Anti-Inflammatory and Immunomodulatory Effects of 0.1 Sub-Terahertz Irradiation in Collagen-Induced Arthritis Mice.

The primary emphasis of photoimmunology is the impact of nonionizing radiation on the immune system. With the development of terahertz (THz) and sub-terahertz (sub-THz) technology, the biological effects of this emerging nonionizing radiation, particularly its influence on immune function, remain insufficiently explored but are progressively attracting attention. Here, we demonstrated that 0.1 sub-THz radiation can modulate the immune system and alleviate symptoms of arthritis in collagen-induced arthritis (CIA) mice through a nonthermal manner. The application of 0.1 sub-THz irradiation led to a decrease in proinflammatory factors within the joints and serum, reducing the levels of blood immune cells and the quantity of splenic CD4+ T cells. Notably, 0.1 sub-THz irradiation restored depleted Treg cells in CIA mice and re-established the Th17/Treg equilibrium. These findings suggested that sub-THz irradiation plays a crucial role in systemic immunoregulation. Further exploration of its immune modulation mechanisms revealed the anti-inflammatory properties of 0.1 sub-THz on LPS-stimulated skin keratinocytes. Through the reduction in NF-κB signaling and NLRP3 inflammasome activation, 0.1 sub-THz irradiation effectively decreased the production of inflammatory factors and immune-active substances, including IL-1ß and PGE2, in HaCaT cells. Consequently, 0.1 sub-THz irradiation mitigated the inflammatory response and contributed to the maintenance of immune tolerance in CIA mice. This research provided significant new evidence supporting the systemic impacts of 0.1 sub-THz radiation, particularly on the immune system. It also enhanced the field of photoimmunology and offered valuable insights into the potential biomedical applications of 0.1 sub-THz radiation for treating autoimmune diseases.

Effects of low-level laser therapy on the organization of articular cartilage in an experimental microcrystalline arthritis model.

The aim of this study was to evaluate the effects of low-level laser therapy using the gallium arsenide laser (λ = 830 nm) on the articular cartilage (AC) organization from knee joint in an experimental model of microcrystalline arthritis in adult male Wistar rats. Seventy-two animals were divided into three groups: A (control), B (induced arthritis), and C (induced arthritis + laser therapy). The arthritis was induced in the right knee using 2 mg of Na4P2O7 in 0.5 mL of saline solution. The treatments were daily applied in the patellar region of the right knee after 48 h of induction. On the 7th, 14th, and 21st days of treatment, the animals were euthanized and their right knees were removed and processed for structural and biochemical analysis of the AC. The chondrocytes positively labeled for the TUNEL reaction were lower in C than in B on the 14th and 21st days. The content of glycosaminoglycans and hydroxyproline in A and C was higher than B on the 21st day. The amount of tibial TNF-α in B and C was lower than in A. The amount of tibial BMP-7 in B and C was higher than in A. The femoral MMP-13 was lower in B and C than for A. The tibial TGF-ß for C was higher than the others. The femoral ADAMT-S4 content of A and C presented similar and inferior data to B on the 21st day. The AsGa-830 nm therapy preserved the content of glycosaminoglycans, reduced the cellular changes and the inflammatory process compared to the untreated group.

Low-intensity laser therapy efficacy evaluation in FVB mice subjected to acute and chronic arthritis.

Rheumatoid arthritis, an autoimmune inflammation, has a high prevalence in the population, and while therapy is available, it required often injection of drugs causing discomfort to patients. This study evaluates the clinical and histological effect of low-intensity laser therapy (LILT) as an alternative treatment, in a murine model of acute and chronic inflammation. FVB mice received either a Zymosan A injection into one knee joint inducing acute inflammation, followed after 15 min or 24 h by LILT or a collagen bovine type II injection emulsified in "Freund's Complete Adjuvant" to induce chronic arthritis, followed at 4 weeks with multiple LILT sessions. LILT mediated by either 660, 808, or 905 nm and tissue response was evaluated based on clinical symptoms and histological analysis of inflammatory infiltrate and damage to the articular surfaces. LILT can be effective in elevating clinical symptoms, so Kruskal-Wallis testing indicated no significant differences between knees affected by acute arthritis and treated once with LILT and an injured knee without treatment (p > 0.05) for 660 and 808 nm with some improvements for the 905-nm LILT. Mice receiving two treatments for acute arthritis showed exacerbation of inflammation and articular resorption following therapy with a 660-nm continuous laser (p < 0.05). For chronic inflammation, differences were not noted between LILT treated and untreated injured knee joints (p > 0.05). Among the lasers, the 905 nm tends to show better results for anti-inflammatory effect in acute arthritis, and the 660 nm showed better results in chronic arthritis. In conclusion, LILT wavelength selection depends on the arthritis condition and can demonstrate anti-inflammatory effects for chronic arthritis and reduced resorption area in this murine model.

Photobiomodulation therapy associated with treadmill training in the oxidative stress in a collagen-induced arthritis model.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by chronic and systemic inflammation, which leads to the destruction of the cartilage and bone and affects tissues in multiple joints. Oxidative stress has been implicated with regards to involvement in various disease conditions, such as diabetes mellitus and neurodegenerative, respiratory, cardiovascular, and RA diseases. In vivo experimental studies using photobiomodulation therapy (PBMT) have shown positive effects in reducing lipid peroxidation and in increasing antioxidant activity. The regular practice of physical exercise has also been reported to be a beneficial treatment capable of reducing oxidative damage. Thus, the aim of this study was to analyze the effects of photobiomodulation therapy at 2- and 4-J doses associated with physical exercise on oxidative stress in an experimental model of RA in protein expression involving superoxide dismutase (SOD), glutathione peroxidase (GPX), and/or catalase (CAT) on thiobarbituric acid reactive substances (TBARS). In this study, 24 male Wistar rats divided into four groups were submitted to an RA model (i.e., collagen-induced arthritis, CIA), with the first immunization performed at the base of the tail on days 0 and 7 were included. After 28 days, a third intraarticular dose was administered in both knees of the animals. After the last induction, PBMT was started immediately, transcutaneously at two points (i.e., the medial and lateral), with a total of 15 applications. Treadmill exercise was also started the day after the last induction, and lasted for 5 weeks. With respect to results, we obtained the decreases in the lipid peroxidation and the increases of the antioxidant activities of SOD, GPX and CAT, with physical exercise associated to PBMT in doses of 2 and 4 J. In conclusion, physical exercise associated with PBMT decreases lipid peroxidation and increases antioxidant activity.

Apoptosis induced by low-level laser in polymorphonuclear cells of acute joint inflammation: comparative analysis of two energy densities.

Anti-inflammatory property of low-level laser therapy (LLLT) has been widely described in literature, although action mechanisms are not always clarified. Thus, this study aimed to evaluate apoptosis mechanisms in the LLLT anti-inflammatory effects on the arthritis experimental model in vivo at two different energy densities (3 and 30 Jcm-2). Arthritis was induced in mice by zymosan solution, animals were distributed into five groups, and morphological analysis, immunocytochemistry and gene expressions for apoptotic proteins were performed. Data showed an anti-inflammatory effect, DNA fragmentation in polymorphonuclear (PMN) cells and alteration in gene expression of proteins related to apoptosis pathways after LLLT. p53 gene expression increased at both energy densities, Bcl2 gene expression increased at 3 Jcm-2, and Bcl2 tissue expression decreased at 30 Jcm-2. In addition, apoptosis was restricted to PMN cells. Results suggest that apoptosis in PMN cells comprise part of LLLT anti-inflammatory mechanisms by disbalance promotion between expression of pro-apoptotic (Bax and p53) and anti-apoptotic (Bcl-2) proteins, with pro-apoptotic gene expression selectively in PMN cells.

Effects of Photobiomodulation Associated with Platelet-Rich Plasma in Acute Rheumatoid Arthritis Induced in Female Wistar Rats' Knee.

Objective: Rheumatoid arthritis causes inflammation, pain, and joint degradation, necessitating treatment with anti-inflammatory drugs and corticosteroids, posing various challenges. We aimed to evaluate the effects of photobiomodulation (PBM) at two different doses associated to platelet-rich plasma (PRP) in an in vivo model of induced acute arthritis in Wistar rats' knee. Methods: Eighty-four Wistar rats were assigned into seven groups, including animals treated with PBM and/or PRP. On day 0, arthritis was induced in sham and treated groups through the intra-articular injection of zymosan (200 µg). Twenty-four hours after induction, the PBM groups were treated with an AsGaAl laser, whereas the PRP-treated groups received intra-articular injections with a concentration of 8 × 105 platelets obtained from another four animals. After 3 days, the animals were euthanized, and the interleukin (IL)-6 and complement C3 gene and protein expression levels were analyzed. Statistical analysis was performed using the mean ± SD with analysis of variance and Tukey's posttest, with a significance level set at 5% (p < 0.05). Results: Synovial inflammation decreased in PBM-treated groups; however, PRP alone showed no significant difference. Gene expression analysis revealed a significant difference in IL-6 and C3 levels in the PBM and PBM+PRP-treated groups. Meanwhile, the PRP alone group exhibited significance for IL-6. Moreover, the PBM and PBM+PRP-treated groups showed a significant difference in C3 protein expression levels, whereas the PRP alone group showed no difference. Conclusion: The increase in cellular activity in the synovial membrane and the decrease protein expression levels are owing to the reduction in proinflammatory mediators following PBM therapy.

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.

BF02, a recombinant TNFR2 fusion protein, alleviates adjuvant arthritis by regulating T lymphocytes in rats.

AIM: To investigate the therapeutic effects of BF02 on adjuvant arthritis (AA) in rats and the regulatory effects of BF02 on T lymphocyte function. METHODS: SD rats received a single intradermal injection of Freund's complete adjuvant emulsion into the right hind metatarsal footpad. After the onset of AA, the rats were injected BF02 (1, 3, or 9 mg/kg, sc) every 3 d for a total of 15 d. Intragastric administration of methotrexate (MTX, 0.5 mg/kg, every 3 d for a total of 15 d) was taken as the positive control drug. Arthritis index, swollen joint count, ankle joint histopathology, spleen histopathology and the paw radiography were used for evaluating the drug effects on AA rats. T lymphocyte function was assessed by measuring T lymphocyte cytokine levels, IL17 and TNF-α mRNA expression levels, and percentage of T lymphocyte subsets. RESULTS: In the AA rats, remarkable secondary inflammatory responses exhibited, accompanied by significantly higher levels of IL-1, IL-6, TNF-α, IL-17, LTα, RANKL, and MMP-13. The expression of IL17 and TNF-α mRNAs was also substantially higher than in normal rats. The percentages of CD3(+)CD4(+) and CD4(+)CD25(+) T lymphocytes were increased, whereas the percentages of CD4(+)CD62L(+) and CD4(+)CD25(+)FoxP3(+) T lymphocytes were decreased. Treatment of the AA rats with BF02 (9 mg/kg) or MTX significantly decreased the arthritis index, swollen joint count and arthritis global assessment. Moreover, both BF02 (9 mg/kg) and MTX significantly inhibited T lymphocyte proliferation, and blocked the above mentioned aberrance in T lymphocyte cytokine levels, IL17 and TNF-α mRNA expression, and percentages of T lymphocyte subsets. CONCLUSION: BF02 exerts therapeutic effects on AA rats via the regulation of T lymphocytes.

Resistance exercise and low-level laser therapy improves grip strength and morphological aspects in the ankle joint of Wistar rats with experimental arthritis.

Rheumatoid arthritis (RA) is an inflammatory disease mainly affecting synovial joints. Photobiomodulation through low-level laser therapy (LLLT) and resistance exercise may improve the inflammatory process. Therefore, we analyzed the effects of resistance exercise, LLLT, and the combination of both treatments on hind paw grip strength and ankle joint histomorphometric aspects of Wistar rats subjected to experimental RA. A total of 64 male Wistar rats were divided into eight groups: control, control LLLT, control exercise, control LLLT and exercise, arthritis, arthritis LLLT, arthritis exercise, and arthritis LLLT and exercise groups. The experimental RA was induced by a complete Freund's adjuvant injection into the knee joint cavity. Climbing exercises and LLLT (660 nm; 5 J/cm2 per point) were performed as the treatment. In addition, muscle strength was evaluated using the grip strength test, and morphometric evaluations were performed on the ankle joint. Generalized mixed models and multivariate analysis of variance tests were used for statistical analysis. Statistical significance was set at a p-value of .05. Arthritis LLLT, exercise, and LLLT and exercise had positive effects on grip strength between the groups (F[7.56] = 5.8, p < .004) and within the groups (F[4.3] = 9.9, p < .002) throughout the evaluations. Morphometry revealed degenerative lesions in the ankle joint as subintima with angiogenesis, inflammatory cells, flocculated articular cartilage, chondrocyte disorganization, and pannus in the arthritis group (p < .001). The treated groups exhibited morphological characteristics similar to those of the control group. LLLT and resistance exercise restored muscle strength and morphological aspects of the ankle joint in rats with experimentally induced RA.

Photodynamic therapy using intra-articular Photofrin for murine MRSA arthritis: biphasic light dose response for neutrophil-mediated antibacterial effect.

BACKGROUND AND OBJECTIVE: Bacterial arthritis does not respond well to antibiotics and moreover multidrug resistance is spreading. We previously tested photodynamic therapy (PDT) mediated by systemic Photofrin® in a mouse model of methicillin-resistant Staphylococcus aureus (MRSA) arthritis, but found that neutrophils were killed by PDT and therefore the infection was potentiated. STUDY DESIGN/MATERIALS AND METHODS: The present study used an intra-articular injection of Photofrin® and optimized the light dosimetry in order to maximize bacterial killing and minimize killing of host neutrophils. MRSA (5 × 10(7) CFU) was injected into the mouse knee followed 3 days later by 1 µg of Photofrin® and 635-nm diode laser illumination with a range of fluences within 5 minutes. Synovial fluid was sampled 6 hours or 1-3, 5, and 7 days after PDT to determine MRSA colony-forming units (CFU), neutrophil numbers, and levels of cytokines. RESULTS: A biphasic light dose response was observed with the greatest reduction of MRSA CFU seen with a fluence of 20 J cm(-2), whereas lower antibacterial efficacy was observed with fluences that were either lower or higher. Consistent with these results, a significantly higher concentration of macrophage inflammatory protein-2, a CXC chemokine, and greater accumulation of neutrophils were seen in the infected knee joint after PDT with a fluence of 20 J cm(-2) compared to fluences of 5 or 70 J cm(-2). CONCLUSION: PDT for murine MRSA arthritis requires appropriate light dosimetry to simultaneously maximize bacterial killing and neutrophil accumulation into the infected site, while too little light does not kill sufficient bacteria and too much light kills neutrophils and damages host tissue as well as bacteria and allows bacteria to grow unimpeded by host defense.

Low-level laser irradiation treatment reduces CCL2 expression in rat rheumatoid synovia via a chemokine signaling pathway.

Rheumatoid arthritis (RA) is an inflammatory joint disorder whose progression leads to the destruction of cartilage and bone. Although low-level laser irradiation (LLLI) is currently being evaluated for the treatment of RA, the molecular mechanisms underlying its effectiveness remain unclear. To investigate possible LLLI-mediated antiinflammatory effects, we utilized a collagen-induced arthritis (CIA) rat model and analyzed gene expression profiles in the synovial membranes of the knee joint. Total RNA was isolated from the synovial membrane tissue of the joints of untreated CIA rats or CIA rats treated with LLLI (830 nm Ga-Al-As diode), and gene expression profiles were analyzed by DNA microarray (41,000 rat genes), coupled with Ingenuity pathways analysis (IPA). DNA microarray analysis showed that CCL2 gene expression was increased in CIA tissue, and that LLLI treatment significantly decreased CIA-induced CCL2 mRNA levels. IPA revealed that chemokine signal pathways were involved in the activation of CCL2 production. These microarray data were further validated using real-time PCR and reverse transcription PCR. Immunohistochemistry confirmed that CCL2 production was decreased in CIA rats treated with LLLI. These findings suggest that decreased CCL2 expression may be one of the mechanisms involved in LLLI-mediated RA inflammation reduction.

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.

The anti-inflammatory effect of low-level laser therapy on experimentally induced inflammation of rabbit temporomandibular joint retrodiscal tissues.

AIMS: To investigate the effect of low-level laser therapy (LLLT) on experimentally induced inflammation in retrodiscal tissues of the rabbit temporo?mandibular joint (TMJ) using scintigraphic imaging. METHODS: Eleven male New Zealand rabbits were included in this study. Six randomly selected rabbits were imaged to provide normal joint images (normal group) before the initiation of the experiment. A 5% formalin solution was locally injected into both right and left TMJs of all rabbits. Subsequently, Ga-Al-As laser (wavelength: 815 nm; energy density: 12 J/cm2; output power: 250 mW) was applied for 48 seconds. The treatment was performed six times for 2 weeks to the left TMJ of all rabbits. The right TMJs of the rabbits were used as the control (nontreated) TMJ group, while left TMJs were used as the treated TMJ group. Static images of TMJ were taken at 24 hours, 7 days, and 14 days after the beginning of the treatment. The images of all TMJs were taken in the posteroanterior direction with the rabbit under sedation and its mouth open. The Mann-Whitney U test was used to compare group differences, and intragroup differences were determined by the Friedman test and Wilcoxon sign test. RESULTS: Significant differences were found between normal and both the control and treated TMJ groups. A reduction of inflammation in both treated and control TMJ groups was obtained, but there was no statistically significant difference between the groups. CONCLUSION: Under the conditions used in this study, quantitative scintigraphic measurements of TMJ inflammation of the treated TMJ group decreased but did not differ significantly from those of the control TMJ group.

Amelioration of adjuvant-induced arthritis by exposure to low dose gamma radiation and resveratrol administration in rats.

Purpose: Low dose radiation has been reported as an effective treatment for rheumatoid arthritis via multiple dose exposures. The present study was designed to increase the therapeutic efficacy of low dose radiation with the minimum exposure level in arthritic rats by concurrent administration of resveratrol (RSV) as an adjunctive therapy with anti-inflammatory properties.Materials and methods: Rats were rendered arthritic by sub-plantar injection of Freund's complete adjuvant (FCA) and exposed to low dose radiation at a total exposure level of 0.5 Gy (2 × 0.25). During the exposure course, RSV (50 mg/kg) was orally administered once daily for two weeks. Diclofenac (3 mg/kg) was administered as a standard anti-inflammatory drug. Paw volume was measured every 4 days. After 28 days of induction, rats were sacrificed and serum was collected for estimation of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß), thiobarbituric acid reactive substances (TBARS), and total nitrate/nitrite (NOx). Furthermore, paws were dissected for histopathological examinations and immuno-histochemical estimation of nuclear factor-kappa B p65 (NF-κB p65) expression.Results: Administration of RSV during the low dose radiation exposure course produced a significant decrease in the paw swelling and a potentiated inhibition in the serum levels of TNF-α, IL-1ß, TBARs, and NOx. The dual treatment strategy alleviated the histopathological damage to a greater extent than that produced by each treatment. Moreover, a pronounced suppression of NF-κB p65 expression in the synovial tissue was observed in the combination group. The combination treatment showed a nearly similar potency to that observed in the diclofenac treated group.Conclusion: Administration of RSV augmented the modulatory activity of low dose radiation with minimum exposure level on the disease progression.

Low-Dose Radiotherapy Ameliorates Advanced Arthritis in hTNF-α tg Mice by Particularly Positively Impacting on Bone Metabolism.

Inflammation and bone erosion are central in rheumatoid arthritis (RA). Even though effective medications for control and treatment of RA are available, remission is only seen in a subset of patients. Treatment with low-dose radiotherapy (LD-RT) which has been already successfully used for amelioration of symptoms in benign diseases should be a promising approach to reduce pain, inflammation, and particularly bone erosion in patients with RA. Even though anti-inflammatory effects of LD-RT are already described with non-linear dose response relationships, and pain-reducing effects have been clinically observed, the underlying mechanisms are widely unknown. Besides immune cells many other cell types, such as fibroblast-like synoviocytes (FLS), osteoclasts, and osteoblast are present in the affected joint and might be modulated by LD-RT. For this study, these cell types were obtained from human tumor necrosis factor-α transgenic (hTNF-α tg) mice and were consecutively exposed to different doses of ionizing radiation (0.1, 0.5, 1.0, and 2.0 Gy, respectively) in vitro. In order to study the in vivo effects of LD-RT within the arthritic joint, hind paws of arthritic hTNF-α tg mice were locally irradiated with 0.5 Gy, a single dose per fraction that is known for good clinical responses. Starting at a dose of 0.5 Gy, proliferation of FLS was reduced and apoptosis significantly enhanced with no changes in necrosis. Further, expression of RANK-L was slightly reduced following irradiation with particularly 0.5 Gy. Starting from 0.5 Gy, the numbers of differentiated osteoclasts were significantly reduced, and a lower bone resorbing activity of treated osteoclasts was also observed, as monitored via pit formation and Cross Laps presence. LD-RT had further a positive effect on osteoblast-induced mineralization in a discontinuous dose response relationship with 0.5 Gy being most efficient. An increase of the gene expression ratio of OPG/RANK-L at 0.1 and 0.5 Gy and of production of OPG at 0.5 and 1.0 Gy was observed. In vivo, LD-RT resulted in less severe arthritis in arthritic hTNF-α tg mice and in significant reduction of inflammatory and erosive area with reduced osteoclasts and neutrophils. Locally applied LD-RT can, therefore, induce a beneficial micro-environment within arthritic joints by predominantly positively impacting on bone metabolism.

Low frequency and low intensity pulsed electromagnetic field exerts its antiinflammatory effect through restoration of plasma membrane calcium ATPase activity.

Rheumatoid arthritis (RA) is a chronic inflammatory disorder affecting 1% of the population worldwide. Pulsed electromagnetic field (PEMF) has a number of well-documented physiological effects on cells and tissues including antiinflammatory effect. This study aims to explore the antiinflammatory effect of PEMF and its possible mechanism of action in amelioration of adjuvant induced arthritis (AIA). Arthritis was induced by a single intradermal injection of heat killed Mycobacterium tuberculosis at a concentration of 500 microg in 0.1 ml of paraffin oil into the right hind paw of rats. The arthritic animals showed a biphasic response regarding changes in the paw edema volume. During the chronic phase of the disease, arthritic animals showed an elevated level of lipid peroxides and depletion of antioxidant enzymes with significant radiological and histological changes. Besides, plasma membrane Ca(2+) ATPase (PMCA) activity was inhibited while intracellular Ca(2+) level as well as prostaglandin E(2) levels was noticed to be elevated in blood lymphocytes of arthritic rats. Exposure of arthritic rats to PEMF at 5 Hzx4 microT x 90 min, produced significant antiexudative effect resulting in the restoration of the altered parameters. The antiinflammatory effect could be partially mediated through the stabilizing action of PEMF on membranes as reflected by the restoration of PMCA and intracellular Ca(2+) levels in blood lymphocytes subsequently inhibiting PGE(2) biosynthesis. The results of this study indicated that PEMF could be developed as a potential therapy for RA in human beings.

Chemistry and biological behavior of samarium-153 and rhenium-186-labeled hydroxyapatite particles: potential radiopharmaceuticals for radiation synovectomy.

Hydroxyapatite (HA), a natural constituent of bone, was studied as a particulate carrier for beta-emitting radionuclides in radiation synovectomy. Particles were radiolabeled with 153Sm or 186Re and their in vivo safety was investigated following intra-articular injection into knees of normal rabbits and rabbits with antigen-induced arthritis (AIA). Radiolabeling efficiency was greater than 95%; in vitro studies showed minimal (< or = 1%) loss of activity from particles over a 6-day period with 153Sm-labeled HA and about 5% loss of activity over a 5-day period with 186Re-labeled HA. The total cumulative extra-articular leakage of 153Sm over 6 days was 0.28% in normal rabbits and 0.09% in AIA rabbits. Leakage of 186Re from the joint was 3.05% over a 4-day period with 80% of extra-articular activity found in the urine. Histopathological evaluation of treated knees showed that HA particles are distributed throughout the synovium, embedded in the synovial fat pad. The ease and efficiency with which this HA carrier is labeled, coupled with observed extremely low leakage rates from the joint, make radiolabeled HA particles an attractive candidate as a radiation synovectomy agent for evaluation in rheumatoid arthritis patients.

Remission induction of adjuvant arthritis in rats by total body irradiation and autologous bone marrow transplantation.

Following the demonstration that adjuvant arthritis in rats can be cured with total body irradiation (TBI) and allogeneic or syngeneic bone marrow, the efficacy of autologous bone marrow was investigated in the experiments reported here. Bone marrow from arthritic rats, harvested at the same time that the recipients were irradiated, and real autologous bone marrow were found to be similarly effective as bone marrow grafts from naive syngeneic donors. Sublethal TBI with lower doses was less effective, but the highest tolerated doses of 8 Gy approached the effect of 9 Gy and bone marrow rescue. In contrast, partial body irradiation of either the affected limbs, or of the whole body except the limbs, resulted in only partial and temporary regression of the arthritis.

Treatment of antigen-induced arthritis in rabbits with dysprosium-165-ferric hydroxide macroaggregates.

Dysprosium-165-ferric hydroxide macroaggregates (165Dy-FHMA) was used as an agent of radiation synovectomy in an antigen-induced arthritis model in New Zealand white rabbits. Animals were killed up to 6 months after treatment. 165Dy-FHMA was found to have a potent but temporary antiinflammatory effect on synovium for up to 3 months after treatment. Treated knees also showed significant preservation of articular cartilage architecture and proteoglycan content compared with untreated controls, but only during the first 3 months after treatment. In animals killed 3 and 6 months after treatment there were only minimal differences between the treated and untreated knees, indicating that the antiinflammatory effects on synovial tissue and articular cartilage preservation were not sustained.

Comparison of the effects of tenoxicam and mid-laser irradiation on chronic adjuvant arthritis in rats.

OBJECTIVE: This controlled experimental study was designed to compare the effects of a well-known NSAID, tenoxicam, with mid-laser irradiation on the inflammatory component of adjuvant-induced arthritis (AIA). Four groups of animals, each consisting of 10 Wistar rats, were included in the study. The primary concern was not to investigate the antiinflammatory effects of tenoxicam, but to compare the previously proven effects of this drug with a physical therapy agent which might be considered to have fewer side effects and/or contraindications. METHOD: The first group received only 0.1 ml of complete Freund's adjuvant (CFA) and served as the control for the other groups. The 2nd, 3rd and 4th groups, after having CFA injected into the plantar surfaces of their right paws, were treated with tenoxicam alone, mid-laser alone, or with a combination of the two, respectively. RESULTS AND CONCLUSION: All 3 groups showed significantly reduced paw edema compared with the control group. Although the reduction in paw edema in the animals treated with tenoxicam or with tenoxicam+ mid-laser was more significant, mid-laser is proposed as an alternative therapy for symptomatic relief in certain conditions well known to limit the use of NSAIDs.