NOVEL NANO THERAPEUTIC MATERIALS FOR THE EFFECTIVE TREATMENT OF RHEUMATOID ARTHRITIS-RECENT INSIGHTS

Recent advances in science and technology and greatly modified the way we stumble on, deal with and prevent special diseases in all components of human lifestyles. Rheumatoid arthritis (RA) is the most not unusual complex multifactorial joint related autoimmune, chronic, severe systemic inflammatory ailment with unknown etiology completed with increased cardiovascular risks. It is regularly associated with critical synovial joint inflammation, autoantibody production, cartilage/bone tissue destruction, cardiovascular, pulmonary, skeletal disorders and massive inflammatory infiltration which might in the end motive extreme disability, huge complications, premature mortality and decreased life quality. Pro-inflammatory cytokines like IL-1, IL-6, IL-8 and IL-10 were dependable for the induction of inflammation in RA patients. It has a global occurrence of around 1% with the incidence among women being 2-3 times extra in men. Preclinical RA, genetic variables, and environmental factors have all been linked to the disease's etiology. Because there is no known cure for RA, the primary goal of treatment is to achieve the shortest possible illness duration and, if possible, rehabilitation. Current clinical remedies of RA display numerous drawbacks which include excessive doses, common administration, speedy metabolism, bad absorption, low responsiveness, higher cost and serious side consequences. These obstacles have inspired extremely good growth of the studies and to enhance those obstacles, nanoparticles that are able to encapsulating and protecting tablets from degradation earlier than they reach the target site in vivo, might also function drug delivery structures. Bioavailability and therapeutic bioactivity can be improved, and limited emphasis on damaged joints can be allowed. The current study provides a platform for different lipid nanoparticle methods for RA therapy, using the newly developing field of lipid nanoparticles to improve a targeted theranostic device for RA treatment. This review aims to present the most recent major application of lipid nanoparticles as a biocompatible and biodegradable transport device for improving RA concentration on over free drugs by presenting tissue-specific concentrated on of ligand-controlled drug release by modulating nanoparticle composition. Additionally, we also discuss the pivotal demanding situations to be addressed, as well as destiny views. Therefore, it is feasible to claim that nanoparticles will, within the near future, play a critical role in advanced treatment and affected person-particular cures for human diseases which include RA.

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Tocilizumab: An Updated Review of Its Use in the Treatment of Rheumatoid Arthritis and Its Application for Other Immune-Mediated Diseases

Clinical Medicine Insights Therapeutics ◽

10.4137/cmt.s9282 ◽

2013 ◽

Vol 5 ◽

pp. CMT.S9282 ◽

Cited By ~ 5

Author(s):

Toshio Tanaka ◽

Atsushi Ogata ◽

Masashi Narazaki

Keyword(s):

Rheumatoid Arthritis ◽

Immune Responses ◽

T Cell Subsets ◽

Unknown Etiology ◽

Autoantibody Production ◽

Future Studies ◽

Effector T Cell ◽

Immune Mediated ◽

Cell Source ◽

Acute Phase Reactions

Interleukin-6 (IL-6), produced by a variety of cells, is a typical cytokine featuring redundancy and pleiotropic activity. IL-6 is promptly and transiently synthesized in response to infections or injuries, and participates in host defense by inducing immune responses, hematopoiesis, and acute-phase reactions. However, since its abnormal persistent production of mostly unknown etiology plays an important pathological role in the development of various immune-mediated diseases, a humanized anti-IL-6 receptor monoclonal antibody, tocilizumab, was developed and is now used as an innovative biologic for rheumatoid arthritis in more than 90 countries. Several factors strongly suggest that a IL-6 blockade strategy may have a broad application for the treatment of various immune-mediated diseases. These factors include favorable results of pilot or case studies with off-label use of tocilizumab, pathological analyses of the contribution of IL-6 to the development of immune-mediated diseases, and the potential capability of tocilizumab to both repair an imbalance of effector T cell subsets and to suppress pathologic autoantibody production. However, clinical trials to evaluate the efficacy and safety of tocilizumab for these diseases are essential. Furthermore, clarification of the cell source of IL-6 production and of the mechanisms through which dysregulated continuous IL-6 synthesis is induced constitutes an important issue for future studies into the pathogenesis of diseases.

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Bridging Insights From Lymph Node and Synovium Studies in Early Rheumatoid Arthritis

Frontiers in Medicine ◽

10.3389/fmed.2021.820232 ◽

2022 ◽

Vol 8 ◽

Author(s):

Aoife M. O'Byrne ◽

Tineke A. de Jong ◽

Lisa G. M. van Baarsen

Keyword(s):

Rheumatoid Arthritis ◽

Lymph Node ◽

Lymph Nodes ◽

Stromal Cells ◽

Clinical Manifestations ◽

Bone Destruction ◽

Peripheral Tolerance ◽

Unknown Etiology ◽

Synovial Joint ◽

Innovative Drug

Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown etiology characterized by inflammation of the peripheral synovial joints leading to pannus formation and bone destruction. Rheumatoid Factor (RF) and anti-citrullinated protein antibodies (ACPA) are present years before clinical manifestations and are indicative of a break in tolerance that precedes chronic inflammation. The majority of studies investigating disease pathogenesis focus on the synovial joint as target site of inflammation while few studies explore the initial break in peripheral tolerance which occurs within secondary lymphoid organs such as lymph nodes. If explored during the earliest phases of RA, lymph node research may provide innovative drug targets for disease modulation or prevention. RA research largely centers on the role and origin of lymphocytes, such as pro-inflammatory T cells and macrophages that infiltrate the joint, as well as growing efforts to determine the role of stromal cells within the synovium. It is therefore important to explore these cell types also within the lymph node as a number of mouse studies suggest a prominent immunomodulatory role for lymph node stromal cells. Synovium and proximal peripheral lymph nodes should be investigated in conjunction with one another to gain understanding of the immunological processes driving RA progression from systemic autoimmunity toward synovial inflammation. This perspective seeks to provide an overview of current literature concerning the immunological changes present within lymph nodes and synovium during early RA. It will also propose areas that warrant further exploration with the aim to uncover novel targets to prevent disease progression.

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Solution of a mathematical model for the treatment of rheumatoid arthritis

Communications in Applied and Industrial Mathematics ◽

10.2478/caim-2019-0003 ◽

2019 ◽

Vol 10 (2) ◽

pp. 12-24 ◽

Cited By ~ 1

Author(s):

L. Matteucci ◽

M. C. Nucci

Keyword(s):

Rheumatoid Arthritis ◽

Mathematical Model ◽

Tumor Necrosis ◽

Unknown Etiology ◽

Synovial Cells ◽

Synovial Joint ◽

Soluble Receptors ◽

Surface Receptors ◽

Necrosis Factor ◽

Pro Inflammatory Cytokines

Abstract Rheumatoid arthritis is an autoimmune disease of unknown etiology that manifests as a persistent inflammatory synovitis and eventually destroys the joints. The immune system recognizes synovial cells as not self and consequently causes lymphocyte and antibody proliferation that is promoted by the pro-inflammatory cytokines, the most significant being tumor necrosis factor TNF-α. In the treatment of rheumatoid arthritis either monoclonal antibodies or soluble receptors are used to neutralize the TNF-α bioactivity, such as sTNFR2, Etanercept and Infliximab. In [M. Jit et al. Rheumatology 2005;44:323-331] a mathematical model that represents the TNF-α dynamics in the inflamed synovial joint within which locally produced TNF-α can bind to cell-surface receptors was proposed. It consists of four coupled ordinary differential equations, that were integrated numerically assuming a range of estimates of the key parameters. In this paper we complement the previous work by determining the general solution of those equations for specific conditions on the parameters. Then we characterize the behavior of TNF-α in the presence of different inhibitors and also evaluate the inhibitors effectiveness in the treatment of rheumatoid arthritis.

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Evaluation of Serum Calprotectin Level and Disease Activity in Patients with Rheumatoid Arthritis

Current Rheumatology Reviews ◽

10.2174/1573397115666190122113221 ◽

2019 ◽

Vol 15 (4) ◽

pp. 316-320

Author(s):

Mir Amir Aghdashi ◽

Seyedmostafa Seyedmardani ◽

Sholeh Ghasemi ◽

Zohre Khodamoradi

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Inflammatory Arthritis ◽

Unknown Etiology ◽

Tender Joint Count ◽

Serum Samples ◽

Tender Joint ◽

Cross Sectional ◽

Calprotectin Level ◽

Remission Phase

Background: Rheumatoid Arthritis (RA) is the most common type of chronic inflammatory arthritis with unknown etiology marked by a symmetric, peripheral polyarthritis. Calprotectin also can be used as a biomarker of disease activity in inflammatory arthritis and other autoimmune diseases. Objective: In this study, we evaluated the association between serum calprotectin level and severity of RA activity. Methods: A cross-sectional study was conducted on 44 RA patients with disease flare-up. Serum samples were obtained from all patients to measure calprotectin, ESR, CRP prior to starting the treatment and after treatment period in the remission phase. Based on Disease Activity Score 28 (DAS28), disease activity was calculated. Results: Of 44 RA patients, 9(20.5%) were male and 35(79.5%) were female. The mean age of our cases was 53±1.6 years. Seventeen (38.6%) patients had moderate DAS28 and 27(61.4%) had high DAS28. The average level of calprotectin in the flare-up phase was 347.12±203.60 ng/ml and 188.04±23.58 ng/ml in the remission phase. We did not find any significant association between calprotectin and tender joint count (TJC; P=0.22), swollen joint count (SJC; P=0.87), and general health (GH; P=0.59), whereas significant associations were found between the calprotectin level and ESR (p=0.001) and DAS28 (p=0.02). The average calprotectin level in moderate DAS28 (275.21±217.96 ng/ml) was significantly lower than that in high DAS28 (392.4±183.88 ng/ml) (p=0.05). Conclusion: We showed that the serum level of calprotectin can be a useful and reliable biomarker in RA activity and its severity. It also can predict treatment response.

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Why Does SARS-CoV-2 Infection Induce Autoantibody Production?

Pathogens ◽

10.3390/pathogens10030380 ◽

2021 ◽

Vol 10 (3) ◽

pp. 380

Author(s):

Ales Macela ◽

Klara Kubelkova

Keyword(s):

Immune Response ◽

Immune System ◽

Host Cell ◽

Critical Role ◽

Cell Interaction ◽

Immune Recognition ◽

Autoantibody Production ◽

Host Cell Interaction ◽

Primary Virus

SARS-CoV-2 infection induces the production of autoantibodies, which is significantly associated with complications during hospitalization and a more severe prognosis in COVID-19 patients. Such a response of the patient’s immune system may reflect (1) the dysregulation of the immune response or (2) it may be an attempt to regulate itself in situations where the non-infectious self poses a greater threat than the infectious non-self. Of significance may be the primary virus-host cell interaction where the surface-bound ACE2 ectoenzyme plays a critical role. Here, we present a brief analysis of recent findings concerning the immune recognition of SARS-CoV-2, which, we believe, favors the second possibility as the underlying reason for the production of autoantibodies during COVID-19.

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Oligonucleotide Therapies in the Treatment of Arthritis: A Narrative Review

Biomedicines ◽

10.3390/biomedicines9080902 ◽

2021 ◽

Vol 9 (8) ◽

pp. 902

Author(s):

Susanne N. Wijesinghe ◽

Mark A. Lindsay ◽

Simon W. Jones

Keyword(s):

Rheumatoid Arthritis ◽

Articular Cartilage ◽

Joint Diseases ◽

Synovial Joint ◽

Pharmacological Treatments ◽

In Vivo Models ◽

Inflammatory Joint Diseases ◽

Joint Pathology ◽

Cellular Pathways

Osteoarthritis (OA) and rheumatoid arthritis (RA) are two of the most common chronic inflammatory joint diseases, for which there remains a great clinical need to develop safer and more efficacious pharmacological treatments. The pathology of both OA and RA involves multiple tissues within the joint, including the synovial joint lining and the bone, as well as the articular cartilage in OA. In this review, we discuss the potential for the development of oligonucleotide therapies for these disorders by examining the evidence that oligonucleotides can modulate the key cellular pathways that drive the pathology of the inflammatory diseased joint pathology, as well as evidence in preclinical in vivo models that oligonucleotides can modify disease progression.

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AB0048 ENZYMATIC PATTERN OF CIRCULATING PRO- AND ANTIOXIDANT ENZYMES IN RHEUMATOID ARTHRITIS PATIENTS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1754 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1056.2-1057

Author(s):

S. Bedina ◽

E. Mozgovaya ◽

A. Trofimenko ◽

S. Spitsina ◽

M. Mamus

Keyword(s):

Rheumatoid Arthritis ◽

Antioxidant Enzymes ◽

Disease Activity ◽

Neutrophil Extracellular Traps ◽

Unknown Etiology ◽

Antioxidant Enzyme Activities ◽

Reference Ranges ◽

Sod Activity ◽

Low Disease Activity ◽

Extracellular Traps

Background:Rheumatoid arthritis (RA) is an autoimmune rheumatic disease of unknown etiology characterized by chronic erosive arthritis and systemic organ involvement resulting in early disability and shorter life expectancy. Neutrophils are suggested to play a substantial role in the induction and promotion of autoimmune inflammation in RA. This ability can be based on newly discovered feature of neutrophils to release neutrophil extracellular traps (NETs) during specific type cell death called NETosis. Hyperproduction of reactive oxygen species (ROS) is one of the factors promoting NETs production. With this background, the study of pro- and antioxidant enzymatic activities in RA patients can be of great interest.Objectives:To assess plasma activities of essential prooxidant and antioxidant enzymes in RA patients.Methods:The research was carried out in agreement with the WMA Declaration of Helsinki principles. 71 RA patients (46 women and 25 men) were enrolled in the study. The diagnosis was verified using ACR/EULAR criteria (2010). RA activity was measured using the Disease Activity Score of 28 joints (DAS28). 30 healthy persons comprise control group. Plasma xanthine oxidase (XO; ЕС 1.17.3.2), xanthine dehydrogenase (XDH; ЕС 1.17.1.4) and superoxide dismutase (SOD; ЕС 1.15.1.1) activities were measured using spectrophotometric technique. XO and XDG activities were expressed as nmol/ml/min, SOD activity – as units of action. Statistical analysis was performed using Statistica 6.0 software package. Differences were considered significant when p<0.05. Reference ranges were calculated as means ±2SD.Results:Mean age of patients was 43.2±3.6 years, mean RA duration was 11.9±2.6 years. 24 (33.8%) RA patients had low disease activity, and 6 (8.5%) patients had high one. Extra-articular manifestations were found in 30 (42.2%) patients. 30% of them had cardiovascular involvement, 23.3% – pulmonary lesions, and 23.3% had renal involvement. Reference ranges for XO, XDG, and SOD activities were 2.28-5.12 nmol/min/ml, 3,96-7,24 nmol/min/ml, and 3,13-6,58 units, respectively. We examined activities of these enzymes in circulation of RA patients with different patterns of clinical manifestations as well as relationship between RA activity and XO, XDG, and SOD activities. RA patients had increased both mean XO and mean SOD activities (p<0.001 for both enzymes). XO activity reached its highest values at maximum disease activity and overt extra-articular involvements, while SOD activity did it in moderate and high disease activities as well as in patients with joint manifestations. XDG activity was increased in low disease activity (р<0.001) and solely joint lesions (р=0.011), while moderate or high disease activities (р=0.008) and extra-articular involvements (р=0.025) were characterized by decreased activity of this enzyme.Conclusion:We have revealed substantial multidirectional changes of plasma XO and XDG activities in RA. Plasma enzymatic pattern in RA patients is characterized by activation of both oxidant and antioxidant metabolic pathways. Activities of XO and SOD were positively correlated with RA activity, while XDG activity was negative correlated with RA activity. The differences between selective articular RA type and RA form with extraarticular manifestations were also revealed. Changes in oxidant and antioxidant enzyme activities can be connected with anticitrulline autoimmunity in RA via production of citrulline-rich neutrophil extracellular traps, thus enhancing rheumatoid autoimmunity.Disclosure of Interests:None declared

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MULTIPLE HEMANGIOMAS IN AN INFANT WITH CARDIAC HYPERTROPHY

PEDIATRICS ◽

10.1542/peds.35.1.27 ◽

1965 ◽

Vol 35 (1) ◽

pp. 27-35

Author(s):

Amiel G. Cooper ◽

Robert P. Bolande

Keyword(s):

Heart Failure ◽

Cardiac Hypertrophy ◽

Unknown Etiology ◽

Developmental Abnormality ◽

Tissue Destruction ◽

Negro Female ◽

Arteriovenous Shunts ◽

Infantile Hemangioendothelioma ◽

Cardiac Enlargement

A case of multiple benign hemangiomas in a 10-week-old Negro female is presented. At autopsy, numerous cutaneous and visceral sites of involvement were found. The hemangiomas are believed to arise from a multicentric developmental abnormality but appear capable of limited independent growth and tissue destruction. Postmortem angiograms demonstrate the existence of numerous arteriovenous shunts, which are believed responsible for the marked cardiac enlargement and early congestive heart failure in this case, as well as in previously reported cases of infantile hemangioendothelioma of the liver. Visceral hemangiomatosis should be considered as a possible extra-cardiac cause of infantile cardiac hypertrophy or failure of unknown etiology, especially in the infant with cutaneous hemangiomas. Angiographic techniques may be of help in the diagnosis and determination of extent of visceral hemangiomas.

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Markers of the early stage of rheumatoid arthritis

Diagnostyka Laboratoryjna ◽

10.5604/01.3001.0008.2523 ◽

2016 ◽

Vol 51 (4) ◽

pp. 305-314

Author(s):

Beata Polińska ◽

Joanna Matowicka-Karna ◽

Halina Kemona

Keyword(s):

Rheumatoid Arthritis ◽

Human Population ◽

Early Stage ◽

Clinical Signs ◽

High Sensitivity ◽

Unknown Etiology ◽

Serological Tests ◽

Citrullinated Peptide ◽

Peptide Antibodies

Rheumatoid arthritis (RA) is a chronic, autoimmune connective tissue disease of unknown etiology. RA affects about 1% of the human population, women suffer three times more often than men, with the peak incidence between the age of 40 to 50. The up-to-date criteria from 2010 for the diagnosis of RA include: occurrence and duration of clinical signs, indicators of inflammation and serological tests. Neopterin, a protein released by macrophages, is a sensitive indicator of inflammation and the severity of RA. Regarding the serological tests, anti-cyclic citrullinated peptide antibodies represent a well-known marker with the specificity for RA of about 98%. The antibodies may be present in the serum of patients even a few years before the first clinical signs of the disease, heralding erosive changes in the joints and more severe course of RA. The literature also contains reports about autoantibodies anti-CarP and anti-Sa/ anti-MCV, which may occur in people with pain and swelling of joints and precede full-blown development of RA as well as reflect disease activity. Serological diagnosis of RA may be supported by some genetic tests based on PCR for detecting mutations e.g. C1858T in the PNPN22 gene. In turn, the quantitative analysis of different classes of miRNAs seems justified in order to better classify patients showing symptoms of RA. Further studies are needed that take into account the role of different markers in the development of RA, and confirm the high sensitivity and specificity of these markers in the diagnosis of the disease.

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Self Management Behaviors in Rheumatoid Arthritis Patients and Associated Factors in Tehran 2013

Global Journal of Health Science ◽

10.5539/gjhs.v8n3p156 ◽

2015 ◽

Vol 8 (3) ◽

pp. 156 ◽

Cited By ~ 5

Author(s):

Mosharafeh Chaleshgar Kordasiabi ◽

Maassoumeh Akhlaghi ◽

Mohammad Hossein Baghianimoghadam ◽

Mohammad Ali Morowatisharifabad ◽

Mohsen Askarishahi ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Health Status ◽

Associated Factors ◽

Demographic Variables ◽

Self Management ◽

Measurement Scale ◽

Unknown Etiology ◽

Physician Global Assessment ◽

Impact Measurement ◽

Management Behaviors

INTRODUCTION: Rheumatoid Arthritis (RA) is a systemic, autoimmune and inflammatory disease with an unknown etiology that is associated with progressive joint degeneration, limitation of physical activity and disability. The aim of the study was to evaluate self-management behaviors and their associated factors in RA patients.MATERIAL & METHOD: This cross-sectional study was performed in 2013 on185 patients in Iran. Data were selected through convenient sampling. The collected data included demographic variables, disease related variables, Arthritis Impact Measurement Scale 2 (AIMS-2SF), and Self-Management Behaviors (SMB). Data were analyzed by SPSS17 using Spearman correlation and logistic regression test.RESULT: In this study drug management, regular follow-up, and food supplement were used as the most frequently applied SMB and aquatic exercise, diet, massage therapy, and relaxation were the least common SMBs. Age, education, health status, occupation, marital status, sex, DAS28 (Disease Activity Score 28 joints), and PGA (Physician Global Assessment) were significantly related with SMB.CONCLUSION: The result of the study highlight the influence of demographic variables, health status, and disease related data on SMB. Thus, more studies are required to find factors influencing SMB in order to improve SMB.

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