SKIN NIRVANA SKIN, COAT, SCAR, BURN & WOUND EXTRACT SERUM * Reparative Skin & Coat Serum Extract 1.76 ounces / 50 grams All Life Stages (* as indicated by a holistic veterinarian)

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Nutrition plays a major role in skin health and animal wellness and affects all systems of the animal body. Healthy skin and coat are the result of a well-functioning and synchronized effort by nutrition and tissues and organs in the body. SKIN NIRVANA contains animal and plant botanicals, nautral antibiotics, proteins, co-enzymes and trace minerals including copper, zinc, and iron, that help support and maintain the skin's ability to withstand and repair the effects of allergies and environmental exposure to toxins, antigens, microorganisms, pollutants, both bacterial and viral. CRUELTY FREE. SKIN NIRVANA is an organic, reparative extract serum used holistically as an antibacterial, anti-fungal, antioxidant, antimicrobial, anti-inflammatory, immune-modulator; to destroy surface and pore pathogens, for dermal conditions related to allergies, scratching, itching, hair loss, geriatria (dull coat, lethargy), for Allergic and Acute Moist Dermatitis, to treat hot spots, ringworm, scars, scar tissue and healed burns; for insect bites of all types, for all types of inflammation and most types of infections, for most types of viral and bacterial diseases, containing a natural antiobitic base capable of fighting skin bacteria related to Escherichia Coli, Staphylococcus aureus, Pseudomona Aeruginosa and Propionibacterium acnes. SKIN NIRVANA extract serum is derived from the Heliz Aspersa Müller snail, which has regenerative properties that boost the production of antimicrobials and is used as a natural remedy to regenerate damaged UV skin tissue and cells, to exfoliate dead skin cells and impurities, to promote new collagen and elastin production, to inhibit bacterial growth and to inhibit free radicals. Also used holistically by veterinarians for its cell-communicating ingredients that treat dermal skin conditions including dermatitis and psoriasis, to treat scars, marks, burns, skin irritations, abrasions, bumps, resistant infections and other surface skin irregularities, to treat and reduce seasonal and chronic allergies related to skin rashes contact allergies, inflammation and swelling.

When SKIN NIRVANA extract serum is applied to clean skin, the snail serum fuses with your pet’s skin cells, stimulating the innate healing processes of skin, boosting the skin's ability to heal from the trauma caused by inflammation and damage, dissolving damaged cells and keratin plugs, due to its amino-acids, minerals, vitamins and other natural element content for the remodeling of healthy cells to replace damaged skin, improving the skins’s capability to emit antimicrobials, kill germs and other microbes and pathogens; useful in the topical treatment of skin irritations. 10B

Containing the highest quality of snail secretion, the snail has the capacity to repair its own shell because it manufactures collagen, elastin, glycosaminoglycans and molecules that deeply moisturize and firm skin and give it strength and capacity to withstand over-stretching and damage. Independent studies have verified that the secreted substance also works to reduce first degree burns and even marks left by effects such as chicken pox. 1B

SKIN NIRVANA: MARINE AND PLANT IDENTIFICATION 12B

Family: Helicidae Genus: Helix Species: aspersa Muller Common Names: garden snail, brown garden snail, European brown snail Parts Used: snail extract secretion 13B

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Some ways SKIN NIRVANA may be used to benefit animal wellness: 18B

Allergies can present as a variety of symptoms, the most common symptoms occur as skin irritations: itching, scratching, digging, and gnawing at the skin, often to the point of creating open, raw wounds over large areas of the body. Chronic ear infections are another common symptom of allergies. Occasionally dogs and cats will have respiratory symptoms such as coughing, sneezing, or a nasal or ocular discharge. Food allergies may also produce skin irritations, vomiting and/or diarrhea. Symptoms can extend to include epileptic form seizures, and many holistic vets feel that allergies can ultimately result in chronic diseases such as arthritis, asthma, chronic urinary tract infections, inflammatory bowel disease (IBD), etc. 19B

According to the Whole Dog Journal, it has been estimated that more than 70 percent of all skin conditions in dogs and cats are allergy-related, but every allergic patient presents a unique diagnostic challenge, and merely deciding which diagnostic tests should be run can be the most challenging of all decisions. In most cases, the dogs and cats suffer from an “immune system run amok.” 20B

Our pet’s bodies work hard to push toxins and waste materials out by a natural process called detoxification. In mainstream medicine the mechanisms of detoxification are often viewed as unpleasant symptoms of illness that need to be remedied. However, when taken into a more holistic perspective, such measures only amount to removal of outward signs of an underlying state of imbalance. Detoxification, as unpleasant as this process may appear, is viewed as a natural part of the healing process that should be supported instead of being suppressed. 21B

The primary goal of a holistic herbal aid is to help the body in its natural abilities to heal itself and remain healthy. Rather than ignore the causes of disease in favor of eliminating only symptoms, as many conventional drug or surgical interventions do, a natural product works in concert with the body’s efforts of correcting itself. 2B

The body’s detoxification system, being extremely complex and very efficient, has the job of eliminating anything that may be harmful to the body, by whatever means necessary. Routine detoxification is ordinarily handled by waste removal mechanisms in the digestive tract and liver, the filtering activities of the lymph system, and at immune system levels, where a complex army of antibodies, toxin-scavenging cells, and special chemicals weed out, destroy, and eliminate toxic waste. 23B

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However, if any of these systems become overburdened with too much waste or toxic overloads, or are rendered dysfunctional in any way by disease or injury, the body may resort to other, less effective means of elimination. The body will try to push potentially harmful excesses out, any way it can. If pushed through the skin, we see evidence in the form of eruption of rashes, dandruff, an oily coat, or pustules. If the body attempts to push excess waste through mucous membranes, runny eyes or nose, diarrhea, or mucus discharge at the rectum or urethra will present. If these efforts fail, the potentially harmful waste compounds that the body is trying to eliminate may accumulate to cause any number of disease problems, ranging from urinary tract disease, dry nose, conjunctivitis, arthritis, chronic allergy and inflammation, skin conditions, and even cancer. Recommended products include Life’s An Itch, which works with the body to clarify and detoxify and to balance bodily systems, as well as I Feel Good; The Daily Paws; All Grins & Shins and Easy Flow. Skin Nirvana is recommended to be applied topically. Allergic Dermatitis is among the most common skin diseases seen in private vet practices. In an allergic (or atopic) pet the animal becomes hyper sensitized to environmental proteins called allergens and produce common clinical signs. In basic language, an antibody is formed when your pet is exposed to an environmental protein and the antibody attaches itself to a tissue cell (mast cell). At the next encounter, the antibody explodes, or releases many chemicals contained in the cell or cell membrane, including histamine, substance P, bradykinin and various prostaglandins. The presence of these chemicals is what manifests the clinical signs of allergic dermatitis. This process is relatively common in dogs but rare in cats. Certain breeds of dogs have a higher rate of incidence due to genetic components of the disease including Cairn Terriers, Sharp-peis, West Highland White Terriers, Scottish Terriers, Lhasa Apsos, Shih Tzus, Wirehaired Fox Terriers, Dalmatians, Pugs, Irish Setters, Boston Terriers, Golden Retrievers, Boxers, English Setters, Labrador Retrievers, Miniature Schnauzers and Belgian Tervurens. Despite breed, this condition may occur in all breeds. No specific cat breed has been identified, however, females appear at more risk than male dogs. The typical pet manifests itching conditions however the coat may appear normal. The exception is the English Bulldog who may develop red skin with minimal itching. Many clinical sings of dermatitis include but not limited to itching during the affected season. Eventually many pets will develop symptoms that last year round. Cat’s Claw Extract is used holistically to treat Acute Moist Dermatitis, more commonly known as Hot Spots, by reducing the internal inflammation and bacterial pathogens associated with the condition. A hot spot is a warm, painful, swollen patch of skin that can be red and patchy, can exude pus and give off a foul odor. Hot spots can cause infection, hair loss, seborrhea, eczema and many other coat and skin conditions. Skin Nirvana! can be applied topically for hot spots, which are typically caused by allergies or pathogens, occurring with greater frequency during summer months or in areas with hot or humid weather. Hot spots occur most often in breeds with heavy coats, and tend to appear just before shedding, when moist, dead hair is trapped next to the skin. The moisture cultures bacteria which overwhelms the immune system and attacks the skin. The condition progresses when a dog or cat scratches or itches the area, opening up the skin to infection, which causes the bacteria to spread. Typically circular patches occur and can appear suddenly and enlarge quickly, sometimes within a few hours. Hot spots can occur anywhere on the body and often in more than one site. Fleas, mites and other skin parasites, skin allergies, irritant skin diseases, ear and anal gland infections and neglected grooming are all other factors

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that can initiate the scratch and itch cycle. Eventually many pets will develop symptoms that become chronic (last year round). The recommended holistic regimen for all types of dermatitis includes: Immune support found in I Feel Good; a multivitamin found in The Daily Paws and Omega 3 Fatty acids EPA and DHA found in Gland Candy, Yelp for Kelp, Joint Ease and Easy Flow. Baby Love Bits is also recommended for dogs and cats who are not allergic to yeast. Flaxseed oil is not recommended as primary source unless it contains lignans because many animals cannot convert ALA. Skin Nirvana is recommended for topical application. 34B

On overage, 27% of dogs and 50% of cats responded favorably to fatty acids (EPA, DHA) alone for allergic conditions, including all types of dermatitis. When combined with an immune support and multivitamin, the response rate increased by 30 percent to include approximately 57% of dogs and 80% of cats. 35B

Ringworm is a common fungal infection affecting puppies and kittens. The disease is highly contagious and may be easily transmitted between pets and their owners. Clinical signs include hair loss, usually in a circular or “ring shaped” pattern, however, ringworm can mimic any skin disease. In kittens, tiny scabs called military lesions may occur in infected pets. 36B

Primary treatments include topical shampoos with herbs such as goldenseal and calendula can be added. Recommend immune boosting herbs such as Shake Ur Groove Thing and I Feel Good are recommended for their antibacterial, antifungal, antiviral and anti-parasitic actions. Other herbs include Hepa Protect for its liver and kidney protective and detoxifying properties and Skin Nirvana to be used topically for ringworm. 37B

SKIN NIRVANA: TEST DRIVE WHAT IT CAN DO FOR YOUR PET 38B

Main Actions: to treat scars and healed burns, to reduce skin pathogens and skin conditions including dermatitis and psoriasis, to reduce inflammation, to reduce scratching and itching around infected areas 39B

Primary Holistic Uses: as an antioxidant, for wounds, scars, burns, topical infections, keloids 40B

Properties/Actions Documented by Research: antioxidant (fights free radicals), antibacterial (glycoconjugates), anti-inflammatory, antimicrobial, reduces scars, promotes collagen synthesis, anti-fungal (kills skin fungus) 41B

Other Properties/Actions Documented by Holistic Use: to reduce skin irritation and redness, to aid in wound healing and to smooth old burns and healed scars, 42B

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Common Uses in the United States: scars, healed burns, keloids 4B

Contraindications: None reported. 45B

Drug Interactions: None reported. 46B

Cautions: For external use only. Avoid the contact with the eyes. If product contacts eyes, rinse thoroughly with water. In cases of extreme dryness of the skin, use a humectant moisturizer with Skin Nirvana. 47B

Ingredients: Extract of Heliz Aspersa Snail, Deionized Water, Vitamins A, C, E, fragrance, Allantoin, the proteins Elastin and Collagen, Glycolic Acid, Amino Acid, Collagen, glycosaminoglycans, enzymes, co-enzymes, antibiotic peptides, proteins and other trace minerals. 48B

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Suggested dosage: Massage a small amount of serum in a smooth, circular motion on clean skin and coat; apply directly to clean wounds, burns, scars and any skin or coat irregularity. Use morning and night as needed. For external use only. Do not apply to eyes or administer internally. The bioactive ingredients of this product are encapsulated in liposome’s to absorb rapidly while ensuring a steady and slow release of moisture and saturation to targeted skin cells up to 12 hours after usage. SKIN NIRVANA: ALL SORTS OF INTERESTING FACTS ABOUT HOW THIS PLANT MIGHT BENEFIT PET HEALTH, ITS BIOLOGICAL ACTIVITIES AND STUDIES CONDUCTED A number of applications exist for use of Caracol Serum within the pet health and wellness industry due to the presence of numerous, natural plant chemicals. In recent years, there has been a resurgence of interest for natural products that support canine and feline health and wellness. The use and acceptance of snail serum to treat skin inflammation related to wounds, burns, allergies and other irritations has grown considerably as trends continue to favor natural products free of unnatural chemicals, excipients and petroleum based byproducts. Snail serum contains natural antibiotics that are capable of fighting bacteria present on the skin, especially Escherichia Coli, Staphylococcus aureus, Pseudomona Aeruginosa and Propionibacterium acnes. Snail cream also includes a variety of proteins and trace minerals which help maintain the nutrition of the skin and metabolic capability. It is now understood that glycoconjugates promote the natural defense mechanisms of skin using glycoproteins to eliminate microbes existing inside skin follicles. Natural antioxidants and anti-inflammatory agents restrict oxidative damage after tissue injury. Healing skin needs to occur in a specific sequence. Helix Aspersa Müller glycoconjugates modulate cell proliferation in order to prevent an excessive inflammatory reaction. Snail serum has long been advocated as possessing healing aspects. From burns to allergies, snail serum can help reduce skin redness and return the skin's natural hue to its pre injury appearance. Helix Aspersa Müller Glycoconjugates are collected from live land snails and provide skin the ability to defend and renew itself naturally. The complex compound is absorbed by the skin and triggers new cell growth in place of dead or dying cells. No harm is done to snails during this process. SKIN NIRVANA! IS CRUELTY FREE. A comprehensive listing of the actions of snail secretion has been scientifically documented as to its ability to: 1. Induce the proliferation of fibroblasts and reconstitute the optimal functional capability of premature, senescent fibroblasts. The action dissolves scar tissues and releases amino acids and other components for the reproduction of fibroblasts which gives rise to new connective tissues and cells. 2. Aid in reducing the inflammatory effect caused by denatured proteins found in damaged and aging skin through collagen and elastin enzymatic activity 3. Include a balanced mixture of natural factors that help recover the normal physiology PH balance of the skin. 4. Low molecular weight proteins; Fibroblast growth factor activity 5. High molecular weight proteins; Oxygen carriers (copper-haemocyanin) 6. Enzymes; Collagenase and gelatinase activities 7. Hyaluronic Acid; Deep tissue hydration

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8. Glycoproteins/mucopolysaccharides; For reconstituting the extracellular matrix 6B

9. Trace elements (Cu, Zn, Fe, Ca2+); Cellular renewal 67B

10. Low molecular weight antioxidant compounds; Not only antioxidant but also anti-inflammatory. 68B

For many years, scientists have studied snails and their secretions, breeding them for their nutritional value and the regenerative capabilities the serum yields on human skin. Snails were relegated to the category of simple creatures that allowed for research and modeling of biological functions thought to be more complex in vertebrates. Scientists have now discovered molecules that classify the snail as worthy of significantly more research. Further research has documented that snails injured by birds are able to repair some of their organs, including eyes and mouth, by bubbling onto themselves what seems to be the same secretion they use to crawl more easily, hold onto something while on a vertical position and defying gravity, or to isolate into their shell by the dry secretion on the opercula as well as to persuade insects to stay away from them. 69B

Companies have been conducting research and development to control how snail serum is collected by submitting the snails to controlled stress tests similar to what they have to respond to when a predator threatens them, or when they come into an atmosphere full of oxygen radicals after hibernating. This type of Research and Development been intent on discovering how to capture the bio-availability of the serum to maximize it ability to target and repair skin damage. 70B

Skin care patents have been granted for the reparative capabilities of snail serum. One was granted for a procedure to gather the secretions by agitating snails in warm water and then filtering the mucin, for the use of the extract in a skin care cream made with petrochemical and other chemical excipients. 71B

The second patent was granted to for a procedure where snails are stressed mechanically to induce the production of their mucin and the use of it for the therapeutic and cosmetic treatment of skin in radio-dermatitis. 72B

A patent was also granted for the use of a complex glyco-molecule, isolated from the body and also present in the mucins of an African snail, as a drug to inhibit angiogenesis. The same patent requested the use be extended for the treatment of cancer and to inhibit an increase in the volume or mass of a tumor cancer tumor growth (2005). 73B

The US patent granted in 2000 was related to acharan sulfate, a glycosaminoglycan isolated from the soft body tissue of a giant snail by proteolysis of defatted tissue and purified by fractional precipitation and ion-exchange chromatography. In this venue, the snails die as a result of retrieving the glycosaminoglycan. Previous patents did not conduct mucus secretion in a way that resulted in mortality. 74B

One of the most reknown applications involving the benefits of snail serum was related to field workers in a Chilean vineyard who handled land snails and their serum on a daily basis that observed an improvement in both in the smoothness and defects of their skin. With this discovery, the potential healing abilities of the serum renewed interest in its application in both human, canine and feline skin care. 75B

Helix Aspersa Müller is a snail that has survived extreme environmental conditions for more than 600 million years. This land gastropod or mollusk has an original defensive mechanism in the form of a complex glycolconjugate secretion which helps the animal rapidly repair any damage to its skin. When snails face hardship, they naturally produce a serum that is packed with antioxidants, anti-inflammatories, immune modulators, proteins, co-enzymes, and cell-communicating ingredients, which are principle ingredient in snail cream. 76B

More than 2000 years ago, Hippocrates studied the therapeutic properties contained in land snail mucus. Hippocrates discovered and documented the healing properties snail serum delivered when applied to the skin, 7B

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which softened and hydrated the skin layers better than any substance of the era. He discovered that snail secretion would heal many skin afflictions, including wounds, resistant infections and would quickly heal the skin without scarring. Further, snail residue was also associated with the ability to diminish and soften wrinkles, scars, keloids, burns, age and sun spots, stretch marks, acne and warts. Hippocrates soon discovered that the natural, fluid secretion produced by the brown garden snail (species Helix Aspersa Müller) protected, moisturized, renewed and regenerated skin damaged by sun exposure as well as burns and overstretching. Snails do not experience skin infections or inflammations. A snail is able to slide across the sharpest knife or a piece of broken glass and does not cut its skin. Snails do not experience an imbalance in their collagen or elastin components because of their ability to biologically produce the only solution in the world solely made for the objective of renewing skin and keeping it healthy. Snail secretion is gathered in a way that does not harm any animals and is cruelty-free. As a snail emits its secretion, it is collected in its pure, unadulterated state and is undiluted in water to avoid the degradation of its enzymes and other molecules by hydrolysis. Hydrolysis is a chemical reaction in which water reacts with a compound to produce other compounds. In this process, snail secretion is not degraded, either by interaction with chemicals or by immediate hydrolysis. Further, the biological ingredient found in the embedded liposomes of snail secretion are not altered and they function as a microscopic, fluid-filled pouch whose walls are made of layers of phospholipids identical to the phospholipids that make up cell membranes. The liposomes then attach themselves to the cellular membrane and appear to fuse with it, releasing their contents into the cell, not losing or reducing secretion strength and allowing the skin to absorb the secretion immediately. SKIN NIRVANA: COOL, NATURAL PLANT CHEMICALS Extract of Caracol serum contain allantoin, the proteins elastin and collagen, glycolic acid and amino acids, glycosaminoglycans, enzymes, co-enzymes, antibiotic peptides and Vitamins A, C and E, proteins and other trace minerals that contribute to skin health. Allantoin is responsible for regeneration of the skin and is effective at repairing scar tissue. It is also is an antioxidant (fights free radicals). Free radicals scavenge healthy skin and speed up the aging process. Glycolic Acid (1.6%) enhances natural exfoliation, aids rehydration, inhibits free radicals and also promotes the body's own production of collagen. Antibiotic Peptides protect the skin from environmental stress and are effective against different types of bacteria commonly found in animal skin infections. Peptides destroy the pathogens present on the surface and in the pores of skin and act as a protective barrier. Vitamins A, C and E. Vitamin A helps maintain the condition of cell membranes. Vitamin C stimulates collagen synthesis, helps to prevent the destruction of collagen and is an antioxidant. Vitamin E acts as an antioxidant which protects against damage to vital cell structure and helps prevent moisture loss. SKIN NIRVANA: FASCINATING RESEARCH 1. The Natural Health Bible for Dogs and Cats, Shawn Messonier, DVM

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2. The Nature of Animal Healing, Goldstein, Marty D.V.M. 91B

3. Veterinarians Guide to Natural Remedies for Cats, Martin Zucker 1999 92B

4. The Complete Handbook for the Dog and Cat, Juliette de Bairacli Levy 93B

5. The Herbal Encyclopedia 94B

6. Whole Dog Journal 95B

7. Dr. Gary, Clinician’s Handbook of Natural Healing 96B

8. Dr. James Duke, The Green Pharmacy 97B

9. Ehow 98B

10. Natural News 9B

11. Natural Ark 10B

Helix Aspersa Müller Glycoconjugates Restores the Natural Skin Repair Mechanism 10B

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1. Induces the proliferation of FIBROBLASTS and reconstitutes the optimal functional capability of prematurely senescent fibroblasts. Fibroblast growth factor-like activity: • (J.P Pivel et al.Dermatología & Cosmética, 1998) • Induces fibroblast proliferation • Provides Hyaluronic Acid • Provides new collagen and elastic fibers Provides fibronectin and other components of the extracellular matrix. The extracellular matrix (ECM) in the dermis is composed primarily of Type-I collagen, associated with a lower amount of Type-III collagen, elastin and associated micro fibrils, proteoglycans and fibronectin. Fibronectin (fi·bro·nec·tin) (fi”bro-nek´tin) [fibro- + nexus] any of several related adhesive glycoproteins, cell-surface proteins, that mediate cellular adhesive interactions. Fibronectins are important in connective tissue, where they cross-link to collagen, and are also involved in aggregation of platelets. 103B

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2. Favors the correct assembly of the fibronectin into appropriate patterns in the extracellular matrix (J.P Alonso-Lebrero et al. Poster # 0235 at IID/Sid Miami 2003) Pattern formation is the activity by which embryonic cells form ordered spatial arrangements of differentiated tissues. The physical complexity of higher organisms arises during embryogenesis through the interplay of cell-intrinsic lineage and cell-extrinsic signaling. Inductive interactions are essential to embryonic patterning in vertebrate development from the earliest establishment of the body plan, to the patterning of the organ systems, to the generation of diverse cell types during tissue differentiation. The effects of developmental cell interactions are varied. Typically, responding cells are diverted from one route of cell differentiation to another by inducing cells that differ from both the uninduced and induced states of the responding cells (inductions). Sometimes cells induce their neighbors to differentiate like themselves (homeogenetic induction); in other cases a cell inhibits its neighbors from differentiating like itself. Cell interactions in early development may be sequential, such that an initial induction between two cell types leads to a progressive amplification of diversity. Moreover, inductive interactions occur not only in embryos, but in adult cells as well, and can act to induce differentiation and establish and 1B

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maintain healthy morphogenetic patterns and avoid abnormal patterns, as those in rosacea or keloid scarring and in photo-aging characterized by rarefaction and disorganization of both collagen fibers framework and deposits of elastotic material. 3. Facilitates the reconstruction of the skin's architecture through its triple action on COLLAGEN FIBERS By Collagenese enzymatic activity on denatured collagen J.P Pivel et al.Dermatología & Cosmética, 1998) By providing copper-haemocyanin to supply the oxygen necessary for proper collagen formation (G.Gimenez, Hosp Princesa, 2002) - By providing a structural support network of fibronectin (J.P Alonso-Lebrero et al. Poster # 0235 Miami 2002) 4. Restores the ELASTIC FIBER network by - Collagenase and gelatinase enzymatic activity on elastotic material in skin (J.P Pivel et al.Dermatología & Cosmética, 1998) Promoting the synthesis of new fibers through its action on fibroblasts (A.Brieva et al Dermatología & Cosmética, 1998) - Providing structural support network of fibronectin (J.P Alonso-Lebrero et al. Poster # 0235 Miami 2002) 5. Increases the natural ability of the dermis to take up and hold water, thus influencing its VOLUME, STRENGTH and ELASTICITY - Provides hyaluronic acid and improves the formation of fibrous tissues - fibroplasia. ENHANCES THE PROTECTIVE MECHANISM OF THE SKIN: 1. 1.- Has strong ANTIOXIDANT ACTIVITY (inhibition of Reactive Oxygen Species (ROS) generation plus free radical sequestration) The mucin has low molecular weight compounds that act against hydroxyl radicals. (OH-); - superoxide Dismutase (SOD) and conjugated enzymes such as Glutathione-S-transferase (GSH-T) activity against superoxide anions (O-); - acts against UVA, the mucin shows double the cytoplasm protection activity of control antioxidants (A.Brieva et al Dermatología & Cosmética, 2001) 2. Helps to maintain the PHYSIOLOGICAL BALANCE between the synthesis and degradation of all structural elements of the skin by stimulating metalloproteinase activity on denatured material; protecting newly synthesized elements from degradation (via Metalloproteinase inhibitors); Matrix metalloproteinases (MMPs) are members of an enzyme family that require a zinc ion in their active site for catalytic activity. MMPs are Zn(2+)- and Ca(2+)-requiring endopeptidases which split peptides and polypeptides into smaller peptides by targeting peptide bonds near the centre of the molecule. These enzymes are collectively capable of degrading or hydrolyzing most of the extracellular matrix components. Four broad types of MMP have been described including collagenases, gelatinases, stromelysins and membrane-type MMP. These enzymes can be produced by several different types of cells in skin such as fibroblasts, keratinocytes, macrophages, endothelial cells, mast cells, and eosinophils and their activity can be specifically inhibited by TIMPs (tissue inhibitors of metalloproteinases), which bind to active MMPs with 1:1 stoichiometry. In general, MMPs are not constitutively expressed in skin but are induced temporarily in response to exogenous signals such as various cytokines, growth factors, cell matrix interactions and altered cell-cell contacts. These proteinases play a central role in many biological processes such as normal tissue remodeling, embryogenesis, wound healing and angiogenesis. Currently about 26 MMP genes have been identified, and most are multidomain zinc endopeptidases. In healthy tissue a strict regulation of MMPs is critical in order to maintain proper ECM homeostasis. Among other levels of regulation, MMPs are precisely regulated by their main endogenous protein inhibitors (TIMPs). Disruption of this balance results in serious diseases such as fibrosis, arthritis, and tumour growth. Several studies have documented the importance of MMP-mediated ECM destruction

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for tumour initiation, growth, migration, angiogenesis, invasion and metastasis. Certain MMPs such as gelatinases (MMP-2, MMP-9) have special mechanisms to localize at leading edges in tumour tissue. MMPs can no longer be thought of solely as ECM destructionists, but as part of an elegant communication system through which epithelial and tumor cells interact with the stroma. Tissue inhibitors of metalloproteinases (TIMPs) are natural inhibitors of matrix metalloproteinases (MMPs) found in most tissues and body fluids. By inhibiting MMPs activities, they participate in tissue remodeling of the extracellular matrix (ECM). The balance between MMPs and TIMPs activities is involved in both normal and pathological events such as wound healing, tissue remodeling, angiogenesis, invasion, tumorigenesis and metastasis. The intracellular signalling controlling both TIMPs and MMPs expression begins to be elucidated and gaining insights into the molecular mechanisms regulated by TIMPs and MMPs could represent a new approach in the development of potential therapeutics. 128B

3. Through its collagenase and gelatinase enzymatic activity, the mucin helps to REDUCE THE INFLAMMATORY EFFECT caused by denatured proteins in injured and aging skin 129B

4. The glycoconjugates INCLUDE A BALANCED MIXTURE OF NATURAL FACTORS THAT HELP RECOVER THE NORMAL PHYSIOLOGY OF THE SKIN • Low molecular weight proteins Fibroblast growth factor activity • High molecular weight proteins Oxygen carriers (copper-haemocyanin) • Enzymes Collagenase and gelatinase activities • Hyaluronic Acid Deep tissue hydration • Glycoproteins/mucopolysaccharides For reconstituting the extracellular matrix • Trace elements (Cu, Zn, Fe, Ca2+) Cellular renewal • Low molecular weight antioxidant compounds 130B

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References Research goes back some 16 years. Its unique mechanisms of action have been well documented and its efficacy and safety tested in a great number of individuals, both as a preventive and therapeutic agent. 1. Evaluation of Anti-Wrinkle and Reaffirming Efficacy of a Cryptomphalus Aspersa Secretion based Product in the treatment of Skin Photo-Aging. M.J. Tribó, E. Serra-Baldrich, M.Asin, J.A Camarasa. Dermatología & Cosmética, March (vol IX), 1999. A clinical study performed at the Hospital del Mar (Barcelona) and the Centro Clínico Dermatológico (Alicante), demostrating the efficacy of the mucin in the treatment of degenerative process associated with photo-aging. A total of 32 patients with symptoms of facial photo-aging were evaluated. 138B

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2. The Effect of Cryptomphalus Aspersa Secretion on the Assembly of the Fibronectin Extracellular Matrix. J.L Alonso-Lebrero, J.P Pivel et al Poster presented at the International Investigative Dermatology Congress, Miami 2003 In vitro assay showing the favourable effects of the snail mucin on the assembly of fibronectin, and promotion of the organisation of senescent fibroblast cytoskeletons. Submited for publication. 142B

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3. Identification of the Major Proteic Component of Cryptomphalus Aspersa Secretion. G.Gimenez et al. Hospital de la Princesa (Madrid), 2003. Not yet published. A copper-haemocyanin subunit was identified as the majority protein of the high molecular weight fraction. The haemocyanin in the mucin facilitates the synthesis of collagen by helping to provide the oxygen required. 14B

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4. Biochemical and Pharmacological Mechanism Related to the Activity of Cryptomphalus Aspersa Secretion in Radiodermatitis. A. Brieva, A. Guerrero, J.P Pivel. Dermatología & Cosmética, 2001. 146B

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Investigations on the mucin’s antioxidant activity: superoxide Dismutase (SOD), conjugated enzymes such as Glutathione-S-transferase (GSH-T), and low molecular weight antioxidants. 5. A Natural Adaptogen for the Skin. A: Brievas, A.Guerrero, J.P Pivel. Dermatología & Cosmética,1998. Detailed description of two of the main biological properties of the mucin: its capacity to stimulate the proliferation of human and murine fibroblasts, particularly those with very low baseline proliferative activity, and the stimulation of collagenese activity. 6. Influence of the addition of Citrate as a Stabilizing Agent of Cryptomphalus Aspersa Secretion Biological Activity. A. Brieva, J.P Pivel, 1999 (unpublished). Study outlining the fibroblast growth factor-like behavior of the mucin. 7. The Discovery and Evaluation of an Active agent for the Topical Prevention and treatment of Ionising Radiation-Induced Burns. Dr. R. Abad Iglesias. (Unpublished) 8. Preliminary research undertaken by Dr. Abad (oncologist and one of the pioneers in the use of the mucin for skin conditions), including preclinical tests suggesting the potential beneficial use of the mucin in radiation-induced skin damage in humans. 9. IUCN (2008). 2008 IUCN Red List of Threatened Species. . Downloaded on 23 February 2009. 10. Müller O. F. (1774). Vermivm terrestrium et fluviatilium, seu animalium infusoriorum, helminthicorum, et testaceorum, non marinorum, succincta historia. Volumen alterum. pp. I-XXVI [= 1-36], 1-214, [110]. Havniae & Lipsiae. (Heineck & Faber). 11. The species was called Cryptomphalus aspersus on p. 244 in the important and widely distributed work Falkner, G. 1990. Binnenmollusken. - pp. 112-280, in: Fechter, R, & Falkner, G.: Weichtiere. Europäische Meeres- und Binnenmollusken. Steinbachs Naturführer 10. -- pp. 1-288. München. (Mosaik). 12. "The Cornu problem". The Living World of Mollusks. http://www.weichtiere.at/english/gastropoda/terrestrial/escargot/cornu.html. Retrieved 2007-03-05. 13. AnimalBase: Genus taxon summary for Cornu (accessed 09 Feb 2011) 14. Falkner, G., Bank, R. A. & Proschwitz, T. von 2001. Check-list of the non-marine molluscan speciesgroup taxa of the states of northern, Atlantic and central Europe. - Heldia 4 (1/2): 1-76. München. 15. Falkner, G., Ripken, T. E. J. & Falkner, M. 2002. Mollusques continentaux de France. Liste de référence annotée et bibliographie. - pp. [1-2], 1-350, [1-3]. Paris. 16. Bank, R., Falkner G. & Proschwitz, T. von 2007. CLECOM-Project. A revised checklist of the nonmarine Mollusca of Britain and Ireland. - Heldia 5 (3): 41-72. München. 17. Manganelli, G., Bodon, M., Favilli, L. & Giusti, F. 1995. Fascicolo 16. Gastropoda Pulmonata. - pp. 160, in: Minelli A., Ruffo, S. & La Posta, S.: Checklist delle specie della fauna italiana. Bologna. (Calderini). 18. Giusti, F., Manganelli, G. & Schembri, P. J. 1995. The non-marine molluscs of the Maltese Islands. - pp. 1-608. Torino.

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19. Neubert, E. 1998. Annotated checklist of the terrestrial and freshwater molluscs of the Arabian Peninsula with descriptions of new species. - Fauna of Arabia 17: 333-461. 164B

20. Manganelli, G., Salomone, N. & Giusti, F. 2005. A molecular approach to the phylogenetic relationships of the western palaearctic Helicoidea (Gastropoda: Stylommatophora). - Biological Journal of the Linnean Society 85: 501-512. 165B

21. Sverlova, N. V. 2006. O rasprostranenii nekotorykh vidov nazemnykh mollyuskov na territorii Ukrainy. - Ruthenica 16 (1/2): 119-139. Moskva. 16B

22. Schileyko, A. A. 2006. Treatise on recent terrestrial pulmonate molluscs, Part 13. Helicidae, Pleurodontidae, Polygyridae, Ammonitellidae, Oreohelicidae, Thysanophoridae. - Ruthenica Supplement 2 (10): 1765-1906. 167B

23. Egorov, R. 2008. Treasure of Russian shells. Supplement 5. Illustrated catalogue of the recent terrestrial molluscs of Russia and adjacent regions. - pp. 1-179, [1]. Moscow. 168B

24. Sysoev, A. & Schileyko, A. 2009. Land snails and slugs of Russia and adjacent countries. - pp. 1-312, Fig. 1-142. Sofia. (Pensoft). 169B

25. Commonwealth of Australia. 2002 (April) Citrus Imports from the Arab Republic of Egypt. A Review Under Existing Import Conditions for Citrus from Israel. Agriculture, Fisheries and Forestry, Australia. Caption: Gastropods, page 12 and Appendix 2. 170B

26. Annie Guiller A. & Madec L. (2010) "Historical biogeography of the land snail Cornu aspersum: a new scenario inferred from haplotype distribution in the Western Mediterranean basin:. BMC Evolutionary Biology 10: 18. doi:10.1186/1471-2148-10-18 17B

27. Pfleger, V. & Chatfield, J. (1983). A guide to snails of Britain and Europe. Hamlyn, London. 172B

28. Arkive: Helix aspersa 173B

29. Juřičková L. & Kapounek F. (18 November 2009) "Helix (Cornu) aspersa (O.F. Müller, 1774) (Gastropoda: Helicidae) in the Czech Republic". Malacologica Bohemoslovaca 8: 53-55. PDF. 174B

30. UF/IFAS Featured Creatures: Helix aspersa 175B

31. Ansart A., Vernon P., Daguzan J. 2002. Elements of cold hardiness in a littoral population of the land snail Helix aspersa (Gastropoda: Pulmonata). Journal of Comparative Physiology B, 172, 619-625. 176B

32. Machin J. 1966. The evaporation of water from Helix aspersa IV. Loss from the mantle of the inactive snail. Journal of Experimental Biology, 45, 269-278. 17B

33. Speed of a Snail 178B

34. Velocity Measurement Units Conversion 179B

35. Attia J. 2004. Behavioural Rhythms of Land Snails in the Field. Biological Rhythm Research, 35: 35-41. Abstract. 180B

36. Fisher TW, Orth RE, Swanson SC. 1980. "Snail against snail." California Agriculture, 34(11): 18-20. Abstract. 18B

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37. Beeby, A., Richmond, L. (1989). The shell as a site of lead deposition in Helix aspersa, Archives of Environmental Contamination and Toxicology 18, 623-628 38. Cowie, R. H. (1984). The life-cycle and productivity of the land snail Theba pisana (Mollusca: Helicidae), The Journal of Animal Ecology 53, 311-325 39. Bezemer T. M. & Knight K. J. 2001. Unpredictable responses of garden snail Helix aspersa populations to climate change. Acta Oecologica, 22, 201-208. 40. Heller J.: Life History Strategies. in Barker G. M. (ed.): The biology of terrestrial molluscs. CABI Publishing, Oxon, UK, 2001, ISBN 0-85199-318-4. 1-146, cited page: 428 LIC Stem Cell Aspersa Muller -Test Results and Scientific Research Support Improving Wrinkles

Clinical results of Uttwiler Spätlauber Apple Stem Cell After used for 4 weeks, wrinkle depth was improved. It maintains the acid-fastness of the skin, and recovers the skin damage. Improving Damaged Skin by Laser treatment and Warts

In vivo Human Skin, experimentally wounded Helix Aspersa Muller Sample Culture : 72 hours, Treatment : One single application A : Damaged skin B : The skin after applying Stem Cell Helix Aspersa Muller β Cream

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Anti-aging Effect by Collagen Synthesis 198B

19B

20B

In-vivo test shows that after 3 month application of the cream, skin tissues are restored to normal level.

www.livestrong.com 201B

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