Access to abstract permanently restricted to Ball State community only / Access to thesis permanently restricted to Ball State community only / School of Physical Education, Sport, and Exercise Science

The thermoneutral zone (TNZ) curve lies between the ambient temperatures (Ta) where an endothermic animal uses the least amount of energy to maintain a balance between the heat production from the animal’s own metabolism and the heat lost to the environment. If the animal is exposed to Ta’s over the upper critical temperature (UCT), which is the highest temperature that is still in the TNZ, the animals have to use energy to cool down. If they are exposed to temperatures lower than the lower critical temperature (LCT), which is the lowest temperature that is still in the TNZ, the animal have to use energy to warm up. In the present study oxygen consumption was measured at different Ta’s to determine the TNZ in two and three week old broiler chickens (Gallus gallus domesticus). Two different protocols were used and compared, a pseudorandom protocol in which chickens were exposed to seven temperatures in two hour periods for each run and a more typical progressive protocol in which Ta decreased gradually, one or two degrees per hour. The TNZ in two weeks old chickens was between 30.7 ˚C- 36.4 ˚C and between 28.8 ˚C- 32.7 ˚C in the three weeks old chickens. In chickens the TNZ shifts remarkably during the first few weeks of life towards lower temperatures as the animals acquire thermoregulatory competence. The method with a pseudorandom protocol takes more factors, like activity, into consideration than a typical progressive protocol.

Several studies have reported beneficial effects of C-peptide supplementation in diabetic patients and animal models of insulinopenic diabetes. However, it is also established that good glycemic control is essential to minimize the risk of diabetes-induced complications. This thesis investigates potential mechanisms for the beneficial effect of C-peptide on glomerular hyperfiltration, and a novel, painless route of insulin administration. The results demonstrate that both C-peptide and its C-terminal penta-peptide sequence reduce the diabetes-induced glomerular hyperfiltration within an hour. The results also indicate that C-peptide possibly reduces diabetes-induced hyperfiltration via three different mechanisms: 1. Constriction of the afferent arteriole was demonstrated on isolated vessels from diabetic mice. 2. A net dilation of the efferent arteriole was evident in vivo. 3. Inhibition of the Na+/K+-ATPase was demonstrated in vivo in diabetic rats as well as in vitro on isolated proximal tubular cells from diabetic rats. All these mechanisms are known regulators of the net glomerular filtration pressure. The last part of this thesis demonstrates that intradermal administration with a newly developed patch-like microneedle device results in similar insulin concentration compared to standard subcutaneous delivery. These findings provide an insight for the beneficial effects of C-peptide on diabetic kidney function, and shows that this effect can be achieved by infusion of the C-terminal penta-peptide sequence alone. This thesis also presents a novel, painless alternative to insulin injections that is controllable, requires minimal training, and therefore presents several advantages compared to current standard therapy.

Antarctic fish from the suborder Notothenioidei inhabit what is perhaps the most thermally stable ocean environment on Earth. Evolutionary theory suggests that by specialising for this environment, Antarctic fish have traded-off their ability to respond to variations in temperature, and like their environment, have become extremely stenothermal. However, previous research has revealed that the Antarctic notothenioid fish Pagothenia borchgrevinki is not as thermally limited as evolutionary theory might predict, and is capable of acclimation to 4 ℃ during a one month period. The purpose of the current research was to investigate the physiological mechanisms that underpin this remarkable acclimatory ability. P. borchgrevinki were acclimated for one month to 4 ℃ and changes in oxygen consumption, prolonged swimming ability, cardiovascular function, enzyme activity and haematology were measured. Significant changes in resting oxygen consumption rate and prolonged swimming ability occurred during the acclimation period, and these changes were mediated by adjustments of enzyme activity and specific aspects of the haematology. By monitoring resting oxygen consumption and prolonged swimming ability over a much longer, six month, acclimation period it was confirmed that the adjustments evident during one month at 4 ℃ were sustainable in the long-term, and were not short-term compensatory mechanisms. Interestingly, fish infected with x-cell gill disease did not possess the same ability to acclimate as was demonstrated by healthy P. borchgrevinki. P. borchgrevinki are unusual among the notothenioids, possessing an active, pelagic lifestyle which differs from the sedentary, benthic lifestyle of most other species within the suborder. Therefore, it was hypothesised that the acclimatory ability demonstrated by this species may also be unusual among the notothenioids. To test this hypothesis, the acclimation ability of three sedentary, benthic notothenioids (Trematomus bernacchii, T. hansoni and T. pennellii) was investigated. Results confirmed the hypothesis, with all three species demonstrating very poor survival at 4 ℃ and absolutely no capacity for acclimation. Such results present a disturbing scenario for the future of Antarctic notothenioid fish in Earth?s rapidly warming climate, and highlights the need for continued research combined with immediate action to combat the warming which currently threatens Antarctic marine biodiversity.

Metabolic depression is a ubiquitous characteristic of dormancy, allowing animals to survive off limited endogenous fuels supplies for extended periods of time. Metabolic depression is characterised by a complex set of physiological and biochemical changes (respiratory depression, bradycardia, hypophagia and cessation of renal function), in addition to a remarkable ability to prevent or minimise damage usually associated with such depressive changes (e.g. gut and muscle atrophy, renal failure and ischemic injuries). A coordinated shut-down of systems is essential to surviving long periods of dormancy, however, the mechanisms involved in regulating metabolic depression remain poorly understood. Aestivation, a period of dormancy that occurs in response to desiccating environments, provides an excellent model system for investigating the regulation of metabolic depression, because unlike other forms of dormancy such as hibernation, it is not confounded by changes in temperature or PO2 and thus represents a true intrinsic metabolic depression. The green striped burrowing frog, Cyclorana alboguttata, is an abundant species of burrowing frog inhabiting arid to semi-arid regions of Queensland and Northern New South Wales. During the dry season, C. alboguttata aestivates in an underground clay chamber; the aestivating period lasts on average for nine months a year, but in drought conditions may last for as long as several years. In recent years, C. alboguttata has become a well studied organism for investigating the physiological processes involved in aestivation, especially regarding muscle disuse atrophy and gut maintenance. Despite this, our understanding of this frog’s capacity to metabolically depress remains limited. The first aim of this study was to extend our current knowledge of metabolic depression during aestivation in C. alboguttata. C. alboguttata reduced whole animal metabolism by 82% within five weeks of aestivation. The effects of aestivation on mass specific in vitro tissue metabolic rate (VO2) varied among individual organs, with muscle and liver slices showing significant reductions in metabolism; kidney VO2 was elevated and there was no change in the VO2 of small intestine tissue slices. Organ size was also affected by aestivation, with significant reductions in the mass of all tissues, except the gastrocnemius. These reductions in organ size, combined with changes in mass specific VO2 of tissue slices, resulted in further energy savings to aestivating animals. Mitochondrial VO2 was significantly reduced during aestivation, by an average of 83%; in addition respiratory control ratios (RCRs), a measurement of mitochondrial coupling efficiency, significantly increased during aestivation, suggesting increased mitochondrial coupling efficiency. The second aim of this study was to investigate the potential role of the endogenous opioid system (EOS) and thyroid hormones in the regulation of metabolic depression in C. alboguttata. When incubated in the presence of opioid agonists, liver and muscle tissue slices from Cyclorana alboguttata underwent tissue- and agonist- specific metabolic depression. In most cases, the effect of opioid agonists on metabolism was more pronounced in tissue slices from aestivating animals. The delta (δ) opioid agonist DADLE was the most consistent in producing a metabolic depression, however the effect of DADLE on the metabolism of tissue slices was not reversible by the general opioid antagonist naloxone. Gene transcript levels for the δ-opioid receptor remained constant in the brain and in the muscle of aestivating C. alboguttata compared to controls. Opioid receptor XOR1 transcript levels also remained constant in the brain during aestivation compared to controls. There was a significant reduction in total thyroid hormone concentration in the plasma of C. alboguttata during aestivation, with thyroxine (T4) decreasing by 75% and an 84% reduction in triiodothyronine (T3). We also examined changes in gene expression of deiodinase 2 (D2) and deiodinase 3 (D3), the major activating and deactivating enzymes of thyroid hormones, respectively. There were no significant changes in gene expression of D2 in the brain or muscle, or of D3 in the brain; however there was a significant down-regulation of D3 transcripts in muscle tissue. In the liver, D2 was significantly down-regulated and D3 showed an increase in transcript levels that was approaching significance. During dormancy energy conservation is a key priority and as such dormant animals undergo a major metabolic depression to conserve their limited endogenous fuel supplies. At the same time, dormant animals are faced with the challenge of maintaining functional organs for immediate use upon arousal. In this study C. alboguttata appeared to selectively down- or up-regulating individual tissues, using both changes in metabolic rate and morphology. This strategy would allow maximal energy savings during aestivation without compromising organ functionality and survival at arousal. In addition, the frogs appeared to decrease rates of mitochondrial proton leak to a greater extent than ATP synthesis, consistent with an increase in mitochondrial coupling efficiency. Again, this ability to selectively down-regulate one process to a greater extent than another allows energy savings to be maximised without compromising processes essential for survival. C. alboguttata can survive in a dormant state for several years and it is hypothesised that these frogs become more energy efficient during aestivation. The regulation of metabolic depression still remains poorly understood. In this study the potential role of the EOS and thyroid hormones in regulating metabolic depression was investigated. The results of this study suggest the δ-opioid system may be responsible for the initiation of metabolic depression, while the mu (μ) and kappa (κ) opioid systems may be important during long term maintenance of aestivation. In addition, the EOS may exert its control over metabolism via both receptor and non-receptor mediated pathways. The significant down-regulation of total thyroid hormones, as well as the changes in gene expression of the thyroid deiodinases indicates thyroid hormones may also play a significant role in regulating metabolic depression. This suggests that the regulation of metabolic depression may involve several interacting systems, or perhaps a ‘systems cascade’.

Diss. (sammanfattning) Linköping : Linköpings universitet, 2005. / Härtill 4 uppsatser.

Lic.-avh. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 2 uppsatser.

Thesis--University of Oklahoma. / Bibliography: leaves 94-96.

Two experiments were conducted to evaluate changes in chemical composition on kikuyu Pennisetum clandestinum hay cut with 50, 70 and 90 days of regrowth, and its effect on intake, digestibility, ruminal fermentation and passage kinetics of solid phase through gastrointestinal tract (Experiment 1) and oxygen utilization by the portal system (Experiment 2) in sheeps. Six and three castrated lambs, mean live weight of 35 ± 3 kg and 33 ± 3 kg were used, in a Double 3 X 3 Latin Square and in a Latin Square experimental design in experiment 1 and 2, respectively. These animals were chronically catheterized in portal and mesenteric veins. Experimental diets were hay fed twice a day ad libitum . Intake of hay components linearly decreased (P<0,05) with the increase of the regrowth age of the plant with the ecxeption of indigestible neutral detergent fiber (NDFi), acid detergent fiber (ADF) and cellulose that were similar between treatments (P<0,05). Aparent digestibility of dry matter (DM), organic matter (OM) and neutral detergente fiber (NDF) were similar between treatments (P<0,05). Nitrogen intake and retention linearly decreased (P<0,05) with the increase of regrowth age of kikuyu but N digestibility and urinary excretion were similar between treatments. Protein synthesis and eficiency were quadratically related (P<0,05) with the regrowth age of kikuyu with maximum values on hay of 70 days. Aminoacids concentrations were similar while N-amonia concentration linearly decreased and (P<0,05) sugar and peptides concentrations were quadratically related (P<0,05) with the regrowth age of kikuyu. The kinetic of solid phase and retention time through the astrointestinal tract were similar between treatmens. Of the parameters that defines the nutritional value of the forage, only intake was correlationated with regrowth age. However, this relationship was not explained for the rate of passage of the solid phase or the hay digestibility. Around 4 5 % of the consumption of energy metabolic was liberated as heat by the organs that compose the portal system, but there was not relation between oxygen consumption and regrowth age. These results indicates that other than dietetic factors, like oxygen disponibility, also can affect oxygen utilization by the tissues. / Este estudo foi conduzido com o objetivo de avaliar a mudança na composição química do feno de quicuio (Pennisetum clandestinum) cortado com 50, 70 e 90 dias de rebrota, e, avaliar seu efeito sobre o consumo, digestão, fermentação ruminal, a taxa de passagem da digesta pelo trato digestivo (Experimento 1) e a utilização do oxigênio pelo sistema portal em ovinos (Experimento 2). No 1º experimento, foram utilizados seis ovinos machos castrados, com peso vivo (PV) médio de 35± 3 kg, num delineamento duplo quadrado Latino 3 X 3, e no 2º experimento foram utilizados três ovinos machos castrados com PV de 33 ± 3 kg. Nestes animais foram implantados catéteres permanentes nas veias porta e mesentérica. As dietas experimentais foram constituídas de feno fornecido duas vezes ao dia em quantidades suficientes para haver sobras de 10 a 20% do oferecido. O consumo dos vários componentes do feno diminuíram linearmente com o avanço da idade de rebrote da planta (P<0.05), com exceção dos consumos de fibra em detergente neutro indigestível (FDNi), fibra em detergente neutro (FDA) e celulose, que foram similares nos diferentes tratamentos (P<0.05). A digestibilidade aparente da matéria seca (MS), matéria orgânica (MO), FDN assim como a digestibilidade verdadeira da MO, não foram influenciados pela idade de rebrote da planta. O consumo e a retenção de nitrogênio (N) diminuíram linearmente (P<0,05) com o aumento da idade de rebrote da planta, mas a digestibilidade e a excreção urinária de N foram similares entre os tratamentos. A síntese protéica microbiana e a eficiência microbiana variaram quadraticamente (P<0,05). A concentração de aminoácidos foi similar, mas a concentração de amônia diminuiu linearmente e, as concentrações de açúcares e peptídeos assim como o pH, variaram quadraticamente (P<0,05), com o aumento da idade de rebrota da forrageira, sendo os máximos valores observados nos animais que receberam feno de 70 dias de rebrote. Os parâmetros de cinética de passagem foram similares nos diferentes tratamentos. Dos parâmetros que definem o valor nutritivo da forragem, apenas o consumo foi relacionado com a idade de rebrota da planta. No entanto, esta relação não foi explicada nem pela taxa de passagem da digesta pelo trato digestivo nem pela digestibilidade da forragem. A produção de calor portal representou 4 a 5% do consumo da EM do feno, mas não houve uma relação clara entre gasto de oxigênio e idade de rebrota da planta. Os resultados indicam que fatores não dietéticos, como a disponibilidade de oxigênio, também podem afetar a utilização deste metabólito pelos tecidos.

Orientador: Otto Bismarck Fazzano Gadig / Resumo: Elasmobrânquios marinhos são reconhecidamente ureotélicos, ou seja, sintetizam, retém e excretam preferencialmente ureia como produto do metabolismo do nitrogênio, mantendo os seus fluídos corpóreos iso-osmóticos, ou ligeiramente hiper-osmóticos, em relação ao meio externo. Assim, o alto requerimento por nitrogênio nesses animais, tanto para o crescimento quanto para a manutenção de sua estratégia ureosmótica, pode tornar os elasmobrânquios limitados pela disponibilidade de alimento. O presente estudo buscou avaliar o efeito do regime de alimentação e da aclimatação a salinidade reduzida sobre respostas fisiológicas e bioquímicas relacionadas ao metabolismo e excreção de nitrogênio em jovens de tubarão bambu (Chiloscyllium punctatum). Para tanto, foram determinados as formas preferenciais de excreção de nitrogênio (amônia_N e ureia_N), consumo de oxigênio, coeficiente de nitrogênio, níveis plasmáticos de compostos nitrogenados (amônia e ureia), principais osmólitos (proteínas totais, [Na+], [Cl-]; osmolaridade total) e glicose em jovens C. punctatum aclimatados em salinidade 32 e 20ppm, e mantidos sob regime regular de alimentação (2-3% da biomassa) e privação alimentar por 7 dias. Nossos resultados evidenciaram que a ureia é a principal excreta nitrogenada nos jovens de tubarão bambu mantidos em ambos os regimes de alimentação e em ambas as salinidades testadas. Após a alimentação os animais em 32ppm aumentam significativamente a excreção de nitrogênio na forma de amônia, ef... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Marine elasmobranchs are ureothelic organisms which synthesize, retain, and excretes preferentially urea as the end-product of nitrogen metabolism, maintaining their internal body fluids iso-osmotic or slightly hyperosmotic relative to the external marine environment. The high requirement for nitrogen in these animals for both growth and maintenance of their ureosmotic strategy, might make elasmobranchs limited by the availability of food. Thus, the present study aimed to evaluate the effect of feeding regime and acclimation to lowered salinity on physiological and biochemical responses associated to nitrogen metabolism and excretion in juvenile of brownbanded bamboo shark (Chiloscyllium punctatum). For this purpose, we determine the rates of waste excretion of the main nitrogen end-products (ammonia_N and urea_N), oxygen consumption, nitrogen quotient, and levels of nitrogen compounds (ammonia and urea), osmolality, major ions (Na+ and Cl-), total protein and glucose in plasma of juvenile C. punctatum acclimated to both 32 and 20ppm, and kept on regular feeding regime (2-3% of body weight) or fasting for 7 days. Our results showed that urea is the main nitrogen product excreted by brownbanded bamboo shark kept at both fasting and feeding regime, at both salinities tested. After feeding, sharks at 32ppm significantly increased ammonia excretion, an effect not seen in animals acclimated to 20ppm. However, at lower salinity, animals quantitatively increased the total nitrogen e... (Complete abstract click electronic access below) / Mestre