Skin/eye/gut Flashcards
Skin permeability overview
Low permeability to aqueous products, but when the skin is permanently wet (trench foot) it becomes compromised.
Lipophilic compounds can cross skin,
Nano-particles can penetrate the skin too.
UV radiation can cause the skin to be more permeable
Symptoms and measures of skin reactions
Erythema (red), oedema, itching, induration (thickening) blistering, necrosis, and burns.
Inflammatory cascade can also occur.
Redness measured using visual scoring.
Oedema measured with swelling thickness
Cytokine release can be measured.
Transepithelial water loss can indicate compromised skin barrier function
Allergic contact dermatitis causes, mechanisms, and treatments
Urushiol (poison ivy), nickel, chromium, cobalt, gold, latex, detergents, isothizolinones (preservatives), phenylenediamine (hair dye), steroids.
toluene di-isocyanate is a model sensitiser that reacts with amine groups.
Occurs through hapten formation, where a (generally) electrophilic compound reacts with nucleophilic AAs. this can interact with MHC-complexes. A T-cell mediated hypersensitivity type IV reaction occurs.
Calamine and steroids are used as treatment
Phototoxicity mechanisms and examples
UV light is a complete carcinogen, however it is also needed for Vit D synthesis.
UVA has also been seen to induce the anti-inflammatory IL-10 in keratinocytes
Certain chemicals can also be photoactivated into reactive metabolites, such as tetracycline, amiodarone, furanocoumarins (celery), 6-methyl-coumarin (in sunscreen) and NSAIDs.
It is also however sometimes utilised therapeutically, such as PUVA (psoralen and UVA) for psoriasis, vitiligo, and cutaneous t-cell lymphoma. The activation of psoralen causes DNA cross links - causes cell cycle arrest
TCDD toxicity mechanisms
Found as a contaminant in agent orange. Also contaminated Seveso, italy.
TCDD activates aryl hydrocarbon receptor (AhR) that causes excess CYP450 1A1 induction. this causes carcinogenic product formation out of aromatic hydrocarbons.
Toxicity is marked by thymic atrophy, immunosuppression, weight loss, and CVD. An endocrine disruptor.
Nickel immune toxicity mechanism and effects
inhibits immune organ development and surveillance. causes lymphocyte apoptosis and suppresses NK cells. it is a type 1 carcinogen
Arsenic toxicity mechanisms, effects, and sources of contamination
In. drinking water, and historical use as skin lotion.
it replaces phosphate groups in ATP-mediated reactions.
Arsenite metabolites have high -SH affinity, thus depleting glutathione - oxidative stress.
Increases incidence of skin cancer. is a skin irritant too.
Eye irritation overview and example
cornea is the organ with highest nerve innervation. contains TRP channels.
Corneal opacity is a measure of eye irritation.
Capsaicin is a severe eye irritant - TRPV1
GIT toxicity overview and examples
benoxaprofen (and other NSAIDs) can cause GI bleeding. It was withdrawn due to its higher incidence of GIT bleeding.
Lectins (e.g., PHA) found in red kidney beans and other pulses inhibit glucose transport, causing bacterial overgrowth. this results in weightloss, increased intestinal permeability and increased bacterial translocation to the liver.
TGN1412 example
it was a CD28 super agonist antibody.
while it caused no ill effect in animal models, a dose 500 times smaller than the safe dose in animals caused severe side effects in 6 human volunteers, including cytokine storm and inflammatory response that lead to multi-organ failure.
