Hyluronan

Hyaluronan

Basic BiologyHyaluronan is a polysaccharide Repeating disaccharide which contains Glucuronic acid and N-acetylglucosamine. Bonding of monosaccharides is 1-4 glycosidic bondBonding of disaccharides is 1-3 glycosidic bond.It is one of the most anionic (negatively charged) molecules produced by animal cells.

Nature of productBY anisah bint ismail, alghaliah alrujaib, sara green

HyaluronanProductsApplicationsInjection for knee osteoarthritis

Hyaluronan is a naturally occurring macromolecule that is an essential part of synovial fluid and is thought to contribute to its viscoelastic properties.

Hyaluronan helps to lubricate the joints by upgrading the concentration of synovial fluid, contributing to increase of joint mobility.

ADVANTAGE : The side effects are mild such as temporary pain and swelling after injection.

DISADVANTAGE : Some people might have a slight allergic reaction and the injections have to be taken frequently as the pain relief is only temporary.Applications2. Beauty product

Hyaluronan is able to absorb up to 1000 times of its weight in H2O, therefore it is suitable to hydrate and firm up skin cells.

Found in various cosmetic products such as lotions, serums, shampoos, conditioners, bath oils, foundations, lipsticks or lip balms. Example : Estee Lauder

3. Skin wound healing

Hyaluronan is one of the first components synthesized at the point of injury.

It creates moist environment in wound to support synthesis of other parts of connective tissues and cell reproduction.ApplicationsInjury results in hyaluronan fragmentation in hyaluronan of very low molecular weight. These small fragments activate the immune cells and thus support the first process of healing which is inflammation.

Hyaluronan is able to eliminate scar formation during the wound healing process. This is similar with embryo tissue, which is rich in hyaluronan.

http://www.hyiodine.com/patients-hyaluronan-in-wound-healing

Process of productBY ASIF HASSAN, ANAND SUBASH,WAJAHAT NASEEM, JUNIOR aGBOOLA

HyaluronanProduction by extraction from animal tissueExtracted from most tissues of vertebrates.Most accessible sources include rooster combs which undergoes mechanical slicing to smaller pieces prior to production.Raw material is full of contaminants and requires proteolytic enzymes to isolate them from the natural complexesWashed with ethanol and then undergoes chloroform extraction and centrifugation.Purified by several intermediate stages of precipitations.Sterile filtration, alcohol precipitation drying and conditioning to eradicate remaining microbial cells.Production using bacteriaStreptococci strains are normally fermented in a batch process under aerobic conditions with unlimited supply of glucose.Overall synthesis of 1 mol of HA- five moles of nucleosides triphosphates, two moles of glucose and one mole of acetyl coenzyme A.ATP levels and reducing equivalents in the cell play a key role in biosynthesis, these substances are consumed and generated in the production of HA.Process takes place at 37C and pH7.The process can yield 6-7 grams per litre.Streptococci C strains are preferred due to its relatively high production of Hyaluronan but also importantly due the C groups strains being non-pathogenic to humans.Safety IssuesBy Athanasie Munyaneza, Harry Wilkinson, Callum dykes, Alexander chilvers

HyaluronanSafety Issues regarding the UsesHyaluronan assists with the metastasis of cancer cells, which means it aids the spread from one part of the body to other parts. It does this by protecting the cell from physical damage.

Another use is in injections aimed to help people suffering from osteoarthritis in knee joints. It has been concluded that the injections are deemed a safe and efficient way of reducing the patients pain. The main adverse effect of concern is joint infection which can be easily overcome if administered correctly.Examples of Safety IssuesIn a clinical study patients were injected with hyaluronic acid as a facial intradermal implant. The worst cases were swelling of the implant, thought to be caused by the hydrophilic properties of hyaluronic acid.Other cases included bruising, swelling, tenderness and erythema but these occurred at the injection site so are not directly linked to the hyaluronic acid but the use itself.

Environmental IssuesBy Giorgio de mitri, silvia lungu, nadhirah Muhammad fithri

HyaluronanHyaluronic acid is safe for most people.Some of the uses: Ageing skin CataractsOsteoarthritis No environmental issues associated with HA. Produced by our body naturally. Large molecule, therefore too large to pass through skin.

HA injection side effectsAnti-ageing treatment:

In general, theside effects are mild: bruising, redness, swelling, pain, tenderness, allergy reaction.

In some cases, serious hyaluronic acid sideeffects happened for those received more than one injection.

Injection into a joint

Increased pain after injection Side effects: redness and tenderness at the site of the injection, increased stiffness, swelling or warmth, inflammation

Less common side effects: Allergy, joint may become severely inflamed after injection, headache, muscle pain, nausea.

https://www.hsc.com.my/ort_arthroscopic.phphttp://www.wisegeek.org/what-is-hyaluronic-acid.htm

Other side effectsUse in pregnancy and breastfeeding Hyaluronic acid has not been tested in pregnant women or women who are breastfeeding. It is important to tell your doctor if you are, or intend to become pregnant or if you are breastfeeding.Use with other medicines Tell the doctor about all medicines you aretaking or plan to take. Mention treatmentwhen seeing other health professionals.

http://images.iherb.com/l/WHE-03548-1.jpgCommercial and Economic IssuesBy Monika Rowczenio, Dinesh SELVANATHAN, jiulio lafontant

HyaluronanScopeHyluronan has a world market value of US$500M and is sold for up to US$100K per kg (Heinz T.J. 2013). Production is based on two methods:Extraction from animal tissuesMicrobial Fermentation using bacteria strains

Pharmaceutical ValueHyaluronan has a pharmaceutical value of $US170m (Novozymes 2012). Below are the figures for the Hyaluronan Division of Lifecore, one company which is extensively involved in its usage.

Commercial and Economic IssuesExtraction from animal Tissues:

Advantages Disadvantages Well-established technologyDue to uncontrolled degradation during extraction and low concentration of Hyaluronan in the waste, the process has a low yield.

Available raw material at low costsRisk of polymer degradationNatural productRisk of contamination with protein, nucleic acids, and virusesLow yieldExtensive purification neededAs you can see, there are currently more issues than benefits in extracting hyaluronan from animal tissues.Commercial and Economic IssuesMicrobial Fermentation using bacteria strains:Due to hyaluronans high viscosity in the fermentation broth, there is a practical (physical) limit of mass transfer during the reaction process.(heinz 2014).High risk of contamination of culture with bacteria endotoxins, proteins, nuclei acids and heavy metals.Carbon source for this process is glucose which is more expensive than starch and lactose.

Competing TechnologyBy Taylor Osborne, Joshua steel, Ben Fowler, chibuikem nwayoHyaluronanCompetitionTreatment of osteoarthritis of the kneePainkillers e.g ParaceutamolNon-steriod Anti-Inflammatory Drugs (NSAIDS0 e.g ibuprofenTranscutaneous Electrical Nerve Stimulation (TENS)[Arthritis Research UK]

Diagnose cancer, check and predict response treatment CA15-3/CA27.29 (used to assess of breast cancer treatment is working)Carcinoembryonic antigen (CEA) (used to check for recurrence and assess respose treatment)Prostate-specific antigen (PSA) (help diagnose, assess response and check for recurrence) [National Cancer Institute, 2011]

CompetitionPost-operation induced tissue healing, notably after cataract surgeryLaser treatmentStem cells[Berthiaume, 2009]

Treatment of atopic dermatitis (eczema)Phototherapy Barrier repair moisturiserCoal tarVitamin B6[EczemaNet, 2007]

25Future of product

HyaluronanFuture perspectivesIntra-articular hyaluronic acid visco-supplementation is becoming popular as non-operative treatment for patients with osteoarthritis. It enhances the lubricating ability of synovial fluid after injury. Helping to prevent osteoarthritis. It contributes to the viscosity of synovial fluid and so can act as a cushion. Intra-articular injections of hyaluronic acid are currently approved for the treatment of knee osteoarthritis but presents potential for other joints.

http://www.trixsyn.com/images/1254_canine_02.jpghttp://huntsvillesportsdoc.squarespace.com/storage/Viscosupplementation2.jpg?__SQUARESPACE_CACHEVERSION=1340809123371Future perspectivesExtensive experimental evidence in cell and animal tumor models have shown that Hyalurana acts a drug carrier.

Hyluranan attaches to the drug which allows the drug to directly attach onto the tumours cells. This is because Hyluranan can selectively attach onto tumours cells via a marker called CD44. This allows the drugs to be more effective as it will not effect the surrounding healthy cells.

It is an increasingly investigated area for applications to anticancer chemotherapeutics.

http://www.mdpi.com/ijms/ijms-12-01009/article_deploy/html/images/ijms-12-01009f3-1024.pngReferencesAustralian Rheumatology Association . (2011).PATIENT INFORMATION ON HYALURONIC ACID .Available: http://www.rheumatology.org.au/downloads/HyaluronicAcid230811.pdf Arthritis Research UK What treatments are there for osteoarthritis of the knee [online]. Available at: http://www.arthritisresearchuk.org/arthritis-information/conditions/osteoarthritis-of-the-knee/treatments.aspx (Accessed: 13 November 2014)Berthiaume, F (2009) Stem cells for skin tissue engineering and wound healing [online]. Available at: http://www.ncbi.nlm.nih.gov/pubmed/20528733 (Accessed: 13 November 2014)EczemaNet (2007) Medications and other therapies for eczema [online]. Available at: www.skincarephysicians.com/eczemanet/medications.html (Accessed: 20 November 2014) JASON R. LUPTON, MD AND TINA S. ALSTER, MD. (2000).Cutaneous Hypersensitivity Reaction to Injectable Hyaluronic Acid Gel.Available: https://www.skinlaser.com/wp-content/uploads/2011/06/Cutaneous-Hypersensitivity-Reaction-to-Injectable-Hyaluronic-Acid-Gel.pdf.Zhang W, Moskovitz R, Nuki G et al. OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis & Cartilage 2008; Available: https://www.myjointpain.org.au/media/injections1.pdf WebMd.HYALURONIC ACID.Available: http://www.webmd.com/vitamins-supplements/ingredientmono-1062-hyaluronic%20acid.aspx?activeingredientid=1062&activeingredientname=hyaluronic%20acid

ReferencesChiara Schiraldi, Annalisa La Gatta and Mario De Rosa (2010). Biotechnological Production and Application of Hyaluronan, Biopolymers, Magdy Elnashar (Ed.), ISBN: 978-953-307-109-1, InTech, Available from: http://www.intechopen.com/books/biopolymers/biotechnological-production-characterization-and-application- of-hyaluronan Carmen G. Boeriu, Jan Springer, Floor K. Kooy, Lambertus A. M. van den Broek, Gerrit Eggink. (2013). International Journal of Carbohydrate Chemistry Volume 2013. Available: http://www.hindawi.com/journals/ijcc/2013/624967/. Last accessed 20th Nov 2014.Gary. H. G., Hales C.A., (2004) Chemistry and biology of hyaluronan. [online] Google scholar. Page 1 available from: books.google.co.uk [accessed 14 October 2014]Heinz. T.J., (2013) International Journal of Carbohydrate Chemistry. Production Methods for Hyaluronan [online] Volume 2013 pages 3-6. Available from www.hindawl.com/journals/iju/2013/624967/ [accessed 19 October 2014Wikipedia (2014) Glycosaminoglycan [online] Available from: http://en.wikipedia.org/wiki/glycosaminoglycan [accessed 19 October 2014]Wikipedia (2014) Hyaluronan [online] available from: http://en.wikipedia.org/wiki/hyaluronan [accessed 19 October 2014] (Wikipedia used for background knowledge)

ReferencesSpyros S. Skandalis*, Chrisostomi Gialeli*, , Achilleas D. Theocharis*, Nikos K. Karamanos. (29 July 2014).Advances in Cancer Research.Available: http://www.sciencedirect.com/science/article/pii/B9780128000922000113. Last accessed 10th Nov 2014.http://onlinelibrary.wiley.com/doi/10.1111/j.1524-4725.1998.tb00007.x/full#leftBorder, Date article first published online: 8 May 2014, Dermatologic Surgery, Volume 24, Issue 12, Pages 1317-1325, December 1998, Authors: Fabrizio Duranti, Giovanni Salti, Bruno Bovani, Mario Calandra and Maria Laura RosatiBaradwaj AG, et al. Spontaneous metastasis of prostate cancer is promoted by excess hyaluornan synthesis and processing. Am J Path. 2009;174:10271036Drug Safety, August 2000,Volume 23,Issue 2,pp 115-130, Date: 21 Nov 2012, Dr Mark E. Adams,Andre J. Lussier,Jacques G. PeyronMicrobial hyaluronic acid production, Barrie Fong Chong . Lars M. Blank . Richard Mclaughlin . Lars K. Nielsen Received: 14 April 2004 / Revised: 13 September 2004 / Accepted: 17 September 2004 / Published online: 13 November 2004 # Springer-Verlag 2004