The Influence of Age, Cardiorespiratory Fitness, Exercise and Sedentary Behaviours on Circulating Angiogenic Cells and Cell Surface Receptor Expression.

Cardiovascular disease (CVD) is the biggest killer of people in western civilisation. Age is a significant risk factor for the development for CVD, and treatments and therapies to address this increased risk are crucial to quality of life and longevity. Exercise is one such intervention which has been shown to reduce CVD risk. Age is also associated with endothelial dysfunction, reduced angiogenic capabilities, and reduced ability to repair the vessel wall. Circulating angiogenic cells (CACs) are a subset of circulating cells which assist in the repair and growth of the vasculature and in the maintenance of endothelial function. Reductions in these cells are observed in those with vascular disease compared to age-matched healthy controls. Exercise may reduce CVD risk by improvements in number and/or function of these CACs. Data was collected from human volunteers of various ages, cardiorespiratory fitness (CRF) levels and latent viral infection history status to investigate the effects of chronological age, CRF, viral serology and other lifestyle factors, such as sedentary behaviours and exercise on CACs. The levels of CACs in these volunteers were measured using four colour flow cytometry using various monoclonal antibodies specific to cell surface markers that are used to identify specific subsets of these CACs. In addition, the response to acute exercise of a specific subset of these CACs, termed ‘angiogenic T-cells’ (TANG) were investigated, in a group of well-trained males aged 20-40 years, using a strenuous submaximal exercise bout. Advancing age was associated with a decline in various subsets of CACs, including bone marrow-derived CD34+ progenitors, putative endothelial progenitor cells (EPCs) and also TANG cells. Individuals with a higher CRF were more likely to have higher circulating numbers of TANG cells, particularly in the CD4+ subset. CRF did not appear to modulate CD34+ progenitors or EPC subsets. Increasing sitting time was associated with reduction in TANG cells, but after correcting for the effects of fitness, sitting time no longer negatively affected the circulating number of these cells. Acute exercise was a powerful stimulus for increasing the number of TANG cells (140% increase), potentially through an SDF-1:CXCR4-dependent mechanism, but more studies are required to investigate this. Latent CMV infection was associated with higher number of TANG cells (CD8+), but only in 18-40 year old individuals, and not in an older age group (41-65 year old). The significance of this has yet to be understood. In conclusion, advancing age may contribute to increased CVD risk partly due to the observed reductions in angiogenic cells circulating in the peripheral compartment. Maintaining a high CRF may attenuate this CVD reduction by modulating TANG cell number, but potentially not CD34+ progenitor or EPC subsets. Acute exercise may offer a short window for vascular adaptation through the mobilisation of TANG cells into the circulation.

Synthesis, characterization and chemical vapor deposition of transition metal di(tert-butyl)amido compounds

Although the transition metal chemistry of many dialkylamido ligands has been well studied, the chemistry of the bulky di(tert-butyl)amido ligand has been largely overlooked. The di(tert-butyl)amido ligand is well suited for synthesizing transition metal compounds with low coordination numbers; such compounds may exhibit interesting structural, physical, and chemical properties. Di(tert-butyl)amido complexes of transition metals are expected to exhibit high volatilities and low decomposition temperatures, thus making them well suited for the chemical vapor deposition of metals and metal nitrides. Treatment of MnBr₂(THF)₂, FeI₂, CoBr₂(DME), or NiBr₂(DME) with two equivalents of LiN(t-Bu)2 in benzene affords the two-coordinate complex M[N(t-Bu)₂]₂, where M is Mn, Fe, Co, or Ni. Crystallographic studies show that the M-N distances decrease across the series: 1.9365 (Mn), 1.8790 (Fe), 1.845 (Co), 1.798 Å (Ni). The N-M- N angles are very close to linear for Mn and Fe (179.30 and 179.45°, respectively), but bent for Co and Ni (159.2 and 160.90°, respectively). As expected, the d⁵ Mn complex has a magnetic moment of 5.53 μΒ that is very close to the spin only value. The EPR spectrum is nearly axial with a low E/D ratio of 0.014. The d⁶ Fe compound has a room temperature magnetic moment of 5.55 μΒ indicative of a large orbital angular momentum contribution. It does not exhibit a Jahn-Teller distortion despite the expected doubly degenerate ground state. Applied field Mössbauer spectroscopy shows that the effective internal hyperfine field is unusually large, Hint = 105 T. The magnetic moments of Co[N(t-Bu)₂]₂ and Ni[N(t-Bu)₂]₂ are 5.24 and 3.02 μΒ respectively. Both are EPR silent at 4.2 K. Treatment of TiCl₄ with three equivalents of LiN(t-Bu)2 in pentane affords the briding imido compound Ti₂[μ-N(t-Bu)]₂Cl₂[N(t-Bu)₂]₂ via a dealkylation reaction. Rotation around the bis(tert-butyl)amido groups is hindered, with activation parameters of ΔH‡ = 12.8 ± 0.6 kcal mol-1 and ΔS‡ = -8 ± 2 cal K-1 ·mol-1, as evidenced by variable temperature 1H NMR spectroscopy. Treatment of TiCl₄ with two equivalents of HN(t-Bu)₂ affords Ti₂Cl₆[N(t-Bu)₂]₂. This complex shows a close-contact of 2.634(3) Å between Ti and the carbon atom of one of the CH₃ substituents on the tert-butyl groups. Theoretical considerations and detailed structural comparisons suggest this interaction is not agostic in nature, but rather is a consequence of interligand repulsions. Treatment of NiI₂(PPh3)₂ and PdCl₂(PPh₃)₂ with LiN(t-Bu)₂in benzene affords Ni[N(t-Bu)₂](PPh₃)I and Pd₃(μ₂-NBut₂)2(μ₂-PPh₂)Ph(PPh₃) respectively. The compound Ni[N(t-Bu)₂](PPh₃)I has distorted T-shape in geometry, whereas Pd₃(μ₂-NBut₂)₂(μ₂-PPh₂)Ph(PPh₃) contains a triangular palladium core. Manganese nitride films were grown from Mn[N(t-Bu)₂]₂ in the presence of anhydrous ammonia. The growth rate was several nanometers per minute even at the remarkably low temperature of 80⁰C. As grown, the films are carbon- and oxygen-free, and have a columnar morphology. The spacings between the columns become smaller and the films become smoother as the growth temperature is increased. The composition of the films is consistent with a stoichiometry of Mn₅N₂.

Characterisation of the Lipid Profile of the Portuguese Population

Cardiovascular disease (CVD), particularly coronary heart disease (CHD) and stroke, are the leading cause of morbidity and mortality worldwide. The common forms of CVD have a complex aetiology in which interactions between multiple genetic and environmental factors play an important roles. The incidence rates of these diseases are increasing in developing countries as a result of the modification of lifestyles and increased prevalence of cardiovascular risk factors. Many independent cardiovascular risk factors could be modifiable, in contrast to the genetic risk factors. However, the associated risk of the genetic factors can be prevented if early identified, making genetic studies a priority in cardiovascular genetics research.

Characterisation of the lipid profile of the portuguese population

Cardiovascular disease (CVD), particularly coronary heart disease (CHD) and stroke, are the leading cause of morbidity and mortality worldwide. The common forms of CVD have a complex aetiology in which interactions between multiple genetic and environmental factors play an important role.

Lifestyle factors, adiposity and cardiometabolic risk factors in South Asian women living in Scotland

South Asians migrating to the Western world have a 3 to 5-fold higher risk of developing type 2 diabetes and double the risk of cardiovascular disease (CVD) than the background population of White European descent, without exhibiting a proportional higher prevalence of conventional cardiometabolic risk factors. Notably, women of South Asian descent are more likely to be diagnosed with type 2 diabetes as they grow older compared with South Asian men and, in addition, they have lost the cardio-protective effects of being females. Despite South Asian women in Western countries being a high risk group for developing future type 2 diabetes and CVD, they have been largely overlooked. The aims of this thesis were to compare lifestyle factors, body composition and cardiometabolic risk factors in healthy South Asian and European women who reside in Scotland, to examine whether ethnicity modifies the associations between modifiable environmental factors and cardiometabolic risks and to assess whether vascular reactivity is altered by ethnicity or other conventional and novel CVD risks. I conducted a cross-sectional study and recruited 92 women of South Asian and 87 women of White European descent without diagnosed diabetes or CVD. Women on hormone replacement therapy or hormonal contraceptives were excluded too. Age and body mass index (BMI) did not differ between the two ethnic groups. Physical activity was assessed and with self-reported questionnaires and objectively with the use of accelerometers. Cardiorespiratory fitness was quantified with the predicted maximal oxygen uptake (VO2 max) during a submaximal test (Chester step test). Body composition was assessed with skinfolds measured at seven body sites, five body circumferences, measurement of abdominal subcutaneous (SAT) and visceral adipose tissue (VAT) with the use of magnetic resonance imaging (MRI) and liver fat with the use MR spectroscopy. Dietary density was assessed with food frequency questionnaires. Vascular response was assessed by measuring the response to acetylcholine and sodium nitroprusside with the use of Laser Doppler Imaging with Iontophoresis (LDI-ION) and the response to shear stress with the use of Peripheral Arterial Tonometry (EndoPAT). The South Asian women exhibited a metabolic profile consistent with the insulin resistant phenotype, characterised by greater levels of fasting insulin, lower levels of high density lipoprotein (HDL) and higher levels of triglycerides (TG) compared with their European counterparts. In addition, the South Asians had greater levels of glycated haemoglobin (HbA1c) for any given level of fasting glucose. The South Asian women engaged less time weekly with moderate to vigorous physical activity (MVPA) and had lower levels of cardiorespiratory fitness for any given level of physical activity than the women of White descent. In addition, they accumulated more fat centrally for any given BMI. Notably, the South Asians had equivalent SAT with the European women but greater VAT and hepatic fat for any given BMI. Dietary density did not differ among the groups. Increasing central adiposity had the largest effect on insulin resistance in both ethic groups compared with physical inactivity or decreased cardiorespiratory fitness. Interestingly, ethnicity modified the association between central adiposity and insulin resistance index with a similar increase in central adiposity having a substantially larger effect on insulin resistance index in the South Asian women than in the Europeans. I subsequently examined whether ethnic specific thresholds are required for lifestyle modifications and demonstrated that South Asian women need to engage with MVPA for around 195 min.week-1 in order to equate their cardiometabolic risk with that of the Europeans exercising 150 min.week-1. In addition, lower thresholds of abdominal adiposity and BMI should apply for the South Asians compared with the conventional thresholds. Although the South Asians displayed an adverse metabolic profile, vascular reactivity measured with both methods did not differ among the two groups. An additional finding was that menopausal women with hot flushing of both ethnic groups showed a paradoxical vascular profile with enhanced skin perfusion (measured with LDI-ION) but decreased reactive hyperaemia index (measured with EndoPAT) compared with asymptomatic menopausal women. The latter association was independent of conventional CVD risk factors. To conclude, South Asian women without overt disease who live in Scotland display an adverse metabolic profile with steeper associations between lifestyle risk factors and adverse cardiometabolic outcomes compared with their White counterparts. Further work in exploring ethnic specific thresholds in lifestyle interventions or in disease diagnosis is warranted.

Perception of health benefits of dietary fibre among the Portuguese population

Introduction: Dietary iber (DF) has been part of human diet since ever, and its beneits for the human health have been well estab-lished and scientiically conirmed. Among these stand improved gastrointestinal functions, prevent cholesterol, diabetes or CVD. Objectives: To study the level of knowledge of people residing in Portugal about the health effects related to an adequate ingestion of DF. Methods: This is a descriptive cross-sectional study carried out on a non-probabilistic sample of 382 adults residing in Portugal. The questionnaire included a section about the socio-demographic characteristics (age, gender, level of education and living environ- ment) and another about the relation between dietary iber and possible beneicial effects to treat and prevent diseases. The data was treated using the SPSS software (V22). Results: The results allowed concluding that people were dif- ferently informed about the effects of DF in preventing and/or treating different diseases, being constipation the most recog- nized, followed in decreasing order by obesity, bowel cancer, cholesterol, cardiovascular diseases, diabetes and breast can- cer. The results also showed that signiicant differences were encountered between age groups for most of the diseases evalu- ated, but not between genders, levels of education or living en- vironments. Conclusions: Generally, it was concluded that the participants in this study were relatively well informed about the roles of DF in preventing and/or treating various diseases.

Oxidative stress and its haemodynamic consequences in chronic kidney disease

Chronic kidney disease (CKD) is associated with increased cardiovascular risk in comparison with the general population. This can be observed even in the early stages of CKD, and rises in proportion to the degree of renal impairment. Not only is cardiovascular disease (CVD) more prevalent in CKD, but its nature differs too, with an excess of morbidity and mortality associated with congestive cardiac failure, arrhythmia and sudden death, as well as the accelerated atherosclerosis which is also observed. Conventional cardiovascular risk factors such as hypertension, dyslipidaemia, obesity, glycaemia and smoking, are highly prevalent amongst patients with CKD, although in many of these examples the interaction between risk factor and disease differs from that which exists in normal renal function. Nevertheless, the extent of CVD cannot be fully explained by these conventional risk factors, and non-conventional factors specific to CKD are now recognised to contribute to the burden of CVD. Oxidative stress is a state characterised by excessive production of reactive oxygen species (ROS) and other radical species, a reduction in the capacity of antioxidant systems, and disturbance in normal redox homeostasis with depletion of protective vascular signalling molecules such as nitric oxide (NO). This results in oxidative damage to macromolecules such as lipids, proteins and DNA which can alter their functionality. Moreover, many enzymes are sensitive to redox regulation such that oxidative modification to cysteine thiol groups results in activation of signalling cascades which result in adverse cardiovascular effects such as vascular and endothelial dysfunction. Endothelial dysfunction and oxidative stress are present in association with many conventional cardiovascular risk factors, and can be observed even prior to the development of overt, clinical, vascular pathology, suggesting that these phenomena represent the earliest stages of CVD. In the presence of CKD, there is increased ROS production due to upregulated NADPH oxidase (NOX), increase in a circulating asymmetric dimethylarginine (ADMA), uncoupling of endothelial nitric oxide synthase (eNOS) as well as other mechanisms. There is also depletion in exogenous antioxidants such as ascorbic acid and tocopherol, and a reduction in activity of endogenous antioxidant systems regulated by the master gene regulator Nrf-2. In previous studies, circulating markers of oxidative stress have been shown to be increased in CKD, together with a reduction in endothelial function in a stepwise fashion relating to the severity of renal impairment. Not only is CVD linked to oxidative stress, but the progression of CKD itself is also in part dependent on redox sensitive mechanisms. For example, administration of the ROS scavenger tempol attenuates renal injury and reduces renal fibrosis seen on biopsy in a mouse model of CKD, whilst conversely, supplementation with the NOS inhibitor L-NAME causes proteinuria and renal impairment. Previous human studies examining the effect of antioxidant administration on vascular and renal function have been conflicting however. The work contained in this thesis therefore examines the effect of antioxidant administration on vascular and endothelial function in CKD. Firstly, 30 patients with CKD stages 3 – 5, and 20 matched hypertensive controls were recruited. Participants with CKD had lower ascorbic acid, higher TAP and ADMA, together with higher augmentation index and pulse wave velocity. There was no difference in baseline flow mediated dilatation (FMD) between groups. Intravenous ascorbic acid increased TAP and O2-, and reduced central BP and augmentation index in both groups, and lowered ADMA in the CKD group only. No effect on FMD was observed. The effects of ascorbic acid on kidney function was then investigated, however this was hindered by the inherent drawbacks of existing methods of non-invasively measuring kidney function. Arterial spin labelling MRI is an emerging imaging technique which allows measurement of renal perfusion without administration of an exogenous contrast agent. The technique relies upon application of an inversion pulse to blood within the vasculature proximal to the kidneys, which magnetically labels protons allowing measurement upon transit to the kidney. At the outset of this project local experience using ASL MRI was limited and there ensued a prolonged pre-clinical phase of testing with the aim of optimising imaging strategy. A study was then designed to investigate the repeatability of ASL MRI in a group of 12 healthy volunteers with normal renal function. The measured T1 longitudinal relaxation times and ASL MRI perfusion values were in keeping with those found in the literature; T1 time was 1376 ms in the cortex and 1491 ms in the whole kidney ROI, whilst perfusion was 321 mL/min/100g in the cortex, and 228 mL/min/100g in the whole kidney ROI. There was good reproducibility demonstrated on Bland Altman analysis, with a CVws was 9.2% for cortical perfusion and 7.1% for whole kidney perfusion. Subsequently, in a study of 17 patients with CKD and 24 healthy volunteers, the effects of ascorbic acid on renal perfusion was investigated. Although no change in renal perfusion was found following ascorbic acid, it was found that ASL MRI demonstrated significant differences between those with normal renal function and participants with CKD stages 3 – 5, with increased cortical and whole kidney T1, and reduced cortical and whole kidney perfusion. Interestingly, absolute perfusion showed a weak but significant correlation with progression of kidney disease over the preceding year. Ascorbic acid was therefore shown to have a significant effect on vascular biology both in CKD and in those with normal renal function, and to reduce ADMA only in patients with CKD. ASL MRI has shown promise as a non-invasive investigation of renal function and as a biomarker to identify individuals at high risk of progressive renal impairment.

Prevalence, types and factors associated with echocardiographic abnormalities among newly diagnosed diabetic patients at Mulago Hospital.

Background: The prevalence of Diabetes mellitus (DM) is on a rise in sub-Saharan Africa and will more than double by 2025. Cardiovascular disease (CVD) accounts for up to 2/3 of all deaths in the diabetic population. Of all the CVD deaths in DM, 3/4 occur in sub Saharan Africa (SSA). Non invasive identification of cardiac abnormalities, such as Left Ventricular Hypertrophy (LVH), diastolic and systolic dysfunction, is not part of diabetes complications surveillance programs in Uganda and there is limited data on this problem. This study sought to determine the prevalence, types and factors associated with echocardiographic abnormalities among newly diagnosed diabetic patients at Mulago National referral hospital in Uganda. Methods: In this cross sectional study conducted between June 2014 and December 2014, we recruited 202 newly diagnosed adult diabetic patients. Information on patients\' socio-demographics, bio-physical profile, biochemical testing and echocardiographic findings was obtained for all the participants using a pre-tested questionnaire. An abnormal echocardiogram in this study was defined as the presence of LVH, diastolic and/or systolic dysfunction and wall motion abnormality. Bivariate and multivariate logistic regression analyses were used to investigate the association of several parameters with echocardiographic abnormalities. Results: Of the 202 patients recruited, males were 102(50.5%) and the mean age was 46±15 years. Majority of patients had type 2 DM, 156(77.2%) and type 1 DM, 41(20.3%) with mean HbA1C of 13.9±5.3%. Mean duration of diabetes was 2 months. The prevalence of an abnormal echocardiogram was 67.8 % (95% CI 60%-74%). Diastolic dysfunction, systolic dysfunction, LVH and wall motion abnormalities were present in 55.0%, 21.8%, 19.3% and 4.0% of all the participants respectively. In bivariate logistic regression analysis, the factors associated with an abnormal echocardiogram were age (OR 1.09 [95% CI 1.06–1.12], P <0.0001), type 2 DM (OR 5.8[95% CI 2.77-12.07], P<0.0001), hypertension (OR 2.64[95% CI 1.44-4.85], P=0.002), obesity (OR 3.51[955 CI 1.25-9.84], P=0.017 and increased waist circumference (OR 1.02[95% CI 1.00-1.04], P=0.024. On Multiple logistic regression analysis, age was the only factor associated with an abnormal echocardiogram (OR 1.09[95%CI 1.05-1.15], P<0.0001). Conclusion: Echocardiographic abnormalities were common among newly diagnosed adults with DM. Traditional CVD risk factors were associated with an abnormal echocardiogram in this patient population. Due to a high prevalence of echocardiographic abnormalities among newly diagnosed diabetics, we recommend screening for cardiac disease especially in patients who present with traditional CVD risk factors. This will facilitate early diagnosis, management and hence better patient outcomes.

Régulation épigénétique de la défense antioxydante et de l'Angiopoietin-like 2 dans le contexte du vieillissement et des maladies cardiovasculaires

Suite à l’exposition à des facteurs de risque incluant la malnutrition, la dyslipidémie, la sédentarité et les désordres métaboliques, les maladies cardiovasculaires (MCV) sont caractérisées par un état pro-oxydant et pro-inflammatoire, et une dérégulation de l’expression de divers facteurs responsables de l’homéostasie de l’environnement rédox et inflammatoire. L’implication d’enzymes antioxydantes telles que les superoxyde dismutases (SOD) et les glutathion peroxydases (Gpx), ainsi que la contribution de médiateurs pro-inflammatoires tels que l’angiopoietin-like 2 (Angptl2) ont été rapportées dans le cadre des MCV. Toutefois, les mécanismes moléculaires sensibles aux facteurs de risque et menant au développement des MCV sont peu connus. L’épigénétique est un mécanisme de régulation de l’expression génique sensible aux stimuli extracellulaires et pourrait donc contribuer au développement des MCV. La méthylation de l’ADN est un des mécanismes épigénétiques pouvant varier tant de manière gène-spécifique qu’à l’échelle génomique, et la conséquence de tels changements sur l’expression des gènes ciblés dépend du site de méthylation. Puisqu’il a été démontré que des variations au niveau de la méthylation de l’ADN peuvent être associées à divers contextes pathologiques incluant les MCV, le but de nos travaux était d’étudier le lien entre la méthylation de gènes antioxydants et pro-inflammatoires avec leurs répercussions fonctionnelles biologiques en présence de facteurs de risques associés aux MCV, tels que le vieillissement, la dyslipidémie et la sédentarité. Dans la première étude, nous avons observé que dans l’artère fémorale de souris vieillissantes, la méthylation au niveau du promoteur du gène Sod2, codant pour l’enzyme antioxydante superoxyde dismutase de type 2 (SOD2 ou MnSOD), diminue avec l’âge. Ceci serait associé à l’induction de l’expression de MnSOD, renforçant ainsi la défense antioxydante endogène. Le vieillissement étant associé à une accumulation de la production de radicaux libres, nous avons étudié la vasodilatation dépendante de l’endothélium qui est sensible au stress oxydant. Nous avons observé que la capacité vasodilatatrice globale a été maintenue chez les souris âgées, aux dépens d’une diminution des facteurs hyperpolarisants dérivés de l’endothélium (EDHF) et d’une contribution accentuée de la voie du monoxyde d’azote (NO). Nous avons ensuite utilisé deux approches visant à réduire les niveaux de stress oxydant in vivo, soit la supplémentation avec un antioxydant, la catéchine, et l’exposition chronique à de l’exercice physique volontaire. Ces interventions ont permis de prévenir à la fois les changements au niveau de la fonction endothéliale et de l’hypométhylation de Sod2. Cette première étude démontre donc la sensibilité de la méthylation de l’ADN à l’environnement rédox. Dans la deuxième étude, nous avons démontré une régulation de l’expression de l’enzyme antioxydante glutathion peroxydase 1 (Gpx1) en lien avec la méthylation de son gène codant, Gpx1, dans un contexte de dyslipidémie sévère. Nos résultats démontrent que dans le muscle squelettique de souris transgéniques sévèrement dyslipidémiques (LDLr-/-; hApoB+/+), Gpx1 est hyperméthylé, ce qui diminue l’expression de Gpx1 et affaiblit la défense antioxydante endogène. Chez ces souris, l’exercice physique chronique a permis d’augmenter l’expression de Gpx1 en lien avec une hypométhylation transitoire de son gène. Cette étude démontre que le stress oxydant associé à la dyslipidémie sévère altère les mécanismes de défense antioxydante, en partie via un mécanisme épigénétique. De plus, on observe également que l’exercice physique permet de renverser ces effets et peut induire des changements épigénétiques, mais de manière transitoire. La troisième étude avait pour but d’étudier la régulation de l’Angptl2, une protéine circulante pro-inflammatoire, dans le contexte des MCV. Nous avons observé que chez des patients coronariens, la concentration circulante d’Angptl2 est significativement plus élevée que chez des sujets sains et ce, en lien avec une hypométhylation de son gène, ANGPTL2, mesurée dans les leucocytes circulants. Nous sommes les premiers à démontrer qu’en réponse à l’environnement pro-inflammatoire associé à une MCV, l’expression de l’Angptl2 est stimulée par un mécanisme épigénétique. Nos études ont permis d’identifier des nouvelles régions régulatrices différentiellement méthylées situées dans les gènes impliqués dans la défense antioxydante, soit Sod2 en lien avec le vieillissement et Gpx1 en lien avec la dyslipidémie et l’exercice. Nous avons également démontré un mécanisme de régulation de l’Angptl2 dépendant de la méthylation d’ANGPTL2 et ce, pour la première fois dans un contexte de MCV. Ces observations illustrent la nature dynamique de la régulation épigénétique par la méthylation de l’ADN en réponse aux stimuli environnementaux. Nos études contribuent ainsi à la compréhension et l’identification de mécanismes moléculaires impliqués dans le développement du phénotype pathologique suite à l’exposition aux facteurs de risque, ce qui ouvre la voie à de nouvelles approches thérapeutiques.

UV and visible photoconductivity of undoped diamond films: morphology and related electrical transport phenomena

UV and visible photoconductivity and electrical features of undoped diamond thin films grown by microwave plasma-assisted chemical vapour deposition (MP-CVD) on silicon and copper substrates are studied. The results are correlated with morphology properties analysed by atomic force microscopy (AFM) and micro-Raman. The photoconductivity presents several bands from 1.8 to 3.8 eV that are dependent on the substrate used to grow the samples in spite of some common bands observed. The J-V curve tin DC) in samples grown on Si has a rectifier behaviour (Schottky emission) in opposition to the samples grown on Cu that have no rectification (SCLC conduction). With these results we can conclude that diamond based optoelectronic devices behaviour is controlled by two kinds of structural defects localized in microcrystal and in its boundaries. A general structure model for the optoelectronic behaviour is discussed. (C) 2000 Elsevier Science S.A. All rights reserved.

Polycrystalline diamond thin film as wide bandgap material: the optoelectronic behaviour and the relationship with the structure

In this work metal - Microwave Plasma CVD diamond Schottky devices were studied. The current density vs. applied voltage reveals rectification ratios up to 10(4) at \ +/- 2V \. Under illumination an inversion and increase of the rectification is observed. The carrier density is 10(15) cm(-3) and the ideality factors near 1.5. The dark current vs. temperature shows that below 150 K the bulk transport is controlled by a hopping process with a density of defects of 10(16) cm(-3). For higher temperatures an extrinsic ionisation with activation energy of 0.3 eV takes place. The correlation with the polycrystalline nature of the samples is focused.

The use of subclinical vascular markers of atherosclerosis in youth

The foundations for cardiovascular disease (CVD) in adults are laid in childhood and accelerated by the presence of comorbid conditions. Early detection of manifestations of cardiovascular pathology is an important clinical objective to identify those at risk for subsequent cardiovascular morbidity and events, and to initiate behavioral and medical interventions to reduce risk. Children were once considered to be at low risk, but with the growing health concerns related to lifestyle, cardiovascular screening may be needed earlier. Several noninvasive procedures are available to assess the cumulative effect of these exposures. These include carotid ultrasound, flow-mediated dilation, pulse wave velocity and measures left ventricular mass. This dissertation analyzes the comorbid conditions that increase cardiovascular risk in youth, namely obesity and low physical fitness, using carotid intima-media thickness to objectively detect early manifestations of cardiovascular pathology. Until recently researchers have not used surrogate markers of subclinical atherosclerosis to examine the role of a single bout of exercise. Utilizing the acute exercise model can be advantageous as it allows for an efficient manipulation of exercise variables and permits greater experimental control of confounding variables. It is possible that the effects of a bout of exercise can predict the effects of chronic exercise. We analyze the physiological factors pertinent to arterial stiffness using arterial distensibility and pulse wave velocity in the context of acute exercise in children and adults. In some instances, those who amend their trajectory by not maintaining risk factors into adulthood experience reductions in subclinical markers to levels associated with never having had the risk factor. Though avoidance of risk factors in youth is ideal, there is still a window for intervention where long-lasting cardiovascular effects might be avoided. In this dissertation we present preliminary findings linking modifiable youth risk factors to subclinical markers of CVD in adulthood.

Dyslipidemia and blood lipid levels in patients tratied in primary care centers in east SAN JOSE

Dyslipidemia, i.e. high levels of blood lipids (cholesterol and triglycerides), is strongly related to cardiovascular disease (CVD). In order to reduce the risk of CVD at any moment in a person ́s life, it is crucial to know his/her –and the population’s– lipid profile. The aim of this study was to assess the (statistical) indicators of blood lipids and the prevalence of dyslipidemia in patients treated in the Integral Health Attention Program from Universidad de Costa Rica. A descriptive study was conducted including 10,044 patients aged 20 to 65 years, who were tested for a blood lipid profile in 2006. A total of 2,969 (29.6%) male and 7,075 (70.4%) female patients took part in the study, with an average age of 43.5 years. General averages for blood lipids were: 203.3 mg/dl for total cholesterol, 50.1 mg/dl for HDL, 120.1 mg/dl for LDL, and 165.6 mg/dl for triglycerides. Prevalence of 17.2% was determined for hypercholesterolemia (≥240 mg/dl), as well as 21.3% for low HDL levels (<40 mg/dl), 11.9% for high LDL levels (≥160 mg/dl), and 26.3% for high triglyceride levels (≥200 mg/dl). Women showed higher overall levels of dyslipidemia than men. Based on health areas, no significant differences were found in general lipid levels by age or sex. Results indicate that the general prevalence of dyslipidemia is close to half the rate reported in worldwide literature and lower than results reported in Costa Rican studies. However, general averages exceeded optimal levels for each blood lipid; consequently, it is important to develop health interventions oriented to reduce the impact of dyslipidemia in the studied population.

UV and visible photoconductivity of undoped diamond films: morphology and related electrical transport phenomena

UV and visible photoconductivity and electrical features of undoped diamond thin films grown by microwave plasma-assisted chemical vapour deposition (MP-CVD) on silicon and copper substrates are studied. The results are correlated with morphology properties analysed by atomic force microscopy (AFM) and micro-Raman. The photoconductivity presents several bands from 1.8 to 3.8 eV that are dependent on the substrate used to grow the samples in spite of some common bands observed. The J-V curve tin DC) in samples grown on Si has a rectifier behaviour (Schottky emission) in opposition to the samples grown on Cu that have no rectification (SCLC conduction). With these results we can conclude that diamond based optoelectronic devices behaviour is controlled by two kinds of structural defects localized in microcrystal and in its boundaries. A general structure model for the optoelectronic behaviour is discussed. (C) 2000 Elsevier Science S.A. All rights reserved.

Polycrystalline diamond thin film as wide bandgap material: the optoelectronic behaviour and the relationship with the structure

In this work metal - Microwave Plasma CVD diamond Schottky devices were studied. The current density vs. applied voltage reveals rectification ratios up to 10(4) at \ +/- 2V \. Under illumination an inversion and increase of the rectification is observed. The carrier density is 10(15) cm(-3) and the ideality factors near 1.5. The dark current vs. temperature shows that below 150 K the bulk transport is controlled by a hopping process with a density of defects of 10(16) cm(-3). For higher temperatures an extrinsic ionisation with activation energy of 0.3 eV takes place. The correlation with the polycrystalline nature of the samples is focused.