A lactoferrina bovina, descoberta em 1939, é uma glicoproteína que se liga reversivelmente a dois íons férricos, sendo capaz de seqüestrá-los de certos patógenos ou do meio, promovendo redução do crescimento microbiano ou se ligar as suas paredes celulares resultando na permeabilização. A lactoferrina vem ganhando notoriedade nas pesquisas, pois investigações têm descrito sua atividade in vitro frente a diversos microrganismos. Em razão desta propriedade, a mesma poderia ter aplicação nas indústrias cosmética e alimentícia, como um conservante natural. Embora alguns conservantes já estejam consagrados na literatura, os mesmos têm sido relacionados com o desencadeamento de reações alérgicas e de sensibilização, motivando a procura do conservante ideal. O objetivo deste trabalho foi avaliar a utilização da lactoferrina como conservante em formulações semi-sólidas tópicas para usos cosmético e farmacêutico, bem como verificar as estabilidades física e físico-química. Com esta finalidade, três diferentes concentrações de lactoferrina foram incorporadas nos cremes não-iônico e aniônico, gel e gel-creme. A atividade da lactoferrina foi avaliada através do teste de eficácia conservante, sendo que as formulações foram contaminadas com concentrações conhecidas dos microrganismos Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans e Aspergillus niger, com posterior contagem do número de Unidades Formadoras de Colônias (UFC), em placas de Petri, nos tempos zero, 2, 4, 6, 12, 24, 48 e 72 horas, bem como em 7, 14, 21 e 28 dias. Para estudo das estabilidades, as formulações foram avaliadas nos tempos zero, 15, 30, 60, 90, 150 e 180 dias, nas temperaturas de 4°, 25° e 40°C. A estabilidade físico-química foi avaliada através das características macroscópicas, estabilidade à centrifugação, pH, densidade e consistência. A estabilidade física, por meio da determinação da viscosidade e comportamento reológico. Os resultados obtidos, nas condições experimentais deste trabalho, permitiram inferir que a lactoferrina bovina não provocou alteração significativa nas estabilidades física e físico-química das formulações estudadas. Quanto à eficácia da lactoferrina, a mesma não pode ser classificada como substância dotada de atividade conservante, pois não atendeu às exigências preconizadas em compêndios oficiais, frente aos microrganismos estudados. Mesmo não tendo atendido às exigências oficiais como conservante, mostrou-se efetiva frente à levedura Candida albicans, nas formulações do creme não-iônico e gel de hidroxietilcelulose. No entanto, estudos posteriores poderão avaliar a associação da lactoferrina a outros conservantes, buscando sinergismo entre eles, conseqüentemente, podendo diminuir as reações adversas e sensibilizações no usuário. / The bovine lactoferrin, discovered in 1939, is a glycoprotein that connects itself reversibly to two ions of iron being able to kidnap them from certain pathogens or from the environment promoting reduction of the microbial growth or, resulting in permeability if connected to its cellular walls. Lactoferrin has become important in researches because investigations have described its activity in vitro before many microorganisms. Due to this property, lactoferrin could be applied in cosmetic and food industries as a natural preservative. Even though some preservatives are already acclaimed in literature, lactoferrin has been related to the unleashing of allergic reactions and sensibility, motivating the search for the preservative. The goal of this paper was to evaluate lactoferrin as a preservative in semi-solid topic formulations for cosmetic and pharmaceutical uses as to verify the physical and physical-chemical stabilities. On this purpose, three different lactoferrin concentrations were incorporated in non-ionic and anionic creams, gel and gel-cream. Lactoferrin\'s performance was evaluated through testing the efficiency of the preservative, being that the formulations were contaminated by known concentrations of the microorganisms Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans e Aspergillus niger, with posterior counting of the number of Former Colony Units (FCT), in Petri plates, on times zero, 2, 4, 6, 12, 24, 48 and 72 hours, as well as 7, 14, 21, 15, 30, 60, 90, 150 and 180 days, in temperatures of 4º, 25º and 40ºC. The physical-chemical stability was evaluated through the macroscopic characteristics,stability to centrifugation, pH, density and consistency. The physical stability through the determination of viscosity and reologic behavior. The results, in the experimental conditions of this paper, allowed inferring that the bovine lactoferrin didnt\'s provoke significant alteration in the physical and physical-chemical stabilities in the studied formulations. As to the efficiency of lactoferrin, it canot be classified as a substance endowed with preservative activity because it didn\'t reach the extolled demands in official compendiums before the studied microorganisms. Although it didn’t reach the official demands as a preservative, lactoferrin showed itself effective before the yeast Candida albicans on the formulations of the non-ionic cream and hidroxiethyl celulose gel. However, posterior studies will be able to evaluate the association of lactoferrin to other preservatives, seeking synergism between them, being able to consequently diminish the adverse reactions and sensibilities in the user.

Gestational Diabetes Mellitus develops in 3.7-18% of Canadian women, and can cause serious maternal-fetal complications. Low-GI foods have been shown to increase β-cell function in subjects with impaired glucose tolerance. Theoretically, this effect should improve glucose tolerance and reduce the risk of gestational hyperglycemia. Thus, we aimed to explore the effects of a low-GI diet on glucose challenge test (GCT) results in women at risk for GDM. Women were randomized to receive education during pregnancy focused on incorporation of low- or medium- to high-GI foods. Key foods were provided to assist compliance. Information was obtained from medical records and questionnaires. Ninety-four (94) women completed the study. After adjustment for confounding variables, there was no significant difference in GCT values between intervention groups. Results suggest that low-GI foods do not affect blood glucose control during pregnancy.

Gestational Diabetes Mellitus develops in 3.7-18% of Canadian women, and can cause serious maternal-fetal complications. Low-GI foods have been shown to increase β-cell function in subjects with impaired glucose tolerance. Theoretically, this effect should improve glucose tolerance and reduce the risk of gestational hyperglycemia. Thus, we aimed to explore the effects of a low-GI diet on glucose challenge test (GCT) results in women at risk for GDM. Women were randomized to receive education during pregnancy focused on incorporation of low- or medium- to high-GI foods. Key foods were provided to assist compliance. Information was obtained from medical records and questionnaires. Ninety-four (94) women completed the study. After adjustment for confounding variables, there was no significant difference in GCT values between intervention groups. Results suggest that low-GI foods do not affect blood glucose control during pregnancy.

A lactoferrina bovina, descoberta em 1939, é uma glicoproteína que se liga reversivelmente a dois íons férricos, sendo capaz de seqüestrá-los de certos patógenos ou do meio, promovendo redução do crescimento microbiano ou se ligar as suas paredes celulares resultando na permeabilização. A lactoferrina vem ganhando notoriedade nas pesquisas, pois investigações têm descrito sua atividade in vitro frente a diversos microrganismos. Em razão desta propriedade, a mesma poderia ter aplicação nas indústrias cosmética e alimentícia, como um conservante natural. Embora alguns conservantes já estejam consagrados na literatura, os mesmos têm sido relacionados com o desencadeamento de reações alérgicas e de sensibilização, motivando a procura do conservante ideal. O objetivo deste trabalho foi avaliar a utilização da lactoferrina como conservante em formulações semi-sólidas tópicas para usos cosmético e farmacêutico, bem como verificar as estabilidades física e físico-química. Com esta finalidade, três diferentes concentrações de lactoferrina foram incorporadas nos cremes não-iônico e aniônico, gel e gel-creme. A atividade da lactoferrina foi avaliada através do teste de eficácia conservante, sendo que as formulações foram contaminadas com concentrações conhecidas dos microrganismos Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans e Aspergillus niger, com posterior contagem do número de Unidades Formadoras de Colônias (UFC), em placas de Petri, nos tempos zero, 2, 4, 6, 12, 24, 48 e 72 horas, bem como em 7, 14, 21 e 28 dias. Para estudo das estabilidades, as formulações foram avaliadas nos tempos zero, 15, 30, 60, 90, 150 e 180 dias, nas temperaturas de 4°, 25° e 40°C. A estabilidade físico-química foi avaliada através das características macroscópicas, estabilidade à centrifugação, pH, densidade e consistência. A estabilidade física, por meio da determinação da viscosidade e comportamento reológico. Os resultados obtidos, nas condições experimentais deste trabalho, permitiram inferir que a lactoferrina bovina não provocou alteração significativa nas estabilidades física e físico-química das formulações estudadas. Quanto à eficácia da lactoferrina, a mesma não pode ser classificada como substância dotada de atividade conservante, pois não atendeu às exigências preconizadas em compêndios oficiais, frente aos microrganismos estudados. Mesmo não tendo atendido às exigências oficiais como conservante, mostrou-se efetiva frente à levedura Candida albicans, nas formulações do creme não-iônico e gel de hidroxietilcelulose. No entanto, estudos posteriores poderão avaliar a associação da lactoferrina a outros conservantes, buscando sinergismo entre eles, conseqüentemente, podendo diminuir as reações adversas e sensibilizações no usuário. / The bovine lactoferrin, discovered in 1939, is a glycoprotein that connects itself reversibly to two ions of iron being able to kidnap them from certain pathogens or from the environment promoting reduction of the microbial growth or, resulting in permeability if connected to its cellular walls. Lactoferrin has become important in researches because investigations have described its activity in vitro before many microorganisms. Due to this property, lactoferrin could be applied in cosmetic and food industries as a natural preservative. Even though some preservatives are already acclaimed in literature, lactoferrin has been related to the unleashing of allergic reactions and sensibility, motivating the search for the preservative. The goal of this paper was to evaluate lactoferrin as a preservative in semi-solid topic formulations for cosmetic and pharmaceutical uses as to verify the physical and physical-chemical stabilities. On this purpose, three different lactoferrin concentrations were incorporated in non-ionic and anionic creams, gel and gel-cream. Lactoferrin\'s performance was evaluated through testing the efficiency of the preservative, being that the formulations were contaminated by known concentrations of the microorganisms Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans e Aspergillus niger, with posterior counting of the number of Former Colony Units (FCT), in Petri plates, on times zero, 2, 4, 6, 12, 24, 48 and 72 hours, as well as 7, 14, 21, 15, 30, 60, 90, 150 and 180 days, in temperatures of 4º, 25º and 40ºC. The physical-chemical stability was evaluated through the macroscopic characteristics,stability to centrifugation, pH, density and consistency. The physical stability through the determination of viscosity and reologic behavior. The results, in the experimental conditions of this paper, allowed inferring that the bovine lactoferrin didnt\'s provoke significant alteration in the physical and physical-chemical stabilities in the studied formulations. As to the efficiency of lactoferrin, it canot be classified as a substance endowed with preservative activity because it didn\'t reach the extolled demands in official compendiums before the studied microorganisms. Although it didn’t reach the official demands as a preservative, lactoferrin showed itself effective before the yeast Candida albicans on the formulations of the non-ionic cream and hidroxiethyl celulose gel. However, posterior studies will be able to evaluate the association of lactoferrin to other preservatives, seeking synergism between them, being able to consequently diminish the adverse reactions and sensibilities in the user.

Introduction: Cough is the commonest reason for which medical advice is sought. In assessment of chronic cough and in developing anti-tussive medications, inhalational cough challenges with capsaicin and citric acid are commonly employed. However the ability of these inhalational cough challenges to distinguish health and disease is not clear and it is not known which end point is best in making such assessments. Methods: Subjects belonging to five different categories (healthy volunteers, subjects with COPD, asthma, healthy current smokers and chronic cough) were compared with each another by using the standard cough challenges employing Capsaicin and Citric acid and also by using newer inhalational cough challenge agents such as prostaglandin E2 and bradykinin. In addition adaptation to repeated inhalations of tussive agents was also assessed. The relationship between the cough reflex sensitivity as gauged by using inhalational cough challenge tests and objective cough recording was explored in all five groups. Finally the change in C5 in Capsaicin evoked cough by using a substance to block TRPV1 channel and its effect on objective cough recording was assessed in subjects with chronic cough. Results: Different tussive agents have different abilities to distinguish between different diagnostic categories and a combination of inhalational cough challenge tests have a better accuracy of predicting diagnostic groups as compared to one on its own. There are significant differences in the rates of adaptation to repeated inhalations of PGE2 and there is a significant reduction in cough response over period of time in all disease groups. Using the TRPV1 antagonist resulted in a modest increase in the Log C5 concentration of capsaicin but this was not matched by a change in objective cough recording or CQLQ scores. Conclusions: The different abilities of tussive agents to distinguish between different diagnostic categories suggest that the information conveyed by the one inhalational cough challenge test is different from that by another test. The choice of the inhalational cough challenge test should therefore depend on which groups are included in the study. There was no significant difference in the rate of adaptation to prolonged challenge with citric acid or capsaicin and no significant correlation of the magnitude of adaptation with objective cough recording suggesting that this is unlikely to be responsible for the increased cough rates seen in diseases such as chronic cough, COPD or asthma. The TRPV1 antagonist did not result in a significant change in objective cough recording or CQLQ scores. The change in C5 with the TRPV1 antagonist was however modest and this may be reason for this study failing to show a relationship between these different measures.

Made available in DSpace on 2014-06-11T19:25:26Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-03-02Bitstream added on 2014-06-13T18:26:30Z : No. of bitstreams: 1 fiorentino_fam_me_arafcf.pdf: 993041 bytes, checksum: 1b0b8ea09b16b4f6483f4923d9584e00 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Os sabonetes são preparações destinadas à higiene e conhecidos há mais de 4000 anos. São constituídos por sais de ácidos graxos com propriedades detergentes, resultantes da saponificação entre ácidos graxos superiores e seus glicerídeos à custa de um material alcalino. Podem ser incorporados com diversas substâncias que possuem algum efeito terapêutico ou preventivo sobre a pele, por facilitarem o contato de tais substâncias com o tecido alvo. Porém, isto nem sempre é possível. Por tratar-se de um tensoativo aniônico carboxilado e ter elevada alcalinidade, muitos dos materiais ou ativos a serem incorporados a este tipo de preparação podem apresentar instabilidade. Com o advento dos detergentes sintéticos tal situação pode ser contornada, e apesar de constituírem-se também em tensoativos aniônicos, e por terem origem em ácidos fortes, permitem o preparo de sabonetes líquidos não alcalinos e apresentam maior compatibilidade frente a diversos ativos. Entre as diversas possibilidades de ativos, os agentes antimicrobianos, merecem atenção especial, uma vez que encontra nos sabonetes um excelente veículo para desempenhar sua função na assepsia da pele. A clorexidina é um anti-séptico de amplo espectro de ação, sendo ativo frente a bactérias Gram-positivas e Gram-negativas, fungos, leveduras e vírus. Atua sobre a membrana celular causando perda de material intracelular, tais como ácido nucléico e potássio, inibição respiratória e coagulação citoplasmática. Pode apresentar-se na forma de diversos sais como acetato, cloridrato, gluconato e digluconato. Neste trabalho foram estudadas formulações contendo solução de digluconato de clorexidina. A solução amostra utilizada para preparação dos sabonetes foi avaliada quanto a alguns parâmetros como pH, densidade relativa, ponto de fusão, cromatografia em camada delgada, espectroscopia... / The soaps are preparation for hygiene and they are well known for 4000 years ago. They are constituited by salts of fatty acids with detergent properties, resulting from saponification of fatty acids superiorities and glycerides using an alkaline material. They may be incorporated with several substances that have a preventive or therapeutic effect on the skin, by facilitating the contact of such substances with the target tissue. However, this is not always possible. The soaps are anionic surfactant and carboxylic and they have high alkalinity, many of the materials or activities to be incorporated into this type of preparation may be instable. With the advent of synthetic detergents such situation can be avoided, and despite of they be also anionic surfactants, and are based on strong acids, allow the preparation of liquid soaps and alkali not have greater compatibility front of several assets. Among the various possibilities of active, antimicrobial agents deserve special attention, since the soap is an excellent vehicle to perform its function in the asepsis of the skin. The chlorhexidine is an antiseptic of wide spectrum of action, being active against the bacteria Gram-positive and Gram-negative, fungi, yeasts and viruses. Chlorhexidine is an excellent antiseptic of wide spectrum of action, being active against the bacteria Gram-positive and Gram-negative, fungi, yeasts and viruses. Acts on the cell membrane causing loss of intracellular material, such as nucleic acid and potassium, respiration inhibition and cytoplasmic coagulation. The salts of chlorhexidine can be acetate, hydrochloride, gluconate and digluconate. In this work formulation were studied with solution of chlorhexidine digluconate. The sample solution employed to prepare the liquid soaps was evaluated for some parameters such as pH, relative density, melting point, thin-layer chromatography... (Complete abstract click electronic access below)

Resumo: Os sabonetes são preparações destinadas à higiene e conhecidos há mais de 4000 anos. São constituídos por sais de ácidos graxos com propriedades detergentes, resultantes da saponificação entre ácidos graxos superiores e seus glicerídeos à custa de um material alcalino. Podem ser incorporados com diversas substâncias que possuem algum efeito terapêutico ou preventivo sobre a pele, por facilitarem o contato de tais substâncias com o tecido alvo. Porém, isto nem sempre é possível. Por tratar-se de um tensoativo aniônico carboxilado e ter elevada alcalinidade, muitos dos materiais ou ativos a serem incorporados a este tipo de preparação podem apresentar instabilidade. Com o advento dos detergentes sintéticos tal situação pode ser contornada, e apesar de constituírem-se também em tensoativos aniônicos, e por terem origem em ácidos fortes, permitem o preparo de sabonetes líquidos não alcalinos e apresentam maior compatibilidade frente a diversos ativos. Entre as diversas possibilidades de ativos, os agentes antimicrobianos, merecem atenção especial, uma vez que encontra nos sabonetes um excelente veículo para desempenhar sua função na assepsia da pele. A clorexidina é um anti-séptico de amplo espectro de ação, sendo ativo frente a bactérias Gram-positivas e Gram-negativas, fungos, leveduras e vírus. Atua sobre a membrana celular causando perda de material intracelular, tais como ácido nucléico e potássio, inibição respiratória e coagulação citoplasmática. Pode apresentar-se na forma de diversos sais como acetato, cloridrato, gluconato e digluconato. Neste trabalho foram estudadas formulações contendo solução de digluconato de clorexidina. A solução amostra utilizada para preparação dos sabonetes foi avaliada quanto a alguns parâmetros como pH, densidade relativa, ponto de fusão, cromatografia em camada delgada, espectroscopia... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The soaps are preparation for hygiene and they are well known for 4000 years ago. They are constituited by salts of fatty acids with detergent properties, resulting from saponification of fatty acids superiorities and glycerides using an alkaline material. They may be incorporated with several substances that have a preventive or therapeutic effect on the skin, by facilitating the contact of such substances with the target tissue. However, this is not always possible. The soaps are anionic surfactant and carboxylic and they have high alkalinity, many of the materials or activities to be incorporated into this type of preparation may be instable. With the advent of synthetic detergents such situation can be avoided, and despite of they be also anionic surfactants, and are based on strong acids, allow the preparation of liquid soaps and alkali not have greater compatibility front of several assets. Among the various possibilities of active, antimicrobial agents deserve special attention, since the soap is an excellent vehicle to perform its function in the asepsis of the skin. The chlorhexidine is an antiseptic of wide spectrum of action, being active against the bacteria Gram-positive and Gram-negative, fungi, yeasts and viruses. Chlorhexidine is an excellent antiseptic of wide spectrum of action, being active against the bacteria Gram-positive and Gram-negative, fungi, yeasts and viruses. Acts on the cell membrane causing loss of intracellular material, such as nucleic acid and potassium, respiration inhibition and cytoplasmic coagulation. The salts of chlorhexidine can be acetate, hydrochloride, gluconate and digluconate. In this work formulation were studied with solution of chlorhexidine digluconate. The sample solution employed to prepare the liquid soaps was evaluated for some parameters such as pH, relative density, melting point, thin-layer chromatography... (Complete abstract click electronic access below) / Orientador: Hérida Regina Nunes Salgado / Coorientador: Marcos Antonio Corrêa / Banca: Maria José Vieira Fonseca / Banca: Maria Stella Gonçalves Raddi / Mestre

<p dir="ltr">Adipose tissue is characterized by the dominant presence of adipocytes, specialized cells adept at lipid metabolism. These adipocytes act as critical nodes, coordinating the complex processes of energy storage and mobilization according to the body's metabolic requirements. Within the adipocyte population of mammals, there are three main subtypes: white, beige, and brown adipocytes. White adipocytes are primarily dedicated to the sequestration of energy in the form of triglycerides. Conversely, beige and brown adipocytes are distinguished by their capacity for thermogenesis, the process of dissipating nutritional energy as heat. The contemporary challenge of chronic overnutrition has precipitated a global surge in obesity and cardiometabolic diseases. Addressing this issue necessitates the maintenance of white adipocyte homeostasis and the enhancement of the quantity and function of thermogenic adipocytes, which are imperative for mitigating the global obesity epidemics.</p><p dir="ltr">Mitochondrion, a multifunctional organelle, is integral to a broad spectrum of cellular processes, including anabolic and catabolic metabolism, bioenergetics, and signal transduction, all of which are essential for maintaining cellular functions and homeostasis. The efficacy of mitochondrial operations is intrinsically linked to their membrane dynamics. In this study, transmission electron microscopy and mass spectrometry were employed to investigate the proteins implicated in the cold-induced mitochondrial membrane remodeling in brown adipocytes. Through this approach, a poorly characterized protein, Family with Sequence Similarity 210 Member A (FAM210A), was identified as a mitochondrial inner membrane protein that is induced by cold stimulation. Subsequent loss-of-function experiments were conducted to elucidate the role of FAM210A in adipocytes. Mice with adipose-specific deletion of <i>Fam210a</i> (<i>Fam210a</i>^<em>AKO</em>) exhibited compromised mitochondrial cristae structure and a reduced thermogenic capacity in brown adipose tissue (BAT), resulting in an increased susceptibility to lethal hypothermia during acute cold challenge. Moreover, in mice with inducible ablation of <i>Fam210a</i> in adipocytes (<i>Fam210</i>^{<em>iAKO</em>}), mitochondrial alterations in BAT were negligible at thermoneutral conditions; however, they exhibited defective cold-induced mitochondrial cristae remodeling, culminating in a progressive loss of cristae and diminished mitochondrial density. Mechanistically, it was determined that FAM210A interacts with mitochondrial protease YME1L and modulates its activity toward OMA1 and OPA1 cleavage, thus compromising cold-induced mitochondrial remodeling in BAT.</p><p dir="ltr">Additionally, this research delved into the role of FAM210A in adipocytes in response to dietary stress by feeding mice with high-fat diet (HFD). The study found a consistent correlation between FAM210A expression and OPA1 cleavage in adipocytes under HFD challenge. Mice lacking FAM210A in all adipocytes and subjected to HFD exhibited lipoatrophy in white adipose tissue (WAT) and a downregulation of genes associated with adipogenesis and lipid metabolism. In contrast, mice with a brown adipocyte-specific ablation of <i>Fam210a </i>(<i>Fam210a</i>^<em>UKO</em>) displayed no significant change in WAT mass but had enlarged livers. Crucially, both <i>Fam210a</i>^<em>AKO</em> and <i>Fam210a</i>^<em>UKO</em> mice presented increased WAT inflammation, deteriorated glucose tolerance, and exacerbated insulin resistance. These findings underscore the pivotal role of FAM210A in brown adipose tissue (BAT) in the preservation of WAT homeostasis and the regulation of systemic glucose clearance in diet-induced obesity.</p><p dir="ltr">In summary, these studies characterize the mitochondrial dynamics in brown adipocytes in response to cold stress, identify a new cold-induced mitochondrial protein, FAM210A, and uncover its functions in adipocytes under cold and dietary stresses. These findings highlight the importance of mitochondrial remodeling in the adaptive response of adipocytes to evolving metabolic demands. This work establishes FAM210A as a key regulator of mitochondrial cristae remodeling, shedding light on the mechanisms that govern mitochondrial plasticity in adipocytes.</p>

Many athletes incorporate high training volumes and limited recovery periods into their training regimes. This may disrupt the fragile balance and the accumulation of exercise stress may exceed an athlete's finite capacity of resistance. A state of elevated fatigue, increased mood disturbance and decreased exercise performance can result. This is commonly known as overreaching and if increased training and limited recovery is continued, it is believed that the more serious state of overtraining may develop. This is relatively commonly experienced in athletes, however little scientific investigation has been conducted to determine the characteristics and underlying mechanisms. The overall aim of this thesis was to gain a greater understanding of the state of overreaching and to specifically provide new information on potential markers of this state as well as possible mechanisms. To study the cumulative effects of exercise stress and subsequent recovery on performance changes, fatigue indicators and possible mechanisms, the training of endurance cyclists was systematically controlled and monitored in two separate investigations. A number of variables were assessed including performance, physiological, biochemical, psychological, immunological and hormonal variables. In addition heart rate variability and serotonergic responsiveness were also assessed. Some of the more pertinent effects of overreaching included an increase in heart rate variability, a reduction in carbohydrate oxidation, an increase in serotonergic responsiveness and a reduction in stress hormone concentrations. These results suggest that autonomic imbalance in combination with decreased hormonal release appears to be related to the decline in performance and elevated fatigue apparent in overreached athletes. Additionally it also appears that alterations in the hypothalamic-pituitary adrenal axis may occur in overreached athletes.

Diabetes mellitus is a frequent endocrinopathy in dogs. Exogenous insulin and nutritional management are the mainstays of therapy. High carbohydrate and fibre diets have been traditionally recommended for canine diabetes mellitus. However, recent studies in healthy and diabetic dogs have challenged the use of these traditional diabetic diets. In addition, dietary carbohydrate content was found to be the main determinant of postprandial blood glucose concentrations over 1.5 hours in healthy dogs. Increasing carbohydrate content increased blood glucose concentration. In a search of the literature, no studies in dogs were found comparing the effects on postprandial plasma glucose, insulin, triglyceride and free fatty acid concentrations of a traditionally recommended high carbohydrate and fibre diabetes diet with a moderate carbohydrate and fibre diet, or a commercially-available maintenance diet. Although fasting plasma triglyceride concentrations are commonly used for diagnosis and management of canine hyperlipidemia, a review of the literature found that in human beings, it may not to be predictive of the highest postprandial concentration. Importantly, in overweight and obese dogs with postprandial plasma triglyceride concentrations >5 mmol/L (>445 mg/dL), it was found there was a 6 fold increase in risk of laboratory evidence of exocrine pancreatic disease. However, there are limited studies on the effect of maintenance diets on postprandial plasma triglyceride concentrations in dogs, and no reference intervals determined for a triglyceride meal challenge test in healthy dogs. For the dietary studies in this thesis, animal welfare was of paramount importance, and minimally invasive peripheral venous catheterization and blood collection techniques were needed to collect 4 mL blood samples over 13 hours in conscious dogs. A search of the literature found no studies evaluating the reliability of using peripheral catheterization via the cephalic vein for the collection of larger blood volumes (for example, 4 mL). The aims of this thesis were firstly, to investigate the influence of three diets with varying carbohydrate and fibre content on postprandial plasma glucose, insulin, triglyceride and free fatty acid concentrations in healthy dogs over 12 hours; secondly, to develop a triglyceride meal challenge test and associated reference intervals; and finally, to evaluate a minimally invasive catheterization and blood collection technique for reliability in collecting the blood volumes required for these studies. For the studies in this thesis, twelve healthy dogs were fed each of three diets for three weeks in a three period cross-over design. For the meal response test at the end of each three-week period, 10 blood samples were collected over 13 hours. Reference intervals for fasting and postprandial triglyceride concentrations at single and multiple time points after eating a standard meal were determined in healthy dogs. Associations between fasting and postprandial triglyceride concentrations, and time to measure highest postprandial triglyceride concentration were also evaluated. Blood volume obtained, resistance on aspirating the blood sample, and methods used to improve blood flow during collection were recorded for the 358 samples collected. The results of the studies in this thesis demonstrated that a moderate carbohydrate diet resulted in lower peak and postprandial glucose concentrations compared with a traditional diabetic diet (CHO 55 %ME) and a maintenance diet (CHO 45 %ME). Fasting triglyceride concentrations were found not to be predictive of peak postprandial triglyceride concentrations. The highest triglyceride concentration measured at 2, 5, and 6 hours after eating had the closest agreement with peak postprandial triglyceride concentration. Glucose, insulin and triglyceride concentrations in some dogs were significantly above baseline concentrations at 12 hours after eating each of the diets. Of 358 blood samples collected, 93 % achieved the required 4 mL volume, while the remaining samples were greater than 1.5 mL, and 87 % were obtained with minimal resistance. It was concluded that the moderate carbohydrate and fibre test diet warrants evaluation in diabetic dogs. It was found that when following the same protocol, blood samples should be collected 2, 5, and 6 hours after eating to determine the highest postprandial plasma triglyceride concentration. For future nutritional studies, dogs may need to be fasted for at least 12 hours, and analytes measured over at least 12 hours after feeding to evaluate fasting and postprandial plasma analyte concentrations. Finally it was demonstrated that percutaneous catheterization of the cephalic vein using a 20-gauge catheter allows for successful collection of multiple 4 mL blood samples over 13 hours in conscious dogs. This thesis presents new information for future nutritional studies in healthy and diabetic dogs by suggesting that there may be no glycemic benefit feeding the high carbohydrate and fibre diet compared with a moderate carbohydrate and fibre diet. A triglyceride meal challenge test was developed to assist the diagnosis of canine hyperlipidemia. Finally, a minimally invasive method for obtaining serial blood samples was evaluated and described. These findings are expected to help in designing future studies in the nutritional management in healthy dogs, and dogs with diabetes mellitus and hyperlipidemia.