O objetivo do estudo foi avaliar o estado nutricional, ingestão alimentar, perfis lipídico e glicêmico além de marcadores inflamatórios de pacientes com Imunodeficiências Primárias (IDPs) e descrever possíveis distúrbios metabólicos associados. Estudo descritivo transversal, realizado com 24 pacientes imunodeficientes (10 Doença Granulomatosa Crônica - DGC; 6 Ataxia-Telangiectasia - AT; 5 Agamaglobulinemia - A; 3 Hiper IgM - HIgM) entre 20 meses a 18 anos acompanhados no ambulatório de Alergia e Imunologia do Instituto da Criança - HCFMUSP, São Paulo, Brasil. Foram realizadas avaliações bioquímicas, antropométricas e dietéticas, longe de processos infecciosos, incluindo peso, altura, Dobra Cutânea Tricipital (DCT), Circunferência Muscular do Braço (CMB) e Circunferência do Braço (CB) (software WHO Antro e WHO Antro Plus e classificados por Frisancho). Para a avaliação do consumo alimentar utilizou-se Recordatório 24h e Registro alimentar de 3 dias (software Virtual - Nutri Plus e Dietary Reference Intakes). A desnutrição ocorreu em 39,2%, 69,5%, 47,9% e 43,5% quando analisadas por Índice de Massa Corporal, CMB, CB, DCT respectivamente, observando-se maior prevalência nos pacientes com DGC e AT. 22 pacientes apresentaram alguma dislipidemia, sendo HDL baixo o mais prevalente. Consumo energético abaixo do recomendado ocorreu em 33,3% dos pacientes enquanto valores inadequados para micronutrientes como Vitamina C, E, Cálcio e Zinco em 41,7%, 70,8%, 62,5% e 41,6% respectivamente; o ácido graxo saturado se mostrou acima do recomendado em metade dos pacientes. O estudo concluiu que todos os grupos de IDPs avaliados apresentaram algum grau de comprometimento nutricional, metabólico ou dietético. Novos estudos de intervenção nutricional em pacientes com imunodeficiências primárias podem determinar uma conduta nutricional individualizada para estes pacientes nos diferentes tipos de imunodeficiência primária / Objective: To evaluate the nutritional status, feeding, lipid and glycemic profile and inflammatory markers of Primary Immunodeficiency (PIDs) patients and describe possible metabolic disorders associated. Methods: This is a crosssectional studies performed with 24 immunodeficiency patients (10-Chronic Granulomatous Disease -CGD; 6- Ataxia-Telangienctasia -AT; 5- Agammaglobulinemia-A; 3-Hyper IgM -HIgM) under 20 months and 18 ages followed at the Children Institute, Allergy and Immunology Unit - HCFMUSP. Biochemical, anthropometric and dietary evaluation were performed out of infectious processes, including weight, body height, Triciptal Skinfold (TSF), Arm Circumference (AC) and Arm Muscle Circumference (AMC) (software WHO Antro and WHO Antroplus and classified according Frisancho). To evaluate the feeding consumption it was used a 24 hours Record and a 3-Day Feeding Record (Software Virtual-Nutri Plus and DRIs). Results: Malnutrition occurred in 39.2%, 69.5%, 47.9% and 43.5% respectively when was analyzed by Body Mass Index (BMI), AMC, AC and TSF being a higher prevalence detected in DGC and AT patients. 22 patients presented some dyslipidemia with higher prevalence to low HDL. Dietary analysis demonstrated that 33.3% of patients were under recommended energy consumption. Regarding micronutrients 41.7%, 70.8%, 62.5% and 41.6% were inappropriate to Vitamin C, Vitamin E, Calcium and Zinc respectively; saturated fatty acids were above recommended levels in 50% of the patients. Conclusions: All types of PIDs assessed had some degree of nutritional, metabolic or food intake disturbances. New studies of nutritional intervention in patients with primary immunodeficiency can determine an individualized nutritional intervention for these patients in different types of primary immunodeficiency

O cupuaçu (Theobroma grandiflorum Willd. Ex Spreng. K. Shum) é um fruto nativo brasileiro com boa palatabilidade e grande potencial agroeconômico. Suas sementes são usadas no preparo de um produto similar ao chocolate de cacau (Theobroma cacao L.), conhecido como cupulate®. Os benefícios do cacau à saúde cardiovascular são amplamente descritos. A proximidade filogenética entre cacau e cupuaçu sugere que este último poderia ter efeitos biológicos semelhantes. Entretanto não há estudos que avaliaram a influência do líquor de cupuaçu em doenças metabólicas. Aqui, nós comparamos a composição centesimal e mineral, os conteúdos de compostos fenólicos totais, proantocianidinas, flavonóides e a capacidade antioxidante in vitro dos líquores de cupuaçu e cacau. As composições, centesimal e mineral, de ambos foram semelhantes. Todos os outros parâmetros foram significativamente maiores no líquor de cacau, contudo, o perfil de flavonóides foi muito distinto. No cupuaçu predominaram os flavonóides derivados de quercetina enquanto que no cacau, as proantocianidinas corresponderam à maior classe de compostos fenólicos. Foram estudados os efeitos dos extratos fenólicos dos líquores de cupuaçu e cacau na atividade das enzimas α-amilase e glicosidase. As inibições das atividades enzimáticas foram semelhantes às relatadas na literatura para outras frutas. A fim de investigar a influência dos líquores de cupuaçu e cacau em algumas disfunções metabólicas, nós estudamos o efeito desses líquores em um modelo de ratos com diabetes induzida por estreptozotocina e em ratos alimentados com ração hiperlipídica (HL). A administração oral dos líquores nas doses de 3,6 e 7,2 g/kg de peso corpóreo a ratos diabéticos melhorou significativamente as atividades das enzimas antioxidantes, perfil lipídico e peroxidação lipídica de maneira dose-dependente. Semelhantemente, os extratos fenólicos dos líquores nas doses 2,1 e 7,2 g/kg de peso corpóreo administrados a animais alimentados com ração hiperlipídica reparou o dano hepático devido à melhora da peroxidação lipídica, capacidade antioxidante plasmática e tecidual com relação dose-dependente. Além disso, a sensibilidade a glicose e insulina nos animais alimentados com ração (HL) foram aumentadas pelo tratamento com a maior dose do extrato fenólico do líquor de cupuaçu. Embora o líquor de cacau possua maior conteúdo de compostos fenólicos e atividade antioxidante in vitro comparado ao cupuaçu, este último mostrou-se mais efetivo na redução do dano causado pela diabetes e dieta hiperlipídica. Essas contradições podem ser explicadas pela diferente composição fenólica entre os dois líquores. A análise conjunta desses resultados sugere que o líquor de cupuaçu, assim como o cacau, poderia auxiliar no tratamento de distúrbios metabólicos associados com o estresse oxidativo. / Cupuassu (Theobroma grandiflorum Willd. Ex Spreng. K. Shum) is a native brazilian fruit with good flavor and great agroeconomic potential. Its seeds are used to prepare a cocoa (Theobroma cacao L.) chocolate-like, known as cupulate®. The cocoa beneficial properties to cardiovascular health have been extensively described. Despite the phylogenetic similarity between cocoa and cupuassu suggests that the later could promote the same biological effects, no study has attempted to examine the role of cupuassu liquor on metabolic disorders. Here, we compared the centesimal and mineral composition, contents of total phenolic compounds, proanthocyanidins, flavonoids and in vitro antioxidant capacity of cupuassu and cocoa liquors. Centesimal and mineral compositions of both were similar. All the other parameters were significantly higher in cocoa liquor. However, flavonoids profile was quite different, where quercetin derivatives predominated in cupuassu whereas in cocoa, the proanthocyanidins corresponded to the major class of phenolic compounds. Studies were undertaken to determine the effect of phenolic extracts on α-amylase and glucosidase activities. The enzymatic activities inhibitions were close to that previously related to other fruits. To further investigate the role of cupuassu and cocoa liquors on metabolic disturbs, we assessed the effect of these liquors in streptozotocin-induced diabetic and high-fat diet (HFD) rats. Oral administrations of liquors at doses 3.6 and 7.2 g/kg body weight to diabetic rats improved significantly antioxidant enzymes activities, lipid profile and peroxidation in dose-dependent manner. Similarly, liquors phenolic extracts at doses 2.1 and 7.2 g/kg body weight administrated to HFD animals repaired the liver damage by ameliorating lipid peroxidation, plasma and tissue antioxidant capacities in dose dependence. Indeed, HFD animal sensitivity for glucose and insulin was markedly augmented in animals treated with the highest dose of phenolic extract of cupuassu. Although cocoa has higher content of phenolic compounds and in vitro antioxidant potential activity than cupuassu, the later showed more effectively in reducing the damage in animal models of diabetes and high-fat diet. These contradictions could be explained due to differences in phenolic composition in cupuassu and cocoa liquors. Taken together, these results suggest the cupuassu liquor, as well as cocoa liquor, could help in treatment of metabolic diseases associated with oxidative stress.

O objetivo do estudo foi avaliar o estado nutricional, ingestão alimentar, perfis lipídico e glicêmico além de marcadores inflamatórios de pacientes com Imunodeficiências Primárias (IDPs) e descrever possíveis distúrbios metabólicos associados. Estudo descritivo transversal, realizado com 24 pacientes imunodeficientes (10 Doença Granulomatosa Crônica - DGC; 6 Ataxia-Telangiectasia - AT; 5 Agamaglobulinemia - A; 3 Hiper IgM - HIgM) entre 20 meses a 18 anos acompanhados no ambulatório de Alergia e Imunologia do Instituto da Criança - HCFMUSP, São Paulo, Brasil. Foram realizadas avaliações bioquímicas, antropométricas e dietéticas, longe de processos infecciosos, incluindo peso, altura, Dobra Cutânea Tricipital (DCT), Circunferência Muscular do Braço (CMB) e Circunferência do Braço (CB) (software WHO Antro e WHO Antro Plus e classificados por Frisancho). Para a avaliação do consumo alimentar utilizou-se Recordatório 24h e Registro alimentar de 3 dias (software Virtual - Nutri Plus e Dietary Reference Intakes). A desnutrição ocorreu em 39,2%, 69,5%, 47,9% e 43,5% quando analisadas por Índice de Massa Corporal, CMB, CB, DCT respectivamente, observando-se maior prevalência nos pacientes com DGC e AT. 22 pacientes apresentaram alguma dislipidemia, sendo HDL baixo o mais prevalente. Consumo energético abaixo do recomendado ocorreu em 33,3% dos pacientes enquanto valores inadequados para micronutrientes como Vitamina C, E, Cálcio e Zinco em 41,7%, 70,8%, 62,5% e 41,6% respectivamente; o ácido graxo saturado se mostrou acima do recomendado em metade dos pacientes. O estudo concluiu que todos os grupos de IDPs avaliados apresentaram algum grau de comprometimento nutricional, metabólico ou dietético. Novos estudos de intervenção nutricional em pacientes com imunodeficiências primárias podem determinar uma conduta nutricional individualizada para estes pacientes nos diferentes tipos de imunodeficiência primária / Objective: To evaluate the nutritional status, feeding, lipid and glycemic profile and inflammatory markers of Primary Immunodeficiency (PIDs) patients and describe possible metabolic disorders associated. Methods: This is a crosssectional studies performed with 24 immunodeficiency patients (10-Chronic Granulomatous Disease -CGD; 6- Ataxia-Telangienctasia -AT; 5- Agammaglobulinemia-A; 3-Hyper IgM -HIgM) under 20 months and 18 ages followed at the Children Institute, Allergy and Immunology Unit - HCFMUSP. Biochemical, anthropometric and dietary evaluation were performed out of infectious processes, including weight, body height, Triciptal Skinfold (TSF), Arm Circumference (AC) and Arm Muscle Circumference (AMC) (software WHO Antro and WHO Antroplus and classified according Frisancho). To evaluate the feeding consumption it was used a 24 hours Record and a 3-Day Feeding Record (Software Virtual-Nutri Plus and DRIs). Results: Malnutrition occurred in 39.2%, 69.5%, 47.9% and 43.5% respectively when was analyzed by Body Mass Index (BMI), AMC, AC and TSF being a higher prevalence detected in DGC and AT patients. 22 patients presented some dyslipidemia with higher prevalence to low HDL. Dietary analysis demonstrated that 33.3% of patients were under recommended energy consumption. Regarding micronutrients 41.7%, 70.8%, 62.5% and 41.6% were inappropriate to Vitamin C, Vitamin E, Calcium and Zinc respectively; saturated fatty acids were above recommended levels in 50% of the patients. Conclusions: All types of PIDs assessed had some degree of nutritional, metabolic or food intake disturbances. New studies of nutritional intervention in patients with primary immunodeficiency can determine an individualized nutritional intervention for these patients in different types of primary immunodeficiency

Thesis (Ph. D.)--University of California, San Diego and San Diego State University, 2007. / Title from first page of PDF file (viewed January 8, 2008). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 75-84).

The aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, plays a crucial role in regulation of xenobiotic metabolism. AhR is also involved in dioxin-induced metabolic disorders and alteration of circadian rhythm. Furthermore, circadian clock disruption and metabolic dysfunction are integrally associated with each other. This study was designed to understand the mechanisms by which AhR contributes to regulation of circadian clocks, fat metabolism and glucose homeostasis. In the first aim, I have tested whether AhR interacts with the core clock gene, brain and muscle AhR nuclear translocator like-1(BMAL1), disrupting circadian locomotor output cycle kaput (CLOCK)/BMAL1 complex activity, and leading to the suppression of period1 gene (Per1) expression rhythm. My studies indicate that AhR activation by its agonists 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and beta-naphoflavone (BNF) disrupts the rhythm and inhibits the expression of Per1 in mouse liver and hepatoma cell lines, respectively. Mechanistically, the disruption of the rhythm and the inhibition of Per1 expression occur secondary to the interaction between AhR and BMAL1, which attenuates transcriptional activity of the core clock complex CLOCK/BMAL1. These results suggest alteration of the circadian clock as a novel signaling event downstream of AhR activation. The integral relationship between the clock and metabolic function further suggest that AhR activation may cause metabolic dysfunction. In the second aim, I have tested whether AhR activation inhibits Per1 gene induction and influences circadian clock resetting through activation of JNK pathway. AhR activation by it agonists TCDD and BNF decreases light-induced phase shifts in the early night and inhibits light-induced Per1 expression in both suprachiasmatic nucleus (SCN) and liver. Inhibition of Per1 induction results from increased phospho-JNK induced by AhR activation. Taken together, activation of AhR disrupts circadian clock resetting which also could cause metabolic dysfunction. In the third aim, I have tested whether AhR deficiency regulates nuclear receptor peroxisome proliferator-activated receptor a; (PPARa) and alters glucose homeostasis. PPARa, a clock-controlled gene (CCG) that acts as a fat metabolism sensor, is important for lipid metabolism and glucose homeostasis. AhR knockout (AhRKO or AhR-/-) mice exhibit enhanced insulin sensitivity and glucose tolerance, accompanied by decreased expression of PPARa, key gluconeogenic genes, glucose-6 phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) and key fatty acid oxidation enzymes, carnitine palmitoyl transferase1b (CPT1b) and acyl-CoA oxidase (ACO). Conversely, AhR agonists increase PPARa; expression in a BMAL1-dependent manner. In addition, AhRKO mice display altered rhythm for clock genes, clock-controlled genes (CCGs) and physiological blood glucose. These data suggest that AhR may modulate the glucose homeostasis through regulation of CCGs such as PPARa and that PPARa may be an important link between the circadian clock and metabolism. In the fourth aim, I have tested the effects of AhR ablation or attenuation in high-fat diet (HFD)-induced obesity, insulin resistance and hepatic steatosis in mice. Recent studies suggest that PPARα expression is elevated with HFD feeding as an adaptive response to attenuate hepatic steatosis, and PPARa deficiency protects against HFD-induced insulin resistance. AhR-/- as well as AhR heterozygous (AhR+/-) mice are protected from the HFD-induced obesity, insulin resistance, hepatic steatosis and show reduced inflammatory cytokine expression. In addition, AhR-/- and AhR+/- mice display protected insulin signaling, a higher adiponectin and a lower leptin and insulin in serum. Food intake and physical activity are not significantly different among WT, AhR-/- and AhR+/- mice with HFD feeding. Indirect calorimetry has demonstrated that the AhR+/- mice have higher oxygen consumption, CO2 production and heat production. In addition, Real-time PCR data show that uncoupling protein 1(Ucp1) is higher in brown adipose tissue which supports the higher heat production; moreover, the muscle gene profile reveals that the fatty acid beta-oxidation genes and mitochondrial respiratory genes are higher in AHR+/- mice which further support higher energy expenditure in these mice. Collectively, these data suggest that AhR signaling could be a potential target for treatment of obesity and type 2 diabetes, and AhR antagonist may be developed into a drug for these metabolic diseases.

O cupuaçu (Theobroma grandiflorum Willd. Ex Spreng. K. Shum) é um fruto nativo brasileiro com boa palatabilidade e grande potencial agroeconômico. Suas sementes são usadas no preparo de um produto similar ao chocolate de cacau (Theobroma cacao L.), conhecido como cupulate®. Os benefícios do cacau à saúde cardiovascular são amplamente descritos. A proximidade filogenética entre cacau e cupuaçu sugere que este último poderia ter efeitos biológicos semelhantes. Entretanto não há estudos que avaliaram a influência do líquor de cupuaçu em doenças metabólicas. Aqui, nós comparamos a composição centesimal e mineral, os conteúdos de compostos fenólicos totais, proantocianidinas, flavonóides e a capacidade antioxidante in vitro dos líquores de cupuaçu e cacau. As composições, centesimal e mineral, de ambos foram semelhantes. Todos os outros parâmetros foram significativamente maiores no líquor de cacau, contudo, o perfil de flavonóides foi muito distinto. No cupuaçu predominaram os flavonóides derivados de quercetina enquanto que no cacau, as proantocianidinas corresponderam à maior classe de compostos fenólicos. Foram estudados os efeitos dos extratos fenólicos dos líquores de cupuaçu e cacau na atividade das enzimas α-amilase e glicosidase. As inibições das atividades enzimáticas foram semelhantes às relatadas na literatura para outras frutas. A fim de investigar a influência dos líquores de cupuaçu e cacau em algumas disfunções metabólicas, nós estudamos o efeito desses líquores em um modelo de ratos com diabetes induzida por estreptozotocina e em ratos alimentados com ração hiperlipídica (HL). A administração oral dos líquores nas doses de 3,6 e 7,2 g/kg de peso corpóreo a ratos diabéticos melhorou significativamente as atividades das enzimas antioxidantes, perfil lipídico e peroxidação lipídica de maneira dose-dependente. Semelhantemente, os extratos fenólicos dos líquores nas doses 2,1 e 7,2 g/kg de peso corpóreo administrados a animais alimentados com ração hiperlipídica reparou o dano hepático devido à melhora da peroxidação lipídica, capacidade antioxidante plasmática e tecidual com relação dose-dependente. Além disso, a sensibilidade a glicose e insulina nos animais alimentados com ração (HL) foram aumentadas pelo tratamento com a maior dose do extrato fenólico do líquor de cupuaçu. Embora o líquor de cacau possua maior conteúdo de compostos fenólicos e atividade antioxidante in vitro comparado ao cupuaçu, este último mostrou-se mais efetivo na redução do dano causado pela diabetes e dieta hiperlipídica. Essas contradições podem ser explicadas pela diferente composição fenólica entre os dois líquores. A análise conjunta desses resultados sugere que o líquor de cupuaçu, assim como o cacau, poderia auxiliar no tratamento de distúrbios metabólicos associados com o estresse oxidativo. / Cupuassu (Theobroma grandiflorum Willd. Ex Spreng. K. Shum) is a native brazilian fruit with good flavor and great agroeconomic potential. Its seeds are used to prepare a cocoa (Theobroma cacao L.) chocolate-like, known as cupulate®. The cocoa beneficial properties to cardiovascular health have been extensively described. Despite the phylogenetic similarity between cocoa and cupuassu suggests that the later could promote the same biological effects, no study has attempted to examine the role of cupuassu liquor on metabolic disorders. Here, we compared the centesimal and mineral composition, contents of total phenolic compounds, proanthocyanidins, flavonoids and in vitro antioxidant capacity of cupuassu and cocoa liquors. Centesimal and mineral compositions of both were similar. All the other parameters were significantly higher in cocoa liquor. However, flavonoids profile was quite different, where quercetin derivatives predominated in cupuassu whereas in cocoa, the proanthocyanidins corresponded to the major class of phenolic compounds. Studies were undertaken to determine the effect of phenolic extracts on α-amylase and glucosidase activities. The enzymatic activities inhibitions were close to that previously related to other fruits. To further investigate the role of cupuassu and cocoa liquors on metabolic disturbs, we assessed the effect of these liquors in streptozotocin-induced diabetic and high-fat diet (HFD) rats. Oral administrations of liquors at doses 3.6 and 7.2 g/kg body weight to diabetic rats improved significantly antioxidant enzymes activities, lipid profile and peroxidation in dose-dependent manner. Similarly, liquors phenolic extracts at doses 2.1 and 7.2 g/kg body weight administrated to HFD animals repaired the liver damage by ameliorating lipid peroxidation, plasma and tissue antioxidant capacities in dose dependence. Indeed, HFD animal sensitivity for glucose and insulin was markedly augmented in animals treated with the highest dose of phenolic extract of cupuassu. Although cocoa has higher content of phenolic compounds and in vitro antioxidant potential activity than cupuassu, the later showed more effectively in reducing the damage in animal models of diabetes and high-fat diet. These contradictions could be explained due to differences in phenolic composition in cupuassu and cocoa liquors. Taken together, these results suggest the cupuassu liquor, as well as cocoa liquor, could help in treatment of metabolic diseases associated with oxidative stress.

O objetivo deste estudo foi avaliar a ocorrência de diarreia e suas consequências no metabolismo animal em bezerros consumindo concentrado inicial contendo coprodutos como polpa cítrica, melaço e xarope de glicose; ou bezerros suplementados com probiótico. Dois experimentos foram conduzidos para avaliar o efeito da substituição de milho por coprodutos. No primeiro experimento, 24 bezerros com idade média de 2 semanas, foram distribuídos em 3 tratamentos e receberam concentrado inicial contendo doses crescentes de polpa cítrica em substituição ao milho. No segundo experimento, 32 bezerros foram divididos em 4 tratamentos, recebendo concentrado inicial contendo xarope de glicose e doses crescentes de melaço em substituição ao milho. Em ambos os experimentos, os animais foram alojados em abrigos individuais, receberam 4 L de sucedâneo lácteo por dia, dividido em duas refeições e tiveram livre acesso à água e concentrado. Após o diagnóstico da ocorrência de diarreia, foram realizadas avaliações de escore fecal, escore clínico, além de medição dos parâmetros fisiológicos, nas seguintes 24, 48 e 72 horas. Foram colhidas amostras de sangue para realização de hemograma, análises bioquímicas, análises gasométricas e eletrolíticas. A adição de coprodutos no concentrado inicial não afetou (P>0,05) o escore fecal, as características das fezes e os sinais clínicos dos animais diarreicos. As análises plasmáticas bioquímicas (glicose, proteínas totais, albumina, ?-hidroxibutirato, nitrogênio ureico plasmático, lactato total, D- e L-lactato) apresentaram valores normais e não sofreram efeito negativo (P>0,05) em resposta da substituição de milho por coprodutos no concentrado. Não houve diferença entre os tratamentos (P>0,05) nas análises gasométricas e no eritrograma, com resultados indicando ausência ou baixo nível de acidose metabólica e desidratação nos animais. De acordo com o leucograma realizado, foi constatada leucocitose e neutrofilia na maioria dos casos, significando que a diarreia foi de origem infecciosa, descartando a possibilidade que o consumo de coprodutos no concentrado fosse a etiologia da diarreia. Um terceiro experimento foi realizado para avaliar o desempenho geral de bezerros suplementados com probíóticos contendo bactérias ruminais. Foram utilizados 20 bezerros divididos em 2 tratamentos (controle e fornecimento oral de 2 gramas de probiótico/dia), sendo os animais avaliados até a 10ª semana de vida. Os animais alojados em abrigos individuais, receberam 6 L de sucedâneo lácteo por dia, e tiveram livre acesso à água e concentrado. O desaleitamento foi realizado na 6ª semana de vida, de forma a causar uma situação de estresse nos animais. O consumo diário de concentrado, ganho de peso, desenvolvimento corporal e escore fecal foram avaliados. Nas semanas 2, 4, 6, 8 e 10 foram colhidas amostras de sangue para determinação de parâmetros bioquímicos e realização do hemograma. O fornecimento de probióticos via oral não afetou (P>0,05) o escore fecal, o desempenho dos animais (ganho de peso e consumo de concentrado). Como conclusão, a substituição de milho por polpa cítrica, melaço ou xarope de glicose no concentrado inicial não apresentou efeitos negativos relacionados à diarreia e não agravou os quadros de desidratação e acidose metabólica. O fornecimento de 2 gramas diários de probióticos de bactérias ruminais não resultou em melhorias no desempenho de bezerros desaleitados precocemente. / The objective of this study was to evaluate the occurrence of diarrhea and the consequences on animal metabolism of calves consuming starter feed containing coproducts such as citrus pulp, molasses and glucose syrup; or calves supplemented with direct-fed microbial (DFM). Two trials were performed to evaluate the effect of replacing corn by coproducts. In the first trial, 24 calves were divided into three treatments, and received starter feed containing increasing doses of citrus pulp replacing corn. In the second trial, 32 calves were divided into four treatments, and received starter feed containing glucose syrup and increasing doses of molasses replacing corn. In both experiments, animals were housed in individual hutches, received 4 L/d of milk replacer, divided into two meals and had free access to water and starter feed. After the diagnosis of the occurrence of diarrhea fecal score, clinical score, and the measurement of physiological parameters were evaluated during the following 24, 48 and 72 hours.Blood samples were taken for complete blood count (CBC), biochemical, electrolytes and gases analysis. The addition of coproducts in the starter feed had no effect (P>0.05) on fecal score, characteristics of the faeces and clinical signs of diarrheic animals. The plasma biochemical analysis (glucose, total protein, albumin, ?-hydroxybutyrate, urea nitrogen, lactate total D-and L-lactate) showed normal values and were negativelly affected (P>0.05) in response to the substitution of corn by coproducts in the stater feed for calves. No alterations (P>0.05) were noted in the erythrocyte and blood gases results, suggesting absence or low level of dehydration, and metabolic acidosis in animals. According to the white blood cell count (WBC), leukocytosis and neutrophilia were observed in most cases, suggesting infectious diarrhea and rejecting the possibility that the consumption of coproducts in the starter feed were the etiology of diarrhea cases. A third trial was performed to evaluate the overall performance of dairy calves supplemented with a probiotic containg ruminal bacterias. Twenty calves divided into two treatments (control and oral and daily supply of 2 grams of probiotic), animals were evaluated up to 10 weeks of age. Animals were housed in individual hutches, received 6 L/d of milk replacer, and had free access to water and starter feed. Weaning was done at the 6th week of age, as a meaning of causing stress in animals. Daily starter feed intake, weight gain, body development, and fecal score were evaluated. At 2nd, 4th, 6th, 8th and 10th weeks, blood samples were collected for biochemical analysis and WBC. The oral supply of probiotic had no effect (P>0.05) on fecal score or animal performance (weight gain and starter feed intake). In conclusion, the substitution of corn by citrus pulp, molasses or glucose syrup in the starter feed for dairy calves had no negative effects related to diarrhea or the agravation of dehydration and metabolic acidosis. The oral and daily supply of 2 grams of probiotics containg ruminal bacteria resulted in no improvements in performance of early-weaned dairy calves.

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.

In Europa leiden etwa 120 Millionen aller 18- bis 80-jährigen an einer Hörbehinderung (16% Prävalenz). Die altersassoziierte Innenohrschwerhörigkeit (Age related hearing impairment, ARHI) hat damit Anschluss gefunden an die großen Volkskrankheiten: Ischämische Herzerkrankungen (5,9 %), Demenz (5,8 %), Diabetes mellitus und Cerebralen Erkrankungen (je 5,5 %). Der erste Teil der Arbeit befasst sich mit der Theorie des Hörens und seinen Störungen, der cochleären Durchblutung, den metabolischen Risikofaktoren, der Molekularbiologie und Epigenetik des Innenohres. Obwohl in der Literatur weitgehend Konsens über den Einfluss exogener Faktoren auf ARHI herrscht, wie Diabetes mellitus, Herz-Kreislauferkrankungen (Framingham Studie und CVD), Hypertonie, Rauchen, Body mass index (BMI) und genderspezifische hormonelle Einflüsse, gibt es kaum HNO-ärztliche Studien dazu. Der zweite Teil geht in einer Praxis-Fallstudie an 202 Patienten folgenden Fragen nach: 1. Gibt es zwischen metabolischen Erkrankungen, wie Adipositas, Störungen des Fett- und Glucosestoffwechsels, der Hypertonie und der Zunahme von Innenohrschwerhörigkeiten im Erwachsenenalter klinische Zusammenhänge? 2. Könnte eine erste Ohrsymptomatik Prädikator einer okkulten pathologischen Stoffwechselveränderung sein? 3. Gibt es Möglichkeiten einer Prävention? Im Ergebnis zeigten sich bei Patienten mit ARHI im Verhältnis Männer/Frauen: Störung des Glukosestoffwechsels bei 97 %/84 %, Lipidstoffwechselstörungen bei 76 %/85 %, eine Homocysteinämien bei 70 %/62 %, ein Anstieg des Plasminogen-Aktivator-Inhibitors (PAI) bei 65 %/38 % und eine Harnsäureerhöhung bei 48 %/15 %. Auch bei ersten Ohrsymptomen (Ohrdruck, Tinnitus, einzelne Frequenzsenken) fanden sich in jedem einzelnen Fall metabolische Veränderungen, die entweder allein oder in unterschiedlichen Kombinationen vorlagen. Männern mit metabolisch initiierten KHK-Erkrankung haben als Prädikator häufig eine erektile Dysfunktion. Erste auditorische Symptomen könnten Prädikator okkulter metabolischer Störungen bei Männern und Frauen sein. Anamnestisch unklare Innenohrprobleme sollten daher auf Stoffwechselstörungen untersucht werden, da diese Risikofaktoren darstellen, die leitlinienbasiert zu therapieren sind. Eine Prognose ist in keinem Einzelfall möglich, da die Folgen auf die molekularbiologischen Prozesse im Innenohres individuell nicht erkennbar sind. Doch sahen wir bei einigen Patienten deutliche Verbesserungen der Symptome und einen Hörschwellenanstieg. Andere Patienten zeigten innerhalb des Beobachtungszeitraums keine Änderung der audiogenen Symptomatik. Behandlungen über einen längeren Zeitraum an einer größeren Fallzahl wären daher sinnvoll. Die Ergebnisse könnten als erste sekundärpräventive Behandlung betrachtet werden, die im Einzelfall eine Hörgeräteversorgung entbehrlich machte. Sie stellen einen Beitrag zu Pfisters Empfehlung dar, mit den vorhandenen Erkenntnissen exogener Risikomechanismen, dringend neue therapeutische Präventionsstrategien für die HNO-ärztliche Tätigkeit zu entwickeln, die die neurale und molekulare Basis anstelle der Symptome der Erkrankung fokussieren.

Altered glucose metabolism is the underlying factor in many metabolic disorders, including diabetes. A novel protein recently linked to diabetes through animal and clinical studies is Sarcolemmal Membrane Associated Protein (SLMAP) but its role in metabolism remains undefined. The data here reveals a novel role for SLMAP isoform1 in glucose metabolism within the myocardium. Neonatal cardiomyocytes (NCMs) harvested from hearts of transgenic mice expressing SLMAP1, presented with increased glucose uptake, glycolytic rate, as well as glucose transporter 4 (GLUT4) expressions with minimal impact on lipid metabolism. SLMAP1 expression markedly increased the machinery required for endosomal trafficking of GLUT4 to the membrane within NCMs, accounting for the observed effects on glucose metabolism. The data here indicates SLMAP1 as a unique regulator of glucose metabolism through endosomal regulation of GLUT4 trafficking and suggests it may uniquely serve as a target to limit cardiovascular disease in metabolic disorders such as diabetes.