Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D01398 (Dermatol)
 262,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Topical and oral retinoids have been successfully used in antipsoriatic therapy over the last 50 years. Development of more selective agents has led to an improved efficacy and safety profile. The first topical receptor-selective retinoid to be approved for the treatment of plaque psoriasis is tazarotene. Topical tazarotene displays an onset of action and efficacy similar to those of other established antipsoriatic agents. Common adverse events of this agent such as pruritus, burning, local skin irritation, and erythema are limited to the skin and generally mild or moderate in severity. Although effective as monotherapy, evidence is accumulating that combining topical tazarotene with other established antipsoriatic therapies results in enhanced efficacy and reduced adverse events. In particular, concomitant use of topical tazarotene with a mid-potency or high-potency corticosteroid in the treatment of psoriatic plaques enhances efficacy and reduces the risk of corticosteroid-induced skin atrophy. Combination of phototherapy with tazarotene accelerates the clinical response and diminishes the cumulative UVB or psoralen plus UVA (PUVA) exposure load. Recently, an oral form of tazarotene has been developed. The results of completed phase III clinical trials of this agent indicate a beneficial effect in moderate to severe plaque psoriasis. Adverse events are generally of mild severity, and most of those observed, such as cheilitis and dry skin, are typical of hypervitaminosis A. Of note, oral tazarotene appears not to be associated with other adverse events that are typical of oral retinoids, including hypertriglyceridemia and hypercholesterolemia. However, since head-to-head trials with acitretin (the only retinoid currently approved for systemic therapy) have not been conducted, it is unclear whether tazarotene is any safer or more effective than acitretin. Moreover, the major drawback of oral tazarotene is teratogenicity, which may limit its use in female patients. Further studies evaluating long-term clinical outcomes with oral tazarotene and its use in combination therapies are awaited.
Am J Clin Dermatol 2006
PMID:Receptor-selective retinoids for psoriasis: focus on tazarotene. 1660 89

Skin irritants and contact allergens reduce the number of Langerhans cells (LCs). It has been assumed that this reduction is due their migration to the draining lymph node (LN) for initiating immune sensitization in a host. Skin irritation, however, as opposed to contact allergy is not considered to be an immunological disease. Nevertheless, skin irritants are also known for their adjuvant-like effects on contact allergy, resulting in skin hypersensitivity reactions like toxic dermatitis. The human organotypic skin explant culture (hOSEC) model is used to study the characteristics of chemical-induced migration of CD1a(+) LCs out of the epidermis in relation to irritancy or toxicity. We analysed cells emigrating out of hOSEC for CD1a(+) LCs, CD83(+) mature dendritic cells (DCs) and CCR7(+) LN homing cells. After exposure to a toxic concentration of a non-immunogenic irritant, an increase of CD1a(+)CD83(+) LCs was found in the culture medium. A non-toxic concentration of an sensitizer induced an increase of CD1a(+) cells. About 50% of skin emigrating CD1a(+) LCs were CD83(-) (immature) but all were CCR7(+). Skin irritation by both non-allergenic and allergenic compounds induces LC migration and maturation. In contrast, only allergenic compounds induced LC migration with partial maturation at subtoxic concentration. This effectively demonstrates that irritation is physiologically needed stimuli for inducing LC maturation.
Exp Dermatol 2006 Jun
PMID:Skin irritants and contact sensitizers induce Langerhans cell migration and maturation at irritant concentration. 1668 59

The subtle dryness of the skin surrounding the lesions of atopic dermatitis (AD) is called atopic dry skin or atopic xerosis (AX). AX is more susceptible to the development of AD skin lesions under various environmental stimuli than the clinically normal skin of the people who have or have had or will have AD, which might be called normal atopic skin (NAS) that shows no functional differences as compared to the skin of normal individuals. Routine histopathologic studies of AX that involve the invasive procedures of biopsy are not so helpful in clarifying the underlying pathogenesis. Modern, noninvasive biophysical instrumentation provides rich and quantitative information about various functional aspects of skin. The stratum corneum (SC) of AX reveals not only decreased hydration but also mildly impaired barrier function demonstrable as an increase in transepidermal water loss, elevated pH values, and an increased turnover rate of the SC consisting of thick layers of smaller-sized corneocytes. These data suggest that AX is related to mildly increased epidermal proliferation as a result of the presence of subclinical cutaneous inflammation. Although AX skin does not display any impairment in the recovery of barrier function after physical skin irritation by tape-stripping, it produces a much more severe, long-lasting inflammatory response together with a delay in barrier repair after chemical irritation such as that induced by sodium lauryl sulphate. The SC of AX is biochemically characterized by reduction in the amounts of ceramides, especially ceramide I, sebum lipids, and water-soluble amino acids. None of these changes in SC functions are seen in NAS, which includes not only the normal-looking skin of AD patients long after regression of all active lesions but also of latent atopic skin such as neonates who later develop AD. This suggests that all of the observed functional as well as biochemical abnormalities of AX are a reflection of subclinical inflammation. The presence of the underlying inflammation in AX also differentiates it from senile xerosis. The mildly impaired SC functions of AX can be improved by daily repeated applications of effective moisturizers, i.e., corneotherapy, which is effective in preventing the exacerbating progression of AX to AD resulting from inadvertent scratching of the skin that facilitates the penetration of environmental allergens into the skin. The biophysical confirmation of such efficacy of moisturizers, including cosmetic bases on the mildly impaired barrier function and decreased water-holding capacity of the SC of AX, definitely substantiates the importance of skin care for the cosmetic skin problems that affect every individual in the cold and dry season ranging from late autumn to early spring.
J Cosmet Dermatol 2006 Jun
PMID:Atopic xerosis: employment of noninvasive biophysical instrumentation for the functional analyses of the mildly abnormal stratum corneum and for the efficacy assessment of skin care products. 1717 89

Despite their beneficial effects on the treatment of acne vulgaris, topical and oral retinoids may cause severe local irritation (retinoid dermatitis) due to their mechanism of action, thereby jeopardizing patient adherence, and thus compromising treatment efficacy. Alleviating dryness and improving skin comfort by using a moisturizer concomitantly to retinoids could enhance efficacy. In the present study, 30 subjects receiving either oral isotretinoin for at least 2 months or topical tretinoin for at least one month applied a moisturizing cream (Cetaphil Moisturizing Cream) twice daily for 15 days on one half of the face while the other side remained untreated. Clinical assessments, confirmed by biophysical measurements, showed that the moisturizer provided a significant improvement in skin dryness, roughness, and desquamation. Skin properties and skin discomfort were also greatly improved and subjects were very satisfied with the product. Retinoid-induced skin irritation can be relieved by the regular use of a gentle moisturizing cream as an adjunctive treatment.
J Drugs Dermatol
PMID:Beneficial effect of a moisturizing cream as adjunctive treatment to oral isotretinoin or topical tretinoin in the management of acne. 1737 48

Previous investigators have reported the occurrence of both allergic and non-allergic systemic complications due to exposure to formaldehyde gas. However, little is known about the pathogenic link between formaldehyde-induced clinical symptoms and patch test results, or about the long-term effects of formaldehyde exposure. In the present study, a questionnaire was administered to 143 medical students, and 60 of them were tested by patch test for formaldehyde at the beginning and end of a human anatomy laboratory course. Another group of 76 students who had finished the course 2-4 years previously were administered another questionnaire, and the patch test was carried out on 58 of them. The frequencies of skin irritation, eye soreness, lacrimation, eye fatigue, rhinorrhea, throat irritation, general fatigue and mood swings increased after repeated exposure. Two (3.3%) of 60 students became positive to 1% formaldehyde at the end of the anatomy course (one male with allergic hand dermatitis due to direct contact with formaldehyde, and one female with an atopic background with unbearable physical symptoms) while the remaining 58 showed a negative reaction throughout the study period. The vast majority of students complained of various non-allergic, physical symptoms, and recovered from such symptoms without subsequent complications. No progression to multiple chemical sensitivity was found. Students with an episode of atopic dermatitis and allergic rhinitis were susceptible to formaldehyde exposure, and developed mucocutaneous symptoms, probably due to the impaired barrier function and remodeling of the skin and mucosa.
J Dermatol 2007 May
PMID:Prospective study of clinical symptoms and skin test reactions in medical students exposed to formaldehyde gas. 1740 35

Emollients play an important part in the management of patients with dry skin disorders, such as atopy, allergy, eczema, psoriasis or dryness following chemotherapy or radiotherapy. Their use in the treatment of diseased and sensitive skin requires not only an efficient hydrating and lipid-replenishing effect on the skin, but minimal risk for skin irritation or sensitization. This will be influenced by their formulation and number and type of ingredients and, due to the nature of their application, requires clinical testing to ensure their appropriateness for dermatological rather than cosmetic use. A new generation of emollients has been developed for the care of dry, or very dry, and sensitive skin. Among these, Dardia Lipo Line (Intendis GmbH, Berlin, Germany) has been formulated specifically for use in post-therapy preventive skin care. The current clinical evidence for this line of emollients is reviewed here.
J Eur Acad Dermatol Venereol 2007 Sep
PMID:Is there room for improvement in the emollients for adjuvant therapy? 1771 87

The OECD guideline for studies on percutaneous penetration to be used in hazard and risk evaluations prescribes experimental conditions with optimal barrier integrity of the skin, which in many occupational settings probably is not true. Thus, workers may have compromised skin due to chemical or mechanical damage, due to different medical conditions (eczema, dermatitis, skin irritation) or related to occupational scenarios involving prolonged wet work. The present study used the OECD guideline procedures to study the in vitro percutaneous penetration through human skin of a number of model substances (glyphosat, caffeine, benzoic acid, malathion) covering a range of solubilities. Further, we studied the extent to which a slightly damaged skin would change the rate, the amount absorbed during dermal exposure and the distribution of chemical deposition between epidermis and dermis. The present study demonstrates that a limited damage to the skin significantly increases the permeability coefficient (K (p)) as well as total percutaneous penetration of chemicals, and most significantly for those compounds that due to their physicochemical characteristics (the most hydrophilic as well as the most lipophilic) have low penetration rates through intact skin. The present experiment not only confirms the proportionality between lipophilicity and potential for percutaneous penetration, but also illustrates that at a certain degree of lipophilicity of a model compound, the different skin compartments become more attractive for temporary deposition of model compounds. Moreover, a clear change from epidermal deposition towards a dominating dermis deposition of chemicals temporarily deposited within the skin is seen following damage to the skin barrier. Thus, the distribution of chemicals within the skin compartments is affected by the physicochemical characteristics of the chemicals as well as by the integrity of the skin. This observation may have implications when evaluating the possibility of removing chemicals from the skin through different cleansing procedures following unintended dermal exposures.
Arch Dermatol Res 2007 Nov
PMID:Defense against dermal exposures is only skin deep: significantly increased penetration through slightly damaged skin. 1788 42

Mice on a calorie-restricted (CR) diet (total calories restricted to 70% of ad libitum; AL) for periods of time ranging from 3 to 18 months were examined for response to topical treatment with all-trans retinoic acid (RA). Daily application of a 0.1% solution of RA to the shaved skin of UM-HET3 mice on an AL diet produced a severe irritation that was evident by day 4, maximal at day 7-8 and still detectable at day 14. Skin irritation was characterized by redness, dryness, flaking and failure of the hair to grow at the treated site. In CR mice, the same treatment produced little detectable irritation. Animals were sacrificed at the end of the retinoid-treatment period (day 7 or day 14) and skin from these animals was examined histologically. In both AL and CR mice, a similar degree of epidermal hyperplasia was observed. Numerous inflammatory cells (mononuclear cells and granulocytes) were present in the skin of both groups. Occasional S100-positive cells (presumably Langerhans cells) were also observed in the epidermis of skin from both groups. S100-positive cells were also observed in the dermis. When skin from CR and AL mice was incubated in organ culture for 3 days (on day 7 after initiation of RA treatment), similar levels of four different pro-inflammatory cytokines were found in the conditioned medium. Soluble type I collagen levels were also similar. In contrast, the level of matrix metalloproteinase-9 was lower in the conditioned medium of skin from CR mice than in conditioned medium from skin cultures of AL mice. Taken together, these studies suggest that CR may provide a way to mitigate the irritation that normally accompanies RA treatment without compromising the beneficial effects of retinoid use. CR appears to exert a protective effect at the target tissue level rather than by a reduction in pro-inflammatory events, per se.
Arch Dermatol Res 2008 Jan
PMID:Inhibition of retinoic acid-induced skin irritation in calorie-restricted mice. 1796 74

In vivo levels of cytokines and presence of neutrophils and eosinophils in skin irritation are not well known. Our objective was to get more insight in inflammatory mediators and markers involved in single and repeated skin irritation. We sampled epidermis-derived fluid using a novel technology that includes application of a negative pressure on the skin after creation of micropores in the stratum corneum by a laser. In nine volunteers, transdermal fluid was sampled after a single 4-h 10% sodium lauryl sulphate exposure and a repeated 3-week exposure (0.1% sodium lauryl sulphate). Twenty-seven cytokines were assessed by multiplex assay, and IL-1alpha, eosinophil cationic protein and myeloperoxidase by enzyme-linked immunosorbent assay. Levels of eosinophil cationic protein were increased after irritation and correlated with levels of myeloperoxidase. The levels of inflammatory mediators showed large interindividual differences in unexposed and exposed skin. Despite this variation, several mediators clearly showed increased levels: CC chemokine ligand (CCL)11, CXCL10 and vascular endothelial growth factor after both single and repeated exposure, IL-1alpha and basic fibroblast growth factor after single exposure and interleukin-1 receptor antagonist (IL-1RA) after repeated exposure. After repeated exposure, CCL5 and the ratio IL-1RA/IL-1alpha both increased compared with single exposure. We conclude that single and repeated irritation induces differential and concerted expression of various inflammatory mediators and markers.
Exp Dermatol 2007 Dec
PMID:Differential cytokine expression in skin after single and repeated irritation by sodium lauryl sulphate. 1803 63

Formulating at acidic pH is a route to improve the chemical or biological stability and the performances of cosmeceuticals. Unfortunately, its potential is limited by the poor differentiation of available acidic agents, and by the risk of skin irritation. Recently, a perfluoropolyether phosphate was proposed to formulate acidic gels and emulsions, with advantages related with the specific active ingredient. The safety of these compositions, evaluated on volunteers, was the main objective of several studies. On the basis of these tests, and of its activity as O/W emulsifier, antimicrobial agent and oil repellent material, it can be asserted that perfluoropolyether phosphate widens the potential of acidic compositions regarding safety and functionality.
Clin Dermatol
PMID:Perfluoropolyether phosphate: a non-irritating acidic agent of cosmeceutical use. 1869 20


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