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The role of ionotropic glutamate receptors in the dorsomedial hypothalamus in the increase in core body temperature evoked by interoceptive and exteroceptive stresses in ratsMoreno, Maria 03 March 2010 (has links)
Indiana University-Purdue University Indianapolis (IUPUI) / Brain responds to an array of diverse challenges that are defined as either exteroceptive stress, involving cognitive processing of sensory information from the external environment and or interoceptive stress, detected through sensory neural or chemical cues from the internal environment. The physiological response to most stresses consists of autonomic responses that are essential for animal survival in the face of a threatening circumstance. However, it is known that exposition to continuous situations of stress is involved in the development of a series of diseases such as hypertension, myocardial infarction and panic syndrome. Several studies have shown that cells in a specific area of the brain, the dorsomedial hypothalamus (DMH), are involved in the response produced during emotional stress. However, the role of glutamatergic transmission in the DMH in the increase in body temperature induced by experimental stress has not been examined. Research findings thus far indicate that neurons in the DMH play a role in thermoregulation and that local glutamate receptors may be involved. The hypothesis of this thesis is that activity at ionotropic glutamate receptors in the DMH is necessary for the thermogenic response induced by experimental stress. In the present work, microinjections of kynurenate, an
excitatory amino acid antagonist, NBQX (2, 3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione), an AMPA/kainate receptor antagonist, DL-2-amino-5-phosphonovaleric acid (APV), an NMDA receptor antagonist, and a mixture of NBQX and APV, were delivered to the DMH before exposure to experimental stress. The stress paradigms used include models for exteroceptive stress and interoceptive stress. The results show that inhibition of both NMDA and non-NMDA receptors is necessary to abolish the thermogenic response produced by all stress paradigms tested. Furthermore, there appears to be a difference in the degree of attenuation of the thermogenic response produced by either inhibition of NMDA receptors or non-NMDA receptors. Together these results support a definite role for ionotropic glutamate receptors within DMH region in the thermogenic response to stress. These results also finally show that the DMH is involved in all the major physiological stress responses including increase in plasma ACTH, increase in heart rate, blood pressure and now temperature as well.
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The Role of Thyroid Hormone across Avian Development Spectrum: Investigations on Systemic Development, Metabolism and Ontogeny of EndothermySirsat, Tushar Saoji 08 1900 (has links)
Achievement of endothernic capacity is vital for independence from ambient temperature changes, sustained activity, optimal biochemical reactions and optimization of parental care. During early avian development, the core tenets of transition from ectothermy to endothermy are development of metabolic capacity (oxygen consumption, mitochondrial bioenergetics), enhanced cardiovascular function (heart rate and cardiac output), pulmonary ventilation and thermogenic capacity. Thyroid hormones, particularly T3, are key metabolic regulators of basal metabolism, thermogenesis, pulmonary ventilation and mitochondrial respiration. Thyroid hormone fluctuation patterns during both precocial and altricial avian endothermic transition suggest a prominent role in maturation of endothermy, cardiovascular, respiratory and skeletal muscle physiology. This body of work explores effects of T3 manipulations in two avian species: the precocial Pekin duck and the altricial Red-winged Blackbird. Increased plasma T3 during late incubation resulted in increased cardiac mass, elevated resting and intrinsic heart rate, intrinsic mean arterial pressure, increased cholinergic tone and blunted alpha-adrenergic tone in the precocial Pekin duck. In both Pekin duck and Red-winged blackbird, plasma T3 levels correlated with changes in the trajectory of endothermic ontogeny, systemic oxygen consumption, thermogenesis, maturation of pulmonary ventilatory function, altered growth and effects on skeletal and cardiac mitochondrial bioenergetics. These observations support the role of thyroid hormones as metabolic and developmental regulators at the time of attainment of endothermy during the perinatal period in precocial and altricial avian species. Insights into the role of thyroid hormone as a metabolic and development regulator at the time of avian endothermic attainment provide a more thorough understanding of metabolic and physical transitions a hatchling bird must undergo to reach the adult endothermic phenotype. Such insights also deepen understanding of the complex role thyroid hormones play in homeostasis and offer implications about the evolutionary history of endothermic capacity.
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Avaliação clínica de enfermagem na termoregulação do recém-nascido pré-termo: do desenvolvimento ao uso de tecnologia educacional digital / Nursing clinical assessment of thermoregulation of preterm neonates: from development to use of digital educational technologyLuizari, Marisa Rufino Ferreira 09 February 2017 (has links)
As tecnologias, fortemente representadas pelos serious games na atualidade, têm ressignificado o processo de ensino-aprendizagem em saúde e enfermagem, contribuindo para o ensino participativo e mediando a aprendizagem não só de estudantes, mas também de profissionais e pacientes. Este estudo consistiu em pesquisa metodológica quanto ao desenvolvimento, baseado na técnica do design participativo, de um jogo educativo denominado e-Baby: avaliação clínica da termorregulação no recém-nascido pré-termo, bem como em um quase-experimento do tipo pré e pós-teste, ao avaliar o nível de aprendizado obtido pelos participantes antes e após uma intervenção, a qual consistiu em um curso semipresencial de 30 horas abordando o tema \'termorregulação do recém-nascido prematuro\' em associação com o jogo desenvolvido, que foi disponibilizado online durante todo o decorrer da atividade de educação permanente. Ao se compararem as médias do pós-teste e as do pré-teste (teste não paramétrico de Wilcoxon), verificou-se aprendizagem significativa pelos participantes (p = 0,0001). O jogo e-Baby voltado à avaliação clínica da termorregulação do recém-nascido pré-termo mostrou-se eficaz como instrumento de intervenção no processo de ensino-aprendizagem, despertando interesse e motivação em seus usuários / Information technology, today remarkably exemplified in serious games, has transformed the teaching-learning process in health and nursing, helping promote participative education and mediating the learning of students, professionals and patients. This study comprised a methodological investigation on the development, based on participative design, of the serious game e-Baby: Clinical Evaluation of Thermoregulation in the Preterm Neonate. A quasi-experimental pre- and post-test study assessed the level of learning available before and achieved after an intervention consisting of a combined on-site/on-line 30-hour refresher course on the topic of thermoregulation in preterm neonates, during which the game was made available online. Comparison between mean scores of post- and pre-assessments (Wilcoxon\'s non-parametric test) revealed significant learning gains (p = 0.0001). The e-Baby serious game for clinically assessing thermoregulation of preterm neonates proved effective as an intervention instrument in the teaching-learning process, sparking the interest and motivation of its users
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The impact of core temperature corrections on exercise-induced hypoxemia.Shipp, Nicholas Jon January 2008 (has links)
The primary purpose of this doctoral dissertation was to investigate the effect of body temperature responses at physiologically relevant sites during an incremental exercise test on the phenomenon of exercise-induced hypoxemia (EIH). This phenomenon has been considered as an important limitation to physical performance with a prevalence of ~50 % in trained male athletes, but described in both sexes, across the range of both age and physical fitness in more recent literature. Previously this phenomenon has been described as a decrement in both arterial oxygen partial pressure (PaO₂) and oxy-haemoglobin saturation (SaO₂or SpO₂) with, particularly important for PaO₂, a lack of or inappropriate correction made for the change in body temperature during intense exercise. The initial study of this thesis determined the thermal response within the body at physiologically relevant sites measured simultaneously during an incremental exercise test. The results demonstrated the inadequacy of rectal temperature as an indicator of the acute temperature changes occurring during an incremental exercise test due to its slow response rate and relative thermal inertia. Radial arterial blood and oesophageal temperatures were shown to behave almost identically during the exercise test, albeit with an offset of approximately 1.3ºC, and were considered much more appropriate and relevant indicators of thermal changes during exercise. As an extension of the initial work active muscle temperature (vastus lateralis) was measured during the exercise test, demonstrating a significantly lower resting temperature than the oft-reported “core” temperatures (rectal and oesophageal) as well as a significantly greater increase in temperature in comparison to all other measurement sites. Overall, the results of this first study indicated that the physiologically relevant temperatures measured at the oesophageal and muscle sites differed markedly to the outdated rectal temperature measurement site and should be used as measures of thermal response when evaluating oxygen loading (oesophageal) or unloading (active muscle). Utilising the definition of EIH as a decrease in PaO₂ of ≥ 10 mmHg, the effect of temperature correcting PaO₂ was evaluated in the second study. Arterial blood gases measured simultaneously to the temperature measurements during the incremental exercise test were adjusted for the temperature changes at each site (every 1ºC increase in temperature will increase a PaO₂ value by ~5 mmHg). Whilst uncorrected PaO₂ values indicated an almost 100% prevalence of EIH in this group, oesophageal temperature corrected PaO₂ values decreased this prevalence to ~50% while muscle temperature corrections resolved all cases of EIH and demonstrated an HYPEROXAEMIA (i.e. the reverse of the well-established phenomenon) in the majority of subjects. Further investigation of arterial oxygen content during the exercise test indicates that there is no disruption in the delivery of oxygen to the active muscles and therefore any performance decrement should be attributed to another mechanism. Whilst the phenomenon of EIH is determined by the definition applied and the use of temperature corrections in the case of PaO₂, its reproducibility in a test-retest situation had not previously been determined. Utilising a subset of previously tested subjects, the reproducibility of both temperature and PaO₂ were determined with results indicating that the blood gas response was highly reproducible, especially the minimum PaO₂ value noted during each exercise test. However, comparing a more statistically relevant definition of a change in PaO₂ of ± 2 standard deviations from the mean resting PaO₂ to the previous delimiter of 10 mmHg indicated a lesser reproducibility of the prevalence of EIH. In summary, this thesis exposes the inadequacies of previous research into EIH with regard to the expected reproducibility of the phenomenon and the need to correctly adjust PaO₂ values for exercise-induce hyperthermia as well as demonstrating the difference in thermal responses to acute exercise in physiologically significant areas of the body. Furthermore, previously described correlations between the change in PaO₂ and VO₂ max were not evident in the subjects tested within this thesis, nor was there any indication of a diffusion limitation based on reduced pulmonary capillary transit time (by association with VO₂ max) or pulmonary oedema (rebuked by a rapid return of PaO₂ to above resting levels following exercise cessation). / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1320633 / Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2008
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Metabolic responses to hyperthermia in two small desert mammals, the Pygmy rock mouse, Petromyscus Collinus and the Namaqua rock mouse, Aethomys Namaquensis.Mowoe, Metoboroghene Oluwaseyi. 07 November 2013 (has links)
The negative consequence of recent climate change on the Earth’s biodiversity has become more evident in recent years. Some animals, due to insularity or habitat fragmentation, are unable to shift their ranges altitudinally and latitudinally. Vulnerable species need to rely on behavioural and, more importantly, physiological responses in order to persist through present climatic changes. It has therefore become more obvious that physiological responses of individuals need to be incorporated into predictive models of the responses of mammals to accelerated climate change.
The primary purpose of this study was to test the ‘Hyperthermic Daily Torpor’ hypothesis proposed recently by Lovegrove et al., (in press). The hypothesis suggests that, based on albeit limited evidence, some small mammals may be capable of hyperthermia induced hypometabolism equivalent to that experienced during torpor and hibernation in response to cold temperatures. These authors argue that such hyperthermic hypometabolism should reduce the risk of entry into pathological hyperthermia and also reduce the rate of water loss driven by heat-induced evaporative cooling. The reaction norms of desert mammals have been selected to be adaptive over a wide range of climatic conditions due to the unpredictability of their habitat. Thus, they are good models for testing the reaction norms that may be expressed in response to accelerated climate change. We therefore tested our hypothesis using two presumably heat-adapted desert rodents; the Namaqua rock mouse, Aethomys namaquensis, and the pygmy rock mouse, Petromyscus collinus, as model species.
We used indirect respirometry to measure metabolic rate at high ambient temperatures. We progressively exposed the animals to high temperatures to induce thermal
tolerance and thus minimize the risks of lethal hyperthermia. We also measured subcutaneous and core temperatures, using temperature-sensitive PIT tags (BioTherm Identipet) and modified iButtons (Maxim Integrated), respectively.
A. namaquensis displayed the capacity for hyperthermia-induced hypometabolism (Q10 79 = 1.27 ± 1.61) whereas the P. collinus did not (Q10 = 2.45 ± 1.41).
The implications of such a physiological response in A. namaquensis are crucial in terms of its capacity to minimize the risks of lethal, pathological hyperthermia. Recent models of endothermic responses to global warming based on ectothermic models predict a dichotomy in the thermoregulatory responses of mammals to high temperatures. This study, to our knowledge, provides some of the first data on these interspecific variations in the thermoregulatory responses of mammals to high temperatures. However, the different physiological responses to hyperthermia between these two species cannot be meaningfully interpreted without phylogenetically independent comparisons with other species, that is, a more expansive interspecific analysis. Nonetheless, we provide some autecological sketches to assist in future multivariate interspecific analyses.
Physiological differences between captive or captive-bred and free-ranging mammals preclude the extrapolation of our findings to free-ranging mammals. It is almost impossible to collect MR data in the field, although a few authors have successfully done so, and it is often not feasible to collect Tb data in small free-ranging mammals. Most studies have therefore made use of externally-mounted temperature-sensitive data loggers in order to collect Tskin data as a proxy for Tcore data in free-ranging mammals. However, misleading gradients between Tskin and Tcore can occur if data loggers are placed too close to major-heat producing tissues and
the effects of the external environment on these data loggers may result in large Tskin – Tcore gradients.
The second objective of this thesis therefore was to test the validity of using subcutaneous temperatures (Tsub) from subcutaneously injected temperature-sensitive PIT tags as a proxy for Tcore using the Namaqua rock mouse, Aethomys namaquensis.
We found that the difference between Tcore and Tsub was minimal (~ 0.34˚C) within the thermoneutral zone (TNZ) with slight, non-significant, differences outside the TNZ. There was a tendency for Tsub to underestimate Tcore below thermoneutrality and overestimate it above thermoneutrality. We attributed these differences to the various heat loss and heat gain mechanisms activated in response to heat and cold stress in order to maintain a setpoint Tb. Nevertheless, we found that the Tcore – Tskin differential never exceeded 1.59˚C above the wide 108 range of Tas (5˚ – 41˚C) measured. Thus, we can conclude that subcutaneous temperatures provide a reasonably reliable proxy for core temperature in small mammals. / Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2012.
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A dynamic mechanistic anaylsis of the thermal interaction between a broiler chicken and its surrounding environment.January 2010 (has links)
Chickens, being open thermodynamic systems, maintain a constant exchange of energy
and matter with their surrounding environment. In order to avoid reaching
thermodynamic equilibrium with the environment the bird makes use of homeostatic
mechanisms. These ensure the reduction of the entropy of the system to values that
guarantee its integrality.
The thermoregulatory response is a major component of the homeostatic machinery of
living systems. This induces modifications of physiological parameters of the bird,
taking the system “bird” to a new steady state. The achievement of this new state is
possible only if the thermoregulatory mechanisms of the birds are able to counteract the
environmental demand/burden. A successful thermoregulatory response depends not
only on the achievement of that steady state, but also on the compatibility of the value
of those parameters with life (especially regarding the value achieved by body
temperature) as well as on the time of exposure to the environmental perturbation.
Based on those premises, this thesis presents a mechanistic analysis of the thermal
interaction between a broiler and its surroundings. The first section of the document
introduces the reader to the general concepts of thermodynamics of living systems and
physics of heat exchange. The second use mechanistic simulation techniques to represent
the environment, the thermal and thermoregulatory properties of a broiler chicken and
the interaction between bird and environment. Finally, the third section describes a
conceptual simulation model able to predict, over a given period of time, the response of
a bird to environmental conditions above those associated with least thermoregulatory
effort. Various simulation exercises are reported, the objectives being to study the
behaviour of certain variables and to question the validity of current theories of
thermoregulation in environmental physiology. / Thesis (Ph.D.)-University of KwaZulu-Natal, Pietermaritzburg, 2010.
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The behavioural thermoregulation and ecophysiology of the leopard tortoise (Geochelone pardalis) in the Nama-Karoo.McMaster, Megan Kay. 30 May 2014 (has links)
The leopard tortoise (Geochelone pardalis) is the largest of the southern African tortoise
species and has a wide distribution range. However, there is a lack of ecological and
physiological information about the species, especially arid and semi-arid regions. The
Nama-Karoo, an arid region of South Africa, is subject to large fluctuations in rainfall, food
availability and ambient temperatures (Ta). This study focused on the thermal behaviour,
thermoregulatory, digestive and metabolic plasticity of the leopard tortoise within the Nama-
Karoo biome.
Seasonal changes in activity patterns and body temperature (Tb) were investigated in
free ranging leopard tortoises in the Nama-Karoo. Leopard tortoises had unimodal daily
activity patterns in winter, bimodal in summer, and there were daily and seasonal differences
in the extent to which certain behaviours were practiced. Daily activity behaviours were
executed at lower Tb and at lower Ta in winter compared to summer. In summer, core Tb of
all tortoises oscillated on a daily basis well below maximum Ta, while core Tb of all tortoises
in winter oscillated well above the daily Ta range. Tortoises were therefore able to maintain
their Tb independently of Ta. Differences in Tb as measured from various positions on the
tortoises body was investigated in relation to Ta. There was a strong seasonal and temporal
influence on the relationship between various Tb’s, with the skin and external shell
temperatures being more variable in response to fluctuating Ta’s compared with cloacal and
core Tb. Cloacal temperatures were significantly different to other Tb measurements
suggesting that it should be treated with circumspection as an exclusive measure of Tb.
Heating and cooling rates of leopard tortoises were investigated in the field and under
controlled laboratory conditions to determine if the tortoises maximise operational daily
activity periods, and to determine the effect of behaviour and size on the rate of heat flux. In
the laboratory, cooling rates were faster than heating rates in summer and winter for all size
classes and decreased with increasing body mass. Leopard tortoises had significantly faster
heating and cooling rates in winter than in summer. Free-ranging leopard tortoises had faster
heating rates than cooling rates and their heat flux was largely independent of Ta. Heating
and cooling rates were dependant on body mass and surface area-to-volume ratio of
individuals. Under experimental conditions, tortoises physiologically adjusted their rate of
heat flux, while free-ranging tortoises used physiological and behavioural mechanisms to
minimise the risk of overheating, to aid thermal inertia and maximise operative activity time.
Seasonal climatic cycles and fluctuating daily temperatures influence the oxygen
consumption (VO2) of reptiles, however the result of these effects on metabolism in
chelonians is poorly understood. The effect of seasonal and daily differences in Ta on VO2
was investigated. Leopard tortoises’ VO2 was slightly higher than reported for other
chelonians. There were significant differences in tortoise VO2 at different Ta’s during the day
and night and in different seasons. This metabolic plasticity is possibly an adaptive
mechanism to cope with unpredictable environmental conditions.
Unpredictable climatic conditions lead to unpredictable food and water availability.
Little is known how tortoises adjust dietary parameters in response to food type and water
availability, and if this affects body mass, energy and water balance. Therefore this study
also considered whether leopard tortoises adjusted food transit rate, food intake and water
loss to cope with a diet fluctuating in fibre and water content, and whether body mass, energy
and water balance were maintained. Leopard tortoises fed a high fibre, low water content diet
had lower food intake rates, longer food transit times, but lower daily energy assimilation
compared with tortoises fed a low fibre, high water content diet. Tortoises fed a high fibre,
low water content diet had lower urine osmolality, but similar total water loss to those fed a
high fibre, low water content diet. The results indicate that tortoises can adjust digestive
parameters according to diet composition and exercise some control over energy and water
balance.
It is concluded that leopard tortoises show a high degree of plasticity in their thermal
behaviour and physiology which allows survival in an unpredictable environment,
particularly where there are fluctuations in rainfall, food availability and Ta’s. Seasonal and
daily variation in thermoregulation, metabolic rate and the uptake of energy allows the
leopard tortoise to maximise the duration of operative temperature, to minimise energy loss
and to use variable and unpredictable seasonal resources. / Thesis (Ph.D.)-University of KwaZulu-Natal, Pietermaritzburg, 2007.
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The impact of core temperature corrections on exercise-induced hypoxemia.Shipp, Nicholas Jon January 2008 (has links)
The primary purpose of this doctoral dissertation was to investigate the effect of body temperature responses at physiologically relevant sites during an incremental exercise test on the phenomenon of exercise-induced hypoxemia (EIH). This phenomenon has been considered as an important limitation to physical performance with a prevalence of ~50 % in trained male athletes, but described in both sexes, across the range of both age and physical fitness in more recent literature. Previously this phenomenon has been described as a decrement in both arterial oxygen partial pressure (PaO₂) and oxy-haemoglobin saturation (SaO₂or SpO₂) with, particularly important for PaO₂, a lack of or inappropriate correction made for the change in body temperature during intense exercise. The initial study of this thesis determined the thermal response within the body at physiologically relevant sites measured simultaneously during an incremental exercise test. The results demonstrated the inadequacy of rectal temperature as an indicator of the acute temperature changes occurring during an incremental exercise test due to its slow response rate and relative thermal inertia. Radial arterial blood and oesophageal temperatures were shown to behave almost identically during the exercise test, albeit with an offset of approximately 1.3ºC, and were considered much more appropriate and relevant indicators of thermal changes during exercise. As an extension of the initial work active muscle temperature (vastus lateralis) was measured during the exercise test, demonstrating a significantly lower resting temperature than the oft-reported “core” temperatures (rectal and oesophageal) as well as a significantly greater increase in temperature in comparison to all other measurement sites. Overall, the results of this first study indicated that the physiologically relevant temperatures measured at the oesophageal and muscle sites differed markedly to the outdated rectal temperature measurement site and should be used as measures of thermal response when evaluating oxygen loading (oesophageal) or unloading (active muscle). Utilising the definition of EIH as a decrease in PaO₂ of ≥ 10 mmHg, the effect of temperature correcting PaO₂ was evaluated in the second study. Arterial blood gases measured simultaneously to the temperature measurements during the incremental exercise test were adjusted for the temperature changes at each site (every 1ºC increase in temperature will increase a PaO₂ value by ~5 mmHg). Whilst uncorrected PaO₂ values indicated an almost 100% prevalence of EIH in this group, oesophageal temperature corrected PaO₂ values decreased this prevalence to ~50% while muscle temperature corrections resolved all cases of EIH and demonstrated an HYPEROXAEMIA (i.e. the reverse of the well-established phenomenon) in the majority of subjects. Further investigation of arterial oxygen content during the exercise test indicates that there is no disruption in the delivery of oxygen to the active muscles and therefore any performance decrement should be attributed to another mechanism. Whilst the phenomenon of EIH is determined by the definition applied and the use of temperature corrections in the case of PaO₂, its reproducibility in a test-retest situation had not previously been determined. Utilising a subset of previously tested subjects, the reproducibility of both temperature and PaO₂ were determined with results indicating that the blood gas response was highly reproducible, especially the minimum PaO₂ value noted during each exercise test. However, comparing a more statistically relevant definition of a change in PaO₂ of ± 2 standard deviations from the mean resting PaO₂ to the previous delimiter of 10 mmHg indicated a lesser reproducibility of the prevalence of EIH. In summary, this thesis exposes the inadequacies of previous research into EIH with regard to the expected reproducibility of the phenomenon and the need to correctly adjust PaO₂ values for exercise-induce hyperthermia as well as demonstrating the difference in thermal responses to acute exercise in physiologically significant areas of the body. Furthermore, previously described correlations between the change in PaO₂ and VO₂ max were not evident in the subjects tested within this thesis, nor was there any indication of a diffusion limitation based on reduced pulmonary capillary transit time (by association with VO₂ max) or pulmonary oedema (rebuked by a rapid return of PaO₂ to above resting levels following exercise cessation). / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1320633 / Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2008
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Human responses to cold and wind /Gavhed, Désirée, January 2003 (has links) (PDF)
Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 6 uppsatser.
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Restrição alimentar intra-uterina e suas repercussões sobre o desenvolvimento da termorregulação da prole / Maternal food restriction and its impact on offspring's development of thermoregulationSouza, Thais Ladeira Vieira de [UNIFESP] 29 April 2009 (has links) (PDF)
Made available in DSpace on 2015-07-22T20:50:46Z (GMT). No. of bitstreams: 0
Previous issue date: 2009-04-29 / Introdução: Estudo previamente realizado em nosso laboratório demonstrou que a restrição alimentar intra-uterina (RAIU) provoca um retardo na termorregulação dos recém-nascidos. Em neonatos o tecido adiposo marrom (TAM) é essencial para a termogênese, principalmente devido à presença de proteínas desacopladoras (UCPs), cuja expressão pode ser modificada pela ação de hormônios como os hormônios da tireóide, a leptina e a insulina, que podem ser afetados pela restrição alimentar. A bomba de cálcio do retículo sarcoplasmático (SERCA1), presente no músculo e recentemente identificada no TAM, pode contribuir para a produção de calor. Objetivo: Avaliar a expressão das proteínas UCP1, UCP2, UCP3 e da SERCA1 no TAM e da UCP3 e da SERCA1 no músculo esquelético (ME) de animais submetidos a RAIU, bem como o perfil plasmático de insulina, leptina e hormônios tireoidianos destes filhotes. Métodos: Ratos fêmeas Wistar EPM-1 controle (C) receberam ração ad libitum durante todo o período gestacional e o grupo restrito (R) recebeu 50% desta quantidade. Quinze horas após o nascimento (pico de expressão das UCPs), os filhotes foram pesados e decapitados para coleta de sangue (pool) para a dosagem plasmática de insulina, leptina, T3 e T4 por ELISA. Foram coletados TAM e ME, para determinação da expressão das UCPs e da SERCA1 por imuno-histoquímica. Para análise dos resultados, utilizou-se o teste “t” de Student não pareado, com nível de significância de 5%. Resultados: Os animais R (n=16) apresentaram durante a gestação um ganho de peso corporal (g) significantemente inferior quando comparado ao C (n=16), (27,6 ± 3,8 e 109,0 ± 4,1). Os filhotes R (n=172) apresentaram redução significante do peso corporal (g) ao nascimento em relação aos filhotes C (n=169) (4,82 ± 0,05 e 5,83 ± 0,04); entretanto, não houve redução no número de filhotes por ninhada. A RAIU levou a um aumento significante na expressão (pixels) da UCP1 e da UCP2 no TAM da prole R em relação à prole C (em 42% e 53%, respectivamente). Não observamos diferença significante entre os grupos em relação à expressão da UCP3 e da SERCA1 no TAM e no ME. A concentração plasmática de insulina (ng/ml) foi significantemente maior nos filhotes R (n=8) em relação aos C (n=13) (3,34 ± 0,78 e 1,17 ± 0,18) e os níveis plasmáticos de T3 (ng/ml) foram significantemente menores nos filhotes R (n=10) quando comparados aos C (n=14) (0,82 ± 0,06 e 1,09 ± 0,08). Não houve diferenças significantes para as dosagens plasmáticas de leptina (pg/ml) (R (n=8) 987,79 ± 261,08 e C (n=11) 1255,54 ± 392,37) e T4 (ng/ml) (R (n=10) 20,99 ± 3,74 e C (n=12) 16,00 ± 1,68). Conclusão: O atraso no desenvolvimento da termorregulação previamente descritos nesses animais não parece resultar de redução na termogênese, mas de aumento na termólise, pois a RAIU provocou baixo peso dos filhotes ao nascimento, levando a uma maior relação superfície/ volume. A maior expressão da UCP1 e UCP2 no TAM observada nos filhotes restritos possivelmente ocorreu como um mecanismo compensatório para aumentar a termogênese, o que pode ter sido modulado por ação hormonal. / Background: Previous study from our laboratory has shown that intrauterine food restriction (IUFR) delayed thermoregulation of the newborns. In neonates brown adipose tissue (BAT) is essential for thermogenesis mainly due to the presence of uncoupling proteins (UCPs) and their expression can be modified by action of hormones such as thyroid hormone, leptin and insulin, which can be affected by food restriction. The sarcoplasmic reticulum Ca++ ATPase, (SERCA1) recently identified in BAT may contribute to heat production. Aim: The aim of this study was to evaluate the protein expression of UCP1, UCP2, UCP3 and SERCA1 in BAT and UCP3 and SERCA1 in skeletal muscle (SM) and the plasmatic concentration of insulin, leptin, T3 and T4 of newborn rats exposed to IUFR. Methods: Female Wistar EPM-1 control rats received chow ad libitum during pregnancy period (C) and food-restricted rats (R) received 50% of the amount ingested by C. Fifteen hours after birth, newborns were weighted and sacrificed by decapitation. Blood was collected for determination of insulin, leptin, T3 and T4 by ELISA. BAT and SM were used for determination of protein expression (UCPs and SERCA1) by immunohistochemistry. Unpaired Student’s t-test was used for statistical analysis of the results (p<0,05). Results: R animals (n=16) showed a significant lower weight gain (g) during pregnancy when compared to C (n=16) (27,6 ± 3,8 and 109,0 ± 4,1). R pups (n=172) showed a significant reduction in their body weight (g) at birth when compared to C (n=169) (4,82 ± 0,05 and 5,83 ± 0,04); however, there was no reduction in number of pups per litter. IUFR caused a significant increase in the expression (pixels) of UCP1 and UCP2 in BAT of the pups (42% and 53% respectively). UCP3 and SERCA1 expression in BAT and SM showed no significant differences between groups. Plasmatic insulin (ng/ml) was significantly higher in R pups (n=8) when compared to C (n=13) (3,34 ± 0,78 and 1,17 ± 0,18) and T3 levels (ng/ml) was significantly lower in R pups (n=10) when compared to C (n=14) (0,82 ± 0,06 and 1,09 ± 0,08). No differences between groups were found for leptin (pg/ml) (R (n=8) 987,79 ± 261,08 and C (n=11) 1255,54 ± 392,37) and T4 (ng/ml) levels (R (n=10) 20,99 ± 3,74 and C (n=12) 16,00 ± 1,68). Conclusion: The delay in development of thermoregulation previously described in these animals appears not to result from impairment in thermogenesis, but from an increase in heat loss, since IUFR caused low birth weight in pups, leading to greater surface/ volume ratio. The higher expression of UCP1 and UCP2 in BAT showed by R pups possibly occurred as a compensatory mechanism to increase thermogenesis, which may have been modulated by hormonal regulation. / TEDE / BV UNIFESP: Teses e dissertações
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