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

The retinoids provide an important new way of treating dermatologic disorders. They have also proved to have a role in the prevention of new lesion formation. New retinoids, of which adapalene is one, have recently been synthesized in order to obtain similar or better efficacy while reducing skin irritation potential. These new molecules are currently under clinical investigation. Preliminary results are encouraging. In the near future, an expanded range of topical retinoids should be available.
Dermatol Clin 1993 Jan
PMID:Topical retinoids. Their uses in dermatology. 843 5

Topically applied all-trans retinoic acid (RA) is often associated with skin irritation. A detailed quantification of RA-induced functional changes in stratum corneum is, however, still limited. Using non-invasive bioengineering techniques of measurements of transepidermal water loss (TEWL), stratum corneum hydration and cutaneous blood flow (CBF), we quantified the irritant effects of 0.05% and 0.1% RA in ethanol on normal skin compared with 1% sodium lauryl sulphate (SLS) in water as a model irritant in a 24-h occlusive patch-test assay. Additionally, in order to document data possibly related to the mechanism of action, skin responses to both compounds applied in tandem was also investigated over 18 days. The extent of the irritant response to 0.05 and 0.1% RA, respectively, were similar, implying analogous irritation potency. While RA caused more intense scaling than SLS, other skin responses to RA were significantly weaker than those due to SLS. An increase in TEWL, on day 7, in RA-exposed sites indicates a secondary delayed impairment of the stratum corneum (SC) barrier. In a tandem-design assay, pretreatment with RA appeared to reduce the irritant effects of SLS on SC hydration and CBF. In contrast, pre-exposure to SLS showed a synergestic response in erythema, scaling and TEWL. Our results demonstrate that RA, like SLS, is capable of impairing SC water barrier function, which may be responsible, in part, for the irritation associated with its topical use. However, the distinctive biological responses to these compounds suggest a different mode of action of RA and SLS. In addition, the precise reason for the unique results observed in the tandem-design assays is not clear.
Br J Dermatol 1996 Mar
PMID:Differential irritant skin responses to topical retinoic acid and sodium lauryl sulphate: alone and in crossover design. 873 64

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.
Br J Dermatol 1996 Oct
PMID:Effects of calcipotriol on stratum corneum barrier function, hydration and cell renewal in humans. 891 43

Calcitriol (1 alpha,25-dihydroxyvitamin D3), applied topically in an ointment base, has been shown to be effective in the treatment of chronic plaque psoriasis. This open study was designed to assess the safety and tolerability of 3 micrograms/g calcitriol ointment applied twice daily over treatment periods of up to 78 weeks. In the 253 evaluable patients with chronic plaque psoriasis no clinically relevant changes were observed in the baseline/end-point analyses of mean serum levels of total calcium, albumin-adjusted total calcium, phosphorus and creatinine, and plasma calcitriol levels. Mean values of 24-h urinary calcium, phosphorus, creatinine and hydroxyproline excretions, creatinine clearance and mean urinary calcium/creatinine ratio also did not show clinically relevant changes in the baseline/end-point analyses. The treatment was well tolerated, with no serious adverse events occurring during the course of the study. Eight patients withdrew from the study due to adverse events which, although not serious, were thought to be treatment-related: in seven patients skin irritation reactions and in one case a transient asymptomatic slight hypercalcaemia was observed. In addition, assessments of global severity, global improvement and Psoriasis Area and Severity Index scores confirmed the therapeutic efficacy of twice daily 3 micrograms/g calcitriol ointment demonstrated in an earlier controlled study. In conclusion, this study demonstrated that twice daily application of 3 micrograms/g calcitriol ointment is safe and well-tolerated in the treatment of chronic plaque psoriasis.
Br J Dermatol 1996 Sep
PMID:A long-term multicentre assessment of the safety and tolerability of calcitriol ointment in the treatment of chronic plaque psoriasis. 894 30

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.
Br J Dermatol 1996 Nov
PMID:Tacalcitol ointment in the treatment of psoriasis vulgaris: a multicentre, placebo-controlled, double-blind study on efficacy and safety. 897 77

Initial clinical investigations on tazarotene, a new acetylenic retinoid, have suggested potential usefulness in the treatment of mild-to-moderate plaque psoriasis. Tazarotene promotes healing of psoriatic lesions by modulating the key pathogenetic factors in this disease. It is not sensitizing, phototoxic, or photoallergenic, but causes moderate dose-related skin irritation. Systemic absorption is minimal and elimination is rapid, providing a low potential for systemic adverse effects. Tazarotene effectively treats mild-to-moderate plaque-type psoriasis, the benefits seem to be sustained after the cessation of therapy, and once-daily treatment is equally effective as more frequent application.
Br J Dermatol 1996 Oct
PMID:Early clinical development of tazarotene. 903 2

Skin irritant reactions are under the control of a network of cytokines and lipid mediators. This study characterized the production of tumor necrosis factor-alpha (TNF) induced by a skin irritant treatment, tributyltin (TBT), in mice through transcription factor activation and its pharmacologic modulation by anti-inflammatory agents. The ears of BALB/c mice were painted with different amounts of TBT (67-536 nmol in acetone) or with acetone alone. At different times thereafter, TNF production was analyzed both at the mRNA and protein level, by semiquantitative RT-PCR and L929 cytotoxicity assay, respectively. TBT induced rapid (1 h) TNF gene expression and protein synthesis. Maximal TNF production was observed 2 h after treatment. The production of TNF was paralleled by accumulation of skin water; this was partially prevented by intraperitoneal injection of antibody against murine TNF. These data indicate that skin irritation induced by TBT is attributable, in addition to the actions of other inflammatory mediators, to the action of keratinocyte-derived TNF. TNF production was preceded by a rapid (5 min) activation of nuclear factor-kappaB (NF-kappaB), which was also maximal 30 min after treatment. TBT-induced accumulation of skin water and TNF production were significantly reduced by topical treatment with dexamethasone and pentamidine, two anti-inflammatory agents. Interestingly, dexamethasone, but not pentamidine, decreased TBT-induced NF-kappaB activation, confirming in vivo that the glucocorticoid receptor interacts functionally within the nucleus with other transcription factors opposing one another's activity.
J Invest Dermatol 1997 Jun
PMID:Induction of tumor necrosis factor-alpha in vivo by a skin irritant, tributyltin, through activation of transcription factors: its pharmacological modulation by anti-inflammatory drugs. 918 17

Oral retinoids are effective in the treatment of psoriasis, but their use is limited by concerns for teratogenic potential and systemic side effects. Tazarotene is a novel acetylenic retinoid undergoing clinical trials for the topical treatment of mild-to-moderate plaque psoriasis. The safety and tolerability of tazarotene 0.1% and 0.05% gels were examined in a series of preclinical and clinical trials. In preclinical studies topically applied tazarotene gel was nonmutagenic, noncarcinogenic, and nonteratogenic. Tazarotene gel was not sensitizing, phototoxic, or photosensitizing in a series of studies in human volunteers. Treatment-related systemic adverse effects were not observed in clinical trials involving approximately 2000 patients treated with tazarotene 0.1% or 0.05% gel for periods of up to 1 year. Adverse effects appear limited to manageable, mainly mild-to-moderate local skin irritation.
J Am Acad Dermatol 1997 Aug
PMID:Clinical safety of tazarotene in the treatment of plaque psoriasis. 927 May 53

In clinical practice, the cutaneous exposure to chemical irritants such as surfactants and topical drugs is frequent. Topical all-trans retinoic acid (RA) is often associated with irritation and induces epidermal changes similar to those produced by sodium lauryl sulphate (SLS). Using bioengineering techniques, e.g. assessing transepidermal water loss (TEWL), capacitance and chromametry, we investigated the variations of the skin response to SLS and RA and to both chemicals applied sequentially, allowing different time periods (from 1 h to 2 weeks) between applications of SLS and RA. Both chemicals caused irritation as assessed by visual scoring, but the values from the objective variables differed at different time periods. TEWL increased dramatically shortly after applying SLS but the increase was delayed after RA. After applying SLS, the capacitance generally decreased then returned to basal values; treatment with RA produced an overall increase. Only the results from chromametry were similar. After tandem application, the drugs were synergistic for all variables except capacitance, showing an antagonistic interaction for skin hydration. These results suggest that non-specific skin irritation profoundly reflects different mechanisms of action at tissue level. With sequential application, SLS injury modified the response to RA for at least 1 week after applying SLS. These late effects of detergents should be considered when studying irritant chemical interactions and in developing strategies for the management of occupational and other irritant dermatitis.
Br J Dermatol 1997 Aug
PMID:Differential irritant skin responses to tandem application of topical retinoic acid and sodium lauryl sulphate: II. Effect of time between first and second exposure. 964 Apr

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.
Exp Dermatol 1997 Aug
PMID:Antiflammin 1 peptide delivered non-invasively by iontophoresis reduces irritant-induced inflammation in vivo. 929 90


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