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

Calcipotriol, a vitamin D analogue utilized for psoriasis, has irritation as its most frequent reported adverse event. However, studies on its irritant properties in humans have produced conflicting data. This study evaluates the effect of calcipotriol on stratum corneum barrier function, hydration and cell turnover in healthy volunteers, compared with sodium lauryl sulphate (SLS) as a model irritant. Calcipotriol 0.005% ointment and 1% aqueous SLS solution were applied for 60 min once daily for 2 weeks (5 consecutive days weekly) on untreated and on dansyl-chloride-labelled skin. Irritant responses were documented by visual scoring and by measurement of the transepidermal water loss (TEWL) and stratum corneum hydration (electrical capacitance), until day 18. Stratum corneum turnover time (SCTT) was the time in days between staining (day 0) and the disappearance of dansyl fluorescence. SLS caused more erythema, scaling, and a significant TEWL increase for 18 days. In contrast, calcipotriol induced erythema, and slightly but significantly increased TEWL on day 11 only, as compared with the vehicle control (P < 0.05). SLS, but not calcipotriol, caused skin dryness from day 4 to day 18. The shortest SCTT was obtained at SLS-exposed sites (11.2 +/- 0.7 days: mean +/- SD). Calcipotriol significantly shortened SCTT (16.3 +/- 1.1 days) when compared with its vehicle. Compared with the skin irritation induced by SLS, under these test conditions, calcipotriol is a far weaker irritant on normal human skin. In addition, calcipotriol accelerates stratum corneum turnover to a significantly greater extent than its vehicle.
 ...
PMID:Effects of calcipotriol on stratum corneum barrier function, hydration and cell renewal in humans. 891 43

This study, conducted in 36 human volunteers, was an evaluation of the effects of saline iontophoresis on skin temperature, irritation, and barrier function. The major objectives were to assess the effects of low-level ionic currents, to validate the proposed methodology of assessment, and to establish reproducibility in repeated saline iontophoresis applications. This was the first of a multistage study designed to assess the safety of 24-hr saline iontophoresis episodes at selected currents and current densities. Since an iontophoresis patch challenges the skin barrier both by occluding the skin surface and by passing ionic current through the skin, the experimental protocol was designed to permit measurement of the contribution of each of these processes to the overall response. In this first stage we investigated the effect of 10 min of current delivery, at 0.1 mA/cm2 on a 1-cm2 area patch and 0.2 mA/cm2 on a 6.5-cm2 area patch compared to unpowered control patches. Twelve subjects were tested under each condition on two separate occasions to examine reproducibility of the response variable measurements. A further 12 subjects were tested once under the 0.2 mA/cm2, 6.5-cm2 condition. Skin irritation was evaluated via repeated measurements of transepidermal water loss, capacitance, skin temperature, skin color, and a visual scoring system, before the iontophoresis episode and after patch removal. No damage to skin barrier function in terms of skin-water loss or skin-water content was detected. Slight, subclinical, short-lasting erythema was observed for both conditions. Assessment of correlation coefficients showed highly statistically significant indications of reproducibility for all five response variables measured. The experimental design, in combination with a repeated measures analysis, provided clear separation of the occlusion and ionic current components of the iontophoretic patch challenge. Further, the repeated measures analysis gave a highly sensitive assessment of skin irritation and resolution after patch removal. We conclude that the experimental methodology is appropriate for assessing possible changes in skin integrity resulting from saline iontophoresis under similar operating conditions for longer durations and for other skin challenges from which a subclinical response is expected.
 ...
PMID:The effect of saline iontophoresis on skin integrity in human volunteers. I. Methodology and reproducibility. 892 20

Tacalcitol is a vitamin D analogue which ahs been developed for the therapy of psoriasis vulgaris. The treatment with a twice daily application of 2 micrograms/g ointment is efficacious and safe in Japanese patients. The objective of this randomized, placebo-controlled, intraindividual right-left comparison was to investigate the efficacy and safety of 8 weeks' therapy with a once daily application of a 4 micrograms/g tacalcitol ointment in Caucasian psoriatics. The data on 122 male and female patients were analysed. The score sum of erythema, infiltration and desquamation was influenced significantly more by tacalcitol ointment than by placebo (P < 0.0001) at every control point, starting from week 2. With regard to the individual symptoms of desquamation, infiltration and erythema, the treatment with tacalcitol was also superior to placebo treatment beginning at week 2. Qualitatively, the same results were obtained with the preference assessment of both treated body sides and also the global assessments of efficacy and benefit. Symptoms of local skin irritation which may be related to the active compound or the ointment base were reported by 12.3% of patients. In only one patient, irritation required discontinuation of tacalcitol treatment. Laboratory criteria, including serum calcium, serum phosphate and serum levels of calcitonin, parathormone, 1 alpha, 24-dihydroxyvitamin D3 and 25-hydroxyvitamin D3, did not reveal any changes of clinical relevance during or after treatment. Furthermore, the global assessment of tolerance was good or very good in more than 90% of cases. The results of this study demonstrate that the once daily application of a 4 micrograms/g tacalcitol ointment is an efficacious therapy for psoriasis vulgaris in Caucasian patients, and that its tolerance is good, wherever the lesion is located, including on the face.
 ...
PMID:Tacalcitol ointment in the treatment of psoriasis vulgaris: a multicentre, placebo-controlled, double-blind study on efficacy and safety. 897 77

Pregnant Sprague-Dawley rats and New Zealand White rabbits were exposed dermally to 0, 10, 25, and 75 mg/kg/day of monoethanolamine (MEA) for approximately 6 hr/day on Days 6 through 15 (rats) or 6 through 18 (rabbits) of gestation. A fifth dose group of 225 mg MEA/kg/day was evaluated in rats only. Dermal exposure of pregnant rats to 225 mg/kg/day and rabbits to 75 mg/kg/day resulted in significant increases in the incidence of skin irritation/lesions and maternal body weight effects. In general, the dermal irritation observed at the high dose was progressive, beginning with erythema and leading to necrosis, scabs, and scar formation. Doses of 25 mg/kg/day to rabbits produced only minor irritation. Despite maternal effects observed in rats and rabbits, no evidence of developmental or fetal toxicity was observed at any dose level tested. Thus, it was concluded that MEA was not developmentally toxic following dermal application at exposure levels up to and including 225 mg/kg/day for rats and 75 mg/kg/day for rabbits.
 ...
PMID:Evaluation of the developmental toxicity of dermally applied monoethanolamine in rats and rabbits. 899 47

Metalworking fluids (MWF) have been reported as being an important cause of irritant contact dermatitis in metal workers. Our purpose was to determine whether the irritancy of different MWF assessed by 2 different types of predictive human in vivo tests could be compared with epidemiological data. 3 water-based MWF were tested in the same panel of subjects. Reactions were assessed by a visual score (VS), evaporimetry to evaluate the transepidermal water loss (TEWL) and chromametry to quantify erythema. Test 1: MWF were applied with Finn Chambers on the volunteers' mid-back, removed after 1 day of exposure, and reapplied for a further 2 days. Test 2: Cumulative irritant contact dermatitis was induced using a repetitive irritation test for 2 weeks (omitting weekends) for 6 h per day. We observed an increase in VS, TEWL, and erythema for all MWF, with the same irritancy ranking in both test models. Differentiation of the substances was better in the D1/D3 test. The experimental results partially correlated with the epidemiological data. Considering the shorter application time and the better discrimination of irritancy, we prefer the D1/D3 model as a predictive test of MWF irritancy. Our results might aid development of a standardized test to reduce cumulative skin irritation in metal workers.
 ...
PMID:Predictive testing of metalworking fluids: a comparison of 2 cumulative human irritation models and correlation with epidemiological data. 903 82

We evaluated the relationship between the cumulative amounts of 5 kinds of beta-blockers (alprenolol, oxprenolol, timolol, acebutolol and atenolol) permeating through the stratum corneum and a* values obtained by measuring the formation of erythema, a skin irritation reaction, with a chromameter after transdermal application of adhesive patches containing 2 beta-blocker to the skin of guinea pigs. The cumulative amount of beta-blocker released from each adhesive patch to the skin increased with the increase in application time. The contents of alprenolol, oxprenolol and timolol in the stratum corneum and in the stripped skin increased markedly up to 4 h after application and thereafter were maintained at high levels up to 24 h. The contents of acebutolol and atenolol, on the other hand, increased up to 24 h, but these values were low. a* values of all adhesive patches 24 h after application were higher than those before application. The correlation coefficients between the cumulative amounts of alprenolol, oxprenolol, timolol, acebutolol or atenolol permeating through the stratum corneum and (delta a* -delta a*Placebo) values were 0.739, 0.717, 0.722, 0.551 and 0.633, respectively. The correlation coefficient calculated by averaging the cumulative amounts of 6 kinds of beta-blockers permeating through the stratum corneum [including propranolol which was reported previously (Kobayashi I., et al., Biol. Pharm. Bull., 19, 839-844 (1996))] was 0.731, higher than the correlation coefficient between contents of these beta-blockers in the stripped skin and (delta a* -delta a*Placebo) values (r = 0.552). This suggests that there was a high correlation between the cumulative amounts of beta-blockers permeating through the stratum corneum and (delta a* -delta a*Placebo) values.
 ...
PMID:Relationship between amount of beta-blockers permeating through the stratum corneum and skin irritation after application of beta-blocker adhesive patches to guinea pig skin. 914 22

Exposure of the skin to sodium dodecyl sulfate (SDS) leads to disruption of barrier and skin irritation. We used repetitive short exposure to a low molarity SDS solution as an in vivo model to mimic the development of irritant contact dermatitis. In this model, we studied clinical (erythema), functional (transepidermal water loss(TEWL)) and cell biological changes. 24 healthy volunteers were patch tested with SDS (0.2%) for 4 h a day for 5 consecutive days. After removal of the patches, the exposed sites were treated 1 X daily either with a topical corticosteroid (triamcinolon acetonide cream 0.05%), a retinoid (tretinoin cream 0.025%), or a vitamin D3 derivative (calcipotriol ointment 50 micrograms/g). Irritant reactions were assessed by erythema scoring and measurement of barrier function with TEWL up to 14 days after the first challenge. Skin biopsies were taken for cell biological changes at day 4. Vehicle-treated sites served as controls. Repetitive exposure of human skin to SDS resulted in a gradual increase in erythema scoring and TEWL associated with the upregulation of proliferative cells as measured by the expression of Ki-67-antigen and of differentiation markers, visualized by increased expression of involucrin and epidermal-fatty-acid binding protein (E-FABP). Skin irritation as assessed by erythema scoring and TEWL was not significantly suppressed by triamcinolone cream. However, a significant reduction of the number of cycling keratinocytes and a decrease in involucrin positive cell layers was observed in this group. Neither treatment with calcipotriol ointment nor with tretinoin cream induced improvement of skin irritation as judged by visual scoring and TEWL. In contrast to steroid treatment, no significant effect of calcipotriol ointment or tretinoin cream treatment was observed with regard to the number of cycling cells and differentiation markers. Further studies are needed to assess whether treatment with topical corticosteroids is an effective modality in skin irritation and irritant contact dermatitis.
 ...
PMID:Effect of a topical corticosteroid, a retinoid and a vitamin D3 derivative on sodium dodecyl sulphate induced skin irritation. 925 81

In a randomized, double-blind study, patients with chronic plaque-type psoriasis were either treated with 30 ml colloidal silicic acid gel, orally, daily, and topically with the same gel (n = 15), or were treated identically with placebo gel (n = 15) for 3 months. One stable psoriatic lesion on the knee or elbow was treated topically and followed throughout the study. Five patients in the treated group and seven controls had psoriatic arthropathy and 11 treated patients and 12 controls had psoriatic onychopathy. Three treated patients and six controls withdrew because of skin irritation or lack of efficacy. In the treated group there were clear improvements in scaling, induration and erythema after treatment. The nail changes were cured in five of 10 evaluable patients in the treated group and joint pain was reduced by almost half in the four evaluable patients with arthropathy. There were no such improvements in the placebo group.
 ...
PMID:Colloidal silicic acid for the treatment of psoriatic skin lesions, arthropathy and onychopathy. A pilot study. 928 94

The potential of an anti-inflammatory peptide (antiflammin 1) to reduce irritation when delivered transdermally by iontophoresis was examined. A model drug irritant, chlorpromazine, was co-delivered with and without antiflammin 1 by iontophoresis to hairless guinea pigs transdermally. Quantitative skin irritation measurements were obtained by monitoring erythema by skin color reflectance with the Minolta Chromameter. Antiflammin 1 delivered by iontophoresis significantly decreased, but did not eliminate, the erythema associated with co-delivery of an irritating drug compound. Lesion formation was also reduced in the presence of antiflammin 1. In vitro flux across hairless guinea pig skin demonstrated no significant differences in flux of the irritant compound in the presence or absence of antiflammin 1. In vivo generation and efflux of the inflammation mediator Prostaglandin E2 increased during 24-h application of irritant and was unchanged in the presence of antiflammin 1. This result is discussed with respect to recent evidence that antiflammins may act on the lipo-oxygenase pathway. In summary, antiflammin 1, an anti-inflammatory peptide, can be delivered transdermally by iontophoresis with retention of its biological activity in vivo.
 ...
PMID:Antiflammin 1 peptide delivered non-invasively by iontophoresis reduces irritant-induced inflammation in vivo. 929 90

Human volunteer studies of skin irritation have been carried out for decades, both for research and for safety evaluation purposes. For the majority of this time, and consequently for the majority of the studies, assessment of the skin reactions has been made visually. Typical endpoints include erythema, oedema, dryness and scaling, some or all of which would be rated on a simple scale, eg 0, +/-, +, ++, + + +. Such approaches can be criticized as subjective, of poor reproducibility, lacking in sensitivity and highly variable between observers and/or institutions. In consequence, instrumental methods of assessment have been strongly promoted and do indeed offer several advantages, not least their objectivity. However, it is possible to use the human eye, which is a very sensitive tool, to make detailed, accurate and reproducible descriptions of skin irritation reactions. To achieve this, it is necessary to give prolonged and thorough training to each observer. In this paper, 3 examples of human volunteer studies, in which different pairs of trained observers independently carried out double blinded scoring of the irritation reactions, are reported. The grading patterns produced were almost identical; statistical analysis showed that properly trained observers are in fact able to reliably measure a grade of erythema to within +/- 1 on a 10 point scale; 97.6% of scores were within 2 grade points on this scale. These results provide evidence that visual scoring can be sensitive, reliable and reproducible within a testing institution.
 ...
PMID:Visual assessment of human skin irritation: a sensitive and reproducible tool. 941 49


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>