Histone demethylase JMJD3 downregulation protects against aberrant force-induced osteoarthritis through epigenetic control of NR4A1 / 国际口腔科学杂志·英文版

Osteoarthritis (OA) is a prevalent joint disease with no effective treatment strategies. Aberrant mechanical stimuli was demonstrated to be an essential factor for OA pathogenesis. Although multiple studies have detected potential regulatory mechanisms underlying OA and have concentrated on developing novel treatment strategies, the epigenetic control of OA remains unclear. Histone demethylase JMJD3 has been reported to mediate multiple physiological and pathological processes, including cell differentiation, proliferation, autophagy, and apoptosis. However, the regulation of JMJD3 in aberrant force-related OA and its mediatory effect on disease progression are still unknown. In this work, we confirmed the upregulation of JMJD3 in aberrant force-induced cartilage injury in vitro and in vivo. Functionally, inhibition of JMJD3 by its inhibitor, GSK-J4, or downregulation of JMJD3 by adenovirus infection of sh-JMJD3 could alleviate the aberrant force-induced chondrocyte injury. Mechanistic investigation illustrated that aberrant force induces JMJD3 expression and then demethylates H3K27me3 at the NR4A1 promoter to promote its expression. Further experiments indicated that NR4A1 can regulate chondrocyte apoptosis, cartilage degeneration, extracellular matrix degradation, and inflammatory responses. In vivo, anterior cruciate ligament transection (ACLT) was performed to construct an OA model, and the therapeutic effect of GSK-J4 was validated. More importantly, we adopted a peptide-siRNA nanoplatform to deliver si-JMJD3 into articular cartilage, and the severity of joint degeneration was remarkably mitigated. Taken together, our findings demonstrated that JMJD3 is flow-responsive and epigenetically regulates OA progression. Our work provides evidences for JMJD3 inhibition as an innovative epigenetic therapy approach for joint diseases by utilizing p5RHH-siRNA nanocomplexes.

Descripción histológica de los daños ocasionados por monoiodo acetato de sodio en articulación humeral de rata / Histologyc description of monosodium iodoacetate damage in rat humeral joint

La inyección con monoiodo acetato de sodio (MIA) es ampliamente utilizada para producir osteoartritis en diversas articulaciones. El objetivo fue describir los daños histológicos provocados por MIA en la articulación humeral de rata. Se inyectó 0,1 mL de mezcla de 0,5 mg de MIA disuelto en 10 mL de solución fisiológica en la articulación humeral izquierda de 21 ratas SpragueDawley. Como control se utilizó la articulación derecha de cada rata. Se realizó la eutanasia a las 4, 8 y 12 semanas post inyección en grupos de 7 ratas. Los miembros mantenidos en formalina tamponada al 10% fueron descalcificados con EDTA por tres meses. Para la evaluación histológica se realizó la inclusión en parafina y se realizaron cortes coronales de 5 µm de espesor, para posterior tinción con azul de toluidina. En el cartílago sano, se observó una superficie lisa sin fisuras, todas las células de las zonas del cartílago se observaron normales. Se observaron cambios en el cartílago articular a partir de las 4 semanas post inyección, los condrocitos de la zona radial hipertróficos con gran producción de proteoglicanos. A las 12 semanas post inyección, se observa un gran deterioro, el espacio articular se ve disminuido, La superficie del cartílago se observa con fisuras y grietas que llegan hasta la zona radial. Las células alrededor de estas fisuras han desaparecido. Se observa una pérdida prominente de proteoglicanos debido a la débil tinción con azul de toluidina. La inyección articular con MIA produce lesiones similares a la OA. La gran ventaja de la OA inducida por MIA, es la facilidad de su aplicación y la rapidez en la progresión de OA.

Injection with monoiode sodium acetate (MIA) is widely used to produce osteoarthritis in various joints. The aim of this work was to describe the histological damage caused by MIA in the rat humeral joint; 0.1 mL of 0.5 mg mixture of MIA dissolved in 10 mL of physiological solution was injected into the left humeral joint of 21 Sprague-Dawley rats. As a control, the right joint of each rat was used. Euthanasia was performed at 4, 8 and 12 weeks post injection in groups of 7 rats. The samples maintained in 10 % buffered formalin were descaled with EDTA for three months. For histological evaluation, paraffin inclusion was performed and 5 µm thick coronal cuts were made for subsequent staining with toluidine blue. In the healthy cartilage, a smooth surface was observed, all cells in the cartilage areas were normal. Changes in articular cartilage were observed after 4 weeks post injection, hypertrophic radial chondrocytes with high proteoglycan production. At 12 weeks post injection, a great deterioration was observed, the articular space was diminished. The surface of the cartilage was observed with fissures and cracks that reach the radial zone. The cells around these fissures have disappeared. A prominent loss of proteoglycans was observed due to weak toluidine blue staining. Joint injection with MIA produced lesions similar to OA. The great advantage of the OA induced by MIA, is the ease of its application and the rapidity in the progression of OA.

Hidrogeles de polimerizacion in situ para la regeneracion de cartilago articular / In-situ hydrogel polymerization for articular cartilage regeneration

Una significativa cantidad de adultos jóvenes activos sufre lesiones condrales focales. Estas lesiones, si no se tratan, pueden progresar hacia la artrosis, que es una de las principales enfermedades musculoesqueléticas debilitantes y de gran carga económica que afectan a toda sociedad. Pese a los tratamientos quirúrgicos disponibles para la reparación de defectos condrales focales sintomáticos que mejoran la calidad de vida a mediano plazo, hay un mayor riesgo de progresión hacia la artrosis prematura. Los tratamientos biológicos (células madre, bioingeniería tisular) han avanzado a grandes pasos en los últimos años. La bioingeniería es un área que ha progresado en la regeneración de cartílago articular y que potencialmente podría progresar en el terreno de tratamientos articulares, promoviendo la regeneración y evitando la degeneración. Las células madre y los hidrogeles pueden proveer un tejido símil biológico de comportamiento dinámico-funcional equivalente que induce la regeneración tisular al ser degradado y reemplazado gradualmente. El abordaje consiste en colocar un hidrogel precursor o un biomaterial tridimensional impreso dentro del defecto condral por ocupar para inducir la regeneración. Esta revisión se focaliza en el uso actual y futuro de hidrogeles y bioimpresión tridimensional para la regeneración de cartílago articular en el tratamiento de lesiones condrales focales y proporciona datos preliminares de dos estudios piloto en animales. Nivel de Evidencia: V

A significant number of young active adults are affected by focal chondral lesions. These lesions, if left untreated, will progress to osteoarthritis (OA). OA is one of the main debilitating musculoskeletal diseases and leads to a high economic and social burden. Despite surgical cartilage repair for focal chondral lesions, which improve patient-reported outcomes at short- and mid-term, there is a risk of early OA progression. Biological treatments (i.e., stem-cell therapy, bioengineering) have made great progress in the last years. Tissue engineering is an evolving field for articular cartilage repair which could potentially be used for the treatment of focal chondral lesions, promoting regeneration and preventing joint surface degeneration. Stem cells and hydrogels may provide a functional, dynamic and biologically equivalent tissue that promotes tissue regeneration while being gradually degraded and replaced. The standard approach to tissue engineering consists in delivering cells within a hydrogel or a three-dimensional printed biomaterial scaffold into the chondral lesion to induce regeneration. This review focuses on the current and future use of hydrogels and tissue scaffold bioprinting for the treatment of focal chondral lesions, and provides preliminary data from two pilot animal studies. Level of Evidence: V

Proposal for a new histological scoring system for cartilage repair

OBJECTIVE: This study aimed to develop a new histological scoring system for use in a partial-thickness cartilage repair animal model. Although previous papers have investigated the regeneration of articular cartilage, the good results achieved in small animals have not been replicated in large animal models or humans, possibly because of the frequent use of models with perforation of the subchondral bone plates. Partial-thickness lesions spare the subchondral bone, and this pattern is the most frequent in humans; therefore, new therapies should be tested using this model. However, no specific histological score exists to evaluate partial-thickness model results. METHODS: Histological sections from 30 ovine knees were reviewed to develop a new scoring system. The sections were subjected to H&E, Safranin O, and Masson's trichrome staining. RESULTS: This paper describes a new scoring tool that is divided into sections in detail: repair of tissue inside the lesion, cartilage around the lesion and degenerative changes at the base of the lesion. Scores range from 0 to 21; a higher score indicates better cartilage repair. DISCUSSION: Unlike existing tools, this new scale does not assign points for the positioning of a tidemark; we propose evaluation of the degenerative changes to the subchondral bone and calcified cartilage layer. It is necessary to remove the whole joint to access and study the evolution of the lesion as well as the surrounding tissue. CONCLUSION: This article emphasizes the importance of a partial-thickness animal model of cartilage repair and presents a new histological scoring system.

Development of a rat model of knee osteoarthritis by a combination of monoiodoacetate and streptozotocin / Desarrollo de un modelo de rata de osteoartritis de rodilla por una combinación de monoiodoacetato y estreptozotocina

SUMMARY: Osteoarthritis (OA) caused by ageing joints or as a secondary complication of diabetes is a common health problem. We sought to develop an animal model of OA induced by a combination of the chondrocyte glycolytic inhibitor mono-iodoacetate (MIA) and streptozotocin (STZ), the agent that induces diabetes mellitus. We then hypothesized that the extent of damages to the knee joint induced by this model can be greater than OA induced by either MIA or STZ. Rats were either injected with MIA (model 1) or STZ (model 2) or both agents (model 3). After 8 weeks, harvested tissues from the knee joint of these groups were examined using scanning and transmission electron microscopy. In addition, blood samples were assayed for tumor necrosis factor alpha (TNF-α) and interleukin -6 (IL-6) that are known to be modulated in OA and diabetes. Compared to control group, substantial damages to the articular cartilage of the knee joint were observed in the three models with the severest in model 3. In addition, rats in model 3 showed significant (P<0.0001) increase in TNF-α and IL-6 compared to model 1 and 2. Thus, we have developed a new model of knee OA in rats that mimics a type of OA that is common among elderly people who have both, "ageing" joints and diabetes.

RESUMEN: La osteoartritis (OA) es un problema generalizado de salud a causa de un envejecimiento de las articulaciones, o bien de una complicación secundaria de la diabetes. El objetivo de este estudio fue desarrollar un modelo animal de OA inducido por una combinación dos drogas, un inhibidor de los condrocitos glucolíticos, el mono-iodoacetato (MIA), y la estreptozotocina (STZ), agente que induce la diabetes mellitus. Se consideró como hipótesis que el alcance de los daños a la articulación de la rodilla inducida por este modelo puede ser mayor que la OA inducida por MIA o STZ. Las ratas fueron inyectadas con MIA (grupo 1) o STZ (grupo 2) o ambos agentes (grupo 3). Se extrajeron muestras de la articulación de la rodilla de estos grupos al término de 8 semanas, y se examinaron mediante microscopía electrónica de barrido y de transmisión. Además, se analizaron muestras de sangre para el factor de necrosis tumoral alfa (TNF-α) e interleucina-6 (IL-6), que están moduladas en OA y en la diabetes. En comparación con el grupo control, se observaron daños sustanciales en el cartílago articular de la articulación de la rodilla en los tres modelos, encontrándose los daños más severos en el grupo 3. Además, las ratas del grupo 3 mostraron un aumento significativo (P <0,0001) de los niveles de TNF-α e IL- 6, en comparación con los grupos 1 y 2. Hemos desarrollado un nuevo modelo de OA de rodilla en ratas que imita un tipo de OA el cual, además de la diabetes, es común entre las personas mayores con un nivel importante de daño en las articulaciones.

Role of HIF-1α signaling pathway in osteoarthritis: A systematic review / Papel da via de sinalização do HIF-1α; na osteoartrite: revisão sistemática

Abstract Osteoarthritis (OA) is the most common form of arthritis and is frequently diagnosed and managed in primary care; it is characterized by loss of articular hyaline cartilage, which is a unique connective tissue that physiologically lacks blood vessels. Articular cartilage survives in a microenvironment devoid of oxygen, which is regulated by hypoxia inducible factor (HIF-1α). HIF-1α is considered the main transcriptional regulator of cellular and developmental response to hypoxia. To date, the relevance of HIF-1α in the assessment of cartilage has increased since its participation is essential in the homeostasis of this tissue. Taking into account the new emerging insights of HIF-1α in the scientific literature in the last years, we focused the present review on the potential role of HIF-1α signaling pathway in OA development, especially in how some genetic factors may influence the maintenance or breakdown of articular cartilage.

Resumo A osteoartrite (OA) é a forma mais comum de artrite e frequentemente é diagnosticada e gerenciada na atenção primária; é caracterizada por perda da cartilagem articular hialina, um tecido conjuntivo único que fisiologicamente carece de vasos sanguíneos. A cartilagem articular sobrevive em um microambiente desprovido de oxigênio, que é regulado pelo fator induzível por hipóxia-1α (HIF-1α). O HIF-1α é considerado o principal regulador transcricional da resposta celular e de desenvolvimento à hipóxia. Na atualidade, a relevância do HIF-1α na avaliação da cartilagem tem aumentado, já que a sua participação é essencial na homeostase desse tecido. Considerando as novas perspectivas emergentes do HIF-1α na literatura científica nos últimos anos, foca-se a presente revisão no potencial papel da via de sinalização do HIF-1α no desenvolvimento da OA, especialmente no modo como alguns fatores genéticos podem influenciar na manutenção ou ruptura da cartilagem articular.

Osteoarthritis model induced by intra-articular monosodium iodoacetate in rats knee

ABSTRACT PURPOSE: To evaluate the usefulness of a knee osteoarthritis model through functional, radiological and microscopic changes of the synovial membrane. METHODS: Forty eight rats were divided randomly into two groups. The first received 0.9% saline in the joint and corresponded to the control group. The second was submitted to experimental osteoarthritis of the right knee induced by monosodium iodoacetate and corresponded to the osteoarthritis group. All animals were subjected to comparative tests of forced ambulation and joint movements, inability to articulate and tactile allodynia on day 1 post-experiment by forced ambulation (Roto-rod test), joint assessment of disability (weight bearing test) and assessment of tactile allodynia (Von Frey test). After inflammatory induction they were divided into four sub-groups corresponding to the scheduled death in 7, 14, 21 and 28 days when they were submitted to radiographic examination of the knee, arthrotomy and collection of the synovial membrane. RESULTS: The osteoarthritis group showed significant differences compared to control group on days 7 and 14 in Roto-rod, in weight bearing and Von Frey tests in all days, and in radiological evaluation. Microscopic examination of the synovial membrane showed abnormalities of inflammatory character at all stages. CONCLUSION: The osteoarthritis induced by intra-articular monosodium iodoacetate in rats knee is a good model to be used in related research, because it provides mensurable changes on joint movements, tactile allodynia, progressive radiological degeneration and microscopic inflammation of the synovial membrane, that represent markers for osteoarthritis evaluation

Comparison between two different experimental models of osteoarthritis in rabbits. Intra-articular collagenase injection and anterior cruciate ligament transection

ABSTRACT PURPOSE: To compare two different experimental models of osteoarthritis in rabbits: intra-articular collagenase injection and anterior cruciate ligament transection. METHODS: Ten adult rabbits were randomly divided in two groups: COLL (collagenase group) and ACLT (anterior cruciate ligament transection). The COLL group was treated with 0.5 ml collagenase solution (2mg collagenase/0.5 ml sterile PBS), and the ACTL group was subjected to anterior cruciate ligament. After six and twelve weeks, respectively, the animals in the COLL and ACTL groups were euthanized. The gross appearance and histological examinations conducted in the cartilage articular surface was blindly scored according to the criteria developed by Yoshimi et al. (1994) and Mankin et al. (1971), respectively. RESULTS: The gross morphologic observation, macroscopic score and histological examinations have demonstrated that the ACTL group presented the highest scores, and lesions more severe than those in the COLL group. CONCLUSIONS: Both methods, anterior cruciate ligament transection and collagenase, applied to the stifle joint of the rabbits have effectively induced degenerative changes in the cartilage tissue, through statistically significant analysis (p≤0.05). The ACTL method has presented more severe lesions.

T2 Relaxation Time Mapping of the Cartilage Cap of Osteochondromas

OBJECTIVE: Our aim was to evaluate the cartilage cap of osteochondromas using T2 maps and to compare these values to those of normal patellar cartilage, from age and gender matched controls. MATERIALS AND METHODS: This study was approved by the Institutional Review Board and request for informed consent was waived. Eleven children (ages 5-17 years) with osteochondromas underwent MR imaging, which included T2-weighted fat suppressed and T2 relaxation time mapping (echo time = 9-99/repetition time = 1500 msec) sequences. Lesion origins were femur (n = 5), tibia (n = 3), fibula (n = 2), and scapula (n = 1). Signal intensity of the cartilage cap, thickness, mean T2 relaxation times, and T2 spatial variation (mean T2 relaxation times as a function of distance) were evaluated. Findings were compared to those of patellar cartilage from a group of age and gender matched subjects. RESULTS: The cartilage caps showed a fluid-like high T2 signal, with mean thickness of 4.8 mm. The mean value of mean T2 relaxation times of the osteochondromas was 264.0 +/- 80.4 msec (range, 151.0-366.0 msec). Mean T2 relaxation times were significantly longer than the values from patellar cartilage (39.0 msec) (p < 0.0001). These findings were observed with T2 spatial variation plots across the entire distance of the cartilage cap, with the most pronounced difference in the middle section of the cartilage. CONCLUSION: Longer T2 relaxation times of the cartilage caps of osteochondromas should be considered as normal, and likely to reflect an increased water content, different microstructure and component.

Effects of physical exercise on the cartilage of ovariectomized rats submitted to immobilization / Efeitos do exercício físico sobre a cartilagem de ratas ooforectomizadas submetidas à imobilização

ABSTRACT Objective To analyze the effects of physical exercise on cartilage histomorphometry in osteoporosis-induced rats subjected to immobilization. Methods We used 36 Wistar rats that were separated into six groups: G1, G2 and G3 submitted to pseudo-oophorectomy, and G4, G5 and G6 submitted to oophorectomy. After 60 days at rest, G2, G3, G5 and G6 had the right hind limbs immobilized for 15 days, followed by the same period in remobilization, being free in the box to G2 and G5, and climb ladder to G3 and G6. At the end of the experiment, the rats were euthanized, their tibias bilaterally removed and submitted to histological routine. Results There was significant increase in thickness of the articular cartilage (F(5;29)=13.88; p<0.0001) and epiphyseal plate (F(5;29)=14.72; p<0.0001) as the number of chondrocytes (F(5;29)=5.11; p=0.0021) in ovariectomized rats, immobilized and submitted to exercise. In the morphological analysis, degeneration of articular cartilage with subchondral bone exposure, loss of cellular organization, discontinuity of tidemark, presence of cracks and flocculation in ovariectomized, immobilized and free remobilization rats were found. In ovariectomized and immobilized remobilization ladder rats, signs of repair of the cartilaginous structures in the presence of clones, pannus, subcortical blood vessel invasion in the calcified zone, increasing the amount of isogenous groups and thickness of the calcified zone were observed. Conclusion Exercise climb ladder was effective in cartilaginous tissue recovery process damaged by immobilization, in model of osteoporosis by ovariectomy in rats.

RESUMO Objetivo Analisar os efeitos do exercício físico sobre a histomorfometria da cartilagem de ratas induzidas à osteoporose e submetidas à imobilização. Métodos Foram utilizadas 36 ratas Wistar separadas em seis grupos: G1, G2 e G3 submetidas à pseudo-ooforectomia e G4, G5 e G6, à ooforectomia. Após 60 dias em repouso, G2, G3, G5 e G6 tiveram o membro posterior direito imobilizado por 15 dias, seguido pelo mesmo período em remobilização, sendo livres na caixa para G2 e G5, e de subida em escada para G3 e G6. Ao final do experimento, as ratas foram eutanasiadas, e suas tíbias foram retiradas bilateralmente e submetidas à rotina histológica. Resultados Houve aumento significativo de espessura da cartilagem articular (F(5;29)=13,88; p<0,0001) e da placa epifisária (F(5;29)=14,72; p<0,0001), bem como do número de condrócitos (F(5;29)=5,11; p<0,0021) em ratas ooforectomizadas, imobilizadas e submetidas ao exercício em escada. Nas análises morfológicas, verificaram-se degeneração da cartilagem articular com exposição de osso subcondral, perda da organização celular, descontinuidade da tidemark, presença de fissuras e floculações em ratas ooforectomizadas, imobilizadas e com remobilização livre. Nas ratas ooforectomizadas, imobilizadas e com remobilização em escada, observaram-se sinais de reparação das estruturas cartilaginosas com presença de clones, pannus, invasão de vasos sanguíneos subcorticais na zona calcificada, aumento da quantidade de grupos isógenos e espessura da zona calcificada. Conclusão O exercício físico de subida em escada mostrou-se efetivo no processo de recuperação do tecido cartilaginoso danificado pela imobilização, em modelo de osteoporose por ooforectomia em ratas.

A comparative study of the areas of osteochondral defects produced in femoral condyles of rabbits treated with sugar cane biopolymer gel

PURPOSE: To assess the histological response of damaged osteochondral tissue in the femoral condyles of rabbits after repairing the wounds with sugar cane biopolymer gel - compared to the control group. METHODS: The study investigated 16 New Zealand rabbits, at 90, 120 and 180 days after surgery. In all the animals, a lesion of 3.2 mm in diameter and 4 mm deep was induced in each right and left femoral condyle. Each animal has provided both knees, divided into medial and lateral condyle, resulting in 64 samples. 32 knees were divided into two groups: Right knee, medial and lateral condyles, filled with biopolymer; Left knee, medial and lateral condyles, unfilled. The anatomical specimens were removed, and subjected to histological techniques and morphometric and statistical analysis. RESULTS: In all the periods of the group under study an inflammatory reaction mediated by giant cells and mononuclear cells was found, while in the control group there was early healing produced by fibroblasts and few mononuclear cells with statistical significance between groups. CONCLUSION: The biopolymer gel caused an inflammatory reaction mediated by giant cells and mononuclear cells while the control group there was cicatrization mediated by fibroblasts.

Influence of different body positions in vital capacity in patients on postoperative upper abdominal / Influência de diferentes posições corporais na capacidade vital em pacientes no pós-operatório abdominal superior / Influencia de diferentes posiciones corporales en la capacidad vital en pacientes en el postoperatorio abdominal superior

RATIONALE: The changes in body position can cause changes in lung function, and it is necessary to understand them, especially in the postoperative upper abdominal surgery, since these patients are susceptible to postoperative pulmonary complications. OBJECTIVE: To assess the vital capacity in the supine position (head at 0° and 45°), sitting and standing positions in patients in the postoperative upper abdominal surgery. METHODS: A cross-sectional study conducted between August 2008 and January 2009 in a hospital in Salvador/BA. The instrument used to measure vital capacity was analogic spirometer, the choice of the sequence of positions followed a random order obtained from the draw of the four positions. Secondary data were collected from the medical records of each patient. RESULTS: The sample consisted of 30 subjects with a mean age of 45.2 ± 11.2 years, BMI 20.2 ± 1.0 kg/m2. The position on orthostasis showed higher values of vital capacity regarding standing (mean change: 0.15 ± 0.03 L; p = 0.001), the supine to 45 (average difference: 0.32 ± 0.04 L; p = 0.001) and 0° (0.50 ± 0.05 L; p = 0.001). There was a positive trend between the values of forced vital capacity supine to upright posture (1.68 ± 0.47; 1.86 ± 0.48; 2.02 ± 0.48 and 2.18 ± 0.52 L; respectively). CONCLUSION: Body position affects the values of vital capacity in patients in the postoperative upper abdominal surgery, increasing in postures where the chest is vertical. .

JUSTIFICATIVA: As alterações no posicionamento corporal podem ocasionar mudanças na função respiratória e é necessário compreendê-las, principalmente no pós-operatório abdominal superior, já que os pacientes estão suscetíveis a complicações pulmonares pós-operatórias. OBJETIVO: Verificar a capacidade vital nas posições de decúbito dorsal (cabeceira a 0° e 45°), sentado e em ortostase em pacientes no pós-operatório de cirurgia abdominal superior. MÉTODOS: Estudo transversal, feito entre agosto de 2008 e janeiro de 2009, em um hospital na cidade de Salvador (BA). O instrumento usado para mensuração da capacidade vital (CV) foi o ventilômetro analógico e a escolha da sequência das posições seguiu uma ordem aleatória obtida a partir de sorteio das quatro posições. Os dados secundários foram colhidos nos prontuários de cada paciente. RESULTADOS: A amostra foi composta por 30 indivíduos com idade média de 45,2 ± 11,2 anos e IMC 20,2 ± 1,0 kg/m2. A posição em ortostase apresentou valores maiores da CV em relação à sedestração (média das diferenças: 0,15 ± 0,03 litros; p = 0,001), ao decúbito dorsal a 45° (média das diferenças: 0,32 ± 0,04 litros; p = 0,001) e 0° (0,50 ± 0,05 litros; p = 0,001). Houve um aumento positivo entre os valores de CVF do decúbito dorsal para a postura ortostática (1,68 ± 0,47; 1,86 ± 0,48; 2,02 ± 0,48 e 2,18 ± 0,52 litros; respectivamente). CONCLUSÃO: A posição do corpo afeta os valores da CV em pacientes no pós-operatório de cirurgia abdominal superior, com aumento nas posturas em que o tórax encontra-se verticalizado. .

JUSTIFICACIÓN: Las alteraciones en el posicionamiento corporal pueden ocasionar cambios en la función respiratoria y es necesario comprenderlas, principalmente en el postoperatorio abdominal superior, ya que los pacientes son susceptibles a complicaciones pulmonares postoperatorias. OBJETIVO: Verificar la capacidad vital en las posiciones de decúbito dorsal (cabeza a 0° y 45°), sentado y en ortostasis en pacientes en el postoperatorio de cirugía abdominal superior. MÉTODOS: Estudio transversal realizado entre agosto de 2008 y enero de 2009, en un hospital en la ciudad de Salvador (BA). El instrumento usado para la medición de la capacidad vital (CV) fue el espirómetro analógico y la elección de la secuencia de las posiciones siguió un orden aleatorio que se obtuvo a partir de un sorteo de las 4 posiciones. Los datos secundarios fueron extraídos de las historias clínicas de cada paciente. RESULTADOS: La muestra se compuso de 30 individuos con edades medias de 45,2 ± 11,2 años e IMC de 20,2 ± 1 kg/m2. La posición en ortostasis presentó valores mayores de CV con relación a la posición sedente (media de las diferencias: 0,15 ± 0,03 L; p = 0,001), al decúbito dorsal a 45° (media de las diferencias: 0,32 ± 0,04 L; p = 0,001) y a 0° (0,50 ± 0,05 L; p = 0,001). Hubo un aumento positivo entre los valores de CV forzada del decúbito dorsal para la postura ortostática (1,68 ± 0,47; 1,86 ± 0,48; 2,02 ± 0,48 y 2,18 ± 0,52 L, respectivamente). CONCLUSIÓN: La posición del cuerpo afecta los valores de la CV en pacientes durante el postoperatorio de cirugía abdominal superior, con aumento en las posturas en las que el tórax está verticalizado. .

Treatment of osteochondral injuries with platelet gel

OBJECTIVES: Treatments for injured articular cartilage have not advanced to the point that efficient regeneration is possible. However, there has been an increase in the use of platelet-rich plasma for the treatment of several orthopedic disorders, including chondral injuries. Our hypothesis is that the treatment of chondral injuries with platelet gel results in higher-quality repair tissue after 180 days compared with chondral injuries not treated with gel. METHODS: A controlled experimental laboratory study was performed on 30 male rabbits to evaluate osteochondral injury repair after treatment with or without platelet gel. Osteochondral injuries were surgically induced in both knees of each rabbit at the medial femoral condyle. The left knee injury was filled with the platelet gel, and the right knee was not treated. Microscopic analysis of both knee samples was performed after 180 days using a histological grading scale. RESULTS: The only histological evaluation criterion that was not significantly different between treatments was metachromasia. The group that was treated with platelet gel exhibited superior results in all other criteria (cell morphology, surface regularity, chondral thickness and repair tissue integration) and in the total score. CONCLUSION: The repair tissue was histologically superior after 180 days in the study group treated with platelet gel compared with the group of untreated injuries. .

Análisis histopatológico del cartílago articular expuesto a metilprednisolona, ropivacaína y ácido hialurónico en un modelo animal de osteoartrosis / Histopathological analysis of the articular cartilage exposed to methylprednisolone, ropivacaine and hyaluronic acid in an animal model of osteoarthrosis

La osteoartrosis es un padecimiento del aparato locomotor con una prevalencia elevada y en crecimiento, paralela al envejecimiento de la población. La infiltración intraarticular de sustancias para aliviar la sintomatología de la osteoartrosis es una práctica común en el consultorio médico de los especialistas que atienden esta enfermedad. Aunque la sintomatología mejora con la infiltración de anestésicos locales, corticoesteroides y suplementos viscosantes, es aún incierto el efecto que estas sustancias tienen sobre la integridad del cartílago articular. Este estudio explora a nivel macroscópico e histológico el efecto de la infiltración de ropivacaína, metilprednisolona y ácido hialurónico sobre el cartílago articular en un modelo de osteoartrosis química en conejos (n=24). Nuestros resultados indican que en los grupos infiltrados con metilprednisolona (n=8) y ropivacaína (n=8) la estructura del cartílago articular presento alteraciones más severas con respecto a su grupo control, además de una disminución importante en la síntesis de matriz extracelular. En el grupo infiltrado con ácido hialurónico (n=8), las alteraciones macroscópicas e histológicas del cartílago articular mejoraron con respecto a su grupo control, presentando una estructura integra y síntesis de matriz extracelular normal.

Osteoarthritis is a musculoskeletal condition with a high prevalence, increasing with the aging of population. The intraarticular infiltration of substances to relieve the symptoms of osteoarthritis is a common practice in medical practice. Although symptoms improved with the infiltration of local anesthetics, corticosteroids and supplements, it is still uncertain what effect these substances have on the integrity of articular cartilage. This study explores the macroscopic and histological effects of infiltration of Ropivacaine, Methylprednisolone and Hyaluronic Acid on articular cartilage in a model of chemical osteoarthritis in rabbits (n=24). Our results indicate that in the infiltrated groups with Methylprednisolone (n=8) and Ropivacaine (n=8) the structure of articular cartilage present more severe alterations with respect to its control group and an important decrease in the synthesis of extracellular matrix. In-group infiltrated with hyaluronic acid (n=8), macroscopic and histological changes of articular cartilage improved with respect to its control group, presenting a normal structure and normal extracellular matrix synthesis.

Effects of immobilization and remobilization on the ankle joint in Wistar rats

A sprained ankle is a common musculoskeletal sports injury and it is often treated by immobilization of the joint. Despite the beneficial effects of this therapeutic measure, the high prevalence of residual symptoms affects the quality of life, and remobilization of the joint can reverse this situation. The aim of this study was to analyze the effects of immobilization and remobilization on the ankle joint of Wistar rats. Eighteen male rats had their right hindlimb immobilized for 15 days, and were divided into the following groups: G1, immobilized; G2, remobilized freely for 14 days; and G3, remobilized by swimming and jumping in water for 14 days, performed on alternate days, with progression of time and a series of exercises. The contralateral limb was the control. After the experimental period, the ankle joints were processed for microscopic analysis. Histomorphometry did not show any significant differences between the control and immobilized/remobilized groups and members, in terms of number of chondrocytes and thickness of the articular cartilage of the tibia and talus. Morphological analysis of animals from G1 showed significant degenerative lesions in the talus, such as exposure of the subchondral bone, flocculation, and cracks between the anterior and mid-regions of the articular cartilage and the synovial membrane. Remobilization by therapeutic exercise in water led to recovery in the articular cartilage and synovial membrane of the ankle joint when compared with free remobilization, and it was shown to be an effective therapeutic measure in the recovery of the ankle joint.

T2 Values of Femoral Cartilage of the Knee Joint: Comparison between Pre-Contrast and Post-Contrast Images

OBJECTIVE: To retrospectively evaluate the relationship between T2 values of pre- and post-contrast magnetic resonance (MR) images of femoral cartilage in patients with varying degrees of osteoarthritis. MATERIALS AND METHODS: A total of 19 patients underwent delayed gadolinium-enhanced MRI of cartilage. Six regions of interest for T2 value measurement were obtained from pre- and post-contrast T2-weighted, sagittal, multi-slice, multi-echo, source images in each subject. Regions with modified Noyes classification grade 2B and 3 were excluded. Comparison of T2 values between pre- and post-contrast images and T2 values among regions with the grade 0, 1 and 2A groups were statistically analyzed. RESULTS: Of a total of 114 regions, 79 regions showing grade 0 (n = 46), 1 (n = 18), or 2A (n = 15) were analyzed. The overall and individual T2 values of post-contrast images were significantly lower than those of pre-contrast images (overall, 35.3 +/- 9.2 [mean +/- SD] vs. 29.9 +/- 8.2, p < 0.01; range of individual, 28.9-37.6 vs. 27.1-36.4, p < 0.01). Pearson correlation coefficients showed a strong positive correlation between pre- and post-contrast images (rho-Pearson = 0.712-0.905). T2 values of pre- and post-contrast images of the grade 0 group were significantly lower than those of the grade 1/2A group (pre T2, p = 0.003; post T2, p = 0.006). CONCLUSION: T2 values of the femoral cartilage of the knee joint are significantly lower on post-contrast images than on pre-contrast images. Furthermore, these T2 values have a strong positive correlation between pre- and post-contrast images.

Cartílago articular: evaluación por resonancia magnética / Articular cartilage: a magnetic resonance imaging study

El presente artículo revisa la evaluación imagenologica de las lesiones del cartílago articular con énfasis en su estudio por resonancia magnética, discutiendo la utilidad de las secuencias convencionales y los estudios avanzados de RM que permiten detectar lesiones condrales incipientes intrasustancia, previo a la ulceración de su superficie.

This article reviews the radiographic evaluation of articular cartilage lesions with emphasis on its magnetic resonance imaging study, we will discuss the usefulness of conventional sequences and advanced MRI studies which allow detection of incipient intrasubstance chondral lesions, prior to the ulceration of its surface.

Osteocondrite dissecante do joelho: diagnóstico e tratamento / Osteochondritis dissecans of the knee: diagnosis and treatment

A osteocondrite dissecante (OCD) é um processo patológico que atinge o osso subcondral do joelho em criança e adolescente (OCDJ) e adultos jovens (OCDA) com efeitos secundários sobre a cartilagem articular com dor, edema, possível formação de corpos livres e sintomas mecânicos, inclusive bloqueio articular. A OCD pode levar a alterações degenerativas precoces da articulação, quando não tratada. Este artigo apresenta uma revisão e atualização sobre o problema com ênfase especial no diagnóstico e tratamento. Este pode incluir os métodos conservadores que mostram resultados mais satisfatórios para a OCDJ e os vários métodos cirúrgicos que incluem: técnicas reparativas como a remoção isolada do fragmento, as perfurações ósseas e a fixação do fragmento osteocondral e as técnicas restaurativas como as microfraturas, o transplante osteocondral autólogo (mosaicoplastia), o implante autólogo de condrócitos e o aloenxerto osteocondral fresco, considerando a lesão estável ou instável e sua viabilidade, bem como a maturidade esquelética e localização do processo. Estudos recentes para a avaliação dos resultados dos vários tipos de tratamento demonstram a falta de estudos com níveis de evidência confiáveis e sugere-se maior número de análises multicêntricas, prospectivas, randomizadas e controladas para estabelecer melhores diretrizes para o manuseio da doença.

Osteochondritis dissecans (OCD) is a pathological process affecting the subchondral bone of the knee in children and adolescents with open growth plates (juvenile OCD) and young adults with closed growth plates (adult OCD). It may lead to secondary effects on joint cartilage, such as pain, edema, possible formation of free bodies and mechanical symptoms, including joint locking. OCD may lead to degenerative changes may develop if left untreated. This article presents a review and update on this problem, with special emphasis on diagnosis and treatment. The latter may include either conservative methods, which show more predictable results for juvenile OCD, or various surgical methods, which include reparative techniques like isolated removal of the fragment, bone drilling and fixation of the osteochondral fragments, and restorative techniques like microfractures, autologous osteochondral transplantation (mosaicplasty), autologous chondrocyte implantation and fresh osteochondral allograft, depending on lesion stability, lesion viability, skeletal maturity and OCD process location. Recent assessments on the results from several types of treatment have shown that there is a lack of studies with reliable levels of evidence and have suggested that further multicenter prospective randomized and controlled studies on management of this disease should be conducted.

Atualização no diagnóstico e tratamento das lesões condrais do joelho / Updating on diagnosis and treatment of chondral lesion of the knee

O tratamento das lesões condrais no joelho ainda permanece um desafio para o cirurgião ortopédico, principalmente pelas próprias características da cartilagem, que promovem um baixo potencial de regeneração. As lesões condrais podem ser causadas por estímulos metabólicos, genéticos, vasculares e traumáticos e são classificadas de acordo com o tamanho e espessura da cartilagem acometida. O diagnóstico clínico pode ser difícil, principalmente pela sintomatologia insidiosa, sendo necessário o uso de exames complementares, em especial, a ressonância magnética. O tratamento dessas lesões é, em geral, iniciado de forma conservadora, ficando o tratamento cirúrgico reservado para pacientes com fragmentos condrais destacados, com bloqueio do arco de movimento, ou pacientes refratários ao tratamento clínico. As técnicas cirúrgicas mais usadas para o tratamento dos defeitos de espessura parcial são o desbridamento e a ablação por radiofrequência. Essas técnicas têm o objetivo de melhorar os sintomas, já que não restauram a estrutura e a função normal da cartilagem. Para os defeitos de espessura total (lesão osteocondral), os tratamentos disponíveis são a abrasão, drilling, microfratura, transplante osteocondral autólogo e alógeno e técnicas biológicas como o uso de transplante autólogo de condrócitos, técnica da cartilagem picada (minced cartilage) e o transplante de células-tronco.

The treatment of chondral knee injuries remains a challenge for the orthopedic surgeon, mainly owing to the characteristics of the cartilage tissue, which promote low potential for regeneration. Chondral lesions can be caused by metabolic stimulation, or by genetic, vascular and traumatic events, and are classified according to the size and thickness of the affected cartilage. Clinical diagnosis can be difficult, especially due to insidious symptoms. Additional tests, as Magnetic Resonance Imaging (MRI), may be needed. The treatment of these lesions usually starts with non-operative management. Surgery should be reserved for patients with detached chondral fragments, blocked range of motion, or the failure of non-operative treatment. The surgical techniques used for the treatment of partial thickness defects are Debridement and Ablation. These techniques aim to improve symptoms, since they do not restore normal structure and function of the cartilage. For full-thickness defects (osteochondral lesion), available treatments are Abrasion, Drilling, Microfracture, Osteochondral Autologous and Allogeneic Transplantation, and biological techniques such as the use of Autologous Chondrocyte Transplantation, Minced Cartilage and stem cells.

Practical Application of Iterative Decomposition of Water and Fat with Echo Asymmetry and Least-Squares Estimation (IDEAL) Imaging in Minimizing Metallic Artifacts

Iterative decomposition of water and fat with echo asymmetry and the least-squares estimation (IDEAL) is a recently developed method for robust separation of fat and water with very high signal-to-noise-ratio (SNR) efficiency. In contrast to conventional fat-saturation methods, IDEAL is insensitive to magnetic field (B0 and B1) inhomogeneity. The aim of this study was to illustrate the practical application of the IDEAL technique in reducing metallic artifacts in postoperative patients with metallic hardware. The IDEAL technique can help musculoskeletal radiologists make an accurate diagnosis particularly in musculoskeletal imaging by reducing metallic artifacts, enabling the use of contrast enhancement, improving SNR performance, and providing various modes of MR images with one scan parameter.