Histamine Serotonin Proteases Nerve growth factor (NGF) Nitrous oxide (NO) Interleukin Tumour necrosis factor- (TNF- ) Vascular endothelial growth factor (VEGF) Other mediators

The mast cell response is regulated at a local level by endogenous chemicals or autocoids, in particular fatty acid amides, which control the mast cell response via a negative feedback loop6. This process is known as autocoid local injury antagonism (ALIA)6.

Selective and controlled degranulation

Normal tissue reaction

Controlled release of:

Normal Stimulation

Endogenous fatty acid amides

Trigger

Mast cells are immune cells which line the surfaces of the body including the skin, the respiratory, gastro-intestinal and genito-urinary tracts1. They are in a prime position to recognise and counter foreign antigens, pathogens or toxins1, and play an important role in the modulation of an appropriate immune response2.

Mast cells respond to a number of triggers including pathogens (bacterial, fungal, viral), allergens, proteins (cytokines, growth factors and hormones) and other triggers (radioactivity, drugs, trauma)3.

Mast cells are involved in allergic reactions, during which degranulation leads to release of chemical mediators including histamine and cytokines4, resulting in an immune response and inflammation. Mast cells are also able to synthesise and release specific mediators in response to pathogens and other triggers without degranulation4,5. Mast cells play an immunomodulatory role, influencing the immune response as a whole (inflammation, tissue remodelling and wound healing) and specifically the mast cell response1.

During persistent physiological stress, the release of chemical mediators from mast cells can become uncontrolled7. This is due to a lack of endogenous fatty acid amides resulting in an uncontrolled release of non-specific mediators from hyper-reactive mast cells leading to inflammation and potential tissue damage8.

Uncontrolled release of:

HistamineSerotoninProteases NGFNOInterleukinTNF- VEGFOther mediators

De-epithelialisationChanges in connective tissueErythemaOedema/swellingErosionUlcerDesquamative changesItchingBurningDrynessPainDevelopment of chronic diseaseAtrophyOxidative damageLoss of resistance/elasticityHyperalgesia

Excess stimulation

Non-selective and uncontrolled degranulation

Physiological stress (radiotherapy, chemotherapy,

heat, trauma, infection, hormonal changes)

Selective and controlled degranulation

In order to avoid potential tissue damage resulting from persistent physiological stress, it is important to regulate the hyper-reactive mast cell and regain homeostasis1. Adelmidrol is a fatty acid amide analogue which acts via the ALIA mechanism to regulate mast cell response to stimuli9.

Adelmidrol modulates the mast cell reaction by controlling the release of chemical mediators and regaining homeostasis10-13.

Histamine Serotonin Proteases NGF NO Interleukin TNF- VEGFOther mediators

Restoration of a normal tissue reaction

Controlled release of:

Excess stimulation

Adelmidrol

Physiological stress (radiotherapy, chemotherapy,

heat, trauma, infection, hormonal changes)

For inflamed, red, desquamated and/or dehydrated skin in patients undergoingradiation or chemotherapy and in patients with burns, post-septic or post-surgical stress.

For the treatment of itching, burning, redness and dryness of the vulva and vaginain patients undergoing radiation or chemotherapy and in patients with burns, post-septic or post-surgical stress.

For the treatment of itching, burning, redness and dryness of the foreskin and penis inpatients undergoing radiation or chemotherapy, and in patients with burns, post-septic, post-surgical stress or after instrumental manoeuvres.

For the treatment of skin/mucosal changes (itching, burning, redness, swelling andtenderness) in the anal and peri-anal area in patients undergoing radiation or chemotherapy and in patients with burns, post-septic or post-surgical stress.

For the treatment of tender and/or fragile nails in patients undergoing radiation or chemotherapy and in patients with burns, post-septic or post-surgical stress. May also be useful for onychorrhexis (longnitudinal nail ridges), onychoschizia (split nails), xanthonychia (yellowed nails), melanonychia (blackened nails) and onychocryptosis (ingrown nails).

For the treatment of changes in hair growth (fragile hair or hair loss) caused byradiation, chemotherapy or environmental stress.

For the treatment of red, painful, swollen and/or dry oral mucosa in patients undergoing radiation or chemotherapy and in patients with burns, post-septic or post-surgical stress.

For the treatment of the oropharyngeal cavity in patients undergoing radiation or chemotherapy and in patients with burns, post-septic or post-surgical stress.

For the treatment of paronychia (skin infection around the nail) in patients undergoing radiation or chemotherapy and in patients with burns, post-septic or post-surgical stress.

For skin changes, including itching, irritation and redness, in patients undergoing radiation or chemotherapy and in patients with burns, post-septic or post-surgical stress.

To combat osmidrosis (foul smelling sweat) and/or bromhidrosis (excessive sweating) in patients with cancer receiving radiation and/or chemotherapy.

DerLifemilk and cream

EvaLifegel and wash

HomoLifegel and wash

GutLifeointment

OnicoLifedrops

ZerLifeshampoo and lotion

OraLifemouthwash and gel

TraLifespray

OnicoLifegel

RaLifemilk and cream

ClinLifemilk and cream

For skin problems

For muco-genital problems

For nail and hair problems

For oral mucosa problems

Adelmidrol from AgainLife

30 ml 100 ml

30 ml 100 ml

30 ml 100 ml

30 ml 100 ml

30 ml 100 ml

30 ml 100 ml

100 ml 100 ml

30 ml

15 ml

30 ml

5 ml

1. Galli SJ, Grimbaldeston M, Tsai M. Immunomodulatory mast cells: negative, as well as positive, regulators of immunity. Nat Rev Immunol 2008;8(6):478-486.

2. Abraham SN, St John AL. Mast cell-orchestrated immunity to pathogens. Nat Rev Immunol 2010;10(6):440-452.

3. Moon TC, St Laurent CD, Morris KE et al. Advances in mast cell biology: new understanding of heterogeneity and function. Mucosal Immunol 2010;3(2):111-128.

4. Theoharides TC, Kempuraj D, Tagen M et al. Differential release of mast cell mediators and the pathogenesis of inflammation. Immunol Rev 2007;217:65-78.

5. Galli SJ, Tsai M. Mast cells: versatile regulators of inflammation, tissue remodeling, host defense and homeostasis. J Dermatol Sci 2008;49(1):7-19.

6. Aloe L, Leon A, Levi-Montalcini R. A proposed autacoid mechanism controlling mastocyte behaviour. Agents Actions 1993;39 Spec No:C145-7.

7. Harvima IT, Nilsson G, Naukkarinen A. Role of mast cells and sensory nerves in skin inflammation. G Ital Dermatol Venereol 2010;145(2):195-204.

8. Re G, Barbero R, Miolo A et al. Palmitoylethanolamide, endocannabinoids and related cannabimimetic compounds in protection against tissue inflammation and pain: potential use in companion animals. Vet J 2007;173(1):21-30.

9. De Filippis D, D’Amico A, Cinelli MP et al. Adelmidrol, a palmitoylethanolamide analogue, reduces chronic inflammation in a carrageenin-granuloma model in rats. J Cell Mol Med 2009;13(6):1086-1095.

10. Micali G, Pulvirenti N, Musumeci ML et al. Topical adelmidrol 2% emulsion, a novel aliamide, in the treatment of mild atopic dermatitis in pediatric subjects: a pilot study. J Am Acad Dermatol 2006; 54 (3): Suppl AB112.

11. Pulvirenti N, Nasca MR, Micali G. Topical adelmidrol 2% emulsion, a novel aliamide, in the treatment of mild atopic dermatitis in pediatric subjects: a pilot study. Acta Dermatovenerol Croat 2007;15(2):80-83.

12. Bonello D, Squarzoni P. Effect of a mucoadhesive gel and dental scaling on gingivitis in dogs. J Vet Dent 2008;25(1):28-32.

13. Abramo F, Sailuzzi D, Leotta R et al. Mast cell morphometry and densitimetry in experimental skin wounds treated with a gel containing adelmidrol: a placebo controlled study. Wounds 2008;20(6):149-157.

References

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