Metformin and resveratrol suppress type 2 diabetes mellitus-induced articular cartilage damage in rats associated with the inhibition of inflammation and augmentation of proteoglycans / La metformina y el resveratrol suprimen el daño del cartílago articular inducido por la diabetes mellitus tipo 2 en ratas asociado con la inhibición de la inflamación y el aumento de proteoglicanos

SUMMARY: Induction of osteoarthritis (OA) following diabetes is characterized by a sever inflammation of the joints that can lead to disability. The cartilage content of proteoglycans can substantially be reduced, following the induction of diabetes mellitus associated with inflammation as well as knee joint injury, and the antidiabetic drug metformin combined with the anti-inflammatory agent resveratrol can prevent these deleterious effects. Therefore, insulin-independent diabetes, type 2 diabetes mellitus (T2DM) was induced in Albino rats by streptozotocin (STZ) injection (50 mg/kg) after being fed on a high carbohydrate and fat diets for 2 weeks. The protective group of rats which also received a single injection of STZ was treated daily with metformin (Met; 200 mg/kg) and resveratrol (Res; 30 mg/kg) for 12 weeks. Harvested knee joint tissues were prepared for basic histology stain and for proteoglycans staining using light microscopy. Histology images showed in diabetic rats (T2DM) OA development as demonstrated by profound injury to the knee joint and severe decrease of articular cartilage proteoglycans content, which were substantialy protected by Met+Res. Met+Res also significantly (p< 0.0001) decreased diabetes induced glycemia, dyslipidemia, and the inflammatory biomarkers, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high sensitivity C-reactive protein (hs-CRP). In addition, there was a significant correlation between OA and glycemia, dyslipidemia, and inflammation. Collectively, we demonstrate an association between knee joint damage and biomarkers of glycemia, dyslipidemia, and inflammation in diabetes-induced OA, with metformin plus resveratrol providing protective effects.

RESUMEN: La inducción de osteoartritis (OA) después de la diabetes se caracteriza por una inflamación severa de las articulaciones que puede conducir a la discapacidad. El contenido de cartílago de proteoglicanos se puede reducir sustancialmente, luego de la inducción de diabetes mellitus asociada con inflamación y lesión en la articulación de la rodilla sin embargo, el fármaco antidiabético metformina combinado con el agente antiinflamatorio resveratrol puede prevenir estos efectos nocivos. Por lo tanto, se indujo diabetes insulino dependiente, diabetes mellitus tipo 2 (T2DM) en ratas albinas mediante inyección de estreptozotocina (STZ) (50 mg/kg) después de haber sido alimentadas con dietas ricas en carbohidratos y grasas durante 2 semanas. El grupo protector de ratas que también recibió una inyección única de STZ fue tratado diariamente con metformina (Met; 200 mg/kg) y resveratrol (Res; 30 mg/kg) durante 12 semanas. Tejidos de la articulación de la rodilla fueon retirados y teñidos con histología básica y tinción de proteoglicanos usando microscopía óptica. Las imágenes histológicas en ratas diabéticas mostraban (T2DM) desarrollo de OA visualizadas por una lesión profunda en la articulación de la rodilla y una disminución severa del contenido de proteoglicanos del cartílago articular, los cuales estaban sustancialmente protegidos por Met+Res. Met+Res. También disminuyó significativamente (p< 0,0001) la glucemia inducida por la diabetes, la dislipidemia y los biomarcadores inflamatorios, el factor de necrosis tumoral alfa (TNF-α), la interleucina-6 (IL-6) y la proteína C reactiva de alta sensibilidad (PCR-hs). Además, hubo una correlación significativa entre la OA y la glucemia, la dislipidemia y la inflamación. En conjunto, demostramos una asociación entre el daño de la articulación de la rodilla y los biomarcadores de glucemia, dislipidemia e inflamación en la OA inducida por diabetes, con metformina más resveratrol que brindan efectos protectores.

Osteoartrosis. Una revisión de literatura / Osteoarthrosis A literature review

Introducción: la osteoartrosis es la más frecuente de las enfermedades articulares. Objetivo: exponer los referentes bibliográficos que actualmente se refieren a la osteoartrosis en el marco de la revisión de literatura realizada. Desarrollo: como síndrome anatomoclínico se identifica por dolor mecánico que usualmente se relaciona con rigidez y que provoca poco a poco una pérdida o mengua de la función articular. Diversos factores de riesgo se relacionan con el progreso de esta enfermedad entre los que destacan, además de la edad y el sexo femenino, la obesidad, los microtraumas repetitivos en la práctica de determinados deportes y el cumplimiento de actividades profesionales específicas. Conclusiones: el tratamiento de la osteoartrosis debería ejecutarse a nivel de medicina familiar, tanto en el componente preventivo, como en el del control y manejo conservador, instruyendo al paciente en sus cuidados y acciones diarias y operando esquemas de medicamentos, ejercicios, apoyos funcionales como rodilleras, bastones y andadores. La educación médica debe asumir este paradigma, y no solicitar acto seguido la interconsulta a la especialidad cuando el paciente no responde, sin tener en cuenta que el manejo del paciente con artrosis se encuentra distante de la prescripción farmacológica(AU)

Introduction: osteoarthrosis is the most frequent joint disease. Objective: to expose the bibliographic references that currently refer to osteoarthrosis in the framework of the literature review carried out. Development: as anatomoclinic syndrome is identified by mechanical pain that is usually related to stiffness and that gradually causes a loss or decline of joint function. Several risk factors are related to the progress of this disease, among which stand out, in addition to age and female sex, obesity, repetitive microtrauma in the practice of certain sports and compliance with specific professional activities. Conclusions: treatment of osteoarthrosis should be carried out at the level of family medicine, both in the preventive component, as well as in the control and conservative management, instructing the patient in his daily care and actions and operating medication schemes, exercises, functional supports such as knee pads, canes and walkers. The medical education must assume this paradigm, and not immediately request the interconsultation to the specialty when the patient does not respond, without taking into account that the management of the patient with osteoarthritis is distant from the pharmacological prescription(AU)

Involvement of TLR4 in the protective effect of intra-articular administration of curcumin on rat experimental osteoarthritis

Abstract Purpose In view of the principal role of Toll-like receptor 4 (TLR4) in mediating sterile inflammatory response contributing to osteoarthritis (OA) pathogenesis, we used lipopolysaccharide (LPS), a known TLR4 activator, to clarify whether modulation of TLR4 contributed to the protective actions of intra-articular administration of curcumin in a classical rat OA model surgically induced by anterior cruciate ligament transection (ACLT). Methods The rats underwent ACLT and received 50μl of curcumin at the concentration of 1 mg mL-1 and 10 μg LPS by intra-articular injection once a week for 8 weeks. Morphological changes of the cartilage and synovial tissues were observed. Apoptotic chondrocytes were detected using TUNEL assay. The concentrations of IL-1β and TNF-ɑ in synovial fluid were determined using ELISA kits. The mRNA and protein expression levels of TLR4 and NF-κB p65 were detected by real-time PCR and Western blotting, respectively. Results Intra-articular administration of curcumin significantly improved articular cartilage injury, suppressed synovial inflammation and down-regulated the overexpression of TLR4 and its downstream NF-κB caused by LPS-induced TLR4 activation in rat osteoarthritic knees. Conclusion The data suggested that the inhibition of TLR4 signal might be an important mechanism underlying a protective effect of local curcumin administration on OA.

Preparation and physicochemical characterization of meloxicam orally fast disintegration tablet using its solid dispersion

ABSTRACT Meloxicam (MLX) is a non-steroidal, anti-inflammatory drug that is prescribed in the treatment of rheumatoid arthritis and osteoarthritis. MLX is practically insoluble in water and exhibits a slow onset of action. In this study, MLX solid dispersions (MLX SDs) were prepared to improve the water solubility of this poorly water-soluble drug. Then orally disintegrating tablets (ODT) of MLX were developed using MLX SD to decrease the onset of action of this drug. MLX, poloxamer 188, and crospovidone of different ratios were melted in molten poloxamer 188 as a hydrophilic carrier. The optimum SD with the highest saturation solubility in water (13.09±0.34 microgram/mL) consisting of MLX: poloxamer 188: crospovidone in the ratio of 1:2:0 was used for the preparation of MLX ODTs. MLX ODTs were prepared by the direct compression method and optimized by the 23 factorial design. The effect of the superdisintegrant concentration, the mannitol-avicel ratio, and the level of compression force on the disintegration time, hardness, and percent of dissolved MLX from MLX ODTs after 30 min was evaluated. DSC and XRD analysis approved an amorphous form of MLX in SDs. The optimized ODT formulation containing 10% of superdisintegrant, and mannitol and avicel in the ratio of 4:1 respectively was compressed using a high level of compression force. The optimized ODT showed hardness (34.37±2.1 N) and friability (1.26±0.04%). This formulation showed a rapid disintegration in 12.66±2.5 seconds, which 82.66±5.1% of the MLX released within 30 min. MLX ODTs, prepared from MLX SD, could be introduced as a suitable dosage form of MLX with improved solubility and the onset of action.

Using agents that suppress bone remodeling to treat or prevent joint disease: quo vadis?

Treatment of osteoarthritis (OA) with antiremodeling agents has had a mixed record of results. It is likely that remodeling suppression is only effective when used in the early phases of OA, before significant progression. Animal and human studies largely bear this out. Treatment of young mice with a RANKL inhibitor suppresses bone resorption and prevents OA progression. Likewise, bisphosphonate treatments in rodents and rabbits with induced injury or inflammatory arthritis, reduced cartilage degeneration when administered preemptively, but later administration did not. The increased prevalence of OA in women after the menopause, and presence of estrogen receptors in joint tissues, suggests that treatment with estrogens or Selective Estrogen Receptor Modulators may be effective. However, in clinical trials of knee and hip, results show decreased or increased risk for OA, or no effect. Raloxifene had positive effects in animal models, but no effect in human studies. More recent potential treatments such as strontium ranelate or cathepsin-K inhibitors may be effective, but may work directly on the cartilage rather than through their well-known effects on bone. The conclusion from these studies is that anti-remodeling agents must be administered pre-emptively or in the very early stages of disease to be effective. This means that better imaging techniques or identification of early structural changes in bone that occur before progressive cartilage destruction must be developed. (AU)

A influência da suplementação de sulfato de condroitina na dor e nos aspectos funcionais associados à osteoartrose / Influence of chondroitin sulfate supplementation in pain and functional aspects associated with osteoarthritis

Introdução: A osteoartrose é a principal causa de limitação da funcionalidade e incapacidade nos idosos. Dentre os tratamentos farmacológicos está a suplementação com sulfato de condroitina. Objetivo: Realizar uma revisão sistemática sobre a influência do sulfato de condroitina na dor e aspectos funcionais associados à osteoartrose. Métodos: Foram utilizados os descritores "osteoarthritis" e "chondroitin". Os artigos foram selecionados de forma independente e cega, por dois pesquisadores. Foram incluídos somente ensaios clínicos primários, escritos na língua portuguesa, inglesa e espanhola entre 2005 a 2013. A escala PEDro foi utilizada como instrumento de avaliação. Resultados: Foram encontrados 1.916 estudos, permanecendo nove artigos para a análise. Dos nove analisados, quatro mostraram a eficácia da suplementação do sulfato de condroitina na redução da dor e da incapacidade funcional, enquanto cinco investigações não mostraram efeitos estatisticamente significantes. Conclusões: A influência do sulfato de condroitina na dor e aspectos funcionais na osteoartrose permanece questionável.

Introduction: Osteoarthritis is the leading cause of limitation of functionality and disability in the elderly. The supplementation with chondroitin sulfate is among the pharmacological treatments. Objective: To conduct a systematic review of the influence of chondroitin sulfate on pain and functional aspects associated with osteoarthritis. Methods: The keywords "osteoarthritis" and "chondroitin" were used. The articles were selected independently and blindly by two researchers. Only primary clinical trial, written in Portuguese, English and Spanish in the period between 2005 to 2013 were included. The PEDro scale was used as an evaluation tool. Results: A total of 1.916 studies with appropriate descriptors were found, and nine of these papers remained for analysis. Of these nine studies analyzed, four showed the effectiveness of supplementation of chondroitin sulfate in reducing pain and functional disability, while five studies showed no statistically significant effects. Conclusions: The influence of chondroitin sulfate in pain and functional aspects in osteoarthritis remains questionable.

Reconstrucción de ligamento cruzado anterior: resultados funcionales / Reconstruction of the anterior cruciate ligament: functional results

Introducción: Las lesiones del ligamento cruzado anterior (LCA) son muy frecuentes y no tratarlas aumenta el riesgo de osteoartrosis en la rodilla, por lo que hoy se recomienda la reconstrucción quirúrgica sobre todo en gente activa como en el grupo de estudio. Materiales y Métodos: Se realizó un estudio observacional, descriptivo. Se evaluaron 48 pacientes a quienes se les realizó reconstrucción de LCA por abordaje único, con injerto autólogo, heterólogo o híbrido fijados con Sistemas Aperfix Cayenne, entre noviembre 2011 y octubre 2012. Solo se incluyeron pacientes con un mínimo de 6 meses post-operatorio los que fueron evaluados con las Escalas de Lysholm y Tegner. Resultados: La escala de Lysholm mostró resultados excelentes y buenos en un 68.7 por ciento y regulares en un 31 por ciento. El puntaje de la escala de Tegner pasó de 3,1 en el preoperatorio a 5.3 en el posoperatorio. La única complicación observada fue la sinovitis. Discusión: Se puede afirmar que los resultados funcionales de las Reconstrucciones de LCA fueron buenos independientemente del tipo de Injerto utilizado; resultados bastantes similares a los reportados en la literatura mundial.

Introduction: Anterior cruciate ligament injury (ACL) is one of the most common and not treating it increases the risk of osteoarthrosis in the knee, so nowadays its surgical reconstruction is recommended especially in active people. Methods: A retrospective study was carried out in order to determine the outcome of all patients who underwent an ACL reconstruction surgery using autograft, allograft or Hybrid graft fixed with Aperfix Cayenne System, from November 2011 to October 2012. Only were included patients with a minimum of 6 months post-operative which were evaluated with the Lysholm and Tegner scales. Results: Results were graded good and excellent in 68.7 per cent of the patients and fair in 31 per cent according to Lysholm. Furthermore, an increase in Tegner scale was well documented. The only complication observed in patients was a postoperative synovitis in some of them. Discussion: Our results has shown that the functional results was good, similar to those found up in overall existing medical literature.

Evaluation of a Community Health Practitioner Self-care Program for Rural Korean Patients with Osteoarthritis

PURPOSE: The purpose of this study was to evaluate a self-care program for elders with osteoarthritis managed by primary health care workers, Community Health Practitioners (CHPs), in rural Korea. METHODS: The self-care program, consisting of 7 areas, was evaluated with a randomized experimental study for patients over age 60 with osteoarthritis in which 150 participants in the experimental group and 140 in the control group were compared. The self-care program was implemented for six weeks, 2 hours per week, at community health posts by CHPs. Data were collected using an interview questionnaire given by the CHPs and laboratory tests before and after the intervention for both groups. Propensity score matching analysis was done to test effectiveness after controlling for confounding variables. RESULTS: The intervention group showed a significant decrease in the number of painful joints (p<.001) and a significant increase in self-care ability (p<.05) compared to the control group. CONCLUSION: Study results indicate that training and utilizing primary health care workers in rural areas is valuable in increasing the generalization and continuity of intervention programs. As arthritis should be managed life-long, CHP directed self-care programs are useful interventions for rural elders with arthritis to learn self-care management.

Lombalgia em eqüinos / Back pain in horses

As lombalgias, sejam elas de origem primária ou secundária, são uma causa importante para a queda de desempenho atlético em eqüinos, mas o tamanho e a biomecânica complexa dificultam o diagnóstico e tratamento desta enfermidade. Sendo assim, o conhecimento da anatomia desta região é de grande importância para a semiologia toracolombar. O diagnóstico das lombalgias se faz por meio do exame físico e dos exames complementares, representados pelos métodos de diagnóstico por imagem, tais como a radiografia, a ultra-sonografia e a termografia. As principais afecções causadoras das lombalgias nos eqüinos são o contato entre processos espinhosos, a desmite supraespinhosa, a osteoartrite dos processos articulares e lesões dos corpos e discos vertebrais. Os principais tratamentos utilizados para estas lesões são os antiinflamatórios não esteroidais, infiltrações locais, acupuntura, fisioterapia, manejo do treinamento e cirurgia.

Back pain, whether they have a primary or secondary origin, is a important cause to the drop of the equine performance , but the size and the complex biomechanics make it difficult to diagnosis and treat the injury. As it is, the knowledge of this anatomic site is of great importance to the thoracolumbar examination. The diagnosis of back pain is done through physical examination and complementary exams, represented by the image methods of diagnosis, such as radiography, ultrasonography and thermography. The most important lesions that cause the back pain in an equine are impingement of the dorsal spinous processes, desmopathy of the supraespinous ligament, osteoarthritis of the articular processes and lesions of the vertebral discs and body. The most common treatments to back pain are the non-steroidal anti-inflammatory drugs, local injections, acupuncture, physiotherapy, training management and surgery.

Alterações músculo-esqueléticas na terceira idade / Changes muscle-eskeletal in the third age

Daremos uma atenção especial à osteoporose, à osteoartrose, à fibromialgia e à prevenção de quedas. No idoso, estas constituem importante fator de risco para a morbi-mortalidade. Existem vários fatores de risco para as quedas, como problemas ortopédicos, alterações de visão, alterações do equilíbrio por causa de doenças labirínticas, doenças neurológicas e circulatórias, fraqueza e diminuição dos reflexos. O uso de medicamentos pode afetar o equilíbrio e obstáculos no meio ambiente também podem favorecer quedas

Osteoartritis: un problema común en la práctica diaria / Osteoarthritis: a problem common in the practice daily

La osteoartritis representa la enfermedad reumática más común en humanos y diferentes estudios epidemiológicos han establecido claramente que su prevalencia se incrementa con la edad. Se pueden encontrar evidencias radiológicas de osteoartritis en alrededor del 80 por ciento de sujetos mayores de 55 años. Los cambios patológicos principales ocurren en el cartílago articular y el hueso subcondral. El daño estructural del cartílago produce erosiones en su superficie y la proliferación de cartílago y hueso ocasiona la formación de osteofitos. Desde que no existen pruebas de laboratorio que definan la presencia de osteoartritis, el diagnóstico se basa en el cuadro clínico y los hallazgos radiológicos. El examen del líquido sinovial es normal o se pueden encontrar cambios inflamatorios leves. El objetivo del tratamiento se alcanza combinando diferentes medidas terapéuticas que incluyen educación del paciente, fisioterapia y rehabilitación, uso racional de fármacos y terapia intralesional.

Effect of sodium hyaluronate on prevention of osteoarthritis

The changes in the surface of articular cartilage of femoral condyle from rabbits were evaluated after degenerative changes were made by the technique advocated by Hulth. The medial collateral and both cruciate ligaments were excised, and a medial menisectomy was done. Then the right knee joint was injected with 1 ml of Na-hyaluronate gel every two weeks. The animals were sacrificed at two, four, six, eight, or sixteen weeks postoperatively. After sacrifice, the medial femoral condyle was excised and prepared for the light microscopic and scanning electron microscopic study. At eight to sixteen weeks, there were chondrocyte clones with clefts to the radial zone and increased loss of the height of articular cartilage on the control side; but, on theexperimental side there was a significant delay and lessening of the arthriticresponse. The biocompatibility and the protective effect of joint degeneration of this device make this material a valuable adjuvant in the treatment ofosteoarthritis and the traumatized joints.