Preventive and therapeutic effects of low-dose whole-body irradiation on collagen-induced rheumatoid arthritis in mice.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by progressive joint inflammation, resulting in cartilage destruction and bone erosion. It was reported that low-dose radiation modulates immune disease. Here, we investigated whether low-dose whole-body irradiation has preventive and therapeutic effects in collagen-induced RA (CIA) mouse models. Fractionated low-dose irradiation (0.05 Gy/fraction, total doses of 0.1, 0.5 or 0.8 Gy) was administered either concurrently with CIA induction by Type II collagen immunization (preventive) or after CIA development (therapeutic). The severity of CIA was monitored using two clinical parameters, paw swelling and redness. We also measured total Immunoglobulin G (IgG) and inflammatory cytokines (interleukine (IL)-6, IL-1ß and tumor necrosis factor-alpha (TNF-α)) in the serum by enzyme-linked immunosorbent assay, and we evaluated histological changes in the ankle joints by immunohistochemistry and hematoxylin and eosin staining. Low-dose irradiation reduced CIA clinical scores by up to 41% in the preventive model and by 28% in the therapeutic model, while irradiation in the preventive model reduced the typical CIA incidence rate from 82 to 56%. In addition, low-dose irradiation in the preventive model decreased total IgG by up to 23% and decreased IL-1ß and TNF-α by 69 and 67%, and in the therapeutic model, decreased total IgG by up to 35% and decreased IL-1ß and IL-6 by 59 and 42% with statistical significance (P < 0.01, 0.05 and 0.001). Our findings demonstrate that low-dose radiation has preventive and therapeutic anti-inflammatory effects against CIA by controlling the immune response, suggesting that low-dose radiation may represent an alternative therapy for RA, a chronic degenerative immune disease.

The Mechanisms and Efficacy of Photobiomodulation Therapy for Arthritis: A Comprehensive Review.

Rheumatoid arthritis (RA) and osteoarthritis (OA) have a significant impact on the quality of life of patients around the world, causing significant pain and disability. Furthermore, the drugs used to treat these conditions frequently have side effects that add to the patient's burden. Photobiomodulation (PBM) has emerged as a promising treatment approach in recent years. PBM effectively reduces inflammation by utilizing near-infrared light emitted by lasers or LEDs. In contrast to photothermal effects, PBM causes a photobiological response in cells, which regulates their functional response to light and reduces inflammation. PBM's anti-inflammatory properties and beneficial effects in arthritis treatment have been reported in numerous studies, including animal experiments and clinical trials. PBM's effectiveness in arthritis treatment has been extensively researched in arthritis-specific cells. Despite the positive results of PBM treatment, questions about specific parameters such as wavelength, dose, power density, irradiation time, and treatment site remain. The goal of this comprehensive review is to systematically summarize the mechanisms of PBM in arthritis treatment, the development of animal arthritis models, and the anti-inflammatory and joint function recovery effects seen in these models. The review also goes over the evaluation methods used in clinical trials. Overall, this review provides valuable insights for researchers investigating PBM treatment for arthritis, providing important references for parameters, model techniques, and evaluation methods in future studies.

Effects of low-level laser therapy in adults with rheumatoid arthritis: A systematic review and meta-analysis of controlled trials.

Rheumatoid arthritis (RA) is an inflammatory, systemic and chronic disease that mainly affects the joints. It is characterized mainly by pain, edema and joint stiffness, which can lead to significant loss of functional capacity and quality of life. Several physical therapy resources are used in the treatment of AR, such as low-level laser therapy (LLLT) and its analgesic and anti-inflammatory effects. However, the efficacy of LLLT in AR is still controversial. The objective of this study is to evaluate the efficacy of low-level laser therapy in adults with RA. Methods and findings: We searched MEDLINE, EMBASE, CENTRAL, PEDro, LILACS, IBECS, CUMED, SCIELO and ClinicalTrials.gov. Two researchers independently selected studies, extracted data, evaluated the risk of bias and assessed the certainty of evidence using GRADE approach. Disagreements were resolved by a third author. Meta-analyses were performed. Currently available evidence was from 18 RCTs, with a total of 793 participants. We found low-quality evidence suggesting there may be no difference between using infrared laser and sham in terms of pain, morning stiffness, grip strength, functional capacity, inflammation, ROM, disease activity and adverse events. The evidence is very uncertain about the effects of red laser compared to sham in pain, morning stiffness. The evidence is also very uncertain about the effects of laser acupuncture compared to placebo in functional capacity, quality of life, range of motion and inflammation. Conclusions: Thus, infrared laser may not be superior to sham in RA patients. There is insufficient information to support or refute the effectiveness of red laser, laser acupuncture and reflexology for treating patients with RA.

Chromosomal radiosensitivity in oncological and non-oncological patients with rheumatoid arthritis and connective tissue diseases.

BACKGROUND: The risk of developing late radiotoxicity after radiotherapy in patients with high chromosomal radiosensitivity after radiotherapy could potentially be higher compared to the risk in patients with average radiosensitivity. In case of extremely high radiosensitivity, dose reduction may be appropriate. Some rheumatic diseases (RhD), including connective tissue diseases (CTDs) appear to be associated with higher radiosensitivity. The question arises as to whether patients with rheumatoid arthritis (RA) also generally have a higher radiosensitivity and whether certain parameters could indicate clues to high radiosensitivity in RA patients which would then need to be further assessed before radiotherapy. METHODS: Radiosensitivity was determined in 136 oncological patients with RhD, 44 of whom were RA patients, and additionally in 34 non-oncological RA patients by three-colour fluorescence in situ hybridization (FiSH), in which lymphocyte chromosomes isolated from peripheral blood are analysed for their chromosomal aberrations of an unirradiated and an with 2 Gy irradiated blood sample. The chromosomal radiosensitivity was determined by the average number of breaks per metaphase. In addition, correlations between certain RA- or RhD-relevant disease parameters or clinical features such as the disease activity score 28 and radiosensitivity were assessed. RESULTS: Some oncological patients with RhD, especially those with connective tissue diseases have significantly higher radiosensitivity compared with oncology patients without RhD. In contrast, the mean radiosensitivity of the oncological patients with RA and other RhD and the non-oncological RA did not differ. 14 of the 44 examined oncological RA-patients (31.8%) had a high radiosensitivity which is defined as ≥ 0.5 breaks per metaphase. No correlation of laboratory parameters with radiosensitivity could be established. CONCLUSIONS: It would be recommended to perform radiosensitivity testing in patients with connective tissue diseases in general. We did not find a higher radiosensitivity in RA patients. In the group of RA patients with an oncological disease, a higher percentage of patients showed higher radiosensitivity, although the average radiosensitivity was not high.

Photobiomodulation ameliorates inflammatory parameters in fibroblast-like synoviocytes and experimental animal models of rheumatoid arthritis.

Introduction: Rheumatoid arthritis (RA) is a chronic destructive inflammatory disease that afflicts over one percent of the world's population. Current pharmacological treatments remain relatively ineffective. In this context, photobiomodulation (PBM) is a potential resource for the treatment of RA. This study investigates investigate the anti-arthritic effects and related mechanisms of PBM on fibroblast-like synoviocytes (FLSs) from RA patients and a mouse model of collagen-induced arthritis (CIA). Methods: The RA-FLSs were irradiated with a light emitting diode (LED) at a wavelength of 610 nm for 20 min, and the corresponding power intensities were 5 and 10 mW/cm2. After the LED irradiation, cell viability, proliferation, migration, and invasion assays were performed. Male DBA/1J mice were used to establish an animal model of CIA. Light stimulation with 10 mW/cm2 was applied to the ankle joints via direct contact with the skin for 40 min, daily for 2 weeks. Results and Discussion: PBM significantly reduced tumor necrosis factor (TNF)-α-induced increase in proliferation, migration, and invasion in RA-FLSs, and downregulated the activation of nuclear factor-κappa B (NF-κB) and NLRP3 inflammasome by TNF-α. Moreover, PBM greatly inhibited the induction and development of CIA, resulting in the inhibition of synovial inflammation and cartilage degradation. PBM therapy decreased the serum levels of pro-inflammatory cytokines, while increasing the anti-inflammatory cytokines. PBM suppressed the translocation of NF-κB and activation of NLRP3 inflammasome in the ankle joint. Furthermore, PBM showed a more pronounced anti-arthritic effect when combined with methotrexate (MTX), a disease-modifying anti-rheumatic drug (DMARD). The results showed that the effectiveness of MTX + PBM in CIA is superior to that of either MTX or PBM and that both work synergistically. Therefore, PBM with LED may be a potential therapeutic intervention for against RA.

[Pain reduction by radiosynoviorthesis in rheumatism-induced synovitis of the elbow : Results of a retrospective multicenter data analysis]. / Schmerzreduktion durch Radiosynoviorthese bei rheumatisch bedingter Synovialitis des Ellenbogens : Ergebnisse einer retrospektiven, multizentrischen Datenanalyse.

BACKGROUND: Radiosynoviorthesis (RSO) is a nuclear medical local treatment modality for inflammatory joint diseases. It is indicated in patients with rheumatoid arthritis (RA) in joints with persistent synovitis despite adequate pharmacotherapy. Arthritis of the elbow joint occurs in up to 2/3 of patients with RA. Intra-articular radiotherapy using the beta emitter [186Re] rhenium sulfide leads to sclerosis of the inflamed synovial membrane with subsequent pain alleviation. The clinical efficacy in cubital arthritis, however, has so far only been described in small monocentric studies. OBJECTIVE: The degree of pain alleviation by RSO was analyzed in patients with rheumatoid cubital arthritis, treated in several nuclear medical practices specialized in RSO. MATERIAL AND METHODS: The subjective pain intensity before and after RSO was documented in a total of 107 patients with rheumatic cubital arthritis using a 10-step numeric rating scale (NRS). A difference of ≥ -2 is rated as a significant improvement. Follow-up examinations were done after a mean interval of 14 months after RSO (at least 3 months, maximum 50 months). RESULTS: The mean NRS value was 7.3 ± 2.1 before RSO and 2.8 ± 2.2 after RSO. A significant pain alleviation was seen in 78.5% of all patients treated. The subgroup analysis also showed a significant improvement in the pain symptoms in all groups depending on the time interval between the RSO and the control examination. A significant pain progression was not observed. The degree of pain relief was independent of the time of follow-up. CONCLUSION: Using RSO for local treatment of rheumatoid cubital arthritis leads to a significant and long-lasting pain relief in more than ¾ of the treated patients.

Heat Shock Protein Is Associated with Inhibition of Inflammatory Cytokine Production by 630 nm Light-Emitting Diode Irradiation in Fibroblast-Like Synoviocytes Based on RNA Sequencing Analysis.

Background: Inflammatory cytokine secretion from fibroblast-like synoviocytes (FLS) plays a vital role in the pathological process of rheumatoid arthritis (RA). Photobiomodulation (PBM) has been widely used in the treatment of RA. However, the mechanism of PBM in RA has not been clarified. Objective: In this study, we investigated the underlying mechanism of 630 nm light-emitting diode (LED) irradiation on anti-inflammation using mRNA sequencing analysis. Methods and results: Reverse transcription (RT)-quantitative polymerase chain reaction (RT-qPCR) results showed that 630 nm LED irradiation significantly inhibited interleukin (IL)-1ß, IL-6, and IL-8 mRNA expression in rheumatoid arthritis fibroblast synovial cells (RA-FLS) and MH7A cells. A total of 1730 differentially expressed genes (DEGs) were identified between tumor necrosis factor α (TNF-α)+LED and TNF-α-treated RA-FLS and 1219 DEGs in MH7A cells by mRNA sequencing analysis. A total of 646 intersecting DEGs from the 2 cell models were used for gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Protein-protein interaction (PPI) network of DEGs was used, and 502 nodes and 1452 edges were found. A total of 14 clusters were generated in MCODE, and the top 3 clusters were selected as hub modules. PPI network showed that most of the nodes were DEGs of the heat shock protein (HSP) family. RT-qPCR verified that 630 nm LED irradiation significantly increased HSP70 mRNA expression in FLS. Conclusions: Taken together, our results revealed the correlation between HSP70 and the inhibition of inflammation caused by 630 nm LED irradiation. These findings suggested that HSP may be a novel target of 630 nm LED irradiation to alleviate inflammation in the treatment of RA.

Long-term clinical results from 10 years follow-up after radiosynoviorthesis: a prospective observational study.

BACKGROUND: The aim of this study was to assess the long-term anti-inflammatory effect and safety of 90-Yttrium and 166-Holmium radiosynoviorthesis (RSO) for treating chronic knee synovitis of various origins. METHODS: A total of 820 patients were included in this study and were followed up to 10 years after the procedure for objective and subjective changes in signs and symptoms of inflammation. RESULTS: Five years after RSO, excellent and good results were seen in 71% (95% CI 67-74%) of patients. Six, seven, eight and nine years following RSO, efficacy did not decrease significantly. Ten years after RSO, the effectiveness of the therapy fell to 65% (95% CI 59-71%). Overall, 64% of patients did not need another joint puncture ten years after RSO. We achieved excellent to good results at 5 years in 79% of patients with rheumatoid arthritis, 59% with ankylosing spondylitis, and 62% with osteoarthritis. Efficacy was mainly affected by the local X-ray stage of the knee joint. A significant association was also found between the diagnosis of the underlying disease and the success of radiosynoviorthesis. Efficacy, however, was not substantially affected by any of the following factors: the duration of synovitis, the number of punctures before radiosynoviorthesis, the number of intraarticular steroid injections before the procedure, or the number of interventions before radiosynoviorthesis (radiotherapy, surgery). CONCLUSIONS: Radiosynoviorthesis is an effective long-term method of treating chronic synovitis. The treatment showed the most favorable effects in patients with rheumatoid arthritis and those with mild to moderate degenerative osseous changes.

Far infrared irradiation suppresses experimental arthritis in rats by down-regulation of genes involved inflammatory response and autoimmunity.

Introduction: Far-infrared radiation (FIR) is widely used in the treatment of various diseases such as insomnia and cardiovascular risk. Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease in which the therapeutic potential of FIR in RA is unclear. Objectives: To determine the therapeutic potential and mechanistic actions of FIR in treatment of RA. Methods: Adjuvant-induced arthritis (AIA) rat models were established to assess the therapeutic potency of FIR in RA treatment. The scoring parameters such as arthritis score, swelling of the hind paw, spleen and thymus indices, micro-CT analysis indices were adopted to estimate the beneficial effects of FIR during RA treatment in AIA model. PCR gene expression arrays were used to analyze inflammatory and autoimmune genes expression profiles in rat synovium. The inflammatory and immunity genes profiling was further analyzed through transcription factor prediction using PROMO. A signaling network map of possible molecular circuits connecting the identified differential genes to the RA's pathogenesis was constructed based on extensive literature reviews, and the major signaling pathways were validated by Western blotting. Results: Thirty minutes of FIR treatment significantly improved the symptoms of AIA in rats. Gene expression profiling indicated that 27 out of 370 genes were down-regulated by FIR. AP-1, CEBPα, CEBPß, c-Fos, GR, HNF-3ß, USF-1, and USF-2 were predicted as key transcription factors that regulated the identified differential genes. In addition, MAPK, PI3K-Akt, and NF-κB signaling are the major molecular pathways down-regulated by FIR treatment. Conclusion: FIR may provide beneficial effects on the AIA rat model of arthritis by suppression of the MAPK, PI3K-Akt and NF-κB signaling pathways. Therefore, we believe that FIR may provide an alternative non-pharmacological and non-surgical therapeutic approach for the treatment of RA.

Morphometric aspects of the articular cartilage of rats treated with low-level laser therapy and exercise in a rheumatoid arthritis model

INTRODUCTION: Rheumatoid arthritis (RA) is classified as an autoimmune, chronic disease affecting diarthrodial joints and periarticular structures. OBJECTIVE: To evaluate whether low-intensity laser treatment (LLLT) and/or exercise reduce the deleterious effects of tissue in a rheumatoid arthritis model. METHODS: 128 rats were divided into two inflammatory periods: acute (7 days) and chronic (28 days) and subdivided into control, injury and treatment. The protocol with Freund's Complete Adjuvant was used in two inoculations, one intradermal and one intraarticular in the tibiofemoral joint, the control animals received saline solution. For treatment, LLLT 660 nm, 5 J/cm² was used in the sensitized joint and climbing exercise in stairways with an overload of 100 grams. After the experimental period, the animals were euthanized and the joints were prepared for morphometric analysis of the total thickness, superficial, deep, and cellular density of the articular cartilage. Generalized Linear Models with Sidak post-test were chosen. RESULTS: The control group was found to be different from the lesion group with greater joint cartilage thickness, andthe animals treated with exercise alone increased the joint cartilage compared to thecontrol group. CONCLUSION: The animals treated with laser association and exercise showed improvement in the morphometric aspects of the articular cartilage.

Infrared radiation from cage bedding moderates rat inflammatory and autoimmune responses in collagen-induced arthritis.

The development of collagen type II (CII)-induced arthritis (CIA), a model of rheumatoid arthritis, in rats housed in cages with bedding composed of Celliant fibres containing ceramic particles, which absorb body heat and re-emit the energy back to the body in the form of infrared radiation (+IRF rats), and those housed in cages with standard wooden shaving bedding (-IRF control rats) was examined. The appearance of the first signs of CIA was postponed, while the disease was milder (judging by the arthritic score, paw volume, and burrowing behaviour) in +IRF compared with -IRF rats. This correlated with a lower magnitude of serum anti-CII IgG antibody levels in +IRF rats, and lower production level of IL-17, the Th17 signature cytokine, in cultures of their paws. This could be partly ascribed to impaired migration of antigen-loaded CD11b + dendritic cells and their positioning within lymph nodes in +IRF rats reflecting diminished lymph node expression of CCL19 /CCL21. Additionally, as confirmed in rats with carrageenan-induced paw inflammation (CIPI), the infrared radiation from Celliant fibres, independently from immunomodulatory effects, exerted anti-inflammatory effects (judging by a shift in pro-inflammatory mediator to anti-inflammatory/immunoregulatory mediator ratio towards the latter in paw cultures) and ameliorated burrowing behaviour in CIA rats.

Development of 186/188Re-Chitosan as an Effective Therapeutic Agent for Rheumatoid Arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory chronic disease characterized by inflammation, pain, swelling and disability, and radiosynovectomy is one of the disease treatment lines. In this study, the possibility of providing rhenium-186/rhenium-188 chitosan radiopharmaceuticals, optimization of conditions for their production and bio-distribution are reported. OBJECTIVE: In order to build perrhenic acid for labeling, natural rhenium was exposed to radiation. Radionuclidic and radiochemical purities of (186/188Re)-NaReO4 were examined by gamma spectroscopy and paper chromatography methods, respectively. METHODS: Labeling of chitosan with rhenium was done in different acidic situations. The radiochemical purity 186/188Re-chitosan was applied by radio thin layer chromatography (RTLC). Lastly, the bio-distribution of the radiolabeled chitosan was studied in various organs after intra articular injection of the complex to lab rats. Gamma spectrometry confirmed the high rhenium radionuclidic purity. Chromatography results showed that perrhenic acid was produced with purity greater than 97% and rhenium chitosan labeling was done over 98% in pH = 3. Dissection results showed a high bio-distribution of 186/188Re-chitosan after injection into the joint with no leakage to surrounding organs. CONCLUSION: According to the results, there is a possibility of labeling rhenium with chitosan in very high radiochemical purity. Regarding the high retention of these radiopharmaceuticals in joints with no leakage to surrounding organs, 186/188Re-chitosan can be applied as new radiosynovectomy drugs for rheumatoid arthritis treatment.

Efficacy assessment of radiosynoviorthesis on the progression of radiological osteoarthritic features of hip and ankle joint in patients with osteoarthritis and rheumatoid arthritis.

OBJECTIVE: The study objective was to evaluate the long-term effect of radiosynoviorthesis (RSO) on the progression of radiological and nuclear-medical osteoarthritic features of hip and ankle joint in patients with osteoarthritis and rheumatoid arthritis. PATIENTS AND METHODS: The study included 89 hip joints of 81 patients, of which 48 had osteoarthritis (OA) and 33 had rheumatoid arthritis (RA). In terms of ankle joints, 64 patients were included of which 43 suffered from OA and 21 from RA. The mean follow-up time was 9.2 years for OA and 8.9 years for RA patients. Patients with RA were the active control group. Structural alterations of the hip joints were evaluated following Kellgren-Lawrence score and of ankle joint following Takakura score for both disease entities. For the evaluation of synovitis 2-phase bone scintigraphy was performed. RESULTS: RSO could prevent radiologic status deterioration among 70.6 % of hip osteoarthritic patients and 73.7 % among the hip RA patients. No structural progression was observed in 79.1 % of the treated ankle joints in patients with OA and in 85.7 % of the ankle joints in patients with RA.The scintigraphic response rate for the hip joints of OA patients was 68.6 %, 76.3 % for hip joints of RA patients, 83.1 %, ankle joints of OA patients, and 90.4 % ankle joints of RA patients.The radiographic and scintigraphic RSO response rates were not significantly higher for both joints in RA than OA patients. CONCLUSION: RSO can be a good alternative in the treatment of synovitis and prevention of deterioration of inflammatory and radiographic features even in patients suffering from osteoarthritis and rheumatoid arthritis. RSO may have also a long-term effect to stop or delay progression of both diseases.

Physical exercise and low-level laser therapy on the nociception and leukocyte migration of Wistar rats submitted to a model of rheumatoid arthritis.

Rheumatoid arthritis denotes hyperplasia and intense inflammatory process. Treatment involves exercise protocols and use of resources such as low-level laser therapy (LLLT) to modulate the inflammatory process and maintain physical capacity. The objective was to investigate whether treatment with LLLT and exercise modulates the inflammatory process and peripheral functionality. Sample is composed of 128 male rats, separated into three groups, control, treated and untreated, in the acute and chronic period of the disease with 64 animals in each group, divided into 8 subgroups with n = 8. The animals were immunized with injection at the base of the tail and 7 days after intra-articular injection with complete Freund adjuvant (CFA) for lesion groups, and saline solution for the controls. Joint disability was evaluated by PET (paw elevation time) and joint edema and treated with LLLT and/or resisted stair climbing exercise. Normality Shapiro-Wilk test, ANOVA mixed for the functional analyses, and ANOVA one-way for the variables of cellular differentiation, with Bonferroni post hoc, p = 5% were used. For the evaluations of joint disability and nociception, there was a significant difference between the evaluations, the groups, and the interaction groups-evaluations. The treated groups showed recovery of functionality; it is still verified that laser therapy increased the nociceptive threshold of the chronic inflammatory period, and the exercise reflected in significant functional improvement and modulation of the inflammatory process both in the acute and chronic periods. LLLT, resistance exercise, or a combination of treatments had a positive effect on the modulation of the inflammatory process, reducing the migration of leukocytes, in addition to helping the return of peripheral functionality by reducing joint disability in a model of rheumatoid arthritis induced by CFA in rats.

The results of 394 consecutive cases of knee joint radiation synovectomy (radiosynoviorthesis) using 90Y.

OBJECTIVE: The aim of this study was to assess the treatment results of 90Y radiation synovectomy for chronic exudative synovitis of knee joints. METHODS: The retrospective data consist of 394 consecutive knee radiation synovectomies performed using 6 mCi (222 MBq) of 90Y. The assessment included 3-point custom pain and joint mobility scale, evaluation of joint's circumference, binary joint's temperature evaluation, patellar ballottement test, indications for puncture and its volume in applicable cases. 21 cases had to be forfeited due to missing data regarding follow-up. RESULTS: The final analysis of 373 treatment procedures performed in 253 patients yielded following results-at 6 months after treatment, 80.9% of the patients reported at least partial pain relief (including 33.3% with complete pain relief), which increased to 86.7% at one year. The pain intensity decreased over time, however, the outcomes were worse in older patients. The probability of pain recurrence was 15% at 6 months, and 28% at one year. It was highest in post-traumatic synovitis, and lowest in pigmented villonodular synovitis. The circumference of the treated knee joints decreased over the course of follow-up, however, the decrease was significantly lower in older patients. The fraction of patients with full knee joint mobility increased from 34.6 to 40.6% at 6 months and 49.2% at one year. The percentage of patients that required articular puncture decreased from 62.8% at baseline to about 35.6% at 6 months, and 32.8% at one year. Positive patellar ballottement was found in 68.5% before treatment and remained at about 40-50% during the course of follow-up. The increased temperature of the joint was reported in 51.2% at baseline and decreased to 33% at 6 months and 28.3% at one year. CONCLUSIONS: (1) Radiation synovectomy is a safe and effective method of treatment in patients with exudative synovitis, however, the pain recurrence rate is significantly higher in post-traumatic exudative synovitis compared to pigmented villonodular, undifferentiated, and rheumatoid arthritis. (2) Our results suggest that older patients have worse treatment results with radiation synovectomy compared to younger patients.

Prospective evaluation of phosphorus-32 radiation synovectomy in patients with severe and chronic rheumatoid arthritis unresponsive to conventional medical treatment.

OBJECTIVES: To determine the efficacy of Phosphorus-32 radiation synovectomy in the treatment of patients with severe rheumatoid arthritis (RA) unresponsive to systematic or local medical therapy. METHODS: Twenty-three knees in 16 patients with severe chronic RA were prospectively treated by intra-articular installation of Phosphorus-32 and evaluated at 1, 3, 6, and 12 months. The Western Ontario and McMaster Universities Arthritis index (WOMAC), visual analog scale (VAS), Health Assessment Questionnaire (HAQ), pain scale, and grade of joint effusion and tenderness were assessed. At the 12-month time interval, the treated knees were classified into four categories: excellent response (no symptoms), good response (significant reduction of symptoms), moderate response (slight decrease), and poor response (no change or worsening). RESULTS: Excellent response or good response was observed in 13/23 (56.5%) of the treated knees, moderate response in 2/23 (8.7%) of the treated knees, and poor response in 8/23 (34.8%) of the treated knees. The grades of effusion and tenderness were significantly decreased one-month posttreatment (P< 0.05); however, these changes did not persist at other time intervals (P > 0.05). There was a significant improvement in the HAQ, WOMAC, VAS, and pain scores at all time points compared with baseline, including at the 12-month time interval (P < 0.05). CONCLUSION: Phosphorus-32 radiosynovectomy is an effective therapeutic treatment for patients with RA of the knee unresponsive to conventional pharmacotherapy.

Photopheresis efficacy in the treatment of rheumatoid arthritis: a pre-clinical proof of concept.

BACKGROUND: Despite major advances in rheumatoid arthritis outcome, not all patients achieve remission, and there is still an unmet need for new therapeutic approaches. This study aimed at evaluating in a pre-clinical murine model the efficacy of extracorporeal photopheresis (ECP) in the treatment of rheumatoid arthritis, and to provide a relevant study model for dissecting ECP mechanism of action in autoimmune diseases. METHODS: DBA/1 mice were immunized by subcutaneous injection of bovine collagen type II, in order to initiate the development of collagen-induced arthritis (CIA). Arthritic mice received 3 ECP treatments every other day, with psoralen + UVA-treated (PUVA) spleen cells obtained from arthritic mice. Arthritis score was measured, and immune cell subsets were monitored. RESULTS: ECP-treated mice recovered from arthritis as evidenced by a decreasing arthritic score over time. Significant decrease in the frequency of Th17 cells in the spleen of treated mice was observed. Interestingly, while PUVA-treated spleen cells from healthy mouse had no effect, PUVA-treated arthritic mouse derived-spleen cells were able to induce control of arthritis development. CONCLUSIONS: Our results demonstrate that ECP can control arthritis in CIA-mice, and clarifies ECP mechanisms of action, showing ECP efficacy and Th17 decrease only when arthritogenic T cells are contained within the treated sample. These data represent a pre-clinical proof of concept supporting the use of ECP in the treatment of RA in Human.

Low-Dose Irradiation Differentially Impacts Macrophage Phenotype in Dependence of Fibroblast-Like Synoviocytes and Radiation Dose.

Rheumatoid arthritis (RA) is a multifactorial autoimmune disease whose main hallmark is inflammation and destruction of the joints. Two cell types within the synovium that play an important role in RA are fibroblast-like synoviocytes (FLS) and macrophages. The latter innate immune cells show a high plasticity in their phenotype and are central in inflammatory processes. Low-dose radiotherapy (LD-RT) with particularly a single dose of 0.5 Gy has been demonstrated to have a positive impact on pain, inflammation, and bone in inflamed joints. We now examined for the first time how LD-RT influences FLS and bone marrow-derived macrophages in co-culture systems of an experimental model of RA to reveal further mechanisms of immune modulatory effects of low and intermediate dose of ionizing radiation. For this, the bone marrow of hTNF-α tg mice was differentiated either with cytokines to obtain key macrophage phenotypes (M0, M1, and M2) or with supernatants (SN) of untreated or irradiated FLS. Flow cytometry analyses were used to analyse the impact of radiation (0.1, 0.5, 1.0, and 2.0 Gy) on the phenotype of macrophages in the presence or absence of SN of FLS. LD-RT had no impact on cytokine-mediated macrophage polarization in M0, M1, or M2 macrophages. However, SN of irradiated FLS particularly reduced CD206 expression on macrophages. Macrophage phenotype was stable when being in contact with SN of nonirradiated FLS, but significantly increased surface expression of CD206 and slightly decreased CD80 and CD86 expression were observed when macrophage themselves were irradiated with 0.5 Gy under these microenvironmental conditions, again highlighting discontinuous dose dependencies in the low and intermediate dose range. One can conclude that FLS-dependent microenvironmental conditions have a slight influence on the modulation of macrophage phenotype under radiation exposure conditions. Future studies are needed to reveal the impact of radiation exposure on the functions of treated macrophages under such microenvironmental conditions.

Post-radiosynovectomy imaging utilizing Erbium-169 citrate.

Currently, there is no imaging procedure for radionuclide therapy utilizing Erbium-169 (Er-169). We have recently published the first post-radiosynovectomy imaging of Er-169 citrate in a case report (Farahati et al., 2017). In this study, we performed in-vitro and in-vivo studies to evaluate the feasibility to assess the distribution of Er-169 citrate after radiosynovectomy in fourteen patients with seventeen affected joints treated for refractory chronic synovitis. Post-radiosynovectomy imaging revealed the feasibility of post-radiosynovectomy detection and distribution utilizing Er-169 citrate in all cases. However, additional in-vitro studies including in-vitro imaging, gamma spectrometry and analysis of half-life indicated that emitted gamma-rays of the Ytterbium-169 in the radiopharmaceutical together with bremsstrahlung induced by Er-169 are the imaging source of emitted counts. Post-radiosynovectomy imaging utilizing Er-169 citrate is feasible and should be implemented in the guidelines for theranostics for quality control, patient safety and therapy monitoring.

Concentration-dependent viscosity and thermal radiation effects on MHD peristaltic motion of Synovial Nanofluid: Applications to rheumatoid arthritis treatment.

BACKGROUND AND OBJECTIVE: The biomedical fluid which fills the Synovial joint cavity is called Synovial fluid which behaves as in the fluid classifications to Non-Newtonian fluids. Also it's described as a several micrometers thick layer among the interstitial cartilages with very low friction coefficient. Consequently, the present paper opts to investigate the influence of the concentration-dependent viscosity on Magnetohydrodynamic peristaltic flow of Synovial Nanofluid in an asymmetric channel in presence of thermal radiation effect. METHOD: Our problem is solved for two models, in the first model which referred as Model-(I), viscosity is considered exponentially dependent on the concentration. Model-(2), Shear thinning index is considered as a function of concentration. Those models are introduced for the first time in peristaltic or Nanofluid flows literature. The governing problem is reformulated under the assumption of low Reynolds number and long wavelength. The resulting system of equations is solved numerically with the aid of Parametric ND Solve. RESULTS: Detailed comparisons have been made between Model-(I) and Model-(2) and found unrealistic results between them. Results for velocity, temperature and nanoparticle concentration distributions as well as pressure gradient and pressure rise are offered graphically for different values of various physical parameters. CONCLUSIONS: Such models are applicable to rheumatoid arthritis (RA) treatment. Rheumatoid arthritis patients can be treated by applying the magnetic field on an electrically conducting fluid, due to the movement of the ions within the cell which accelerates the metabolism of fluids.