Glucosamine Group Research Articles

This house believes that we should advise our patients with osteoarthritis of the knee to take glucosamine.

sound, randomized, placebo-controlled double-blind studies. Ineach case, the group of patien ts treated with glucosamine showed reduced narrowing of the tibiofemoral joint space at 3 yr compared with the placebo group. This supports the hypothesis that glucosamine acts as a disease-modifying drug in osteoarthritis of the knee. Pavelka’s group also reported that fewer patients in the glucosamine group reached a cut-off value of 0.5 mm joint space narrowing during the period of the study. This level was considered to represent severe narrowing of the tibiofemoral joint space. Furthermore, the glucosamine-treated group in each study had significantly better functional outcomes than the placebo group, as measured onthe WesternOntario and McMaster Universities (WOMAC) index. Although mild adverse effects such as abdominal pain and dyspepsia were reported, these tended to be transient. There was no convincing evidence that glucosamine causes severe adverse effects such as diabetes mellitus. In conclusion, glucosamine is a safe drug for which a body of evidence suggests effectiveness in relieving symptoms, increasing function and modifying disease progressioninosteoarthritis of the kn ee. We should recommend it to our patients.

The effect of glucosamine supplementation on people experiencing regular knee pain

Objective: The purpose of this study was to examine the effects of oral glucosamine supplementation on the functional ability and degree of pain felt by individuals who had regular knee...

Enhanced healing of cartilaginous injuries by glucosamine hydrochloride

We investigated the restorative effect of orally administered glucosamine hydrochloride (GlcN) on the experimentally produced cartilaginous injuries in rabbits. A total of three holes in the left stifle joint including one in the medial trochlear ridge and two in the trochlear sulcus (proximal and distal) of articular cartilage were made surgically using a drill. For the control group, only tap water and for the glucosamine group, a water based solution of GlcN (1 g/head) was administered daily, respectively. We observed the clinical symptoms daily and the condition of the injured part was observed visually and histologically at 3 weeks after the operation. There was no difference in body weight or general conditions between the two groups. However, in the control group, the muscle weight of the biceps of the left femur was significantly reduced ( p<0.05). With respect to the medial trochlear injury, four out of six cases in the control group and five out of six cases in the glucosamine group were cured, respectively. With respect to the proximal and the distal holes in sulcus, only two out of six cases in the control group and five expansive out of six cases in the glucosamine group were cured. There was significant difference between the glucosamine group and the control with respect to healing of the proximal hole ( p<0.05) and the total points ( p<0.05), indicating that the artificial cartilage injuries were facilitated by GlcN. On histological examination, the injured parts were covered by fibrous connective tissues in the control, whereas in the glucosamine group, the massive proliferation of matured cartilaginous tissues was observed, and the regenerated cartilaginous tissues were surrounded by the proliferation of chondroblast cells. In the regenerated tissue, matured cartilage substrate was about to be formed. Safranin O and alcian blue stains marked significantly dense in the glucosamine group than in the control ( p<0.01) in injured parts as well as in non-injured joint cartilage.

Exercise-Stimulated Glucose Turnover in the Rat Is Impaired by Glucosamine Infusion

The infusion of glucosamine causes insulin resistance, presumably by entering the hexosamine biosynthetic pathway; it has been proposed that this pathway plays a role in hyperglycemia-induced insulin resistance. This study was undertaken to determine if glucosamine infusion could influence exercise-stimulated glucose uptake. Male SD rats were infused with glucosamine at 0.1 mg x kg(-1) x min(-1) (low-GlcN group), 6.5 mg x kg(-1) x min(-1) (high-GlcN group), or saline (control group) for 6.5 h and exercised on a treadmill for 30 min (17 m/min) at the end of the infusion period. Glucosamine infusion caused a modest increase in basal glycemia in both experimental groups, with no change in tracer-determined basal glucose turnover. During exercise, glucose turnover increased approximately 2.2-fold from 46 +/- 2 to 101 +/- 5 pmol x kg(-1) x min(-1) in the control group. Glucose turnover increased to a lesser extent in the glucosamine groups and was limited to 88% of control in the low-GlcN group (47 +/- 2 to 90 +/- 3 pmol x kg(-1) x min(-1); P < 0.01) and 72% of control in the high-GlcN group (43 +/- 1 to 73 +/- 3 pmol kg(-1) 1 min(-1); P < 0.01). Similarly, the metabolic clearance rate (MCR) in the control group increased 72% from 6.1 +/- 0.2 to 10.5 +/- 0.7 ml kg(-1) x min(-1) in response to exercise. However, the increase in MCR was only 83% of control in the low-GlcN group (5.2 +/- 0.5 to 8.7 +/- 0.5 ml x kg(-1) x min(-1); P < 0.01) and 59% of control in the high-GlcN group (4.5 +/- 0.2 to 6.2 +/- 0.3 ml x kg(-1) x min(-1); P < 0.01). Neither glucosamine infusion nor exercise significantly affected plasma insulin or free fatty acid (FFA) concentrations. In conclusion, the infusion of glucosamine, which is known to cause insulin resistance, also impaired exercise-induced glucose uptake. This inhibition was independent of hyperglycemia and FFA levels.

Predicted Influence of N-Acetyl Group Content on the Conformational Extension of Chitin and Chitosan Chains

ABSTRACT Conformational analysis of chitosan molecules has been performed using the MM3(92) force field to investigate the role played by the acetamido groups on the stiffness of these chains. A high dielectric constant value was needed to model an aqueous environment and to reproduce the distribution of the N-acetyl glucosamine group orientation that is observed by NMR. Disaccharidic fragments, differently substituted at C2, were selected as models for chitin and chitosan chains. Their conformational space has been explored by means of adiabatic mapping of the glycosidic Φ,Ψ torsion angles. Although the overall features of all the potential energy surfaces created appear similar, the accessible conformational space of a glycosidic bond is affected by the nature of the substituent at C2 on the non-reducing residue of the disaccharide unit. This is illustrated by the differences in the calculated partition functions together with the predicted average homonuclear and heteronuclear coupling constants. Computed maps were used to predict polymeric unperturbed dimensions, characteristic ratio and persistence length of idealized chitin and chitosan chains, by Monte Carlo methods. Pure chitosan is predicted to be more coiled than pure chitin chains. At low N-acetyl group contents, chain extension appears to be dependent on the degree of substitution. Average chain dimensions increase monotonically for increases in content up to 60% of N-acetyl groups, but show no significant variation at higher contents. For molecules consisting of 50% amino and 50% N-acetylated residues, random, alternate and block patterns of substitution have been investigated. It has also been shown that the spatial extension of the polymer chains is dependent on the primary structure. Comparison with the literature experimental data is difficult because of the extreme diversity of the reported conformationally dependent values. However, such study provides a unique insight into the dependence of these two factors (degree of acetylation and distribution of acetyl groups) on the stiffness and flexibility of different chitin and chitosan chains.

Glucosamine infusion in rats mimics the β-cell dysfunction of non—insulin-dependent diabetes mellitus

Sustained hyperglycemia can cause peripheral insulin resistance and pancreatic β-cell dysfunction and has been termed glucose toxicity or glucose-induced desensitization. Glucosamine, a product of glucose flux through the hexosamine biosynthetic pathway (HBP), causes insulin resistance in peripheral tissues and has been shown to cause abnormal glucose-insulin secretion coupling, and thus has been implicated in the pathogenesis of glucose toxicity. Here, we investigate whether glucosamine-induced insulin secretory dysfunction is specific to glucose or also extends to nonglucose secretagogues such as arginine. Two groups of 12 weight-matched Sprague-Dawley rats underwent hyperglycemic clamp studies (steady-state blood glucose, ∼220 mg · dL −1) during infusion of normal saline or glucosamine 3.5 mg · kg −1 · min −1 over a 100-minute period. Insulin levels were measured at baseline and between 90 and 100 minutes. One hundred minutes into the hyperglycemic clamp, subgroups of seven rats each (saline- and glucosamine-infused rats) received a bolus of arginine (100 mg · kg −1) while the glucose infusion rate was unaltered. Glucose and insulin levels were measured at 1, 3, 5, 10, 15, and 30 minutes after the arginine bolus. Both groups had similar fasting glucose and insulin levels. At steady state (60 to 100 minutes), glucose levels were almost identical in both groups (223.58 ± 3.94 v 224.58 ± 4.34 mg · dL −1), but the glucose infusion rate (26.55 ± 1.60 v 8.83 ± 1.35 mg · kg −1 · min −1, P < .0001) and insulin level (41.36 ± 6.47 v 18.04 ± 2.95 mU · mL −1, P < .0001) were markedly reduced in animals receiving glucosamine. Peak insulin levels 1 minute after the arginine bolus were lower in rats infused with glucosamine versus saline (274.00 ± 30.38 v 176.25 ± 20.12 μU · ml −1, P = .0319). Total insulin secretion in response to arginine was significantly lower in the glucosamine group as determined by the area under the curve (1,268.09 ± 142.27 v 706.77 ± 84.79 μU · mL −1 · min, P = .0054). In conclusion, glucosamine causes severe impairment in glucose-induced insulin secretion. Further, glucosamine-induced β-cell secretory dysfunction extends to nonglycemic stimuli like arginine. This pattern of insulin secretory dysfunction is similar to that observed in patients with non—insulin-dependent diabetes mellitus (NIDDM). These data suggest that glucosamine may participate in the pathogenesis of glucose toxicity at the level of the β cell in NIDDM patients.

Glucosamine.

To review the pharmacology and pharmacokinetics of glucosamine and critically evaluate currently available literature regarding its safety and efficacy. A MEDLINE search was conducted between January 1965 and May 1997. Key words used in the search were osteoarthritis, osteoarthrosis, gonarthrosis, and glucosamine. In addition, references cited in articles obtained from the MEDLINE search were reviewed for additional literature. All articles were considered for inclusion in the review. Articles were excluded from critical evaluation for lack of randomization, lack of a control group, 30 or fewer study participants, inconsistent treatment regimen, incomplete dosing information, or incomplete reporting of results. Osteoarthritis affects approximately 12% of the US population; the incidence increases with increasing age. Currently used pharmacologic treatments, including acetaminophen and nonsteroidal antiinflammatory drugs, do not slow or reverse the degenerative process in osteoarthritis. Glucosamine has recently received a great deal of attention from the public as a potential treatment of osteoarthritis, prompting healthcare professionals to investigate its clinical usefulness and potential for adverse effects. The drug has been proposed to stop and possibly reverse the degenerative process in osteoarthritis. Following absorption of an oral dose, glucosamine is incorporated into plasma proteins during first-pass metabolism, resulting in 26% bioavailability. Unbound glucosamine is concentrated in the articular cartilage. Each of the three critically evaluated studies reported a decrease in the symptoms of osteoarthritis (e.g., decreased Lequesne index, decreased pain severity, increased range of motion) for the glucosamine group, which was greater than that obtained in the control group. Flaws in study design, however, prevent the use of these results in modifying current clinical practice. Reported short-term adverse effects include mild gastrointestinal problems, drowsiness, skin reactions, and headache. Improvement in the symptoms of osteoarthritis associated with the use of glucosamine has been observed in clinical trials; however, those trials have flaws in design and data analysis. Further research needs to be conducted before glucosamine can be recommended as a treatment for osteoarthritis.

Preparation and Properties of Chitosan-Derived Biodegradable Polymeric Surfactant

Partially N-acylated and dicarboxylated chitosans (Cn-DC-Chs) consisting of hydrophobic and hydrophilic portions as well as a glucosamine group as the biodegradable segment were prepared by partial N-acylation with subsequent dicarboxylation of chitosan, followed by assessment of biodegradability and interfacial activity. The former was found to depend on the glucosamine content in the polymer chain. From the TOC-biodegradation, it was found that C6-DC-Chs containing more than 4mol% of the glucosamine group, C10-DC-Chs and C12-DC-Chs having more than 7mol% glucosamine content exhibited good biodegradation. The longer alkyl chain in the N-acylated chitosan generally showed greater interfacial activity. C12-DC-Chs with acylation degree from 21-27mol% exhibited the highest interfacial activities.

Glucosamine sulfate compared to ibuprofen in osteoarthritis of the knee

Glucosamine sulfate is able to stimulate proteoglycan synthesis by chondrocytes and has mild anti-inflammatory properties. In clinical trials, glucosamine sulfate was more effective than placebo in controlling the symptoms of osteoarthritis (OA). In order to better characterize this therapeutic activity, we conducted a randomized, double-blind, parallel-group study of glucosamine sulfate 500 mg t.i.d. vs ibuprofen 400 mg t.i.d., orally for 4 weeks. The study included 200 hospitalized patients with active OA of the knee, symptoms for at least 3 months and a Lequesne's index of at least 7 points. Patients were evaluated weekly. Response was defined as a reduction in the Lequesne's index by at least 2 points if the enrollment value was higher than 12 points, or by at least 1 point if the enrollment value was 12 or less points, together with a positive overall assessment by the investigator. The improvement tended to be sooner under ibuprofen (48% responders vs 28% after the 1st treatment week; P = 0.06, Fisher's Exact test), but there was no difference from the 2nd week onward, with a success rate of 52% in the ibuprofen group and of 48% in the glucosamine group (P = 0.67) at the end of treatment. The average Lequesne's index at enrollment was around 16 points and decreased by over 6 points in both groups, again with the above described trend. On the other hand, 35% of patients on ibuprofen reported adverse events, mainly of gastrointestinal origin, vs 6% adverse events with glucosamine (P < 0.001, Fisher's Exact test). The number of adverse event related drop-outs was different between the two groups (7% vs 1%, respectively; P = 0.035). Glucosamine sulfate was therefore as effective as ibuprofen on symptoms of knee OA. These data confirm glucosamine sulfate as a safe symptomatic Slow Acting Drug for OA.

Hyaluronan affects extravascular water in lungs of unanesthetized rabbits

We have determined whether changes in lung hyaluronan content affect extravascular water in lungs of unanesthetized rabbits. Three groups of experiments were performed. In group 1 (n = 12), no infusions were given; in group 2, nine pairs of rabbits received either intravenous hyaluronidase (750 U.kg-1.min-1) or an equivalent volume of saline; in group 3, nine pairs of rabbits received either hyaluronidase or saline, followed by intravenous saline infusion amounting to 24% of body weight. At the end of each experiment, one lung was analyzed for extravascular lung water by the wet-dry method. Except for group 3, in all animals the other lung was analyzed for hyaluronan content by a method that involved hydrolyzing lung hyaluronan with fungal hyaluronidase to release reducing N-acetyl glucosamine groups, which were quantified. In group 1, lung hyaluronan, which varied from 50 to 159 micrograms/g dry wt (mean 106 +/- 35 micrograms/g dry wt), significantly correlated with variation in extravascular lung water (mean 4.2 +/- 0.3 g/g dry wt). In group 2 rabbits given hyaluronidase, lung hyaluronan was 40% lower and extravascular lung water was 14.6% lower than in paired controls (P less than 0.01). In group 3, volume expansion did not affect lung water, except after hyaluronidase when lung water was 47% higher than paired controls. We conclude that in the lung the content of hyaluronan is one of the determinants of extravascular water content.

Phase behaviour of mixtures of lipid X with phosphatidylcholine and phosphatidylethanolamine

The effect of increasing concentrations of lipid X (2,3-bis(3-hydroxymyristoyl)-α- d-glucosamine 1-phosphate) on the phase behaviour of EPC (egg phosphatidylcholine) and EPE (egg phosphatidylethanolamine) is studied at a pH⩾ 7 where lipid X carries one to two negative charges. Small amounts of lipid X (molar ratio≈ 0.01) induce continuous swelling of EPC and EPE bilayers and consequently the formation of large unilamellar vesicles in excess water. In many respects, the effect of lipid X on EPC and EPE bilayers is similar to that of phosphatidic acid. However, lipid X/EPC mixtures form micelles in excess lipid X whereas mixtures of phosphatidic acid/EPC vesiculate at all ratios. The same is true for lipid X/EPE mixtures. Small unilamellar vesicles of an average diameter of 40 nm form spontaneously upon dispersion of a dry lipid X/EPE film (molar ratio = 10). Unsonicated dispersions of lipid X/EPC (molar ratio = 1) are subjected to pH-jump treatment which involves raising of the pH to 11–12 and subsequent lowering of the pH to between 7.5 and 8.5. Such a treatment has little effect on the vesicle size and size distribution as compared to a control dispersion at pH 8.2. The mean size is determined to be92 ± 60nm. Electron micrographs of freeze-fractured samples of lipid X/EPC (molar ratio = 1) reveal the presence of mainly micelles at pH 12. Upon lowering the pH to neutrality these micelles become unstable and aggregate/fuse rapidly to unilamellar vesicles (average diameter95 ± 40nm). Sonication of equimolar mixtures of lipid X and EPC at pH 7 yields small unilamellar vesicles of a diameter of 20–25 nm as well as mixed micelles of a size between 15 and 17 nm. This behaviour is again different from that of mixed EPC/phosphatidic acid dispersions which form small unilamellar vesicles. The presence of lipid X in such mixtures does not prevent the aggregation/fusion to larger vesicles during freezing of the dispersion. As with pure EPC bilayers, stabilization is, however, achieved in the presence of 10% sucrose. This indicates that the covalently bonded glucosamine group of lipid X cannot substitute water of hydration in neighbouring EPC molecules.

Polymers Having Pendant Amino Sugar Groups: Synthesis and Bioactivity of Polymers Having Free Glucosamine and N-Acetylglucosamine

Synthesis and some properties of polymers having pendant amino sugars are described. Radical polymerization of the p-vinylphenyl glycoside of 3,4,6-tri-O-acetyl-D-glucosamine gave the corresponding polymer with ηinh 0.38—0.75 in high yield, which was soluble in DMAc, methanol, and pyridine. Deacetylation of the polymer by alkaline hydrolysis afforded a polymer having free glucosamine groups linked at the C-1 position. N-Acetylation of the original polymer followed by selective O-deacetylation converted the pendant groups to N-acetyl-glucosamine residues. The interaction of these polymers with wheat germ agglutinin and potato lectin was examined, and the N-acetylglucosamine-containing polymer was found to have a strong affinity for the lectins.