Dissertations / Theses on the topic 'Lead exposure; cognitive; development'

The modern comprehensive approach in problem solving was adopted in this study to resolve the analytical problems associated with the differential diagnosis of various degrees of exposure to lead. Thorough investigation of all the analytical steps was undertaken starting with the sampling procedure, through the proper choice of the analytical methods for the analysis of indicators of dose and indicators of effect, to the data reduction and evaluation. Reliable, selective and sensitive analytical techniques were developed for the direct analysis of lead, bismuth, antimony and the porphyrin carboxylic acids in body fluids. The sampling step was arbitrarily re-defined on the basis of the lead metabolic model to include two sampling conditions: the non-steady state and the steady state conditions. For diagnostic purposes the results obtained when sampling is done in the non-steady state proved to be more valuable. Analytical results obtained from the steady state condition were also quite revealing. A direct, sensitive, selective and reliable potentiometric stripping analysis method for the trace determination of lead as an indicator of dose in blood,plasma and urine was developed. The various parameters and experimental conditions were investigated. The signals obtained from dearated solutions of the samples using Hg(II) as the oxidant were compared with those obtained from nondearated solutions in which dissolved oxygen acted as the oxidant. The low detection limits of the former method ensured that during the analysis of control specimens in particular, the analyst ',\/ill not be working near the detection limits of the method. Freedom from organic and inorganic interferences coupled with enhancement of the sensitivity due to matrix effects rendered the method particularly useful. By slight modification of the pro- xcedure a wide working range can be attained. Good correlation coefficients bet'ofJeen added and measured Pb(Il) were obtained and method comparison with the thermal ionization stable isotope dilution mass spectrometry and the atomic absorption spectrometry gave a correlation of 0.9999. The adopted PSA in dilute dearated samples of body fluids was adapted for the determination of trace concentrations of Bi(!Il) and Sb(IlI) in body fluids. Slight modifications of the electrolyzing potential using the in situ plating procedure and longer deposition periods were necessary. The results indicated that in subjects highly exposed to lead, high concentrations of Si(lIl) and Sb(III) were detected. An ion pair reversed phase HPLC method coupled with fluorescence detection proved valuable for the analysis of blood and urinary porphyrin carboxylic acids. By optimization of the chromatographic conditions using either the fast RP-C18 Ultrasphere XL-DDS column or the Lichrosorb RP-C2 column and multinear gradient eiution with a mobile phase consisting of methanol/water, both containing 5 mMol/1 tetrabutylammonium phosphate as the counter ion, we were able to detect the earliest biochemical changes that occur in the haem biosynthetic pathway resulting from exposure to lead. The developed method permitted the detection of porphyrins in trace concentrations of 0.2 ng directly in urine samples without tedious sample pretreatment. A wide linear response curve was obtained. The method allows the differential diagnosis of the various diseases that produce derangements in the haem biosynthetic pathway.

This study explored educators’ perceptions of the impact of exposure to violence on children and their intellectual development. Substitute concepts such as corporal punishment, child maltreatment, and others were considered relevant to formation of an individual’s identity. The study also explored the psychological impact of trauma over time, and its effect on an individual’s cognitive development, identity formation, and relational development. Various aspects of exposure to violence were examined, as questions arose regarding how these multiple forms of exposure to violence impact an individual’s level of functionality. This study utilized a general qualitative approach informed by case study methodologies.

Four educators who worked with children previously exposed to violence were interviewed. Although both teachers and tutors were solicited, only tutors responded to the invitation to participate; therefore, the results are based upon interviews with four tutors. Four specific themes emerged from the participant interviews, namely: the realities of children exposed to violence, the impact of violence, academic performance, and the role of the tutor. Within some themes, subthemes emerged such as emotional violence, physical violence, limited family support, the impact of violence, resiliency, combativeness, and lack of friendships. A narrative of themes and subthemes was presented. Commensurate with the focus of the research, the predominant theme identified in this research was that of violence and aggression on the part of adults, seen through the prism of the experiences of the children in their care.

A major consequence of contamination at the local level’s population as it relates to environmental health and environmental engineering is childhood lead poisoning. Environmental contamination is one of the pressing environmental concerns facing the world today. Current approaches often focus on large contaminated industrial size sites that are designated by regulatory agencies for site remediation. Prior to this study, there were no known published studies conducted at the local and smaller scale, such as neighborhoods, where often much of the contamination is present to remediate. An environmental health study of local lead-poisoning data in Liberty City, Little Haiti and eastern Little Havana in Miami-Dade County, Florida accounted for a disproportionately high number of the county’s reported childhood lead poisoning cases. An engineering system was developed and designed for a comprehensive risk management methodology that is distinctively applicable to the geographical and environmental conditions of Miami-Dade County, Florida. Furthermore, a scientific approach for interpreting environmental health concerns, while involving detailed environmental engineering control measures and methods for site remediation in contained media was developed for implementation. Test samples were obtained from residents and sites in those specific communities in Miami-Dade County, Florida (Gasana and Chamorro 2002). Currently lead does not have an Oral Assessment, Inhalation Assessment, and Oral Slope Factor; variables that are required to run a quantitative risk assessment. However, various institutional controls from federal agencies’ standards and regulation for contaminated lead in media yield adequate maximum concentration limits (MCLs). For this study an MCL of .0015 (mg/L) was used. A risk management approach concerning contaminated media involving lead demonstrates that the linkage of environmental health and environmental engineering can yield a feasible solution.

Les perturbateurs endocriniens (PE) sont des composés synthétiques capables de se lier aux récepteurs cellulaires et d'imiter ou de bloquer le fonctionnement des hormones naturelles, pouvant ainsi entraîner des effets néfastes sur la santé. Ces dernières années, des hypothèses ont été émises selon lesquelles les PE pourraient également contribuer au développement de maladies allergiques et respiratoires. En outre, il est probable que les PE pourraient déjà agir pendant la grossesse en provoquant un diabète gestationnel (DG) et une hypertension induite par la grossesse, pouvant également provoquer une hypertension et un diabète plus tard dans la vie. Ce travail de thèse a permis de mettre en évidence que l'exposition maternelle aux phtalates et aux métaux lourds (plomb, cadmium et manganèse) pendant la grossesse pourrait être associée au diabète gestationnel, à l'hypertension induite par la grossesse et à l'eczéma/dermatite atopique chez l'enfant. Nous avons utilisé les données de la cohorte Française de naissance mère-enfant, EDEN (Étude des déterminants pré et post-natals du développement de la santé de l’enfant) pour examiner les hypothèses de ce travail de thèse. Nos résultats apportent de nouvelles preuves potentielles sur la relation entre les perturbateurs endocriniens (phtalates et métaux lourds étudiés) et la santé de la mère et de l’enfant, selon lesquelles l’exposition prénatale à certains phtalates et métaux toxiques lourds pourrait jouer un rôle dans le développement du diabète gestationnel et de l’hypertension induite par la grossesse pendant la grossesse et, ultérieurement, un eczéma pendant la petite enfance
All humans are exposed to chemicals in everyday life, from food, indoor environment, cosmetics and other products that surround us at home and at work. Endocrine disruptors (EDCs) are man-made compounds that can bind to cell receptors and mimic or block the functions of natural hormones potentially resulting in adverse health effects. In recent years, hypotheses have been put forward that EDCs may contribute also to the development of allergic and respiratory diseases. In addition, it is likely that EDCs could act already during pregnancy by causing gestational diabetes mellitus and pregnancy induced hypertension, which may also trigger to develop hypertension and diabetes mellitus later in life. This dissertation provides evidence that maternal exposure to phthalates and heavy metals (Lead, Cadmium and Manganese) during pregnancy may be associated with gestational diabetes mellitus, pregnancy induced hypertension and later eczema/atopic dermatitis in children. We used ongoing French EDEN-mother child cohort data for our three studies. Our results add new suggestive evidence on the relationship between EDCs (phthalates and heavy metals we studied) and maternal and children health, that prenatal exposure to certain phthalates and heavy toxic metals may play a role in the development of gestational diabetes mellitus and pregnancy induced hypertension during pregnancy and later eczema in early childhood. Future research focusing on larger populations and addressing multiple exposures assessed prenatally and postnatally are required to provide more evidence on possible contributions of emerging pollutants to study the role of phthalates and heavy metals

A violência e a agressividade fazem são parte integral do comportamento humano. Crianças criadas em ambientes violentos apresentam maior chance de desenvolver psicopatologias como ansiedade e depressão, apresentam menor desempenho escolar e regulação alterada do eixo de resposta ao estresse. Os mecanismos que levam a tais desfechos são complexos e difíceis de estudar em humanos. Até o presente momento, não existem modelos animais especificamente desenvolvidos para estudo do ambiente violento precoce e suas consequências. O presente trabalho objetivou o desenvolvimento e caracterização de um modelo animal para estudo do impacto do ambiente violento precoce sobre o desenvolvimento, com validade de construto, validade de face (aparente) e validade preditiva. Para tal, utilizamos o estresse social durante a lactação pela inserção de um macho intruso na caixa moradia da fêmea e sua prole por 5 minutos durante o ciclo claro nos dias 3, 5, 7 e 9 de vida pós-natal. Os desfechos avaliados para validade de face foram ansiedade juvenil e adulta, resposta ao estresse e capacidade cognitiva. Os desfechos avaliados para validade preditiva foram os efeitos da variação do comportamento maternal sobre os desfechos que conferem validade de face ao modelo. A intervenção com macho intruso teve forte impacto sobre a prole e a genitora. Houve redução do comportamento de amamentação nos 30 minutos após cada intervenção em comparação com ninhadas controles em horário semelhante. As genitoras do grupo violência apresentaram aumento da fração de corticosterona plasmática ligada a proteínas. Filhotes machos do grupo violência apresentaram redução da concentração basal de corticosterona 30-40 minutos após a segunda intervenção, perdurando na idade juvenil e adulta. A intervenção levou ao aumento do comportamento semelhante a ansiedade na idade juvenil em machos e fêmeas. Filhotes machos apresentaram aumento do comportamento semelhante à ansiedade e redução no desempenho cognitivo na idade adulta, além de redução da massa corporal ao longo de toda a vida e resposta exacerbada ao estresse psicológico repetido na idade adulta. Comportamentos maternais tidos como de qualidade (amamentação com dorso arqueado e lambida) foram frequentemente relacionados com proteção contra os efeitos do ambiente violento. Ansiedade da genitora teve correlação direta com os desfechos deletérios sobre os filhotes. Os desfechos de validação esperados foram confirmados. A Intervenção se mostrou um modelo consistente de ambiente violento precoce, com validade de construto, de face e preditiva.
Violence and aggressive behavior are part of human society from the begining. Although there are several public policies for violence control, it is still common and its consequences are present in modern society. Children raised in a violent environment have increased odds of developing psychopathology, like anxiety and depressive behavior, show decreased school performance and poor regulation of the hypothalamic-pituitary-adrenal axis. Mechanisms underlying those outcomes are complex and difficult to study in humans. Until present time, there are no animal models developed specifically for the study of early violent environment and its consequences. The aim of the present study was to develop and describe an animal model of early violent environment, with construct validity, face validity and predictive validity. We choose social stress during lactancy by the insertion of a male intruder in the dams home cage in the presence of its offspring as an intervention. A adult male rat was inserted for 5 minutes in dams home cage on post-natal days 3, 5, 7 and 9, during lights-on period. The outcomes assessed for face validity were Anxiety, stress response and cognitive performance. The outcomes assessed for predictive validity were maternal care variation and its impact on anxiety, cognitive performance and stress response regulation. The selected intervention had strong effects on the dams and offspring. Nursing behavior was decreased on the 30 minutes after each intervention. Violent environment dams displayed a shift in plasma corticosterone from the free to the bound fraction. Male pups showed decreased plasma corticosterone 30-40 minutes after the second intruder session, lasting throughout life. Male and female pups had increased juvenile anxiety. Male pups had increased anxiety, decreased cognitive performance and increased response to repeated psychological stress in adulthood. Maternal care quality was frequently associated with reduction better outcomes in the offspring. Maternal anxiety was found to be correlated to deleterious outcomes in the offspring. The intervention proved to be a consistent model of early violent environment, showing strong construct validity, face validity and predictive validity.

La néophobie et la sélectivité alimentaire des jeunes enfants ont des conséquences préoccupantes sur la santé notamment parce qu’elles concernent les fruits et les légumes. Il est donc essentiel de promouvoir l’adoption de comportements alimentaires sains chez le jeune enfant. Dans ce contexte, le premier objectif de la thèse était de développer un questionnaire pour mesurer efficacement la néophobie et la sélectivité alimentaire chez les enfants français dès l'âge de 2 ans. Le questionnaire développé dans cette thèse est un outil efficace pour étudier les rejets chez cette population. Le deuxième objectif était de mieux définir le concept de sélectivité alimentaire et d’étudier la relation entre néophobie et sélectivité. Les résultats ont montré que la néophobie et la sélectivité capturent un même type de peur pour les aliments nouveaux et potentiellement toxiques. Le troisième objectif était d'étudier directement la relation entre le développement de la catégorisation des aliments chez les jeunes enfants et leur niveau de néophobie et sélectivité alimentaire. Les résultats ont montré des liens négatifs entre développement cognitif et rejets alimentaires. L'acceptation des aliments dépend probablement de la maturité du système de catégorisation alimentaire. Enfin, le quatrième objectif était de concevoir une intervention, en exploitant les données empiriques sur la relation entre développement cognitif et rejets alimentaires, afin d'influencer positivement ces derniers chez les enfants. Les résultats montrent que l'exposition visuelle est efficace pour diminuer les comportements de rejets alimentaires
Food neophobia and pickiness in young children are two strong barriers to fruit and vegetable consumption. It is therefore essential to understand the mechanisms underpinning these two kinds of food rejections to promote the adoption of healthy eating behaviors among preschoolers. In this context, the first objective of the thesis was to develop a hetero-assessment scale to measure efficiently food neophobia and pickiness for French children as young as 2 years of age. The scale developed represents an efficient tool for studying food rejection dispositions in this young population. The second objective was to clarify the concept of pickiness and to provide an insight into the relationship between food neophobia and pickiness. The results revealed that food neophobia and pickiness capture a same kind of fear for new and potentially toxic food. The third objective was to directly investigate the relationship between food categorization development in young children and their food neophobia and pickiness. The thesis is one of the first studies to investigate directly this relationship.This investigation revealed negative connections between cognitive development and food rejection dispositions. Food acceptance probably depends on the maturity of the food categorization system. Finally, the fourth objective was to design an intervention, exploiting the empirical evidence on the relationship between food categorization and food rejections, to positively influence children food rejections. The results add to the promising body of evidence that visual exposure is effective to decrease food rejection behaviors

This study explores the relationship between children‘s cognitive abilities and lead (Pb) exposure within the theoretical framework provided by the Cattell-Horn-Carroll (CHC) taxonomy of cognitive abilities. An abundance of research has centered upon the environmental neurotoxicant Pb and the outcomes of severe Pb poisoning (like brain damage and coma) are undisputed. Whilst people in industrialised societies have 500-to-1000 times more Pb in their bodies than their prehistoric ancestors, successful abatement programs have meant that Pb levels in humans are currently their lowest in 50 years. Paradoxically, questions have emerged about the effects of even these low levels of Pb exposure on children‘s cognitive abilities. Indeed, research (Lanphear, Hornung, Khoury, Yolton, Baghurst, Bellinger et al., 2005) has suggested that lower levels of Pb exposure may have a more deleterious impact on children's cognitive abilities than exposure at higher levels. This study investigates the relationship between low-level Pb exposure (mean blood lead (PbB) concentration = 4.97 μg/dL, standard deviation (SD) = 3.52, range = 1.0 – 19.3) and child outcomes in two Australian communities (Port Pirie and Broken Hill) where Pb derived from ore bodies through mining and smelting remains a source of exposure. One hundred and six children (mean age = 7.96 years, SD = 0.59) were assessed using a battery measuring broad factors delineated in CHC theory by supplementing Wechsler IQ (Wechsler Intelligence Scale for Children-Fourth Edition; WISC-IV) scores with measures of CHC abilities (e.g., subtests from the Woodcock Johnson-III Tests of Cognitive Abilities). Information about parental cognitive functioning and a range of potential demographic, familial, psycho-social and environmental and pre- and post-natal variables was also collected. In unadjusted analyses, moderate, inverse significant associations were identified between PbB levels and performance on the WISC-IV and CHC factor scores. The shape of the curve of the association between PbB levels and WISC-IV Full Scale IQ (FSIQ) and the g factor, respectively, was non-linear. In covariate adjusted analyses (controlling for maternal IQ (Wechsler Adult Intelligence Scale-Third Edition), birth weight, Middle child Home Observation for Measurement of the Environment Inventory (MC HOME) scores, number of stressful life events, annual combined family income, smoking during pregnancy and duration of breast-feeding), consistent findings emerged that suggested that low-level Pb may detrimentally impact children‘s speed of information processing capabilities (across the three measurement approaches used in this study: WISC-IV Processing Speed Index, the Speed of Information Processing factor and Gs Invaders). When the PbB terms were added to models of WISC-IV Working Memory Index and the Woodcock Johnson-III Tests of Cognitive Abilities (WJ-III) Long-term storage and retrieval factor, these PbB variables contributed significantly to variance in children‘s memory performance above and beyond the variance already explained by variables considered to impact cognitive development. The variables that consistently explained the most variance in cognitive performance, aside from PbB level, were incidence and duration of breastfeeding and family income level. Higher PbB levels were significantly associated with lower paternal cognitive ability, parental education, combined family income and quality of the home environment, larger family size and later birth order. This research supports the assertion that there is no safe level of paediatric Pb exposure and therefore contributes to the ongoing debate about whether the intervention level for childhood PbB levels should be reconsidered. In addition, this thesis discusses the confounding effects of socio-cultural and environmental factors that influence children‘s cognitive abilities.
Thesis (Ph.D.) -- University of Adelaide, School of Psychology, 2011

碩士
高雄醫學大學
牙醫學研究所
99
Objective: This study evaluates effects of maternal exposure to different dose and time of lead on tooth development in rats fetuses. Materials &Methods: Pregnant rats were randomly divided into five groups: groups I was given deionized water, groups II and III drank lead acetate water in dose of 50 and 200 mg/L respectively throughout gestation, groups IV and V drank lead acetate water in dose of 50 and 200 mg/L respectively throughout lactation. Rat fetuses were sacrificed at 35 days postnatally and first molar were collected for morphometric studies. Results: No abnormalities in cusp number, form were noticed in the experimental groups. Many deep and longitudinal groves was noticed near enamo-dentinal junction on the molar surface. Analysis with ANOVA indicated a statically significant difference in linear measurement of crown size (P<0.0001). Further analysis revealed that the mesiodistal and buccolingual diameters were significantly smaller in lactation groups. Both bone morphogenetic protein-4 and fibroblast growth factor were immunohistochemical staining in stellate reticulum and ameloblast zone in the gestation groups and lactation groups. No differences were found in immunostaining intensity between the experimental groups and control groups. Conclusions: The administration of lead during gestation and lacation period cause adverse effect on molar size in the laboratory rat.

Tese de mestrado, Neurociências, Universidade de Lisboa, Faculdade de Medicina, 2018
Lead is a toxic metal which widespread use has resulted in environmental contamination and significant health problems. It is a cumulative toxicant that affects multiple body systems, including the cardiovascular, hematopoietic, reproductive, and renal systems. Lead is also a well-known neurotoxin, inducing changes in neurogenesis, neurodegeneration and changes on glial cells. These changes in the molecular and cellular processes lead to cognitive and behaviour alterations, particularly during developmental phases, persisting throughout the lifetime. Most of the studies that have been performed in both humans and animals were focused in a continuous chronic exposure to lead. This lead exposure causes behavioural changes, cognitive impairment and hypertension associated with sympathoexcitation, baroreceptor reflex hyposensitivity and increased chemoreceptor reflex sensitivity. But the effects of an intermittent lead exposure are scarse and standardized animal models are non-existent. This pattern of exposure has been increasing in the last years due to migrations, implementation of school exchange programs and/or residential changes. Therefore, the overall purpose of this work was to evaluate lead effects on mammal’s physiology along different profiles of lead exposure, including a new animal model of intermittent low-level lead exposure. Animal models of lead exposure were developed by replacing the tap water of seven-day pregnant Wistar females with 0.2% (p/v) solution of lead acetate. After being weaned at 21 days, rat pups, both sexes, were divided into 3 groups of lead exposure: long-term (exposure from foetal period until 28 weeks of age), short-term (exposure from foetal period until 12 weeks) and intermittent (exposure from foetal period until 12 weeks, lead-free period until 20 weeks and a second exposure between 20 and 28 weeks of age). At 12, 20 and 28 weeks of age, behavioural tests were performed for anxiety (Elevated Plus Maze Test), locomotor activity (Open Field Test), spatial working memory (Y-Maze) and episodic long-term memory (Novel Object Recognition test) assessment. Blood pressure (BP), electrocardiogram (ECG), heart rate (HR) and respiratory frequency (RF) were recorded at the same timepoints in the acute experiment. Baroreflex gain (BRG), chemoreflex sensitivity (ChS), cardiovascular variability were also evaluated. Immunohistochemistry studies for neuronal nuclear antigen (NeuN), Synaptophysin (Syn), ionized calcium binding adapter molecule-1 (Iba-1) and Glial fibrillary acidic protein (GFAP) stainings were performed in brain slices, and confocal imaging acquired and stainings quantified at dentate gyrus (DG) of the hippocampus. Blood lead levels were assessed by atomic absorption spectroscopy and metabolic evaluation of all groups was done using metabolic cages. A control group of Wistar rats without lead exposure, of both sexes, with the same number of individuals, underwent the same protocol and were evaluated in the same time points. Student T-test and one-way ANOVA with Tukey’s multiple comparison between means were used (significance p<0.05) for statistical analysis. Our data showed a clear association between lead exposure, hypertension and cardiorespiratory reflexes impairment, without heart rate changes, independently of the type of lead exposure profile. We also demonstrated for the first time that lead intermittent exposure causes adverse health effects, i.e, hypertension, sympathetic overactivity, increased chemoreflex sensitivity and baroreflex impairment, similar to a chronic exposure, however less pronounced. In fact, at 28 weeks, PbI group, the intermittent animal model of lead exposure developed, had a less severe hypertension when compared to the long-term exposure group (PbP), which might suggest that the duration of Pb exposure is more relevant than the time of exposure. Moreover, the effect on diastolic blood pressure produced by lead exposure was more evident than that of systolic blood pressure. Lead exposure from foetal period until 12 weeks of age causes long lasting hypertension and chemoreceptor reflex dysfunction even after a 16 weeks period without exposure. However, the clearance of lead promoted an improvement in baroreceptor reflex function, with repercussions on blood pressure values, since these values decreased, but did not reached the normotensive values. Regarding the autonomic data, in our study, the overactivity of the sympathetic nervous system, evaluated by the LF band, is concomitant with baroreceptor reflex impairment and/or hypertension. This means that the sympathetic nervous system may be involved in the modulation of the baroreceptor reflexes responses or in the hypertension development due to lead exposure. Concerning the effect of lead at behavioural level, all groups exposed to lead, evaluated in the three different time points, had behavioural changes, namely anxiety, hyperactivity and/or long-term memory impairment and molecular changes in the hippocampus region, more specifically, reactive astrogliosis and microgliosis were detected, indicating the presence of neuroinflammation. However, these alterations seem to reverse after lead abstinence for a certain period (single exposure) and are enhanced when a second exposure occurs (intermittent exposure), along with a synaptic loss. In summary, this study shows, that exposure to lead during the developmental phase can alter the normal course of development, with lifelong health consequences. Since all exposed Pb groups had the same route of exposure (i.e. exposure to lead by water) and the same dose and, despite the different time of exposure, all were exposed to lead since foetal period until adulthood, the most susceptible period to adverse health effects. Therefore, we can conclude that the different effects of lead toxicant between groups mainly depends on the total duration of lead exposure. This comparative study brings new insights on the environmental factors that influence nervous and cardiovascular systems during development, which can help creating public policy strategies to prevent and control the adverse effects of Pb toxicity.
A identificação de agentes potencialmente tóxicos e a avaliação dos seus efeitos sobre o organismo humano constituem um tema importante de saúde pública. O chumbo encontra-se neste grupo de agentes, sendo bastante utilizado em todo o mundo, devido às suas propriedades únicas, como a alta maleabilidade, baixo ponto de fusão, suavidade, ductilidade e resistência à corrosão. O vasto uso deste metal pesado em indústrias, como a automóvel, cerâmica, de tintas e do plástico levou ao aumento da quantidade de chumbo livre no ambiente e a sua ocorrência nos sistemas biológicos, devido à sua natureza não biodegradável. A toxicidade do chumbo, como resultado da sua ingestão, inalação ou por contacto direto, mesmo em pequenas quantidades, pode evocar efeitos adversos irreversíveis em várias funções do corpo, afetando principalmente os sistemas cardiovascular (sendo uma das causas da hipertensão, promovendo aterosclerose, trombose, arteriosclerose e doenças cardiovasculares), hematopoiético, reprodutivo e renal. O chumbo é também uma neurotoxina já bem estudada, que induz alterações na neurogénese, nas células gliais e neurodegeneração. Estas alterações nos mecanismos celulares e moleculares, quando ocorrem durante as fases de desenvolvimento, provocam alterações cognitivas e comportamentais, que persistem durante toda a vida. Em termos de classificação, dois tipos de toxicidade de chumbo podem ser definidos: a toxicidade aguda, que geralmente ocorre pela exposição ocupacional a níveis elevados de chumbo, sendo esta bastante incomum, e a toxicidade crónica, uma exposição a níveis baixos de chumbo, mais comum no ambiente familiar. A maioria dos estudos realizados até à data em seres humanos e animais, focam-se na exposição crónica contínua e/ou permanente ao chumbo e nas consequências adversas na saúde deste tipo de exposição. Existem já, vários modelos animais descritos para a exposição contínua a níveis baixos de chumbo. No entanto, em determinadas situações, como nas migrações, nos programas de intercâmbio escolar e/ou nas mudanças residenciais, a exposição intermitente ao chumbo pode ocorrer, mas os estudos disponíveis em seres humanos são escassos e os modelos animais padronizados inexistentes para este tipo de exposição, que tem vindo a crescer exponencialmente nos últimos anos. Posto isto, o objetivo geral deste trabalho consistiu em avaliar os efeitos de diferentes perfis de exposição a níveis baixos de chumbo na fisiologia de ratos Wistar, incluindo o desenvolvimento de um novo modelo animal de exposição intermitente a chumbo. Os modelos animais de exposição ao chumbo foram desenvolvidos substituindo a água dos biberões das fêmeas Wistar grávidas de sete dias por uma solução de acetato de chumbo a 0,2% (p/v). Após os 21 dias de desmame, as crias, de ambos sexos, foram divididas em 3 grupos de exposição ao chumbo: de longo prazo (PbP - exposição do período fetal até às 28 semanas de idade), de curto prazo (Short-term PbS - exposição do período fetal até às 12 semanas, com abstinência ao chumbo até às 28 semanas) e intermitente (PbI - exposição do período fetal até 12 semanas, seguida por um período sem chumbo até 20 semanas e uma segunda exposição entre 20 e 28 semanas de idade). Em três diferentes pontos temporais (12, 20 e 28 semanas de idade), os diferentes grupos de animais foram sujeitos a testes comportamentais, para a avaliação dos níveis de ansiedade (EPM), da atividade locomotora (OFT), da memória espacial de trabalho (Y-Maze) e da memória episódica de longo prazo (NOR). Para avaliação dos parâmetros fisiológicos nos diferentes pontos temporais, os animais foram sujeitos a uma experiência aguda, onde foram registados os seguintes parâmetros: pressão arterial (PA), eletrocardiograma (ECG), frequência cardíaca (FC) e frequência respiratória (FR). Nesta experiência também se avaliaram os reflexos baro- e quimiorrecetores e obtiveram-se registos para a análise da variabilidade da FC e da PA sistólica. Após o término da experiência aguda, os animais foram sacrificados e os cérebros extraídos para estudos de imunohistoquímica em secções coronais, nas quais se analisou a morfologia das células e se quantificou a perda neuronal (neuronal nuclear antigen - NeuN), a astrogliose (Glial fibrillary acidic protein – GFAP) e a microgliose (ionized calcium binding adapter molecule-1 - Iba-1), bem como alterações na transmissão sináptica (Synaptophysin – Syn) no girus dentado do hipocampo. Os níveis de chumbo no sangue foram avaliados por espectroscopia de absorção atómica e a avaliação metabólica realizada através do uso de gaiolas metabólicas. Um grupo controlo de ratos Wistar sem exposição ao chumbo, de ambos os sexos e com o mesmo número de indivíduos, foi submetido ao mesmo protocolo e foi avaliado nos mesmos pontos temporais (12, 20 e 28 semanas de idade). Para a análise estatística foi utilizado o teste T de Student e a análise de Variância (ANOVA) unidirecional com o teste post-hoc de Tukey, considerando-se significativas diferenças com p < 0,05. Os resultados deste estudo mostram que, independentemente do tipo de perfil de exposição ao chumbo, existe uma associação clara entre exposição a chumbo, hipertensão e diminuição do ganho do barorreflexo, sem alterações de frequência cardíaca. Também demonstramos, pela primeira vez, que uma exposição intermitente a chumbo provoca efeitos adversos para a saúde, como hipertensão, hiperatividade simpática, aumento da sensibilidade quimiorreflexa e diminuição do ganho do barorreflexo, efeitos adversos semelhantes ao de uma exposição crónica permanente (PbP), porém menos pronunciada. De facto, às 28 semanas, o grupo PbI, o modelo animal intermitente de exposição ao chumbo desenvolvido, apresentou uma hipertensão menos grave em relação ao grupo de exposição de longo prazo (PbP), o que pode sugerir que a duração da exposição ao chumbo é mais relevante do que o tempo de exposição. Além disso, o efeito da exposição ao chumbo sobre a pressão arterial diastólica foi mais evidente do que sobre a pressão arterial sistólica. A exposição ao chumbo, desde o período fetal até as 12 semanas de idade, provoca hipertensão e disfunção quimiorreflexa duradoura, mesmo com um período de 16 semanas sem exposição. No entanto, a abstinência do chumbo promoveu uma melhoria na função barorreflexa, com repercussões nos valores da pressão arterial, uma vez que estes valores diminuíram, apesar de não atingirem os valores de normotensão. Em relação à avaliação autonómica, os dados indicam que quando existe um aumento do tónus simpático, avaliado pela banda LF, este é concomitante com disfunção barorreflexa e/ou hipertensão arterial. Isso significa que o sistema nervoso simpático deve estar envolvido na modulação da resposta barorreflexa ou no desenvolvimento da hipertensão decorrente da exposição ao chumbo. Relativamente ao efeito do chumbo a nível comportamental, todos os grupos expostos ao chumbo, avaliados nos diferentes pontos temporais, apresentaram alterações comportamentais, nomeadamente ansiedade, hiperatividade e / ou défices de memória a longo prazo, bem como alterações moleculares, mais especificamente, astrogliose e microgliose reativa, que indicam a presença de neuroinflamação. No entanto, estas alterações parecem reverter após a abstinência do chumbo durante um determinado período (PbS - exposição de curta duração), sendo mais evidentes quando ocorre uma segunda exposição a chumbo (PbI - exposição intermitente), levando mesmo a perda sináptica mais pronunciada. Em resumo, este estudo mostra, que exposições a chumbo durante as fases de desenvolvimento podem alterar o seu curso normal, com consequências adversas para a saúde que podem persistir para toda a vida. Uma vez que todos os grupos expostos a chumbo tiveram a mesma via de exposição (isto é, exposição ao chumbo através da água) e a mesma dose e, apesar do tempo de exposição diferente, todos foram expostos ao chumbo desde o período fetal até a idade adulta, período em que são mais suscetíveis a efeitos adversos na saúde. Portanto, podemos concluir que os diferentes efeitos tóxicos do chumbo entre os grupos dependem principalmente da duração total da exposição ao chumbo. As novas evidências obtidas por este estudo comparativo permitem-nos contribuir para o esclarecimento sobre os fatores ambientais que influenciam os sistemas nervoso e cardiovascular durante o desenvolvimento, o que pode ajudar a criar estratégias de políticas públicas para prevenir e controlar os efeitos adversos da toxicidade do chumbo.

Intellectual stimulation of young children is crucial, because it helps to break the cycle of poverty by giving each child the skills needed to reach his or her maximum potential. There is a growing need for more extensive early childhood development programmes in South Africa. Several studies in early childhood development have been shown to directly draw a parallel with enhanced student achievement at school and in life (Ackerman, 2005; Bueno, Darling-Hammond, & Gonzales 2010; Frede, Jung, Barnett, & Figueras, 2009). This study therefore explored the effects of an intervention programme introducing numbers, shapes and colours to infants between the ages of three months and 12 months. The sample consisted of 63 infants, with a control group of 34 and an experimental group of 29. The participants were selected from the middle-income group and consisted of infants from three different ethnic groups (black, white and coloured). Nine participants from the experimental group formed part of the focus group, which met every two weeks to give feedback and discuss the development of the infants and experiences of the parents involved in the intervention programme. In this study quantitative and qualitative data was collected. This data was assessed and analysed in order to achieve the four aims of the research study. The Bayley Scales of Infant Development (III) was used to assess three areas of development, namely cognitive ability, language skills and motor skills for the quantitative part of the study. The adaptive behaviour and social-emotional functioning of the infants was also assessed using the BSID (III), and this data was used in conjunction with the focus group feedback and problem-solving scenarios for the qualitative part of the study. Gender and the two age categories (3–7 and 8–12 months) for both the experimental and the control groups were examined and excluded from possible explanations for any significant findings. It was also determined that the control and experimental groups were well matched at the start of the intervention programme. The findings for aim A, the pre-test and post- test results showed that an average of 60 days involved in intervention programme had a statistically significant effect (z = -4.32, p < 0.001) on the cognitive ability of the infants. The findings for aim B, for the comparison between the control and experimental groups after the intervention programme, indicated significant results for the cognitive subscale (U = 732, p < 0.01, r = 0.42). Although the language and motor scores showed an increase in the descriptive statistics for the experimental group after the intervention, the Mann-Whitney U test did not show a significant difference. The findings for the qualitative study for aim C revealed that there was no effect on the adaptive behaviour of the infants. The findings for the social-emotional scales descriptive statistics for the qualitative study in aim D showed that there was a fairly large increase in the composite score means of the experimental group in comparison with the control group. The large increase in results complements the social-emotional functioning theme that emerged from the focus group. Three main themes emerged from the focus group, namely the cognitive ability, communication skills and social-emotional functioning of the infants.The increase in the social-emotional scale for the intervention group and the increase in the cognitive scale as mentioned in aim B were interrelated. These early social-emotional experiences are linked to long-term positive outcomes in both the social and cognitive areas of development (Landry, Smith, Swank, & Miller-Loncar, 2000). The parents all reported the ability to interpret the communication from their infants when participating in the flashcard sessions. This communication forms a foundation for establishing language development. Relationships between an infant’s nonverbal communication skills and subsequent language development have been reported (Brooks & Meltzoff, 2005). The problem-solving scenarios that were assessed during the second assessment showed that the infants who participated in the intervention programme were able to correctly identify a flashcard 73% of the time in comparison with the control group who were only able to identify a flashcard 1.4% correctly. The results of the study show that an early intervention programme has the potential to increase an infant’s cognitive ability and enhance his or her social-emotional functioning. However, the long-term impact of these findings would have to be explored in a longitudinal study.
Psychology
M.A. (Psychology)

Indiana University-Purdue University Indianapolis (IUPUI)
Despite warnings about the dangers of drinking during pregnancy, little progress has been made in reducing alcohol drinking among women of childbearing age. Even after the recognition of pregnancy, 15% of women continue to drink, 3% of which admit to binge drinking. Because we cannot stop women from drinking during pregnancy, and many children with fetal alcohol spectrum disorders (FASD) are adopted, there is a significant need to develop postnatal interventions that can improve the long-term outcome of children adversely affected by prenatal alcohol exposure. This thesis aims to evaluate one promising new treatment in the rehabilitation or rescue of specific learning deficits long after the damage has occurred. The treatment evaluated herein (40µg D-NAP + 40µg D-SAL) has long been used in the prevention of the detrimental effects of long-term and binge-like alcohol exposures in rodent models of fetal alcohol syndrome and FASD. Until recently this peptide treatment had only been shown to be effective in preventing some of the consequences of alcohol exposure when administered concurrently with the prenatal alcohol exposure. A recent report by Incerti and colleagues (2010c), however, reported that these peptides could completely reverse a profound spatial learning deficit induced by one episode of a heavy binge-like alcohol exposure (5.9g.kg in a single intraperitoneal injection) on gestational day 8 (G8) in C57BL/6 mice. In that report, the peptide treatment was administered starting in late adolescence, beginning three days prior to and throughout water maze training, and the profound deficits in their alcohol-placebo group were completely eliminated in the alcohol-peptide group. There are currently no FDA-approved treatments for FASD. An effective treatment for the cognitive and behavioral dysfunctions suffered by the 1% of people born today could potentially improve the lives of millions of children and adults. The first aim of this thesis was to determine whether the peptide treatment could reverse the significant spatial learning deficits we have demonstrated in adult C57BL/6 mice given high-dose binge-like alcohol exposure (2.5 g/kg in each of two intraperitoneal injections separated by two hours) on postnatal day (P)7. When administered three days prior to and throughout water maze testing (P67-76), the peptide treatment had no effect on spatial learning. The second aim sought to determine whether the same peptide treatment could reverse water maze spatial learning deficits in G8 binge-like exposure models, as reported by Incerti et al. (2010c). For this analysis, the first study used a different binge-like alcohol exposure model that is more commonly used than that employed by the Incerti et al. (2010c) study, namely administration of 2.8g/kg in each of two intraperitoneal injections separated by four hours (Sulik et al., 1981). This model has been shown to produce high peak blood alcohol concentrations and neuroanatomical aberrations in the hippocampal formation and septal regions (Parnell et al., 2009), which have been implicated in learning and memory. Surprisingly, this G8 binge-like alcohol exposure failed to produce a spatial learning deficit, undermining the usefulness of this model in evaluating the peptide effects. In direct contrast to the outcomes of Incerti et al. (2010c), the G8 Webster alcohol exposure was also unable to produce any deficits in acquisition of spatial learning in the Morris water maze. Surprisingly, neither of the heavy binge-like alcohol exposures on G8 were able to produce spatial learning deficits in the Morris water maze. The binge-like alcohol exposure on P7 did yield the expected spatial learning deficit, but the peptide treatment was unsuccessful in recovering water maze learning. These findings fail to support oral administration of 40µg D-NAP and 40 µg D-SAL as a potential therapy for postnatal alcohol-induced spatial learning deficits in adult mice.