The objectives were to 1) conduct a meta-analysis to assess the association between alpha-linolenic acid (ALA) and prostate cancer; 2) analyze a trial of ALA on coronary heart disease with PSA as a post hoc outcome; 3) assess the effect of trial serum and also ALA directly on LNCaP cell growth. 1) The ALA meta-analysis of prospective and case-control studies showed no overall effect on prostate cancer. However, removal of one study from the analysis of prospective studies changed the result to a significant protective effect (RR=0.91; 95%CI:0.83,0.99). 2) No significant treatment difference was seen in the change in PSA in the randomized controlled trial. 3) The ALA treatment serum from the clinical trial did not affect LNCaP cell growth. However, ALA decreased LNCaP cell growth in a dose dependent manner when added to cell culture. The results provide no positive evidence for an effect of ALA on prostate cancer.

The objectives were to 1) conduct a meta-analysis to assess the association between alpha-linolenic acid (ALA) and prostate cancer; 2) analyze a trial of ALA on coronary heart disease with PSA as a post hoc outcome; 3) assess the effect of trial serum and also ALA directly on LNCaP cell growth. 1) The ALA meta-analysis of prospective and case-control studies showed no overall effect on prostate cancer. However, removal of one study from the analysis of prospective studies changed the result to a significant protective effect (RR=0.91; 95%CI:0.83,0.99). 2) No significant treatment difference was seen in the change in PSA in the randomized controlled trial. 3) The ALA treatment serum from the clinical trial did not affect LNCaP cell growth. However, ALA decreased LNCaP cell growth in a dose dependent manner when added to cell culture. The results provide no positive evidence for an effect of ALA on prostate cancer.

In this study, pharmaceutical-grade and food-grade linker-based lecithin self-emulsifying delivery systems (SEDS) were developed with a combination of lipophilic and hydrophilic linkers. These additives at suggested concentrations are safe for pharmaceutical and food applications. The ratio of surfactant lecithin and linkers in these systems was optimized to develop surfactant in oil preconcentrates. The preconcentrates containing different surfactant concentrations and oil were diluted with fed state simulated intestinal fluid to produce pseudo-ternary phase diagrams and to identify the formulations that produced self-emulsifying or self-microemulsifying delivery systems. Optimal SEDS preconcentrates were evaluated using a dialyzer model to simulate intestinal uptake. An uptake of 39.6 mg/cm2 for the pharmaceutical-grade SEDS was obtained within 72 minutes, which promises substantial improvement in the bioavailability of hydrophobic actives. The optimal uptake of 12.2 mg/cm2 for food-grade SEDS suggests enhancement in the bioavailability of omega-3 fatty acids.

Thesis (Ph. D.)--University of Oklahoma. / Bibliography: leaves 155-161.

Thesis (Ph.D.)--Flinders University, School of Medicine, Dept. of Gastroenterology. / Typescript bound. Includes bibliographical references: (leaves 215-233) Also available in an electronic version via the Web.

Η χρήση θαλασσίου ύδατος για ψύξη μηχανών σε βιομηχανικές εγκαταστάσεις και σταθμούς παραγωγής ηλεκτρικής ενέργειας επιτυγχάνεται μέσω εγκαταστάσεων άντλησης θαλασσίου ύδατος. Οι δεξαμενές αυτών των εγκαταστάσεων πρέπει να σχεδιάζονται σύμφωνα με τις οδηγίες του Hydraulic Institute (1998) ώστε να αποφεύγονται ανεπιθύμητα φαινόμενα που επηρεάζουν την απόδοση και τη διάρκεια ζωής των αντλιών. Τέτοια φαινόμενα είναι οι στρόβιλοι, υποβρύχιοι και ελεύθερης επιφάνειας, η υπερβολική προ-ελίκωση της ροής ανάντη κάθε αντλίας, η ανομοιομορφία της ροής στην πτερωτή κάθε αντλίας, οι υπερβολικές χρονικές διακυμάνσεις της ταχύτητας και της ελίκωσης και η συμπαράσυρση αέρα και η δημιουργία φυσαλίδων. Στην παρούσα διατριβή εξετάζεται η δεξαμενή της εγκατάστασης άντλησης θαλασσίου ύδατος μέσω δύο αντλιών που βρίσκεται στον υπό κατασκευή Θερμοηλεκτρικό Σταθμό Φυσικού Αερίου της Δ.Ε.Η. στο Αλιβέρι. Σκοπός της διατριβής είναι η μελέτη της ροής στη συγκεκριμένη δεξαμενή ως προς την κυκλοφορία του ύδατος (γραμμές ροής και τύρβη), τις διατμητικές τάσεις στα τοιχώματα των αγωγών και της δεξαμενής, την προ-ελίκωση της ροής που προσεγγίζει την αντλία και την ανομοιομορφία της στο επίπεδο της πτερωτής της αντλίας, καθώς και η συμπεριφορά της ελίκωσης της ροής στους αγωγούς άντλησης. Η διερεύνηση της ροής γίνεται για αρκετές καταστάσεις λειτουργίας της δεξαμενής ως προς το βάθος ύδατος και τον αριθμό θυροφραγμάτων και αντλιών. Η γεωμετρία του υπολογιστικού πεδίου, το υβριδικό μη-δομημένο πλέγμα και η αριθμητική επίλυση των εξισώσεων ροής πραγματοποιήθηκαν με τα προγράμματα Design Modeler, Meshing και Fluent του ANSYS. Ειδικότερα για το Fluent επιλέχθηκαν τα μοντέλα τύρβης k-ε και k-ω. Τα αποτελέσματα αναλύονται και συγκρίνονται με τα πειραματικά του υδραυλικού μοντέλου (Dimas & Vouros, 2012) σε κλίμακα 1:8.7 κατά Froude. Στις περιπτώσεις όπου είναι ανοικτό μόνο το ένα θυρόφραγμα, έχουμε κυκλοφορία της ροής μεταξύ των δύο θαλάμων των αντλιών κυρίως κοντά στην ελεύθερη επιφάνεια του ύδατος. Στις περιπτώσεις όπου λειτουργεί μόνο η μία αντλία, έχουμε και έντονη κυκλοφορία στο θάλαμο της δεξαμενής που δεν γίνεται άντληση. Η φορά της ελίκωσης της ροής στον αγωγό συμπίπτει στις περισσότερες περιπτώσεις με αυτήν του υδραυλικού μοντέλου. Η γωνία ελίκωσης θ, η οποία υπολογίστηκε με βάση το μέτρο της εφαπτομενικής ταχύτητας, ήταν μεγαλύτερη στο μεγάλο βάθος ύδατος και διαφορετική σε όλες τις περιπτώσεις από αυτήν που μετρήθηκε στο υδραυλικό μοντέλο. / -

El documento digital no refiere un asesor / Publicación a texto completo no autorizada por el autor / Evalúa semillas provenientes de tres orígenes, dos localidades de la sierra ecuatoriana, Colta y Cotacachi y una semilla en presentación comercial como Testigo; la evaluación se realiza en dos fases de análisis del perfil nutricional. En la primera fase se evalúa, de forma preliminar, la semilla de las dos localidades y, en una fase posterior, se aplican pruebas experimentales a la semilla de los tres orígenes con la evaluación de la concentración de grasa, contenido de ácidos grasos, concentración de proteína, minerales, peso y humedad para establecer comparaciones y definir la semilla de interés según los objetivos de estudio. El primer objetivo, se basa en la caracterización de la grasa de la semilla de los tres orígenes. El segundo, en la identificación de la relación entre el contenido de omega-3 y el origen de la semilla y, el tercero, en la selección del material de chía más abundante en omega-3 para la recomendación de su cultivo y aprovechamiento industrial en la línea de panificación. Los ácidos grasos encontrados en la semilla de los tres orígenes son: linolénico (omega-3), linoleico (omega-6) y oleico (omega-9) y, entre los saturados, los ácidos palmítico y esteárico. La relación entre el contenido de omega-3 y el origen de la semilla se fundamenta en el factor temperatura de la zona de cultivo, donde, el incremento de la temperatura ambiental incide en el incremento del contenido de ácidos grasos insaturados; la semilla proveniente de Cotacachi, muestra el contenido más alto en omega-3 con 66.05 % y la semilla Testigo el menor, 62.73 %. Finalmente, la aplicación de la semilla de chía, según análisis de la literatura revisada, representa una alternativa para el desarrollo de productos farináceos de características nutricionales, organolépticas y tecnológicas superiores a los productos elaborados con base en ingredientes convencionales en la citada línea de producción. / Tesis

A menopausa é identificada como uma fase onde é desencadeada uma série de distúrbios fisiológicos e metabólicos devido à queda brusca dos hormônios sexuais, que desempenham funções importantes como o controle dos ciclos ovulatórios e antioxidantes naturais. Com o hipoestrogenismo ocorre uma variedade de desordens que vão desde aumento de peso e mudanças no humor até doenças cardiovasculares e neurodegenerativas. Muitas destas doenças estão relacionadas com o estresse oxidativo. A reposição hormonal com estrogênio vem sendo repensada devido seus possíveis efeitos colaterais. A suplementação com antioxidantes de fontes variadas é uma alternativa para amenizar os sintomas da menopausa, melhorando assim a qualidade de vida das mulheres que se encontram nesta fase. Este estudo teve por finalidade avaliar a resposta do estresse oxidativo no coração de ratas Wistar ovariectomizadas, após suplementação com ácidos graxos (AG) eicosapentaenóico (EPA) e docosahexaenóico (DHA), provenientes do ômega-3 e o ácido lipoico (AL), em um período de 3 meses. Foram realizadas as análises de biomarcadores, quantificando antioxidantes enzimáticos e não enzimáticos, bem como marcadores de danos em lipídeos e proteínas com a quantificação de Malondialdeído (MDA) e identificação de grupos carbolinados, respectivamente. Como resultados deste estudo, a ovarectomia gerou alterações no perfil oxidativo das ratas. A suplementação com EPA, DHA e AL demonstrou a recuperação dos níveis normais de consumo de H2O2 (catalase, peroxirredoxinas), da atividade de glutationa S-transferase (GST), superóxido dismutase (SOD) e glutationa total (GSHt) nas ratas tratadas. A atividade da glutationa peroxidase (GPx) retornou aos níveis normais com a suplementação com DHA. Já o tratamento com EPA foi mais efetivo para o aumento da Vit E, quando comparado ao grupo controle. Os danos em proteínas foram menores em todos os grupos suplementados. Os danos em lipídios foram menores no grupo tratado com AL, quando comparados ao grupo SHAM (grupo controle).Os resultados sugerem um efeito protetor do ácido lipoico e do ômega-3 no coração de ratas ovariectomizadas em relação ao dano oxidativo. / Menopause is identified as a phase where triggers a series of physiological and metabolic disorders due to the sharp drop of sex hormones, which play important functions like controlling the ovulatory cycles and natural antioxidants. With hypoestrogenism occurs a variety of disorders ranging from weight gain and changes in the mood to cardiovascular and neurodegenerative diseases. Many of these diseases are associated with oxidative stress. Hormone replacement with estrogen is being rethought because of their possible side effects. Supplementation with antioxidants from different sources is an alternative to alleviate menopausal symptoms, thus improving the quality of life of women who are at this stage. This study aimed to evaluate the response of oxidative stress in the heart of Wistar ovariectomized rats, after supplementation with fatty acids (FA) eicosapentaenoic (EPA) and docosahexaenoic acid DHA), derived from omega-3 and lipoic acid (LA), in a 3 month period. The biomarker analyzes were performed by quantifying enzymatic and non-enzymatic antioxidants and damage markers in lipids and proteins with the quantification of Malondialdehyde (MDA) and identifying carbonylated groups, respectively. As a result of this study, ovariectomy generated changes in oxidative profile of rats. The supplementation with EPA, DHA and LA showed recovery of normal levels of H2O2 consumption (catalase peroxiredoxins), glutathione activity S-transferase (GST), superoxide dismutase (SOD), and total glutathione (GSHt) in treated rats. The activity of glutathione peroxidase (GPx) returned to normal levels with supplementation with DHA. Since treatment with EPA was more effective for increasing vitamin E compared to the control group. Protein damage were lower in all supplemented groups. The damage in lipids were lower in the group treated with LA when compared to SHAM group (group control). The results suggest a protective effect of lipoic acid and omega-3 in the heart of ovariectomized rats compared to oxidative damage.

Evidências crescentes na literatura demonstram que a fisiopatologia da ansiedade e transtornos relacionados é multifatorial, envolvendo a hiperatividade glutamatérgica, o estresse oxidativo e a neuroinflamação. Na primeira parte deste trabalho, através de uma revisão da literatura, mostramos que a N-acetilcisteína (NAC), agomelatina e os ácidos graxos ômega-3 são os principais agentes com mecanismo de ação multialvo envolvendo a modulação da hiperatividade glutamatérgica, do estresse oxidativo e da neuroinflamação que demonstram efeitos ansiolíticos tanto em estudos pré-clínicos quanto em ensaios clínicos. Os resultados dos ensaios clínicos são geralmente preliminares, mas revelam efeitos ansiolíticos promissores e um bom perfil de segurança e tolerância aos efeitos adversos desses agentes. A NAC, a agomelatina e os ácidos graxos ômega-3 mostram efeitos benéficos em condições clínicas relacionadas a ansiedade nas quais os ansiolíticos disponíveis atualmente apresentam eficácia modesta, sendo considerados candidatos promissores a ansiolíticos inovadores, efetivos e bem tolerados pelos pacientes. Mostramos também que a NAC possui efeitos ansiolíticos em camundongos nos testes de campo aberto, claro/escuro, placa-perfurada, interação social e hipertermia induzida por estresse, tanto após o tratamento agudo quanto subagudo (4 dias). Esses resultados fornecem evidências adicionais para sustentar a validade dos ensaios clínicos com NAC no contexto dos transtornos de ansiedade, destacando-se o perfil de segurança de uso da NAC em longo prazo em comparação com ansiolíticos como o diazepam. A NAC é um fármaco seguro, de baixo custo e que demonstra benefícios em outras condições psiquiátricas que frequentemente se apresentam em comorbidade com os transtornos de ansiedade. / Increasing evidence in the literature demonstrates that the pathophysiology of anxiety and related disorders is multifactorial, involving glutamatergic hyperactivity, oxidative stress, and neuroinflammation. In the first part of this work, through a review of the literature, we showed that N-acetylcysteine (NAC), agomelatine and omega-3 fatty acids are the main agents with multitarget mechanism of action involving the modulation of glutamatergic hyperactivity, oxidative stress, and neuroinflammation that demonstrate anxiolytic effects in both preclinical studies and clinical trials. Clinical trials data are generally preliminary but show promising anxiolytic effects and an adequate safety profile and tolerance to adverse effects. NAC, agomelatine and omega-3 fatty acids show beneficial effects under clinical conditions related to anxiety in which available anxiolytics show moderate efficacy, and are considered promising candidates for innovative, effective and well tolerated anxiolytic agents by patients. We also showed that NAC has anxiolytic effects in mice in the open field, light/dark, hole-board, social interaction and stress-induced hyperthermia tests, either after acute or subacute treatment (4 days). These results provide additional evidence to support the validity of NAC clinical trials in the context of anxiety disorders, highlighting the long-term safety profile of NAC use compared to anxiolytics as diazepam. NAC is a safe, low-cost agent that demonstrates benefits in other psychiatric conditions that often present in comorbidity with anxiety disorders.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Western diet has undergone major changes in recent decades, mainly due to the large consumption of processed foods and fast foods, which contains a large proportion of fats rich in trans fatty acids (TFA). Polyunsaturated fatty acids (PUFA) are essential components of the neuronal membranes, and the main PUFAs are the omega-3 series (n-3) and omega 6 (n-6), which are obtained solely from the diet. Trans fatty acids (TFAs) can inhibit the activity of enzymes such as desaturases and elongases, and also compete with PUFA for incorporation into neuronal membranes, modifying its fluidity and affecting physiological functions in neurochemical brain. The quality of fat consumed during periods of pregnancy and lactation determines a significant transfer of PUFA and TFA through the placenta and breast milk. Different mechanisms related to the change in composition of fatty acids can cause behavioral changes which can especially be reflected on dopaminergic neurotransmission, thus increasing anxiety and hedonia, which may exacerbate the additive effect of psychostimulant drugs. Adolescence is the period in which there is a great novelty seeking, which increases the likelihood for early experiences that may culminate in addition. The protocol conditioned place preference (CPP) is a widely used animal model for understanding the mechanisms involved in the abuse of psychoactive drugs, also serving as a research tool, enabling the prevention and/or treatment of addiction. The aim of this study was to evaluate the influence of supplementation of different fats rich in n-3 fatty acids (fish oil-FO), n-6 (soybean oil-SO) and trans fatty acids-TFA (hydrogenated vegetable fat-HVF) since pre-conception, pregnancy and lactation, and maintained until adolescence on anxiety parameters and preference to amphetamine (AMPH) in young rats, which were evaluated with analyzes of cerebral oxidative status. During 6 weeks, 24 female Wistar rats were supplemented with SO, FO and HVF, comprising the periods from conception, pregnancy until the end of breastfeeding. After weaning, only 1 male puppy from each litter was separated and kept with the original supplementation until 40 days of age when they were subjected to the conditioning protocol (8 days) with AMPH to conduct behavioral and biochemical tests. HVF increased conditioned place preference by AMPH and showed anxiety-like symptoms during withdrawal, indicating a greater potential for abuse in this experimental group. The HVF supplementation during development and growth was also associated with higher oxidative damage and reduced antioxidant activity, while the FO supplemented group showed lower protein carbonyls. This study showed the deleterious influence of consumption of TFA during the perinatal period and during development, which can be evidenced by symptoms especially preference at psychostimulants, anxiety and oxidative damage in the brain. / A dieta ocidental sofreu grandes modificações nas últimas décadas, principalmente em decorrência do grande consumo de alimentos industrializados e fast foods, que contém uma grande proporção de gorduras ricas em ácidos graxos trans (AGT). Ácidos graxos poliinsaturados (AGPI) são componentes essenciais nas membranas neuronais, sendo que os principais AGPI são os da série ômega-3 (n-3) e ômega-6 (n-6), os quais são obtidos exclusivamente da dieta. Os ácidos graxos trans (AGT) podem inibir a atividade de enzimas como as dessaturases e elongases, e também competir com os AGPI pela incorporação nas membranas neuronais, modificando sua fluidez e afetando as funções fisiológicas neuroquímicas cerebrais. A qualidade das gorduras consumidas durante os períodos de gestação e lactação determina uma significativa transferência de AGPI e AGT através da placenta e do leite materno. Diferentes mecanismos relacionados à alteração da composição dos AG podem provocar alterações comportamentais, as quais podem ser especialmente refletidas sobre a neurotransmissão dopaminérgica, aumentando assim a ansiedade e a hedonia, os quais podem exacerbar o efeito aditivo de drogas psicoestimulantes. A adolescência é o período em que há grande busca por novidades, o que aumenta a probabilidade para o início de experiências que podem culminar em adição. O protocolo de preferência condicionada de lugar (PCL) é um modelo animal bastante utilizado para a compreensão dos mecanismos envolvidos no abuso de drogas psicoativas, servindo também como uma ferramenta de estudos que permitam a prevenção e/ou tratamento da adição. O objetivo deste estudo foi avaliar a influência da suplementação de diferentes gorduras ricas em ácidos graxos n-3 (óleo de peixe-OP), n-6 (óleo de soja-OS) e ácidos graxos trans-AGT (gordura vegetal hidrogenada-GVH) desde o período pré-concepcional, gestação e lactação, e mantidas até a adolescência sobre parâmetros de ansiedade e de preferência à anfetamina (ANF) em ratos jovens, os quais foram avaliados em conjunto com análises do status oxidativo cerebral. Durante 6 semanas, 24 ratas Wistar adultas foram suplementadas com OS, OP e GVH, compreendendo os períodos desde a concepção, prenhez até o final da amamentação. Após o desmame, apenas 1 filhote macho de cada ninhada foi separado e mantido com a mesma suplementação da projenitora até atingir 40 dias de idade, quando foram submetidos ao protocolo de condicionamento (8 dias) com ANF a fim de conduzir os testes comportamentais e bioquímicos. GVH aumentou a preferência de lugar condicionado por ANF e apresentou sintomas de ansiedade durante a abstinência, indicando um maior potencial de abuso neste grupo experimental. A suplementação de GVH durante o desenvolvimento e crescimento também foi associada aos maiores danos oxidativos e reduzida atividade antioxidante, enquanto o grupo suplementado com OP mostraram menores níveis de proteína carbonil. Este estudo permitiu observar a influência deletéria do consumo de AGT durante o período perinatal e durante o desenvolvimento, a qual pode ser especialmente evidenciada através dos sintomas de preferência à psicoestimulantes, ansiedade e danos oxidativos no cérebro.