Thesis (M.Eng.)--Memorial University of Newfoundland, 2005. / Bibliography: leaves 112-116.

The Siberian hamster (Phodopus sungorus) undergoes a suite of physiological changes in response to short day (SD) photoperiod which includes a marked reduction in body mass (up to 40%). This altered physiology can be reversed by a return to long day (LD) photoperiod and is driven by changes hypothalamic gene expression. Additionally, stimulation of weight regain occurs through spontaneous exercise when hamsters are provided with a running wheel (RW), despite intact photoperiod appropriate hypothalamic gene expression. The foundation hypothesis for this investigation was that the change in body weight in both paradigms is underpinned by an alteration of the growth hormone (GH) axis. Pasireotide, a somatostatin agonist, was utilised to inhibit GH secretion from the pituitary in both paradigms. Measurement of body mass, mass of internal organs, body composition by magnetic resonance imaging, hormonal analysis and in situ hybridization were used to determine the effect of a blockade of GH secretion by pasireotide. Pasireotide suppressed the GH axis in Siberian hamsters; with reduced circulating insulin-like growth factor-1 and altered hypothalamic gene expression of somatostatin (srif) and growth hormone – releasing hormone (ghrh) consistent with an inhibition of pituitary GH secretion. Pasireotide treatment inhibited RW and LD stimulated growth, and when administered to LD hamsters caused weight loss in a similar manner to that which occurs in SD and accompanied by testicular atrophy. In addition, pasireotide increased the incidence of torpor and increased bout length of this hypometabolic state in sedentary SD hamsters. In conclusion, evidence is provided for the hypothalamic – pituitary – growth hormone axis in the determination of photoperiod and RW induced body weight changes. Furthermore, the data show evidence for a novel muscle – brain pathway and evidence for a neuroendocrine pathway involved in torpor induction.

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Opioid-based agents represent the cornerstone of analgesia in modern clinical practice. Additionally however opioids produce a range of unwelcome side-effects including immunomodulation. It has been suggested that this immunomodulation may result either as a direct effect of opioids on circulating immune cells or via a central action. Meanwhile studies show that classical opioid receptors are up-regulated in peripheral inflammation, while endogenous opioids are released from circulating immune cells producing local analgesia. Expression of opioid receptors on immune cells however remains contentious. This thesis has made a significant contribution to understanding the interaction between opioids and a neurovascularimmune axis by employing radioligand binding, flow cytometry and polymerase chain reaction techniques to make a systematic and detailed examination of the expression of the classical opioid receptors (MOP, DOP and KOP) and the non-classical opioid receptor (NOP) and the precursor for its endogenous ligand N/OFQ (ppN/OFQ) in the peripheral blood mononuclear cells (PBMCs) of healthy volunteers. Using these techniques we have shown (1) that naïve human PBMCs do not express classical opioid receptors, (2) that PCR techniques support the view that PBMCs do express gene transcripts for NOP and ppN/OFQ. In an additional clinical study during a profound vascular insult we have used quantitative PCR and radioimmunoassay techniques to follow the expression of the opioid receptors and native N/OFQ throughout a septic episode in patients admitted to the intensive care unit (ICU). Here we report for the first time an elevation in plasma N/OFQ concentration in non-survivors of sepsis requiring ICU admission, 3.0 [2.5 – 5.0]pg ml-1 in non-survivors vs. 1.0 [1.0 – 2.5]pg ml-1 in survivors (p=0.028). Similarly we are first in reporting an elevation in plasma N/OFQ following major abdominal surgery in septic patients. These findings lead us to suggest an amendment to the previously proposed neuroimmune axis to include the N/OFQ-NOP system.

A spherometer is often used to precisely measure the radius of curvature of a spherical surface. It can also measure the vertex radius of a more complex surface such as an off-axis parabola (OAP). This paper provides a reliable algorithm to find the vertex radius of an OAP by solving a few equations based on the test geometry. This algorithm can also be easily expanded to any conic surface with high-order aspheric coefficients. The algorithm was verified by measuring an 8-inch diameter OAP and comparing the results with its known prescription. Results show good agreement. An example of measuring the vertex radius of a 4-m diameter OAP is also presented. In addition to this, a calculation was done to show that the coma and astigmatism are independent of the clocking of the spherometer on the optic. (C) 2016 Society of Photo-Optical Instrumentation Engineers (SPIE)

The gut and the brain are in constant communication through pathways that include the immune system, the nervous system, neurotransmitters, and hormones. Modifications in the gut, especially the gut microbiome, have the potential to cause changes in the brain resulting in behavioral and cognitive changes. A healthy and diverse microbiome, which may be achieved by a high fiber diet or probiotic or prebiotic treatments, is associated with improvements in cognition. Gut dysbiosis and a decrease in diversity of the microbiota, which may be caused by a western diet or antibiotic treatments, is associated with cognitive decline and decreased memory. There are many possible pathways through which these changes in the gut act to change cognition, including the immune system, the expression of brain derived neurotropic factor, metabolites such as short chain fatty acids, gut hormones, and neurotransmitters. If researchers can decipher which pathways are involved in modifying cognition, they may be able to identify treatments that can help improve memory and specifically decrease age-related cognitive decline.

Dynamic interactions of behavior-related traits and the physiological stress response bear upon the beef industry by impacting animal welfare, health, and productivity. The specific mechanisms of hypothalamic-pituitary-adrenal (HPA) axis dysfunction as related to cattle temperament remain unclear. To further characterize endophenotypes associated with the complex interaction of environment and genotype, the following experiments focused on stimulation and regulation of the pituitary gland in cattle of differing genetic background and temperament. Using serial blood sampling, via jugular cannula, the pituitary and subsequent adrenal response to exogenous vasopressin (VP) was characterized for steers of an excitable or calm temperament. Exit velocity (EV) measured at weaning was used to determine steer temperament. Endocrine parameters were measured for 6 h before and 6 h after the VP administration to quantify the stress response to both the handling associated with the experimental procedures and pharmacological challenge. Elevated concentrations of cortisol in excitable steers during the pre-challenge period reflected an increased initial adrenal reactivity to interactions with humans. Subsequent acclimation to the experimental surroundings yielded greater baseline cortisol concentrations in the cattle with an excitable temperament. Pituitary stimulation with VP resulted in a greater adrenocorticotropic hormone (ACTH) output from the excitable compared to the calm animals. A separate experiment employed the same 12-h blood sampling protocol with a different pituitary secretagogue, corticotrophin-releasing hormone (CRH), in order to evaluate pituitary-adrenal responsiveness in cattle with differing temperaments and genetic backgrounds. Measures of EV at weaning identified the calmest and most excitable steers from two separate calf crops; one Angus and the other Brahman. Within breed, adrenal medullary response to initial handling was influenced by temperament as concentrations of epinephrine and norepinephrine were higher in the excitable steers of both breedtypes. Additionally, concentrations of cortisol also differed by temperament in the Angus steers at this time point. An effect of temperament on pituitary responsiveness to exogenous CRH was observed in the Angus but not the Brahman steers. Unlike what was observed with the previously described VP challenge, the pituitary responsiveness to CRH was blunted in the excitable steers. The specific endophenotypes which have been identified or reinforced through these experiments suggest that there are aspects of HPA dysfunction associated with bovine temperament.

Swallowing accelerometry may provide a portable and cost-effective bedside alternative to currently available instrumentation. In this study, dual-axis accelerometry signals were collected simultaneous to videofluoroscopic records from 29 pediatric participants (age 6.8 $\pm$ 4.8 years; 20 males) previously diagnosed with neurogenic dysphagia. Videofluoroscopic records were reviewed by a clinical expert to extract swallow timings and ratings. The dual-axis accelerometry signals corresponding to each identified swallow were pre-processed, segmented and trimmed prior to feature extraction from time, frequency, time-frequency and information theoretic domains. Feature space dimensionality was reduced via principal components. Using 8-fold cross-validation, 16-18 dimensions and a support vector machine classifier with an RBF kernel, an adjusted accuracy of 89.6\% $\pm$ 0.9 was achieved for the discrimination between swallows with and without airway entry. Our results suggest that dual-axis accelerometry has merit in the non-invasive detection of unsafe swallows in children and deserves further consideration as a pediatric medical device.