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Fulltext 2019 revised algorithm for the management of knee osteoarthritis: the Southeast Asian viewpoint

Yeap SS, Tanavalee A, Perez EC, Tan MP, Reyes BHM, Lee JK, et al.

Aging Clin Exp Res, 2021 May;33(5):1149-1156.
PMID: 33774784 DOI: 10.1007/s40520-021-01834-x

BACKGROUND: Since 2014, the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) algorithm for the management of knee osteoarthritis (OA) is available worldwide.
AIM: Based on this document, a Southeast Asia Working Group (SEAWG) wished to see how the new ESCEO algorithm developed in 2019 was perceived by Southeast Asian experts and how it was integrated into their clinical practice.
METHODS: A SEAWG was set up between members of the international ESCEO task force and a group of Southeast Asian experts.
RESULTS: Non-pharmacological management should always be combined with pharmacological management. In step 1, symptomatic slow-acting drugs for osteoarthritis are the main background therapy, for which high-quality evidence is available only for the formulations of patented crystalline glucosamine sulfate and chondroitin sulfate. In step 2, oral NSAIDs are a useful option, considering the cardiovascular/renal/gastrointestinal profiles of the individual patient. Intra-articular hyaluronic acid and corticosteroids are a possible alternative to oral NSAIDs, but limited evidence is available. If steps 1 and 2 do not give adequate relief of symptoms, tramadol can be used, but its safety is debated. In general, the indications of the ESCEO algorithm are important in Southeast Asian countries, but the reimbursement criteria of local health systems are an important aspect for adherence to the ESCEO algorithm.
CONCLUSION: This guidance provides evidence-based and easy-to-follow advice on how to establish a treatment algorithm in knee OA, for practical implementation in clinical practice in Southeast Asian countries.

Matched MeSH terms: Glucosamine/therapeutic use
Differentiation of patented crystalline glucosamine sulfate from other glucosamine preparations will optimize osteoarthritis treatment

Saengnipanthkul S, Waikakul S, Rojanasthien S, Totemchokchyakarn K, Srinkapaibulaya A, Cheh Chin T, et al.

Int J Rheum Dis, 2019 Mar;22(3):376-385.
PMID: 28332780 DOI: 10.1111/1756-185X.13068

Symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) are recommended for the medium- to long-term management of knee osteoarthritis (OA) due to their abilities to control pain, improve function and delay joint structural changes. Among SYSADOAs, evidence is greatest for the patented crystalline glucosamine sulfate (pCGS) formulation (Mylan). Glucosamine is widely available as glucosamine sulfate (GS) and glucosamine hydrochloride (GH) preparations that vary substantially in molecular form, pharmaceutical formulation and dose regimen. Only pCGS is given as a highly bioavailable once-daily dose (1500 mg), which consistently delivers the plasma levels of around 10 μmol/L required to inhibit interleukin-1-induced expression of genes involved in the pathophysiology of joint inflammation and tissue destruction. Careful consideration of the evidence base reveals that only pCGS reliably provides a moderate effect size on pain that is higher than paracetamol and equivalent to non-steroidal anti-inflammatory drugs (NSAIDs), while non-crystalline GS and GH fail to reach statistical significance for pain reduction. Chronic administration of pCGS has disease-modifying effects, with a reduction in need for total joint replacement lasting for 5 years after treatment cessation. Pharmacoeconomic studies of pCGS demonstrate long-term reduction in additional pain analgesia and NSAIDs, with a 50% reduction in costs of other OA medication and healthcare consultations. Consequently, pCGS is the logical choice, with demonstrated medium-term control of pain and lasting impact on disease progression. Physician and patient education on the differentiation of pCGS from other glucosamine formulations will help to improve treatment selection, increase treatment adherence, and optimize clinical benefit in OA.

Matched MeSH terms: Glucosamine/adverse effects; Glucosamine/economics; Glucosamine/pharmacokinetics; Glucosamine/therapeutic use*
Fulltext Host, pathogen and environment: a bacterial gbpA gene expression study in response to magnesium environment and presence of prawn carapace and commercial chitin

Tiruvayipati S, Bhassu S

Gut Pathog, 2016;8:23.
PMID: 27231485 DOI: 10.1186/s13099-016-0105-5

Vibrio parahaemolyticus is a Gram-negative halophilic bacterium which is found largely in estuarine and coastal waters. The bacteria has been a main focus in gastro-intestinal infections caused primarily due to the consumption of contaminated seafood. It was shown to survive in magnesium concentrations as high as 300 mM which are toxic to various other micro-organisms. Several genes of V. parahaemolyticus were studied, among which gbpA (N-acetyl glucosamine binding protein) was reported in Vibrio cholerae.

Matched MeSH terms: Glucosamine
Statistical optimization of process conditions for cellulase production by liquid state bioconversion of domestic wastewater sludge

Alam MZ, Muyibi SA, Wahid R

Bioresour Technol, 2008 Jul;99(11):4709-16.
PMID: 17981027

A two-level fractional factorial design (FFD) was used to determine the effects of six factors, i.e. substrate (domestic wastewater sludge - DWS) and co-substrate concentration (wheat flour - WF), temperature, initial pH, inoculum size and agitation rate on the production of cellulase enzyme by Trichoderma harzianum in liquid state bioconversion. On statistical analysis of the results from the experimental studies, optimum process conditions were found to be temperature 32.5 degrees C, substrate concentration (DWS) 0.75% (w/w), co-substrate (WF) concentration 2% (w/w), initial pH 5, inoculum size 2% (v/w) and agitation 175 rpm. Analysis of variance (ANOVA) showed a high coefficient of determination (R2) of 0.975. Cellulase activity reached 10.2 FPU/ml at day 3 during the fermentation process which indicated about 1.5-fold increase in production compared to the cellulase activity obtained from the results of design of experiment (6.9 FPU/ml). Biodegradation of DWS was also evaluated to verify the efficiency of the bioconversion process as a waste management method.

Matched MeSH terms: Glucosamine/metabolism
Design, synthesis, and biological evaluation of 1,8-naphthyridine glucosamine conjugates as antimicrobial agents

Mohammed AAM, Suaifan GARY, Shehadeh MB, Okechukwu PN

Drug Dev Res, 2019 02;80(1):179-186.
PMID: 30570767 DOI: 10.1002/ddr.21508

In the quest for discovering potent antimicrobial agents with lower toxicity, we envisioned the design and synthesis of nalidixic acid-D-(+)-glucosamine conjugates. The novel compounds were synthesized and evaluated for their in vitro antimicrobial activity against Gram positive bacteria, Gram negative bacteria and fungi. Cytotoxicity using MTT assay over L6 skeletal myoblast cell line, ATCC CRL-1458 was carried out. In vitro antimicrobial assay revealed that 1-ethyl-7-methyl-4-oxo-N-(1,3,4,6-tetra-O-acetyl-2-deoxy-D-glucopyranose-2-yl)-[1,8]-naphthyridine-3-carboxamide (5) and 1-ethyl-7-methyl-4-oxo-N-(2-deoxy-D-glucopyranose-2-yl)-[1,8]-naphthyridine-3-carboxamide(6) possess growth inhibitory activity against resistant Escherichia coli NCTC, 11954 (MIC 0.1589 mM) and Methicillin resistant Staphylococcus aureus ATCC, 33591 (MIC 0.1589 mM). Compound (5) was more active against Listeria monocytogenes ATCC 19115 (MIC 0.1113 mM) in comparison with the reference nalidixic acid (MIC 1.0765 mM). Interestingly, compound (6) had potential antifungal activity against Candida albicans ATCC 10231 (MIC <0.0099 mM). Remarkably, the tested compounds had low cytotoxic effect. This study indicated that glucosamine moiety inclusion into the chemical structure of the marketed nalidixic acid enhances antimicrobial activity and safety.

Matched MeSH terms: Glucosamine/chemical synthesis*; Glucosamine/pharmacology
In vitro cytotoxicology model of oligo-chitosan and n, o-carboxymethyl chitosan using primary normal human epidermal keratinocyte cultures

Lim CK, Halim AS, Lau HY, Ujang Z, Hazri A

J Appl Biomater Biomech, 2007 May-Aug;5(2):82-7.
PMID: 20799177

Chitosan (beta-1, 4-D-glucosamine) is a deacetylated form of chitin with excellent biological properties in wound management. The natural properties of chitosan have the physical and chemical limitations to be widely used in biomedical fields. The improvement of the physical and chemical properties of chitosan with some additional chemicals will alter its biocompatibility. Therefore, the biological attribute of the modified chitosan must be evaluated. In this study, the cytotoxicity of oligo-chitosan (OC) and N, O- carboxymethyl-chitosan (NO-CMC) derivatives (O-C 1%, O-C 5%, NO-CMC 1% and NO-CMC 5%) was evaluated using primary normal human epidermal keratinocyte (pNHEK) cultures as an in vitro toxicology model at standardized cell passages (fourth passages). 3-[4, 5-dimethyl-2-thiazolyl]-2, 5-diphenyl tetrazolium bromide (MTT) was used as a cell viability assay. The O-C 1% is one of the most compatible chitosan derivatives because it steadily sustained >70% of viable cells until 72 hr post-treatment. This was followed by O-C 5%, NO-CMC 5% and NO-CMC 1%. Therefore, oligo-chitosan had the ideal properties of a biocompatible material compared to N, O- carboxymethyl-chitosan in this study.

Matched MeSH terms: Glucosamine
A preliminary study of the effects of glucosamine sulphate and chondroitin sulphate on surgically treated and untreated focal cartilage damage

Kamarul T, Ab-Rahim S, Tumin M, Selvaratnam L, Ahmad TS

Eur Cell Mater, 2011 Mar 15;21:259-71; discussion 270-1.
PMID: 21409755

The effects of Glucosamine Sulphate (GS) and Chondroitin Sulphate (CS) on the healing of damaged and repaired articular cartilage were investigated. This study was conducted using 18 New Zealand white rabbits as experimental models. Focal cartilage defects, surgically created in the medial femoral condyle, were either treated by means of autologous chondrocyte implantation (ACI) or left untreated as controls. Rabbits were then divided into groups which received either GS+/-CS or no pharmacotherapy. Three rabbits from each group were sacrificed at 12 and 24 weeks post-surgery. Knees dissected from rabbits were then evaluated using gross quantification of repair tissue, glycosaminoglycan (GAG) assays, immunoassays and histological assessments. It was observed that, in contrast to untreated sites, surfaces of the ACI-repaired sites appeared smooth and continuous with the surrounding native cartilage. Histological examination demonstrated a typical hyaline cartilage structure; with proteoglycans, type II collagen and GAGs being highly expressed in repair areas. The improved regeneration of these repair sites was also noted to be significant over time (6 months vs. 3 months) and in GS and GS+CS groups compared to the untreated (without pharmacotherapy) group. Combination of ACI and pharmacotherapy (with glucosamine sulphate alone/ or with chondroitin sulphate) may prove beneficial for healing of damaged cartilage, particularly in relation to focal cartilage defects.

Matched MeSH terms: Glucosamine/pharmacology*
D-glucosamine chitosan base molecule-assisted synthesis of different shape and sized silver nanoparticles by a single pot method: A greener approach for sensor and microbial applications

Ranjani B, Pandian K, Kumar GA, Gopinath SCB

Int J Biol Macromol, 2019 Jul 15;133:1280-1287.
PMID: 31051204 DOI: 10.1016/j.ijbiomac.2019.04.196

Silver nanoparticle was synthesized using D-glucosamine chitosan base as green reducing agent at elevated temperature in alkaline pH ranges. The excess of D-glucosamine chitosan base was used as it is both stabilizing and reducing agent at different pHs, regulates the shape and size of the silver nanoparticles. The progressive growth of silver nanoparticles was monitored by UV-Visible spectral studies. A sharp peak at 420 nm indicates the formation of spherical silver nanoparticles. The size and shape of silver nanoparticles were observed from Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) methods. The anisotropically grown nanoparticles were used as probe for Surface Enhanced Raman Studies (SERS) using ATP (4-aminothiophenol) as a model system. The catalytic behavior of silver nanoparticles was exploited for 4-nitrophenol reduction and observed that the reduction reaction follows pseudo first order kinetics with a rate constant 0.65 min. The antibacterial activity of silver nanoparticles was also tested for both gram-positive and -negative microorganisms, in which higher zone of inhibition was observed for gram negative microorganism.

Matched MeSH terms: Glucosamine/chemistry*
Cytochrome P450 2C9-natural antiarthritic interactions: Evaluation of inhibition magnitude and prediction from in vitro data

Tan BH, Ahemad N, Pan Y, Palanisamy UD, Othman I, Yiap BC, et al.

Biopharm Drug Dispos, 2018 Apr;39(4):205-217.
PMID: 29488228 DOI: 10.1002/bdd.2127

Many dietary supplements are promoted to patients with osteoarthritis (OA) including the three naturally derived compounds, glucosamine, chondroitin and diacerein. Despite their wide spread use, research on interaction of these antiarthritic compounds with human hepatic cytochrome P450 (CYP) enzymes is limited. This study aimed to examine the modulatory effects of these compounds on CYP2C9, a major CYP isoform, using in vitro biochemical assay and in silico models. Utilizing valsartan hydroxylase assay as probe, all forms of glucosamine and chondroitin exhibited IC50 values beyond 1000 μM, indicating very weak potential in inhibiting CYP2C9. In silico docking postulated no interaction with CYP2C9 for chondroitin and weak bonding for glucosamine. On the other hand, diacerein exhibited mixed-type inhibition with IC50 value of 32.23 μM and Ki value of 30.80 μM, indicating moderately weak inhibition. Diacerein's main metabolite, rhein, demonstrated the same mode of inhibition as diacerein but stronger potency, with IC50 of 6.08 μM and Ki of 1.16 μM. The docking of both compounds acquired lower CDOCKER interaction energy values, with interactions dominated by hydrogen and hydrophobic bondings. The ranking with respect to inhibition potency for the investigated compounds was generally the same in both in vitro enzyme assay and in silico modeling with order of potency being diacerein/rhein > various glucosamine/chondroitin forms. In vitro-in vivo extrapolation of inhibition kinetics (using 1 + [I]/Ki ratio) demonstrated negligible potential of diacerein to cause interaction in vivo, whereas rhein was predicted to cause in vivo interaction, suggesting potential interaction risk with the CYP2C9 drug substrates.

Matched MeSH terms: Glucosamine/pharmacology
Fulltext Palm vitamin E and glucosamine sulphate in the treatment of osteoarthritis of the knee

Haflah NH, Jaarin K, Abdullah S, Omar M

Saudi Med J, 2009 Nov;30(11):1432-8.
PMID: 19882056

OBJECTIVE: To assess the efficacy of oral palm vitamin E in reducing symptoms of patients with osteoarthritis (OA) of the knee compared to oral glucosamine sulphate.
METHODS: This open study was carried out at the Universiti Kebangsaan Malaysia Medical Center, Kuala Lumpur, Malaysia between March 2006 and November 2007. Seventy-nine patients were recruited to receive either 1.5 g oral glucosamine sulphate or 400 mg oral palm vitamin E for 6 months. Symptoms were assessed using the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index and visual analogue scale (VAS).
RESULTS: Sixty-four patients completed the trial (vitamin E n=33, glucosamine sulfate n=31). After 6 months of treatment, both groups showed a significant improvement in WOMAC scale and significant reduction in the VAS score during standing and walking. There was no significant difference in WOMAC scale and VAS score between the 2 groups. Except for mild allergic reaction and abdominal discomfort in one patient, there were no other serious adverse effects reported. Serum malondialdehyde was significantly higher in the glucosamine group compared to palm vitamin E treated group at the end of the study. Serum of vitamin E was significantly higher in the palm vitamin E group compared to glucosamine.
CONCLUSION: The finding of this study suggests that oral palm vitamin E in a dose of 400 mg taken daily has a potential role in reducing symptoms of patients with OA of the knee. It may be just as effective as glucosamine sulphate in reducing the symptoms and free from serious side effects. Further study is required to ascertain the mechanism of action beside its antioxidant effect.

Matched MeSH terms: Glucosamine/administration & dosage*
A survey of the primary care management of osteoarthritis in Malaysia: A view from a rheumatologist's perspective

Arshad A, Rashid R, Das Gupta E

Int J Rheum Dis, 2008;11(3):246-250.
DOI: 10.1111/j.1756-185X.2008.00367.x

Objective: Primary care management of knee osteoarthritis (OA) has received little attention in the scientific literature and the main reason for this survey is to study and explore the variations and patterns of primary care management and assess both conventional and complementary therapy usage in knee OA in the primary care setting.
Methods: A cross-sectional survey of 200 randomly selected general practitioners (GPs) in the peninsular states of Malaysia was undertaken using a questionnaire. The GPs involved were asked about basic knowledge of OA in terms of diagnosis, investigation, and treatment. They were also asked about their usage of conventional and complementary medication.
Results: One hundred and eighty (90%) GPs responded to the questionnaires sent: 77% were in solo practice and 33% in group practice. Most of the GPs surveyed (60%) had been in practice for more than 10 years, 30% for 5-10 years and 10% were in practice for less than 5 years. Of GPs surveyed, 55% saw an average of more than 20 patients per week, 35% about 10-20 patients and 10% less than 10 patients per week. Of GPs surveyed, 65% would arrange an X-ray, 55% would arrange a blood test, mostly serum uric acid, rheumatoid factor and erythrocyte sedimentation rate. Pharmacological management consists of first-line treatment with non-steroidal anti-inflammatory drugs (NSAIDs) (61%), analgesics (35%) or a combination of the two (4%). Non-pharmacological management consisted of advice on exercise (27%), weight reduction (33%) and referral to physiotherapy (10%). Of GPs surveyed, 85% prescribed some form of complementary medications, 60% prescribed glucosamine sulphate, 21% chondroitin sulphate, 11% cod liver oil and 9% evening primrose oil. Only 10% of GPs surveyed perform intra-articular injections.
Conclusion: The data suggest that in the primary care setting, the majority of GPs over-investigate the diagnosis of OA. Pharmacological interventions largely concentrate on analgesics and NSAIDs. The use of physiotheraphy and non-drug approaches were significantly under-utilized. There is a need to further educate GPs in the management of OA.

Matched MeSH terms: Glucosamine
Fulltext A pilot study of the primary care management of knee osteoarthritis in the Northern States of Malaysia.

Arshad, A., Rashid, R.

International Medical Journal Malaysia, 2008;7(2):31-36.
MyJurnal

Introduction: Primary care management of knee osteoarthritis OA has received little attention in the scientific literature and the main reason of this survey is to study and explore the variations and patterns of primary care management and assess both conventional and complementary therapy usage in knee OA in the primary care setting. Materials and Methods: A cross sectional survey of 100 randomly selected general practitioners (GPs) in the northern states of Malaysia (Kedah, Perlis, Pulau Pinang) was undertaken using questionnaires. The GPs involved were asked about basic knowledge of OA in terms of diagnosis, investigation, and treatment of OA. They were also asked their usage of conventional and complementary medication. Results: 80 (80%) GPs responded to the questionnaires sent. 85% of GPs were in solo practice and 15% in group practice. Most of the GPs surveyed (69%) were in practice for more than 10 years, 21% in 5- 10 years and 10% were in practice for less than 5 years. 65% GPs surveyed see an average of more than 20 patients per week, 25% see about 10- 20 patients and 10% see less than 10 patients per week. 75% of GPs surveyed would arrange an X-ray. 65% of GPs surveyed will arrange a blood test, mostly serum uric acid, rheumatoid factor and ESR. Pharmacological management consists of first line treatment with analgesics (32%), NSAIDs (59%) or a combination of the two (4%). Non-pharmacological management consist of advise an exercise (37%), weight reduction (23%) and referral to physiotherapy (8%). 89% of GPs surveyed prescribed some form of complementary medications. 68% prescribed glucosamine sulphate, 29% chondroitin sulphate, 18% cod liver oil, 12% evening primrose oil. Only 5% of GPs surveyed perform intra- articular injection. Conclusion: The data suggest that in the primary care, majority of GP over investigate the diagnosis of OA. Pharmacological interventions largely concentrate on analgesic and NSAIDs. The use of physiotherapy and non drug approach were enormously under-utilized. There is a need to further educate GPs in the management of OA.

Matched MeSH terms: Glucosamine
Fulltext Cell-based therapy for the treatment of focal articular cartilage lesions: a review of six years od studies in a Malaysian University Medical Centre

Samsudin EZ, Kamarul T

JUMMEC, 2014;17(2):1-11.
MyJurnal

Autologous chondrocyte implantation (ACI) is a significant technique that has gained widespread use for the treatment of focal articular cartilage damage. Since its inception in 2004, the Tissue Engineering Group (TEG) of the Faculty of Medicine, University Malaya has been dedicated to carrying out extensive research on this cell-based therapy. The objective of this report, comprising one clinical case report, six animal studies and one laboratory study, is to summarise and discuss TEG’s key findings. On the whole, we observed that the ACI technique was effective in regenerating hyaline-like cartilage in treated defects. Autologous chondrocytes and mesenchymal stem cells (MSC) were found to produce comparable tissue repair irrespective of the state of MSC differentiation, and the use of alginate-based scaffolding and oral pharmacotherapy (Glucosamine and Chondroitin Sulphate) was shown to enhance ACI-led tissue repair. ACI is suggested to be an efficient therapeutic option for the treatment of articular cartilage defects of the knee.

Matched MeSH terms: Glucosamine

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