Epidermal reversibility

Nevirapine is a non-nucleoside reverse transcriptase inhibitor used to treat HIV-infected patients that causes mild to severe skin rash and even Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) in a substantial proportion (16%) of patients. Nevirapine also induces hepatotoxicity. These adverse clinical symptoms may also occur in non-HIV subjects taking the drug as postoperative prophylaxis [15]. 

Dermal exposure of mice to 3.6 mg/kg of mirex, three times/week for 4 weeks, resulted in mild epidermal proliferation (Moser et al. 1992). Application of an unspecified amount of mirex to the skin of rabbits for 6-7 hours/day, 5 days/week for 9 weeks, resulted in slight erythema and scaling after day 5 (Larson et al. 1979a). This effect was reported to be reversible after 2 days without treatment. No signs of dermal irritation were observed in rabbits exposed to varying amounts of a 20% solution of chlordecone in corn oil (Larson et al. 1979b). 

Another TIR/FRAP study on biological cell membranes has examined the reversible but specific binding kinetics of fluorescence-labeled epidermal growth factor to the surface of cells.(125) The background problem here was solved simply by choosing cells with a very large concentration of epidermal... 

Nakamura, Y., Oka, M., Soda, H., et al. (2005) Gefitinib ( Iressa, ZD1839), an epidermal growth factor receptor tyrosine kinase inhibitor, reverses breast cancer resistance protein/ ABCG2-mediated drug resistance. Cancer Res. 65, 1541-1546. 

Fry DW. Inhibition of the epidermal growth factor receptor family of tyrosine kinases as an approach to cancer chemotherapy progression from reversible to irreversible inhibitors. Pharmacol Ther 1999 82 207-218. 

Burris HA, 3rd, Hurwitz HI, Dees EC et al. Phase I safety, pharmacokinetics, and clinical activity study of lapatinib (GW5720I6), a reversible dual inhibitor of epidermal growth factor receptor tyrosine kinases, in heavily pretreated patients with metastatic carcinomas. JCfiri Oncol2005 23 5305-5313. Zaks T, Akkari A, Briley L et al. Role of pharmacogenetic studies in early clinical development Phase I studies with lapatinib. JCfiW Oncol 2006 24 3029. 

Studies on the white clover -Rhizobium trifolii interaction are the most advanced. Trifoliin A, a lectin present in clover-seedling roots, binds hapten reversibly to carbohydrate antigens cross-reactive on the capsular polysaccharide of R. trifolii and clover epidermal-cells.244 A specific hapten that inhibits binding of trifoliin A to both surfaces is 2-deoxy-D-arabino-hexose.245 It has also been shown that levels of trifoliin A on root hairs decline with increasing concentrations of nitrate, in parallel to root-nodule development,246 and that lectin receptors are transient on R. trifolii, in a way coinciding with its capacity to be adsorbed to clover roots.247... 

PORE. I A minute cavity in epidermal tissue as in skin, leaves, or leather, having a capillary channel to the surface that permits transport of water vapor from within outward but not the reverse. 2. A void of interstice between particles of a solid such as sand minerals or powdered metals, that permits passage of liquids or gases through the material in either direction. I11 some structures, such as gaseous diffusion barriers and molecular sieves, the pores ate of molecular dimensions, i.e 4-10 A units. Such microporous structures are useful for filtration and molecular separation purposes in various industrial operations. 3. A cell in a spongy structure made by gas formation (foamed plastic) that absorbs water on immersion but releases it when stressed. 

Nicotinic acid disturbs the normal cornification of the skin, occasionally leading to reversible ichthyosis and acanthosis nigricans (SEDA-19, 206). Two mechanisms are advanced to explain this effect insulin resistance induced by nicotinic acid, with compensatory hyperinsu-linemia (which in turn leads to increased insulin binding to insulin-like growth factor receptors and stimulation of keratinocytes), or a disturbance of epidermal lipid homeostasis. 

Another conceivable therapeutic approach for Alzheimer s disease could be based on the administration of neurotrophic factors. Nerve growth factor (NGF) is a 118 amino acid polypeptide with no blood-brain barrier penetrance. Other substances with neurotrophic activity such as epidermal growth factor, brain-derived neurotrophic factor, gangliosides, and the (11-28 peptide of the b-amyloid protein might also have a therapeutic potential. Intracerebroventricular (ICV) administration of NGF has been shown to partially reverse lesion-induced deficits of cortical AChE and choline acetyltransferase (CHAT) activities to promote survival of septal cholinergic neurons after fimbrial transection in adult rats and to reverse behavioral deterioration in rats with such lesions. 

Because the sulfide may be reoxidized to the inactive prodrug in the kidney, sulindac may inhibit renal COX less than other NSAIDs, though reversible renal failure and nephrotic syndrome have been observed with this drug. Among the more severe reactions, Stevens-Johnson epidermal necrolysis syndrome, thrombocytopenia, agranulocytosis, and nephrotic syndrome have all been observed. Like diclofenac, sulindac may have some propensity to cause elevation of serum aminotransferases it is also sometimes associated with cholestatic liver damage, which disappears or becomes quiescent when the drug is stopped. 

Lee SR, Kwon KS, Kim SR, Rhee SG. 1998. Reversible inactivation of protein-tyrosine phosphatase IB in A431 cells stimulated with epidermal growth factor. J Biol Chem 273 15366-15372. 

Dithranol in combination with urea is widely used in psoriasis to improve the clinical efficacy, to minimize the dithranol concentration, to achieve the desired effect, to shorten the contact, to get a better hydration of the stratum corneum, and to decrease the proliferation rate of the keratinocytes. Gabard and Bieli showed an increased keratolytical effect of salicylic acid by adding 10% urea.54 Hagemann and Proksch55 showed in 10 patients with psoriasis under a 2-week treatment with a 10% urea ointment increased stratum corneum hydration, a small decrease in TEWL, a reduction in epidermal thickness (-29%), and a decreased epidermal proliferation (-51%). The altered expression of involucrin and cytokeratins as marker for epidermal proliferation was partially reversed.55... 

Length of epidermal and cortex radish radicle cells in presence and absence of reverse osmosis fraction (RO) at different dilutions. 

Electron microscopy of radish radicle. Details of roots from seeds treated with 1/14-diluted reverse osmosis fraction, (a) Cortical cells showing protein-body-derived vacuoles (V) with remnants of electron-opaque protein material. Extremely swollen mitochondria (M) look like vacuoles with fine granular contents, (b) Detail of epidermal cell, showing swollen mitochondria (M), lipid droplets (L) and two dictyosomes (D). (c) The area enclosed in the rectangle in (b) is enlarged to show the two-membrane envelope and residual cristae (arrows) in a swollen mitochondrion. 

Yarden, Y, and Schlessinger, J. (1987). Epidermal growth factor induces rapid, reversible aggregation of the purified epidermal growth factor receptor. Biochemistry 26, 1443-1451. 

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