Interethnic diversity of NAT2 polymorphisms in Brazilian admixed populations

<p>Abstract</p> <p>Background</p> <p>N-acetyltransferase type 2 (Nat2) is a phase II drug- metabolizing enzyme that plays a key role in the bioactivation of aromatic and heterocyclic amines. Its relevance in drug metabolism and disease susceptibility remains a central theme for pharmacogenetic research, mainly because of its genetic variability among human populations. In fact, the evolutionary and ethnic-specific SNPs on the <it>NAT2 </it>gene remain a focus for the potential discoveries in personalized drug therapy and genetic markers of diseases. Despite the wide characterization of <it>NAT2 </it>SNPs frequency in established ethnic groups, little data are available for highly admixed populations. In this context, five common <it>NAT2 </it>SNPs (<it>G191A</it>, <it>C481T</it>, <it>G590A</it>, <it>A803G </it>and G<it>857A</it>) were investigated in a highly admixed population comprised of Afro-Brazilians, Whites, and Amerindians in northeastern Brazil. Thus, we sought to determine whether the distribution of <it>NAT2 </it>polymorphism is different among these three ethnic groups.</p> <p>Results</p> <p>Overall, there were no statistically significant differences in the distribution of <it>NAT2 </it>polymorphism when Afro-Brazilian and White groups were compared. Even the allele frequency of <it>191A</it>, relatively common in African descendents, was not different between the Afro-Brazilian and White groups. However, allele and genotype frequencies of <it>G590A </it>were significantly higher in the Amerindian group than either in the Afro-Brazilian or White groups. Interestingly, a haplotype block between <it>G590A </it>and <it>A803G </it>was verified exclusively among Amerindians.</p> <p>Conclusions</p> <p>Our results indicate that ethnic admixture might contribute to a particular pattern of genetic diversity in the <it>NAT2 </it>gene and also offer new insights for the investigation of possible new <it>NAT2 </it>gene-environment effects in admixed populations.</p

Dissociations between cognitive and motor effects of psychostimulants and atomoxetine in hyperactive DAT-KO mice

International audiencePsychostimulants such as amphetamine and methylphenidate, which target the dopamine transporter (DAT), are the most frequently used drugs for the treatment of hyperactivity and cognitive deficits in humans with attention deficit hyperactivity disorder (ADHD). While psychostimulants can increase activity in healthy subjects, they exert a "paradoxical" calming effect in humans with ADHD as well as in hyperactive mice lacking the dopamine transporter (DAT-KO mice). However, the mechanism of action of these drugs and their impact on cognition in the absence of DAT remain poorly understood

Repetitive transcranial magnetic stimulation induces long-lasting changes in protein expression and histone acetylation

The use of non-invasive brain stimulation like repetitive transcranial magnetic stimulation (rTMS) is an increasingly popular set of methods with promising results for the treatment of neurological and psychiatric disorders. Despite great enthusiasm, the impact of non-invasive brain stimulation on its neuronal substrates remains largely unknown. Here we show that rTMS applied over the frontal cortex of awaken mice induces dopamine D2 receptor dependent persistent changes of CDK5 and PSD-95 protein levels specifically within the stimulated brain area. Importantly, these modifications were associated with changes of histone acetylation at the promoter of these genes and prevented by administration of the histone deacetylase inhibitor MS-275. These findings show that, like several other psychoactive treatments, repeated rTMS sessions can exert long-lasting effects on neuronal substrates. This underscores the need of understanding these effects in the development of future clinical applications as well as in the establishment of improved guidelines to use rTMS in non-medical settings

Variação genética em progênies de Myracrodruon urundeuva F.F. & M.F. Allemão em três sistemas de cultivo Genetic variation in progenies of Myracrodruon urundeuva F.F. & M.F. Allemao in three cultivation systems

Myracrodruon urundeuva (aroeira) é uma das espécies arbóreas que apresentam madeira de maior durabilidade em contato com o solo. Em razão dessa característica, populações naturais de M. urundeuva, distribuídas por quase todo o Brasil, vêm sendo dizimadas. Desse modo, o presente trabalho teve por objetivo avaliar a expressão da variação genética em uma população natural de M. urundeuva procedente da Estação Ecológica do Instituto Florestal, localizada em Paulo de Faria, SP. Coletaram-se sementes de 30 árvores de polinização livre, em setembro de 1996. Com esse material, foram instalados três testes de progênies em diferentes sistemas de plantio em Selvíria, MS, obedecendo a um delineamento em blocos casualizados, com 30 tratamentos (progênies) e três repetições. Foi assumido o modelo de cruzamento misto para essa espécie. Verificou-se que houve diferença significativa nos efeitos de progênies e ambiente (testes de progênies), e a interação progênies x ambientes não foi significativa. Desse modo, as progênies apresentaram comportamento semelhante nos diferentes ambientes. A melhor "performance" das progênies foi no plantio envolvendo M. urundeuva, Guazuma ulmifolia (Lam) e Anandenanthera falcata (Benth. Speg.), as quais também apresentaram considerável variação genética, indicando alto valor para programas de conservação e melhoramento genético.<br>Myracrodruon urundeuva is one of the tree species the wood that presents the longest durability when in contact with soil. Because of this characteristic, populations of M. urundeuva have been decimated throughout Brazil. Therefore, this work aimed at analyzing the expression of genetic variation in a natural population of M. urundeuva from the Ecological Station of the Forest Institute, located in Paulo de Faria-SP. Seeds were collected from 30 free-pollination trees in September, 1996. By using this material, three progeny trials were installed in different planting systems in Selvíria - MS, following a block design with 30 treatments (progenies) and three replications. The mixed crossbreeding model for M. urundeuva was assumed. Significant differences were observed for progeny effects (progeny trials) although the progenies-environments interaction was not significant. Thus, progenies presented the same behavior in different environments; however, their best performance was in the planting involving M. urundeuva, Guazuma ulmifolia (Lam) and Anandenanthera falcata (Benth. Speg.). The progenies also presented considerable genetic variation; hence its utilization in programs for conservation and genetic improvement

Factors influencing possible delay in the diagnosis of Alzheimer's disease Findings from a tertiary Public University Hospital

Abstract Alzheimer's disease (AD) is characterized by impairment in memory and autonomy, causing excessive pressure on family and an overburdened health care system. Early diagnosis, with the appropriate treatment, is important to reduce the pattern of disease progression. Objective: The study sought to identify the most probable causes of delay in diagnosis. Methods: A cross-sectional study involving AD patients followed at an Outpatient Geriatric Clinic from a tertiary public university hospital was conducted between June 2009 and February 2011. Results: Ninety-four patients were evaluated (66% women), aged 77.76±6.8 years and with median educational level of 3 years (95% CI 2.7-3.80). Regarding severity of dementia, 51.8% of patients were classified as having mild dementia (CDR 1), 40% moderate dementia (CDR 2) and 8.2% severe dementia (CDR 3). Mean educational level of caregivers was 8.3±3.9 years. Among those who believed there was a delay, 36% stated that the "family thought that the changes were normal for the age of the patient" reporting average delay of 1.8 years (95% CI: 1.3-2.5) while 45.3% stated that the "doctor did not reach a diagnosis" reporting a median delay of 1.5 years (95% CI: 1.4-2.3). Conclusion: Based on these results, it can be concluded the time between onset of symptoms and diagnosis was excessive. This study may be useful to help increase awareness of issues not sufficiently discussed in the literature, such as diagnostic delay and influence of caregivers' educational level on treatment