Multicellular coupling fermentation for 3'-sialyllactose conversion using N-acetyl-glucosamine and lactose / 生物工程学报

Sialyllactose is one of the most abundant sialylated oligosaccharides in human milk oligosaccharides (HMOs), which plays an important role in the healthy development of infants and young children. However, its efficient and cheap production technology is still lacking presently. This study developed a two-step process employing multiple-strains for the production of sialyllactose. In the first step, two engineered strains, E. coli JM109(DE3)/ pET28a-BT0453 and JM109(DE3)/pET28a-nanA, were constructed to synthesize the intermediate N-acetylneuraminic acid. When the ratio of the biomass of the two engineered strains was 1:1 and the reaction time was 32 hours, the maximum yield of N-acetylneuraminic acid was 20.4 g/L. In the second step, E. coli JM109(DE3)/ pET28a-neuA, JM109(DE3)/ pET28a-nst and Baker's yeast were added to the above fermentation broth to synthesize 3'-sialyllactose (3'-SL). Using optimal conditions including 200 mmol/L N-acetyl-glucosamine and lactose, 150 g/L Baker's yeast, 20 mmol/L Mg2+, the maximum yield of 3'-SL in the fermentation broth reached 55.04 g/L after 24 hours of fermentation and the conversion rate of the substrate N-acetyl-glucosamine was 43.47%. This research provides an alternative technical route for economical production of 3'-SL.

Content determination of 5-HMF in glucosamine hydrochloride tablets and formation kinetics study / 中国药房

OBJECTIVE To establish the method for the content determination of 5-hydroxymethylfurfural （5-HMF） in glucosamine hydrochloride tablets， and to analyze its regularity and influential factors. METHODS Quantitative analysis of 5-HMF was performed using high-performance liquid chromatography. The analysis was conducted on Shim-pack GIST C18-AQ column with mobile phase consisted of 0.1% phosphoric acid solution-methanol （90∶10， V/V） at the flow rate of 1.0 mL/min. The column temperature was 30 ℃， and detection wavelength was 284 nm. The injection volume was 20 μL. Reaction kinetics test of different temperatures was adopted to analyze the relationship of 5-HMF content with reaction temperature and reaction time， and utilized to build its formation kinetic model. RESULTS The linger range of 5-HMF was 0.057-5.698 μg/mL （r＝0.999 9）. The limits of detection and quantitation were 5.70 and 17.09 ng/mL； RSDs of precision， repeatability and stability （24 h） tests were all lower than 1.0% （n＝6）. The average recoveries ranged from 99.38% to 99.73%（RSD＝0.53%， n＝9）. The contents of the 5-HMF in 8 batches of samples ranged 4.10-35.13 μg/g. Results of data fitting in reaction kinetics test showed that the higher reaction temperature and the longer reaction time， the higher 5-HMF content in the sample. At 50， 60， 70 and 80 ℃ ， the relationship between the content of 5-HMF and the reaction time was linear， in accordance with a zero-order kinetic model. The reaction rate constants were 6.789， 7.715， 8.815 and 11.430， respectively. CONCLUSIONS The established method has strong specificity， high sensitivity， and good accuracy； the reaction temperature and reaction time are important influential factors for the formation of 5-HMF in glucosamine hydrochloride tables. The change rule of its content conforms to the zero-order kinetic model.

Synthesis and antibacterial activity of D-glucosamine-fluoroquinolone derivatives / 药学学报

Based on the idea of modification of sugar drugs, or transforming other active substances with sugar molecules, sixteen D-glucosamine-fluoroquinolone (FQ) derivatives were designed by combining D-glucosamine with FQs and synthesized by a multi-step reaction with shared intermediates. The assay results of anti-human pathogenic bacteria and anti-citrus canker showed that the inhibitory activities of two target molecules TM2b and TM2d against Staphylococcus aureus ATCC14125 were stronger than those of all tested positive control drugs, and the inhibitory rates of target molecules TM2m and TM2n against citrus canker were higher than that of the positive control streptomycin at the concentrations of 0.5 and 0.2 µg·mL-1, respectively, which all were worthy of further study. In this study, a series of novel molecules composed of D-glucosamine and FQs were synthesized for the first time, and super antibacterial molecules were found, which expanded the types and biological activities of D-glucosamine derivatives.

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.

Therapeutic effect of sodium hyaluronate combined with glucosamine sulfate on patients with knee osteoarthritis / 中华地方病学杂志

Objective:To explore the therapeutic effect of sodium hyaluronate combined with glucosamine sulfate in the treatment of knee osteoarthritis.Methods:A total of 90 outpatients and inpatients with knee osteoarthritis who visited the Department of Orthopedics and Traumatology, Daishan County Hospital of Traditional Chinese Medicine from January to June 2020 were selected, and they were divided into sodium hyaluronate group (control group) and sodium hyaluronate combined with glucosamine sulfate group (observation group) by random number table method, with 45 patients in each group. Visual analog scale (VAS) score was used to evaluate the changes of pain in the two groups before treatment, 5 weeks and 6 months after treatment, respectively; at the same time, the total effective rate of 5 weeks and 6 months after treatment was compared between the two groups.Results:Before treatment, there was no significant difference in VAS scores [(7.4 ± 1.5) vs (7.3 ± 1.7) points] between the two groups ( t = 0.24, P = 0.812); at 5 weeks [(5.3 ± 1.1) vs (4.1 ± 1.2) points] and 6 months after treatment [(4.0 ± 0.8) vs (3.2 ± 0.9) points], the VAS scores of the observation group were significantly lower than those of the control group, and the differences were statistically significant ( t = 5.54, 5.32, P < 0.001). Compared with the same group before treatment, VAS scores were lower in the two groups at 5 weeks and 6 months after treatment, and the differences were statistically significant ( P < 0.05). At 5 weeks after treatment, there was no significant difference in the total effective rates [44.4% (20/45) vs 48.9% (22/45)] between the two groups (χ 2 = 0.18, P = 0.672); at 6 months after treatment, the total effective rate of the observation group (91.1%, 41/45) was significantly higher than that of the control group (66.7%, 30/45), and the difference was statistically significant (χ 2 = 8.07, P = 0.004). Conclusion:Sodium hyaluronate combined with glucosamine sulfate can significantly reduce the pain in patients with knee osteoarthritis, the total effective rate is higher, and is better than the effect of sodium hyaluronate alone.

The effect of deproteinization methods on the properties of glucosamine hydrochloride from shells of white leg shrimp (Litopenaeus vannamei) and black tiger shrimp (Penaeus monodon) / Efeito de métodos de desproteinização nas propriedades do cloridrato de glucosamina de cascas de camarão de pernas brancas (Litopenaeus vannamei) e cascas de camarão de tigre preto (Penaeus monodon)

ABSTRACT: The effect of methods to remove protein content on the properties of glucosamine hydrochloride from the shells of white leg shrimp (Litopenaeus vannamei) and black tiger shrimp (Penaeus monodon) was investigated. Chitin from shrimp shells was obtained by demineralization in 6% HCl for 12h, deproteinization by two different methods (first group soaked in 8% NaOH for 36h and second group treated in Alcalase enzyme at the concentration of 0.2% for 36h). Two group samples were converted to glucosamine hydrochloride by soaking in 36.76% HCl solution for 5h at 85 °C. The results of fourier transform infrared spectroscopy (FTIR), solubility and recovery yield analysis showed that deproteinization methods did not significantly affect the properties of glucosamine hydrochloride. However, glucosamine hydrochloride from white leg shrimp shells contained higher recovery yield and solubility than black tiger shrimp shells.

RESUMO: Investigou-se o efeito de métodos para remover o conteúdo de proteínas nas propriedades do cloridrato de glucosamina das conchas de camarão de pernas brancas (Litopenaeus vannamei) e camarão de tigre preto (Penaeus monodon). A quitina das cascas de camarão foi obtida por desmineralização em HCl a 6% por 12 h, desproteinização por dois métodos diferentes (primeiro grupo embebido em NaOH a 8% por 36 h e segundo grupo tratado na enzima Alcalase na concentração de 0,2% por 36 h). Duas amostras de grupo foram convertidas em cloridrato de glucosamina por imersão em solução de 12M HCl por 5 h a 85 °C. Os resultados das análises de FTIR, solubilidade e rendimento de recuperação mostraram que os métodos de desproteinização não afetaram significativamente as propriedades do cloridrato de glucosamina. No entanto, o cloridrato de glucosamina de cascas de camarão de pernas brancas continha maior rendimento e solubilidade de recuperação do que as cascas de camarão tigre preto.

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

Efecto fisiológico de elicitores en el crecimiento y desarrollo de papa (Solanum tuberosum L.) variedad Diacol Capiro / Physiological effect of elicitors on the growth and development of potato (Solanum tuberosum L.) variety Diacol Capiro

RESUMEN La utilización de elicitores es frecuente en la inducción de diferentes respuestas relacionadas con la resistencia sistémica de las plantas; no obstante, no se ha caracterizado el gasto metabólico que generan en el cultivo de papa variedad Diacol Capiro, que es la más utilizada para el procesamiento industrial en Colombia, debido a su calidad y alta producción. En esta investigación, se evaluó el efecto de cuatro elicitores en el crecimiento y desarrollo del cultivo de papa, en la vereda El Toval, del municipio de Tutazá, Boyacá. El diseño experimental fue en parcelas divididas, en donde la parcela principal fue la etapa fenológica, en la que se hizo la aplicación (E1; formación de tallos secundarios), época dos (E2; floración) y época tres (E3; aplicación tanto en formación de tallos secundarios como en floración) y la subparcela, con los elicitores aplicados (glucosamina, ácido γ-amino butírico, fosfito de potasio y ácido salicílico) y el testigo sin aplicación. Los datos fueron tomados a los 60, 80 y 100 días después de la siembra, teniendo como variables: altura de la planta, número de foliolos, clorofilas totales, eficiencia fotosintética, biomasa seca y producción. La glucosamina fue el tratamiento que obtuvo menores resultados en la mayoría de variables evaluadas con respecto al testigo; asimismo, los elicitores tienen efectos diferentes, dependiendo del estado fenológico del cultivo, especialmente, en la época de formación de tallos secundarios. El ácido salicílico (AS) presentó un comportamiento estadísticamente similar al del testigo, mientras que los demás elicitores aplicados, disminuyeron la producción de papa.

ABSTRACT Elicitors are frequently employed for the induction of different responses related to the systemic resistance of plants, however, it has not been fully characterized in the metabolic expenditure generated in the cultivation of the potato variety Diacol Capiro, the most planted for industrial processing in Colombia due to its quality and production. In this research, the effect of four elicitors on the growth and development of the potato crop was evaluated, in the municipality of Tutazá, Boyacá. The experimental design was divided plots, being the main plot the phenological stage in which the application was made (E1; formation of secondary stems), season two (E2; flowering) and season three (E3; application both in formation of secondary stems as in flowering) and the subplot, the applied elicitors (glucosamine, γ-amino butyric acid, potassium phosphite and salicylic acid) and the control without application. Data were taken 60, 80 and 100 days after sowing, having as variables: plant height, number of leaflets, total chlorophylls, photosynthetic efficiency, dry biomass and production. With the use of glucosamine the lowest results were obtained in most of the variables evaluated with respect to the control, likewise, elicitors had different effects depending on the phenological state of the crop, especially at the moment of secondary stem formation. Salicylic acid (AS) presented a statistically similar behavior to that of the control while the other applied elicitors decreased potato production.

A comparative study of the efficacy of glucosamine sulfate and diacerein in the treatment of adult Kashin-Beck disease / 中华地方病学杂志

Objective:To observe and compare the therapeutic effects of glucosamine sulfate (GS) and diacerein (DCN) on adult Kashin-Beck disease (KBD).Methods:A clinical randomized controlled trial was conducted in the historical severe KBD areas Fanrong Township, Fulu Town, Long'anqiao Town, Lianghe Town, Shaowen Township of Heilongjiang Province, and 240 patients were selected according to the criteria of "Diagnosis of Kashin-Beck Disease" (WS/T 207-2010), then divided into GS and DCN groups (gender, age, and KBD condition balanced) via the random number table method, with 120 patients in each group. Followed up once a month to investigate the patient's medication and clinical symptoms, and distributed drugs for the next stage. Fasting blood samples and urine samples were collected before, during, and at the end of treatment (0, 90, and 180 days). Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum interleukin (IL)-1β level and urine pyridinol (PYD) level. Visual analog scale (VAS) scores, evaluation of affected joints, self-evaluated efficacy, and evaluation of adverse reactions were carried out through questionnaires. Joint dysfunction scores and medications efficacy determination were performed according to the "Judgment of Kaschin-Beck Disease Treatment Effect" (WS/T 79-2011).Results:Expression of cytokines related to cartilage metabolism: after 180 days of treatment, serum IL-1β levels, urine PYD levels in GS group and urine PYD levels in DCN group were lower than those in the same group at 0 day of treatment ( Z = - 2.332, - 5.420, - 5.204, P < 0.05). VAS scores: after 90 days of treatment, the pain, stiffness scores of patients in GS group and the pain, stiffness, and function scores in DCN group were lower than those in the same group at 0 day of treatment ( Z = - 2.612, - 2.359, - 3.637, - 2.881, - 2.238, P < 0.05); after 180 days of treatment, the pain, stiffness and function scores of patients in GS and DCN groups were significantly lower than those of the same group at 0 day of treatment ( Z = - 6.738, - 9.530, - 7.781, - 5.428, - 3.761, - 3.587, P < 0.01). Evaluation of affected joints: after 90 and 180 days of treatment, except for pain of weather changes in DCN group, the scores of symptomatic joints in the two groups were lower than those at 0 day of treatment ( P < 0.05). Efficacy self-evaluation: after 180 days of treatment, the self-evaluated efficacy ratio of DCN group was higher than that of GS group and the same group after 90 days of treatment (χ 2 = 4.165, 4.022, P < 0.05). Evaluation of adverse reactions: after 90 and 180 days of treatment, the main adverse reactions of patients in GS and DCN groups were gastrointestinal symptoms. Joint dysfunction scores: after 90 days of treatment, the sum of the effective rate and the markedly effective rate of GS group was higher than that of DCN group (χ 2 = 4.993 , P < 0.05); while after the 180 days of treatment, there was no significant difference between the two groups (χ 2 = 0.417 , P > 0.05). Conclusions:Both GS and DCN have a certain therapeutic effect on adult KBD and can improve clinical symptoms. The GS takes effect quickly, and long-term use can protect cartilage from inflammatory factors 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.

Efficacy and Safety of Xianling Gubao Capsule Combined with Glucosamine in the Treatment of Knee Osteoar- thritis：A Meta-analysis / 中国药房

OBJECTIVE：To systematically evaluate the efficacy and safety of Xianling gubao capsule combined with glucosamine in the treatment of knee osteoarthritis （KOA），and to provide evidence-based reference for clinical treatment of KOA. METHODS：Retrieved from Cochrane library ，PubMed，Embase，CNKI，Wanfang database ，CBM and VIP during the inception to Nov. 2020，randomized controlled trials （RCTs）about glucosamine （control group ）combined with Xianling gubao capsule （trial group）in the treatment of KOA were collected. After data extraction ，Cochrane 5.1.0 system evaluator manual was used to evaluate the quality of the included clinical studies met inclusion criteria ，and Rev Man 5.4 software was used for Meta-analysis. RESULTS ： A total of 11 RCTs with 970 patients were included in this study. Results of Meta-analysis showed that cure rate [OR ＝2.41，95％CI （1.48，3.93），P＜0.001]，marked effective rate [OR ＝1.95，95％CI（1.49，2.56），P＜0.001]，total effective rate [OR ＝4.00，95％CI （2.57，6.24），P＜0.001]，visual analogue scale （VAS）score [MD ＝－2.34，95％CI（－2.51，－2.17），P＜0.001]，knee function score [MD ＝31.32，95％CI（27.89，34.75），P＜0.001]，Japanese Orthopaedic Association （JOA）low back pain score [MD ＝ 12.22，95％CI（9.68，14.76），P＜0.001] and pain relief time [MD ＝－1.55，95％CI（－1.84，－1.25），P＜0.001] of trial group were all significantly better than those of control group. The incidence of ADR in trial group was significantly lower than control group [OR ＝0.04，95％CI（0.02，0.12），P＜0.001]. CONCLUSIONS ：Xianing gubao capsule combined with glucosamine in the treatment of KOA is significantly better in cure rate ，marked effective rate ，total effective rate ，VAS，score，knee function score，JOA low back pain score and pain relief time ，and could significantly reduce the incidence of ADR.

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)

Evaluation of Glucosamine Effect Against Heart and Brain Damage Induced by Y-radiation or Aluminium Chloride in Female Rats

Abstract Glucosamine is known as anti-inflammatory, antioxidant and as neuroprotective as well as using to treat many of diseases. This work aimed to investigate the remedial effect of glucosamine (20mg/kg b.wt) against the damage induced by a single dose of γ-radiation (8Gy) or aluminium chloride (AlCl3) (100mg/kg b.wt) in the heart and brain tissues of female rats. Serum aspartate aminotransferase (AST), cholesterol, triglycerides (TGs), LDH and creatine kinase (CPK) were measured. Moreover, gene expression of amyloid protein precursor (APP) and seladin-1 were estimated in the brain tissue. Also, acetylcholinesterase activity (AChE) and p-tau protein expression were estimated in brain homogenate. Metallothioneine (MT) was estimated in the heart and brain tissues. Heart and brain histopathological examination was performed. Irradiation significantly decreased serum AST, CPK and LDH, as well as MT levels in heart and brain tissues. Also, gene expression of seladin-1 decreased. On the other hand, irradiation significantly increased serum TGs level and brain AchE activity, tau protein, and β-amyloid percursor (APP). AlCl3 administration (21 days) induced disturbance in most of the estimated parameters, especially AST, TGs, and MT. Glucosamine treatment with irradiation or AlCl3 improved most of the measured parameters. In addition, histopathological examination confirmed the biochemical results. In conclusion: Glucosamine could be used to improve the heart and brain damages induced by γ-radiation exposure or AlCl3.

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.

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.

Glucosamine combined with chondroitin sulfate for knee osteoarthritis:a systematic review / 中华风湿病学杂志

Objective To evaluate the efficacy and safety of glucosamine (GS) combined with chondroitin sulfate (CS) for knee osteoarthritis (OA).Methods We searched the CENTRAL (Issue 1,2016),PUBMED (1946 to 2016.1.20),EMBASE (1947 to 2016.1.20),CBM (1978 to 2016.1.20),CNKI (1994 to 2016.1.20),WanFang Data (1980 to 2016.1.20) and VIP (1989 to 2016.1.20) and we searched randomized controlled trials (RCT) of GS combined with CS for knee OA.Two reviewers independently identified the included trials,evaluated the quality of methodology and extracted data.The Review manager 5.3 software was used for data analysis.Results Four RCTs were included in this systematic review.The combination group compared with GS group,a total number of 1 145 patients,and the combination group compared with CS group,a total number of 1 067 patients.The outcomes showed:① Among those 4 RCTs that comparing the combination with GS,three RCTs reported western ontario and mcmaster universities osteoarthritis index (WOMAC) score.Summarized results of these 3 RCTs showed no significant difference between combination group and GS group (all P values ＞0.05).MDs of WOMAC score in pain,stiffnessand function were-6.60[95％CI(-18.79,5.59),-15.90(-43.09,11.29) and-6.44 (-16.46,3.59)].② Two long-term (≥6 months) study (n=937) compared the combination with CS group and showed no significant difference (all P values ＞0.05).Pooled MD of WOMAC score in pain and function were-0.80 (-4.96,3.36) and-1.76 (-4.46,0.94) respectively.③ Subgroup analysis in 1 RCT showed that in moderate-to-severe knee pain group (n=142) combination obviously improve the WOMAC score in pain,stiffnessand function compared with CS groupand the differences werestatistically significant (all P values ＜0.05).MDs were-10.46(-17.98,-2.94),-9.70(-18.48,0.92) and 9.39 (-17.33,-1.45).Conclusion There is no evidence to support that the combination of GS and CS for knee OA cansignificantlyimprovethe WOMAC score compared with either GS or CS.For patients with-moderate-to-severe knee pain,combination might be superior toeither GS or CS.

Therapeutic effect of combined drug therapy on knee joint of Kaschin-Beck disease / 中华地方病学杂志

Objective To investigate the effect of knee joint injection of sodium hyaluronate combined with oral administration of diacerein and/or glucosamine sulfate on knee joint of Kaschin-Beck disease.Methods The method of prospective study was used,80 patients with Kaschin-Beck disease admitted to the General Internal Medicine,Guang'an People's Hospital from January 2015 to December 2017 were selected as subjects.They were divided into 4 groups according to the difference of their medication methods,20 cases per group.Group A was treated with intra-articular injection of sodium hyaluronate,Group B was treated with intra-articular injection of sodium hyaluronate + oral diacerein,Group C was treated with intra-articular injection of sodium hyaluronate + oral glucosamine sulfate,Group D was treated with intra-articular injection of sodium hyaluronate + oral diacerein and glucosamine sulfate,and the overall therapeutic effects of the 4 groups were compared.Results The knee joint scores of Group D at 7,14,90,and 180 days after treatment were (6.25 ± 2.01),(4.22 ± 1.15),(2.21 ± 1.01),and (1.15 ± 0.15) scores,respectively,they were significantly lower than those of Group A [(12.11 ± 3.02),(11.91 ± 2.98),(11.85 ± 2.85),(11.05 ± 2.52) scores],Group B [(9.11 ± 2.85),(8.32 ± 2.45),(7.55 ± 2.32),(6.15 ± 2.01) scores] and Group C [(9.12 ± 2.84),(8.23 ± 2.32),(7.43 ± 2.29),(6.11 ± 2.00) scores],the differences were statistically significant (P ＜ 0.05).The total effective rates of the 4 groups were 60％ (12/20),65％ (13/20),70％ (14/20),and 90％ (18/20),respectively,Group D was significantly higher than those of other 3 groups (x2 =18.250,18.250,16.000,P ＜ 0.05).The scores of 20 m walking pain and joint tenderness in Group D after treatment and follow-up period were lower than those of other 3 groups (P ＜ 0.05).Conclusions In the clinical practice of Kaschin-Beck disease,intra-articular injection of sodium hyaluronate combined with oral diacerein and glucosamine sulfate can improve the knee joint function of patients,alleviate pain and enhance the overall therapeutic effect.The combined therapy has great clinical value.

Synthesis and biosafety evaluation of four acryl acetyl glucosamine with cell membrane binding ability / 国际生物医学工程杂志

Objective To synthesize and characterize four acryl acetyl glucosamine (DA-NAG), and to determine its biocompatibility and cell membrane binding properties, so as to provide basis for its application in medical self agglutination gels. Methods DA-NAG was synthesized by esterification reaction. The products were characterized by mass spectrometry and hydrogen spectrum. Cytotoxicity test and subcutaneous implantation test were performed on the synthesized DA-NAG. The binding properties of DA-NAG to mouse fibroblast L929 cell membrane were detected using high performance liquid chromatography (HPLC). Results The characterization of mass spectrum and hydrogen spectrum are consistent with the characteristics of DA-NAG. The product has no cytotoxicity, and the subcutaneous implantation shows that the DA-NAG can be degraded at 4 weeks without obvious stimulation to the surrounding tissues. The result of HPLC shows the binding effect between the DA-NAG and cell membrane. Conclusions DA-NAG is successfully synthesized, and it has good cytocompatibility and binding ability to cell membrane.

Protective effect of glucosamine and risedronate (alone or in combination) against osteoarthritic changes in rat experimental model of immobilized knee / 대한해부학회지