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The epidermis- The defense of the body

The epidermis- The defense of the body. The epidermis- The defense of the body. The epidermis- The defense of the body. Epidermal permeability barrier. After secretion to the SG-SC interface. Content of lamellar bodies enter SC interstice

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The epidermis- The defense of the body

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  1. The epidermis- The defense of the body

  2. The epidermis- The defense of the body

  3. The epidermis- The defense of the body

  4. Epidermal permeabilitybarrier

  5. After secretion to the SG-SC interface • Content of lamellar bodies enter SC interstice • enzymatic processes transform lipids into a mixture of ceramides, free fatty acids and cholesterol • The mixture creates multilamellar membrane sheets between corneocytes

  6. Co-localization: corneocytes & extracellular lipid matrix

  7. Stress & the epidermal barrier • Physiological stress & psychological stress can influence epidermal barrier function • PS affects multiple functions of the barrier

  8. Psychological stress can affect skin permeability in animals • PS in experimental animals- insomnia, crowding and auditory stimulation • Studies in rodents - different forms of PS provoke an abnormality in permeability barrier homeostasis

  9. Psychological stress can affect skin permeability in rodents • Immobilization stress alters barrier recovery after tape stripping • Damage was more obvious in cases of longer stress exposures the degree of stress influence is due to the "dose" of stress

  10. Psychological stress can affect skin permeability in rodents • Diazepam and chlorpromazine (tranquillizers) block the influence of immobilization stress on barrier homeostasis emotional stress was involved in the process

  11. Psychological stress can affect skin permeability in rodents - II • Transfer of mice to a different cage can also delay barrier recovery rates • Pre-treatment with chlorpromazine (sedative) before transfer - restored the kinetics of barrier recovery towards normal The impact of the drug suggest that PS is the basis for this alteration in barrier homeostasis

  12. Psychological stress can affect skin permeability in rodents - II • Plasma corticosterone levels showed a marked increase after the animals were transferred to the new cages • Pre-treatment with the chlorpromazine blocked this increase

  13. Psychological stress can affect skin permeability in rodents - II • When corticosterone was systemically administered - a similar delayed barrier recovery was noticed • Pre-treatment with a glucocorticoid receptor antagonist (RU-486) blocked the delay in barrier recovery produced by stressful stimuli

  14. Psychological stress can affect skin permeability in rodents - II This data proved that endogenous glucocorticosteroids play a major role in the linkage between PS and derangements in barrier homeostasis

  15. Psychological stress can affect skin permeability in humans • PS & physiological stress can inhibit recovery of skin barrier function in healthy humans • The stressors used: a simulation of a job interview & sleep deprivation

  16. Psychological stress can affect skin permeability in humans- II • Medical, dental and pharmacy students without coexistent skin disease • The stressors - their final examinations

  17. Psychological stress can affect skin permeability in humans- II • Decline in permeability barrier recovery kinetics after barrier disruption by tape stripping - in parallel with an increase in perceived PS • The more stressed the student felt, the longer it took permeability barrier function to recover

  18. Psychological stress can affect skin permeability in humans- II • The greatest deterioration in barrier function - in subjects with largest increase in perceived PS • Barrier function returned to normal coincident with a reduction of PS (subsequent vacation)

  19. The mechanism

  20. Glucocorticoids play a major role • In rodents & humans, PS is associated with increased endogenous GCs production • The administration of systemic GCs adversely affects barrier homeostasis, epidermal integrity & epidermal cell proliferation in rodents

  21. Glucocorticoids play a major role Blockade of GCs along with psychological stressors: • blocks the development of barrier abnormality • normalizes permeability barrier function • normalizes resistance to group-A streptoccocci

  22. How do GCs alter EB GC-TREATED MICE PS- AFFECTED SKIN Application of exogenous physiologic lipids normalizes barrier recovery kinetics and SC's integrity • Topical treatment with physiologic lipids, which mimic the SC lipid composition, normalizes permeability barrier homeostasis

  23. How do GCs alter EB

  24. SC intergrity , stress & corneodesmosomes PS can cause a decrease in SC's integrity through a reduction in the size and number of corneodesmosomes (CD) in the lower stratum corneum

  25. Single application of lipids suffices to correct abnormality in permeability barrier homeostasis • Multiple applications of topical lipids correct deficits in SC integrity The abnormalities in both permeability barrier homeostasis and SC integrity induced by PS could be mediated by increased endogenous GC

  26. PS has an impact on the epidermal barrier in several ways. Most epidermal changes induced by PS are mimicked by systemic GC treatment, suggesting that the increase in GC during PS is a major factor in the production of those changes

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