Progress of research on application of chondroitin sulfate in osteogenic repair materials / 口腔医学

@#Chondroitin sulfate is an important component of extracellular matrix (ECM) in animal and human body. In recent years, chondroitin sulfate has been proven to have potential efficacy in biomedical application and has been widely used in bone regeneration and osteogenesis, especially in craniofacial reconstruction and dental medicine. Research shows that chondroitin sulfate derivatives and chondroitin sulfate composite scaffolds have great potential in promoting osteogenesis and biomineralization. However, due to the variety of chondroitin sulfate and various application forms, study on its mechanism of osteogenic repair is still insufficient. In this paper, biological characteristics, bone regeneration and osteogenesis of chondroitin sulfate, its application in different biomaterial design and future prospect are discussed.

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

A Pilot Observational Study of Topical Glucosamine and Chondroitin Sulfate in Patients with Knee Osteoarthritis

Objective : To determine the efficacy and safety of topical glucosamine and chondroitin sulfate in the treatment of knee Osteoarthritis (OA). Materials and Methods : Thirty-three patients diagnosed with knee OA were included in the study. Subjects received topical application of glucosamine and chondroitin sulfate on the affected knee two times a day for four weeks. Pain, joint stiffness, and physical functions were evaluated by the Western Ontario and McMaster Osteoarthritis Index (WOMAC). A Visual Analog Scale (VAS) was used to evaluate the severity of the initial pain. The patients were assessed before the treatment and four weeks after the initiation of the treatment. Results : The WOMAC scores for pain, stiffness, and function, as well as the VAS score, were significantly improved (P<0.01) in subjects at week four compared to the baseline. There was a 44.02% improvement in the total WOMAC scores and a 51.11% improvement in the VAS scores with glucosamine and chondroitin sulfate topical gel after four weeks. Conclusion : Topical glucosamine and chondroitin sulfate are safe and effective in improving knee pain, stiffness, and physical function in knee OA.

Development and validation of a HILIC-HPLC-ELSD method for simultaneous determination of glucosamine hydrochloride and chondroitin sulfate in dietary supplements

Abstract The objective of the present study is to develop and validate a simple, selective and accurate hydrophilic interaction liquid chromatography - a high performance liquid chromatography incorporating an evaporative light scattering detector (HILIC-HPLC-ELSD) method for simultaneously determining glucosamine hydrochloride and chondroitin sulfate in dietary supplements. The chromatographic separation was carried out on a ZIC-HILIC column (150 mm x 4.6 mm x 5µm) in isocratic system mode with a mobile phase of acetonitrile, 30 mM ammonium formate and water (77:20:3, v/v/v) at pH 4.5, a column temperature of 35°C, a flow rate of 1 mL.min-1, and an injection volume of 5 µL. An evaporative light scattering (ELS) detector was used. Effective separation was achieved by means of analyte resolution of more than 1.5 with an analysis run time of approximately 20 minutes. The linearity of glucosamine hydrochloride and chondroitin sulfate ranged from 0.4 to 2.5 mg.mL-1. The limits of the detection and quantification of glucosamine hydrochloride were 20 and 80 mg.mL-1 respectively, while for chondroitin sulfate they were 80 and 400 mg.mL-1. All validation parameters satisfied the acceptance criteria in accordance with International Conference on Harmonisation (ICH) guidelines. The method was successfully applied to the assay of commercial dietary supplement samples

Effects of miR-515-5p on the proliferation and metastasis of ovarian cancer cell A2780 by regulating the expression of chondroitin sulfate proteoglycan 4 and its mechanism / 解剖学报

Objective To investigate the targeted regulation of miR-515-5p on chondroitin sulfate proteoglycan 4 (CSPG4) and its effect on the proliferation and metastasis of ovarian cancer cell A2780. Methods The target genes of miR-515-5p were predicted by bioinformatics tools. Real-time PCR and Western blotting were used to detect the expression of miR-515-5p and CSPG4 in 65 cases ovarian cancer tissues and adjacent tissues. Ovarian cancer cells A2780 were divided into miR-NC group, miR-515-5p group, si-NC group, si-CSPG4 group, miR-515-5p + pcDNA group, miR-515-5p + pcDNA-CSPG4 group. MTT assay was used to detect cell proliferation. Transell was applied to detect cell migration and invasion, and Western blotting was selected to detect cyclinD1, P21, matrix metalloproteinase (MMP)-2 and MMP-9 protein expression. The double luciferase reporter gene experiment and Western blotting confirmed the regulation effect of miR-515-5p on CSPG4 gene. Results Bioinformatics analysis showed that CSPG4 was one of the potential target genes of miR-515-5p. Compared with the adjacent tissues, the expression of miR-515-5p was lower in ovarian cancer tissues, and the expression of CSPG4 was higher (P< 0. 05). Compared with the miR-NC group, the expression of cyclinD1, MMP-2 and MMP-9 protein was lower in A2780 cells of miR-515-5p group, the expression of P21 protein was higher, the cell viability was lower, and the number of cell migration and invasion was lower (P<0. 05). Compared with the si-NC group, the expression of cyclinD1, MMP-2 and MMP-9 proteins were lower in A2780 cells in si-CSPG4 group, P21 protein was higher, cell viability was lower, and the number of cell migration and invasion was lower (P<0. 05). Compared with the miR-515-5p + pcDNA group, the expression of cyclinD1, MMP-2 and MMP-9 proteins was higher in A2780 cells of miR-515-5p + pcDNA-CSPG4 group, the expression of P21 protein was lower, and the cell viability was higher, the number of cell migration and invasion was higher (P<0. 05). MiR-515-5p targeted and negatively regulated CSPG4 expression. Conclusion MiR-515-5p could inhibit the proliferation and metastasis of ovarian cancer cell A2780 by targeting CSPG4.

Manejo no quirúrgico de la artrosis de rodilla: ¿Son efectivos los medicamentos orales complementarios? / Non-surgical management of knee osteoarthritis: are complementary oral medications effective?

La artrosis es una enfermedad progresiva de las articulaciones sinoviales que causa dolor, impotencia funcional, discapacidad, y degeneración progresiva de la articulación. En sus tratamientos, sobre todo en etapas tempranas, existen distintas intervenciones para evitar tanto su desarrollo y progresión como también para lograr un adecuado manejo de los síntomas, y hay tratamientos médicos orales no convencionales con evidencia controvertida. El objetivo de este trabajo es proporcionar una actualización, dirigida a especialistas en Ortopedia y Traumatología, respecto a la evidencia actual sobre las terapias complementarias orales en el tratamiento de la artrosis de rodilla. Se hace referencia a los métodos fármacológicos complementarios más usados y estudiados, mencionando el método de acción y las consecuencias estudiadas sobre la artrosis de rodilla. Se finaliza con una tabla de recomendaciones basada en evidencia actual.

Osteoarthritis (OA) is a progressive disease of the synovial joints that causes pain, functional impairment, disability, and progressive degeneration of the joint. Regarding its treatments, especially in early stages, there are different interventions to avoid its development and progression and also to achieve an adequate management of symptoms, and there are unconventional oral medical treatments with controversial evidence. The objective of the present paper is to provide an update, to specialists in Orthopedics and Traumatology, regarding the current evidence on complementary oral therapies in the treatment of knee osteoarthritis. References are made to the most widely used and studied complementary pharmacological methods, mentioning the method of action and the consequences studied on knee osteoarthritis. The article ends with a table of recommendations based on current evidence.

Reducción de la cobertura social para los fármacos antiartrósicos sintomáticos de acción lenta: una iniciativa de desinversión en Argentina, 2015-2017 / Reduction of social coverage for symptomatic slow-acting drugs for osteoarthritis: a disinvestment initiative in Argentina, 2015-2017

RESUMEN En abril de 2016, el Instituto Nacional de Servicios Sociales para Jubilados y Pensionados excluyó del subsidio social la cobertura al 100% de 159 fármacos, entre ellos, los antiartrósicos sintomáticos de acción lenta o symptomatic slow-acting drugs for osteoarthritis (SySADOA), por insuficiente evidencia de beneficio clínico significativo. Evaluamos el efecto de esta medida sobre la utilización de SySADOA y de los antiinflamatorios no esteroides (AINE), no afectados por la medida. Se compararon las dispensas ambulatorias de los SySADOA y los AINE de 2015 a 2017, midiendo unidades dispensadas, precio de venta al público y gasto de bolsillo del beneficiario para cada mes. Luego de la medida, descendieron un 61,6% los envases de SySADOA dispensados y un 63,4% el monto total del precio de venta al público, medido en valores constantes. La dispensa no se reorientó hacia los AINE, que descendieron un 6,1%. Disminuyó tanto la incidencia de nuevos tratamientos (de 6,4 a 3,3 tratamientos por 1.000 beneficiarios por mes) como su continuidad. El gasto de bolsillo de los beneficiarios en SySADOA aumentó un 75,8% (a valores constantes). La desinversión en intervenciones de valor terapéutico cuestionable es una herramienta valiosa para la sustentabilidad de los sistemas de salud.

ABSTRACT In April 2016, the National Institute of Social Services for Retirees and Pensioners discontinued its policy of 100% coverage for 159 drugs (the "social subsidy"), including symptomatic slow-acting drugs for osteoarthritis (SYSADOAs), due to insufficient evidence of significant clinical benefit. We evaluated the effect of this measure on the use of SYSADOAs as well as non-steroidal anti-inflammatory drugs (NSAIDs), which were unaffected by this policy change. We compared outpatient dispensations of SYSADOAs and NSAIDs from 2015 to 2017, measuring dispensed units, retail price, and out-of-pocket expenses for beneficiaries each month. After the change in coverage, there was a 61.6% total decrease in SYSADOA units dispensed, and a 63.4% decrease in the final sales price to the public, measured in constant values. Dispensation was not reoriented towards NSAIDs, which fell by 6.1%. The incidence of new treatments decreased (from 6.4 to 3.3 treatments per 1,000 beneficiaries per month), as did their continuity. Beneficiaries' out-of-pocket spending on SYSADOAs increased by 75.8% (at constant values). Disinvestment in interventions with questionable therapeutic value is an important tool in working toward the sustainability of health systems.

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)

Chondroitin sulfate from fish waste exhibits strong intracellular antioxidant potential

Chondroitin sulfate (CS) is a type of glycosaminoglycan described as an antioxidant molecule that has been found in animal species such as fish. Tilapia (Oreochromis niloticus) represents an eco-friendly source of this compound, since its economical processing generates usable waste, reducing the negative environmental impact. This waste was used for CS extraction, purification, characterization by enzymatic degradation, and evaluation of its antioxidant effect. CS obtained from tilapia presented sulfation mainly at carbon 4 of galactosamine, and it was not cytotoxic at concentrations up to 200 µg/mL. Furthermore, 100 µg/mL of CS from tilapia reduced the levels of reactive oxygen species to 47% of the total intracellular reactive oxygen species level. The ability of CS to chelate metal ions in vitro also suggested an ability to react with other pathways that generate oxidative radicals, such as the Haber-Weiss reaction, acting intracellularly in more than one way. Although the role of CS from tilapia remains unclear, the pharmacological effects described herein indicate that CS is a potential molecule for further study of the relationship between the structures and functions of chondroitin sulfates as antioxidants.

Tissue-engineered cartilage nanoscaffolds prepared with collagen, hyaluronic acid and chondroitin sulfate / 中华医学美学美容杂志

Objective:To explore the possibility of constructing tissue-engineered cartilage three-dimensional nanoscaffolds with collagen Ⅱ (COLⅡ), hyaluronic acid (HA) and chondroitin sulfate (CS).Methods:The tissue-engineered cartilage scaffolds were prepared by electrospinning techniques with the mixture COLⅡ-HA-CS solvent, which dissolved by 3-trifluoroethanol-water. The surface topography was observed under electron microscope (SEM). And the diameter of nanofibers, the water absorption rate, contact angle and degradation rate were also detected. Generation 2 rabbit chondrocytes were seeded into the scaffold. The cell survival rate and proliferation were evaluated by Cell Counting Kit-8.Results:When the concentration range of electrospinning was 80-120 mg/ml and the mixing ratio of Col, HA and CS was 6-8∶1∶1-2, the tissue engineered cartilage nanoscaffolds could be successfully prepared. Their diameters were mainly distributed between 126.5±23.3 nm and 374.7±14.1 nm. The scaffolds had satisfactory hydrophilicity and degradability. The chondrocytes could well adhere and proliferate on the scaffold.Conclusions:The COLⅡ-HA-CS tissue-engineered cartilage nanoscaffolds have good physical and biological properties, which suggests its promising application in tissue-engineered cartilage.

Difference in extracellular matrix loss between KBD and osteoarthritis / 西安交通大学学报(医学版)

【Objective】 To study the major missing components of extracellular matrix in cartilage from Kashin-Beck disease (KBD) and osteoarthritis (OA). 【Methods】 The articular cartilage specimens discarded in clinical surgery were collected; paraffin sections were prepared; and HE staining, toluidine blue, and crocusin staining were used to semi-quantitatively analyze the differences in the content of extracellular matrix in cartilage from KBD and OA. 【Results】 The percentage of HE staining area in the normal group (NC group) (83.65±8.38)% was significantly higher than that in the primary osteoarthropathy group (OA group) (57.90±21.88)% and the KBD group (KBD group) (43.67±23.91)%. The stained area percentage of the OA group was higher than that of the KBD group (P=0.034). In the NC group (75.66±12.54)% of the saffron essence O stained area percentage was significantly higher than that of the OA group (53.81±10.48)% and the KBD group (62.07±14.66)%; the KBD group was higher than the OA group (P=0.011). No statistically significant difference in area percentage was found among the NC group, OA group and KBD group stained with toluidine blue (P>0.05). 【Conclusion】 The total loss of extracellular matrix of KBD cartilage tissue is more than that of OA cartilage. The loss of proteoglycan in OA articular cartilage is more serious than that in KBD cartilage, suggesting that the lost extracellular matrix of KBD cartilage tissue is mainly type 2 collagen.

Research progress of sulfation modification of chondroitin sulfate and chondroitin sulfate preparation in Kashin-Beck disease and osteoarthritis / 中华地方病学杂志

Chondroitin sulfate (CS) is a sulfurated glycosaminoglycan, a major component of the extracellular matrix, widely distributed in skin, cartilage and vascular tissue. CS plays an important role in the physiological state regulation of articular cartilage, which affects tensile strength and elasticity of tissues by influencing aggrecan. Previous studies have shown that CS sulfate modification may be related to the growth and development disorders of cartilage tissue and the occurrence of osteoarticular diseases. At the same time, CS is also a common joint supplement, often used in the treatment of osteoarthritis and Kashin-Beck disease. In this paper, the research progress of CS sulfate modification characteristics in Kashin-Beck disease and osteoarthritis and the application of the preparation in the treatment of Kashin-Beck disease and osteoarthritis are reviewed, aiming to provide help for the investigation of the etiology of Kashin-Beck disease and the treatment of osteoarthritis and Kashin-Beck disease.

Expression of GFAP, β-tubulin Ⅲ and synaptophsin and intervention effects of chondroitin sulfate in brain of rats with chronic fluorosis / 中华地方病学杂志

Objective:To observe the expression levels of glial fibrillary acidic protein (GFAP), β-tubulin Ⅲ and synaptophsin, and explore the role of tripartite synapse in the mechanism of central nervous system (CNS) injury and the neuroprotective effect of chondroitin sulfate (CS).Methods:One month old clean grade, 48 female Sparague-Dawley rats and 48 male Sparague-Dawley rats, were randomly divided into 8 groups according to body weight (90 - 120 g) by random number table method, with 12 rats in each group, half male and half female. These rats were fed with water containing different concentrations of sodium fluoride (NaF) [ < 0.5 mg/L (control, CN), 10.0 mg/L (low dose fluoride, LF) and 50.0 mg/L (high dose fluoride, HF)]. Some rats were fed directly for 185 days (CN, LF and HF groups). In addition, rats of CN + normal saline (NS), LF + NS, HF + NS groups and LF + CS, HF + CS groups, were intraperitoneally injected with NS or 0.66 mg/kg CS for 5 consecutive days after 180 days of feeding. After the experiment, the pathological changes of hippocampal CA4 of brain tissue in each group were observed by hematoxylin eosin staining under light microscope, and the expression and distribution of GFAP, β-tubulin Ⅲ and synaptophsin in hippocampal CA4 of rats were detected by immunohistochemistry, the expression of GFAP, β-tubulin Ⅲ and synaptophsin at protein level in hippocampus of rats were detected by Western blotting.Results:Under light microscope, eosinophilic change, loss and irregular arrangement of neuron in the hippocampal CA4 were observed in LF, HF, LF + NS and HF + NS groups. The morphology of LF + CS and HF + CS groups was not significantly changed compared with CN group, but was significant changed compared with LF, HF, LF + NS and HF + NS groups. Immunohistochemical results showed that the rates of positive area of GFAP, β-tubulin Ⅲ and synaptophsin in female and male rats in LF and HF groups were significantly decreased than those in CN group ( P < 0.05); the positive area rates of female and male rats in LF + CS and HF + CS groups were higher than those in LF and HF groups, respectively ( P < 0.05). Western blotting results showed that the proten expression levels of GFAP, β-tubulin Ⅲ and synaptophsin of female and male rats in LF and HF groups (LF group: 0.90 ± 0.09, 0.82 ± 0.08, 1.43 ± 0.14, 0.92 ± 0.02, 1.21 ± 0.15, 0.87 ± 0.02, HF group: 0.58 ± 0.14, 0.73 ± 0.03, 0.63 ± 0.06, 0.67 ± 0.03, 0.87 ± 0.04, 0.70 ± 0.05) were lower than those in CN group (1.24 ± 0.08, 1.09 ± 0.10, 2.64 ± 0.30, 1.54 ± 0.09, 1.72 ± 0.10, 1.13 ± 0.06, P < 0.05). Conclusions:The tripartite synapse and extracellular matrix may take part in pathogenesis of the damages of CNS results from chronic fluorosis; CS may reduce the injury to a certain extent.

Comparative study of glucosamine sulfate and chondroitin sulfate in the treatment of adult Kashin-Beck disease / 中华地方病学杂志

Objective:To observe and compare the efficacy and safety of glucosamine sulfate (GS) and chondroitin sulfate (CS) in the treatment of adult Kashin-Beck disease (KBD), so as to provide effective medical evidence for the standardized treatment of adult KBD.Methods:A clinical randomized controlled trial was conducted in Fuyu County and Shangzhi City, KBD historical seriously ill areas in Heilongjiang Province. A total of 247 patients were selected according to the standard of "Diagnosis of Kashin-Beck Disease" (WS/T 207-2010). According to gender, age and KBD condition, they were randomly divided into GS and CS groups, 124 and 123 respectively. Follow up once a month to investigate the medication and clinical symptoms of patients, and distribute drugs for the next stage. Fasting blood and urine samples were collected before, during and at the end of treatment (0, 90 and 180 d). Serum interleukin (IL)-1β content and urine pyridine (PYD) level were measured by enzyme-linked immunosorbent assay (ELISA). The visual analogue scale (VAS) score, affected joints, self-evaluation of curative effect and side effects were evaluated through the questionnaire, joint dysfunction and drug efficacy were evaluated according to the criteria of "Evaluation of Therapeutic Effect of Kashin-Beck Disease" (WS/T 79-2011).Results:Expression of cytokines related to cartilage metabolism: at 180 d of treatment, serum IL-1β contents and urinary PYD levels in GS and CS groups were lower than those at 0 d of treatment ( Z = - 2.461, - 2.160, - 5.075, - 5.471, P < 0.05). VAS score: at 90 and 180 d of treatment, the scores of knee pain, stiffness and function in GS and CS groups were lower than those at 0 d of treatment ( P < 0.05); and at 180 d of treatment, the scores of knee stiffness and function in GS group were lower than those in CS group ( P < 0.05). Evaluation of affected joints: at 90 and 180 d of treatment, the scores of joint pain, swelling and stiffness in GS and CS groups were lower than those at 0 d of treatment ( P < 0.05). Self-evaluation of curative effect: at 180 d of treatment, the self-evaluation of curative of CS group were better than that at 90 d of treatment (χ 2 = 9.376, P < 0.05). Evaluation of side effects: at 90 and 180 d of treatment, the side effects in GS and CS groups were mainly gastrointestinal symptoms. Joint dysfunction score: at 90 d of treatment, the sum of effective rate and markedly effective rate in GS group was higher than that in CS group (χ 2 = 4.042, P < 0.05), but there was no significant difference between the two groups at 180 d of treatment (χ 2 = 0.869, P > 0.05). Conclusion:GS and CS have certain therapeutic effects on adult KBD, which can improve symptoms and reduce serum IL-1β content and urinary PYD level, but GS takes effects quickly, and its effect on improving joint stiffness and function are better than CS.

Evaluation of mesalazine polymeric conjugate in the treatment of actinic proctitis in rats

ABSTRACT Purpose: The present study aimed at testing a new formulation of mesalazine linked to chondroitin sulfate and its components alone in the treatment of actinic proctitis in rats. Methods: Forty-seven female Wistar rats were submitted to pelvic radiation and divided into eight groups: control A, mesalazine A, chondroitin A, and conjugate A, gavage of the according substance two weeks after irradiation and sacrifice three weeks after oral treatment; control C, mesalazine C, chondroitin C, and conjugate C, sacrifice six weeks after oral treatment. The rectum was submitted to histological characterization for each of the findings: inflammatory infiltrate, epithelial degeneration, mucosal necrosis, and fibrosis. Results: The inflammatory infiltrate was more intense in chondroitin A, mesalazine A, and conjugate C. The collagen deposition was less intense in chondroitin A, and mesalazine A, and more intense in control C. Conclusions: Mesalazine and chondroitin alone were efficacious in inducing a delayed inflammatory response, hence reducing the late fibrosis. The conjugate was able to induce an ever more delayed inflammatory response.

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.

Comparative study on chemical constituents of Cervi Cornu Pantotrichum in different forms of Cervus nipport / 中草药

Objective: In order to study the differences in chemical constituents of Cervi Cornu Pantotrichum in different forms of Cervus nipport. Methods: The content of polysaccharides, crude protein, amino acids, collagen, fatty acids, mineral elements, biogenic amines, nucleosides, and chondroitin sulfate composition of Cervi Cornu Pantotrichum in different forms of C. nipport was determined and compared by using UV spectrophotometer, Dumas azotometer, automatic amino acid analyzer, UPLC, HPLC, gas chromatograph, inductively coupled plasma mass spectrometer and atomic fluorescence photometer. Principal component analysis was used to evaluate the quality of Cervi Cornu Pantotrichum. Results: The content of polysaccharide, crude protein, amino acid, collagen, fatty acid, mineral element, biogenic amine, nucleoside and chondroitin sulfate in one-branched velvet antler was 8.40 mg/g, 44.82%, 42.24%, 23.23%, 6 234.69 mg/kg, 145.69 mg/g, 55.12 mg/kg, 2 271.87 mg/kg, and 0.74 mg/g, respectively; The content in two-branched velvet antler was 8.14 mg/g, 52.12%, 48.57%, 21.50%, 8 684.27 mg/kg, 126.40 mg/g, 76.14 mg/kg, 3 438.37 mg/kg, and 1.94 mg/g, respectively; The content in three-branched velvet antler was 8.64 mg/g, 51.86%, 45.49%, 22.31%, 9 100.78 mg/kg, 138.36 mg/g, 70.75 mg/kg, 2 507.82 mg/kg, and 1.84 mg/g, respectively. Conclusion: The chemical composition of Cervi Cornu Pantotrichum in different forms of C. nipport was different. The results of principal component analysis showed that the quality of the two-branched velvet antler was the best, the three-branched velvet antler was the second, the one-branched velvet antler was the worst. This study provides a reference for the quality evaluation and grading standards of different forms of Cervi Cornu Pantotrichum.

Oral glucosamine and chondroitin sulfate on synovial fluid biomarkers from osteoarthritic equine joints / Efeitos da glucosamina e condroitim sulfato oral sobre biomarcadores do líquido sinovial de articulações osteoartríticas de equinos

ABSTRACT: Several studies, mainly in vitro, have shown that chondroitin sulfate (CS) and glucosamine (GlcN) do have chondro protective and anti-inflammatory actions. The aim of the present study was to investigate whether oral CS/GlcN supplementation has effects on the CS, hyaluronic acid (HA) and prostaglandin E2 (PGE2) concentrations on synovial fluid of equine osteoarthritic joints. Horses with mild osteoarthritis (OA) in tibiotarsal joint received daily PO doses of CS and GlcN (2.8/3.1 g) for 25 days. Synovial fluid (SF) and urine samples were collected before treatment (day 0), and every 7 days, until day 55 (30 days after the end of treatment). Urinary CS increased upon oral treatment, indicating that this compound was systemically distributed. Concerning the SF, CS concentration increased after the end of the treatment and returning to baseline afterwards, while HA and PGE2 concentrations did not change. Despite the systemic distribution, oral supplementation of CS/GlcNfor 25 days was insufficient as an anti-inflammatory support. However, it is possible to infer that there was an anabolic effect upon cartilage matrix.

RESUMO: Vários estudos, principalmente in vitro, têm mostrado que o condroitim sulfato (CS) e a glucosamina (GLcN) possuem ação condroprotetora e anti-inflamatória. O objetivo deste trabalho foi investigar se a administração oral de CS/GLcN possui efeito sobre as concentrações de CS, ácido hialurônico (AH) e prostaglandina E2 (PGE2) do liquido sinovial (LS) de articulações equinas com osteoartrite (OA). Cavalos diagnosticados com OA tibiotársica grau leve receberam por via oral doses diárias de CS e GlcN (2,8g/3,1g) por 25 dias. Amostras de LS e urina foram coletadas antes do tratamento (dia 0) e a cada 7 dias até o dia 55 (30 dias após o fim do tratamento). Houve aumento do CS urinário, indicando a distribuição sistêmica desse composto. No LS, a concentração de CS aumentou após o final do tratamento e retornou aos valores basais em seguida, enquanto as concentrações de HA e PGE2 não apresentaram alterações. Apesar da distribuição sistêmica, a suplementação oral de CS/GlcNpor 25 dias foi insuficiente como medida anti-inflamatória. Contudo, pode-se inferir que houve efeito anabólico sobre a matriz cartilagínea.

Generating evidence and understanding the treatment of osteoarthritis in Brazil: a study through Delphi methodology

OBJECTIVES: This study aimed to provide evidence for understanding how to treat osteoarthritis (OA) in our country. Therefore, it was necessary to match information and investigations related to the treatment of the disease from the three main types of specialists involved: physiatrists, orthopedists and rheumatologists. METHODS: The authors acted as a scientific advisory committee. From the initial discussions, a structured questionnaire was developed for use with a group of specialists on OA using the Delphi technique. The questionnaire was sent to 21 experts appointed by the authors, and the results obtained were critically analyzed and validated. RESULTS: The prevalence of OA was 33% in Brazil, corresponding to one-third of the individuals in the reference population, which included individuals over 25 years of age. Another significant finding was that most patients did not receive any form of treatment in the early stages of OA. CONCLUSION: The committee pointed to the need for early intervention and that the available medicinal resources can fulfil this important role, as is the case with SYSADOA treatments. Glucosamine-based medicinal products with or without chondroitin could also fulfill this need for early treatment. The other generated evidence and included investigations were then grouped together and are the subject of this publication.

Production and application of 3-phosphoadenosine-5- phosphosulfate / 生物工程学报

Sulfated compounds are widely present in cytoplasm, on cell surface, and in extracellular matrix. These compounds play important roles in cell development, differentiation, immune response, detoxication, and cell signal transduction. 3-Phosphoadenosine-5-phosphosulfate (PAPS) is the universal sulfate group donor for the biosynthesis of sulfated compounds. Up to now, the synthesis of PAPS is still too expensive for industrial applications. This review focuses on the recent progress of PAPS production and summaries the application of PAPS, particularly in the production of glucosinolate, heparin, condroitin sulfate, and oxamniquine production.