Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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31776035 | A review on anti-inflammatory activity of green synthesized zinc oxide nanoparticle: Mecha | 2020 Jan | Inflammation plays a very important role in the pathogenesis of various diseases like atherosclerosis, rheumatoid arthritis, asthma, and cancer. Lack of anti-inflammatory drugs and vectors provokes the need for developing new molecules for the management of inflammatory disorders. Nanotechnology has emerged as a wonderful research area in the past decade owing to its enhanced properties than bulk counterparts. This paper discusses the green synthesis of zinc oxide nanoparticle (ZnO NPs) and various characterization tools employed to comprehend the physiochemical properties of nanoparticles. ZnO NPs interaction with cells and its pharmacokinetic behavior inside the cells has also been discussed. The anti-inflammatory activity of ZnO NPs has been elucidated with the mechanism-based approach. A concise literature review has been included which summarizes the size, shape of ZnO NPs and the inflammatory model used for analyzing the anti-inflammatory activity of ZnO NPs. ZnO NPs potential offering towards anti-inflammatory activity like stable nature, selective targeting has been discussed briefly. The present study highlights the potential of ZnO NPs as an anti-inflammatory drug molecule or a vector for drug delivery. | |
33372173 | Multi-Site Insufficiency Pelvic Fracture Following Total Hip Arthroplasty. | 2020 Dec 29 | BACKGROUND The indication of total hip arthroplasty (THA) has been increasing among older and more frail patients who possibly have suboptimal bone quality. Pelvic insufficiency fractures (PIF) are rarely observed after THA. The appropriate diagnosis of fracture location is crucial, but its symptoms are non-specific and radiographic abnormality is often subtle; thus, diagnosis can be challenging, particularly in case of concomitant fractures at multiple locations. CASE REPORT A 47-year-old woman with rheumatoid arthritis and ongoing long-term oral corticosteroid therapy had groin pain in her left hip, which gradually developed without traumatic events 2.5 years after THA. Follow-up radiographs revealed an ipsilateral inferior pubic ramus fracture and a contralateral ischium fracture. The acetabular component of THA was slightly shifted upward, but further diagnostic examination was not conducted at that time. The pain was improved temporarily, but subsequently worsened and made her return to the clinic 6 months later, and radiographs revealed a medial wall fracture and superomedial migration of the acetabular component. She required a 2-stage revision procedure with massive allograft. At 1 year after these procedures, the patient is able to walk without a walking aid and does not report groin pain or present signs of dislocation, and radiographs show no loosening of the implant. CONCLUSIONS This case highlights that medial wall post-THA PIF can occur along with pubic/ischial fractures, which mask the symptoms of the medial wall fracture. We also reviewed the current literature and discussed the diagnostic strategy to be applied when suspecting this rare injury. | |
32382949 | Tirabrutinib: First Approval. | 2020 Jun | Tirabrutinib (Velexbru(®)) is an orally administered, small molecule, Bruton's tyrosine kinase (BTK) inhibitor being developed by Ono Pharmaceutical and its licensee Gilead Sciences for the treatment of autoimmune disorders and haematological malignancies. Tirabrutinib irreversibly and covalently binds to BTK in B cells and inhibits aberrant B cell receptor signalling in B cell-related cancers and autoimmune diseases. In March 2020, oral tirabrutinib was approved in Japan for the treatment of recurrent or refractory primary central nervous system lymphoma. Tirabrutinib is also under regulatory review in Japan for the treatment of Waldenström's macroglobulinemia and lymphoplasmacytic lymphoma. Clinical development is underway in the USA, Europe and Japan for autoimmune disorders, chronic lymphocytic leukaemia, B cell lymphoma, Sjogren's syndrome, pemphigus and rheumatoid arthritis. This article summarizes the milestones in the development of tirabrutinib leading to the first approval of tirabrutinib for the treatment of recurrent or refractory primary central nervous system lymphoma in Japan. | |
32038189 | Contributions of Interleukin-1 Receptor Signaling in Traumatic Brain Injury. | 2019 | Traumatic brain injury (TBI) in various forms affects millions in the United States annually. There are currently no FDA-approved therapies for acute injury or the chronic comorbidities associated with TBI. Acute phases of TBI are characterized by profound neuroinflammation, a process that stimulates the generation and release of proinflammatory cytokines including interleukin-1α (IL-1α) and IL-1β. Both forms of IL-1 initiate signaling by binding with IL-1 receptor type 1 (IL-1R1), a receptor with a natural, endogenous antagonist dubbed IL-1 receptor antagonist (IL-1Ra). The recombinant form of IL-1Ra has gained FDA approval for inflammatory conditions such as rheumatoid arthritis, prompting interest in repurposing these pharmacotherapies for other inflammatory diseases/injury states including TBI. This review summarizes the currently available preclinical and clinical literature regarding the therapeutic potential of inhibiting IL-1-mediated signaling in the context of TBI. Additionally, we propose specific research areas that would provide a greater understanding of the role of IL-1 signaling in TBI and how these data may be beneficial for the development of IL-1-targeted therapies, ushering in the first FDA-approved pharmacotherapy for acute TBI. | |
33164447 | [Textual research on origin and efficacy of Tibetan medicine "Shengdeng"]. | 2020 Oct | "Shengdeng" is a traditional Tibetan medicine, which has many synonyms. It is complex in origin and serious in mi-xing. In order to clarify the origin of "Shengdeng" and its medicinal use, this paper makes a textual research on the name, variety and efficacy of "Shengdeng" by consulting Tibetan medicine classics such as The Four Medical Trantras and Jingzhu Materia Medica, combined with modern literature of Tibetan medicine. It is clear that the synonyms, primitive species, mainstream varieties and functions of Tibetan medicine "Shengdeng". The collation and analysis of the literature shows that "Shengdeng" has effects of treating rheumatism, drying "Huangshui", detumescence and relieving pain, and is mainly used for the treatment of rheumatoid arthritis in Tibetan medicine. Its original varieties include 14 species of plants belonging to 6 families: Spicaceae, Rhamnaceae, Cephalotaxus, Leguminosae, Hematoxylaceae and Taxaceae. Combined with the collection of legal standards at all levels, the distribution of resources and the application of clinical prescriptions, it is considered that the mainstream species of "Shengdeng" are Rhamnella gilgitica, Xanthoceras sorbifolia, Rhamnus parvifolia. As a substitute, Acacia catechu is also widely used in clinic. The literature review and variety textual research on Tibetan medicine "Shengdeng" is helpful to improve the safety, effectiveness and quality controllability of its clinical application, and provide scientific basis for its further standard setting, pharmacodynamics research, new drug development and so on. | |
32999177 | Intratendinous Ganglion of the Extensor Pollicis Longus: Case Report and Literature Review | 2021 Nov 17 | Ganglion cysts are common benign lesions in the hand and wrist. However, intratendinous ganglion cysts are uncommon. We present a case of intratendinous ganglion cyst in the extensor pollicis longus (EPL) tendon of the right hand of a 73-year-old woman. The subcutaneous mass moved in concert with the EPL tendon in her right thumb. Magnetic resonance imaging showed a space-occupying lesion in the EPL tendon. Biochemical and hemato-immunological examinations ruled out diabetes, rheumatoid arthritis, and other connective tissue diseases. She reported motion pain during thumb extension, for which she desired surgery. An intratendinous cyst was identified intraoperatively within the tendon substance of the EPL, in which a part of the cyst was herniated into a slit in the tendon substance, just distal to the extensor retinaculum, without notable proliferative synovial tissue. The EPL tendon was opened longitudinally, and a cystic lesion was enucleated. Pathological examination showed that the cyst wall consisted of fibrous tissue with degeneration and no epithelial lining. Postoperative recovery was uneventful. Six months after surgery, the patient had no residual pain and no cyst recurrence. The rarity of intratendinous ganglion cysts makes diagnosis and treatment challenging. Because intratendinous ganglion cysts and associated synovitis frequently weaken the structure of affected tendons, prompt diagnosis and surgical excision are necessary. | |
32787818 | Hundreds of rice bodies in the subacromial-subdeltoid bursa: report of two cases and liter | 2020 Aug 12 | BACKGROUND: Multiple rice bodies (RB) in the shoulder joint is a rare disorder of unknown etiology that requires percutaneous drainage or surgical operation. CASE PRESENTATION: We reported arthroscopic removal of hundreds of RB in the subacromial-subdeltoid bursa in two cases by our "chopsticks technique". One was associated with seropositive rheumatoid arthritis and the other was a rare synovial origin possibly due to microinfarction and ischemia after the radiotherapy. Radical debridement of necrotic tissue, "red tissue" and synovitis by arthroscopic radiofrequency ablation was essential for eliminating the cause of RB. A favorable clinical evolution was observed for both patients. CONCLUSIONS: We highlight the importance of patient-specific differential diagnosis and the clinical course of RB to help us further understand the pathogenesis of this uncommon disorder. Meanwhile, evacuation of RB and "red tissue" ablation by arthroscopy showed good results. | |
32730376 | [Lymphadenopathies in patients with rheumatic diseases. Review of 19 cases]. | 2020 Mar | BACKGROUND: The presence of multiple lymphadenopathies can be a diagnostic challenge. AIM: To describe the clinical, laboratory and imaging characteristics of 19 patients with lymphadenopathies of rheumatologic origin. MATERIAL AND METHODS: Review of medical records of 19 patients aged 16 to 72 years (68%) with lymphadenopathies presumably secondary to a rheumatic disease. RESULTS: Six patients had systemic lupus erythematosus, six had Sjogren's disease, three had sarcoidosis, two had rheumatoid arthritis, one had IgG4 related disease and one had mixed connective tissue disease. A lymph node biopsy was performed in 11 patients and in eight a lymphoid follicular hyperplasia was found. Systemic symptoms were reported by 68% of patients. Blood lactate dehydrogenase was elevated only in cases associated with hemolytic anemia. There was no specific or predictable localization of the lymphadenopathies in imaging studies, except in the cases of sarcoidosis. The average size of the lymphadenopathies was 13.5 mm in diameter in short axis and there was no presence of necrosis, calcification, or conglomerate formation. Only one case presented splenomegaly. All patients responded favorably to corticosteroids. CONCLUSIONS: Lymphadenopathies associated with rheumatologic diseases can occur in a wide variety of diseases, especially systemic lupus erythematosus and Sjögren's disease. The absence of LDH elevation and splenomegaly and the absence of imaging findings such as conglomerates can orient to a rheumatologic origin. | |
32719151 | 'Should we stop or continue conventional synthetic (including glucocorticoids) and targete | 2020 Jul | Total hip and total knee arthroplasty) remain important interventions to treat symptomatic knee and hip damage in patients with rheumatoid arthritis, with little change in utilisation rates despite the increasingly widespread use of potent conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and targeted DMARDs including Janus kinase inhibitors and biologics. The majority of patients are receiving these immunosuppressing medications and glucocorticoids at the time they present for arthroplasty. There is minimal randomised controlled trial data addressing the use of DMARDs in the perioperative period, yet patients and their physicians face these decisions daily. This paper reviews what is known regarding perioperative management of targeted and csDMARDs and glucocorticoids. | |
32702733 | A Novel RP-HPLC-DAD Method Development for Anti-Malarial and COVID-19 Hydroxy Chloroquine | 2020 May 5 | Hydroxychloroquine sulfate is one of a large series of 4-aminoquinolines with antimalarial activity. Moreover, it is used for the treatment of rheumatoid arthritis. Sometimes Hydroxychloroquine sulfate is very effective for the treatment of autoimmune diseases. Based on the recent clinical experiments it is exploiting for the treatment of COVID-19, corona virus across the globe. A Reverse phase RP-HPLC method have been developed and validated as per the current ICH guidelines for estimation of Hydroxychloroquine sulfate tablets. As part of method validation specificity, linearity, precision and recovery parameters were verified. The concentration and area relationships were linear (R (2) > 0.999), over the concentration range of 25 to 300 µg mL (-1) for HCQ. The relative standard deviations for precision and intermediate precision were less than 1.5%. The proposed RP-HPLC generic method was applied successfully for evaluation of invitro dissolution profile with different pH conditions like 0.1N HCl, pH 4.5 Acetate buffer and pH 6.8 Phosphate buffers of US marketed reference product. | |
32475947 | [A case of acute pneumonia with prolonged false-positive results using an influenza test k | 2020 | Influenza (flu) is a prominent infectious disease that worsens the general prognosis of older adults. We herein report a case of a clinically odd and rare reaction on an instant diagnostic kit for influenza. An 81-year-old man with a fever and rhinorrhea consulted our hospital. He had a history of dementia of Alzheimer's type and rheumatoid arthritis and had been treated with oral prednisolone (10 mg/day). Instant diagnostic test kit A using exudation from the upper pharynx showed positivity for antigen of flu A virus, and computed tomography indicated acute pneumonia. Immediately after the diagnosis, 150 mg/day of oseltamivir was started for 5 days. However, a high fever over 38.0°C persisted, and flu A antigen from the upper pharynx was repeatedly detected using test kit A. Despite subsequent oral treatment with 100 mg/day of amantadine and single venous infusion of 300 mg/day of peramivir, the high fever continued, and the detection of C-reactive protein in the serum as well as flu A antigen in the upper pharynx persisted. We suspected test failure, and the results of another test kit (kit B) were indeed negative. Furthermore, polymerase chain reaction performed by two independent laboratories failed to detect flu gene fragments. We concluded that the patient did not have the flu, and results of test kit A had been a false positive. The patient was successfully treated with ABPC/SBT infusions. We should consider the implications of diagnosing flu using instant test kits. | |
32072586 | Defining Efficacy Estimands in Clinical Trials: Examples Illustrating ICH E9(R1) Guideline | 2020 Mar | This paper provides examples of defining estimands in real-world scenarios following ICH E9(R1) guidelines. Detailed discussions on choosing the estimands and estimators can be found in our companion papers. Three scenarios of increasing complexity are illustrated. The first example is a proof-of-concept trial in major depressive disorder where the estimand is chosen to support the sponsor decision on whether to continue development. The second and third examples are confirmatory trials in severe asthma and rheumatoid arthritis respectively. We discuss the intercurrent events expected during each trial and how they can be handled so as to be consistent with the study objectives. The estimands discussed in these examples are not the only acceptable choices for their respective scenarios. The intent is to illustrate the key concepts rather than focus on specific choices. Emphasis is placed on following a study development process where estimands link the study objectives with data collection and analysis in a coherent manner, thereby avoiding disconnect between objectives, estimands, and analyses. | |
31983907 | Stimulation of Erythrocyte Membrane Blebbing by Naproxen Sodium. | 2020 Jan | Naproxen sodium is a nonsteroidal anti-inflammatory drug (NSAID) having antipyretic and analgesic properties, mainly used for the treatment of rheumatoid arthritis and osteoarthritis. Eryptosis is an alternative term used for suicidal erythrocyte death. In the current study, eryptotic effect of naproxen sodium characterized by membrane blebbing was investigated in erythrocytes after 48 hours of treatment with different concentrations (1-25 µM). The experimental work related to investigation of eryptosis was done by cell size measurement and confirmation of calcium role in the induction of membrane blebbing. As a possible mechanism of eryptosis, oxidative stress induced by naproxen sodium was determined by catalase, glutathione peroxidase, and superoxide dismutase activities. Similarly, hemolytic effect of naproxen sodium was also determined by hemolysis measurement. Results of our study illustrated that the therapeutic doses (10-25 µM) of naproxen sodium induce oxidative stress, confirmed by significant decrease in superoxide dismutase, catalase, and glutathione peroxidase activities that lead to the triggering of cell death by eryptosis and hemolysis. | |
31863819 | The past, present and future perspectives of matrix metalloproteinase inhibitors. | 2020 Mar | Matrix metalloproteinases (MMPs) are a large family of enzymes that degrade the extracellular matrix (ECM). Under pathologic conditions, overexpression of MMPs or insufficient control by tissue inhibitors of MMPs (TIMPs) results in the dysregulation of tissue remodeling and causes a variety of diseases such as encephalomyelitis, rheumatoid arthritis, Alzheimer's disease and tumors. Therefore, the high affinity of MMPs for biomolecules renders them attractive targets for inhibition when homeostasis breaks down in the ECM. There are 4 generations of MMP inhibitors (MMPIs), ranging from small molecules or peptides to antibodies and protein-engineered inhibitors of metalloproteinase. Although a plethora of MMPIs has been synthesized, most of them have failed in clinical trials or are still in the laboratory stage of development. The present review summarizes the development of MMPIs, their associated problems and discusses future directions for the development of the future generations of MMPIs. | |
31831256 | The immunobiology of mTOR in autoimmunity. | 2020 Jun | The mechanistic target of rapamycin (mTOR) is a master regulator of the inflammatory response in immune and non-immune cells. In immune cells mTOR regulates metabolism to fuel cell fate decision, proliferation and effector functions. In non-immune cells, such as fibroblast, it controls inflammation-associated proliferation and migration/invasion, shapes the expression of cytokines and chemokines and promotes extracellular matrix remodeling and fibrosis. Hence, mTOR plays a critical role in chronic inflammation, where a continuous feedback between stromal cells and infiltrating immune cells result in tissue remodeling and organ damage. Activation of mTOR has been implicated in a number of chronic inflammatory diseases, especially rheumatic diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), sjögren syndrome (SS) and seronegative spondyloarthropathy (SpA). Here we review recent advances in our understanding of the mechanism of mTOR activation in inflammation, especially in rheumatic diseases. We further discuss recent findings regarding the beneficial and side effects of mTOR inhibition in rheumatic conditions. | |
30945961 | The contradictory inefficacy of methotrexate in hidradenitis suppurativa: a need to revise | 2020 Jun | The pathogenesis of hidradenitis suppurativa (HS) centers around Th17/Treg dysfunction illustrated by lesional elevation of IL-17A, IL-6, and other inflammatory mediators resulting in a chronic feed-forward inflammatory cascade. Similar inflammatory mechanisms have been identified in psoriasis and rheumatoid arthritis (RA) in which traditional immunosuppressants (including methotrexate) are routinely used with reasonable levels of disease control. Methotrexate's mechanism of action in these instances includes downregulation of the Th17 axis via alterations in dendritic cell and T-cell activity and maturation. Published data suggest methotrexate in an ineffective therapy in HS, which does not pair with our current understanding of the mechanisms of disease. The reasons behind this, including are discussed. Some HS patients may benefit from drugs such as methotrexate, and acknowledgment of the potential of disease heterogeneity will allow exploration of which factors may enable identification of such individuals. | |
32965257 | ; LIVER LESION IN CHILDREN WITH JUVENILE IDIOPATHIC ARTHRITIS WITH DIFFERENT DURATION OF M | 2020 Jul | The aim of the research was to determine liver lesion in patients with Oligoarticular and RF-negative Polyarticular forms of JIA by noninvasive methods depending on duration of Methotrexate treatment. The study included 42 patients with Rheumatoid factor (RF) negative oligo- and polyarticular joints forms of JIA from 3 to 18 years old. They were investigated by measurement of alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), haptoglobin, triglycerides, gamma glutamine transferase (GGT), apolipoprotein-A (Apo-A), a2-macroglobulin, cholesterine levels. The equation for calculating the FibroTest score regression coefficient had been done according U.S. patent 6.631.330. Student -Fisher Test, Mann - Whitney U-test were used for the statistical processing. In spite of MTX treatment progression of JIA was determined according assessment of joints functional class and radiological stage (p<0.05). Increased level of ALAT was prominent (40%) in children taken MTX for 1-5 years in comparison with other studied patients (p<0.05). 17 % of children who took MTX longer than 5 years had increased GGT content. Metabolic liver function was not changed because levels of Apo-A, haptoglobin, total bilirubin, cholesterine were within normal limits due to all stages of MTX taking. The increased level of a2-macroglobulin as a predictor of liver fibrosis was determined in all studying groups with the average frequency 36 % and it did not correspond to the duration of MTX treatment. According FibroTest score regression 14% of patients had liver fibrosis F1, which did not depend on duration of MTX treatment. According to our findings, patients using MTX for JIA management had joint damage progresses despite usage of MTX. Hepatic cytolysis is most frequently appeared within 15 years of MTX taking. Risk of liver fibrosis does not depend on duration of MTX treatment. | |
34327480 | GlycA measured by NMR spectroscopy is associated with disease activity and cardiovascular | 2020 Dec | GlycA is a biomarker of systemic inflammation, quantifying both the protein concentrations and glycosylation states of several acute phase proteins. GlycA has been shown to be associated with both subclinical atherosclerosis and with cardiovascular disease (CVD). GlycA levels are higher in acute and chronic inflammation. During ongoing systemic inflammatory processes, GlycA specific acute phase reactants and proteins undergo circulating concentration and glycosylation pattern changes, and these alterations are reflected in the GlycA NMR signal. Additionally, levels associate with ongoing disease severity in individuals with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and psoriasis thus capturing active inflammation. Furthermore, in these disease states, GlycA is associated with cardiovascular disease (CVD) independent of traditional risk factors including C-reactive protein (CRP). Finally, GlycA levels decrease with exercise, weight loss, and systemic anti-inflammatory agents. Therefore, GlycA appears to be a promising new composite biomarker of active systemic inflammation including assessing CVD risk in patients with inflammatory diseases. | |
33512928 | Infectious Rice Body Formation in a Patient with Anti-aminoacyl-t RNA Synthetase Syndrome: | 2020 Dec 10 | CASE: An adult woman with anti-aminoacyl-t RNA synthetase syndrome developed pain and swelling of both hands and her left forearm, initially diagnosed as seronegative rheumatoid arthritis. Surgical exploration revealed multiple "rice bodies," and the specimen grew Mycobacterium intracellurale. She subsequently received antibiotic therapy. CONCLUSION: In the diagnosis of rice body formation in musculoskeletal tissues, it is necessary to consider not only rheumatic diseases but also mycobacterial infection. | |
33585266 | The Role of Porphyromonas gingivalis Outer Membrane Vesicles in Periodontal Disease and Re | 2020 | Periodontal disease is a chronic infectious disease associated with a variety of bacteria, which can cause damage to the periodontal support structure and affect a variety of systemic system diseases such as cancer, cardiovascular disease, diabetes, rheumatoid arthritis, non-alcoholic fatty liver, and Alzheimer's disease. Porphyromonas gingivalis (P. gingivalis) is the most important pathogenic bacteria for periodontal disease. It can produce outer membrane vesicles (OMVs) and release them into the environment, playing an important role in its pathogenesis. This article focuses on P. gingivalis OMVs, reviews its production and regulation, virulence components, mode of action and related diseases, with a view to providing new ideas for the prevention and treatment of diseases related to P. gingivalis infections. |