Submitted by Sandro Camargo (sandro.camargo@unipampa.edu.br) on 2015-03-08T18:46:59Z No. of bitstreams: 1 117110030.pdf: 781395 bytes, checksum: 4d3ce136e6aafcc485b383ab0b275336 (MD5) / Made available in DSpace on 2015-03-08T18:46:59Z (GMT). No. of bitstreams: 1 117110030.pdf: 781395 bytes, checksum: 4d3ce136e6aafcc485b383ab0b275336 (MD5) Previous issue date: 2013-07-30 / O presente estudo foi realizado com o objetivo de avaliar e comparar os parâmetros hematológicos e do líquido peritoneal em equinos de tração urbana naturalmente parasitados e após tratamento com anti-helmíntico. Utilizaram-se 21 equinos de tração, com idades entre dois e 19 anos, sem raça definida e com resultado de exame parasitológico superior a 300 ovos por grama de fezes. Os animais foram submetidos à avaliação física e colheita de fezes, líquido peritoneal e sangue em dois momentos do experimento (dia zero - D0 e dia quinze - D15), sendo realizado tratamento antiparasitário no D0. No fluido peritoneal foram avaliadas as características físicas, bioquímicas, bem como contagem total de células nucleadas e diferenciação das linhagens celulares. No sangue foram determinados valores eritrocitários, leucocitários e bioquímicos, que incluíram proteínas plasmáticas totais, glicose, fibrinogênio, albumina, aspartato-transaminase e fosfatase alcalina. A média de ovos por grama de fezes observada foi de 796,4 ±468,8, com predominância de ovos da ordem Strongylida e Ascaridida. A comparação de todos os parâmetros avaliados não demonstrou diferença significativa entre animais naturalmente parasitados e após administração de anti-helmíntico e as médias se mantiveram dentro dos intervalos de referência, com exceção da contagem total de células nucleadas do líquido peritoneal no D0. No líquido peritoneal, houve predominância de neutrófilos segmentados, seguida por macrófagos, linfócitos e eosinófilos em ambos os momentos de avaliação. Na avaliação do hemograma, houve uma tendência do quadro eritrocitário em se manter próximo aos limites inferiores de referência e leve leucocitose no D0. A infestação parasitária nos animais estudados foi predominantemente moderada, o que oferece poucos riscos clínicos. Presume-se que equinos naturalmente parasitados possuem uma relação parasito-hospedeiro simbiótica, possivelmente devido à constante exposição aos agentes parasitários. E nessa situação, pode-se afirmar que os parâmetros hematológicos e de líquido peritoneal auxiliam, mas não são conclusivos no diagnóstico das parasitoses gastrintestinais crônicas. / This study was conducted with the objective to evaluate and compare the hematological and peritoneal fluid parameters in horses used for traction naturally parasitized and after the use of anthelmintic. Twenty one horses, aged between two and nineteen years old, mixed breed and with results of parasitological examination more than 300 eggs per gram of feces were studied. The animals were subjected to physical assessment and collection of feces, blood and peritoneal fluid in two phases of the experiment (day zero – D0 and day fifteen – D15), with antiparasitic treatment being performed in D0. Peritoneal fluid was evaluated for physical and biochemical features, as well as total count of nucleated cells and differentiation of cells lineages. The blood was determined for erythrocyte, leukocyte and biochemical values, which included plasma protein concentration, glucose, fibrinogen, albumin, aspartate transaminase and alkaline phosphatase. The average number of eggs per gram of feces observed was 796,4 ±468,8, with a predominance of eggs of the order Strongylida and Ascaridida. The comparison of all parameters evaluated showed no significant difference between animals naturally parasitized and after administration of anthelmintic and averages remained within the reference ranges, except for the total count of nucleated cells in the peritoneal fluid in D0. In the peritoneal fluid, there was a predominance of segmented neutrophils, followed by macrophages, lymphocytes and eosinophils in both evaluations. In assessing the complete blood count, there was a trend in the framework erythrocyte remaining close to the lower limits of reference and mild leukocytosis in D0. Parasitic infestation of the animals studied was predominantly moderate, which offers minimal clinical risks. It is assumed that horses naturally parasitized have a symbiotic host-parasite relationship, probably due to the constant exposure to parasites. And in this situation, it can be stated that the hematological and peritoneal fluid parameters help, but they are not conclusive in the diagnosis of chronic gastrointestinal parasites.

Hintergrund: Patienten mit hämatologischen Neoplasien sind in den spezialisierten palliativmedizinischen Versorgungsstrukturen im Vergleich zu Patienten mit soliden Tumoren unterrepräsentiert. Im Falle eines palliativmedizinischen Einbezuges erfolgt dieser deutlich später. Hierfür werden verschiedene Gründe diskutiert: Schwierigkeiten in der Prognosefestlegung, das Auftreten von akuten Komplikationen und plötzlichem Krankheitsprogress oder die Notwendigkeit von fortgesetzten invasiven Therapiemaßnahmen. Methodik: In dieser Studie wurden die deutschlandweit erhobenen Daten der Hospiz- und Palliativerhebung (HOPE) von 2006 bis 2008 sekundär ausgewertet, um die klinische Charakteristik und spezielle Therapie- und Versorgungsaspekte von hämatologischen Patienten in spezialisierten Palliativeinrichtungen zu analysieren und mit denen von Patienten mit überwiegend soliden Tumoren sowie mit den prospektiv gewonnen Daten von inkurabel hämatologisch erkrankten Patienten der Abteilung für Hämatologie und Onkologie der Universitätsmedizin Göttingen ohne Anschluss an eine palliativmedizinische Versorgung zu vergleichen. Ergebnisse: Von den insgesamt 5.487 in der HOPE-Erhebung erfassten Palliativpatienten wiesen nur 220 Patienten (4%) eine maligne hämatologische Grunderkrankung auf. Es wurden 50 inkurabel erkrankte hämatologische Patienten der Klinik für Hämatologie und Onkologie erfasst, die einen deutlich besseren Allgemeinzustand und subjektives Gesamtbefinden aufwiesen, weniger fokale Symptome, zeigten, jedoch häufiger an psychischen Symptomen litten, als die Patienten in den palliativmedizinischen Einrichtungen. Hämatologische Patienten erhielten deutlich mehr interventionelle Therapiemaßnahmen wie fortgesetzte palliative Chemotherapie oder Transfusionen. Diskussion: Die Ergebnisse dieser Arbeit zeigen die spezifischen Charakteristika und Bedürfnisse von Patienten mit fortgeschrittenen malignen hämatologischen Grunderkrankungen und machen so die speziellen Anforderungen an die palliativmedizinische Versorgung dieser Patientengruppe deutlich. Auch auf Grundlage dieser Erkenntnisse bedarf es der Entwicklung von neuen, flexiblen Behandlungskonzepten, um hämato-onkologischen Patienten den Zugang zur Palliativversorgung zu erleichtern bzw. eine frühere und bedürfnis- anstatt prognoseorientierte palliativmedizinische Mitbehandlung zu ermöglichen.

The theoretical part is concerned with the functional application of selenium and iodine supplementation methods, risks disproportionate to their income, including changes in biochemical and hematological parameters and evaluation methods of adequate saturation. The practical part analyzes the results of experiments on sheep with a defined content of selenium and iodine in the ration evaluation of selected indicators of the metabolic profile of ewes and their lambs. The results are processed statistically. It reflected the dynamics and interactions of monitored parameters.

Made available in DSpace on 2016-06-02T19:31:44Z (GMT). No. of bitstreams: 1 2308.pdf: 3472152 bytes, checksum: de972462448f54f70c4fafbbaf2ba066 (MD5) Previous issue date: 2008-07-04 / Financiadora de Estudos e Projetos / The aim of this study was to evaluate the morphofunctional structure of the gills and the hematological variables of Astyanax fasciatus and Pimelodus maculatus living on Furnas Dam Reservoir (Minas Gerais State, Brazil) and analyses the influence of water quality on these parameters. The fishes were collected in five sites (FU10: Turvo; FU20: Guapé; FU30: Barranco Alto; FU40: Fama and FU50: Porto Fernandes) during June and December/2006. Physico-chemical variables and organochlorides content of the water and heavy metals on the sediment were performed. Gills and blood samples were taken for check inquire of the composition of the water on the presence of histopathologys and differentiation of chloride and mucous cells and differences on the hematological variables of the fishes collected on the different sites. Hyperplasia and hypertrophy of the respiratory epithelium, lamellar fusion, epithelial lifting, oedema and chloride cells proliferation were the most common histopathological damages observed on the gills for both species. The histopathological alteration index of the gills indicates some degree of lesions that engage the normal function of the organ in A. fasciatus collected in June. Heavy metals, as copper seems to promote alterations on the red blood cells for both fishes during the sampling. While, some pollutants as endosulfan, metolachloride, copper and chromium seems to causes a stimulation of the immune system of the fishes; this effect was most common on the fishes collected in the sites: FU10, FU20 and FU30. The condition factor (K and Kn) of the fishes has been affected by the presence of chromium on the sediment, especially in the site FU30 during the two months. Over all, these results indicates that the water quality in June and December (2006) of Furnas Dam reservoir could promote physiological and morphological alterations on the gills fishes to maintain the homeostase. / O presente estudo teve como objetivo avaliar a estrutura morfuncional das brânquias e as variáveis hematológicas de exemplares de duas espécies de peixes, Astyanax fasciatus e Pimelodus maculatus, coletados na UHE de Furnas, MG e a possível interferência da qualidade da água nos parâmetros estudados. Peixes, amostras de água e de sedimento foram coletados em cinco pontos de amostragem na UHE de Furnas (FU10: Turvo; FU20: Guapé; FU30: Barranco Alto; FU40: Fama e FU50: Porto Fernandes) nos meses de Junho e Dezembro/2006. Foram realizadas análises físicas e químicas da água, determinar a concentração de organoclorados e a presença de elementos-traço. Amostras de brânquias e de sangue foram retiradas para verificar possíveis interações entre organoclorados na água e elementos-traço no sedimento e a presença de histopatologias e diferenciação de células cloreto e mucosa e diferenças nas variáveis hematológicas (série vermelha e série branca) dos peixes coletados nos diferentes locais. Hipertrofia e proliferação de células pavimentosas, fusão lamelar, descolamento do epitélio lamelar, edema e proliferação de células cloreto foram as histopatologias mais encontradas nas brânquias das duas espécies. O IAH (Índice de Alterações Histopatológicas) apontou lesões que comprometem o funcionamento normal do órgão em indivíduos de A. fasciatus coletados em Junho. A presença de elementos-traço, como o cobre, parece promover alteração na série vermelha de A. fasciatus e P. maculatus coletados durante os dois meses. Organoclorados como o endosulfan e metolacloro e elementos traço como cobre e cromo parecem causar uma estimulação do sistema imunológico das duas espécies, especialmente nos locais FU10, FU20 e FU30. Alterações no K e Kn dos animais aparentemente foram influenciados pela presença de cromo no sedimento, especialmente no local FU30 durante os dois meses. O conjunto de todas as alterações observadas indica que a qualidade da água nos diferentes locais durante os dois meses de coleta podem promover alterações nos organismos a fim de manter a homeostasia interna.

La protéine p53 (« Gardien du génome ») doit être altérée pour que le cancer puisse se développer. Les nombreuses thérapies anti-cancéreuses disponibles sont très efficaces mais la réponse clinique est souvent transitoire et les cancers disséminés rechutent ou progressent du fait de l'évolution de sous-populations cancéreuses résistantes au traitement, impliquant souvent TP53 qui est le gène le plus muté dans les formes agressives de nombreux cancers. Nous l’avons étudié dans la leucémie lymphoïde chronique (LLC) et les syndromes myélodysplasiques avec délétion 5q (SMD del(5q)). Grâce à l’étude rétrospective longitudinale de 40 patients atteints de SMD del(5q), nous avons généré des données de NGS ciblé et montré que le statut mutationnel de TP53 au diagnostic ne permettait pas de prédire la progression tumorale, contrairement à ce qui avait été publié précédemment (Jädersten et al., JCO 2011). Nous avons montré que c’était l’évolution clonale du gène TP53 qui était l’élément clé de la progression des SMD del(5q). Nous avons observé de nombreuses émergences de clones mutés entre le stade diagnostique et un stade ultérieur de la maladie, toujours après initiation du traitement par lénalidomide.Le lénalidomide a été approuvé comme nouveau traitement spécifique et très efficace contre l’anémie liée aux SMD del(5q), permettant à la plupart des patients d’être indépendants des transfusions sanguines. Le lénalidomide permet souvent d’éradiquer le clone tumoral porteur de l’anomalie génétique del(5q) isolée, induisant une rémission clinique. Malheureusement, cette rémission est courte avec une durée médiane de 2 ans, puis, dans environ 1 cas sur 2, survient une transformation en leucémie aiguë secondaire de pronostic péjoratif.Nous avons étudié un possible lien entre le traitement par lénalidomide et l’évolution clonale de TP53 par annotation clinico-bio-thérapeutiques des résultats de séquençage de TP53 chez les 24 patients dont les échantillons séquentiels avaient été analysés. Dans notre étude, les patients avec progression tumorale (dont 10 évolutions clonales de TP53 et 1 évolution clonale de RUNX1) avaient reçu une dose cumulée de lénalidomide supérieure à celle reçue par les patients dont la tumeur était restée stable (p = 0.036). Nous avons observé chez plusieurs patients que l’éradication de la tumeur n’était pas utile à l’amélioration de la qualité de vie des patients. La non-éradication semblait même permettre un maintien de l’équilibre clonal et une compétition entre les différents sous-clones de la tumeur, résistants ou non au lénalidomide.Nous discutons de l’évolution de l'écologie de la tumeur au cours du traitement, i.e., l’évolution de ses interactions avec son micro-environnement qui se modifie après chaque nouvelle dose de traitement. Un modèle évolutif dit théorie de la thérapie adaptative, développée récemment remet en question les protocoles conventionnels de thérapie anti-cancéreuse qui préconisent souvent d'administrer la dose maximale tolérée par le patient (Gatenby, 2009). Elle suggère que la dose minimale efficace présenterait l’avantage de ne pas éradiquer les cellules cancéreuses sensibles au traitement pour qu'elles restent en compétition avec les cellules cancéreuses résistantes et limiter la progression ou la rechute. Nous suggérons de prendre en compte également la diminution des effets indésirables pour le patient, améliorant ainsi sa qualité de vie, et enfin la diminution des dépenses de santé pour la collectivité. A ce jour, peu d’études cliniques évaluent l’intérêt de l’adoption de tels protocoles de thérapie adaptative.Néanmoins, des modèles in vivo (xénogreffes) et in silico (modèles statistiques) ont permis d’analyser la dynamique évolutive des populations tumorales en fonction du traitement reçu. Ces modèles prédisent que la survie de l’hôte peut être maximisée par la mise en place d’une thérapie adaptative. / P53 protein is named «guardian of the genome » because it must be altered to let cancer grow.TP53 is the most mutated gene in agressive cancers.Numerous systemic therapies are successful for treatment of disseminated cancers. However, clinical response is often transient, and cancer undergo relapse or progression due to emergence of resistant populations. These latter often harbour TP53 mutations. We studied TP53 in chronic lymphoid leukemia (CLL) and lower-risk myelodysplastic syndroms with del(5q), MDS del(5q). We conducted a retrospective longitudinal study in 40 patients suffering from MDS del(5q). We obtained targeted NGS data showing that TP53 mutational status at diagnosis could not predict tumor progression, by contrast with previously published data (Jädersten et al., JCO 2011). We show that TP53 clonal evolution is the key feature of tumor progression in MDS del(5q). We observed numerous mutated sub-clones emerging between diagnosis and follow-up. In our study, this emergence always followed onset of lenalidomide treatment. Lenalidomide was recently approved as a new therapy specifically improving anemia in patients with MDS del(5q). It allows most patients to become red-blood-cells-transfusion independent. Lenalidomide often eradicates the major tumor clone harbouring the isolated genetic abnormality deletion (5q) and allows clinical remission. Unfortunately, this remission is short (median, 2 years) and is followed, in 1 case out of 2, by a secondary acute leukemic transformation with a very poor prognosis.We studied the issue of a possible link between lenalidomide therapy and TP53 clonal evolution by annotating TP53 sequencing results with acute biological, clinical and therapeutic features in the 24 patients with sequential samples analyzed. In our study, patients with tumor progression (10 TP53 clonal evolution and 1 RUNX1 clonal evolution) were given a higher cumulative dose of lenalidomide compared to patients with stable disease (p = 0.036). Similarly to « adaptive therapy theory »(Gatenby 2009), we observed that eradication of the tumor wasn’t useful for improvement of quality of life. Absence of eradication might even allow to maintain a clonal equilibrium and a clonal competition between the distinct tumor sub-clones, resistant to lenalidomide or not, and therefore maintain stable disease.This theory of adaptive therapy questions the classical protocols of treatments against cancer, in which the maximal tolerated dose is preferred to the minimal effective dose. The latter might however slow down cancer progression or cancer relapse, with decreased side effects in patients, and decreased health costs.To date, few clinical trials (if any) questions such protocols of adaptive therapy. However, in vivo experiments (xenografts) and in silico statistical models allowed to study evolutionary dynamics of tumor sub-populations with and without therapy.The models predict that host survival can be maximized if “treatment-for-cure strategy” is replaced by “treatment-for-stability.” Specifically, the models predict that an optimal treatment strategy will modulate therapy to maintain a stable population of chemosensitive cells that can, in turn, suppress the growth of resistant populations under normal tumor conditions, Dr Gatenby said.

O principal fator de risco para tuberculose (TB) em receptores de transplante de células-tronco hematopoiéticas (TCTH) é viver em regiões de alta endemicidade da doença, uma vez que a imunossupressão favorece a reativação da tuberculose latente (TBL). O diagnóstico da TBL pela prova tuberculínica (PT) tem limitações nos imunocomprometidos e testes de detecção de interferon gama podem ser vantajosos. Os objetivos do presente estudo foram comparar a PT com o QuantiFERON® TB-Gold In-Tube (QFT-GIT) no diagnóstico da TBL e determinar a incidência de TB em duas coortes de pacientes submetidos ao TCTH. Duas coortes foram analisadas prospectivamente. Coorte1: receptores de TCTH incluídos desde o período pré-transplante. Coorte 2: receptores de TCTH com doença do enxerto contra o hospedeiro (DECH) crônica em atividade. A PT e o QFT-GIT foram realizados imediatamente após a inclusão em ambas as coortes. Pacientes na coorte 1 com diagnóstico de TBL receberam profilaxia com isoniazida (INH) por nove meses. Na coorte 2, os pacientes foram acompanhados clinicamente, sem receber profilaxia. TB ativa foi investigada prospectivamente de acordo com definição de caso e por coletas periódicas de escarro. Entre os candidatos ao TCTH, a prevalência de TBL detectada pela PT foi de 4,7% e de 7,1% pelo QFT-GIT. Entre os receptores com DECH crônica a prevalência de TBL detectada pela PT foi de 5,3% e de 12,5% pelo QFT-GIT. A comparação entre as técnicas revelou boa concordância (kappa=0.60). Não houve casos de TB na coorte 1. A incidência cumulativa de TB na coorte 2 foi de 3%. Em comparação com alguns estudos, nossos resultados apresentaram menor prevalência de TB, com menos resultados indeterminados pelo QFT-GIT e melhor concordância entre ambos os testes. É provável que a introdução de profilaxia com INH seja benéfica também para os pacientes com DECH crônica. / The main risk factor for tuberculosis (TB) in hematopoietic stem cell transplant recipients (HSCT) is to live in regions of high endemicity of the disease, since immunosuppression favors the reactivation of latent tuberculosis infection (LTBI). The diagnosis of LTBI by the tuberculin test (TT) has limitations in the immunocompromised hosts and the interferon gamma release assays (IGRAs) may be advantageous. The objectives of the present study were to compare the TT with QuantiFERON® TB-Gold In-Tube (QFT-GIT) in the diagnosis of LTBI and to determine the incidence of TB in two cohorts of patients undergoing HSCT. Two cohorts were analyzed prospectively. Cohort 1: HSCT recipients included since the pre-transplant period. Cohort 2: TCTH recipients with active chronic graft versus host disease (GVHD). TT and QFT-GIT were performed immediately after inclusion in both cohorts. Patients in cohort 1 with diagnosis of LTBI received prophylaxis with isoniazid (INH) for 9 months. In cohort 2, the patients were followed up clinically, without receiving prophylaxis. Active TB was investigated prospectively according to a case definition criteria and periodic sputum sampling. Among the HSCT candidates, the prevalence of LTBI detected by TT was 4.7% and 7.1% by QFT-GIT. Among the recipients with chronic GVHD, the prevalence of LTBI detected by TT was 5.3% and 12.5% by QFT-GIT. The comparison between the techniques showed good agreement (kappa = 0.60). There were no cases of TB in cohort 1. The cumulative incidence of TB in cohort 2 was 3%. Compared with some studies, our results showed a lower prevalence of LTBI, with less indeterminate results by QFT-GIT and better agreement between both tests. It is likely that prophylaxis with INH is also beneficial for patients with chronic GVHD.

Submitted by (edna.saturno@ufrpe.br) on 2016-11-04T16:06:58Z No. of bitstreams: 1 Sandra Regina Fonseca Araujo Valença.pdf: 256054 bytes, checksum: 8a79a96aeb7492a7703d18cc17301540 (MD5) / Made available in DSpace on 2016-11-04T16:06:58Z (GMT). No. of bitstreams: 1 Sandra Regina Fonseca Araujo Valença.pdf: 256054 bytes, checksum: 8a79a96aeb7492a7703d18cc17301540 (MD5) Previous issue date: 2007-02-15 / It was objectified with this work to search the parasitism frequncy related by farmers and to identify the possible association between the clinical signals, hematological alterations and parasitic infection of goats and sheeps livestock of two cities on Pernambuco State semiarid region, as a part of this State Program of caprine and ovine healthy. A total of 263 goats and 98 sheeps of different breed, young and adults, male and female were used to clinical evaluation and blood and feces sample gasthering whose therefore were send to laboratorial analysis for hematocrit (Ht) measurement, total plasmatic protein dosage (TPP), nematode faecal egg counts (FECs) and fecal culture. The results were evaluated through descriptive association analysis using the EpiInfo 6.02 Statistic Program. Anemia was the most frequent problem, related for 50% of the interviewed farmers, followed by diarrhea with 47,6% of the reports. At about 27% of the ovine samples showed low values of Ht (17% - 23%) whose more than 77% had no clinical disturbs. In the same way, from 25% of caprine samples with low Ht values (8% - 18%) at about68% showed no clinical signs. Just 14,28% of the sheep samples had low TPP values (5 – 5,8 g/dl) whose 85% had no clinical altertions. On caprine population studied, only 5,32% had low TPP values (3,4 – 5,8 g/dl) and of them 85% were considered clinically healthy. Fecal culture was positive for 46,35% of sheep whose at least 57% were considered clinically healthy by clinical evaluation. The OPG was positive for 60% of the goats samples and 73% of them shoned no clinical disturbs. Hematocrit low values (8 – 18%) were observed in 36,58% of sheep and 22% of goats samples in the same way, low values were observed on TPP dosage (3,4 – 5,8 g/dl) in 19,51%. Of ovine and 5,51% of caprine samples, with no dependence of FECs results.The qualitative evaluation (clinical parameters) were not decisive in the identification of parasitized animals and the quantitative analysis (HT, TPP and OPG) were not conclusive for indicate animal illness. It is possible to conclude that rusticity and resistance are important characteristics on the investigated flock. / Objetivou-se com este trabalho pesquisar a freqüência do parasitismo segundo relato de criadores, e identificar a possível associação entre sinais clínicos, alterações hematológicas e infecção parasitária em caprinos e ovinos, criados em dois municípios do Sertão do Estado de Pernambuco, como parte do Programa de Sanidade Caprina e Ovina deste Estado. Foram utilizados 263 caprinos e 98 ovinos, de diferentes raças, jovens e adultos, de ambos os sexos, para avaliação clínica e colheita das amostras de sangue e fezes, destinadas à análise laboratorial para mensuração do hematócrito, dosagem da proteína plasmática total, contagem de ovos de nematóides por gramas de fezes e coprocultura. Os resultados foram avaliados através de análise descritiva de associação, utilizando-se programa estatístico EpiInfo versão 6.02. A anemia foi o problema de maior frequência, sendo relatada por 50% dos criadores, seguida das diarréias com 47,6% dos relatos. Cerca de 27% dos ovinos apresentaram valores de Ht baixos (17% - 23%), dos quais mais de 77% não apresentaram alteração clinica. Da mesma forma, pouco mais de 25% dos caprinos apresentaram valores de Ht baixos (8% – 18%) estando pelo menos 68% destes sem alteração clinica. Apenas 14,28% dos ovinos apresentaram valores de PPT baixos (5 - 5,8 g/dl), destes, cerca de 85% não manifestaram alteração clínica. Entre os caprinos, apenas 5,32% demonstraram valores de PPT baixos (3,4 – 5,8 g/dl), também com pouco mais de 85% dos animais sadios quanto à avaliação clínica. Dos ovinos avaliados, 46,35% foram positivos ao exame coproparasitológico, destes, pelo menos 57% apresentaram-se sadios quanto à avaliação clínica. Entre os caprinos, 60% foram positivos à contagem de OPG, estando pelo menos 73% destes sem alteração clínica. Valores baixos de Ht (8 – 18%) foram observados em apenas36,58% dos ovinos e em 22% dos caprinos, bem como, valores baixos de PPT (3,4 – 5,8 g/dl) foram observados em 19,51% dos ovinos e em 5,51% dos caprinos, independente do resultado da contagem de OPG. As avaliações qualitativas (exame clínico) não foram decisivas na identificação de indivíduos parasitados e as análises quantitativas (Ht, PPT e Contagem de OPG) não significaram animais enfermos. Os achados demonstraram que a rusticidade e a resistência dos animais do rebanho foram características predominantes nesta pesquisa.

The effects of glyphosate (1.0 and 5.0 mg/L) on growth, digestive enzymes and toxicology parameters were evaluated in piavas (Leporinus sp.) after 90 days of exposure. A control group was kept in water without herbicide. Fish were fed to satiety twice a day with commercial fish pellets (38% crude protein, Purina®). Water quality was kept by suction of food and fecal residues. The water in the box was renewed every 48 h to maintain herbicide concentration constant during the exposure period. After experimental period (90 days) blood was quickly collected for determining hematological parameters. Liver, white muscle, brain, stomach and intestine were removed and use to determine toxicology parameters and digestive enzymes. After 90 days exposure, fish weight gain, specific growth rate, and feed efficiency wede reduced as glyphosate concentration increased in the water. The activity of all digestive enzymes verified increased with the increase of glyphosate concentration. Results indicate that AChE activity significantly decreased in the brain of fish exposed to 5 mg/L of glyphosate, but in the muscle this parameter was increased in the fish exposed to 1mg/L of glyphosate. Exposure to this herbicide produced a decrease in all hematological parameters tested in both concentrations used. Fish exposed to all glyphosate concentrations showed a significant decrease in liver glycogen and glucose, but a significant increase in muscle glycogen after exposure to 5 mg/L herbicide. Muscle glucose was not altered. Lactate and protein (5 mg/L) of fish exposed to all glyphosate concentrations increased in the liver. Similar results were showed in the muscle for lactate, but protein was reduced after exposure to 5 mg/L of glyphosate. These results indicate that glyphosate affect growth, hematologic and metabolic parameters as well digestive enzymes of piavas. All parameters tested may be indicators of herbicide contamination after prolonged exposure. / Os efeitos do herbicida glifosate (1,0 e 5,0 mg/L) sobre o crescimento, enzimas digestivas e parâmetros toxicológicos foram avaliados em juvenis de piavas (Leporinus sp.), após 90 dias de exposição. O grupo controle foi mantido em água sem herbicida. Os peixes foram alimentados até a saciedade aparente, duas vezes ao dia, com ração comercial peletizada (38% de proteína bruta, Purina®). A qualidade da água foi mantida através de sifonagem de resíduos de alimento e fezes. A água das caixas foi renovada a cada 48 horas para manter a concentração do glifosate constante durante o período de exposição. Após o período experimental (90 dias), o sangue dos peixes foi rapidamente coletado para determinação dos parâmetros hematológicos. Fígado, músculo branco, cérebro, estômago e intestino foram removidos e utilizados para determinar parâmetros toxicológicos e enzimas digestivas. Depois de 90 dias de exposição, o ganho de peso, taxas de crescimento específico e conversão alimentar diminuíram com o aumento da concentração de glifosate na água. Todas as enzimas digestivas verificadas aumentaram com o aumento da concentração de glifosate. A atividade da acetilcolinesterase (AChE) diminuiu significativamente no cérebro dos peixes expostos a 5 mg/L, e aumentou, no músculo dos peixes expostos a 1mg/L de glifosate. Exposição a este herbicida diminuiu todos os parâmetros hematológicos testados em ambas as concentrações utilizadas, mas redução significativa no glicogênio do fígado e glicose, e aumento no glicogênio muscular, ocorreu apenas em 5 mg/L. A glicose muscular não foi alterada. Lactato dos peixes expostos a todas as concentrações de glifosate, e proteína (5 mg/L) apresentaram um aumento significativo no fígado. Resultados semelhantes, para o lactato, foram encontrados no músculo, mas a proteína diminuiu depois da exposição a 5 mg/L de glifosate. Estes resultados indicam que glifosate afeta parâmetros de crescimento, hematológicos e metabólicos, bem como enzimas digestivas de piavas. Todos os parâmetros testados podem ser indicadores de contaminação por herbicida depois de exposição prolongada.

I proposed the study of two distinct aspects of Ten-Eleven Translocation 2 (TET2) protein for understanding specific functions in different body systems. In Part I, I characterized the molecular mechanisms of Tet2 in the hematological system. As the second member of Ten-Eleven Translocation protein family, TET2 is frequently mutated in leukemic patients. Previous studies have shown that the TET2 mutations frequently occur in 20% myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN), 10% T-cell lymphoma leukemia and 2% B-cell lymphoma leukemia. Genetic mouse models also display distinct phenotypes of various types of hematological malignancies. I performed 5-hydroxymethylcytosine (5hmC) chromatin immunoprecipitation sequencing (ChIP-Seq) and RNA sequencing (RNA-Seq) of hematopoietic stem/progenitor cells to determine whether the deletion of Tet2 can affect the abundance of 5hmC at myeloid, T-cell and B-cell specific gene transcription start sites, which ultimately result in various hematological malignancies. Subsequent Exome sequencing (Exome-Seq) showed that disease-specific genes are mutated in different types of tumors, which suggests that TET2 may protect the genome from being mutated. The direct interaction between TET2 and Mutator S Homolog 6 (MSH6) protein suggests TET2 is involved in DNA mismatch repair. Finally, in vivo mismatch repair studies show that the loss of Tet2 causes a mutator phenotype. Taken together, my data indicate that TET2 binds to MSH6 to protect genome integrity. In Part II, I intended to better understand the role of Tet2 in the nervous system. 5-hydroxymethylcytosine regulates epigenetic modification during neurodevelopment and aging. Thus, Tet2 may play a critical role in regulating adult neurogenesis. To examine the physiological significance of Tet2 in the nervous system, I first showed that the deletion of Tet2 reduces the 5hmC levels in neural stem cells. Mice lacking Tet2 show abnormal hippocampal neurogenesis along with 5hmC alternations at different gene promoters and corresponding gene expression downregulation. Through the luciferase reporter assay, two neural factors Neurogenic differentiation 1 (NeuroD1) and Glial fibrillary acidic protein (Gfap) were down-regulated in Tet2 knockout cells. My results suggest that Tet2 regulates neural stem/progenitor cell proliferation and differentiation in adult brain.

The one-humped or the dromedarian camel is a pseudo-ruminant mammal, well adapted to the hot and dry climates of the desert. Its ability to withstand torrid heat and extreme desiccation is of paramount importance to its survival. The studies presented in this thesis were designed to investigate and document the effect of dehydration in the presence or absence of angiotensin II (Ang II) AT1 receptor blocker (losartan) on blood constituents, electrolytes, hormones, neurotransmitters as well as liver and kidney enzymes in a subset of dehydrated camels and to compare them with hydrated camels. Additionally, we studied the response of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) and revealed for the first time the cardiac storage form of BNP in the camel heart. Dehydration induced significant increments in packed cell volume (PCV), white blood cells (WBC), gamma glutamyl-transferase (GGT), serum sodium, creatinine and urea levels, and a doubling in plasma cortisol and arginine vasopressin (AVP) levels. At the same time dehydration caused significant decrease in body weights, plasma insulin like growth factor-1 (IGF-1) and its binding protein-3 (IGFBP-3), and a 50% decrement in ANP and BNP levels. Moreover, dehydration with and without losartan resulted in significant changes in stress hormones and anti-oxidants in plasma, liver and kidney homogenates. Losartan on one hand enhanced the effect of dehydration resulting in significant increases in sodium, creatinine and urea levels. In addition losartan raised the  binding affinity of Ang II AT2 receptors in the small intestine with 8-fold and with 16-fold for liver AT1 receptors, indicating that Ang II AT1 and AT2 receptor binding sites were present in camel's small intestine while only AT1 receptor binding sites were found in the camel liver. One the other hand losartan resulted in significant decrease in body weights impaired the rise in anti-diuretic hormone and reduced aldosterone level. Finally, we showed that the proBNP is the storage form of BNP in the camel heart.