Autonomic regulation and blood pressure in children

Vagal baroreflex sensitivity (BRS) is a measure of short term blood pressure (BP) regulation through alterations in heart rate. Low BRS reflects impaired autonomic system regulation and has been found to be a surrogate marker for cardiovascular health. In particular, it has found to be associated with the pathogenesis of adult hypertension. However, only limited information exists as to the negative consequences of childhood BP on baroreflex function. The objective of this study was to investigate BRS in children with 2 different BP profiles while controlling for the effects of age, maturation, sex, and body composition. A preliminary subsample of 11-14 year-old children from the HBEAT (Heart Behavioural Environmental Assessment Team) Study was selected. The children were divided into 2 BP groups; high BP (HBP; 2:95tl1 percentile, n=21) and normal BP (NBP; <90th percentile, n=85). Following an initial 15 minutes of supine rest, 5 minutes of continuous beat-to-beat BP (Finapres) and RR interval (RRI) were recorded (standard ECG). Spectral indices were computed using Fast Fourier Transform and transfer function analysis was used to compute BRS. High frequency (HF) and low frequency (LF) power spectral areas were set to 0.15-0.4 Hz and 0.04-0.15 Hz, respectively. Body composition was measured using body mass index. After adjusting for body composition, maturation, age and sex ANCOV A results were as follows; LF and HF BRS, LF and HF RRI, and RRI total power were lower in the HBP versus NBP participants (p<0.05). As well, LF IHF SBP ratio was significantly higher in the HBP compared to the NBP group (p<0.05). The regression coefficients (unstandardized B) indicated that in changing groups (NBP to HBP) LF and HF BRS decreases by 4.04 and 6.18 ms/mmHg, respectively. Thus, as BP increases, BRS decreases. These data suggest that changes in autonomic activity occur in children who have HBP, regardless of age, sex, maturation, and body composition. Thus, despite their young age and relatively short amount of time having high BP compared with adults, these children are already demonstrating poor BP regulation and reduced cardiovagal activity. Given that childhood BP is associated with hypertension in adulthood, there is a growing concern in regards to the current cardiovascular health of our children and future adults.

The association between blood pressure and vascular characteristics in children

Hypertension is thought to exist in up to five percent of children. A select number of studies have investigated the role elevated blood pressure plays in pediatric atherosclerotic progression. However these studies contain significant methodological flaws and fail to recognize important confounding factors. Therefore, the influence of elevated blood pressure on arterial health in children remains to be clearly understood. The purpose of this study was to investigate the association between blood pressure (BP) and arterial thickness and stiffuess in children. Common carotid artery (CCA) intima-media thickness (IMT) and distensibility (Dist), as well as systemic pulse wave velocity (PWV) were measured in 21 elevated blood pressure (EBP; BP ~ 95th percentile) and 83 normal blood pressure (NBP; BP < 90th percentile) children 11-14 years of age. Both EBP and NBP groups demonstrated BP within the normal clinical range, but EBP showed significantly elevated BP as compared to the NBP group. Independent t-tests failed to show significant differences between the EBP and NBP groups for CCA IMT (0.43 ± 0.05 mm and 0.42 ± 0.06 mm, respectively) and Dist (0.0058 ± 0.0024 mmHg-1 and 0.0064 ± 0.0019 mmHil respectively). In contrast, a significantly elevated PWV (p

The Structural and Functional Changes of Blood Vessels during Aging

The vascular adventitia is recognized as a dynamic mediator of vascular structure and function, yet its role in aging is not understood. The purpose of this thesis was to examine the age-related changes of the vascular adventitia and determine the underlying mediators responsible. Male Sprague-Dawley rats were aged to 15, 30, 50 and 80 weeks before being anesthetised and euthanized by exsanguination. Thoracic aortas, mesenteric and pudental arteries were isolated, formalin fixed, and embedded in paraffin then sectioned at 5μm. Vessels were examined by microscopy and protein expression was determined by indirect immunofluorescence. The thickness of the adventitia increased dramatically with age. Immunofluorescence revealed a robust expression of endothelin system proteins in the adventitia. Additionally, extracellular matrix proteins collagen and fibronectin, and the proliferation marker Ki67 showed strong adventitial origin. The changes observed in the vascular adventitia with aging clearly demonstrate an important role in the process of vascular aging.

The structural and functional changes of blood vessels during aging

The vascular adventitia is recognized as a dynamic mediator of vascular structure and function, yet its role in aging is not understood. The purpose of this thesis was to examine the age-related changes of the vascular adventitia and determine the underlying mediators responsible. Male Sprague-Dawley rats were aged to 15,30,50 and 80 weeks before being anesthetised and euthanized by exsanguination. Thoracic aortas, mesenteric and pudental arteries were isolated, formalin fixed, and embedded in paraffin then sectioned at 51lm. Vessels were examined by microscopy and protein expression was determined by indirect immunofluorescence. The thickness of the adventitia increased dramatically with age. Immunofluorescence revealed a robust expression of endothelin system proteins in the adventitia. Additionally, extracellular matrix proteins collagen and fibronectin, and the proliferation marker Ki67 showed strong adventitial origin. The changes observed in the vascular adventitia with aging clearly demonstrate an important role in the process of vascular aging.

Blood, Sweat and Cheers: Absurdist Crime Films and Contemporary Society

Within the crime film tradition there is a plethora of sub-genres all of which relate to crime and its consequences. However, directors Joel and Ethan Coen, Quentin Tarantino and David Lynch, all of whom create plots around crime and criminality, have been difficult to pin down and attribute to any given sub-genre. This thesis demonstrates that an absurdist philosophy can be used to effectively examine the content of the previously mentioned filmmakers. Through an analysis of these filmmakers and their better known works compelling evidence is revealed suggesting that these filmmakers may all belong to the emerging crime film sub-genre known as absurdist crime films.

All of My Blood is Red: Contemporary Metis Visual Culture and Identity

This thesis explores notions of contemporary Metis identity through the lens of visual culture, as articulated in the works of three visual artists of Metis ancestry. I discuss the complexities of being Metis with reference to specific art works by Christi Belcourt, David Garneau and Rosalie Favell. In addition to a visual culture analysis of these three Metis artists, I supplement my discussion of Metis identity with a selection of autoethnographic explorations of my identity as a Metis woman through out this thesis. The self-reflexive aspect of this work documents the ways in which my understanding of myself as a Metis woman have been deepened and reworked in the process of conducting this research, while also offering an expanded conception of contemporary Metis culture. I present this work as an important point of departure for giving a greater presence to contemporary Metis visual culture across Canada:

Effect of increased milk intake combined with endurance exercise training on body composition, blood-lipids and inflammatory markers in overweight young males

Consuming low-fat milk (LFM) after resistance training leads to improvements in body composition. Habitual aerobic exercise and dairy intake are relatively easy lifestyle modifications that could benefit a population at risk for becoming obese. Thus, the purpose of this study was to investigate combining increased LFM intake with endurance exercise on body composition, blood-lipid profile and metabolic markers. 40 young males were randomized into four groups: one ingesting 750mL LFM immediately post-exercise, the other 6hrs post-exercise; and two isocaloric carbohydrate groups ingesting at the two different times. Participants completed a 12 week endurance-training program (cycling 1 hour/day at ~60%VO2peak, 5 days/week). 23 participants completed the study. Increases in lean mass (p < 0.05), and decreases in anti-inflammatory marker adiponectin (p < 0.05) were seen in all groups. No other significant changes were observed. Future analyses should focus on longer duration exercise and include a larger sample.

DONATION DECISIONS: THE ROLES OF FINANCIAL AND EMOTIONAL INFORMATION

This paper investigates the impact of personal affinity toward a charity and information regarding financial management of potential recipient charitable organizations on decisions to donate. Using an experiment, the study examines how personal donation decisions differ from corporate donation decisions made by managers and how the emotional intelligence of donors affects donation decisions. The results indicate that threshold and financial information on charities assembled by the Better Business Bureau, a charity rating agency, made a significant impact on corporate donation decisions. The study also shows that emotional intelligence plays an important role that aids both individual donors and managers to regulate their donation decisions.

Examining the roles of core and local temperature on forearm skin blood flow

The interaction between local and reflexive control of skin blood flow (SkBF) is unclear. This thesis isolated the roles of rectal (Tre) and local (Tloc) temperature on forearm SkBF regulation at normal and elevated body temperatures, and to investigate the interaction between local and reflexive SkBF control. While either normothermic (Tre ~37.0°C) or hyperthermic (∆Tre +1.1°C), SkBF was assessed on the dorsal aspect of each forearm in 10 participants while Tloc was manipulated in an A-B-A-B fashion between neutral (33.0°C) and hot (38.5°C). Finally, local heating to 44°C was performed to elicit maximal SkBF. Data are presented as a percentage of maximal cutaneous vascular conductance (CVC), calculated as laser-Doppler flux divided by mean arterial pressure. Tloc manipulations performed during normothermia had significantly greater effects on CVC than during hyperthermia. The decreased modification to SkBF from the Tloc changes during hyperthermia suggests that strong reflexive vasodilation attenuates local SkBF control mechanisms.

Effects of Cerebral Blood Flow and PETCO2 on Cognitive Function During Passive Heat Stress

This thesis tested whether cognitive performance during passive heat stress may be affected by changes in cerebrovascular variables as opposed to strictly thermally-induced changes. A pharmacological reduction in cerebral blood flow (CBF) using indomethacin along with a hypocapnia-induced CBF reduction during passive heat stress (Tre ~1.5°C above baseline) were used to investigate any cerebrovascular-mediated changes in cognitive performance. Repeated measures analysis of variance indicated that One-Touch Stockings of Cambridge (OTS) performance was not affected by a significant reduction in CBF during passive heat stress. More specifically, OTS accuracy measures did not change as a result of either a reduction in CBF or increasing passive heat stress. However, it was found that OTS response time indices improved with increasing passive heat stress independent of CBF changes. In conclusion, a significant reduction in CBF does not cause additional changes in performance of an executive functioning task during severe passive heat stress.

The Influence of Cerebral Blood Flow and Carbon Dioxide on Neuromuscular Responses During Environmental Stress

Although reductions in cerebral blood flow (CBF) may be implicated in the development of central fatigue during environmental stress, the contribution from hypocapnia-induced reductions in CBF versus reductions in CBF per se has yet to be isolated. The current research program examined the influence of CBF, with and without consequent hypocapnia, on neuromuscular responses during hypoxia and passive heat stress. To this end, neuromuscular responses, as indicated by motor evoked potentials (MEP), maximal M-wave (Mmax) and cortical voluntary activation (cVA) of the flexor carpi radialis muscle during isometric wrist flexion, was assessed in three separate projects: 1) hypocapnia, independent of concomitant reductions in CBF; 2) altered CBF during severe hypoxia and; 3) thermal hyperpnea-mediated reductions in CBF, independent of hypocapnia. All projects employed a custom-built dynamic end-tidal forcing system to control end-tidal PCO2 (PETCO2), independent of the prevailing environmental conditions, and cyclooxygenase inhibition using indomethacin (Indomethacin, 1.2 mg·Kg-1) to selectively reduce CBF (estimated using transcranial Doppler ultrasound) without changes in PETCO2. A primary finding of the present research program is that the excitability of the corticospinal tract is inherently sensitive to changes in PaCO2, as demonstrated by a 12% increase in MEP amplitude in response to moderate hypocapnia. Conversely, CBF mediated reductions in cerebral O2 delivery appear to decrease corticospinal excitability, as indicated by a 51-64% and 4% decrease in MEP amplitude in response to hypoxia and passive heat stress, respectively. The collective evidence from this research program suggests that impaired voluntary activation is associated with reductions in CBF; however, it must be noted that changes in cVA were not linearly correlated with changes in CBF. Therefore, other factors independent of CBF, such as increased perception of effort, distress or discomfort, may have contributed to the reductions in cVA. Despite the functional association between reductions in CBF and hypocapnia, both variables have distinct and independent influence on the neuromuscular system. Therefore, future studies should control or acknowledge the separate mechanistic influence of these two factors.

Umbilical Cord Blood Banking

The umbilical cord, previously considered as waste and discarded at birth, is a source of haematopoietic stem cells. Current therapeutic uses of umbilical cord blood stem cells and the promise of these cells for the treatment of degenerative diseases in the future have led to the establishment of cord blood banks in many parts of the world. Although umbilical cord blood banking raises many ethical and legal issues, this article focuses on the controversy created by the coexistence of public and private cord blood banks in many countries. Policy statements adopted by professional associations and advisory groups indicate that, based on the current state of medical evidence, childbearing women with no current or potential familial need of stem cell transplantation should be encouraged to donate cord blood to public banks.

The importance of the Hedgehog signaling pathway at the level of the blood-brain barrier

La barrière hémato-encéphalique (BHE) protège le système nerveux central (SNC) en contrôlant le passage des substances sanguines et des cellules immunitaires. La BHE est formée de cellules endothéliales liées ensemble par des jonctions serrées et ses fonctions sont maintenues par des astrocytes, celles ci sécrétant un nombre de facteurs essentiels. Une analyse protéomique de radeaux lipidiques de cellules endothéliales de la BHE humaine a identifié la présence de la voie de signalisation Hedgehog (Hh), une voie souvent liées à des processus de développement embryologique ainsi qu’au niveau des tissus adultes. Suite à nos expériences, j’ai déterminé que les astrocytes produisent et secrètent le ligand Sonic Hh (Shh) et que les cellules endothéliales humaines en cultures primaires expriment le récepteur Patched (Ptch)-1, le co-récepteur Smoothened (Smo) et le facteur de transcription Gli-1. De plus, l’activation de la voie Hh augmente l’étanchéité des cellules endothéliales de la BHE in vitro. Le blocage de l’activation de la voie Hh en utilisant l’antagoniste cyclopamine ainsi qu’en utilisant des souris Shh déficientes (-/-) diminue l’expression des protéines de jonctions serrées, claudin-5, occcludin, et ZO-1. La voie de signalisation s’est aussi montrée comme étant immunomodulatoire, puisque l’activation de la voie dans les cellules endothéliales de la BHE diminue l’expression de surface des molécules d’adhésion ICAM-1 et VCAM-1, ainsi que la sécrétion des chimiokines pro-inflammatoires IL-8/CXCL8 et MCP-1/CCL2, créant une diminution de la migration des lymphocytes CD4+ à travers une monocouche de cellules endothéliales de la BHE. Des traitements avec des cytokines pro-inflammatoires TNF-α and IFN-γ in vitro, augmente la production de Shh par les astrocytes ainsi que l’expression de surface de Ptch-1 et de Smo. Dans des lésions actives de la sclérose en plaques (SEP), où la BHE est plus perméable, les astrocytes hypertrophiques augmentent leur expression de Shh. Par contre, les cellules endothéliales de la BHE n’augmentent pas leur expression de Ptch-1 ou Smo, suggérant une dysfonction dans la voie de signalisation Hh. Ces résultats montrent que la voie de signalisation Hh promeut les propriétés de la BHE, et qu’un environnement d’inflammation pourrait potentiellement dérégler la BHE en affectant la voie de signalisation Hh des cellules endothéliales.