No description available.

Interferons (IFNs) are a class of structurally related proteins first discovered to be produced by virus-infected cells. By now, several other inducing agents have been described. IFNs exert multiple effects on cells exemplified by the establishment of an antiviral state, inhibition of cell proliferation and alteration of different immune reactions. In the present thesis the inhibition of cellular growth concentrated on effects in the early cell cycle have been studied. The human glioma cell line 251 MG was found to be blocked in the S phase of the cell cycle upon addition of IFN both to exponentially growing and growth-factor depleted, synchronized cells. Thymidine kinase and DNA-polymerase activities were reduced in parallel with the S phase effect. 2-5 oligo Anucleotides transfected into glioma cells lead to inhibition of cell growth, exponentially growing cells being blocked in the S phase as during IFN treatment. In contrast, synchronized, restimulated cells were blocked in the cellcycle phase where they resided at the time of transfection. As 2-5 oligo A synthetase activity was induced in the middle of the Gl phase, these results might indicate that the kinetics of expression of oligonucleotides after IFN additiondetermines the type of cell cycle block obtained in differenttumor cells. IFN inhibited preferentially proteins originating from newly synthesized mRNA in Sw 3T3 cells, c-mvc did not seem to be included among these proteins. In both cell systems c-myc expression was unaltered after IFN treatment. In clone T1 selected from the the Sw 3T3 cell line , c-mvc expression was uncoupled to growth and seemed to be growth factor independent. The change in c-myc expression in clone T1 compared to SW 3T3 cells did not render the cells sensitive to IFN. Hence, c-myc regulation does not seem to be the mechanism by which IFN regulates cell growth in this system. The proliferation marker KI-67 antigen was shown not to be causatively involved in growth inhibition of IFN. The reduced levels of the antigen was proposed to be a secondary effect caused by the G0/G1 arrest. / <p>Diss. (sammanfattning) Umeå : Umeå universitet, 1991, härtill 6 uppsatser</p> / digitalisering@umu

Critical illness associated muscle weakness and muscle dysfunction in intensive care unit (ICU) patients lead to severe morbidity and mortality as well as significant adverse effect on quality of life. Immobilization, mechanical ventilation, neuromuscular blocking agents, corticosteroids, and sepsis have been implicated as important risk factors, but the underlying molecular and cellular mechanisms remain unclear.  A unique porcine ICU model was employed to investigate the effect of these risk factors on the expression profiles, gene expression and contractile properties of limb and diaphragm muscle, in the early phase of ICU stay. This project has focused on unraveling the underlying molecular and cellular pathways or networks in response to ICU and critical illness interventions. Upregulation of heat shock proteins indicated to play a protective role despite number of differentially transcribed gene groups that would otherwise have a negative effect on muscle fiber structure and function in response to immobilization and mechanical ventilation.  Mechanical ventilation appears to play a critical role in development of diaphragmatic dysfunction. Impaired autophagy, chaperone expression and protein synthesis are indicated to play a pivotal role in exacerbating muscle weakness in response to the combined effect of risk factors in ICU. These results may be of therapeutic importance in alleviating critical illness associated muscle weakness.

Les fibres amyloïdes sont souvent à l’origine de nombreuses maladies dégénératives telles que la maladie d’Alzheimer ou la maladie de Parkinson. La formation de ces plaques insolubles est due à une agrégation anormale de protéines. Les études structurales et biologiques des amyloïdes sont hautement complexes du fait de leur organisation sous forme de superstructures unidirectionnelles composées d’une infinité d’unités peptidiques ou protéiques, mais aussi à cause de leur hétérogénéité conformationnelle et polymorphique. Au cours de ces différents travaux de thèse en collaboration avec différents laboratoires d’analyses structurales, nous avons développé plusieurs outils de synthèse tant pour la formation de différents polymorphes de fibres amyloïdes que pour la formation d’espèces oligomériques de tailles conséquentes qui sont un challenge du point de vue synthétique et méthodologique mais aussi pour leur caractérisation. Ces différentes avancées permettront de mieux comprendre les mécanismes de formation de fibres amyloïdes et de préparer des échantillons homogènes pour les analyses structurales et biologiques. L’étude de modifications chimiques telles que la N-méthylation ou les polypeptides D est également un enjeu important pour l’élucidation des interactions protéine-protéine vis-à-vis des structures amyloïdogéniques et ainsi permettre l’élaboration de nouveaux composés inhibant la formation de plaques amyloïdes. / Amyloid fibrils are associated with many human disorders including Alzheimer’s or Parkinson’s diseases. The formation of insoluble plaques is the result of protein misfolding and aggregation due to abnormal conformational isomerization of the involved protein. The structural and biological studies of amyloids are highly complex. In this thesis, we report on the development of different synthetic methodologies for the preparation of distinct amyloid fibril polymorphs as homogeneous samples for structural and biological studies. We also synthesized covalently-tethered oligomers composed of nine copies of an amyloidogenic peptide segment, where we were able to control the self-assembly of the structure by insertion of N-methylated amino-acids and to obtain monomeric oligomers mimicking a cross section of an amyloid fibril. We also report on the chiral recognition of L-peptides and L-proteins towards corresponding D-enantiomers during amyloid formation. Moreover, we studied various N-methylated peptide analogues to suppress amyloid growth. Overall, the results obtained in this thesis pave the way towards rational design of peptide-based inhibitors and diagnostics against amyloid propagation.

Neurons connect to their remote targets via axons, which usually survive for the lifetime of an organism. Spatiotemporal regulation of the axonal proteome by local protein synthesis (LPS) plays a critical role in neuronal wiring and axon survival, raising the intriguing possibility that some neurological disorders involve LPS dysfunction. To visualise LPS in situ, I optimised multiple imaging techniques to investigate Netrin-1-induced translation in cultured retinal axons. Total axonal protein synthesis measured by metabolic and puromycin labelling indicates axons experience stage-dependent alterations in translation rate upon Netrin-1 stimulation. Remarkably, Netrin-1 triggers a burst of β-actin synthesis starting within 20 seconds of cue application at multiple non-repetitive sites visualised by single molecule translation imaging, an approach that allows direct visualisation of translation dynamics in response to external stimuli. Further studies have shown that local translation can occur on Rab7a-associated late endosomes, where mRNA recruitment and translation are coordinately regulated. Notably, mRNAs encoding mitochondria-related proteins are found translating on late endosomes docking in the vicinity of mitochondria, suggesting late endosomes act as ‘platforms’ for the localised synthesis of mitochondrial proteins necessary for maintaining mitochondrial integrity. Moreover, this process is affected in axons expressing the Charcot-Marie-Tooth disease type 2B (CMT2B)-related Rab7a mutants, leading to abnormal mitochondrial biogenesis and activity and compromised axon survival. Finally, attenuated de novo protein synthesis is observed in axons expressing amyotrophic lateral sclerosis (ALS)-associated fused in sarcoma (FUS) mutants and hypomethylated wild-type FUS. Live imaging reveals mislocalised mutant or hypomethylated FUS granules are transported along axons and accumulate at growth cones, possibly irreversibly trapping RNA molecules, resulting in reduced distance travelled by RNA granules in axons. Furthermore, mutant FUS expression results in defective retinal projections in vivo, highlighting the importance of RNA metabolism and local translation in axonal homeostatic mechanisms. In conclusion, aberrant translational activity in axons leads to prominent axonopathy, which recapitulates features of early stages of neurological diseases, providing the basis for novel therapeutic strategies.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / Eight Texel x Polwarth crossbred wethers (31.1±3.8 kg BW), four with duodenal cannulae were used in a replicated 4x4 Latin square design to evaluate effects of canola meal (44.4% CP, 29.5% NDF and 3.2% EE; DM basis) on intake, whole-tract digestibility, microbial protein synthesis and nitrogen retention. The basal diet consisted of ad libitum access to sudangrass (10% refusals). Treatments were sudangrass only (control), or supplemented with 5, 10, or 15 g/kg BW of concentrate, offered twice daily at 0800 and 1700h. Concentrate was 90% canola meal and 10% finely ground corn. Wethers were adapted to diets for 10 d followed by a 5-d collection period. Forage DMI decreased linearly (P<0.001) as supplement intake increased, and was 26.1% lower in supplemented animals in relation to the control group. Total DMI, which included forage and supplement, increased 30.6% and digestible OM intake increased 41% with supplementation. Supplementation did not affect DM and OM digestibility, while depressed NDF digestibility and improves N digestibility. Microbial protein synthesis and microbial efficiency were not affected by supplementation. Nitrogen retention was markedly higher in supplemented animals (236% higher), and was due mainly to the higher duodenal flow of amino acids. Supplementation with canola meal improves total nutrient supply, however, exerted a negative effect on forage intake and fiber digestibility in wethers. / Este estudo foi conduzido com o objetivo de avaliar a inclusão de farelo de canola na dieta de ovinos e seus efeitos sobre o consumo de volumoso, digestibilidade, síntese protéica microbiana ruminal e retenção de nitrogênio. Oito ovinos machos cruzados Texel x Polwarth (31,1±3,8 kg PV), quatro destes implantados com cânula duodenal foram utilizados em um delineamento quadrado Latino 4x4 duplo com períodos de 15 dias, sendo 10 dias adaptação e cindo dias coleta de dados. A dieta experimental basal foi composta de capim Sudão (ad libitum, 10% de sobras) e os tratamentos foram: capim Sudão (controle), ou suplementado com 5, 10 ou 15 g/kg PV de concentrado, ofertados duas vezes ao dia às 08:00 e 17:00h. O concentrado foi 90% farelo de canola e 10% de milho moído. O consumo de MS da forragem decresceu linearmente (P<0,001) com o aumento no consumo de suplemento e foi em média 26,1% menor em relação ao grupo controle. O consumo total de MS que inclui forragem e suplemento aumentou 30,6% e o consumo de MOD aumentou 41% nos animais suplementados. Não houve efeito da suplementação sobre a digestibilidade da MS e da MO, todavia, houve redução na digestibilidade da FDN e aumento na digestibilidade do N. A síntese e a eficiência de síntese protéica microbiana ruminal não foram afetadas (P>0,05) pela adição do suplemento à dieta. A retenção de N foi substancialmente maior(P<0,001) nos animais recebendo o farelo de canola (236%), e foi devida principalmente à maior oferta de aminoácidos. A suplementação aumentou a oferta total de nutrientes e a retenção de nitrogênio em ovinos, todavia, exerceu um efeito negativo sobre o consumo de forragem e a digestibilidade da fibra.

Submitted by Jos? Henrique Henrique (jose.neves@ufvjm.edu.br) on 2018-07-19T20:36:06Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) katharine_kelly_azevedo.pdf: 1197322 bytes, checksum: 47b2dff938cb953a1d3c90817b658008 (MD5) / Approved for entry into archive by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2018-08-22T12:59:16Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) katharine_kelly_azevedo.pdf: 1197322 bytes, checksum: 47b2dff938cb953a1d3c90817b658008 (MD5) / Made available in DSpace on 2018-08-22T12:59:16Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) katharine_kelly_azevedo.pdf: 1197322 bytes, checksum: 47b2dff938cb953a1d3c90817b658008 (MD5) Previous issue date: 2018 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / Objetivou-se avaliar o efeito de n?veis crescentes de substitui??o da PB do concentrado (0, 25, 50 e 75% com base na MS) pela PB do farelo de crambe (FC) em dietas para ovinos, sobre o consumo e digestibilidade de nutrientes, par?metros ruminais, N ureico no plasma sangu?neo (NUP), excre??o urin?ria de N ureico (EUNU), balan?o de N, fluxo intestinal de N microbiano (NMIC) e efici?ncia de s?ntese de prote?na microbiana (EFIM). Foram utilizados quatro ovinos fistulados no r?men, SRD, machos, castrados, alojados em gaiolas metab?licas, com idade m?dia inicial de 18 meses e peso vivo m?dio inicial de 50 kg, distribu?dos em delineamento quadrado latino 4 x 4 (4 tratamentos e 4 per?odos). Cada per?odo foi composto de 14 dias, sendo sete dias destinados ? adapta??o dos animais ? dieta e ?s condi??es experimentais e sete dias para as coletas. As dietas foram compostas por 50% de volumoso (silagem de milho) e 50% de concentrado (%MS). Os resultados foram submetidos ? an?lise de vari?ncia e estudo de regress?o a 5% de signific?ncia, utilizando-se o programa estat?stico SAS. Foi verificado efeito linear crescente para o consumo de extrato et?reo e linear decrescente para o consumo de carboidratos n?o fibrosos corrigidos para cinzas e prote?na. Com o aumento dos n?veis de FC nas dietas observou-se redu??o na digestibilidade de todos os nutrientes avaliados, exceto para PB e EE. N?o houve efeito para o pH do l?quido ruminal, por?m para os valores de N amoniacal no l?quido ruminal foi observado efeito linear decrescente com a inclus?o do FC na dieta. Tamb?m n?o foi observado efeito das dietas para o balan?o de N e EUNU. Contudo, para a concentra??o de NUP houve efeito linear decrescente. O NMIC e EFIM apresentaram efeito linear crescente com a inclus?o do FC. De acordo com os resultados alcan?ados no presente estudo, o FC possui potencial como alimento proteico alternativo na dieta de ovinos, pois assegura consumo e utiliza??o do N semelhante a alimentos convencionais e contribui pra melhor s?ntese de prote?na microbiana. Apesar da redu??o da digestibilidade dos nutrientes com a inclus?o do FC ?s dietas, o consumo de NDT n?o foi prejudicado. / Disserta??o (Mestrado) ? Programa de P?s-Gradua??o em Zootecnia, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2017. / The objective of this study was to evaluate the effect of increasing levels of CP replacement of concentrate (0, 25, 50 and 75% based on DM) for crambe meal (CM) CP in sheep diets regarding on nutrient intake, digestibility, ruminal parameters, blood plasma urea nitrogen (NUP), urinary urea nitrogen excretion (EUNU), N balance, intestinal flow of microbial nitrogen (NMIC), and efficiency of microbial protein synthesis (EFIM). Four rumen fistulated male sheep of undefined breed, castrated, housed in metabolic cages, with initial mean age of 18 months and initial mean body weight (BW) of 50 kg, were distributed in a 4 x 4 Latin square design (4 treatments and 4 periods). Each period was composed of 14 days, seven days for the adaptation of the animals to the diet and the experimental conditions and seven days sampling. The diets were composed of 50% of roughage (corn silage) and 50% of concentrate (% MS). The results were submitted to analysis of variance and regression study at 5% of significance using the SAS statistical program. It was verified crescent linear effect for the intake of ethereal extract and linear effect decreasing for the intake of non-fibrous carbohydrates corrected for ashes and protein. It was observed a reduction of the digestibility of all the nutrients with increase of CM levels in the diets, except for PB and EE. There was no effect on the ruminal fluid pH, but it was observed linear decreasing effect for the values of ammoniacal nitrogen in the rumen according to the inclusion of the CM in the diets. It was not observed effect of diets on N balance and EUNU. However, there was a linear decreasing effect for NUP. The was in increasing linear effect on NMIC and the EFIM with the inclusion of CM. According to the results obtained in the present study, the CM has potential as an alternative protein food in the diets of sheep, because the intake and use of N is similar to conventional foods and improves the microbial protein synthesis. Even with the reduction of nutrient digestibility with the inclusion of CM in diets, the intake of TDN was not affected.

O objetivo deste estudo foi avaliar o efeito do teor de proteína bruta (PB) e da fonte nitrogenada da dieta para vacas lactantes, utilizando cana-de-açúcar como volumoso sobre a síntese de proteína microbiana, composição da fração nitrogenada do leite, balanço nitrogenado e parâmetros metabólicos sangüíneos. Foram utilizadas 12 vacas Holandesas com média de 235 dias em lactação, agrupadas em três quadrados latinos contemporâneos 4x4, com período experimental de 21 dias, sendo 14 para adaptação as dietas e os 7 últimos para coletas. Os animais foram alimentados com rações isoenergéticas (1,29 Mcal/Kg de MS), com duas fontes nitrogenadas principais (farelo de soja e uréia) e dois teores de PB (14,5 e 16,0 %) na ração: A) 14,21% de PB e farelo de soja (FS) como fonte nitrogenada principal, com 65% de PDR, B) 15,57% de PB e FS, com 65% PDR, C) 14,23% de PB e Ureia, com 70% de PDR, D) 15,62% de PB e Uréia, com 70% PDR. Para a determinação da contagem de células somáticas e de nitrogênio ureico no leite (NUL) foram coletadas amostras de leite do 14&ordm; ao 18&ordm; dia de cada período. Para a determinação dos teores de proteína bruta, nitrogênio não protéico, nitrogênio não caseinoso, proteína verdadeira, caseína e proteína do soro do leite, foram coletadas amostras de leite do 18&ordm; ao 21&ordm; dia de cada período. Para a determinação da síntese de proteína microbiana foram coletadas amostras de leite e amostras spot de urina no 15&ordm; dia de cada período. A coleta de sangue foi realizada no 16&ordm; dia de cada período. Houve interação entre fonte nitrogenada e teor de PB da dieta sobre o NUL (mg/dL) e tendência de interação entre fonte nitrogenada e teor de PB da dieta sobre a excreção total de urina (L/dia) (P = 0,052) e proteína verdadeira do leite do leite (%) (P = 0,06). A excreção total de urina (L/dia), o NUL e a uréia no soro foram maiores para as dietas com 16% de PB, independentemente da fonte nitrogenada. As dietas com uréia como fonte nitrogenada principal apresentaram maior concentração de albumina sangüínea (g/L). Houve maior eficiência nitrogenada para as dietas com 14,5% de PB. / The aim of this study was to evaluate effects of crude protein (CP) content and dietary nitrogen source for lactating cows using cane sugar as forage on microbial protein synthesis, composition of milk nitrogen fraction, nitrogen balance and blood parameters. Twelve Holstein cows (235 days in milk) were allocated in three Latin squares balanced 4x4, with a trial period of 21 days where 14 days were for diet adaptation and the last seven for sample collection. The animals receive isocaloric diets (1.29 Mcal / kg DM), with two major nitrogen sources (soybean meal and urea) and two crude protein levels (14.5 and 16.0%): A) 14.21% CP, soybean meal (SBM) as the main nitrogen source, with 65% PDR, B) 15.57% CP as SBM and 65% PDR, C) 14.23% CP and urea as the main nitrogen source, with 70% PDR, D) 15.62% CP as urea and 70% PDR. To determine the somatic cell count and milk urea nitrogen, milk samples were collected from day 14th to 18th of each period. To determine crude protein, non-protein nitrogen, non-casein nitrogen, true protein, casein and whey protein, milk samples were collected from day18th to 21st of each period. To determine microbial protein synthesis milk and spot urine samples were collected at day 15th of each period. Blood collection was performed on the 16th day of each period. There was interaction between nitrogen source and diet protein content on milk urea nitrogen (MUN), and interaction tendency on urine excretion (L/day) (P = 0.052) and milk true protein (%) (P =0.06). Total urine excretion (liters/day), MUN and urea in blood serum were higher for diets with 16% CP, regardless of nitrogen source. Diets with urea as main nitrogen source had higher concentration of blood albumin (g/L). There was higher nitrogen efficiency for diets with 14.5% CP.

Estudos em animais mostram que a desnutrição proteica intrauterina pode acarretar redistribuição do fluxo sanguíneo intraútero, podendo promover modificações permanentes na estrutura e funcionalidade de alguns órgãos, o que ocasiona modificações no metabolismo. Além disso, a desnutrição intrauterina pode afetar a secreção de hormônios que atuam no crescimento fetal, podendo conduzir à restrição do crescimento intrauterino. Esse fenômeno pode parcialmente ser explicado pela hipótese da programação fetal, na qual é sugerido que ocorra uma adaptação metabólica e fisiológica do feto a uma condição intrauterina adversa, que pode induzir o desenvolvimento de doenças crônicas não transmissíveis na vida adulta. Neste contexto, pesquisas com suplementação de aminoácidos de cadeia ramificada (BCAA) têm verificado a capacidade desses nutrientes promoverem a síntese proteica mesmo em condições catabólicas, por meio da ativação de uma via bioquímica intracelular intercedida pela proteína quinase Alvo da Rapamicina em Mamíferos (mTOR), a qual está envolvida no estímulo à etapa de tradução proteica. Assim, o presente trabalho avaliou o efeito da suplementação de BCAA em proles submetidas à desnutrição proteica materna. Para tanto, ratas Wistar foram acasaladas com ratos adultos de mesma raça. Uma vez constatada a gravidez, as matrizes foram distribuídas em grupos de acordo com a dieta que seria fornecida no decorrer da gestação: CON (20% proteína); VAL/ISO (5% proteína + 2% VAL + 2% ISO); AAE (5% proteína + 4% AAE); e BCAA (5% proteína + 4% BCAA). O protocolo de restrição proteica materna adotado causou redução no crescimento corporal e na massa de órgãos das proles. Embora a suplementação com VAL/ISO e AAE não tenha recuperado os efeitos mediados pela deficiência de proteína, foi constatado que a suplementação com BCAA reverteu parte do déficit observado no crescimento das proles, uma vez que foi eficaz em minimizar ou mesmo em restaurar plenamente diversos parâmetros como peso de órgãos, massa de gordura da carcaça e parâmetros indicativos do estado nutricional proteico, como as concentrações de proteína e RNA hepáticas e musculares. Estes efeitos podem parcialmente ser explicados pelo estímulo induzido pela suplementação com BCAA, na via de sinalização da mTOR, considerando que foi verificado no fígado das proles de matrizes que receberam esta suplementação, aumento na fosforilação desta proteína (P < 0,05), a qual é responsável por desencadear uma cascata de eventos biomoleculares que culminam, em última instância, no acréscimo da síntese proteica. Diante disto, torna-se relevante a realização de pesquisas que avaliem em longo prazo, os efeitos da suplementação com BCAA em proles submetidas à dieta materna restrita em proteína. / Animal studies show that intrauterine malnutrition may cause redistribution of blood flow in uterus, which may promote permanent changes in structure and function of some organs, which causes changes in metabolism. Furthermore, intrauterine malnutrition can affect the secretion of hormones that act on fetal growth and may lead to intrauterine growth restriction. This phenomenon can partly be explained by the hypothesis of fetal programming, which is suggested that occur a metabolic and physiological adaptation of the fetus to an adverse intrauterine condition, which can induce the development of chronic diseases in later life. In this context, researches with supplementation of branched chain amino acids (BCAA), especially leucine, have verified the ability of these nutrients to promote protein synthesis in catabolic conditions, through the activation of an intracellular biochemical pathway interceded by protein kinase Mammalian Target of Rapamycin (mTOR), which is involved in the stimulating of protein translation stage. Thus, this study evaluated the effect of BCAA supplementation in offspring subjected to maternal protein-restrict diet. To this, Wistar rats were mated with adult rats of the same race. Once was confirmed the pregnancy, the pregnants were distributed into groups according to the diet that would be provided during pregnancy: CON (20% protein); VAL/ISO (5% protein + 2% + 2% VAL/ISO), AAE (5% protein + 4% EAA) and BCAA (5% protein + 4% BCAA). The protocol adopted maternal protein restriction caused a reduction in body growth and weight of the offspring\'s organs. Although supplementation with VAL/ISO and AAE has not recovered the effects mediated by protein deficiency, it was found that supplementation with BCAA has reversed part of the deficit observed in the growth of the offspring, since it was effective in minimizing or even fully restoring various parameters such as organ weight, carcass fat mass and parameters indicative of nutritional protein, such as the concentrations of protein and RNA in liver and muscle. These effects may be partially explained by the stimulation induced by BCAA supplementation on the mTOR signaling pathway, considering that was verified in the liver of the offspring from dams that received this supplementation augment on the phosphorylation of this protein (P < 0,05), which is responsible for triggering a cascade of molecular events that culminate, ultimately, in increased protein synthesis. Given this, it becomes relevant to conducting research to assess long-term effects of supplementation with BCAA in offspring subjected to maternal protein-restricted diet.

Orientador: Maria Cristina Cintra Gomes Marcondes / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-04T06:14:31Z (GMT). No. of bitstreams: 1 Ventrucci_Gislaine_D.pdf: 735812 bytes, checksum: 9ccc59181ffe68918015bc1467e83a50 (MD5) Previous issue date: 2005 / Resumo: Caquexia, presente na maioria dos hospedeiros com câncer, é um estado caracterizado pela perda involuntária de peso. Pacientes com caquexia apresentam expectativa de vida muito reduzida e menor qualidade de vida. Nos pacientes com câncer-caquexia há intensa mobilização de substratos dos tecidos da carcaça do organismo hospedeiro ocorrendo, preferencialmente, depleção de proteína muscular em função da redução da síntese e/ou aumento da degradação protéica no músculo. Este aumento da taxa de proteólise muscular tem como função prover aminoácidos para síntese de glutamina, bem como para a demanda de síntese das células neoplásicas. Trabalhos da literatura mostram que o desenvolvimento de câncer dá-se de forma mais agressiva e severa quanto mais jovem for o paciente. Pacientes acometidos pelo crescimento de neoplasia maligna concomitante à gravidez sofrem da mesma agressividade desta doença, com um agravante maior tratam se de dois pacientes: mãe e feto. Neste trabalho analisamos os efeitos de uma dieta rica em leucina sobre o metabolismo protéico em animais jovens prenhes portadores ou não do carcinossarcoma de Walker 256. Ratas Wistar foram distribuídas em grupos experimentais de acordo com a inoculação ou não do carcinossarcoma de Walker 256 e submetidas ou não a dieta rica em leucina. Após 20 dias de experimento foi realizado ensaios com o músculo esquelético (gastrocnêmio) a fim de elucidar o mecanismo de catabolismo tecidual que ocorre durante o processo de câncer-caquexia. Os grupos apresentaram aumento da taxa de proteólise muscular e redução da taxa de síntese protéica muscular. Porém, o grupo inoculado com tumor e tratado com dieta rica em leucina apresentou aumento da síntese protéica e menor espoliação de proteína muscular quando comparado com o grupo inoculado com tumor e não tratado com leucina na dieta. A suplementação de leucina na dieta, uma vez que este aminoácido é utilizado como fonte energética pelo músculo esquelético pode prevenir a depleção da carcaça, preservar a massa protéica corpórea e impedir o estado caquético do animal / Doutorado / Fisiologia / Doutor em Biologia Funcional e Molecular