A hipóxia crônica intermitente (HCI) é um modelo experimental no qual o quimiorreflexo é ativado a cada episódio de hipóxia, assim como em alguns casos de apneia obstrutiva do sono. A HCI promove aumento da atividade simpática, hipertensão e alterações no acoplamento simpático-respiratório no tronco encefálico. No presente trabalho estudamos os parâmetros cardiorrespiratórios concomitantemente com o ciclo sono-vigília em uma janela temporal de 3 horas no período do dia em que esses registros são feitos no nosso laboratório. Foram também registradas ao longo deste período as respostas cardiovasculares associadas a inspirações profundas (IPs) que acontecem normalmente nos ratos. Ratos Wistar (~ 250 g) foram divididos nos grupos HCI (n = 12) e controle (CTL) (n = 12). Os animais foram submetidos à cirurgia de implantação de eletrodos no crânio e nos músculos cervicais para obtenção de registros eletrocorticográficos (ECoG) e eletromiográficos (EMG), respectivamente, para determinarmos as fases do ciclo sono-vigília (vigília, sono NREM (non-rapid eye movement) e sono REM (rapid eye movement)). Um grupo de animais CTL (n=5) e outro de animais HCI (n=6) tiveram também eletrodos implantados nos músculos diafragma (DIA) e abdominal oblíquo (ABD) para registros da atividade muscular respiratória. Após 48 horas, o grupo HCI foi exposto a um protocolo de hipóxia intermitente durante 10 dias (6% de O2 por 40 s, a cada 9 min, 8 h/d), enquanto o grupo CTL foi mantido em normoxia (20,8% de O2) pelo mesmo período. No último dia do protocolo, os ratos tiveram uma artéria femoral canulada para registros de pressão arterial (PA). No dia seguinte, ECoG, EMG e a PA foram registrados por 3 horas para análise da latência para o sono, o tempo total em cada uma das fases do ciclo sonovigília, o número e a duração dos episódios de sono REM e os parâmetros cardiovasculares pressão arterial sistólica (PAS), pressão arterial diastólica (PAD), pressão arterial média (PAM) e frequência cardíaca (FC) nas diferentes fases do ciclo. Os parâmetros respiratórios foram registrados por 2 horas para análise de frequência respiratória (fR), volume corrente (VT) e volume minuto (VE) nas diferentes fases do ciclo sono-vigília. Os animais dos grupos utilizados para avaliação da atividade respiratória muscular foram registrados por 2 horas. O protocolo de 10 dias de HCIpromoveu alterações significativas apenas na duração dos episódios de sono REM nos ratos HCI. Entretanto, os animais do grupo HCI apresentaram níveis médios mais elevados de PAS (145,0 ± 1,8 vs 129,3 ± 2,2 mmHg), PAD (104,1 ± 1,7 vs 91,4 ± 1,8 mmHg), PAM (121 ± 9 vs 107,7 ± 1,9 mmHg) e FC (387, ± 5,4 vs 363,5 ± 8,7 bpm) no período de 3 horas de registro, sendo estes aumentos igualmente observados em todas as fases do ciclo sono-vigília. A HCI também promoveu aumento significativo de VT durante os sonos NREM (6,6 ± 0,2 vs 5,8 ± 0,2 mL/kg) e REM (6,4 ± 0,2 vs 5,3 ± 0,2 mL/kg), porém este parâmetro não foi significativamente diferente durante a vigília nos animais HCI em relação aos animais CTL. Ambos os grupos apresentaram expirações ativas apenas durante a vigília, porém estas foram muito mais frequentes nos animais HCI. Além disso, nos animais HCI as respostas de queda da PAM (-18 ± 0,8 vs -14 ± 0,6 mmHg) e aumento da FC (28,4 ± 1,8 vs 21,8 ± 1,1 bpm) associadas às IPs apresentaram maiores magnitudes em relação aos animais CTL, embora o intervalo temporal entre as IPs não tenha se alterado. Esses achados indicam que a HCI aplicada durante 10 dias promove alterações significativas na duração dos episódios de sono REM, aumento da PA e FC em todas as fases do ciclo sono-vigília, aumento do VT durante o sono, aumento da ocorrência de expirações ativas durante a vigília e aumento das respostas hemodinâmicas associadas às IPs. Portanto, as alterações cardiovasculares observadas após a HCI são decorrentes dos episódios repetidos de hipóxia que acontecem ao longo desse protocolo, mas não parecem ser dependentes de alterações no ciclo sono-vigília, pois ainda que a duração dos episódios de sono REM tenha sido maior nos ratos HCI, os parâmetros cardiovasculares se apresentaram igualmente elevados em todas as fases do ciclo sono-vigília desses animais. / Chronic intermittent hypoxia (CIH) is an experimental model in which the chemoreflex is activated at each episode of hypoxia, as observed in some cases of obstructive sleep apnea. CIH induces increased sympathetic activity, hypertension, and changes in the sympathetic-respiratory coupling in the brainstem. In the present study, we recorded cardiorespiratory parameters concomitantly with the sleep-wake cycle during a 3-hour time window which corresponds to the period of the day in which these recordings are collected in our laboratory. During this period, we also studied the cardiovascular responses associated with the normally occurring deep breaths (DBs) in rats. Male Wistar rats (~ 250 g) were divided into CIH (n = 12) and control (CTL) groups (n = 12). Animals underwent implantation of electrodes in the skull and in the cervical muscles for electrocorticographic (ECoG) and electromyographic (EMG) recordings, respectively, to determine the phases of the sleep-wake cycle (wakefulness, NREM sleep and REM sleep). A group of CTL animals (n=5) and another of HCI animals (n=6) had electrodes implanted also in the diaphragm (DIA) and oblique abdominal muscle (ABD) for recordings of respiratory muscle activity. After 48 hours, the CIH group was exposed to an intermittent hypoxia protocol for 10 days (6% O2 for 40 s, every 9 min, 8 h/d), while the CTL group was maintained in normoxia (20.8 % of O2) for the same period. On the last day of the protocol, rats had a femoral artery cannulated for blood pressure (BP) recordings. On the following day, ECoG, EMG and BP were recorded for 3 hours for analysis of time for sleep onset, total time in each phase of the sleep-wake cycle, number and duration of REM sleep episodes, and the cardiovascular parameters systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and heart rate (HR) in the different phases of the cycle. The respiratory parameters were recorded for 2 hours for analysis of ventilatory frequency (fR), tidal volume (VT) and minute volume (VE) in the different phases of the sleep-wake cycle. The groups of animals used for analysis of respiratory muscle activity were recorded for only 2 hours. CIH promoted significant alterations only in the duration of REM episodes. However, animals from CIH group had higher average levels of SBP (145,0 ± 1,8 vs 129,3 ± 2,2 mmHg), DBP (104,1 ± 1,7 vs 91,4 ± 1,8mmHg), MAP (121 ± 9 vs 107,7 ± 1,9 mmHg) e HR (387, ± 5,4 vs 363,5 ± 8,7 bpm) in the 3-hour recording period. These increases were also observed in all phases of the sleep-wake cycle. CIH also promoted a significant increase in VT during NREM (6,6 ± 0,2 vs 5,8 ± 0,2 mL/kg) and REM (6,4 ± 0,2 vs 5,3 ± 0,2 mL/kg), although this parameter was not significantly different during wakefulness in CIH animals compared to CTL animals. Both groups presented active expiration only during wakefulness, however it was much more frequent in HCI rats. In addition, in CIH animals, the fall in MAP (-18 ± 0,8 vs -14 ± 0,6 mmHg) and the increase in HR (28,4 ± 1,8 vs 21,8 ± 1,1 bpm) associated with DBs presented higher magnitudes in relation to CTL animals, although the time interval between DBs did not change. These findings indicate that CIH for 10 days promotes longer REM episodes, increased BP and HR in all phases of the cycle, increased VT during sleep, increased active expiration occurrence and higher magnitudes of the hemodynamic responses associated with DBs. Therefore, the cardiovascular alterations observed after CIH are due to the intermittent hypoxia episodes that occur throughout this protocol, but do not seem to be related to changes in the sleep-wake cycle, for although the duration of REM episodes was longer, the cardiovascular parameters were equally increased in all phases of the sleep-wake cycle.

Made available in DSpace on 2016-08-10T10:54:01Z (GMT). No. of bitstreams: 1 SIDNEI JULIANI.pdf: 1930649 bytes, checksum: b2dfc9fb97117b01bdba43a40e44ccb6 (MD5) Previous issue date: 2012-03-14 / Obesity is classified as a chronic non transmissible disease, the same as cardiovascular diseases, diabetes and neoplasms. Due to precocious atherosclerosis lesions, the obese child has a higher probability of developing cardiovascular, metabolic or neoplastic diseases when adult. Besides all physical problems, obesity stigmatization, which leads to social, psychological and behavioral problems. This study drew the nutritional profile and determined the life habits of obese students from a sample of 125 children, ages 7 to 12 years, from a public elementary school in the town of Pontal do Araguaia, state of Mato Grosso , Brazil. Possible biochemical alterations that lead to metabolic alteration were sought, as well as their relationship with gender. Alterations were analyzed in: total cholesterol, triglycerides, HDL cholesterol, glucose, uric acid and insulin. In addition, the quality of life of the selected group of obese children with that of an eutrophic group selected from the same sample of 125 children, using the AUQEI (Autoquestionnaire Qualité de Vie Enfant Imagé) scale. The results showed that 18% of the children were obese, 12% were overweight, 64.5% had normal weight and 5,5% were underweight. Unhealthy habits may have contributed to the obesity, e.g., having an overweight person in the family (75%), eating candies between the main meals (60%) and having the main meals in the living room, watching TV (60%). Biochemical alterations were identified in at least two analyzed parameters for 40% of the obese. The most altered metabolite was total cholesterol, which was elevated in 50% of the obese. Several metabolites were more compromised in boys than in girls, with significant a difference at p<0.05. The fact that alterations were verified in most children suggests a tendency to express metabolic syndrome. The eutrophic children had a better quality of life, with an average score of 52.55, while the obese group presented an average score of 47.50 (p<0.05). Furthermore, the quality of life of the obese children was below the cutoff point of 48. We conclude that the metabolism and the quality of life are impaired in the obese group. The prevalence of child obesity in the sample is similar to that found in other regions of the country. The presence of non-healthy habits can influence the susceptibility to obesity. We suggest that national efforts need to be made to prevent and treat child obesity by implementing public health and educational programs, aiming to reduce the negative impacts that obesity has on the child, which impair their physical and emotional health. / A obesidade é classificada como doença crônica não transmissível, assim como as doenças cardiovasculares, diabetes e neoplasias, e devido às lesões precoces de aterosclerose a criança obesa tem maior possibilidade de desenvolver doenças cardiovasculares, metabólicas ou neoplásicas, quando adulto. Além de todos os problemas relacionados à parte física, a obesidade pode prejudicar a qualidade de vida da criança, em razão das discriminações e estigmatizações sociais que a criança obesa pode sofrer, levando-a a ter problemas sociais, psicológicos e comportamentais. Este trabalho teve como objetivos verificar o perfil nutricional e os hábitos de vida de escolares obesos, a partir de uma amostra 125 crianças de 7 a 12 anos de uma escola pública municipal do município de Pontal do Araguaia - MT; verificar as possíveis alterações bioquímicas, precursoras de alterações metabólicas em crianças obesas e a relação dessas alterações com o sexo, submetidas aos exames de colesterol total, triglicérides, HDL colesterol, glicemia, ácido úrico e insulina. E finalmente, analisar comparativamente a qualidade de vida do grupo de crianças classificadas como obesas, com um grupo de eutróficas selecionadas a partir da mesma amostra de 125 crianças; utilizando-se como instrumento a Escala de AUQEI (Autoquestionnaire Qualité de Vie Enfant Imagé). Os resultados mostraram que 18% estavam com obesidade, 12% com sobrepeso, 64,5% com peso normal e 5,5% com déficit de peso, também verificou-se a presença de certos hábitos não saudáveis que podem estar contribuindo com a obesidade, como por exemplo: ter alguém na família com sobrepeso (75%), comer guloseimas entre as principais refeições (60%) e fazer as principais refeições na sala, assistindo televisão (60%). Foram identificadas alterações bioquímicas em pelo menos dois parâmetros analisados em 40% dos obesos. O metabólito que mais se alterou foi o colesterol total, aumentado em 50% dos obesos, além de ser constatado que vários metabólitos estavam mais comprometidos nos meninos do que nas meninas, com diferença significativa (p<0,05). As alterações verificadas em boa parte das crianças obesas sugerem certa propensão delas em apresentar síndrome metabólica. Verificou-se que as crianças eutróficas têm melhor qualidade de vida, apresentando escore médio de 52.55, enquanto o grupo de obesos apresentou escore médio de 47,50, que é uma diferença estatisticamente significativa (p=0,024), além disso, a qualidade de vida das crianças obesas encontra-se prejudicada, pois apresentou escore abaixo da nota de corte 48. Após os vários estudos realizados, concluímos que as alterações metabólicas e a qualidade de vida estão prejudicadas no grupo de obesos, além da prevalência de obesidade infantil na amostra estudada ser semelhante ao de outras regiões do país e de ser constatada a presença de hábitos não saudáveis nas crianças obesas que podem influenciar na obesidade. Verificouse assim com esse estudo a complexidade e a gravidade da questão da obesidade infantil. Dessa forma, sugere-se que sejam feitos esforços, em nível nacional, principalmente na prevenção e também no tratamento, por meio da implantação de políticas públicas na área de saúde pública e educação, visando diminuir o impacto negativo que a obesidade provoca na criança, comprometendo sua saúde física e emocional.

Made available in DSpace on 2016-08-10T10:55:51Z (GMT). No. of bitstreams: 1 MARIA PAULA THEES PERILLO RODRIGUES.pdf: 616615 bytes, checksum: ff241c7f4362c3709564d808bc919f92 (MD5) Previous issue date: 2005-06-17 / Xylene is an aromatic hydrocarbon of oily consistency, practically insoluble in water, inflammable and toxic. Its contamination is persistent and bioaccumulative and can damage health and environment. Due to increasing amounts of work-related injuries, mainly those caused by chemical intoxication, health and safety programs have been implemented. Regulatory rules were created aiming workers&#8217; integrity and health, such as the NR7 that established biological parameters to occupational exposure to chemicals and NR15 that determined the allowed tolerance limit in an occupational setting. This study aimed evaluating hematological and immunological parameters of technicians in histological laboratories exposed to xylene and non-exposed individuals. The urine methylhippuric acid level was measured by high performance liquid chromatography. The hematological indices were evaluated in technicians exposed to xylene and non-exposed controls. The T lymphocytes (CD3+) and subpopulations (CD4+ and CD8+), NK cells (CD56+) and B cells (CD19+) were evaluated by flow cytometry. Phagocytic index was assessed in peripheral blood neutrophiles in technicians and normal controls using Saccharomyces cerevisiae yeast sensitized or not with serum. Methylhippuric acid levels present in the urine of technicians and controlled groups were within the allowed tolerance limits. No significant quantitative alterations of hematological indices were shown in technicians when compared to normal controls. However, peripheral blood neutrophils phagocytic index in technicians was significantly higher than in normal controls. Data shows that xylene use in this occupational activity does not imply in quantitative hematological and immunological alterations. Nonetheless, increased phagocytic capacity of the peripheral blood neutrophils of technicians suggest hyperactivation of these cells. / O xilol é um hidrocarboneto aromático de consistência líquida oleosa, praticamente insolúvel em água, inflamável e tóxico. Sua contaminação é persistente e bioacumulativa podendo causar danos à saúde e ao meio ambiente. Devido ao aumento de ocorrências de doenças profissionais principalmente as provocadas por intoxicação de produtos químicos, programas de saúde e segurança foram implementados. Foram criadas normas regulamentadoras que visam a saúde e integridade do trabalhador, como a NR7 que estabeleceu parâmetros biológicos à exposição ocupacional a produtos químicos, o utilizado para o xilol é o ácido metilhipúrico; e a NR15 que determinou o limite de tolerância permitido no ambiente ocupacional. O presente trabalho objetivou avaliar parâmetros hematológicos e imunológicos em histotécnicos de laboratório de anatomia patológica expostos ao xilol e indivíduos não expostos. A metodologia utilizada para a quantificação do ácido metilhipúrico na urina foi a cromatografia líquida de alta perfomance. Através do hemograma automatizado foram demonstrados os índices hematimétricos, leucocitário e plaquetário do sangue periférico de histotécnicos e controles não expostos ao xilol. A imunofenotipagem de linfócitos T totais ( CD3+) e subpopulações (CD4+, CD8+), células NK (CD56+) e células B (CD19+) foi avaliada por citometria de fluxo. O índice fagocitário foi avaliado em neutrófilos do sangue periférico de histotécnicos e controles normais utilizando leveduras de Saccharomyces cerevisiae sensibilizadas ou não. Os níveis de ácido metilhipúrico na urina dos histotécnicos e controles se apresentaram dentro dos limites de tolerância permitidos. Não foram demonstradas alterações quantitativas significativas dos índices hematimétricos, leucocitário e plaquetário de histotécnicos quando comparadas ao controles normais. Entretanto, o índice fagocitário de neutrófilos do sangue periférico de histotécnicos foi significativamente maior do que o de controles normais. Nossos dados indicam que a utilização do xilol nesta atividade ocupacional não induz alterações quantitativas hematológicas e imunológicas. Entretanto foram observadas alterações na atividade fagocitária de neutrófilos do sangue periférico sugerindo a hiperativação destas células.

Orientador: Lucilene Arilho Ribeiro-Bicudo / Resumo: As cardiopatias congênitas (CCs) podem ser definidas como qualquer anormalidade na estrutura e/ou na função cardiocirculatória presente ao nascimento. Constituem as malformações congênitas mais comuns entre recém-nascidos vivos, podendo se apresentar de duas formas: isoladas (ou não sindrômicas) e sindrômicas. De caráter multifatorial, o surgimento de CCs envolve fatores ambientais, genéticos e epigenéticos. A etiologia genética de CCs ainda é pouco conhecida. Entre as causas genéticas conhecidas, podemos destacar: aneuploidias, alterações na estrutura dos cromossomos, desequilíbrios citogenômicos (perdas e ganhos genômicos ou variações no número de cópias genômicas – CNVs), mutações pontuais, variações em um único nucleotídeo, entre outras. Dentre essas, as CNVs contribuem com aproximadamente 10% na etiologia genética de CCs não sindrômicas, e cerca de 20% entre as sindrômicas. O objetivo deste trabalho foi investigar possíveis desequilíbrios citogenômicos em pacientes diagnosticados com CCs sindrômicas e não sindrômicas idiopáticas. Foram recrutados 31 pacientes, sendo 13 sindrômicos e 18 não sindrômicos. Todos foram submetidos à avaliação genético-clínica. As amostras foram coletadas a partir do sangue periférico, e realizou-se o cariótipo convencional para todos os sindrômicos. A análise por MLPA foi realizada em 27 pacientes. O DNA genômico dos pacientes sindrômicos selecionados foi submetido a duas plataformas de CMA (array-CGH/SNP arrays): SNP-array 850K HumanCytoSNP (... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Congenital heart defects (CHD) can be defined as any abnormality in the structure and /or cardiocirculatory function present at birth. Congenital malformations are more common among live newborns. CHD can be presented at two forms: isolated (or non syndromic) and syndromic ones. Of multifactorial spectrum, the emergence of CHD involves environmental, genetic and epigenetic factors. The genetic etiology of CHD is still poorly understood. Among the known genetic causes, we can highlight: aneuploidies, changes in chromosome structure, cytogenetic imbalances (losses and genomic gains, can be also called copy number variations - CNVs), point mutations, variants in a single nucleotide, among others. Among these, CNVs contribute to approximately 10% in the genetic etiology of non-syndromic CHD, and about 20% among syndromic ones. The aim of this study was to investigate possible cytogenetic imbalances in patients diagnosed with idiopathic syndromic and non-syndromic CHD. Thirty one patients were recruited, of which 13 syndromic and 18 non-syndromic. Each patient were submitted to genetic-clinical evaluation. Only patients with an undefined syndromic condition were included in cytogenetic investigations. Samples were collected from the peripheral blood, and the conventional karyotype was performed for all syndromic patients. MLPA analysis was performed in 27 patients. The genomic DNA of the selected patients was analyzed into two CMA (array-CGH / SNP arrays) platforms: SNP-array 850K... (Complete abstract click electronic access below) / Mestre

Major depressive disorder (MDD) is a heritable and highly debilitating condition with antidepressants, first-line treatment, demonstrating low to modest response rates. No current biological mechanism substantially explains MDD but both neurostructural and neurochemical pathways have been suggested. Further explication of these may aid in identifying subgroups of MDD that are better defined by their aetiology. Specifically, genetic stratification provides an array of tools to do this, including the intermediate phenotype approach which was applied in this thesis. This thesis explores genetic overlap with regional brain volume and MDD and the genetic and non-genetic components of antidepressant response. The first study utilised the most recent published data from ENIGMA (Enhancing Neuroimaging Genetics through Meta-analysis) Consortium's genome-wide association study (GWAS) of regional brain volume to examine shared genetic architecture between seven subcortical brain volumes and intracranial volume (ICV) and MDD. This was explored using linkage disequilibrium score regression (LDSC), polygenic risk scoring (PRS) techniques, Mendelian randomisation (MR) analysis and BUHMBOX (Breaking Up Heterogeneous Mixture Based On Cross-locus correlations). Results indicated that hippocampal volume was positively genetically correlated with MDD (rg= 0.46, P= 0.02), although this did not survive multiple comparison testing. Additionally, there was evidence for genetic subgrouping in Generation Scotland: Scottish Family Health Study (GS:SFHS) MDD cases (P=0.00281), however, this was not replicated in two other independent samples. This study does not support a shared architecture for regional brain volumes and MDD, however, provided some evidence that hippocampal volume and MDD may share genetic architecture in a subgroup of individuals, albeit the genetic correlation did not survive multiple testing correction and genetic subgroup heterogeneity was not replicated. To explore antidepressant treatment resistance, the second study utilised prescription data in (GS:SFHS) to define a measure of (a) treatment resistance (TR) and (b) stages of resistance (SR) by inferring antidepressant switching as non-response. GWAS were conducted separately for TR in GS:SFHS and the GENDEP (Genome-based Therapeutic Drugs for Depression) study and then meta-analysed (meta-analysis n=4,213, cases=358). For SR, a GWAS on GS:SFHS only was performed (n=3,452). Additionally, gene-set enrichment, polygenic risk scoring (PRS) and genetic correlation analysis were conducted. No significant locus, gene or gene-set was associated with TR or SR, however power analysis indicated that this analysis was underpowered. Pedigree-based correlations identified genetic overlap with psychological distress, schizotypy and mood disorder traits. Finally, the role of neuroticism, psychological resilience and coping styles in antidepressant resistance was investigated. Univariate, moderation and mediation models were applied using logistic regression and structural equation modelling techniques. In univariate models, neuroticism and emotion-orientated coping demonstrated significant negative association with antidepressant resistance, whereas resilience, task-orientated and avoidance-orientated coping demonstrated significant positive association. No moderation of the association between neuroticism and TR was detected and no mediating effect of coping styles was found. However, resilience was found to partially mediate the association between neuroticism and TR. Whilst the first study does not indicate a genetic overlap between regional brain volumes and MDD, it demonstrates the utility of the intermediate approach in complex disease. Antidepressant resistance was associated with neuroticism both genetically and phenotypically, indicating its role as an intermediate phenotype. Nonetheless, larger sample sizes are needed to adequately address the components of antidepressant resistance. Further work in antidepressant non-response may help to identify biological mechanisms responsible in MDD pathology and help stratify individuals into more tractable groups.

Submitted by Henriette Gellert Moranza null (henriette.moranza@hotmail.com) on 2017-03-14T00:20:55Z No. of bitstreams: 1 Dissertação Henriette Moranza.pdf: 1760193 bytes, checksum: 2f7508b39b048f746c69e728ec197fa7 (MD5) / Approved for entry into archive by LUIZA DE MENEZES ROMANETTO (luizamenezes@reitoria.unesp.br) on 2017-03-20T18:56:34Z (GMT) No. of bitstreams: 1 moranza_hg_me_jabo.pdf: 1760193 bytes, checksum: 2f7508b39b048f746c69e728ec197fa7 (MD5) / Made available in DSpace on 2017-03-20T18:56:34Z (GMT). No. of bitstreams: 1 moranza_hg_me_jabo.pdf: 1760193 bytes, checksum: 2f7508b39b048f746c69e728ec197fa7 (MD5) Previous issue date: 2017-02-22 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Objetivo: investigar o comportamento, concentrações de corticosterona, lactato e glicose de ratos Wistar submetidos a um protocolo de "overtraining" (PO) para o desenvolvimento de "Functional" (FOR) ou "Nonfunctional Overreaching" (NFOR). Métodos: inicialmente a amostragem de indivíduos foi de 49. O grupo controle (C, n= 16) realizou um programa de condicionamento leve (1 sessão/dia/ 2x/sem./12 m.min-1). Os outros ratos (n= 33) foram submetidos ao PO, com duração de 12 sem., prescrito para produzir um desequilíbrio entre as sessões de exercício e o período de recuperação. Em 8 sem. foram realizadas sessões de treino diárias, por 5 d consecutivos seguidas por 2 d de recuperação. Nas 4 sem. subsequentes, houve aumento da frequência de treino (2, 3, 4 e 4 x/d) e redução do tempo de recuperação entre as sessões (4, 3, 2 e 2 h). Para avaliação da aptidão física, os ratos foram submetidos a sete testes de esforço máximo (T-máx) durante e dois testes após o PO. Dois grupos foram identificados pela diferença da inclinação (α) obtida a partir da regressão linear dos desempenhos individuais nos Tmáx-3, 4, 5, 6 e 7. Ratos NFOR (n= 14) tiveram α= < -0.98. Analisou-se a recuperação passiva de 2 sem., sendo realizado testes de Campo Aberto (CA) e Labirinto em Cruz Elevado (LCE). Neste período, dois Tmáxs (8 e 9) foram realizados para verificação da continuidade das condições FOR e NFOR. Em Tmáx-2, Tmáx-6 e Tmáx-9 realizaram-se coletas sanguíneas para quantificação das concentrações plasmáticas de lactato ([lac]antes e [lac]após) e glicose ([glic]antes e [glic]após). Quantificou-se corticosterona durante o repouso e após os Tmáx-7 e 9, ([cort]repouso e [cort]após). Glândulas adrenais foram coletadas e pesadas. Para análise estatística aplicaram-se ANOVA de uma via e para medidas repetidas no tempo, testes t de Student pareado e não pareado e foi realizada correlação de Pearson (P< 0.05). Resultados: FOR e NFOR tiveram aumento de desempenho a partir do Tmáx-2 (303.8±13.8; 294.3±18.9 e 190.2±12.2 kg.m, respectivamente). O grupo NFOR teve o desempenho reduzido no Tmáx-7 (292.2±36.4 kg.m). No teste CA, ocorreu aumento da frequência de levantar para os grupos FOR e NFOR em relação ao grupo C. Houve redução da [lac]após para FOR e NFOR no Tmáx-6 em relação ao grupo C (3.61±0.38; 5.43±0.63; 7.64±0.43 mmol/L, respectivamente) sendo que NFOR obteve lactatemia maior que FOR. Ainda no Tmáx-6, a [glic]após foi menor em FOR em relação ao grupo C (5.66±0.17 vs. 6.52±0.21). Não houve diferença para as concentrações de corticosterona. Houve aumento do índice adrenosomático para o grupo NFOR no Tmáx-7 e redução deste após o Tmáx-9. Conclusões: "functional" ou "nonfunctional overreaching" provocou ansiedade e alterações nas concentrações de lactato e glicose em ambos os grupos bem como aumento do índice adrenosomático nos ratos que demonstraram a condição NFOR. / Purpose: To investigate the behavior, corticosterone and lactate concentrations of Wistar rats submitted to an overtraining protocol (OP) for the development of functional (FOR) or nonfunctional overreaching (NFOR). Methods: Sampling of rats was 49. The control group (C, n= 16) performed a mild conditioning program (1 session/day / 2x/wk/12 m.min-1). The other rats, n= 33, were submitted to 12-week OP prescribed to produce an imbalance between the exercise sessions and the recovery period. In 8 wks. daily training sessions were performed for 5 consecutive d followed by 2 d of recovery. In the following 4 wks. (2, 3, 4 and 4 x / d) there was an increase in training frequency and reduction of recovery time between sessions (4, 3, 2 and 2 h). To evaluate physical fitness, the rats were submitted to seven maximum tests (Tmax) during and two tests after the PO. Two groups were identified by the slope difference (α) obtained from the linear regression of individual performances at Tmax-3, 4, 5, 6 and 7. NFOR rats (n= 14) had α = -0.98. Passive recovery of 2 wks was analyzed, and Open Field (OF) and Elevated Plus Maze (EPM) tests were performed. In this period, 2 Tmaxs (8 and 9) were performed to verify the continuity of FOR and NFOR conditions. Blood samples were collected for Tmax-2, Tmax-6 and Tmax-9 for the quantification of plasma lactate concentrations ([lac]before and [lac]after) and glucose ([glic]before and [glic]after). Corticosterone was measured at rest and after Tmax-7 and 9, ([cort]rest and [cort]after). Adrenal glands were collected and weighed. For statistical analysis one-way ANOVA and repeated measures ANOVA, paired and unpaired Student's t-tests and a Pearson correlation were performed (P < 0.05). Results: NFOR and FOR had an increase in performance from Tmax-2 (303.8±13.8, 294.3±18.9 and 190.2±12.2 kg.m, respectively). The NFOR group had reduced performance in Tmax-7 (292.2±36.4 kg.m). In the OF test, there was an increase in the frequency of rearing for the FOR and NFOR groups in relation to the C group. There was reduction of [lac]after for FOR and NFOR in Tmax-6 compared to group C (3.61±0.38, 5.43±0.63 , 7.64 ± 0.43 mmol/L, respectively) and NFOR obtained lactate concentrations greater than FOR. Still in Tmax-6, [glic]after was lower in FOR compared to group C (5.66±0.17 vs. 6.52±0.21). In Tmax-7, resting was lower for the NFOR group compared to C. There was no difference in corticosterone concentrations. There was an increase in the adrenosomatic index for the NFOR group in the Tmax-7 and a reduction in the latter after the Tmax-9. Conclusion: functional and nonfunctional overreaching caused anxiety and changes in lactate and glucose concentrations in both groups as well as increase in the adrenosomatic index in rats that demonstrated the NFOR condition.

Submitted by Sandra Pereira (srpereira@ufrrj.br) on 2017-01-24T15:47:47Z No. of bitstreams: 1 2016 - L?via da Rocha Natalino Monteiro.pdf: 1451629 bytes, checksum: c984d90970fa9192a11dedd19eb857df (MD5) / Made available in DSpace on 2017-01-24T15:47:47Z (GMT). No. of bitstreams: 1 2016 - L?via da Rocha Natalino Monteiro.pdf: 1451629 bytes, checksum: c984d90970fa9192a11dedd19eb857df (MD5) Previous issue date: 2016-02-17 / Funda??o Carlos Chagas Filho de Amparo ? Pesquisa do Estado do RJ - FAPERJ / The constant regulation of sodium and water balance is essential for the maintenance of life. From the simplest to the most complex organisms, conservation of such elements at appropriate levels is a vital issue for the homeostasis of the individual. In order to maintain this balance, organisms resort a set of neurohumoral mechanisms that constantly regulate the content of bodily water and sodium. In recent decades, studies of neural mechanisms involved in the regulation of sodium appetite have gained ground since the excessive intake of sodium chloride has been directly related to functional changes which can lead to diseases such as hypertension. Besides the high daily consumption of sodium chloride by occidental societies, there is also a growing number cases of hypertension, particularly the so-called ?salt-sensitive?. Therefore, it is necessary that the mechanisms involved in these changes are intensively studied in scientific models. Thus, through the use of an animal model, we investigated the functional changes arising from the modification of sodium content in the diet of animals. Wistar male rats were randomly divided into 4 groups: i) control (CTRL); ii) low-sodium diet (LSD); iii) furosemide (FURO); iv) saline overload (SO). From this division, we draw the hydroelectrolytic, cardiovascular and molecular profiles of these paradigms four days after the protocols beginning. We found that low-sodium diet and furosemide were able to induce a sustained sodium appetite 4 hours after reintroduction of fluids when compared to control group (LSD: 4.1 ? 0.8 and FURO: 8.5 ? 1.0 vs. CTRL 0.15 ? 0.08 mL/100g body weight, p<0.05, respectively). Besides we have confirmed the occurrence of hypernatremia in SO group (163.7 ? 1.6 vs. 143.2 ? 0.7 mEq/L, p<0.05) we surprisingly have found higher plasma sodium levels in LSD (148.7 ? 1.0 vs. 143.2 ? 0.7 mEq/L, p<0.05) when compared to control group. During the assessment of cardiac parameters, only the FURO group showed smaller mean arterial pressure than control after administration of phenylephrine at both 10 and 50 ?g/mL concentrations (Phe10: 142.6 ? 19.1 vs. 222.4 ? 14 bpm, p<0.05; Phe50: 261.0 ? 74.8 vs. 190.9 ? 19.6 mmHg, p<0.05, respectively), probably due to hypovolemia, a factor which could also explain the absence of hyponatremia in these animals. Concerning the molecular parameters within the PVN, SO group showed an increased mRNA expression of AVP (2.61 ? 0.16 vs. 1.04 ? 0.04 a.u., p<0.05) and OT (1.52 ? 0.12 vs. 1.01 ? 0.05 a.u., p<0.05), while in the LSD group, these parameters are reduced (AVP: 0.65 ? 0.07 vs. 1.04 ? 0.04 a.u., p<0.05; OT: 0.65 ? 0.06 vs. 1.01 ? 0.05 a.u., p<0.05), when compared to control group, respectively. Finally, we found increased levels of AT1 receptor mRNA in SO group (2.94 ? 0.26 vs. 1.14 ? 0.25 a.u, p<0.05) and FURO (3.08 ? 0.51 vs. 1.14 ? 0.25 a.u, p<0.05) compared to control, respectively. Thus, these results underscore the central role of neuroendocrine systems in the modulation of electrolyte and cardiovascular homeostasis / A regula??o constante do balan?o de ?gua e s?dio ? essencial para a manuten??o da vida. Desde os organismos mais simples at? os mais complexos, a conserva??o de tais elementos em n?veis adequados constitui ponto crucial para a homeostase do indiv?duo. Para tanto, os organismos lan?am m?o de uma s?rie de mecanismos neuro-humorais que regulam a todo momento o conte?do de ?gua e s?dio corporal. Nas ?ltimas d?cadas, estudos sobre mecanismos neurais envolvidos na regula??o do apetite ao s?dio t?m ganhado destaque, uma vez que o consumo exagerado de cloreto de s?dio est? diretamente relacionado a altera??es funcionais que podem gerar doen?as como a hipertens?o arterial. Al?m do alto consumo di?rio de s?dio pelas sociedades ocidentais, h? tamb?m um crescente n?mero de casos de hipertens?o arterial, particularmente do tipo denominado sal-sens?vel. Assim, ? necess?rio que os mecanismos envolvidos nessas altera??es sejam intensamente estudados em modelos cient?ficos. Desta forma, atrav?s do uso de modelo animal, investigamos neste trabalho as altera??es funcionais advindas da modifica??o do conte?do de s?dio presente na dieta dos animais. Para tanto, ratos Wistar machos foram randomicamente divididos em 4 grupos experimentais: i) controle (CTRL); ii) dieta pobre em s?dio (DP); iii) furosemida (FURO); iv) sobrecarga salina (SS). A partir desta divis?o, tra?amos os perfis hidroeletrol?tico, cardiovascular e molecular desses paradigmas de desafio ao balan?o hidroeletrol?tico. Verificamos que a dieta hiposs?dica e a furosemida foram capazes de induzir o apetite ao s?dio de forma sustentada at? 4 horas ap?s reapresenta??o de fluidos (DP 4,1 ? 0,8 de peso corporal; FURO 8,5 ? 1,0 vs. CTRL 0,15 ? 0,08 mL/100g; p<0,05). Confirmamos a ocorr?ncia de hipernatremia a partir da sobrecarga salina (SS 163,7 ? 1,6 vs. CTRL 143,2 ? 0,7 mEq/L; p<0,05) e, surpreendentemente, encontramos n?veis natr?micos maiores que o controle no grupo DP (DP 148,7 ? 1,8 vs. Ctrl 143,2 ? 0,7 mEq/L; p<0,05). Quanto ? avalia??o dos par?metros card?acos, somente o grupo furosemida apresentou PAM menor que o controle ap?s a administra??o de fenilefrina nas concentra??es de 10 e 50 ?g/mL ( Phe10 = Furo 142,6 ? 19,1 vs. Ctrl 222,4 ? 14,2 ; Phe50 = Furo 261,0 ? 74,8 vs. Ctrl 190,9 ? 19,6 mmHg; p<0,05), provavelmente devido ? hipovolemia nestes animais. Verificamos ainda que no grupo submetido ? sobrecarga salina ocorre aumento da express?o de mRNA para AVP (SS 2,61 ? 0,16 vs. CTRL 1,04 ? 0,04 a.u - unidades arbitr?rias; p<0,05) e OT (SS 1,52 ? 0,12 vs. CTRL 1,01 ? 0,05 a.u; p<0,05), enquanto que no grupo dieta pobre estes par?metros s?o reduzidos (AVP - DP 0,65 ? 0,07vs. CTRL 1,04 ? 0,04; OT - DP 0,65 ? 0,06vs. CTRL 1,01 ? 0,05 a.u; p<0,05). Por fim, encontramos n?veis aumentados de mRNA do receptor AT1 nos grupos sobrecarga salina (SS 2,94 ? 0,26 vs. CTRL 1,14 ? 0,25 a.u; p<0,05) e furosemida (Furo 3,08 ? 0,51 vs. CTRL 1,14 ? 0,25 a.u; p<0,05). Deste modo, estes resultados refor?am o importante papel dos sistemas neuroend?crinos centrais na modula??o da homeostase hidroeletrol?tica e cardiovascular

Os sarcomas uterinos são tumores mesodérmicos raros que compreendem cerca de 3% de todos os cânceres nesse órgão. Apresentam diversidade histológica, comportamento agressivo, disseminação precoce e altas taxas mortalidade. Recentemente, os carcinossarcomas (CS) foram reclassificados histologicamente como carcinomas. Neste trabalho, os CS foram incluídos na casuística tanto para fins de comparação de seu componente mesenquimal, como por ainda fazerem parte da maioria dos estudos sobre sarcomas de corpo uterino e também da última classificação da WHO (Word Health Organization). Devido à sua diversidade e raridade, não há consenso relacionado aos fatores de risco para pior prognóstico e tratamento adequados para esses tumores. Informações sobre seus perfis gênicos e proteicos poderiam contribuir na caracterização de marcadores moleculares que auxiliassem no diagnóstico e prognóstico desses tumores, bem como no entendimento de sua biologia e comportamento clínico. Assim, nos propusemos a avaliar a presença de alterações gênicas nesses tumores, utilizando um painel de 409 genes, oncogenes e supressores de tumor, frequentemente mutados em tumores sólidos. Para isso, foram selecionadas 66 amostras, das quais 14 foram sequenciadas, incluindo, 5 carcinossarcomas (CCS), 4 leiomiossarcomas (LMS), 4 sarcomas de estroma endometrial (SEE) e 1 adenossarcoma (ADS). As reações foram realizadas utilizando a plataforma Ion Proton System (ThermoFisher) de Sequenciamento de Nova Geração. Nas 14 amostras encontramos 27 LoF e 40 mutações missenses, numa média de 39 inserções e 52 deleções por amostra, totalizando 70 mutações. Dessas, 25 encontram-se no banco de dados COSMIC. Os genes mais comumente mutados em nossa amostragem foram: TP53 (50%), KMT2D (36%), ATM (29%), DICER1 (21%), PIK3CA (21%), TRRAP (21%). Nosso objetivo principal era encontrar mutações específicas para cada subtipo histológico, porém apenas os SEEs (PDE4DIP) e os CCS (ERBB4 e PIK3CA) tiveram mutações especificas. Em outra análise, observamos que todos os subtipos histológicos compartilham o gene KMT2D. Embora não tenha sido possível estabelecer um perfil mutacional para cada subtipo histológico avaliado, nossos resultados abrem perspectivas para uma nova linha de pesquisa nos sarcomas de corpo do útero e certamente contribuem para um melhor entendimento dessas neoplasias / Uterine sarcomas are rare mesodermal tumors that comprise about 3% of all cancers in this organ. They present histological diversity, aggressive behavior, early dissemination and high mortality rates. Recently, carcinosarcomas (CCS) were histological reclassified as carcinomas. Here, we have included them in our series for purposes of comparison of the mesenchymal component and also because these tumors still form part of both the majority of studies and the WHO\'s latest classification for uterine sarcomas (Word Health Organization). Because of their diversity and rarity, there is no consensus regarding the risk factors for poor prognosis and appropriate treatment for these tumors. Thus, information about their gene and protein profiles can help in the diagnosis and prognosis of these tumors, as well as in the understanding of their biology and clinical behavior. We performed the New Generation Sequencing of 14 samples of uterine sarcomas (5 CCS, 4 LMS, 4 SEE and 1 ADS, using the Ion Proton System platform (ThermoFisher).) Among the 14 samples, we found 27 LoF (loss of gene function) and 40 missense mutations, with a mean of 39 insertions and 52 deletions per sample, totaling 70 mutations, 25 described in the COSMIC database. The most commonly mutated genes in our sample were TP53 (50%), KMT2D (36%), ATM (29%), DICER1 (21%), PIK3CA (21%), TRRAP (21%).Our main objective was to find specific mutations for each histological subtype, but only SEEs (PDE4DIP) and CCS (ERBB4 and PIK3CA) had specific mutations. In another analysis, we observed that all the histological subtypes share the KMT2D gene, which will be studied in future analyzes. Others analyzes, using a custom panel, are necessary to understand these mutations and its biological implication in uterine carcinosarcoma and sarcomas

Acrylamide, 2,5-hexanedione, Tri-o-tolyl phosphate and leptophos belong to three fundamentally different chemical classes but all four chemicals cause central-peripheral distal axonopathy. Some of these compounds have been shown to alter brain steady state levels of neurotransmitters or to inhibit the activities of adenosine triphosphatases which are involved in the uptake and storage of biogenic amines. Tests were performed to determine alterations in steady state levels of rat brain norepinephrine and dopamine in response to doses of the above chemicals and of the central nervous system toxin, methyl mercuric chloride sufficient to cause ataxia. Catecholamine synthesis rate constant estimations were performed. Specific activities of tyrosine in brains of control and treatment groups following intravenous injection of labelled tyrosine were compared to determine if passage of tyrosine across the blood-brain barrier were affected by treatments. Levels of the dopamine metabolite, dihydroxyphenylacetic acid were assayed in all cases. Levels of the norepinephrine metabolite, 3-methoxy-4-hydroxymethylethyleneglycol sulfate, were assayed in response to acrylamide administration. Animal weights were recorded at the beginning and end of the treatment period. Rats treated with a cumulative dose of 250 mg/kg acrylamide had significantly lower norepinephrine levels than controls. 2,5-hexanedione administration significantly increased the dopamine synthesis rate constant at a cumulative dose of 210 mg/kg. Cumulative doses of 700 and 2100 mg/kg also appeared to elevate norepinephrine and dopamine synthesis rate constants, but values were not statistically significant. Leptophos caused a slight but significant increase in dopamine levels in rats administered a cumulative dose of 75 mg/kg. Methyl mercuric chloride caused variable effects to norephinephrine synthesis rate and lowered dopamine synthesis rate constant at cumulative doses of 5 to 50 mg/kg. No other alterations were seen in levels of catecholamines or of their metabolites, nor in synthesis rate constants of the catecholamines in response to administration of the five neurotoxic compounds. No evidence of altered blood-brain transport of tyrosine was observed at any level of neurotoxins administered. Rats given the highest cumulative doses of all neurotoxins except tri-o-tolyl phosphate gained significantly less weight than control animals. It was concluded that the four compounds which cause delayed distal neurotoxicity do not alter levels of turnover rates of brain catecholamines in a consistent manner.

This research used Geographical Information System (GIS) data to estimate the acreage of wetland loss due to small-scale activities (taking into account exempt, permitted, and unauthorized activities) in the Southwest District of the Department of Environmental Protection (DEP) between 2006 and 2011 and compared that net loss with the unmitigated wetland net loss that DEP documented during that time for authorized activities and violations that were discovered. The comparison allowed an estimation of the extent of undocumented small-scale unmitigated wetland loss that occurred during those six years. DEP records show that 88% of non-compliance cases remain unresolved, and the net loss of wetlands that was documented by DEP is 28.66 acres. The change in acreage of DEP-regulated wetlands (and wetlands on agricultural parcels) as determined by GIS analysis is 1,250 acres gained. However, evidence shows that some of the water features categorized as wetlands in the GIS interface are reservoirs which may not be providing the functions necessary to mitigate for wetland loss. Evidence also shows that many small-scale wetland alterations were not detected by remote sensing, indicating that there is a great level of uncertainty in the GIS interpretation. Consequently, achievement of the No Net Loss goal in Florida cannot be determined using documented alterations, nor can it be determined by use of medium-high resolution aerial imagery. The analysis can be extrapolated to the rest of Florida, where State wetland protection regulations are constant.