Hyaluronic acid

Hyaluronic acid is an alternating copolymer, namely poly[jS-(1 4)-glucuronic acid-alt-j8-(l 3)-2-acetamido-2-deoxyglucose] (Table 31-7). It occurs in the lubricating fluid (synovial fluid) of the joints and the eyes and acts as a kind of cement for the extracellular basic material of connective tissues. 

Hyaluronic acid was first isolated by Karl Meyer from vitreous humor (30) and later from umbilical cord, synovial fluid, skin, cock s comb, certain fowl tumors, groups A and C hemolytic streptococci, and other sources 31). Historically, it has been a major and frequent if not universal component of Levene s so-called mucoitin sulfates. The polysaccharide acts in animal tissue presumably as an integral part of the gel-like ground substance of connective tissue (and other tissues). Another important function of hyaluronic acid in animals is serving as a lubricant and shock ab-sorbant in the joints. 

Hyaluronic acid is generally prepared from umbilical cords. Most of the protein is removed by digestion with pepsin and trypsin, and the residual protein is separated by the chloroform - amyl alcohol procedure. Hyaluronic acid may be precipitated by fractionation with ammonium sulfate in the presence of pyridine (32). This step also removes a contaminating polysaccharide sulfate. 

Hyalbiouronic acid, the deacetylated disaccharide obtained by action of 

In some samples of hyaluronic acid, the molar ratio of glucuronic acid to glucosamine appears to be greater than one (39), The molecular weight of umbilical hyaluronic acid as determined by light scattering has been reported as three to four million (40) and also as eight million (41). 

Mucosin (43) and mucoitin (43) appear to be identical with hyalbiouronic acid and hyaluronic acid, respectively. 

The action of spreading factors, e. g., hyaluronidases on hyaluronic acid both in vivo and in vitro is often quite dramatic, and the effect in vitro appears to go in three stages (a) a separation of the protein residue  

McClean, Rogers and Williams have devised a most timely use for hyaluronic acid, viz., its use as an early diagnostic test in gas gangrene infections. 

The destruction of hyaluronic acid by spreading factors in sperms may play an important role in fertilization processes.  

Preparations from various sources show closely similar properties, 

No structural studies on the chemistry of this important substance have yet been completed. 

The stability of complexes between some proteinases and the proteinase inhibitor c -macroglobulin has been examined. The cleavage of a proteinase-susceptible site may lead to covalent-bond formation between the enzyme and c -macro-globulin at a region not involving the active site of the enzyme. Although the ability to form covalent links is not essential for the inhibitory capacity of the 

Niewiaiowski, B. Rucinski. P. James, and U. UndaU, FEBS Lett., 1979,102,75. 

Fragmentation of human c -macroglobulin (mol. wt. 1.85 x 10 ) has been achieved by heating in the presence of sodium dodecyl sulphate and dithiothreitol, two fragments (mol. wt. 1.2 x 10 and 6.2 x 10 ) being produced. On the basis of amino-acid sequencing studies, the native glycoprotein is composed of four identical polypeptide chains.  

The receptors for Factor Vlll/von Willebrand factor that are present on human platelets are directly proportional to the extent of ristocetin-induced platelet aggregating activity. Factor Vlll-related protein aggregates are multimers of pairs of basic sub-unit chains. Further studies support the hypothesis that the underlying defect in von Willebrand type II disease may be incomplete assembly of Factor Vlll/von Willebrand factor monomer molecules into oligomers at the quaternary level of molecular organization. In von Willebrand Type I disease reduced synthesis of the Factor Vlll/von Willebrand factor sub-unit or of primary polymers (mol. wt. 1.0 x 10 ) may be the defect. When prepared from lipid-poor plasma the size heterogeneity ranges from 6.0 x 10 to 2.0 x 10 .  

Purified and reduced human Factor VIII exhibits an eight band sub-unit structure (mol. wt. 3.0 X 10 —2.3 x 10 ) as shown by polyacrylamide gel electrophoresis. Rabbit antibody to Factor VIII reacts with all of the sub-units whereas haemophilic antibody reacts with low-molecular-weight sub-units only. Sub-units derived from the largest Factor VIII multimers have a higher binding affinity for D-galactose-specific lectins than have those obtained after reduction of smaller oligomers. Ristocetin cofactor activity of purified Factor VIII is competitively inhibited by two Ricinus communis lectins and by concanavalin A. 

It can be degraded either enzymatically or by various other ways that are highlighted below. Hyalorunidases refer to a family of prokaryotic and eukaryotic enzymes that primarily degrade HA, but also other GAGs such as chondroitin and chondroitin sulphate to a lower extent [239]. They can be divided in three distinct classes that can be found intercellularly or in the serum and include two eukaryotic hydrolases of glucosidase type and a prokaryotic lyase one. 

The eukaryotic enzymes are hydrolases that have a wide range of pH optima and proceed by adding water to one cleavage site or by removing non-reducing termini sugars of the HA chain. Hydrolytic degradation follows first-order kinetics [240], 

The prokaryotic enzymes are lyases that through an elimination reaction preferentially cleave the (3-(l- 4) bond in HA or chondroitin sulphate, leaving an rmsaturated bond. Absolute specificity for HA as substrate though, can be obtained by a specific class of prokaryotic hyaluronidases, produced by Streptomyces hyalurolyticus [241]. 

HA can be otherwise degraded by both acid and alkaline hydrolysis in one or two steps, thermal degradation, ultrasonic degradation, oxidative degradation and photodegradation [242] in the human body it undergoes degradation by free radicals. 

Up to date hyaluronan has been used to incorporate a wide variety of drugs for local delivery that include corticosteroids, immunosuppressants, antihistamines. 

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Lahajnar, G., Zupancic, L, Rupprecht, A. Proton NMR relaxation and diffusion study of water sorbed in oriented DNA and hyaluronic acid samples. In Biophysics of Water (Franks, F., Mathias, S., eds) Wiley, New York (1982) 231-234... 

There are other glycosaminoglycans. Hyaluronic acid [9004-61-9] occurs both free and in noncovalent association with proteoglycan molecules. Heparin [9005-49-6] and heparan sulfate [39403-40-2] also known as heparitin sulfate [9050-30-0] occur in mast cells and in the aorta, Hver, and lungs. 

Anionic Polyacrylic acid (Na) Polyalginic acid (Na) Hyaluronic acid Carrageenan 0.1 M NaNOj... 

Hyaluronic acid y binding domain (link-protein like)... 

The second type of material includes spores, which may or may not produce disease symptoms but which can germinate in the insect gut and give rise to vegetative bacterial cells which in turn may produce, and exoenzymes such as phospholipases (lecithinases) or hyaluronidase. The phospholipases may produce direct toxic symptoms owing to their action on nervous or other phospholipid-containing tissue. Hyaluronidase breaks down hyaluronic acid and produces effects on animal tissue which are morphologically similar to the breakdown of insect gut wall in the presence of microbial insecticide preparations. 

Highly purified hyaluronic acid, useful in medicine and cosmetic areas, has been prepared from body tissues by different treatments with the help of sodium dodecyl sulfate [199]. 

FIGURE 8.46 Hyaluronic acid has the consistency of a soft gel. It absorbs water easily and bonds with the proteins in the skin, making it useful in the repair of wounds and joint injuries. 

Hiroshima, 721 histidine, 443, 774 hole, 195 homeostasis, 386 HOMO, 126, 580 homogeneous alloy, 202 homogeneous catalyst, 565 homogeneous equilibria, 362 homogeneous mixture, F53 homolytic dissociation, 80 homonuclear diatomic molecule, 103 Hooke s law, 92 hormone, 670 horsepower, A4, 791 hour, A4 HPLC, 354 HRF products, 723 HTSC, 192 Humphreys series, 51 Hund, F 35 Hund s rule, 35, 37 Hurricane Rita, 144 hyaluronic acid, 344 hybrid orbital, 109 hybridization bond angle, 131 molecular shape, 111 hydrangea color, 463 hydrate, F32 hydrate isomer, 676 hydration, 178 hydrazine, 627... 

Fingerprinting the Hyaluronic Acid Component of Normal and Pathological Synovial Fluids, S. A. Barker, S. H. I. Bayyuk, J. S. Brimacombe, C. F. Hawkins, and M. Stacey, Clin. Chim. Acta, 8 (1963) 902-909. 

Acetamido-2-deoxy-D-gluco)-o-glucuronoglycan (hyaluronic acid or hyaluronan)... 

Polyelectrolyte complexes composed of various weight ratios of chitosan and hyaluronic acid were found to swell rapidly, reaching equilibrium within 30 min, and exhibited relatively high swelling ratios of 250-325% at room temperature. The swelling ratio increased when the pH of the buffer was below pH 6, as a result of the dissociation of the ionic bonds, and with increments of temperature. Therefore, the swelling ratios of the films were pH-and temperature-dependent. The amount of free water in the complex films increased with increasing chitosan content up to 64% free water, with an additional bound-water content of over 12% [29]. 

The optimum conditions for polyion complex formation between chitosan and hyaluronate were identified fhe compression exerfed fo manufacture the implant had no role to play in the release kinetics [28,92]. Various authors published data confirming fhaf fhe combinafion of chifosan and hyaluronic acid is always suscepfible fo swelling, even in fhe presence of cross-hnking. 

Molecular weights of polysaccharides in solution can also be measured by osmotic pressure and light scattering. Osmotic pressure yields the number average molecular weight, which can be usefully used with Mw from sedimentation equilibrium as a measure of polydispersity Preston and Wik [28] have done this for example with hyaluronic acid. The ratio Mw/Mn the polydispersity index is often given as a measure of polydispersity, and can be related to the width of a molecular weight distribution via the well-known Herdan [96] relation ... 

Reported studies have shown its anti-inflammatory effects and anti-oxidant action. It acts by thinning the stratum corneum, promoting epidermolysis, dispersing basal layer melanin and epidermal and dermal hyaluronic acid and collagen gene expression that increases through an elevated secretion of IL-6 [3]. 

Bernstein EF, Lee J, Brown DB, Yu R, Van Scott E (2001) Glycolic acid treatment increases type I collagen mRNA and hyaluronic acid content of human skin. Dermatol Surg 27(5) 429-433... 

Hyaluronic acid is a linear polysaccharide found in the highest concentrations in soft connective tissues where it fills an important structural role in the organization of the extracellular matrix (23,24). It has been used in ophthalmic preparations to enhance ocular absorption of timolol, a beta blocker used for the treatment of glaucoma (25), and in a viscoelastic tear formulation for conjunctivitis (26). The covalent binding of adriamycin and daunomycin to sodium hy-aluronate to produce water-soluble conjugates was recently reported (27). 

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