Made available in DSpace on 2016-12-23T13:53:40Z (GMT). No. of bitstreams: 1 Cesar Otaviano Penna Junior.pdf: 505984 bytes, checksum: cd67e240dbaac144ea465c0209566a1b (MD5) Previous issue date: 2010-08-30 / The cross-breeding derived from specialized milk producing European breeds with zebu breeds that are adapted to tropical conditions form the basis of the majority of Brazil s milk producing systems. However, researches regarding the metabolic profile (MP) for bovine dairy cows focus on pure breeds coming mostly from temperate to subtropical regions. Therefore, the behaviour of the hematobiochemical components indicators on the energy metabolism in second calving rate order ½ and ¾ Holstein x Gir (HG) dairy cows, in two stages of lactation, became the object of the evaluation, as well as to determine its relationship with body condition (BCS) and milk production during the dry season in tropical environment. The experiment was conducted at Santa Luzia Farm, located in Minas Gerais - Brazil. This study used data collected in the months of May and August 2009 from 37 ½ HG cows and 35 ¾ HG cows. By our definition studies were focused on two lactation periods, the first being from 28 to 60 days (P1 lactation) and the second from 110 to130 days (P2 of lactation). The cows received complete feed in the trough. The biochemical indicators of the metabolic energy profile were analyzed through the beta-hydroxybutyrate (βHB), cholesterol and the enzyme Aspartate transaminase (AST) quantifications. The metabolite average values, with their standard errors, analyzed by Student test, were established for both blood degrees, in their respective lactation periods. Given the scarcity of information on reference values for the genetic group investigated in this study, reference values were methodically sought from studies using larger number of variables equal to the present study. There were statistical differences between the periods for βHB, milk production and BCS, whereas the other parameters did not differ for cows ½ and ¾ HG. There were statistical differences between the periods in βHB, milk production and BCS, whereas the other parameters did not differ for ½ and ¾ HG cows. Between blood degrees, the statistical differences occurred within each period concerning the βHB and milk production parameters and no other differences occurred in relation to the remaining parameters. Having obtained the results and taking the conditions to which the animals were exposed in this study into consideration, we have concluded that the genetic groups were effective in sustaining their respective levels of milk production without experiencing complications of metabolic order. We suggest such studies to be continuated as to equate Reference Values / Os cruzamentos derivados de raças européias especializadas para produção de leite com raças zebuínas adaptadas às condições tropicais formam a base da maioria dos sistemas de produção de leite no Brasil. Porém, verifica-se que os estudos a respeito de perfil metabólico (PM) para vacas bovinas leiteiras se concentram em raças puras, em sua grande maioria em regiões de clima temperado ou subtropical. Assim, com a revisão objetivou-se destacar a importância do uso do Perfil Metabólico energético na avaliação do desempenho produtivo de vacas leiteiras, seja no quesito nutricional, seja nas questões relacionadas ao diagnóstico e prevenção de transtornos de ordem metabólica nutricional e com a pesquisa aferir os valores e avaliar o comportamento dos marcadores bioquímicos energéticos entre dois períodos da lactação e entre diferentes graus genéticos de vacas HG de 2ª OP, no período da seca, em região tropical. O experimento foi realizado na Fazenda Santa Luzia, localizada no Estado de Minas Gerais Brasil. Foram utilizados dados coletados nos meses de maio e agosto de 2009, provenientes de 37 vacas ½ HG e 35 vacas ¾ HG. Definiu-se concentrar os estudos em dois períodos da lactação, sendo o primeiro de 28 a 60 dias (P1 da lactação) e o segundo de 110 a 130 dias (P2 da lactação). As vacas receberam ração total. Foram analisados os indicadores bioquímicos do perfil metabólico energético por meio da quantificação do Beta-hidroxibutirato (βHB), do colesterol e da enzima Aspartato transaminase (AST). Os valores médios dos metabólitos, com seus erros-padrão, analisados pelo teste t de Student, foram estabelecidos para ambos os graus de sangue, nos respectivos períodos da lactação. Dada a escassez de informações sobre valores referenciais para o grupo genético investigado nesse estudo, metodologicamente buscaram-se valores referenciais de estudos que utilizaram o maior número de variáveis iguais ao do presente trabalho. Ocorreram diferenças estatísticas (p<0,05) entre períodos para βHB, produção de leite e ECC, enquanto que os demais parâmetros não apresentaram diferenças (p>0,05) para vacas ½ e ¾ HG. Entre graus de sangue, as diferenças estatísticas (p<0,05) ocorreram dentro de cada período para os parâmetros βHB e produção de leite, não tendo ocorrido diferenças (p>0,05) para os demais parâmetros. Aferidos os valores, conclui-se que para as condições a que foram submetidos os animais no presente estudo, os grupos genéticos foram eficientes para sustentarem seus respectivos níveis de produção de leite, sem apresentarem complicações de ordem metabólica. Sugere-se a continuidade de estudos dessa natureza para equacionar Valores de Referência

The nicotinamide riboside (NR) form of vitamin B3and the ketone body ß-hydroxybutyrate (BHB) are two of the most promising natural compounds yet identified for the treatment of aging and aging-related diseases. Forms of vitamin B3are precursors for the synthesis of the coenzymes nicotinamide adenine dinucleotide (NAD(H)) and nicotinamide adenine dinucleotide phosphate (NADP(H)). In aged cells levels of NAD+decline, decreasing metabolism and decreasing activity of protective sirtuin protein deacetylases. In aged cells NR, but not more common forms of vitamin B3, boost NAD+levels. BHB is naturally produced by the body when individuals fast or consume a ketogenic (KD) or calorically restricted (CR) diet. These diets have been shown to extend lifespan in mice, while they are also protective in many disease models. Caenorhabditis elegans, a roundworm with a short mean lifespan of roughly 2 to 3 weeks depending upon the temperature, is used as a model system to study aging. BHB has been previously shown to increase lifespan by roughly 20% when administered to C. elegans.We administered NR and BHB individually and together to C. elegans starting at two different developmental stages (larval stages 1 and 4) and measured lifespan. We found that administration of 20 mM DL-BHB decreased lifespan when first given at the L1 stage, while it robustly increased lifespan when first given at the L4 stage. Administration of 0.5 mM NR increased lifespan when first given at L1, with only a very slight increase when first given at L4. When initiating administration at L1, NR greatly mitigated the BHB-mediated decline in longevity, however, NR did not increase BHB-mediated lifespan extension when first administered at L4.

Supplementation with nicotinamide riboside (NR), a form of vitamin B3 and a precursor of nicotinamide adenine dinucleotide (NAD+) extends lifespan in the nematode C. elegans and delays aging-related pathologies in mammals. During aging, levels of NAD+ decline causing metabolic dysfunction and oxidative damage. Studies in C. elegans found that when NR was administered during larval development it induced the mitochondrial unfolded protein response (UPRmt), which is frequently associated with lifespan extension. Both calorie restriction (CR) and ketogenic diets (KD) have been shown to extend lifespan, in part through increasing NAD+ and through increasing levels of the pro-longevity ketone body beta-hydroxybutyrate (BHB). In a previous study from my lab, NR increased C. elegans lifespan to a much larger extent when administered starting at the L1 larval stage as compared to when started at the L4 larval stage. Conversely, a high dose of BHB greatly increased lifespan when administered starting at the L4 stage. But this same dose decreased lifespan when it was first administered at the L1 stage. I further found that NR greatly extended lifespan when only administered during larval development and that the combination of both individual pro-longevity NR and BHB treatments significantly decreased lifespan. These chemical epistasis experiments suggest that NR and BHB function in parallel pathways to extend C. elegans lifespan through a common downstream target with hormesis playing a role. Therefore, human subjects who supplement with both NAD+ precursors and ketone esters should be aware of possible negative interactions when high doses of both are administered.

We now report an in depth analysis of the successful in vitro enzymatic synthesis of PHB utilizing the three-enzyme system from the bacteria Cupriavidus necator. Using HPLC methodology developed in this laboratory, and by adding each enzyme in a step-wise manner, we follow each individual stage in the three-enzyme route for PHB synthesis and delineate all stoichiometric relationships. We report the construction of the first metabolic model developed specifically for analyzing in vitro enzymatic PHB synthesis. We developed a hands-on student laboratory for culturing, producing, isolating, and purifying the bacterial biopolyesters PHB. We now report the first structural characterizations of iso-CoA, acetyl-iso-CoA, acetoacetyl-iso-CoA, and beta-hydroxybutyryl-iso-CoA using MS, MS/MS, and homo- and hetero-nuclear NMR analyses.We describe HPLC methodology to separate the isomers of several iso-CoA-containing compounds and report the first examples of iso-CoA-containing compounds acting as substrates in enzymatic acyl-transfer reactions. We describe a simple regioselective synthesis of iso-CoA from CoA. We also demonstrate a plausible mechanism, which accounts for the existence of iso-CoA isomers in commercial preparations of CoA-containing compounds. Herein we report that phenylaminoethyl selenide compounds protect DNA from peroxynitrite-mediated single-strand breaks. The mechanism of protection against peroxynitrite mediated DNA damage was investigated by HPLC. The chemistry of the reaction between peroxynitrite and HOMePAES was investigated using HPLC and HPLC/MS. The unique chemistry of the reaction between peroxynitrite and HOMePAES was investigated using HPLC and HPLC/MS. We report the development of novel CDB derivatives, which are selective COX-II inhibitors. A series of compounds were assayed with an in vitro colorimetric inhibitor screening and with a whole blood ELISA screening and the results indicate that MST is a selective inhibitor of COX-II.