Association of glutathione-S-transferase polymorphisms with atopic dermatitis risk in preschool age children

Background: Glutathione S-transferase (GST) enzymes are critical for detoxifying reactive oxygen species (ROS) and their products which have been implicated in the pathology of inflammatory diseases such as atopic dermatitis (AD). Methods: We investigated the effects of genetic polymorphisms of GST on the risk of AD in preschool age children. Biomarkers for oxidative stress were also evaluated with respect to GST genotype. Results: The GSTP1 Val105 allele was significantly associated with an increased risk of AD [odds ratio (OR)=1.62, p<0.05]. The combination of the GSTP1 Val105 allele and the GSTT1 null genotype further increased this risk by 2.3-fold (p<0.01). No association was observed for the GSTM1 null or GSTT1 null genotype alone. In children with AD, blood total antioxidant capacity was significantly less (p<0.001), while malondialdehyde was higher (p=0.12). Children with the GSTP1 Val105 allele had significantly lower concentrations of erythrocyte glutathione compared to GSTP1 Ile/Ile homozygotes (p=0.03). Conclusions: Our study suggests that the GSTP1 Val105 allele is an important determinant of susceptibility to AD in preschool age children and increased oxidative stress may play a role in the pathogenesis of AD. Clin Chem Lab Med 2009;47:1475–81.Peer Reviewe

Effects of various metal ions on the gene expression of iron exporter ferroportin-1 in J774 macrophages

Macrophages play a key role in iron metabolism by recycling iron through erythrophagocytosis. Ferroportin-1 (FPN1) is a transporter protein that is known to mediate iron export from macrophages. Since divalent metals often interact with iron metabolism, we examined if divalent metals could regulate the expression of FPN1 in macrophages. J774 macrophage cells were treated with copper, manganese, zinc, or cobalt at 10, 50, or 100 µM for 16 to 24 h. Then, FPN1 mRNA and protein levels were determined by quantitative real-time PCR and Western blot analyses, respectively. In addition, effects of divalent metals on FPN1 promoter activity were examined by luciferase reporter assays. Results showed that copper significantly increased FPN1 mRNA levels in a dose-dependent manner. The copper-induced expression of FPN1 mRNA was associated with a corresponding increase in FPN1 protein levels. Also, copper directly stimulated the activity of FPN1 promoter-driven reporter construct. In contrast, manganese and zinc had no effect on the FPN1 gene expression in J774 cells. Interestingly, cobalt treatment in J774 cells decreased FPN1 protein levels without affecting FPN1 mRNA levels. In conclusion, our study results demonstrate that divalent metals differentially regulate FPN1 expression in macrophages and indicate a potential interaction of divalent metals with the FPN1-mediated iron export in macrophages

Cadmium increases ferroportin-1 gene expression in J774 macrophage cells via the production of reactive oxygen species

Cadmium intoxication has been associated with the dysregulation of iron homeostasis. In the present study, we investigated the effect of cadmium on the expression of ferroportin 1 (FPN1), an important iron transporter protein that is involved in iron release from macrophages. When we incubated cadmium with J774 mouse macrophage cells, FPN1 mRNA levels were significantly increased in a dose- and time-dependent manner. Furthermore, the cadmium-induced FPN1 mRNA expression was associated with increased levels of FPN1 protein. On the other hand, cadmium-mediated FPN1 mRNA induction in J774 cells was completely blocked when cells were co-treated with a transcription inhibitor, acitomycin D. Also, cadmium directly stimulated the activity of the FPN1-promoter driven luciferase reporter, suggesting that the cadmium up-regulates FPN1 gene expression in a transcription-dependent manner. Finally, cadmium exposure to J774 macrophages increased intracellular reactive oxygen species (ROS) levels by ~ 2-fold, compared to untreated controls. When J774 cells were co-treated with antioxidant N-acetylcystein, the cadmium-induced FPN1 mRNA induction was significantly attenuated. In summary, the results of this study clearly demonstrated that cadmium increased FPN1 expression in macrophages through a mechanism that involves ROS production, and suggests another important interaction between iron and cadmium metabolism

Association between Dietary Patterns and Atopic Dermatitis in Relation to GSTM1 and GSTT1 Polymorphisms in Young Children

Previous research suggests the association of glutathione S-transferase (GST) gene polymorphisms or diet, but no interactions between these factors in atopic dermatitis (AD). We conducted a community-based case-control study including 194 AD and 244 matched non-AD preschoolers. Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) present/null genotypes were evaluated uisng a multiplex PCR method. We measured dietary intakes by a validated food frequency questionnaire and constructed three dietary patterns such as “traditional healthy”, “animal foods”, and “sweets” diets. In stratified analyses by GST genotypes, the “traditional healthy” diet and reduced AD showed association only in the GSTM1-present group (odd ratio (OR) 0.31, 95% confidence interval (CI) 0.13–0.75). A similar pattern of the association existed in the combined GSTM1/T1 genotype that indicated the inverse association between the “traditional healthy” diet and AD in the double GSTM1/T1-present genotype group (OR 0.24, 95% CI 0.06–0.93). Results from the multiplicative test analyses showed that the “traditional healthy” diet on reduced AD was significant or borderline significant in the GSTM1-present group (OR 0.71, 95% CI 0.54–0.92 vs. GSTM1-null group) or the GSTM1/T1 double present group (OR 0.63, 95% CI 0.39–1.03 vs. GSTM1/T1 double null group). These findings demonstrate that the present type of GSTM1 may increase susceptibility to the potential effect of the “traditional healthy” diet on AD

Salty Taste Acuity Is Affected by the Joint Action of αENaC A663T Gene Polymorphism and Available Zinc Intake in Young Women

Salty taste perception affects salt intake, of which excess amounts is a major public health concern. Gene polymorphisms in salty taste receptors, zinc status and their interaction may affect salty taste perception. In this study, we examined the relationships among the α-epithelial sodium channel (αENaC) A663T genotype, zinc intake, and salty taste perception including salty taste acuity and preference in healthy young adults. The αENaC A663T genotype was determined by the PCR-restriction fragment length polymorphism in 207 adults. Zinc intake was examined by one 24-h recall and a two-day dietary record. Salty taste acuity and preference were determined by measuring the salty taste recognition threshold and the preferred salinity of beansprout soup, respectively. Men had significantly higher thresholds and preferences for salty taste than women did (p < 0.05). In women, the salty taste threshold was significantly lower in the highest tertile of available zinc intake than in the lowest tertile (12.2 mM and 17.6 mM, respectively, p = 0.02). Interestingly, a significant inverse association between available zinc intake and salty taste threshold was found only in women with αENaC AA homozygotes (β = −0.833, p = 0.02), and no such association was found in T663 allele carriers. The salty taste preference was not associated with the αENaC A663T genotype or available zinc intake in either sex. In conclusion, our data suggest that gene-nutrient interactions between the αENaC A663T genotype and available zinc intake play a role in determining the salty taste acuity in young women

Iron Supplementation Reverses the Reduction of Hydroxymethylcytosine in Hepatic DNA Associated With Chronic Alcohol Consumption in Rats

Alcohol is known to affect two epigenetic phenomena, DNA methylation and DNA hydroxymethylation, and iron is a cofactor of ten-eleven translocation (TET) enzymes that catalyze the conversion from methylcytosine to hydroxymethylcytosine. In the present study we aimed to determine the effects of alcohol on DNA hydroxymethylation and further effects of iron on alcohol associated epigenetic changes

O cálculo mental na resolução de problemas por crianças com necessidades educativas especiais : estudo de caso no 1º ciclo do ensino básico

O presente estudo tem como questão central “Que alterações se verificam nas estratégias de cálculo mental e de resolução de problemas utilizadas por crianças do 1.º ciclo do ensino básico com Atraso Global de Desenvolvimento (NEE), num contexto de uso de tarefas matemáticas que envolvem multiplicações e divisões?”. Para substanciar a investigação utilizou-se uma metodologia de natureza qualitativa e interpretativa com a forma de estudo de caso simples. Trata-se de uma investigação onde foi estudada uma aluna com NEE de caráter permanente, de forma mais pormenorizada, de uma turma do 4.º ano de escolaridade, em que a investigadora é simultaneamente professora titular. Como principais fontes de recolha de dados privilegiou-se as folhas de resolução das tarefas exploradas e dos testes implementados, no início e no final da observação, entrevista, processo individual da aluna e Plano de Trabalho de Turma. Os dados permitem afirmar que nas estratégias de resolução de problemas a aluna recorreu ao desenho, diagrama ou esquema e, também a descobrir um padrão, regra ou lei de formação. Relativamente ao cálculo mental, recorreu com mais frequência às estratégias como se recorresse ao lápis e papel e decompor um dos fatores. Ao longo da realização das tarefas foi notória a evolução em termos do tempo de execução das mesmas e a forma como comunicava as estratégias utilizadas fazendo conexões com outras tarefas já realizadas. Estas tarefas permitiram desenvolver na aluna estratégias de cálculo com base em conhecimentos que já possuía, aquisição de novas estratégias através da discussão em grande grupo, consolidação de aprendizagens pré-adquiridas e capacidade para comunicar matematicamente.Abstract The central question of the present study is "What changes are occurring in the mental calculation strategies and problem solving used by children of the 1st cycle of basic education with Global Development Delay (SEN) in the context of use of mathematical tasks involving multiplication and division?" To substantiate the research the methodology used was of qualitative and interpretative nature, in the form of a simple case study. The present is an investigation in which a student with special education needs (SEN) of a permanent character was followed. The student belongs to the 4th grade in secondary school, where the researcher is simultaneously the professor. The main sources of data collection were privileged papers on solving the tasks explored as well as tests conducted at the beginning and at the end of the observation, interviews with the individual student and the Work Plan of the Class. The data has revealed that the student´s strategies for solving problems the student include drawing, diagrams or schemes, and also pattern recognition, and rule or law training. Regarding the mental calculation process, the student resorted more often to strategies like using the pencil and paper and decomposition of the factors. Throughout the period of task completion there was a clear evolution in terms of the duration of the execution of the tasks, as well as in the way in which the strategies used were communicated, by making connections with other tasks already accomplished. These tasks contributed to the development of the student’s calculus capabilities based on the knowledge she already possessed, to the acquisition of new strategies through discussions in large groups, to the consolidation of pre-acquired knowledge, and to the ability to communicate mathematically