Made available in DSpace on 2016-06-02T19:22:53Z (GMT). No. of bitstreams: 1 3123.pdf: 1732601 bytes, checksum: 95a08dc70700db9a729e2895f7464b4d (MD5) Previous issue date: 2010-06-23 / Financiadora de Estudos e Projetos / Cyanobacteria, in favorable conditions can form large superficial masses of green color called blooms. Some genera of cyanobacteria are producing toxins, and during the bloom, there may be risks of contamination of water bodies and thus of those organisms that depends on this. Among the toxins produced by cyanobacteria, stands the microcystin. This type of toxin has pronounced effects on the liver, although it may show its effects in several organs. Moreover, it is the cyanotoxin which is more widely distributed in various types of ecosystems. The aim of this study was to examine the cardiorespiratory responses of Nile tilapia, Oreochromis niloticus, in control situation and 48 h after intraperitoneal injection of microcystin-LR (MC-LR - 100 μg.Kg-1 body weight) submitted to gradual hypoxia. Exposure to MC-LR decreased metabolic rate ( VO2 ) and significantly increased the critical O2 tension (PcO2), reducing the ability to maintain constant the 2 VO . The gill ventilation (Vg) increased significantly and progressively in both experimental groups in order to maintain 2 VO during hypoxia. Both groups showed the same pattern of respiratory response, while increases in G V& were characterized by increases in tidal volume (VT), while respiratory frequency (fR) remained little changed. However the magnitude of this response was markedly lower in the group exposed to MC-LR, showing that the toxin somehow interfered in the homeostasis of the animal preventing it from developing a respiratory response normal. The MC-LR also reduced the ability to extract O2 during acute hypoxia, probably due to its action injuring the gill tissues of infected animals. Heart rate (fH) was significantly reduced by microcystin-LR in all the experimental concentrations of O2. The control group developed bradycardia only in tension of 10 mmHg, while the group exposed to MC-LR has exhibited such a response to 20 mmHg. The direct effect of MC-LR on the cardiac tissue was probably the cause of the decrease in heart rate in the exposed group compared to the control and relative to their normoxic values. Together, the results of this study showed that exposure to MC-LR reduces the chances of survival of the species studied in hypoxic environments. / As cianobactérias, em condições favoráveis podem formar grandes massas superficiais de coloração verde intensa, denominadas florações. Alguns gêneros de cianobactérias são produtoras de toxinas, e durante as florações, pode haver riscos de contaminação da água e conseqüentemente dos organismos dependentes desta. Dentre as toxinas produzidas pelas cianobactérias, destaca-se a microcistina. Esse tipo de toxina apresenta efeitos pronunciados sobre o fígado, embora possa exibir seus efeitos em diversos órgãos. Ademais, é a cianotoxina que se encontra mais amplamente distribuída nos mais variados tipos de ecossistemas. O objetivo do presente estudo foi analisar as respostas cardio-respiratórias de tilápias-do-nilo, Oreochromis niloticus, em situação controle e após 48 h de injeção intraperitoneal de microcistina-LR (MC-LR - 100 μg.Kg-1 de peso corpóreo) submetidos à hipóxia gradual. A exposição à MC-LR reduziu a taxa metabólica, ( VO2 ) e aumentou significativamente a tensão crítica de O2 (PcO2), reduzindo a capacidade de manutenção da 2 VO constante. A ventilação branquial (Vg) aumentou significativa e progressivamente em ambos os grupos experimentais a fim de manter a 2 V&O durante a hipóxia. Ambos os grupos apresentaram o mesmo padrão de resposta respiratória, sendo que os aumentos na G V& foram caracterizados por aumentos no volume ventilatório (VT), enquanto que a freqüência respiratória (fR) se manteve pouco alterada. Entretanto a magnitude dessa resposta foi marcadamente inferior no grupo exposto à MCLR, mostrando que a toxina interferiu de alguma maneira na homeostase do animal impossibilitando-o de desenvolver uma resposta respiratória normal. A MC-LR também reduziu a capacidade de extração de O2 durante a hipóxia severa, provavelmente devido à sua ação lesiva nos tecidos branquiais dos animais contaminados. A freqüência cardíaca (fH) foi significativamente reduzida pela MC-LR em todas as concentrações de O2 experimentais. O grupo controle desenvolveu bradicardia apenas na tensão de 10 mmHg, enquanto que o grupo exposto à MC-LR já exibiu tal resposta a 20 mmHg. O efeito direto da MC-LR sobre o tecido cardíaco provavelmente foi a causa da diminuição da freqüência cardíaca do grupo exposto em relação ao controle e em relação aos seus valores normóxicos. Em conjunto, os resultados do presente trabalho mostraram que a exposição à MC-LR reduz as chances de sobrevivência da espécie estudada em ambientes hipóxicos.

Aux Antilles, la faible fréquence des coronaropathies pourrait être liée à des facteurs génétiques, ethniques et/ou une distribution spécifique des facteurs de risque cardio-vasculaire (FDRCV). Les propriétés l'ANP (Atrial Natriuretic Peptide) et l'influence de certains polymorphismes de son gène, fréquents dans les populations d'ascendance Africaine pourraient également être en cause. L'analyse des dossiers de 638 patients coronariens consécutifs a mis en évidence une forte prévalence de l'hypertension artérielle et du diabète dans cette population et révélé des différences significatives dans la prévalence des FDRCV entre Afro-Caribéens (AC), Caucasiens et descendants de migrants Indiens. L'analyse angiographique de 420 patients AC a révélé que le diabète était le FDRCV le plus fortement lié à la sévérité des lésions coronaires alors l'obésité apparaissait comme un facteur protecteur. La transfection in vitro, de cellules musculaires lisses artérielles par une construction adénovirale porteuse du gène de l'ANP a entrainé une inhibition de la prolifération et de la migration cellulaire de 31 % et 25% respectivement. In vivo, cet effet s'est traduit par une réduction de 25% de la formation néotimale et de 28% du rapport intima/média dans un modèle d'hyperplasie de carotide de rat. Dans étude transversale incluant 210 sujets diabétiques AC nous avons mis en évidence une association entre le polymorphisme rs5065 (22381>C) du gène de l'ANP et l'existence d'une coronaropatbie. Dans cette étude, l'odds ratio de la présence d'une coronaropathie chez les porteurs de l'allèle mineur de cette mutation (TC/CC) était de 0,50 (0,26- 0,96; P = 0,038). / In Guadeloupe and Martinique, the low frequency ofcoronary artery disease (CAD) could be related to genetic or ethniefactors and/or specifie distribution ofcardiovascular risk factors (CRFs). Atrial Natriuretic Peptide (ANP) properties and influence of sorne of ANP gene polymorphism that are frequent in populations of African descent could also be involved in CAD occurrence. We retrospectively studied 638 consecutive patients with documented CAO and found a high prevalence of hypertension and diabetes in this population. This study also demonstrated significant differences in the prevalence of CRFs between Afro-Caribbean (AC), Caucasians and Indians migrants. The angiographie analysis of420 patients revealed that in AC, diabetes emerged as the strongest CFR related to the severity ofcoronary lesions while obesity appeared as a protective factor. After transfection by an adenoviral construct carrying the ANP gene, vascular smooth muscle cell proliferation stimulated by 10% fetal calf serum was reduced by 31% and migration by 25%. In vivo, in rat carotid artery model ofvascular injury, neointima formation and intima/media ratio was reduced by 25% and 28% respectively. In a cross-sectional study inc1uding 210 AC diabetics we found an association between rs5065 (22381> C) polymorpbism and the presence of coronary artery disease suggesting that the minor allele could have a protective effect against CAD. The odds ratio for the presence ofCAD in carriers ofthe minor allele ofthis mutation (TC / CC) was 0.50 (0.26-0.96, P = 0.038).

The importance of physical exercise tends to be neglected in today’s modern lifestyle. This increased passive way of life conveys a notable increase in the prevalence of lifestyle disorders such as hypertension and vascular pathology which lead to cardiovascular strain. Taking this into account, the aim of this investigation was to explore the empirical association between the heart health status of an active and sedentary South African lifestyle, thus intending to provide insight into impact of the significant changes that are associated with the modernised society. With the aforementioned objective in mind, four separate studies were completed: Study 1 sought to investigate the cardiovascular status of 162 undergraduate university students in order to determine whether, despite their youth, students remained at risk of cardiovascular complications. Astonishingly, results indicate that a number of students between the ages of 18 and 25 in a university setting present with preeminent cardiovascular risk. This data highlights some serious concerns regarding the cardiovascular health among the youth. In sequel to study 1, study 2 permitted the comparison of a sedentary and active South African population, however some discrepancies originated due to the notable age difference between the groups. Nevertheless, results gained from this crosssectional comparison between the populations indicate significantly higher cardiac risk amongst the sedentary population. Study 3 was conducted on 202 infantry service recruits between the ages of 18 and 24 years. A pre- post intervention study design was incorporated in pursuit of determining the influence of an intense training programme on cardiovascular variables of a population over a 20 week time-frame. Results yielded from this study indicate a significant decrease in overall cardiovascular risk, as tested over three intervals (week 1, week 12, and week 20) during the 20 week training period. Study 4 was designed as a longitudinal study with self-controls for within group comparisons, as well as a comparative study between the two contrasting populations. Thus, affording the opportunity to determine the impact of physical activity on cardiovascular risk by comparing two divergent South African lifestyles over a 20-week time frame. The 202 infantry service recruits of study 3 served as the intervention group, while the control group comprised of 126 sedentary university students. Findings from this study conveyed strong association between the active population and decreased cardio-stress index and related heart health measurements in comparison to results of the sedentary population. This research validates the positive correlation between a physically active lifestyle and improved heart health, thereby implying reduced cardiovascular risk. In the combat against cardiovascular disease it is clear that focus should be shifted from pharmacological treatment to behavioural prevention. As a principle component of this preventative approach it is vital that individuals are equipped with screening technology that enables early detection and monitoring of probable cardiovascular complications. Several novel ideas were introduced in this research, including the endorsement of the cardio-stress index method as an efficient non-invasive technique to directly observe cardiovascular stress. / Dissertation (MSc)--University of Pretoria, 2014. / lk2014 / Physiology / MSc / Unrestricted

This work sought to investigate the clinical phenotypes and molecular basis of cardio-facio-cutaneous syndrome (CFC), a germline disorder of the Ras-MAPK pathway, like Noonan syndrome (NS) and neurofibromatosis type I, caused by mutations in genes encoding proteins that act within this signal transduction pathway. CFC is most commonly due to mutation in BRAF, and less commonly MAP2K1, MAP2K2 or KRAS. A proportion of patients currently have no mutation identified. Mutations and clinical features of patients with a molecular diagnosis of CFC were investigated, which demonstrated a wide range of causative mutations, and some unclassified variants. Both known and novel clinical features of CFC were identified. A strong association between severe contractures and the p.(Tyr130Cys) mutation in MAP2K1 was found, which has not previously been reported. In contrast to the large number of patients with a confirmed molecular diagnosis, several with a highly suggestive clinical phenotype have been found to have no mutationin any of the known CFC genes. The molecular basis of these presentations was investigated by conventional Sanger sequencing of candidate genes. Fourteen patients with the p.(Ser2Gly) mutation in SHOC2 were identified, with clinical presentations consistent with CFC, NS or CS. Target enrichment and massively parallel sequencing of selected genes was undertaken in ten patients. Mutations in known genes were identified in four patients (including the positive control). Candidate causative variants in novel genes were suggested in two further patients, one of which was confirmed on Sanger sequencing. Whole exome sequencing of patient-parent trios was also undertaken to identify de novo variants. Three trios were analysed, and in one patient with a clinical diagnosis of CFC, a frameshift mutation in NF1 was identified, which was confirmed by Sanger sequencing to be present and de novo. The molecular effects of CFC-associated mutations in BRAF on Ras-MAPK pathway signalling were studied in cell culture systems, using Western blotting for ERK1/2 phosphorylation, in vitro kinase assays and luciferase assays, to assess activity of downstream targets of the Ras-MAPK pathway. Altered pathway activity was demonstrated for novel variants that had not previously been characterised at the molecular level, which was in keeping with the findings of the effects of previously studied mutations. The cardiac phenotype in animal models of CFC, CS and NS/CFC was explored using expression microarrays to identify potentially important genes and pathways in the pathogenesis of hypertrophic cardiomyopathy (a progressive but potentially treatable disease feature) in these conditions. A signature of increased expression of Myh7, the embryonic form of myosin, was identified in the heart of the mouse model of CFC due to a B-Raf mutation at four weeks postnatal age, but comparative analysis suggested significant differences in either the mechanisms causing cardiac phenotypes, or the timescales over which these may exert their effects, in the three models. In summary, the most significant findings of this work were that SHOC2 mutation is a frequent cause of a severe NCFC presentation, and massively parallel sequencing can be an effective means of molecular investigation of this group of disorders. Novel features of CFC syndrome that were identified include severe contractures in association with p.(Tyr130Cys) mutations in MAP2K1. The analysis of mouse models of the NCFCs was hampered by heterogeneity within the expression microarray results, and low levels of expression of the H-Ras mutant allele in the mouse model of Costellosyndrome.

The short-term regulation of blood pressure is influenced by many influences, some being represented by cardiovascular signals and their changes. Because of the complexity of this system, the linear methods for its analysis are not sufficient. Non-linear methods for time series analysis have been devised quite a lot. In the course of this work, the analysis of the relations of several signals was evaluated as the most suitable conditional entropy and the resulting indexes of affinity and directionality. This method was applied to a set of heart-rate signals and systolic and diastolic pressure signals measured on eight adults and nine children. Relationships were analyzed but unfortunately after the statistical test was held the expected information links between the individual signals were not established. The indices were very small - in the hundredths of bits. Finally, optimization of the algorithm of the whole method has been performed and the newly modified function already shows significantly better results, for example strong information binding from the time-series of systolic pressure to a series of diastolic pressures.

The short-term regulation of blood pressure is influenced by many influences, some being represented by cardiovascular signals and their changes. Because of the complexity of this system, the linear methods for its analysis are not sufficient. Non-linear methods for time series analysis have been devised quite a lot. In the course of this work, the analysis of the relations of several signals was evaluated as the most suitable conditional entropy and the resulting indexes of affinity and directionality. This method was applied to a set of heart-rate signals and systolic and diastolic pressure signals measured on eight adults and sixteen children. Relationships were analyzed and after the statistical test was held some information links between the individual signals were not established.

Un nombre croissant d’études suggèrent que le rôle des facteurs psychologiques dans le risque cardio-métabolique pourrait différer selon la position socio-économique des individus.Les travaux de cette thèse ont utilisé les données du Centre d'Investigations Préventives et Cliniques, de l'Etude Prospective Parisienne 3 et de la cohorte CONSTANCES pour examiner le rôle modérateur de la profession et catégorie socioprofessionnelle (PCS) sur les relations entre stress ou dépression et différents marqueurs du risque cardio-métabolique.Les résultats montrent que la PCS était un facteur modérateur de l'association du stress perçu avec la PA élevée chez les femmes (étude no 1), le diabète (étude no 2) et l'athérosclérose préclinique (étude no 3), de telle sorte que les individus des PCS les moins favorisées étaient les plus à risque. Cela semblait également être le cas pour l'association entre la dépression et le risque de maladie coronarienne à 10 ans chez les hommes (étude no 4).Ces résultats montrent l'importance de prendre systématiquement en compte le rôle modérateur des inégalités socioprofessionnelles dans la relation entre facteurs psychologiques et risque cardio-métabolique, aussi bien dans les études épidémiologiques pour mieux caractériser ce risque, qu’en santé publique et pratique clinique pour mieux le prévenir. / A growing body of studies suggests that the association between psychological factors and cardiometabolic risk might depend upon individual's socio-economic status.Data of Centre d'Investigations Préventives et Cliniques, Paris Prospective Study 3 and CONSTANCES cohort were used to examine the moderating role of occupational status (OS) on the associations between stress or depression and cardiometabolic risk markers.OS was a moderating factor of the association between perceived stress and high blood pressure among women (study No. 1), diabetes(study No. 2) and subclinical atherosclerosis (study No. 3), with increased risk for the individuals of lower OS. Similar pattern of results were observed for the association between depression and 10-year coronary heart disease risk among men (study No. 4).These results highlight the importance to systematically take into account the moderating effect of occupational inequalities when examining the association between psychological factors and cardiometabolic risk in epidemiological studies to better characterize this risk but also in public health policies and clinical practice for a better prevention.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21296号 / 医博第4385号 / 新制||医||1030(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 小池 薫, 教授 福原 俊一, 教授 木村 剛 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

The clinical usage of Seismocardiography (SCG) is increasing as it is being shown to be an effective non-invasive measurement for heart monitoring. SCG measures the vibrational activity at the chest surface and applications include non-invasive assessment of myocardial contractility and systolic time intervals. Respiratory activity can also affect the SCG signal by changing the hemodynamic characteristics of cardiac activity and displacing the position of the heart. Other clinically significant information, such as systolic time intervals, can thus manifest themselves differently in an SCG signal during inspiration and expiration. Grouping SCG signals into their respective respiratory cycle can mitigate this issue. Prior research has focused on developing machine learning classification methods to classify SCG events as according to their respiration cycle. However, recent research at the Biomedical Acoustics Research Laboratory (BARL) at UCF suggests grouping SCG signals into high and low lung volume may be more effective. This research aimed at com- paring the efficiency of grouping SCG signals according to their respiration and lung volume phase and also developing a method to automatically identify the respiration and lung volume phase of SCG events.

No description available.