Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0152030 (skin irritation)
 2,146 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Predictive skin irritation test methods, which do not require use of animals, are needed for the pre-market assessment of detergent formulations. The utility of a novel and ethical human acute skin irritation patch test method, originally developed for chemical skin irritation assessment, was evaluated. In this IRB-approved method, subjects were patched under occlusion for increasing periods of time up to 4h in duration. The total incidence of positive skin reactions for test products was compared to a positive control (20% aqueous sodium dodecyl sulfate [SDS]). Acutely irritating formulas were defined as those showing a significantly increased or equal incidence of positive responders compared with that of SDS. The time of exposure required for 50% of subjects to show a positive skin reaction (TR50 value) was calculated for each product and enabled test product comparisons within and between studies. Using this approach, 24 detergent formulations of various types were tested in seven individual studies. The skin irritation profiles were generally consistent within product types, which could be categorized as follows (by decreasing irritancy): mold/mildew removers (average TR50 = 0.37 h) > disinfectants/sanitizers (0.64 h) > fabric softener concentrate (1.09 h) = aluminum wash (1.20 h) > 20% SDS (1.81 h) > liquid laundry detergents (3.48 h) > liquid dish detergents (4.16 h) = liquid fabric softeners (4.56 h) = liquid hand soaps (4.58 h) = shampoos (5.40 h) = hard surface cleaners (6.34 h) > powder automatic dish detergents (>16 h) = powder laundry detergents (>16 h). In addition to formulation effects, some seasonal effects were noted; particularly greater winter-time reactivity to 20% SDS and the hard surface cleaner and liquid laundry formulations. These results demonstrate the utility of this patch test method for the comparative skin irritation assessment of these different product types.
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PMID:Comparative assessment of the acute skin irritation potential of detergent formulations using a novel human 4-h patch test method. 1602 14

The purpose of this study was to determine the permeation of the hydrophilic compound 5-fluorouracil through human epidermal membranes, Ehrlich Ascites Carcinoma (EAC) cells were used as a model cell line to evaluate the cytotoxic concentration and anti-tumor activity of 5-fluorouracil (5-FU) through transdermal drug delivery for tumors. Cytotoxicity was assessed by exposing cell suspension to increased concentration of drug from 20-100 microg/ml and measuring the viable cell count by tryphan blue exclusion method. Results confirmed that 100 microg/ml of 5-FU was cytotoxic. The increase in the life span (ILS) was 87.05% with maximum survival time of 30.5+/-1.87 days. For 5-fluorouracil monolithic matrix transdermal patch, the results were statistically significant (p<0.05) compared to untreated control, anti-tumor activity was very effective compared to intravenous therapy. Patches did not show any sign of erythema, vesiculations or bullaous reaction. Mean cumulative skin irritation and adherence scoring for both animal and humans proved that none of the irritation sensitization reactions score were zero and less than one, while good adherence score was 0, with complete adherence to the skin, without leaving any adhesive residue on skin with scores = 0 in human subjects. Transdermal patches showed 100% flatness, thickness 150+/-0.03 mm, good content uniformity, folding endurance (>500 foldings), smoothness, transparency, flexibility and appearance. Pharmacokinetic studies of 5-FU transdermal patch in rabbits showed half-life 95+/-0.5 min, C(max) (ng/ml) 863.25,AUC(0-infinity) (ng/ml/h)1567+/-36 and T(max) (h) 1.5 with controlled release for 24 h which was very significant (p<0.001) compared to intravenous route. Recent patents has been reported for suitable treatment of tumors and cancer, by topical and transdermal applications. Velcro protection jackets were suitable for this study and protected our applied transdermal patched from being licked, scratched and rubbed off.
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PMID:Transdermal delivery of 5-fluorouracil for induced ehrlich ascites carcinoma tumor in BALB/c mice and pharmacokinetic study. 1822 Oct 66

Basal cell carcinoma (BCC) is a distinctive manifestation in nevoid basal cell carcinoma syndrome (NBCCS) patients. Both inherited and acquired mutations of patched 1 (PTCH1), a tumor-suppressor gene controlling the activity of Smoothened (SMO), are the primary cause of the constitutive activation of the Hedgehog (HH) pathway, leading to the emergence of BCCs in NBCCS. LDE225, a distinct, selective antagonist of SMO, showed potent inhibition of basaloid tumor nest formation and mediated regression of preformed basaloid tumors in organ cultures of skin derived from Ptch1 heterozygous knockout mice. In a double-blind, randomized, vehicle-controlled, intraindividual study, a total of 8 NBCCS patients presenting 27 BCCs were treated twice daily with 0.75% LDE225 cream or vehicle for 4 weeks. Application of 0.75% LDE225 cream was well tolerated and showed no skin irritation. Of 13 LDE225-treated BCCs, 3 showed a complete, 9 a partial, and only 1 no clinical response. Except for one partial response, the vehicle produced no clinical response in any of the 14 treated BCCs. Treatment with 0.75% LDE225 cream in NBCCS patients was very well tolerated and caused BCC regression, thus potentially offering an attractive therapeutic alternative to currently available therapies for this indication.JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article, please go to http://www.nature.com/jid/journalclub.
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PMID:Topical treatment of Basal cell carcinomas in nevoid Basal cell carcinoma syndrome with a smoothened inhibitor. 2175 61