Vascular calcification is prevalent in ageing, in atherosclerosis, and especially in patients with Chronic Kidney Disease (CKD), with associated increased morbidity and mortality. The phenotypic transition of Vascular Smooth Muscle Cells (VSMCs) into osteoblastic/chondrogenic-like cells is critical for the development of calcification in CKD patients. Osteocytes, terminally differentiated osteoblasts, have recently emerged as major regulators of calcification in bone. Recently, osteocytelike cells have been observed in human peripheral arteries with medial vascular calcification. However, it remains undetermined as to whether VSMCs can undergo osteocytic differentiation within a calcifying environment and the functional role of osteocyte formation in the development of medial vascular calcification. Initial studies have characterised the ectonucleotide pyrophosphatase/phosphodiesterase 1 knockout (Enpp1-/-) mouse as a valid model of medial vascular calcification, which is employed throughout this thesis. This thesis has compared VSMCs to osteoblasts undergoing osteocytic differentiation in vitro. VSMC in vitro calcification was accompanied by up-regulated expression of osteocyte markers, including Sost, E11, Dmp1, Phex, Mepe and Fgf23. Immunohistochemistry confirmed the appearance of sclerostin and E11 in calcified aortae from the Enpp1-/- mouse. Further studies have identified a direct inhibitory role for the osteocyte specific gene FGF23 in modulating vascular calcification. The inhibitory effect of FGF23 on VSMC calcification was mediated through the MAPK/ERK signalling pathway. This thesis has also determined the role of BMP9, a highly osteogenic bone morphogenic protein, in vascular calcification, which induces VSMC calcification through a Smad signalling mechanism. Furthermore, VSMC expression of the osteocytic marker Sost was markedly increased following BMP9 treatment. Intriguingly, BMP9 was markedly elevated in serum from dialysis patients and a significant correlation was observed between dialysis time and BMP9 concentration in patients receiving haemodialysis. The work described herein has demonstrated that vascular calcification is associated with an osteocyte phenotype, and reports a direct inhibitory effect of the osteocyte specific gene FGF23 on vascular calcification. Furthermore, this thesis has shown that BMP9 induces the expression of the osteocytic marker Sost in VSMCs, and appears to play a critical role in vascular calcification.

Background: Coronary artery calcification (CAC) is common in chronic kidney disease (CKD) patients, and is demonstrable in fifty percent of incident dialysis patients. Therefore, the process of CAC initiation likely occurs in the pre-dialysis period. Pre-dialysis CKD patients have been shown to have a substantially higher burden of CAC than age and sex matched controls from the general population. Consequently, the hypothesis that CKD itself is a risk factor for CAC occurrence is biologically plausible. Objective: 1) To quantify the relationship between CKD and CAC in stage three to five CKD patients without known cardiovascular disease. 2) To estimate the strengths of associations between traditional cardiovascular disease risk factors, non- traditional cardiovascular disease risk factors and CAC in this patient population. Methods: This cross-sectional study investigated one hundred and nineteen CKD patients (excluding dialysis) receiving care at a single hospital in Kingston, Ontario, Canada. For the primary objective, correlational analyses were performed to evaluate associations between a priori selected variables of kidney function and CAC scores, as well as other a priori chosen variables of interest. Results: Mean and median CAC scores were 566.5 SD: 1108 and 111 (inter-quartile range 2 to 631.5) respectively. CAC correlated with age (r = 0.44, p<0.001), body mass index (r = 0.28, p = 0.002), high density lipoprotein cholesterol (r = -0.23, p = 0.01), diabetes mellitus (r = 0.23, p = 0.01), and the cardiovascular risk score (r = 0.35; p < 0.001). By multivariable linear regression controlling for eGFR and diabetes, age (ß = 0.05, 95% CI 0.03-0.06; p<0.001), body mass index (ß = 0.04, 0.02 - 0.07; p=0.001), and serum calcium (ß = 0.9, 0.15 - 1.6; p=0.02), were risk factors for CAC. Results from multivariable logistic regression modeling demonstrated consistent findings. Limitations: Inadequate sample size and uncontrolled confounding are possible limitations, but are unlikely to have changed the main study findings. Conclusions: In this study, traditional cardiovascular disease risk factors and serum calcium were associated with coronary artery calcification. No association was demonstrated between CKD and CAC. Studies exploring potential protective mechanisms against coronary artery calcification are needed.

Thesis (Ph. D.)--School of Dentistry. University of Missouri--Kansas City, 2006. / "A dissertation in oral biology and cell biology and biophysics." Advisor: Lynda F. Bonewald. Typescript. Vita. Title from "catalog record" of the print edition Description based on contents viewed Nov. 12, 2007. Includes bibliographical references (leaves 121-139). Online version of the print edition.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1959. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves [95]-98).

Th.--Sci. phys.--Toulouse--I.N.P., 1984. N°: 81.

Total alkalinity (TA) is an important parameter in determining the uptake capacity of anthropogenic CO2 by the ocean. So far, oceanic carbon cycle models do not accurately represent TA and its variations. A spectrophotometric method was developed to measure variations of TA during two JGOFS cruises to the Northeast Atlantic in the early summer of 1990 and 1991 and in Emiliania huxleyi batch cultures. Short-term precision averaged around ± 0.1 %. A discrepancy of < 0.5% with coulometric results was observed in Na2COa standards. In natural seawater photometric TA was lower than potentiometric and calculated (pCOl, TC02) TA by about 1 and 2%, respectively. Discrepancies varied with hydrographic and/ or biological regime. Possible reasons for methodological shortcomings were considered, but without certified TA standards for different sample types, it was not possible to make an absolute statement about the accuracy of the methods involved. Combining the cruise results, photometric TA ranged by 90 and 20 p.eq kgSW-l in the surface mixed layer (SML) and at sub-thermocline depths, respectively. Some horizontal variation in the SML was related to salinity, but most of it could be linked to coccolithophorid growth during a bloom in 1991. Associated small-scale changes in TA of up to 40 J.leq kgSW-t occurred over 40 km. Independent estimates of seasonal net production of PlC and its relation to that of particulate organic carbon (POC) were established. Based on preceding investigations, a seasonal and latitudinal sequence of changes in surface TA was proposed which was corroborated by the photometric results from this study. The culture experiments revealed reductions in photometric TA which were half of those expected from parallel changes in measured PlC and nitrate concentrations. Proposed explanations for this included methodological shortcomings of all three methods and increases in final TA due to algal sulphate uptake and/or organic acid release. As the main conclusion, further targeted intercomparisons of TA methods are needed to identify the causes for errors in various TA methods in samples covering realistic hydrographic and biological ranges.

Made available in DSpace on 2014-06-11T19:32:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-11-05Bitstream added on 2014-06-13T21:03:37Z : No. of bitstreams: 1 vannini_fcd_dr_botfm.pdf: 438750 bytes, checksum: 52c4a11cc872d6dddca37fa4ef815423 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / As doenças cardiovasculares são a causa mais frequente de morte em pacientes em hemodiálise (HD). A calcificação vascular (CV) é extremamente comum nesses pacientes, e está associada com vários desfechos clínicos, como isquemia cardíaca e mortalidade cardiovascular. A CV está associada com fatores de risco tradicionais como aterosclerose, idade, hipertensão arterial, diabetes mellitus (DM) e dislipidemia, e a fatores de risco não tradicionais, como inflamação, hiperfosfatemia e hiperparatireoidismo. Este estudo de coorte prospectivo observacional teve como objetivo avaliar em pacientes em HD a presença e progressão da CV e a evolução nutricional, assim como identificar variáveis associadas com a progressão da CV e depleção do estado nutricional. Também foi determinado, após 24 meses, o impacto da CV e de variáveis clínicas, demográficas e nutricionais sobre a ocorrência de eventos cardiovasculares e óbito. Quarenta e nove pacientes em HD por no mínimo 90 dias foram incluídos. Ao início do seguimento e após 12 meses foi estimado o escore de calcificação vascular (ECV) pelos métodos de Kauppila e de Adragão, assim como avaliados marcadores clínicos, nutricionais, dialíticos, bioquímicos, hemotológicos e inflamatórios. Duas análise foram realizadas, a primeira com todos os pacientes e a segunda, incluindo apenas aqueles com menos de 60 anos. O modelo de regressão logística foi utilizado para avaliar preditores independentes da presença, progressão e velocidade de progressão da CV, assim como da depleção do estado nutricional, definido pela variação negativa do ângulo de fase (Â) obtido pela biompedância ou mudança da classificação do estado nutricional de bem nutrido para desnutrido pela avaliação subjetiva global (SGA). O modelo múltiplo de regressão de Cox foi utilizado para identificar... / Cardiovascular diseases are the most frequent causes of death in hemodialysis (HD) patients. Vascular calcification (VC) is very common in these patients, and it is associated with many adverse clinical outcomes, including ischemic cardiac events and subsequent cardiovascular mortality. VC has been associated with numerous „traditional‟ risk factors to atherosclerosis such as aging, hypertension, diabetes or dyslipidemia, as well as with „nontraditional‟ risk factors, such as inflammation, hyper phosphatemia, and hyperparathyroidism. This prospective observational cohort study was designed in order to evaluate HD patients regarding the presence and progression of VC, nutritional evolution, as well as to identify variables associated with VC progression rate and nutritional impairment. Also, we aimed to determine the impact of VC and nutritional characteristics on cardiovascular outcomes and death risk. Forty-nine patients on regular HD over at least 90 days were included. At baseline and after 12 months, VC scores (VCS) were estimated by Kauppila and Adragão methods; nutritional and clinical assessment were performed, dialytic, biochemical, hematologic, and inflammatory markers were obtained. After the follow-up, cardiovascular events and deaths from all causes were recorded over an additional 24 month period. Two analyses were performed, the first with all patients and the second involving those younger than 60 years old. Binary logistic regression models were constructed to evaluate independent predictors of VC presence, progression, and progression rate as well as nutritional impairment, defined by the negative variation of phase angle (A0) in the electrical bioimpedance or subjective global assessment (SGA) change from well-nourished to malnourished. The Cox proportional regression model was used to... (Complete abstract click electronic access below)

As anthropogenically-forced ocean temperatures continue to rise, the physiological response of marine macrophytes becomes exceedingly relevant. The Red Sea is a semi-isolated sea- the warmest in the world (SST up to 34°C) - already exhibiting signs of rapid warming rates exceeding those of other tropical oceans. This will have profound effects on the physiology of marine organisms, specifically marine macrophytes, which have direct influence on the dynamic carbonate system of the Red Sea. The aim of this paper is to define the physiological capability and thermal optima and limits of six ecologically important Red Sea macrophytes- ranging from seagrasses to calcifying and non-calcifying algae- and to describe the effects of increasing thermal stress on the performance and limits of each macrophyte in terms of activation energy. Of the species considered, Halophila stipulacae, Halimeda optunia, Halimeda monile and Padina pavonica thrive in thermal extremes and may be more successful in future Red Sea warming scenarios. Specifically, Halimeda opuntia increased productivity and calcification rates up to 38°C, making it the most thermally resilient macrophyte. Halophila stipulacae is the most productive seagrass, and hence has the greatest positive effect on Omega saturation state and offers chemical buffer capacity to future ocean acidification.

The geographic location of the Sulu Sea in the far western equatorial Pacific results in the basin’s oceanographic sensitivity to: 1.) the East Asian Monsoon strength, 2.) the Kuroshio Current and open western Pacific conditions, 3.) Indonesian Strait geometry, 4.) past sea level, and 5.) the Indonesian Throughflow (ITF). Due to the sea’s unique bathymetry as a deep basin (~5,000 m maximum depth) surrounded by shallow sills with maximum depths of 440 m, Sulu Sea bottom water is relatively warm with minimum temperature of ~10°C, low dissolved oxygen, high carbonate concentrations, excellent CaCO3 preservation, and low bioturbation which combine to produce a remarkable sedimentological record. Sulu Sea sediments have previously been utilized to generate high-resolution paleoclimate records of past variability of surface ocean conditions using the planktonic foraminifera Globigerinoides ruber. However, past changes in the Sulu Sea subsurface and thermocline have been largely unexplored until now. Here I will show that reconstructing subsurface upper ocean conditions in the Sulu Sea reveals a rich archive of paleoclimatic information relating to past upper ocean dynamics. In this dissertation I seek to understand Indo-Pacific and global glacial-interglacial variability over the last four glacial cycles by generating foraminiferal δ18O, Mg/Ca-based temperature, and seawater δ18O (δ18Ow) records using the thermocline calcifying foraminifera Globorotalia tumida from high-resolution sediment core MD97-2141 from the Sulu Sea. Additionally, I extend existing G. ruber Mg/Ca-based temperature and δ18Ow paleoclimatic results to now span intervals of the last four glacial cycles. Sulu Sea thermocline reconstructions monitor regional paleoclimate on their own while also providing insight into surface variability when the surface and thermocline depth paleoclimatic records are compared.In Chapter 1 of this dissertation, I use Sulu Sea G. tumida reconstructions to investigate the North Equatorial Current (NEC) bifurcation latitude. After flowing east to west across the Equatorial Pacific, the NEC bifurcates into the northward flowing Kuroshio Current and the southward flowing Mindanao Current. The latitude of bifurcation migrates seasonally and interannually, controlling the partitioning of water between the two currents and the transfer of energy to the North Pacific. Using modern instrumental data, I show that by controlling the strength of the Kuroshio Current, the NEC bifurcation latitude also controls the leakage of relatively salty western Pacific water into the South China and Sulu Sea thermoclines, thus playing a major role in the salinity of the thermocline in both basins. I then use Sulu Sea thermocline δ18Ow generated using the foraminifera G. tumida from core MD97-2141 to show that the NEC bifurcation latitude was north during Heinrich Stadial I (17.5-15 ka), the Younger Dryas Chronozone (12.9-11.6 ka), and from ~9.5-8.5 ka and south during the Bølling-Allerød and early Holocene. Understanding the calcification depth of foraminifera is crucial for interpreting paleoclimate records. In Chapter 2 of this dissertation, I present δ18O records from six foraminiferal species and size fraction combinations from core MD97-2141 spanning ~12.75-10.75 ka. I calculate the δ18O difference between those records and previously published G. ruber data from the same core and use modern instrumental temperature and salinity data from the Sulu Sea to estimate calcification depths for each species and size fraction combination. I estimate that Sulu Sea G. tumida in the 400-600 μm size fraction calcify at a mean depth of 115m with the middle 95% of foraminifera geochemically analyzed yielding calcification depths between 99-131 m. G. tumida with no size constraint and in the >600 μm size fraction calcify at mean depths of 112 m and 107 m with the middle 95% of individual samples at 99-120 m and 88-117 m respectively. Globorotalia menardii was found to calcify at a mean depth of 106 m and the middle 95% of samples between 92-117 m. Neogloboquadrina dutertrei calcifies at a mean depth of 112 m (middle 95% between 102-120 m). Lastly, Pulleniatina obliquiloculata calcifies at a mean depth of 93 m (middle 95% between 68-108 m). Estimated calcification depth ranges for the all six species and size fraction combinations overlap. My results suggest that larger G. tumida calcify shallower in the Sulu Sea. I also show evidence that calcification depths in the Sulu Sea did not change for any of these species through time. Chapter 3 focuses on Marine Isotope Stage 3 (MIS3) (60-26 ka). I present results which demonstrate that the opening and closing of the ~36 m deep Karimata Strait at the southern terminus of the South China Sea with rising and falling sea level plays a substantial role in Sulu Sea surface salinity. I generated surface and thermocline δ18Ow records spanning ~125-20 ka in order to determine when the Karimata Strait was open and closed. I then use the depth history of the Karimata Strait to constrain maximum sea level during MIS 3 to -22±6 m relative to modern sea level and minimum possible sea level during MIS 5a and 5c (117-72 ka) to -12±7 m relative to modern. My record is the first to unequivocally demonstrate the Karimata Strait was subaerial during MIS 3 and suggests it could have facilitated the first human migration to the island of Borneo which occurred during that time. During the Younger Dryas paleoclimatic event (~12.9-11.6 ka), there was a return to near glacial conditions during the transition from the Last Glacial Maximum to the early Holocene (Termination I) (~18-11 ka). This was the most significant climate event during Termination I, but it is still unknown if it was a one-off event or if such millennial-scale events are intrinsic to glacial terminations. In Chapter 4 of this dissertation, I present Sulu Sea thermocline δ18O and Mg/Ca-based temperature records and a surface ocean Mg/Ca record to investigate millennial-scale events during Terminations II (~135-125 ka), III (~252-240 ka), and IV (~341-330 ka) in order to determine if the Termination II-IV events in the Sulu Sea demonstrate the same structure as the event during the Younger Dryas Chronozone. My results show that the millennial-scale event in the Sulu Sea thermocline during Termination III was most similar to the Younger Dryas Chronozone event, while the Termination II and IV events were largely similar to the Younger Dryas Chronozone with some differences. My reconstructions of these events are very consistent with the Termination III event in the Sulu Sea and somewhat consistent with the Termination II and IV events in the Sulu Sea being driven by the same mechanism as the Sulu Sea Younger Dryas Chronozone event. As a whole, my dissertation takes a unique approach to characterizing millennial-scale climatic events by combining surface and thermocline foraminiferal δ18O and Mg/Ca reconstructions and attributing mechanistic drivers to each. In doing so, I am able to draw the most possible information from a core. Such an approach that utilizes both the surface and the subsurface of the water column also allows interpretation of the differences between the surface and thermocline and these differences can improve our interpretations of previously existing surface records. Furthermore, my dissertation develops a new approach to constraining sea level using foraminiferal δ18O results by tying them to physical structures such as the Karimata Strait that have a direct relationship to sea level. The conclusions I reach in my dissertation shed light on North Equatorial Current bifurcation latitude variability since the Last Glacial Maximum, furthering our understanding of the controls of Indo-Pacific and western Pacific climate variability and the Indonesian Throughflow. They also improve our understanding of foraminiferal calcification depth in the Sulu Sea and through time, help constrain sea level during Marine Isotope Stages 3 and 5, and help develop our understating of millennial scale events during glacial terminations.

Calcified atheromatous aortic lesion causing significant narrowing of the aorta is an uncommon clinical entity. This calcified atheroma leads to obstruction of the lumen of the aorta simulating acquired coarctation of aorta causing impaired perfusion of lower limbs, visceral ischemia, and hypertension. We report a case of 58-year-old patient who presented with dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea, 25-lb weight gain, lower extremity edema, and chest pain. Extensive workup including computed tomography and magnetic resonance imaging revealed a large calcific mass in the aortic arch causing his presenting symptoms. After surgical correction his symptoms resolved. Any patient presenting with heart failure symptoms in the setting of uncontrolled renovascular hypertension, intermittent claudication symptoms, or visceral ischemia with normal ejection fraction but moderate to severe left ventricular hypertrophy should be in high suspicion for acquired coarctation of aorta. The routine thorough examination of pulses in bilateral upper and lower extremities in all hypertensive patients is a very simple and useful clinical tool to diagnose acquired aortic coarctation.