Snippets

1. Snippets The following items will be discussed: @ Skin markers @ Rosacea: flaring factors @ Cosmoticals: Peeling @ Phtotherapy @ Biological therapies @ Transdermal drug delivery @ Therapeutic tips

2. S 1OO • S 1OO stains a calcium binding protein that is expressed in melanocytes & melanocytic tumors. However, it is not specific for melanocytes. It also stains glial & Schwann cell tumors, granular cell tumors, eccrine coil neoplasm, Langerhans cells, chondrocytes, smooth & skeletal muscle & their tumors, sarcomas & occasionally breast adenocarcinoma. • Stains for malignant melanoma: • @ S 1OO : sensitive but not specific. • @ HMB 45:highly specific but poorly sensitive • @ Melan –A/ MART -1: specific but poorly sensitive • **************************** • CD 31 • A sensitive marker for vascular tumors such as angiosarcoma • CD 34 • A less sensitive marker for vascular tumors, also positive in dermatofibrosarcoma protuberance, leukemia, lymphoma • CD 45 • Positive in most leukemias & lymphomas.

3. Immunofluorecense • Immunoglobulin deposits in the skin are a valuable source of diagnostic information. Best results are usually obtained from peri-lesional skin . The biopsy tissue has to be frozen & stained with fluorecein isothiocynate labeled antibodies to IgG, IgM, IgA, C3 & fibrin. • Direct immune-fluorescernceis useful in: • @ Immunobullous disorders • @ Lupus @ Vasculitis. • ****************************************** • Amyloid stain • Amyloid is an amorphous material that can deposit in the skin leading to a variety of clinical appearances. Congo red stains amyloid an orange – red color & under polarised light green birefringence is seen, There are a number of other stains used for amyloid including crystal violet, methyl violet, PAS & Sirins red.

4. RosaceaFlaring factors • @ Heat: • Hot bath, saunas, excessively worm environments, overdressing • @ Exertion: @ Alcohol • Exercise, lifting Red wine, liquor, beer • @ Emotions: Anxiety , stress, embarrassment • @ Drugs: vasodilators, anxiety , topical steroid • @ Medical conditions: Chronic cough, menopause • @ Weather: • Sun, hot, cold, strong winds, humidity • @Food: • Spicy & thermally hot foods , foods high in histamine • @ Topical products: • Some cosmetics & hair sprays especially those containing alcohol, witchhazel or fragrances, hydro alcohol or acetone

5. cosmecuetals BotanicalsA. Lighteners/ brighteners • @ Aloesin ,@ Bearberry .@ Black mulberry ,@ Blueberry ,@ Carrot ,@ Citrus fruit ,@ Cranberry .@ Cucumber .@ Echinacea ,@ Ginseng ,@ Gingko ,@ Grape seed ,@ Indian gooseberry ,@ Licorice ,@ Pear ,@ Soy , @ White mulberry ,@ White willow • B. Tighteners • @ Birch ,@ Gingko ,@ Horse chestnut ,@ Peppermint , @ Red sandalwood ,@ Spearmint ,@ Witchhazel • C. Photoprotective • @ Black tea , @ Cocoa ,@ Golden fern , @ Grape seed ,@ Green tea ,.@ Oat , @ Olive ,@ Pomegranate , @ White sandalwood • D. Emollients: • are substances that makes the skin feels smooth & soft, which is important to consumer acceptability • @ Almond ,@ Aloe ,@Avocado ,@ Borage ,@ Coconut , @ Cucumber ,@Grape , @Jojoba ,@Licorice , @Peanut ,@ Pomegranate ,@ Sattflower , @Sesame ,@Slippery elm.

6. MoisturizersCommonly used moisturizingingredients • A. Occlusion: • @ Petrolatum, @ Waxes , @Lanolin ,@ Mineral oil ,@ Ceramides @ Sunflower oil ,@ Soybean oil ,@ Jojoba oil @ Olive oil ,@ Evening primrose oil • B. Humectants :Draws water from the formulation base, atmosphere, & from underlying epidermis to increase skin hydration: • @ Glycerol ,/Glycerin , @ Sorbitol ,@ Propylene glycol , @ Amino acids ,@ Lactate ,@ Urea ,@ Salts. • ************************************************************************************ • Symptoms of hair damage by perm products • @ Hair loss : (Rare) ,@ Hair breakage (may be at hair root, in hair length, near the ends) ,@ Hair modifications ( unwanted kinky curls, Curls without springiness) ,@ Wet hair: feels plastified, spongy, extensible ,@ Dry hair: , dry hair feels rough, brittle, uncombable, “matting” ,dull, ready to break) • @ Skin damage : @ redness, ,@ pustules & @ irritant skin

7. Superficial chemical peelsPeeling agents • @ Alfa hydroxy acid , @ TCA (Trichloroacetic acid) (1O-2O%) ,@ Salicylic acid ,@ Tretinoin ,@ Resorcinol ,@ Solid carbon dioxide ,@ Pyruvic acid (alfa-keto acid) ,@ Jessner’s solution ( resorcinol 14%, lactic acid 14%, & salicylic acid 14% in alcohol) • Photobiologyof topical retinoids: • Owing to their side chain containing multiple double bonds, retinoids strongly absorb UV light. Therefore, it is recommended to avoid UV exposure when using topical retinoids. • Complications associated with superficial peels: • @ Pigmentary changes ,@ Infection ,@ Reactivation of herpes simplex ,@ Contact dermatitis ,@ Prolonged erythema /pruritus ,@ Lines of demarcation ,@ Milia ,@ Enlarged pores

8. Medium depth chemical peels • A. Agents used: • @ 4O- 5O% TCA • @ Combination 35% TCA + Solid CO2 (Brody : Chemical peeling & resurfacing , Mosby(1997) p. 11O • @ Combination 35% TCA + Jessner’s solution (Monheit:J. Dermatol. Surg. Oncol 15,945 , 1989). • @ Combination of 35% TCA + 7O% glycolic acid ( Coleman & Futrell: J. Dermatol. Surg Oncol 2O, 76,1994) • B. Indications: • @ Treatment of actinic keratose\s ,@ Resurfacing moderate to advanced photoaged skin ,@Improving pigmentary dyschromias , @ Improving mild acne scars ,

9. MicrodermasbrasionA. Indications • @ Acne , @Hyperpigmentaion ( Melasma ; Pos inflammatory) , @ Oily skin (enlarged pores) , @ Photodamage ,@ Wrinkles • B. Complications: • @ Milia & acne flare , @ Herpes simplex “breakthrough” infection • @ Bacterial infection , @ Fungal infection ,@ Hyperpigmentation ,@ Hypopigmentation , @ Scarring. • *********************************************************************** • Hydroxy acids • I. Alfa-hydroxy acids : Glycolic acid (sugar cane); Lactic acid (sour milk): Water soluble, Action: exfoliative (Penetrate at high concentration) • II. Beta-hydroxy acid: Salicylic acid . Lipid soluble .Source: Willow bark, wintergreen, sweet birch. Action: It is exfoliative comedolytic, anti-inflammatory

10. Types of phototherapy • Phototherapy is the use of UV radiation to treat skin disorders, four main types of phototherapy are used in dermatology practice as shown in the following table. • UVB phototherapy is most commonly used for psoriasis & purities. Recently, there has been a trend towards using narrow band UVB rather than broad band as it clears psoriasis more efficiently with reduced erythema & reduced carcinogenicity. The commonest short term side effect is a sunburn-like response, long term there is a risk of photo aging & skin cancer • RePUVA is the combination of a systemic retinoid & PUVA, it is more effective than PUVA with psoriasis clearing quicker with lower dose of UVA radiation. • Advantage of PUVA phototherapy over UVB: @ Less frequent treatment @ More effective @ Often works in UVB resistant dermatoses. • :

11. Types of phototherapy (continue) • Advantages of UVB phototherapy over PUVA: • @ No photosensitizing agent is needed • @ Eye protection is more needed after treatment (systemic psoralen) • @ Less side effects • @ Safe in pregnancy & safer in young patients • @Shorter irradiation time.

12. Types of phototherapy

13. Biological agents • The introduction of biological agents has transformed the treatment of severe psoriasis. The use of these agents has been limited by their high cost. • U.K criteria for a patient to be eligible for treatment with biological agents: • @severe psoriasis for over 6 months with a Psoriasis Area& Severity Index (PASI) greater than 1O& Life Quality Index (DLQI) greater than 1O & one of: • @ have developed or at risk of developing drug related toxicity from a systemic therapy for psoriasis • @ Intolerance of or contraindicated for standard systemic therapies • @ Poor clinical response for standard systemic therapies • @ Repeated inpatient admissions due to psoriasis. • @ Severe ,unstable or life threatening psoriasis. • A patient may also meet the criteria for a biological agent due to associated psoriatic arthropathy.

14. Biological agents used in psoriasis

15. Side effects of biological therapies • @Injection site reactions occur with all biologic agents but are most commonly seen with etanercept, they are rarely serious. • @ There is an increased risk of infection& serious infection with with all biological agents, reactivation of latent tuberculosis is well recognised. • @ All biological agents carry small risk of malignancy, especially lymphoma. • @ Anti-TNF biological agents are associated with new onset demyelinasting disorders & excerbation of pre- existing multiple sclerosis. • @ Some patients develop ANA antibodies whilst on biol;ogical therapies, only rarely does this lead to a drug induced lupuswhich tends to resolve on stopping the medication. • @ Patients may develop antibodies to the biological agents but this is only clinically relevant for infliximab where antibodies are associatedf with an increased risk of infusion reactions & reduced efficacy. • @ 2O% of patients on infliximab develop non serious infusion reactions such as headache, flushing & nausea, 1% develop serious reactions as anaphylaxis, hypotension & chest pain

16. Side effects of biological therapies • @ adalinumab can be associated with leucopenia & thrombocytopenia; alefacept with lymphopenia & efalizumab with thrombocytopenia • Absolutecontraindications of biological agents: • @ sensitivity to the drug @ pregnancy @ Active or chronic infection • Relativecontraindications for biological agents: • @ A family or personal history of demyelinating diseases @ history of malignancy @ concomitant immunosuppressive treatment • Congestive heart failure is a contraindication for inflixmab & etancept. Thrombocytopenea is a contraindication for treatment with efalizumamb & lymphopenia is a contraindication for using alefacept. Patients treated with biologic agents should not receive liver vaccine.

18. Liposomes size: 25 nm – 1OO umDendrimers size: 3 – 1O nm • Dendrimers: are highly branched polymer with a controlled 3 dimensional structure & a central core .They can accommodate more than 1Oo terminal group.

19. Control of transdermal drug delivery • Can we control the transdermal drug delivery? • Yes, by use of polymers whether natural or synthetic, is sensibly combined with a drug or other active agent in such a way that active agent is released from the material in presdesigned manner. The release of the active agent may be constant over a long period. It may be cyclic over a long period or it may be activated by the environment or other external events. • The purpose of controlling the drug daily : is to eliminate the potential for both under or overdosing

20. Control of transdermal drug delivery • Examples of polymers used for controllingtransdermaldrug delivery: • @ Poly (3 hydroxy ethyl methacrylate) • @ Poly ( N- vinyl pyrrolidone) @ Poly Methyl methacrylate • @ Poly vinyl alcohol @ Poly acrylic acid • @ Polyacrylamide @ Poly ethyline -co - vinyl acetate • @ Poly ethylene glycol @ Poly methacrylic acid. • @ Polylactides (PLA) @ Polyglyclides (PGA) • @ Polyanhydrides @ Poly orthoesters. • The control release of the active agent of the drug can occur in the form: • @ Diffusion @ Degradiation @ Swelling followed by diffusion. The swelling ability can be triggered by environmental surrounding e.g. PH, temperature & ionic strength.

21. Control of transdermal drug delivery Swelling release Diffusion system A. Bulk eroding B. Surface eroding

22. Natural polymers • Natural polymers: starch, lecithen, chitosan , gelatin in nano. In drug industry , they have been used as binders, diluents, disintegrate & matrixing agents. Nano technology helps make significant advances in their biomedical applications, including drug delivery techniques

23. Lecithen is yellow brownish fatty substance occurring in animal & plant tissues.. Lecithen can be isolated from egg yolk Sun flowers oil, brain tissue, fish. It can act as LiPOSOMES, MICELLS for transdermal drug delivery. It can also as a type of surfactant , emulsifiers, lubricant. It is also taken as medicine in treating Alzheimer disease . It is also used for treating eye , gall bladder , liver diseases & skin eczema

24. Transdermal drug delivery

25. Transdermal drug delivery

26. Temperature sensitive drug delivery for treatment of tumors

27. Part INeedles for mesotherapy 3O g X 4 mm needle for mesotherapy

28. No needle mesotherapy (needle free procedure or electroporation)

29. needle free procedure (electrophoresis) • Electric current is used for introducing the ions of the drug mixture into the tissues through water channels of the skin

30. Needles free procedure for Botox : mesotherapy • Totally non invasive

32. Isophoresis (mesotherapy): Dermal roller needle freeIt creates a pinpoint punctures into the dermis , It sends a special electrical wavesA pulsed or modulated current to achieve molecules so as to allow them to permeate the skin & penetrate into the tissue

34. Medical joke • In the Egyptian pharmaceutical market, There is a great propaganda about using selective serotonin reuptake inhibitors (SSRIs) which were developed initially to treat psychiatric disorders , are being increasingly used as unlicensed treatment of premature ejaculation based on their side effect of delayed ejaculation ( Medascape news, MNT today) .Some tricyclic antidepressants (anfranil) with SSRI like activity are used for their side effect to delay premature ejaculation. • Taking advantage of a side effect common to these medications (Mayo clinic for health information) for treatmentof premature ejaculationis a realmedical joke. Moreover, SSRI can have another side effects: psychiatric problems, skin reactions, changes in body weight, sexual side effect as loss of libido , deleterious effect on semen parameters.

37. Tincture benzoin co. • Tincture of benzoin has two medical uses :as a treatment for damaged skin in the “compound” form & as an inhalant in the non compound form for bronchial asthmas. The compound tincture of benzoin is used in the following conditions: • @ During electrocautery of verruca vulgaris :If there is bleeding during the treatment of wart, one can apply tincture benzoin co. as an emergency bleeding control for contracting blood vessels (styptic action). • @ For treatment of bleeding fissures on palmer or planter surfaces. The fissures occur in cases of palmoplanter hyperkeratosis. They are recurrent and painful fissures • @ Treatment of cracked nipple in a nursing mother. • @ For minor cuts after shaving. • @ For canker sores in oral mucosa

38. This question was from one of my patients. Of course healthy diet is most important item. Vitamins are most important supplement particularly biotin. Put your fingers in a bowel containing water & add 2 tablets of Alka-seltzer & soak your nails in them twice daily, Preparation of Alka- seltzer at home is as follows: - Two gram citric acid - Four grams of sodium bicarbonate. - four tablets of aspirin. How do I grow my fingernails faster?

39. OnychoschiziaBrittle breaking nail • Brittle nail may be due to underlying nutritional problem. However, it is usually due to overexposure of the nail to water e.g. excessive dishwashing without gloves, over use of nail polish removers, exposure to harsh activities with repeated trauma to nail bed or even exposure to cold. • Splitting of nail can be cured by: • @ Reduce exposure to water. • @ Alter your manicure practice. • @ Apply moisturizers to your nail bed • @ The use of vitamins like biotin, as a supplement, is sometimes disappointing. • @ Soaking your nails in a gelatin or massaging gelatin into your nail ( Tyson, T. L.: J. Investigative Derm. 14: 323, 195O can actually strengthen them & stimulate growth & hardness. However, the results are sometimes disappointing.

40. Nail cuticle & hang nail @ Jagged nail cuticle: baking soda helps to soften & smooth jagged cuticles, making them easier to push back . @Yellow or discolored nails: Using whitening tooth paste & brush your finger nails regularly everyday which can help to reduce or even eliminate the yellow tint in your nails. “ Toothpaste : it is not just for teeth any more”

41. The longest finger nailsHuman fingernails grow up to four times faster than toenails

42. The rate of cell division in the hair matrix determines the linear growth rate, & the duration of anagen growth phase determines the maximum hair length that the fiber can achieve. • These 3 sisters had an anagen duration in excess of 7 years. Their hair can reach a length in excess of 2 m without breaking. Protection from chemical insult & weathering or measures to strengthen hair are important to achieve maximum potential length • Sinclair et al. British J. Derm. 166 (suppl 2) 27, 2O12

43. Hair damage • Acquired: • A. Abnormal hair fibers damage: • @ Environmental weathering @ Repeated cosmetic treatment • @ Exposure to ultraviolet radiation @ Strong detergents • @ Chemical used permanent wave treatments & hair bleach • @ Brushing knotted hair, back combing& straightening hair while wet. • B.Abnormal hair follicle: conditions that lead to programmed hair follicle deletion include: • @ Marie – Unna hypotrichosis @ Keratosis pilaris decalvans • @ Acquired cicatricial alopecia • C. Abnormal hair cycles: • @ Androgenic alopecia @ Telogen efflavium • @ Alopecia areata @ Trichotillomania • As a result of acquired hair damage, the following hair shaft disorders can be seen: • 1. Trichorrhexis nodosa 2. Split ends • 3. Bubble hair 4. Knotted hair

44. Hair damage ( Continue) • Congenital • A. Abnormal hair fibers • 1. Associated hair fragility: • @ Monilethrix @ Trichothiodystrophy • @ Netherton syndrome @ Pili torti • @ Menkes syndrome • B. No associated fragility • @ Pili annulati @ Uncombable hair • @ Wooly hair @ Loose anagen hair • @ Marie – Unna hypotrichosis • B. Abnormal hair follicle: (congenital hair follicle agenesis or programed hair follicle deletion) • Examples of agenesis include atrichia congenita, papular atrichia, hereditary hypotrichosis, hereditary hypotrichosis & hypotrichosis simplex • C. Abnormal hair cycles: • @ Triangular alopecia @ Short anagen hair @ Loose anagen hair

45. Moisturizers in Egyptian market December 2O12 • @ Vano cream: panthenol, Dimethicone, chamomile oil, zinc sulfate , cocoa butter, tea tree oil, thyme oil , almond oil, glycerin. • @ Brother care: Propolis, glycerin, vitamin C, urea. • @Zerol cream: silicon fluid, poly dimethyl siloxan copolyl ( dimethicon copolyl), hydrophilic onion extract, emu oil, cocoa butter, bees wax, almond oil , liquid paraffin, propylene glycol. (N.B.: Propylene glycol is carcinogenic). • @Synobar skin cleanser: tea tree extract, salicylic acid, lexol 3OO, thyme extract, glycerin, citric acid. • @Skin tone cream: allantoin, olive oil, vitamin E, glycerin, promulogen D, mineral oil, triethonolamine, methyl parapen (carcinogen). • @Physiogel A. I cream: N-palmitoyletholamine, N – acetylethanolamine, olive oil, glycerin, pentylene glycol, palm glycerides, vegetable oil, hydrogenated lecthin, squalane, betaine, sarcosine, sodium carbomer, carbomer xantham gum, water.

46. Moisturizers in Egyptian market December 2O12 • @Revie 2: dimethicon, panthenol, chamomile extract, triclosan, vitamin A ,E, olive oil, almond oil, glycerin. • @ Divozinecream:Triclosan, zinc pyrithione, honey, zinc oxide, olive oil, aloa vera, almond oil, glycerin, vitamin C, lanoline. • @ Emo softcream: each 1OO gm contains: zinc oxide (1O gm), caprylic,capric triglyceride ( 5 gm), hexyl laurate (2 gm), pantrhenol (O.5 gm), glycerol ( 4 gm), bisabolol ( O.2 gm). • @ Oiliderm cream: arachis oil. • @ Carbamide cream: urea 1O% • @ Heel fort ointment: urea 1O^, salicylic acid 12% • @ Foot smart ointment:urea 8%, lactic acid 2% • @ Neetoderm plus cream: urea 5%, sodium aclerate.

47. Wrinkling of the hands from water immersionSmooth soft hands is aim of the game A patient asked that she wants her hands to be smooth & soft. Wrinkles occur particularly after prolonged immersion of her hands in water. The answer was the use of moisturizers. ( see lectures in this site)

48. Genomics in the cosmetic treatment of skin aging & discolorationBritish J. of Dermatology 166 (supplement 2), 16, 2O12 • The cosmetic aspects of aging skin that can be improved include: matrix production, barrier, lipid synthesis, antioxidant capacity & hyper pigmentation. The cosmetic compounds that can be used to improve aging skin were identified after the use of global gene expression profiling( transcriptomics or genomic ). They are: • @ Niacinamide • @ Pal-KTTKS : It contain matrikine peptide: palmteyl, lysine, threonine, lysine, threonine, lysine, serine. It benefit collagen matrix (collagen I for renewal & healing), fibrnoectin & basement membrane strengthening (collagen II). It reduce facial wrinkles around the eye( crows feet). • @ Pal-KT • @Hexamidine • @ Retinyl propionate • @ Sodium dehydroacetate • @ Olive- derived fatty acid ethoxylates: They restore antioxidant capacity of aged skin to form antiageing ingredients • @ Undecylenoyl phenylalanine: It is a skin lightening agent. It is formed from natural amino acids with a lipid residue. It reduces melanin production by an adrenergic receptor mechanism in melanocytes & inhibiting melanotropin.

49. NiacinamideVitamin B3 • It can be used in treatment of aging & photo ageing , including uneven texture, wrinkles, red blotchiness & hyper pigmentation. • @ Topical preparations are associated with reduced transepidermal water loss indicating improved barrier function. This is due to increase in lipids such as ceramides & barrier layer keratin, involucrin& filaggrin. The improved barrier translates into less irritation& redness, thus contributing to a visible color benefits. .(British J. Derm. 166 (suppl. 2) 1,2O12 )

50. Pal –KT peptide • Prox wrinkles smooth cream contain Pal –KT peptides. • It smoothes uneven texture & the look of fine lines