Cristais líquidos são sistemas que se apresentam em um estado intermediário entre o estado sólido e líquido. A monoleína é um lipídio polar com capacidade de formar diferentes tipos de cristais líquidos liotrópicos na presença de água, caracterizados como fase lamelar, cúbica e hexagonal. Devido à capacidade de controlar a liberação dos fármacos incorporados e às propriedades mucoadesivas, estes sistemas são considerados potenciais veículos para a liberação controlada de fármacos na mucosa bucal. Sabendo que o desenvolvimento da cárie e doença periodontal está relacionado com a formação do biofilme, é necessário seu controle e prevenção para manutenção da saúde bucal. Dentre os agentes químicos disponíveis para prevenir e/ou diminuir a formação do biofilme, cloreto de cetilpiridínio (CCP), polihexametileno biguanida (PHMB) e Triclosan® têm sido amplamente utilizados. Em vista disso, o objetivo deste estudo foi desenvolver e caracterizar sistemas líquido-cristalinos de fase lamelar e cúbica formados por monoleína e água contendo antimicrobianos com aplicabilidade bucal. Os sistemas foram desenvolvidos usando monoleína e água e os antimicrobianos avaliados foram o CCP, o PHMB e o Triclosan®. A formação das fases líquido-cristalinas com e sem a presença de cada fármaco estudado foi identificada por microscopia de luz polarizada. Além disso, foi avaliado o intumescimento dos sistemas contendo os fármacos estudados após contato com saliva artificial; a atividade antimicrobiana e o perfil de liberação in vitro, bem como o tempo de permanência e a força de mucoadesão ex vivo em mucosa de bochecha de porco. Foi possível obter os sistemas líquido-cristalinos para os fármacos avaliados, e o intumescimento de todos os sistemas foi caracterizado como cinética de segunda ordem. Os resultados do perfil de liberação e da atividade antimicrobiana in vitro para PHMB e Triclosan® foram favoráveis para aplicação bucal, no entanto, o CCP não é adequado para veiculação neste sistema. O perfil de liberação dos fármacos à partir desses sistemas foi influenciado pelas propriedades físico-químicas e concentração dos fármacos, bem como pelo intumescimento. Ainda, a fase lamelar apresentou maior tempo de permanência que a fase cúbica e a força de mucoadesão média da fase lamelar foi de 1,02 ± 0,50 N e da fase cúbica foi de 0,45 ± 0,10 N. Logo, os sistemas líquido-cristalinos de monoleína e água são um interessante veículo com potencial para liberação controlada dos antimicrobianos PHMB e Triclosan® na mucosa bucal com o objetivo de otimizar a eficácia destes fármacos. / Liquid crystals are systems which are in an intermediate state between solids and liquids. Monoolein is a polar lipid capable of forming different types of lyotropic liquid crystals in aqueous environment, which can be classified into lamellar, cubic and hexagonal mesophases. Due to its ability to control drug release and its mucoadhesive properties, these systems have been considerated as potential vehicle to control drug release on buccal mucosa. Based on the knowledge that the development of caries and periodontal disease is related to the biofilm formation, it is necessary their control and prevention to maintain the buccal health. Among the available chemical agents to prevent and/or reduce biofilm formation, cetylpyridinium chloride (CPC), polyhexamethylene biguanide (PHMB) and Triclosan® have been widely used. Based on these facts, the objective of this study was to develop and characterize liquid-crystalline systems formed by monoolein and water, containing antimicrobial agents with buccal applicability. The systems were developed using monoolein and water, and the antimicrobial agents evaluated were CCP, PHMB and Triclosan®. The liquid-crystalline phases with and without the presence of each drug was identified by polarized light microscopy. Furthermore, it was evaluated the swelling of the systems containing the drugs studied after contact with artificial saliva; the in vitro antimicrobial activity and its release profile, as well as the residence time and ex vivo mucoadhesion strength on pig cheek mucosa. It was possible to obtain liquid-crystalline phases for all drugs, and the swelling of all systems was characterized according to second-order kinetics. The results of release profile and antimicrobial activity in vitro to PHMB and Triclosan® were favorable for buccal application, however CCP is not suitable to be released from these systems. The drug release profile from these systems was influenced by the physicochemical properties and loading of the drugs, as well as by swelling. Furthermore, the lamellar phase showed greater residence time that the cubic phase and the mucoadhesion strength average of lamellar phase was 1.02 ± 0.50 N and for cubic phase was 0.45 ± 0.10 N. Thus, the liquid crystalline systems forming by monoolein and water are an interesting vehicle with potential to control release of the PHMB and Triclosan® on the buccal mucosa in order to optimize the drug effectiveness.

Os filmes poliméricos a base de DNA (DNA-PFs) são um sistema de veiculação de fármacos extremamente promissor aplicado à medicina moderna além de convergir busca de alternativas mais seletivas para o tratamento de câncer de boca via Terapia Fotodinâmica. A Ftalocianina de alumínio-cloro (AlClPc) é um fotossensibilizador de segunda geração aplicado em terapia fotodinâmica (TFD) caracterizado por seu caráter anfifílico e tendência de autoagregação em meio aquoso, prejudicando diretamente seu potencial de aplicação. Objetivando a busca das melhores condições de incorporação da (AlClPc) ao (DNA) foram determinadas as melhores proporções dos componentes a serem estudadas em diferentes condições de solubilidade. Os (DNA-PFs) foram preparados via Casting e para esclarecer sua compatibilidade e aplicabilidade, foram avaliados os aspectos morfológicos, bioquímicos e adesão celular das células de carcinoma escamosas orais (OSCC) nos (DNA-PFs). Foi observada uma alteração inicial e temporária na morfologia das células, devido ao processo de ligação ao filme nos estágios iniciais, conforme esperado, que retorna então a um estado morfológico normal mais tarde na configuração. Os estudos de citometria de fluxo mostraram baixa citotoxicidade de (DNA-PFs) no sistema, apresentando viabilidade superior a 90% em todos os (DNA-PFs) testados. Corroboram com esses resultados as análises da cinética do ciclo celular, mostrando que a cinética das células OSCC é mantida na presença de (DNA-PFs). Esses resultados indicam uma alta biocompatibilidade dos (DNA-PFs) produzidos. Após a incorporação da (Al- ClPc) aos (DNA-PFs) efetuou-se o uso do novo do sistema de veiculação aplicado a (TFD). Ficando evidente o aumento da morte celular, nas respectivas doses aplicadas. Tento em vista a redução de viabilidade celular apresentada pelo tratamento dos (DNA-PFs-AlClPc) verificou- se ainda o tipo de morte celular induzida pelo tratamento indicando como via preferencial de morte celular ocasionado por apoptose Estes resultados servem como base e possibilitam a abertura de novas perspectiva do potencial uso dos (DNA-PFs) aplicados como sistema de veiculação de fármacos para o tratamento fotodinâmico. / DNA-based polymer films (DNA-PFs) are an active drug delivery system applied to modern medicine besides converging search for more selective alternatives for the treatment of oral cancer through Photodynamic Therapy (PDT). Aluminum chlorine phthalocyanine (AlClPc) is a second-generation photosensitizer applied in PDT characterized by amphiphilic and tendency for self-aggregation in the aqueous medium, directly damaging its application potential. Aiming the search for the best conditions of incorporation of AlClPc to DNA the best proportions of the components to be studied under different solubility conditions were determined. The DNA-PFs were prepared via Casting and to clarify their compatibility and applicability, the morphological, biochemical and cell adhesion aspects of oral squamous cell carcinoma (OSCC) were evaluated in DNA-PFs. An initial and temporary alteration in cell morphology was observed due to the process of binding to the film in the initial stages, as expected, which then returns to a normal morphological state later in the configuration. Flow cytometry studies showed low cytotoxicity of DNA-PFs in the system, presenting viability higher than 90% in all DNA-PFs tested. They corroborate with these results the analyzes of the cell cycle kinetics, showing that the kinetics of OSCC cells is maintained in the presence of DNA-PFs. These results demonstrate high biocompatibility of the DNA-PFs produced. After incorporation of AlClPc to the DNA-PFs, the new one of the delivery system applied to PDT was used. The increase in cell death was evident in the several doses applied. Given the reduction of cell viability presented by the treatment of DNA-PFs-AlClPc, the type of cell death induced by the treatment was also showing, as the preferential route of cell death caused by apoptosis. These results allow new opportunities for potential use DNA-PFs DNA applied as a drug delivery system for PDT.

Introdução Este trabalho objetivou analisar a recente inserção da saúde bucal no Programa Saúde da Família (PSF) no que se refere ao vínculo, ao acesso, à integralidade da atenção e à resolutividade dos problemas de saúde bucal. Objetivo - Identificar as opiniões, percepções e necessidades dos usuários adultos da UBS Vila Espanhola, município de São Paulo, em relação à sua saúde bucal e ao serviço de atenção à saúde bucal a eles oferecido pelo PSF. Metodologia Pesquisa qualitativa, composta pelas seguintes etapas: observação sistemática das atividades da equipe de saúde bucal da UBS estudada e entrevista com os usuários adultos, maiores de 18 anos, que tiveram algum tipo de atendimento odontológico na UBS nos últimos 6 meses. Na fase de análise optou-se pela técnica de análise de conteúdo. Resultados Realizaram-se 25 entrevistas e percebeu-se que a inserção do PSF aumentou o acesso da população estudada na região da UBS, aumento que trouxe maior demanda por serviços especializados em odontologia. Contudo, os usuários não estão conseguindo utilizar esses serviços de atenção secundária em saúde bucal. As entrevistas também trouxeram algumas questões levantadas pelos usuários, como a constante troca de dentistas na equipe, comprometendo o vínculo, a falta de autonomia dos usuários com relação à própria saúde bucal, a da falta de credibilidade no setor público, a do papel do ACS na equipe, a da forma como são efetuados os grupos de escovação, a questão do espaço físico onde são realizados os atendimentos e a forma como é aplicado o princípio da equidade para priorizar os atendimentos. Conclusão - A inserção da saúde bucal no PSF trouxe alguns avanços, porém precisa ser reavaliada para realmente conseguir atingir suas principais propostas, como a integralidade da atenção, a equidade, entre outras. / Introduction This study aims to analyze the recent insertion of oral health in the Family Health Program PSF considering link, access, integrity of attention and in to oral problems resolution. Buccal Health, which has always been apart from health public politics in this country, has now the opportunity to, at last, be part of the Unified Health System. Objective Identify opinions, perceptions and necessities of the adults patients from Vila Espanhola UBS (Health Basic Unity), São Paulo city, in relation to dental health and the service of attention to buccal health offered by the PSF. Methodology Qualitative research made of the following steps: systematic observation of the activities done by the buccal health team of the studied UBS, and interview with the adult patients, older than 18, that had any kind of attention in the past six months. In the analyses phase, we opted by the content analysis. Results: It was done 25 interviews and it was noticed that the insertion of PSF increased the access of the studied population in the UBS region, however this increase brought a bigger demand by specialized oral services. The patients are not being able to have access to those secondary attentions in buccal health. The interviews also brought some patients question such as the constant changing of the dentists in the team - compromising the link, lack of patients autonomy in relation to their own oral health, lack of credibility of public politics, the roll of the ACS in the team, the way how it is applied the equity principle to prioritize the cares. Conclusion: The insertion of buccal health in the PSF brought some advances, however it needs to be reevaluated to really reach its main proposals as integrality of attention, equity among others needs.

[Truncated abstract] The collection of buccal cells is common practise in the epidemiological and forensic science. Unlike venipuncture collection of blood; it is a safer, non-invasive method for collection of biological material. The methods by which these cells are collected from the inner cheek of an individual and stored are the key elements in preserving DNA. Typically, forensic samples require long term storage. Samples are commonly collected on cotton swabs and stored moist at low to ultra-low temperatures (less than -20oC). Although this is the method of choice in most forensic facilities, there are drawbacks. The samples are inherently contaminated with microflora within the oral cavity and the moisture allows a plethora of microorganisms to grow. As the time frame that has elapsed from collection to storage increases, there is an exponential increase in bacterial cells. Storage of containers containing swabs coated with cells at temperatures below 20oC is also costly due to requirements for large freezers which are running and monitored over 24 hours. In the pass 10 to 15 years, researchers have focussed on alternative ways to store buccal cells. The FTA card system by Whatman is one such development. The FTA card is unique in that it provides a means for the collection of buccal cells for storage at room temperature. DNA profiling from samples stored in this way for 11 years has been successfully achieved. The filter paper matrix of the FTA card binds and subsequently lyses cells. ... (2) The second component of this thesis describes a study which subjected cells on buccal swabs to various conditions of increased temperature over periods of time to establish if DNA could be amplified. The aim was to mimic exposure to the vigours of field conditions, particularly in the extreme local environments that prevail in the United Arab Emirates. a. Initially, buccal cells stored at -20oC over 360 days were used to mimic standard archiving procedures. The cells were subsequently transferred to FTA cards, amplified and profiled by using ABI AmpFLSTR Identifiler PCR Amplification Kit (Applied Biosystems, Foster City, CA). Complete STR profiles were successfully recovered from the archived swabs. In most cases 100% of alleles were recovered, suggesting that it is feasible to transfer DNA from properly archived buccal swabs to FTA cards. b. The second phase involved the storage of fresh swabs that had been artificially aged by using incubation temperatures ranging from 40oC to 100oC. Partial profiles resulted from artificially aged samples, indicating that the prevailing conditions prior to low temperature storage of the swabs plays an important role in ensuring cellular integrity and thus, DNA quality. Results from this study suggest that it is possible for biological samples stored under correct conditions to be transferred from swabs to FTA card. In combination, the two chapters presented in this study show that it is feasible to transfer achieved forensic biology samples from swabs to the FTA card system. However, it is necessary to ensure that the samples are treated in the correct manner so as to minimise contamination from external sources and to maintain the correct environmental state to maintain intact cells and usable DNA.

A. A study of Stichodactyla helianthus toxin’s potential to penetrate the buccal mucosa Introduction:  Buccal mucosa is an alternative route for drug administration and has advantages over other conventional routes by avoiding both enzymes in the gastro intestinal system and the hepatic first passage mechanism. Stichodactyla helianthus toxin (ShK) is a peptide toxin that blocks potassium channels in T lymphocytes and could be a future treatment for autoimmune diseases when finding a suitable way of administration. Aim:  The purpose of this part of the study was to develop a robust and reproducible assay for identification and quantification of ShK. The method was then employed for a proof of principle study; determining the concentration of ShK following an in vitro permeability experiment, to evaluate the potential of ShK penetrating the buccal mucosa in porcine tissue.  Materials and Methods:  An HPLC method was developed and validated. A piece of porcine buccal mucosa was used as a membrane because of its similarities with human buccal mucosa, and cinched in between a modified Ussing Chamber consisting of a donor and a receptor chamber. Samples were withdrawn from the receptor chamber to determine the amount of ShK that had penetrated the membrane. Results: The HPLC method developed for quantification of ShK demonstrated high accuracy and precision. No concentrations of ShK were able to be quantified from the receptor chambers. Conclusions:  A robust assay for quantification of ShK was developed but the results from the experiment indicated that ShK could not penetrate the buccal mucosa membrane. B. An investigation of the permeability alterations in the blood-brain barrier associated with Alzheimer’s disease   Introduction:  The blood brain barrier (BBB) protects the brain from potential dangerous substances by different barrier properties such as tight junctions and efflux transporters such as P-glycoprotein. Previous studies have showed that the barrier functions may be altered in Alzheimer’s disease and thereby increase the exposure to substances that are normally excluded from the brain parenchyma. This could be an issue regarding safety and toxicity of medications used among Alzheimer patients. Aim:  The aim of this part of the study was to investigate the difference in brain uptake of verapamil, digoxin, loperamide, propanolol, diazepam and sucrose between 3xTg-AD mice and wild type control mice. Materials and Methods: Female 3xTg-AD mice and control mice of the age 11.5-13.5 months were used. In Situ brain perfusion with radiolabeled substances (n=5-12) was performed and the brain uptake ratio of the substances was compared and statistically analyzed.  Results: No difference in the vascular volume was found when comparing 3xTg-AD with control mice. The ratio of diazepam was observed to be higher in the cortex and propranolol higher in the hippocampus, of 3xTg-AD mice. The uptake ratio of verapamil was higher in both the hippocampus and cortex of 3xTg-AD mice whereas digoxin appeared to be lower in the cortex of 3xTg-AD mice. There was no difference in uptake ratio of loperamide between 3xTg-AD and control mice. Conclusions:  This study in addition to previously executed studies in our laboratory, showed that the membrane thickness is age dependent in 3xTg-AD and that further studies needs to be conducted on the expression of P-glycoprotein in the BBB in 3xTg-AD and control mice.

PurposeThe purpose of this pilot study was to explore nutritional injury in the context of oral mucositis (OM). It was a beginning look at oral L-glutamine (L-Gln) treatment efficacy through investigation of three "Reaction-to-Nutritional Injury" hypotheses defining OM as a localized secondary nutritional disorder of deficiency (Van Itallie, 1977) resulting from absence of/limited nutritional collateral systems (Kight, 1994):(1) OM severity and human buccal epithelial cell glutamine synthetase (HBEC GS) abundance,(2) HBEC GS abundance and L-Gln treatment, and(3) OM severity and L-Gln treatment.Patients and MethodsThree female colorectal cancer (CRC) outpatients between 61 and 70 years of age receiving FOLFIRI chemotherapy regimen and diagnosed with grades 1 and 2 OM were followed daily throughout treatment cycles and randomly assigned into a two-week mouthwash regimen of 1.0 gm/m2 qid L-Gln or placebo. Treatment crossover occurred every two weeks without defined washout periods. Four controls were recruited as controls for single Western blot (WB) analyses.ResultsOral L-Gln effect on OM severity was statistically significant in all three study participants, although two of the relationships had positive direction. Treatment and OM severity were moderately correlated with a negative direction in one patient. Glutamine appeared to be most efficacious in severe grade 2 OM erythema. Western blot analysis demonstrated absence of HBEC GS activity in cancer patients receiving FOLFIRI treatment for colorectal cancer suggesting competitive inhibition of GS enzyme by chemotherapy. Higher WB bands observed at 55 and 66 kDa may be O-linked glycosylation posttranslational modifications, a possible explanation for the Gln-influenced mechanism of Hsp70 biosynthesis and apoptosis prevention. This may be suggestive of compression of the nutritional injury clinical horizon from stage 4 to stage 1 or 2 where adaptation to absence of/limited nutritional collateral systems theoretically begins after chemotherapy insult. An extended definition of nutritional injury may be the acquired loss of nutritional status at the biomolecular level by way of drug-induced disruption of normal, adaptive metabolic pathways resulting in absence of/limited HBEC GS abundance affecting Gln and Hsp70 availability. This may suggest the need for preemptive L-Gln treatment prior to initiation of a 5-fluorouracil-based chemotherapy regimen.

Objective: To collect data regarding Canadian laypersons perceptions of smile esthetics and compare these data to US data in order to evaluate cultural differences. Methods: Using Adobe® Photoshop® 7, a digital image of a posed smile of a sexually ambiguous lower face was prepared so that hard and soft tissue could be manipulated to alter Buccal Corridor (BC), Gingival display (GD), Occlusal Cant (OC), Maxillary Midline to Face Discrepancy (MMFD) and Lateral Central Gingival Discrepancy (LCGD). Adult Canadian laypersons (n=103) completed an interactive computer-based survey of 29 randomized images to compare smile preferences for these variable. The custom survey was developed to display fluid, continuously appearing modifiable smile variables using MATLAB® R2008 for presentation. These data were compared to previously published data for US laypersons. Statistical inference was determined using Wilcoxon Rank Sum tests. Results: Canadian laypersons were more sensitive in detecting deviations from ideal and had a narrower range of acceptability thresholds for BC, GD, OC, MMFD and LCGD. Ideal esthetic values were significantly different only for BC. Conclusions: It appears cultural differences do exist related to smile characteristics. Clinically significant differences in the preference of the smile characteristics were found between Canadian and US laypersons. Canadian laypersons, on average, were more discriminating to deviations from ideal and had a narrower range of acceptability.

Objective: To collect data regarding Canadian laypersons perceptions of smile esthetics and compare these data to US data in order to evaluate cultural differences. Methods: Using Adobe® Photoshop® 7, a digital image of a posed smile of a sexually ambiguous lower face was prepared so that hard and soft tissue could be manipulated to alter Buccal Corridor (BC), Gingival display (GD), Occlusal Cant (OC), Maxillary Midline to Face Discrepancy (MMFD) and Lateral Central Gingival Discrepancy (LCGD). Adult Canadian laypersons (n=103) completed an interactive computer-based survey of 29 randomized images to compare smile preferences for these variable. The custom survey was developed to display fluid, continuously appearing modifiable smile variables using MATLAB® R2008 for presentation. These data were compared to previously published data for US laypersons. Statistical inference was determined using Wilcoxon Rank Sum tests. Results: Canadian laypersons were more sensitive in detecting deviations from ideal and had a narrower range of acceptability thresholds for BC, GD, OC, MMFD and LCGD. Ideal esthetic values were significantly different only for BC. Conclusions: It appears cultural differences do exist related to smile characteristics. Clinically significant differences in the preference of the smile characteristics were found between Canadian and US laypersons. Canadian laypersons, on average, were more discriminating to deviations from ideal and had a narrower range of acceptability.

Submitted by (lucia.rodrigues@ufrpe.br) on 2016-11-03T12:09:24Z No. of bitstreams: 1 Eduardo Henriques de Melo.pdf: 703764 bytes, checksum: c360edd05aff9a48a94de6c65a86a2b0 (MD5) / Made available in DSpace on 2016-11-03T12:09:24Z (GMT). No. of bitstreams: 1 Eduardo Henriques de Melo.pdf: 703764 bytes, checksum: c360edd05aff9a48a94de6c65a86a2b0 (MD5) Previous issue date: 2005-02-23 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / This study was aimed to identify, to describe and to interpret the aspects under consideration during a teachers trainning process in buccal health, which were implemented in classroom practice by a group of primary teachers in a public school in Garanhuns-PE, Brazil. Interviews were conducted whith these teachers in order to identify their previous conceptions about buccal health, as well as the aspects considered by them as the most important in trainning process, which was supervised by a dentist. Some lessons given by these teachers were videotaped. Thus, the data collected were qualitative as well as quantitative. Among several contents in buccal health, these teachers emphasized dental caries, especially their prevention by means of adequate feeding, brushing and use of dental floss. These teachers also presented some conceptual failures, which indicated the necessity of transforming this trainning process in a continous education process, under the supervision of health and education specialists, in order to achieve a high standard in an educative work involving buccal health. / Este estudo objetivou identificar, descrever e interpretar os aspectos trabalhados em um processo de capacitação em saúde bucal, que foram implementados na sala de aula por um grupo de professoras das séries iniciais de uma escola da Rede Pública Estadual em Garanhuns-PE. Foram realizadas entrevistas para identificar as concepções prévias das professoras acerca da Saúde Bucal, bem como os aspectos mais importantes por elas percebidos no processo de capacitação, que foi mediado por um cirurgião-dentista. Também foram gravadas algumas aulas das professoras em vídeo. Dessa forma, a coleta de dados teve um enfoque qualitativo e descritivo. Entre os diversos conteúdos de saúde bucal trabalhados nesse processo, durante suas aulas, as professoras privilegiaram a abordagem da cárie dental, sua prevenção através da alimentação, da escovação e do uso do fio dental. Algumas falhas conceituais foram apresentadas pelas professoras, demonstrando a necessidade de transformar essa capacitação num processo de formação continuada, que mantivesse em contato direto especialistas da sociedade e profissionais da educação, visando à qualidade do trabalho educativo em saúde bucal.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Polymorphisms in the apolipoprotein E (APOE) have constituted the major rationale to identify potential risk groups for developing late-onset Alzheimer's disease and help to predict recovery of cognitive function after brain injury. However, the APOE impact on cognitive development in children living in poor areas of the developing world, where we have discovered profound significant associations of early childhood diarrhea (at 0-2 yo) with lasting impairments of growth, cognition and school performance, is not known. Therefore, we conducted APOE genotyping in 72 Brazilian shantytown children under active surveillance since birth, using purified DNA extracted from buccal cell samples. We found a high frequency of APOE4 alleles (18% vs 9-11% expected) in children with lower diarrhea burdens. When we examined the children who experienced the heavier diarrhea burdens (+/- median of 7 illnesses in the first 2 years of life), those with APOE4 did significantly better in the coding subtest (39 +/- 9.9; n=7, p=0.01), when compared with APOE4 negative children with similar diarrhea burdens (25 +/- 12.7; n=27). Positive correlations between the APOE4 occurrence and coding scores remained even after adjusting for family income, maternal education and breast-feeding (p<0.05). Moreover, the APOE4 positive group, under heavy burdens of diarrhea, preserved semantic fluency and the mean difference in fluency scores (DIFF), n=73, p=0.025, a standardized coefficient for disproportional verbal fluency impairment. Our findings show that APOE4 is relatively common in children from the GonÃalves Dias Community in the Northeast Brazil and suggest a protective role of APOE4 allele in children with a history of heavy burdens of diarrhea in their first 2 years of life. / Os polimorfismos da apolipoproteÃna E (APOE) tÃm se constituÃdo no principal mÃtodo para identificar grupos de risco para desenvolver a doenÃa de Alzheimer de inÃcio tardio e para servir de prognÃstico da recuperaÃÃo da funÃÃo cognitiva apÃs traumatismo craniano. Entretanto, o impacto da APOE no desenvolvimento cognitivo de crianÃas de Ãreas pobres do Brasil, onde nÃs jà temos encontrado associaÃÃes profundas e significativas entre os eventos de diarrÃia infantil precoce (aos 0-2 anos de idade) com o comprometimento duradouro do crescimento, cogniÃÃo e performance escolar, nÃo à ainda conhecido. Portanto, nÃs conduzimos um estudo da genotipagem da APOE em 72 crianÃas da Comunidade GonÃalves Dias, em Fortaleza, Nordeste do Brasil, acompanhadas por um projeto coorte desde o nascimento, utilizando DNA extraÃdo de amostras de cÃlulas bucais. Nesse trabalho, encontramos uma elevada freqÃÃncia dos alelos da APOE4 (18% vs 9-11% esperada) em crianÃas com baixa morbidade de diarrÃia. Quando avaliamos as crianÃas que apresentaram elevada morbidade de diarrÃia (+/- mediana de 7 episÃdios nos primeiros 2 anos de vida), Ãquelas portadores do alelo APOE4 mostraram uma melhor performance cognitiva no subteste de coding (39 +/- 9,9; n=7, p=0,01), quando comparadas com crianÃas negativas para o alelo APOE4 com similar morbidade de diarrÃia (25 +/- 12,7; n=27). CorrelaÃÃes positivas entre a ocorrÃncia do alelo APOE4 e os escores de coding permaneceram, mesmo apÃs controlar para renda familiar, educaÃÃo materna e aleitamento materno (p<0,05). AlÃm disso, o grupo positivo para APOE4, com elevada morbidade de diarrÃia, preservou a fluÃncia semÃntica e a diferenÃa mÃdia dos escores de fluÃncia semÃntica (DIFF), n=73, p=0,025, um coeficiente padrÃo para avaliar o impedimento desproporcional da fluÃncia verbal. Nossos achados, portanto, mostram que o alelo APOE4 à relativamente comum em crianÃas da Comunidade GonÃalves Dias, no Nordeste do Brasil, e sugerem um papel protetor do alelo APOE4 em crianÃas com histÃria de alta morbidade de diarrÃia nos primeiros dois anos de idade.