L’émergence et la ré-émergence de maladies que nous connaissons depuis ces cents dernières années représentent une véritable crise sanitaire en grande partie due aux perturbations anthropiques qui modifient les écosystèmes et les interactions entre les parasites et leurs hôtes. La prévention et le contrôle des maladies infectieuses nécessitent la compréhension de leur dynamique dans l’ensemble des compartiments dans lesquels elles circulent. Parmi ces maladies, la fasciolose est une maladie particulièrement sensible aux changements liés à l’Homme. Cette zoonose causée par le parasite Fasciola hepatica, est communément reconnue comme un problème vétérinaire, mais aussi de santé publique, dans certaines régions du monde. Notre étude vise à comprendre la dynamique de circulation et les risques d'émergence de la fasciolose dans un contexte de forte anthropisation. Il s'agit (1) d'étudier la dynamique de l’hôte intermédiaire, un mollusque de la famille des lymnaieidae. (2) de comprendre la dynamique et la diversité du parasite entre et au sein de ses différents compartiments hôtes définitifs. Ces travaux ont été menés sur le territoire camarguais sur le domaine de la Tour du Valat, nous permettant d’avoir accès aux hôtes définitifs, sauvages (ragondins et sangliers), domestiques (taureaux traités et non traités) et à l’hôte intermédiaire, Galba truncatula appelé communément limnée tronquée. Dans un premier temps, nous avons caractérisé la végétation des habitats favorables à la présence du mollusque et nous avons trouvé que les mares semblaient être des zones présentant un risque plus important que les canaux d’irrigation pour la transmission de la fasciolose. Puis, nous nous sommes intéressée à l’influence des habitats sur la dynamique de G. truncatula par des approches de génétique des populations. Nos résultats ont permis de montrer que la permanence des habitats et la connectivité influencent le mode de reproduction, la structuration des populations et la dispersion des limnées en Camargue. Dans un second temps, nous avons étudié la dynamique et la circulation du parasite au sein du compartiment hôte définitif. Nos résultats de la génétique des populations du parasite chez les hôtes définitifs, nous ont indiqué qu’il existait sur notre site d’étude plusieurs sites de transmission constituant un seul grand foyer global. Par ailleurs, l’étude de la circulation du parasite entre les hôtes définitifs suggère le rôle des sangliers dans la dispersion de la maladie et le rôle des ragondins dans le maintien du cycle de la fasciolose. Cette étude met en évidence l’intérêt de mener des études à long terme et l’importance de prendre en compte tous les compartiments impliqués pour comprendre l’épidémiologie d’une maladie. Elle souligne également le rôle des activités humaines et de l’écosystème dans la dynamique de la fasciolose. Le but final de cette étude est de proposer une gestion intégrée adaptée au contexte camarguais afin de limiter l’impact sanitaire de la fasciolose mais aussi des autres maladies liées à l’élevage dans cette région. / The emergence and re-emergence of diseases encountered over the last hundred years represent a real health crisis largely due to anthropic disturbances that affect the ecosystems as well as the interactions between parasites and hosts. The prevention and control of emerging infectious diseases require an in-depth understanding of their dynamics in all the compartments in which they occur. Among these diseases, Fasciolosis is particularly sensitive to human related changes. This zoonosis caused by the parasite Fasciola hepatica, is commonly recognized as a veterinary problem and major public health issue in certain countries. Our study aims to understand the circulation dynamics and risks of fasciolosis emergence in a context of high anthropization. Our objective is (1) to study the dynamics of the intermediate host, a mollusc of the lymnaieidae family. (2) to understand the dynamics and diversity of the parasite between and within its different definitive host compartments. This work was carried out in the Camargue in the Tour du Valat estate, allowing us to have access to the definitive hosts, wild (nutria and wild boars), domestic (treated and untreated bulls) and the intermediate host, Galba truncatula. First, we characterized the habitats that are favorable to the intermediate host G. truncatula, presence in Camargue and we found that ponds appear to be areas of higher risk than irrigation channels for fasciolosis transmission. Then, we became interested in the influence of habitats on the dynamics of G. truncatula through population genetics approaches, our results showed that habitat permanence and connectivity influence the reproduction mode, population structure and dispersal of G. truncatula in the Camargue. In a second step, we studied the dynamics and circulation of the parasite within the definitive host compartment. Our results of the population genetic analyses of definitive hosts indicated that there were several transmission sites on our study area that constituted a single large global outbreak. In addition, the study of the circulation of the parasite between wildlife and domestic animals suggests the role of wild boars in the spread of the disease and the role of nutrias in maintaining the fasciolosis cycle. Our work highlights the value of long term studies and the importance of taking into account all the compartments involved to understand the epidemiology of a disease. They also emphasize the role of human activities and ecosystem in the dynamics of fasciolosis. The ultimate goal of this study is to propose integrated management measures adapted to the Camargue context in order to limit the health impact of fasciolosis and other livestock diseases in the region.

Este trabalho foi realizado com o objetivo de melhor identificar e estudar comparativamente as lesões histológicas do fígado decorrente da fasciolose hepática em três espécies de animais domésticos. Foram examinados fígados infectados por Fasciola hepatica de bovinos e bubalinos provenientes de matadouros e frigoríficos oficialmente inspecionados no Estado do Paraná e fígados de ovinos de propriedades particulares, onde o abate era realizado no local. O material foi processado pela técnica de rotina para histopatologia. As colorações utilizadas foram Hematoxilina-Eosina, Tricrômico de Schorr, Tricrômico de Mallory e Azul de Toluidina. As principais lesões observadas foram cortes de parasitas em ductos biliares, fibrose portal, hiperplasia de ducto biliar, fibrose de parede de ducto biliar e infiltração por linfócitos, plasmócitos, eosinófilos e neutrófilos. Considerando os resultados obtidos, conclui-se que a fasciolose em bovinos e bubalinos se trata de uma fasciolose crônica, principalmente devido a idade de abate ser maior nessas espécies. Nos ovinos o predomínio de eosinófilos caracteriza fase inicial de fasciolose crônica, sendo a idade de abate dos mesmos inferior as outras espécies

Made available in DSpace on 2015-03-26T13:46:32Z (GMT). No. of bitstreams: 1 texto completo.pdf: 1301950 bytes, checksum: 6fbbf4b2a61f2a6e15625bb5f54e5cd6 (MD5) Previous issue date: 2008-02-19 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The in vitro effects of four isolates of the nematophagous fungi Duddingtonia flagrans (AC001), Monacrosporium sinense (SF53) and Pochonia chlamydosporia (VC1 and VC4) on eggs of Fasciola hepatica and Schistosoma mansoni was evaluated in two assays (A and B). Eggs of F. hepatica (assay A) and S. mansoni (assay B) were incubated in Petri dishes with 2% water-agar inoculated with the grown fungal isolates and a control without fungus. After seven, 14 and 21 days post- inoculation, one hundred eggs were removed and classified according to the following parameters: type 1, lytic effect without morphological damage to eggshell; type 2, lytic effect with morphological alteration of embryo and eggshell; and type 3, lytic effect with morphological alteration of embryo and eggshell, with hyphal penetration and internal egg colonization. In assay A, D. flagrans (AC001) and M. sinense (SF53) showed results only for type-1 effect on F. hepatica eggs, but with no significant difference (p>0.01) between them. P. chlamydosporia (VC1 and VC4) showed percentage results for ovicidal activity of type-1, -2 and -3 effects on F. hepatica eggs, with type-3 effect of 12.8% (VC1) and 16.5% (VC4); 14.4% (VC1) and 18.7% (VC4), 20.1% (VC1) and 21.5% (VC4) at seven, 14 and 21 days respectively. At the end of assay A no difference was found in the action of VC1 and VC4 for type-1, -2 and -3 effects over the three studied periods. In assay B, D. flagrans (AC001) and M. sinense (SF53) showed percentage results only for type 1 effect on S. mansoni eggs, with no significant difference (p>0.01) between them. P. chlamydosporia showed ovicidal activity on S. mansoni eggs with percentage results for type-1, -2 and -3 effects showing type 3 effect of: 26.6% (VC1) and 17.2% (VC4); 25.6% (VC1) and 22.6% (VC4); 26.3% (VC1) and 23.0% (VC4) at seven, 14 and 21 days respectively. At the end of the assay B, no difference was found in the action between the isolates VC1 and VC4 for type-1, -2 and -3 effects as well. The results of the A and B in vitro assays showed that P. chlamydosporia (VC1 and VC4) negatively affected F. hepatica and S. mansoni eggs and can therefore be used as biological control agent for these helminths. / Avaliou-se, em dois ensaios experimentais (A e B), a ação in vitro de quatro isolados de fungos nematófagos dos gêneros Duddingtonia flagrans (AC001), Monacrosporium sinense (SF53) e Pochonia chlamydosporia (VC1 e VC4) sobre ovos de Fasciola hepatica e Schistosoma mansoni. Ovos de F. hepatica (ensaio A) e ovos de S. mansoni (ensaio B) foram vertidos em placas de Petri com ágar-água 2% com os isolados fúngicos crescidos, e em placas de Petri sem fungo como controle. Ao completarem sete, 14 e 21 dias, aproximadamente cem ovos foram removidos e classificados de acordo com os seguintes parâmetros: efeito do tipo 1, efeito lítico sem prejuízo morfológico à casca do ovo; efeito do tipo 2, efeito lítico com alteração morfológica da casca e embrião; e efeito do tipo 3, efeito lítico com alteração morfológica do embrião e da casca, além de penetração de hifas e colonização interna do ovo. No ensaio A, os fungos D. flagrans (AC001) e M. sinense (SF53) apresentaram resultados percentuais somente para o efeito do tipo 1 sobre os ovos de F. hepatica, porém sem apresentar diferença significativa (p>0,01) entre eles. O fungo P. chlamydosporia (VC1 e VC4) demonstrou resultados percentuais de atividade ovicida para os efeitos dos tipos 1, 2 e 3 sobre os ovos de F. hepatica, com efeito do tipo 3 de 12,8% (VC1) e 16,5% (VC4); 14,4% (VC1) e 18,7% (VC4), 20,2% (VC1) e 21,5% (VC4), respectivamente aos sete, 14 e 21 dias. Ao final do ensaio experimental A, não foi observada diferença na ação de VC1 e VC4 para os efeitos dos tipos 1, 2 e 3 ao longo dos três períodos estudados. No ensaio experimental B, os fungos D. flagrans (AC001) e M. sinense (SF53) apresentaram somente resultados percentuais para o efeito do tipo 1 sobre os ovos de S. mansoni, sem contudo apresentar diferença significativa (p>0,01) entre eles. P. chlamydosporia demonstrou atividade ovicida sobre ovos de S. mansoni com resultados percentuais para os efeitos dos tipos 1, 2 e 3 apresentando um efeito do tipo 3 de 26,6% (VC1) e 17,2% (VC4); 25,6% (VC1) e 22,6% (VC4); 26,3% (VC1) e 23,0% (VC4) respectivamente aos sete, 14 e 21 dias. Contudo ao final do ensaio experimental B, também não foi observada diferença na ação entre os isolados VC1 e VC4 para os efeitos dos tipos 1, 2 e 3. Os resultados dos ensaios experimentais in vitro A e B demonstraram que P. chlamydosporia (VC1 e VC4) influenciou de forma negativa os ovos de F. hepatica e S. mansoni, e assim pode ser considerado como um potencial candidato a controlador biológico desses helmintos.

Made available in DSpace on 2014-06-11T19:22:13Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-02-12Bitstream added on 2014-06-13T19:07:27Z : No. of bitstreams: 1 vulcano_dsb_me_botfm.pdf: 1165851 bytes, checksum: ae1702dfaee6063d32a01859daa38f20 (MD5) / A doença hepática crônica influencia direta e indiretamente o estado nutricional do paciente, sendo a desnutrição bastante prevalente nesta população. As causas da desnutrição são multifatoriais, relacionadas à alteração na ingestão, na absorção e no metabolismo dos macro e micronutrientes. O diagnóstico nutricional torna-se difícil, pois, não existe um método considerado padrão-ouro e os métodos disponíveis podem não ser fidedignos pela influência da própria doença no resultado. O objetivo do trabalho foi avaliar os indicadores do estado nutricional e a composição corporal dos pacientes portadores de cirrose hepática e relacioná-los com o sexo, a etiologia e a gravidade da doença hepática. Os indicadores nutricionais avaliados foram os antropométricos (Índice de Massa Corpórea específico para pacientes cirróticos, dobras cutâneas e circunferências), os funcionais (dinamometria e espessura do músculo adutor do polegar), a avaliação nutricional subjetiva global e os laboratoriais (albumina, hemoglobina, hematócrito e contagem total de linfócitos). Para a avaliação da composição corporal foi utilizada a bioimpedância elétrica unifrequencial (BIA) que mensurou a resistência (R), a reactância (Xc), o ângulo de fase (AF) e a massa celular corpórea (MCC). A gravidade da doença hepática foi estimada pelos critérios de Child-Pugh e pelo Meld (The model end-stage liver disease). Os indicadores do estado nutricional foram dicotomisados em: desnutrição e sem desnutrição ou com depleção e sem depleção. Os pacientes cirróticos de etiologia alcoólica apresentaram maior depleção em todos os parâmetros antropométricos, funcionais e na avaliação nutricional subjetiva global (ANSG), sendo estatisticamente significante para Circunferência do Braço (CB), Circunferência Muscular do Braço (CMB) e ANSG... / The chronic hepatic disease directly and indirectly influences on patient’s nutritional status and malnutrition is highly prevalent in this population. The causes of malnutrition are multifactorial, related to alterations on ingestion, absorption and metabolism of macro and micronutrients. The nutritional diagnosis is difficult, because there isn’t a gold standard method, and available methods are not reliable, once the disease itself interferes in the result. The objective of the work was to appraise nutritional status indicators and body composition of cirrhotic patients treated in the nutrition first aid posts of Faculdade de Medicina de Botucatu – UNESP, and relate them to gender, etiology and severity of the liver disease. The nutritional indicators appraised have been the anthropometrical (specific body mass index for cirrhotic patients, skinfolds and circumferences), the functional (dynamometry and thickness of the adductor pollicis muscles), the Subjective Global Assessment of Nutritional Status (SGA) and the laboratorial (albumin, hemoglobin, hematocrit, lymphocytes total count). On the appraisement of body composition, unifrequency bioelectrical impedance analysis (BIA) has measured resistance (R), reactance (Xc), phase angle (PA) and body cell mass (BCM). The severity of the liver disease has been estimated by the Child-Pugh score and by Meld (The Model end-stage liver disease). The nutritional status indicators have been dichotomized as following: malnutrition and without malnutrition, or with depletion and without depletion. Cirrhotic patients with alcoholic etiology have exhibited more depletion in all the anthropometrical and functional parameters and in the Subjective Global Assessment of Nutritional Status (SGA) and they have been statistically relevant for Arm Circumference (AC), Arm Muscular Circumference (AMC) and SGA... (Complete abstract click electronic access below)

Avaliou-se os efeitos do β-caroteno e da vitamina A sobre o processo de proliferação de células ovais em modelo de diferenciação celular hepática. Para tanto, ratos machos Wistar foram tratados com β-caroteno (grupo BC - 70 mg/kg de peso corpóreo [pc]), vitamina A (grupo VA - 10 mg/kg pc) ou óleo de milho (CO - grupo controle) por via intragástrica e em dias alternados, durante 4 semanas consecutivas. Após este período, os animais foram submetidos ao modelo AAF/PH (6 x 20 mg AAF [2-acetilaminofluoreno] / kg pc e hepatectomia parcial) e sacrificados em diferentes dias após a cirurgia (HP). Foram colhidas amostras de fígado para determinação das concentrações de β-caroteno, retinol e palmitato de retinila (por CLAE - cromatografia líquida de alta eficiência); para análises histológica (hematoxilina e eosina) e imuno-histoquímica (com anticorpos anti-GST-P), bem como para avaliação das expressões gênicas (por northern blot) para as conexinas (cx) 43 e 32. Observou-se, através das análises histológica e imuno-histoquímica, que o pico de proliferação das células ovais foi deslocado para dias mais tardios após HP, de forma análoga nos grupos BC e VA, quando comparados ao grupo controle. Além disso, foi constatado que o pico de expressão gênica para cx 43 foi também deslocado para dias mais tardios pós-HP, de forma similar nos grupos BC e VA, e que houve um aumento na expressão gênica para cx 43 entre o 10º e 16º dias após HP no grupo VA, em relação ao controle. Não foi observada diferença na expressão gênica para cx 32 entre os grupos. Conclui-se que o β-caroteno modulou a proliferação de células ovais e a expressão gênica para cx 43, retardando ambos os fenômenos, e que esta ação foi mediada em parte via retinóides ativos. Ainda, o carotenóide mostrou uma tendência em induzir, de forma intrínseca, a diferenciação das células ovais em hepatócitos. / The aim of this work was to investigate the β-carotene and vitamin A effects in the process of oval cells proliferation at hepatic cellular differentiation model. Wistar male rats were treated with β-carotene (BC group - 70 mg/kg body wt), vitamin A (VA group - 10 mg/kg body wt) or com oil (CO - control group) administrated by gavage, on alternate days, during 4 consecutive weeks. Since, the animals were submitted to a AAF/PH model (6 x 20 mg AAF [2-acetylaminofluorene] / kg body wt and partial hepatectomy - PH) and sacrified at different days after PH. Liver samples were picked for analysing β-carotene, retinol and retinyl palmitate concentration (by HPLC); for histology (HE) and immunohistochemistry (with antibody anti-GST-P), and for evaluating connexins 43 and 32 gene expression (by northem blot). Histological and immunohistochemical analysis showed that the oval cells proliferation peak was delayed to the late days after PH, by similar way in the BC and VA groups, when compared with control group. Northem blot evaluation revealed that the cx 43 gene expression was also delayed to the late days after PH, by analogue way in the BC and VA groups, and vitamin A enhanced cx 43 gene expression in the late days after PH. Connexin 32 gene expression did not change among the experimental groups. Thereby, the β-carotene and vitamin A delayed the oval cells proliferation and the cx 43 gene expression. Moreover, β-carotene showed a tendency to induce the oval cells differentiation to hepatocytes.

5'-Deoxy-5'-methylthioadenosine (MTA) is derived from s-adenosylmethionine (AdoMet) during the synthesis of the polyamines spermidine and spermine. Methionine can be regenerated from MTA by one of two mechanisms. In mammalian cells and some microorganisms, MTA is degraded to adenine and 5-methylthioribose-1-phosphate (MTR-1-P) via MTA phosphorylase. In certain other microbes, however, MTA is catabolized in two steps; first to adenine and 5-methylthioribose (MTR) via MTA nucleosidase followed by conversion of MTR to MTR-1-P via MTR kinase. This study was to demonstrate the presence of MTA nucleosidase or MTA phosphorylase in both redia containing cercariae and adult Fasciola hepatica Linnaeus, 1758. If MTA nucleosidase was present, it was wanted to determine if MTR kinase was also present. The phosphate-dependent cleaving activity of MTA phosphorylase was demonstrated in the cell-free extracts of adult Fasciola hepatica along with an unidentified MTR metabolizing activity. Redia containing cercariae showed MTA nucleosidase and MTR kinase activity.

The liver flukes Fasciola hepatica and F. gigantica cause infectious disease in ruminants and humans. The geographical range of these two parasite species (temperate and tropical respectively) ensures that infection can occur worldwide. Although anthelmintic treatment is effective against disease, emerging drug resistant strains leads to the development of a vaccine. However, despite several decades of research, there is no commercial vaccine available. The main challenge at present is to produce recombinant proteins in an immunologically active form using recombinant DNA technology. This is an essential step in Fasciola vaccine production. Cysteine proteases are probably the most important facilitators of virulence in flukes and are produced by all stages of the fluke life-cycle. Two classes of cysteine protease are found in the excretory and secretory material of liver flukes- these are cathepsin L and cathepsin B. As such, the major aims of this thesis were to investigate the expression and purification of Fasciola recombinant cysteine proteins, and characterisation by SDS-PAGE and immunoblotting using monoclonal and polyclonal antibodies. These studies demonstrate the production of functionally active cathepsin proteins in S. cerevisiae BJ3505 cells which will lead to vaccine candidate analysis. The second aim of this thesis was to determine the protective efficacy of stage specific target antigens against experimental infection. In addressing this issue, the protective efficacy of single and multivalent recombinant protein vaccinations of adult stage F. hepatica cathepsin L5, immature F. gigantica cathepsin L1g and juvenile F. hepatica cathepsin B were analysed in Sprague Dawley rats against F. hepatica infection. This study demonstrates that juvenile fluke target antigen-cathepsin B induces better immune protection than adult fluke antigen-cathepsin L5. Cocktails of juvenile and adult stage fluke recombinant proteins (cathepsin B and L5) elicited the highest protective immunity against experimental infection and this combination showed not only reduction in fluke recovery and size of flukes, but also marked diminution in the intensity of liver lesions in vaccinated rats. In order to assess the immunogenic property of an early infective stage fluke secreting cysteine protease as a vaccine candidate, DNA vaccination vectors encoding cathepsin B were analysed in BALB/c mice. In this study, the ability of four DNA vaccination strategies such as secretory, chemokine-activating, lymph node targeting vectors encoding cathepsin B were assessed by antibody titre, antibody avidity, western blotting and ELIPSOT assay. The results have further validated the immunoprophylactic potential of a cathepsin B vaccine against F. hepatica. In this study, we have expressed and attained high yields of F. gigantica cathepsin L1g from E. coli BL21, and compared this to a yeast-expressed system. This protease was over-expressed and formed insoluble inclusion bodies that were subsequently solubilised with urea or guanidine hydrochloride. In order to purify the urea-solubilised protein, step-wise urea gradient chromatography was used. For refolding of solubilised protein, a dilution and dialysis procedure was utilised. Proteolytic activity was confirmed by gelatin SDS-PAGE analysis. In conclusion, the determination of the immune potential of recombinant stage specific antigens allows the development of effective vaccines against Fasciola infection.

Schistosoma mansoni and Fasciola hepatica are parasitic trematodes which contain cytochrome c peroxidase (CcP) in their mitochondria, an enzyme that is absent in mammalian tissues. CcP reduces hydrogen peroxide to H2O using cytochrome c as the electron donor. Both parasites are catalase deficient; thus, cytochrome c peroxidase and glutathione peroxidase are the enzymes involved in the detoxification of H2O 2 in these organisms. The enzymatic activity of these two peroxidases may enable S. mansoni and F. hepatica to survive oxidative stress. The main objective of this study was to characterize cytochrome c peroxidase from S. mansoni and F. hepatica . Kinetic studies of this enzyme in crude homogenate and isolated mitochondria of S. mansoni were initially performed, followed by purification studies from S. mansoni and F. hepatica . The parasite enzyme has affinity for horse heart and yeast cytochrome c and it is inhibited by sodium azide and potassium cyanide. CcP was purified close to homogeneity and identified as a protein containing heme. The antioxidant capability of F. hepatica CcP was tested in vitro , demonstrating that CcP protected the sugar deoxyribose from oxidative degradation. Exposure of adult worms to H2O2 caused a decrease in S. mansoni CcP activity in vivo. An attempt was made to clone the S. mansoni CcP gene. The experiments did not result in the cloning of the CcP gene, but led to the identification and cloning of another protein, a component of a cytosolic chaperonin, t-complex polypeptide one (TCP-1). TCP-1 from S. mansoni is highly homologous to TCP-1 proteins from different organisms including, Chinese hamster, human, Drosophila and yeast and carries ATP binding amino acid motifs indicating that it has ATPase activity.

Nos dois primeiros artigos deste estudo descrevem-se a ocorrência de duas intoxicações espontâneas por Trema micrantha em caprinos. Características clínicas e patológicas da hepatite tóxica aguda causada por Trema são comparadas com as diferentes plantas que causam hepatite tóxica aguda O terceiro artigo desse estudo descreve a intoxicação experimental por Trema micrantha em bovinos. Foram intoxicados 13 animais. Oito bovinos manifestaram sinais clínicos e seis desses morreram. Os sinais clínicos iniciavam a partir de 16 horas após a ingestão da planta. As mortes ocorriam entre 67 a 153 horas após a ingestão da planta. Os bovinos apresentavam apatia, sialorréia, fraqueza progressiva, coma e morte. A lesão mais importante foi observada no fígado, que era friável, com padrão lobular acentuado e áreas de hemorragia. Um animal apresentou edema perirrenal, rim pálido com hemorragias petequiais. Necrose massiva associada a hemorragia acentuada foi observado no fígado de cinco bovinos. Um animal apresentou necrose centrolobular. No sistema nervoso central de 5 animais foram observados edema perineuronal e perivascular com basofilia e retração de neurônios. Necrose tubular renal foi observada em 2 bovinos. Trema micrantha causou sinais clínicos com 50g/kg e morte a partir de 54g/kg de peso vivo.

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde. Mestrado Profissional Associado à Residência Médica em Cuidados Intensivos e Paliativos / Made available in DSpace on 2012-10-26T11:37:47Z (GMT). No. of bitstreams: 1 310452.pdf: 738905 bytes, checksum: 0bcc62fdd79111a6eb1b838c5fca307b (MD5) / Introdução: IGF-I e IGFBP-3 fazem parte do sistema IGF e, por terem síntese predominantemente hepática, parecem se correlacionar com a intensidade da disfunção hepática. Objetivos: Estudar o significado dos níveis séricos de IGF-I e IGFBP-3 em pacientes admitidos por complicações da cirrose hepática. Material e Métodos: Estudo transversal que incluiu pacientes cirróticos admitidos por complicação da doença. Os níveis séricos de IGF-I e IGFBP-3 foram determinados por quimioluminescência. A correlação entre as variáveis numéricas foi avaliada pelo coeficiente de correlação de Spearman e as demais comparações foram feitas pelo teste Mann-Whitney ou Kruskal-Wallis. Resultados: Foram incluídos 74 pacientes com média de idade de 53,1 ± 11,6 anos, 73% homens. Os níveis de IGF-I se correlacionaram positivamente com IGFBP-3 e albumina e negativamente com a pontuação total do escore de Child-Pugh, escore de MELD, creatinina, RNI e razão-TTPA. Os níveis de IGFBP-3 se correlacionaram positivamente com IGF-I e albumina e negativamente com a pontuação total do escore Child-Pugh, escore de MELD, creatinina, RNI, bilirrubina total e razão-TTPA. Níveis significativamente mais baixos de IGF-I e IGFBP-3 foram observados em pacientes com maiores valores de MELD e estádios mais elevados da classificação de Child-Pugh (P< 0,05). Conclusões: Em pacientes cirróticos admitidos por complicações da doença, níveis séricos de IGF-I e IGFBP-3 se associaram a variáveis relacionadas à disfunção hepática e doença hepática mais avançada. Os níveis destes marcadores parecem sofrer pouca interferência de outras variáveis clínicas e laboratoriais, refletindo, portanto majoritariamente a capacidade de síntese hepática