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Climbazole boosts activity of retinoids in skin.
Adamus, J, Feng, L, Hawkins, S, Kalleberg, K, Lee, JM
International journal of cosmetic science. 2017;(4):411-418
Abstract
OBJECTIVE To explore whether climbazole enhances retinoid-associated biological activities in vitro and in vivo. METHODS Primary human dermal fibroblasts (HDFs) were treated from six to 48 h with either retinoids (retinol, retinyl propionate, retinyl palmitate) alone or in combination with climbazole, and then assessed for cellular retinoic acid-binding protein 2 (CRABP2) mRNA expression by RT-qPCR. Next, skin equivalent (SE) cultures were topically treated with retinol or retinyl propionate, with or without climbazole, and then measured for biological changes in retinoid biomarkers. Lastly, an IRB-approved clinical study was conducted on the outer forearm of 16 subjects to ascertain the effects of low (0.02%) or high (0.1%) levels of retinol, retinyl propionate (0.5%), climbazole (0.5%) or a combination of retinol (0.02%)/climbazole (0.5%). Indicators of retinoid activities were measured after 3 weeks. RESULTS Treatment of HDFs with retinol or retinyl propionate was unaffected by climbazole but alone, resulted in a significantly (P < 0.01) higher sustained CRABP2 mRNA expression than those treated with retinyl palmitate or vehicle control. In SEs, climbazole combined with either retinol or retinyl propionate boosted retinoid related activity greater than the retinoid only, reflected by a dose-response, downregulation of loricrin (LOR) and induction of keratin 4 (KRT4) proteins. In vivo, retinol (0.1%) and retinyl propionate (0.5%) significantly increased most evaluated biomarkers, as expected. Low-dose retinol or climbazole alone did not increase these biomarkers; however, in combination, significant (P < 0.05) increases in retinoid and ageing biomarkers were detected. CONCLUSION Climbazole boosted retinoid activity both in the SE model, after a combined topic treatment with either retinol or retinyl propionate, and in vivo, in combination with a low level of retinol. Based upon the evidence presented here, we suggest that the topical skin application of climbazole in combination with retinoids could deliver skin ageing benefits more than a less robust retinoid alone.
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2.
Chemoprevention of head and neck cancer with retinoids: a negative result.
Perry, CF, Stevens, M, Rabie, I, Yarker, ME, Cochrane, J, Perry, E, Traficante, R, Coman, W
Archives of otolaryngology--head & neck surgery. 2005;(3):198-203
Abstract
OBJECTIVE To determine whether isotretinoin (or 13-cis-retinoic acid) decreases the risk of second primary cancers in patients previously treated for cure of head and neck squamous cell carcinoma. DESIGN Randomized, double-blind, placebo-controlled trial. SETTING Two head and neck multidisciplinary cancer clinics in university teaching hospitals taking cases from 4 to 5 million people in Queensland, Australia, combined to enter appropriate patients into this trial. PATIENTS One hundred fifty-one patients with their first head and neck squamous cell carcinoma treated with high expectation for cure and living close by. They were randomized into 3 arms to receive 3 years of treatment. INTERVENTIONS Patients took isotretinoin at a high dose (1.0 mg/kg per day) or a moderate dose (0.5 mg/kg per day) or placebo. Group 1 took the high dose for 1 year and then the moderate dose for 2 years. Group 2 took the moderate dose for 3 years. Group 3 took placebo for 3 years. MAIN OUTCOME MEASURES The diagnosis of a second primary malignancy of the head and neck, lung, or bladder was regarded as the end point signifying failure of therapy. Issues of drug adverse effect profile and impact on survival were measured. RESULTS There was no significant difference in the occurrence of second primary disease (P = .90), the recurrence of primary disease (P = .70), or disease-free time (P = .80) between the treatment and nontreatment arms. Numbers were too small to find differences in survival. CONCLUSION With evidence that retinoid treatment adversely affects survival of lung cancer and with this drug not significantly decreasing the incidence of second primary tumors of head and neck squamous cell carcinoma, the use of this drug in head and neck cancer patients for second cancer prophylaxis is not indicated.
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3.
Amounts and types of fatty acids in meals affect the pattern of retinoids secreted in human chylomicrons after a high-dose preformed vitamin A intake.
Sauvant, P, Mekki, N, Charbonnier, M, Portugal, H, Lairon, D, Borel, P
Metabolism: clinical and experimental. 2003;(4):514-9
Abstract
High doses of preformed vitamin A are commonly used to correct vitamin A deficiency. Newly absorbed vitamin A is secreted mainly as retinyl esters in chylomicrons. The effect of changing types and amounts of fatty acids on fatty acid composition of chylomicron retinoid esters when a high dose of vitamin A is ingested have not been studied previously. In the present study, 10 healthy young men ingested, in a random order, mixed meals containing 15,000 retinol equivalents (RE) of vitamin A (as retinyl palmitate) and either no fat or 40 g of fat provided as butter, olive oil, or sunflower oil. Fasting and postprandial blood samples were obtained for 7 hours after meals. Free retinol and the main retinyl esters (retinyl palmitate/oleate, stearate, and linoleate) were measured in chylomicrons by high-performance liquid chromatography (HPLC). Chylomicron retinyl palmitate/oleate and retinyl stearate concentrations significantly increased after intake of the 4 test meals. Conversely, chylomicron retinyl linoleate and chylomicron free retinol significantly increased only after the sunflower and the fat-free meals, respectively. The main retinoid secreted in chylomicrons after the intake of the fat-rich meals was retinyl palmitate/oleate, accounting for 63% to 79% of total RE, but it was free retinol after the fat-free meal (51% of total RE). Thus, the retinoid pattern secreted in chylomicrons after the intake of a high dose of preformed vitamin A depends on type and amounts of fatty acids ingested. To explain this result we suggest that the esterification process of retinol in the enterocyte by lecithin:retinol acyltransferase can be overwhelmed by a high load of vitamin A. Consequently, a significant proportion of the retinol is esterified by acyl coenzyme A:retinol acyltransferase (ARAT) with ingested fatty acids, explaining the appearance of retinyl linoleate in chylomicrons after the sunflower oil meal. If a high dose of preformed vitamin A is ingested with a fat-free meal, a significant proportion of retinol is not esterified, owing to the lack of fatty acids for ARAT, which explains the appearance of free retinol in chylomicrons.
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4.
Successful treatment of acne vulgaris using a new method: results of a randomized vehicle-controlled trial of short-contact therapy with 0.1% tazarotene gel.
Bershad, S, Kranjac Singer, G, Parente, JE, Tan, MH, Sherer, DW, Persaud, AN, Lebwohl, M
Archives of dermatology. 2002;(4):481-9
Abstract
CONTEXT Short-contact application of 0.1% tazarotene gel for acne was devised to minimize local adverse effects. Its efficacy and safety are unknown. OBJECTIVES To assess acne improvement and tolerability during 12 weeks of short-contact treatment with 0.1% tazarotene gel vs a nonmedicated gel control. DESIGN A randomized, masked, vehicle-controlled trial. SETTING Outpatient facilities at an urban medical school and an affiliated suburban office practice. PARTICIPANTS Ninety-nine volunteers with facial acne were enrolled; 81 completed the study. INTERVENTION Thirty-three patients were randomly assigned to each of 3 groups: T + T applied 0.1% tazarotene gel twice daily, T + V applied 0.1% tazarotene gel once daily and vehicle gel once daily, and V + V applied vehicle gel twice daily. Patients adjusted the contact period as tolerated, between 30 seconds and 5 minutes per application. MAIN OUTCOME MEASURES Acne efficacy by reduction in acne lesions, treatment success (50%-100% improvement in global response to treatment) and improvement in overall disease severity. Local adverse effects, scored from none to severe. RESULTS By week 12, T + T and T + V achieved significantly greater improvement in acne than V + V based on mean percentage reduction in noninflammatory lesions (46% and 41% vs 2%; P =.002) and inflammatory lesions (38% and 34% vs 9%; P =.01), percentage of treatment successes (64% and 61% vs 15%; P<.001), and reduction in overall disease severity (30% and 29% vs 3%; P<.001). Local adverse effects did not differ significantly among the 3 groups after week 4. CONCLUSION Short-contact 0.1% tazarotene gel therapy is a safe and effective new method of acne treatment.
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5.
Management of guttate and generalized psoriasis vulgaris: prospective randomized study.
Caca-Biljanovska, NG, V'lckova-Laskoska, MT
Croatian medical journal. 2002;(6):707-12
Abstract
AIM: To assess the efficacy of betamethasone dipropionate 0.05% cream plus ultraviolet B (UVB) radiation with and without additional penicillin therapy in the treatment of guttate psoriasis, and to compare the efficacies of oral psoralen plus ultraviolet A (PUVA) therapy and systemic retinoids therapy for treatment of generalized psoriasis. METHODS Sixty patients with guttate (n = 20) and generalized psoriasis vulgaris (n = 40) of various intensity and duration treated at the Department of Dermatology, Medical School in Skopje, from February 2000 to January 2002, were included in this prospective, open-label, randomized, parallel group study. The clinical features of the patients were quantified according to the mean psoriasis area and severity index (PASI) values. Student s t-test for paired samples and two independent samples were used in statistical analysis. RESULTS The final PASI values were not significantly different for the patients receiving different treatments of guttate psoriasis or generalized psoriasis. The initial PASI values for guttate psoriasis patients treated with betamethasone dipropionate plus UVB with and without penicillin treatment (5.7 +/- 2.1 and 5.9 +/- 2.5, respectively) declined to 0.5 +/- 0.8 and 1.0 +/- 0.9, respectively, after the therapy. The initial PASI values in generalized psoriasis patients receiving PUVA dropped from 24.1 +/- 3.6 to 1.7 +/- 1.5 by the end of the therapy. Finally, pre-treatment PASI values in patients with generalized psoriasis receiving retinoids decreased from 24.6 +/- 3.5 to 0.9 +/- 1.1 after treatment. However, patients receiving systemic retinoids for generalized psoriasis had statistically higher incidence of side effects than patients receiving PUVA therapy (t = 6.458, df = 38, p < 0.001). CONCLUSION Penicillin should be applied in addition to local corticosteroids with UVB in the treatment of guttate psoriasis, since the disease may be triggered by a streptococcal infection. In cases of generalized psoriasis vulgaris, PUVA therapy caused fewer side effects than did systemic retinoids.