Inflammatory Joint Conditions Research Articles

Antioxidant potential and xanthine oxidase inhibition of flavonol glycosides from Phyllanthus emblica L. leaves

Context: Hyperuricemia is the cause of gout in the inflammatory joint condition. The xanthine oxidase enzyme is a therapeutic target for gout treatment because it plays a role in the generation of uric acid. Allopurinol is used to treat gout. It prevents the xanthine oxidase enzyme from producing as much uric acid. When selecting a medication, one must consider the various adverse effects of allopurinol. Phyllanthus emblica plants are among the medicinal plants that can be used as an alternative treatment for gout. Aims: To evaluate isolated compounds from the Phyllanthus emblica as antihyperuricemia candidates. Methods: The isolated compounds were characterized using High-Performance Liquid Chromatography Analysis and Thin Layer Chromatography-Densitometry. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) and cupric ion (CUPRAC) antioxidant capacity procedures were used to develop the antioxidant activity index. The ability to inhibit xanthine oxidase was determined using a spectrophotometer. Results: Compound 1 was indicated as rutin having antioxidant capacity with an antioxidant activity index (AAI) DPPH value of 7.89 ± 0.03 and AAI CUPRAC value of 15.83 ± 0.04 stronger than compound 2 (quercitrin) with an AAI DPPH value of 3.72 ± 0.01 and AAI CUPRAC 3.24 ± 0.03. The IC50 for quercitrin's inhibition of xanthine oxidase is 23.85 ± 2.04, which was higher than rutin’s IC50 value of 32.77 ± 4.49 µg/mL. Conclusions: Flavonol glycosides present in the ethanol extract of Phyllanthus emblica leaves gave potent xanthine oxidase inhibitory activity stronger than the extract. Quercitrin gave stronger xanthine oxidase inhibitory activity, but this compound has weaker antioxidant capacity compared to rutin.

Treatment of Reactive Arthritis with Biological Agents.

Reactive arthritis (ReA) is an inflammatory joint condition triggered by an infection elsewhere in the body, and this review aims to provide a comprehensive synthesis of recent studies including case reports and case series to determine whether biologics are a treatment option. Recent studies indicate that biological agents, including anti-TNF agents (infliximab, adalimumab, etanercept), anti-IL17 (secukinumab), and anti-IL6 (tocilizumab), are effective in treating refractory cases of ReA. Evidence suggests these agents are associated with significant clinical improvement. Notably, the data reveal that these biologics are generally well-tolerated, with a low incidence of major adverse events, which supports their safety profile for use in ReA. Biological agents, including anti-TNF, anti-IL17, and anti-IL6 therapies, can be safely and effectively used in the treatment of ReA when conventional therapies fail. It further emphasizes the need for a well-designed controlled trial to provide scientific basis for better informed clinical decisions in cases not responding to conventional treatment.

Phytoconstituents-Based Nanotherapeutic Approach for the Effective Management of Joint Inflammatory Condition: Arthritis.

Arthritis, a prevalent inflammatory joint condition, presents challenges for effective therapeutic interventions, with conventional treatments often limited in efficacy and associated with adverse effects. Recent years have witnessed a growing interest in exploring natural compounds, particularly phytoconstituents, renowned for their anti-inflammatory and joint-protective properties. This review aims to illuminate the potential of employing nanotherapeutic approaches with phytoconstituents for enhanced arthritis management. The integration of nanotechnology with phytoconstituents emerges as a promising strategy, addressing limitations in traditional arthritis treatments. Nanocarriers like liposomes and nanoparticles provide a platform for targeted drug delivery, improving the bioavailability of phytoconstituents. Furthermore, the combined effects of phytoconstituents can be leveraged to target multiple pathways in arthritis pathogenesis, including inflammation, oxidative stress, and cartilage degradation. Key phytoconstituents, such as curcumin, resveratrol, and quercetin, exhibit anti-inflammatory and immunomodulatory properties. Nevertheless, their therapeutic potential is often impeded by challenges like poor solubility, stability, and bioavailability. Nanocarriers offer solutions by enhancing pharmacokinetics and enabling sustained release, thereby boosting overall therapeutic efficacy. The review explores the mechanisms underlying the anti-arthritic effects of phytoconstituents and their nanoformulations, including the modulation of pro-inflammatory cytokines, inhibition of matrix metalloproteinases, and reduction of oxidative stress. In summary, the integration of phytoconstituents with nanotechnology presents a promising avenue for developing targeted and effective arthritis therapies. This comprehensive review serves as a valuable resource for researchers, clinicians, and pharmaceutical developers seeking innovative approaches to address the intricate challenges associated with arthritis management.

Dexamethasone Palmitate Encapsulated in Palmitic Acid Modified Human Serum Albumin Nanoparticles for the Treatment of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory joint condition characterized by symmetric, erosive synovitis leading to cartilage erosion and significant disability. Macrophages, pivotal in disease progression, release pro-inflammatory factors upon activation. We developed a nanoparticle delivery system (DXP-PSA NPs), based on palmitic acid modified human serum albumin (PSA), to deliver dexamethasone palmitate (DXP) directly to sites of inflammation, enhancing treatment effectiveness and minimizing possible side effects. The system actively targets scavenger receptor-A on activated macrophages, achieving selective accumulation at inflamed joints. In vitro effect and preliminary targeting abilities were investigated on LPS-activated RAW264.7 cells. The in vivo efficacy and safety were evaluated and compared side to side with commercially available lipid emulsion Limethason® in an advanced adjuvant-induced arthritis rat model. DXP-PSA NPs offer a novel approach to RA treatment and presents promising prospects for clinical translation.

Undenatured type II collagen protects against collagen-induced arthritis by restoring gut-joint homeostasis and immunity

Oral administration of harmless antigens can induce suppression of reactive immune responses, a process that capitalises on the ability of the gastrointestinal tract to tolerate exposure to food and commensal microbiome without triggering inflammatory responses. Repeating exposure to type II collagen induces oral tolerance and inhibits induction of arthritis, a chronic inflammatory joint condition. Although some mechanisms underlying oral tolerance are described, how dysregulation of gut immune networks impacts on inflammation of distant tissues like the joints is unclear. We used undenatured type II collagen in a prophylactic regime -7.33 mg/kg three times/week- to describe the mechanisms associated with protective oral immune-therapy (OIT) in gut and joint during experimental Collagen-Induced Arthritis (CIA). OIT reduced disease incidence to 50%, with reduced expression of IL-17 and IL-22 in the joints of asymptomatic mice. Moreover, whilst the gut tissue of arthritic mice shows substantial damage and activation of tissue-specific immune networks, oral administration of undenatured type II collagen protects against gut pathology in all mice, symptomatic and asymptomatic, rewiring IL-17/IL-22 networks. Furthermore, gut fucosylation and microbiome composition were also modulated. These results corroborate the relevance of the gut-joint axis in arthritis, showing novel regulatory mechanisms linked to therapeutic OIT in joint disease.

TNF-α in the serum and synovial fluid of patients with rheumatoid arthritis: correlation with sonographic parameters: a cross-sectional study

BackgroundRheumatoid arthritis (RA) is a chronic, inflammatory joint condition characterized by overproduction of pro-inflammatory cytokines. We aimed to assess TNF-α levels in both serum and synovial fluid in effusive knees in RA patients and find out if synovial fluid levels correlate with ultrasound (US)-detected local knee inflammatory and/or destructive changes in these patients.ResultsThis study included 40 patients (20 with RA, 10 with systemic lupus erythematosus (SLE), and 10 with osteoarthritis (OA)) who had knee effusion (unilateral or bilateral) upon clinical examination. The mean age of RA patients was 48.4 years; most of them were females (80%), with a median (min–max) duration of knee effusion of 2 (1.5–3) months. Serum TNF-α was significantly higher in RA vs. non-RA and in OA cases (p = 0.052, 0.022, respectively), while in the synovial fluid, the difference was not statistically significant (3.73 ± 0.72 vs. 3.48 ± 0.58 U/ml, p = 0.252). Serum TNF-α at a cut point of > 3.24 U/ml can significantly discriminate RA from OA with 65% sensitivity and 90% specificity (AUC = 0.725, P = 0.018). There was no statistically significant correlation between synovial TNF-α and US parameters of the knee, either in RA or non-RA patients.ConclusionsRA, OA, and SLE effusive joints share the presence of local articular joint inflammation, while systemic inflammation is more discriminative for RA patients regarding the level of TNF-α. The lack of correlation of TNF-α with ultrasonographic findings reflects the multifactorial complexity of these autoimmune diseases.

Enhanced intra-articular therapy for rheumatoid arthritis using click-crosslinked hyaluronic acid hydrogels loaded with toll-like receptor antagonizing peptides

Rheumatoid arthritis (RA) is a chronic inflammatory disorder that results in the deterioration of joint cartilage and bone. Toll-like receptor 4 (TLR4) has been pinpointed as a key factor in RA-related inflammation. While Toll-like receptor antagonizing peptide 2 (TAP2) holds potential as an anti-inflammatory agent, its in vivo degradation rate hinders its efficacy. We engineered depots of TAP2 encapsulated in click-crosslinked hyaluronic acid (TAP2+Cx-HA) for intra-articular administration, aiming to enhance the effectiveness of TAP2 as an anti-inflammatory agent within the joint cavity. Our data demonstrated that FI-TAP2+Cx-HA achieves a longer retention time in the joint cavity compared to FI-TAP2 alone. Mechanistically, we found that TAP2 interacts with TLR4 on the cell membranes of inflammatory cells, thereby inhibiting the nuclear translocation of NF-κB and maintaining it in an inactive cytoplasmic state. In a rat model of RA, the TAP2+Cx-HA formulation effectively downregulated the inflammatory cytokines TNF-α and IL-6, while upregulating the anti-inflammatory cytokine IL-10 and the therapeutic protein 14-3-3ζ. This led to a more rapid restoration of cartilage thickness, increased deposition of glycosaminoglycans, and new bone tissue formation in the regenerated cartilage, in comparison to a single TAP2 treatment after a six-week period. Our results suggest that TAP2+Cx-HA could serve as a potent intra-articular treatment for RA, offering both symptomatic relief and promoting cartilage regeneration. This innovative delivery system holds significant promise for improving the management of RA and other inflammatory joint conditions. Statement of significanceIn this study, we developed a therapy by creating toll-like receptor 4 (TLR4)-antagonizing peptide (TAP2)-loaded click-crosslinked hyaluronic acid (TAP2+Cx-HA) depots for direct intra-articular injection. Our study demonstrates that FI-TAP2+Cx-HA exhibits a more than threefold longer lifetime in the joint cavity compared to FI-TAP2 alone. Furthermore, we found that TAP2 binds to TLR4 and masks the nuclear localization signals of NF-κB, leading to its sequestration in an inactive state in the cytoplasm. In a rat model of RA, TAP2+Cx-HA effectively suppresses inflammatory molecules, specifically TNF–α and IL-6, while upregulating the anti-inflammatory cytokine IL-10 and the therapeutic protein 14-3-3ζ. This resulted in faster regeneration of cartilage thickness, increased glycosaminoglycan deposits in the regenerated cartilage, and a twofold increase in new bone tissue formation compared to a single TAP2 treatment.

From Inflammation to Resolution: Specialized Pro-resolving Mediators in Posttraumatic Osteoarthritis.

To provide a comprehensive overview of the inflammatory response following anterior cruciate ligament (ACL) injury and to highlight the relationship between specialized pro-resolving mediators (SPMs) and inflammatory joint conditions, emphasizing the therapeutic potential of modulating the post-injury resolution of inflammation to prevent posttraumatic osteoarthritis (PTOA). The inflammatory response triggered after joint injuries such as ACL tear plays a critical role in posttraumatic osteoarthritis development. Inflammation is a necessary process for tissue healing, but unresolved or overactivated inflammation can lead to chronic diseases. SPMs, a family of lipid molecules derived from essential fatty acids, have emerged as active players in the resolution of inflammation and tissue repair. While their role in other inflammatory conditions has been studied, their relationship with PTOA remains underexplored. Proinflammatory mediators contribute to cartilage degradation and PTOA pathogenesis, while anti-inflammatory and pro-resolving mediators may have chondroprotective effects. Therapies aimed at suppressing inflammation in PTOA have limitations, as inflammation is crucial for tissue healing. SPMs offer a pro-resolving response without causing immunosuppression, making them a promising therapeutic option. The known onset date of PTOA makes it amenable to early interventions, and activating pro-resolving pathways may provide new possibilities for preventing PTOA progression. Harnessing the pro-resolving potential of SPMs may hold promise for preventing PTOA and restoring tissue homeostasis and function after joint injuries.

C9 immunostaining as a tissue biomarker for periprosthetic joint infection diagnosis.

Culture-negative periprosthetic joint infections (PJI) are often false diagnosed as aseptic implant failure leading to unnecessary revision surgeries due to repeated infections. A marker to increase the security of e PJI diagnosis is therefore of great importance. The aim of this study was to test C9 immunostaining of periprosthetic tissue as a novel tissue-biomarker for a more reliable identification of PJI, as well as potential cross-reactivity. We included 98 patients in this study undergoing septic or aseptic revision surgeries. Standard microbiological diagnosis was performed in all cases for classification of patients. Serum parameters including C-reactive protein (CRP) serum levels and white blood cell (WBC) count were included, and the periprosthetic tissue was immunostained for C9 presence. The amount of C9 tissue staining was evaluated in septic versus aseptic tissue and the amount of C9 staining was correlated with the different pathogens causing the infection. To exclude cross-reactions between C9 immunostaining and other inflammatory joint conditions, we included tissue samples of a separate cohort with rheumatoid arthritis, wear particles and chondrocalcinosis. The microbiological diagnosis detected PJI in 58 patients; the remaining 40 patients were classified as aseptic. Serum CRP values were significantly increased in the PJI cohort. Serum WBC was not different between septic and aseptic cases. We found a significant increase in C9 immunostaining in the PJI periprosthetic tissue. To test the predictive value of C9 as biomarker for PJI we performed a ROC analyses. According to the Youden's criteria C9 is a very good biomarker for PJI detection with a sensitivity of 89% and a specificity of 75% and an AUC of 0.84. We did not observe a correlation of C9 staining with the pathogen causing the PJI. However, we observed a cross reactivity with the inflammatory joint disease like rheumatoid arthritis and different metal wear types. In addition, we did not observe a cross reactivity with chondrocalcinosis. Our study identifies C9 as a potential tissue-biomarker for the identification of PJI using immunohistological staining of tissue biopsies. The use of C9 staining could help to reduce the number of false negative diagnoses of PJI.

ID:16534 Prescription Opioids and Steroid Misuse Masking Underlying Infection of Spinal Hardware

The use of opioids for benign rheumatological disorders has been limited by concerns about adverse events and potential misuse. There has been an increase in use of opioids seen over the years for nonmalignant rheumatologic diseases. Opioids are currently approved as complementary therapy in inflammatory joint and rheumatological conditions. Severe adverse events, including abnormal drug-seeking behavior, although relatively rare, have been documented in a number of cases. This specific case report highlights opioid misuse and is an example of a patient becoming obtunded from a constellation of adverse events because of opioid misuse and overdose.

Treating ‘Septic’ With Enhanced Antibiotics and ‘Arthritis’ by Mitigation of Excessive Inflammation

Bacterial infection within the synovial joint, commonly known as septic arthritis, remains a clinical challenge as it presents two concurrent therapeutic goals of reducing bacterial burden and preservation of articular cartilage from destructive host inflammation. We hypothesized that mitigation of MRSA-induced inflammatory signaling could diminish destruction of articular cartilage in the setting of septic arthritis when used in conjunction with antibiotics. Herein, we provide evidence which supports a new therapeutic notion that concurrent antimicrobial therapy to address the ‘septic’ component of the disease with inflammation mitigation to manage the destructive ‘arthritis’ component. We established a murine model to mimic septic knee arthritis, as well as a variety of other inflammatory joint conditions. This murine septic arthritis model, in conjunction with in vitro and ex-vivo models, was utilized to characterize the inflammatory profile seen in active septic arthritis, as well as post-antibiotic treatment, via transcriptomic and histologic studies. Finally, we provided the clinical rationale for a novel therapeutic strategy combining enhanced antibiotic treatment with rifampin and adjuvant immunomodulation to inhibit post-infectious, excess chondrolysis and osteolysis. We identified that septic arthritis secondary to MRSA infection in our murine model led to increased articular cartilage damage compared to various types of inflammatory arthritis. The activation of the pERK1/2 signaling pathway, which is implicated with the mounting of an immune response and generation of inflammation, was increased in intracellular MRSA-infected synovial tissue and persisted despite antibiotic treatment. Trametinib, an inhibitor of ERK signaling through suppression of MEK1/2, alleviated the inflammation produced by the addition of intra-articular, heat-killed MRSA. Further, when combined with vancomycin and rifampin, mitigation of inflammation by pERK1/2 targeting improved outcomes for MRSA septic arthritis by conferring chondroprotection to articular cartilage and diminishing inflammatory osteolysis within bone. Our results support a new therapeutic notion that cell/biofilm-penetrating antibiotics alongside adjuvant mitigation of excessive intra-articular inflammation accomplish distinct therapeutic goals: reduction of bacterial burden and preservation of articular cartilage integrity.

Physiotherapy in Psoriatic Arthritis

Psoriatic arthritis is an inflammatory joint condition. It is a chronic condition that includes pinkish-red plaque formation on the skin, leading to its changes. The purpose of this article is to review the literature on the role of physiotherapy in psoriatic arthritis. We performed a critical systematic review on the role of physiotherapy in psoriatic arthritis. The article selection process was systematic. The inclusion criteria of the review were (1) physiotherapy practice with psoriatic arthritis; (2) physical activity in psoriatic arthritis; and (3) chronic psoriatic arthritis and co-morbidities. The current review included 11 studies that fulfill these inclusion criteria. Evidence demonstrates that there is potential benefit of physiotherapy treatment and rehabilitation in psoriatic arthritis. Patients with psoriatic arthritis have impaired function and quality of life. It may involve co-morbidities such as obesity, musculoskeletal disease, cardiovascular disease, or fibromyalgia, which can be improved by non-pharmacological approach, such as aerobic exercise and cardiorespiratory exercise. Low level laser therapy increases not only self-repair activities of living tissues but also cell membrane permeability and metabolism, and education of patients is also necessary to improve clinical conditions. Hydrotherapy, resistance exercise, cryotherapy, and interferential therapy are also beneficial in psoriatic arthritis.

Long Non-coding RNAs in Rheumatology.

The last decade has seen an enormous increase in long non-coding RNA (lncRNA) research within rheumatology. LncRNAs are arbitrarily classed as non-protein encoding RNA transcripts that exceed 200 nucleotides in length. These transcripts have tissue and cell specific patterns of expression and are implicated in a variety of biological processes. Unsurprisingly, numerous lncRNAs are dysregulated in rheumatoid conditions, correlating with disease activity and cited as potential biomarkers and targets for therapeutic intervention. In this chapter, following an introduction into each condition, we discuss the lncRNAs involved in rheumatoid arthritis, osteoarthritis and systemic lupus erythematosus. These inflammatory joint conditions share several inflammatory signalling pathways and therefore not surprisingly many commonly dysregulated lncRNAs are shared across these conditions. In the interest of translational research only those lncRNAs which are strongly conserved have been addressed. The lncRNAs discussed here have diverse roles in regulating inflammation, proliferation, migration, invasion and apoptosis. Understanding the molecular basis of lncRNA function in rheumatology will be crucial in fully determining the inflammatory mechanisms that drive these conditions.

Novel strategy of cartilage repairing via application of P. atlantica with stem cells and collagen.

Osteoarthritis (OA) is an inflammatory joint condition, still lacking effective treatments. Some factors consider as the main causes of OA, including biochemical, mechanical, and genetic factors. The growth of studies confirmed that modern medicine in combination with folk medicine regarding the arrival of reliable, efficient, and safe therapeutic products against OA. In the present study, the effects of various single and combinatorial treatments of knee articular cartilage, including stem cells, collagen, and P. atlantica hydroalcoholic leaves extract were investigated in a rat-induced OA model. On week 12 after OA confirmation, histopathology and radiography assessments were evaluated and the serum and synovial fluid levels of TAC, TNF-α, PEG2, MPO, MMP3, MMP13, and MDA were also measured. Combination therapy of OA-induced rats with hydroalcoholic extract of P. atlantic leaves, stem cells, and collagen considerably increased the efficacy of treatment as evidenced by increasing the TAC and lowering TNF-α, MPO, MMP3, and MMP13 compared to control group and even groups received single therapy. This is in agreement with a high amount of total phenolic compounds and antioxidant capacities of the hydroalcoholic extract of P. atlantic leaves. It is concluded that multifunctional agents targeting the pathophysiology of OA has exhibited significant therapeutic effects against OA.

Measures of cardiovascular function suggest autonomic nervous system dysregulation in the male lewis rat after surgical induction of joint injury

Purpose: A recent review entitled “The brain-joint axis in osteoarthritis: nerves, circadian clocks and beyond” by Prof. Francis Berenbaum provides a framework for the contribution of the autonomic nervous system in osteoarthritis (OA). The autonomic nervous system is comprised of two branches, the parasympathetic (PNS) and sympathetic nervous systems (SNS) with reciprocal effects on involuntary actions throughout the body, such as heart rate and blood pressure. In homeostasis, the PNS and SNS balance these body functions, and serve as important regulators of immune system homeostasis and allostasis. An imbalance between the PNS and SNS functions is known as autonomic dysregulation. Because the two branches have reciprocal effects on heart rate, heart rate parameters may be used as an indicator of autonomic dysregulation. Autonomic balance is dysregulated in chronic inflammatory diseases, such as rheumatoid arthritis, hypertension, and diabetes, among others. To be clear, the etiologies of each of these diseases are different, but the commonality is inflammation that fails to resolve. Similarly, OA presents with chronic inflammation, but OA-related inflammation is low-grade and local, often failing to alter circulating levels of cytokines. Despite the emerging evidence for autonomic nervous system dysregulation in inflammatory joint conditions, changes have not yet been characterized in a rodent model of OA. Methods: Radiotelemetry probes were implanted into the descending aorta to collect blood pressure measurements from which the heart rate was derived from the peaks in pulse pressure. Heart rate was evaluated as an indirect assessment of vagal nerve function, a key part of the autonomic nervous system. Measurements were collected for 5 minutes each hour for 24 hours. Recordings occurred at baseline and every other week for 8 weeks after induction of OA via medial collateral ligament transection plus medial meniscus transection (MCLT+MMT; n=13) or MCLT alone (n=5), with skin incision (n=9) used as a control. Because stress is known to exaggerate autonomic responses, characteristics of heart rate responses to novel environment stress were also assessed (n=4-8/group). A 5-HT3a agonist, 1-phenylbiguanide, with reported vagal activation properties was used to indirectly assess vagal nerve function. Heart rate and blood pressure responses to the 5-HT3a agonist were recorded in anesthetized rats (n=5-8/group). Heart rate responses to mechanical stimuli applied at the knee via a weight and pulley system were used to indirectly assess cardiac vagal responses. Results: Longitudinal heart rate measurements revealed decrease in mean heart rate over time (Fig. 1a; p=0.037, week main effect) in all groups. Additionally, MCLT and MCLT+MMT had a tendency for a more rapid decline in heart rate over the 8 week study period (p=0.082, surgery*week interaction). Introduction to novel environment produced a typical increase in heart rate in all groups, confirming a stressful stimulus. This response was significantly different between groups (Figure 1b; p=0.045, surgery main effect), with a trend of attenuation in MCLT (p=0.067) and MCLT + MMT (p=0.09) groups. Mechanical stimuli at the knee resulted in a sudden drop in heart rate and blood pressure, with no differences seen between groups (Fig. 2a & 2b). However, the 5-HT3a agonist produced a dose-dependent drop in heart rate in all groups (p<0.001; dose main effect) with a larger drop in heart rate in both MCLT (p=0.014) and MCLT+MMT (p=0.010) animals at the highest dose compared to control (Fig. 2c & 2d).Figure 2Heart rate and blood pressure responses to mechanical stimulation at the knee (a,b) and systemic administration of a 5-HT3a agonist (c,d). Sudden drops in heart rate and blood pressure were observed with mechanical stimulation at the knee, with no differences seen between groups. Responses to the 5-HT3a agonist were dose-dependent with MCLT and MCLT+MMT groups having a larger drop in heart rate at the highest dose (bar indicates p<0.05).View Large Image Figure ViewerDownload Hi-res image Download (PPT) Conclusions: Measurement of cardiovascular responses to novelty stress and pharmacological stimulation of 5-HT3a receptors, which are reportedly able to induce acute cardiac vagal responses, demonstrate for the first time a shift in ANS function in rodent knee injury models of OA. Our data suggest a sensitization of cardiac vagal activation to acute stress and 5-HT3a agonist in OA groups, which was also supported by the tendency for a more prominent chronic reduction in heart rate in OA groups. Lastly, acute mechanical stimulation of the knee produced an immediate reduction in heart rate, suggesting a direct neural joint-brain connection that may modulate autonomic responses in OA. Although we did not observe a difference in these responses between control and OA groups, further studies should delineate this using direct measurements of vagal nerve activity in response to mechanical stimulus of the joint in OA.

Ultrasonographic Findings in Symptomatic Knee Osteoarthritis in Relation to Pain

Background: Osteoarthritis (OA) is the most common form of arthritis and one of the leading causes of disability. OA affects around 250 million people worldwide. Musculoskeletal ultrasound (MSUS) has become important and primary diagnostic tool in visualization of inflammatory and degenerative conditions of joints, ligaments, cartilage and muscles. Aims: To study the cross-sectional association between ultrasonographic findings and pain in knee osteoarthritis. Patients and methods: Fifty patients fulfilling the clinical criteria for knee OA had undergone US examination of the most symptomatic knee and pain assessment; studies were performed at Benha teaching hospital.Statistical analysis:The statistical analysis and presentation of data was conducted using the mean, slandered deviation, t-test and Pearson’s correlation by SPSS version 20.Results:After data acquisition and statistical analysis no association between US findings and the level of knee pain was found.Conclusion:In this cohort, no association between US features and the degree of knee pain was found. Despite the attractiveness of US (easy accessible, inexpensive and no radiation involvement), it remains uncertain which part of pain in knee OA is explained by pathology in soft tissue structures and whether US of the knee is the imaging tool of choice to visualize this pathology. Key message:No association between US features and the degree of knee pain, was found.

Impact of chitosan membrane culture on the expression of pro- and anti-inflammatory cytokines in mesenchymal stem cells.

Osteoarthritis (OA) is a chronic inflammatory joint condition caused by various inflammatory cytokines. The pro-inflammatory cytokines controlling OA include interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6 and IL-18. The anti-inflammatory cytokines include IL-4, IL-10, IL-13, leukemia inhibitory factor (LIF), glycoprotein 130 (IL6ST), TNF-α-stimulated gene 6 and transforming growth factor (TGF)-β1. Mesenchymal stem cells (MSCs) serve an anti-inflammatory role in the treatment of OA by secreting various cytokines. Previous studies demonstrated that the anti-inflammatory ability of MSCs decreased rapidly in a traditional plate culture. Maintaining the anti-inflammatory properties of MSCs in vitro remains challenging. Therefore, it is necessary to develop a more stable and efficient method to culture MSCs in vitro. Chitosan is a deacetylated derivative of chitin and is the second most abundant natural polysaccharide worldwide. The present study demonstrated that that MSCs cultured on chitosan membranes (CM) spontaneously formed multicellular spheroids. Compared with the control group without CM, the formation of multicellular spheres in the CM enhanced the anti-inflammatory properties of MSCs. Expression levels of pro- and anti-inflammatory genes mRNA and their proteins in MSCs were detected by reverse transcription-quantitative PCR, western blot analysis and immunofluorescence assay. Protein and mRNA expression levels of pro-inflammatory cytokines IL-1β, TNF-α, IL-6 and IL-18 were significantly decreased in CM-cultured MSCs compared with the control group (P<0.05). Furthermore, mRNA and protein expression levels of anti-inflammatory cytokines TGF-β1 in CM-cultured MSCs were significantly increased compared with the control group (P<0.01). These results indicated that the formation of multicellular spheroids by CM-cultured MSCs aided in maintaining anti-inflammatory effects.

Smartphone Apps Targeting Physical Activity in People With Rheumatoid Arthritis: Systematic Quality Appraisal and Content Analysis.

BackgroundRheumatoid arthritis (RA) is a disabling, inflammatory joint condition affecting 0.5%-1% of the global population. Physical activity (PA) and exercise are recommended for people with RA, but uptake and adherence tend to be low. Smartphone apps could assist people with RA to achieve PA recommendations. However, it is not known whether high quality, evidence-informed PA apps that include behavior change techniques (BCTs) previously identified as effective for PA adherence are available for people with RA.ObjectiveThis study aims to systematically identify apps that include goals to facilitate PA for adults with RA and assess app quality and content for the inclusion of relevant BCTs against recommendations for cardiorespiratory, resistance, flexibility, and neuromotor PA and exercise.MethodsA systematic search of the Apple App Store and Google Play Store in the United Kingdom was conducted to identify English language apps that promote PA for adults with RA. Two researchers independently assessed app quality (mobile app rating scale [MARS]; range 0-5) and content (BCT Taxonomy version 1, World Health Organization, the American College of Sports Medicine, and the European League against Rheumatism recommendations for PA). The completeness of reporting of PA prescription was evaluated using a modified version of the Consensus on Exercise Reporting Template (CERT; range 0-14).ResultsA total of 14,047 apps were identified. Following deduplication, 2737 apps were screened for eligibility; 6 apps were downloaded (2 on the Apple App Store and 4 on the Google Play Store), yielding 4 unique apps. App quality varied (MARS score 2.25-4.17). Only 1 app was congruent with all aspects of the PA recommendations. All apps completely or partially recommended flexibility and resistance exercises, 3 apps completely or partially advised some form of neuromotor exercise, but only 2 offered full or partial guidance on cardiorespiratory exercise. Completeness of exercise reporting was mixed (CERT scores 7-14 points) and 3-7 BCTs were identified. Two BCTs were common to all apps (information about health consequences and instruction on how to perform behavior). Higher quality apps included a greater number of BCTs and were more closely aligned to PA guidance. No published trials evaluating the effect of the included apps were identified.ConclusionsThis review identifies 4 PA apps of mixed quality and content for use by people with RA. Higher quality apps were more closely aligned to PA guidance and included a greater number of BCTs. One high-quality app (Rheumatoid Arthritis Information Support and Education) included 7 BCTs and was fully aligned with PA and exercise guidance. The effect of apps on PA adherence should be established before implementation.

THERAPEUTIC OPPORTUNITIES OF CARBOXYTHERAPY IN ORTHOPEDICS

Diseases of the musculoskeletal system are quite common diseases. Moreover, the use of pharmacotherapy may not always be effective, which is associated with a large number of side effects of modern non-steroidal anti-inflammatory drugs (NSAIDs). The way out of the situation can be the use of carboxytherapy (CO2 therapy), which has a complex of pharmacological effects: analgesic, anti-inflammatory, antispasmodic, antihypoxic and antioxidant.These CO2 effects are used to eliminate the symptom complex associated with pain, inflammation, ischemia, hypoxia, and joint stiffness. The use of carboxytherapy in orthopedics is primarily aimed at eliminating pain in various diseases of the spine, joints, muscles in the back, neck, thighs, knees and other organs. The main target of the action of carboxytherapy in diseases of the musculoskeletal system are Zakharyin – Geda zones, trigger points, myofibralgia zones and acupuncture points.When CO2 affects these zones and points, vasodilation, muscle relaxation and increased tissue oxygenation reflexively occur, which leads to a decrease in inflammation, pain and other functional disorders in the joints and muscles. Due to the polypathopathogenetic pharmacodynamics of CO2, carboxytherapy is often used for post-traumatic and inflammatory conditions of joints, arthrosis, and other acute and chronic joint pathologies of various etiologies.In addition, with combined pharmacotherapy of these diseases, carboxytherapy reduces the duration of NSAIDs and other drugs, reduces their dosage, which reduces the risk of side effects and increases the effectiveness of CO2 therapy.

EP12 Bilateral lipoma arborescens as a presenting feature of ankylosing spondylitis

Abstract Background Lipoma arborescens (LA) is a rare, slow growing lesion defined as a villous lipomatous proliferation of the synovial membrane with replacement of the synovial tissue by mature fatty cells. It usually involves the knee and can be associated with degenerative joint disease, trauma, diabetes mellitus and very occasionally with inflammatory arthritis. Diagnosis is made using MRI which shows a synovial mass that is isointense relative to fat and joint effusion. Histologically there is diffuse replacement of the subsynovial layer with mature adipocytes and infiltration of mononuclear cells. Treatment is with synovectomy and treating any underlying condition. Methods We present the first case bilateral knee LA as a presenting feature of ankylosing spondylitis. Results A 29-year-old Caucasian male presented to a knee orthopaedic surgeon with a two-year history of atraumatic bilateral knee swelling. He had a ten-year history of intermittent knee pain and stiffness which was unresponsive to non-steroidal anti-inflammatory drugs (NSAIDs) and physiotherapy. Examination revealed large bilateral knee effusions with restriction of movement. Plain radiographs of his knee joints showed minor osteophytic lipping laterally on his right knee. He had an MRI of both his knees which showed bilateral joint effusions and bilateral LA. He was referred to the rheumatology team for consideration of underlying inflammatory arthritis. Further questioning revealed no history of uveitis, dactylitis, psoriasis, inflammatory bowel disease but lower back pain which was long standing. Blood tests showed rheumatoid factor, anti-CCP, anti-DsDNA, ENA were negative with ANA positive in a homogenous pattern. C-reactive protein (CRP) was only slightly raised at 5.6mg/L. Knee aspirate showed mixed inflammatory cells. Radiographs of his spine showed no syndesmophytes but sacroiliac joints showed established bilateral sacroiliitis. A diagnosis of ankylosing spondylitis with secondary LA was made. He was commenced on sulfasalazine to treat his peripheral inflammatory arthritis along with continuation of NSAID. He remained symptomatic with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of 8 and Spinal pain VAS of 9. As he fulfilled NICE guidelines for biologic use in AS, he was commenced on adalimumab 40 mg fortnightly injections and had a good response to treatment with improvement in BASDAI, pain VAS, knee swelling and normalisation of CRP. Conclusion There have been reports of LA in association with inflammatory joint disease. This is the first case of bilateral LA as a presenting feature of ankylosing spondylitis. It has been demonstrated that LA plays a role in joint inflammation and damage through tumour necrosis factor alpha (TNFα) and matrix metalloproteinase 3 (MMP3). MMP3 is known to cause joint erosion in inflammatory joint conditions such as rheumatoid arthritis and ankylosing spondylitis. It is therefore proposed that while managing LA, looking for underlying inflammatory arthritis may provide the answer. Disclosures S. Khalid None. M. Cox None. M. Kazmi None.