Rheumatoid Joint Inflammation Research Articles

Formulation and evaluation of dosage form of fast dissolving oral film of Rofecoxib

Rofecoxib is utilized for the treatment of osteoarthritis, rheumatoid joint inflammation, intense torment in grown-ups, and essential dysmenorrhea, just as intense therapy of headache assaults with or without emanations. Rofecoxib is strong. This compound has a place with the stilbenes. These are natural mixes containing a 1,2-diphenylethylene moiety. Stilbenes (C6-C2-C6 ) are acquired from the normal phenylpropene (C6-C3) skeleton building block. The presentation of at least one hydroxyl gathering to a phenyl ring leads to stilbenoids. Rofecoxib has a half-existence of 17 hours and its mean oral bioavailability at restoratively suggested dosages of 125,25,and 50 mg is roughly 93%. The proteins that rofecoxib target incorporate elastin and prostaglandin G/H synthase Cytochrome P4501A2, Cytochrome P4503A4, Cytochrome P4502C9, Cytochrome P4502C8, and Prostaglandin G/H synthase1 are known to processor of Rofecoxib. Rofecoxib oral thin films were prepared from the evaluation studies RCX2 with 98.14% drug release is considered as the optimized formulation.

Ammodaucus Leucotrichus Seed Extract as a Potential Therapy in Animal Models of Rheumatoid Arthritis Induced by Complete Freund Adjuvant and Chicken Cartilage Collagen.

This study assessed the efficacy of an Ammodaucus leucotrichus seed extract to treat rheumatoid arthritis in rat models of this disease. Rheumatoid arthritis was induced in rats using two methods: immunization with 100 µL of Complete Freund Adjuvant (CFA) and immunization with 100 µL of a 3mg/ml solution of type II collagen (CII) from chicken cartilage. The therapeutic potential of the extract was assessed at different doses (150, 300, and 600mg/kg/day for 21 days in the CII-induced arthritis model and for 14 days in the CFA-induced arthritis model) and compared with methotrexate (MTX; 0.2mg/kg for the same periods), a commonly used drug for rheumatoid arthritis treatment in humans. In both models (CII-induced arthritis and CFA-induced arthritis), walking distance, step length, intra-step distance and footprint area were improved following treatment with the A. leucotrichus seed extract (all concentrations) and MTX compared with untreated animals. Both treatments increased the serum concentration of glutathione and reduced that of complement C3, malondialdehyde and myeloperoxidase. Radiographic data and histological analysis indicated that cartilage destruction was reduced already with the lowest dose of the extract (100mg/kg/dose) in both models. These results show the substantial antiarthritic potential of the A. leucotrichus seed extract, even at the lowest dose, suggesting that it may be a promising alternative therapy for rheumatoid arthritis and joint inflammation. They also emphasize its efficacy at various doses, providing impetus for more research on this extract as a potential therapeutic agent for arthritis.

Exosomes as Rheumatoid Arthritis Diagnostic Biomarkers and Therapeutic Agents.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disorder that causes systemic inflammation, autoimmunity, and joint abnormalities that result in permanent disability. Exosomes are nanosized extracellular particles found in mammals (40-100 nm). They are a transporter of lipids, proteins, and genetic material involved in mammalian cell-cell signaling, biological processes, and cell signaling. Exosomes have been identified as playing a role in rheumatoid arthritis-related joint inflammation (RA). Uniquely functioning extracellular vesicles (EVs) are responsible for the transport of autoantigens and mediators between distant cells. In addition, paracrine factors, such as exosomes, modulate the immunomodulatory function of mesenchymal stem cells (MSCs). In addition to transporting genetic information, exosomes convey miRNAs between cells and have been studied as drug delivery vehicles. In animal models, it has been observed that MSCs secrete EVs with immunomodulatory properties, and promising results have been observed in this area. By understanding the diversity of exosomal contents and their corresponding targets, it may be possible to diagnose autoimmune diseases. Exosomes can be employed as diagnostic biomarkers for immunological disorders. We here discuss the most recent findings regarding the diagnostic, prognostic, and therapeutic potential of these nanoparticles in rheumatoid arthritis and provide an overview of the evidence pertaining to the biology of exosomes in RA.

Treatment of Periprosthetic Femoral Fractures after Total Hip Replacement. Literature Review

Peri-prosthetic femoral fractures are a serious problematic complication after primary and revision hip replacements. These fractures are associated with adverse outcomes, heavy mortality and often incomplete functional recovery.The aim of this review article is to study the frequency and factors that contribute to the occurrence of peri-prosthetic fractures of the proximal femur (PFPF) after total hip arthroplasty (THA). In order to achieve this goal, we conduct a comprehensive search in medical literature in the MEDLINE and EMBASE databases in order to familiarize with publications related to PPFF, their frequency and risk factors. The study showed that the frequency of PPFF after primary THA is generally lower than after revision, both for intraoperative and postoperative cases of PPFF. The frequency of intraoperative fractures varies from 0.1% to 27.8%, and postoperative fractures from 0.07% to 18%. Bone loss, rheumatoid joint inflammation, surgical technique of open treatment, the use of cementless stem and revision hip arthroplasty are predisposing factors for intraoperative PPFFs. In the case of postoperative PPFF, significant risk factors are old age, female gender, post-traumatic osteoarthritis, bone loss and rheumatoid joint inflammation, deformities of the proximal femal bone, previous operations on the affected hip joint, the type of implant (especially cementless stems and molds).Key words: endoprosthesis replacement, periprosthetic fracture, femur, proximal femur, hip joint, osteosynthesis.

An Efficient CNN for Hand X-Ray Classification of Rheumatoid Arthritis.

Hand Radiography (RA) is one of the prime tests for checking the progress of rheumatoid joint inflammation in human bone joints. Recognizing the specific phase of RA is a difficult assignment, as human abilities regularly curb the techniques for it. Convolutional neural network (CNN) is the center for hand recognition for recognizing complex examples. The human cerebrum capacities work in a high-level way, so CNN has been planned depending on organic neural-related organizations in humans for imitating its unpredictable capacities. This article accordingly presents the convolutional neural network (CNN) which has the ability to naturally gain proficiency with the qualities and anticipate the class of hand radiographs from an expansive informational collection. The reproduction of the CNN halfway layers, which depict the elements of the organization, is likewise appeared. For arrangement of the model, a dataset of 290 radiography images is utilized. The result indicates that hand X-rays are rated with an accuracy of 94.46% by the proposed methodology. Our experiments show that the network sensitivity is observed to be 0.95 and the specificity is observed to be 0.82.

Hydroxychloroquine And Dexamethasone Are Both Possible For Treatment Of Covid-19

The antimalarial operators chloroquine and hydroxychloroquine have been utilized generally for the treatment of rheumatoid joint inflammation and fundamental lupus erythematosus. These mixes lead to progress of clinical and research facility parameters, however their moderate beginning of activity recognizes them from glucocorticoids and nonsteroidal mitigating operators. Chloroquine and hydroxychloroquine increment pH inside intracellular vacuoles and adjust procedures, for example, protein corruption by acidic hydrolases in the lysosome, get together of macromolecules in the endosomes, and posttranslation change of proteins in the Golgi mechanical assembly. It is suggested that the antirheumatic properties of these mixes results from their obstruction with "antigen preparing" in macrophages and other antigen-introducing cells. Acidic cytoplasmic compartments are required for the antigenic protein to be processed and for the peptides to collect with the alpha and beta chains of MHC class II proteins. Thus, antimalarials reduce the arrangement of peptide-MHC protein edifices required to animate CD4+ T cells and result in down-guideline of the safe reaction against autoantigenic peptides. Since this system varies from other antirheumatic drugs, antimalarials are appropriate to supplement these different mixes in blend medicate treatment[1].

Controlled release alginate-chitosan microspheres of tolmetin sodium prepared by internal gelation technique and characterized by response surface modeling

Tolmetin sodium (TS) is a powerful non-steroidal mitigating drug for the treatment of rheumatoid joint inflammation, osteoarthritis, and adolescent rheumatoid joint pain. In addition to its gastrointestinal (GIT) problems, TS has a short biological half-life (1 hr). In a trial to overcome these side effects and control the rate of (TS) release, chitosan coated alginate microspheres are recommended. A Box-Behnken experimental design was employed to produce controlled release microspheres of TS in the sodium alginate and chitosan copolymers (Alg-Ch) by emulsification internal gelation methodology. The effect of critical formulation variables namely, drug to polymer ratio (D:P ratio), speed of rotation and span 80% on drug encapsulation efficiency (% EE), drug release at the end of 2 hours (Rel2) and drug release at the end of 8 hours (Rel8) were analyzed using response surface modeling. The parameters were assessed using the F test and mathematical models containing only the significant terms were generated for each parameter using multiple linear regression analysis. The produced microspheres were spherical in shape with extensive pores at D:P ratio 1:1 and small pores at a drug to polymer ratio (D:P ratio) 1:3. Differential scanning calorimetry (DSC) affirmed the steady character of TS in microspheres and revealed their crystalline form. All formulation variables examined exerted a significant influence on the drug release, whereas the speed emerged as a lone factor significantly influencing % EE. Increasing the D: P ratio decreases the release of the drug after two and 8 hours. The increase in speed results in an increase in drug release after two and eight hours. The drug release from the microspheres followed zero order kinetics. TS Alg-Ch microspheres exhibited a significant anti-inflammatory effect on incited rat paw edema after eight hours. These results revealed that the internal gelation technique is a promising method to control TS release and eradicate GIT side effects using Alg-Ch copolymers.

THE EPIDEMIOLOGICAL CHARACTERISTIC OF DISEASES OF MUSCULOSKELETAL SYSTEM

The purpose of the study. To analyze prevalence of diseases of musculoskeletal system in the Arkhangelsk region. The methods. The data of official statistics was used to implement analysis of general morbidity of main diseases of musculoskeletal system of adult population the Arkhangelsk region during 2010-2015 as compared with corresponding morbidity in the North-Western Federal and the Russian Federation in general. The results. In the Arkhangelsk region, among general morbidity percentage of diseases of musculoskeletal system made up to 4.2% (7th rank). The increasing of common morbidity of diseases of musculoskeletal system in adult population was marked in the Arkhangelsk region up to 14% and in the Russian Federation up to 7%. Since 2010, in the Arkhangelsk region the study established increasing of common morbidity rheumatoid joint inflammation up to 22%, spondylopathy up to 65%, osteoarthrosis up to 32.4%, osteoporosis up to 46% and systemic diseases of connective tissue up to 11.5% surpassing average Russian indices. At that, number of cases of reactive arthritis decreased up to 17.2% Conclusions. In the Arkhangelsk region, the register of diseases of musculoskeletal system on the basis of region rheumatological center is to be developed to implement an objective assessment in the existent situation.

From Molecular Mechanism to the Etiology of Sjogren Syndrome.

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.

Comparative gene expression profiles in healthy and autoimmune mice

Comparative gene expression profiles in healthy and autoimmune mice

Comparative gene expression profiles in healthy and autoimmune mice

Comparative gene expression profiles in healthy and autoimmune mice

Transplantation and Alternatives to Treat Autoimmune Diseases.

Transplantation is considered as one of the methods for the treatment of autoimmune diseases. There are different sorts of transplantation which improved the situation for the cure of different kinds of autoimmune diseases. Cord blood transplantation is favored over other transplant techniques. The propelled treatments incorporate interferon administrative elements and mesenchymal stromal cells for the management of immune system issue particularly in the treatment of rheumatoid joint inflammation. According to the studies conducted, it was proven that cord blood/UC mesenchymal cells along with DMARDs, without consistent organization expanded the level of administrative regulatory T-cells of the peripheral blood which might be a protected and huge technique for the treatment of patients experiencing rheumatoid joint inflammation. This review article focusses on different organ transplantation and alternative methods to treat autoimmune condition like rheumatoid arthritis. Using 3D printing and artificial intelligence are some of the recent trends that may be used for the management of autoimmune diseases.

ω-3 polyunsaturated fatty acids use for optimization of children inflammatory joints diseases treatment

The use of additional treatment methods in inflammatory joints disease therapy is very important. But the main principles of diet therapy for patients with rheumatoid joint inflammation and reactive arthritis and possibility of focused impact on disease activity by means of alimentary factors have not still been formed out. The aim of the investigation was to study the effect of diet therapy including ω-3 polyunsaturated fatty acids (PUFAs) on joint syndrome evidence and on bone turnover markers of children with inflammatory joint diseases. With parents' agreement children aged 5-16 hospitalized with inflammatory joint diseases (53 with juvenile rheumatoid arthritis and 35 with reactive arthritis) were enrolled in this research. According to the treatment mode 2 subgroups were separated in each group: the first subgroup underwent backbone therapy, the second - backbone therapy along with ω-3 PUFAs (cod liver oil 1000 mg containing 115 mg of docosahexaenoic and 23 mg of eicosapentaenoic acids). Children aged 3-5 years received 1 capsule 2 times a day, over 6 years old - 1 capsule 3 times per day with meals for 3 months. Disease activity, joint syndrome evidence (counting of joint pain, Ritchie index, number of inflammatory joints, morning stiffness duration) and biochemical values of connective tissue metabolism were estimated while being introduced into research and at the end of treatment. More apparent improvement of joint syndrome indexes at the end of supervision was diagnosed in the groups undergoing backbone therapy along with ω-3 PUFAs. Statistically significant (p<0.05) reduce of morning stiffness time by 3 fold vs 2 fold in children treated with basic therapy, reduce of joint index by 2.9-5.7 fold vs 2.0-3.8 fold, the number of inflammatory joints by 4.5-5.8 fold vs 2.0-2.3 fold, blood serum level of hydroxyl proline and antibodies to rumalon were observed in main groups of patients. Disease activity index DAS 4 decreased in the group undergoing backbone therapy by 0.44 (p<0.05) and in the group undergoing modified therapy - by 1.20 (p<0.05). No adverse effects of PUFAs have been observed. It was concluded that ω-3 PUFAs increased the action of basic therapy favoring advances in inflammatory process activity control, provided decrease of non-steroidal antiinflammatory drugs (NSAID) intake and proved to be an important supplement in diet therapy of children inflammatory joints diseases.

Abnormal PTPN11 enhancer methylation promotes rheumatoid arthritis fibroblast-like synoviocyte aggressiveness and joint inflammation.

The PTPN11 gene, encoding the tyrosine phosphatase SHP-2, is overexpressed in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) compared with osteoarthritis (OA) FLS and promotes RA FLS invasiveness. Here, we explored the molecular basis for PTPN11 overexpression in RA FLS and the role of SHP-2 in RA pathogenesis. Using computational methods, we identified a putative enhancer in PTPN11 intron 1, which contained a glucocorticoid receptor- binding (GR-binding) motif. This region displayed enhancer function in RA FLS and contained 2 hypermethylation sites in RA compared with OA FLS. RA FLS stimulation with the glucocorticoid dexamethasone induced GR binding to the enhancer and PTPN11 expression. Glucocorticoid responsiveness of PTPN11 was significantly higher in RA FLS than OA FLS and required the differentially methylated CpGs for full enhancer function. SHP-2 expression was enriched in the RA synovial lining, and heterozygous Ptpn11 deletion in radioresistant or innate immune cells attenuated K/BxN serum transfer arthritis in mice. Treatment with SHP-2 inhibitor 11a-1 reduced RA FLS migration and responsiveness to TNF and IL-1β stimulation and reduced arthritis severity in mice. Our findings demonstrate how abnormal epigenetic regulation of a pathogenic gene determines FLS behavior and demonstrate that targeting SHP-2 or the SHP-2 pathway could be a therapeutic strategy for RA.

IKRAI: Intelligent Knee Rheumatoid Arthritis Identification

Rheumatoid joint inflammation is characterized as a perpetual incendiary issue which influences the joints by hurting body tissues Therefore, there is an urgent need for an effective intelligent identification system of knee Rheumatoid arthritis especially in its early stages. This paper is to develop a new intelligent system for the identification of Rheumatoid arthritis of the knee utilizing image processing techniques and neural classifier. The system involves two principle stages. The first one is the image processing stage in which the images are processed using some techniques such as RGB to grayscale conversion, rescaling, median filtering, background extracting, images subtracting, segmentation using canny edge detection, and features extraction using pattern averaging. The extracted features are used then as inputs for the neural network which classifies the X-ray knee images as normal or abnormal (arthritic) based on a backpropagation learning algorithm which involves training of the network on 400 X-ray normal and abnormal knee images. The system was tested on 400 xray images and the network shows good performance during that phase, resulting in a good identification rate 95.5 %.

Crystal structure of an arthritogenic anticollagen immune complex

In rheumatoid arthritis, joint inflammation and cartilage destruction are mediated by autoantibodies directed to various self antigens. Type II collagen (CII)-specific antibodies are likely to play a role in this process and have been shown to induce experimental arthritis in susceptible animals. The purpose of this study was to reveal how arthritogenic autoantibodies recognize native CII in its triple-helical conformation. Site-directed mutagenesis and crystallographic studies were performed to reveal crucial contact points between the CII antibody and the triple-helical CII peptide. The crystal structure of a pathogenic autoantibody bound to a major triple-helical epitope present on CII was determined, allowing a first and detailed description of the interactions within an arthritogenic complex that is frequently occurring in both mice and humans with autoimmune arthritis. The crystal structure emphasizes the role of arginine residues located in a commonly recognized motif on CII and reveals that germline-encoded elements are involved in the interaction with the epitope. The crystal structure of an arthritogenic antibody binding a triple-helical epitope on CII indicates a crucial role of germline-encoded and arginine residues as the target structures.

Role of regulatory T cells in rheumatoid arthritis: facts and hypothesis.

Regulatory T cells (Treg) are a CD4+ lymphocyte subset involved in self-tolerance and autoimmunity prevention. There is evidence for a phenotypic and/or functional impairment of this cell subset during the natural history of several chronic autoimmune/inflammatory diseases, including rheumatoid arthritis (RA). Although the intracellular transcription factor FoxP3 is thought to be the master regulator of Treg cell function, a number of other molecules expressed on the cell surface have been proposed for the identification of Treg cells. This is important in order to favour their possible selective isolation and in the development of new therapeutic strategies. In the present paper, available data on phenotypic and functional characterization of Treg cells in both peripheral blood and synovial fluid from RA patients are reviewed and their possible pathogenic role in triggering and perpetuating rheumatoid joint inflammation is discussed.

Doppler ultrasonography in rheumatoid arthritis therapy monitoring

Within the last decade, musculoskeletal ultrasonography is playing an increasingly important role in the evaluation and monitoring of patients with chronic inflammatory arthritis. High-resolution musculoskeletal ultrasonography allows direct assessment of intra-articular and periarticular inflammatory activity and structural damage in inflammatory arthritis. There have been a growing number of studies on the criterion and construct validity of ultrasonography with color Doppler or power Doppler techniques for evaluating inflammatory activity in rheumatoid arthritis. Ultrasonography has been proven to be more sensitive and reproducible than clinical evaluation in assessing rheumatoid joint inflammation. Recent studies have demonstrated the responsiveness of grayscale and Doppler parameters in the monitoring of response to therapy in patients with rheumatoid arthritis.

Tumor Necrosis Factor Promotes Runx2 Degradation through Up-regulation of Smurf1 and Smurf2 in Osteoblasts

Tumor necrosis factor (TNF) plays an important role in the pathogenesis of inflammatory bone loss through stimulation of osteoclastic bone resorption and inhibition of osteoblastic bone formation. Compared with the well established role of TNF in osteoclastogenesis, mechanisms by which TNF inhibits osteoblast function have not been fully determined. Runx2 is an osteoblast-specific transcription factor whose steady-state protein levels are regulated by proteasomal degradation, mediated by the E3 ubiquitin ligases, Smurf1 and Smurf2. We hypothesized that TNF inhibits osteoblast function through Smurf-mediated Runx2 degradation. We treated C2C12 and 2T3 osteoblast precursor cell lines and primary osteoblasts with TNF and found that TNF, but not interleukin-1, significantly increased Smurf1 and Smurf2 expression. TNF increased the degradation of endogenous or transfected Runx2 protein, which was blocked by treating cells with a proteasomal inhibitor or by infecting cells with small interfering (si)RNA against Smurf1 or Smurf2. TNF inhibited the expression of bone morphogenetic protein and transforming growth factor-beta signaling reporter constructs, and the inhibition of each was blocked by Smurf1 siRNA and Smurf2 siRNA, respectively. Overexpression of Smurf1 and/or Smurf2 siRNAs prevented the inhibitory effect of TNF on Runx2 reporter. Consistent with these in vitro findings, bones from TNF transgenic mice or TNF-injected wild type mice had increased Smurf1 and decreased Runx2 protein levels. We propose that one of the mechanisms by which TNF inhibits bone formation in inflammatory bone disorders is by promoting Runx2 proteasomal degradation through up-regulation of Smurf1 and Smurf2 expression.

Ultrasonography in rheumatoid arthritis: a very promising method still needing more validation.

Through recent technological advances, ultrasonography allows high-resolution visualization of inflammatory and destructive changes in the small superficial joints of hands and feet, and ultrasonography is increasingly used by rheumatologists for assessment of rheumatoid arthritis patients. It is, therefore, highly relevant to consider the validity of ultrasonographic measures of rheumatoid joint inflammation and damage. Organized by type of validity, data on ultrasonography in rheumatoid arthritis are reviewed. Encouraging reports of high agreement of ultrasonographic findings between observers, with MRI and, in knee and hip joints, histopathologic assessments were recently published. New quantitative and semiquantitative evaluation methods have been suggested, and the first systematic follow-up studies suggest an ability of ultrasonography to monitor joint inflammation and damage. However, a number of essential issues are still largely unexplored, including interscanner variability, sensitivity to change, prognostic value, and value in the diagnosis of rheumatoid arthritis. Suggested areas of priority in research and development of ultrasonography in rheumatoid arthritis are outlined. Ultrasonography is a very promising method in the assessment of rheumatoid arthritis joints, but still needs more validation before it can take up its expected role on a scientific basis as an important tool for diagnosis, monitoring, and prognostication of patients with rheumatoid arthritis and suspected rheumatoid arthritis.