Plant-Based Approaches for Rheumatoid Arthritis Regulation: Mechanistic Insights on Pathogenesis, Molecular Pathways, and Delivery Systems.

Rheumatoid arthritis (RA) is classified as a chronic inflammatory autoimmune disorder, associated with a varied range of immunological changes, synovial hyperplasia, cartilage destructions, as well as bone erosion. The infiltration of immune-modulatory cells and excessive release of proinflammatory chemokines, cytokines, and growth factors into the inflamed regions are key molecules involved in the progression of RA. Even though many conventional drugs are suggested by a medical practitioner such as DMARDs, NSAIDs, glucocorticoids, etc., to treat RA, but have allied with various side effects. Thus, alternative therapeutics in the form of herbal therapy or phytomedicine has been increasingly explored for this inflammatory disorder of joints. Herbal interventions contribute substantial therapeutic benefits including accessibility, less or no toxicity and affordability. But the major challenge with these natural actives is the need of a tailored approach for treating inflamed tissues by delivering these bioactive agentsat an appropriate dose within the treatment regimen for an extended periodof time. Drug incorporated with wide range of delivery systems such as liposomes, nanoparticles, polymeric micelles, and other nano-vehicles have been developed to achieve this goal. Thus, inclinations of modern treatment are persuaded on the way to herbal therapy or phytomedicines in combination with novel carriers is an alternative approach with less adverse effects. The present review further summarizes the significanceof use of phytocompounds, their target molecules/pathways and, toxicity and challenges associated with phytomolecule-based nanoformulations.

Effect of Curcuma longa extract on serum inflammatory markers and MRI-based synovitis in knee osteoarthritis: secondary analyses from the CurKOA randomised trial.

BACKGROUND: Curcuma longa (CL) extract is modestly effective for relieving knee symptoms in knee osteoarthritis (OA) patients; however, its mechanism of action is unclear. PURPOSE: We aimed to determine the effects of CL treatment on serum inflammatory markers over 12 weeks and to explore its potential effects on synovitis assessed by contrast-enhanced magnetic resonance imaging (CE-MRI) of the knee. METHODS: Secondary analyses were conducted on the CL for knee OA (CurKOA) trial, which compared CL (n = 36) and placebo (n = 34) over 12 weeks for the treatment of knee OA. Systemic inflammatory markers (TNFα, IL6, and hsCRP) and a cartilage extracellular matrix degradative enzyme (MMP-3) were measured. A subgroup of participants (CL, n = 7; placebo, n = 5) underwent CE-MRI at baseline and a 12-week follow-up. RESULTS: Over 12 weeks, there were no between-group differences in change in hsCRP, IL-6, and TNFα levels. MMP-3 levels decreased in both CL (-1.31 ng/ml [95%CI: -1.89 to -0.73]) and placebo (-2.34 ng/ml [95%CI: -2.95 to -1.73]) groups, with the placebo group having a slightly greater decrease (1.03 ng/ml [95%CI: 0.19 to 1.88]). Most (10 of 12) sub-study participants had normal synovial thickness scores at baseline. One participant had mild synovitis in each of the placebo and CL groups. Synovitis status was stable for all except two participants, one each in the CL and placebo group, whose synovitis score increased. CONCLUSION: This is the first study that explored the effect of CL treatment on local and systemic inflammation using biochemical markers and CE-MRI outcomes on knee OA patients. Secondary analyses from this pilot study suggest that CL is unlikely to have clinically significant effects on systemic (inflammatory and cartilage) or local synovitis (CE-MRI) biomarkers compared to placebo. The mechanism of action for CL effect on pain remains unclear.

Evidencia científica del tratamiento ortopodológico en pie afectado por artritis reumatoide / Evidence of orthopodiatric treatment affected by rheumatoid arthritis on foot

Antecedentes: La artritis reumatoide afecta más a mujeres. La prevalencia en nuestro país es de 0.5%. Se debe abordar mediante un equipo multidisciplinar. Los signos característicos en el pie son sinovitis de las articulaciones, entesitis, nódulos reumatoides y vasculitis. Las modalidades de tratamiento conservador son: ortesis, calzado, estiramientos, terapia manual e incluso ejercicios terapéuticos mediante Tai-chi. Objetivos: Valorar la evidencia científica sobre el tratamiento conservador del pie reumático mediante ortesis plantares y calzado terapéutico. Conocer los últimos avances y que opción es la más indicada para tratar esta patología que afecta al pie. Material y métodos: Se ha realizado una revisión bibliográfica de los últimos 15 años en Pubmed. Resultados: Se ha encontrado relación entre el dolor de antepié, subluxación metatarsofalángica y erosión del cartílago articular con el aumento de presión a nivel metatarsal plantar lo que justifica la realización de tratamiento ortopodológico encaminado a reducir la misma. El tratamiento conservador está enfocado a la utilización de ortesis y de zapato terapéutico para mejorar el dolor, la marcha y la funcionalidad. Hay evidencia científica para tratar la metatarsalgia con diferentes tipos de ortesis, que no solo ayudan a mejorar el dolor sino que además reducen el nº de articulaciones inflamadas. La combinación con zapato terapéutico con o sin modificaciones externas produce mejores resultados. Conclusión: Existe escasa evidencia científica sobre el uso de tratamiento ortopodológico para el pie reumático pero se han encontrado algunos artículos que avalan su eficacia, por lo que es imprescindible realizar estudios en este campo (AU)

Background: Rheumatoid arthritis affects more women. The prevalence in our country is 0.5%. It should be approached by a multidisciplinary team. Characteristic foot signs' are synovitis of joints, enthesitis, rheumatoid nodules and vasculitis. The conservative treatment modalities are: orthotics, footwear, stretching, manual therapy and therapeutic exercises even by Tai-chi. Objectives: To evaluate the scientific evidence on the conservative treatment of rheumatoid foot with orthotics and therapeutic footwear. Aware of progress and that is the most suitable option for treating this disease that affects the feet. Material and methods: We carried out a literature review of the past 15 years in Pubmed. Results: We found the relationship between pain forefoot metatarsophalangeal subluxation and erosion of articular cartilage with increasing pressure to plantar metatarsal level which justifies conducting orthosis treatment aimed at reducing it. Conservative treatment is aimed at the use of orthoses and shoe therapy to improve pain, gait and functionality. There is scientific evidence for treating metatarsalgia with different types of orthotics that not only help improve the pain but also reduce the number of swollen joints. The combination with therapeutic shoe with or without external changes produces better results. Conclusion: There is little scientific evidence on the use of orthosis treatment for rheumatoid foot but found some articles that support its effectiveness, so it is essential to carry out studies in this field (AU)

Evidence of the symptomatic and structural efficacy of methotrexate in daily practice as the first disease-modifying drug in rheumatoid arthritis despite its suboptimal use: results from the ESPOIR early synovitis cohort.

OBJECTIVE: To describe the use of MTX in early arthritis (EA) in daily clinical practice and to evaluate its 6-month symptomatic efficacy and 12-month structural efficacy. METHODS: Patients included in the French observational ESPOIR cohort were assessed. Evaluation of the symptomatic and structural efficacy was performed by generalized linear regression after adjustment on propensity score (PS) in the group of patients receiving at least 3 months of MTX vs the ones receiving any other treatment except LEF, SSZ or TNF inhibitors. RESULTS: Within the first 6 months of follow-up of 777 EA patients, 59% received a DMARD, which was MTX in 68% (N = 313) of patients. The mean dose of MTX was 12.7 ± 3.8 mg/week. Only 53.7% of the patients received folic acid supplementation. MTX was initiated in patients with more active and severe disease. At 6 months, in unadjusted analysis, patients starting MTX had a significantly higher DAS-28 (3.58 vs 3.23; P = 0.001) and a significantly higher HAQ (0.60 vs. 0.48; P = 0.01) compared with controls. After adjustment by PS, there were no significant differences. Adjustment for the PS also revealed a statistically significant decrease in the radiological progression at 12 months in the MTX group [total Sharp-van der Heijde score (SHS), 1.05 ± 0.29 vs 2.02 ± 0.29, P = 0.025]. CONCLUSION: This study confirms the symptomatic and structural efficacy of MTX in EA in daily practice despite the non-optimal use of MTX, including low doses and infrequent concomitant folic acid supplementation.

Interexaminer reliability of T2-weighted magnetic resonance imaging for lumbar bright facet sign.

OBJECTIVE: The aims of this study were to characterize the bright facet response within the lumbar spine, to identify a constellation of findings associated with the response, and to quantify the interexaminer agreement on the previous objectives. METHODS: A retrospective study of lumbar magnetic resonance images obtained on 105 (N = 105) adult subjects (62 men and 43 women; age range, 18-84 years; mean age, 46.51 +/- 16.01 years) were reviewed by 2 musculoskeletal radiologists for the presence of high signal within the facet articulations (bright facet response) on fast spin echo T2-weighted images. RESULTS: Of the 630 lumbar facet articulations imaged (L3/L4 through L5/S1), 340 (54%) and 346 (55%) respectively, per examiner, did show a bright facet response. Interexaminer agreement with respect to the level and grading of a bright facet response was almost perfect with kappa ranging from 0.85 to 0.91 (SE, 0.06). Prevalence of bright facet responses averaged 40.5% at L5/S1, 56.5% at L3/L4, and 66.5% at the L4/L5 level. There was an association with degenerative facet and disk changes. CONCLUSION: The bright facet response was a common phenomenon on T2-weighted magnetic resonance imaging of the lumbar spine in these cases. There was sufficient agreement with respect to the presence and extent of the bright facet response to conclude that the examiners' determinations were not made by random chance. There exist sufficient repeatability and reliability that a single descriptive term can be applied to unify the bright facet response, the bright facet sign.

Artritis séptica por Salmonella no typhi: presentación de un caso y revisión de la bibliografía / Non-typhi Salmonella septic arthritis: case report and review of the literature

La artritis séptica por Salmonella no typhi representa menos del 2 por ciento del total de las artritis sépticas1. El serotipo etiológico más frecuente es Salmonella enteritidis. Su clínica, precedida o no de una gastroenteritis, no difiere de otras artritis sépticas, y se presenta con fiebre y sinovitis monoarticular, habitualmente en rodilla, cadera y hombro. La inmunosupresión (terapéutica, virus de la inmunodeficiencia humana [VIH], lupus eritematoso sistémico [LES], etc.) es el principal factor de riesgo en su desarrollo. La drepanocitosis, la hemofilia, las neoplasias y las edades extremas de la vida también predisponen a su aparición. El diagnóstico se realiza por cultivo de líquido sinovial. El tratamiento está condicionado por las resistencias descritas a múltiples antibióticos, incluso a los más actuales, como son las fluoroquinolonas. Las complicaciones locales más frecuentes son la limitación residual funcional y la osteomielitis. El pronóstico, marcado por la enfermedad de base, presenta una elevada mortalidad (AU)

La mano reumatológica: exploración y tratamiento. Revisión / The rheumatoid hand: assessment and treatment. Review

Puesto que la mano reumatológica es motivo de atención fisioterapéutica diaria, se revisarán en este artículo aquellos aspectos que puedan ser de utilidad para su valoración y posterior tratamiento. Metodología: Revisión bibliográfica en distintas bases de datos (Cochrane, PEDro, Medline y OT seeker), libros y revistas de interés. Resultados: En cuanto a la valoración no existen escalas específicas validadas en España. Las herramientas utilizadas habitualmente por el fisioterapeuta (fuerza, grado de edema, dolor, amplitud articular, destreza para las actividades de la vida diaria) son aconsejadas por algunos autores como medida de la evolución del paciente. Se discuten otros índices de valoración funcional más específicos. En cuanto al tratamiento, las revisiones sistemáticas de los métodos propuestos por la literatura clásica no son nada concluyentes. A pesar de estas limitaciones metodológicas de los trabajos analizados se concluye que los métodos que cuentan con mayor evidencia científica para su aplicación en la mano reumatológica son el láser, la electroestimulación, la electroacupuntura y los ultrasonidos. Conclusiones: Faltan estudios que den soporte a la actividad del fisioterapeuta tanto referente a las escalas de valoración como a las modalidades de tratamiento (AU)

32P Radiosynoviorthesis in children with hemophilia.

BACKGROUND: This study was performed to prospectively evaluate the safety, efficacy, and cost of injecting P-colloid into joints of children with hemophilia and synovitis to decrease the rate of joint bleeding. PATIENTS AND METHODS: Eligibility included a diagnosis of hemophilia, history of more than six hemorrhages into a joint within a 6-month period, and evidence of synovitis by objective imaging. With written, informed consent, 0.25 to 1.0 mCi of P-colloid was injected into the problem joints. Safety was monitored by external beta-scanning and physical assessment. Efficacy was determined by analysis of the change in joint hemorrhage frequency from 6 months before and up to 96 months after the injection using a signed-rank test. Physical assessment and pain assessment were analyzed similarly using values obtained within 1 week before and 6 months after the radiosynoviorthesis. Cost was modeled using charges from the authors' institution in relation to existing alternative therapies. RESULTS: One hundred injections were given into 91 joints in 59 children. Seven children had high-titer neutralizing antibodies to factor VIII or IX. Nine children were infected with HIV. Joints injected included 44 ankles, 19 knees, 27 elbows, and 1 shoulder. Nine joints required reinjection. All children showed a significant decrease in bleeding rate (P < 0.0001) and pain (P = 0.03), with improved physical function (P = 0.02). In one child acute lymphocytic leukemia developed, but it was judged unrelated to the two P injections that he had received 3 and 10 months before the leukemia diagnosis. There were no cases of bleeding, infection, or inflammation caused by the injection. Cost was substantially less than medical and surgical alternatives. CONCLUSIONS: Radiosynoviorthesis is effective in limiting the frequency of joint hemorrhage, decreasing pain and improving function in children with hemophilia. However, long-term safety studies are needed.

Low frequency TENS is less effective than high frequency TENS at reducing inflammation-induced hyperalgesia in morphine-tolerant rats.

Both transcutaneous electrical nerve stimulation (TENS) and morphine are commonly used for relief of pain. Extensive research has been done on the effectiveness of each of these two methods for pain relief when given independently. However, very little literature exists examining the effectiveness of their combined use. Systemically administered morphine activates mu opioid receptors and when administered for prolonged periods results in analgesic tolerance. Low (4 Hz) and high (100 Hz) frequency TENS activate mu- and delta-opioid receptors, respectively, It is thus possible that TENS would be less effective in morphine-tolerant subjects. The current study investigated the effectiveness of high- and low-frequency TENS in the reversal of hyperalgesia in inflamed rats that were morphine-tolerant. Morphine tolerance was induced by subcutaneous implantation of morphine pellets over 10 days. Knee joint inflammation was induced by injection of kaolin and carrageenan into the knee joint cavity. Secondary heat hyperalgesia was tested by measuring the paw withdrawal latency to radiant heat (1) before pellet implantation (either morphine or placebo), (2) after pellet implantation and before inflammation, (3) after inflammation and (4) after TENS. Both high (100 Hz) and low (4 Hz) frequency TENS caused nearly 100% inhibition of secondary hyperalgesia in animals receiving placebo pellets. In contrast, the hyperalgesia in morphine-tolerant animals with knee joint inflammation was unaffected by low frequency TENS but fully reversed by high frequency TENS. These results suggest that patients who are tolerant to morphine may respond better to high frequency TENS than to low frequency TENS.

Manipulation under joint anesthesia/analgesia: a proposed interdisciplinary treatment approach for recalcitrant spinal axis pain of synovial joint origin.

BACKGROUND: Manipulation under joint anesthesia/analgesia (MUJA) is an approach to treatment for patients with chronic, recalcitrant spinal axis pain of synovial joint origin. MUJA is the synthesis of fluoroscopically and corticosteroid agents with targeted, manual mobilizations and/or manipulations of the injected joint(s). DISCUSSION: MUJA should be viewed with guarded optimism because its success is based solely on anecdotal experience. Many physicians (specializing in targeted intraarticular "blocks" of spinal synovial joints) and chiropractors (specializing in manual mobilization and manipulation of spinal synovial joints) in the Tyler, Texas, area have treated more than 1000 patients over a 7-year period with the MUJA protocol. This protocol includes treatment of the atlanto-occipital and lateral atantoaxial joints of the upper cervical spine, the zygapophysial joints of the cervical spine from C2-3 to C6-7, the thoracic spine and the lumbar spine, and the pelvic sacroiliac joints. CONCLUSION: The following patient types are suitable candidates for MUJA: patients with dominant spinal axis pain who have been unable to progress despite the passage of sufficient time (>2 months) and the delivery of prior treatments, including spinal manipulative therapy; patients with pain so severe that standard manipulative therapy cannot be delivered with technical success; and patients with complex problems in whom the diagnosis of synovial joint-mediated spinal pain must be established before the safe delivery of manipulative therapy.

Acceleration of experimental lapine osteoarthritis by calcium pyrophosphate microcrystalline synovitis.

OBJECTIVE: To investigate the effects of chronic calcium pyrophosphate dihydrate (CPPD) synovitis on the development of osteoarthritic (OA) lesions in an animal model. METHODS: OA was induced in the right knees of 30 male New Zealand white rabbits by partial lateral meniscectomy and section of the fibular collateral and sesamoid ligaments (PLM/LS), followed by 8 weekly intraarticular (IA) injections of 1 mg (low-dose) or 10 mg (high-dose) of CPPD crystals in 3 sets of experiments (10 rabbits each). The contralateral left knees served as controls: experiment 1 PLM/LS alone, experiment 2 8 weekly IA injections of CPPD crystals alone, and experiment 3 sham surgery plus 8 weekly IA injections of CPPD crystals. RESULTS: At 8 weeks, repeated IA injections of low-dose and high-dose CPPD crystals into meniscectomized right knees resulted in more severe OA than in meniscectomized but noninjected left knees (experiment 1) (P = 0.003 and P = 0.001, respectively). One-fourth of the meniscectomized knees (11 of 40), both CPPD-injected and noninjected, showed embedded synovial cartilage shards. CONCLUSION: The data demonstrate a worsening effect of chronic CPPD crystal-induced synovitis on experimental OA produced in the rabbit knees by PLM/LS, and support a possible role for CPPD microcrystalline inflammation in the progression of OA lesions in clinical CPPD crystal deposition disease.

Day case arthroscopy under local anaesthesia.

A prospective study of the effectiveness of local anaesthesia in arthroscopy of the knee was performed in 212 consecutive patients. Arthroscopic surgery was undertaken successfully in 121 cases (57%), including meniscectomy and drilling of osteochondral defects. Dynamic evaluation of the patellofemoral joint articulation was possible and demonstration of pathological abnormalities was felt to be beneficial by some patients. The method described is safe, reliable, confers good postoperative analgesia and enables physiotherapy to begin immediately. Conversion to general anaesthesia was necessary in one case due to pain localised to a stiff and osteoarthritic hip. Intra-articular haemorrhage was found to be a problem in one case with synovitis. Only ten patients complained of moderate pain, none had severe pain. Local anaesthesia is contraindicated in cases with ipsilateral osteoarthritis of the hip or with significant synovitis of the knee. This technique is particularly suited to day case surgery.

Rheumatological lesions in individuals with human immunodeficiency virus infection.

One hundred and twenty-three patients with human immunodeficiency virus infection have been referred to rheumatologists at our hospitals between October 1985 and April 1989 because of musculoskeletal symptoms. Thirty-four homosexual men presented with acute, peripheral, non-erosive arthritis (mean number of four joints affected) with the knees being involved in 23. Other features developing concurrently with arthritis included psoriasis, keratoderma blenorrhagica, plantar fasciitis, urethritis, conjunctivitis and anterior uveitis. Four of five patients investigated were HLA-B27-positive; none of 15 patients tested had raised titres of rheumatoid or antinuclear factors. Various infections were associated with the onset of arthritis and two patients with a recent history of diarrhoea had serological evidence of yersinia infection. No micro-organisms were identified within the joint except for HIV itself. At the time of onset of arthritis four of these individuals had the acquired immunodeficiency syndrome (AIDS); 11 were not known to be HIV-positive before testing which was performed following referral for arthritis. Six patients have since developed AIDS and four have died. In 15 individuals, including those who progressed to AIDS, joint symptoms have been severe, persistent and poorly responsive to non-steroidal anti-inflammatory drugs. In only five patients has the arthritis been known to resolve. Synovitis has also been seen in two women: in one of these HIV infection was thought to have been acquired through intravenous drug abuse. Other rheumatic lesions included myalgia/myositis, non-inflammatory peripheral arthritis, spinal pain, soft tissue lesions, arthralgia or myalgia of unknown cause and infective lesions including septic arthritis and bony infection due to histoplasmosis and atypical mycobacterial infection. It appears likely that HIV infection is a risk factor for the development of seronegative arthritis and other rheumatic lesions.

[1,25-(OH)2-D3 treatment of hypophosphoremic osteomalacia associated with villonodular synovitis]. / Traitement par le 1,25 (OH)2 D3 d'une ostéomalacie hypophosphorémique associée à une synovite villonodulaire.

The authors report a case of hypophosphoremic osteomalacia due to a soft tissue tumor. This case confirm 1,25 (OH)2 cholecalciferol deficiency. Treatment with phosphorus and 1,25 (OH)2 cholecalciferol cured osteomalacia. Accountable tumor (villonodular synovitis) had never been described previously.