Made available in DSpace on 2014-12-17T14:14:03Z (GMT). No. of bitstreams: 1 IramiAF.pdf: 222778 bytes, checksum: 19ba0c4bd484b69016b906c3ab34fc7f (MD5) Previous issue date: 2005-10-27 / Laparoscopic surgery is associated with reduced surgical trauma, and less acute phase response, as compared with open surgery. Cytokines are important regulators of the biological response to surgical and anesthetic stress. The aim of this study was to determine if CO2 pneumoperitoneum would change cytokine expression, gas parameters and leukocyte count in septic rats. Methods: Wistar rats were randomly assigned to five groups: control (anesthesia only), laparotomy, CO2 pneumoperitoneum, cecum ligation and puncture by laparotomy, and laparoscopic cecum ligation and puncture. After 30 min of the procedures, arterial blood samples were obtained to determine leukocytes subpopulations by hemocytometer. TNF&#945;, IL-1&#946;, IL-6 were determined in intraperitoneal fluid (by ELISA). Gas parameters were measured on arterial blood, intraperitoneal and subperitoneal exsudates. Results: Peritoneal TNF&#945;, IL-1&#946; and IL-6 concentrations were lower in pneumoperitoneum rats than in all other groups (p<0.05). TNF&#945;, IL-1&#946; and IL-6 expression was lower in the laparoscopic than in laparotomic sepsis (p<0.05). Rats from laparoscopic cecum ligation and puncture group developed significant hypercarbic acidosis in blood and subperitoneal fluid when compared to open procedure group. Total white blood cells and lymphocytes were significantly lower in laparoscopic cecum ligation and puncture rats than in the laparotomic (p<0.01). Nevertheless, the laparotomic cecum ligation rats had a significant increase in blood neutrophils and eosinophils when compared with controls (p<0.05). Conclusions: This study demonstrates that the CO2 pneumoperitoneum reduced the inflammatory and immune response in an animal model of peritonitis with respect to intraperitoneal cytokines, white blood cell count and clinical correlates of sepsis. The pneumoperitoneum produced hypercarbic acidosis in septic animals / A cirurgia laparosc?pica est? associada com trauma reduzido e baixa resposta metab?lica na fase aguda do trauma, quando comparada com a cirurgia aberta. As citocinas e o balan?o ?cido-base s?o fatores importantes da resposta biol?gica ao trauma cir?rgico-anest?sico. O objetivo deste estudo foi determinar se o pneumoperit?nio com CO altera a express?o das citocinas intraperitoneais, a gasometria do sangue arterial, dos exsudatos intraperitoneal e subperitoneal, e a contagem diferencial de leuc?citos em ratos com sepse abdominal. M?todo: Ratos Wistar foram aleatoriamente distribu?dos em cinco grupos: controle (somente 2anestesia), laparotomia, pneumoperit?nio com CO2, ligadura e pun??o do ceco por laparotomia, ligadura e pun??o do ceco por laparoscopia. Ap?s 30 minutos dos procedimentos, sangue arterial foi colhido para leucometria em hemocit?metro. FNT&#945;, IL-1&#946; e IL-6 foram dosadas no lavado intraperitoneal (por ELISA). Os par?metros gasosos foram medidos no sangue arterial e nos exsudatos intraperitoneal e subperitoneal. Resultados: Os valores de FNT&#945;, IL-1&#946; e IL-6 foram significantemente menores nos ratos submetidos ao pneumoperit?nio do que em todos os outros grupos (p<0.05). Express?o de FNT&#945;, IL-1&#946; e IL-6 foi menor no grupo sepse induzida por laparoscopia do que por laparotomia (p<0.05). Os ratos submetidos ? ligadura e pun??o do ceco por via laparosc?pica desenvolveram acidose hiperc?rbica no sangue arterial e exsudato subperitoneal, mais intensa do que no grupo sepse laparot?mica. Leucopenia e linfopenia foram mais acentuadas no grupo sepse laparosc?pica (p<0.01). Entretanto, os animais submetidos a sepse laparot?mica desenvolveram significante aumento de neutr?filos e eosin?filos quando comparados com os controles (p<0.05). Conclus?es: Este estudo demonstrou que o pneumoperit?nio com CO contribuiu para reduzir a resposta inflamat?ria e imunol?gica em ratos submetidos a modelo de sepse abdominal, no que diz respeito a citocinas intraperitoneais e leucometria diferencial. O pneumoperit?nio tamb?m contribuiu para instala??o de acidose hiperc?rbica nos ratos s?pticos

Orientador: José Luiz Moraes Vasconcelos / Banca: Mário Binelli / Banca: Mário De Beni Arrigoni / Abstract: The objective of this trial was to evaluate the effects of different nutritional diet density on conception rate (CR) in bovine females. The experiment was achieved at Agropecuária Água Preta, Cocalinho, MT. It was made use 220 no pregnant Nelore females, on average with 2.79 body condition score (BCS), housed at a commercial feedlot, randomly divided in two pens. All animals received an adaptation diet (AP) for 15 days, with 50.1% of Neutral Detergent Fiber (NDF) and 28.8% of Non-Structural Carbohydrate (NSC). On day 0 the diet of Treatment A was changed (TA= higher nutritional density diet - 43.9% of NDF and 35.5% of NSC) and the Treatment B carried on receiving the AD (TB= lower nutritional density diet). The total mixed rate, settled of sorghum silage, sorghum whole cracked, rice whole cracked, cottonseed high lint and minerals, was offered four times a day. On day 0 it started the breeding period (BP), with natural service, using 4 Nelore bulls and 4 crossbred bulls in each pen, until day 21. The females where observed for estrus during the BP and only the cows that presented service were kept on the experiment. The CR was determined 27 days after BP by ultrasound. The CR was analyzed by logistic regression of SAS. The effects of variables: treatment, phase (phase 1, from day 0 until day 10 of the BP; phase 2, grom day 11 until day 21 of the BP) and interactions were included in the model, BCS and body weigh gain (BWG) were included as a co-variables. Tendency (P=0.077) of treatment effect on CR (TA=65.7 vs TB=76.1%) was detected. There was no effect of phase and interaction phase x treatment. The BWG was similar between TA and TB, however a linear effect (P<0.05) of BWG on CR was detected. Effect of BCS was no detect (P>0.10) on CR. As conclusion, the higher nutritional density diet intake decrease the CR. / Resumo: O objetivo do trabalho foi avaliar o efeito de dietas com diferentes densidades nutricionais na taxa de concepção (TC) de fêmeas bovinas. O trabalho foi realizado na Agropecuária Água Preta, Cocalinho, MT. Foram utilizadas 220 fêmeas Nelores vazias, mantidas em confinamento a céu aberto, com escore de condição corporal (ECC) médio de 2,79, alojadas aleatoriamente em duas baias. Todos os animais receberam dieta de adaptação (DA) por 15 dias, apresentando 50,1% de Fibra em Detergente Neutro (FDN) e 28,8% de Carboidrato Não Estrutural (CNE). No dia 0 a dieta do Tratamento A foi alterada (TA = dieta com maior densidade nutricional - 43,9% de FDN e 35,5% de CNE) e o Tratamento B continuou a receber a DA (TB = dieta com menor densidade nutricional). A dieta total, composta por: silagem de sorgo, sorgo integral triturado, arroz integral triturado, caroço de algodão e núcleo mineral, foi oferecida 4 vezes ao dia aos animais. No dia 0 inciou-se o período de monta (PM), no qual 4 touros nelores e 4 touros cruzados foram colocados junto às fêmeas em cada baia, permanecendo por 22 dias. No dia 21 os touros foram retirados de ambos os tratamentos. Os animais foram observados durante o PM, e somente as fêmeas que foram cobertas permaneceram no experimento. O diagnóstico de gestação (DG) foi realizado por ultra-sonografia 27 dias após a retirada dos touros. A TC foi analisada por regressão logística, por meio dos procedimentos LOGISTIC do SAS. Foram incluídos no modelo os efeitos das variáveis: tratamento, fase (fase 1, do dia 0 ao dia 10 do PM e a fase 2, do dia 11 ao dia 21 do PM) e interação fase x tratamento, e das co-variáveis: ganho de peso médio diário (GMD) e ECC. Foi detectada tendência (P=0,077) de efeito de tratamento na TC (TA=65,7 vs TB=76,1%). Não houve efeito de fase e da interação fase x tratamento. O GMD não foi diferente entre TA e TB, porém foi... (Resumo completo, clicar acesso eletrônico abaixo) / Mestre

O estudo consistiu de dois experimentos com o objetivo de avaliar os efeitos da acidose ruminal e restrição nutricional na ocorrência de processos inflamatórios nos animais e relacionar com as alterações na produção e composição do leite. Foram utilizadas doze vacas Holandês e Mestiças Holandês Jersey. Experimento 1: Na fase de adaptação, os animais receberam uma dieta formulada para atender 100% das necessidades nutricionais de energia e proteína. Na indução foi administrada uma dieta com restrição de 50% das necessidades em energia e proteína. Na recuperação os animais receberam uma das três dietas experimentais, para recuperar a estabilidade do leite: (1) suprimento somente de energia; (2) suprimento somente de proteína; (3) suprimento de energia e proteína. A restrição nutricional em energia e/ou proteína afeta negativamente a produção de leite, o peso vivo e o escore de condição corporal. Além de reduzir a eficiência de utilização de proteína da dieta e provocar uma maior instabilidade do leite ao teste do álcool. Entretanto, não altera o perfil sanguíneo e metabólico. Experimento 2: Os animais foram divididos em dois grupos (1) controle e (2) acidose. O delineamento experimental foi reversível simples com dois tratamentos e dois períodos experimentais. Foram analisados parâmetros referente às características físico-quimica, saúde da glândula mamária, medidas fisiológica, perfil metabólico e parâmetros sanguíneos. A indução da acidose ruminal subaguda (SARA) causou redução da produção e estabilidade do leite ao teste do álcool, pH urinário, pH fecal, pH ruminal. Entretanto, a indução a SARA não alterou os parâmetros sanguíneos avaliados. A SARA altera as características físico-químicas do leite, sem influenciar nas concentrações proteínas de fase aguda, caracterizando uma resposta inflamatória. A SARA pode acometer os animais sem apresentar mudanças no perfil sanguíneo dos mesmos. / The study consisted of two experiments with the aim of evaluating the effects of ruminal acidosis and nutritional restriction on the occurrence of inflammatory processes in animals and correlate with changes in milk production and composition. Twelve Holstein and cross bred Holstein and Jersey cows were used. In the first study, in the adaptation phase, the animals received a diet formulated to supply 100% of the nutritional needs of energy and protein. In the induction, a diet composed by 50% restriction of energy and protein requirements was administered. In the recuperation, the animals received one of the three experimental diets to recover milk stability: (1) only energy supply; (2) supply only of protein; (3) supply of energy and protein. The nutritional restriction in energy and / or protein can affects negatively milk production, weight and condition score body. In addition to reduce the efficiency of protein utilization of the diet and cause greater instability of the milk to the alcohol test. However, it does not changed the blood and metabolic profile. In second study, the animals were divided into two groups (1) control and (2) acidosis. The experimental design was simple reversible with two treatments and two experimental periods. Physiochemical characteristics, health of the mammary gland, physiological measures, metabolic profile and blood parameters were analyzed. Losses in milk production, reduction of alcohol stability test, urinary pH, fecal pH, ruminal pH were caused by Subacute ruminal acidosis (SARA) induction. However, induction of SARA did not changed the blood parameters evaluated. SARA changes the physical-chemical characteristics of the milk, without influencing the acute phase proteins concentrations, characterizing an inflammatory response. SARA can affect the animals without demostrate changes in the blood profile of the animals.

Submitted by Franciele Moreira (francielemoreyra@gmail.com) on 2018-09-04T14:51:59Z No. of bitstreams: 2 Dissertação - Antônio Ferreira Garcia Neto - 2018.pdf: 2308172 bytes, checksum: d20521dd121eebd70319e9435511febd (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2018-09-05T11:09:44Z (GMT) No. of bitstreams: 2 Dissertação - Antônio Ferreira Garcia Neto - 2018.pdf: 2308172 bytes, checksum: d20521dd121eebd70319e9435511febd (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2018-09-05T11:09:44Z (GMT). No. of bitstreams: 2 Dissertação - Antônio Ferreira Garcia Neto - 2018.pdf: 2308172 bytes, checksum: d20521dd121eebd70319e9435511febd (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2018-07-27 / Fundação de Amparo à Pesquisa do Estado de Goiás - FAPEG / Best zootechnical indexes are important in beef cattle breeding. It is allied to the satisfactory conditions of creation and sanity. If not observed, metabolic imbalances may occur. The post mortem relationship between ruminal disturbances, hepatic abscesses and foot diseases was evaluated in beef cattle finished in pasture in a southwestern state of Goias. Then, an evaluation of the financial losses was carried out due to ruminal condemnations of cattle slaughtered in southwestern state of Goias. About the relationship, 970 male bovines, Nelore, 25 to 36 months of age, were evaluated by ante-mortem and post-mortem examination of the hoof, liver and rumen. It was considered the presence or absence of diseases. Data analyzed by the chi-square test (p <0.05). In the financial study, we considered the findings of 1,275 male bovine animals, Nellore, 25 to 36 months of age, 597 confined and 678 to pasture. Data analyzed by descriptive statistics. 363 cattle with hoof diseases, hepatic abscesses or ruminal disorders. 52 with hoof diseases, nine with hepatic abscess and 302 with ruminal alterations. Of these, 27 with two associated diseases. None with three simultaneous lesions. Ruminal lesions were found in 47 confined animals and 29 to pasture. The mean rumen weight with lesion was 4.55 kg and the mean rumen weight healthy was 4.50. The total condemned weight was 345.50 kg, 213.50 of confined cattle and 132 of pasture. The loss was R $ 2,245.75 (US $ 688.88), if sold domestically, or R $ 3,154.41 (US $ 967.62), if exported. There was no postmortem relationship between ruminitis, hepatic abscess and hoof diseases in the evaluated animals. The financial impact of ruminal condemnations was significant. / Melhores índices zootécnicos são prementes na bovinocultura de corte. Alia-se às condições satisfatórias de criação e sanidade. Se não observados, desequilíbrios metabólicos podem ocorrer. Avaliou-se a relação post mortem entre os lesões ruminais, abscessos hepáticos e enfermidades podais em bovinos terminados a pasto em um frigorífico no sudoeste goiano. Sequencialmente, promoveu-se uma avaliação dos prejuízos financeiros devido as condenações ruminais de bovinos abatidos no sudoeste goiano. Sobre a relação, avaliou-se 970 bovinos machos, raça Nelore, 25 a 36 meses de idade, pelo exame ante mortem e post mortem dos pés, fígado e rúmen. Considerou- se a presença ou ausência das lesões. Dados foram analisados pelo teste qui-quadrado (p<0,05). No estudo financeiro, considerou-se os achados de 1.275 bovinos machos, Nelore, 25 a 36 meses de idade, 597 confinados e 678 a pasto. Dados foram analisados por estatística descritiva. 363 bovinos com lesões podais, abscessos hepáticos ou distúrbios ruminais, sendo 52 com lesões podais, nove com abscesso hepático e 302 com alterações ruminais. Desses, 27 com duas enfermidades associadas e nenhum com três lesões simultâneas. Constatou-se lesões ruminais em 47 animais confinados e 29 a pasto. O peso ruminal médio lesionado foi 4,55 quilos e os saudáveis 4,50. O peso total condenado foi 345,50 quilos, 213,50 de bovinos confinados e 132 a pasto. O prejuízo foi R$ 2.245,75 (U$ 688,88), se vendidas nacionalmente, ou R$ 3.154,41 (U$ 967,62), se exportadas. Não houve relação post mortem entre ruminite, abscesso hepático e enfermidades podais nos animais avaliados. O impacto financeiro pelas condenações ruminais foi expressivo.

Submitted by MARCOS LEANDRO TEIXEIRA DE OLIVEIRA (marcosteixeira@ufv.br) on 2018-08-08T12:23:44Z No. of bitstreams: 1 texto completo.pdf: 611136 bytes, checksum: bf9d8a0089c4630399316fa33aa12280 (MD5) / Made available in DSpace on 2018-08-08T12:23:44Z (GMT). No. of bitstreams: 1 texto completo.pdf: 611136 bytes, checksum: bf9d8a0089c4630399316fa33aa12280 (MD5) Previous issue date: 2018-02-23 / Muitos problemas associados ao uso de dietas de alto grão são relatados por produtores e cientistas, como os efeitos negativos associados à acidose. Visando melhorar as condições ruminais, estudos vem sendo realizados para se encontrar um nível ótimo de fibra a ser incluída nestas dietas, principalmente naquelas ditas como sem volumoso. Sendo assim o objetivo deste trabalho foi avaliar os efeitos da inclusão de fibra fisicamente efetiva (FDNfe) proveniente de volumoso em dietas contendo grão inteiro de milho, em substituição ao pellet, sob os parâmetros ingestivos, digestivos e ruminais. O experimento foi realizado no Departamento de Zootecnia da Universidade Federal de Viçosa. Foram utilizados cinco bovinos Nelore machos não castrados fistulados no rúmen com média de 393 ± 9 Kg e idade de 14 meses. O delineamento experimental foi em quadrado latino 5 x 5, sendo constituído por cinco dietas, cinco animais e cinco períodos experimentais. As dietas foram à base de grão de milho inteiro com inclusão de níveis crescentes de cana-de- açúcar in natura, sendo constituídas respectivamente por: Controle (CON) – Dieta com 85% de milho grão inteiro e 15% de um núcleo mineral-proteico peletizado; D5 – Dieta com 85% de milho grão inteiro, 5% de cana-de-açúcar in natura e 10% de um suplemento mineral proteico; D15 – Dieta com 75% de milho grão inteiro, 15% de cana-de-açúcar in natura e 10% de um suplemento mineral proteico; D25 – Dieta com 65% de milho grão inteiro, 25% de cana-de-açucar in natura e 10% de um suplemento mineral proteico; D35 – Dieta com 55% de milho grão inteiro, 35% de cana de açúcar in natura e 10% de um suplemento mineral proteico. Os períodos experimentais tiveram duração de 20 dias (14 dias para adaptação e seis dias de coletas). Os três primeiros dias de coletas foram destinados à amostragem de digestas omasais, coleta spot de fezes, e coletas de amostras para estimação das concentrações de amônia e ácidos orgânicos. Também foi realizada a mensuração do pH ruminal. No quarto e sexto dia do período de coleta, foi feito o esvaziamento no ponto cheio e vazio do rúmen, respectivamente. Nestes dias também foram coletadas amostras de digestas para isolamento de microrganismos ruminais. O teor de FDN fisicamente efetiva (FDNfe) de cada dieta foi mensurado ao final de cada período experimental com o auxilio de um conjunto de três peneiras chamado Pen State Particle Sepatator (PSPS), as quais apresentavam crivos de 19, 8 e 4 mm. Para as análises estatísticas, foi utilizado o procedimento MIXED do SAS ® (Versão 9.4). As médias foram comparadas por meio do teste de Dunnett, assumindo 5% para o erro tipo I, e foram testados os efeitos linear e quadrático para os níveis de inclusão de FDNfe de volumoso na dieta, sendo a concentração de amônia avaliada como medida repetida. Os consumos de matéria orgânica (MO), fibra insolúvel em detergente neutro corrigida para cinzas e proteína (FDNcp) e fibra insolúvel em detergente neutro corrigida para cinzas e proteína potencialmente digestível (FDNcpPD), proteína bruta (PB), extrato etéreo (EE), carboidratos não fibrosos (CNF) e amido responderam de forma linear decrescente ou quadrática em função dos níveis de FDNfe de volumoso. As digestibilidades de todos os constituintes reduziram com a inclusão de FDNfe de volumoso, com exceção da FDNcp potencialmente digestível (PD). O pH ruminal respondeu de forma linear crescente à adição de volumoso na dieta. A concentração e o pool de propionato reduziram de forma linear e a concentração de butirato e o pool de acetato tenderam a reduzir e elevar, respectivamente. A concentração de nitrogênio amoniacal ruminal aumentou de forma linear. Sendo assim, um nível de FDNfe proveniente de volumoso de 20,47 g/kg, corresponente a 5% de cana-de-açúcar, pode ser utilizado em substituição ao pellet em dietas de grão inteiro de milho, de forma a melhorar os parâmetros nutricionais e metabólicos deste tipo de matriz alimentar. / Many problems associated with the use of high-grain diets are reported by growers and scientists as the negative effects associated with acidosis. In order to improve the ruminal conditions, studies have been carried out to find an optimal level of fiber to be included in these diets, especially in the so-called non-voluminous diets. Therefore, the objective of this work was to evaluate the effects of the inclusion of physically effective fiber (NDF) from bulks in diets containing whole grains of corn, replacing the pellet, under ingestive, digestive and ruminal parameters. The experiment was carried out at the Animal Science Department of the Federal University of Viçosa. Five rumen fistulated, uncastrated male Nellore cattle with a mean of 393 ± 9 kg and age of 14 months were used. The experimental design was in a 5 x 5 Latin square, consisting of five diets, five animals and five experimental periods. The diets were based on whole corn grain with inclusion of increasing levels of sugarcane in natura, being constituted respectively by: Control (CON) - Diet with 85% of whole grain corn and 15% of a mineral- pore protein; D5 - Diet with 85% of whole grain corn, 5% of sugar cane in natura and 10% of a mineral protein supplement; D15 - Diet with 75% of whole grain corn, 15% of sugar cane in natura and 10% of a mineral protein supplement; D25 - Diet with 65% of whole grain corn, 25% of sugar cane in natura and 10% of a protein mineral supplement; D35 - Diet with 55% of whole grain corn, 35% of sugar cane in natura and 10% of a protein mineral supplement. The experimental periods had a duration of 20 days (14 days for adaptation and six days of collection). The first three days of sampling were used for the sampling of omasal digests, spot collection of feces, and sampling of samples for estimation of concentrations of ammonia and organic acids. Ruminal pH was also measured. On the fourth and sixth day of the collection period, emptying was performed on the full and empty spot of the rumen, respectively. During these days samples were also collected for the isolation of ruminal microorganisms. The physically effective NDF content of each diet was measured at the end of each experimental period with the aid of a set of three sieves called Pen State Particle Sepatator (PSPS), which had 19, 8 and 4 mm sieves. Statistical analyzes were performed using the SAS® MIXED procedure (Version 9.4). The averages were compared using the Dunnett test, assuming 5% for the type I error, and the linear and quadratic effects were tested for inclusion levels of NDF in the diet and the ammonia concentration was evaluated as a repeated measure. The organic matter (OM), neutral detergent insoluble fiber corrected for ash and protein (FDNcp) and neutral detergent insoluble fiber corrected for ash and potentially digestible protein (NDFcpPD), crude protein (CP), ethereal extract , non-fibrous carbohydrates (CNF) and starch responded in a linear decreasing or quadratic manner as a function of the levels of NDF of roughage. The digestibilities of all the constituents reduced with the inclusion of NDF of roughage, with the exception of the potentially digestible NDFcp (PD). The ruminal pH responded in an increasing linear fashion to the addition of voluminous in the diet. The concentration and the pool of propionate linearly reduced and the concentration of butyrate and the acetate pool tended to reduce and elevate, respectively. The concentration of ruminal ammoniacal nitrogen increased linearly. Thus, a level of NDF from volumine of 20.47 g / kg, corresponding to 5% of sugarcane, can be used instead of pellets in whole corn diets, in order to improve the parameters nutritional and metabolic characteristics of this type of food matrix.

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2017-10-13T13:11:07Z No. of bitstreams: 2 Tese - Antônio Dionísio Feitosa Noronha Filho - 2017.pdf: 2777014 bytes, checksum: 9324069d4bdcef5e18cd1f0e45577c3e (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-10-13T13:11:46Z (GMT) No. of bitstreams: 2 Tese - Antônio Dionísio Feitosa Noronha Filho - 2017.pdf: 2777014 bytes, checksum: 9324069d4bdcef5e18cd1f0e45577c3e (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-10-13T13:11:46Z (GMT). No. of bitstreams: 2 Tese - Antônio Dionísio Feitosa Noronha Filho - 2017.pdf: 2777014 bytes, checksum: 9324069d4bdcef5e18cd1f0e45577c3e (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-03-10 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Among diseases that can affect cattle in intensive production systems are rumen acidosis laminitis. It was produced initially a literature review about experimental induction of rumen acidosis and after this, was evaluated rumen acidosis and initial phase of laminitis in calves, both induced by intrarruminal administration of oligofructose. In the different protocols, in both acute and subacute forms of acidosis, are usually evaluated fermentative and clinical aspects. In the study was used six crossbred male calves (Bos taurus X Bos indicus) aging one year and weighting 175 ± 22,6 kg. Initially were used three animals in a pilot group (GP), receiving oligofructose in the dose of 13g/kg and after this, three animals were used as experimental group (GE) receiving oligofructose in the dose of 17 g/kg. Were evaluated parameters from clinical exam, hematocrite, plasmatic protein, blood gas analysis and histology of hoof samples. Oligofructose overload induced rumen acidosis in both groups. It was also observed metabolic acidosis with reduction of blood pH, PCO2, bicarbonate and base excess. Was observed neither elevation in hoof sensibility nor lameness. Despite this, many animals presented apathy and slower gait, possibly due to metabolic acidosis. In histologic evaluation, were observed circulatory changes and inflammatory infiltrate in dermis, irregularities in basement membrane and morphologic changes in basal epidermis. Protocol for laminitis induction with intrarruminal administration of oligofructose in crossbred calves was well succeeded. In the initial phase, laminitis was characterized by clinical signs of the primary disease, in this case rumen acidosis, and histologic lesions indicative of acute inflammation and compromise of basement membrane and basal epidermis. / Entre as doenças que acometem bovinos em sistemas de alta produtividade estão a acidose ruminal e a laminite. Objetivou-se inicialmente realizar revisão de literatura sobre indução experimental de acidose ruminal em bovinos e, posteriormente, avaliar o quadro de acidose ruminal e da fase inicial de laminite induzidas pela administração de oligofrutose em bezerros. Nos diferentes protocolos de indução podem ser avaliados aspectos fermentativos e clínicos da acidose ruminal, nas formas aguda e subaguda. Para o estudo, utilizaram-se seis bezerros mestiços (Bos taurus X Bos indicus) de um ano de idade. Inicialmente usaram-se três animais em um grupo piloto (GP) recebendo oligofrutose na dose de 13 g/kg e em seguida um grupo experimental (GE) recebendo na dose de 17 g/kg. Avaliaram-se alterações clínicas, laboratoriais e histológicas do casco. A sobrecarga de oligofrutose provocou acidose ruminal caracterizada por baixo pH em ambos os grupos. Observou-se também acidose metabólica com redução de pH, PCO2, bicarbonato e excesso de base. Não se observou aumento da sensibilidade dos cascos ou claudicação. Apesar disso, muitos animais apresentaram apatia e marcha mais lenta, possivelmente devido a acidose metabólica. Histologicamente observaram-se alterações circulatórias e infiltrado inflamatório na derme, irregularidades de membrana basal e alterações morfológicas na camada basal da epiderme. O protocolo de indução de laminite com administração intrarruminal de oligofrutose se mostrou eficaz em bezerros mestiços de um ano. Na fase inicial a laminite se caracterizou por sinais clínicos da enfermidade primária, no caso acidose ruminal, e por alterações histológicas indicativas de inflamação aguda e comprometimento de membrana basal e epiderme.

O acúmulo intramuscular de íons H+ decorrente do exercício de alta intensidade inibe enzimas da via glicolítica, além de prejudicar diversas etapas do processo contrátil levando à fadiga. Especula-se que a suplementação combinada de betaalanina (via aumento da concentração de carnosina) e bicarbonato de sódio aumentaria a capacidade tamponante intra e extracelular refletindo em efeitos sinérgicos no metabolismo energético e no desempenho, do que quando suplementados isoladamente. Poucos estudos investigaram a eficácia da combinação dos suplementos durante o exercício e não há informações sobre os efeitos desta combinação nos sistemas energéticos. Portanto, esse estudo teve por objetivo investigar a eficácia da suplementação combinada ou isolada de betaalanina e bicarbonato de sódio enquanto estratégias de aumento da capacidade tamponante, bem como seu potencial na modulação do metabolismo energético e no desempenho do exercício intermitente de alta intensidade. O estudo contou com um desenho duplo-cego em que 77 voluntários (idade 38,6 ± 9,9 anos; massa corporal 76,6 ± 8,4 kg; VO2pico 59,3 ± 5,2 ml.kg-1.min-1) foram randomizados e aleatoriamente alocados em um dos 4 grupos sendo; beta-alanina (BA; n= 19), bicarbonato de sódio (BIC; n = 19), beta-alanina e bicarbonato de sódio (BA + BIC; n = 20) ou dextrose (PLA; n = 19). A eficácia das substâncias na contribuição dos sistemas energéticos foi comparada antes e após um período de 28 dias de suplementação de 6,4g/dia de beta-alanina e de 0,3g/kg de massa corporal de bicarbonato de sódio administrada 60 minutos antes de um exercício intermitente em cicloergômetro, que consistia de 4 séries de 1 minuto a 110% da potência aeróbia máxima com 1 minuto de intervalo e cadência constante. Após 10 minutos de repouso passivo, o desempenho era avaliado em um teste time-trial cuja meta era completar um trabalho total de 30 kJ, no menor tempo possível. Foram mensuradas as concentrações sanguíneas de pH, bicarbonato, excesso de base e lactato antes, durante e após os exercícios. As frações dos sistemas oxidativo e alático (ATP-CP) foram estimadas com base no consumo de oxigênio e o glicolítico pelo delta da concentração do lactato. O perfil energético do exercício intermitente consistiu na maior parte do sistema oxidativo (45 - 55%), seguido do sistema ATP-CP (35 - 40%) e do glicolítico (8 - 15%). A suplementação de bicarbonato de sódio elevou (P<0,001) as concentrações sanguíneas de bicarbonato (~ 6 mmol/L) e pH (~ 0,06 unidades) nos grupos BIC e BA + BIC, gerando uma maior concentração do lactato nas séries iniciais o que refletiu no aumento do custo energético glicolítico na primeira série do exercício intermitente, sendo estatisticamente significativo somente no grupo BIC (9,9 ± 7,2 kJ vs 18,7 ± 9,4 kJ; pré vs pós-suplementação). Não houve efeito da suplementação no tempo para completar o time-trial entre os grupos ou períodos de suplementação (BA -0,5%; BIC -1,4%; BA + BIC -4% e PLA 0%). A suplementação de bicarbonato de sódio, independentemente da suplementação de beta-alanina melhorou as variáveis de controle do equilíbrio ácido-base sanguíneo resultando na maior participação da via glicolítica, entretanto não conferiu benefícios adicionais ao desempenho / Intramuscular accumulation of H+ ions during high-intensity exercise inhibits glycolytic pathway enzymes and impairs several steps in the muscle-contraction process, causing fatigue. It has been suggested that a combined supplementation of betaalanine (through an increase in carnosine concentration) and sodium bicarbonate would increase intra- and extracellular buffering capacity causing synergetic effects on energy metabolism and performance, more than each supplement alone. Few studies investigate the effectiveness of combined supplements during exercise and there is no literature on the effects of this combination on energy system contribution. Therefore, the present study investigated the effectiveness of both beta-alanine and sodium bicarbonate alone and together in increasing buffering capacity as well as the potential for modulating energy metabolism and performance during high-intensity intermittent exercise. The study was double-blind and 77 volunteers (aged 38.6 ± 9.9 year, body mass 76.6 ± 8.4 kg; VO2peak 59,3 ± 5,2 ml.kg-1.min-1) were randomly assigned to four groups: beta-alanine (BA; n = 19), sodium bicarbonate (BIC; n = 19), beta-alanine and sodium bicarbonate (BA + BIC; n = 20), dextrose (PLA; n = 19). The efficacy of the substances in contributing to energy systems was compared before and after a 28-day period of supplementing 6.4g/day of beta-alanine and of 0.3g/kg of body mass of sodium bicarbonate administered 60 minutes before a cycling intermittent exercise, consisting of 4 sets of 1-minute each at 110% of maximum aerobic power with 1-minute intervals between each set and at an even pace. After 10 minutes of passive rest, performance was measured during a time-trial test in which participants were asked the complete 30 kJ of total work as fast as possible. Blood concentration of pH, bicarbonate, base excess, and lactate were measured before, during, and after intermittent and time trial protocols. The contributions of oxidative and anaerobic alactic (ATP-CP) were estimated based on oxygen consumption and the glycolytic system by the delta of lactate concentration. The energy demand of the intermittent exercises mostly consisted of the oxidative system (45-55%), followed by the ATP-CP system (35-40%), lastly glycolytic (8-15%). The sodium bicarbonate supplement elevated (P>0.001) blood concentration of bicarbonate (~6mmol/L) and pH (~0.06) units in the BIC and BA + BIC groups, generated a high concentration of lactate in the first sets, reflecting the increase in glycolytic energy cost in the first set of intermittent exercise, but was only statistically significant in the BIC group (9.9 ± 7.2 KJ vs 18.7 ± 9.4 KJ; pre vs postsupplementation). Supplementation did not have an effect on the time-trial times between groups or supplement periods (BA -0.5%, BIC -1.4%, BA + BIC -4%, PLA 0%). Supplementing with sodium bicarbonate, both alone and together with betaalanine improved blood acid-base control during high-intensity intermittent exercise resulting in high participation of the glycolytic metabolism, however it did not lead to additional performance

Le tubule proximal participe à la diurèse en modifiant la composition de l'ultrafiltrat glomérulaire. Grâce à de nombreux transports transépithéliaux, il le glucose, les acides aminés et les protéines de bas poids moléculaires, ainsi que 80 % des ions HPO42- ou HCO3-, 60 % des ions Na+, Cl-, K+, Ca2+, 75 % de l’eau et 30 % des ions Mg2+ ultrafiltrés.Durant ma thèse, j'ai étudié les rôles physiologiques et physiopathologiques de deux protéines de transport exprimées dans le tubule proximal.Dans le cadre de ma première étude, j'ai évalué in vivo la fonction rénale de souris n'exprimant pas une protéine appelée Kir4.2, dont le rôle est inconnu. Nos résultats montrent que Kir4.2, associée à Kir5.1, forme un canal potassique basolatéral Kir4.2/Kir5.1 dans le tubule proximal. L'absence de Kir4.2 provoque chez la souris une acidose tubulaire proximale isolée, consécutive à une ammoniogénèse altérée. De fait, la perte de fonctionnalité de Kir4.2 pourrait être à l'origine d'acidoses tubulaires proximales isolées familiales idiopathiques.Dans le cadre de ma seconde étude, j'ai analysé in vitro la fonctionnalité d'un mutant pathogène de l'échangeur 2Cl-/H+ ClC-5 impliqué dans la maladie de Dent. Cette maladie, caractérisée par une protéinurie de bas poids moléculaire associées à divers troubles du tubule proximal, serait liée à un défaut d'acidification des endosomes précoces par ClC-5. Toutefois, le mutant de ClC-5 que nous avons étudié, converti en canal chlorure, acidifie autant les endosomes précoces que le ClC-5 sauvage. Surprenants, ces résultats suggèrent que la maladie de Dent puisse être causée par un défaut d'accumulation d'ions chlorure dans l'endosome. / The proximal tubule is involved in diuresis by modifying the content of the glomerular ultrafiltrate. Using a variety of transepithelial transports systems, it reabsorbs all ultrafiltrated glucose, amino-acids and low molecular weight proteins, as well as 80% of HPO42- and HCO3- ions, about 60% of Na+, Cl-, K+, and Ca2+ ions, 75% of water and 30% of Mg2+.During this thesis, I determined the physiological and physiopathological roles of two transport proteins present in proximal tubule. Firstly, I evaluated the renal function of mice invalidated for the Kir4.2 protein, whose role was undetermined. Our results show that Kir4.2, in association with Kir5.1, form a Kir4.2/Kir5.1 potassium channel at the basolateral membrane of proximal tubular cells. Furthermore, Kir4.2-null mice exhibit a reduced ammoniagenesis leading to an isolated proximal renal tubular acidosis. This study provides the gene encoding Kir4.2 as a candidate gene for the yet unexplained autosomal dominant isolated proximal renal tubular acidosis.Secondly, I evaluated in vitro the functional consequences of a pathogenic mutation of the 2Cl-/H+ exchanger ClC-5, involved in Dent’s disease. This disease, characterized by a low-molecular-weigth-proteinuria in the context of a general proximal tubule dysfunction, is currently thought to be due to an acidification defect of early endosomes linked to a loss of function of ClC-5. Surprisingly, our results show that ClC-5, converted into a chloride channel by this mutation, indeed acidifies the early endosomes as well as the ClC-5 wild-type. Thus, Dent’s disease may originate from a defect in the accumulation of chloride ions into the early endosomes.

Le syndrome de Leigh version canadienne-française (LSFC) est une maladie autosomale récessive causée par une mutation du gène LRPPRC. Le rôle principal de la protéine LRPPRC est la traduction des gènes mitochondriaux qui encodent certains complexes de la chaine respiratoire. La mutation provoque une diminution de l’expression de LRPPRC, qui induit un déficit tissu spécifique du cytochrome c oxydase (COX). Principalement dans le foie et le cerveau, cette diminution provoque un retard de développement global et la survenue de crises d’acidose souvent fatales chez des enfants atteints avant l’âge de 3-4 ans. L’impact de LRPPRC sur les cellules du système immunitaire est peu étudié aujourd’hui. Cependant les infections, et donc l’activation du système immunitaire, font partie des stress induisant les crises d’acidose métabolique. Afin d’étudier la relation entre LRPPRC et les cellules immunitaires, nous avons tiré profit de sérum de patients récolté dans une étude précédente, nous permettant de quantifier la réponse au vaccin des patients LSFC. Nous avons également développé deux nouveaux modèles murins à délétion conditionnelle permettant d’étudier l’impact de l’absence de LRPPRC et de sa mutation sur la composition du système immunitaire. Lors de mes travaux de doctorat, j’ai montré que certains patients atteints du LSFC ne répondaient pas au vaccin contre la rougeole, la rubéole et les oreillons, semblant indiquer une atteinte de la réponse humorale. Lors de la caractérisation des modèles murins développés au laboratoire, j’ai mis en évidence une forte altération du développement des lymphocytes B, dû, entre autres à un défaut de prolifération. La mise en place et la validation des modèles murins permettant d’étudier la mutation de LRPPRC dans tous les organes des souris est une avancée majeure pour la recherche sur le LSFC. L’étude de la réponse immunitaire dans ces modèles permettra de mieux comprendre le rôle du système immunitaire dans le déclenchement des crises d’acidose métabolique afin de pouvoir envisager des pistes de traitements préventifs. / The French-Canadian version of Leigh syndrome (LSFC) is an autosomal recessive disease caused by a mutation in the LRPPRC gene. The main role of the LRPPRC protein is the translation of mitochondrial genes that encode certain complexes of the respiratory chain. The mutation results in a decrease in LRPPRC expression, which induces a tissue-specific deficiency of cytochrome c oxidase (COX). Mainly in the liver and brain, this decrease causes an overall developmental delay and the onset of often fatal acidotic crises in affected children before the age of 3-4 years. The impact of LRPPRC on immune system cells is poorly studied. However, infections, and therefore activation of the immune system, are among the stresses inducing metabolic acidotic crises. In order to study the relationship between LRPPRC and immune cells, we took advantage of serum from patients collected in a previous study, allowing us to quantify the vaccine response of LSFC patients. We have also developed two new conditional knockout mouse models to study the impact of the absence of LRPPRC and its mutation on the composition of the immune system. During my doctoral work, I showed that some LSFC patients did not respond to the measles, mumps and rubella vaccine, suggesting an impairment of the humoral response. During the characterization of the mouse models developed in the laboratory, I highlighted a strong alteration in the development of B lymphocytes, due, among other things, to a proliferation defect. The establishment and validation of mouse models to study the role of the LRPPRC mutation in all organs of mice is a major advance for LSFC research. The study of the immune response in these models will help to better understand the role of the immune system in triggering metabolic acidotic crises in order to consider preventive treatment options.

L’optimisation hémodynamique péri-opératoire est une stratégie qui vise à maximaliser le transport artériel en oxygène et/ou le volume d’éjection systolique lors de chirurgie à risque. Ce concept a beaucoup évolué lors de ces trente dernières années, vers une approche plus simple, plus réalisable en pratique clinique et moins invasive. Les principales thérapeutiques utilisées dans les différents protocoles d’optimisation hémodynamique sont le remplissage vasculaire, l’administration d’agents inotropes et de vasopresseurs. Cependant, les conséquences physiopathologiques de l’agression chirurgicale peuvent impacter grandement les modalités d’administration et l’efficacité des thérapeutiques précitées. Dans la première étude, nous avons décrit l’impact de l’acidose respiratoire et métabolique (fréquemment rencontrées lors de chirurgie majeure et/ou de coeliochirurgie) sur l’efficacité des agents α et β-adrénergiques sur le myocarde sain de rat. Dans un deuxième travail nous avons mis en évidence que le remplissage vasculaire ne pouvait pas être guidé par des indices dynamiques de précharge dépendance lors du clampage chirurgicale de l’aorte abdominale sous-rénale, dans un modèle porcin. Enfin, dans la troisième étude, nous avons montré dans un modèle clinique, que le positionnement en décubitus ventral lors d’une chirurgie du rachis entrainait des modifications majeures des interactions cardiorespiratoires et que les indices dynamiques devaient être interprétés avec prudence pour guider le remplissage vasculaire dans ce contexte. Ces études translationnelles soulignent trois situations fréquentes impactant l’efficacité et/ou les modalités d’administration des thérapeutiques nécessaires à une optimisation hémodynamique peropératoire / The aim of perioperative haemodynamic optimization is to maximize oxygen delivery and/or stroke volume during high risk surgery. This concept has evolved during the last thirty years, to a simpler, more feasible and less invasive approach. Main treatments used in different hemodynamic optimization protocols are fluid loading, inotropes and vasopressors administration. However, pathophysiological consequences of surgical stress can greatly impact the mode of administration and the efficacy of the above therapeutics. In the first study, we described the impact of respiratory and metabolic acidosis (frequently encountered during major surgery and/or laparoscopic surgery) on the effectiveness of α and β-adrenergic agents in healthy rat myocardium. In a second work, we demonstrated that intravenous fluids cannot be guided by dynamic indices of preload dependency during surgical clamping of the infrarenal abdominal aorta in a porcine model. Finally, in the third study, we demonstrated in a clinical model, that positioning in prone position during spine surgery induced major changes in cardiorespiratory interactions and dynamic indices should be interpreted with caution to guide fluid therapy in this context. These translational studies highlight three common situations impacting the effectiveness and/or administration of therapeutic necessary for intraoperative hemodynamic optimization.