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)

The aim of this study was to compare the efficacy and tolerability of twice-daily vs. once-daily regimes of dithranol (anthralin) in Lassar's paste. Over a 4-year period, 61 inpatients with stable plaque psoriasis gave informed consent and entered a randomized controlled trial, having twice or once-daily application of dithranol in Lassar's paste as part of otherwise standard Ingram's regime. Primary outcome measurements were time required in hospital, nursing time, changes in total body surface area affected by psoriasis and thickness of a target plaque and in some patients, an assessment of the recurrence of psoriasis. Doctors were blinded as to the regime being used. At entry, mean patient age, lesional surface area and target plaque thickness were comparable in both groups and no patient had received systemic therapy in the preceding 3 months. Forty-two patients completed the study, two (11%) in the twice-daily group withdrawing due to skin irritation or 'burning'. Mean lesional surface area and target plaque thickness were similar in both groups at hospital discharge. Mean (+/- SD) time spent in hospital was not significantly different in each group, being 13.3 (+/- 6.2) days and 13.9 (+/- 4.5) days for the twice-daily and once-daily groups, respectively (P = 0.36). Duration of hospitalization did not correlate with surface area or plaque thickness on admission. Mean (+/- SD) nursing time spent on treatment was significantly greater in the twice-daily group, at 0.82 (+/- 0.33) hours per day compared with 0.51(+/- 0.25) hours per day in the once-daily group. Relapse rate at 6 months was not different between the two groups.
Clin Exp Dermatol 2002 Nov
PMID:Twice-daily vs. once-daily inpatient dithranol for psoriasis. 1247 49

For the investigation of the skin irritancy potential of chemicals in an in vitro model it is necessary to have sensitive endpoints that predict the effects of those compounds on native human skin. Recently, we have identified that 27-kDa heat shock protein (HSP27) can serve as a sensitive marker of skin irritation, as exposure of human skin to sodium lauryl sulfate (SLS) both in vitro and in vivo induced relocalization of HSP27 from the cytoplasm to the cell nucleus. The aim of the present study was to determine whether nuclear localization of HSP27 could be used as a parameter for evaluation of potential skin irritants in screening assays in vitro. For this purpose, human skin equivalent consisting of epidermis reconstructed on de-epidermized dermis was exposed to SLS or UV light. Stress-induced nuclear relocalization of HSP27 was observed in excised skin exposed to SLS or UV light and in reconstructed epidermis only when the latter was generated in the absence of vitamin C. The omission of vitamin C results in an impaired barrier function. In the presence of vitamin C, however, the barrier function was comparable with excised skin, suggesting that vitamin C may control the response to stress in the reconstructed epidermis. Besides the presence of vitamin C, the response of skin equivalents may strongly depend on other conditions under which they are generated, because the stress-induced HSP27 relocalization was not detected in the commercially available epidermal kit EpiDerm. The results of the present study show that HSP27 nuclear staining can serve as a sensitive marker for skin irritation or cellular stress in excised skin as well as in certain well-characterized human skin equivalents in vitro.
Exp Dermatol 2002 Dec
PMID:Induction of HSP27 nuclear immunoreactivity during stress is modulated by vitamin C. 1247 58

The exact role of epidermal fatty acid binding protein (E-FABP) in skin is unknown. A restoration of the barrier function may be associated with an upregulation of E-FABP. Moreover, E-FABP is upregulated in a variety of cells in response to oxidative stress. A recent observation that dithranol induced irritation is not associated with skin barrier impairment prompted us to investigate the expression of E-FABP in this skin condition to elucidate the unknown function of this protein in skin. This study shows lack of E-FABP upregulation after a single application of dithranol on uninvolved skin of patients with psoriasis. The expression of E-FABP in dithranol irritation correlates with the unimpaired skin barrier function as assessed by measurements of TEWL. Furthermore, we did not find evidence for the recently introduced hypothesis that E-FABP functions as an antioxidant protein in the skin irritation induced by dithranol as oxidative stressor.
Eur J Dermatol
PMID:Lack of upregulation of epidermal fatty acid binding protein in dithranol induced irritation. 1280 84

This review examines the commonly available topical acne agents and factors that determine their percutaneous absorption. Reported and theoretical adverse effects from systemic exposure are detailed. The topical retinoid class, which includes tretinoin, adapalene and tazarotene, and the topical antibacterials, clindamycin and erythromycin, are regulated by prescription in most countries. Used appropriately, the above-mentioned drugs deliver, at most, miniscule amounts of active ingredient into the circulation. Clear-cut links to systemic toxicity in humans are practically nonexistent, except in the case of topical clindamycin, which has been associated with diarrhea rarely, and there have been 2 cases of pseudomembranous colitis reported. Birth defects have occurred in two patients treated with tretinoin and one patient treated with adapalene, but causation was not proven. Another prescription drug, 20% azelaic acid, is associated with relatively high systemic exposure, which is presumed innocuous because it is a normal dietary constituent whose endogenous levels are not altered by topical use. Benzoyl peroxide, salicylic acid, sulfur, and sodium sulfacetamide are available in concentrations of 2% or more in over-the-counter acne treatments and some prescription products. All of these agents are known to exhibit some degree of percutaneous absorption. They remain largely unregulated because, other than skin irritation, only local allergic contact dermatitis from benzoyl peroxide in about 2.5% of patients and rare local and systemic hypersensitivity reactions from sodium sulfacetamide have been reported. Salicylism has occurred using methyl salicylate ointments and high concentrations of salicylic acid on widespread areas of hyperkeratotic skin, but there are no known cases resulting from salicylic acid acne products. Caution is advised in special circumstances, such as during childhood, pregnancy, lactation and concomitant therapy with other drugs, because relevant studies are lacking. Animal data support avoidance of many topical agents, particularly known teratogens such as retinoids and salicylic acid, in pregnant women. Salicylate avoidance is advised during lactation, because aspirin use carries the risk of bleeding disorders in nursing infants.
Am J Clin Dermatol 2003
PMID:Topical acne drugs: review of clinical properties, systemic exposure, and safety. 1281 37

A role for protein kinase C (PKC)-alpha has been implicated in the growth of mouse hair. Topical application of PKC activators, hair plucking, allergic contact dermatitis and skin irritation can all enhance growth of mouse hair, and a significant increase in PKC-alpha level in whole mouse skin in mature anagen has been demonstrated in these processes. Overexpression of PKC-alpha in anagen hair follicles has also been reported in natural growth of mouse hair. It is known that overexpression of PKC-alpha is associated with the acceleration of cell growth. Therefore, we postulated that overexpression of PKC-alpha in mature anagen may relate to enhancement of hair growth. The distribution of PKC-alpha in hair follicles during induced growth of mouse hair has not previously been studied. In this study, hair growth in C57BL/6 mice was induced by plucking the telogen hairs on one side of the back. The undepilated contralateral side served as a control. Expression of PKC-alpha in hair follicles during the hair growth cycle induced was evaluated by immunohistochemistry using cryosections and a specific polyclonal anti-PKC-alpha immunoglobulin G (IgG) antibody. No PKC-alpha was detected in telogen hair follicles or in the hair follicles at 1 day post-depilation, when the induced hair cycle was in early anagen. At 4 days after plucking, when the induced hair cycle was in mid-anagen, intense staining for PKC-alpha was found in hair papillae. At 10 and 17 days after depilation, when the induced hair cycle was in mature anagen and early catagen, respectively, all outer root sheath (ORS) cells and outer connective sheaths of hair follicles were stained positive. Because no PKC-alpha was detected in telogen hair follicles in this study, down-regulation of PKC-alpha in early anagen could not be observed. However, consistent with our previous findings, overexpression of PKC-alpha was found in mid-anagen and mature anagen. As overexpression of PKC-alpha has been shown to be associated with acceleration of cell growth, our results support the notion that PKC-alpha may play an important role in growth of hair follicle cells in induced growth of hair. As PKC levels are known to increase in hyperglycaemia, overexpressed PKC-alpha in mature anagen hair follicles may be related to the putative function of the ORS in mobilizing glycogen stores for anagen growth.
Clin Exp Dermatol 2003 Jul
PMID:Overexpression of skin protein kinase C-alpha in anagen hair follicles during induced growth of mouse hair. 1282 8

The purpose of this open-label study was to determine the adverse event rate of topical 4HA/tretinoin when used twice daily for up to 24 weeks with concomitant sunscreen in the treatment of solar lentigines and related hyperpigmented lesions. There were two treatment areas: bilateral dorsal forearms, including the back of the hands; and the face, including the forehead and cheek areas. Each treatment area had a target lesion at least 5 mm in diameter and was moderately darker than the surrounding skin. A nine-point bipolar scale was used for evaluation of Target Lesion Pigmentation (0 = extremely lighter than pigment of the surrounding skin, 4 = equal with pigment of surrounding skin, 8 = extremely darker than pigment of surrounding skin). The other solar lentigines present in the treatment areas also had to have an overall pigmentation grade of at least Grade 6. Twice daily applications to individual lesions in each treatment area were made for up to 24 weeks followed by a 4-week follow-up phase. Sunscreen applications (sunscreen with sun protection factor (SPF) 25 or greater) were made every morning and reapplied after six hours if additional sun exposure was expected. Clinical evaluations were performed at weeks 0, 4, 8, 16, 24 and 28. The clinical signs of Target Lesion Pigmentation and Overall Lesion Pigmentation were evaluated at each visit. A total of 96 subjects were enrolled at four study centers; 77 (80%) subjects completed the study. Treatment-related adverse events (AEs) for 4HA/tretinoin included erythema, burning/stinging/tingling, desquamation, pruritus, skin irritation, halo hypopigmentation and hypopigmentation. Five (5%) subjects discontinued from the study due to adverse events considered to be related to study medication. When used with sunscreen of SPF 25 or greater, 4HA/tretinoin was safe and well tolerated and did not produce any unexpected or unusual adverse events.
J Drugs Dermatol 2003 Apr
PMID:A promising new treatment for solar lentigines. 1285 66

Keratinocytes play an important role in skin irritation. In an attempt to investigate mechanistic bases of human skin irritation response, we recently identified the upregulation by skin irritants of adipose differentiation related protein (ADRP) in reconstituted human epidermis. ADRP is a lipid-storage-droplet-associated protein, governing deposition and release of lipids from droplets. The purpose of this study was to characterize, in a human keratinocyte cell line (NCTC 2544), sodium-dodecyl-sulfate-induced ADRP expression, to identify the biochemical events that lead to ADRP expression, and to understand its function in sodium dodecyl sulfate cytotoxicity. Sodium dodecyl sulfate induced a concentration- and time-related production of ADRP that was associated with lipid droplet accumulation. Lipid accumulation following sodium dodecyl sulfate treatment was due to intracellular redistribution rather than lipid neosynthesis, as indicated by equivalent 14C-oleate and 14C-acetate incorporations. Other skin irritants, namely benzalkonium chloride, tributyltin, and 12-O-tetradecanoylphorbol 13-acetate, also induce lipid droplet accumulation. Sodium-dodecyl-sulfate-induced ADRP expression and lipid droplet accumulation were modulated by the calcium chelator BAPTA, indicating a role of calcium in ADRP induction. Decrease of sodium-dodecyl-sulfate-induced ADRP expression by specific ADRP antisense oligonucleotide resulted in increased cytotoxicity, indicating a protective role of ADRP and lipid accumulation in the process of cell damage induced by skin irritants. ADRP expression was also induced in vivo following treatment with sodium dodecyl sulfate in an experimental model of skin irritation, indicating that the in vitro model represents irritation.
J Invest Dermatol 2003 Aug
PMID:Induction of adipose differentiation related protein and neutral lipid droplet accumulation in keratinocytes by skin irritants. 1288 Apr 48

Hyperhidrosis is a common and distressing condition involving increased production of sweat. A variety of treatment modalities are used to try to control or reduce sweating. Sweat is secreted by eccrine glands innervated by cholinergic fibers from the sympathetic nervous system. Primary hyperhidrosis most commonly affects palms, axillae and soles. Secondary hyperhidrosis is caused by an underlying condition, and treatment involves the removal or control of this condition. The treatment options for primary hyperhidrosis involve a range of topical or systemic medications, psychotherapy and surgical or non-surgical invasive techniques. Topical antiperspirants are quick and easy to apply but they can cause skin irritation and have a short half life. Systemic medications, in particular anticholinergics, reduce sweating but the dose required to control sweating can cause significant adverse effects, thus, limiting the medications' effectiveness. Iontophoresis is a simple and well tolerated method for the treatment of hyperhidrosis without long-term adverse effects; however, long-term maintenance treatments are required to keep patients symptom free. Botulinum toxin A has emerged as a treatment for hyperhidrosis over the past 5-6 years with studies showing good results. Unfortunately, botulinum toxin A is not a permanent solution, and patients require repeat injections every 6-8 months to maintain benefits. Psychotherapy has been beneficial in a small number of cases. Percutaneous computed tomography-guided phenol sympathicolysis achieved good results but has a high long-term failure rate. Surgery has also been shown to successfully reduce hyperhidrosis but, like other therapies, has several complications and patients need to be informed of these prior to undergoing surgery. The excision of axillary sweat glands can cause unsightly scarring and transthoracic sympathectomy (either open or endoscopic) can be associated with complications of compensatory and gustatory hyperhidrosis, Horner syndrome and neuralgia, some of which patients may find worse than the condition itself.
Am J Clin Dermatol 2003
PMID:Management of primary hyperhidrosis: a summary of the different treatment modalities. 1450 30

The ability of the synthetic retinoid MDI-301, in which the carboxylic acid of 9- cis-retinoic acid (9-cis-RA) is replaced with an ester linkage, to induce epidermal and dermal thickening and skin irritation (erythema and flaking) in hairless (rhino) mice following its topical application was investigated in comparison with that of 14-all- trans-retinoic acid (14-all-trans-RA) and 9-cis-RA. MDI-301 induced epidermal proliferation leading to a thickened epidermis. Treated animals also demonstrated a prominent band of organized connective tissue immediately below the epidermis. In its ability to induce epidermal thickening, MDI-301 was quantitatively similar to 14-all-trans-RA and 9-cis-RA. However, unlike 14-all-trans-RA and 9-cis-RA, which produced skin irritation associated with a perivascular influx of mononuclear leukocytes into the dermis, there was no evidence of irritation with MDI-301 and little leukocyte infiltration. Intraperitoneal injection of either 14-all-trans-RA or MDI-301 also resulted in epidermal and dermal thickening. Irritation of skin was not observed in these animals but splenomegaly was prominent in animals treated with either agent.
Arch Dermatol Res 2003 Nov
PMID:Separation of retinoid-induced epidermal and dermal thickening from skin irritation. 1456 58

Differences have been found among blacks, whites, Asians, and Hispanics in various areas of skin structure and function. Among them is the stratum corneum lipid (ceramide) content, which is highest in Asians, then Hispanics, then whites, and lowest in blacks. Melanosomal packaging and percutaneous absorption rates for specific compounds also vary among the different races. Reports supporting the occurrence of difference in TEWL, tyrosinase levels, skin elasticity, and water absorption rates between blacks and whites, and reaction to skin irritation have been conflicting. No significant differences in corneocyte size, skin thickness, and skin biomechanics have been reported.
Dermatol Clin 2003 Oct
PMID:Structure and function of ethnic skin and hair. 1471


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