Submitted by PPG Biologia Celular e Molecular (bcm@pucrs.br) on 2017-10-11T12:59:22Z No. of bitstreams: 1 PEDRO_VARGAS_DIS.pdf: 3468332 bytes, checksum: 563022a7fa710bed810c652069a0777c (MD5) / Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-10-11T20:09:27Z (GMT) No. of bitstreams: 1 PEDRO_VARGAS_DIS.pdf: 3468332 bytes, checksum: 563022a7fa710bed810c652069a0777c (MD5) / Made available in DSpace on 2017-10-11T20:19:08Z (GMT). No. of bitstreams: 1 PEDRO_VARGAS_DIS.pdf: 3468332 bytes, checksum: 563022a7fa710bed810c652069a0777c (MD5) Previous issue date: 2017-03-10 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Glioblastoma multiform (GBM) is considered the most aggressive tumors of central nervous system (CNS), and the most lethal among primary tumors presenting low survival prognosis, resistance to radiotherapy and chemotherapy. P2Y12 is considered a chemoreceptor for adenosine diphosphate (ADP). Its expression is documented in some cancer types, such as the C6 lineage of rat glioma, renal carcinoma and colon carcinoma. However, its role in the development of tumour progression and the resistance mechanism in chemotherapy are not well elucidated. Currently, it is well established that normal platelet function is an important factor for the progression of tumors, with thrombocytopenic rats demonstrating a significant reduction of metastases. Clopidogrel bisulfate is a drug, which belongs to the class of antiplatelet agents, being a P2Y12 receptor antagonist whose endogenous ligand is ADP. The aim of the present study was to determine the effects of tumor cells exposed to the treatment with clopidogrel. The C6 rat cell line was sensitive to the drug tested (150 ?M) in the viability and cell counts (69.63 ? 8.70) and (53.05 ? 20.06). Both cell lines showed a significant reduction in the number of colonies after 10 days of treatment with clopidogrel. The U251-MG strain demonstrated a significant increase in the G1 phase and a significant reduction in the S phase in the cell cycle (20.32 ? 3.05) and (19.45 ? 2.35) in the concentration of 500 ?M. Other results demonstrate important antiproliferative activity in both tumor lines, suggesting an important participation of the P2Y12 receptor in this process. / O glioblastoma multiforma (GBM) ? considerado o mais agressivo dos tumores do sistema nervoso central (SNC) e o mais letal entre os tumores prim?rios apresentando baixo progn?stico de sobrevida, resist?ncia ? radioterapia e a quimioterapia. O P2Y12 ? considerado um quimiorreceptor para a adenosina difosfato (ADP). Sua express?o ? documentada em algumas linhagens de c?ncer, como a linhagem C6 de glioma de rato, carcinoma renal e carcinoma de c?lon. Contudo, seu papel no desenvolvimento da sinaliza??o e resposta ? quimioterapia n?o est? bem elucidado. Atualmente, est? bem estabelecido que o funcionamento normal das plaquetas ? um importante fator para a progress?o de tumores, sendo que ratos com trombocitopenia demonstraram uma redu??o significativa de met?stases. O bissulfato de clopidogrel ? um f?rmaco pertencente ? classe dos antiagregantes plaquet?rios, sendo um antagonista do receptor P2Y12, cujo ligante end?geno ? o ADP. O presente trabalho teve como objetivo averiguar quais os efeitos ocasionados ?s c?lulas de gliomas quando expostas ao clopidogrel. Para isto, foram utilizadas duas linhagens de gliomas, U251-MG de glioma humano e C6 de ratos, e o tratamento com clopidogrel (150, 300, e 500 ?M), foi avaliado nos par?metros de viabilidade celular, contagem de c?lulas, RT-PCR e citometria de fluxo. A linhagem de rato C6 mostrou-se sens?vel ao f?rmaco testado (150 ?M) com redu??o da viabilidade e contagem celular (69.63?8,70) e (53,05 ? 20.06), respectivamente. Ambas as linhagens tapresentaram uma redu??o significativa no n?mero de col?nias ap?s 10 dias tratamento com clopidogrel. A linhagem U251-MG demonstrou um aumento significativo na fase G1 e uma redu??o significativa na fase S e do ciclo celular (20,32 ? 3.05) e (19.45? 2.35 ) na concentra??o de 500 ?M, por?m nos ensaios de viabilidade e contagem n?o houve diferen?a significativa. Nossos resultados demonstram atividade antiproliferativa importante em ambas as linhagens tumorais, sugerindo uma participa??o importante do receptor P2Y12 neste processo.

Submitted by PPG Medicina e Ci?ncias da Sa?de (medicina-pg@pucrs.br) on 2018-06-14T11:20:47Z No. of bitstreams: 1 CARLA_FERNANDA_FURTADO_GARDANI.pdf: 1897020 bytes, checksum: 89528b1ce682182124c46409102c1c92 (MD5) / Approved for entry into archive by Sheila Dias (sheila.dias@pucrs.br) on 2018-06-25T13:28:22Z (GMT) No. of bitstreams: 1 CARLA_FERNANDA_FURTADO_GARDANI.pdf: 1897020 bytes, checksum: 89528b1ce682182124c46409102c1c92 (MD5) / Made available in DSpace on 2018-06-25T13:36:30Z (GMT). No. of bitstreams: 1 CARLA_FERNANDA_FURTADO_GARDANI.pdf: 1897020 bytes, checksum: 89528b1ce682182124c46409102c1c92 (MD5) Previous issue date: 2018-03-28 / Prostate cancer (PC) is the second most diagnosed neoplasm in men, with the exception of non- melanocytic skin tumors. Its global incidence is 1.1 million cases per year and its mortality rate is around 307,000 deaths. Around the world, there are 3,850,000 CP survivors, since their survival in five years reaches values exceeding 80%. Therefore, adequate stratification in the diagnosis and follow-up of these patients is so relevant. In this study, we aimed of evaluating ATP / ADP / AMP hydrolysis as a prognostic biomarker in the CP; CD39 and CD73 enzymes are known to be responsible for the transformation of ATP or ADP into AMP and into adenosine, respectively. Blood samples were collected from 29 patients treated at the Cruz Alta Oncology and Hematology Center (COHCA) and 17 healthy controls (CS), in order to evaluate the hydrolysis activity of ATP, ADP and AMP and to correlate the data between the cases and controls. In addition, the results of hydrolysis were correlated with recognized prognostic factors as Gleason Score (EG), clinical stage (EC) and PSA levels. The mean age of the selected patients was 63.3 years, 71.4% presented PSA <10 at diagnosis, 82.7% were grouped as low in EG and 48.3% of patients belonged to EC IIB. The results demonstrated statistically significant differences in the nucleotide hydrolysis profiles of the cases and controls. In the CP patients the AMP hydrolysis was higher when compared to the hydrolysis of ATP and ADP. Regarding the clinical staging, it was observed that the hydrolysis of ATP was higher in the initial clinical stages, whereas the AMPase remained high regardless of clinical stage. Therefore, we can conclude that the understanding of the ectonucleotidases activities and their influence on tumor progression can collaborate for the diagnostic and improve the therapeutic approach for this neoplasia. / O c?ncer de pr?stata (CP) ? a segunda neoplasia mais diagnosticada no sexo masculino, excetuando-se os tumores de pele n?o melanoc?ticos, por ano sua incid?ncia mundial ? de 1,1 milh?es de casos e sua taxa de mortalidade de cerca de 307.000 ?bitos. Ao redor do mundo h? 3.850.000 sobreviventes de CP, visto que sua sobrevida em cinco 5 anos chega a valores superiores a 80%. Portanto, a estratifica??o adequada no diagn?stico e no seguimento destes pacientes ? muito relevante. Neste estudo objetivou-se avaliar a hidr?lise dos nucleot?deos ATP/ADP/AMP como biomarcadores progn?sticos no CP. Sabidamente as enzimas CD39 e CD73 s?o as principais respons?veis, respectivamente, pela transforma??o de ATP ou ADP em AMP, e este em adenosina. Foram coletadas amostras sangu?neas de 29 pacientes tratados no Centro de Oncologia e Hematologia de Cruz Alta ? COHCA e 17 controles sadios (CS), com o objetivo de avaliar a atividade de hidr?lise do ATP, ADP e AMP e correlacionar os dados entre os casos e controles. Al?m disso, os dados de hidr?lise foram correlacionados com fatores progn?sticos reconhecidos como escala de Gleason (EG), est?gio cl?nico (EC) e n?veis de PSA. A m?dia de idade dos pacientes selecionados foi de 63,3 anos, 71,4% apresentavam PSA < 10 no diagn?stico, 82,7% estavam agrupados como baixo grau na EG e 48,3% dos pacientes pertenciam ao EC IIB. Os resultados demonstraram diferen?as estatisticamente significativas nos perfis de hidr?lise de nucleot?deos entre casos e controles. Nos portadores de CP a hidr?lise do AMP foi mais elevada quando comparada com as hidr?lises de ATP e ADP. Em rela??o ao estadiamento cl?nico, observou-se que a hidr?lise de ATP foi maior nos est?gios cl?nicos iniciais, enquanto que a AMPase se manteve elevada independentemente do est?gio cl?nico. Portanto, pode-se concluir que o estudo da atividade das enzimas ectonucleotidases e o entendimento do CP pode colaborar na compreens?o dos fatores que influenciam a progress?o tumoral, visando melhorar o diagn?stico e a abordagem terap?utica para esta neoplasia.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-08-23T00:10:42Z No. of bitstreams: 1 CintiaMirelaGuimaraesNobre_DISSERT.pdf: 2892729 bytes, checksum: 15d799d4d877b912519dfec4b25a526b (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-08-23T00:16:57Z (GMT) No. of bitstreams: 1 CintiaMirelaGuimaraesNobre_DISSERT.pdf: 2892729 bytes, checksum: 15d799d4d877b912519dfec4b25a526b (MD5) / Made available in DSpace on 2016-08-23T00:16:57Z (GMT). No. of bitstreams: 1 CintiaMirelaGuimaraesNobre_DISSERT.pdf: 2892729 bytes, checksum: 15d799d4d877b912519dfec4b25a526b (MD5) Previous issue date: 2015-08-05 / A doen?a periodontal (DP) e o diabetes mellitus (DM) apresentam uma associa??o bidirecional, na qual o diabetes favorece o desenvolvimento da DP e esta, quando n?o tratada, pode piorar o controle metab?lico do DM. Logo, a DP deve ser tratada para restabelecer a sa?de dos tecidos periodontais e diminuir as complica??es do diabetes. Portanto, objetiva-se avaliar clinicamente o efeito da terapia periodontal de descontamina??o da boca completa (Full Mouth Scaling and Root Planning - FMSRP) em pacientes diab?ticos tipo II portadores de periodontite cr?nica durante 12 meses. Trinta e um participantes no grupo controle (GC), sem diabetes e com periodontite cr?nica, e 12 no grupo teste (GT) foram avaliados no baseline, aos 03, 06, 09 e 12 meses. Foram analisados os seguintes par?metros cl?nicos periodontais: ?ndice de sangramento a sondagem (ISS), ?ndice de placa vis?vel (IPV), profundidade de sondagem (PS), n?vel cl?nico de inser??o (NCI) e recess?o gengival (RG). Para o GT, tamb?m foram realizados exames laboratoriais para avaliar os par?metros sangu?neos de glicose em jejum e hemoglobina glicada (HbA1c). Os resultados foram analisados de duas formas distintas: uma utilizando todos os s?tios presentes na boca e outra apenas com os s?tios doentes. Foram utilizados o teste de Mann-Whitney, Friedman e Wilcoxon com um n?vel de signific?ncia de 5%. Na an?lise intergrupo de todos os s?tios, percebe-se que n?o houve diferen?a significativa ao longo do tempo em rela??o ? PS, ISS, IPV, NCI e RG (p>0,05). Entretanto, ao avaliar os s?tios doentes, observamos diferen?a significativa somente para o NCI, sendo maior para o GT. A an?lise intragrupo de todos os s?tios mostrou uma redu??o estatisticamente significativa para a PS, IPV e ISS em ambos os grupos. Para os s?tios doentes, a an?lise intragrupo mostrou uma redu??o estatisticamente significativa na PS, ISS e NCI em ambos os grupos. Apesar de haver diminui??o nos valores no ISS nos dois grupos, apenas no GC pode-se perceber uma redu??o estatisticamente significativa. N?o houve altera??o no grupo teste em rela??o ? HbA1c e a glicemia em jejum nos per?odos avaliados. Logo, conclui-se que houve melhoras nos par?metros cl?nicos periodontais ao longo dos 12 meses da pesquisa, por?m sem altera??es nos n?veis glic?micos dos pacientes diab?ticos. Portanto, a terapia periodontal mostrou-se eficiente para os cuidados da sa?de bucal. / There is a bidirectional association between periodontal disease (PD) and diabetes mellitus, in which diabetes favors the development of PD and PD, if left untreated, can worsen the metabolic control of diabetes. Thus, periodontal disease should be treated to restore periodontal health and reduce the complications of diabetes. Therefore, the objective is assess the effect of full mouth periodontal therapy decontamination (Full Mouth Desinfection - FMD) in diabetic type II patients with chronic periodontitis during 12 months. Thirty-one patients in group one (G1) and 12 in group two (G2) were followed at baseline, 03, 06 09 and 12 months. There following clinical parameters were accessed: probing on bleeding (BOP), visible plaque index (PI), probing depth (PD), clinical attachment level (CAL) and gingival recession (GR). For diabetic patients, there were also made laboratory tests to evaluate blood parameters: fasting glucose and glycated hemoglobin. The results had been analyzed in two ways: all sites in the mouth and another with diseased sites. The Mann-Whitney, Friedman and Wilcoxon tests were used with 5% significance. Intergroup analysis of all sites it is clear that there was no significant difference over time concerning PD, BOP, PI, CAL and RG. However, when evaluating the diseased sites, we observed significant difference for CAL and PD, with higher values in G1. The intragroup analysis for all sites showed a statistically significant reduction at PD, PI and BOP in both groups. Intragroup analysis of periodontal affected sites showed a statistically significant reduction in PD, BOP and CAL in both groups. There was also a statistically significant increase in RG values. There was no significant change concerning glycated hemoglobin and fasting glucose in the G1. Therefore, it can be concluded that there were improvements in periodontal parameters over the 12 months of research, but without changes in glycemic levels of diabetic patients. Thus, periodontal therapy proved effective in maintaining oral health.

Submitted by Ismael Pereira (ismael@neuro.ufrn.br) on 2017-11-03T14:45:12Z No. of bitstreams: 1 Tese_AdrianoTort_2005.pdf: 1861214 bytes, checksum: 93eb092dffbce7414f26253895b0ad28 (MD5) / Approved for entry into archive by Ismael Pereira (ismael@neuro.ufrn.br) on 2017-11-03T14:46:05Z (GMT) No. of bitstreams: 1 Tese_AdrianoTort_2005.pdf: 1861214 bytes, checksum: 93eb092dffbce7414f26253895b0ad28 (MD5) / Made available in DSpace on 2017-11-06T11:41:34Z (GMT). No. of bitstreams: 1 Tese_AdrianoTort_2005.pdf: 1861214 bytes, checksum: 93eb092dffbce7414f26253895b0ad28 (MD5) Previous issue date: 2005-12 / Os objetivos da presente tese de doutorado foram os de buscar novos antipsic?ticos at?picos de baixo pre?o comercial e tamb?m procurar entender o mecanismo de a??o que leva a um perfil antipsic?tico at?pico. Os resultados da tese s?o divididos em duas partes, de acordo com sua natureza, em experimentais (primeira parte) e te?ricos (segunda parte). Para o desenvolvimento da primeira parte, foi necess?ria primeiramente a programa??o de um software para medir locomo??o em roedores ap?s filmagem com webcam. A seguir, foram investigados os efeitos da guanosina, flunarizina e cinarizina em modelos animais de psicose, bem como em outros paradigmas comportamentais. A guanosina foi escolhida para estudo uma vez que tem se mostrado que ela interage com o sistema glutamat?rgico ? que sabidamente est? envolvido na fisiopatologia da esquizofrenia ? promovendo a capta??o astrocit?ria de glutamato. J? a flunarizina e a cinarizina, dois bloqueadores de canal de c?lcio empregados para tratar enxaqueca e vertigem foram escolhidas pelo fato delas produzirem sinais e sintomas extrapiramidais em pacientes idosos, o que posteriormente foi relacionado ?s suas propriedades como antagonistas moderados dos receptores dopamin?rgicos do tipo D2. A guanosina diminuiu o aumento de locomo??o induzido por um antagonista NMDA (MK-801), enquanto que n?o apresentou efeito sobre o aumento de locomo??o induzido por anfetamina, de forma que sua utilidade como potencial antipsic?tico deve ser ainda melhor estudada. Tanto a flunarizina quanto a cinarizina foram capazes de diminuir o aumento de locomo??o induzido por MK-801 e por anfetamina em doses que n?o causam efeitos catal?pticos importantes. Portanto, foi conclu?do que estes dois compostos apresentam um potencial perfil de antipsic?tico at?pico, com as vantagens de j? estarem dispon?veis para uso comercial, boa tolerabilidade e baixo custo quando comparados com os antipsic?ticos at?picos dispon?veis comercialmente nos dias de hoje. A segunda parte da tese apresenta alguns resultados te?ricos matem?ticos que podem ser derivados da teoria da lei de a??o das massas aplicada ao binding de receptores, utilizando tamb?m resultados experimentais j? conhecidos de PET. Estes resultados apresentam insights ao entendimento das diferen?as entre os perfis antipsic?ticos at?picos e t?picos em rela??o ? gera??o de sinais extrapiramidais. ? discutido que fatores culturais e comerciais relacionados ? posologia atual empregada no tratamento com antipsic?ticos t?picos podem ser os respons?veis pelas diferen?as de perfis, uma vez que alguns deles s?o prescritos em doses proporcionalmente maiores em rela??o ? sua afinidade, atingindo assim maiores n?veis de bloqueio dopamin?rgico no estriado. Uma curta meia-vida plasm?tica tamb?m ? apontada como um poss?vel par?metro importante na gera??o de um perfil at?pico. ? mostrado ainda alguns erros de concep??o relacionados ao curso temporal da ocupa??o dopamin?rgica que tem sido atualmente cometidos na literatura cient?fica, como o conceito de meia-vida de ocupa??o de receptores. Como um ?ltimo resultado te?rico, ? proposto um algoritmo para a redu??o de dose em pacientes tratados com antipsic?ticos apresentando sinais e sintomas extrapiramidais. / The aims of this work were the search for new atypical antipsychotics presenting low cost and the understanding of the mechanism of action leading to atypical antipsychotic profile. The results obtained are presented in two distinct parts based on their nature, namely, experimental (first part) or theoretical (second part). For the development of the first part, a webcam based software to measure locomotion of rodents was programmed. After that, it was investigated the effect of guanosine, flunarizine and cinnarizine on animal models of psychosis, as well as in other behavioral tasks. Guanosine was chosen because it has been shown to interact with the glutamatergic system ? which is known to be involved in the pathophysiology of schizophrenia ? by promoting astrocytic glutamate reuptake. Flunarizine and cinnarizine, two calcium channel blockers commonly used in many countries to treat vertigo and migraine, were chosen because they were shown to induce extrapyramidal signs in elder patients, which was later related to moderate antagonist properties at dopamine D2 receptors. Guanosine was able to reduce a NMDA antagonist (MK-801) induced hyperlocomotion, whereas it had no effect on the hyperlocomotion induced by amphetamine, and it is discussed that its utility as antipsychotic drug should be further evaluated. Both cinnarizine and flunarizine were able to reduce the hyperlocomotion induced by MK-801 and amphetamine at doses that presented no significant cataleptic behavior. It was therefore concluded that these compounds have a potential atypical antipsychotic profile, with the advantage of already approved for commercial use, presenting well tolerability and very low cost when compared to current commercially available atypical antipsychotics. The second part of this thesis presents some theoretical mathematical results that can be derived from the law of mass action theory applied to receptor binding linked with known PET experimental data. These results present insights to the understanding of the differences between typical and atypical profile of antipsychotics regarding the generation of extrapyramidal syndrome. It is argued that cultural and commercial aspects related to the nowadays employed posology of typical antipsychotics can be responsible for the difference seen in profile, once some typical antipsychotics are prescribed in proportionally higher doses in relation to their affinities, leading therefore to higher dopaminergic blockade. A short plasmatic half-life is also pointed as a possible important factor leading to an atipical profile. Moreover, the second part of this thesis also points to some misconception currently being used in the scientific literature regarding the time-course of dopaminergic occupation, such as the concept of receptor occupation half-life. As a last theoretical based result, it is proposed an algorithm for antipsychotic dose reduction in patients presenting extrapyramidal signs and symptoms.

Submitted by PPG Pediatria e Sa?de da Crian?a (pediatria-pg@pucrs.br) on 2018-05-17T17:25:42Z No. of bitstreams: 1 TESE Thiago Viola Final.pdf: 3221820 bytes, checksum: 98e6a1c6936e1a12973e6fe2d7d12ce5 (MD5) / Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2018-05-30T16:45:08Z (GMT) No. of bitstreams: 1 TESE Thiago Viola Final.pdf: 3221820 bytes, checksum: 98e6a1c6936e1a12973e6fe2d7d12ce5 (MD5) / Made available in DSpace on 2018-05-30T16:49:19Z (GMT). No. of bitstreams: 1 TESE Thiago Viola Final.pdf: 3221820 bytes, checksum: 98e6a1c6936e1a12973e6fe2d7d12ce5 (MD5) Previous issue date: 2018-03-12 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Introduction: Child development in adverse environments and conditions, such as with the lack of economic resources or with parental care deprivation, is considered a major risk factor for neurological and psychiatric diseases. Altered cognitive processing is thought to mediate this relationship, however, the neurobiological mechanisms underlying the effects of early adverse experiences on cognition have not yet been fully revealed. Evidence indicates that dopaminergic neurotransmission and the corticotrophinergic system have important functions in the neurobiology of decision-making and risk assessment, which are cognitive processes associated with the functionality of the cerebral cortex. Similarly, working memory is another cognitive domain that underlies cortical activity, and some studies indicate that alterations in neuroimmunologic signaling may contribute to the decline of these higher order cognitive functions. Objectives: To investigate the effects of impoverished housing conditions during early life on risk assessment processing and its associated cortical neurobiological and epigenetic mechanisms in C57BL/6 adolescent mice. In addition, we investigated the effects maternal care deprivation during early life, and the effects of systemic activation of the toll-type receptor (TLR)-3 on working memory performance, and its associated cortical neurobiological mechanisms in male BALB/c mice. Methods: Two studies with rodent experimental models were proposed. The first study used a model of impoverished housing from the postnatal day (P) 2 to P9. During adolescence, risk assessment was investigated using a behavioral paradigm that explores the conflict between two biologically relevant stimuli: the motivation to consume a sweet and highly palatable solution while being threatened by predatory olfactory cues. The expression of dopaminergic (Drd1, Drd2) and corticotrophinergic (Cfr, Crfr1) genes in the medial prefrontal cortex (mPFC) were investigated by real-time PCR. The accumulation of histone marks (H3K9me3, H3R2me2s) were assessed at the promoter region of genes associated with behavioral outcomes. In addition, plasma corticosterone levels were assessed by ELISA. In the second study, a rodent model of maternal care deprivation from P2 to P15 was applied. During adolescence, animals were injected with a TLR-3 agonist, which is a viral receptor implicated with inflammatory signaling, and then tested in a working memory task. The expression of pro-inflammatory genes (Nfkb1, Il6 and Tnf-?) and the receptor itself (Tlr3), were performed in the mPFC by real-time PCR. Results: In the first study, we found increased anxiety-like behavior, increased HPA axis response to stress and impaired RA processing in female adolescent mice, with no effect in males. These sex-specific effects were associated with increased Crfr1 mRNA expression in the medial prefrontal cortex (mPFC), which correlated with an increase in the occupancy of the histone mark H3R2me2s, a histone modification known to be involved in transcriptional activation and epigenetic priming, within the promoter of the Crfr1 gene. In the second study, we found that systemic administration of a TLR-3 agonist can modulate and exacerbate early life stress induced working memory impairments, and that higher gene expression levels of Nfkb1 in the mPFC was associated a lower working memory performance. Conclusions: The findings of the first study indicated a deleterious effect of impoverished housing exposure on risk assessment processing in females, which could be detrimental for cognitive performance in potentially dangerous situations, and suggest that the epigenetic priming of the Crfr1 gene may represent a critical factor mediating the relationship between early life stress and altered cognitive processing later in life in females. Finally, the findings of the second study demonstrated that the systemic activation of TLR-3 can induce working memory impairments, revealing an important mediating role of the neuroinflammatory signalling in the cerebral cortex associated with the cognitive changes resulting from maternal care deprivation exposure during early in life. / Introdu??o: O desenvolvimento infantil em ambientes e condi??es adversas, como frente a escassez de recursos econ?micos ou de cuidado parental, ? considerado fator de risco para doen?as neurol?gicas e psiqui?tricas. Altera??es em processos cognitivos parecem mediar esta rela??o, contudo, os mecanismos neurobiol?gicos adjacentes aos efeitos de experi?ncias adversas precoces sobre a cogni??o ainda n?o foram completamente revelados. Evid?ncias apontam que a neurotransmiss?o dopamin?rgica e o sistema corticotrofin?rgico possuem importantes fun??es na neurobiologia da tomada de decis?o e avalia??o do risco, que s?o processos cognitivos associados a funcionalidade do c?rtex cerebral. Similarmente, a mem?ria de trabalho ? outro dom?nio cognitivo que envolve atividade cortical, e alguns estudos apontam que altera??es na sinaliza??o neuroimunol?gica podem contribuir para o decl?nio destas fun??es cognitivas superiores. Objetivos: Investigar o efeito da exposi??o a moradia empobrecida na inf?ncia sobre o processamento cognitivo de avalia??o do risco e mecanismos neurobiol?gicos e epigen?ticos corticais associados em camundongos adolescentes da linhagem C57BL/6. Al?m disso, investigar o efeito da priva??o do cuidado materno na inf?ncia e da ativa??o sist?mica do receptor do tipo toll (TLR)-3 sobre a mem?ria de trabalho e mecanismos neurobiol?gicos corticais associados em camundongos machos adolescentes da linhagem BALB/c. M?todos: Foram propostos dois estudos com modelos experimentais murinos. O primeiro estudo utilizou um modelo de moradia empobrecida do dia p?s-natal (P) 2 ao P9. Quando os animais encontravam-se no per?odo da adolesc?ncia, o processamento de avalia??o do risco foi investigado por uma tarefa que explora um conflito entre dois est?mulos biologicamente fundamentais na vida de um roedor, a motiva??o de consumir uma solu??o doce e altamente palat?vel (leite condensado) tendo que se expor a pistas olfativas de um predador natural, o coiote. Os n?veis de express?o de genes dopamin?rgicos (Drd1, Drd2) e corticotrofin?rgicos (Cfr, Crfr1) no c?rtex medial pr?-frontal (mPFC) foram investigados por PCR em tempo real. Os n?veis de altera??es de histonas (H3K9me3, H3R2me2s) foram avaliados na regi?o promotora de genes associados aos desfechos comportamentais. Adicionalmente, os n?veis de corticosterona plasm?tica foram avaliados por ELISA. No segundo estudo, o modelo de adversidade utilizado foi o de priva??o do cuidado materno do P2 ao P15. Similarmente, quando os animais encontravam-se no per?odo da adolesc?ncia, ocorreu a administra??o sist?mica de um agonista de TLR-3, um receptor viral relacionado a sinaliza??o inflamat?ria, e posteriormente os animais foram testados em uma tarefa de mem?ria de trabalho. Os n?veis de express?o g?nica de genes pr?-inflamat?rios (Nfkb1, Il6 e Tnf-?) e do pr?prio receptor (Tlr3), foram avaliados no mPFC por PCR em tempo real. Resultados: no primeiro estudo, observou-se um aumento de comportamentos do tipo ansioso, maior responsividade do eixo Hipot?lamo-Pituit?ria-Adrenal (HPA) e uma diminui??o do processamento de avalia??o do risco nas f?meas expostas a moradia empobrecida, ao passo que n?o ocorreram altera??es nos animais machos. A diminui??o de avalia??o do risco foi associada a um aumento na express?o de Crfr1 no mPFC, o que se correlacionou com um aumento dos n?veis de H3R2me2s na regi?o promotora deste gene. No segundo estudo, observou-se que a ativa??o sist?mica de TLR-3 exacerbou os preju?zos de mem?ria de trabalho decorrentes da exposi??o a priva??o do cuidado materno, e este efeito correlacionou-se aos n?veis de express?o de Nfkb1 no mPFC. Conclus?es: os achados do estudo 1 indicam um efeito delet?rio da exposi??o a moradia prec?ria na inf?ncia sobre o processamento de avalia??o do risco em f?meas, revelando um preju?zo espec?fico referente ao engajamento cognitivo frente a situa??es potencialmente perigosas. Al?m disso, evidenciou-se um efeito a n?vel epigen?tico de regula??o da express?o cortical de Crfr1, indicando um importante papel deste gene sobre a rela??o entre pobreza na inf?ncia e altera??es cognitivas em f?meas adolescentes. Por fim, os achados do estudo 2 demonstraram que a ativa??o sist?mica do TLR-3 pode exacerbar os preju?zos de mem?ria de trabalho induzidos pelo estresse precoce, revelando um papel mediador da sinaliza??o neuroinflamat?ria no c?rtex cerebral relacionada as altera??es cognitivas decorrentes da exposi??o a priva??o do cuidado materno.

Made available in DSpace on 2016-04-28T20:18:31Z (GMT). No. of bitstreams: 1 2008 - Jose Luis Acceta.pdf: 1494804 bytes, checksum: 4db4aa22a40640a9df16fa4956f3db06 (MD5) Previous issue date: 2008-07-03 / This work?s objective was to evaluate the occlusion?s viability of the bronchial stump by use of cyanoacrylate, verifying your efficacy and velocity of adhesion, and after-surgery animals recovery. Fifteen dogs, without defined races, males and females, adults were utilized and submited to the partial lobectomy (after traumatism), and the bit extremity was full-filed with cyanoacrylate. The clinical evolution was observed on the 15 subsequent days, by verifying the breath pattern, blood presence and seroma and air in thoracic cavity. The dogs stay housed during 15 days; then the sucture points were take out and the animals go home. / O objetivo deste trabalho foi avaliar clinicamente a viabilidade da oclus?o do coto br?nquico com utililiza??o de adesivo a base de cianoacrilato ap?s lobectomia. Foram utilizados 15 c?es, SRD, machos e f?meas, acima de dois anos de idade, atendidos na Cl?nica Veterin?ria S?o Francisco e no Hospital das Cl?nicas Veterin?rias (HCV) da UNIPLI em emerg?ncia, com les?es pulmonares cujo tratamento cir?rgico necessitou lobectomia pulmonar. Realizou-se a lobectomia completa do lobo pulmonar comprometido, e a extremidade do coto foi preenchida com adesivo ? base de cianoacrilato. A evolu??o cl?nica foi avaliada nos 15 dias subsequentes, atrav?s da verifica??o do padr?o respirat?rio e presen?a de sangue, seroma ou ar na cavidade tor?cica. Os c?es ficaram internados por 15 dias, quando ent?o os pontos foram retirados e os animais receberam alta. O adesivo de cianoacrilato mostrou-se clinicamente eficiente na execu??o e manuten??o da pneumostasia de coto bronquial remanescente em lobectomias totais.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2018-01-16T17:59:55Z No. of bitstreams: 1 ClaraVivianeSilvaDaCosta_DISSERT.pdf: 2160720 bytes, checksum: 6f0b40fd44b02d69cd2f7b13af06ba85 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2018-01-22T11:22:59Z (GMT) No. of bitstreams: 1 ClaraVivianeSilvaDaCosta_DISSERT.pdf: 2160720 bytes, checksum: 6f0b40fd44b02d69cd2f7b13af06ba85 (MD5) / Made available in DSpace on 2018-01-22T11:22:59Z (GMT). No. of bitstreams: 1 ClaraVivianeSilvaDaCosta_DISSERT.pdf: 2160720 bytes, checksum: 6f0b40fd44b02d69cd2f7b13af06ba85 (MD5) Previous issue date: 2017-07-28 / Objetivou-se avaliar a substitui??o da suplementa??o da ractopamina pelo uso dos ?leos de c?rtamo e coco na dieta de su?nos em termina??o. Foram utilizados 24 su?nos machos castrados mesti?os com peso m?dio de 78,00 ? 8,76 kg, distribu?dos em delineamento em blocos casualizados, com quatro tratamentos e seis repeti??es. Os tratamentos constitu?ram de Ra??o Basal (RB); RB + 10 ppm de ractopamina; RB + 4g de ?leo de coco e RB + 4g de ?leo de c?rtamo. Avaliou-se os par?metros de desempenho, peso dos ?rg?os, caracter?sticas de carca?a, qualidade da carne e perfil de ?cidos graxos por cromatografia gasosa. Os animais alimentados com ractopamina e o ?leo de c?rtamo apresentaram melhor convers?o alimentar. O maior ganho de peso foi observado (p ? 0,05) nos animais suplementados com o ?leo de coco e a ractopamina. Em rela??o ao peso dos ?rg?os, observou-se redu??o (p ? 0,05) no peso do est?mago dos animais suplementados com o ?leo de coco. Constatou-se redu??o significativa (p ? 0,05) na espessura de toucinho no ponto 3 dos animais suplementados com ?leo de c?rtamo e para ?rea de olho de lombo houve efeito significativo (p ? 0,05) nos alimentados com ractopamina. Os demais par?metros de carca?a n?o foram observados (p > 0,05) diferen?a entre os tratamentos utilizados. Nas avalia??es do perfil de ?cidos graxos, observou-se maior concentra??o (p ? 0,05) de C12:0 e C14:0 no tecido adiposo dos su?nos suplementados com ?leo de coco. No m?sculo Longissimus dorsi houve o enriquecimento com ?-9, redu??o do C18:1n9t nos animais suplementados com ?leo c?rtamo e eleva??o de C16:1 nos suplementados com ?leo de coco. Recomenda-se a utiliza??o do ?leo de c?rtamo em substitui??o a ractopamina, por apresentar melhor convers?o alimentar, reduzir a espessura de toucinho e promover o enriquecimento da carne com ?-9. / This study aimed to evaluate the replacement of supplementation of ractopamine by the use of safflower and coconut oils in pig diet termination. 24 crossbred barrows were used with an average weight of 78.00 ? 8.76 kg, distributed in a randomized block design with four treatments and six replications. The treatments constituted of Basal Ration (BR); BR + 10 ppm of ractopamine; BR + 4g of coconut oil and BR + 4g of safflower oil. Assessed the performance parameters, organ weight, carcass characteristics, meat quality and profile of fatty acids by gas chromatography. Animals fed ractopamine and safflower oil showed better feed conversion. The highest weight gain was observed (p ? 0.05) in the animals supplemented with coconut oil and ractopamine. In relation to the weight of the organs, it was observed reduction (p ? 0.05) in the stomach weight of animals supplemented with coconut oil. There was a significant (p ? 0.05) reduction in the backfat thickness at point 3 of the animals supplemented with safflower oil and in the loin eye area there was a significant effect (p ? 0.05) on the ractopamine fed. The other carcass parameters were not observed (p > 0.05) difference between the treatments used. In the evaluation of the fatty acid profile, a higher concentration (p ? 0.05) of C12:0 and C14:0 was observed in the adipose tissue of the pigs supplemented with coconut oil. In the longissimus muscle dorsi there was the enrichment with ?-9, reduction of C18:1n9t in animals supplemented with oil safflower and elevation of C16:1 in supplemented with coconut oil. The use of safflower oil is recommended to replace the ractopamine, for presenting better feed conversion, reduce the backfat thickness and promote meat enrichment with ?-9.

Submitted by Helmut Patrocinio (hell.kenn@gmail.com) on 2017-11-09T01:14:16Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Eduardo_Sequerra_2008_TESE.pdf: 15865584 bytes, checksum: fcfa610e8add1f0dd217541746ae3a44 (MD5) / Approved for entry into archive by Ismael Pereira (ismael@neuro.ufrn.br) on 2017-11-09T11:57:09Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Eduardo_Sequerra_2008_TESE.pdf: 15865584 bytes, checksum: fcfa610e8add1f0dd217541746ae3a44 (MD5) / Made available in DSpace on 2017-11-09T11:57:29Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Eduardo_Sequerra_2008_TESE.pdf: 15865584 bytes, checksum: fcfa610e8add1f0dd217541746ae3a44 (MD5) Previous issue date: 2008 / A zona subventricular (SVZ) ? um s?tio de cont?nua neurog?nese em mam?feros p?s-natos e adultos. Ao longo de toda a vida, os progenitores neuronais gerados destinam-se ao bulbo olfat?rio (BO) para onde migram atrav?s da via migrat?ria rostral (RMS). Uma vez no BO, os novos neur?nios se diferenciam em neur?nios GABA?rgicos que integram-se ? circuitaria local. A express?o de GABA inicia ainda na zona germinativa. Essa express?o precoce poderia levar a hip?tese de que estes progenitores j? estariam comprometidos com o fen?tipo GABA?rgico. Por?m, para demonstrar seu comprometimento GABA?rgico, um dos passos necess?rios ? mostrar que a descarboxilase do ?cido glut?mico (GAD), a enzima que sintetiza GABA em neur?nios maduros, est? presente nestas c?lulas. Nesta tese mostramos que a express?o e atividade enzim?tica de GAD, s?o muito baixas na SVZ. Revelamos que o GABA presente em neur?nios imaturos da SVZ prov?m de uma via de s?ntese alternativa, a via da putrescina. Para analisar a import?ncia do GABA proveniente de putrescina para estas c?lulas realizamos a inibi??o farmacol?gica de sua s?ntese atrav?s da administra??o de DFMO. Observamos que o tratamento com DFMO regula positivamente a express?o de GAD na SVZ e RMS. Mostramos tamb?m que os neuroblastos da SVZ que expressam GABA s?o realmente pl?sticos quanto a sua escolha de fen?tipo neuroqu?mico. Quando explantes de SVZ s?o co-cultivados com fatias de telenc?falo embrion?rio dorsal, s?tio de gera??o de neur?nios glutamat?rgicos, uma subpopula??o se diferencia em neur?nios GABA?rgicos e outra menor em glutamat?rgicos. Sugerimos, portanto, que a via da putrescina permite que neur?nios imaturos sintetizem GABA sem, no entanto, haver comprometimento com o fen?tipo GABA?rgico. Esta produ??o de GABA parece ser importante para a migra??o de neuroblastos da SVZ, embora n?o tenhamos tido sucesso em mostrar um papel na prolifera??o com o decr?scimo na produ??o do precursor putrescina. Mostramos que a libera??o de GABA de putrescina parece ter um papel em inibir a express?o de GAD nestes neuroblastos. Em contrapartida, a subregula??o desta sinaliza??o levaria ao comprometimento pelo fen?tipo GABA?rgico. Se mudarmos os sinais apresentados ?s c?lulas da SVZ, como ?queles presentes na VZ do telenc?falo embrion?rio, pelo menos uma de suas subpopula??es ? capaz de mudar seu destino fenot?pico, e diferenciar-se em neur?nios glutamat?rgicos piramidais. / The subventricular zone (SVZ) is proliferative epithelium that continuously gives rise to new neurons in postnatal and adult mammals. The neurons generated in the SVZ migrate through the rostral migratory stream (RMS) where they differentiate in GABAergic interneurons. A characteristic of these neuron precursors is that they start to express GABA while they are still in the SVZ. This fact can lead to the conclusion that at this time they are already commited to the GABAergic phenotype. However, to affirm this one has to show that the origin of GABA in these cells is the same as in mature neurons. One of the most important steps to define GABAergic commitment in neurons is to demonstrate the expression of glutamic acid decarboxylase (GAD), the synthetic enzyme for GABA in mature neurons. Here we show that SVZ cells display low levels of GAD immunocytochemistry and enzyme activity as compared with the olfactory bulb. We also show that these cells are able to synthesize GABA using an alternative source, the putrescine pathway. To test the importance of putrescine made GABA in vivo, we pharmacolgically inhibited putrescine synthesis through DFMO administration. We observed that this treatment lead to an increase of GAD expression in the SVZ and RMS. We also show here that SVZ cells can display phenotypic plasticity. Co-culturing SVZ explants and dorsal telencephalic slices, a spot of glutamatergic neurogenesis, we observed that a subpopulation of SVZ derived neurons differentiated into GABAergic neurons and another into glutamatergic pyramidal neurons. Our working hypothesis is that the putrescine pathway is a mechanism to synthesize GABA without commitment to the GABAergic phenotype. The release of putrescine derived GABA inhibits GAD expression leaving these neuroblasts in an undifferentiated state. The inhibition of putrescine synthesis caused an upregulation of GAD expression which would lead to GABAergic commitment. If we present these neuroblasts with different signals, as those present in the embryonic dorsal telencephalon, they would show plasticity in their phenotypic fate and differentiate into other neurochemical and morphological phenotypes, one of which is the glutamatergic pyramidal neuron.

Made available in DSpace on 2016-04-28T20:18:34Z (GMT). No. of bitstreams: 1 2009 - Ana Paula de Magalhaes Nunes.pdf: 2100747 bytes, checksum: 71718bf8a01eaa5a22f6b041a009a396 (MD5) Previous issue date: 2009-03-13 / Funda??o Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro / In order to investigate the hypothesis of the influence of serotonergic system on the control of dipsogenic and sodium appetite, we examined the effects of chronicallytreated rats with the brain serotonin releaser, fenfluramine, the 5-HT1A agonist, 8-OHDPAT and the selective serotonin re-uptake inhibitor, sertraline. Animals treated with 5- HT1A agonist and brain serotonin releaser were sodium depleted and then their fluids intake analyzed. The first group decreased significantly the salt intake response while the second group intensified the sodium appetite 2 weeks after the first administration of fenfluramine. The water consumption was not altered in none of the groups when compared to their respective controls. Sodium-depleted animals that were treated with sertraline showed a more intense natriorexigenic response. On the other hand, water deprivation induced a lower water intake in SERT-treated rats than the controls. Osmotic simulation evoked a dipsogenic response significantly lower in SERT group. Fluids and food deprivation induced a weak dipsogenic response in SERT treated-rats compared to controls but without difference on saline intake. An increased urinary density and decreased plasma sodium levels in SERT-treated rats correlated with the highest plasma vasopressin and oxytocin levels at the 3rd week post-treatment. The obtained results in chronically-treated rats with the 5-HT1A agonist and the brain serotonin releaser, suggest that the alteration on the brain serotoninergic activity influences the sodium appetite expression, possibly after 5-HT1A autoreceptor desensitization produced by 8-OH-DPAT or brain serotonin depletion achieved with fenfluramine treatment. The results of chronically-treated rats with sertraline, constitute the first evidence of alterations on the threshold for thirst and sodium appetite response in SERT-chronically-treated rats. These alterations possibly are consequence of the hyponatremia provided by inappropriate secretion of AVP and OT. / Para investigar a hip?tese da influ?ncia do status do sistema seroton?rgico no controle da resposta dipsog?nica e do apetite ao s?dio, analisamos os efeitos de ratos tratados cronicamente com um liberador cerebral de serotonina, fenfluramina, um agonista 5-HT1A, 8-OH-DPAT e um inibidor da recapta??o pr?-sin?ptica de serotonina, sertralina (SERT). Animais tratados com agonista 5-HT1A e com liberador cerebral de serotonina, foram submetidos a deple??o de s?dio e, posteriormente, a ingest?o de fluidos foi aferida. O primeiro grupo diminuiu significativamente a ingest?o de salina hipert?nica, enquanto o segundo grupo intensificou o apetite ao s?dio 2 semanas ap?s o ?n?cio do tratamento com fenfluramina. O consumo de ?gua n?o foi alterado em nenhum dos grupos, quando comparados aos seus respectivos grupo controle. Os animais tratados cronicamente com SERT que sofreram deple??o de s?dio, obtiveram uma intensa resposta natriorexig?nica. Por outro lado, a priva??o de ?gua induziu uma menor ingest?o de ?gua em ratos tratados cronicamente com SERT quando comparado-os aos do grupo controle. O est?mulo osm?tico evocou uma resposta dipsog?nica significativamente menor no grupo SERT. A priva??o de fluidos e de alimentos induziu uma baixa resposta dipsog?nica em ratos tratados com SERT quando comparados aos controles, mas sem diferen?a significativa na ingest?o de salina hipert?nica. O aumento da densidade urin?ria em ratos tratados com SERT correlaciona-se com os maiores n?veis plasm?ticos do horm?nio anti-diur?tico e ocitocina na 4? semana p?s-tratamento. Os resultados obtidos em ratos tratados cronicamente, com o agonista 5-HT1A e com o liberador cerebral de serotonina, sugerem uma poss?vel altera??o da atividade cerebral serotonin?rgica, influenciando assim a express?o do apetite ao s?dio, pois possivelmente ocorreu uma dessensibiliza??o de autoreceptores 5-HT1A com o tratamento com 8-OH-DPAT, e deple??o cerebral de serotonina, obtida com o tratamento com fenfluramina. Os resultados relativos aos animais tratados cronicamente com sertralina, constituem as primeiras evid?ncias de altera??o no limiar de sede e de apetite ao s?dio. Essas altera??es s?o possivelmente conseq??ncia da hiponatremia gerada pela secre??o inapropriada de ADH e OT.

Submitted by Jorge Silva (jorgelmsilva@ufrrj.br) on 2017-06-14T19:34:21Z No. of bitstreams: 1 2015 - Veronica Cristina Lopes Menezes.pdf: 1388664 bytes, checksum: eb95b2be98ffd5f3a96140f14377f8f2 (MD5) / Made available in DSpace on 2017-06-14T19:34:21Z (GMT). No. of bitstreams: 1 2015 - Veronica Cristina Lopes Menezes.pdf: 1388664 bytes, checksum: eb95b2be98ffd5f3a96140f14377f8f2 (MD5) Previous issue date: 2015-07-30 / CAPES / The distribution of estrogen receptors in brain structures that are envolved in the hidroelectrolyte balance such as the lamina terminalis (LT), subfornical organ (SFO) and dorsal raphe nucleus (DRN) demonstrated that estradiol can modulate important responses in body fluids. In the literature experimental data support that estrogen can increase the triptofan-hydroxilase type 2 , the main enzyme for the serotonin synthesis. The primary question here is whether or not differences in the baseline or stimulated intake are a function of different levels of circulating gonadal hormones in female ovariectomized rats. Female Wistar intact rats (~230 g) were previously aclimated in metabolic cages during 5 days and ad libitum access to water and hypertonic saline (1.8%) bottles and food. Room temperature was maintained at 22?2 ?C with 12:12 h light-dark cycle (lights off at 19:00). Rats were anesthetized with intraperitoneal injections of a mixture of ketamine (75 mg/kg) and xylazine (5 mg/kg) and then bilaterally ovariohysterectomized. There were four experimental groups: OVX (replaced with corn oil), 2,5 ?g/kg (E2 2,5), 10,0 ?g/kg (E2 10,0) and 40,0 ?g/kg (E2 40,0), daily during seven days, s.c. After 24 h of the surgery the hormonal replacement initiated (estradiol cypionate, EC, Pfizer, Animal Health). We did three experimental protocols: baseline evaluations, sodium depletion and fluid replacement. The estrogen replacement exibitted a dose dependent effect in the following parameters under basal conditions: daily body weight, daily urinary volume and daily food intake. After sodium depletion there were no difference in the urinary volume after 2 and 24 hours of the experiment. But after fluid reposition we observed a dose dependent effect in the ingestive behaviour of water and hypertonic saline intake in sodium depleted and control animals. Our data support that estradiol can alter the natriorexigenic and dipsogenic responses especially after sodium depletion depending of the estrogenic status. / A distribui??o de receptores estrog?nicos em estruturas centrais envolvidas na regula??o da homeostase hidroeletrol?tica como o ?rg?o vasculoso da l?mina terminal, n?cleo subfornicial, n?cleo dorsal da rafe indica que o estradiol pode atuar nessas estruturas em resposta a altera??es nos fluidos corporais. Nosso objetivo foi verificar se a reposi??o hormonal pode influenciar de maneira concentra??o-dependente o status hidroeletrol?tico e neuroend?crino de ratas castradas com reposi??o hormonal em diferentes doses de forma comparativa. Ratas Wistar (~230 g) foram previamente adaptadas, por 5 dias, em gaiolas metab?licas, com acesso ad libitum aos bebedouros volum?tricos de ?gua e salina hipert?nica e ao alimento, sendo mantidas sob ciclo claro-escuro de 12 horas em sala com temperatura controlada em 22??2 ?C. Ao final da adapta??o, as ratas previamente anestesiadas com cetamina (75 mg/kg) e xilazina (5 mg/kg) foram submetidas ? cirurgia de ovariectomia bilateral. Os animais foram divididos em 4 grupos: OVX, reposi??o com ?leo de milho), repostos com ?leo de milho cipionato de estradiol (E2) 2,5 ?g/kg (E2 2,5), 10,0 ?g/kg (E2 10,0) e 40 ?g/kg (E2 40,0). O tratamento de reposi??o foi feito pela via subcut?nea, diariamente durante 7 dias tendo sido iniciado no dia seguinte ? cirurgia. Foram realizados tr?s protocolos experimentais: avalia??o sob condi??es basais, deple??o de ?ons s?dio e reapresenta??o de fluidos. Neste estudo o estradiol apresentou efeito dose dependente nos seguintes par?metros sob condi??es basais: peso corporal di?rio, volume urin?rio di?rio, ingest?o de alimento di?rio. Ap?s deple??o de s?dio n?o houve diferen?a em rela??o ao volume urin?rio de 2 e de 24 horas ap?s o experimento. No entanto ap?s a reapresenta??o dos fluidos houve efeito dose-dependente no comportamento ingestivo de ?gua e de salina hipert?nica tanto nos animais depletados de s?dio quanto nos animais controles.Os dados suportam que o estradiol modula o comportamento ingestivo dos animais sob condi??es basais e ap?s a deple??o de s?dio.