Premature death from cardiovascular disease is especially high in patients with chronic kidney disease (CKD). Vascular calcification is a potent risk factor for developing cardiac-related morbidity and mortality and is especially prominent within the CKD population. Deficiencies in serum levels of fetuin-A as well as inadequate production of matrix Gla protein (MGP) correlate inversely with the extent of vascular calcification and time spent on dialysis. Fetuin-A is a well-known systematic regulator of bone metabolism and MGP is a local antagonist of bone forming proteins. To meet the clinical need of at-risk patients prone to cardiac-related mortality. We propose a targeted protein therapy to treat arteriosclerotic arteries. The focus of this thesis was to characterize the binding interactions of fetuin-A with calcium mineral in a simulated body fluid and to study the in vitro effects of a fetuin vitamin K2 co-therapy on the prevention of calcification of vascular smooth muscle cells.

Histoplasmosis involving mediastinum is very rare which can present as a mediastinal mass or fibrosing mediastinitis. Fibrosing mediastinitis can be life-threatening if left untreated due to the involvement of the surrounding visceral and vascular structures. We present an interesting case of fibrosing mediastinitis due to histoplasmosis presented with palpitations, chest pain and dyspnea. The patient had mediastinal and hilar lymphadenopathy with calcification on chest imaging. The patient was diagnosed on lymph node biopsy and treated with antifungals.

La sténose aortique (SA) calcifiante est la troisième maladie cardiovasculaire en importance dans le monde. De surcroît, elle est au premier rang du palmarès des maladies valvulaires dans les pays industrialisés. Elle a longtemps été perçue comme étant une pathologie aux mécanismes dégénératifs passifs. Néanmoins, un nombre grandissant d'études ont démontré que cette maladie est active et régulée par diverses voies de signalisations. D'ailleurs, plusieurs facteurs de risques influencent le développement de la SA. Les mécanismes les plus importants, mais mal définis, qui sont impliqués dans la pathobiologie de la SA sont l'infiltration lipidique, l'inflammation, la fibrose et la calcification. Les liens qui unissent ces voies sont en investigations constantes. De meilleures connaissances vont permettre de découvrir une ou des avenues thérapeutiques contre le développement de la SA. D'une part, le système rénine-angiotensine (SRA) serait une cible thérapeutique possible contre le développement de la SA. Deux médicaments peuvent bloquer le SRA: les antagonistes des récepteurs de type 1 de l'angiotensine II (ARA) et les inhibiteurs de l'enzyme de conversion de l'angiotensine (IECA). Il est connu que l'activation du SRA est impliquée dans les processus d'inflammation, de fibrose et de remodelage des tissus de la valve aortique. D'autre part, la modulation de l'inflammation pourrait avoir des effets dans le développement de la SA. Cependant, son impact réel sur la progression active de la calcification dans le SA n'est pas encore établi. Dans un premier temps, nous avons démontré que la prise d'ARA et non d'IECA est reliée à une diminution du degré de remodelage, de fibrose, de certains marqueurs d'inflammation et de la progression de la SA. Dans un deuxième temps, nous avons démontré que l'inflammation est un régulateur actif de la SA. Elle est associée à des indices de sévérités hémodynamiques augmentés, à une haussée de la néovascularisation et à l'apparition de métaplasie osseuse. Pour terminer, il a été établi que la calcification est un élément crucial dans la développement de la SA. L'accumulation de dépôts calciques sur les feuillets de la valve aortique crée un obstacle au passage du sang. Parallèlement, dans l'os, le système ecto-purinergique est essentiel pour le maintient d'une balance efficace entre la formation et la résorption osseuse. Dans la SA, il n'a jamais été étudié en profondeur. Dans cette thèse, il a été montré que l'inhibition de l'ectonucléotide pyrophosphatase/phosphodiesterase 1 (ENPP1) favorise l'activation du récepteur à nucleotide, le P2Y2 ainsi que sa signalisation anti-apoptotique et anti-calcifiante. En somme, les travaux effectués pendant ce doctorat suggèrent que l'utilisation d'ARA et d'inhibiteurs des ectonucléotidases ENPP1 s'avèrent être des avenues thérapeutiques prometteuses dans le traitement de la SA.

Biologically controlled mineralization implies that organisms devote a part of their physiological activity to build up a specific mineralized skeleton. A preliminary comprehensive general view of the morphology and physiology of a given organism is therefore required before trying to understand where and how its biomineralizing system functions. Furthermore, the entire biomineralization sequence is not mediated by purely inorganic mineralogical rules but rather by a cellular machinery. Accordingly, a mineralogical characterization should be linked to a histological and cytological investigation of mineralizing cells to understand how a skeleton is produced. In the present thesis, we developed such a multi-disciplinary approach of some biomineralization processes of the massive basal skeleton in a few Recent hypercalcified sponges, likely survivors from Palaeozoic and early Mesozoic seas.<p>The three first chapters of this thesis are dedicated to the Mediterranean Calcarea Petrobiona massiliana, a conveniently accessible living hypercalcified sponge whereas all other Recent hypercalcified species are tropical and less easily reached. This model species permitted an initial morphological approach followed by an integrated biological and mineralogical study of biomineralization mechanisms. The fourth chapter aims at the comparative mineralogical study of the basal skeleton of eight tropical Recent hypercalcified demonsponges.<p>In the first chapter, important modifications and/or morphogenesis at the tissular or cellular level in response to life cycle phases and environmental conditions were depicted in specimens of Petrobiona massiliana. A survey of “storage cells” filling trabecular tracts, which are specific to P. massiliana, suggested that these cells may provide energy and a pool of toti- or pluripotent cells able to restructure the aquiferous system and repopulate cell types like pinacocytes. This potentiality of "storage cells would allow the sponge to sustain important physiological activities, like calcification, along its life cycle. Furthermore, basopinacocytes, cells delineating basally the soft tissue from the underlying basal skeleton, were identified through ultrastructural observations as the most probable cell type involved in the formation of the basal skeleton.<p>In the second chapter, the skeleton was found to be composed of ca. 50 to 100 nm crystallized grains as the smallest skeletal units, likely initially deposited in a mushy amorphous state. TEM and SEM observations further highlighted that these submicronic grains were assembled in clusters or fibres, the later even laterally associated into bundles. A model of crystallization propagation through amorphous submicronic granular units is proposed to explain the single-crystal feature of these micron-scale structural units, as demonstrated by selected area electron diffraction (SAED) in TEM. Finally, these units were assembled into a defined microstructure forming flattened growth layers called "sclerodermites", which superposed to produce the massive basal skeleton. In addition, X-ray diffraction (XRD) and energy electron loss spectroscopy (EELS) analyses highlighted respectively heterogeneous concentration and spatial distribution of Mg and Ca ions in the skeleton and structural units. This characterization highlighted mineralogical features, not conforming to the inorganic principles, and presuming a highly biologically regulated construction of the basal skeleton.<p>Accordingly, in the third chapter, it arose that the endomembrane system of basopinacocytes might play a dual function in the production and transport of both mineralizing ions and organic matrices. Combining partial decalcification methods with histochemical dyes and observing ultra-thin sections of the mature basal skeleton in TEM, very spatially and functionally diverse organic matrix components were found to occur in growing and mature portions of the skeleton. The following model of biomineralization was proposed for Petrobiona massiliana: basopinacocytes would use the endomembrane system pathway to produce and carry organic-coated submicronic amorphous grains in a mushy state within intracellular vesicles. These would then be released through the basal cell membrane toward the growing layer of the skeleton, where a highly structured gel-like organic framework, rich in sulfated/acidic GAGs-rich macromolecules, secreted by basopinacocytes, would ensure their assemblage into oriented fibres or clusters.<p>In the fourth chapter, the basal skeleton of eight tropical Recent hypercalcified species belonging to demosponges: Acanthochaetetes wellsi, Willardia caicosensis, Astrosclera willeyana, Ceratoporella nicholsoni, Goreauiella auriculata, Hispidopetra miniana, Stromatospongia norae and Calcifibrospongia actinostromarioides, were compared. Some mineralogical nano- to submicronic patterns already observed in the Calcarea P. massiliana, appeared as general features: the occurrence of submicronic granular units, their coherent assemblage into monocrystalline fibres and bundles and the likely presence of organic material around all structural units. Additional features brought new insights in our comprehension of biomineralization mechanisms in hypercalcified sponges. Among them, micro-twin and stacking-fault planes aligned with the fibres/bundles axis and crossing over submicronic granular units characterized the skeleton of most aragonitic species. This highly supports the crystallization propagation model proposed for P. massiliana, although it additionally suggests that it should occur only after the oriented assemblage of submicronic grains. Furthermore, lighter transverse striations separated by few nanometres occurred systematically in fibres and bundles of the eight basal skeletons investigated, suggesting the involvement of nanoscale intracrystalline fibrils in the biological control.<p>In conclusion, this comparative study of nine Recent hypercalcified sponges belonging to phylogenetically distant taxa resulted in the proposition of a shared biomineralization model based on the production of micron and submicron-scale structural units to build up macro-scale basal skeletons under a high biological control. We suggest that the cellular toolkit used for the biologically controlled biomineralization in these sponges is very ancient<p>and was already developed by their early Palaeozoic ancestors. Furthermore, this model supports recent concepts of calcium carbonate biomineralization developed for example in corals, molluscs and echinoderms, suggesting an even more universal and ancestral character of initial biomineralization mechanisms in all Metazoa producing a calcium carbonate skeleton.<p><p>La minéralisation biologiquement contrôlée implique qu’un organisme consacre une partie de son activité physiologique à l'élaboration de son squelette. La connaissance de sa morphologie et de sa physiologie est donc une étape préliminaire indispensable pour comprendre les mécanismes de formation de celui-ci. L’entièreté du processus de biominéralisation ne dépend pas simplement de principes fondamentaux issus de la minéralogie inorganique mais aussi de mécanismes cellulaires particuliers. La caractérisation minéralogique d'un squelette devrait donc être systématiquement liée à une étude histologique et cytologique des cellules impliquées dans la formation du biominéral. La thèse présentée ici a suivi une telle approche multidisciplinaire de certains mécanismes de biominéralisation du squelette basal de plusieurs éponges hypercalcifiées actuelles, considérées comme reliques d'espèces plus anciennes du Paléozoïque et Mésozoïque.<p>Les trois premiers chapitres de cette thèse concernent l'espèce calcaire de Méditerranée, Petrobiona massiliana, une éponge hypercalcifiée actuelle plus accessible que d'autres principalement distribuées dans les mers tropicales. Une approche de sa morphologie générale a été réalisée en préliminaire à une étude de ses mécanismes de biominéralisation, intégrant une caractérisation minéralogique et biologique. Le quatrième chapitre compare d’un point de vue minéralogique le squelette basal de huit autres espèces hypercalcifiées tropicales appartenant aux démosponges.<p>Au cours du premier chapitre, d'importantes modifications morphogénétiques à l'échelle tissulaire et cellulaire, liées à certaines phases du cycle biologique et aux conditions environnementales, ont ainsi été mises en évidence chez Petrobiona massiliana. Par l'observation de modifications de l'organisation et de l'ultrastructure des cellules de réserves remplissant les cordons trabéculaires, structures spécifiques de l'espèce, un rôle dans l'approvisionnement nutritif des cellules de l'éponge ainsi qu'un caractère toti- ou pluripotent leur ont été conférés. Les fonctions potentielles de ces cellules dites de réserves pourraient permettre à l'éponge de maintenir des activités physiologiques importantes, telles que la calcification, au cours de son cycle vital. Finalement, l'analyse ultrastructurale des tissus de P. massiliana a permis d'identifier les basopinacocytes, cellules délimitant les tissus mous du squelette basal, comme le type cellulaire ayant le plus de probabilité d'être impliqué dans la formation de ce dernier.<p>Dans le deuxième chapitre, des granules de 50 à 100 nm de diamètre se sont avérés les plus petites unités structurales du squelette basal de Petrobiona massiliana, probablement déposées initialement dans un état amorphe à consistance molle. Des observations en MEB et MET ont mis en évidence l'assemblage de ces granules en amas ou fibres, ces dernières étant elles-mêmes latéralement associées en faisceaux. Un modèle impliquant la propagation de la<p>cristallisation au travers de ces assemblages de granules submicroniques a été établi pour expliquer le caractère monocristallin des unités microstructurales, démontré par diffraction électronique en MET. Leur assemblage en une microstructure particulière produisant des couches\ / Doctorat en Sciences / info:eu-repo/semantics/nonPublished

Calcifications in carotid atheromas can be detected in a panoramic radiograph (PR) of the jaws. A carotid artery calcification (CAC) can indicate presence of significant (≥ 50%) carotid stenosis (SCS). The aim of this thesis was to (1) determine the prevalence of SCS and burden of atherosclerotic disease among patients revealing CACs in PRs, (2) determine the prevalence of CACs in PRs among patients with SCS, (3) analyze whether the amount of calcium and/or (4) the radiographic appearance of the CACs, can improve the positive predictive value (PPV) for SCS detection among patients with CACs in PRs. The thesis is based on four cross-sectional studies. Two patient groups were prospectively and consecutively studied. Group A represented a general adult patient population in dentistry examined with PR presenting incidental findings of CACs. These patients were examined with carotid ultrasound for presence or absence of SCS and their medical background regarding atherosclerotic related diseases and risk factors was reviewed. An age and gender matched reference group was included for comparisons. Group B comprised patients with ultrasound verified SCS, examined with PR prior to carotid endarterectomy. The PRs were analysed regarding presence of CACs. The extirpated plaques were collected and examined with cone-beam computed tomography (CBCT) to determine the amount of calcium. The radiographic appearance of CACs in PRs from Group A and B were evaluated for possible association with presence of SCS. In Group A, 8/117 (7%) of patients with CAC in PRs revealed SCS in the ultrasound examination, all were found in men (8/64 (12%)). Patients with CACs in PRs revealed a higher burden of atherosclerotic disease compared to participants in the reference group (p &lt;0.001). In Group B, where all patients had SCS, 84% revealed CACs in PRs and 99% of the extirpated plaques revealed calcification. CACs with volumes varying between 1 and 509 mm3 were detected in the PRs. The variation in volume did not correlate to degree of carotid stenosis. The radiographic appearance that was most frequently seen in neck sides with SCS (65%) was also frequently found in neck sides without SCS (47%) and therefore the PPV did not improve compared to the PPV solely based on presence of CACs. CACs in PRs are more associated with SCS in men than in a general population and patients with CACs in PRs have a higher burden of atherosclerotic disease. The majority of patients with SCS show CACs in PRs and the majority of extirpated carotid plaques reveal calcification. The volume of CAC and specified radiographic appearance does not increase the PPV for SCS in patients with CACs in PRs. In conclusion patients with CACs in PRs, and without previous record of cardiovascular disease, should be advised to seek medical attention for screening of cardiovascular risk factors. / Bakgrund Inom ramen för specialist- och allmäntandvård utförs panoramaröntgen-undersökningar dagligen på såväl barn som vuxna. En panoramaröntgenbild (PB) är en översiktsbild som är specifikt anpassad till att återge området för tänder och käkar. Utöver det, avbildas även delar av halsen och som bifynd ibland förkalkningar belägna i området för halspulsådern (karotiskärlet). Dessa förkalkningar kallas för karotisförkalkningar och är ett tecken på åderförkalkning. Åderförkalkning består i huvudsak av en fettrik plackansamling i kärlväggen. Placket kan med tiden förkalkas till varierande grad. Det är dessa förkalkningar vi kan se i PB. När en åderförkalkning ökar i volym kan den utgöra en förträngning i kärlet. Då förträngningen av kärldiametern är ≥ 50% benämns åderförkalkningar belägna i karotiskärlet för ”signifikanta karotisstenoser” (SKS). Graden av förträngning bedöms som regel med ultraljudsundersökning av halskärlen. Bitar av SKS kan lossna varvid det bildas små blodproppar. Eftersom halspulsådern försörjer främre hjärnhalvan med blod så kan dessa bitar täppa till ett av hjärnans blodförsörjande kärl och leda till stroke (slaganfall). För att minska risken att drabbas av stroke kan man ibland operera bort SKS (karotisplacket). Syfte Syftet med denna avhandling var att ta reda på (1) hur många av de patienter som blir undersökta med PB inom tandvården som uppvisar karotisförkalkningar, hur stor andel som har SKS samt utreda om patienter med förkalkningar i PB i större utsträckning är drabbade av hjärtkärlsjukdomar/risk faktorer, (2) hur ofta utopererade karotisplack innehåller kalk och hur ofta patienter med känd SKS uppvisar karotisförkalkningar i PB, (3) huruvida förkalkningsmängden i utopererade karotisplack är korrelerad till förträngningsgrad, och (4) huruvida det finns något specifikt radiografiskt utseende på karotisförkalkningar i PB som kan användas för att identifiera en större andel patienter med SKS bland patienter som uppvisar karotisförkalkningar i PB, det vill säga minska risken för att skicka patienter utan SKS på ultraljudsundersökning. Material och metoder Materialet bestod av två huvudgrupper av patienter. Grupp A bestod av patienter undersökta inom tandvården med PB som uppvisat karotisförkalkningar. Alla dessa patienter undersöktes med ultraljud för att bedöma förekomst av SKS. Den medicinska journalen granskades avseende tidigare förekomst av åderförkalkningsrelaterade sjukdomar och risk faktorer. En köns- och åldersmatchad kontrollgrupp utan karotisförkalkningar i PB analyserades på motsvarande sätt för jämförelse. Grupp B bestod av patienter med känd SKS som före operativt avlägsnande av karotisplack undersöktes med PB. PB granskades avseende förekomst av karotisförkalkning och utopererade karotisplack avseende kalkinnehåll. Förkalkningsmängden i de utopererade karotisplacken korrelerades dels till möjlighet att identifiera karotisförkalkning i PB samt till förträngningsgraden i kärlen. Karotisförkalkningarnas utseende delades in i grupper för att utvärdera om vissa utseenden i större utsträckning kunde associeras till förekomst av SKS. Resultat I Grupp A uppvisade 8/117 (7%) patienter SKS, alla var män, 8/64 (12%). Patienter med karotisförkalkningar i PB hade oftare åderförkalkningsrelaterade sjukdomar och risk faktorer (p &lt; 0,001). I Grupp B hade 84% av patienterna med SKS karotisförkalkning i PB. Bland de utopererade karotisplacken innehöll 99% förkalkningar och förkalkningsvolymen varierade från 1-509 mm3. Möjligheten att upptäcka karotisförkalkning i PB var oberoende av om förkalkningsvolymen var stor eller liten. Förkalkningsvolymen var heller inte korrelerad till hur stor förträngning av kärlet en SKS (≥ 50%) orsakat. Ett radiografiskt utseende på karotisförkalkningar i PB noterades i 65% av de halssidor som hade en SKS. Detta specifika radiografiska utseende återfanns dock även i 47% av halssidor utan SKS. Andelen falskt positiva patienter var således fortsatt hög. Slutsats Vi fann att 12% män med karotisförkalkningar i PB, undersökta i en generell population inom tandvården, uppvisar SKS. Patienter med karotisförkalkningar i PB uppvisar fler riskfaktorer och är oftare drabbade av hjärt-kärlsjukdomar än patienter utan karotisförkalkningar i PB. Majoriteten av patienter med SKS uppvisar karotisförkalkningar i PB och nära 100% av utopererade karotisplack innehåller kalk. Förkalkningsmängden påverkar inte möjligheten att upptäcka karotisförkalkning i PB. Förkalkningsmängd och specificerade radiografiska utseenden hos karotisförkalkningar i PB förutsäger inte SKS bättre än definitionen ”förkalkning ja eller nej”. Dessa parametrar kan således inte användas till att förfina urvalet bland patienter som uppvisar karotisförkalkning i PB mot högre andel patienter med SKS. Individer med karotisförkalkningar i PB bör uppmanas konsultera vården för undersökning av eventuella risk faktorer för hjärt-kärlsjukdom.

published_or_final_version / Community Medicine / Master / Master of Public Health

No description available.

Introduction Coronary artery disease (CAD) is the most common cause of death in Europe and North America and early detection of atherosclerosis is a clinical priority. Diagnosis of CAD remains conventional angiography, although recent technology has introduced non-invasive imaging of coronary arteries using computed tomographic coronary angiography (CTCA), which enables the detection and quantification of coronary artery calcification (CAC). CAC forms within the arterial wall and is usually found in or adjacent to atherosclerotic plaques and is consequently known as sub-clinical atherosclerosis.  The conventional cardiovascular (CV) risk factors used to quantify the estimated 10-year coronary event risk comprise dyslipidaemia, hypertension, diabetes mellitus, obesity, smoking and family history of CAD. Nevertheless, their relationship with significant (&gt;50%) stenosis, their interaction with the CAC score and their predictive ability for CAC presence and extent has not been fully determined in symptomatic patients.   Methods   For Papers 1-4 we took patients from the Euro-CCAD cohort, an international study established in 2009 in Umeå, Sweden. The study data gave us the CAC score and the CV risk factor profile in 6309 patients, together with angiography results for a reduced cohort of 5515 patients. In Papers 1 and 2 we assessed the risk factors for significant stenosis, including CAC as a risk factor. Paper 2 carried out this analysis by geographical region: Europe vs USA and northern vs southern Europe. Paper 3 investigated the CV risk factors for CAC presence, stratified by age and gender, while Paper 4 assessed the CV risk factors for CAC extent, stratified by gender.  In paper 5 we carried out a systematic review and meta-analysis of all studies of the risk factor predictors of CAC presence, extent and progression in symptomatic patients. From a total of 884 studies, we identified 10 which fitted our inclusion criteria, providing us with a total of 15,769 symptomatic patients. All 10 were entered in the systematic review and 7 were also eligible for the meta-analysis.   Results Paper 1:           Among risk factors alone, the most powerful predictors of significant coronary stenosis were male gender followed by diabetes, smoking, hypercholesterolaemia, hypertension, family history of CAD and age; only obesity was not predictive. When including the log transformed CAC score as a risk factor, this proved the most powerful predictor of &gt;50% stenosis, but hypercholesterolaemia and hypertension lost their predictive ability. The conventional risk factors alone were 70% accurate in predicting significant stenosis, the log transformed CAC score alone was 82% accurate but the combination was 84% accurate and improved both sensitivity and specificity.  Paper 2:           Despite some striking differences in profiles between Europe and the USA, the most important risk factors for &gt;50% stenosis in both groups were male gender followed by diabetes. When the log CAC score was included as a risk factor, it became by far the most important predictor of &gt;50% stenosis in both continents, followed by male gender. In the northern vs southern Europe comparison the result was similar, with the log CAC score being the most important predictor of &gt;50% stenosis in both regions, followed by male gender.  Paper 3:           Independent predictors of CAC presence in males and females were age, dyslipidaemia, hypertension, diabetes and smoking, with the addition of family history of CAD in males; obesity was not predictive in either gender. The most important predictors of CAC presence in males were dyslipidaemia and diabetes, while among females the most important predictors of CAC presence were diabetes followed by smoking. When analysed by age groups, in both males and females aged &lt;70 years, diabetes, hypertension and dyslipidaemia were predictive, with diabetes being the strongest; in females aged &lt;70 years, smoking was also predictive. Among those aged ≥70 years, the results are completely different, with only dyslipidaemia being predictive in males but smoking and diabetes were predictive in females.  Paper 4:           In the total cohort, age, male gender, diabetes, obesity, family history of CAD and number of risk factors predicted an increasing CAC score, with the most important being male gender and diabetes. In males, hypertension and dyslipidaemia were also predictive, although diabetes was the most important predictor. Diabetes was similarly the most important risk factor in females, followed by age and number of risk factors. Among patients with CAC, hypertension, dyslipidaemia and diabetes predicted CAC extent in both males and females, with diabetes being the strongest predictor in males followed by dyslipidaemia, while diabetes was also the strongest predictor in females, followed by hypertension. Quantile regression confirmed the consistent predictive ability of diabetes.  Paper 5:           In the systematic review, age was strongly predictive of both CAC presence and extent but not of CAC progression. The results for CAC presence were overwhelmed by data from one study of almost 10,000 patients, which found that white ethnicity, diabetes, hypertension and obesity were predictive of CAC presence but not male gender, dyslipidaemia, family history or smoking. With respect to CAC extent, only male gender and hypertension were clearly predictive, while in the one study of CAC progression, only diabetes and hypertension were predictive. In the meta-analysis, hypertension followed by male gender, diabetes and age were predictive of CAC presence, while for CAC extent mild-moderate CAC was predicted by hypertension alone, whereas severe CAC was predicted by hypertension followed by diabetes.   Conclusion Our investigation of the Euro-CCAD cohort showed that the CAC score is far more predictive of significant stenosis than risk factors alone, followed by male gender and diabetes, and there was little benefit to risk factor assessment over and above the CAC score for &gt;50% stenosis prediction. Regional variations made little difference to this result. Independent predictors of CAC presence were dyslipidaemia and diabetes in males and diabetes followed by smoking in females. The risk factor predictors alter at age 70. The most important risk factor predictors of CAC extent were male gender and diabetes; when analysed by gender, diabetes was the most important in both males and females. Our studies have consistently shown the strong predictive ability of male gender in the total cohort and diabetes in males and females and this is reflected in the meta-analysis, which also found hypertension to be independently predictive. Interestingly, dyslipidaemia does not appear to be a strong risk factor.

Orientador: João Martins Pizauro Junior / Banca: Sandra Regina Pombeiro Sponchiado / Banca: Flávio José dos Santos / Banca: Luis Henrique Souza Guimarães / Banca: Marcio Hipolito / Resumo: Os processos de formação, crescimento, remodelação e, quando necessário, reparo do tecido ósseo ocorrem pela ação coordenada e regulada dos eventos químicos e fisiológicos que participam das ossificações intramembranosa e endocondral, sendo assim, o desequilíbrio das biomoléculas envolvidas no processo, pode levar ao desenvolvimento de patologias ósseas. Durante a metamorfose dos anuros, ocorrem acentuadas e perceptíveis alterações morfológicas que possibilitam a transição do animal do ambiente aquático para o terrestre, sendo a remodelação do esqueleto uma das transformações mais notáveis. Dentre as formas de se estudar o mecanismo de calcificação biológica, as enzimas fosfatase alcalina e fosfatase ácida tartarato-resistente são utilizadas por serem consideradas marcadores bioquímicos da ação dos osteoblastos e dos osteoclastos, respectivamente. Neste sentido, foram realizados estudos em girinos e rãs de Lithobates catesbeianus com o objetivo de se compreender melhor tais processos de ossificação. A média da atividade específica para a hidrólise do pNFF (pH=10,5) pela fosfatase alcalina solubilizada por fosfatidilinositol fosfolipase C-específica (PIPLC) de Bacillus cereus, entre as diferentes regiões ósseas nas diferentes idades do animal, foi de 1142,57 U.mg-1, enquanto que para a hidrólise do PPi (pH=8,0) foi de 1433,82 U.mg-1. Dentre os compostos testados sobre a atividade enzimática, aquele que mais influenciou foi o EDTA, com aproximadamente 67% de inibição para a ati... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The processes of formation, growth, remodeling and, when necessary, repair of the bone tissue occur through the coordinated and regulated action of the chemical and physiological events that participate in the intramembranous and endochondral ossifications, thus, the imbalance of the biomolecules involved in the process,maylead to the development of bone pathologies. During anuran's metamorphosis, there are marked and perceptible morphological changes that allow thetransition of the animal from the aquatic to the terrestrial environment, and the skeleton remodeling is one of the most remarkable transformations. Among the ways to study the mechanism of biological calcification, the enzymes alkaline phosphatase and tartrate-resistant acid phosphatase are used as biochemical markers of the action of osteoblasts and osteoclasts, respectively. In this sense, studies were carried out on tadpoles and frogs of Lithobates catesbeianusin order to better understand such ossification processes. The mean of the specific activity for the hydrolysis of pNPP(pH=10.5) by the alkaline phosphatase solubilised by Bacilluscereusphosphatidylinositol-specific phospholipase C (PIPLC)between the different bone regions at different ages of the animal was 1142.57 U.mg-1, while for the hydrolysis of PPi (pH=8.0) was 1433.82 U.mg-1. Among the compounds tested on the enzymatic activity, the one that most influenced was EDTA, with approximately 67% inhibition for pNPPase activity, and77% for PPase. In the ... (Complete abstract click electronic access below) / Doutor

Thesis (M.Sc. (Med.))--University of the Witwatersrand, Faculty of Health Sciences, 1962.