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PubMed1996

Assessment of damage and recovery of sinusoidal endothelial cell function by in vivo hyaluronic acid uptake in cold-preserved and transplanted rat livers.

We sought to evaluate the significance of endogenous hyaluronic acid levels and in vivo uptake of exogenous hyaluronic acid as markers of liver endothelial cell damage and correlate these findings to graft survival/function in a rat orthotopic liver transplant model. Endogenous hyaluronic acid levels were measured after orthotopic liver transplantation performed with freshly explanted livers, with livers preserved for 30 hr, and after sham operation. Exogenous hyaluronic acid uptake was evaluated in six study groups: fresh liver grafts, livers preserved for 12 hr, 24 hr, 30 hr and 48 hr, and sham-operated livers. Endogenous hyaluronic acid levels fell after orthotopic liver transplantation with freshly harvested livers and after sham operation, but rose in animals transplanted with livers preserved for 30 hr (P<0.01 vs. sham operation). In the preserved group, there was no difference in endogenous hyaluronic acid levels between survivors and nonsurvivors. Uptake of exogenous hyaluronic acid was significantly lower after orthotopic liver transplant with grafts preserved for 12 hr than after sham operation or orthotopic liver transplant with nonpreserved livers (P<0.05). Hyaluronic acid uptake further deteriorated in the 24-, 30-, and 48-hr groups. No significant difference in hyaluronic acid elimination rate was found when results obtained from livers preserved for extended periods (>12 hr) were compared in survivors and nonsurvivors. Hyaluronic acid uptake was reevaluated in surviving animals after 2 weeks. Completely restored function was observed in all survivors, indicating recovery of endothelial cells. We conclude that endogenous hyaluronic acid levels and exogenous hyaluronic acid uptake are reliable markers of liver sinusoidal endothelial cell function and that normal or moderately compromised hyaluronic acid uptake is associated with good graft function. On the other hand, endothelial cell dysfunction suggested by poor hyaluronic acid elimination is not a completely reliable predictor of subsequent deterioration of graft function in rat liver transplantation.

Animals↗
PubMed2006

Expression and distribution of CD44 and hyaluronic acid in human vocal fold mucosa.

OBJECTIVES: Expression of CD44 (a cell surface receptor for hyaluronic acid) and the distribution of hyaluronic acid were examined in the human vocal fold mucosa. METHODS: Light microscopic investigation was carried out on 10 normal larynges of newborn, infant, younger adult, and older adults with Alcian blue staining, a hyaluronidase digestion study, and immunohistochemistry for CD44. RESULTS: Before the appearance of hyaluronic acid in the newborn vocal fold mucosa, CD44 was expressed on the stellate cells in the macula flava and on the fibroblasts in Reinke's space. During infancy, hyaluronic acid appeared and was distributed in the vocal fold mucosa. Many more stellate cells in the macula flava showed CD44 expression, and a large amount of hyaluronic acid was present around the infant stellate cells; however, the fibroblasts in Reinke's space expressed little CD44. During adulthood, hyaluronic acid was distributed in the vocal fold mucosa. Almost all of the stellate cells in the macula flava showed CD44 expression, and much hyaluronic acid existed around the stellate cells in the adult macula flava. However, fibroblasts in the adult Reinke's space expressed little CD44, and hyaluronic acid density in that space was lower than that in the macula flava. CONCLUSIONS: Stellate cells in the macula flava and CD44 cooperatively play important roles in maintaining hyaluronic acid in the human vocal fold mucosa as a vibrating tissue.

Adult↗
PubMed1984

Purification and characterization of hyaluronic acid from the horny layer of guinea pigs.

Hyaluronic acid was purified from the horny layer of guinea pigs and its biochemical and physical properties were studied. The horny layer, obtained by applying n-hexadecane to guinea pig skin, was digested with pronase, and glycosaminoglycans in the digest were separated from UV-absorbing material by Sephadex G-75 chromatography (sample A, 17.5 mg). On DEAE-Sephadex chromatography, the fraction obtained with 0.5 M NaCl was found to contain 94% of the total uronic acid. This fraction, consisting mainly of hyaluronic acid, was dialyzed and lyophilized (sample B, 12.5 mg). Sample B, consisting of 26.1% uronic acid and 27.0% glucosamine on a dry weight basis, could be digested completely with Streptomyces hyaluronidase. Sample B had a low reduced viscosity which showed almost no concentration dependence. The intrinsic viscosity of sample B was 0.83 dl/g and its molecular weight, calculated from its viscosity, was 34,000. Sample B was eluted from Sepharose CL-6B as a broad peak between the void volume and the total column volume. The enzyme levels of hyaluronidase, beta-glucuronidase, and beta-N-acetylglucosaminidase in the n-hexadecane treated guinea pig skin increased to 1.7 to 2.5 fold those of controls after 6 days of the experiment. These results suggested that hyaluronic acid in the horny layer of n-hexadecane treated guinea pig skin might be degraded by hyaluronic acid degrading enzymes in the hyperkeratinized tissue.

Animals↗
PubMed1980

Participation of hyaluronic acid in the macrophage disappearance reaction.

Hyaluronic acid accumulates in the peritoneal cavity of mice during the macrophage disapperance reaction. Macrophages reappear in the exudates during the depletion of hyaluronate. The disappearance reaction is simulated by the intraperitional (i.p.) injection of hyaluronic acid into normal mice. The disapperance reaction largely is inhibited by the simultaneous injection (i.p.) of specific hyaluronidase with the challenge dose of BCG. We propose that hyaluronic acid makes a major contribution to the macrophage disappearance reaction.

Animals↗
PubMed1990

Concentration and degradation of hyaluronic acid in knee synovial fluid from carrageenin-induced rabbit arthritis.

The concentration and degradation of hyaluronic acid in the synovial fluid of carrageenin-induced arthritic joints of rabbits was studied. A 0.5-ml volume of 1% lambda-carrageenin was intra-articularly injected three times into a right knee joint, and saline into a left. After 5 d from the last injection, inflammatory changes were observed in the synovial membrane and synovial fluid, but not in the articular cartilage. In the inflammatory synovial fluid, lipid peroxide content, phosphatase activity and cell counts were significantly increased, but the copper concentration was not changed. Concentration of polymeric hyaluronic acid and total hyaluronic acid were determined by high-performance liquid chromatography using gel-permeation columns. Total hyaluronic acid was appreciably decreased in the inflammatory fluid. The polymeric hyaluronic acid determined was 38% of the total hyaluronic acid in the inflammatory fluid and 74% in the control fluid. This suggests that in the inflammatory fluid, molecular weights of hyaluronic acid are distributed in the broader range. The concentration of chondroitin sulphates was similar in both the inflammatory fluid and the control fluid, but the content ratio of chondroitin sulphates to hyaluronic acid was higher in the inflammatory fluid. In the inflamed synovial membrane, synthesis of hyaluronic acid as measured by incorporation of [14C]glucosamine into glycoconjugates was increased by about twice that in the control membrane.

Animals↗
PubMed2001

Efficacy of intraarticular hyaluronic acid injections in knee osteoarthritis.

Intraarticular injections of hyaluronic acid have been advocated for treatment of symptomatic knee osteoarthritis. Appropriate indications and favorable patient response factors, such as radiographic disease severity and age, are not clearly defined for this therapy. The current review of 80 knees with symptomatic osteoarthritis treated with hyaluronic acid revealed that approximately 2/3 of treated knees received 2/3 relief of pain. Hyaluronic acid treatment is not appropriate for all patients with knee osteoarthritis. Overall, less than 50% of treated knees achieved satisfactory results, and only 35% reported increased activity. Twenty-two patients (28% of knees; 22 knees) underwent surgery within 7 months of their index injection, suggesting an inadequate response to treatment. The treatment is not without complication because 11 patients (15% of knees; 12 knees) experienced adverse reactions, including one case of septic arthritis. The authors recommend intraarticular hyaluronic acid only for patients with symptoms and significant surgical risk factors and for patients with mild radiographic disease in whom conservative treatment has failed (physical therapy, weight loss, nonsteroidal antiinflammatory medication, and intraarticular steroid injection). It is inadvisable to treat patients with a complete collapse of joint space or bone loss with intraarticular hyaluronic acid, given their poor clinical response.

Adjuvants, Immunologic↗
PubMed1991

Hyaluronic acid as a medium for human sperm migration tests.

Hyaluronic acid was used as a substitute for human cervical mucus as a medium for sperm migration since its viscosity, molecular weight and structure are similar to constituent glycoproteins of human cervical mucus. Parameters of sperm motility were comparable in human cervical mucus and hyaluronate as measured by a computerized sperm motion analysis system (Hamilton-Thorn 2030 and Strömberg-Mika System). Sperm migration rates were also similar in human cervical mucus, bovine mucus and hyaluronic acid and the reproducibility was best in hyaluronic acid. Sperm survival for 24 h was maintained in human cervical mucus and hyaluronic acid but not in bovine mucus. The use of hyaluronic acid in sperm migration tests is recommended.

Animals↗
PubMed1980

Hyaluronic acid--an indicator of pulmonary injury?

Hyaluronic acid was the only glysosaminoglycan detected in the pulmonary secretions of healthy adult rats exposed to inhalation to methylene chloride, but not of control animals. The compound migrated as a single spot with the mobility of standard hyaluronic acid on cellulose acetate electrophoresis and disappeared after digestion with testicular hyaluronidase. Its identification was confirmed by finding hexuronate/hexosamine in a molar ratio of approx. 1. Glucosamine represented over 97% of the total hexosamine, the remaining 3% being galactosamine. No hexose or sulfate could be detected. Sodium dodecyl sulfate--polyacrylamide gel electrophoresis showed no protein associated with this glycosaminoglycan. It appears that the secretion of hyaluronic acid into the airways may be the result of pulmonary inflammation induced by the toxic effects of methylene chloride.

Animals↗
PubMed2006

Efficacy and safety of hyaluronic acid in the management of acute wounds.

INTRODUCTION: Hyaluronic acid (hyaluronan) is a key component of the extracellular matrix and is known to be involved in several mechanisms of the wound healing process. It has been shown to improve and accelerate the healing process of chronic wounds. This open-label study investigated whether application of hyaluronic acid could also improve the healing progression of acute wounds. METHODS: Forty-three patients with acute wounds, including trauma wounds, surgical sutures, burns, and dermabrasions, were included in the study. Hyaluronic acid (ialuset) was applied either as a cream or as a dressing, and the progression and quality of healing were evaluated at each application for a maximum of nine applications. RESULTS: The mean surface area of the wounds decreased from 556 mm(2) at baseline to 169 mm(2) by the sixth evaluation, an average reduction of 70% in the surface area of the wounds. Complete healing occurred in 56% of cases by the sixth application. Little or no fibrin was observed in 91% of cases, and 84% of wounds showed little or no exudate. Both formulations of hyaluronic acid were well tolerated and were rated highly by nurses and patients for ease of use and treatment satisfaction. CONCLUSION: Interpretation of the results of this open-label study is limited by the lack of a standard wound dressing as a comparator and by the varying types of wounds selected for inclusion. Nevertheless, the results of this study indicate that hyaluronic acid provides good healing of acute wounds and is well accepted by both patients and nurses.

Acute Disease↗
PubMed2005

Stable production of hyaluronic acid in Streptococcus zooepidemicus chemostats operated at high dilution rate.

Hyaluronic acid is routinely produced through fermentation of both Group A and C streptococci. Despite significant production costs associated with short fermentations and removal of contaminating proteins released during entry into stationary phase, hyaluronic acid is typically produced in batch rather than continuous culture. The main reason is that hyaluronic acid synthesis has been found to be unstable in continuous culture except at very low dilution rates. Here, we investigated the mechanisms underlying this instability and developed a stable, high dilution rate (0.4 h-1) chemostat process for both chemically defined and complex media operating for more than 150 h of production. In chemically defined medium, the product yield was 25% higher in chemostat cultures than in conventional batch culture when arginine or glucose was the limiting substrate. In contrast, glutamine limitation resulted in higher ATP requirements and a yield similar to that observed in batch culture. In complex, glucose-limited medium, ATP requirements were greatly reduced but biomass synthesis was favored over hyaluronic acid and no improvement in hyaluronic acid yield was observed. The successful establishment of continuous culture at high dilution rate enables both commercial production at reduced cost and a more rational characterization and optimization of hyaluronic acid production in streptococci.

Amino Acids↗
PubMed2003

Endoscopic treatment with dextranomer-hyaluronic acid for vesicoureteral reflux: histological findings.

PURPOSE: Dextranomer-hyaluronic acid co-polymer is the first endoscopic bulking agent approved for vesicoureteral reflux in the United States. We evaluated the histopathological changes associated with this treatment in children with vesicoureteral reflux. MATERIALS AND METHODS: Children 1 to 11 years old in whom treatment with dextranomer-hyaluronic acid co-polymer for grades III or greater vesicoureteral reflux had failed were eligible for the study. Failure was defined as persistent vesicoureteral reflux on voiding cystourethrography done approximately 3 months after implantation. At ureteral reimplantation the implant and surrounding ureteral tissue were resected and fixed for histopathological analysis. Tissue sections (4 to 5 microm.) were stained for routine histology and examined under a light microscope. Patients with a similar grade of vesicoureteral reflux who had not undergone endoscopic treatment served as the control group. RESULTS: The study population comprised 23 patients with vesicoureteral reflux, of whom 13 with a mean age of 2 years 8 months at diagnosis underwent 1 to 3 treatments with dextranomer-hyaluronic acid co-polymer. The remaining 10 patients with a mean age of 1 year 10 months at diagnosis did not receive the bulking agent before ureteral reimplantation. The implant remained in situ 13 to 39 months (mean 22). On ureteral reimplantation the implant was located at the site of injection in 12 of the 13 patients. Histologically a granulomatous inflammatory reaction indicated by giant cell infiltration was observed at the implantation site. At ureteral reimplantation 9 implants were pseudo-encapsulated. Calcification was present in 9 ureters, while the eosinophil count was greater than 5 cells per 0.125 mm2 in 7 ureters treated with dextranomer-hyaluronic acid co-polymer. Mast cell infiltration was similar in the treatment and control groups. CONCLUSIONS: Endoscopic treatment with dextranomer-hyaluronic acid co-polymer for vesicoureteral reflux is associated with a granulomatous reaction of the giant cell type, inflammatory cell infiltration and implant pseudo-encapsulation. They are typical histological findings associated with implantation of a foreign material. Dextranomer-hyaluronic acid co-polymer remains safe and effective for vesicoureteral reflux in children.

Adolescent↗
PubMed1981

Induction of hyaluronic acid synthetase by estrogen in the mouse skin.

Hyaluronic acid synthetase activity was measured in male mouse skin following the topical application of estradiol in vivo. The enzyme activity increased in parallel with the hyaluronic acid content of the skin, and showed a similar response in the skin of ovariectomized female mice. The increase in enzyme activity was reduced by the anti-estrogen agents, tamoxifene citrate and clomiphene citrate, which block competitively the binding of estrogen to the estrogen receptor. The increase in hyaluronic acid synthetase activity was also reduced by topical application of cycloheximide or by subcutaneous injection of actinomycin D. The results suggest that the stimulation of hyaluronic acid synthesis in mouse skin in response to estrogen treatment is mediated through estrogen receptors and involves the induction of the enzyme hyaluronic acid synthetase.

Animals↗
PubMed2001

CD44 is the principal mediator of hyaluronic-acid-induced melanoma cell proliferation.

Interactions of the extracellular matrix component hyaluronic acid and its cellular receptors CD44 and RHAMM/IHABP have been linked to tumor progression and metastasis formation. We investigated the expression and hyaluronic-acid-dependent functions of CD44 and RHAMM/IHABP in human melanoma. Immunohistochemistry of tumor specimens at different stages of melanoma progression revealed an increased expression of CD44 and RHAMM/IHABP. High mRNA expression of CD44 was found in three highly tumorigenic melanoma cell lines compared with less tumorigenic melanoma cells or nontransformed melanocytes. RHAMM/IHABP expression was upregulated in all cell lines analyzed but not in melanocytes. In contrast to the cell surface localization of CD44, RHAMM/IHABP was detected exclusively within the cytoplasm of melanoma cells. Binding and adhesion of melanoma cells to hyaluronic acid is mainly CD44 dependent as it was inhibited to 60%--80% by an anti-CD44 monoclonal antibody whereas anti-RHAMM/IHABP sera had no effect. Culture of melanoma cells in the presence of hyaluronic acid resulted in a dose-dependent, CD44-mediated increase of melanoma cell proliferation and enhanced release of basic fibroblast growth factor and transforming growth factor beta 1. We conclude that (i) the expression of CD44 and RHAMM/IHABP is increased during melanoma progression, (ii) CD44 is the principal hyaluronic acid surface receptor on melanoma cells, and (iii) the hyaluronic-acid-induced increase of the proliferative capacity of melanoma cells is mainly dependent on CD44--hyaluronic acid interactions.

Antigens, Surface↗
PubMed1986

Hyaluronic acid synthesized by fibroblasts cultured from normal and chronically inflamed human gingivae.

Hyaluronic acid is an important component of the extracellular matrix of gingivae and its quantity and molecular size appear to be altered under inflammatory conditions. Whether gingival fibroblasts from inflamed tissues synthesize quantities and molecular sizes of hyaluronic acid that differ from normal gingival fibroblasts is not known. To determine this, we isolated fibroblasts from three biopsies each of healthy and chronically inflamed human gingiva and incubated them in the presence of [3H]glucosamine. The release of labeled macromolecules into the medium was approximately 50% greater for the inflamed tissue fibroblasts than for the normal tissue fibroblasts. Of this labeled material, 35% was identified as hyaluronic acid in the medium of inflamed cell cultures, compared to only 25% in normal fibroblast cultures. Sepharose CL-4B chromatography of the labeled material revealed that most of the newly synthesized hyaluronic acid was of large molecular size in inflamed fibroblast cultures. The proportions of [3H]-labeled hyaluronic acid in these peaks varied and indicated that an increase in the amount of large molecular size hyaluronic acid was responsible for the increase in labeled hyaluronic acid noted in the medium of the inflamed tissue fibroblasts. Thus, the decrease in molecular size of hyaluronic acid previously noted in inflamed tissue most likely arises from extracellular factors rather than synthesis of smaller molecular weight species by the fibroblasts. More importantly, however, the differences noted between normal and inflamed gingival fibroblasts persisted over time in culture. This indicates that such differences between the cells may be of a stable and heritable nature.

Chromatography, Gel↗
PubMed2002

[Zymohydrolysis with chondroitinase ABC and high performance liquid chromatography used for the determination of hyaluronic acid in shark fin].

A method for the determination of hyaluronic acid in shark fin by high performance liquid chromatography (HPLC) is described. At 37 degrees C, with 0.2 mol/L Tris-HCl buffer solution, hyaluronic acid was converted to the hyaluronic acid disaccharide by zymohydrolysis with chondroitinase ABC. The chromatographic conditions were as follows: ZORBAX carbohydrate analysis column (4.6 mm i.d. x 250 mm, 5 microns); room temperature; UV-VIS detector set at 226 nm; mobile phase V(acetonitrile): V(0.5% phosphoric acid) = 2:98; 0.45 micron filter membrane, pumping filter; injection volume 10 microL; flow rate 1 mL/min. The calibration curve for the hyaluronic acid disaccharide was linear over the range of 25 g/L-600 g/L. This method was applied to the analysis of shark fin with satisfactory results. The hyaluronic acid contents in different shark fins were from 0.86% to 1.96%.

Animals↗
PubMedDate not supplied

Serum hyaluronic acid as a reliable parameter of allograft viability in porcine liver transplantation.

BACKGROUND/AIMS: Hyaluronic acid is an endogenous glycosaminoglycan which is selectively degraded by hepatic sinusoidal endothelial cells. We evaluated the significance of serum hyaluronic acid clearance as an early indicator of allograft viability in porcine liver transplantation. MATERIALS AND METHODS: According to the survival period, animals were divided into two groups: Group I (n = 8) for survival equal or over four days and Group II (n = 5) for survival less than four days. Serial serum hyaluronic acid concentrations were measured before and after reperfusion in the recipient. RESULTS: In both groups, serum hyaluronic acid levels during the anhepatic period increased rapidly 9-fold from the preoperative value due to the absence of clearance by hepatic endothelial cells. In Group I, serum hyaluronic acid peaked at 15 min postreperfusion and decreased thereafter. In contrast, Group II failed to show clearance of hyaluronic acid after reperfusion. The serum hyaluronic acid value 120 min after reperfusion was 1,029 +/- 357 micrograms/L in Group I, and 1,856 +/- 263 micrograms/L in Group II (p < 0.01). Conventional parameters of liver function such as aspartate transaminase, lactic dehydrogenase, ammonia, lactate, and total bile acids were comparable between the two groups. CONCLUSIONS: The clearance of the serum hyaluronic acid reflects hepatic sinusoidal endothelial cell function and is a reliable and early marker of hepatic allograft viability.

Animals↗
PubMedDate not supplied

[Biological role of hyaluronic acid (review)].

The most important studies on hyaluronic acid carried out within the recent 5-7 years are reviewed. Chemical structure, physical parameters and properties of hyaluronic acid are considered. Various functions of hyaluronic acid are discussed on the basis of current information.

Animals↗
PubMed2003

Intra-articular hyaluronic acid in treatment of knee osteoarthritis: a meta-analysis.

CONTEXT: Intra-articular hyaluronic acid is a US Food and Drug Administration-approved treatment for knee osteoarthritis (OA); however, its efficacy is controversial. OBJECTIVE: To evaluate whether intra-articular hyaluronic acid is efficacious in treating knee OA. DATA SOURCES: We searched for human clinical trials in MEDLINE (1966 through February 2003) and the Cochrane Controlled Trials Register, using the search terms (osteoarthritis, osteoarthrosis, or degenerative arthritis) and (hyaluronic acid, Hyalgan, Synvisc, Artzal, Suplasyn, BioHy, or Orthovisc). We also hand searched manuscript bibliographies that met inclusion criteria, selected rheumatic disease journals, and abstracts from scientific meetings. STUDY SELECTION: Included were published or unpublished, English and non-English, single- or double-blinded, randomized controlled trials comparing intra-articular hyaluronic acid with intra-articular placebo injection for the treatment of knee OA. Trials also were required to have extractable data on pain reported by 1 of the outcome measures recommended by the Osteoarthritis Research Society. DATA EXTRACTION: Two reviewers independently performed data extraction using standardized data forms. For each trial, we calculated an effect size (small-effect sizes, 0.2-0.5; large-effect sizes, 1.0-1.8, equivalent to a total knee replacement). We used a random-effects model to pool study results, the Cochrane Q test to evaluate heterogeneity, and a funnel plot and the Egger test to evaluate publication bias. DATA SYNTHESIS: The overall dropout rate in the 22 selected trials was 12.4%. The pooled effect size for hyaluronic acid was 0.32 (95% confidence interval [CI], 0.17-0.47). There was significant heterogeneity among studies (P<.001). Two outlier trials, both evaluating the highest-molecular-weight hyaluronic acid, had effect sizes in excess of 1.5. However, the third trial of the same compound showed a nearly null effect. When the 3 trials of this compound were removed, heterogeneity was no longer significant (P =.58), and the pooled effect size for intra-articular hyaluronic acid decreased to 0.19 (95% CI, 0.10-0.27). There was evidence of publication bias with an asymmetric funnel plot, a positive Egger test, and identification of 2 unpublished trials whose pooled effect size was 0.07 (95% CI, - 0.15 to 0.28). CONCLUSION: Intra-articular hyaluronic acid has a small effect when compared with an intra-articular placebo. The presence of publication bias suggests even this effect may be overestimated. Compared with lower-molecular-weight hyaluronic acid, the highest-molecular-weight hyaluronic acid may be more efficacious in treating knee OA, but heterogeneity of these studies limits definitive conclusions.

Clinical Trials as Topic↗