Thesis (PhD)--Stellenbosch University, 2005. / ENGLISH ABSTRACT: A high fat diet (HFD) reduces beta-cell mass, impairs glucose signalling and is involved in the development of Type 2 diabetes. Malnutrition during gestation is hypothesized to irreversibly damage beta-cell development. The transcription factors Pdx-1 and Pax 4 are involved in islet cell development. Pdx-1 is reported to regulate expression of GLUT-2, glucokinase (GK) and the insulin gene. Aims The aim of this study is to investigate, in the neonatal and weanling rat, the effect of exposure to a HFD in utero and/or lactation on weight, glucose and insulin concentrations, islet cell development, pancreatic transcription factors and glucose sensing genes. Methods Neonatal and weanling rats were exposed to a maternal HFD for defined periods of gestation and/or lactation. After termination, pups were weighed and glucose and insulin concentrations determined. mRNA expression of Pdx-1, Pax 4, GLUT-2 and GK was quantified by LightCycler PCR. Pancreatic sections were immunostained for insulin and glucagon (islet cell development), and for Pdx-1, GLUT-2 and GK (beta-cell function) followed by image analysis. Results: Exposure to an in utero HFD throughout gestation resulted in hyperglycaemic pups with reduced beta-cell volume and number, Pdx-1 and GK immunoreactivity. In contrast the alpha-cell volume, number and size were augmented in neonates exposed to a HFD throughout gestation. Most weanlings were hyperglycaemic and hypoinsulinaemic. In some weanlings, reduced beta-cell number and beta- and alpha-cell size was observed. Pdx-1 mRNA was overexpressed in weanlings exposed to a maternal HFD for the final week of gestation or throughout both gestation and lactation, but reduced in those only exposed throughout lactation. Pax 4 mRNA was reduced in weanlings exposed to a maternal HFD for the first or final week of gestation, throughout gestation or throughout lactation. In most of the weanlings, GLUT-2 mRNA expression was reduced whereas immunoreactivity for GLUT-2 was increased. Both GK mRNA expression and immunoreactivity were reduced in most of the weanlings. Conclusions • Exposure to an in utero HFD throughout gestation induced hyperglycaemia in neonates. The reduced Pdx-1 expression appears to play a role in the compromised beta-cell development, and concomitant with the reduced GK levels, contributes to the hyperglycaemia in these neonates and may make them susceptible to beta-cell failure. • In most weanlings exposed to a HFD in utero and/or during lactation the hyperglycaemia and hypoinsulinaemia suggest compromised beta-cell function. The GK mRNA expression and immunoreactivity were reduced thereby impairing glycolysis which would result in reduced insulin secretion contributing to the hyperglycaemia. Furthermore, beta-cell development is adversely affected by the HFD in some weanlings. This would contribute to reduced beta-cell function and may eventually result in beta-cell failure. GLUT-2 immunoreactivity was increased in some, suggesting a compensatory adaptative mechanism to restore glucose homeostasis. • A maternal HFD has adverse effects both in neonates and weanlings on beta-cell development, transcription factor and glucose sensing gene expression and induced hyperglycaemia and hypoinsulinaemia in some of the offspring. Ways to ameliorate the HFD-induced attenuation of key beta-cell genes to ensure normal beta-cell function are important for future research in Type 2 diabetes. / AFRIKAANSE OPSOMMING: ‘n Hoe vet diet (HVD) verminder beta-sel masse, glukose signale en speel ‘n rol in Tipe 2 diabetes. Die hipothese is dat wanvoeding gedurende swangerskap lei tot onomkeerbare betasel beskadiging. Die transkripsiefaktore Pdx-1 en Pax 4 speel rolle in eilandselontwikkeling. Daar is bewyse dat Pdx-1 die uitdrukking van die GLUT-2, glucokinase (GK) en insulin gene reguleer. Doelstelling: Die doel van hierdie studie is om, in die pasgebore en gespeende rot, die effek van ’n HVD in utero en/of laktasie op gewig, glukose en insulin konsentrasies, eilandselontwikkeling, pankreatiese transksripsiefaktore en op glukosewaarnemingsgene te ondersoek. Metodes: Pasgebore en gespeende rotte is vir bepaalde periodes van gestasie en/of laktasie blootgestel aan ’n HVD van die moeder. Na terminase, is kleinjies geweeg en die glukose- en insulienkinsentrasies bepaal. mRNA uitdrukking van Pdx-1, Pax 4, GLUT-2 en GK is geoes met LightCycler PCR. Snitte van die pankreas is gekleur met insulien en glukagon (eilandsontwikkeling) en vir Pdx-1, GLUT-2 en GK (betaselfunksie) gevolg deur beeldanalise. Resultate: Bloodstelling aan ’n in utero HVD regdeur gestasie het hiperglisemie versoorsaak in pasgebore rotte met verlaagde betasel volume en aantal, Pdx-1 en GK immunoreaktiwiteit. In teenstelling daarmee was die alfasel se volume, aantal en grootte verhoog in pasgebore rotte wat regdeur gestasie aan 'n HVD blootgestel was. Meeste van die gespeende rotte was hiperglisemies en hipoinsulinemies. In sommige gespeende rotte, was daar ’n verlaging van betasel hoeveelheid en grootte en in alfasel groote. Oormatige uitdrukking van Pdx-1 mRNA het plaasgevind in speenlinge wat aan ’n HVD van die moeder vir die laaste week van gestasie of regdeur gestasie en laktasie blootgestel was, maar dit was verlaag in die speenlinge wat net tydens laktasie blootgestel was. Pax 4 mRNA was verlaag in speenlinge wat aan ’n HVD van die moeder blootgestel was vir die eerste of laaste week van gestasie, regdeur gestasie of regdeur laktasie. In meeste van die speenlinge is onder-uitdrukking van GLUT-2 mRNA, maar ’n verhoging van GLUT-2 immunoreaktiwiteit gevind. Beide GK mRNA uitdrukking en immunoreaktiwiteit was laer in meeste van die speenlinge. Gevolgtrekkings: • Blootstelling aan ’n in utero HVD regdeur gestasie lei tot hiperglisemie in pasgebore rotte. Die verlaagde Pdx-1 immunoreaktiwiteit speel klaarblyklik ’n rol by die geaffekteerde betaselontwikkeling. Dit, saam met die verlaagde immunoreaktiwiteit vir GK, kan bydra tot die hiperglisemie in hierdie pasgebore rotte. In die meeste van die speenlinge wat aan ’n HVD blootgestel was, dui die hiperglisemie en hipoinsulinemie op geaffekteerde betaselfunksie. Die GK mRNA uitdrukking en immunoreaktiwiteit is verlaag, wat weer glikolise benadeel, en dit sal lei tot verminderde insulienafskeiding wat bydra tot die hiperglisemie. Betaselontwikkeling word voorts negatief beinvloed deur die HVD, wat blyk uit die verlaagde aantal en grootte van betaselle. Dit sal bydra tot verminderde betaselfunksie. Dit kan uiteindelik tot betaselversaking lei. GLUT-2 immunoreaktiwiteit was verhoog in hierdie speenlinge, wat dui op ’n kompenserende aanpassingsmeganisme om glukose homeostase te herstel. ’n HVD van die moeder het ’n negatiewe uitwerking op betaselontwikkeling, transkripsiefaktor en glukosewaarneming geenuitdrukking in beide die pasgebore en gespeende rotte, en geinduseerde hiperglisemie en hipoinsulinemie in sommige kleintjies. Dis belangrik vir toekomstige Tipe 2 diabetes navorsing dat daar na gekyk moet word om die HVD-geinduseerde verlaging van sleutel betaselgene te verbeter vir optimale betaselfunksie.

This study examines whether obesity affects the accuracy of estimating age-at-death as measured by the age-related changes of the pubic symphysis and auricular surfaces. I scored the hip bones of 119 adults of normal body mass and 126 obese adults (total n = 254) using the SucheyBrooks (1990) method for the pubic symphysis and the Buckberry and Chamberlain (2002) method for the auricular surface. Compared to normal weight individuals, obese individuals exhibited greater inaccuracy in age-at-death estimates when aged from the auricular surface, but not the pubic symphysis. However, age was estimated with less precision in obese individuals using both methods. Obese males are more likely to be aged inaccurately than obese females. The pubic symphysis method may be the preferred method when estimating age in obese individuals, especially males, but forensic anthropologists should use caution when assessing age-at-death in obese adults using either method. / by Jessica L. Drew. / Thesis (M.A.)--Florida Atlantic University, 2010. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2010. Mode of access: World Wide Web.

Typescript / Bibliography: leaves 127-139 / x, 139 leaves : ill ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Pathology, 1988

A review of the literature revealed that diet plays an important role in serious human noninfectious large bowel diseases including cancer and inflammatory bowel diseases. Dietary protein (especially as red and processed meats) has been implicated as a positive risk factor for colorectal cancer while starch which is not digested in the small intestine (resistant starch, RS) appears to be protective. The series of experiments described in this thesis were aimed to determine the effects of dietary proteins and RS on indices of colon health in an animal model, the laboratory rat. Genetic damage is a prerequisite for carcinogenesis and this was assessed by a specific assay (the comet assay) which gives a measure of DNA strand breaks. Loss of mucus barrier function is thought to contribute to inflammatory bowel disease by permitting bacterial translocation and this was measured optically using a microscope micrometer. Other biomarkers were measured as described below. There were four major experiments. 1. Effects of dietary red meat and casein on colonic DNA damage and interaction with resistant starch Previous studies had shown that higher dietary protein (as casein) induced genetic damage in rat colonocytes and that RS (fed as a high amylose maize starch) was protective. This study was aimed at establishing whether a high protein diet fed as cooked red meat had similar effects and whether RS was protective. Rats were fed diets containing either 15 % or 25% casein or 25% barbecued lean red beef, each with or without 48% high amylose maize starch (as a source of RS) for 4 weeks. As expected, high dietary casein caused a 2-fold increase in colonic single-strand DNA breaks compared with a low casein diet and reduced the thickness of the colonic mucus layer by 41%. High levels of cooked meat caused 26% more DNA damage than the high casein diet but reduced mucus thickness to a similar degree as casein. Addition of RS to the diet abolished the increase in DNA damage and the loss of colonic mucus thickness induced by either high protein diet. It is thought that RS promotes large bowel health through the SCFA produced by the large bowel bacteria. One acid in particular (butyrate) has been associated particularly with promotion of normal large bowel function and protection against disease. In keeping with this hypothesis, caecal and faecal short chain fatty acid pools (including those of butyrate) were increased by inclusion of RS in the diet. DNA damage is an early step in the initiation of cancer and these findings agree with the population data which suggest that total dietary protein and red meat promote risk of colorectal cancer. However, inclusion of resistant starch in the diet could significantly reduce that risk. 2. Differential effects of dietary whey, soy and casein on colonic DNA damage and interaction with resistant starch The preceding experiments showed that high levels of animal-derived proteins increased colonocyte genetic damage and loss of the mucus barrier in rats. This second experiment was designed to determine whether diets high in different types of dairy protein (casein or whey) or a plant protein isolate (soy) had similar adverse effects on colonic DNA and mucus barrier function and whether inclusion of RS in the diet was protective. Adult male Sprague Dawley rats were fed a diet containing 15 % or 25 % casein, whey or soy protein, each with or without 48 % high amylose maize starch for 4 weeks. In confirmation of the earlier studies, higher levels of dietary casein increased colonocyte DNA damage significantly. However, whey did not increase genetic damage. Colonic DNA damage was highest for soy when fed at both 15% and 25% protein in the absence of RS. Inclusion of RS in the diet attenuated colonocyte DNA damage due to higher dietary protein in all three groups. The colonic mucus barrier was thinner in rats fed higher dietary protein but the effect was reversed by feeding RS. Caecal total SCFA and butyrate pools were low in rats fed the digestible starch and were higher in rats fed RS. However, there was no relationship between caecal or faecal SCFA and genetic damage or mucus thickness. Caecal and colonic tissue weight and colon length were higher in rats fed RS, consistent with greater SCFA supply. These data confirm that higher dietary protein of animal (casein) or plant (soy) origin increases genetic damage and loss of the mucus barrier indicating that this is an effect of protein and not its source. These findings accord with the epidemiological data which link dietary protein to greater risk of colorectal cancer and inflammatory bowel disease. However, the data show also that dietary proteins differ in their specific actions on genetic damage and mucus thickness. Further, the data from the feeding of whey suggest that not all proteins are equivalent in their capacity to provoke adverse changes in colonic integrity. While the data show that RS raised large bowel and faecal SCFA, they indicate their levels were not related directly to these biomarkers. 3. Dose response effects of resistant starch on protein induced colonic DNA damage The accumulated data linking greater protein intakes to adverse changes in the colon were obtained at dietary levels which were not unreasonable in terms of animal or human consumption. However, the dietary level of RS which were fed were relatively high (48% by weight) so this study was conducted to determine its effectiveness at lower levels of dietary inclusion. It was also important to ascertain whether there was a dose-response relationship between RS intake and the observed effects. One of the mechanisms proposed for the induction of colorectal cancer by high dietary protein intakes is oxidative damage to DNA. In this experiment, this was done by assaying with endonuclease III. Adult male rats were fed a diet containing 25% casein with 0%, 10%, 20%, 30% or 40% high amylose maize starch for 4 weeks. As in the preceding studies comet tail moment was greatest and the mucus barrier thinnest in rats fed 0% RS. DNA damage was reduced and the mucus barrier thickened in a logarithmic dose-dependent manner by RS. There was no significant difference between dietary groups associated with oxidative DNA damage as measured by endonuclease III. Caecal and faecal short chain fatty acid (SCFA) pools rose with the increased level of dietary RS. DNA damage of colonocytes correlated negatively with caecal SCFA but the strongest correlation was with caecal butyrate, which is consistent with the proposed role of this SCFA in promoting a normal cell phenotype. The data show that RS prevents protein induced colonic DNA damage in a dose-dependent manner. Inclusion of 10% high amylose maize starch was found to be sufficient to oppose colonocyte DNA damage, and to increase caecal and faecal SCFA pools. Intakes of this order are not unreasonable in terms of human consumption of RS. 4. Dose response effects of red and white meat on colonic DNA damage and interaction with resistant starch The accumulated evidence from large prospective human studies links diet to colorectal cancer risk strongly. The evidence from the animal studies described in this thesis that dietary protein induces colonocyte genetic damage supports a role for high protein intakes in increasing risk. Recently, several large epidemiological studies and a meta-analysis of prospective studies have found that consumption of dietary red or processed meats, but not white (poultry) meat, is associated with increased risk of colorectal cancer. This is consistent with the data from the preceding studies that specific proteins affected colonic integrity differentially. A large prospective European study (European Prospective Investigation into Cancer and Nutrition) has reported that dietary fibre was protective. The findings reported in this thesis that RS opposes the effects of high dietary protein accord with that conclusion. This study aimed to compare the effects of cooked red (beef) or white (chicken) meat on DNA damage and mucus barrier thickness in rats. The study was designed to determine whether the relationship between the intakes of these meats was dose-dependent. Double-strand DNA breaks are thought to relate more closely to carcinogenesis than single-strand breaks so both were measured. Adult male Sprague-Dawley rats were fed a diet containing 15%, 25% or 35% cooked beef or cooked chicken each with or without 20% high amylose maize starch for four weeks. Both red and white meat increased colonic DNA damage dose-dependently. However, both single and double strand breaks were significantly greater when the rats were fed the red meat diets compared to those fed the white meat. Colonocyte DNA damage was reduced by the consumption of RS while large bowel SCFA were increased. The findings of this study are consistent with the epidemiological data which show that red meat consumption is associated with greater risk of colorectal cancer but that white meat is not. Summary The data reported in this thesis support the findings of prospective population studies that high dietary protein, red meat in particular, appears to be harmful to the health of the large bowel. However, the data demonstrate also that different protein types have differential effects on the integrity of the colonocyte DNA. Furthermore, the addition of RS to the diet protects against protein-induced colonic DNA damage and maintenance of the colonic mucus barrier, apparently through increased SCFA production by colonic fermentation. The results of these experiments indicate a strong potential for RS to be effective in maintenance of large bowel integrity in the face of high dietary protein. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1292858 / Thesis(Ph.D.)-- School of Molecular and Biomedical Science, 2007.

A review of the literature revealed that diet plays an important role in serious human noninfectious large bowel diseases including cancer and inflammatory bowel diseases. Dietary protein (especially as red and processed meats) has been implicated as a positive risk factor for colorectal cancer while starch which is not digested in the small intestine (resistant starch, RS) appears to be protective. The series of experiments described in this thesis were aimed to determine the effects of dietary proteins and RS on indices of colon health in an animal model, the laboratory rat. Genetic damage is a prerequisite for carcinogenesis and this was assessed by a specific assay (the comet assay) which gives a measure of DNA strand breaks. Loss of mucus barrier function is thought to contribute to inflammatory bowel disease by permitting bacterial translocation and this was measured optically using a microscope micrometer. Other biomarkers were measured as described below. There were four major experiments. 1. Effects of dietary red meat and casein on colonic DNA damage and interaction with resistant starch Previous studies had shown that higher dietary protein (as casein) induced genetic damage in rat colonocytes and that RS (fed as a high amylose maize starch) was protective. This study was aimed at establishing whether a high protein diet fed as cooked red meat had similar effects and whether RS was protective. Rats were fed diets containing either 15 % or 25% casein or 25% barbecued lean red beef, each with or without 48% high amylose maize starch (as a source of RS) for 4 weeks. As expected, high dietary casein caused a 2-fold increase in colonic single-strand DNA breaks compared with a low casein diet and reduced the thickness of the colonic mucus layer by 41%. High levels of cooked meat caused 26% more DNA damage than the high casein diet but reduced mucus thickness to a similar degree as casein. Addition of RS to the diet abolished the increase in DNA damage and the loss of colonic mucus thickness induced by either high protein diet. It is thought that RS promotes large bowel health through the SCFA produced by the large bowel bacteria. One acid in particular (butyrate) has been associated particularly with promotion of normal large bowel function and protection against disease. In keeping with this hypothesis, caecal and faecal short chain fatty acid pools (including those of butyrate) were increased by inclusion of RS in the diet. DNA damage is an early step in the initiation of cancer and these findings agree with the population data which suggest that total dietary protein and red meat promote risk of colorectal cancer. However, inclusion of resistant starch in the diet could significantly reduce that risk. 2. Differential effects of dietary whey, soy and casein on colonic DNA damage and interaction with resistant starch The preceding experiments showed that high levels of animal-derived proteins increased colonocyte genetic damage and loss of the mucus barrier in rats. This second experiment was designed to determine whether diets high in different types of dairy protein (casein or whey) or a plant protein isolate (soy) had similar adverse effects on colonic DNA and mucus barrier function and whether inclusion of RS in the diet was protective. Adult male Sprague Dawley rats were fed a diet containing 15 % or 25 % casein, whey or soy protein, each with or without 48 % high amylose maize starch for 4 weeks. In confirmation of the earlier studies, higher levels of dietary casein increased colonocyte DNA damage significantly. However, whey did not increase genetic damage. Colonic DNA damage was highest for soy when fed at both 15% and 25% protein in the absence of RS. Inclusion of RS in the diet attenuated colonocyte DNA damage due to higher dietary protein in all three groups. The colonic mucus barrier was thinner in rats fed higher dietary protein but the effect was reversed by feeding RS. Caecal total SCFA and butyrate pools were low in rats fed the digestible starch and were higher in rats fed RS. However, there was no relationship between caecal or faecal SCFA and genetic damage or mucus thickness. Caecal and colonic tissue weight and colon length were higher in rats fed RS, consistent with greater SCFA supply. These data confirm that higher dietary protein of animal (casein) or plant (soy) origin increases genetic damage and loss of the mucus barrier indicating that this is an effect of protein and not its source. These findings accord with the epidemiological data which link dietary protein to greater risk of colorectal cancer and inflammatory bowel disease. However, the data show also that dietary proteins differ in their specific actions on genetic damage and mucus thickness. Further, the data from the feeding of whey suggest that not all proteins are equivalent in their capacity to provoke adverse changes in colonic integrity. While the data show that RS raised large bowel and faecal SCFA, they indicate their levels were not related directly to these biomarkers. 3. Dose response effects of resistant starch on protein induced colonic DNA damage The accumulated data linking greater protein intakes to adverse changes in the colon were obtained at dietary levels which were not unreasonable in terms of animal or human consumption. However, the dietary level of RS which were fed were relatively high (48% by weight) so this study was conducted to determine its effectiveness at lower levels of dietary inclusion. It was also important to ascertain whether there was a dose-response relationship between RS intake and the observed effects. One of the mechanisms proposed for the induction of colorectal cancer by high dietary protein intakes is oxidative damage to DNA. In this experiment, this was done by assaying with endonuclease III. Adult male rats were fed a diet containing 25% casein with 0%, 10%, 20%, 30% or 40% high amylose maize starch for 4 weeks. As in the preceding studies comet tail moment was greatest and the mucus barrier thinnest in rats fed 0% RS. DNA damage was reduced and the mucus barrier thickened in a logarithmic dose-dependent manner by RS. There was no significant difference between dietary groups associated with oxidative DNA damage as measured by endonuclease III. Caecal and faecal short chain fatty acid (SCFA) pools rose with the increased level of dietary RS. DNA damage of colonocytes correlated negatively with caecal SCFA but the strongest correlation was with caecal butyrate, which is consistent with the proposed role of this SCFA in promoting a normal cell phenotype. The data show that RS prevents protein induced colonic DNA damage in a dose-dependent manner. Inclusion of 10% high amylose maize starch was found to be sufficient to oppose colonocyte DNA damage, and to increase caecal and faecal SCFA pools. Intakes of this order are not unreasonable in terms of human consumption of RS. 4. Dose response effects of red and white meat on colonic DNA damage and interaction with resistant starch The accumulated evidence from large prospective human studies links diet to colorectal cancer risk strongly. The evidence from the animal studies described in this thesis that dietary protein induces colonocyte genetic damage supports a role for high protein intakes in increasing risk. Recently, several large epidemiological studies and a meta-analysis of prospective studies have found that consumption of dietary red or processed meats, but not white (poultry) meat, is associated with increased risk of colorectal cancer. This is consistent with the data from the preceding studies that specific proteins affected colonic integrity differentially. A large prospective European study (European Prospective Investigation into Cancer and Nutrition) has reported that dietary fibre was protective. The findings reported in this thesis that RS opposes the effects of high dietary protein accord with that conclusion. This study aimed to compare the effects of cooked red (beef) or white (chicken) meat on DNA damage and mucus barrier thickness in rats. The study was designed to determine whether the relationship between the intakes of these meats was dose-dependent. Double-strand DNA breaks are thought to relate more closely to carcinogenesis than single-strand breaks so both were measured. Adult male Sprague-Dawley rats were fed a diet containing 15%, 25% or 35% cooked beef or cooked chicken each with or without 20% high amylose maize starch for four weeks. Both red and white meat increased colonic DNA damage dose-dependently. However, both single and double strand breaks were significantly greater when the rats were fed the red meat diets compared to those fed the white meat. Colonocyte DNA damage was reduced by the consumption of RS while large bowel SCFA were increased. The findings of this study are consistent with the epidemiological data which show that red meat consumption is associated with greater risk of colorectal cancer but that white meat is not. Summary The data reported in this thesis support the findings of prospective population studies that high dietary protein, red meat in particular, appears to be harmful to the health of the large bowel. However, the data demonstrate also that different protein types have differential effects on the integrity of the colonocyte DNA. Furthermore, the addition of RS to the diet protects against protein-induced colonic DNA damage and maintenance of the colonic mucus barrier, apparently through increased SCFA production by colonic fermentation. The results of these experiments indicate a strong potential for RS to be effective in maintenance of large bowel integrity in the face of high dietary protein. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1292858 / Thesis(Ph.D.)-- School of Molecular and Biomedical Science, 2007.

Thesis (Dr. P.H.)--University of Texas Health Science Center at Houston, School of Public Health, 2007. / Source: Dissertation Abstracts International, Volume: 68-11, Section: B, page: 7285. Adviser: Lu Ann Aday. Includes bibliographical references.

Increased emphasis is being given to nutritional assessment and the related protein-energy malnutrition findings in hospital populations. A nutritional survey conducted in the general medical ward of an urban teaching hospital showed forty-four percent of the patients assessed in a state of protein-energy malnutrition. A similar survey among patients in the surgical wards of the same hospital found fifty-nine percent of the patients assessed in a state of protein-energy malnutrition. Patients in chronic renal failure maintained on hemodialysis have been suspected of having protein-energy malnutrition due to their restricted dietary regimens. Blumekrantz and Kopple have found anthropometric and biochemical wasting or malnutrition in patients undergoing maintenance peritoneal or hemodialysis. This however, may have been due to inadequate protein and/or energy intake. Advances in the technique and frequency of hemodialysis treatments have allowed patients in chronic renal failure to be maintained on diets with a more liberal intake of protein than had been allowed in the past. The purpose of this study was to determine the incidence of protein-energy malnutrition in fifty adult subjects with chronic renal failure who were being maintained on hemodialysis, and who were on prescribed protein intakes of a least one ram of protein per kilogram of ideal body eight per ay. The subjects of the study had varying types of renal lesions and the frequency of their dialysis treatments was determine by the degree of deterioration of renal function. The subjects were eighteen years of age or older, male and female, representing various ethnic backgrounds, and were sedentary in terms of activity level.

Orientador : Jaime Amaya-Farfan / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-07-28T22:43:45Z (GMT). No. of bitstreams: 1 HozUrrejola_Luciadela_M.pdf: 3166668 bytes, checksum: ea395892c3c0bb881db55ec3169422d8 (MD5) Previous issue date: 2001 / Resumo: O presente trabalho teve por objetivo testar a aplicabilidade da técnica de eletroforese capilar de alta eficiência (HPCE) no estudo dod poddiveis peptídeos urinários em crianças autistas e normais. Estudos recentes têm mostrado que a (HPCE) é uma técnica alternativa e/ou complementar a outras técnicas analíticas como cromatografia liquida de alta eficiência (HPLC), na análise qualitativa e na separação de misturas de peptídeos / Abstract: This study aimed to test the applicability of the technique of high-performance capillary electrophoresis (HPCE) in the study dod poddiveis urinary peptides in autistic children and normal. Recent studies have shown that the (HPCE) is an alternative technique and / or complementary to other analytical techniques such as high performance liquid chromatography (HPLC), in qualitative analysis and the separation of mixtures of peptides / Mestrado / Mestre em Alimentos e Nutrição

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, characterised by deficits in language, behaviour and memory. Increasing evidence suggests that mid-life obesity and a diet high in fat are risk factors for AD. In contrast, life-threatening weight loss occurs and worsens as the disease progresses, despite adequate or increased food intake. A greater understanding of energy balance in AD may therefore uncover novel targets for therapy. The aim of this thesis was to test the hypothesis that 3xTgAD mice display altered energy balance and that experimental changes to this balance will alter cognition. To address this hypothesis, three key objectives were set up; to characterise the energy balance profile, characterise behaviour and memory, and evaluate the response to an high fat (HF) diet in a triple transgenic (3xTgAD) model, an experimental mouse model of AD. Energy balance was characterised in non-transgenic (Non-Tg) control and 3xTgAD mice, demonstrating altered body weight, food intake and metabolic rate in the 3xTgAD mouse model of AD. At 2-month of age male 3xTgAD mice displayed greater food intake and body weight, but no difference in metabolic rate, whereas from 12 months of age 3xTgAD mice weighed less, despite eating more, and had a higher metabolic rate than Non-Tg control mice. This provides evidence that there is a shift towards a hypermetabolic state from 12 months of age in 3xTgAD mice, which may represent a key stage in advancement of the disease process. Behaviour and memory were characterised in Non-Tg control and 3xTgAD mice in a battery of tests at different ages. 3xTgAD mice showed changes in open-field activity/anxiety from 3 months of age. Memory impairments were first detected in 3xTgAD mice at 3 months of age as deficits in odour recognition memory, mirroring early impairments seen in AD patients. Deficits in spatial memory were then observed in both the Y-maze spontaneous alternation and Morris water maze tests from 5 months of age. Finally, deficits in non-spatial visual object memory were observed in 3xTgAD mice in the novel object recognition test at 8 months of age. Energy balance, behaviour and memory were assessed in Non-Tg control and 3xTgAD mice in response to an HF diet. Non-Tg control and 3xTgAD mice displayed similar energy balance profiles in response to an HF diet. The HF diet was found to worsen memory in Non-Tg mice in odour recognition at 3-4 and 7-8 months of age, in the Morris water maze at 7-8 months of age and in novel object recognition and spontaneous alternation at 11-12 and 15-16 months of age. Similarly, the HF diet worsened memory in 3xTgAD mice in odour discrimination at 3-4 and 7-8 months of age, the Morris water maze at 7-8 and 11-12 months of age, and in spontaneous alternation at 15-16 months of age. As an HF diet induced memory impairments, in both Non-Tg control and 3xTgAD mice, it suggests that diet-induced deficits may therefore, not be specific to AD, but rather to cognition in general. Overall, these data demonstrate that 3xTgAD mice show AD-like age-dependent changes in energy balance, behaviour and memory. Furthermore, an HF diet produced impairments in memory in 3xTgAD mice, but these effects were not specific to AD, as an HF diet also led to deficits in control animals. These data support a role for energy balance in the progression of AD, although the underlying mechanisms remain poorly understood. 3xTgAD mice may therefore represent a good model to examine energy balance during AD and to evaluate targets for future therapies.

The prevalence of obesity is growing worldwide partly due to an increase in consumption of diets high in fat. Obesity is known as a risk factor for developing Alzheimer’s disease (AD) later in life. Both obesity and AD are associated with cognitive deficits and experimental high-fat diets can impair memory in cognitively normal rodents but also worsen memory deficits in AD mouse models. What is still unclear is the molecular mechanisms behind the detrimental effects of a high-fat diet on memory and if sex can influence its effect. Data in this thesis demonstrated that compared to females, male control non-transgenic (Non-Tg) mice had earlier deficits in memory after a high-fat diet that were associated with hyperinsulinemia. However, female Non-Tg mice were more vulnerable to ultrastructural changes in mitochondria morphology and loss of synapses after 6 months of a high-fat diet, changes that were similar to those observed in control-fed female triple-transgenic mice (3xTgAD). Finally, the memory deficits observed after a high-fat diet in cognitively normal mice were not associated with obesity and adiposity, as treatment with resveratrol (RSV) an anti-obesogenic compound, attenuated body weight gain and adipose tissue but failed to reverse memory impairment. In control fed 3xTgAD mice, RSV rescued memory deficits. In all experiments a high-fat diet had no detectable effect on cognitive impairment in 3xTgAD mice. In conclusion, the present thesis demonstrates that the sex-dependent differences in the effect a high-fat diet on memory are likely due to hyperinsulinemia and mitochondrial impairment and do not depend on obesity phenotype. These results demonstrate the importance of gender when studying both obesity and AD and are relevant for future clinical trials.