BACKGROUND:All-trans-retinoic acid (RA) and all-trans-retinol (ROL) are not widely used as anti-wrinkle agents due to their irritancy and photo-stability, respectively. Therefore, the safety and photo-stability in the development of RA or ROL derivatives have been an important issue.AIM:To identify the efficacy of retinyl retinoate as an anti-aging agent of cosmetics in treating females over 30 years old with periorbital wrinkles.METHODS:The clinical study was a prospective, double-blind, randomized, and controlled study with a total of 11 Korean women. At every 4 weeks, the effectiveness was assessed with a global photodamage score, photographs, and image analysis using replicas and visiometers. The dermal distance and intensity was also evaluated using Dermascan C.RESULTS:A statistically significant improvement in facial wrinkles (P<0.05) in eleven volunteers was observed in a clinical trial. The successive application of 0.06% retinyl retinoate cream for 3 months showed decreased depth and area of wrinkles in comparison with 0.075% retinol cream. The visual wrinkle improvement and the maximum roughness improvement rate (R2) for retinyl retinoate cream were 22% higher than that of retinol cream after 12 weeks. A statistically significant increase was observed after 8 and 4 weeks for dermal distance and dermal intensity, respectively (P<0.05).CONCLUSIONS:Retinyl retinoate had characteristic features of new anti-aging agents, and effectively improved facial wrinkle conditions.

RATIONALE: Recently ORMDL3 gene has been reported to be associated with childhood asthma and a few studies have confirmed it in ethnically diverse population. However, its clinical significance in asthma has not been reported. METHODS: Children with asthma (n = 908) and nonatopic healthy children (n = 373) were genotyped by PCR-RFLP analysis. The differences in the allele frequencies of ORMDL3 gene (rs7216389) were compared in two groups in terms of the severity of asthma such as the level of serum total IgE and airway hyperresponsiveness (PC20). RESULTS: Asthmatics (n = 908) and atopic asthmatics (n = 704) showed a significantly higher frequency of the TT homozygosity versus TC + CC compared to controls (OR, 1.49; 95% CI, 1.17-1.90 and OR, 1.56; 95% CI, 1.21-2.01, respectively) but not significant in children with non-atopic asthma. The frequency of TT homozygosity versus TC + CC was correlated positively with the increase of total IgE [OR, 1.51; 95% CI, 1.11-2.06 in 2nd tertile (143∼430 KU/L), OR, 1.63; 95% CI, 1.20-2.22 in 3rd tertile (> 430 KU/L)] and PC20 [OR, 1.56; 95% CI, 1.14-2.14 in 2nd tertile (1.42∼3.92 mg/ml), OR, 1.63; 95% CI, 1.19-2.24 in 3rd tertile (< 1.42 mg/ml)] respectively. CONCLUSIONS: There was a significant association of the ORMDL3 (rs7216389) genotype with childhood atopic asthma, total IgE level, and airway hyperresponsiveness. These findings suggest that the ORMDL3 gene polymorphism may be related with the development and severity of asthma in Korean children.

BACKGROUND:Photoaged skin can be treated with retinoids, which are natural and synthetic vitamin A derivatives. However, these are photounstable and can cause skin irritation, which is a major limitation in their use in general cosmetics. Retinyl retinoate, which is an ester of all-trans retinoic acid (RA) and all-trans retinol, has reduced toxicity due to blocking of the carboxyl end group of RA and higher skin regeneration activity than retinol.OBJECTIVES:To assess the efficacy of a photostable retinyl retinoate in treating women over 30 years old with periorbital wrinkles.METHODS:We conducted two clinical studies with a total of 46 Korean women with periorbital wrinkles, who were not pregnant, nursing or undergoing any concurrent therapy. In the first clinical study, the efficacy of retinyl retinoate was compared with placebo. Twenty-four patients completed a 12-week trial of 0.06% retinyl retinoate applied twice daily to one side of the face and a placebo applied to the other side. In the second clinical study, the efficacy of retinyl retinoate was compared with retinol. Twenty-two patients completed an 8-week trial of 0.06% retinyl retinoate applied twice daily to one side of the face and 0.075% retinol applied to the other side. Efficacy was based on a global photodamage score, photographs, and image analysis using replicas and visiometer analysis (Skin-Visiometer SV 600; Courage & Khazaka, Cologne, Germany) every 4 weeks. The standard wrinkle and roughness parameters used in assessing skin by visiometer were calculated and statistically analysed.RESULTS:The retinyl retinoate-treated wrinkles improved compared with wrinkles treated with placebo or retinol, as assessed by both the investigators and the subjects. Also, skin replica analysis indicated significant improvements in retinyl retinoate-treated skin in both studies, especially in average roughness.CONCLUSIONS:Retinyl retinoate applied twice daily was significantly more effective than a placebo or retinol in treating periorbital wrinkles. Importantly, no severe side-effects were observed.

RATIONALE: Atopic dermatitis is a chronic inflammatory pruritic skin disease that affects a large number of children and adults in industrialized countries. But there have been few reports of atopic dermatitis prevalence in Korean adolescence. METHODS: A questionnaire survey was conducted among 1499 high school students, from 3 regions in Korea between April and May, 2006. They responded to a modified International Study of Asthma and Allergies in Childhood (ISAAC) written questionnaires (WQ). Seven hundred twenty four subjects of them underwent eosinophil ratio, total serum IgE levels, skin prick test and metacholine challenge test. RESULTS: The WQ showed that the lifetime and last twelve month prevalences of atopic dermatitis were 22.2% and 11.4%. The lifetime prevalence of atopic dermatitis diagnosis was 18.5% and last twelve month prevalence of atopic dermatitis treatment was 8.4%. Factors which increase of last twelve month prevalence of atopic dermatitis include body mass index (adjusted odds ratio [aOR] = 1.064, 95% confidence interval [C.I.] 1.011-1.119); current asthma ([aOR] = 2.864, 95% [C.I.] 1.128-7.270); current allergic rhinitis ([aOR] = 2.219, 95% [C.I.] 1.289-3.819); paternal atopic dermatitis. ([aOR] = 5.527, 95% [C.I.] 2.866-10.658) In a multiple logistic regression model, paternal atopic dermatitis was a significant risk factor for the twelve month prevalence of atopic dermatitis. CONCLUSIONS: Paternal atopic dermatitis was a significant risk factor for the twelve month prevalence of atopic dermatitis in adolescence. Genetic factors may contribute to the persistence of atopic dermatitis.

Active smoking by adults deteriorates asthma symptoms and pulmonary function and also increases bronchial responsiveness, but evidences from studies on adolescents are scare. We conducted a cross-sectional survey of 1,492 adolescents that involved questionnaires and urinary cotinine levels in 3 urban areas of South Korea. Active smoking was defined as smoking more than 20 cigarettes during last month or urinary cotinine >40 ng/ml. Spirometry, allergy skin test, a bronchial challenge test were done for subpopulation (n = 724, mean age 15.7 yrs, girls 23.2%). The prevalence of active smoking was 9.0% in boys and 1.8% in girls. Active smoking was found to be significantly related with the prevalence of current wheeze, ever wheeze and current exercise-induced wheeze. In subgroup analysis, FEV1/FVC in active smokers was lower than nonsmokers (p = 0.027). Urinary cotinine showed negative correlation with serum IgE (r = −0.290, p = 0.032) and positive correlation with PC20 (r = 0.259, p = 0.056) among those who reported wheeze during the last 12 months. In a multiple logistic regression model, active smoking was a significant risk factor for wheeze ever (OR = 2.023, 95% CI 1.222-3.348). Active smoking in non-atopic subjects was associated with increased prevalence of current wheezing (OR = 4.02, 95% CI 1.417-11.407), current exercise-induced wheezing (OR = 23.120, 95% CI 2.074-257.7) and current asthma treatment (OR = 5.424 95% CI 2.100-14.007). Active smoking may be associated with current wheeze, current exercise-induced wheeze and deterioration of pulmonary function in Korean adolescent population. Active smoking in non-atopic subjects may play a role in the development of asthma symptom.

Although there is a clinical index for defining asthma risk, it would be useful to identify genetic markers for predicting asthma development in young children with recurrent wheezing. TNF-α and CD14 are associated with childhood asthma. Children with recurrent wheezing (n = 449) and nonatopic healthy children without previous wheezing (n = 241) were genotyped by PCR-RFLP analysis. The Asthma Predictive Index was used to classify recurrent wheezers as having high (n = 266) or low (n = 183) asthma risk. Recurrent wheezers showed a significantly higher frequency of the TNF-α -308A allele compared to controls (odds ratio [OR], 2.00; 95% confidence interval [CI], 1.20-3.35; p = 0.007), and frequency of homozygosity for the CD14 -159C allele (OR, 1.78; 95% CI, 1.05-3.02; p = 0.031) was higher only in high risk wheezers. Comparison of allele frequencies in the high- and low-risk groups revealed that CD14 -159CC homozygotes were more frequent in the high-risk group (OR, 1.908; 95% CI, 1.04-3.48; p = 0.035), while there was no significant difference for the TNF-α -308A allele. Finally, children co-inheriting the TNF-α -308A and CD14 -159C alleles had a significantly higher risk for recurrent wheezing (OR, 3.88; 95% CI; 1.66-9.09; p = 0.003). These findings suggest that the TNF-α -308G/A and CD14 -159T/C polymorphisms may prove useful as genetic markers for predicting asthma risk among young Korean children with recurrent wheezing.

RATIONALE: Tumor necrosis factor (TNF)-α and IL-13 are pivotal proinflammatory cytokines increased in asthmatic airways, which may be linked to asthma or BHR (bronchial hyperresponsiveness). We investigated the association between asthma susceptibility or asthma-related phenotypes and TNF-α (-308G/A) polymorphism, and examined the combined effect with IL-13 polymorphisms in Korean children with asthma. METHODS: Asthmatic children (N=719) and non-atopic healthy control children (N=243) were evaluated for asthma phenotypes including total serum IgE and BHR to methacholine. Genotypes were determined by PCR-RFLP. RESULTS: The allele frequencies of TNF-α (-308A) in asthmatics (14.1%) were much higher than that in control group (8.7%, OR 1.72, 95% CI 1.05-2.82). Significantly lower PC20 values were seen in asthmatic children with one or two copies of the TNF-α risk allele (-308A) than homozygous for common allele (P = .026). Higher frequencies of combination with risk alleles of TNF-α -308G/A and IL-13 +2044G/A were found in asthmatic children compared to control children (aOR 1.91, 95% CI 1.00-3.65). In addition, asthmatic children including risk alleles of TNF-α and IL-13 +2044G/A had significantly lower PC20 than those with homozygous for the common alleles (P = .024). CONCLUSIONS: The TNF-α promoter polymorphism (-308G/A) may be associated with asthma susceptibility and BHR in Korean children with asthma. In addition, these children show a synergistic effect between the TNF-α promoter and IL-13 coding region polymorphisms in terms of asthma susceptibility and BHR.

RATIONALE: The cysteinyl-leukotrienes are important inflammatory mediators in the pathogenesis of asthma, especially in the exercise-induced bronchoconstriction(EIB). LTC4 synthase(LTC4S) is a key enzyme in the cysteinyl-leukotrienes synthetic pathway.We conducted an association study between LTC4S(A-444C) promoter polymorphism and the occurrence and severity of exercise-induced asthma in Korean children. METHODS: Asthmatic children(n=445) and non-atopic healthy children(n=146) were enrolled. An exercise challenge test was performed in 270 asthmatic children and we measured bronchial responsiveness to methacholine and exercise, and lung function in the children. LTC4S(A-444C) gene polymorphism was determined by genotyping using PCR-RFLP assays. RESULTS: The AC and CC genotypes were significantly less frequent in severe EIB(+) asthmatics (26.0%) showing more than 30% fall of FEV1(%) after exercise versus EIB(-) asthmatics(43.0%). In asthmatic children, maximum percent fall of FEV1(%) was significantly lower in children with AC and CC genotypes (24.0±17.5%) compared to those with AA homozygotes (29.5±18.4%, P = .012). In addition, maximum percent fall of FEV1(%) after exercise in children with combination of -1512C or -1112T allele of IL-13 polymorphism and C allele for LTC4S polymorphism was significantly higher compared with those carrying wild-type alleles (P = .012, P = .045, respectively). CONCLUSIONS: The C allele of LTC4S(A-444C) promoter polymorphism may be associated with the severity of bronchoconstriction after exercise in Korean children with asthma. In addition, there was a significant gene-gene interaction between promoter polymorphisms of IL-13 and LTC4S and the severity of exercise-induced asthma. These results suggest that LTC4S(A-444C) gene may be a disease-modifying gene in asthma.

RATIONALE: Interleukin(IL)-13 plays a pivotal role of allergic inflammation. Binding of IL-13 to the IL-4 receptor α(IL-4Rα) initiates signal transduction that leads to IgE production, eosinophilia and bronchial hyperresponsiveness(BHR). We investigated the association of asthma-related phenotypes with four polymorphisms of IL-13(-1512A/C, -1112C/T, +2044G/A and +2525G/A) and with the combined effect between IL-13 polymorphisms and IL-4Rα polymorphism(Arg551Gln). METHODS: 335 atopic asthmatic, 79 non-atopic asthmatic, and 111 non-atopic healthy children were enrolled. The evaluated asthma phenotypes were eosinophil fraction(%), total serum IgE, pulmonary function test, and BHR to methacholine. The genotypes of IL-13 polymorphisms and IL-4Rα polymorphism were indentified by using a PCR-RFLP method. RESULTS: Children with one or two copies of mutant allele IL-13(-1512A/C and -1112C/T) were associated with increased total IgE levels in atopic asthma(P=.0124 and P=.0132, respectively) and increased eosinophil fraction(%) in non-atopic asthma(P=.0110 and P=.0043, respectively). Children with one or two copies of mutant allele of IL-4Rα(Arg551Gln) were associated with decreased FEV1 and FEF25-75% in non-atopic asthma(P=.0469 and P=.0471). In all children of this study, combined effect between IL-13 +2044 AA/AG genotype and the IL-4Rα ArgGln/ArgArg genotype was associated with decreased FEF25-75%(P=.0207). CONCLUSION: These findings suggest that polymorphisms of promoter regions in IL-13 may be associated with elevated IgE phenotype in atopic asthma and with elevated eosinophil phenotype in non-atopic asthma. And IL-4Rα may be associated with decreased pulmonary function in non-atopic asthma. In addition, a potential combined effect between IL-13 +2044G/A and IL-4Rα Arg551Gln may be associated with decreased pulmonary function in Korean children.