Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
29743863 Metabolic fingerprinting of joint tissue of collagen-induced arthritis (CIA) rat: In vitro 2018 Rheumatoid arthritis (RA) is a systemic autoimmune disease whose major characteristics persistent joint inflammation that results in joint destruction and failure of the function. Collagen-induced arthritis (CIA) rat is an autoimmune disease model and in many ways shares features with RA. The CIA is associated with systemic manifestations, including alterations in the metabolism. Nuclear magnetic resonance (NMR) spectroscopy-based metabolomics has been successfully applied to the perchloric acid extract of the joint tissue of CIA rat and control rat for the analysis of aqueous metabolites. GPC (Glycerophosphocholine), carnitine, acetate, and creatinine were important discriminators of CIA rats as compared to control rats. Level of lactate (significance; p = 0.004), alanine (p = 0.025), BCA (Branched-chain amino acids) (p = 0.006) and creatinine (p = 0.023) was significantly higher in CIA rats as compared to control rats. Choline (p = 0.038) and GPC (p = 0.009) were significantly reduced in CIA rats as compared to control rats. Choline to GPC correlation was good and negative (Pearson correlation = -0.63) for CIA rats as well as for control rats (Pearson correlation = -0.79). All these analyses collectively considered as metabolic fingerprinting of the joint tissue of CIA rat as compared to control rat. The metabolic fingerprinting of joint tissue of CIA rats was different as compared to control rats. The metabolic fingerprinting reflects inflammatory disease activity in CIA rats with synovitis, demonstrating that underlying inflammatory process drives significant changes in metabolism that can be measured in the joint tissue. Therefore, the outcome of this study may be helpful for understanding the mechanism of metabolic processes in RA. This may be also helpful for the development of advanced diagnostic methods and therapy for RA.
30268354 GANT61 alleviates arthritic symptoms by targeting fibroblast-like synoviocytes in CIA rats 2019 Mar BACKGROUND: Studies have identified that the fibroblast-like synoviocytes (FLS) exhibited tumor-like characteristics and was the key factor in the pathogenesis of Rheumatoid arthritis (RA). GANT61, an antagonist of the sonic hedgehog pathway, has been verified with inhibitory effect on many cancers. Here we investigated the effect of GANT61 on FLS and the development of collagen-induced arthritis (CIA). METHODS: 40 Sprague Dawley (SD) rats were randomly divided into four groups: normal, CIA, CIA+10 mg/kg GANT61 and CIA+20 mg/kg GANT61. CIA was induced in rat with collagen injecting. The GANT61 was administered by intraperitoneal injection every 2 days for 3 weeks. The CIA model was identified with the paw swelling, arthritis score and the pathologic changes in joint. The FLS of different group were primary cultured. The proliferative capacity of FLS was detecteded via Cell Counting Kit-8 (CCK-8) method, and the apoptosis was detecteded by flow cytometry. The Bcl-2, Bax, Caspases3 and cleaved Caspases3 in synovium and FLS were detecteded by Western Blot. RESULTS: The 20 mg/kg GANT61 treatment reduced the incidence of CIA and relieved the arthritis symptoms in CIA rats. The Bcl-2 was upregulated and the Bax was downregulated in the CIA rats synovium. The 10 mg/kg and 20 mg/kg GANT61 diminished the Bcl-2 expression, 20 mg/kg GANT61 increased the Bax and activated the Caspases3 in the CIA synovium. The proliferation of CIA-FLS was significantly higher and the apoptosis of the CIA-FLS was lower than that of the control group. The 10 mg/kg and 20 mg/kg GANT61 treatment can reduce cell proliferation and induce apoptosis by diminishing Bcl-2 and increasing the Bax in CIA-FLS. CONCLUSIONS: The GANT61 inhibit the proliferation of FLS and alleviated the arthritic symptoms in CIA rats, this implied the GANT61 may be recommended as a possible candidate for the therapy of RA.
30005104 Successful Treatment of Severe Alopecia Areata With Oral or Topical Tofacitinib. 2018 Jul 1 Alopecia areata is an autoimmune disease involving the hair follicle with a chronic, relapsing course. Tofacitinib is Janus kinase inhibitor approved for treatment of rheumatoid arthritis that has been shown to be effective in treatment of alopecia areata. We present a case series of 11 patients with severe alopecia areata on longstanding, regular to high dose oral tofacitinib with marked hair regrowth. Additionally, we present a case of moderate to severe alopecia areata successfully treated with topical tofacitinib cream. J Drugs Dermatol. 2018;17(7):800-803.
29878656 Gaining insight into the complexity of pain in patients with haemophilia: State-of-the-art 2018 May Despite the high prevalence of recurrent, constant and/or widespread pain in patients with haemophilia (PwH), there is an immense lack of studies examining the (patho)physiology of pain in this population. This contrasts to the bulk of literature in other pain conditions, such as osteoarthritis, low back pain or rheumatoid arthritis. Understanding the complexity of pain allows to better assess and manage pain. In PwH, the first priority is always to exclude bleeding as a cause of pain. An important next step in pain assessment is the evaluation of the predominant pain mechanism (ie nociceptive, neuropathic pain or altered central pain processing) as the treatment approach will be very different according to the underlying pain mechanism. Pain assessment should include both physiological and psychological components. This review summarizes the evidence regarding nociceptive, neuropathic and altered central pain processing in PwH and serves as a research agenda to prioritize pain research in PwH.
29952085 Identification of pyrazolopyridine derivatives as novel spleen tyrosine kinase inhibitors. 2018 Jun 27 Inhibition of spleen tyrosine kinase (Syk) is a promising strategy for the treatment of various allergic and autoimmune disorders such as asthma, rheumatoid arthritis, and allergic rhinitis. Previously, a Syk inhibitor with novel indazole scaffold was discovered by structure-based virtual screening. Herein, the structure-activity relationship of the indazole Syk inhibitors was investigated. Several new inhibitors demonstrated potent activity against Syk. In particular, compound 18c showed good Syk inhibitory activity (IC(50)  = 1.2 µM), representing a good lead compound for further optimization.
30572135 Th17 cells in renal inflammation and autoimmunity. 2019 Feb Th17 cells are a distinct lineage of T-cells. These T-cells express IL-17A and the lineage-defining transcription factor RORγt. Th17 cells have a pivotal, physiological role in host defense against pathogens. These pro-inflammatory T-cells are also key players in autoimmunity and a pathogenic role has been demonstrated in several diseases such as rheumatoid arthritis or psoriasis. Recently, there is evidence that Th17 cells may drive renal inflammation and renal autoimmunity in anti-neutrophil-cytoplasmic-antibody-(ANCA)-vasculitis and systemic lupus erythematosus. The aim of this review is to discuss the possible involvement of Th17 cells in renal autoimmunity and its value for future therapeutic approaches.
30244459 Production of Lentiviral Particles. 2018 Lentiviral-mediated transfection technique is a powerful tool for gene modification in preclinical studies. By using this technique, the desired gene modification can be achieved easily in immune cells, nondividing and terminally differentiated cells, including hematopoietic stem cells, neurons, and even tumor cells, which other viral vectors cannot do. The main considerations of therapeutic gene delivery using a lentiviral system are the risk of insertional mutagenesis and the immune reaction elicited by infected cells. Although some biosafety concerns need to be addressed before clinical trials in rheumatoid arthritis, the lentiviral system targeting therapeutic targets has been widely used for in vivo gene transfer in animal models. In this chapter, the protocols for production of viral particles and viral concentration are provided.
29854640 Erasmus Syndrome: Association of Silicosis and Systemic Sclerosis. 2018 May Silicosis is an inflammatory disease of the lung characterized by irreversible lung fibrosis which develops from prolonged pulmonary inhalation and retention of crystalline silica and immune reaction. It mainly appears as an occupational hazard in persons involved in stone-quarrying, mining, and sand blasting. Crystalline silica is not only known to be responsible for silicosis but also for other autoimmune diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA)-Caplan syndrome, systemic sclerosis (SSc), and antineutrophil cytoplasmic antibody (ANCA)-related vasculitis. Erasmus syndrome is the association of silica exposure and subsequent development of SSc. The limited numbers of cases reported in the literature were miners and only sporadically involved in other professionals. Here, we report a case of a 52 -year-old stone cutter who developed silicosis and SSc after 25 years of exposure.
29721441 Indolent, T-cell, large granular lymphocytic leukaemia in a dog presenting with severe neu 2018 In humans, large granular lymphocytic leukaemia (LGLL) is a low-grade, indolent lymphoproliferative disorder of large granular lymphocytes (LGL) associated with autoimmune disorders; including rheumatoid arthritis and single or multiple cytopenias; particularly neutropenia. Therapy largely centres around immunosuppression which aims to resolve the immune-mediated secondary pathology, often without eradicating the neoplastic clone. The most effective agents appear to be cyclophosphamide, cyclosporine and methotrexate. This case report describes the presentation, diagnostics, therapeutic approach and outcome of a 6 year-old Golden Retriever presenting with severe neutropenia. Chlorambucil, prednisolone and cyclosporine failed to improve the neutropenia but subsequent cyclophosphamide resulted in a sustained albeit temporary improvement in neutrophil count and the ability to withdraw prophylactic antibacterials. This case closely mirrors the diagnostics and therapeutic response in human LGLL.
29706737 A Rare Case of Triceps Brachii Injury after Electrocution. 2018 Apr Injuries of the triceps brachii muscle are a rare entity and mostly concern its distal tendon. These represent the least common of all muscle and tendons injuries. The most common reported causes are repeated strong physical efforts, a fall on an outstretched forearm when a sudden deceleration is put on contract triceps, or a direct trauma. High-dosed and prolonged corticosteroid therapies, repeated local steroid injections, chronic renal failure, diabetes, rheumatoid arthritis, hyperparathyroidism, and osteogenesis imperfecta are reported as systemic causes. Even rarer are lesions of muscle fibers and avulsions or rupture at its musculotendinous junction, and these can be caused by direct trauma or by forced elbow flexion during triceps contraction. To the best of our knowledge, there is no article in the literature describing this type of injury that occurred after electrocution. In this article, we report an uncommon case of intramuscular tear associated with insertional distal tendon injury occurred in a man survived to high-voltage electric discharge.
29394026 Medicinal Chemistry of Gold Anticancer Metallodrugs. 2018 Feb 5 Since ancient times gold and its complexes have been used as therapeutics against different diseases. In modern medicine gold drugs have been applied for the treatment of rheumatoid arthritis, however, recently other medical applications have come into the focus of inorganic medicinal chemistry. This chapter provides a non-comprehensive overview of key developments in the field of gold anticancer drugs. Exciting findings on gold(I) and gold(III) complexes as antitumor agents are summarized together with a discussion of relevant aspects of their modes of action.
30425933 Postpartum nephrotic syndrome related to new onset of systemic lupus erythematosus: A case 2018 Oct Postpartum nephrotic syndrome in a pregnant woman with rheumatoid arthritis in long-standing remission is rare. Systemic lupus erythematosus can remain undiagnosed, especially in the absence of clinical manifestations. We present the case of a 34-year-old woman (gravida 2, para 1) who underwent a lower-segment cesarean section at 34 weeks and 6 days of gestation because she had developed preeclampsia and nephrotic syndrome. The concomitant presence of significant hypoproteinemia, hypoalbuminemia, uremia, elevated creatinine serum levels, hyperuricemia and hypertriglyceridemia is indicative of impaired renal function and nephrotic syndrome. This woman was diagnosed with systemic lupus erythematosus nephritis. It is imperative for clinicians to investigate the exact pathophysiological causes of nephrotic syndrome with onset in the puerperium and implement the appropriate therapeutic regimens.
30344019 Constrained Implant Arthroplasty for Distal Radioulnar Joint Arthrosis: Evaluation and Man 2019 Jul PURPOSE: Distal radioulnar joint (DRUJ) prostheses designed as semiconstrained devices aiming to replace the function of the ulnar head, sigmoid notch of the radius, and triangular fibrocartilage complex have demonstrated the capacity to restore the functional status of the DRUJ. However, soft tissue complications including tendons, nerves, and wounds, although documented, have not been the primary focus of prior reports. This study investigated short- to medium-term soft tissue complications after DRUJ semiconstrained implant arthroplasty. METHODS: We performed a retrospective review of patients undergoing semiconstrained DRUJ implant arthroplasty with clinical and radiological follow-up greater than 1 year. Data were reviewed with a focus on soft tissue complications after arthroplasty. RESULTS: Fifty DRUJ implant arthroplasties were performed over 10 years in 49 patients. Patients' average age was 47.8 years. Average duration of follow-up was 35.8 ± 3.7 months. A total of 46 patients underwent multiple operations before DRUJ arthroplasty. Postoperative pronosupination range of motion, grip strength, and visual analog scale pain scores were significantly improved after DRUJ arthroplasty. Wound-healing problems occurred in 11 arthroplasties; however, all wounds subsequently healed without operative intervention. Wound-related complications were significantly increased in patients with a history of rheumatoid arthritis or immunosuppression. Eighteen operations were required to address complications in 8 patients. Extensor tendinopathy was the most common indication for reoperation; 5 tenosynovectomy procedures were required in 4 wrists. A prominent screw requiring removal was identified in 3 cases of tenosynovitis. Periprosthetic fractures were identified in 3 wrists; 2 of these required reoperation for open treatment. Removal of hardware was required in 2 patients; these patients required 9 subsequent reoperations. CONCLUSIONS: Distal radioulnar joint arthrosis is a major problem and patients commonly undergo multiple reconstructive surgeries before DRUJ implant arthroplasty. No instances of wound-related complications or tendinopathy occurred in patients without previous surgeries, and wound-related complications occurred at a higher frequency with a history of rheumatoid arthritis or immunosuppression. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.
29519738 Alleviating CYP and hERG liabilities by structure optimization of dihydrofuran-fused tricy 2018 Apr 15 In an effort to identify CYP and hERG clean mPGES-1 inhibitors from the dihydrofuran-fused tricyclic benzo[d]imidazole series lead 7, an extensive structure-activity relationship (SAR) studies were performed. Optimization of A, D and E-rings in 7 afforded many potent compounds with human whole blood potency in the range of 160-950 nM. Selected inhibitors 21d, 21j, 21m, 21n, 21p and 22b provided selectivity against COX-enzymes and mPGES-1 isoforms (mPGES-2 and cPGES) along with sufficient selectivity against prostanoid synthases. Most of the tested analogs demonstrated required metabolic stability in liver microsomes, low hERG and CYP liability. Oral pharmacokinetics and bioavailability of lead compounds 21j, 21m and 21p are discussed in multiple species like rat, guinea pig, dog, and cynomolgus monkey. Besides, these compounds revealed low to moderate activity against human pregnane X receptor (hPXR). The selected lead 21j further demonstrated in vivo efficacy in acute hyperalgesia (ED(50): 39.6 mg/kg) and MIA-induced osteoarthritic pain models (ED(50): 106 mg/kg).
29364741 Obesity is a significant susceptibility factor for idiopathic AA amyloidosis. 2018 Mar BACKGROUND: To investigate obesity as susceptibility factor in patients with idiopathic AA amyloidosis. METHODS: Clinical, biochemical and genetic data were obtained from 146 patients with AA amyloidosis. Control groups comprised 40 patients with long-standing inflammatory diseases without AA amyloidosis and 56 controls without any inflammatory disease. FINDINGS: Patients with AA amyloidosis had either familial Mediterranean fever (FMF) or long-standing rheumatic diseases as underlying inflammatory disease (n = 111, median age 46 years). However, in a significant proportion of patients with AA amyloidosis no primary disease was identified (idiopathic AA; n = 37, median age 60 years). Patients with idiopathic AA amyloidosis were more obese and older than patients with AA amyloidosis secondary to FMF or rheumatic diseases. Serum leptin levels correlated with the body mass index (BMI) in all types of AA amyloidosis. Elevated leptin levels of more than 30 µg/l were detected in 18% of FMF/rheumatic + AA amyloidosis and in 40% of patients with idiopathic AA amyloidosis (p = .018). Finally, the SAA1 polymorphism was confirmed as a susceptibility factor for AA amyloidosis irrespective of the type of the disease. CONCLUSIONS: Obesity, age and the SAA1 polymorphism are susceptibility factors for idiopathic AA amyloidosis. Recent advances in treatment of FMF and rheumatic disorders will decrease the incidence of AA amyloidosis due to these diseases. Idiopathic AA, however, might be an emerging problem in the ageing and increasingly obese population.
30533362 Intraosseous Bioplasty for a Chondral Cyst in the Lateral Tibial Plateau. 2018 Nov Subchondral lesions are the result of osseous modifications seen in a different array of pathologies such as osteoarthritis, rheumatoid arthritis, calcium pyrophosphate deposition, and osteonecrosis. The physiopathologic changes in all of the aforementioned pathologies are not clear yet. What is clear is that the development of a cystic change in the subchondral bone can cause pain and can lead to modification of the activity of daily life. To provide relief and treatment for such a condition, there are different options with joint replacement as last resort when the cyst develops in communication with the joint; if the cyst is not in communication with the joint, it is possible to perform a bioplasty as we present in this technical report. It is crucial to assess the bone continuity, especially when traumas are reported in the patient history. In our case, the tibial plateau did not have signs of collapse. The technique here presented is a minimally invasive technique that can be reproduced for focal and localized subchondral cysts.
30147913 Therapeutic failure and eventual solution for skin necrosis and exposed tendon of the dors 2018 Aug For the treatment of skin necrosis with exposed tendons in rheumatoid arthritis (RA) foot, we should perform microvascular free flap surgery at an early stage without conservative treatment considering the increased risk of infection and the decreased physical activity.
29766547 Potent and selective CC chemokine receptor 1 antagonists labeled with carbon-13, carbon-14 2018 May 15 1-(4-Fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid (2-methanesulfonyl-pyridin-4-ylmethyl)-amide (1) and its analogs (2) and (3) are potent CCR1 antagonists intended for the treatment of rheumatoid arthritis. The detailed syntheses of these 3 compounds labeled with carbon-13 as well as the preparation of (1) and (2) labeled with carbon-14, and (1) labeled with tritium, are described.
30221683 Aspirin promotes apoptosis and inhibits proliferation by blocking G0/G1 into S phase in rh 2018 Dec Rheumatoid arthritis (RA) is a commonly occurring autoimmune disease. Its defining pathological characteristic is the excessive proliferation of fibroblast‑like synoviocytes (FLS), which is similar to tumor cells and results in a range of clinical problems. As a commonly used antipyretic, analgesic and anti‑inflammatory drug, aspirin is the first‑line treatment for RA. However, its mechanism of action has not been well explained. The goal is to investigate the biological effects of aspirin on primary RA‑FLS and its underlying mechanisms. In this experiment we treated cells with various concentrations of aspirin (0, DMSO, 1, 2, 5, 10 mM). Cell proliferation activity was detected with CCK‑8 assays. Apoptosis and cell cycle distribution were detected via flow cytometry. Apoptosis and cell cycle‑associated proteins (Bcl‑2, Bax, PRAP1, Cyclin D1, P21), as well as the key proteins and their phosphorylation levels of the NF‑κB and JAK/STAT3 signaling pathways, were detected via western blot analysis. Bioinformatics prediction revealed that aspirin was closely associated with cell proliferation and apoptosis, including the p53 and NF‑κB signaling pathways. By stimulating with aspirin, cell viability decreased, while the proportion of apoptotic cells increased, and the number of cells arrested in the G0/G1 phase increased in a dose‑dependent manner. The expression of Bax increased with aspirin stimulation, while the levels of Bcl‑2, PRAP1, Cyclin D1 and P21 decreased; p‑STAT3, p‑P65 and p‑50 levels also decreased while STAT3, P65, P50, p‑P105 and P105 remained unchanged. From our data, it can be concluded that aspirin is able to promote apoptosis and inhibit the proliferation of RA‑FLS through blocking the JAK/STAT3 and NF‑κB signaling pathways.
30207563 Fibromyalgia Syndrome and Vitiligo: A Novel Association. 2018 Jun OBJECTIVES: This study aims to assess the relationship between fibromyalgia syndrome (FMS) and vitiligo in Iraqi patients and evaluate the predictors of this relationship, if present. PATIENTS AND METHODS: The case-control study included 100 Iraqi patients (46 males, 54 females; mean age 30.4±14 years; range 15 to 65 years) with vitiligo and 200 age- and sex-matched healthy controls (74 males, 126 females; mean age 30.3±9.4 years; range 15 to 62 years). Baseline characteristics of patients and controls were recorded. The 2012 Canadian Guidelines criteria were used for the diagnosis of FMS and applied to all patients and controls. RESULTS: Prevalence of FMS in vitiligo patients and controls was 12% and 7%, respectively (p=0.15, odds ratio=1.8, 95% confidence interval=0.8-4.08). FMS symptoms in vitiligo patients were fatigue (46%), diffuse body pain (34%), sleep disturbance (33%), cognitive dysfunction (30%), and mood disorders (23%), while visceral involvements were central nervous system (52%), skin (35%), gastrointestinal tract (32%), cardiovascular system- respiratory system (16%), genitourinary tract (8%), and ear nose throat (7%). Of vitiligo patients, FMS was significantly more common among females (22.2%) compared to none among males (0%) (p<0.05). Prevalence of FMS was restricted to female sex only and a significantly higher prevalence rate of FMS was found among female vitiligo patients (22.2%) compared to controls (9.5%). Receiving phototherapy significantly increased the risk of having FMS by 5 times compared to female patients not receiving phototherapy. Use of any steroid reduced the risk of having FMS by 2.5 times (inverse of odds ratio=0.4) among females patients (p>0/05). No significant association was found between FMS in vitiligo patients and age, disease duration, type of vitiligo, use of any immunosuppressant and body mass index (p>0.05). CONCLUSION: Fibromyalgia syndrome was more prevalent in vitiligo patients compared to controls, which was clinically important but statistically not significant. There was a significant association between FMS in vitiligo patients and female sex, severe form of vitiligo, and receiving phototherapy. This may suggest that early diagnosis of FMS in vitiligo patients may help in early treatment and subsequently improve patients' quality of life.