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Results for “HYALURONIC ACID”

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PubMed1978

Stimulatory effect of exogenous hyaluronic acid distinguishes cultured fibroblasts of Marfan's disease from controls.

Fibroblasts cultured from patients with Marfan's disease show metachromasia with toluidine blue and accumulate increased amounts of glycosaminoglycan (GAG). Compared to fibroblasts from controls, more of the newly synthesized GAG is hyaluronic acid. Cycloheximide has a modest inhibiting effect on GAG accumulation compared to protein inhibition while serum depletion has a greater effect on inhibiting GAG accumulation than on reducing synthesis of new protein. Exogenous hyaluronic acid restores new accumulation of hyaluronic acid in serum depleted Marfan-derived cultures towards baseline while having almost no effect on cultures derived from controls. The effect is specific for hyaluronic acid as chondroitin sulfate or dextran sulfate are not stimulatory and is not due to stimulation of new protein synthesis.

Adolescent↗

PubMed2003

A comparison of molecular mass determination of hyaluronic acid using SEC/MALLS and sedimentation equilibrium.

Hyaluronic acid (HA) is a natural polysaccharide with importance in the pharmaceutical, medical and cosmetic industries. Determining factors in its final applications are its physicochemical properties, particularly molecular mass. A high molecular mass HA was degraded using five different hydroxyl free-radical starting concentrations chemically produced from ascorbic acid and hydrogen peroxide. The aims of the study were to investigate the effect of different hydroxyl free-radical concentrations on the chain length of HA and compare the molecular masses obtained from analytical ultracentrifugation using sedimentation equilibrium experiments and size exclusion chromatography/multi-angle laser light scattering (SEC/MALLS). The results indicated that their molecular masses varied, depending on the degree of hydroxyl free-radical starting concentration. Molecular mass values obtained from sedimentation equilibrium experiments for each sample showed the same trend as those obtained from the SEC/MALLS in the range of molecular masses studied. The molecular masses obtained from sedimentation equilibrium for high molecular mass samples from reciprocal plots of apparent weight average molecular mass against concentration gave values similar to those obtained by SEC/MALLS. In contrast, the molecular mass from conventional plots for high molecular mass samples were much lower than those from SEC/MALLS, even when high ionic strength buffers were used.

Centrifugation, Density Gradient↗

PubMed1979

Significance of the quantification and demonstration of hyaluronic acid in tissue specimens for the diagnosis of pleural mesothelioma.

Hyaluronic acid in pleural tissues from patients with mesothelioma, carcinoma, and asbestosis of the lung was quantified by using specific glycosaminoglycan-degrading enzymes. In all cases of pleural mesothelioma, the quantity of hyaluronic acid in mg/g of dry tissue was at least 0.10 mg, whereas carcinomatous pleural tissue and pleura in asbestosis contained 0.02 to 0.03 mg/g of dry tissue.

Asbestosis↗

PubMed1997

Crosslinking of hyaluronic acid with water-soluble carbodiimide.

Hyaluronic acid (HA) was chemically crosslinked with a water-soluble carbodiimide (WSC) to produce low-water-content films when brought into contact with water. The crosslinking reaction was performed in two different ways; one was by using HA films and the other by casting HA solutions. Both methods produced water-insoluble HA films. The lowest water content of the crosslinked HA films subjected to swelling with water was 60 wt % at 37 degrees C, which was lower than any reported values. Infrared spectra of the crosslinked films suggested that intermolecular formation of ester bonds between the hydroxyl and carboxyl groups belonging to different polysaccharide molecules led to crosslinking. For comparison, pectin which possesses hydroxyl and carboxyl groups in one molecule, similar to HA, was subjected to crosslinking with WSC. The finding on pectin also supported ester formation between different polysaccharide molecules. The crosslinking of HA film with WSC in the presence of L-lysine methyl ester prolonged the in vivo degradation of HA film, probably because of amide bond formation as the crosslink.

Carbodiimides↗

PubMed2000

Sulfated glycosaminoglycans and glucosamine may synergize in promoting synovial hyaluronic acid synthesis.

High-molecular-weight hyaluronic acid (HA) produced by the synovium may function physiologically to aid preservation of cartilage structure and prevent arthritic pain; both the size and concentration of HA in synovial fluid are diminished in osteoarthritis (OA). Glucosamine therapy for OA can be expected to increase synovial HA production by providing rate-limiting substrate. In addition, certain sulfated glycosaminoglycans and polysaccharides - including chondroitin sulfate (CS), dermatan sulfate, and pentosan polysulfate - stimulate synovial HA production, apparently owing to a hormone-like effect triggered by the binding of these polymers to membrane proteins of synovial cells. Surprisingly, a significant proportion of orally administered CS is absorbed as intact polymers - apparently by pinocytosis. These considerations may rationalize clinical studies concluding that oral CS provides slow-onset but durable pain relief and functional improvement in OA. The possibility that oral glucosamine and CS may interact in a complementary or synergistic fashion to improve synovial fluid HA content in OA should be assessed in clinical studies, and the potential of adjunctive CS administration to improve the clinical response achievable with optimal intakes of glucosamine should likewise be evaluated. In light of the fact that the synovium virtually functions as a 'placenta' for cartilage, focusing on synovium as the target for therapeutic intervention in OA may be a rational strategy.

Administration, Oral↗

PubMedDate not supplied

Nonanimal stabilized hyaluronic acid for lip augmentation and facial rhytid ablation.

OBJECTIVE: To evaluate the effectiveness of nonanimal stabilized hyaluronic acid as an injectable filling agent. DESIGN: Nonrandomized, retrospective, interventional case series. RESULTS: A total of 1446 consecutive patients (1029 women and 417 men) underwent intradermal injection of commercially available nonanimal stabilized hyaluronic acid (2242 treatments) for the enhancement of lip volume and contour and the reduction of visible facial rhytids. Almost 61% of all patients remained satisfied with their results after 9 months. The effect was longest in the glabellar and nasolabial fold areas. Minimal transient sequelae were noted. CONCLUSIONS: Nonanimal stabilized hyaluronic acid is an effective and safe facial soft tissue expander. Its duration varies with each facial area treated.

Female↗

PubMed1995

Prolongation of lidocaine-induced epidural anesthesia by medium molecular weight hyaluronic acid formulations: pharmacodynamic and pharmacokinetic studies in the rabbit.

We evaluated the utility of medium molecular weight hyaluronic acid for prolonging the local anesthetic activity of lidocaine in a rabbit model of epidural analgesia. Equiviscous formulations were prepared as either a physical mixture of lidocaine hydrochloride and sodium hyaluronate (where drug release occurred via diffusion) or as a lidocaine-hyaluronate complex (where drug release occurred via diffusional and electrostatic processes). The novel hyaluronic acid formulations were functionally evaluated, relative to lidocaine solution, in an intact, conscious rabbit model. The hyaluronate formulations were well tolerated. The duration of sensory block and loss of weight-bearing was prolonged twofold by the lidocaine-hyaluronate complex relative to the solution (P < 0.05). In terms of motor block, flaccid paresis occurred after administration of the solution formulation, whereas only partial motor block was evident after administration of the viscous formulations. Pharmacokinetic modeling of the lidocaine plasma concentration-time data indicated that the rate of drug absorption from the lidocaine-hyaluronate complex was decreased fourfold relative to the solution (P < 0.05). These observations indicate that ionic complexes of local anesthetics with medium molecular weight hyaluronic acid may offer advantages for the prolongation of epidural analgesia.

Anesthesia, Epidural↗

PubMed2004

Anti-inflammatory drug delivery from hyaluronic acid hydrogels.

Two different types of hyaluronic acid (HA) hydrogels were synthesized by crosslinking HA with divinyl sulfone (DVS) and poly(ethylene glycol)-divinyl sulfone (VS-PEG-VS). Vitamin E succinate (VES), an anti-inflammatory drug, and bovine serum albumin (BSA), a model of anti-inflammatory protein drugs, were loaded into the gels and their release kinetics were measured in vitro. VES and BSA released with a burst from both HA hydrogels during the first few hours, and release continued gradually for several days. The rate of release from HA-VS-PEG-VS-HA hydrogels was faster than that from HA-DVS-HA hydrogels, presumably due to the lower crosslink density in the former. The anti-inflammatory action of released VES was tested by incubating peripheral blood mononuclear cells (PBMC) on HA hydrogels with and without VES in the gel. The number of cells adhering on HA hydrogels was very low compared to that on tissue culture polystyrene (TCPS), which might be one of the important advantages of using HA hydrogels for implant coatings or tissue engineering applications. ELISA test results showed that the tumor necrosis factor-alpha (TNF-alpha) concentration was very low in the supernatant of the wells containing the HA hydrogel with VES in contact with the activated macrophages compared to that without VES. This is probably the effect of the released VES reducing the production of anti-inflammatory cytokine, TNF-alpha. HA hydrogels containing anti-inflammatory drugs may have potential for use in tissue engineering and also as biocompatible coatings of implants.

Animals↗

PubMed2005

Intra-articular treatment of hip osteoarthritis: a randomized trial of hyaluronic acid, corticosteroid, and isotonic saline.

OBJECTIVE: Hyaluronic acid (HA) and corticosteroids are both widely used for intra-articular treatment of knee osteoarthritis (OA). We examined the effect of both drugs in intra-articular treatment for hip OA. METHODS: One hundred and one patients with hip OA were included in a prospective double blind study, using a randomized controlled trial with a three-armed parallel-group design. Three ultrasound-guided, intra-articular injections were given at 14 days interval. The primary outcome measure was 'pain on walking', registered on a visual analogue scale (VAS). Evaluation was performed at baseline and after 14, 28 and 90 days. The study adhered to the Consolidated Standards of Reporting Trials. All analyses were based on intention-to-treat analyses, and used 'mixed-procedures' with the baseline-observation as covariate. RESULTS: There were no significant interactions with respect to Treatment x Time for any of the analyzed outcome measures. There was a significant treatment effect for 'pain on walking' (P=0.044) due to a significant improvement following corticosteroid compared to saline with an effect-size of 0.6 (95% confidence interval: 0.1-1.1, P=0.021). By contrast, HA compared to saline had an effect size of 0.4 (-0.1 to 0.9; P=0.13). The peak-effect was obtained after 2 weeks. There was no difference between the treatment groups at endpoint. No significant side effects of the injections were observed. CONCLUSIONS: Patients treated with corticosteroids experienced significant improvement during the 3 months of intervention, with an effect size indicating a moderate clinical effect. Although a similar significant result following treatment with HA could not be shown, the effect size indicated a small clinical improvement. A higher number of patients in future HA studies would serve to clarify this point.

Adjuvants, Immunologic↗

PubMed2006

Expression, processing, and glycosaminoglycan binding activity of the recombinant human 315-kDa hyaluronic acid receptor for endocytosis (HARE).

The hyaluronic acid (HA) receptor for endocytosis (HARE; also designated stabilin-2 and FEEL-2) mediates systemic clearance of glycosaminoglycans from the circulatory and lymphatic systems via coated pit-mediated uptake. HARE is primarily found as two isoforms (315- and 190-kDa) in sinusoidal endothelial cells of the liver, lymph node, and spleen. Here we characterize the ligand specificity and function of the large stably expressed 315-HARE isoform in Flp-In 293 cell lines. Like human spleen sinusoidal endothelial cells, Flp-In 293 cell lines transfected with a single cDNA encoding the full-length 315-HARE express both the 315-kDa and the proteolytically truncated 190-kDa isoforms in a ratio of approximately 3-4:1. The 190-kDa HARE isoform generated from the 315-kDa HARE and the 315-kDa HARE specifically bound 125I-HA. Like the 190-kDa HARE expressed alone (Harris, E. N., Weigel, J. A., and Weigel, P. H. (2004) J. Biol. Chem. 279, 36201-36209), the 190- and 315-kDa HARE isoforms expressed in 315-HARE cell lines were recognized by anti-HARE monoclonal antibodies 30, 154, and 159. All 315-HARE cell lines could endocytose and degrade 125I-HA. Competition studies with live cells indicate that 190-HARE and 315-HARE bind HA with higher apparent affinity (Kd approximately 10-20 nM) than chondroitin sulfate (CS) types A, C, D, or E. Only slight competition of HA endocytosis was observed with CS-B (dermatan sulfate) and chondroitin. Direct binding assays with the 315-HARE ectodomain revealed high affinity HA binding, and lower binding affinities for CS-C, CS-D, and CS-E. A majority of each HARE isoform was intracellular, within the endocytic system, suggesting transient surface residency typical of an active endocytic recycling receptor.

Base Sequence↗

PubMed2006

CD44-dependent intracellular and extracellular catabolism of hyaluronic acid by hyaluronidase-1 and -2.

Hyaluronic acid (HA) is a high molecular weight glycosaminoglycan involved in a wide variety of cellular functions. However, its turnover in living cells remains largely unknown. In this study, CD44, a receptor for HA, and hyaluronidase-1, -2, and -3 (Hyal-1, -2 and -3) were stably expressed in HEK 293 cells and the mechanism of HA catabolism was systematically investigated using fluorescein-labeled HA. CD44 was essential for HA degradation by both endogenous and exogenously expressed hyaluronidases. Hyal-1 was not able to cleave HA in living cells in the absence of CD44. Intracellular HA degradation was predominantly mediated by Hyal-1 after incorporation of HA by CD44. Although Hyal-1 was active only in intracellular space in vivo, a certain amount of the enzyme was secreted to extracellular space. This extracellular Hyal-1 was found to be incorporated by cells and such uptake of Hyal-1 was, in part, involved in the intracellular degradation of HA. Hyal-2 was involved in the extracellular degradation of HA. Hyal-2 activity was also dependent on the expression of CD44 in both living cells and enzyme assays. Immunofluorescent microscopy demonstrated that both Hyal-2 and CD44 are present on the cell surface. Without CD44 expression, Hyal-2 existed in a granular pattern, and did not show hyaluronidase activity, suggesting that localization change could contribute to Hyal-2 function. A convenient and quantitative enzyme assay was established for the measurement of Hyal-2 activity. Hyal-2 activity was detected in the membrane fraction of cells co-expressing Hyal-2 and CD44. The pH optimum for Hyal-2 was 6.0-7.0. The membrane fraction of cells expressing Hyal-2 alone did not show hyaluronidase activity. Hyal-3 did not show any hyaluronidase activity in our experimental conditions. Based on these findings, Hyal-1 and -2 contribute to intracellular and extracellular catabolism of HA, respectively, in a CD44-dependent manner, and their HA degradation occurs independently from one another.

Animals↗

PubMed1980

[Extraction and purification of brain glycoprotein NSA3 by binding with hyaluronic acid].

Brain glycoprotein NSA3 was found to bind to immobilised hyaluronic acid. The binding was reversible and gave pure antigen (99%) in high yields (80%). The binding was suppressed by incubating the affinosorbent with hyaluronidase. It was not suppressed by trypsin. The presence of glycosaminoglycans other than hyaluronic acid in the sample did not inhibit the binding. This property is relevant to those already known for the brain glycoprotein NSA3, and to its localisation at the nodes of Ranvier. We propose to coin the name hyaluronectin for the brain glycoprotein NSA3.

Brain Chemistry↗

PubMed2002

Serum hyaluronic acid as a comprehensive marker to assess severity of liver disease in schistosomiasis.

Schistosomiasis mansoni is a non-cirrhotic fibrogenic disease model. The mild form shows normal liver function with slight or no liver fibrosis whereas in the periportal fibrosis form the manifestations of portal hypertension prevail over hepatocellular failure. We assessed serum hyaluronic acid as a marker of the course of the disease. We studied 24 patients presenting with pure chronic forms of schistosomiasis and seven with cirrhosis. In order to measure serum hyaluronic acid we developed a sandwich fluorescent ELISA-like assay. alpha2-Macroglobulin, prothrombin index, gamma-glutamyltransferase, platelets and ultrasound parameters were also assessed. The 20 micro g/l (ROC plot) hyaluronic acid level differentiated patients with the mild form (with no portal hypertension) from those with the severe form of schistosomiasis with 78% diagnostic efficacy. The 80 micro g/l cut-off value differentiated patients with the severe form of schistosomiasis from the cirrhotic group with similar diagnostic efficacy. alpha2-Macroglobulin provided no distinction between the groups studied. The hyaluronic acid serum concentration correlated positively with the splenic vein diameter (P=0.004) and marginally with alpha2-macroglobulin (P=0.059). Serum hyaluronic acid is a good marker for the initial phase of hepatic fibrosis and it was able to assess severity of liver disease in schistosomiasis.

Adult↗

PubMed1998

Increased serum levels of hyaluronic acid in pregnancies complicated by preeclampsia or hemolysis, elevated liver enzymes, and low platelets syndrome.

OBJECTIVE: Fifteen percent of patients who later have hemolysis, elevated liver enzymes, and low platelets syndrome develop initially have nonspecific symptoms. Early diagnosis could ensure adequate obstetric management; however, prognostic biochemical tests are lacking. We hypothesized that elevated hyaluronic acid serum levels might be an early indicator of hemolysis, elevated liver enzymes, and low platelets syndrome because it is known to be a sensitive marker of liver cell function. STUDY DESIGN: Hyaluronic acid in serum was measured in patients with normal pregnancies (n = 109) and in those patients with pregnancies complicated by preeclampsia (n = 14) or hemolysis, elevated liver enzymes, and low platelets syndrome (n = 11). RESULTS: A significant increase in hyaluronic acid serum concentrations was observed in patients with hemolysis, elevated liver enzymes, and low platelets syndrome or with preeclampsia (p < 0.05). The extent of hyaluronic acid serum levels in hemolysis, elevated liver enzymes, and low platelets syndrome correlated with the clinical severity of the individual course of disease as measured by intensive care unit time (r = 0.72; p < 0.02). CONCLUSIONS: Serum levels of hyaluronic acid in preeclampsia and hemolysis, elevated liver enzymes, and low platelets syndrome are significantly elevated and might play an important diagnostic and prognostic role in patients with hemolysis, elevated liver enzymes, and low platelets syndrome.

Adult↗

PubMedDate not supplied

Effect of topical hyaluronic acid on experimental cholesteatoma.

PURPOSE: Inflammation and connective tissue hyperplasia are believed to be important etiological factors in cholesteatoma pathogenesis. Previous work has shown that topically applied hyaluronic acid can reduce connective tissue proliferation in healing wounds and accelerate healing of tympanic membrane perforations. This study was undertaken to determine whether the antiproliferative effect of hyaluronic acid may inhibit propylene glycol-induced cholesteatoma in an animal model. MATERIALS AND METHODS: A 60% propylene glycol solution was injected bilaterally into the middle ear cavities of 20 adult chinchillas. The control group (N = 10) received propylene glycol alone. In addition to propylene glycol injections, the experimental group (N = 10) received repeated bilateral topical applications of 1.5% hyaluronic acid onto the tympanic membranes. Animals were killed at 4 weeks for gross and light microscopic examination. RESULTS: Seven control and 10 experimental animals survived the full 1-month study period. At the end of that time, cholesteatoma was found in 71% (10/14) of control ears and 70% (14/20) of experimental ears. Tympanic membrane structure did not differ significantly between groups by light microscopy and, in all animals, cholesteatomas originated by migration of hyperplastic epidermis through the tympanic membrane, as has been observed in previous studies using this animal model. CONCLUSION: Under the conditions of this study, topical hyaluronic acid had no significant effect on cholesteatoma formation.

Administration, Topical↗

PubMed1975

Viscosity and molecular weight of hyaluronic acids.

The intrinsic viscosity ([eta]) and the molecular weight (M) by sedimentation equilibrium were determined for hyaluronic acids of low (M=104--7.2X10(4)) and high (M=3.1X10(5)--1.5X10(6)) molecular weights. Double logarithmic plot of [eta] against M gave different lines for the two groups. The relationship between [eta] and M was [eta]=3.0X10(6)XM1,20 for the former and [eta]=5.7X10(-4)XM0.46 for the latter group. The molecular weight at the point of intersection of the two lines was about 1.5X10(5). The rheological behavior of the hyaluronic acids below M=2.1X10(4), for which the value of reduced viscosity was independent of concentration, was different from that of the hyaluronic acids above M=5.1X10(4), for which the value of reduced viscosity increased with concentration.

Female↗

PubMed1983

Molecular weight distribution of hyaluronic acid of human synovial fluid in rheumatic diseases.

New methods to isolate and characterize the molecular weight distribution of hyaluronic acid have been applied to human synovial fluids from arthritic patients. Considerable variations in molecular weight distribution were found between the individual fluids. These methods facilitate a detailed characterization of hyaluronic acid--a prerequisite for understanding the role of hyaluronic acid for normal joint function and to evaluate the therapeutic use of local application in joint diseases.

Adult↗

PubMedDate not supplied

[Hyaluronic acid: biological role, structure, synthesis, isolation, purification, and application (review)].

The methods for isolation and purification of hyaluronic acid are summarized. The structural properties of this mucopolysaccharide are discussed, and hyaluronic acid-hydrolyzing enzymes are characterized. Data on the biological role, properties, and content of hyaluronic acid in tissues are reviewed. The possibilities of the application of hyaluronic acid in medicine, cosmetology, veterinary science, and hygiene are discussed.

Hyaluronic Acid↗