Eficácia e segurança da combinação Glicosamina e Condroitina comparada a medicamentos disponíveis no SUS para o tratamento de osteoartrite: revisão rápida / Effectiveness and safety of Glucosamine and Chondroitin combination compared to drugs available in Brazilian Public Health System for the treatment of Osteoarthritis: rapid review

Tecnologia: Combinação de glicosamina e condroitina. Indicação: Tratamento de osteoartrite em adultos. Pergunta: O tratamento com a combinação de glicosamina e condroitina é mais eficaz e seguro que os demais tratamentos para osteoartrite disponíveis no SUS? Métodos: Uma revisão rápida de evidências, uma revisão de revisões sistemáticas, com levantamento bibliográfico realizado na base de dados PUBMED, utilizando estratégia estruturada de busca. A qualidade metodológica das revisões sistemáticas foi avaliada com AMSTAR-2. Resultados: Foi selecionada uma revisão sistemática, que atendiam aos critérios de inclusão. Conclusão: A combinação de glicosamina com condroitina, comparados ao placebo, mostrou ser mais eficaz para tratamento da dor e função e alcançou o segundo lugar nas alternativas terapêuticas para tratamento da dor e função

Technology: Combination of glucosamine and chondroitin. Indication: Treatment of osteoarthritis in adults. Question: Is the treatment with the combination of glucosamine and chondroitin more effective and safer than the other treatments for osteoarthritis available in the Brazilian Public Health System? Methods: A rapid review of evidence, a overview of systematic reviews, with bibliographic search done in PUBMED database, using a structured search strategy. The methodological quality of systematic reviews was assessed using AMSTAR-2. Results: A systematic review was selected, which met the inclusion criteria. Conclusion: The combination of glucosamine and chondroitin, compared to placebo, proved to be more effective for the treatment of pain and function and reached second place in therapeutic alternatives for the treatment of pain and function

Treatment of knee osteoarthritis with a new formulation of a fixed-dose combination of glucosamine sulfate and bovine chondroitin: a multicenter, randomized, single-blind, non-inferiority clinical trial

Abstract Objectives: To compare the efficacy and safety of a new formulation of a fixed dose combination of glucosamine sulfate (GS; 1500 mg) and bovine chondroitin sulfate (CS; 1200 mg) versus the reference product (RP) in patients with knee osteoarthritis (OA). Methods: In this multicenter, randomized, single-blind trial, 627 patients with knee osteoarthritis (OA)—Kellgren-Lawrence grades 2 or 3 and mean score ≥ 40 mm in the WOMAC pain subscale—were randomized to receive GS/ CS or the RP for 24 weeks. The primary efficacy endpoint was the absolute change in WOMAC pain subscale score. The secondary endpoints included the following: WOMAC total and subscale scores, overall assessment of the disease by the patient and the investigator, SF-12 score, OMERACT-OARSI response rate to the treatment, and rescue medication use. Results: Mean reductions of WOMAC pain score were - 35.1 (sd = 23.2) mm in the GS/CS group and - 36.5 (sd = 24.9) mm in the RP group. The difference between the adjusted means of both treatments confirmed the noninferiority of GS/CS versus the RP. Improvement was observed in pain, stiffness, physical function and total WOMAC score, as well as in overall OA assessment by the patient and the investigator for both groups. No improvement was observed in SF-12. The rate of OMERACT-OARSI responders was 89.4% in GS/CS group and 87.9% in the RP group. Headache and changes in glucose tolerance were the most frequent treatment-related adverse events. Conclusions: The new formulation of a fixed-dose combination of glucosamine sulfate and bovine chondroitin sulfate was non-inferior to the RP in symptomatic treatment of knee OA, with a high responder rate and good tolerability profile. Trial registration: ClinicalTrials.gov; Registration number NCT02830919; Date of registration: July 13, 2016; First randomization date: December 05, 2016).(AU)

Hepatotoxicidad inducida por glucosamina-condroitina en un hospital público de Lima (Perú): reporte de caso / Case report of glucosamine-chondroitin induced hepatotoxicity in a public hospital in Lima, Peru

Resumen En el cuerpo humano tenemos glucosamina y condroitina de forma natural. Estas sustancias constituyen un componente importante del sistema cartilaginoso. Como medicamentos, tienen múltiples indicaciones clínicas, principalmente la osteoartritis. La hepatotoxicidad inducida por estas biomoléculas es infrecuente, pues cuentan solo con reportes de casos aislados en la literatura mundial. En este trabajo, presentamos el caso de una paciente con una lesión hepática inducida por glucosamina-condroitina del tipo hepatocelular, que fue admitida en el hospital por causa de una sintomatología respiratoria y malestar general. En ella, se destacó una marcada hipertransaminasemia durante los exámenes de laboratorio. Asimismo, se descartaron etiologías como el alcohol, hepatitis virales y hepatopatías autoinmunes, principalmente. De igual forma, no se llegó a evidenciar una enfermedad hepática crónica mediante la ecografía abdominal. Al suspenderse el medicamento, se observó una disminución considerable de la hipertransaminasemia luego de 1 semana, y una mejoría total de esta a los 2 meses del alta hospitalaria. Este caso se añade a los pocos reportados a nivel mundial y cobra una importancia relevante para la publicación de posteriores estudios sistemáticos que aclaren el panorama de esta enfermedad.

Abstract The human body naturally produces glucosamine and chondroitin which are important components of the cartilaginous system. There are multiple clinical indications for them as medicines, but they are primarily used for osteoarthritis. Hepatotoxicity induced by these biomolecules is uncommon, and the only reports in the world literature are isolated individual cases. This article presents the case of a patient with glucosamine-chondroitin-induced hepatocellular damage who was admitted to the hospital with respiratory symptoms and malaise. Marked hypertransaminemia was found in laboratory tests. Etiologies such as alcohol, viral hepatitis and autoimmune liver diseases were ruled out, and abdominal ultrasound found no evidence of chronic liver disease. Discontinuance of glucosamine and chondroitin led to a considerable decrease in hypertransaminemia after one week with total improvement two months of hospital discharge. This case adds to the small number reported worldwide and is relevant for future systematic studies to clarify the outlook for this disease.

Synthesis and Biocompatibility Characterizations of in Situ Chondroitin Sulfate–Gelatin Hydrogel for Tissue Engineering

Novel hydrogel composed of both chondroitin sulfate (CS) and gelatin was developed for better cellular interaction through two step double crosslinking of N-(3-diethylpropyl)-N-ethylcarbodiimide hydrochloride (EDC) chemistries and then click chemistry. EDC chemistry was proceeded during grafting of amino acid dihydrazide (ADH) to carboxylic groups in CS and gelatin network in separate reactions, thus obtaining CS–ADH and gelatin–ADH, respectively. CS–acrylate and gelatin–TCEP was obtained through a second EDC chemistry of the unreacted free amines of CS–ADH and gelatin–ADH with acrylic acid and tri(carboxyethyl)phosphine (TCEP), respectively. In situ CS–gelatin hydrogel was obtained via click chemistry by simple mixing of aqueous solutions of both CS–acrylate and gelatin–TCEP. ATR-FTIR spectroscopy showed formation of the new chemical bonds between CS and gelatin in CS–gelatin hydrogel network. SEM demonstrated microporous structure of the hydrogel. Within serial precursor concentrations of the CS–gelatin hydrogels studied, they showed trends of the reaction rates of gelation, where the higher concentration, the quicker the gelation occurred. In vitro studies, including assessment of cell viability (live and dead assay), cytotoxicity, biocompatibility via direct contacts of the hydrogels with cells, as well as measurement of inflammatory responses, showed their excellent biocompatibility. Eventually, the test results verified a promising potency for further application of CS–gelatin hydrogel in many biomedical fields, including drug delivery and tissue engineering by mimicking extracellular matrix components of tissues such as collagen and CS in cartilage.

Análisis de costo-efectividad del condroitín más glucosamina comparado con acetaminofén, AINEs y celecoxib para el tratamiento sintomático de adultos con osteoartrosis de rodilla y mano en Colombia / Cost-effectiveness analysis of chondroitin plus glucosamine compared to acetaminophen, AINEs and celecoxib for the symptomatic treatment of adults with knee and hand osteoarthrosis in Colombia

Problema de investigación: Analizar los costos y la efectividad del condroitín más glucosamina, cetaminofén, celecoxib y AINEs para pacientes mayores de 50 años con osteoartrosis sintomática (primaria y secundaria) en Colombia. Tipo de evaluación económica: Análisis de costo-efectividad. Población objetivo: Personas mayores de 50 años de edad (hombres y mujeres) con osteoartrosis sintomática (primaria y secundaria) en Colombia. intervención y comparadores: I: condroitín más glucosamina, C: acetaminofén, celecoxib y AINEs. Horizonte temporal: Se empleó como horizonte temporal la expectativa de vida promedio de los pacientes con OA mayores a 50 años en Colombia. Puesto que la expectativa de vida promedio en Colombia es de 74 años para la población general (hombres y mujeres), se utilizó un horizonte de tiempo del modelo de 24 años con base en las estadísticas vitales del DANE. Perspectiva: La del Sistema General de Seguridad Social en Salud (SGSSS). Tasa de descuento: Tanto los costos como los beneficios son descontados al valor presente, utilizando una tasa de descuento del 5%. Estructura del modelo: Se estructuró un modelo Markov reflejando el curso clínico de la enfermedad con ciclos anuales. Fuentes de datos de efectividad y seguridad: Revisión de ensayos clínicos, meta-análisis y literatura clínica para la obtención de los parámetros para la modelación dinámica de la osteoartrosis sintomática en Colombia, y para la determinación de la efectividad de las alternativas de comparación. Desenlaces y valoración: Años de vida ganados. Costos incluidos: Costo de medicamentos para el tratamiento, Costo relacionados al manejo de eventos adversos, Costo de procedimientos e insumos. Fuentes de datos de costos: SISMED, Manual tarifario ISS 2001, Guía de práctica clínica para el síndrome coronario agudo. Resultados del caso base: El costo esperado por año de vida ajustado por calidad ganado de condroitín más glucosamina fue de $ 4.218.759,75 por persona, de $5.694.205,75 con AINEs, de $3.312.855,30 con celecoxib y de $2.616.444,62 con acetaminofén. El acetaminofén resultó en el mayor número de años de vida ajustados por calidad ganados (6,917). Estos resultados implican que el acetaminofén sería costo-efectivo y que es una estrategia dominante respecto a sus comparadores. Análisis de sensibilidad: Los análisis de sensibilidad llevados a cabo sobre la tasa de descuento y las variables con mayor impacto sobre la RICE evidencian que ninguno de estos parámetros \r\nmodifica los resultados encontrados. La dominancia del acetaminofén es consistente ante los escenarios \r\nplanteados. Adicionalmente, con el umbral establecido de mínimo un PIB y máximo tres PIB per cápita, se observa que el acetaminofén tiene una probabilidad de cerca de 100% de ser más costo-efectivo que los otros medicamentos incluidos en este estudio. Conclusiones: En Colombia, desde la perspectiva del sistema general de seguridad social en salud, la terapia combinada de condroitín más glucosamina para el tratamiento sintomático de pacientes mayores de 50 años de edad con osteoartrosis de rodilla o mano, es una tecnología dominada, indicando que no sería una alternativa costo-efectiva para el país. Entre las opciones evaluadas, el acetaminofén es la tecnología con mejor costo-efectividad, pues se asocia con costos más bajos y un incremento en años de vida ajustados por calidad.(AU)

Análisis de impacto presupuestal de condroitín más glucosamina comparado con acetaminofén, AINES y celecoxib para osteoartrosis sintomática (primaria y secundaria) de la rodilla en Colombia / Analysis of budgetary impact of chondroitin plus glucosamine compared to acetaminophen, AINES and celecoxib for symptomatic (primary and secondary) osteoarthritis of the knee in Colombia

Tecnologías evaluadas: Nuevas: condroitín más glucosamina y AINES (celecoxib y meloxicam) Actuales: acetaminofén y AINES (ibuprofeno, naproxeno y diclofenaco). Población: Pacientes mayores de 50 años con osteoartrosis sintomática (primaria y secundaria) en Colombia. Perspectiva: La perspectiva del presente AIP corresponde al tercero pagador, que en este caso es el Sistema General de Seguridad Social en Salud (SGSSS) en Colombia. Horizonte temporal: El horizonte temporal de este AIP en el caso base corresponde a un año. Adicionalmente se reportan las estimaciones del impacto presupuestal para los años 2 y 3, bajo el supuesto de la inclusión en el POS en el año 1. Costos incluidos: Costos por mg de los medicamentos analizados y costos de eventos adversos relacionados al uso de los medicamentos. Fuente de costos: Los precios de cada tecnología considerada fueron calculados con la base de datos SISMED 2014 y los precios relacionados con los eventos adversos fueron extraídos de la guía de práctica clínica para el síndrome coronario agudo. Escenarios: En el escenario 1 se considera que la adopción de las nuevas tecnologías no llevaría a ningún cambio en el mercado, debido a la fuerte preferencia de los médicos para el uso de las tecnologías actuales. En el escenario 2 se asume que la adopción de las nuevas tecnologías resultará en una disminución en el costo de dichas tecnologías, implicando un pequeño aumento en su participación de mercado. Resultados: Se requeriría una inversión de $324.848.741.965,21 para el año 1, $408.850.393.031,63 para el año 2 y $516.306.727.474,66 para el año 3 para la adopción de las terapias condroitín más glucosamina, meloxicam y celecoxib en el POS para el tratamiento de pacientes con osteoartrosis sintomática (primaria y secundaria) de la rodilla en Colombia, bajo el presupuesto que la inclusión de los nuevos medicamentos no llevaría a un cambio en la participación del mercado. Asumiendo que el precio de las nuevas terapias disminuyera y por tal razón la participación del mercado de dichas terapias aumentaría,\tel impacto presupuestal aumentaría a \r\n$33.328.838.947,92 en el año 1, de $44.301.385.949,68 en el año 2 y de $59.253.690.046,56 en el año 3.(AU)

Effects of gangliosides from deer bone extract on the gene expressions of matrix metalloproteinases and collagen type II in interleukin-1β-induced osteoarthritic chondrocytes

BACKGROUND/OBJECTIVES: We investigated the anti-osteoarthritic effects of deer bone extract on the gene expressions of matrix metalloproteinases (MMPs) and collagen type II (COL2) in interleukin-1β-induced osteoarthritis (OA) chondrocytes. MATERIALS/METHODS: Primary rabbit chondrocytes were treated as follows: CON (PBS treatment), NC (IL-1β treatment), PC (IL-1β + 100 µg/mL glucosamine sulphate/chondroitin sulphate mixture), and DB (IL-1β + 100 µg/mL deer bone extract). RESULTS: The results of the cell viability assay indicated that deer bone extract at doses ranging from 100 to 500 µg/mL inhibits cell death in chondrocytes induced by IL-1β. Deer bone extract was able to significantly recover the mRNA expression of COL2 that was down-regulated by IL-1β (NC: 0.79 vs. DB: 0.87, P < 0.05) and significantly decrease the mRNA expression of MMP-3 (NC: 2.24 vs. DB: 1.75) and -13 (NC: 1.28 vs. DB: 0.89) in OA chondrocytes (P < 0.05). CONCLUSIONS: We concluded that deer bone extract induces accumulation of COL2 through the down-regulation of MMPs in IL-1β-induced OA chondrocytes. Our results suggest that deer bone extract, which contains various components related to OA, including chondroitin sulphate, may possess anti-osteoarthritic properties and be of value in inhibiting the pathogenesis of OA.

Intravesical Sodium Chondroitin Sulphate to Treat Overactive Bladder: Preliminary Result / 대한배뇨장애요실금학회지

PURPOSE: This study aimed to verify the efficacy and safety of intravesical treatment with sodium chondroitin sulfate (CS) in patients with overactive bladder (OAB) who are refractory to previous antimuscarinic treatment. METHODS: This study was performed between June 2012 and January 2015 and included 31 consecutive women (mean age, 42.10+/-7.34 years) with OAB who had been previously treated with two types of antimuscarinic drugs. The results of gynecologic and cystoscopic examinations were normal, and OAB comorbidity was absent. Treatment with intravesical instillations containing 40 mL CS (0.2%; 2 mg/mL) was administered for 6 weeks; after weekly treatments, monthly treatments were administered. The OAB-validated 8 (OAB-V8) symptom scores, nocturia, frequency, urgency, urge incontinence, and urinary volumes measured by uroflowmetry were evaluated for all the patients. The values obtained before the treatment were statistically compared with those obtained six months after the treatment. RESULTS: The duration of the symptoms was 18.36+/-6.19 months. A statistically significant improvement of the patients' conditions was observed in terms of the OAB-V8 symptom scores, nocturia, frequency, urgency, urge incontinence, and urinary volumes measured by uroflowmetry after the treatment. CONCLUSIONS: Despite the limitations of this study, the outcomes confirmed that CS therapy is safe and effective for the treatment of OAB.

Efectividad y seguridad de condroitín comparado con acetaminofén, antiinflamatorios no esteroideos, glucosamina, condroitín más glucosamina, diacereina, ácido hialurónico ó fitoterapéuticos, en pacientes con osteoartrosis / Effectiveness and safety of chondroitin compared to acetaminophen, non-steroidal anti-inflammatory drugs, glucosamine, chondroitin plus glucosamine, diacerein, hyaluronic acid or phytotherapeutic agents in patients with osteoarthrosis

Introducción: la OA es la forma más común de enfermedad de las articulaciones y la principal causa de discapacidad de las personas de la tercera edad. Su alta prevalencia en una población que usualmente tiene comorbilidades asociadas que requieren otros medicamentos obliga a buscar otras alternativas terapéuticas con mínimos eventos adversos y pocas interacciones medicamentosas. Condroitín es un medicamento regenerador de cartílago que se ha usado en el manejo de estos pacientes. Esta evaluación tecnológica se desarrolló en el marco de la actualización integral del Plan Obligatorio de Salud para el año 2015. Objetivo: evaluar la efectividad y seguridad del uso de condroitín comparado con acetaminofén, antiinflamatorios no esteroideos, glucosamina, condroitín más glucosamina, diacereina, ácido hialurónico ó fitoterapéuticos, en pacientes osteoartrosis. Metodología: la evaluación fue realizada de acuerdo con un protocolo definido a priori por el grupo desarrollador. Se realizó una búsqueda sistemática en MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects y LILACS, con restricción al idioma inglés y español y limitada a revisiones sistemáticas publicadas en los últimos cinco años y ensayos clínicos sin restricción de tiempo. Las búsquedas electrónicas fueron hechas entre octubre y diciembre de 2014 y se complementaron mediante búsqueda manual en bola de nieve y una consulta con expertos temáticos. La tamización de referencias se realizó por un revisor. La selección de estudios fue realizada mediante la revisión en texto completo de las referencias preseleccionadas, verificando los criterios de elegibilidad. La calidad de los estudios fue valorada con la herramienta de riesgo de sesgo de la Colaboración Cochrane. Las características de los estudios fueron extraídas a partir de las publicaciones originales. Se realizó una síntesis narrativa de las estimaciones del efecto para las comparaciones y desenlaces de interés a partir de los estudios de mejor calidad. Se estimaron medidas combinadas del efecto a través de un metanálisis con el método de Mantel-Haenszel y un modelo de efectos aleatorios, empleando el programa RevMan 5.2. Resultados: condroitín es semejante a los AINEs, glucosamina y glucosamina más condroitín en mejorar los desenlaces como dolor y funcionalidad a los seis meses y el desenlace radiológico proporción de pacientes con progresión de la disminución de la amplitud del espacio articular. Los AINEs, glucosamina y glucosamina más condroitín son superiores en los desenlaces rigidez a los seis meses según puntaje en la escala WOMAC (RR=5.97 IC 95% 1.45, 10.49). Condroitín sulfato es no inferior a pascledina en estos mismos desenlaces. Además en relación a seguridad no se reportó ningún evento adverso serio a ninguno de los medicamentos evaluados, incluyendo condroitín. La adherencia al tratamiento fue muy buena tanto a los seis meses como a los 24 meses y la percepción de tolerancia fue superior al 94%. Conclusiones: condroitín es semejante en efectividad y seguridad a glucosamina, glucosamina más condroitín, AINEs y pascledina en pacientes con osteoartrosis.(AU)

Eficácia e segurança da associação de sulfato de glucosamina e sulfato de condroitina no tratamento sintomático da osteoartrite de joelho / Efficacy and safety of the association of glucosamine sulfate and chondroitin sulfate in the treatment of symptomatic knee osteoarthritis

Objetivos: Avaliar a eficácia e a segurança da associação glucosamina e condroitina (GC) no tratamento da osteoartrite (OA) de joelho. Métodos: Ensaio clínico, randomizado, duplo-cego, controlado por placebo. Pacientes portadores de OA de joelho com índice algofuncional total de Lequesne (Leqt) entre 5 e 13 pontos e graus 2 ou 3 de Kellgren-Lawrence foram aleatorizados para receber a associação de sulfato de glucosamina (1,5 g) e sulfato de condroitina (1,2g) ou placebo durante 12 semanas, sendo acompanhados por 12 semanas adicionais. Empregou-se paracetamol como medicamento de resgate. Resultados: Observou-se redução de Leqt médio nos dois grupos de tratamento, de maior magnitude no grupo GC. A diferença se tornou evidente após quatro semanas, aumentando no decorrer do tratamento, embora sem atingir significância estatística (p = 0,1643 na população com intenção de tratar [ITT] e p = 0,0681 na população por protocolo [PP]). A quantidade de paracetamol consumido foi significativamente maior no grupo placebo nas populações ITT (p = 0,0394) e PP (p = 0,0257). Durante o seguimento, Leqt médio mostrou valores inferiores no grupo GC (p = 0,1061 e p = 0,0494 nas populações ITT e PP, respectivamente). Leqt começou a aumentar logo após o final do tratamento apenas no grupo placebo, observando-se redução adicional de seu valor médio no grupo GC, evidenciando o efeito terapêutico residual da associação. Os grupos foram semelhantes quanto aos eventos adversos relatados. Conclusão: Os resultados foram consistentes quanto à efetividade da associação GC. A associação se mostrou segura e bem tolerada.

Use of glucosamine and chondroitin to treat osteoarthritis: a review of the literature / Uso de glucosamina e condroitina no tratamento da osteoartrose: uma revisao da literatura

To evaluate the current evidence that support or disprove the use of glucosamine and chondroitin in the treatment of patients with osteoarthritis. We performed a literature review using the databases of Medline, PubMed and the Cochrane Controlled Trial Register and Cochrane Databases Systematic Reviews (Cochrane Library).We considered only studies with high level of evidence.The study included analysis of randomized controlled trials that included at least 100 patients in each intervention group, meta-analyzes and systematic reviews. Seven meta-analysis, one systematic review and five randomized clinical trials fit inclusion criteria of this review. Considering the best evidences until now, the use of glucosamine and chondroitin does not provide clinical relevant benefits to patients with osteoarthritis of the knee or hip (Level I of evidence and grade A of recommendation). Further trials with adequate technology are necessaries to elucidate this question. .

Avaliar evidências que apoiem ou refutem o uso de glucosamina e condroitina no tratamento de pacientes com osteoartrose. Foi feita uma revisão da literatura com o uso dos bancos de dados Medline, Pubmed e Cochrane Controlled Trial Register e Cochrane Databases Systematic Reviews (Cochrane Library). Foram considerados apenas estudos com elevado nível de evidências. O estudo incluiu a análise de ensaios clínicos randomizados que incluíram pelo menos 100 pacientes em cada grupo de intervenção, metanálises e revisões sistemáticas. Sete metanálises, uma revisão sistemática e cinco ensaios clínicos randomizados preencheram os critérios de inclusão desta revisão. Frente às melhores evidências existentes até o momento, o uso da glucosamina sulfatada/hidroclorídrica e da condroitina não produz benefícios clinicamente relevantes em pacientes com osteoartrose do joelho e do quadril (nível de evidência I e grau de recomendação A). Futuros estudos com metodologia adequada são necessários para elucidação dessa questão. .

A ROCK Inhibitor Blocks the Inhibitory Effect of Chondroitin Sulfate Proteoglycan on Morphological Changes of Mesenchymal Stromal/Stem Cells into Neuron-Like Cells

Chondroitin sulfate proteoglycan (CSPG) inhibits neurite outgrowth of various neuronal cell types, and CSPG-associated inhibition of neurite outgrowth is mediated by the Rho/ROCK pathway. Mesenchymal stromal/stem cells (MSCs) have the potential to differentiate into neuron-like cells under specific conditions and have been shown to differentiate into neuron-like cells by co-treatment with the ROCK inhibitor Y27632 and the hypoxia condition mimicking agent CoCl2. In this study, we addressed the hypothesis that a ROCK inhibitor might be beneficial to regenerate neurons during stem cell therapy by preventing transplanted MSCs from inhibition by CSPG in damaged tissues. Indeed, dose-dependent inhibition by CSPG pretreatment was observed during morphological changes of Wharton's jelly-derived MSCs (WJ-MSCs) induced by Y27632 alone. The formation of neurite-like structures was significantly inhibited when WJ-MSCs were pre-treated with CSPG before induction under Y27632 plus CoCl2 conditions, and pretreatment with a protein kinase C inhibitor reversed such inhibition. However, CSPG treatment resulted in no significant inhibition of the WJ-MSC morphological changes into neuron-like cells after initiating induction by Y27632 plus CoCl2. No marked changes were detected in expression levels of neuronal markers induced by Y27632 plus CoCl2 upon CSPG treatment. CSPG also blocked the morphological changes of human bone marrow-derived MSCs into neuron-like cells under other neuronal induction condition without the ROCK inhibitor, and Y27632 pre-treatment blocked the inhibitory effect of CSPG. These results suggest that a ROCK inhibitor can be efficiently used in stem cell therapy for neuronal induction by avoiding hindrance from CSPG.

[Investigation of the preventive effect of glucosamine, chondroitin alone and in combination on cartilage insult caused by quinolone in juvenile rats]

Osteoarthritis is considered the most common joint disease in the world, especially among the aged population. But it may affect the kids as a secondary type when kids were administered some groups of drugs such as quinolones which cause cartilage deformations and predispose to secondary type of osteoarthritis. This study aims to investigate the protective effect of glucosamine and chondroitin alone and in combination in the treatment of arthritis in Juvenile Rats. This study was applied on 5 groups of juvenile wistar rats, which divided as: normal group, control group, the group of GA, group of CS, the group of combination between GA+CS. At the end of the study all of rats were killed, then measurement of maximum extension of the right knee were performed, also histological and functional analysis of the articular cartilage of the knee were performed. Control group showed the degenerative changes as compared to the normal group, which is improved into the groups of GA, CS, which distinguished from the combination group. This study shows that GA and CS have protective effect able to opposite the destructive effect of quinolone on immature cartilages

The effect of the removal of chondroitin sulfate on bond strength of dentin adhesives and collagen architecture / 대한치과보존학회지

Proteoglycan is highly hydrophilic and negatively charged which enable them attract the water. The objective of study was to investigate the effects of Proteoglycan on microtensile bond strength of dentin adhesives and on architecture of dentin collagen matrix of acid etched dentin by removing the chondroitin sulphate attached on Proteoglycan. A flat dentin surface in mid-coronal portion of tooth was prepared. After acid etching, half of the specimens were immersed in 0.1 U/mL chondroitinase ABC (C-ABC) for 48 h at 37degrees C, while the other half were stored in distilled water. Specimens were bonded with the dentin adhesive using three different bonding techniques (wet, dry and re-wet) followed by microtensile bond strength test. SEM examination was done with debonded specimen, resin-dentin interface and acid-etched dentin surface with/without C-ABC treatment. For the subgroups using wet-bonding or dry-bonding technique, microtensile bond strength showed no significant difference after C-ABC treatment (p > 0.05). Nevertheless, the subgroup using rewetting technique after air dry in the Single Bond 2 group demonstrated a significant decrease of microtensile bond strength after C-ABC treatment. Collagen architecture is loosely packed and some fibrils are aggregated together and relatively collapsed compared with normal acid-etched wet dentin after C-ABC treatment. Further studies are necessary for the contribution to the collagen architecture of noncollagenous protein under the various clinical situations and several dentin conditioners and are also needed about long-term effect on bond strength of dentin adhesive.

A Case of Cataract Surgery without Pupillary Device in the Eye with Iridoschisis

PURPOSE: To introduce a case of iridoschisis patient who underwent cataract surgery successfully without pupil device. METHODS: A 64-year-old female who showed iridoschisis of her both eyes underwent cataract operation at her right eye without a pupillary device. The preoperative and postoperative ophthalmologic examinations including visual acuity, intraocular pressure, reaction of anterior chamber, and degree of damage on iris was evaluated respectively. RESULTS: Cataract surgery was performed under topical anesthesia through a clear corneal incision. Iris fibrils were held in place by ophthalmic viscosurgical device (OVD, sodium hyaluronate 3%-sodium chondroitin sulfate 4%, Viscoat(R)) that was injected into the anterior chamber. A small capsulorrhexis was made and the nucleus was delivered with low-power phacoemulsification, most of which was performed under the anterior capsule. The iris came into contact with the OVDs only and received no mechanical trauma. There were no intraoperative complications such as tear of the iris, hyphema, loss of mydriasis, or rupture of the posterior lens capsule. The edema of corneal stroma and inflammation of anterior chamber was shown at immediate-postoperative period, but completely subsided 2 weeks later. The visual acuity showed improvement from 20/400 to 20/30. CONCLUSIONS: In iridoschisis patients, there is a risk of aspiration of iris fibers during cataract surgery. With adequate use of OVD and careful modulation of surgical devices, cataract surgery was successfully performed without using extra pupil-supporting device.

A Case of Cataract Surgery without Pupillary Device in the Eye with Iridoschisis

PURPOSE: To introduce a case of iridoschisis patient who underwent cataract surgery successfully without pupil device. METHODS: A 64-year-old female who showed iridoschisis of her both eyes underwent cataract operation at her right eye without a pupillary device. The preoperative and postoperative ophthalmologic examinations including visual acuity, intraocular pressure, reaction of anterior chamber, and degree of damage on iris was evaluated respectively. RESULTS: Cataract surgery was performed under topical anesthesia through a clear corneal incision. Iris fibrils were held in place by ophthalmic viscosurgical device (OVD, sodium hyaluronate 3%-sodium chondroitin sulfate 4%, Viscoat(R)) that was injected into the anterior chamber. A small capsulorrhexis was made and the nucleus was delivered with low-power phacoemulsification, most of which was performed under the anterior capsule. The iris came into contact with the OVDs only and received no mechanical trauma. There were no intraoperative complications such as tear of the iris, hyphema, loss of mydriasis, or rupture of the posterior lens capsule. The edema of corneal stroma and inflammation of anterior chamber was shown at immediate-postoperative period, but completely subsided 2 weeks later. The visual acuity showed improvement from 20/400 to 20/30. CONCLUSIONS: In iridoschisis patients, there is a risk of aspiration of iris fibers during cataract surgery. With adequate use of OVD and careful modulation of surgical devices, cataract surgery was successfully performed without using extra pupil-supporting device.

Avaliação do efeito da glicosamina e condroitina na consolidação de fratura: estudo experimental em ratos / Evaluating the effects of glucosamine and chondroitin in bone healing: experimental study in rats

Objetivo: Avaliar o efeito da administração da condroitina e da glicosamina na consolidação de fratura em modelo animal. Métodos: Este estudo experimental envolveu a utilização de 40 ratos machos adultos da raça Lewis. Os animais foram randomicamente divididos em quatro grupos de 10 animais cada, assim constituídos: grupo I, com administração de glicosamina; grupo II, com administração de condroitina; grupo III, administração da associação de glicosamina e condroitina; grupo IV, administração de água destilada (grupo controle). Realizou-se uma fratura fechada médio-diafisária da tíbia e fíbula direitas em cada animal, seguida da administração diária das drogas de acordo com o grupo, durante 30 dias. Após esse período, os animais foram sacrificados para estudo dos calos ósseos formados. Os critérios de avaliação foram a avaliação clínica da consolidação óssea, mensuração da densidade mineral do calo ósseo utilizando-se a densitometria óssea e cálculo da área do calo formado por meio de planigrafia. Os dados coletados foram avaliados com a técnica da análise de variância (ANOVA) para verificar diferenças entre as médias nos quatro grupos estudados e com o teste de Tukey para comparação das médias duas a duas. Adotou-se nível de significância de 5% (a = 0,05). Resultados: A utilização da condroitina e da glicosamina, tanto de maneira isolada quanto associadas, não resultou em aumento da área do calo ósseo ou da sua densidade mineral óssea, e não havendo melhora clínica da consolidação óssea. Conclusão: A administração de condroitina e glicosamina, neste estudo, não influenciou – quer de maneira positiva ou negativa – a consolidação de fraturas experimentais em ratos.

Estudio de la eficacia del condroitín 4 y 6 sulfato en los síntomas de la artrosis de rodilla / Study of the effectiveness of condroitín 4 and 6 sulphate in the symptoms of the artrosis of knee

We developed a prospective, open study to evaluate the efficacy of chondroitin sulfate in the treatment of kneeosteoarthritis. Methodology: We studied 61 patients with primary knee osteoarthritis. They were given 800mg/day chondroitin 4-and 6- sulfate (Condrosulf, IBSA, Switzerland) for a period of three months. Patients were controlled every 30 days using the Lequesne index and the visual analogue pain scale. Medication was suspended after 90 days and patients were reevaluated 90 days later. Only Paracetamol was allowed as analgesic. Results: After 90 days a significant improvement of45 percent was observed in the Lequesne index, and 59 percent for knee pain. Once medication is suspended, the effect tends to slowly revert, with final study results significantly better than basal levels. Residual effect is better in patients under age 65 and in those with less basal radiological damage. Subjective opinion of both patient and doctor concurs with results. Conclusions: Chondroitin 4-and 6- sulfate is effective for the symptomatic treatment of knee osteoarthritis. Its effect lasts several months after drug suspension.

Nonsurgical Treatment of Osteoarthritis

Osteoarthritis (OA) is the most common cause of localized or generalized joint pain in adults. OA is a condition that represents a complex of interactive degradative and reparative processes in the cartilage and bone with secondary inflammatory changes, particularly in the synovium. Although there is no known cure for OA, the treatment designed for the individual patients can reduce pain, maintain joint mobility, and limit the functional impairment. Guidelines for the treatment of OA include patient education and physical and occupational therapy. Weight loss has been shown to slow the progression of disease and to relieve symptoms in obese patients with OA of the knee. While low-impact exercise is beneficial, the adverse effects of high-impact and high-intensity activitiesy on the aggravation of OA have been documented. Most drug therapies with drugs are targeted to specific symptomsatic response. It is certainly worthwhile to initiate a trial of acetaminophen, known to be beneficial in OA patients with mild to moderate pain, on the basis of the risk-to-benefit ratio and cost. However, previous studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with a better efficacy. The COX-2-specific inhibitors appear to be better tolerated, with a lower incidence of GI side effects, than comparator nonselective NSAIDs. However, the potential cardiovascular thrombotic events of these medications are considerable in the patients with hypertension or coronary artery disease. Although a number of agents are on the horizon, including glucosamine, chondroitin, diacerein, S-Adenosyl-LMethionine, and hyaluronan, no agent has been shown to have a disease-modifying OA drug (DMOAD) effect at this time.