Hyaluronic acid summary

Hyaluro-nan's Biological synthesis

Cell receptors for hyaluronan

Role of hyaluronan(hyaluronic acid) in cancer metastasis

The Medical applications of hyaluronic acid

What are the differences between glycolic acid, salicyclic acid, and hyaluronic acid? What is the benefit of each type for skin?

What are the differences between glycolic acid, salicyclic acid, and hyaluronic acid? What is the benefit of each type for skin?

Glycolic Acid is the most active and beneficial of the Alpha-Hydroxy-Acids in skin care and is made from sugar canes. It is the only AH-A which is able to penetrate through the cell walls by virtue of its small molecular size. Once inside the cell, it will trigger new formation of collagen and turn on the synthesis of dermal glycosaminoglycans to plump up the cell and the ground substances in the skin to reduce wrinkles on the skins surface. Glycolic Acid also affects the newly forming keratin cells at the bottom of the stratum corneum causing the bulk of the stratum corneum to lift off and separate from the underlying skin. This gives the skin a much smoother look and feel. Salicylic acid is a mild acid that works as a keratolytic agent � it encourages the sloughing of dead skin cells. It�s a safe, effective treatment for mild acne, oily skin, textural changes and post-inflammatory hyperpigmentation in patients of most skin types. Mild acid solutions, such as salicylic acid and glycolic acid, encourage the peeling of the top layer of skin and the opening of plugged follicles, which helps reestablish the normal skin-cell replacement cycle. For milder acne, salicylic acid helps unclog pores to resolve and prevent lesions. It does not have any effect on the production of sebum or the presence of P. acnes bacteria. Like many other topical acne treatments, salicylic acid must be used continuously, even after acne lesions have healed. Its effects stop when you stop using it, so your skin will return to its uneven shedding; pores become clogged, and acne returns. Hyaluronic acid（Sodium Hyaluronate for injection grade） is a component of connective tissue whose function is to cushion and lubricate. Hyaluro-nan occurs throughout the body in abundant amounts in many of the places people with hereditary connective tissue disorders have problems such as joints, heart valves and eyes. Hyaluronic acid abnormalities are a common thread in connective tissue disorders. Interestingly, they are also common biochemical anomalies in most of the individual features of connective tissue disorders such as mitral valve prolapse, TMJ, osteoarthritis, and keratoconus. Hyaluronic acid, or commercial preparations containing hyaluronic acid, are in use or being studied to be used, to prevent, treat or aid in the surgical repair for many the types of problems people with connective tissue disorders tend to have such as scar prevention, wrinkled skin, cartilage damage and wound healing.

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http://www.answerbag.com/q_view/4204

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Hyaluronan's Biological synthesis

Hyaluronan （Sodium Hyaluronate for injection grade）is synthesized by a class of integral membrane proteins called hyaluronan synthases, of which vertebrates have three types: H-AS1, H-AS2, and H-AS3. These enzymes lengthen hyaluro-nan by repeatedly adding glucuronic acid and N-acetylglucosamine to the nascent polysaccharide as it is extruded via ABC-transporter through the cell membrane into the extracellular space. Hyaluro-nan synthesis (H-AS) has been shown to be inhibited by 4-Methylumbelliferone (hymecromone, heparvit), a 7-Hydroxy-4-methylcoumarin derivative.This selective inhibition (without inhibiting other Glycosaminoglycans) may prove useful in preventing metastasis of malignant tumor cells.

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http://en.wikipedia.org/wiki/Hyaluronan

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Cell receptors for hyaluronan

So far, cell receptors that have been identified for HA fall into three main groups: CD44, RH-AMM (Receptor for Sodium Hyaluronate for injection grade-Mediated Motility) and ICAM-1 (Intracellular adhesion molecule-1). CD44 and ICAM-1 were already known as cell adhesion molecules with other recognized ligands before their H-A binding was discovered. CD44 is widely distributed throughout the body, and the formal demonstration of H-A-CD44 binding was proposed by Aruffo et al.in 1990. To date, it is recognized as the main cell surface receptor for HA. CD44 mediates cell interaction with H-A and the binging of the two functions as an important part in various physiologic events,such as cell aggregation, migration, proliferation and activation; cell-cell and cell-substrate adhesion; endocytosis of H-A, which leads to HA catabolism in macrophages; and assembly of petircellular matrices from HA and proteoglycan. Two significant roles of CD44 in skin were proposed by Kaya et al.The first one is regulation of keratinocyte proliferation in response to extracellular stimuli, and the second one is the maintenance of local Sodium Hyaluronate for injection grade homeostasis. ICAM-1 is known mainly as a metabolic cell surface receptor for HA, and this protein may be responsible mainly for the clearance of HA from lymph and blood plasma, which accounts for perhaps most of its whole-body turnover Ligand binding of this receptor, thus, triggers a highly co-ordinated cascade of events that includes the formation of an endocytotic vesicle, its fusion with primary lysosomes, enzymatic digestion to monosccharides, active transmembrane transport of these sugars to cell sap, phosphorylation of GlcNAc and enzymatic deacetylation. Like its name, ICAM-1 may also serve as a cell adhesion molecule and the binding of HA to ICAM-1 may contribute to the control of ICAM-1-mediated inflammatory activation.

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http://en.wikipedia.org/wiki/Hyaluronan

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Role of hyaluronan(hyaluronic acid) in cancer metastasis

As shown in Figure 1, the various types of molecules that interact with hyaluro-nan can contribute to many of the stages of cancer metastasis. Hyaluro-nan synthases play roles in all of the stages of cancer metastasis. By producing anti-adhesive H-A(Sodium Hyaluronate for injection grade), H-AS can allow tumor cells to release from the primary tumor mass and if H-A associates with receptors such as CD44, the activation of Rho GTPases can promote epithelial-mesenchymal transition (EMT) of the cancer cells. During the processes of intravasation or extravasation, the interaction of H-AS produced H-A with receptors such as CD44 or RH-AMM promote the cell changes that allow for the cancer cells to infiltrate the vascular or lymphatic systems. While traveling in these systems, H-A produced by H-AS protects the cancer cell from physical damage. Finally, in the formation of a metastatic lesion, H-AS produces HA(Sodium Hyaluronate for injection grade) to allow the cancer cell to interact with native cells at the secondary site and to produce a tumor for itself. Hyaluronidases (H-Aase or HYAL) also play many roles in cancer metastasis. By helping to degrade the ECM surrounding the tumor, hyaluronidases help the cancer cell escape from the primary tumor mass and play a major role in intravasation by allowing degradation of the basement membrane of the lymph or blood vessel. Hyaluronidases again play these roles in establishment of a metastatic lesion by helping with extravasation and clearing the ECM of the secondary site. Finally, hyaluronidases play a key role in the process of angiogenesis. H-A fragments promote angiogenesis and hyaluronidases produce these fragments.Interestingly, hypoxia also increases production of H-A（Sodium Hyaluronate for injection grade） and activity of hyaluronidases. The hyaluro-nan receptors, CD44 and RH-AMM, are most thoroughly studied in terms of their roles in cancer metastasis. Increased clinical CD44 expression has been positively correlated to metastasis in a number of tumor types. In terms of mechanics, CD44 affects adhesion of cancer cells to each other and to endothelial cells, rearranges the cytoskeleton through the Rho GTPases, and increases the activity of ECM degrading enzymes. Increased RH-AMM expression has also been clinically correlated with cancer metastasis. In terms of mechanics, RH-AMM promotes cancer cell motility through a number of pathways including focal adhesion kinase (FAK), Map Kinase (MAPK), pp60 (c-src), and the downstream targets of Rho Kinase (ROK).RH-AMM can also cooperate with CD44 to promote angiogenesis toward the metastatic lesion.

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http://en.wikipedia.org/wiki/Hyaluronan

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The Medical applications of hyaluronic acid

Hyaluro-nan（Sodium Hyaluronate for injection grade） is found in many tissues of the body, such as skin, cartilage, and the vitreous humour. Therefore, it is well suited to biomedical applications targeting these tissues. The first hyaluro-nan biomedical product, Healon, was developed in the 1970s and 1980s by Pharmacia, and is approved for use in eye surgery (i.e., corneal transplantation, cataract surgery, glaucoma surgery, and surgery to repair retinal detachment). Other biomedical companies also produce brands of hyaluronan(Sodium Hyaluronate for injection grade) for ophthalmic surgery. In the late 1970s, intra-ocular lens implantation was often followed by severe corneal edema, due to endothelial cell damage during the surgery. It was evident that a viscous, clear, physiologic lubricant to prevent such scrapping of the endothelial cells was needed.Endre Balazs patented a process for purifying hyaluronic acid, a physiologic lubricant (which he called Healon) from rooster combs in the early 1970s. At first, Balazs saw Healon as a non inflammatory vitreous substitute. Claus Dohlman had used Balazs’ Healon in one case in which the anterior chamber flattened after a complicated corneal transplant. Although one might imagine that the viscous hyaluronic acid would have caused a rise in IOP, Dohlman reported no such rise in his case. Since that time, Balazs had licensed the synthesis process to Pharmacia, a Swedish drug company. Although Pharmacia saw no market for a vitreous substitute, when their scientists figured out a way to increase the viscosity of hyaluronic acid（Sodium Hyaluronate for injection grade） , they felt it might work as an injectable agent in the treatment of both human and equine arthritis. The equine arthritis market proved to be small and the treatment of human osteoarthritis produced only marginal improvement and so Pharmacia decided to abandon Healon. At this time, David Miller realized that Healon was the lubricant needed by the eye surgeon. Balazs arranged to have Pharmacia send 20 sterile vials to Dr. David Miller for rabbit experiments. By 1976, Miller and colleagues published a study showing that Healon worked well in protecting the rabbit corneal endothelium during IOL implantation. With a new possible use for Healon. Miller met with Pharmacia and performed a lens extraction and IOL implantation using Healon in a rabbit eye. The demonstration ignited an new enthusiasm for eye surgery with Healon. A small human pilot study at Boston’s Beth Israel Hospital by Miller confirmed Healon’s beneficial effects. In a large, well-controlled clinical trial, Dr. Robert Stegmann, of Pretoria, South Africa was able to quantify the advantages of Healon in IOL implantation by showing significantly higher post operative corneal endothelial counts in the Healon eyes as opposed to the controls. The FDA quickly approved Healon as a surgical device in 1980 and Healon was successfully launched. By the year 2009, an estimated quarter of a billion patients had benefited from the useful properties of Healon in eye surgery. In 1992, Miller and Stegmann received the Innovators Award by the American Society of Cataract and Refractive Surgery for developing the use of healon in repairing injured eyes. Hyaluro-nan is also used to treat osteoarthritis of the knee. Such treatments, called viscosupplementation, are administered as a course of injections (Sodium Hyaluronate,Sodium Hyaluronate for injection grade) into the knee joint and are believed to supplement the viscosity of the joint fluid, thereby lubricating the joint, cushioning the joint, and producing an analgesic effect. It has also been suggested that hyaluro-nan has positive biochemical effects on cartilage cells. However, some placebo-controlled studies have cast doubt on the efficacy of Hyaluronic Acid injections(Sodium Hyaluronate for injection grade), and hyaluro-nan is recommended primarily as a last alternative to surgery. Oral use of hyaluronan has been lately suggested, although its effectiveness needs to be demonstrated. At present, there are some preliminary clinical studies that suggest that oral administration of Hyaluro-nan has a positive effect on osteoarthritis, but it remains to be seen if there is any real benefit to the treatment. Dry, scaly skin (xerosis) such as that caused by atopic dermatitis (eczema) may be treated with a prescription skin lotion containing sodium hyaluronate as its active ingredient. Due to its high biocompatibility and its common presence in the extracellular matrix of tissues, hyaluronan is gaining popularity as a biomaterial scaffold in tissue engineering research.In particular, a number of research groups have found that hyaluro-nan's properties for tissue engineering and Regenerative medicine are significantly improved with crosslinking, producing a hydrogel. This added feature allows a researcher to form a desired shape as well as to deliver therapeutic molecules into a host. Hyaluro-nan can be crosslinked by attaching thiols (trade names: Extracel, HyStem), methacrylates,and tyramines (trade name: Corgel). Hyaluro-nan can also be crosslinked directly with formaldehyde (trade name: Hylan-A) or with divinyl sulfone (trade name: Hylan-B). In some cancers, hyaluro-nan levels correlate well with malignancy and poor prognosis. Hyaluro-nan is, thus, often used as a tumor marker for prostate and breast cancer. It may also be used to monitor the progression of the disease. Hyaluronan (Sodium Hyaluronate for injection grade) may also be used postoperatively to induce tissue healing, notably after cataract surgery. Current models of wound healing propose that larger polymers of hyaluronic acid appear in the early stages of healing to physically make room for white blood cells, which mediate the immune response. Hyaluro-nan has also been used in the synthesis of biological scaffolds for wound-healing applications. These scaffolds typically have proteins such as fibronectin attached to the hyaluronan to facilitate cell migration into the wound. This is particularly important for individuals with diabetes suffering from chronic wounds. In 2007, the EMA extended its approval of Hylan GF-20 as a treatment for ankle and shoulder osteoarthritis pain. Hyaluro-nan is also used in anti-adhesive products such as Hyalobarrier, widely used in pelvic and abdominal surgery to prevent post-operative adhesions.

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http://en.wikipedia.org/wiki/Hyaluronan

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Hyaluronic acid summary

Hyaluro-nan (HA,also called hyaluronic acid or hyaluronate) is a glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues. It is one of the chief components of the extracellular matrix, contributes significantly to cell proliferation and migration, and may also be involved in the progression of some malignant tumors. The average 70-kg man has roughly 15 grams of hyaluro-nan in his body, one-third of which is turned over (degraded and synthesised) every day. Hyaluro-nan is a common ingredient in skin care product, and the branded version Restylane is used as injections (Sodium Hyaluronate,Sodium Hyaluronate for injection grade) to temporarily smooth wrinkles by adding volume under the skin or the brand Macrolane to increase breast size by adding volume using a natural tissue chemical. Hyaluro-nan is a polymer of disaccharides, themselves composed of D-glucuronic acid and D-N-acetylglucosamine, linked together via alternating β-1,4 and β-1,3 glycosidic bonds. Hyaluro-nan can be 25,000 disaccharide repeats in length. Hyaluro-nan is an important component of articular cartilage, where it is present as a coat around each cell (chondrocyte). When aggrecan monomers bind to hyaluro-nan in the presence of link protein, large highly negatively-charged aggregates form. These aggregates imbibe water and are responsible for the resilience of cartilage (its resistance to compression). Hyaluro-nan is also a major component of skin, where it is involved in tissue repair. When skin is excessively exposed to UVB rays, it becomes inflamed (sunburn) and the cells in the dermis stop producing as much hyaluro-nan, and increase the rate of its degradation. Hyaluro-nan degradation products also accumulate in the skin after UV exposure. Hyaluro-nan also contributes to tissue hydrodynamics, movement and proliferation of cells, and participates in a number of cell surface receptor interactions. Hyaluro-nan is naturally found in many tissues of the body, such as skin, cartilage, and the vitreous humor. It is therefore well suited to biomedical applications targeting these tissues. The first hyaluro-nan biomedical product, Healon, was developed in the 1970s and 1980s by Pharmacia, and is approved for use in eye surgery. In 2003 the FDA approved hyaluro-nan injections (Sodium Hyaluronate,Sodium Hyaluronate for injection grade) for filling soft tissue defects such as facial wrinkles. Restylane is a common trade name for the product, injections of Restylane temporarily smooth wrinkles by adding volume under the skin, with effects typically lasting for six months, it is also used to give volume to lips. More recently, Macrolane, another trade name has been used as a non-surgical body shaping treatment that can naturally regenerate body contours. This can be used for large volume restoration and shaping of body surfaces, for example, calves and buttocks. Macrolane can also even out discrepancies in the skin surface, for example those caused by liposuction. In 2008, Macrolane has started to be used for breast shaping, and is aimed to be used for women whom have asymmetry, loss of volume as a result of breast feeding or weight loss, or under-developed breasts. Marketing suggests it is suitable for women to increase by a cup size without the need for surgery. Of course, the body naturally processes hyaluronan（Sodium Hyaluronate for injection grade）, so shaping only last for 12-18 months and top-ups would be required to retain shape or smooth skin.

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http://www.3dchem.com/molecules.asp?ID=425

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