: A total of 60 patients were genotyped for CYP2D6*2XN, CYP2D6*4, CYP3A4*1B and CYP3A5*2. They were receiving HCQ for the treatment of RA. The patients were evaluated clinically for fever and dry cough, radiologically via chest computed tomography (CT) and immunologically via anti-Covid-19 IgG and IgM titers. RESULTS: Variants in CYP2D6 significantly affected the grade of ground glass (CYP2D6*4 AA carriers showed the higher risk for grade 3) and the risk of positive anti-Covid-19 IgM (CYP2D6*2XN CC and CYP3A4*1B AA had the lowest risk), the duration of HCQ, the use of corticosteroids or gender did not affect the Covid-19 status significantly. CONCLUSIONS: In general, the outcome of the studied patients receiving HCQ was good (no deaths, no intubation needed). CYP2D6 variants could affect the outcome of Covid-19 infection.
33501406 Mitral valvulitis as a severe extra-articular manifestation of rheumatoid arthritis: a cas 2021 Jan BACKGROUND: Extra-articular manifestations (EAMs) are common in patients with rheumatoid arthritis (RA). Cardiac EAMs are rare but may cause complete heart block and damage to the heart valves. CASE SUMMARY: We present the case of a middle-aged woman with long-standing RA and EAMs as the most prominent symptoms. The patient experienced complete atrioventricular heart block and developed nodular vegetations affecting the mitral valve, ultimately leading to severe mitral regurgitation and valve replacement. DISCUSSION: The diagnosis of cardiac EAMs in RA may be challenging for the clinicians. Symptoms and findings may mimic more common conditions such as malignancy and infectious endocarditis. A multidisciplinary approach is of paramount importance in order to make an early diagnosis and to provide optimal treatment to patients with RA and cardiac complications.
33099639 High-frequency follow-up studies in musculoskeletal disorders: a scoping review. 2021 Jan 5 OBJECTIVES: This scoping review identifies research in musculoskeletal disorders that uses high frequency follow-up of symptoms. The aim was to investigate whether symptom variability is investigated as a predictor of disease outcome and how intensive follow-up methods are used in musculoskeletal research. METHODS: Embase, MEDLINE and PsycInfo were searched using OVID, and the Institute of Electrical and Electronic Engineers was also searched using the Institute of Electrical and Electronic Engineers Xplore search engine. Studies were systematically reviewed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses, but no meta-analysis was done because the priority in this study is to identify gaps in available literature. RESULTS: Twenty-one papers were included. There was a mean of 54 patients per study (s.d. of 27.7). Two-thirds of the papers looked at how a symptom influences another in the short-term (subsequent assessment in the same day or next day), but none looked at the long-term. Only one study considered symptom variability investigating how higher variability in pain (defined by the s.d.) is associated with higher average pain severity and lower average sleep quality. CONCLUSION: The methodology of musculoskeletal disorder research has changed from completing paper booklets to using electronic data capture (smartphones). There has also been a trend of collecting more intensive longitudinal data, but very little research utilizes these data to look at how symptom variability affects symptom outcomes. This demonstrates a gap in research where furthering understanding of this will help clinicians decide on the most important symptom to address in future patients.
33725241 Effect of Ester Derivative of Indomethacin on Immune Inflammation. 2021 Feb The anti-inflammatory effect of the ester derivative of indomethacin (IML) in doses of 6.25, 12.5, and 25 mg/kg was studied in rats with modeled rheumatoid arthritis (adjuvant arthritis) and compared to the effects of the reference drug indomethacin in a dose of 1 mg/kg. IML in doses of 12.5 and 25 mg/kg reduced joint inflammation and promoted recovery of the microstructure of the synovial membrane and articular cartilage better than indomethacin. IML produced no ulcerogenic effect, while indomethacin concentration in the stomach wall after administration of IML was 1.8-3.4 times lower than after administration of the reference drug (p<0.05).
34402367 Anti-inflammatory activities of a new VEGF blocker, Conbercept. 2021 Oct BACKGROUND: Angiogenesis and inflammation exhibit a mutually reinforcing relationship in many human diseases. Vascular endothelial growth factor (VEGF) is one of the most important proangiogenic mediators. Conbercept is a novel VEGF inhibitor. METHOD: Type II collagen-induced rat rheumatoid arthritis (CIA) model was established to evaluate the anti-chronic inflammation activities of Conbercept. ELISA was used to measure the concentrations of immune factors in the blood of arthritis rats. The xylene-induced ear edema was conducted to evaluate the effect of Conbercept on acute inflammation. RESULT AND DISCUSSION: Our results showed that Conbercept significantly reduced the paw edema volume and the arthritis index in CIA rats. Furthermore, we found that Conbercept decreased the serum levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in CIA rats. Xylene-induced ear edema is a widely used method to study acute inflammation. Conbercept significantly inhibited xylene-induced ear edema. CONCLUSION: All results indicate that Conbercept exhibits significant inhibition of acute and chronic inflammation.
34037987 Angiotensin involvement in kidney injury induced by rheumatoid arthritis in rat. 2021 Sep Renal injury induced by rheumatoid arthritis is not clear and may be related to the angiotensin II. We aim to investigate the adjuvant-induced arthritis (AIA) injury in rat kidney, focusing the angiotensin II/AT(1) pathway. Male Wistar rats were allocated in to three groups: Control, AIA and AIA plus losartan. The AIA was induced by injection of 100 µL of an emulsion of dissected Mycobacterium tuberculosis (50 mg/mL) on the paw. Treatment with losartan was initiated on the first day of immunization (daily subcutaneous injection, 1 mg/kg). After 60 days post immunization, we evaluated kidney function by plasma creatinine, urea and uric acid levels and creatinine depuration; kidney injury by apoptosis analysis and inflammation markers such as macrophages, transforming growth factor beta (TGF-β) and inducible nitric oxide synthase (iNOS) expression; oxidative stress by plasma thiobarbituric acid reactive substances (TBARS); renal expression of angiotensin receptors subtype 1 (AT(1) ) and 2 (AT(2) ) and plasma concentration of angiotensin II. AIA rats showed elevated plasma levels of creatinine, urea, uric acid, TBARS and Ang II and reduced creatinine depuration, and enhanced kidney macrophage number, TGF-β, caspase-3, iNOS and AT(1) /AT(2) receptors expression. The losartan reduced plasma creatinine and its clearance, reduced macrophages and the expression of TGF-β and iNOS in renal tissues, and reduced plasma TBARS. We conclude that AIA causes kidney injury by a physiopathological mechanism that involves AT(1)  stimulation in renal tissue, elevating the presence of macrophages, the expression of TGF-β and iNOS, as well the local oxidative stress, which contribute to renal function deterioration.
32170834 Association of Rural Setting With Poorer Disease Outcomes for Patients With Rheumatic Dise 2021 May OBJECTIVE: To assess whether clinical and patient-reported outcomes are poorer for individuals with inflammatory and noninflammatory rheumatic diseases living in rural locations. METHODS: We searched 6 databases for articles that reported on primary peer-reviewed research, published in English between 1990 and 2019, that focused on selected rheumatic diseases (rheumatoid arthritis [RA], psoriatic arthritis, axial spondyloarthritis, or osteoarthritis [OA]) and quantified either patient-reported or clinically measured outcomes by a measure of rurality or remoteness. Selected articles were synthesized narratively. RESULTS: Eight eligible publications, including 753 rural and 929 urban patients, evaluated outcomes in RA (5 studies) and OA (3 studies). Studies were small, single center, and rarely provided a definition of rurality. Aspects relating to rurality, such as access to services, were not measured. In RA, some studies suggested greater functional disability and disease activity in rural dwellers. In OA, there was some evidence to suggest that rural dwellers presented with more advanced degenerative hip changes, and that illness perceptions and coping differed between rural and urban dwellers. No studies examined work outcomes. Potentially important confounding factors such as socioeconomic status were rarely considered. CONCLUSION: There remains considerable uncertainty whether outcomes differ for patients with rheumatic disease in rural settings. There is a need for larger scale studies characterizing participants in relation to place of residence in order to determine whether rurality is an independent predictor of outcome or a surrogate marker for socioeconomic factors.