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)

Chemical enhancers and vehicles were tested for their ability to improve the percutaneous absorption of leuprolide, a nonapeptide (luteinizing hormone releasing hormone analogue; MW 1209.4). In vitro permeabilities in nude mouse, snake, and cadaver skin were evaluated in either Franz diffusion cells or a Bronaugh flow-through system using an HPLC assay. Skin irritation caused by the formulations was evaluated in the rabbit. The chemical enhancer systems investigated strongly enhanced skin penetration of leuprolide. Maximum permeability enhancement of leuprolide acetate can be achieved with a nonirritating formulation containing ethanol, menthol, camphor, methyl salicylate, urea, and hydrogel. The in vitro permeability in nude mouse skin was 10 or 100 times higher than that obtained in cadaver skin, depending on the type of enhancer that was used in the formulation. Snake skin was at least 10 times less permeable than cadaver skin in this study. However, the effects of chemical enhancers on skin permeability were highly dependent on the skin model. Further, the in vitro permeability of leuprolide in the base form was 10 times higher than in the acetate form with the enhancers.
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PMID:Percutaneous absorption enhancement of leuprolide. 148

Eighteen potential penetration enhancers, some at concentrations that might be used for that purpose, have been examined to evaluate their irritancy potential on nude mouse skin. A biopsy technique was employed followed by histological examination. Up to 50% glycerol, 10% hydroxyethyl lactamide (HELA), 10% oleyl alcohol, 10% Solketal, 10% glycofurol, 100% tetrahydrofurfuryl alcohol (THFA) and 10% urea induced no discernible change in the histological appearance of the skin whereas 100% dimethyl sulphoxide (DMSO), 100% dimethyl formamide (DMF), 100% N-methyl-2-pyrrolidone, 10% Azone, 10% oleic acid, 10% methyl laurate, 10% benzyl alcohol and 10% glycerol formal caused severe skin irritation.
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PMID:Topical application of penetration enhancers to the skin of nude mice: a histopathological study. 256 19

Dithranol (anthralin) is one of the basic compounds used in the treatment of psoriasis vulgaris. However, in outpatients its use is largely restricted as it may cause discoloration of skin, clothes, and bedding as well as significant skin irritation. The combination of dithranol with urea results in a better benefit/side-effect ratio. Even at relatively low dithranol concentrations (0.1%/0.2%) combined preparations have been found to be effective over several weeks of application. The therapeutic results of such treatment are comparable to those of topical glucocorticosteroid preparations.
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PMID:[Urea in combination with dithranol in treating psoriasis vulgaris]. 268 Oct 78

The effect of urea and urea derivatives on the percutaneous absorption of salicylic acid and sodium salicylate through the skin of rabbit from petrolatum ointment was investigated. It was found that addition of urea or urea derivatives to the ointment base significantly increased the percutaneous absorption of the drugs in proportion to the concentration of the additive. The percutaneous absorption-enhancing activities of these compounds were that urea derivatives with the more and longer alkyl substituents showed the stronger activities. These activities of urea and urea derivatives were ascribed to the binding of these compounds with the lipids and proteins of the stratum corneum of the skin and the swelling of the tissues, which leads to the reduction of the barrier property of the layer. The preliminary skin irritation test showed that urea and urea derivatives were quite non-irritating to the skin. These results suggest that urea derivatives have a strong possibility to be developed as a percutaneous absorption enhancer.
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PMID:Percutaneous absorption-enhancing activity of urea derivatives. 1031 14

Therapy of Darier disease is rarely satisfactory. Oral retinoids can improve the skin lesions. Because of previous positive results with topical retinoids, which were often not practical because of marked skin irritation, two patients were treated with the new, topical acetylene-retinoid tazarotene in a 0.01% gel preparation. In both patients skin cleared within 2 to 4 weeks. After stopping the medication patients did not develop any new skin lesions for 12 months. In a third patient, healing with tazarotene gel 0.025% was faster than with a topical preparation containing 10% urea. Tazarotene is an important addition to the therapeutic possibilities in Darier disease.
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PMID:[Follicular dyskeratosis: successful treatment with local retinoid]. 1078 83

In the present study, matrix type transdermal patches containing glibenclamide were prepared using different ratios of ethyl cellulose (EC)/polyvinylpyrrolidone (PVP) and Eudragit RL-100 (ERL)/Eudragit RS-100 (ERS) by solvent evaporation technique. The possible drug and polymer interaction was studied by infrared spectroscopy, differential scanning calorimetry, and HPTLC analysis. All the prepared formulations were subjected to physicochemical studies (thickness, weight variation, drug content, moisture content and uptake, and flatness), in vitro release and in vitro permeation studies through mouse skin. The results suggested that there was no interaction between drug and polymers. Variations in drug release/permeation profiles among the formulations studied were observed. The microphotographs obtained by scanning electron microscopy showed the formation of pores on the surface of the patches after in vitro skin permeation studies. Based on physicochemical and in vitro skin permeation studies, the formulations with EC:PVP (3:2) and ERL:ERS (4:1) were selected for in vivo experiments. The hypoglycemic activity of the patches in comparison with oral glibenclamide administration was studied for acute (24 h) and long-term (6 weeks) effect in both normal and streptozotocin-induced diabetic mice. Various biochemical parameters (serum levels of high-density lipoprotein-cholesterol, triglycerides, total cholesterol, alanine transaminase, aspertate transaminase, urea, and creatinine and liver protein and glycogen content) and histopathological (liver, pancreas and stomach) studies were carried out in diabetic mice after treating for 6 weeks. The patches were subjected to skin irritation test (by both visual observation and histopathological evaluation), oral glucose tolerance test and pharmacokinetic evaluation in mice. The results revealed that the patches successfully prevented the severe hypoglycemia in the initial hours, which is the major side effect associated with oral route. The patches maintained similar effect during long-term treatment also. The transdermal systems produced better improvement with all the tested biochemical parameters compared to oral administration. They produced improved repair of the tissues after diabetes induced tissue injury and exhibited negligible skin irritation. The pharmacokinetic evaluation showed that the patches could maintain almost steady-state concentration of drug within the pharmacologically effective range for prolonged period of time. The better in vivo performance of the transdermal patches of glibenclamide in comparison with oral administration could be due to day-to-day glycemic control on long-term application.
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PMID:Glibenclamide transdermal patches: physicochemical, pharmacodynamic, and pharmacokinetic evaluations. 1512 15

The anti-cancer activities and toxicities of retinoic acid (RA) and synthetic retinoids are mediated through nuclear RA receptors (RARs) and retinoid X receptors (RXRs) that act as transcription factors. Heteroarotinoids (Hets), which contain a heteroatom in the cyclic ring of an arotinoid structure, exhibit similar anti-cancer activities, but reduced toxicity in vivo, in comparison to parent retinoids and RA. A new class of Flexible Hets (Flex-Hets), which contain 3-atom urea or thiourea linkers, regulate growth and differentiation similar to RA, but do not activate RARs or RXRs. In addition, Flex-Hets induce potent apoptosis in ovarian cancer and in head and neck cancer cell lines through the intrinsic mitochondrial pathway. In this study, 4 cervical cancer cell lines were growth inhibited by micromolar concentrations of Flex-Hets to greater extents than RAR/RXR active retinoids. The most potent Flex-Het (SHetA2) inhibited each cell line of the National Cancer Institute's human tumor cell line panel at micromolar concentrations. Oral administration of Flex-Hets (SHetA2 and SHetA4) inhibited growth of OVCAR-3 ovarian cancer xenografts to similar extents as administration of a RAR/RXR-panagonist (SHet50) and Fenretinide (4-HPR) in vivo. None of these compounds induced evidence of skin, bone or liver toxicity, or increased levels of serum alanine aminotransferase (ALT) in the treated mice. Topical application of Flex-Hets did not induce skin irritation in vivo, whereas a RAR/RXR-panagonist (NHet17) and a RARgamma-selective agonist (SHet65) induced similar irritancy as RA. In conclusion, Flex-Hets exhibit improved therapeutic ratios for multiple cancer types over RAR and/or RXR agonists.
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PMID:Flexible heteroarotinoids (Flex-Hets) exhibit improved therapeutic ratios as anti-cancer agents over retinoic acid receptor agonists. 1613 93

Safety of two new ultraviolet (UV) filters, 2-ethylhexyl-2,4,5-trimethoxycinnamate (E8) and 2-ethylhexyl-2,4,5-trimethoxybenzalmalonate (B8), has been evaluated through the human melanoma cytotoxicity test and seven-day acute oral toxicity studies in rats. At 2.5 mg/mL, both compounds gave similar cell viability to the control. LD50 values for E8 and B8 are more than 5000 and 1000 mg/kg body weight, respectively. No significant difference in body weight and hematological parameters among the 0, 5, 50, 500, and 5000 mg/Kg E8-treated animals could be detected. Pathological examination of rat tissues collected at the end of the study period revealed no significant difference between the control and all E8-administered rats. There was no significant difference in all clinical blood chemistry parameters (aspartate aminotransferase, creatinine, blood urea nitrogen, and cholesterol), except alanine aminotransferase (ALT), between the control and the E8-treated animals. All ALT values were, however, in the normal range of SD rats. E8 showed negative results for the skin irritation study on human volunteers, using patch and photopatch tests. Excitation of respiratory signs of dypsnea in 10, 100, and 1000 mg/Kg B8-treated rats could be observed during 1-24 h. All groups were, however, normal during the second to the seventh day. Hematological parameters of the 0, 10, 100, and 1000 mg/Kg B8-treated animals showed no significant difference. Pathological examination revealed no significant difference between the control and all B8-administered rats. However, significant differences in some clinical blood chemistry parameters and body weights between the control and some B8-treated animals could be detected. All values, however, were in the normal ranges of the SD rats.
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PMID:Cytotoxicity, acute oral toxicity, and skin irritation of 2-ethylhexyl-2,4,5-trimethoxycinnamate and di(2-ethylhexyl)-2,4,5-trimethoxybenzalmalonate. 1833 Jul 89

Plant-based therapeutic preparations are cyclically returning to complement dermatologic therapy, however, data on the toxicity profile of such plants are lacking. In the present study, Plumbago zeylanica, a medicinal plant commonly used in Ethiopia for skin diseases was subjected to a systematic dermatotoxicity study. To this effect, the dermatotoxicity of 80% methanol extract of the root part of Plumbago zeylanica was investigated in animals following standard procedures for irritation, sensitization, acute toxicity and repeated toxicity tests. Extraction of plant material with 80% methanol resulted in 9.45% of crude extract of Plumbago zeylanica. The skin irritation test on rabbits showed Plumbago zeylanica extract to be a moderate irritant, with a primary irritation index of 2.00. Sensitization test on mice by the Mouse Ear Swelling Test method revealed the extract to be non-sensitizer in a dose range of 4-10mg/ml and the percent responder was zero. Acute dermal toxicity test on rats did not produce any overt signs of toxicity, except that there was a weight gain difference between the test and control groups of female rats. This was not, however, supported by other parameters, like the absolute and relative organ weights. Repeated dose toxicity test was associated with increased relative testis weight (P<0.05) as well as higher values for Blood urea nitrogen and K+ (P<0.05) in both sexes with the highest dose (1000 mg/kg) group, although histopathological analyses failed to lend support to these observations. Taken together, the dermatotoxicity test results from this study suggest that Plumbago zeylanica toxic effects might be limited to effects like moderate irritation.
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PMID:Toxicity studies on dermal application of plant extract of Plumbago zeylanica used in Ethiopian traditional medicine. 1833 96

N-Phenyl-p-phenylenediamine (N-PPDA) is known to cause strong skin irritation and a sensitization reaction in exposed persons. In a previous in vitro study with portions of skin, N-PPDA exhibited appreciable binding affinity, which suggests a likely involvement of collagen. The present study was therefore undertaken to assess the potential and kinetics of N-PPDA uptake onto collagen. A linear relationship between t-PPDA concentration and its uptake on collagen fibrils was observed. The higher the exposure or contact time the greater the uptake, until a saturation of available sites was reached. The binding was dependent on temperature, with greatest uptake noted at 35 degrees C, and a sharp decline observed at about 50 degrees C. The importance of the intact helical structure of collagen fibrils in offering optimal binding sites was evident from the diminished binding response of collagen denaturated by heat and urea and from the limited affinity towards gelatin. There appeared to be no involvement of sulphydryl groups in the N-PPDA uptake on collagen. A striking resemblance between the binding kinetics of t-PPDA onto collagen and that observed previously with skin portions in vitro, suggests that the collagen fibril model may have a use as a simple preliminary tool to screen chemicals that show binding potential towards skin, in order to make predictions about their dermal toxicity.
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PMID:N-phenyl-p-phenylenediamine uptake onto reconstituted collagen fibrils. 2070 99


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