No description available.

Thesis (PhD)--Stellenbosch University, 2013. / ENGLISH ABSTRACT: Exposure to food contaminates such as mycotoxins have been associated with a variety of animal and human diseases worldwide. In South Africa, maize is the most To further refine risk assessment in the socio-demographic heterogeneous population of South Africa, the development and evaluation of a sensitive and interactive model the Mycotoxin Risk Assessment Model (MYCORAM) proofed to be more sensitive compared to the classical probable daily intake (PDI). The development of the MYCORAM was based on mycotoxin distribution during dry milling of maize in milling fractions intended for human consumption which was superimposed on the maize intake profiles of the South African population. Although dry milling, including a degerming step, is an effective way to reduce mycotoxins, risk and exposure assessment are influenced by maize dietary intakes, gender and ethnicity. This became evident when considering FB dietary exposure in rural maize subsistence farming communities in the Eastern Cape Province, South Africa confirmed the vulnerability of this subpopulation to risk of fumonisin exposure. Specific maximum tolerated maximum levels (MTL) to safeguard these communities fall outside the international regulatory processes and need to be urgently addressed. With the complex nature of cancer development in mind, integration of basic science and nutritional epidemiology will be important to contribute to our understanding of the adverse effects of FB and to define relevant risk assessment parameters. important commercial grain crop not just economically but also as a local food commodity both commercially and in subsistence rural farming communities. In order to control and manage mycotoxin contamination in food, evidence-based risk assessment is needed that includes mechanistic and human exposure studies. From this perspective the current study was conducted and aimed in further unravelling fumonisin B1 (FB1) mycotoxin induced hepatocarcinogenesis via the disruption of the lipid metabolism. The study also critically evaluates aspects of human risk assessment due to its relevance and importance to food safety known to impact on food security. This entails mycotoxin distribution during maize dry milling and the assessment of mycotoxin exposure in the South African population and vulnerable rural communities at risk. Fumonisin B1 affects the integrity of biological membranes by altering key lipid and fatty acid parameter in plasma, microsomal, mitochondrial and nuclear subcellular membrane fractions in rat liver. Changes in the major lipid constituents entailing an increase in cholesterol (CHOL) and phosphatidylethanolamine (PE) whilst sphingomyelin (SM) and phosphatidylcholine (PC) tended to decrease. Isolated plasma membrane lipid rafts, from rat primary hepatocytes exposed to FB1 augments the intricate effects exerted on the lipid metabolism regarding CHOL, SM and PE. The disruption of lipid and fatty acid constituents, such as arachidonic acid and ceramide, are likely to be key determinants affecting growth regulatory signaling pathways relevant to the critical balance between cell proliferation and apoptosis during cancer promotion. These changes provide further evidence that FB1 induce cancer promotion by differential inhibition and/or stimulation process whereby a few resistant “initiated” hepatocytes proliferate in an environment where the growth of normal cells is inhibited. A specific lipogenic phenotype is effected by FB1 which is closely associated with cancer development and considered to occur via an epigenetic-type of mechanism. These effects are not adequately addressed in defining risk assessment parameters. / AFRIKAANSE OPSOMMING: Die blootstelling aan voedsel-kontaminante soos mikotoksienes word wêreldwyd met ‘n verskeidenheid van dierlike en menslike siektes geassosiseer. In Suid-Afrika word mielies as ‘n belangrike graanoes beskou, nie net vir die ekonomie nie maar ook as ‘n plaaslike voedselproduk beide kommersieel en vir bestaansboere in landelike gemeenskappe. Ten einde mikotoksien-kontaminasie van voedsel te kan beheer en bestuur, vereis bewys-gebaseerde risiko-evaluering wat insluit meganistiese en menslike blootstelling studies. Vanuit hierdie perspektief is die huidige studie uitgevoer en gemik op die verdere ontleding van die fumonisin B1 (FB1) mikotoksien geïnduseerde lewer-karsinogenese deur die ontwrigting van die lipiedmetabolisme. Die studie ondersoek terselfdetyd aspekte van menslike risiko-evaluering ingevolge die relevansie en belangrikheid hiervan in voedselveiligheid wat ook ‘n impak op voedselsekerheid sal maak. Dit sluit in die verspreiding van mikotoksiene gedurende die droëmaalproses van mielies en mikotoksien blootstelling in Suid-Afrika asook onder kwesbare landelike gemeenskappe. Fumonisin B1 beïnvloed die integriteit van biologiese membrane deur die modulasie van die belangrike lipied en vetsuur samestelling van plasma, mikrosomale, mitochondriale en kern subsellulêre membraan-fraksies in rot lewer. Veranderinge in die belangrike lipiedbestanddele, insluitende ‘n verhoging in cholesterol (CHOL) en phosphatidylethanolamine (PE), terwyl sphingomyelin (SM) en phosphatidylcholine (PC) geneig was om te verlaag. Geïsoleerde plasma membraan lipied vlotte (lipid rafts), vanaf primêre rot hepatosiete blootgestel aan FB1, versterk die ingewikkelde gevolge wat uitgeoefen word op die lipiedmetabolisme insluitende die voorgestelde veranderings in CHOL, SM en PE vlakke. Die versteuring van lipiede en vetsure soos aragidoonsuur (arachidonic acid) en ceramied kan beskou word as belangrike determinante wat inmeng in groei-regulerende seinbane verwant aan die kritiese balans tussen selgroei en seldood. Die versteurings verskaf verdere bewyse dat FB1 kanker bevorder deur ‘n seleksie proses wat onderskeidelike die onderdrukking en\of die stimulasie van ‘n paar weerstandige of geneties veranderde hepatosiete laat vermeerder in ‘n omgewing waar die groei van normale selle geïnhibeer word. Die spesifieke lipogeniese fenotipe wat FB1 versoorsaak hou ten nouste verband met kankerontwikkeling en die voorkoms van epigenetiese-soort meganismes word voorgestel. Hierdie oorsake word tans nie voldoende aangespreek tydens die bepaling van risiko-evaluerings limiete nie. Om risiko-bepaling verder te verbeter in die sosio-demografies heterogene populasie van Suid-Afrika, was die ontwikkeling en evalueering van ‘n sensitiewe en interaktiewe model, die “Mycotoxin Risk Assessment Model” (MYCORAM) meer doeltreffend vergeleke met die gewone waarskynlike daaglikse inname. Die ontwikkeling van die MYCORAM was gebaseer op die mikotoksien verspreiding tydens die droëmaalproses van mielies in fraksies wat vir menslike verbruik bedoel was tesame met mielie dieetinnames van die Suid-Afrikaanse populasie. Alhoewel, die droëmaalproses van mielies, insluitende die verwydering van die kiem doeltreffende maniere is om mikotoksienes te verminder, word risiko- en blootstellings evaluering beinvloed deur mielie dieetinnames, geslag en etnieseverbandskap. Hierdie was veral opmerklik gedurende blootstelling aan FB in die dieet van landelike mielie bestaansboer gemeenskappe in die Oos-Kaap van Suid- Afrika en bevestig hoe kwesbaar hierdie populasie is. Spesifieke maksimum toelaatbare vlakke om hierdie gemeenskappe te beskerm val buite die huidige internasionale regulatoriese prosesse en benodig dringende aandag. Met die ingewikkelde aard van kankerontwikkeling in gedagte, sal die integrasie van basiese wetenskappe en voedingsepidemiologie, ‘n belangrik bydrae lewer tot die kennis van die negatiewe eienskappe van FB om toepaslike risiko-evaluerings limiete te kan bepaal.

published_or_final_version / Biological Sciences / Master / Master of Philosophy

No description available.

The purpose of this study was to determine if surgically-induced menopause in younger women affects substrate utilization during submaximal exercise while controlling for other potential confounds. METHODS: Thirteen untrained female subjects (33-50 years old) were recruited: oophorectomized (Group O = 5) and premenopausal controls (Group C = 8). Two separate visits included: body composition and maximal treadmill exercise test; followed by substrate utilization via open-circuit spirometry during 45 minutes of treadmill walking at 50% VO2max. RESULTS: When controlling for multiple variables affecting whole-body substrate utilization (age, VO2max, physical activity, body composition, fasting glucose, menstrual phase and diet), there was no difference in substrate utilization between pre- and postmenopausal women as measured by respiratory exchange ratio (RER) (0.83 ± 0.04 v 0.84 ± 0.03, p=0.47). CONCLUSIONS: Menopausal status does not appear to have an effect on substrate utilization during submaximal exercise in younger women. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2015. / FAU Electronic Theses and Dissertations Collection

Introdução: Os efeitos do treinamento físico sobre o metabolismo de lípides têm sido bastante estudados, mas a situação diametralmente oposta, qual seja, a de pacientes acamados sob cuidados prolongados, tem sido pouco investigada. A avaliação de possíveis impactos derivados da imobilização é importante, pois o período de restrição ao leito pode gerar fatores de risco aterogênicos. Outro ponto relevante é a concentração e o aspecto funcional da HDL, que é fator de proteção anti-aterogênico e estudos têm mostrado a concentração diminuída em indivíduos sedentários. Objetivo: Investigar os efeitos da imobilização prolongada sobre o perfil de lípides, apolipoproteínas e a transferência de lípides para a HDL em pacientes acamados. Métodos: Foram estudados 23 pacientes acamados por um período maior que 90 dias de internação no Hospital Auxiliar de Suzano do Hospital das Clínicas da Faculdade de Medicina da USP. Foram avaliados o perfil lipídico, a concentração das apolipoproteínas, CETP, LCAT e LDL oxidada. No ensaio de transferência de lípides, as amostras de plasma foram incubadas com a nanopartícula artificial marcada com 3H-éster de colesterol, 14C-fosfolípides, 3H-triglicérides e 14C-colesterol livre. A quantificação da transferência de lípides da nanopartícula foi feita após a precipitação da fração não HDL. Os dados dos pacientes acamados foram comparados com os obtidos de 26 voluntários sedentários saudáveis, pareados por idade e sexo. Resultados: A média de internação dos acamados foi de 817 dias. As concentrações de colesterol não-HDL (148 ± 36 vs 125±40 mg/dL, p<0,05), LDL-C (124±31 vs 96±36 mg/dL, p<0,01), HDL-C (45±10 vs 36±13 mg/dL, p<0,01) foram menores no grupo acamado, enquanto que os triglicérides foram iguais entre os grupos. A apo A-I (134±20 vs 111±24 mg/dL) foi menor nos acamados (p<0,01), e a apo B não apresentou diferença entre os grupos. A LDL oxidada (53±13 vs 43±12 mg/dL) foi menor no grupo acamado (p<0,05), enquanto que a CETP e LCAT não diferiu entre os grupos. As transferências para HDL de éster de colesterol (6,24±1,1% vs 4,80±1,2%), colesterol livre (4,04±1,1% vs 3,05±1,1%), fosfolípides (19,06±1,3% vs 17,32±2,0%) e triglicérides (3,65±0,7% vs 3,06±0,6%) estavam diminuídas nos acamados comparado ao grupo sedentário (p<0,01). Conclusões: O sedentarismo extremo dos pacientes acamados afetou a concentração do HDL-C, apo A-I e as transferências lipídicas da nanopartícula para HDL. Mesmo a menor atividade física exercida no dia-a-dia dos sedentários pode ser determinante na concentração e no metabolismo da HDL. Apesar da menor concentração do LDL-C e os triglicérides não serem diferentes dos sedentários, o status de HDL mostrou-se alterado nos acamados. Devido à importante função anti-aterogênica da HDL, essas alterações metabólicas devem ser um motivo de atenção adicional na assistência a esses pacientes para a prevenção de eventos cardiovasculares. / Introduction: The effects of physical training on lipid metabolism have been deeply studied, but the diametrically opposite situation such as the long-term care bedridden patients, has been little investigated. The evaluation of immobilization impacts is important, because the bedridden period may take to atherogenic risk factors. Another relevant point is the concentration and functional aspects of HDL, that is an anti-atherogenic protection factor and studies have shown lower concentration in sedentary subjects. Objective: To investigate the effects of long-term immobilization on lipid profile, apolipoproteins and lipid transfer to HDL in bedridden patients. Methods: Twenty-tree bedridden patients under a period over than 90 days from the Auxiliary Hospital of the University of São Paulo Medical School in the city of Suzano, state of São Paulo were selected for the study. The lipid profile, apolipoproteins, CETP, LCAT and oxidized LDL concentration were evaluated. In the lipid transfer assay, the plasma samples were incubated with an artificial nanoparticle labeled with 3H-cholesteryl-esters, 14C-phospholipids, 3H-triglycerides and 14C-unesterified cholesterol. The lipids transferred from nanoparticle to HDL were quantified in the supernatant after chemical precipitation of non-HDL fractions. Data from bedridden patients were compared with those obtained from 26 healthy sedentary volunteers, paired for age and sex. Results: The average of hospitalization period of the bedridden was 817 days. The concentration of non-HDL cholesterol (148±36 vs 125±40 mg/dL, p<0.05), LDL-C (124±31 vs 96±36 mg/dL, p<0.01), HDL-C (45±10 vs 36±13 mg/dL, p<0.01), were lower in bedridden group, whereas the triglycerides were equal between the groups. The apo A-I (134±20 vs 111±24 mg/dL) was lower in bedridden (p<0.01), and the apo B was not different between the groups. The oxidized LDL (53±13 vs 43±12 mg/dL) was lower in bedridden group (p<0.05), whereas the CETP and LCAT was not different between the groups. The lipid transfer to HDL of cholesteryl-esters (6.24±1.1% vs 4.80±1.2%), unesterified cholesterol (4.04±1.1% vs 3.05±1.1%), phospholipids (19.06±1.3% vs 17.32±2.0%) and triglycerides (3.65±0.7% vs 3.06±0.6%) were decreased in bedridden patients compared to sedentary group (p<0.01). Conclusions: The extreme sedentary of bedridden patients affected the HDL-C and apo A-I concentration and the lipid transfer from nanoparticle to HDL. Even the low levels of physical activity exerted in the day-to-day life of sedentary subjects can be determinants of HDL concentration and metabolism. Despite their lower LDL-C and the triglycerides not different from sedentary subjects, the HDL status was clearly further altered in the bedridden. Due to the important anti-atherogenic functions of HDL, those metabolic alterations should be an additional matter of concern in the management of those patients to prevent cardiovascular events.

Type 2 diabetes is a metabolic disease marked by an abnormally high level of glucose (sugar) in the blood. Type 2 diabetes is now reaching an epidemic level with more than 30 million adults in the United States afflicted and 1.5 million new cases documented every year. Type 2 diabetes is linked with obesity, heart disease, hypertension, and liver disease, and individuals with type 2 diabetes are at an increased risk for heart failure, stroke, blindness, kidney failure, and amputation. According to the Centers for Disease Control and Prevention, more than $245 billion was spent in the United States in 2012 on medical expenses related to diabetes and despite that, nearly a quarter of a million Americans are losing their lives due to this disease each year. Indeed, type 2 diabetes is one of the leading causes of death in the United States and worldwide; its prevalence has almost doubled in the last 35 years, from 4.7% of the total population in 1980 to 8.5% in 2014. Consequently, more than 400 million people are at high risk for severe health problems and complications, poor quality of life, and early death. Research such as the Diabetes Prevention Program (DPP), the Finnish Diabetes Prevention Study (DPS), the Vesterbotten Intervention Program (VIP), and the Diabetes Prevention Program Outcome Study (DPPOS) suggests that type 2 diabetes can be delayed, and even prevented, with a lifestyle behavioral modification program that includes healthy eating and/or exercise. Therefore, focus has been shifted from management to prevention. An early manifestation of dysfunction in the progression of type 2 diabetes is insulin resistance, a metabolic impairment associated with obesity. Indeed, it is estimated that ~90% of people with type 2 diabetes also are obese. The link between insulin resistance and obesity is well-established; however, the mechanistic basis(es) underpinning this link is/are still debated with multiple candidate molecules, systems, and pathways potentially involved. One theory that has gained traction in recent years suggests that type 2 diabetes, and the insulin-resistant state that predates it, are rooted in dysfunctional lipid metabolism (i.e., a reduced capacity to use lipid for energy production in circumstances where lipid would be preferred, such as in the basal fasting condition, after a high-fat meal, and during light- and moderate-intensity exercise). However, there are conflicting findings regarding the degree to which the ability to oxidize lipid during these circumstances is compromised for individuals with the overweight/obesity that is associated with the disease progression. The reason(s) for this ambiguity is/are unclear but might have to do with a number of factors that were poorly controlled when substrate selectivity (i.e., lipid vs. carbohydrate oxidation rates) were compared between normal-weight individuals and those with the overweight/obese condition. These include: (a) acute energy balance and macronutrient composition of the diet; (b) the intensity and duration of the exercise bout; and (c) subject characteristics including the amount of muscle tissue they possess, their cardiorespiratory fitness level, and, perhaps most importantly, their insulin-sensitivity state. The purpose of this dissertational work is to: (a) help to resolve this ambiguity by identifying the degree to which conflicting results that have been reported might be explained by factors that were left unaccounted for and/or inadequately controlled in previous research; and (b) compare substrate selectivity in normal-weight individuals and those with the overweight/obesity condition during a physiologically-equivalent exercise challenge with the aforementioned factors rigidly controlled.

A doença arterial coronária (DAC) tem sido a maior causa de morte por doenças nos paises ocidentais. Existem vários fatores responsáveis pela iniciação e progressão desta doença - fatores ambiental ou genético. Muitos fatores de risco para a DAC estão relacionados a alterações do metabolismo lipídico, como acúmulo de lipoproteína de baixa densidade (LDL) no plasma seguida da deposição da lipoproteína na parede arterial. Recentemente, foi demonstrado que uma emulsão rica em colesterol que se assemelha a composição lipídica da LDL liga-se aos receptores que captam a lipopoteína da circulação e internalizam-na no citoplasma. A emulsão, denominada LDE, é feita sem proteína mas quando injetada na circulação sangüínea adquire várias apolipoproteínas (apo) como apo E que pode ser reconhecida pelo receptor de LDL. A apo E tem mais afinidade pelo receptor do que a apo B, a apo que liga a LDL nativa ao receptor. No presente estudo, para esclarecer o processo metabólico que a LDL enfrenta no plasma e o processo de captação da lipoproteína pelos vasos, a LDE marcada com colesterol livre-3H (CL) e oleato de colesterol-14C (CE) foi injetada em 10 pacientes portadores de DAC (57 ± 2,2 anos) submetidos à cirurgia de revascularização miocárdica. Amostras de sangue foram coletadas em intervalos de tempo pré-determinados. A radioatividade presente nas alíquotas de plasma foi determinada por cintilação líquida e a taxa fracionai de remoção (TFR) calculada por análise compartimental. Os fragmentos dos enxertos de aorta, artérias radial e torácica interna, veia safena e pericárdio removidos durante o procedimento cirúrgico foram coletados para extração lipídica, separação por cromatografia de camada delgada e quantificação radioativa. A remoção plasmática do CE da LDE foi similar a do CL da LDE (0,0617 ± 0,0087 vs 0,0528 ± 0,0123, p = 0,5635, respectivamente). A captação do CL da LDE foi maior do que a do CE da LDE na aorta (21% vs 3,1%, p = 0,0049), artéria torácica interna (10,3% vs 2%, p = 0,0007) e veia safena (8% vs 2%, p = 0,0326). Nos fragmentos de artéria radial (14,4% vs 4,3%) e de pericardio (2,2% vs 0,3%), a captação do CL tendeu ser maior do que a captação do CE, porém não foi estatisticamente confirmado. A taxa de esterificação foi maior nos fragmentos de aorta, de toráxica interna e de pericárdio do que nos fragmentos de veia safena (p < 0,001). Concluindo, a LDE foi captada pelos vasos e pericardio em quantidades concideráveis e a captação do CL pelos tecidos foi maior do que a do CE. Ainda, a taxa de esterificação do colesterol livre foi mais intensa nos fragmentos de aorta e torácica interna do que nos fragments de veia safena. / Coronary artery disease (CAD) is the main mortality cause in western countries. There are many factors responsible for the onset and progression of the disease - either environmental or genetic. Many risk factors in CAD are related with disorders of lipid metabolism, such as accumulation of low-density lipoprotein (LDL) in the plasma with deposition of the lipoprotein in the arterial wall. Recently, it was shown that a cholesterol-rich emulsion that mimics the lipid composition of LDL binds to the receptors that take-up the lipoprotein from the circulation and internalizes it into the cytoplasm. The emulsion, denominated LDE, is made without protein but when injected into the bloodstream it picks-up several apolipoproteins (apo) such as apo E that can be recognized by the LDL receptor. Apo E has even more affinity for the receptor than apo B, the apo that binds native LDL to the receptors. In the current study, aiming to clarity the metabolic processes that LDL undergoes in the plasma and the process of lipoprotein uptake by the vessels, LDE labeled with 3H- Cholesterol (CL) and 14C-Cholesteryl Oleate (CE) was injected into 10 CAD patients (57 ± 2,2 yr.) scheduled to be submitted to myocardial revascularization surgery. Blood samples were collected over 24 hour at pre-established intervals. Radioactivity present in plasma aliquots was determined in a scintillation solution and the fractional clearance rate (FCR) was calculated by compartimental analysis. The gratt\'s fragments of aortic, radial, internal thoracic arteries, safenous vein and pericardium discarded during the surgical procedure were collected for lipid extraction, separation by thin layer chromatography and radioactive counting. The removal from plasma of the LDE CE was similar to that of the LDE CL (0,0617 ± 0,0087 vs 0,0528 ± 0,0123, p = 0,5635, respectively). The uptake of LDE CL was greater than that of LDE CE in aorta (21% vs 3,1%, p = 0,0049), internal toracic artery (10,3% vs 2%, p = 0,0007) and safenous vein (8% vs 2%, p = 0,0326). In the radial artery (14,4% vs 4,3%) and pericardium (2,2% vs 0,3%) fragments, the CL uptake also tended to be greater than that of CE, but this was not statistically confirmed. The esterification rate was greater in the aorta, internal thoracic artery and pericardium fragments than in safenous vein fragments (p < 0,001). In conclusion, LDE was taken-up by vessels and pericardium at considerable amounts and LDE CL uptake by those tissues was greater than that of CE. In addition, the cholesterol esterification rate was more intense in the aorta and internal thoracic artery than in venous fragments.

Abstract not available

Eight men were studied before and after an endurance training program to assess changes in the lipid metabolism of skeletal muscle. Training consisted of eight weeks of outdoor running with daily mileage increasing from one-half mile at the onset to four miles at the eighth veekof training. In vitro analyses of palmityl-CoA oxidation and the activities of carnitine palmityltransferase (CPT) and succinate dehydrogenase (SDH) were observed in muscle samples obtained by needle biopsy from the gastrocnemius before and after training.The subjects' maximal oxygen uptake increased from 3.47 1/min (± 0.26) to 3.82 1/min (± 0.21) as a result of the training. At the same time, muscle CPT and SDH increased (P <.01) 23% and 36%, respectively. The muscle's capacity to oxidize palmityl-CoA increased from 6.36 nmoles/min/g to 13.32 nmoles/min/g, a significant increase of 116% (P <.01).This investigation supports earlier findings with rats and emphasizes the influence of chronic endurance exercise on lipid metabolism in the skeletal muscle of man.Ball State UniversityMuncie, IN 47306