The purpose of this investigation was to determine the effects of post pubertal caloric restriction on bone architecture, strength, and medullary adipose quantity. A randomized control comparison design was utilized and the study was conducted in a laboratory setting. All procedures were approved by the Institutional Animal Care and Use Committee (IACUC) at Temple University (protocol number 3396). Female Sprague Dawley rats (23days-of-age, n=120) were randomly assigned into seven groups, baseline (BL) (n=18), control (C) (n=17), caloric restriction (FR) (n=17), control recovery (RC) (n=17), caloric restriction recovery (RFR) (n=17), control ovariectomy (COVX) (n=17) and food restricted ovariectomy (FROVX) (n=17). On day 65, a 6 week 30% caloric restriction protocol was administered. Following food restriction, a subset of the control and food restricted groups were sacrificed (n=34) and the remaining animals (n=68) control recovery (RC) and food restricted recovery (RFR) groups had a 10 week recovery with ad lib food. Recovery groups, RC and RFR: were sacrificed after the 10 week recovery period at 183 days of age (n=34). The remaining animals were ovariectomized (OVX) and grouped into control ovariectomy (COVX) and food restricted ovariectomy (FROVX). Six weeks post OVX the animals were sacrificed at 270 days of age. After sacrifice blood was taken by cardiac puncture, bones were harvested, cleaned of soft tissue, fixed and prepared for analysis. Anthropometric measurements were taken including retroperitineal and gonadal fat pad weights as well as adrenal glands, ovaries, uteri, and tricep surae muscle group weights. Main Outcome Measures: The outcome variables for this study were bone mechanical competence, trabecular and cortical bone mass and architecture, marrow adipocyte number as well as serum markers of bone formation and resorption. Insulin - like growth factor - 1 (IGF-1) and C- terminal telopeptide (CTX) was measured to determine bone formation and resorption. Statistical Analysis: One-way Analysis of Variance (ANOVA) was performed to determine differences between all groups. Tukey's honestly significant difference (HSD) post hoc analysis was conducted to determine differences between groups. Student's t - tests were used to detect differences between age groups (acute, recovery, post-OVX) A p value was set at less than or equal to 0.05 for all statistical tests. All statistical analysis was performed using (GraphPad Prism version 5.00 for Windows, GraphPad Software, San Diego California USA). Variables were normalized with a linear regression-based correction using body weight. All variables with an R2 level greater than 0 were normalized to avoid choosing an arbitrary R2 value as a cut-off for normalization. Results: Body weight was 18% lower than control animals following caloric restriction. Weight loss was due to fat mass predominately; muscle mass was maintained relative to body weight. Bone length and growth rates were diminished however no differences were found following refeeding. No differences were found in bone strength at any time point. However relative to body weight peak moment and stiffness were significantly higher following caloric restriction. Cortical bones mass and cross sectional moment of inertia were enhanced in the femoral diaphysis with bone mass greater post OVX in the calorically restricted group (FR-OVX). No significant differences were found in ash percent in the femur was found between any groups at any time point however vertebral bone mineral density in acute FR and post OVX time points in FROVX was significantly greater indicating an enhanced bone quality in the restricted. No change in trabecular quantity or quality were observed in the distal femur between groups however vertebral trabecular architecture was enhanced in number and thickness in acute FR and post OVX time points in FROVX. No significant difference in number of marrow adipocytes were found at any time point. Serum CTX decreased significantly in acute in FR and increased at recovery in RFR and post OVX in FROVX. Serum IGF - 1 decreased in the acute FR with IGF - 1 significantly greater after recovery in RFR. Conclusions: Evidence was found to suggest that moderate caloric restriction (nutrient replete) post puberty was positive for bone. Bone quantity was increased with relative cortical area and bone area relative to body weight increased in the FR group. Significant increases in FROVX bone quantity post OVX suggests that bone mass gains during caloric restriction attenuated cortical bone loss at maturity post OVX. Bone quality increases in cross sectional moment of inertia relative to body weight may have accounted for the transient increase in FR bone strength in the femur. Decreases in acute CTX and IGF- 1 levels indicates that bone formation and resorption were decreased during development that may have been the mechanism for bone loss attenuated post OVX in calorically restricted. Growth rate slowing during caloric restriction may have decreased the rate of formation and resorption during a crucial time of peak bone mass accrual and bone modeling. This decrease in one modeling may have been mechanism that preserved bone quantity during acute caloric restriction. Increases in femur quality in polar moment of inertia coupled with a decrease in bone length changed the shape of the bone making it more robust. A shorter bone with a thicker cortex with no change in mineral content may have been the mechanism in the transient increase in bone strength in the femur. Quality changes in mineral density in vertebrae acting as a mineral storage back up as a last resort if quantity and quality changes were not sufficient in maintain bone strength. Moderate caloric restriction transiently increased strength, by increasing bone mass relative to body, altering bone geometry and increased vertebral mineral density. / Kinesiology

The effects of two hypocaloric diets on body weight (BW), percent body fat (%BF), lean body mass (LBM) and static muscular endurance were studied in college aged experienced male weightlifters for 7 days. Nineteen (X age = 20.6) volunteers were randomly assigned to one of three groups: control (n=5), High Protein/Moderate Carbohydrate - HP/MC (n=7) or Moderate Protein/High Carbohydrate - MP/HC (n=7). The two hypocaloric groups consumed 18 kcal/kg body weight for 7 days. The HP/MC group's diet contained 1.6 g/kg body weight/day of protein while the MP/HC group consumed 0.8 g/kg body weight/day of protein. Fat content of both diets was approximately equal so that carbohydrate content varied inversely with protein content. The control group was asked to follow a weight maintenance diet. All groups followed a similar supervised weight training regimen approximately 2 hours per day, six of the seven days of the study. Analysis of variance revealed that weight loss for the control group was not significant over the seven day experiment but that the two experimental groups showed a similar significant decrease in body weight of 3.6 kg for the HP/MC group and 4.0 kg for the MP/HC group. %BF of all subjects was significantly lower over the 7 day study using both skinfold measurements and hydrostatic weighing but there was no significant difference between the groups. LBM losses calculated from skinfold measurements were seen over time for all subjects and a significant interaction showed the 2 experimental groups to lose significantly more LBM over the 7 day study. LBM determined from hydrostatic weighing produced losses as well, but no differences were noted between the groups. All groups experienced quadricep endurance decrements over the 7 day study, but did not differ from each other. No significant changes were found for bicep endurance. It was concluded that neither the HP/MC diet nor the MP/HC diet was effective for maintaining LBM or quadricep endurance. However, both diets did produce significant losses in BW and %BF over the week long study. / M.S.

Twelve obese young women (aged 22-36) were studied to determine the·effects of the combination of an exercise program with either a high carbohydrate (HC) hypocaloric diet or low carbohydrate (LC) hypocaloric diet on total cholesterol, high density lipoprotein (HDL) cholesterol and triglycerides. Subjects were randomly placed in one of the diet groups (530 kcal/day) and participated in submaximal (60% VO₂ max) exercise sessions three times per week for a period of 28 days. After the treatment period, the subjects consumed a 1000 kcal/day mixed diet for one week while continuing the exercise program. Blood samples were drawn weekly for the analysis of total cholesterol, HDL cholesterol and triglycerides. Weight significantly decreased in both groups (mean decrease = 9.8% for LC; 8.8% for HC). After week one of the diet, total cholesterol and HDL cholesterol decreased significantly throughout the rest of the study. Due to the changes in total cholesterol, the total cholesterol/HDL cholesterol ratio decreased throughout the study, reaching significance by the post-treatment period when the ratio was 20.6% below baseline levels for both groups. There were no significant changes in triglycerides for either group. However, triglycerides increased throughout the dietary treatment (mean increase 9.5% for LC; 18.7% for HC). Triglyceride concentrations also changed during the post-treatment week as the LC group had a mean decrease of 38.3% and HC group, 8.2% from baseline values. These data suggest that both diets are equally effective in reducing body weight in young women. Also, in spite of the decreases noted in HDL cholesterol in both groups, total cholesterol decreased even further, thus producing a lower, more favorable total cholesterol/HDL cholesterol ratio. / Master of Science

Capillary electrophoresis mass spectrometry (CE-MS) is a versatile instrumental method for metabolomics, which allows for comprehensive metabolite profiling of volume-limited biological specimens in order to better understand the molecular mechanisms associated with chronic diseases, including an alarming epidemic of obesity worldwide. Multiplexed CE separations enable high-throughput metabolite screening with quality assurance to prevent false discoveries when combined with rigorous method validation, robust experimental designs, complementary statistical methods, and high-resolution tandem mass spectrometry (MS/MS) for unknown metabolite identification. In this thesis, multiplexed CE-MS technology is applied for both targeted and untargeted metabolite profiling of various biological fluids, including covalently bound thiol-protein conjugates, as well as free circulating metabolites in serum and plasma, and excreted/bio-transformed compounds in urine due to complex host-gut microflora co-metabolism. This work was applied to characterize aberrant metabolic responses of obese subjects in response to dietary challenges, and measure the benefits of dietary interventions that reduce adiposity without deleterious muscle loss. Chapter 2 presents, a simple, sensitive yet robust analytical protocol to expand metabolome coverage in CE-MS for the discovery of labile protein thiols in human plasma using a rapid chemical derivatization method based on N-tert-butylmaleimide (NTBM). Chapter 3 describes targeted metabolite profiling of serum and plasma to investigate the differential metabolic responses between healthy and unhealthy obese individuals before and after consumption of a standardized high-caloric meal, respectively. Chapter 4 of this thesis describes an untargeted metabolite profiling strategy for urine using multisegment-injection (MSI)-CE-MS for elucidating the effects of protein supplementation following a short-term dietary weight-loss intervention study. This work revealed six urinary metabolites that were classified as top-ranking treatment response biomarkers useful for discriminating between subjects consuming carbohydrate (control), soy, and whey supplemented diets. In summary, this thesis demonstrated the successful implementation of multiplexed CE-MS technology for biomarker discovery in nutritional-based metabolomic studies as required for more effective treatment and prevention of obesity for innovations in public health. / Thesis / Doctor of Philosophy (PhD)

The null hypothesis for this study was there were no differences in caloric intake, cholesterol, and sodium intakes of food prepared at home as contrasted with food prepared outside of the home when consumed by men 45-54 years old. The three dietary intakes have been associated with medical conditions that cause death in humans. This study provided information which could enable nutrition educators, foodservice managers, and men aged 45-54 who are employed at a factory to understand how consumption of these three intakes differs when foods were prepared at home as contrasted with outside of the home. Therefore, this study provided information to help lower the risk factors of heart diseases, hypertension, and obesity which are associated with caloric intake, cholesterol and sodium consumption.Participants completed three days of food frequencies and dietary records. The Sign Test was used to analyze the differences between food prepared at homeand outside of the home for caloric, cholesterol, and sodium intakes.Statistical analysis of the data revealed:(1) A significant difference in caloric intake of food prepared at home as contrasted with food prepared outside of the home when consumed by men 45-54 years old (p < 0.05).(2) No significant difference in cholesterol intake of food prepared at home as contrasted with food prepared outside of the home when consumed by men 45-54 years old (p > 0.05).(3) No significant difference in sodium intake of food prepared at home as contrasted with food prepared outside of the home when consumed by men 45-54 years old (p > 0.05). / Department of Home Economics

Au cours du vieillissement, les artères cérébrales subissent des modifications structurelles et fonctionnelles, notamment au niveau des cellules musculaires lisses (CML). La CML a pour rôle de maintenir la réactivité vasculaire via une signalisation calcique qui fait intervenir différents acteurs pouvant ainsi réguler deux phénomènes : la contraction et la relaxation. Ces acteurs rassemblent, au sein d’une même cellule, des canaux (CCVD, RYR, IP3R), des pompes calciques (SERCA, PMCA, NCX, STIM/ORAI) et leurs régulateurs (PLB, FKBP12.6, TRPP2, SARAF, TRIC). La restriction calorique (RC), apparaît comme étant un facteur retardant le vieillissement et ses pathologies. Notre travail s’est donc fortement impliqué dans l’étude de la signalisation calcique de la CML, en se focalisant sur les altérations génomiques et fonctionnelles au cours du vieillissement des artères cérébrales chez la souris C57Bl6/j. Nous avons ainsi pu mettre en évidence une altération de la signalisation calcique qui passe en partie par une modulation des niveaux d’expressions génique et protéique des canaux et pompes calciques impliqués dans ce phénomène, et par une modification fonctionnelle en termes de signaux calciques et de contraction. Après 5 mois de régime RC, il a été mis en évidence un ralentissement des altérations de la signalisation calcique liées au vieillissement et une diminution de l’oxydation des CML. / During aging, cerebral arteries undergo structural and functional changes, particularly in smooth muscle cells (SMC). SMC is responsible for maintaining vascular reactivity via calcium signaling involving different actors and can regulate two phenomena: contraction and relaxation. These actors regroup channels (CCVD, RYR, IP3R) calcium pumps (SERCA, PMCA, NCX, STIM / ORAI) and their regulators (PLB, FKBP12.6, TRPP2, SARAF, TRIC). Caloric restriction (CR) appears as a factor in delaying aging and its pathologies. Our work is strongly involved in the study of calcium signaling in SMC, focusing on genomic and functional alterations during aging of cerebral arteries in mice C57BL6/J. We were able to demonstrate an altered calcium signaling, which is partly through modulation of gene and protein expression levels of calcium channels and pumps involved in this phenomenon, and a functional change in terms of calcium signals and contraction. After 5 months under RC, it was highlighted a slow calcium signaling alterations associated with aging and a decrease of SMC oxidation by SAMP8.

L’autophagie est un processus d’autodigestion dans lequel la cellule dégrade ses propres composants dans le but de maintenir l’homéostasie dans ses conditions basales. En absence de nutriments, l’autophagie est activée et favorise la survie cellulaire en fournissant des substrats énergétiques résistant aux conditions de stress. Autophagie et métabolisme communiquent à différents niveaux; une baisse en métabolites richement énergétiques, tels qu’en ATP et en NADH, est détectée par des senseurs cellulaires (AMPK et SIRT1 respectivement) et mène à l’activation de l’autophagie. Ici, nous définissons un niveau supplémentaire de régulation de l’autophagie induite par le jeûne. Dans ce travail, nous montrons que cette privation en nutriments est caractérisée par une diminution rapide de l’Acétyl CoA, intégrateur majeur de l’état nutritionnel au carrefour du catabolisme des graisses, des sucres et des protéines. La baisse en AcCoA s’accompagne de la réduction proportionnelle des niveaux généraux d’acétylation des protéines ainsi que par l’induction de l’autophagie. Les manipulations destinées à augmenter ou diminuer les niveaux cytosoliques d’AcCoA, ciblant soit la synthèse mitochondriale soit son transport dans le cytoplasme, résultent en la suppression ou l’induction de l’autophagie aussi bien dans les cultures cellulaires que dans les tissus de souris. La déplétion en AcCoA impacte directement l’activité des KATs utilisant l’AcCoA comme substrat pour l’acétylation protéique. Nous avont montré que cette baisse en AcCoA réduit spécifiquement l’activité de EP300; cette KAT est en effet nécessaire à la suppression de l’autophagie à des niveaux élevés d’AcCoA, se comportant ainsi comme le senseur des niveaux cytosoliques d’AcCoA. A son tour, EP300 contrôle l’autophagie en inhibant les protéines autophagiques clés. Dans l’ensemble, nos résultats illustrent les fonctions de l’AcCoA cytosolique comme régulateur métabolique central de l’autophagie, délimitant ainsi des stratégies pharmacologiques centrées sur l’AcCoA qui permettent la manipulation thérapeutique de l’autophagie. En effet, la privation en nutriments et la restriction calorique sont connues pour jouer un rôle positif sur la santé et la longévité en promouvant leurs effets. Néanmoins, les stratégies basées sur la restriction calorique sont difficilement applicables en clinique. Ici, nous proposons une nouvelle définition biochimique des Mimétiques de la Restriction Calorique, composés imitant l’effet positif du jeûne. Dans notre contexte, un MRC est un composé capable de réduire l’acétylation protéique par des mécanismes distincts mais convergents: premièrement, par diminution des niveaux d’AcCoA, deuxièmement par inhibition directe des KATs, et enfin, par activation des protéines déacétylases. Ces résultats de l’exécution d’un programme cellulaire conduisent finalement à des effets pro-santé liés à la restriction calorique incluant mais non limités à l’autophagie. / Autophagy is a self-digestion process in which cell degrades its own components in order to maintain homeostasis in basal conditions. In absence of nutrients, autophagy is activated and promotes cell survival by providing energetic substrates to sustain stressful condition. Autophagy and metabolism crosstalk at different levels; a drop in energy-rich metabolites, such as ATP and NADH, is detected by cellular sensors (AMPK and SIRT1 respectively) and leads to autophagy activation. Here, we define a further regulatory level of starvation-induced autophagy. In this work, we show that nutrient deprivation is characterized by a rapid depletion of Acetyl CoA, a major integrator of the nutritional status at the crossroads of fat, sugar, and protein catabolism.Decrease in AcCoA is accompanied by the commensurate reduction in overall protein acetylation levels as well as by autophagy induction. Manipulations designed to increase or reduce cytosolic levels of AcCoA, either targeting mitochondrial synthesis or its transport in the cytoplasm, resulted in the suppression or induction of autophagy both in cultured cells and in mice tissues. Depletion of AcCoA directly impacts on the activity of cellular KATs, which use AcCoA as substrate for acetylating proteins. We showed that a drop in AcCoA specifically reduces the activity of EP300; this KAT was indeed required for the suppression of autophagy by high AcCoA levels, thus behaving as the sensor of cytosolic AcCoA levels. In turn, EP300 controls autophagy by inhibiting key autophagic proteins. Altogether, our results indicate that cytosolic AcCoA functions as a central metabolic regulator of autophagy, thus delineating AcCoA-centered pharmacological strategies that allow for the therapeutic manipulation of autophagy. Indeed, nutrient deprivation and caloric restriction are known to play pro-healthy and longevity promoting effects. Nonetheless, CR-based strategies are hardly suitable in clinical settings. Here, we propose a new biochemical definition of Caloric Restriction Mimetics, compounds that mimic the positive effects of nutrient starvation. In our setting, a CRM is a compound able to reduce protein acetylation through distinct but convergent mechanisms: first, by decreasing AcCoA levels, second by directly inhibiting KATs, third by the activation of protein deacetylases. This results in the execution of a cellular program ultimately leading to CR-related pro-healthy effects, including but not limited to autophagy.

Introdução. O consumo de açúcares aumentou consideravelmente nas últimas décadas, bem como a incidência e a prevalência da obesidade, gerando a elaboração de recomendações para moderá-lo. Os açúcares contribuem para a palatabilidade dos alimentos, podendo também aumentar sua densidade energética (DE), outro fator de risco para obesidade. Uma alternativa seria a substituição por adoçantes não calóricos, que também aumentam a palatabilidade dos alimentos, porém são isentos calorias. No entanto, ainda não existe consenso a respeito das implicações desta substituição principalmente na redução da ingestão energética e do peso corporal. Objetivo. Identificar a DE da dieta, a ingestão energética total e de macronutrientes, segundo consumo de adoçantes e/ou alimentos processados com adoçantes por adultos e idosos. Métodos. Estudo transversal, no qual foram coletados dados de sexo; idade; peso e estatura, para cálculo do IMC; consumo de adoçantes, por questionário adaptado e pelo recordatório de 24 horas, foram calculadas as médias de DE, de ingestão energética total e de macronutrientes. Para verificar associação entre variáveis independentes (idade, sexo, IMC, uso de adoçantes não calóricos) com a dependente \"classificação da DE foi realizada regressão logística, considerando dietas com alta DE aquelas com 1,5 Kcal/g ou mais. Para comparação das médias de ingestão energética e de macronutrientes, entre usuários de adoçantes e não usuários, foi utilizado o Teste t de Student (p 0,05) pelo Stata 10.0. Resultados. Participaram do estudo 168 indivíduos, com idade média de 54,8 anos (DP = 14,9 anos), sendo 84,5 por cento do sexo feminino, 67,9 por cento com sobrepeso ou obesidade e 44,1 por cento usuários de adoçantes. A média da DE das dietas de usuários de adoçantes foi 1,15 Kcal/g (IC 95 por cento [1,11; 1,19]), e de não usuários 1,28 Kcal/g (IC 95 por cento [1,23; 1,33]). Para regressão logística, as variáveis contínuas, idade e IMC, foram categorizadas, porém esta última não permaneceu no modelo final (p > 0,10). Apesar de não significativo, a variável sexo permaneceu no modelo como ajuste. A classificação da idade (p = 0,042) e o uso de adoçantes (p = 0,002) apresentaram associação com os menores valores de DE. Não foi encontrada diferença nas médias de ingestão energética e de macronutrientes entre os grupos. Conclusão. Uso de adoçantes se associou com menores valores de DE, mas não houve diferença no consumo energético total e de macronutrientes entre grupos / The consumption of sugar has increased considerably in recent decades, as well as the incidence and prevalence of obesity, leading the development of recommendations to moderate this consumption. Sugars contribute to the palatability of food, but may also increase their energy density (ED), which is an important obesitys risk factor. An alternative would be replacing sugar by non-caloric sweeteners, which increase the palatability of foods, but with free calories. However, the implications of this substitution in reducing energy intake and body weight are controversial. Objective. Identify the ED of diets, the total energy intake and macronutrient consumption according to the consumption of sweeteners and/or processed foods with sweeteners by adults and elderly. Methods. A cross sectional study, that collected data on gender, age, weight and height, to calculate BMI, consumption of non-caloric sweeteners, by questionnaire and with data from 24-hour recall, were calculated the average of ED, total energy intake and total macronutrient intake. Logistic regression was performed to assess the association between independent variables (age, gender, BMI, use of non-caloric sweeteners) and the dependent classification of ED, considering diets with high ED those with 1.5 kcal/g or more. To compare the means of total energy intake and total macronutrient intake, among noncaloric sweeteners users and nonusers, was used the Students t test (p 0.05) by Stata 10.0. Results. Were collected data form 168 individuals, with an average age of 54.8 years (SD = 14.9 years), 84.5 per cent female, 67.9 per cent overweight or obese and 44.1 per cent users of sweeteners. The mean of ED diets of non-caloric sweeteners users was 1.15 kcal/g (CI 95 per cent [1.11; 1.19]), and 1.28 Kcal/g (CI 95 per cent [1.23; 1.33]) for non-users. For logistic regression the continuous variables, BMI and age, were categorized, but the former did not remained in the final model. Although the variable gender was not significant it remained in the model for adjustment. The classification of age (p = 0.042) and the use of sweeteners (p = 0.002) were associated with lower values of ED. No difference was found in the means of total energy intake and total macronutrient intake between the groups. Conclusion. The use of sweeteners was associated with lower values of ED, but there was no difference in the means of total energy intake and total macronutrient intake between the groups

Os últimos anos se caracterizaram pelo aumento significativo da população idosa mundial. Por esta razão, a preocupação com o idoso está se tornando uma constante em nossa sociedade, uma vez que o envelhecimento resulta em comprometimento das funções fisiológicas, acompanhado ou não de alterações estruturais. No trato gastrointestinal (TGI), o processo de envelhecimento pode provocar alterações morfofuncionais significativas. A regulação da motilidade do TGI é controlada principalmente pelos neurônios mioentéricos do sistema nervoso entérico. A diminuição na densidade destes neurônios no cólon pode levar à redução na frequência e na amplitude da contração colônica manifestada como constipação. As ações que visam diminuir os efeitos do envelhecimento no TGI incluem aquelas relacionadas à dieta alimentar, entre as quais se destaca a restrição calórica. A restrição calórica, além de apresentar efeito protetor nos neurônios mioentéricos durante o envelhecimento, também é responsável pela diminuição da morte neuronal por apoptose, processo este acentuado com o envelhecimento. Assim sendo, este trabalho teve por objetivo avaliar os efeitos de diferentes níveis de restrição calórica sobre a plasticidade dos neurônios mioentéricos NADPH e acetilcolinesterase positivos do cólon de ratos Wistar durante o processo de envelhecimento por meio das análises ultraestrutural (microscopia eletrônica de transmissão) e morfoquantitativa. Para tanto foram utilizados 40 ratos machos (Rattus norvegicus), da linhagem Wistar, distribuídos em quatro grupos (n= 10/grupo): CI- animais de seis meses; SR- animais de 18 meses alimentados com dieta normal; RCI- animais de 18 meses alimentados com dieta com 12% de restrição calórica; RCII- animais de 18 meses submetidos à restrição calórica de 30%. Aos seis meses de idade, os animais foram transferidos para o biotério setorial, onde permaneceram até aos 18 meses sob condições ambientais controladas de temperatura e de iluminação e água ad libitum. Foi possível observar que a RC em nível de 30% minimizou de forma eficaz os efeitos deletérios do envelhecimento nos neurônios mioentéricos, podendo ser adotada como alternativa contra os distúrbios gastrointestinais comuns em indivíduos idosos. / The last years were characterized by a significant increase in the elderly population. For this reason, concern for the elderly is becoming a constant in our society, since the aging results in impairment of bodily function, or not accompanied by structural changes. In the gastrointestinal tract (GI), the aging process can cause significant morphological changes. The regulation of motility of the gut is controlled mainly by myenteric neurons of the enteric nervous system. The decrease in the density of neurons in the colon can lead to a reduction in the frequency and amplitude of contraction expressed as colonic constipation. The actions aimed at reducing the effects of aging on the GI system include those related to diet, among which stands out caloric restriction. Caloric restriction, and have a protective effect on the myenteric neurons during aging, is also responsible for the decrease of neuronal death by apoptosis, a process accentuated with aging. Thus, this study was to evaluate the effects of different levels of calorie restriction on the plasticity of myenteric neurons NADPH and acetylcholinesterase positive of the colon of rats during the aging process by means of ultrastructural (transmission electron microscopy) and morphoquantitative analysis. Therefore, we used 40 male Wistar rats (Rattus norvegicus), divided into four groups (n = 10): CI- animals six months; SR- animals 18 month fed a normal diet; RCI - animals 18 months fed a diet with 12% caloric restriction; RCII- animals 18 months fed a diet with 30% caloric restriction. At six months, the animals were transferred to the vivarium sector, where they remained up to 18 months under controlled conditions of temperature and light and water ad libitum. It was observed that the RC level of 30% effectively minimized the deleterious effects of aging on myenteric neurons, which may be adopted as an alternative against the common gastrointestinal disorders in the elderly.

Made available in DSpace on 2016-04-28T14:16:18Z (GMT). No. of bitstreams: 1 Eliade Amanda Alves.pdf: 797025 bytes, checksum: 7b8d100a42540d8c12a1bd758578ffd9 (MD5) Previous issue date: 2013-05-14 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This work has the purpose to understand the role of experiment in constructing knowledge. Here we have analyzed the radiation of cold experiment performed by Rumford in 1802 and its theoretical implication concerning the heat. Regarding this we reviewed some Rumford s early studies which led us to a better understanding of his trajectory until he could perform his experiment. We can say that the hypothesis adopted by Rumford related to the nature of heat determined decisively the interpretation given by him to the experiment results. We consider here original texts published by Rumford, specially An Experimental Inquiry Concerning the Source of Heat Which is Excited by Friction in which he described his radiation of cold experiment. Through this study we concluded that although experiments results are very important for the construction of knowledge, they are not sufficient to validate or refute a hypothesis definitely / O objetivo desse trabalho é compreender o papel do experimento na construção do conhecimento. Analisamos o experimento da radiação do frio realizado pelo Conde Rumford em 1802, e suas implicações de natureza teórica em relação à concepção de calor. Para tanto, revisamos alguns estudos anteriores realizados por Rumford que propiciaram uma melhor compreensão de sua trajetória até ele realizar o experimento. Podemos dizer que a hipótese adotada por Rumford sobre a natureza do calor, determinou de forma decisiva a interpretação dada aos resultados experimentais. Para a realização dessa pesquisa recorremos a textos originais publicados pelo Conde Rumford, principalmente aquele em que ele descreve o experimento da radiação do frio. Por meio desta análise, concluímos que, apesar de muito importante para a construção do conhecimento, o resultado experimental não é suficiente para validar ou refutar uma hipótese definitivamente