Vascular calcification: When should we interfere in chronic kidney disease patients and how?

PubMed Central

Sharaf El Din, Usama Abdel Azim; Salem, Mona Mansour; Abdulazim, Dina Ossama

2016-01-01

Chronic kidney disease (CKD) patients are endangered with the highest mortality rate compared to other chronic diseases. Cardiovascular events account for up to 60% of the fatalities. Cardiovascular calcifications affect most of the CKD patients. Most of this calcification is related to disturbed renal phosphate handling. Fibroblast growth factor 23 and klotho deficiency were incriminated in the pathogenesis of vascular calcification through different mechanisms including their effects on endothelium and arterial wall smooth muscle cells. In addition, deficient klotho gene expression, a constant feature of CKD, promotes vascular pathology and shares in progression of the CKD. The role of gut in the etio-pathogenesis of systemic inflammation and vascular calcification is a newly discovered mechanism. This review will cover the medical history, prevalence, pathogenesis, clinical relevance, different tools used to diagnose, the ideal timing to prevent or to withhold the progression of vascular calcification and the different medications and medical procedures that can help to prolong the survival of CKD patients. PMID:27648404

Magnesium reduces calcification in bovine vascular smooth muscle cells in a dose-dependent manner

PubMed Central

Peter, Mirjam E.; Sevinc Ok, Ebru; Celenk, Fatma Gul; Yilmaz, Mumtaz; Steppan, Sonja; Asci, Gulay; Ok, Ercan; Passlick-Deetjen, Jutta

2012-01-01

Background. Vascular calcification (VC), mainly due to elevated phosphate levels, is one major problem in patients suffering from chronic kidney disease. In clinical studies, an inverse relationship between serum magnesium and VC has been reported. However, there is only few information about the influence of magnesium on calcification on a cellular level available. Therefore, we investigated the effect of magnesium on calcification induced by β-glycerophosphate (BGP) in bovine vascular smooth muscle cells (BVSMCs). Methods. BVSMCs were incubated with calcification media for 14 days while simultaneously increasing the magnesium concentration. Calcium deposition, transdifferentiation of cells and apoptosis were measured applying quantification of calcium, von Kossa and Alizarin red staining, real-time reverse transcription–polymerase chain reaction and annexin V staining, respectively. Results. Calcium deposition in the cells dramatically increased with addition of BGP and could be mostly prevented by co-incubation with magnesium. Higher magnesium levels led to inhibition of BGP-induced alkaline phosphatase activity as well as to a decreased expression of genes associated with the process of transdifferentiation of BVSMCs into osteoblast-like cells. Furthermore, estimated calcium entry into the cells decreased with increasing magnesium concentrations in the media. In addition, higher magnesium concentrations prevented cell damage (apoptosis) induced by BGP as well as progression of already established calcification. Conclusions. Higher magnesium levels prevented BVSMC calcification, inhibited expression of osteogenic proteins, apoptosis and further progression of already established calcification. Thus, magnesium is influencing molecular processes associated with VC and may have the potential to play a role for VC also in clinical situations. PMID:21750166

Association of vascular fluoride uptake with vascular calcification and coronary artery disease.

PubMed

Li, Yuxin; Berenji, Gholam R; Shaba, Wisam F; Tafti, Bashir; Yevdayev, Ella; Dadparvar, Simin

2012-01-01

The feasibility of a fluoride positron emission tomography/computed tomography (PET/CT) scan for imaging atherosclerosis has not been well documented. The purpose of this study was to assess fluoride uptake of vascular calcification in various major arteries, including coronary arteries. We retrospectively reviewed the imaging data and cardiovascular history of 61 patients who received whole-body sodium [¹⁸F]fluoride PET/CT studies at our institution from 2009 to 2010. Fluoride uptake and calcification in major arteries, including coronary arteries, were analyzed by both visual assessment and standardized uptake value measurement. Fluoride uptake in vascular walls was demonstrated in 361 sites of 54 (96%) patients, whereas calcification was observed in 317 sites of 49 (88%) patients. Significant correlation between fluoride uptake and calcification was observed in most of the arterial walls, except in those of the abdominal aorta. Fluoride uptake in coronary arteries was demonstrated in 28 (46%) patients and coronary calcifications were observed in 34 (56%) patients. There was significant correlation between history of cardiovascular events and presence of fluoride uptake in coronary arteries. The coronary fluoride uptake value in patients with cardiovascular events was significantly higher than in patients without cardiovascular events. sodium [¹⁸F]fluoride PET/CT might be useful in the evaluation of the atherosclerotic process in major arteries, including coronary arteries. An increased fluoride uptake in coronary arteries may be associated with an increased cardiovascular risk.

Close association of vascular and valvular calcification and prognosis of patients on continuous ambulatory peritoneal dialysis.

PubMed

Gen, Shikou; Inoue, Tsutomu; Nodaira, Yuka; Ikeda, Naofumi; Kobayashi, Kazuhiro; Watanabe, Yusuke; Kanno, Yoshihiko; Nakamoto, Hidetomo; Suzuki, Hiromichi

2008-01-01

In the present study, we examined the association between vascular and valvular calcification and the prognosis of patients on continuous ambulatory peritoneal dialysis (CAPD). Data were collected from the records of patients introduced onto CAPD therapy during 1999 - 2006 at the Department of Nephrology, Saitama Medical University. At the start of CAPD, cardiac and vascular echography were used to examine 162 patients (average age: 56 +/- 5 years; 58 men, 104 women; 43 with and 119 without diabetes) for evaluation of vascular and valvular calcification. Both vascular and valvular calcification were found in 32 patients. Vascular calcification was found in 16, and valvular calcification in 11. Over 5 years, 11 patients suffered from cardiovascular disease (7 with stroke, 4 with myocardial infarction). All of these patients had vascular or valvular calcification at the start of CAPD therapy. We also used Cox hazard analysis to examine values for Ca, P, Ca x P, intact parathyroid hormone (iPTH), and lipids. None of these values were independent contributory factors for incidence of cardiovascular disease in patients on CAPD. These data suggest the importance of vascular and valvular echography to evaluate patients on CAPD, especially at the start of CAPD therapy. Vascular and valvular calcification are important factors for determining the prognosis of patients on CAPD.

Inflammatory, metabolic, and genetic mechanisms of vascular calcification

PubMed Central

Demer, Linda L.; Tintut, Yin

2014-01-01

This review centers on updating the active research area of vascular calcification. This pathology underlies substantial cardiovascular morbidity and mortality, through adverse mechanical effects on vascular compliance, vasomotion, and, most likely, plaque stability. Biomineralization is a complex, regulated process occurring widely throughout nature. Decades ago, its presence in the vasculature was considered a mere curiosity and an unregulated, “dystrophic” process that does not involve biological mechanisms. While it remains controversial whether the process has any adaptive value or past evolutionary advantage, substantial advances have been made in understanding the biological mechanisms driving the process. Different types of calcific vasculopathy, such as inflammatory vs. metabolic, have parallel mechanisms in skeletal bone calcification, such as intramembranous and endochondral ossification. Recent work has identified important regulatory roles for inflammation, oxidized lipids, elastin, alkaline phosphatase, osteoprogenitor cells, matrix gamma-carboxyglutamic acid protein (MGP), transglutaminase, osteoclastic regulatory factors, phosphate regulatory hormones and receptors, apoptosis, prelamin A, autophagy, and microvesicles or microparticles similar to the matrix vesicles of skeletal bone. Recent work has uncovered fascinating interactions between MGP, vitamin K, warfarin and transport proteins. And, lastly, recent breakthroughs in inherited forms of calcific vasculopathy, have identified the genes responsible as well as an unexpected overlap of phenotypes. PMID:24665125

Dietary magnesium supplementation prevents and reverses vascular and soft tissue calcifications in uremic rats.

PubMed

Diaz-Tocados, Juan M; Peralta-Ramirez, Alan; Rodríguez-Ortiz, María E; Raya, Ana I; Lopez, Ignacio; Pineda, Carmen; Herencia, Carmen; Montes de Oca, Addy; Vergara, Noemi; Steppan, Sonja; Pendon-Ruiz de Mier, M Victoria; Buendía, Paula; Carmona, Andrés; Carracedo, Julia; Alcalá-Díaz, Juan F; Frazao, Joao; Martínez-Moreno, Julio M; Canalejo, Antonio; Felsenfeld, Arnold; Rodriguez, Mariano; Aguilera-Tejero, Escolástico; Almadén, Yolanda; Muñoz-Castañeda, Juan R

2017-11-01

Although magnesium has been shown to prevent vascular calcification in vitro, controlled in vivo studies in uremic animal models are limited. To determine whether dietary magnesium supplementation protects against the development of vascular calcification, 5/6 nephrectomized Wistar rats were fed diets with different magnesium content increasing from 0.1 to 1.1%. In one study we analyzed bone specimens from rats fed 0.1%, 0.3%, and 0.6% magnesium diets, and in another study we evaluated the effect of intraperitoneal magnesium on vascular calcification in 5/6 nephrectomized rats. The effects of magnesium on established vascular calcification were also evaluated in uremic rats fed on diets with either normal (0.1%) or moderately increased magnesium (0.6%) content. The increase in dietary magnesium resulted in a marked reduction in vascular calcification, together with improved mineral metabolism and renal function. Moderately elevated dietary magnesium (0.3%), but not high dietary magnesium (0.6%), improved bone homeostasis as compared to basal dietary magnesium (0.1%). Results of our study also suggested that the protective effect of magnesium on vascular calcification was not limited to its action as an intestinal phosphate binder since magnesium administered intraperitoneally also decreased vascular calcification. Oral magnesium supplementation also reduced blood pressure in uremic rats, and in vitro medium magnesium decreased BMP-2 and p65-NF-κB in TNF-α-treated human umbilical vein endothelial cells. Finally, in uremic rats with established vascular calcification, increasing dietary magnesium from 0.1% magnesium to 0.6% reduced the mortality rate from 52% to 28%, which was associated with reduced vascular calcification. Thus, increasing dietary magnesium reduced both vascular calcification and mortality in uremic rats. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Aortic Stenosis and Vascular Calcifications in Alkaptonuria

PubMed Central

Hannoush, Hwaida; Introne, Wendy J.; Chen, Marcus Y.; Lee, Sook-Jin; O'Brien, Kevin; Suwannarat, Pim; Kayser, Michael A.; Gahl, William A.; Sachdev, Vandana

2011-01-01

Alkaptonuria is a rare metabolic disorder of tyrosine catabolism in which homogentisic acid (HGA) accumulates and is deposited throughout the spine, large joints, cardiovascular system, and various tissues throughout the body. In the cardiovascular system, pigment deposition has been described in the heart valves, endocardium, pericardium, aortic intima and coronary arteries. The prevalence of cardiovascular disease in patients with alkaptonuria varies in previous reports . We present a series of 76 consecutive adult patients with alkaptonuria who underwent transthoracic echocardiography between 2000 and 2009. A subgroup of 40 patients enrolled in a treatment study underwent non-contrast CT scans and these were assessed for vascular calcifications. Six of the 76 patients had aortic valve replacement. In the remaining 70 patients, 12 patients had aortic sclerosis and 7 patients had aortic stenosis. Unlike degenerative aortic valve disease, we found no correlation with standard cardiac risk factors. There was a modest association between the severity of aortic valve disease and joint involvement, however, we saw no correlation with urine HGA levels. Vascular calcifications were seen in the coronaries, cardiac valves, aortic root, descending aorta and iliac arteries. These findings suggest an important role for echocardiographic screening of alkaptonuria patients to detect valvular heart disease and cardiac CT to detect coronary artery calcifications. PMID:22100375

Aortic stenosis and vascular calcifications in alkaptonuria.

PubMed

Hannoush, Hwaida; Introne, Wendy J; Chen, Marcus Y; Lee, Sook-Jin; O'Brien, Kevin; Suwannarat, Pim; Kayser, Michael A; Gahl, William A; Sachdev, Vandana

2012-02-01

Alkaptonuria is a rare metabolic disorder of tyrosine catabolism in which homogentisic acid (HGA) accumulates and is deposited throughout the spine, large joints, cardiovascular system, and various tissues throughout the body. In the cardiovascular system, pigment deposition has been described in the heart valves, endocardium, pericardium, aortic intima and coronary arteries. The prevalence of cardiovascular disease in patients with alkaptonuria varies in previous reports. We present a series of 76 consecutive adult patients with alkaptonuria who underwent transthoracic echocardiography between 2000 and 2009. A subgroup of 40 patients enrolled in a treatment study underwent non-contrast CT scans and these were assessed for vascular calcifications. Six of the 76 patients had aortic valve replacement. In the remaining 70 patients, 12 patients had aortic sclerosis and 7 patients had aortic stenosis. Unlike degenerative aortic valve disease, we found no correlation with standard cardiac risk factors. There was a modest association between the severity of aortic valve disease and joint involvement, however, we saw no correlation with urine HGA levels. Vascular calcifications were seen in the coronaries, cardiac valves, aortic root, descending aorta and iliac arteries. These findings suggest an important role for echocardiographic screening of alkaptonuria patients to detect valvular heart disease and cardiac CT to detect coronary artery calcifications. Published by Elsevier Inc.

Treatment of hypophosphatemic rickets in generalized arterial calcification of infancy (GACI) without worsening of vascular calcification.

PubMed

Ferreira, Carlos R; Ziegler, Shira G; Gupta, Ashutosh; Groden, Catherine; Hsu, Kevin S; Gahl, William A

2016-05-01

Patients with generalized arterial calcification of infancy (GACI) develop vascular calcifications early in life. About half of them die within the first 6 months despite optimal medical care. A subset of those who survive eventually develop hypophosphatemic rickets. Since hypophosphatemia and hyperphosphaturia have been previously associated with increased survival in GACI patients, physicians often avoid phosphate repletion as treatment for rickets. As a consequence, GACI patients develop severe rachitic complications such as short stature and skeletal deformities. It appears that the recognition of hypophosphatemia later in life in some GACI patients is a consequence of having survived the first few months of life, and not the cause of their survival per se. Here, we report the long-term follow-up of a GACI patient who was phosphate-repleted for his rickets for more than 7 years without worsening of vascular calcification. © 2016 Wiley Periodicals, Inc.

Eotaxin Augments Calcification in Vascular Smooth Muscle Cells.

PubMed

Raghuraman, Gayatri; Hsiung, Joseph; Zuniga, Mary C; Baughman, Brittanie D; Hitchner, Elizabeth; Guzman, Raul J; Zhou, Wei

2017-03-01

Calcification of atherosclerotic plaques in elderly patients represents a potent risk marker of cardiovascular events. Plasma analyses of patients with or without calcified plaques reveal significant differences in chemokines, particularly eotaxin, which escalates with increased calcification. We therefore, hypothesize that eotaxin in circulation augments calcification of vascular smooth muscle cells (VSMCs) possibly via oxidative stress in the vasculature. We observe that eotaxin increases the rate of calcification significantly in VSMCs as evidenced by increased alkaline phosphatase activity, calcium deposition, and osteogenic marker expression. In addition, eotaxin promotes proliferation in VSMCs and triggers oxidative stress in a NADPH oxidase dependent manner. These primary novel observations support our proposition that in the vasculature eotaxin augments mineralization. Our findings suggest that eotaxin may represent a potential therapeutic target for prevention of cardiovascular complications in the elderly. J. Cell. Biochem. 118: 647-654, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Arterial ageing: from endothelial dysfunction to vascular calcification.

PubMed

Tesauro, M; Mauriello, A; Rovella, V; Annicchiarico-Petruzzelli, M; Cardillo, C; Melino, G; Di Daniele, N

2017-05-01

Complex structural and functional changes occur in the arterial system with advancing age. The aged artery is characterized by changes in microRNA expression patterns, autophagy, smooth muscle cell migration and proliferation, and arterial calcification with progressively increased mechanical vessel rigidity and stiffness. With age the vascular smooth muscle cells modify their phenotype from contractile to 'synthetic' determining the development of intimal thickening as early as the second decade of life as an adaptive response to forces acting on the arterial wall. The increased permeability observed in intimal thickening could represent the substrate on which low-level atherosclerotic stimuli can promote the development of advanced atherosclerotic lesions. In elderly patients the atherosclerotic plaques tend to be larger with increased vascular stenosis. In these plaques there is a progressive accumulation of both lipids and collagen and a decrease of inflammation. Similarly the plaques from elderly patients show more calcification as compared with those from younger patients. The coronary artery calcium score is a well-established marker of adverse cardiovascular outcomes. The presence of diffuse calcification in a severely stenotic segment probably induces changes in mechanical properties and shear stress of the arterial wall favouring the rupture of a vulnerable lesion in a less stenotic adjacent segment. Oxidative stress and inflammation appear to be the two primary pathological mechanisms of ageing-related endothelial dysfunction even in the absence of clinical disease. Arterial ageing is no longer considered an inexorable process. Only a better understanding of the link between ageing and vascular dysfunction can lead to significant advances in both preventative and therapeutic treatments with the aim that in the future vascular ageing may be halted or even reversed. © 2017 The Association for the Publication of the Journal of Internal Medicine.

Interleukin-24 attenuates β-glycerophosphate-induced calcification of vascular smooth muscle cells by inhibiting apoptosis, the expression of calcification and osteoblastic markers, and the Wnt/β-catenin pathway.

PubMed

Lee, Ki-Mo; Kang, Haeng-A; Park, Min; Lee, Hwa-Youn; Choi, Ha-Rim; Yun, Chul-Ho; Oh, Jae-Wook; Kang, Hyung-Sik

2012-11-09

Vascular calcification is a hallmark of cardiovascular disease. Interleukin-24 (IL-24) has been known to suppress tumor progression in a variety of human cancers. However, the role of IL-24 in the pathophysiology of diseases other than cancer is unclear. We investigated the role of IL-24 in vascular calcification. IL-24 was applied to a β-glycerophosphate (β-GP)-induced rat vascular smooth muscle cell (VSMC) calcification model. In this study, IL-24 significantly inhibited β-GP-induced VSMC calcification, as determined by von Kossa staining and calcium content. The inhibitory effect of IL-24 on VSMC calcification was due to the suppression of β-GP-induced apoptosis and expression of calcification and osteoblastic markers. In addition, IL-24 abrogated β-GP-induced activation of the Wnt/β-catenin pathway, which plays a key role in the pathogenesis of vascular calcification. The specificity of IL-24 for the inhibition of VSMC calcification was confirmed by using a neutralizing antibody to IL-24. Our results suggest that IL-24 inhibits β-GP-induced VSMC calcification by inhibiting apoptosis, the expression of calcification and osteoblastic markers, and the Wnt/ β-catenin pathway. Our study may provide a novel mechanism of action of IL-24 in cardiovascular disease and indicates that IL-24 is a potential therapeutic agent in VSMC calcification. Copyright © 2012 Elsevier Inc. All rights reserved.

Vascular calcification and 25-hydroxyvitamin D levels in non-dialysis patients with chronic kidney disease stages 4 and 5.

PubMed

García-Canton, Cesar; Bosch, Elvira; Ramírez, Ana; Gonzalez, Yeray; Auyanet, Ingrid; Guerra, Rita; Perez, Miguel A; Fernández, Ernesto; Toledo, Agustín; Lago, Mar; Checa, Maria D

2011-07-01

Cardiovascular disease (CVD) is the leading cause of death among chronic kidney disease (CKD) patients. Vascular calcification is highly prevalent in this population and is an independent predictor of cardiovascular mortality. Vascular calcification in uraemic patients is known to be an active and regulated process subject to the action of many promoting and inhibitory factors. The role of vitamin D in this process remains controversial. We evaluated the relationship between serum levels of 25-hydroxyvitamin D (25(OH)D) and vascular calcification evaluated by plain X-ray images, in predialysis patients with CKD stages 4 and 5. We performed a cross-sectional study with 210 CKD patients stages 4 and 5 managed at our predialysis unit. Patients were 63.5 ± 13 years of age, 60.5% males, 64.8% diabetics and 47.1% with a history of CVD. Plain X-ray images of pelvis, hands and lateral lumbar spine from all subjects were studied for calculation of semiquantitative vascular calcification scores as described by Adragao and Kauppila. We found a high prevalence of vascular calcification in our population. Adragao scores revealed only 47 patients (22.4%) without vascular calcification and 120 (57.1%) with scores higher than 3. Kauppila scores revealed only 29 patients (13.8%) without aortic calcifications and 114 patients (54.3%) with scores higher than 7. Higher vascular calcification scores were related to older age, diabetes, history of CVD and lower levels of 25(OH)D. Only 18.5% of patients had adequate levels of 25(OH)D (> 30 ng/mL), 53.7% of them had insufficient levels (15-30 ng/mL) and 27.8% had deficient levels (< 15 ng/mL). Multivariate analysis showed that age, diabetes and CVD were directly associated and 25(OH)D levels were inversely associated with vascular calcifications. Our results show an independent and negative association between serum levels of 25(OH)D and vascular calcification. Further and larger prospective studies are needed to clarify the possible

Dietary vitamin K and therapeutic warfarin alter susceptibility to vascular calcification in experimental chronic kidney disease

USDA-ARS?s Scientific Manuscript database

The leading cause of death in patients with chronic kidney disease (CKD) is cardiovascular disease (CVD), with vascular calcification (VC) being a key modifier of disease progression. A local regulator of vascular calcification is vitamin K. This gamma-glutamyl carboxylase substrate is an essential ...

Gallic acid inhibits vascular calcification through the blockade of BMP2-Smad1/5/8 signaling pathway.

PubMed

Kee, Hae Jin; Cho, Soo-Na; Kim, Gwi Ran; Choi, Sin Young; Ryu, Yuhee; Kim, In Kyeom; Hong, Young Joon; Park, Hyung Wook; Ahn, Youngkeun; Cho, Jeong Gwan; Park, Jong Chun; Jeong, Myung Ho

2014-11-01

Vascular calcification is associated with increased risk of morbidity and mortality in patients with cardiovascular diseases, chronic kidney diseases, and diabetes. Gallic acid, a natural compound found in gallnut and green tea, is known to be antifungal, antioxidant, and anticancer. Here we investigated the effect of gallic acid on vascular smooth muscle cell (VSMC) calcification and the underlying mechanism. Gallic acid inhibited inorganic phosphate-induced osteoblast differentiation markers as well as calcification phenotypes (as determined by calcium deposition, Alizarin Red, and Von Kossa staining). Knockdown of BMP2 or Noggin blocked phosphate-induced calcification. Gallic acid suppressed phosphorylation of Smad1/5/8 protein induced by inorganic phosphate. Taken together, we suggest that gallic acid acts as a novel therapeutic agent of vascular calcification by mediating BMP2-Smad1/5/8 signaling pathway. Copyright © 2014 Elsevier Inc. All rights reserved.

[Vascular calcifications in subjects with and without chronic renal failure: types, sites and risk factors].

PubMed

Marinelli, Annibale; Di Napoli, Anteo

2017-04-01

Vascular calcifications worse outcomes in the general population and in patients on dialysis. We investigated 146 patients on chronic hemodialysis and 63 healthy controls with normal renal function under 65 years of age. All subjects underwent B-mode ultrasonography of common and internal carotid artery, abdominal aorta, common and superficial femoral artery and posterior tibial artery to assess the presence of intimal and medial calcifications. Intimal and media calcifications were present at the level of the carotid vessel, the abdominal aorta, the common femoral artery, the superficial femoral artery and the posterior tibial artery, respectively in 45%, 50%, 45%, 50%, 42% of patients on dialysis and in 5%, 15%, 24%, 5%, 2% of controls (p <0,01). On multivariate logistic analysis of regression, after adjustment for potential confounders, carotid intimal calcification, abdominal aortic calcification, medial calcification of the superficial femoral artery and posterior tibial artery calcification were associated with dialysis and with cardiovascular disease. Only intimal arterial calcification were associated with older age and smoking. Vascular calcifications are extremely common in middle-aged patients on chronic hemodialysis. Ultrasonography currently available in Nephrology, is a sensitive, reproducible, inexpensive imaging technique to identify arterial intimal and medial calcification in high-risk cardiovascular subjects. Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.

Quercetin Attenuates Vascular Calcification through Suppressed Oxidative Stress in Adenine-Induced Chronic Renal Failure Rats.

PubMed

Chang, Xue-Ying; Cui, Lei; Wang, Xing-Zhi; Zhang, Lei; Zhu, Dan; Zhou, Xiao-Rong; Hao, Li-Rong

2017-01-01

This study investigated whether quercetin could alleviate vascular calcification in experimental chronic renal failure rats induced by adenine. 32 adult male Wistar rats were randomly divided into 4 groups fed normal diet, normal diet with quercetin supplementation (25 mg/kg·BW/d), 0.75% adenine diet, or adenine diet with quercetin supplementation. All rats were sacrificed after 6 weeks of intervention. Serum renal functions biomarkers and oxidative stress biomarkers were measured and status of vascular calcification in aorta was assessed. Furthermore, the induced nitric oxide synthase (iNOS)/p38 mitogen activated protein kinase (p38MAPK) pathway was determined to explore the potential mechanism. Adenine successfully induced renal failure and vascular calcification in rat model. Quercetin supplementation reversed unfavorable changes of phosphorous, uric acid (UA) and creatinine levels, malonaldehyde (MDA) content, and superoxide dismutase (SOD) activity in serum and the increases of calcium and alkaline phosphatase (ALP) activity in the aorta ( P < 0.05) and attenuated calcification and calcium accumulation in the medial layer of vasculature in histopathology. Western blot analysis showed that iNOS/p38MAPK pathway was normalized by the quercetin supplementation. Quercetin exerted a protective effect on vascular calcification in adenine-induced chronic renal failure rats, possibly through the modulation of oxidative stress and iNOs/p38MAPK pathway.

Magnesium Counteracts Vascular Calcification: Passive Interference or Active Modulation?

PubMed

Ter Braake, Anique D; Shanahan, Catherine M; de Baaij, Jeroen H F

2017-08-01

Over the last decade, an increasing number of studies report a close relationship between serum magnesium concentration and cardiovascular disease risk in the general population. In end-stage renal disease, an association was found between serum magnesium and survival. Hypomagnesemia was identified as a strong predictor for cardiovascular disease in these patients. A substantial body of in vitro and in vivo studies has identified a protective role for magnesium in vascular calcification. However, the precise mechanisms and its contribution to cardiovascular protection remain unclear. There are currently 2 leading hypotheses: first, magnesium may bind phosphate and delay calcium phosphate crystal growth in the circulation, thereby passively interfering with calcium phosphate deposition in the vessel wall. Second, magnesium may regulate vascular smooth muscle cell transdifferentiation toward an osteogenic phenotype by active cellular modulation of factors associated with calcification. Here, the data supporting these major hypotheses are reviewed. The literature supports both a passive inorganic phosphate-buffering role reducing hydroxyapatite formation and an active cell-mediated role, directly targeting vascular smooth muscle transdifferentiation. However, current evidence relies on basic experimental designs that are often insufficient to delineate the underlying mechanisms. The field requires more advanced experimental design, including determination of intracellular magnesium concentrations and the identification of the molecular players that regulate magnesium concentrations in vascular smooth muscle cells. © 2017 American Heart Association, Inc.

MR imaging of iliofemoral peripheral vascular calcifications using proton density-weighted, in-phase three-dimensional stack-of-stars gradient echo.

PubMed

Ferreira Botelho, Marcos P; Koktzoglou, Ioannis; Collins, Jeremy D; Giri, Shivraman; Carr, James C; Gupta, NavYash; Edelman, Robert R

2017-06-01

The presence of vascular calcifications helps to determine percutaneous access for interventional vascular procedures and has prognostic value for future cardiovascular events. Unlike CT, standard MRI techniques are insensitive to vascular calcifications. In this prospective study, we tested a proton density-weighted, in-phase (PDIP) three-dimensional (3D) stack-of-stars gradient-echo pulse sequence with approximately 1 mm 3 isotropic spatial resolution at 1.5 Tesla (T) and 3T to detect iliofemoral peripheral vascular calcifications and correlated MR-determined lesion volumes with CT angiography (CTA). The study was approved by the Institutional Review Board. The prototype PDIP stack-of-stars pulse sequence was applied in 12 patients with iliofemoral peripheral vascular calcifications who had undergone CTA. Vascular calcifications were well visualized in all subjects, excluding segments near prostheses or stents. The location, size, and shape of the calcifications were similar to CTA. Quantitative analysis showed excellent correlation (r 2  = 0.84; P < 0.0001) between MR- and CT-based measures of calcification volume. In one subject in whom three pulse sequences were compared, PDIP stack-of-stars outperformed cartesian 3D gradient-echo and point-wise encoding time reduction with radial acquisition (PETRA). In this pilot study, a PDIP 3D stack-of-stars gradient-echo pulse sequence with high spatial resolution provided excellent image quality and accurately depicted the location and volume of iliofemoral vascular calcifications. Magn Reson Med 77:2146-2152, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Vascular smooth muscle cell calcification is mediated by regulated exosome secretion.

PubMed

Kapustin, Alexander N; Chatrou, Martijn L L; Drozdov, Ignat; Zheng, Ying; Davidson, Sean M; Soong, Daniel; Furmanik, Malgorzata; Sanchis, Pilar; De Rosales, Rafael Torres Martin; Alvarez-Hernandez, Daniel; Shroff, Rukshana; Yin, Xiaoke; Muller, Karin; Skepper, Jeremy N; Mayr, Manuel; Reutelingsperger, Chris P; Chester, Adrian; Bertazzo, Sergio; Schurgers, Leon J; Shanahan, Catherine M

2015-04-10

Matrix vesicles (MVs), secreted by vascular smooth muscle cells (VSMCs), form the first nidus for mineralization and fetuin-A, a potent circulating inhibitor of calcification, is specifically loaded into MVs. However, the processes of fetuin-A intracellular trafficking and MV biogenesis are poorly understood. The objective of this study is to investigate the regulation, and role, of MV biogenesis in VSMC calcification. Alexa488-labeled fetuin-A was internalized by human VSMCs, trafficked via the endosomal system, and exocytosed from multivesicular bodies via exosome release. VSMC-derived exosomes were enriched with the tetraspanins CD9, CD63, and CD81, and their release was regulated by sphingomyelin phosphodiesterase 3. Comparative proteomics showed that VSMC-derived exosomes were compositionally similar to exosomes from other cell sources but also shared components with osteoblast-derived MVs including calcium-binding and extracellular matrix proteins. Elevated extracellular calcium was found to induce sphingomyelin phosphodiesterase 3 expression and the secretion of calcifying exosomes from VSMCs in vitro, and chemical inhibition of sphingomyelin phosphodiesterase 3 prevented VSMC calcification. In vivo, multivesicular bodies containing exosomes were observed in vessels from chronic kidney disease patients on dialysis, and CD63 was found to colocalize with calcification. Importantly, factors such as tumor necrosis factor-α and platelet derived growth factor-BB were also found to increase exosome production, leading to increased calcification of VSMCs in response to calcifying conditions. This study identifies MVs as exosomes and shows that factors that can increase exosome release can promote vascular calcification in response to environmental calcium stress. Modulation of the exosome release pathway may be as a novel therapeutic target for prevention. © 2015 American Heart Association, Inc.

Effect of cross-linked chitosan iron (III) on vascular calcification in uremic rats.

PubMed

de Castro, Barbara Bruna Abreu; do Carmo, Wander Barros; de Albuquerque Suassuna, Paulo Giovani; Carminatti, Moises; Brito, Julia Bianchi; Dominguez, Wagner Vasques; de Oliveira, Ivone Braga; Jorgetti, Vanda; Custodio, Melani Ribeiro; Sanders-Pinheiro, Helady

2018-05-01

Cross-linked chitosan iron (III) is a chitin-derived polymer with a chelating effect on phosphorus, but it is untested in vascular calcification. We evaluated this compound's ability to reduce hyperphosphatemia and its effect on vascular calcification in uremic rats using an adenine-based, phosphorus-rich diet for seven weeks. We used a control group to characterize the uremia. Uremic rats were divided according the treatment into chronic kidney disease, CKD-Ch-Fe(III)CL (CKD-Ch), CKD-calcium carbonate, or CKD-sevelamer groups. We measured creatinine, phosphorus, calcium, alkaline phosphatase, phosphorus excretion fraction, parathyroid hormone, and fibroblast growth factor 23. Vascular calcification was assessed using the aortic calcium content, and a semi-quantitative analysis was performed using Von Kossa and hematoxylin-eosin staining. At week seven, rats in the chronic kidney disease group had higher creatinine, phosphorus, phosphorus excretion fraction, calcium, alkaline phosphatase, fibroblast growth factor 23, and aortic calcium content than those in the Control group. Treatments with cross-linked chitosan iron (III) and calcium carbonate prevented phosphorus increase (20%-30% reduction). The aortic calcium content was lowered by 88% and 85% in the CKD-Ch and CKD-sevelamer groups, respectively. The prevalence of vascular changes was higher in the chronic kidney disease and CKD-calcium carbonate (62.5%) groups than in the CKD-Ch group (37.5%). In conclusion, cross-linked chitosan iron (III) had a phosphorus chelating effect similar to calcium carbonate already available for clinical use, and prevented calcium accumulation in the aorta. Impact statement Vascular calcification (VC) is a common complication due to CKD-related bone and mineral disorder (BMD) and is characterized by deposition of calcium in vessels. Effective therapies are not yet available but new phosphorus chelators can prevent complications from CV. We tested the effect of chitosan, a new

Protective effects of estrogen against vascular calcification via estrogen receptor α-dependent growth arrest-specific gene 6 transactivation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nanao-Hamai, Michiko; Son, Bo-Kyung; Institute of Gerontology, The University of Tokyo, Tokyo

Vascular calcification is one of the major complications of cardiovascular disease and is an independent risk factor for myocardial infarction and cardiac death. Postmenopausal women have a higher prevalence of vascular calcification compared with premenopausal women, suggesting protective effects of estrogen (E2). However, the underlying mechanisms of its beneficial effects remain unclear. In the present study, we examined the inhibitory effects of E2 on vascular smooth muscle cell (VSMC) calcification, and found that growth arrest-specific gene 6 (Gas6), a crucial molecule in vascular calcification, is transactivated by estrogen receptor α (ERα) in response to E2. In human aortic smooth musclemore » cells, physiological levels of E2 inhibited inorganic phosphate (Pi)-induced calcification in a concentration-dependent manner. This inhibitory effect was significantly abolished by MPP, an ERα-selective antagonist, and ERα siRNA, but not by PHTPP, an ERβ-selective antagonist, and ERβ siRNA, implicating an ERα-dependent action. Apoptosis, an essential process for Pi-induced VSMC calcification, was inhibited by E2 in a concentration-dependent manner and further, MPP abolished this inhibition. Mechanistically, E2 restored the inhibited expression of Gas6 and phospho-Akt in Pi-induced apoptosis through ERα. Furthermore, E2 significantly activated Gas6 transcription, and MPP abrogated this E2-dependent Gas6 transactivation. E2-BSA failed to activate Gas6 transcription and to inhibit Ca deposition in VSMC, suggesting beneficial actions of genomic signaling by E2/nuclear ERα. Taken together, these results indicate that E2 exerts inhibitory effects on VSMC apoptosis and calcification through ERα-mediated Gas6 transactivation. These findings indicate a potential therapeutic strategy for the prevention of vascular calcification, especially in postmenopausal women. - Highlights: • E2 inhibits Pi-induced calcification in vascular smooth muscles cells. • E2

Association of conjunctival and corneal calcification with vascular calcification among hepatitis-C-seropositive hemodialysis patients.

PubMed

AbouSeif, Khaled; Sany, Dawlat; Elshahawy, Yasser; Seddik, Ayman; Rahman, Khedr; Gaber, Moustapha

2016-01-01

Disorders associated with the hepatitis C virus (HCV) have been reported including cardiovascular, metabolic, and central nervous system diseases. Since chronic HCV infections may be curable, their identification as causal contributors to cardiovascular risk could offer new perspectives in the prevention of cardiovascular disease. The aim of this study is to investigate the association between HCV and aortic arch calcification (AAC) and corneal and conjunctival calcification (CCC) in maintenance hemodialysis (MHD) patients; further, we assessed the correlation of CCC with vascular calcification. A total of 100 patients undergoing hemodialysis (HD) in our hospital were included in this study. Patients underwent a complete ocular examination including intraocular pressure, and CCC was looked for by slit lamp and fundoscopy. CCC was graded according to modified Porter and Crombie classification system described by Tokuyama et al. Helical computerized tomographic chest examination was used to evaluate the grading of AAC. Demographic, hematological, biochemical, and dialysis-related data were obtained. There was significant difference between seropositive (n = 51) and seronegative patients (n = 49) regarding grading of AAC and CCC (P <0.001). Significant positive correlation was found between grading of CCC, AAC, age (P <0.001), duration on HD (P <0.001), HCV-antibody positivity (P <0.001), serum calcium level (P <0.001), serum phosphorus level (P <0.001), calcium × phosphorus product (P <0.001), and i-parathormone level (P < 0.001). In addition, CCC grading positively correlated with AAC. Our results suggest that patients undergoing HD infected with the HCV have high degree of CCC, AAC, and mineral metabolism disorder. The strong correlation between CCC and AAC indicates that CCC evaluation is an easy, fast, non-invasive method, and might be used as an indirect indicator to detect vascular calcification in patients undergoing MHD.

Can Intestinal Phosphate Binding or Inhibition of Hydroxyapatite Growth in the Vascular Wall Halt the Progression of Established Aortic Calcification in Chronic Kidney Disease?

PubMed

Neven, Ellen; Opdebeeck, Britt; De Maré, Annelies; Bashir-Dar, Rida; Dams, Geert; Marynissen, Rita; Behets, Geert J; Verhulst, Anja; Riser, Bruce L; D'Haese, Patrick C

2016-11-01

Vascular calcification significantly contributes to mortality in chronic kidney disease (CKD) patients. Sevelamer and pyrophosphate (PPi) have proven to be effective in preventing vascular calcification, the former by controlling intestinal phosphate absorption, the latter by directly interfering with the hydroxyapatite crystal formation. Since most patients present with established vascular calcification, it is important to evaluate whether these compounds may also halt or reverse the progression of preexisting vascular calcification. CKD and vascular calcification were induced in male Wistar rats by a 0.75 % adenine low protein diet for 4 weeks. Treatment with PPi (30 or 120 µmol/kg/day), sevelamer carbonate (1500 mg/kg/day) or vehicle was started at the time point at which vascular calcification was present and continued for 3 weeks. Hyperphosphatemia and vascular calcification developed prior to treatment. A significant progression of aortic calcification in vehicle-treated rats with CKD was observed over the final 3-week period. Sevelamer treatment significantly reduced further progression of aortic calcification as compared to the vehicle control. No such an effect was seen for either PPi dose. Sevelamer but not PPi treatment resulted in an increase in both osteoblast and osteoid perimeter. Our study shows that sevelamer was able to reduce the progression of moderate to severe preexisting aortic calcification in a CKD rat model. Higher doses of PPi may be required to induce a similar reduction of severe established arterial calcification in this CKD model.

Exogenous BMP7 in aortae of rats with chronic uremia ameliorates expression of profibrotic genes, but does not reverse established vascular calcification

PubMed Central

Gravesen, Eva; Lerche Mace, Maria; Nordholm, Anders; Hofman-Bang, Jacob; Hruska, Keith; Haagen Nielsen, Carsten; Kjær, Andreas; Olgaard, Klaus

2018-01-01

Hyperphosphatemia and vascular calcification are frequent complications of chronic renal failure and bone morphogenetic protein 7 (BMP7) has been shown to protect against development of vascular calcification in uremia. The present investigation examined the potential reversibility of established uremic vascular calcification by treatment of uremic rats with BMP7. A control model of isogenic transplantation of a calcified aorta from uremic rats into healthy littermates examined whether normalization of the uremic environment reversed vascular calcification. Uremia and vascular calcification were induced in rats by 5/6 nephrectomy, high phosphate diet and alfacalcidol treatment. After 14 weeks severe vascular calcification was present and rats were allocated to BMP7, vehicle or aorta transplantation. BMP7 treatment caused a significant decrease of plasma phosphate to 1.56 ± 0.17 mmol/L vs 2.06 ± 0.34 mmol/L in the vehicle group even in the setting of uremia and high phosphate diet. Uremia and alfacalcidol resulted in an increase in aortic expression of genes related to fibrosis, osteogenic transformation and extracellular matrix calcification, and the BMP7 treatment resulted in a decrease in the expression of profibrotic genes. The total Ca-content of the aorta was however unchanged both in the abdominal aorta: 1.9 ± 0.6 μg/mg tissue in the vehicle group vs 2.2 ± 0.6 μg/mg tissue in the BMP7 group and in the thoracic aorta: 71 ± 27 μg/mg tissue in the vehicle group vs 54 ± 18 μg/mg tissue in the BMP7 group. Likewise, normalization of the uremic environment by aorta transplantation had no effect on the Ca-content of the calcified aorta: 16.3 ± 0.6 μg/mg tissue pre-transplantation vs 15.9 ± 2.3 μg/mg tissue post-transplantation. Aortic expression of genes directly linked to extracellular matrix calcification was not affected by BMP7 treatment, which hypothetically might explain persistent high Ca-content in established vascular calcification. The present

Step down Vascular Calcification Analysis using State-of-the-Art Nanoanalysis Techniques

PubMed Central

Curtze, Sven C.; Kratz, Marita; Steinert, Marian; Vogt, Sebastian

2016-01-01

New insights into the architecture and formation mechanisms of calcific lesions down to the nanoscale open a better understanding of atherosclerosis and its pathogenesis. Scanning electron – and atomic force microscope based nano-analytical characterization techniques were adapted to the assessment of an ex-vivo calcified coronary artery. Human atherosclerotic tissue and bone tissue reside a typical chemistry of Magnesium and Sodium rich Calcium phosphates, identified as whitlockite and Calcium apatite, respectively. Despite the obvious similarities in both chemistry and crystallography, there are also clear differences between calcified vascular tissue and bone such as the highly oriented growth in bone, revealing meso-crystal character, as opposed to the anisotropic character of calcified vascular lesions. While the grain size in vascular calcified plaques is in the range of nanometers, the grain size in bone appears larger. Spherical calcific particles present in both the coronary artery wall and embedded in plaques reveal concentric layers with variations in both organic content and degree of hydration. PMID:26980376

Step down Vascular Calcification Analysis using State-of-the-Art Nanoanalysis Techniques.

PubMed

Curtze, Sven C; Kratz, Marita; Steinert, Marian; Vogt, Sebastian

2016-03-16

New insights into the architecture and formation mechanisms of calcific lesions down to the nanoscale open a better understanding of atherosclerosis and its pathogenesis. Scanning electron - and atomic force microscope based nano-analytical characterization techniques were adapted to the assessment of an ex-vivo calcified coronary artery. Human atherosclerotic tissue and bone tissue reside a typical chemistry of Magnesium and Sodium rich Calcium phosphates, identified as whitlockite and Calcium apatite, respectively. Despite the obvious similarities in both chemistry and crystallography, there are also clear differences between calcified vascular tissue and bone such as the highly oriented growth in bone, revealing meso-crystal character, as opposed to the anisotropic character of calcified vascular lesions. While the grain size in vascular calcified plaques is in the range of nanometers, the grain size in bone appears larger. Spherical calcific particles present in both the coronary artery wall and embedded in plaques reveal concentric layers with variations in both organic content and degree of hydration.

Calcitriol accelerates vascular calcification irrespective of vitamin K status in a rat model of CKD with hyperphosphatemia and secondary hyperparathyroidism.

PubMed

McCabe, Kristin M; Zelt, Jason G; Kaufmann, Martin; Laverty, Kimberly; Ward, Emilie; Barron, Henry; Jones, Glenville; Adams, Michael A; Holden, Rachel M

2018-06-14

Patients with chronic kidney disease have a markedly increased risk for developing cardiovascular disease. Non-traditional risk factors, such as increased phosphate retention, and deficiencies in vitamins D and K metabolism, likely play key roles in the development of vascular calcification during CKD progression. Calcitriol (1,25-(OH)2-D3) is a key transcriptional regulator of Matrix Gla protein (MGP), a vitamin K dependent protein that inhibits vascular calcification. The objective of this study was to determine if calcitriol treatment could inhibit the development of vascular calcification and if this inhibition was dependent on vitamin K status in a rat model of CKD. Rats were treated with dietary adenine (0.25%) to induce CKD, with either 0, 20 or 80 ng/kg of calcitriol with low or high dietary vitamin K1 (0.2 or 100 mg/kg) for 7 weeks. Calcitriol at both low (20 ng/kg) and moderate (80 ng/kg) doses increased the severity of vascular calcification and, contrary to our hypothesis, this was unaffected by high dietary vitamin K1. Calcitriol had a dose-dependent effect on: (i) lowering serum PTH, (ii) increasing serum calcium and (iii) increasing serum FGF-23. Calcitriol treatment significantly increased aortic expression of the calcification genes Runx2 and Pit-1. This data also implicates impaired vitamin D catabolism in CKD, which may contribute to the development of calcitriol toxicity and increased vascular calcification. The present findings demonstrate that in an adenine-induced rat model of CKD, calcitriol treatment at doses as low as 20 ng/kg can increase the severity of vascular calcification regardless of vitamin K status. The American Society for Pharmacology and Experimental Therapeutics.

Skin autofluorescence associates with vascular calcification in chronic kidney disease.

PubMed

Wang, Angela Yee-Moon; Wong, Chun-Kwok; Yau, Yat-Yin; Wong, Sharon; Chan, Iris Hiu-Shuen; Lam, Christopher Wai-Kei

2014-08-01

This study aims to evaluate the relationship between tissue advanced glycation end products, as reflected by skin autofluorescence, and vascular calcification in chronic kidney disease. Three hundred patients with stage 3 to 5 chronic kidney disease underwent multislice computed tomography to estimate total coronary artery calcium score (CACS) and had tissue advanced glycation end product assessed using a skin autofluorescence reader. Intact parathyroid hormone (P<0.001) displaced estimated glomerular filtration rate as third most significant factor associated with skin autofluorescence after age (P<0.001) and diabetes mellitus (P<0.001) in multiple regression analysis. On univariate multinomial logistic regression analysis, every 1-U increase in skin autofluorescence was associated with a 7.43-fold (95% confidence intervals, 3.59-15.37; P<0.001) increased odds of having CACS ≥400 compared with those with zero CACS. Skin autofluorescence retained significance in predicting CACS ≥400 (odds ratio, 3.63; 95% confidence intervals, 1.44-9.18; P=0.006) when adjusting for age, sex, serum calcium, phosphate, albumin, C-reactive protein, lipids, blood pressure, estimated glomerular filtration rate, and intact parathyroid hormone but marginally lost significance when additionally adjusting for diabetes mellitus (odds ratio, 2.23; 95% confidence intervals, 0.81-6.14; P=0.1). Combination of diabetes mellitus and higher intact parathyroid hormone was associated with greater skin autofluorescence and CACS versus those without diabetes mellitus and having lower intact parathyroid hormone. Tissue advanced glycation end product, as reflected by skin autofluorescence, showed a significant novel association with vascular calcification in chronic kidney disease. These data suggest that increased tissue advanced glycation end product may contribute to vascular calcification in chronic kidney disease and diabetes mellitus and warrant further experimental investigation. © 2014

ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis

ClinicalTrials.gov

2014-07-14

Chronic Kidney Disease; End Stage Renal Disease; Coronary Artery Calcification; Vascular Calcification; Calcification; Cardiovascular Disease; Chronic Renal Failure; Hyperparathyroidism; Kidney Disease; Nephrology; Secondary Hyperparathyroidism

Sodium thiosulfate protects brain in rat model of adenine induced vascular calcification.

PubMed

Subhash, N; Sriram, R; Kurian, Gino A

2015-11-01

Vascular bed calcification is a common feature of ends stage renal disease that may lead to a complication in cardiovascular and cerebrovascular beds, which is a promoting cause of myocardial infarction, stroke, dementia and aneurysms. Sodium thiosulfate (STS) due to its multiple properties such as antioxidant and calcium chelation has been reported to prevent vascular calcification in uremic rats, without mentioning its impact on cerebral function. Moreover, the previous studies have not explored the effect of STS on the mitochondrial dysfunction, one of the main pathophysiological features associated with the disease and the main site for STS metabolism. The present study addresses this limitation by using a rat model where 0.75% adenine was administered to induce vascular calcification and 400 mg/kg b wt. of STS was given as preventive and curative agent. The blood and urine chemistries along with histopathology of aorta confirms the renal protective effect of STS in two modes of administration. The brain oxidative stress assessment was made through TBARS level, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, found to be in the near normal level. STS administration not only reduced the mitochondrial oxidative stress (measured by TBARS, SOD, GPx and CAT) but also preserved the mitochondrial respiratory enzyme activities (NADH dehydrogenase, Succinate dehydrogenase and Malate dehydrogenase) and its physiology (measured by P/O ratio and RCR). In fact, the protective effect of STS was prominent, when it was administered as a curative agent, where low H2S and high thiosulfate level was observed along with low cystathionine β synthase activity, confirms thiosulfate mediated renal protection. In conclusion, STS when given after induction of calcification is protective to the brain by preserving its mitochondria, compared to the treatment given concomitantly. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ghrelin improves vascular autophagy in rats with vascular calcification.

PubMed

Xu, Mingming; Liu, Lin; Song, Chenfang; Chen, Wei; Gui, Shuyan

2017-06-15

This study aimed to investigate whether ghrelin ameliorated vascular calcification (VC) through improving autophagy. VC model was induced by nicotine plus vitamin D 3 in rats and β-glycerophosphate in vascular smooth muscle cell (VSMC). Calcium deposition was detected by von Kossa staining or alizarin red S staining. ALP activity was also detected. Western blot was used to assess the protein expression. Ghrelin treatment attenuated the elevation of calcium deposition and ALP activity in VC model both in vivo and in vitro. Interesting, the protein levels of autophagy markers, LC3 and beclin1 were significantly upregulated by ghrelin in VC model. An autophagy inhibitor, 3-methyladenine blocks the ameliorative effect of ghrelin on VC. Furthermore, protein expressions of phosphate-AMPK were increased by ghrelin treatment both in calcified aorta and VSMC. The effect of ghrelin on autophagy induction and VC attenuation was prevented by AMPK inhibitor, compound C. Our results suggested that ghrelin improved autophagy through AMPK activation, which was resulted in VC amelioration. These data maybe throw light on prevention and therapy of VC. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of water fluoridation on the development of medial vascular calcification in uremic rats.

PubMed

Martín-Pardillos, Ana; Sosa, Cecilia; Millán, Ángel; Sorribas, Víctor

2014-04-06

Public water fluoridation is a common policy for improving dental health. Fluoride replaces the hydroxyls of hydroxyapatite, thereby improving the strength of tooth enamel, but this process can also occur in other active calcifications. This paper studies the effects of water fluoridation during the course of vascular calcification in renal disease. The effect of fluoride was studied in vitro and in vivo. Rat aortic smooth muscle cells were calcified with 2mM Pi for 5 days. Fluoride concentrations of 5-10 μM--similar to those found in people who drink fluoridated water--partially prevented calcification, death, and osteogene expression in vitro. The anticalcifying mechanism was independent of cell activity, matrix Gla protein, and fetuin A expressions, and it exhibited an IC50 of 8.7 μM fluoride. In vivo, however, fluoridation of drinking water at 1.5mg/L (concentration recommended by the WHO) and 15 mg/L dramatically increased the incipient aortic calcification observed in rats with experimental chronic kidney disease (CKD, 5/6-nephrectomy), fed a Pi-rich fodder (1.2% Pi). Fluoride further declined the remaining renal function of the CKD animals, an effect that most likely overwhelmed the positive effect of fluoride on calcification in vitro. Ultrastructural analysis revealed that fluoride did not modify the Ca/P atomic ratio, but it was incorporated into the lattice of in vivo deposits. Fluoride also converted the crystallization pattern from plate to rode-like structures. In conclusion, while fluoride prevents calcification in vitro, the WHO's recommended concentrations in drinking water become nephrotoxic to CKD rats, thereby aggravating renal disease and making media vascular calcification significant. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Pathology of Human Coronary and Carotid Artery Atherosclerosis and Vascular Calcification in Diabetes Mellitus.

PubMed

Yahagi, Kazuyuki; Kolodgie, Frank D; Lutter, Christoph; Mori, Hiroyoshi; Romero, Maria E; Finn, Aloke V; Virmani, Renu

2017-02-01

The continuing increase in the prevalence of diabetes mellitus in the general population is predicted to result in a higher incidence of cardiovascular disease. Although the mechanisms of diabetes mellitus-associated progression of atherosclerosis are not fully understood, at clinical and pathological levels, there is an appreciation of increased disease burden and higher levels of arterial calcification in these subjects. Plaques within the coronary arteries of patients with diabetes mellitus generally exhibit larger necrotic cores and significantly greater inflammation consisting mainly of macrophages and T lymphocytes relative to patients without diabetes mellitus. Moreover, there is a higher incidence of healed plaque ruptures and positive remodeling in hearts from subjects with type 1 diabetes mellitus and type 2 diabetes mellitus, suggesting a more active atherogenic process. Lesion calcification in the coronary, carotid, and other arterial beds is also more extensive. Although the role of coronary artery calcification in identifying cardiovascular disease and predicting its outcome is undeniable, our understanding of how key hormonal and physiological alterations associated with diabetes mellitus such as insulin resistance and hyperglycemia influence the process of vascular calcification continues to grow. Important drivers of atherosclerotic calcification in diabetes mellitus include oxidative stress, endothelial dysfunction, alterations in mineral metabolism, increased inflammatory cytokine production, and release of osteoprogenitor cells from the marrow into the circulation. Our review will focus on the pathophysiology of type 1 diabetes mellitus- and type 2 diabetes mellitus-associated vascular disease with particular focus on coronary and carotid atherosclerotic calcification. © 2016 American Heart Association, Inc.

Severe vascular calcification and tumoral calcinosis in a family with hyperphosphatemia: a fibroblast growth factor 23 mutation identified by exome sequencing

PubMed Central

Shah, Anuja; Miller, Clinton J.; Nast, Cynthia C.; Adams, Mark D.; Truitt, Barbara; Tayek, John A.; Tong, Lili; Mehtani, Parag; Monteon, Francisco; Sedor, John R.; Clinkenbeard, Erica L.; White, Kenneth; Mehrotra, Rajnish; LaPage, Janine; Dickson, Patricia; Adler, Sharon G.; Iyengar, Sudha K.

2014-01-01

Background Tumoral calcinosis is an autosomal recessive disorder characterized by ectopic calcification and hyperphosphatemia. Methods We describe a family with tumoral calcinosis requiring amputations. The predominant metabolic anomaly identified in three affected family members was hyperphosphatemia. Biochemical and phenotypic analysis of 13 kindred members, together with exome analysis of 6 members, was performed. Results We identified a novel Q67K mutation in fibroblast growth factor 23 (FGF23), segregating with a null (deletion) allele on the other FGF23 homologue in three affected members. Affected siblings had high circulating plasma C-terminal FGF23 levels, but undetectable intact FGF23 or N-terminal FGF23, leading to loss of FGF23 function. Conclusions This suggests that in human, as in experimental models, severe prolonged hyperphosphatemia may be sufficient to produce bone differentiation proteins in vascular cells, and vascular calcification severe enough to require amputation. Genetic modifiers may contribute to the phenotypic variation within and between families. PMID:25378588

Interleukin-18 Enhances Vascular Calcification and Osteogenic Differentiation of Vascular Smooth Muscle Cells Through TRPM7 Activation.

PubMed

Zhang, Kun; Zhang, Yinyin; Feng, Weijing; Chen, Renhua; Chen, Jie; Touyz, Rhian M; Wang, Jingfeng; Huang, Hui

2017-10-01

Vascular calcification (VC) is an important predictor of cardiovascular morbidity and mortality. Osteogenic differentiation of vascular smooth muscle cells (VSMCs) is a key mechanism of VC. Recent studies show that IL-18 (interleukin-18) favors VC while TRPM7 (transient receptor potential melastatin 7) channel upregulation inhibits VC. However, the relationship between IL-18 and TRPM7 is unclear. We questioned whether IL-18 enhances VC and osteogenic differentiation of VSMCs through TRPM7 channel activation. Coronary artery calcification and serum IL-18 were measured in patients by computed tomographic scanning and enzyme-linked immunosorbent assay, respectively. Primary rat VSMCs calcification were induced by high inorganic phosphate and exposed to IL-18. VSMCs were also treated with TRPM7 antagonist 2-aminoethoxy-diphenylborate or TRPM7 small interfering RNA to block TRPM7 channel activity and expression. TRPM7 currents were recorded by patch-clamp. Human studies showed that serum IL-18 levels were positively associated with coronary artery calcium scores ( r =0.91; P <0.001). In VSMCs, IL-18 significantly decreased expression of contractile markers α-smooth muscle actin, smooth muscle 22 α, and increased calcium deposition, alkaline phosphatase activity, and expression of osteogenic differentiation markers bone morphogenetic protein-2, Runx2 (runt-related transcription factor 2), and osteocalcin ( P <0.05). IL-18 increased TRPM7 expression through ERK1/2 (extracellular signal-regulated kinase 1/2) signaling activation, and TRPM7 currents were augmented by IL-18 treatment. Inhibition of TRPM7 channel by 2-aminoethoxy-diphenylborate or TRPM7 small interfering RNA prevented IL-18-enhanced osteogenic differentiation and VSMCs calcification. These findings suggest that coronary artery calcification is associated with increased IL-18 levels. IL-18 enhances VSMCs osteogenic differentiation and subsequent VC induced by β-glycerophosphate via TRPM7 channel activation

Mismatch between stiffness in elastic and muscular arteries as a predictor of vascular calcification in dialysis patients.

PubMed

Laucyte-Cibulskiene, Agne; Petraviciute, Modesta; Gudynaite, Migle; Gumbys, Liutauras; Valanciene, Dileta; Galiauskiene, Kristina; Ryliskyte, Ligita; Rimsevicius, Laurynas; Miglinas, Marius; Strupas, Kestutis

2018-04-01

Vascular calcification is one of the risk factors for arterial stiffness in patients with chronic kidney disease. We hypothesized that a mismatch between elastic and muscular arteries, represented as pulse wave velocity (PWV) ratio, could depict the extent of vascular calcification in end-stage renal disease. We also aimed to compare the predictive PWV ratio value to other factors possibly related to vascular calcification in dialysis population. In this cross-sectional study, in 60 chronic dialysis patients without previous cerebrovascular events, cardiovascular disease and events or clinically evident peripheral artery disease (ankle-brachial index >0.9), carotid-femoral and carotid-radial PWV as well as central hemodynamic parameters were measured by applanation tonometry (SphygmoCor). The PWV ratio using carotid-femoral PWV divided by carotid-radial PWV was calculated. Each patient underwent blood tests and chest X-ray for aortic arch calcification scoring. Two experienced radiologists blinded to patient's medical data evaluated chest X-rays (Cohen's kappa coefficient 0.76) and calculated how many sectors were calcified (Ogawa et al. in Hemodial Int 13:301-306, 2009). Differently scored chest X-rays were repeatedly reviewed and a consensus was reached. The study population consisted of 31 (51.7%) males and 29 (48.3%) females, mean age 52.73 ± 13.76 years. Increased risk for aortic arch calcification was associated with higher PWV ratio even after adjustment for age, height, heart rate, ferritin level and C-reactive protein level (OR 2.59E+04, 95% CI 2.43E+01, 2.65E+09, p = 0.021). PWV ratio together with above-mentioned variables could predict the presence of aortic arch calcification with specificity of 93% (95% CI 78, 99%) and sensitivity of 53% (95% CI 34, 72%). The elastic and muscular arteries' stiffness mismatch was strongly associated with the extent of aortic arch calcification in this dialysis population and had better calcification

Sodium-dependent phosphate cotransporters and phosphate-induced calcification of vascular smooth muscle cells: Redundant roles for PiT-1 and PiT-2

PubMed Central

Crouthamel, Matthew H.; Lau, Wei Ling; Leaf, Elizabeth M.; Chavkin, Nick; Wallingford, Mary C.; Peterson, Danielle F.; Li, Xianwu; Liu, Yonggang; Chin, Michael T.; Levi, Moshe; Giachelli, Cecilia M.

2014-01-01

Objective Elevated serum phosphate has emerged as a major risk factor for vascular calcification. The sodium-dependent phosphate cotransporter, PiT-1, was previously shown to be required for phosphate-induced osteogenic differentiation and calcification of cultured human VSMCs, but its importance in vascular calcification in vivo, as well as the potential role of its homologue, PiT-2, have not been determined. We investigated the in vivo requirement for PiT-1 in vascular calcification using a mouse model of chronic kidney disease, and the potential compensatory role of PiT-2 using in vitro knockdown and over-expression strategies. Approach and Results Mice with targeted deletion of PiT-1 in VSMCs were generated (PiT-1Δsm). PiT-1 mRNA levels were undetectable whereas PiT-2 mRNA levels were increased 2 fold in the vascular aortic media of PiT-1Δsm compared to PiT-1flox/flox control. When arterial medial calcification was induced in PiT-1Δsm and PiT-1flox/flox by chronic kidney disease followed by dietary phosphate loading, the degree of aortic calcification was not different between genotypes, suggesting compensation by PiT-2. Consistent with this possibility, VSMCs isolated from PiT-1Δsm mice had no PiT-1 mRNA expression, increased PiT-2 mRNA levels, and no difference in sodium-dependent phosphate uptake or phosphate-induced matrix calcification compared to PiT-1flox/flox VSMCs. Knockdown of PiT-2 decreased phosphate uptake and phosphate-induced calcification of PiT-1Δsm VSMCs. Furthermore, over-expression of PiT-2 restored these parameters in human PiT-1-deficient VSMCs. Conclusions PiT-2 can mediate phosphate uptake and calcification of VSMCs in the absence of PiT-1. Mechanistically, PiT-1 and PiT-2 appear to serve redundant roles in phosphate-induced calcification of vascular smooth muscle cells. PMID:23968976

Defective interplay between mTORC1 activity and endoplasmic reticulum stress-unfolded protein response in uremic vascular calcification.

PubMed

Panda, Dibyendu K; Bai, Xiuying; Sabbagh, Yves; Zhang, Yan; Zaun, Hans-Christian; Karellis, Angeliki; Koromilas, Antonis E; Lipman, Mark L; Karaplis, Andrew C

2018-06-01

Vascular calcification increases the risk of cardiovascular disease and death in patients with chronic kidney disease (CKD). Increased activity of mammalian target of rapamycin complex 1 (mTORC1) and endoplasmic reticulum (ER) stress-unfolded protein response (UPR) are independently reported to partake in the pathogenesis of vascular calcification in CKD. However, the association between mTORC1 activity and ER stress-UPR remains unknown. We report here that components of the uremic state [activation of the receptor for advanced glycation end products (RAGE) and hyperphosphatemia] potentiate vascular smooth muscle cell (VSMC) calcification by inducing persistent and exaggerated activity of mTORC1. This gives rise to prolonged and excessive ER stress-UPR as well as attenuated levels of sestrin 1 ( Sesn1) and Sesn3 feeding back to inhibit mTORC1 activity. Activating transcription factor 4 arising from the UPR mediates cell death via expression of CCAAT/enhancer-binding protein (c/EBP) homologous protein (CHOP), impairs the generation of pyrophosphate, a potent inhibitor of mineralization, and potentiates VSMC transdifferentiation to the osteochondrocytic phenotype. Short-term treatment of CKD mice with rapamycin, an inhibitor of mTORC1, or tauroursodeoxycholic acid, a bile acid that restores ER homeostasis, normalized mTORC1 activity, molecular markers of UPR, and calcium content of aortas. Collectively, these data highlight that increased and/or protracted mTORC1 activity arising from the uremic state leads to dysregulated ER stress-UPR and VSMC calcification. Manipulation of the mTORC1-ER stress-UPR pathway opens up new therapeutic strategies for the prevention and treatment of vascular calcification in CKD.

Vitamin K2 inhibits rat vascular smooth muscle cell calcification by restoring the Gas6/Axl/Akt anti-apoptotic pathway.

PubMed

Qiu, Cuiting; Zheng, Haijun; Tao, Huiren; Yu, Wenjun; Jiang, Xiaoyu; Li, Aiqin; Jin, Hui; Lv, Anlin; Li, Huan

2017-09-01

Vascular calcification is associated with cardiovascular disease as a complication of hypertension, hyperlipidemia, diabetes mellitus, and chronic kidney disease. Vitamin K2 (VK2) delays vascular calcification by an unclear mechanism. Moreover, apoptosis modulates vascular smooth muscle cell (VSMC) calcification. This paper aimed to study VK2-modified VSMC calcification and survival cell signaling mediated by growth arrest-specific gene 6 (Gas6) and its tyrosine kinase receptor Axl. Primary-cultured VSMCs were dose-dependently treated with VK2 in the presence of calcification medium for 8 days, or pre-treated for 1 h with/without the Axl inhibitor R428 (2 μmol/L) or the caspase inhibitor Z-VAD-fmk (20 μmol/L) followed by treatment with VK2 (10 μmol/L) or rmGas6 (200 nmol/L) in calcification medium for 8 days. Calcium deposition was determined by the o-cresolphthalein complexone assay and Alizarin Red S staining. Apoptosis was determined by TUNEL and flow cytometry using Annexin V-FITC and propidium iodide staining. Western blotting detected the expressions of Axl, Gas6, p-Akt, Akt, and Bcl2. VK2 significantly inhibited CaCl 2 - and β-sodium glycerophosphate (β-GP)-induced VSMC calcification and apoptosis, which was dependent on restored Gas6 expression and activated downstream signaling by Axl, p-Akt, and Bcl2. Z-VAD-fmk significantly inhibited CaCl 2 - and β-GP-induced VSMC calcification and apoptosis. Augmented recombinant mouse Gas6 protein (rmGas6) expression significantly reduced VSMC calcification and apoptosis. Furthermore, the Gas6/Axl interaction was inhibited by R428, which abolished the preventive effect of VK2 on CaCl 2 - and β-GP-induced apoptosis and calcification. These results suggest that Gas6 is critical in VK2-mediated functions that attenuate CaCl 2 - and β-GP-induced VSMC calcification by blocking apoptosis.

Losartan Inhibits Vascular Calcification by Suppressing the BMP2 and Runx2 Expression in Rats In Vivo.

PubMed

Li, Mincai; Wu, Panfeng; Shao, Juan; Ke, Zhiqiang; Li, Dan; Wu, Jiliang

2016-04-01

The blockade of renin-angiotensin II system has been shown to reduce morbidity and mortality in hypertension, atherosclerosis, diabetes and chronic kidney disease. Since vascular calcification (VC) is commonly found in these diseases, the aim of this study was to examine whether or not losartan, a widely used angiotensin II receptor blockers, inhibits VC in rats in vivo. A rat model of VC was generated by treating rats with a combination of warfarin and vitamin K1. Two weeks after the treatments, the rats were treated with vehicle or without losartan (100 ng/kg/day) for 2 weeks. At the end of the experiments, aortic arteries were isolated for the examination of calcification morphology, mRNA and protein expression of BMP2 and Runx2, and osteoblast differentiation. Warfarin and vitamin K instigated vascular remodeling with calcified plaques in the aortic arteries in rats. Losartan significantly attenuated warfarin- and vitamin K-induced vascular injury and calcification. Consistently, losartan suppressed the levels of mRNA and protein expression of BMP2 and Runx2, two key factors for VC. Further, vascular calcified lesion areas expressed angiotensin II 1 receptor (AT1R). Finally, losartan treatment significantly inhibited apoptosis in vascular smooth muscle cell (VSMC) in rat arteries. We conclude that losartan suppresses VC by lowering the expression of AT1R, Runx2 and BMP2, and by inhibiting the apoptosis of VSMC in rat aortic arteries.

Measurement of vascular calcification using CT fistulograms.

PubMed

Toussaint, Nigel D; Lau, Ken K; Polkinghorne, Kevan R; Kerr, Peter G

2007-02-01

Vascular calcification (VC), precipitated by calcium and phosphate imbalance, is a major contributor to cardiovascular disease (CVD) in chronic kidney disease (CKD). Electron-beam computed tomography (EBCT) quantitatively assesses coronary artery calcification (CAC), with VC scores predictive of atherosclerosis and cardiac events in the general and CKD population. EBCT is not readily available but spiral CT can also provide quantitative assessment of the extent of VC. CT fistulograms can be used as initial investigation for arterio-venous fistula (AVF) problems in haemodialysis (HD). The images obtained include thoracic aorta, brachio-cephalic, subclavian and common carotid arteries which allow assessment of the extent of VC in these vessels. No study to date has combined the CT fistulogram with concurrent determination of VC. We hypothesize that a single investigation for AVF management may also provide information on VC. We retrospectively analysed CT fistulograms on 28 HD patients determining VC scores (in Hounsfield units) in AVF, subclavian and carotid arteries and aorta. We correlated these scores with patient demographics, serum markers of mineral metabolism (time averaged for the period 6 months prior to CT) and calcium-based phosphate binders. Patients (60.7% male) had a median age of 59 years and 46.4% were diabetic. The mean duration of dialysis was 17.5 months. CT fistulograms showed predominantly aortic (75% of patients) and subclavian (75%) calcifications, with only 21.4% having carotid VC and minimal VC at the level of AVF. Median VC scores were 619.8 (0-1481.4) for aorta and 521.7 (0-1139.6) for subclavian (scores of >400 indicate severe atherosclerotic disease), but there was no significant correlation with serum markers or duration of HD. Increasing age correlated significantly with greater VC in aortic (R = 0.53, P = 0.003) and subclavian (R = 0.40, P = 0.03) vessels, as well as with the number of VC sites involved. CAC was present in most

A magnesium based phosphate binder reduces vascular calcification without affecting bone in chronic renal failure rats.

PubMed

Neven, Ellen; De Schutter, Tineke M; Dams, Geert; Gundlach, Kristina; Steppan, Sonja; Büchel, Janine; Passlick-Deetjen, Jutta; D'Haese, Patrick C; Behets, Geert J

2014-01-01

The alternative phosphate binder calcium acetate/magnesium carbonate (CaMg) effectively reduces hyperphosphatemia, the most important inducer of vascular calcification, in chronic renal failure (CRF). In this study, the effect of low dose CaMg on vascular calcification and possible effects of CaMg on bone turnover, a persistent clinical controversy, were evaluated in chronic renal failure rats. Adenine-induced CRF rats were treated daily with 185 mg/kg CaMg or vehicle for 5 weeks. The aortic calcium content and area% calcification were measured to evaluate the effect of CaMg. To study the effect of CaMg on bone remodeling, rats underwent 5/6th nephrectomy combined with either a normal phosphorus diet or a high phosphorus diet to differentiate between possible bone effects resulting from either CaMg-induced phosphate deficiency or a direct effect of Mg. Vehicle or CaMg was administered at doses of 185 and 375 mg/kg/day for 8 weeks. Bone histomorphometry was performed. Aortic calcium content was significantly reduced by 185 mg/kg/day CaMg. CaMg ameliorated features of hyperparathyroid bone disease. In CRF rats on a normal phosphorus diet, the highest CaMg dose caused an increase in osteoid area due to phosphate depletion. The high phosphorus diet combined with the highest CaMg dose prevented the phosphate depletion and thus the rise in osteoid area. CaMg had no effect on osteoblast/osteoclast or dynamic bone parameters, and did not alter bone Mg levels. CaMg at doses that reduce vascular calcification did not show any harmful effect on bone turnover.

Systemic vascular load in calcific degenerative aortic valve stenosis: insight from percutaneous valve replacement.

PubMed

Yotti, Raquel; Bermejo, Javier; Gutiérrez-Ibañes, Enrique; Pérez del Villar, Candelas; Mombiela, Teresa; Elízaga, Jaime; Benito, Yolanda; González-Mansilla, Ana; Barrio, Alicia; Rodríguez-Pérez, Daniel; Martínez-Legazpi, Pablo; Fernández-Avilés, Francisco

2015-02-10

Systemic arterial load impacts the symptomatic status and outcome of patients with calcific degenerative aortic stenosis (AS). However, assessing vascular properties is challenging because the arterial tree's behavior could be influenced by the valvular obstruction. This study sought to characterize the interaction between valvular and vascular functions in patients with AS by using transcatheter aortic valve replacement (TAVR) as a clinical model of isolated intervention. Aortic pressure and flow were measured simultaneously using high-fidelity sensors in 23 patients (mean 79 ± 7 years of age) before and after TAVR. Blood pressure and clinical response were registered at 6-month follow-up. Systolic and pulse arterial pressures, as well as indices of vascular function (vascular resistance, aortic input impedance, compliance, and arterial elastance), were significantly modified by TAVR, exhibiting stiffer vascular behavior post-intervention (all, p < 0.05). Peak left ventricular pressure decreased after TAVR (186 ± 36 mm Hg vs. 162 ± 23 mm Hg, respectively; p = 0.003) but remained at >140 mm Hg in 70% of patients. Wave intensity analysis showed abnormally low forward and backward compression waves at baseline, increasing significantly after TAVR. Stroke volume decreased (-21 ± 19%; p < 0.001) and correlated with continuous and pulsatile indices of arterial load. In the 48 h following TAVR, a hypertensive response was observed in 12 patients (52%), and after 6-month follow-up, 5 patients required further intensification of discharge antihypertensive therapy. Vascular function in calcific degenerative AS is conditioned by the upstream valvular obstruction that dampens forward and backward compression waves in the arterial tree. An increase in vascular load after TAVR limits the procedure's acute afterload relief. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Reversal of Vascular Calcification and Aneurysms in a Rat Model Using Dual Targeted Therapy with EDTA- and PGG-Loaded Nanoparticles

PubMed Central

Nosoudi, Nasim; Chowdhury, Aniqa; Siclari, Steven; Karamched, Saketh; Parasaram, Vaideesh; Parrish, Joe; Gerard, Patrick; Vyavahare, Narendra

2016-01-01

Degeneration of elastic lamina and vascular calcification are common features of vascular pathology such as aortic aneurysms. We tested whether dual therapy with targeted nanoparticles (NPs) can remove mineral deposits (by delivery of a chelating agent, ethylene diamine tetraacetic acid (EDTA)) and restore elastic lamina (by delivery of a polyphenol, pentagalloyl glucose (PGG)) to reverse moderate aneurysm development. EDTA followed by PGG NP delivery led to reduction in macrophage recruitment, matrix metalloproteinase (MMP) activity, elastin degradation and calcification in the aorta as compared to delivery of control blank NPs. Such dual therapy restored vascular elastic lamina and improved vascular function as observed by improvement in circumferential strain. Therefore, dual targeted therapy may be an attractive option to remove mineral deposits and restore healthy arterial structures in moderately developed aneurysms. PMID:27698934

Effects of Gingko biloba extract (EGb 761) on vascular smooth muscle cell calcification induced by β-glycerophosphate.

PubMed

Li, En-Gang; Tian, Jun; Xu, Zhong-Hua

2016-01-01

To investigate the effects of Gingko biloba extract (EGb 761) on calcification induced by β-glycerophosphate in rat aortic vascular smooth muscle cells. Rat aortic vascular smooth muscle cells were cultured with various concentrations of EGb 761 and β-glycerophosphate for 7 days. Calcium content in the cells, alkaline phosphatase activity, cell protein content, NF-κB activation, and reactive oxygen species production were assayed, respectively. The calcium depositions of vascular smooth muscle cells of the β-glycerophosphate group were significantly higher than those of the control group (p < 0.01), and were inhibited by EGb 761 in a concentration-dependent manner (p < 0.05). Data showed β-glycerophosphate induced the enhanced expression of alkaline phosphatase, up-regulated the NF-κB activity and increased reactive oxygen species production of vascular smooth muscle cells while these decreased when administrated with EGb 761(p < 0.05). EGb 761 significantly reduced deposition of calcium induced by β-glycerophosphate in rat aortic vascular smooth muscle cells. It not only reduced the deposition of calcium, but also inhibited osteogenic transdifferentiation, which may be associated with decreasing expression of alkaline phosphatase, down-regulating the NF-κB activity, and reducing reactive oxygen species production of vascular smooth muscle cells, and may have the potential to serve as a role for vascular calcification in clinical situations.

Relationship between Fetuin A, Vascular Calcification and Fracture Risk in Dialysis Patients

PubMed Central

Chen, Hung Yuan; Chiu, Yen Ling; Hsu, Shih Ping; Pai, Mei Fen; Yang, Ju Yeh; Peng, Yu Sen

2016-01-01

Background Fractures are a common morbidity that lead to worse outcomes in dialysis patients. Fetuin A inhibits vascular calcification (VC), potentially promotes bone mineralization and its level positively correlates with bone mineral density in the general population. On the other hand, the presence of VC is associated with low bone volume in dialysis patients. Whether the fetuin A level and VC can predict the occurrence of fractures in dialysis patients remains unknown. Methods We performed this prospective, observational cohort study including 685 dialysis patients (629 hemodialysis and 56 peritoneal dialysis) from a single center in Taiwan for a median follow-up period of 3.4 years. The baseline fetuin A level and status of presence of aortic arch calcification (VC) and incidence of major fractures (hip, pelvis, humerus, proximal forearm, lower leg or vertebrae) were assessed using adjusted Cox proportional hazards models, recursive partitioning analysis and competing risk models. Results Overall, 177 of the patients had major fractures. The incidence rate of major fractures was 3.29 per 100 person-years. In adjusted analyses, the patients with higher baseline fetuin A levels had a lower incidence of fractures (adjusted hazard ratio (HR), 0.3; 95% CI, 0.18‒0.5, fetuin A tertile 3 vs. tertile 1 and HR, 0.52; 95% CI, 0.34‒0.78, tertile 2 vs. tertile 1). The presence of aortic arch calcification (VC) independently predicted the occurrence of fractures (adjusted HR, 1.95; 95% CI, 1.34‒2.84) as well. When accounting for death as an event in competing risk models, the patients with higher baseline fetuin A levels remained to have a lower incidence of fractures (SHR, 0.31; 95% CI, 0.17‒0.56, fetuin A tertile 3 vs. tertile 1 and 0.51; 95% CI, 0.32‒0.81, tertile 2 vs. tertile 1). Interpretations Lower baseline fetuin A levels and the presence of VC were independently linked to higher risk of incident fractures in prevalent dialysis patients. PMID:27398932

[Expression of OPG/RANK/RANKL in the rat dental pulp tissue of periodontitis combined with vascular calcification and its clinical significance].

PubMed

Pan, Ke-Qing; Zhang, Peng-Mei; Deng, Jing; Lou, Xiu-Xiu; Meng, Yun; Liu, Gui-Rong

2016-08-01

To study the expression and possible role of OPG/RANK/RANKLin the rat dental pulp of periodontitis combined with vascular calcification. Thirty-six male Wister rats were randomly divided into 4 groups: control group(group C), periodontitis group(group CP), vascular calcification group(group VDN) and compound group(group CP+VDN). Each group underwent corresponding management to establish animal model. When the model was successful, the maxillae including molars were sectioned, pulp tissue was examined by H-E staining; Immunohistochemical staining method was used to evaluate the expression and ratio of OPG and RANKL in pulp tissues. Statistical analysis was carried out using SPSS 19.0 software package. The pulp tissue of group CP, VDN, CP+VDN showed varied degrees of damage, neutrophil infiltration, pulp vascular congestion, odontoblasts vacuolar changes, pulp necrosis by H-E staining, and the changes in CP+VDN group was the most significant, followed by CP group, VDN group. Immunohistochemistry showed OPG in pulp tissues in group CP, VDN, CP+VDN were significantly lower than that in normal group (P<0.05), and the expression in group CP+VDN was the least;Expression of RANKL in pulp tissues in group CP, VDN, CP+VDN were significantly higher than that in normal group(P<0.05)，and the expression in group CP+VDN was the highest. The ratio of OPG/RANKL in normal group was the highest, and the ratio in CP+VDN group was the lowest. Periodontitis and vascular calcification can damage the pulp tissue, periodontitis compound with vascular calcification may aggravate the injury; OPG/RANKL/RANK system may play an important role in pulp tissue injury.

Vascular calcification and cardiac function according to residual renal function in patients on hemodialysis with urination.

PubMed

Shin, Dong Ho; Lee, Young-Ki; Oh, Jieun; Yoon, Jong-Woo; Rhee, So Yon; Kim, Eun-Jung; Ryu, Jiwon; Cho, Ajin; Jeon, Hee Jung; Choi, Myung-Jin; Noh, Jung-Woo

2017-01-01

Vascular calcification is common and may affect cardiac function in patients with end-stage renal disease (ESRD). However, little is known about the effect of residual renal function on vascular calcification and cardiac function in patients on hemodialysis. This study was conducted between January 2014 and January 2017. One hundred six patients with residual renal function on maintenance hemodialysis for 3 months were recruited. We used residual renal urea clearance (KRU) to measure residual renal function. First, abdominal aortic calcification score (AACS) and brachial-ankle pulse wave velocity (baPWV) were measured in patients on hemodialysis. Second, we performed echocardiography and investigated new cardiovascular events after study enrollment. The median KRU was 0.9 (0.3-2.5) mL/min/1.73m2. AACS (4.0 [1.0-10.0] vs. 3.0 [0.0-8.0], p = 0.05) and baPWV (1836.1 ± 250.4 vs. 1676.8 ± 311.0 cm/s, p = 0.01) were significantly higher in patients with a KRU < 0.9 mL/min/1.73m2 than a KRU ≥ 0.9 mL/min/1.73m2. Log-KRU significantly negatively correlated with log-AACS (ß = -0.29, p = 0.002) and baPWV (ß = -0.19, P = 0.05) after factor adjustment. The proportion of left ventricular diastolic dysfunction was significantly higher in patients with a KRU < 0.9 mL/min/1.73m2 than with a KRU ≥ 0.9 mL/min/1.73m2 (67.9% vs. 49.1%, p = 0.05). Patients with a KRU < 0.9 mL/min/1.73m2 showed a higher tendency of cumulative cardiovascular events compared to those with a KRU ≥ 0.9 ml/min/1.73m2 (P = 0.08). Residual renal function was significantly associated with vascular calcification and left ventricular diastolic dysfunction in patients on hemodialysis.

Diabetes confers in vitro calcific potential on serum which associates with in vivo vascular calcification.

PubMed

Patidar, Ashish; Singh, Dhruv K; Thakur, Shori; Winocour, Peter; Farrington, Ken; Baydoun, Anwar R

2017-05-01

Although vascular calcification (VC) is prevalent in Type 2 diabetes mellitus (T2DM), underlying mechanisms remain unclear. Neither is it known whether T2DM confers calcific potential (CP) on serum, enabling it to induce VC outside the disease milieu. We, therefore, investigated the CP of serum from controls and subjects with T2DM with and without in vivo VC . Samples from 20 healthy controls and 44 age- and sex-matched patients with T2DM with modification of diet in renal disease estimated glomerular filtration rate (MDRD-4 eGFR) > 60 ml·min -1 were analysed for CP using rat aortic smooth muscle cells in vitro CT scans of femoral arteries identified individuals with in vivo calcification. Serum from subjects with T2DM revealed significantly greater CP than controls. This was further enhanced in the presence of in vivo VC. Addition of β-glycerophosphate (β-GP) plus CaCl 2 increased the CP of T2DM serum but not of controls. Along with age, CP was an independent predictor of the presence of VC. In receiver operator curve (ROC) analysis, CP was a significant predictor of femoral arterial VC (C-statistic 0.70: P =0.009). The distribution of CP was bimodal around a cutoff of 100 nmoles of Ca 2+ protein mg -1 , with a higher proportion of Type 2 diabetes subjects with in vivo calcification (T2DM+) sera above the cutoff value. This group also showed elevated levels of osteoprotegerin (OPG) and matrix Gla protein (MGP). Diabetes confers CP on the serum which is enhanced by the presence of in vivo VC. The CP acquired may be dependent on levels of OPG and MGP. These findings may be clinically relevant for early identification of individuals at risk of VC and for informing therapeutic strategies. © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Something more to say about calcium homeostasis: the role of vitamin K2 in vascular calcification and osteoporosis.

PubMed

Flore, R; Ponziani, F R; Di Rienzo, T A; Zocco, M A; Flex, A; Gerardino, L; Lupascu, A; Santoro, L; Santoliquido, A; Di Stasio, E; Chierici, E; Lanti, A; Tondi, P; Gasbarrini, A

2013-09-01

Vascular calcification and osteoporosis share similar etiopathogenetic mechanisms. Vitamin K2 deficiency could be responsible of the so called "calcium paradox", that is the lack of calcium in the bone and its storage in the vessel wall. These events may have clinically relevant consequences, such as cardiovascular accidents, and bone fractures. To review the biological function of vitamin K2 metabolism, the main factors related to its deficiency and the consequent clinical significance. Vitamin K2 is essential for the function of several proteins, involved in the maintenance of the normal structure of arterial wall, osteoarticular system, teeth, and for the regulation of cell growth. It has been demonstrated to have a pivotal role in the inhibition of vascular foci of calcification, and in the regulation of calcium deposition in the bone. Vitamin K2 deficiency is often subclinic in a large part of healthy population. This deficiency is related to the interaction of various factors, such as the reduced dietary intake, the alteration of intestinal absorption or production, with a possible role of intestinal microbiota and the increased consumption at the vessel wall. Vitamin K2 deficiency has recently been recognized as a protagonist in the development of vascular calcification and osteoporosis. Data reported so far are promising and, dietary supplementation seems a useful tool to contrast these diseases. However, large studies or solid clinical correlations regarding vitamin K2 deficiency and its pathologic consequences are needed to confirm these preliminary experiences.

The influence of phosphate, calcium and magnesium on matrix Gla-protein and vascular calcification: a systematic review.

PubMed

Houben, E; Neradova, A; Schurgers, L J; Vervloet, Marc

2016-01-01

Vitamin K-dependent matrix Gla protein (MGP) is a key inhibitor of vascular calcification (VC). MGP is synthesized by chondrocytes and vascular smooth muscle cells (VSMC) and the absence or inactivity of MGP results in excessive calcification of both growth plate and vasculature. Apart from its vitamin K dependency little is known about other factors that influence MGP metabolism. Phosphate, calcium and magnesium are involved in bone mineralization and play an important role in VC. In this review we provide a summary of the effect of phosphate, calcium, and magnesium on MGP metabolism. Elevated phosphate and calcium levels promote VC, in part by increasing the release of matrix vesicles (MV) that under the influence of calcium and phosphate become calcification competent. Phosphate and calcium simultaneously induce an upregulation of MGP protein and gene expression, which possibly inhibits calcification. Elevated phosphate levels did not change MGP protein levels in MV. On the contrary, elevated calcium concentrations caused a decrease of MGPloading in MV, which might in part explainthe calcifying effects of MV. Magnesium is a known inhibitor of VC. However, magnesium has been shown to have an inhibitory effect on MGP synthesis induced through downregulation of the calcium-sensing receptor and hereby causing a decrease in calcium induced MGP upregulation. There might also be stimulatory effect of magnesium on MGP in which the TRPM7 channel is involved. In conclusion there is a clear interaction between MGP and phosphate, calcium and magnesium. The upregulation of MGP by phosphate and calcium might be a cellular response that possibly results in the mitigation of VC.

PKA-induced receptor activator of NF-kappaB ligand (RANKL) expression in vascular cells mediates osteoclastogenesis but not matrix calcification.

PubMed

Tseng, Wendy; Graham, Lucia S; Geng, Yifan; Reddy, Aneela; Lu, Jinxiu; Effros, Rita B; Demer, Linda; Tintut, Yin

2010-09-24

Vascular calcification is a predictor of cardiovascular mortality and is prevalent in patients with atherosclerosis and chronic renal disease. It resembles skeletal osteogenesis, and many bone cells as well as bone-related factors involved in both formation and resorption have been localized in calcified arteries. Previously, we showed that aortic medial cells undergo osteoblastic differentiation and matrix calcification both spontaneously and in response to PKA agonists. The PKA signaling pathway is also involved in regulating bone resorption in skeletal tissue by stimulating osteoblast-production of osteoclast regulating cytokines, including receptor-activator of nuclear κB ligand (RANKL) and interleukins. Therefore, we investigated whether PKA activators regulate osteoclastogenesis in aortic smooth muscle cells (SMC). Treatment of murine SMC with the PKA agonist forskolin stimulated RANKL expression at both mRNA and protein levels. Forskolin also stimulated expression of interleukin-6 but not osteoprotegerin (OPG), an inhibitor of RANKL. Consistent with these results, osteoclastic differentiation was induced when monocytic preosteoclasts (RAW264.7) were cocultured with forskolin-treated aortic SMC. Oxidized phospholipids also slightly induced RANKL expression in T lymphocytes, another potential source of RANKL in the vasculature. Because previous studies have shown that RANKL treatment alone induces matrix calcification of valvular and vascular cells, we next examined whether RANKL mediates forskolin-induced matrix calcification by aortic SMC. RANKL inhibition with OPG had little or no effect on osteoblastic differentiation and matrix calcification of aortic SMC. These findings suggest that, as in skeletal tissues, PKA activation induces bone resorptive factors in the vasculature and that aortic SMC calcification specifically induced by PKA, is not mediated by RANKL.

Disruption of the Aortic Elastic Lamina and Medial Calcification Share Genetic Determinants in Mice

PubMed Central

Wang, Susanna S.; Martin, Lisa J.; Schadt, Eric E.; Meng, Haijin; Wang, Xuping; Zhao, Wei; Ingram-Drake, Leslie; Nebohacova, Martina; Mehrabian, Margarete; Drake, Thomas A.; Lusis, Aldons J.

2010-01-01

Background Disruption of the elastic lamina, as an early indicator of aneurysm formation, and vascular calcification frequently occur together in atherosclerotic lesions of humans. Methods and Results We now report evidence of shared genetic basis for disruption of the elastic lamina (medial disruption) and medial calcification in an F2 mouse intercross between C57BL/6J and C3H/HeJ on a hyperlipidemic apolipoprotein E (ApoE−/−) null background. We identified 3 quantitative trait loci (QTLs) on chromosomes 6, 13, and 18, which are common to both traits, and 2 additional QTLs for medial calcification on chromosomes 3 and 7. Medial disruption, including severe disruptions leading to aneurysm formation, and medial calcification were highly correlated and occurred concomitantly in the cross. The chromosome 18 locus showed a striking male sex-specificity for both traits. To identify candidate genes, we integrated data from microarray analysis, genetic segregation, and clinical traits. The chromosome 7 locus contains the Abcc6 gene, known to mediate myocardial calcification. Using transgenic complementation, we show that Abcc6 also contributes to aortic medial calcification. Conclusions Our data indicate that calcification, though possibly contributory, does not always lead to medial disruption and that in addition to aneurysm formation, medial disruption may be the precursor to calcification. PMID:20031637

Impact of magnesium:calcium ratio on calcification of the aortic wall.

PubMed

Villa-Bellosta, Ricardo

2017-01-01

An inverse relationship between serum magnesium concentration and vascular calcification has been reported following observational clinical studies. Moreover, several studies have been suggesting a protective effect of magnesium on the vascular calcification. However, the exact mechanism remains elusive, and investigators have speculated among a myriad of potential actions. The effect of magnesium on calcification of the aortic wall is yet to be investigated. In the present study, the effects of magnesium and calcium on the metabolism of extracellular PPi, the main endogenous inhibitor of vascular calcification, were investigated in the rat aorta. Calcium and magnesium have antagonist effects on PPi hydrolysis in the aortic wall. Km and Ki values for PPi hydrolysis in rat aortic rings were 1.1 mmol/L magnesium and 32 μmol/L calcium, respectively, but ATP hydrolysis was not affected with calcium. Calcium deposition in the rat aortic wall dramatically increased when the magnesium concentration was increased (ratio of Mg:Ca = 1:1; 1.5 mmol/L calcium and 1.5 mmol/L magnesium) respect to low magnesium concentration (ratio Mg:Ca = 1:3, 1.5 mmol/L calcium and 0.75 mmol/L magnesium). Data from observational clinical studies showing that the serum magnesium concentration is inversely correlated with vascular calcification could be reinterpreted as a compensatory regulatory mechanism that reduces both PPi hydrolysis and vascular calcification. The impact of magnesium in vascular calcification in humans could be studied in association with calcium levels, for example, as the magnesium:calcium ratio.

Impact of magnesium:calcium ratio on calcification of the aortic wall

PubMed Central

2017-01-01

Objective An inverse relationship between serum magnesium concentration and vascular calcification has been reported following observational clinical studies. Moreover, several studies have been suggesting a protective effect of magnesium on the vascular calcification. However, the exact mechanism remains elusive, and investigators have speculated among a myriad of potential actions. The effect of magnesium on calcification of the aortic wall is yet to be investigated. In the present study, the effects of magnesium and calcium on the metabolism of extracellular PPi, the main endogenous inhibitor of vascular calcification, were investigated in the rat aorta. Approach and results Calcium and magnesium have antagonist effects on PPi hydrolysis in the aortic wall. Km and Ki values for PPi hydrolysis in rat aortic rings were 1.1 mmol/L magnesium and 32 μmol/L calcium, respectively, but ATP hydrolysis was not affected with calcium. Calcium deposition in the rat aortic wall dramatically increased when the magnesium concentration was increased (ratio of Mg:Ca = 1:1; 1.5 mmol/L calcium and 1.5 mmol/L magnesium) respect to low magnesium concentration (ratio Mg:Ca = 1:3, 1.5 mmol/L calcium and 0.75 mmol/L magnesium). Conclusion Data from observational clinical studies showing that the serum magnesium concentration is inversely correlated with vascular calcification could be reinterpreted as a compensatory regulatory mechanism that reduces both PPi hydrolysis and vascular calcification. The impact of magnesium in vascular calcification in humans could be studied in association with calcium levels, for example, as the magnesium:calcium ratio. PMID:28570619

MicroRNA-34b/c inhibits aldosterone-induced vascular smooth muscle cell calcification via a SATB2/Runx2 pathway.

PubMed

Hao, Jianbing; Zhang, Lei; Cong, Guangting; Ren, Liansheng; Hao, Lirong

2016-12-01

Increasing evidence shows that aldosterone and specific microRNAs (miRs) contribute to vascular smooth muscle cell (VSMC) calcification. In this study, we aim to explore the mechanistic links between miR-34b/c and aldosterone in VSMC calcification. VSMC calcification models were established both in vitro and in vivo. First, the levels of aldosterone, miR-34b/c and special AT-rich sequence-binding protein 2 (SATB2) were measured. Then, miR-34b/c mimics or inhibitors were transfected into VSMCs to evaluate the function of miR-34b/c. Luciferase reporter assays were used to demonstrate whether SATB2 was a direct target of miR-34b/c. Aldosterone and SATB2 were found to be markedly upregulated during VSMC calcification, whereas miR-34b/c expression was downregulated. Treatment with the mineralocorticoid receptor (MR) antagonist eplerenone inhibited VSMC calcification. In aldosterone-induced VSMC calcification, miR-34b/c levels were downregulated and SATB2 protein was upregulated. Furthermore, miR-34b/c overexpression alleviated aldosterone-induced VSMC calcification as well as inhibited the expression of SATB2 protein, whereas miR-34b/c inhibition markedly enhanced VSMC calcification and upregulated SATB2 protein. In addition, luciferase reporter assays showed that SATB2 is a direct target of miR-34b/c in VSMCs. Overexpression of SATB2 induced Runx2 overproduction and VSMC calcification. Therefore, miR-34b/c participates in aldosterone-induced VSMC calcification via a SATB2/Runx2 pathway. As miR-34b/c appears to be a negative regulator, it has potential as a therapeutic target of VSMC calcification.

Peritoneal delivery of sodium pyrophosphate blocks the progression of pre-existing vascular calcification in uremic apolipoprotein-E knockout mice.

PubMed

de Oliveira, Rodrigo B; Louvet, Loïc; Riser, Bruce L; Barreto, Fellype C; Benchitrit, Joyce; Rezg, Raja; Poirot, Sabrina; Jorgetti, Vanda; Drüeke, Tilman B; Massy, Ziad A

2015-08-01

Chronic kidney disease (CKD) is generally associated with disturbances of mineral and bone metabolism. They contribute to the development of vascular calcification (VC), a strong, independent predictor of cardiovascular risk. Pyrophosphate (PPi), an endogenous inhibitor of hydroxyapatite formation, has been shown to slow the progression of VC in uremic animals. Since in patients with CKD treatment is usually initiated for already existing calcifications, we aimed to compare the efficacy of PPi therapy with that of the phosphate binder sevelamer, using a uremic apolipoprotein-E knockout mouse model with advanced VCs. After CKD creation or sham surgery, 12-week-old female mice were randomized to one sham group and four CKD groups (n = 18-19/group). Treatment was initiated 8 weeks after left nephrectomy allowing prior VC development. Uremic groups received either intraperitoneal PPi (high dose, 1.65 mg/kg or low dose, 0.33 mg/kg per day), oral sevelamer (3 % in diet), or placebo treatment for 8 weeks. Both intima and media calcifications worsened with time in placebo-treated CKD mice, based on both quantitative image analysis and biochemical measurements. Progression of calcification between 8 and 16 weeks was entirely halted by PPi treatment, as it was by sevelamer treatment. PPi did not induce consistent bone histomorphometry changes. Finally, the beneficial vascular action of PPi probably involved mechanisms different from that of sevelamer. Further studies are needed to gain more precise insight into underlying mechanisms and to see whether PPi administration may also be useful in patients with CKD and VC.

Etidronate prevents dystrophic cardiac calcification by inhibiting macrophage aggregation.

PubMed

Bauer, Carolin; le Saux, Olivier; Pomozi, Viola; Aherrahrou, Redouane; Kriesen, Rene; Stölting, Stephanie; Liebers, Annett; Kessler, Thorsten; Schunkert, Heribert; Erdmann, Jeanette; Aherrahrou, Zouhair

2018-04-11

Cardiovascular calcification is associated with high risk of vascular disease. This involves macrophage infiltration of injured vascular tissue and osteoclast-related processes. Splenic monocytes from mice, that are predisposed (C3H) or resistant (B6) to calcification, were isolated and differentiated in vitro with M-CSF to generate macrophages, which aggregate to form multinucleated (MN) cells in the presence of RANKL. MN cell formation was significantly decreased in monocytes from resistant compared with calcifying mice. Conditioned media from C3H macrophages strongly induced calcification in vitro. However, medium from B6 macrophages inhibited calcification. An increase in ICAM-1 was detected in conditioned media from C3H macrophages compared with B6, suggesting a key role for this molecule in calcification processes. Due to natural genetic loss of Abcc6, the causal gene for cardiac calcification, C3H mice have reduced plasma levels of inorganic pyrophosphate (PPi), a potential calcification inhibitor. Supplementation of C3H mice with PPi or Etidronate prevented but did not completely reverse cardiac calcification. Our data provide strong evidence of the pathogenesis of macrophages and MNs during tissue calcification and suggest PPi or its analogue Etidronate as a potential inhibitor of MN formation and calcification. Furthermore, the adhesion molecule ICAM-1 was shown to play a key role in calcification.

Calcium Overload Accelerates Phosphate-Induced Vascular Calcification Via Pit-1, but not the Calcium-Sensing Receptor.

PubMed

Masumoto, Asuka; Sonou, Tomohiro; Ohya, Masaki; Yashiro, Mitsuru; Nakashima, Yuri; Okuda, Kouji; Iwashita, Yuko; Mima, Toru; Negi, Shigeo; Shigematsu, Takashi

2017-07-01

Vascular calcification (VC) is a risk factor of cardiovascular and all-cause mortality in patients with chronic kidney disease (CKD). CKD-mineral and bone metabolism disorder is an important problem in patients with renal failure. Abnormal levels of serum phosphate and calcium affect CKD-mineral and bone metabolism disorder and contribute to bone disease, VC, and cardiovascular disease. Hypercalcemia is a contributing factor in progression of VC in patients with CKD. However, the mechanisms of how calcium promotes intracellular calcification are still unclear. This study aimed to examine the mechanisms underlying calcium-induced calcification in a rat aortic tissue culture model. Aortic segments from 7-week-old male Sprague-Dawley rats were cultured in serum-supplemented medium for 10 days. We added high calcium (HiCa; calcium 3.0 mM) to high phosphate (HPi; phosphate 3.8 mM) medium to accelerate phosphate and calcium-induced VC. We used phosphonoformic acid and the calcimimetic R-568 to determine whether the mechanism of calcification involves Pit-1 or the calcium-sensing receptor. Medial VC was significantly augmented by HPi+HiCa medium compared with HPi alone (300%, p＜0.05), and was associated with upregulation of Pit-1 protein. Pit-1 protein concentrations in HPi+HiCa medium were greater than those in HPi medium. Phosphonoformic acid completely negated the augmentation of medial VC induced by HPi+HiCa. R-568 had no additive direct effect on medial VC. These results indicated that exposure to HPi+HiCa accelerates medial VC, and this is mediated through Pit-1, not the calcium-sensing receptor.

Effect of vitamin K2 on progression of atherosclerosis and vascular calcification in nondialyzed patients with chronic kidney disease stages 3-5.

PubMed

Kurnatowska, Ilona; Grzelak, Piotr; Masajtis-Zagajewska, Anna; Kaczmarska, Magdalena; Stefańczyk, Ludomir; Vermeer, Cees; Maresz, Katarzyna; Nowicki, Michał

2015-01-01

Observational studies have shown that high dietary intake of vitamin K2 is associated with reduced risk of coronary vascular disease and vascular calcification. We assessed the effect of vitamin K2 substitution on the progression of atherosclerosis and calcification in nondialyzed patients with CKD stages 3-5. The study included 42 nondialyzed patients with CKD. The following measurements were taken at baseline and after 270 ±12 days of supplementation with vitamin K2 at a dose of 90 μg (menaquinone, MK-7) together with 10 μg of cholecalciferol (K+D group) or 10 μg of cholecalciferol (group D): common carotid intima-media thickness (CCA-IMT), coronary artery calcification score (CACS), basic biochemical parameters, lipids, and calcification modulators: matrix Gla protein (MGP), desphosphorylated-uncarboxylated MGP (dp-ucMGP), osteoprotegerin (OPG), fetuin A, osteocalcin (OC), and fibroblast growth factor 23. The increase of CCA-IMT was significantly lower in the K+D group compared with the D group: from 0.95 ±0.2 mm to 1.01 ±0.3, P = 0.003 vs from 1.02 ±0.2 mm to 1.16 ±0.3, P = 0.003 (ΔCCA-IMT, 0.06 ±0.08 vs 0.136 ±0.05 mm, P = 0.005, respectively). The increase in CACS was slightly lower in the K+D group than in the D group (ΔCACS, 58.1 ±106.5 AU vs 74.4 ±127.1 AU, P = 0.7). In the K+D group, a significant decrease in the level of dp-ucMGP and total OC was observed. A 270-day course of vitamin K2 administration in patients with CKD stages 3-5 may reduce the progression of atherosclerosis, but does not significantly affect the progression of calcification. Vitamin K2 significantly changes the levels of calcification promoters and inhibitors: dp-ucMGP, OC, and OPG.

Accelerated vascular calcification and relative hypoparathyroidism in incident haemodialysis diabetic patients receiving calcium binders.

PubMed

Galassi, Andrea; Spiegel, David M; Bellasi, Antonio; Block, Geoffrey A; Raggi, Paolo

2006-11-01

Vascular calcification and low bone turnover with a relatively low parathyroid hormone (PTH) often coexist in diabetic patients undergoing haemodialysis. Since calcium salts (CaS) are used extensively as primary phosphate binders and have been associated with progressive vascular calcification, we studied the effects of CaS on coronary arteries and parathyroid activity in incident haemodialysis diabetic patients. We measured the change in coronary artery calcium scores (CACS) with sequential electron beam computed tomography (EBCT) in 64 diabetic and 45 non-diabetic patients, randomized to CaS or sevelamer within 90 days of starting haemodialysis. CACS measurements were repeated after 6, 12 and 18 months. Serum intact PTH (iPTH), calcium and phosphorus were serially tested. During the study period, serum phosphate was similar in diabetic and non-diabetic patients. Serum calcium levels were similar at baseline (2.3+/-0.25 mmol/l for both) and increased significantly with CaS treatment (P<0.05) both in diabetic and non-diabetic patients but not with sevelamer. Diabetic patients treated with CaS showed a significantly greater CACS progression than sevelamer-treated patients (median increase 177 vs 27; P=0.05). During follow-up, diabetic patients receiving CaS were significantly more likely to develop serum iPTH values<16 pmol/l than diabetic patients treated with sevelamer (33% vs 6%, P=0.005) and had a lower mean iPTH level (24+/-16 vs 31+/-14 pmol/l; P=0.038). The management of hyperphosphataemia with CaS in haemodialysis diabetic patients is associated with a significantly greater progression of CACS than with sevelamer. These effects are accompanied by iPTH changes suggestive of low bone turnover.

Conditioned medium from bone marrow-derived mesenchymal stem cells inhibits vascular calcification through blockade of the BMP2-Smad1/5/8 signaling pathway.

PubMed

Wang, Shuangshuang; Hu, Siwang; Wang, Jian; Liu, Yahui; Zhao, Ruochi; Tong, Maoqing; Cui, Hanbin; Wu, Nan; Chen, Xiaomin

2018-06-13

Arterial calcification is associated with cardiovascular disease as a complication of advanced atherosclerosis and is a significant contributor to cardiovascular morbidity and mortality. Osteoblastic differentiation of vascular smooth muscle cells (VSMCs) plays an important role in arterial calcification and is characterized by cellular necrosis, inflammation, and lipoprotein and phospholipid complexes, especially in atherosclerotic calcification. The conditioned medium from bone marrow-derived mesenchymal stem cells (MSC-CM) is well known as a rich source of autologous cytokines and is universally used for tissue regeneration in current clinical medicine. Here, we demonstrate that MSC-CM inhibits beta-glycerophosphate (β-GP)-induced vascular calcification through blockade of the bone morphogenetic protein-2 (BMP2)-Smad1/5/8 signaling pathway. VSMC calcification was induced by β-GP followed by treatment with MSC-CM. Mineral deposition was assessed by Alizarin Red S staining. Intracellular calcium content was determined colorimetrically by the o-cresolphthalein complexone method and alkaline phosphatase (ALP) activity was measured by the para-nitrophenyl phosphate method. Expression of BMP2, BMPR1A, BMPR1B, BMPR2, msh homeobox 2 (Msx2), Runt-related transcription factor 2 (Runx2), and osteocalcin (OC), representative osteoblastic markers, was assessed using real-time polymerase chain reaction analysis while the protein expression of BMP2, Runx2, and phosphorylated Smad1/5/8 was detected by western blot analysis. Our data demonstrated that MSC-CM inhibits osteoblastic differentiation and mineralization of VSMCs as evidenced by decreased calcium content, ALP activity, and decreased expression of BMP-2, Runx2, Msx2, and OC. MSC-CM suppressed the expression of phosphorylated Smad1/5/8 and the β-GP-induced translocation from the cytoplasm to the nucleus. Further study demonstrated that human recombinant BMP-2 overcame the suppression of VSMC calcification by MSC

Doxycycline affects gene expression profiles in aortic tissues in a rat model of vascular calcification.

PubMed

Lu, Hailin; Jiang, Wenhong; Yang, Han; Qin, Zhong; Guo, Si-En; Hu, Ming; Qin, Xiao

2017-11-01

Vitamin D 3 -induced vascular calcification (VC) in rats shares many phenotypical similarities with calcification occurring in human atherosclerosis, diabetes mellitus and chronic kidney disease, thereby it is a reliable model for identifying chemopreventive agents. Doxycycline has been shown to effectively attenuated VC. This study aimed to explore the effects of doxycycline on gene expression profiles in VC rats. The model of VC in rats was established by subcutaneous injection of vitamin D3 for 3days. Doxycycline at 120mgkg -1 day -1 was given via subcutaneous injection for 14days. Rat pathological changes, calcium deposition and calcium content in aortic tissues were measured by Hematoxylin-eosin, von Kossa staining and colorimetry, respectively. The gene change profile of aortic tissues after doxycycline treatment was assessed by Gene Microarray analysis using the Agilent Whole Rat Genome Oligo Microarray. The results showed that doxycycline significantly decreased the deposition of calcium, reduced the relative calcification area and alleviated pathological injury in aortic tissues. In addition, doxycycline treatment altered 88 gene expressions compared with untreated VD group. Of these, 61 genes were down-regulated and 27 genes were up-regulated. The functions of differentially expressed (DE) genes were involved in neutrophil chemotaxis, chronic inflammatory response, negative regulation of apoptotic process, cellular response to mechanical stimulus and immune response, etc. In conclusions, this study might provide the potential novel insights into the molecular mechanisms of doxycycline on VC. Copyright © 2017. Published by Elsevier Inc.

Vascular effects of advanced glycation end-products: content of immunohistochemically detected AGEs in radial artery samples as a predictor for arterial calcification and cardiovascular risk in asymptomatic patients with chronic kidney disease.

PubMed

Janda, Katarzyna; Krzanowski, Marcin; Gajda, Mariusz; Dumnicka, Paulina; Jasek, Ewa; Fedak, Danuta; Pietrzycka, Agata; Kuźniewski, Marek; Litwin, Jan A; Sułowicz, Władysław

2015-01-01

Our aim was to determine whether vascular deposition of advanced glycation end-products (AGEs) is associated with arterial calcification and cardiovascular mortality in chronic kidney disease (CKD) patients and to assess the relationships between vascular content of AGEs and selected clinical and biochemical parameters. The study comprised 54 CKD patients (33 hemodialyzed, 21 predialyzed). Examined parameters included BMI, incidence of diabetes, plasma fasting glucose, AGEs, soluble receptor for AGEs and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging, serum C-reactive protein (hsCRP), plasminogen activator inhibitor-1 (PAI-1), and fetuin-A. Fragments of radial artery obtained during creation of hemodialysis access were stained for calcifications using alizarin red. AGEs deposits were identified immunohistochemically and their relative content was quantified. Vascular content of AGEs was positively correlated with BMI, hsCRP, fetuin-A, PAI-1, and DPPH scavenging in simple regression; only fetuin-A was an independent predictor in multiple regression. There was a significant positive trend in the intensity of AGEs immunostaining among patients with grades 1, 2, and 3 calcifications. AGEs immunostaining intensity predicted 3-year cardiovascular mortality irrespective of patient's age. The present study demonstrates an involvement of AGEs in the development of medial arterial calcification and the impact of arterial AGE deposition on cardiovascular mortality in CKD patients.

Vascular Disease and Kidney Stones: Abdominal Aortic Calcifications Are Associated with Low Urine pH and Hypocitraturia.

PubMed

Patel, Nishant D; Ward, Ryan D; Calle, Juan; Remer, Erick M; Monga, Manoj

2017-09-01

Vascular calcifications are associated with nephrolithiasis. Although studies have demonstrated correlations with vascular disease and calcium stones in kidney stone formers (KSF), an etiologic link has remained elusive. As a noncontrast CT (NCCT) scan is typically part of a stone evaluation, our objective was to evaluate the association of NCCT-based assessment of abdominal aortic calcifications (AACs) with 24-hour urine parameters and stone composition. Ninety-seven KSF were included with CT imaging and 24-hour urine studies. For each patient, semi-automated CT software was utilized to provide an AAC Agatston score from the celiac axis to the aortic bifurcation. Univariate analysis was performed to compare patients with or without AAC. Multivariate logistic regression was performed to assess for variables associated with 24-hour urine parameters and stone composition. The presence of AAC was associated with hypertension, diabetes, peripheral vascular disease, and coronary artery disease. Patients with any AAC showed lower 24-hour urine citrate (399 vs 593 mg/day, p < 0.001) and lower 24-hour urine pH (5.862 vs 6.328, p = 0.003). When controlling for age, system comorbidities, the presence of AAC was associated with low urine pH <6 (odds ratio [OR] 2.86, p = 0.032) and hypocitraturia <320 mg/day (OR 4.37, p = 0.005). The receiver operating characteristic curve showed that increasing AAC was associated with low urine pH (area under the curve [AUC] 0.683, p = 0.002) and uric acid stone formation (AUC 0.698, p = 0.045). NCCT-based diagnosis of AAC is associated with low urine pH, hypocitraturia, and uric acid stone formation. The presence of AAC could be considered an additional prognosticator for the utility of alkalinization therapy.

Acute and 3-month effects of calcium carbonate on the calcification propensity of serum and regulators of vascular calcification: secondary analysis of a randomized controlled trial.

PubMed

Bristow, S M; Gamble, G D; Pasch, A; O'Neill, W C; Stewart, A; Horne, A M; Reid, I R

2016-03-01

Calcium supplements have been associated with increased cardiovascular risk, but the mechanism is unknown. We investigated the effects of calcium supplements on the propensity of serum to calcify, based on the transition time of primary to secondary calciprotein particles (T50). Changes in serum calcium were related to changes in T50. Calcium supplements have been associated with increased cardiovascular risk; however, it is unknown whether this is related to an increase in vascular calcification. We investigated the acute and 3-month effects of calcium supplements on the propensity of serum to calcify, based on the transition time of primary to secondary calciprotein particles (T50), and on three possible regulators of calcification: fetuin-A, pyrophosphate and fibroblast growth factor-23 (FGF23). We randomized 41 postmenopausal women to 1 g/day of calcium as carbonate, or to a placebo containing no calcium. Measurements were performed at baseline and then 4 and 8 h after their first dose, and after 3 months of supplementation. Fetuin-A, pyrophosphate and FGF23 were measured in the first 10 participants allocated to calcium carbonate and placebo who completed the study. T50 declined in both groups, the changes tending to be greater in the calcium group. Pyrophosphate declined from baseline in the placebo group at 4 h and was different from the calcium group at this time point (p = 0.04). There were no other significant between-groups differences. The changes in serum total calcium from baseline were significantly related to changes in T50 at 4 h (r = -0.32, p = 0.05) and 8 h (r = -0.39, p = 0.01), to fetuin-A at 3 months (r = 0.57, p = 0.01) and to pyrophosphate at 4 h (r = 0.61, p = 0.02). These correlative findings suggest that serum calcium concentrations modulate the propensity of serum to calcify (T50), and possibly produce counter-regulatory changes in pyrophosphate and fetuin-A. This provides a possible mechanism by which

New modalities of ultrasound-based intima-media thickness, arterial stiffness and non-coronary vascular calcifications detection to assess cardiovascular risk.

PubMed

Flore, R; Ponziani, F R; Tinelli, G; Arena, V; Fonnesu, C; Nesci, A; Santoro, L; Tondi, P; Santoliquido, A

2015-04-01

Carotid intima-media thickness (c-IMT), arterial stiffness (AS) and vascular calcification (VC) are now considered important new markers of atherosclerosis and have been associated with increased prevalence of cardiovascular events. An accurate, reproducible and easy detection of these parameters could increase the prognostic value of the traditional cardiovascular risk factors in many subjects at low and intermediate risk. Today, c-IMT and AS can be measured by ultrasound, while cardiac computed tomography is the gold standard to quantify coronary VC, although concern about the reproducibility of the former and the safety of the latter have been raised. Nevertheless, a safe and reliable method to quantify non-coronary (i.e., peripheral) VC has not been detected yet. To review the most innovative and accurate ultrasound-based modalities of c-IMT and AS detection and to describe a novel UltraSound-Based Carotid, Aortic and Lower limbs Calcification Score (USB-CALCs, simply named CALC), allowing to quantify peripheral calcifications. Finally, to propose a system for cardiovascular risk reclassification derived from the global evaluation of "Quality Intima-Media Thickness", "Quality Arterial Stiffness", and "CALC score" in addition to the Framingham score.

Cross-sectional relations of arterial stiffness, pressure pulsatility, wave reflection, and arterial calcification.

PubMed

Tsao, Connie W; Pencina, Karol M; Massaro, Joseph M; Benjamin, Emelia J; Levy, Daniel; Vasan, Ramachandran S; Hoffmann, Udo; O'Donnell, Christopher J; Mitchell, Gary F

2014-11-01

Arterial hemodynamics and vascular calcification are associated with increased risk for cardiovascular disease, but their inter-relations remain unclear. We sought to examine the associations of arterial stiffness, pressure pulsatility, and wave reflection with arterial calcification in individuals free of prevalent cardiovascular disease. Framingham Heart Study Third Generation and Offspring Cohort participants free of cardiovascular disease underwent applanation tonometry to measure arterial stiffness, pressure pulsatility, and wave reflection, including carotid-femoral pulse wave velocity, central pulse pressure, forward wave amplitude, and augmentation index. Participants in each cohort (n=1905, 45±6 years and n=1015, 65±9 years, respectively) underwent multidetector computed tomography to assess the presence and quantity of thoracic aortic calcification, abdominal aortic calcification, and coronary artery calcification. In multivariable-adjusted models, both higher carotid-femoral pulse wave velocity and central pulse pressure were associated with greater thoracic aortic calcification and abdominal aortic calcification, whereas higher augmentation index was associated with abdominal aortic calcification. Among the tonometry measures, carotid-femoral pulse wave velocity was the strongest correlate of all calcification measures in multivariable-adjusted models (odds ratio per SD for thoracic aortic calcification, 2.69 [95% confidence interval, 2.17-3.35]; abdominal aortic calcification, 1.47 [95% confidence interval, 1.26-1.73]; and coronary artery calcification, 1.48 [95% confidence interval, 1.28-1.72]; all P<0.001, respectively). We observed stronger relations of carotid-femoral pulse wave velocity, central pulse pressure, and forward wave amplitude with nearly all continuous calcification measures in the younger Third Generation Cohort as compared with the Offspring Cohort. In community-dwelling individuals without prevalent cardiovascular disease

The GLUT-1 XbaI gene polymorphism is associated with vascular calcifications in nondiabetic uremic patients.

PubMed

Rufino, Margarita; Hernández, Domingo; Barrios, Ysamar; Salido, Eduardo

2008-01-01

Glucose transporters mediate the facilitative uptake of glucose into cells, with GLUT-1 being the predominant isoform in vascular smooth muscle cell (VSMC). Clones of human cells overexpressing the GLUT-1 transporter showed a high increase in intracellular glucose concentrations, mimicking the diabetic milieu. It is possible that high intracellular glucose together with uremic factors may play an important role in vascular calcification by transforming VSMC into osteoblast-like cells. The XbaI polymorphism in the GLUT-1 gene has been linked to variations in GLUT-1 expression, with consequent changes in intracellular glucose concentration. To assess the association between the GLUT-1 XbaI gene polymorphism and the presence of VC in nondiabetic uremic patients, a total of 105 nondiabetic patients on hemodialysis were studied. VC were evaluated by conventional simple X-ray. Mean values of serum calcium, phosphorous, cholesterol, triglycerides, HbA1c, PTH and insulin were measured. Height, weight, BMI and waist circumference were also determined. The GLUT-1 XbaI polymorphism in the second intron of the gene was ascertained by means of the polymerase chain reaction and restriction fragment length polymorphism analysis on DNA isolated from peripheral blood DNA. In the absence of an XbaI site, a fragment of 305 bp was seen (so-called x allele), whereas fragments of 232 and 73 bp were generated if the XbaI site was present (X allele). Genotype distribution in all patients was similar to the Caucasian population. However, when the patients were grouped according to the presence or absence of VC, there were marked differences in the frequency of the GLUT1 genotypes: the xx GLUT-1 genotype was more prevalent in the group with VC (30.7 vs. 4.5%, p = 0.001). Stepwise logistic regression demonstrated that the xx GLUT-1 genotype was independently associated with the presence of VC after adjusting for other variables such as age, calcium x phosphrus product, BMI and time on

Vascular Calcification and Stone Disease: A New Look towards the Mechanism

PubMed Central

Yiu, Allen J.; Callaghan, Daniel; Sultana, Razia; Bandyopadhyay, Bidhan C.

2015-01-01

Calcium phosphate (CaP) crystals are formed in pathological calcification as well as during stone formation. Although there are several theories as to how these crystals can develop through the combined interactions of biochemical and biophysical factors, the exact mechanism of such mineralization is largely unknown. Based on the published scientific literature, we found that common factors can link the initial stages of stone formation and calcification in anatomically distal tissues and organs. For example, changes to the spatiotemporal conditions of the fluid flow in tubular structures may provide initial condition(s) for CaP crystal generation needed for stone formation. Additionally, recent evidence has provided a meaningful association between the active participation of proteins and transcription factors found in the bone forming (ossification) mechanism that are also involved in the early stages of kidney stone formation and arterial calcification. Our review will focus on three topics of discussion (physiological influences—calcium and phosphate concentration—and similarities to ossification, or bone formation) that may elucidate some commonality in the mechanisms of stone formation and calcification, and pave the way towards opening new avenues for further research. PMID:26185749

Magnesium prevents phosphate-induced calcification in human aortic vascular smooth muscle cells.

PubMed

Louvet, Loïc; Büchel, Janine; Steppan, Sonja; Passlick-Deetjen, Jutta; Massy, Ziad A

2013-04-01

Vascular calcification (VC) is prevalent in patients suffering from chronic kidney disease. Factors promoting calcification include abnormalities in mineral metabolism, particularly high phosphate levels. Inorganic phosphate (Pi) is a classical inducer of in vitro VC. Recently, an inverse relationship between serum magnesium concentrations and VC has been reported. The present study aimed to investigate the effects of magnesium on Pi-induced VC at the cellular level using primary HAVSMC. Alive and fixed HAVSMC were assessed during 14 days in the presence of Pi with increasing concentrations of magnesium (Mg(2+)) chloride. Mineralization was measured using quantification of calcium, von Kossa and alizarin red stainings. Cell viability and secretion of classical VC markers were also assessed using adequate tests. Involvement of transient receptor potential melastatin (TRPM) 7 was assessed using 2-aminoethoxy-diphenylborate (2-APB) inhibitor. Co-incubation with Mg(2+) significantly decreased Pi-induced VC in live HAVSMC, no effect was found in fixed cells. At potent concentrations in Pi-induced HAVSMC, Mg(2+) significantly improved cell viability and restored to basal level increased secretions of osteocalcin and matrix gla protein, whereas a decrease in osteopontin secretion was partially restored. The block of TRPM7 with 2-APB at 10(-4) M led to the inefficiency of Mg(2+) to prevent VC. Increasing Mg(2+) concentrations significantly reduced VC, improved cell viability and modulated secretion of VC markers during cell-mediated matrix mineralization clearly pointing to a cellular role for Mg(2+) and 2-APB further involved TRPM7 and a potential Mg(2+) entry to exert its effects. Further investigations are needed to shed light on additional cellular mechanism(s) by which Mg(2+) is able to prevent VC.

Vascular calcification abrogates the nicorandil mediated cardio-protection in ischemia reperfusion injury of rat heart.

PubMed

Ravindran, Sriram; Murali, Jeyashri; Amirthalingam, Sunil Kumar; Gopalakrishnan, Senthilkumar; Kurian, Gino A

2017-02-01

The present study was aimed to determine the efficacy of nicorandil in treating cardiac reperfusion injury with an underlying co-morbidity of vascular calcification (VC). Adenine diet was used to induce VC in Wistar rat and the heart was isolated to induce global ischemia reperfusion (IR) by Langendorff method, with and without the nicorandil (7.5mg/kg) pre-treatment and compared with those fed on normal diet. The adenine-treated rats displayed abnormal ECG changes and altered mitochondrial integrity compared to a normal rat heart. These hearts, when subjected to IR increased the infarct size, cardiac injury (measured by lactate dehydrogenase and creatine kinase activity in the coronary perfusate) and significantly altered the hemodynamics compared to the normal perfused heart. Nicorandil pretreatment in rat fed on normal diet enhanced the hemodynamics significantly (P<0.05) along with a substantial reduction in the mitochondrial dysfunction (measured by high ADP to oxygen consumption ratio, respiratory control ratio, enzyme activities and less swelling behavior) when subjected to IR. However, this cardio-protective effect of nicorandil was absent in rat heart with underlying calcification. Our results suggest that, the protective effect of nicorandil, a known mitochondrial ATP linked K + channel opener, against myocardial reperfusion injury was confined to normal rat heart. Copyright © 2017 Elsevier Inc. All rights reserved.

Atypical moyamoya syndrome with brain calcification and stenosis of abdominal aorta and renal arteries.

PubMed

Uchikawa, Hideki; Fujii, Katsunori; Fujita, Mayuko; Okunushi, Tomoko; Shimojo, Naoki

2017-09-01

Moyamoya syndrome is a progressive cerebrovascular disease that is characterized by stenosis of the terminal portion of the internal carotid artery and its main branches, in combination with an accompanying disease. We herein describe an 8-year-old boy exhibiting transient loss of consciousness, who had recurrent seizures in infancy with progressive brain calcification. On admission, he was alert but magnetic resonance angiography showed bilateral stenosis of the whole internal carotid artery and proliferation of vascular collaterals, and brain CT revealed calcification on bilateral putamen. Given that this fulfilled diagnostic criteria, we finally diagnosed him as having moyamoya syndrome, though the etiology was unclear. Interestingly, a whole vessel survey revealed vascular stenosis of abdominal aorta and renal arteries, in which the former has not been reported in moyamoya syndrome. We considered that brain calcification was gradually formed by decreased cerebral vascular flow from infancy, and stenosis of abdominal aorta was possibly extended from renal arteries. This is, moyamoya syndrome with brain calcification and stenosis of abdominal aorta, suggesting that morphological screening of whole vessels containing cerebral and abdominal arteries should be considered in cases of slowly progressive brain calcification. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

The combination of lanthanum chloride and the calcimimetic calindol delays the progression of vascular smooth muscle cells calcification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ciceri, Paola; Volpi, Elisa; Brenna, Irene

2012-02-24

Highlights: Black-Right-Pointing-Pointer Lanthanum reduces the progression of high phosphate-induced calcium deposition. Black-Right-Pointing-Pointer Calcium receptor agonists and the calcimimetic calindol reduce calcium deposition. Black-Right-Pointing-Pointer Lanthanum and calindol cooperate on reducing calcium deposition. Black-Right-Pointing-Pointer Lanthanum and calindol may interact with the same receptor. -- Abstract: Phosphate (Pi)-binders are commonly used in dialysis patients to control high Pi levels, that associated with vascular calcification (VC). The aim of this study was to investigate the effects of lanthanum chloride (LaCl{sub 3}) on the progression of high Pi-induced VC, in rat vascular smooth muscle cells (VSMCs). Pi-induced Ca deposition was inhibited by LaCl{sub 3}, withmore » a maximal effect at 100 {mu}M (59.0 {+-} 2.5% inhibition). Furthermore, we studied the effects on VC of calcium sensing receptor (CaSR) agonists. Gadolinium chloride, neomycin, spermine, and the calcimimetic calindol significantly inhibited Pi-induced VC (55.9 {+-} 2.2%, 37.3 {+-} 4.7%, 30.2 {+-} 5.7%, and 63.8 {+-} 5.7%, respectively). To investigate the hypothesis that LaCl{sub 3} reduces the progression of VC by interacting with the CaSR, we performed a concentration-response curve of LaCl{sub 3} in presence of a sub-effective concentration of calindol (10 nM). Interestingly, this curve was shifted to the left (IC{sub 50} 9.6 {+-} 2.6 {mu}M), compared to the curve in the presence of LaCl{sub 3} alone (IC{sub 50} 19.0 {+-} 4.8 {mu}M). In conclusion, we demonstrated that lanthanum chloride effectively reduces the progression of high phosphate-induced vascular calcification. In addition, LaCl{sub 3} cooperates with the calcimimetic calindol in decreasing Ca deposition in this in vitro model. These results suggest the potential role of lanthanum in the treatment of VC induced by high Pi.« less

Vinpocetine Attenuates the Osteoblastic Differentiation of Vascular Smooth Muscle Cells

PubMed Central

Chen, Xiu-Juan; Wang, Na; Yi, Peng-Fei; Song, Min; Zhang, Bo; Wang, Yu-Zhong; Liang, Qiu-Hua

2016-01-01

Vascular calcification is an active process of osteoblastic differentiation of vascular smooth muscle cells; however, its definite mechanism remains unknown. Vinpocetine, a derivative of the alkaloid vincamine, has been demonstrated to inhibit the high glucose-induced proliferation of vascular smooth muscle cells; however, it remains unknown whether vinpocetine can affect the osteoblastic differentiation of vascular smooth muscle cells. We hereby investigated the effect of vinpocetine on vascular calcification using a beta-glycerophosphate-induced cell model. Our results showed that vinpocetine significantly reduced the osteoblast-like phenotypes of vascular smooth muscle cells including ALP activity, osteocalcin, collagen type I, Runx2 and BMP-2 expression as well as the formation of mineralized nodule. Vinpocetine, binding to translocation protein, induced phosphorylation of extracellular signal-related kinase and Akt and thus inhibited the translocation of nuclear factor-kappa B into the nucleus. Silencing of translocator protein significantly attenuated the inhibitory effect of vinpocetine on osteoblastic differentiation of vascular smooth muscle cells. Taken together, vinpocetine may be a promising candidate for the clinical therapy of vascular calcification. PMID:27589055

Vinpocetine Attenuates the Osteoblastic Differentiation of Vascular Smooth Muscle Cells.

PubMed

Ma, Yun-Yun; Sun, Lin; Chen, Xiu-Juan; Wang, Na; Yi, Peng-Fei; Song, Min; Zhang, Bo; Wang, Yu-Zhong; Liang, Qiu-Hua

2016-01-01

Vascular calcification is an active process of osteoblastic differentiation of vascular smooth muscle cells; however, its definite mechanism remains unknown. Vinpocetine, a derivative of the alkaloid vincamine, has been demonstrated to inhibit the high glucose-induced proliferation of vascular smooth muscle cells; however, it remains unknown whether vinpocetine can affect the osteoblastic differentiation of vascular smooth muscle cells. We hereby investigated the effect of vinpocetine on vascular calcification using a beta-glycerophosphate-induced cell model. Our results showed that vinpocetine significantly reduced the osteoblast-like phenotypes of vascular smooth muscle cells including ALP activity, osteocalcin, collagen type I, Runx2 and BMP-2 expression as well as the formation of mineralized nodule. Vinpocetine, binding to translocation protein, induced phosphorylation of extracellular signal-related kinase and Akt and thus inhibited the translocation of nuclear factor-kappa B into the nucleus. Silencing of translocator protein significantly attenuated the inhibitory effect of vinpocetine on osteoblastic differentiation of vascular smooth muscle cells. Taken together, vinpocetine may be a promising candidate for the clinical therapy of vascular calcification.

Calcific band keratopathy in an alpaca.

PubMed

Pucket, Jonathan D; Boileau, Melanie J; Sula, Mee Ja M

2014-07-01

A 4-year-old female Suri alpaca was presented for evaluation of acute onset weakness, lethargy, and recent development of opacities in both eyes. On ophthalmic examination, bilaterally symmetrical corneal opacities were noted along the interpalpebral fissures with a few corneal blood vessels intermingled. A presumed diagnosis of calcific band keratopathy was made based on location and appearance. The patient was euthanized a short while after diagnosis due to reasons unrelated to the eyes and histologic examination of the corneas revealed subepithelial calcium and vascularization, consistent with calcific band keratopathy. This case report is the first to document this ocular condition in an alpaca. © 2013 American College of Veterinary Ophthalmologists.

Association between vascular calcification assessed by simple radiography and non-fatal cardiovascular events in hemodialysis patients.

PubMed

Petrauskiene, Vaida; Vaiciuniene, Ruta; Bumblyte, Inga Arune; Kuzminskis, Vytautas; Ziginskiene, Edita; Grazulis, Saulius; Jonaitiene, Egle

2016-12-01

Vascular calcification (VC) is one of the factors associated with cardiovascular mortality in hemodialysis (HD) patients. Recommendations concerning screening for VC differ. Possible ability to prevent and reversibility of VC are major subjects on debate whether screening for VC could improve outcomes of renal patients. The objective of the study was to evaluate the significance of simple vascular calcification score (SVCS) based on plane radiographic films and to test its association with non-fatal cardiovascular events in patients on chronic HD. A study population consisted of 95 prevalent HD patients in the HD unit of Hospital of Lithuanian University of Health sciences Kaunas Clinics. Clinical data and laboratory tests information were collected from medical records. SVCS was evaluated as it is described by Adragao et al. After measurement of VC, HD patients were observed for novel non-fatal cardiovascular events. Patients were divided into two groups: SVCS≥3 (57 patients [60%]) and <3 (38 patients [40%]). The Kaplan-Meier survival curves show a significant difference in non-fatal cardiovascular events in the group with SVCS≥3 vs. <3 group (26.3% vs. 7.8%; log rank 5,49; P=0.018). Multivariate Cox regression analysis confirmed a negative impact of VC, hyperphosphatemia, and lower ejection fraction on cardiovascular events. No statistically significant differences were observed comparing parameters of Ca-P metabolism disorders between groups with different SVCS. On separate analysis, the presence of VC in hands was also associated with higher rate of novel cardiovascular events (score 0 goup-5 events [10.6%] vs. score≥1 group-13 events [27%], log rank P=0.035). VC assessed by simple and inexpensive radiological method was an independent predictor of novel non-fatal cardiovascular events in HD patients. Copyright © 2016 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Presence of intracranial artery calcification is associated with mortality and vascular events in patients with ischemic stroke after hospital discharge: a cohort study.

PubMed

Bugnicourt, Jean-Marc; Leclercq, Claire; Chillon, Jean-Marc; Diouf, Momar; Deramond, Hervé; Canaple, Sandrine; Lamy, Chantal; Massy, Ziad A; Godefroy, Olivier

2011-12-01

Although intracranial artery calcification (IAC) has been reported to be a risk factor for ischemic stroke, the prognostic implications of IAC in stroke outcome are unknown. The purpose of this study was to determine the association between IAC and risk of vascular events and death in patients with stroke after hospital discharge. All patients with ischemic stroke over a 1-year period were included (n=302). IAC, assessed by multidetector CT, was defined as hyperdense foci (peak density>130 Hounsfield units) and assessed in the 7 major cerebral arteries. The IAC scores ranged from 0 (no calcification) to 7. Follow-up information on major clinical events (including fatal or nonfatal ischemic stroke, cardiac and peripheral artery events, and all-cause death) was obtained by means of a structured phone interview. IAC was present in 260 patients (83%). With a mean follow-up of 773±223 days, 88 major clinical events occurred in 67 patients (22%): 45 new ischemic vascular events (ischemic stroke: n=22; cardiac event: n=15; peripheral artery event: n=8) and 43 deaths from any cause. Patients with the highest IAC scores had significantly higher rates of death and vascular events than those with the lowest IAC scores (log rank test, P=0.029). In the Cox proportional hazards regression model, the IAC score was significantly associated with major clinical events (hazard ratio, 1.34; 95% CI, 1.11-1.61; P=0.002). In patients with ischemic stroke, IAC detection may constitute a simple marker of a high risk of future major clinical events.

Pathological Calcification and Ossification in Relation to Leriche and Policard's Theory.

PubMed

Jones, W; Roberts, R E

1933-05-01

(1) Pathology of calcification and ossification.-The Leriche-Policard theories. Hyperaemia of bone causes decalcification. Reduced blood supply causes sclerosis. Diminution of vascularity of fibrous tissue causes calcification. Excess of calcium, adequate blood supply and fibroblasts give rise to bone anywhere. Subperiosteal ossification. "Myositis ossificans."(2) Radiological significance of density of bone shadows.-Decalcification of disuse, of infections, of neoplasms. Traumatic and infective scquestra. Evidence that a fragment of bone is avascular.(3) Hyperaemic decalcification of bone.-Delayed and non-union of fractures. Kummel's disease. Spontaneous hyperaemic dislocation of the atlas. Hyperaemic decalcification and nephrolithiasis.(4) Anaemic sclerosis of bone.-Syphilitic bone disease. Malignant bone disease. Fragility of sclerosed bone-Paget's, Kienboch's, Kohler's and Panner's, Albers-Schönberg's diseases.(5) Pathological calcification.-Calcification of supraspinatus tendon. Calcification of tumours-angioma, haematoma, and thrombosed vessels, lipoma, cysts, etc. Calcification of semilunar cartilages and intervertebral discs.(6) Pathological ossification.-Ossification of tendons. Ossification of semilunar cartilages.

Systematic review and meta-analysis for the association of bone mineral density and osteoporosis/osteopenia with vascular calcification in women.

PubMed

Zhang, Yiyun; Feng, Bo

2017-02-01

The relationships of osteoporosis/osteopenia and bone mineral density (BMD) with vascular calcification (VC) remain controversial. Thus, we performed this systematic review and meta-analysis to evaluate the association between BMD, osteoporosis/osteopenia risk and VC. PubMed, Embase and Springer databases were searched from inception to March, 2015 for studies involving the association of vascular calcification with BMD and osteopenia/osteoporosis in women. A manual search of the references cited in the publications was also employed for more relevant studies. The heterogeneity was assessed using Cochran's Q statistic and I 2 test. Weighted mean difference (WMD) or odds ratio (OR) and 95% confidence interval (CI) in the VC group and control group were appropriately pooled. Four studies were enrolled in the meta-analysis. The pooled effects indicated that the spine BMD (WMD = -0.08, 95% CI: -0.11 to -0.06) and hip BMD (WMD = -0.06, 95% CI: -0.10 to -0.07) in VC group were significantly lower than those in control group, respectively. Moreover, patients with VC were prone to develop osteoporosis (OR = 4.39, 95% CI: 2.82-6.83) and osteopenia (OR = 1.72, 95% CI: 1.14-2.60). The results suggest that patients with VC have lower lumbar spine and hip BMD levels and increased risk for developing osteoporosis/osteopenia. Thus, VC patients should be evaluated for the presence of osteoporosis/osteopenia, as well as susceptibility to fractures. © 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Discoidin Domain Receptor-1 Deficiency Attenuates Atherosclerotic Calcification and Smooth Muscle Cell-Mediated Mineralization

PubMed Central

Ahmad, Pamela J.; Trcka, Daniel; Xue, Siming; Franco, Christopher; Speer, Mei Y.; Giachelli, Cecilia M.; Bendeck, Michelle P.

2009-01-01

Intimal calcification is a feature of advanced atherosclerotic disease that predicts a two- to eightfold increase in the risk of coronary events. Type I collagen promotes vascular smooth muscle cell-mediated calcification, although the mechanism by which this occurs is unknown. The discoidin domain receptor 1 (DDR1) is a collagen receptor that is emerging as a critical mediator of atherosclerosis. To determine whether DDR1 is involved in intimal calcification, we fed male Ddr1−/−;Ldlr−/− and Ddr1+/+;Ldlr−/− mice an atherogenic diet for 6, 12, or 24 weeks. DDR1 deficiency significantly reduced the calcium content of the aortic arch, and microcomputed tomography demonstrated a significant decrease in hydroxyapatite deposition after 24 weeks of atherogenic diet. Reduced calcification was correlated with decreases in macrophage accumulation and tumor necrosis factor α staining, suggesting that the reduction in calcification was in part due to decreased inflammation. The chondrogenic markers type II collagen, type X collagen, and Sox-9 were expressed within the mineralized foci. An in vitro assay performed with vascular smooth muscle cells revealed that DDR1 was required for cell-mediated calcification of the matrix, and Ddr1+/+ smooth muscle cells expressed more alkaline phosphatase activity, whereas Ddr1−/− smooth muscle cells expressed elevated levels of mRNA for nucleotide pyrophosphatase phosphodiesterase 1, an inhibitor of tissue mineralization. Taken together, our results demonstrate that DDR1 mediates an important mechanism for atherosclerotic calcification. PMID:19893047

Discoidin domain receptor-1 deficiency attenuates atherosclerotic calcification and smooth muscle cell-mediated mineralization.

PubMed

Ahmad, Pamela J; Trcka, Daniel; Xue, Siming; Franco, Christopher; Speer, Mei Y; Giachelli, Cecilia M; Bendeck, Michelle P

2009-12-01

Intimal calcification is a feature of advanced atherosclerotic disease that predicts a two- to eightfold increase in the risk of coronary events. Type I collagen promotes vascular smooth muscle cell-mediated calcification, although the mechanism by which this occurs is unknown. The discoidin domain receptor 1 (DDR1) is a collagen receptor that is emerging as a critical mediator of atherosclerosis. To determine whether DDR1 is involved in intimal calcification, we fed male Ddr1(-/-);Ldlr(-/-) and Ddr1(+/+);Ldlr(-/-) mice an atherogenic diet for 6, 12, or 24 weeks. DDR1 deficiency significantly reduced the calcium content of the aortic arch, and microcomputed tomography demonstrated a significant decrease in hydroxyapatite deposition after 24 weeks of atherogenic diet. Reduced calcification was correlated with decreases in macrophage accumulation and tumor necrosis factor alpha staining, suggesting that the reduction in calcification was in part due to decreased inflammation. The chondrogenic markers type II collagen, type X collagen, and Sox-9 were expressed within the mineralized foci. An in vitro assay performed with vascular smooth muscle cells revealed that DDR1 was required for cell-mediated calcification of the matrix, and Ddr1(+/+) smooth muscle cells expressed more alkaline phosphatase activity, whereas Ddr1(-/-) smooth muscle cells expressed elevated levels of mRNA for nucleotide pyrophosphatase phosphodiesterase 1, an inhibitor of tissue mineralization. Taken together, our results demonstrate that DDR1 mediates an important mechanism for atherosclerotic calcification.

Uncarboxylated matrix Gla protein (ucMGP) is associated with coronary artery calcification in haemodialysis patients.

PubMed

Cranenburg, Ellen C M; Brandenburg, Vincent M; Vermeer, Cees; Stenger, Melanie; Mühlenbruch, Georg; Mahnken, Andreas H; Gladziwa, Ulrich; Ketteler, Markus; Schurgers, Leon J

2009-02-01

Matrix gamma-carboxyglutamate (Gla) protein (MGP) is a potent local inhibitor of cardiovascular calcification and accumulates at areas of calcification in its uncarboxylated form (ucMGP). We previously found significantly lower circulating ucMGP levels in patients with a high vascular calcification burden. Here we report on the potential of circulating ucMGP to serve as a biomarker for vascular calcification in haemodialysis (HD) patients. Circulating ucMGP levels were measured with an ELISA-based assay in 40 HD patients who underwent multi-slice computed tomography (MSCT) scanning to quantify the extent of coronary artery calcification (CAC). The mean ucMGP level in HD patients (193 +/- 65 nM) was significantly lower as compared to apparently healthy subjects of the same age (441 +/- 97 nM; p < 0.001) and patients with rheumatoid arthritis (RA) without CAC (560 +/- 140 nM; p < 0.001). Additionally, ucMGP levels correlated inversely with CAC scores (r = -0.41; p = 0.009), and this correlation persisted after adjustment for age, dialysis vintage and high-sensitivity C-reactive protein (hs-CRP). Since circulating ucMGP levels are significantly and inversely correlated with the extent of CAC in HD patients, ucMGP may become a tool for identifying HD patients with a high probability of cardiovascular calcification.

Pathological Calcification and Ossification in Relation to Leriche and Policard's Theory

PubMed Central

Jones, Watson; Roberts, R. E.

1933-01-01

(1) Pathology of calcification and ossification.—The Leriche-Policard theories. Hyperæmia of bone causes decalcification. Reduced blood supply causes sclerosis. Diminution of vascularity of fibrous tissue causes calcification. Excess of calcium, adequate blood supply and fibroblasts give rise to bone anywhere. Subperiosteal ossification. “Myositis ossificans.” (2) Radiological significance of density of bone shadows.—Decalcification of disuse, of infections, of neoplasms. Traumatic and infective scquestra. Evidence that a fragment of bone is avascular. (3) Hyperæmic decalcification of bone.—Delayed and non-union of fractures. Kummel's disease. Spontaneous hyperæmic dislocation of the atlas. Hyperæmic decalcification and nephrolithiasis. (4) Anæmic sclerosis of bone.—Syphilitic bone disease. Malignant bone disease. Fragility of sclerosed bone—Paget's, Kienboch's, Kohler's and Panner's, Albers-Schönberg's diseases. (5) Pathological calcification.—Calcification of supraspinatus tendon. Calcification of tumours—angioma, hæmatoma, and thrombosed vessels, lipoma, cysts, etc. Calcification of semilunar cartilages and intervertebral discs. (6) Pathological ossification.—Ossification of tendons. Ossification of semilunar cartilages. PMID:19989304

Pelvic artery calcification detection on CT scans using convolutional neural networks

NASA Astrophysics Data System (ADS)

Liu, Jiamin; Lu, Le; Yao, Jianhua; Bagheri, Mohammadhadi; Summers, Ronald M.

2017-03-01

Artery calcification is observed commonly in elderly patients, especially in patients with chronic kidney disease, and may affect coronary, carotid and peripheral arteries. Vascular calcification has been associated with many clinical outcomes. Manual identification of calcification in CT scans requires substantial expert interaction, which makes it time-consuming and infeasible for large-scale studies. Many works have been proposed for coronary artery calcification detection in cardiac CT scans. In these works, coronary artery extraction is commonly required for calcification detection. However, there are few works about abdominal or pelvic artery calcification detection. In this work, we present a method for automatic pelvic artery calcification detection on CT scan. This method uses the recent advanced faster region-based convolutional neural network (R-CNN) to directly identify artery calcification without a need for artery extraction since pelvic artery extraction itself is challenging. Our method first generates category-independent region proposals for each slice of the input CT scan using region proposal networks (RPN). Then, each region proposal is jointly classified and refined by softmax classifier and bounding box regressor. We applied the detection method to 500 images from 20 CT scans of patients for evaluation. The detection system achieved a 77.4% average precision and a 85% sensitivity at 1 false positive per image.

Daily peritoneal administration of sodium pyrophosphate in a dialysis solution prevents the development of vascular calcification in a mouse model of uraemia.

PubMed

Riser, Bruce L; Barreto, Fellype Carvalho; Rezg, Raja; Valaitis, Paul W; Cook, Chyung S; White, Jeffrey A; Gass, Jerome H; Maizel, Julien; Louvet, Loic; Drueke, Tilman B; Holmes, Clifford J; Massy, Ziad A

2011-10-01

The high rate of cardiovascular mortality in patients with end-stage renal disease (ESRD) is a significant barrier to improved life expectancy. Unique in this population is the marked development and aggressive worsening of vascular calcification (VC). Pyrophosphate (PPi), an endogenous molecule, appears to naturally inhibit soft tissue calcification, but may be depressed in chronic kidney disease (CKD) and ESRD. Although once thought to be a promising therapeutic, PPi's very short half-life in circulation curtailed earlier studies. We tested the possibility that a slow, continuous entry of PPi into the circulation and prevention of VC might be achieved by daily peritoneal dialysis (PD). Pharmacokinetic studies were first carried out in rats with renal impairment resulting from a 5/6 nephrectomy. Efficacy studies were then performed in the apolipoprotein E gene knockout mouse model overlaid with CKD. PPi was delivered by means of a permanent peritoneal catheter in a solution simulating PD, but without the timed removal of spent dialysate. von Kossa's staining followed by semiquantitative morphological image processing, with separation of inside (intimal) and outside (presumed medial) lesions, was used to determine aortic root calcification. In comparison to an intravenous bolus, delivery of PPi in a PD solution resulted in a slower, extended delivery over >4 h. Next, the efficacy studies showed that a 6-day/week PD-simulated administration of PPi resulted in a dose-dependent inhibition of aortic calcification in both intimal and medial lesions. A dose-response effect on total aortic calcification was also documented, with a full inhibition seen at the highest dose. A limited peritoneal catheter-related inflammation was observed, as expected, and included the placebo-treated control groups. This inflammatory response could have masked a lower level PPi-specific adverse effect, but none was observed. Our findings suggest potential for PPi, administered during PD, to

A novel ultrasound-based vascular calcification score (CALCS) to detect subclinical atherosclerosis.

PubMed

Flore, R; Zocco, M A; Ainora, M E; Fonnesu, C; Nesci, A; Gasbarrini, A; Ponziani, F R

2018-02-01

To quantify non-coronary vascular calcifications (VC) in asymptomatic patients at low-intermediate cardiovascular risk by a new color Doppler ultrasound (DUS)-based score (the carotid, aortic, lower limbs calcium score, CALCs), and to correlate this score with classical parameters associated with cardiovascular risk [carotid intima media thickness (IMT), and arterial stiffness (AS)]. All consecutive asymptomatic patients who underwent a screening DUS of non-coronary circulation were evaluated and patients at low-intermediate cardiovascular risk were selected according to Framingham risk score (FRS). Among them, we enrolled 70 patients with US evidence of VC and 71 age, sex and FRS matched controls. The presence of VC was correlated with classical markers of cardiovascular risk, such as AS and intima-media thickness (IMT). AS, expressed as pulse wave velocity (PWV) and arterial distensibility, carotid IMT and CALCs were measured for both groups. AS and c-IMT were assessed by a new Radio-Frequency (RF) DUS-based method. CALCs was generated by our previously described B-mode DUS-based method according to number/size of VC in 11 non-coronary segments (range 0-33). Patients with VC presented higher AS and IMT values than controls (PWV 8.34±0.98 m/s vs. 6.74±0.68 m/s, p<0.0001; arterial distensibility 267±12 mm vs. 315±65 mm, p=0.001; IMT 687±132 mm vs. 572±91 mm, p<0.0001). Mean CALCs of patients with VC was 8.41±7.78. CALCs were significantly correlated with c-IMT (p<0.0001; r=0.3), PWV (p<0.0001; r=0.4) and arterial distensibility (p=0.002; r=-0.1). DUS-based CALCs is highly correlated with other validated markers of subclinical atherosclerosis, such as c-IMT and AS. Our results demonstrated the ability of CALCs to identify individual predictive factors beyond the traditional risk factors by quantifying an interesting and novel step of the atherogenic process. Future studies on larger series and with adequate follow up are necessary to confirm these results and

MiR-29-mediated elastin down-regulation contributes to inorganic phosphorus-induced osteoblastic differentiation in vascular smooth muscle cells.

PubMed

Sudo, Ryo; Sato, Fumiaki; Azechi, Takuya; Wachi, Hiroshi

2015-12-01

Vascular calcification increases the risk of cardiovascular mortality. We previously reported that expression of elastin decreases with progression of inorganic phosphorus (Pi)-induced vascular smooth muscle cell (VSMC) calcification. However, the regulatory mechanisms of elastin mRNA expression during vascular calcification remain unclear. MicroRNA-29 family members (miR-29a, b and c) are reported to mediate elastin mRNA expression. Therefore, we aimed to determine the effect of miR-29 on elastin expression and Pi-induced vascular calcification. Calcification of human VSMCs was induced by Pi and evaluated measuring calcium deposition. Pi stimulation promoted Ca deposition and suppressed elastin expression in VSMCs. Knockdown of elastin expression by shRNA also promoted Pi-induced VSMC calcification. Elastin pre-mRNA measurements indicated that Pi stimulation suppressed elastin expression without changing transcriptional activity. Conversely, Pi stimulation increased miR-29a and miR-29b expression. Inhibition of miR-29 recovered elastin expression and suppressed calcification in Pi-treated VSMCs. Furthermore, over-expression of miR-29b promoted Pi-induced VSMC calcification. RT-qPCR analysis showed knockdown of elastin expression in VSMCs induced expression of osteoblast-related genes, similar to Pi stimulation, and recovery of elastin expression by miR-29 inhibition reduced their expression. Our study shows that miR-29-mediated suppression of elastin expression in VSMCs plays a pivotal role in osteoblastic differentiation leading to vascular calcification. © 2015 The Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

Magnesium prevents phosphate-induced vascular calcification via TRPM7 and Pit-1 in an aortic tissue culture model.

PubMed

Sonou, Tomohiro; Ohya, Masaki; Yashiro, Mitsuru; Masumoto, Asuka; Nakashima, Yuri; Ito, Teppei; Mima, Toru; Negi, Shigeo; Kimura-Suda, Hiromi; Shigematsu, Takashi

2017-06-01

Previous clinical and experimental studies have indicated that magnesium may prevent vascular calcification (VC), but mechanistic characterization has not been reported. This study investigated the influence of increasing magnesium concentrations on VC in a rat aortic tissue culture model. Aortic segments from male Sprague-Dawley rats were incubated in serum-supplemented high-phosphate medium for 10 days. The magnesium concentration in this medium was increased to demonstrate its role in preventing VC, which was assessed by imaging and spectroscopy. The mineral composition of the calcification was analyzed using Fourier transform infrared (FTIR) spectroscopic imaging, scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) mapping. Magnesium supplementation of high-phosphate medium dose-dependently suppressed VC (quantified as aortic calcium content), and almost ablated it at 2.4 mm magnesium. The FTIR images and SEM-EDX maps indicated that the distribution of phosphate (as hydroxyapatite), phosphorus and Mg corresponded with calcium content in the aortic ring and VC. The inhibitory effect of magnesium supplementation on VC was partially reduced by 2-aminoethoxy-diphenylborate, an inhibitor of TRPM7. Furthermore, phosphate transporter-1 (Pit-1) protein expression was increased in tissues cultured in HP medium and was gradually-and dose dependently-decreased by magnesium. We conclude that a mechanism involving TRPM7 and Pit-1 underpins the magnesium-mediated reversal of high-phosphate-associated VC.

Technetium-99m and rhenium-188 complexes with one and two pendant bisphosphonate groups for imaging arterial calcification.

PubMed

Bordoloi, Jayanta Kumar; Berry, David; Khan, Irfan Ullah; Sunassee, Kavitha; de Rosales, Rafael Torres Martin; Shanahan, Catherine; Blower, Philip J

2015-03-21

The first (99m)Tc and (188)Re complexes containing two pendant bisphosphonate groups have been synthesised, based on the mononuclear M(v) nitride core with two dithiocarbamate ligands each with a pendant bisphosphonate. The structural identity of the (99)Tc and stable rhenium analogues as uncharged, mononuclear nitridobis(dithiocarbamate) complexes was determined by electrospray mass spectrometry. The (99m)Tc complex showed greater affinity for synthetic and biological hydroxyapatite, and greater stability in biological media, than the well-known but poorly-characterised and inhomogeneous bone imaging agent (99m)Tc-MDP. It gave excellent SPECT images of both bone calcification (mice and rats) and vascular calcification (rat model), but the improved stability and the availability of two pendant bisphosphonate groups conferred no dramatic advantage in imaging over the conventional (99m)Tc-MDP agent in which the bisphosphonate group is bound directly to Tc. The (188)Re complex also showed preferential uptake in bone. These tracers and the biological model of vascular calcification offer the opportunity to study the biological interpretation and clinical potential of radionuclide imaging of vascular calcification and to deliver radionuclide therapy to bone metastases.

Dietary fatty acids on aortic root calcification in mice with metabolic syndrome.

PubMed

Naranjo, Maria C; Bermudez, Beatriz; Garcia, Indara; Lopez, Sergio; Abia, Rocio; Muriana, Francisco J G; Montserrat-de la Paz, Sergio

2017-04-19

Metabolic syndrome (MetS) is associated with obesity, dyslipidemia, type 2 diabetes, and chronic low-grade inflammation. The aim of this study was to determine the role of high-fat low-cholesterol diets (HFLCDs) rich in SFAs (HFLCD-SFAs), MUFAs (HFLCD-MUFAs) or MUFAs plus omega-3 long-chain PUFAs (HFLCD-PUFAs) on vascular calcification by the modulation of the RANKL/RANK/OPG system in the aortic roots of Lep ob/ob LDLR -/- mice. Animals fed with HFLCD-SFAs had increased weight and a greater atheroma plaque size, calcification, and RANKL/CATHK expression in the aortic root than mice on MUFA-enriched diets, with an increasing OPG expression in the aortic roots of the latter. Our study demonstrates that compared to dietary SFAs, MUFAs from olive oil protect against atherosclerosis by interfering with vascular calcification via the RANKL/RANK/OPG system in the setting of MetS. These findings open opportunities for developing novel nutritional strategies with olive oil as the most important dietary source of MUFAs (notably oleic acid) to prevent cardiovascular complications in MetS.

Serum Fetuin-A Levels in Patients with Bilateral Basal Ganglia Calcification.

PubMed

Demiryurek, Bekir Enes; Gundogdu, Asli Aksoy

2018-02-14

The idiopathic basal ganglia calcification (Fahr syndrome) may occur due to senility. Fetuin-A is a negative acute phase reactant which inhibits calcium-phosphorus precipitation and vascular calcification. In this study, we aimed to evaluate whether serum fetuin-A levels correlate with bilateral basal ganglia calcification. Forty-five patients who had bilateral basal ganglia calcification on brain CT were selected according to the inclusion and exclusion criteria, and 45 age and gender-matched subjects without basal ganglia calcification were included for the control group. Serum fetuin-A levels were measured from venous blood samples. All participants were divided into two groups; with and without basal ganglia calcification. These groups were divided into subgroups regarding age (18-32 and 33-45 years of age) and gender (male, female). We detected lower levels of serum fetuin-A in patients with basal ganglia calcification compared with the subjects without basal ganglia calcification. In all subgroups (female, male, 18-32 years and 33-45 years), mean fetuin-A levels were significantly lower in patients with basal ganglia calcification (p = 0.017, p = 0.014, p = 0.024, p = 0.026, p = 0.01 respectively). And statistically significantly lower levels of fetuin-A was found to be correlated with the increasing densities of calcification in the calcified basal ganglia group (p-value: <0.001). Considering the role of fetuin-A in tissue calcification and inflammation, higher serum fetuin-A levels should be measured in patients with basal ganglia calcification. We believe that the measurement of serum fetuin-A may play a role in the prediction of basal ganglia calcification as a biomarker. Copyright © 2017 Elsevier B.V. All rights reserved.

Protective role of Smad6 in inflammation-induced valvular cell calcification

PubMed Central

Li, Xin; Lim, Jina J.; Lu, Jinxiu; Pedego, Taylor M.; Demer, Linda; Tintut, Yin

2016-01-01

Calcific aortic vascular and valvular disease (CAVD) is associated with hyperlipidemia, the effects of which occur through chronic inflammation. Evidence suggests that inhibitory small mothers against decapentaplegic (I-Smads; Smad6 and 7) regulate valve embryogenesis and may serve as a mitigating factor in CAVD. However, whether I-Smads regulate inflammation-induced calcific vasculopathy is not clear. Therefore, we investigated the role of I-Smads in atherosclerotic calcification. Results showed that expression of Smad6, but not Smad7, was reduced in aortic and valve tissues of hyperlipidemic compared with normolipemic mice, while expression of tumor necrosis factor alpha (TNF-a) was upregulated. To test whether the effects are in response to inflammatory cytokines, we isolated murine aortic valve leaflets and cultured valvular interstitial cells (mVIC) from the normolipemic mice. By immunochemistry, mVICs were strongly positive for vimentin, weakly positive for smooth muscle alpha actin, and negative for an endothelial cell marker. TNF-a upregulated alkaline phosphatase (ALP) activity and matrix mineralization in mVICs. By gene expression analysis, TNF-a significantly upregulated bone morphogenetic protein 2 (BMP-2) expression while downregulating Smad6 expression. Smad7 expression was not significantly affected. To further test the role of Smad6 on TNF-a-induced valvular cell calcification, we knocked down Smad6 expression using lentiviral transfection. In cells transfected with Smad6 shRNA, TNF-a further augmented ALP activity, expression of BMP-2, Wnt- and redox-regulated genes, and matrix mineralization compared with the control cells. These findings suggest that TNF-a induces valvular and vascular cell calcification, in part, by specifically reducing the expression of a BMP-2 signaling inhibitor, Smad6. PMID:25864564

Gene expression analysis in calcific tendinopathy of the rotator cuff.

PubMed

Oliva, F; Barisani, D; Grasso, A; Maffulli, N

2011-06-20

We evaluated the expression of several genes involved in tissue remodelling and bone development in patients with calcific tendinopathy of the rotator cuff. Biopsies from calcified and non-calcified areas were obtained from 10 patients (8 women and 2 men; average age: 55 years; range: 40-68) with calcific tendinopathy of the rotator cuff. To evaluate the expression of selected genes, RNA extraction, cDNA synthesis and quantitative polymerase chain reaction (PCR) were performed. A significantly increased expression of tissue transglutaminase (tTG)2 and its substrate, osteopontin, was detected in the calcific areas compared to the levels observed in the normal tissue from the same subject with calcific tendinopathy, whereas a modest increase was observed for catepsin K. There was also a significant decrease in mRNA expression of Bone Morphogenetic Protein (BMP)4 and BMP6 in the calcific area. BMP-2, collagen V and vascular endothelial growth factor (VEGF) did not show significant differences. Collagen X and matrix metalloproteinase (MMP)-9 were not detectable. A variation in expression of these genes could be characteristic of this form tendinopathy, since an increased level of these genes has not been detected in other forms of tendon lesions.

Magnesium intake is inversely associated with coronary artery calcification: the Framingham Heart Study

USDA-ARS?s Scientific Manuscript database

OBJECTIVES: The aim of this study was to examine whether magnesium intake is associated with coronary artery calcification (CAC) and abdominal aortic calcification (AAC). BACKGROUND: Animal and cell studies suggest that magnesium may prevent calcification within atherosclerotic plaques underlying c...

Automated aortic calcification detection in low-dose chest CT images

NASA Astrophysics Data System (ADS)

Xie, Yiting; Htwe, Yu Maw; Padgett, Jennifer; Henschke, Claudia; Yankelevitz, David; Reeves, Anthony P.

2014-03-01

The extent of aortic calcification has been shown to be a risk indicator for vascular events including cardiac events. We have developed a fully automated computer algorithm to segment and measure aortic calcification in low-dose noncontrast, non-ECG gated, chest CT scans. The algorithm first segments the aorta using a pre-computed Anatomy Label Map (ALM). Then based on the segmented aorta, aortic calcification is detected and measured in terms of the Agatston score, mass score, and volume score. The automated scores are compared with reference scores obtained from manual markings. For aorta segmentation, the aorta is modeled as a series of discrete overlapping cylinders and the aortic centerline is determined using a cylinder-tracking algorithm. Then the aortic surface location is detected using the centerline and a triangular mesh model. The segmented aorta is used as a mask for the detection of aortic calcification. For calcification detection, the image is first filtered, then an elevated threshold of 160 Hounsfield units (HU) is used within the aorta mask region to reduce the effect of noise in low-dose scans, and finally non-aortic calcification voxels (bony structures, calcification in other organs) are eliminated. The remaining candidates are considered as true aortic calcification. The computer algorithm was evaluated on 45 low-dose non-contrast CT scans. Using linear regression, the automated Agatston score is 98.42% correlated with the reference Agatston score. The automated mass and volume score is respectively 98.46% and 98.28% correlated with the reference mass and volume score.

Survival of Atherosclerotic Calcifications in Skeletonized Material: Forensic and Pathological Implications.

PubMed

Biehler-Gomez, Lucie; Cappella, Annalisa; Castoldi, Elisa; Martrille, Laurent; Cattaneo, Cristina

2018-03-01

Atherosclerosis is a chronic inflammatory disease creating calcifying plaques in the arterial walls. Because its paleopathological diagnosis remains little studied on skeletal remains, its impact on forensic and archeological data is completely underestimated. Here, 24 skeletal remains from the Milano Cemetery Skeletal Collection have been studied to evaluate the chance of atherosclerotic calcification survival, retrieval, and identification. Through direct comparison with a known autopsy collection and literature, the identification and categorization of several types of calcifications were performed. Clothing elements such as tights or socks played a definitive role in the preservation of the calcifications; hence they are more likely to be found in forensic cases than in archeological ones. Therefore, vascular calcifications are possible to collect and identify in skeletal remains if sufficient care is given to their recovery. Consequently and as markers of the disease, such identification can provide valuable pathological information for forensic and archeological cases. © 2017 American Academy of Forensic Sciences.

Protective Role of Smad6 in Inflammation-Induced Valvular Cell Calcification.

PubMed

Li, Xin; Lim, Jina; Lu, Jinxiu; Pedego, Taylor M; Demer, Linda; Tintut, Yin

2015-10-01

Calcific aortic vascular and valvular disease (CAVD) is associated with hyperlipidemia, the effects of which occur through chronic inflammation. Evidence suggests that inhibitory small mothers against decapentaplegic (I-Smads; Smad6 and 7) regulate valve embryogenesis and may serve as a mitigating factor in CAVD. However, whether I-Smads regulate inflammation-induced calcific vasculopathy is not clear. Therefore, we investigated the role of I-Smads in atherosclerotic calcification. Results showed that expression of Smad6, but not Smad7, was reduced in aortic and valve tissues of hyperlipidemic compared with normolipemic mice, while expression of tumor necrosis factor alpha (TNF-α) was upregulated. To test whether the effects are in response to inflammatory cytokines, we isolated murine aortic valve leaflets and cultured valvular interstitial cells (mVIC) from the normolipemic mice. By immunochemistry, mVICs were strongly positive for vimentin, weakly positive for smooth muscle α actin, and negative for an endothelial cell marker. TNF-α upregulated alkaline phosphatase (ALP) activity and matrix mineralization in mVICs. By gene expression analysis, TNF-α significantly upregulated bone morphogenetic protein 2 (BMP-2) expression while downregulating Smad6 expression. Smad7 expression was not significantly affected. To further test the role of Smad6 on TNF-α-induced valvular cell calcification, we knocked down Smad6 expression using lentiviral transfection. In cells transfected with Smad6 shRNA, TNF-α further augmented ALP activity, expression of BMP-2, Wnt- and redox-regulated genes, and matrix mineralization compared with the control cells. These findings suggest that TNF-α induces valvular and vascular cell calcification, in part, by specifically reducing the expression of a BMP-2 signaling inhibitor, Smad6. © 2015 Wiley Periodicals, Inc.

Side-Specific Endothelial-Dependent Regulation of Aortic Valve Calcification

PubMed Central

Richards, Jennifer; El-Hamamsy, Ismail; Chen, Si; Sarang, Zubair; Sarathchandra, Padmini; Yacoub, Magdi H.; Chester, Adrian H.; Butcher, Jonathan T.

2014-01-01

Arterial endothelial cells maintain vascular homeostasis and vessel tone in part through the secretion of nitric oxide (NO). In this study, we determined how aortic valve endothelial cells (VEC) regulate aortic valve interstitial cell (VIC) phenotype and matrix calcification through NO. Using an anchored in vitro collagen hydrogel culture system, we demonstrate that three-dimensionally cultured porcine VIC do not calcify in osteogenic medium unless under mechanical stress. Co-culture with porcine VEC, however, significantly attenuated VIC calcification through inhibition of myofibroblastic activation, osteogenic differentiation, and calcium deposition. Incubation with the NO donor DETA-NO inhibited VIC osteogenic differentiation and matrix calcification, whereas incubation with the NO blocker l-NAME augmented calcification even in 3D VIC–VEC co-culture. Aortic VEC, but not VIC, expressed endothelial NO synthase (eNOS) in both porcine and human valves, which was reduced in osteogenic medium. eNOS expression was reduced in calcified human aortic valves in a side-specific manner. Porcine leaflets exposed to the soluble guanylyl cyclase inhibitor ODQ increased osteocalcin and α-smooth muscle actin expression. Finally, side-specific shear stress applied to porcine aortic valve leaflet endothelial surfaces increased cGMP production in VEC. Valve endothelial-derived NO is a natural inhibitor of the early phases of valve calcification and therefore may be an important regulator of valve homeostasis and pathology. PMID:23499458

Direct comparison of regulators of calcification between bone and vessels in humans.

PubMed

Schweighofer, N; Aigelsreiter, A; Trummer, O; Graf-Rechberger, M; Hacker, N; Kniepeiss, D; Wagner, D; Stiegler, P; Trummer, C; Pieber, T; Obermayer-Pietsch, B; Müller, H

2016-07-01

Calcification is not only physiologically present in bone but is a main pathophysiological process in vasculature, favouring cardiovascular diseases. Our aim was to investigate changes in the expression of calcification regulators during vascular calcification in bone and vasculature. Levels of gene expression of osteoprotegerin (OPG), receptor activator of NF-κB ligand (RANKL), osteopontin (OPN), matrix gla protein (MGP), bone sialoprotein (BSP), SMAD6, and runt-related transcription factor 2 (RUNX2) were determined in bone, aorta, and external iliac artery tissue samples of transplant donors. Histological stages of atherosclerosis (AS) in vessels are defined as "no changes", "intima thickening", or "intima calcification". Patients' bone samples were subgrouped accordingly. We demonstrate that in vessels BSP and OPN expression significantly increased during intima thickening and decreased during intima calcification, whereas the expression of regulators of calcification did not significantly change in bone during intima thickening and intima calcification. At the stage of intima thickening, MGP, OPG, and SMAD6 expression and at stage of intima calcification only MGP expression was lower in bone than in vessel. The expression of BSP and RANKL was regulated in opposite ways in bone and vessels, whereas the expression of MGP, OC, RUNX2, and OPN was regulated in a tissue-specific manner. Our study is the first direct comparison of gene expression changes during AS progression in bone and vessels. Our results indicate that changes in the expression of regulators of calcification in the vessel wall as well as in bone occur early in the calcification process, even prior to deposition of calcium/phosphate precipitation. Copyright © 2016. Published by Elsevier Inc.

Calcified telangiectatic hyperplastic nodule associated with vascular malformation in a child: a case report.

PubMed

Marti, Josep; Trivedi, Anshu; D'Alessandro, Valentina; Roayaie, Sasan; Rosen, Ally; Arnon, Ronen; Thung, Swan

2015-04-01

This is a case report of an asymptomatic 4-year-old girl who was found to have a nodule at the lateral left lobe of the liver. She underwent transabdominal liver ultrasound and abdominal MRI that showed calcification and intense arterial enhancement but they failed to clearly exclude malignancy. The patient underwent an unremarkable laparoscopic wedge liver resection of the lesion because of its location and size. Pathological examination showed features compatible with a benign telangiectatic hyperplastic nodule with vascular malformation and calcification. CD34 immunostained the proliferative vascular lining cells while CK7 and CK19 highlighted the normal bile ducts present within the lesion. The diagnosis of a telangiectatic hyperplastic nodule associated with vascular malformation has been scarcely reported in children and our case shows for the first time that it can also present with calcifications.

Policosanol as a new inhibitor candidate for vascular calcification in diabetic hyperlipidemic rats.

PubMed

Elseweidy, Mohamed M; Zein, Nabila; Aldhamy, Samih E; Elsawy, Marwa M; Saeid, Saeid A

2016-11-01

This work mainly aimed to investigate the probable changes of aortic calcification by policosanol, omega-3 fatty acids in comparison with atorvastatin and subsequent progression of atherosclerosis in diabetic hyperlipemic rat model. Adult male albino rats of wistar strain (30) were divided into five groups (n = 6/group); one was fed normal diet and was used as a normal group, the other groups received alloxan, atherogenic diet (CCT - rat chow diet supplemented with 4% cholesterol, 1% cholic acid, and 0.5% thiouracil) and categorized as follows: the second group received no treatment and kept as control (diabetic hyperlipidemic control group (DHC)). The other groups received daily oral doses of atorvastatin, policosanol (10 mg/kg body weight) and ω-3 (50 mg/kg body weight), respectively, for eight weeks. Different biomarkers were used for the evaluation that included inflammatory (C reactive protein (CRP), tumor necrosis factor α (TNF-α)), oxidative stress (glutathione (GSH), malondialdehyde (MDA)) bone calcification markers (alkaline phosphatase (ALP), Vitamin D, parathyroid hormone (PTH)), lipogram pattern in addition to histochemical demonstration of calcium in the aorta. Diabetic hyperlipemic group demonstrated significant hyperglycemia, hyperlipidemia, and increased inflammation, oxidative stress, calcification, and finally atherogenesis progression. Treatment of diabetic hyperlipemic rats with, policosanol, omega-3 fatty acids (natural products) and atorvastatin for eight weeks significantly increased high-density lipoprotein cholesterol (HDL-C), Vitamin D, decreased aortic vacuoles number, and inhibited calcification process. Policosanol induced more remarkable reduction in the density and number of foam cells and improved the intimal lesions of the aorta as compared to atorvastatin. Drugs under study exerted hypoglycemic effect along with an inhibition of inflammation, oxidative stress, and calcium deposition with certain variations but

Calcium intake is not associated with increased coronary artery calcification: The Framingham Study

USDA-ARS?s Scientific Manuscript database

Adequate calcium intake is known to protect the skeleton. However, studies that have reported adverse effects of calcium supplementation on vascular events have raised widespread concern. We assessed the association between calcium intake (from diet and supplements) and coronary artery calcification...

Vascular Damage and Kidney Transplant Outcomes: An Unfriendly and Harmful Link.

PubMed

Hernández, Domingo; Triñanes, Javier; Armas, Ana María; Ruiz-Esteban, Pedro; Alonso-Titos, Juana; Duarte, Ana; González-Molina, Miguel; Palma, Eulalia; Salido, Eduardo; Torres, Armando

2017-07-01

Kidney transplant (KT) is the treatment of choice for most patients with chronic kidney disease, but this has a high cardiovascular mortality due to traditional and nontraditional risk factors, including vascular calcification. Inflammation could precede the appearance of artery wall lesions, leading to arteriosclerosis and clinical and subclinical atherosclerosis in these patients. Additionally, mineral metabolism disorders and activation of the renin-angiotensin system could contribute to this vascular damage. Thus, understanding the vascular lesions that occur in KT recipients and the pathogenic mechanisms involved in their development could be crucial to optimize the therapeutic management and outcomes in survival of this population. This review focuses on the following issues: (1) epidemiological data framing the problem; (2) atheromatosis in KT patients: subclinical and clinical atheromatosis, involving ischemic heart disease, congestive heart failure, stroke and peripheral vascular disease; (3) arteriosclerosis and vascular calcifications; and (4) potential pathogenic mechanisms and their therapeutic targets. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Periodontal Disease Is an Independent Predictor of Intracardiac Calcification

PubMed Central

Pressman, Gregg S.; Qasim, Atif; Verma, Nitin; Arishiro, Kumiko; Notohara, Yasuhiro; Crudu, Vitalie; Figueredo, Vincent M.

2013-01-01

Background. Periodontitis is the most common chronic inflammatory condition worldwide and is associated with incident coronary disease. Hypothesis. We hypothesized that periodontal disease would also be associated with cardiac calcification, a condition which shares many risk factors with atherosclerosis and is considered a marker of subclinical atherosclerosis. Methods. Cross-sectional study at two sites (USA and Japan) involving subjects with both clinical echocardiograms and detailed dental examinations. Semiquantitative scoring systems were used to assess severity of periodontal disease and echocardiographic calcification. Results. Fifty-six of 73 subjects (77%) had cardiac calcifications, and 51% had moderate to severe periodontal disease (score > 2). In unadjusted analysis, a significant relationship between periodontal score and cardiac calcification (Spearman rho = 0.4, P = 0.001) was noted, with increases in mean calcification score seen across increasing levels of periodontal disease. On multivariate logistic regression, adjusted for age, gender, race, glomerular filtration rate, and traditional risk factors, this association remained significant (P = 0.024). There was no significant interaction by study site, race, or gender. Conclusions. In a multiracial population, we found a significant association between the degree of periodontal disease, a chronic inflammatory condition, and cardiac calcification. Further, higher periodontal scores were associated with greater degrees of calcification. PMID:24106721

Inverse relationship between body mass index and coronary artery calcification in patients with clinically significant coronary lesions.

PubMed

Kovacic, Jason C; Lee, Paul; Baber, Usman; Karajgikar, Rucha; Evrard, Solene M; Moreno, Pedro; Mehran, Roxana; Fuster, Valentin; Dangas, George; Sharma, Samin K; Kini, Annapoorna S

2012-03-01

Mounting data support a 'calcification paradox', whereby reduced bone mineral density is associated with increased vascular calcification. Furthermore, reduced bone mineral density is prevalent in older persons with lower body mass index (BMI). Therefore, although BMI and coronary artery calcification (CAC) exhibit a positive relationship in younger persons, it is predicted that in older persons and/or those at risk for osteoporosis, an inverse relationship between BMI and CAC may apply. We sought to explore this hypothesis in a large group of patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). We accessed our single-center registry for 07/01/1999 to 06/30/2009, extracting data on all patients that underwent PCI. To minimize bias we excluded those at the extremes of age or BMI and non-Black/Hispanic/Caucasians, leaving 9993 study subjects (age 66.6±9.9 years). Index lesion calcification (ILC) was analyzed with respect to BMI. Comparing index lesions with no angiographic calcification to those with the most severe, mean BMI decreased by 1.11 kgm(-2); a reduction of 3.9% (P<0.0001). By multivariable modeling, BMI was an independent inverse predictor of moderate-severe ILC (m-sILC; odds ratio [OR] 0.967, 95% CI 0.953-0.980, P<0.0001). Additional fully adjusted models identified that, compared to those with normal BMI, obese patients had an OR of 0.702 for m-sILC (95% CI 0.596-0.827, P<0.0001). In a large group of PCI patients, we identified an inverse correlation between BMI and index lesion calcification. These associations are consistent with established paradigms and suggest a complex interrelationship between BMI, body size and vascular calcification. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Vitamin K2 can suppress the expression of Toll-like receptor 2 (TLR2) and TLR4, and inhibit calcification of aortic intima in ApoE-/- mice as well as smooth muscle cells.

PubMed

Wang, Zhaojun; Wang, Zhongqun; Zhu, Jie; Long, Xinguang; Yan, Jinchuan

2018-02-01

Background and objectives Vascular calcification is a common complication in atherosclerosis. Accumulating evidence showed that Toll-like receptors (TLRs) mediate pro-inflammatory and atherosclerosis. Recent studies demonstrated that vascular calcification is one of the detrimental effects of vitamin K (Vit K) antagonists. However, the effects of Vit K on the expression of TLR2 and 4 and intimal calcification in artery remained unidentified. Methods and results Eighteen ApoE -/- mice were randomly divided into model group, Vit K-treated group, and control group. The mice of model and Vit K-treated group were fed with high-fat diet, while control group mice were fed with normal diet. Mice of Vit K-treated group were administered orally with vitamin K2 (40 mg.kg -1 .day -1 ) for 12 weeks. Twelve weeks later the aortic sections of mice were acquired and stained with hematoxylin and eosin and von Kossa, respectively. Calcium content and activity of alkaline phosphatase (ALP) at aortic tissues were measured. The expression levels of TLR2 and TLR4 in aorta sections were detected by immunohistochemisty and RT-PCR, respectively. The effects of Vit K on cellular calcification were further studied in A7r5 SMCs. Results demonstrated that high-fat diet induced typical atherosclerosis with intimal calcification in ApoE -/- mice, while in Vit K-treated group atherosclerosis and calcium deposits were not serious; Vit K2 also inhibited cellular calcification in A7r5 SMCs. Quantitative analysis showed that calcium and ALP activity at aortic tissues in the Vit K-treated mice were significantly lower than that of the model group ( P < 0.01); Compared to the control group, the expression levels of TLR2 and TLR4 in the model group were significantly higher ( P < 0.05), while in Vit K-treated group the levels of TLR2 and 4 were significantly lower than that in the model group. Furthermore, the content of calcium was positively related to the expression levels of TLR2 and TLR4

Rectus Femoris Tendon Calcification

PubMed Central

Zini, Raul; Panascì, Manlio; Papalia, Rocco; Franceschi, Francesco; Vasta, Sebastiano; Denaro, Vincenzo

2014-01-01

Background: Since it was developed, hip arthroscopy has become the favored treatment for femoroacetabular impingement. Due to recent considerable improvements, the indications for this technique have been widely extended. Injuries of the rectus femoris tendon origin, after an acute phase, could result in a chronic tendinopathy with calcium hydroxyapatite crystal deposition, leading to pain and loss of function. Traditionally, this condition is addressed by local injection of anesthetic and corticosteroids or, when conservative measures fail, by open excision of the calcific lesion by an anterior approach. Purpose: To assess whether arthroscopic excision of calcification of the proximal rectus is a safe and effective treatment. Study Design: Case series; Level of evidence, 4. Methods: Outcomes were studied from 6 top amateur athletes (age range, 30-43 years; mean, 32.6 years) affected by calcification of the proximal rectus who underwent arthroscopic excision of the calcification. Patients were preoperatively assessed radiographically, and diagnosis was confirmed by a 3-dimensional computed tomography scan. To evaluate the outcome, standardized hip rating scores were used pre- and postoperatively (at 6 and 12 months): the Hip disability and Osteoarthritis Outcome Score, Oxford Hip Score, and Modified Harris Hip Score. Moreover, visual analog scales (VAS) for pain, sport activity level (SAL), and activities of daily living (ADL) were also used. Results: One year after surgery, all patients reported satisfactory outcomes, with 3 of 6 rating their return-to-sport level as high as preinjury level, and the remaining 3 with a percentage higher than 80%. Five patients ranked their ability to carry on daily activities at 100%. Statistical analysis showed significant improvement of the Oxford Hip Score, the Modified Harris Hip Score, and all 3 VAS subscales (pain, SAL, and ADL) from pre- to latest postoperative assessment (P < .05). Conclusion: Arthroscopic excision of

Effects of the Use of Non-Calcium Phosphate Binders in the Control and Outcome of Vascular Calcifications: A Review of Clinical Trials on CKD Patients

PubMed Central

Bolasco, Piergiorgio

2011-01-01

Vascular calcifications produce a high impact on morbidity and mortality rates in patients affected by chronic kidney disease and mineral bone disorder (CKD-MBD). Effects are manifested from the more advanced stages of CKD (stages 3-4), particularly in patients undergoing dialysis (CKD5D). In recent years, a large number of therapeutic options have been successfully used in the treatment of secondary hyperparathyroidism (SHPT), despite eliciting less marked effects on nonbone calcifications associated with CKD-MBD. In addition to the use of Vitamin D and analogues, more recently treatment with calcimimetic drugs has also been undertaken. The present paper aims to analyze comparative and efficacy studies undertaken to assess particularly the impact on morbidity and mortality rates of non-calcium phosphate binders. Moreover, the mechanism of action underlying the depositing of calcium and phosphate along blood vessel walls, irrespective of the specific contribution provided in reducing the typical phosphate levels observed in CKD largely at more advanced stages of the disease, will be investigated. The aim of this paper therefore is to evaluate which phosphate binders are characterised by the above action and the mechanisms through which these are manifested. PMID:21716706

Effects of the Use of Non-Calcium Phosphate Binders in the Control and Outcome of Vascular Calcifications: A Review of Clinical Trials on CKD Patients.

PubMed

Bolasco, Piergiorgio

2011-01-01

Vascular calcifications produce a high impact on morbidity and mortality rates in patients affected by chronic kidney disease and mineral bone disorder (CKD-MBD). Effects are manifested from the more advanced stages of CKD (stages 3-4), particularly in patients undergoing dialysis (CKD5D). In recent years, a large number of therapeutic options have been successfully used in the treatment of secondary hyperparathyroidism (SHPT), despite eliciting less marked effects on nonbone calcifications associated with CKD-MBD. In addition to the use of Vitamin D and analogues, more recently treatment with calcimimetic drugs has also been undertaken. The present paper aims to analyze comparative and efficacy studies undertaken to assess particularly the impact on morbidity and mortality rates of non-calcium phosphate binders. Moreover, the mechanism of action underlying the depositing of calcium and phosphate along blood vessel walls, irrespective of the specific contribution provided in reducing the typical phosphate levels observed in CKD largely at more advanced stages of the disease, will be investigated. The aim of this paper therefore is to evaluate which phosphate binders are characterised by the above action and the mechanisms through which these are manifested.

The influence of vitamin D analogs on calcification modulators, N-terminal pro-B-type natriuretic peptide and inflammatory markers in hemodialysis patients: a randomized crossover study

PubMed Central

2014-01-01

Background The risk of cardiovascular disease is tremendously high in dialysis patients. Dialysis patients treated with vitamin D analogs show decreased cardiovascular morbidity and mortality compared with untreated patients. We examined the influence of two common vitamin D analogs, alfacalcidol and paricalcitol, on important cardiovascular biomarkers in hemodialysis patients. Anti-inflammatory effects and the influence on regulators of vascular calcification as well as markers of heart failure were examined. Methods In 57 chronic hemodialysis patients enrolled in a randomized crossover trial comparing paricalcitol and alfacalcidol, we examined the changes in osteoprotegerin, fetuin-A, NT-proBNP, hs-Crp, IL-6 and TNF-α, during 16 weeks of treatment. Results NT-proBNP and osteoprotegerin increased comparably in the paricalcitol and alfacalcidol-treated groups. Fetuin-A increased significantly in the alfacalcidol-treated group compared with the paricalcitol-treated group (difference 32.84 μmol/l (95% C.I.; range 0.21–67.47)) during the first treatment period. No difference was found between the groups during the second treatment period, and IL-6, TNF-α and hs-Crp were unchanged in both treatment groups. Conclusions Paricalcitol and alfacalcidol modulate regulators of vascular calcification. Alfacalcidol may increase the level of the calcification inhibitor fetuin-A. We did not find any anti-inflammatory effect or difference in changes of NT-proBNP. Trial registry ClinicalTrials.gov NCT00469599 May 3 2007. PMID:25112372

Association between vascular calcification scores on plain radiographs and fatty acid contents of erythrocyte membrane in hemodialysis patients.

PubMed

Son, Young K; Lee, Su M; Kim, Seong E; Kim, Ki H; Lee, Seon Y; Bae, Hae R; Han, Jin Y; Park, Yongsoon; An, Won S

2012-01-01

Vascular calcification (VC) scores determined by using simple plain radiographic films are known to be associated with coronary artery disease and mortality in patients undergoing hemodialysis (HD). Omega-3 fatty acid (FA) has been shown to reduce ectopic calcifications in an animal model, and it has also been shown that erythrocyte membrane omega-3 FA content is an independent discriminator of coronary artery disease. The present study was designed to demonstrate relations between VC scores and erythrocyte membrane FA contents in patients undergoing HD. A cross-sectional study was carried out. The study was carried out at an outpatient hemodialysis unit at Dong-A University Hospital, Busan, Republic of Korea. A total of 31 patients undergoing HD were recruited. Patients with significant malnutrition, a short duration of dialysis (<12 months), a history of recent infection, malignancy, or liver disease were excluded. Plain radiographic films of the feet, hands, pelvis, and lateral lumbar spine were examined and VC scores were determined using previously reported methods. Erythrocyte membrane FA contents were analyzed by gas chromatography. The erythrocyte membrane contents of eicosapentaenoic acid and docosahexaenoic acid were not found to be related with VC on simple plain radiographic films. However, erythrocyte membrane contents of oleic acid and total monounsaturated FA (MUFA) were significantly higher in patients with significant VC scores. Furthermore, erythrocyte membrane contents of MUFA and oleic acid were found to be negatively associated with high-density lipoprotein cholesterol level and positively associated with triglyceride level. Erythrocyte membrane contents of MUFA and oleic acid were found to be associated with VC scores determined using plain radiographs and with dyslipidemia in patients undergoing HD. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Inflammation disrupts the LDL receptor pathway and accelerates the progression of vascular calcification in ESRD patients.

PubMed

Liu, Jing; Ma, Kun Ling; Gao, Min; Wang, Chang Xian; Ni, Jie; Zhang, Yang; Zhang, Xiao Liang; Liu, Hong; Wang, Yan Li; Liu, Bi Cheng

2012-01-01

Chronic inflammation plays a crucial role in the progression of vascular calcification (VC). This study was designed to investigate whether the low-density lipoprotein receptor (LDLr) pathway is involved in the progression of VC in patients with end-stage renal disease (ESRD) during inflammation. Twenty-eight ESRD patients were divided into control and inflamed groups according to plasma C-reactive protein (CRP) level. Surgically removed tissues from the radial arteries of patients receiving arteriovenostomy were used in the experiments. The expression of tumour necrosis factor-α (TNF-α) and monocyte chemotactic protein-1 (MCP-1) of the radial artery were increased in the inflamed group. Hematoxylin-eosin and alizarin red S staining revealed parallel increases in foam cell formation and calcium deposit formation in continuous cross-sections of radial arteries in the inflamed group compared to the control, which were closely correlated with increased LDLr, sterol regulatory element binding protein-2 (SREBP-2), bone morphogenetic proteins-2 (BMP-2), and collagen I protein expression, as shown by immunohistochemical and immunofluorescent staining. Confocal microscopy confirmed that inflammation enhanced the translocation of the SREBP cleavage-activating protein (SCAP)/SREBP-2 complex from the endoplasmic reticulum to the Golgi, thereby activating LDLr gene transcription. Inflammation increased alkaline phosphatase protein expression and reduced α-smooth muscle actin protein expression, contributing to the conversion of the vascular smooth muscle cells in calcified vessels from the fibroblastic to the osteogenic phenotype; osteogenic cells are the main cellular components involved in VC. Further analysis showed that the inflammation-induced disruption of the LDLr pathway was significantly associated with enhanced BMP-2 and collagen I expression. Inflammation accelerated the progression of VC in ESRD patients by disrupting the LDLr pathway, which may represent a

Phosphate toxicity and vascular mineralization.

PubMed

Razzaque, Mohammed S

2013-01-01

Vascular calcification or mineralization is a major complication seen in patients with advanced stages of chronic kidney disease (CKD), and it is associated with markedly increased morbidity and mortality. Most of the CKD-related vascular mineralization is attributable to abnormal mineral ion metabolism. Elevated serum calcium and phosphate levels, along with increased calcium-phosphorus byproduct, and the use of active vitamin D metabolites are thought to be the predisposing factors for developing vascular mineralization in patients with CKD. Recent experimental studies have shown that vascular mineralization can be suppressed by reducing serum phosphate levels, even in the presence of extremely high serum calcium and 1,25-dihydroxyvitamin D levels, indicating that reducing 'phosphate toxicity' should be the important therapeutic priority in CKD patients for minimizing the risk of developing vascular mineralization and the disease progression. Copyright © 2013 S. Karger AG, Basel.

Aortic stiffness and calcification in men in a population-based international study.

PubMed

Sekikawa, Akira; Shin, Chol; Curb, J David; Barinas-Mitchell, Emma; Masaki, Kamal; El-Saed, Aiman; Seto, Todd B; Mackey, Rachel H; Choo, Jina; Fujiyoshi, Akira; Miura, Katsuyuki; Edmundowicz, Daniel; Kuller, Lewis H; Ueshima, Hirotsugu; Sutton-Tyrrell, Kim

2012-06-01

Aortic stiffness, a hallmark of vascular aging, is an independent risk factor of cardiovascular disease and all-cause mortality. The association of aortic stiffness with aortic calcification in middle-aged general population remains unknown although studies in patients with end-stage renal disease or elderly subjects suggest that aortic calcification is an important determinant of aortic stiffness. The goal of this study was to examine the association of aortic calcification and stiffness in multi-ethnic population-based samples of relatively young men. We examined the association in 906 men aged 40-49 (81 Black Americans, 276 Japanese Americans, 258 White Americans and 291 Koreans). Aortic stiffness was measured as carotid-femoral pulse wave velocity (cfPWV) using an automated waveform analyzer. Aortic calcification from aortic arch to iliac bifurcation was evaluated using electron-beam computed tomography. Aortic calcium score was calculated and was categorized into four groups: zero (n=303), 1-100 (n=411), 101-300 (n=110), and 401+ (n=82). Aortic calcification category had a significant positive association with cfPWV after adjusting for age, race, and mean arterial pressure (mean (standard error) of cfPWV (cm/s) from the lowest to highest categories: 836 (10), 850 (9), 877 (17) and 941 (19), P for trend <0.001). The significant positive association remained after further adjusting for other cardiovascular risk factors. The significant positive association was also observed in each race group. The results suggest that aortic calcification can be one mechanism for aortic stiffness and that the association of aortic calcification with stiffness starts as early as the 40s. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Aortic stiffness and calcification in men in a population-based international study

PubMed Central

Sekikawa, Akira; Shin, Chol; Curb, J. David; Barinas-Mitchell, Emma; Masaki, Kamal; El-Saed, Aiman; Seto, Todd B.; Mackey, Rachel H.; Choo, Jina; Fujiyoshi, Akira; Miura, Katsuyuki; Edmundowicz, Daniel; Kuller, Lewis H.; Ueshima, Hirotsugu; Sutton-Tyrrell, Kim

2012-01-01

Objectives Aortic stiffness, a hallmark of vascular aging, is an independent risk factor of cardiovascular disease and all-cause mortality. The association of aortic stiffness with aortic calcification in middle-aged general population remains unknown although studies in patients with end-stage renal disease or elderly subjects suggest that aortic calcification is an important determinant of aortic stiffness. The goal of this study was to examine the association of aortic calcification and stiffness in multi-ethnic population-based samples of relatively young men. Methods We examined the association in 906 men aged 40–49 (81 Black Americans, 276 Japanese Americans, 258 White Americans and 291 Koreans). Aortic stiffness was measured as carotid-femoral pulse wave velocity (cfPWV) using an automated waveform analyzer. Aortic calcification from aortic arch to iliac bifurcation was evaluated using electron-beam computed tomography. Results Aortic calcium score was calculated and was categorized into four groups: zero (n=303), 1–100 (n=411), 101–300 (n=110), and 401+ (n=82). Aortic calcification category had a significant positive association with cfPWV after adjusting for age, race, and mean arterial pressure (mean (standard error) of cfPWV (cm/second) from the lowest to highest categories: 836 (10), 850 (9), 877 (17) and 941 (19), p for trend <0.001). The significant positive association remained after further adjusting for other cardiovascular risk factors. The significant positive association was also observed in each race group. Conclusions The results suggest that aortic calcification can be one mechanism for aortic stiffness and that the association of aortic calcification with stiffness starts as early as the 40’s. PMID:22537531

Peripheral vascular calcification in long-haemodialysis patients: associated factors and survival consequences.

PubMed

Jean, Guillaume; Bresson, Eric; Terrat, Jean-Claude; Vanel, Thierry; Hurot, Jean-Marc; Lorriaux, Christie; Mayor, Brice; Chazot, Charles

2009-03-01

Vascular calcifications (VCs) are frequently observed in chronic kidney disease (CKD) and haemodialysis (HD) patients. They have been associated with numerous factors, particularly hyperphosphataemia, excess calcium load, hypertension and increased mortality rate. The purpose of this study is to measure VCs in long-HD patients with good blood pressure and phosphate control, with the occasional use of sevelamer, using a plain radiological score to identify the associated factors and effects on the 1-year survival rate. We studied HD patients from one centre using a semi-quantitative score ranging from 0 to 3 according to the severity and extent of VCs. The following patients' characteristics were compared according to their VC scores: medical history, treatments, blood pressure, standard biological data, fibroblast growth factor (FGF) 23, osteoprotegerin (OPG), whole PTH, beta-crosslaps, bone alkaline phosphatases and bone mineral density scores. One-year survival analyses were also performed. Among the 250 HD patients of the centre, 161 were studied; the mean age was 67.2 +/- 13 years, 45% of the subjects were females, 35% were diabetics, and they had been on dialysis for between 1-486 months (median: 45 months) with a 3 x 5-3 x 8 h dialysis schedule using 1.5 mmol/l dialysate calcium and providing a mean 2.25 +/- 0.5 Kt/V. Only 17% of the patients were free from VCs and 11% had severe VCs. The factors associated with VCs were classified into 'classic' (age, diabetes, male gender, tobacco use, inflammation, more frequent warfarin treatment and peripheral vascular and cardiac diseases) and 'non-traditional' (higher FGF-23 and OPG serum levels, low albumin serum levels and low alfacalcidol and CaCO(3) use). In logistic regression, only age, diabetes and FGF-23 serum levels were associated with VC scores of 2 and 3. The patients with a score of 3 had a higher 1-year mortality rate (RR 2.1; P = 0.01) as compared to patients with a 0 score. A plain radiological score

Dual-energy digital mammography for calcification imaging: scatter and nonuniformity corrections.

PubMed

Kappadath, S Cheenu; Shaw, Chris C

2005-11-01

Mammographic images of small calcifications, which are often the earliest signs of breast cancer, can be obscured by overlapping fibroglandular tissue. We have developed and implemented a dual-energy digital mammography (DEDM) technique for calcification imaging under full-field imaging conditions using a commercially available aSi:H/CsI:Tl flat-panel based digital mammography system. The low- and high-energy images were combined using a nonlinear mapping function to cancel the tissue structures and generate the dual-energy (DE) calcification images. The total entrance-skin exposure and mean-glandular dose from the low- and high-energy images were constrained so that they were similar to screening-examination levels. To evaluate the DE calcification image, we designed a phantom using calcium carbonate crystals to simulate calcifications of various sizes (212-425 microm) overlaid with breast-tissue-equivalent material 5 cm thick with a continuously varying glandular-tissue ratio from 0% to 100%. We report on the effects of scatter radiation and nonuniformity in x-ray intensity and detector response on the DE calcification images. The nonuniformity was corrected by normalizing the low- and high-energy images with full-field reference images. Correction of scatter in the low- and high-energy images significantly reduced the background signal in the DE calcification image. Under the current implementation of DEDM, utilizing the mammography system and dose level tested, calcifications in the 300-355 microm size range were clearly visible in DE calcification images. Calcification threshold sizes decreased to the 250-280 microm size range when the visibility criteria were lowered to barely visible. Calcifications smaller than approximately 250 microm were usually not visible in most cases. The visibility of calcifications with our DEDM imaging technique was limited by quantum noise, not system noise.

Dual-energy digital mammography for calcification imaging: Scatter and nonuniformity corrections

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kappadath, S. Cheenu; Shaw, Chris C.

Mammographic images of small calcifications, which are often the earliest signs of breast cancer, can be obscured by overlapping fibroglandular tissue. We have developed and implemented a dual-energy digital mammography (DEDM) technique for calcification imaging under full-field imaging conditions using a commercially available aSi:H/CsI:Tl flat-panel based digital mammography system. The low- and high-energy images were combined using a nonlinear mapping function to cancel the tissue structures and generate the dual-energy (DE) calcification images. The total entrance-skin exposure and mean-glandular dose from the low- and high-energy images were constrained so that they were similar to screening-examination levels. To evaluate the DEmore » calcification image, we designed a phantom using calcium carbonate crystals to simulate calcifications of various sizes (212-425 {mu}m) overlaid with breast-tissue-equivalent material 5 cm thick with a continuously varying glandular-tissue ratio from 0% to 100%. We report on the effects of scatter radiation and nonuniformity in x-ray intensity and detector response on the DE calcification images. The nonuniformity was corrected by normalizing the low- and high-energy images with full-field reference images. Correction of scatter in the low- and high-energy images significantly reduced the background signal in the DE calcification image. Under the current implementation of DEDM, utilizing the mammography system and dose level tested, calcifications in the 300-355 {mu}m size range were clearly visible in DE calcification images. Calcification threshold sizes decreased to the 250-280 {mu}m size range when the visibility criteria were lowered to barely visible. Calcifications smaller than {approx}250 {mu}m were usually not visible in most cases. The visibility of calcifications with our DEDM imaging technique was limited by quantum noise, not system noise.« less

Genetics in Arterial Calcification

PubMed Central

Rutsch, Frank; Nitschke, Yvonne; Terkeltaub, Robert

2011-01-01

Artery calcification reflects an admixture of factors such as ectopic osteochondral differentiation with primary host pathological conditions. We review how genetic factors, as identified by human genome-wide association studies, and incomplete correlations with various mouse studies, including knockout and strain analyses, fit into “pieces of the puzzle” in intimal calcification in human atherosclerosis, and artery tunica media calcification in aging, diabetes mellitus, and chronic kidney disease. We also describe in sharp contrast how ENPP1, CD73, and ABCC6 serve as “cogs in a wheel” of arterial calcification. Specifically, each is a minor component in the function of a much larger network of factors that exert balanced effects to promote and suppress arterial calcification. For the network to normally suppress spontaneous arterial calcification, the “cogs” ENPP1, CD73, and ABCC6 must be present and in working order. Monogenic ENPP1, CD73, and ABCC6 deficiencies each drive a molecular pathophysiology of closely related but phenotypically different diseases (generalized arterial calcification of infancy (GACI), pseudoxan-thoma elasticum (PXE) and arterial calcification caused by CD73 deficiency (ACDC)), in which premature onset arterial calcification is a prominent but not the sole feature. PMID:21852556

Cardiomyocyte-specific desmin rescue of desmin null cardiomyopathy excludes vascular involvement.

PubMed

Weisleder, Noah; Soumaka, Elisavet; Abbasi, Shahrzad; Taegtmeyer, Heinrich; Capetanaki, Yassemi

2004-01-01

Mice deficient in desmin, the muscle-specific member of the intermediate filament gene family, display defects in all muscle types and particularly in the myocardium. Desmin null hearts develop cardiomyocyte hypertrophy and dilated cardiomyopathy (DCM) characterized by extensive myocyte cell death, calcific fibrosis and multiple ultrastructural defects. Several lines of evidence suggest impaired vascular function in desmin null animals. To determine whether altered capillary function or an intrinsic cardiomyocyte defect is responsible for desmin null DCM, transgenic mice were generated to rescue desmin expression specifically to cardiomyocytes. Desmin rescue mice display a wild-type cardiac phenotype with no fibrosis or calcification in the myocardium and normalization of coronary flow. Cardiomyocyte ultrastructure is also restored to normal. Markers of hypertrophy upregulated in desmin null hearts return to wild-type levels in desmin rescue mice. Working hearts were perfused to assess coronary flow and cardiac power. Restoration of a wild-type cardiac phenotype in a desmin null background by expression of desmin specifically within cardiomyocyte indicates that defects in the desmin null heart are due to an intrinsic cardiomyocytes defect rather than compromised coronary circulation.

NT5E Mutations and Arterial Calcifications

PubMed Central

St. Hilaire, Cynthia; Ziegler, Shira G.; Markello, Thomas C.; Brusco, Alfredo; Groden, Catherine; Gill, Fred; Carlson-Donohoe, Hannah; Lederman, Robert J.; Chen, Marcus Y.; Yang, Dan; Siegenthaler, Michael P.; Arduino, Carlo; Mancini, Cecilia; Freudenthal, Bernard; Stanescu, Horia C.; Zdebik, Anselm A.; Chaganti, R. Krishna; Nussbaum, Robert L.; Kleta, Robert; Gahl, William A.; Boehm, Manfred

2011-01-01

BACKGROUND Arterial calcifications are associated with increased cardiovascular risk, but the genetic basis of this association is unclear. METHODS We performed clinical, radiographic, and genetic studies in three families with symptomatic arterial calcifications. Single-nucleotide-polymorphism analysis, targeted gene sequencing, quantitative polymerase-chain-reaction assays, Western blotting, enzyme measurements, transduction rescue experiments, and in vitro calcification assays were performed. RESULTS We identified nine persons with calcifications of the lower-extremity arteries and hand and foot joint capsules: all five siblings in one family, three siblings in another, and one patient in a third family. Serum calcium, phosphate, and vitamin D levels were normal. Affected members of Family 1 shared a single 22.4-Mb region of homozygosity on chromosome 6 and had a homozygous nonsense mutation (c.662C→A, p.S221X) in NT5E, encoding CD73, which converts AMP to adenosine. Affected members of Family 2 had a homozygous missense mutation (c.1073G→A, p.C358Y) in NT5E. The proband of Family 3 was a compound heterozygote for c.662C→A and c.1609dupA (p.V537fsX7). All mutations found in the three families result in nonfunctional CD73. Cultured fibroblasts from affected members of Family 1 showed markedly reduced expression of NT5E messenger RNA, CD73 protein, and enzyme activity, as well as increased alkaline phosphatase levels and accumulated calcium phosphate crystals. Genetic rescue experiments normalized the CD73 and alkaline phosphatase activity in patients’ cells, and adenosine treatment reduced the levels of alkaline phosphatase and calcification. CONCLUSIONS We identified mutations in NT5E in members of three families with symptomatic arterial and joint calcifications. This gene encodes CD73, which converts AMP to adenosine, supporting a role for this metabolic pathway in inhibiting ectopic tissue calcification. (Funded by the National Human Genome Research

Association of ectopic fat with abdominal aorto-illiac and coronary artery calcification in african ancestry men.

PubMed

Kuipers, Allison L; Zmuda, Joseph M; Carr, J Jeffrey; Terry, James G; Nair, Sangeeta; Cvejkus, Ryan; Bunker, Clareann H; Patrick, Alan L; Wassel, Christina L; Miljkovic, Iva

2017-08-01

There is strong evidence that fat accumulating in non-adipose sites, "ectopic fat", is associated with cardiovascular disease (CVD), including vascular calcification. Most previous studies of this association have assessed only a single ectopic fat depot. Therefore, our aim was to assess the association of total, regional, and ectopic fat with abdominal aorto-illiac calcification (AAC) and coronary artery calcification (CAC) in 798 African ancestry men. Participants (mean age 62) were from the Tobago Bone Health Study cohort. Adiposity was assessed via clinical examination, dual x-ray absorptiometry, and computed tomography (CT). Ectopic fat depots included: abdominal visceral adipose tissue (VAT), liver attenuation, and calf intermuscular adipose tissue (IMAT). Vascular calcification was assessed by CT and quantified as present versus absent. Associations were tested using multiple logistic regression adjusted for traditional cardiovascular risk factors. Models of ectopic fat were additionally adjusted for total body fat and standing height. All adiposity measures, except VAT, were associated with AAC. Lower liver attenuation or greater calf IMAT was associated with 1.2-1.3-fold increased odds of AAC (p < 0.03 for both), though calf IMAT was a stronger predictor than liver attenuation (p < 0.001) when entered in a single model. No ectopic fat measure was associated with CAC. Greater adiposity in the skeletal muscle and liver, but not in the visceral compartment, was associated with increased odds of AAC in African ancestry men. These results highlight the potential importance of both quantity and location of adiposity accumulation throughout the body. Copyright © 2017 Elsevier B.V. All rights reserved.

[Effects of intermediate conductance calcium-activated potassium channel blocker TARAM-34 on β-glycerophosphate induced vascular smooth muscle cells calcification].

PubMed

Zhang, S L; Xu, J S; Yang, S; Bai, Y L; Zhang, J X; Cui, L W; Yu, Q Y

2016-06-24

To observe the role of TRAM-34 (1-((2-chlorophenyl)diphenylmethyl)-1H-pyrazole), the blocker of intermediate conductance calcium-activated potassium channel (KCa3.1), on β-glycerophosphate induced vascular calcification in vitro. Vascular smooth muscle cells(VSMCs) were obtained from rat thoracic aorta, and VSMCs after the fourth passage and aortic rings were divided into control group (cultured in DMEM with 10% fetal bovine serum), high phosphorus group (cultured in DMEM with 10% fetal bovine serum and 10% β-glycerophosphate) and TRAM-34 group(20 nmol/L TRAM-34 was added into high phosphorus DMEM). Calcium deposition of VSMCs and aortic rings were measured by o-cresolphthalein complexone method.Calcium influx of VSMCs was measured by immunofluorescence probe Fluo-3 AM.The expression of runt-related transcription factor 2(Runx2)was detected by RT-PCR and Western blot for cells and immunohistochemistry for aortic rings.ALP activity was measured by alkaline phosphatase activity detection kit. (1) Compared with control group, calcification was significantly increased in high phosphorus group ((121.67±6.17) mg/g vs. (84.38±8.17) mg/g, P<0.05) and this effect could be attenuated by TRAM-34 ((93.31±11.36) mg/g, P<0.05 vs. high phosphorus group) after 12 days culture. Similar results were found in aortic rings cultured for 12 days-high phosphorus group: (7.17±0.57) mg/g vs. (1.18±0.13) mg/g (P<0.05) and TRAM-34: (4.71±0.42) mg/g, P<0.05 vs. high phosphorus group.(2) Compared with control group, the calcium influx was higher in high phosphorus group (349.22±40.47 vs. 151.67±16.94, P<0.05) and reduced in TRAM-34 group (194.67±22.21, P<0.05 vs. high phosphorus group) in VSMCs simulated for 4 days. (3) Both mRNA and protein expressions of Runx2 in high phosphorus groups were higher than in control group (0.630±0.033 vs.0.340±0.058 and 0.865±0.031 vs.0.414±0.011, both P<0.05) and lower in TRAM-34 group (0.399±0.023 and 0.575±0.014, both P<0.05 vs. high

Prevention of arterial calcification corrects the low bone mass phenotype in MGP-deficient mice.

PubMed

Marulanda, Juliana; Gao, Chan; Roman, Hassem; Henderson, Janet E; Murshed, Monzur

2013-12-01

Matrix gla protein (MGP), a potent inhibitor of extracellular matrix (ECM) mineralization, is primarily produced by vascular smooth muscle cells (VSMCs) and chondrocytes. Consistent with its expression profile, MGP deficiency in mice (Mgp-/- mice) results in extensive mineralization of all arteries and cartilaginous ECMs. Interestingly, we observed a progressive loss of body weight in Mgp-/- mice, which becomes apparent by the third week of age. Taking into account the new paradigm linking the metabolic regulators of energy metabolism and body mass to that of bone remodeling, we compared the bone volume in Mgp-/- mice to that of their wild type littermates by micro-CT and bone histomorphometry. We found a decrease of bone volume over tissue volume in Mgp-/- mice caused by an impaired osteoblast function. In culture, early differentiation of Mgp-/- primary osteoblasts was not affected; however there was a significant upregulation of the late osteogenic marker Bglap (osteocalcin). We examined whether the prevention of arterial calcification in Mgp-/- mice could correct the low bone mass phenotype. The bones of two different genetic models: Mgp-/-;SM22-Mgp and Mgp-/-;Eln+/- mice were analyzed. In the former strain, vascular calcification was fully rescued by transgenic overexpression of Mgp in the VSMCs, while in the latter, elastin haploinsufficiency significantly impeded the deposition of minerals in the arterial walls. In both models, the low mass phenotype seen in Mgp-/- mice was rescued. Our data support the hypothesis that the arterial calcification, not MGP deficiency itself, causes the low bone mass phenotype in Mgp-/- mice. Taken together, we provide evidence that arterial calcification affects bone remodeling and pave the way for further mechanistic studies to identify the pathway(s) regulating this process. © 2013.

Harmful Effects of the Azathioprine Metabolite 6-Mercaptopurine in Vascular Cells: Induction of Mineralization

PubMed Central

Tölle, Markus; Prüfer, Nicole; Höhne, Matthias; Zidek, Walter; van der Giet, Markus

2014-01-01

Vascular mineralization contributes to the high cardiovascular morbidity and mortality in patients who suffer from chronic kidney disease and in individuals who have undergone solid organ transplantation. The immunosuppressive regimen used to treat these patients appears to have an impact on vascular alterations. The effect of 6-mercaptopurine (6-MP) on vascular calcification has not yet been determined. This study investigates the effect of 6-MP on vascular mineralization by the induction of trans-differentiation of rat vascular smooth muscle cells in vitro. 6-MP not only induces the expression of osteo-chondrocyte-like transcription factors and proteins but also activates alkaline phosphatase enzyme activity and produces calcium deposition in in vitro and ex vivo models. These processes are dependent on 6-MP-induced production of reactive oxygen species, intracellular activation of mitogen-activated kinases and phosphorylation of the transcription factor Cbfa1. Furthermore, the metabolic products of 6-MP, 6-thioguanine nucleotides and 6-methyl-thio-inosine monophosphate have major impacts on cellular calcification. These data provide evidence for a possible harmful effect of the immunosuppressive drug 6-MP in vascular diseases, such as arteriosclerosis. PMID:25029363

Harmful effects of the azathioprine metabolite 6-mercaptopurine in vascular cells: induction of mineralization.

PubMed

Prüfer, Jasmin; Schuchardt, Mirjam; Tölle, Markus; Prüfer, Nicole; Höhne, Matthias; Zidek, Walter; van der Giet, Markus

2014-01-01

Vascular mineralization contributes to the high cardiovascular morbidity and mortality in patients who suffer from chronic kidney disease and in individuals who have undergone solid organ transplantation. The immunosuppressive regimen used to treat these patients appears to have an impact on vascular alterations. The effect of 6-mercaptopurine (6-MP) on vascular calcification has not yet been determined. This study investigates the effect of 6-MP on vascular mineralization by the induction of trans-differentiation of rat vascular smooth muscle cells in vitro. 6-MP not only induces the expression of osteo-chondrocyte-like transcription factors and proteins but also activates alkaline phosphatase enzyme activity and produces calcium deposition in in vitro and ex vivo models. These processes are dependent on 6-MP-induced production of reactive oxygen species, intracellular activation of mitogen-activated kinases and phosphorylation of the transcription factor Cbfa1. Furthermore, the metabolic products of 6-MP, 6-thioguanine nucleotides and 6-methyl-thio-inosine monophosphate have major impacts on cellular calcification. These data provide evidence for a possible harmful effect of the immunosuppressive drug 6-MP in vascular diseases, such as arteriosclerosis.

Pineal Calcification Among Black Patients

PubMed Central

Fan, Kuang-Jaw

1983-01-01

A postmortem histopathological study was done in 233 pineal glands of black patients. Among them, 70 percent showed microscopic evidence of calcification in the pineal parenchyma. The frequency of calcification increased with age. However, the severity of calcification reached the peak in the 60 to 69 year old age group and then gradually declined. As compared to males, females had slightly higher frequency and reached the peak of severity in younger age groups. When pineal calcification was compared among patients with various malignancies, a higher frequency and more severe calcification were observed in patients with carcinoma of the prostate and the pancreas. A lower frequency and less severe calcification were observed in patients with carcinoma of the breast and the cervix. The results of this study emphasize the important role of sex hormone in genesis of pineal calcification. PMID:6631985

Increased activity of TNAP compensates for reduced adenosine production and promotes ectopic calcification in the genetic disease ACDC

PubMed Central

Jin, Hui; Hilaire, Cynthia St.; Huang, Yuting; Yang, Dan; Dmitrieva, Natalia I.; Negro, Alejandra; Schwartzbeck, Robin; Liu, Yangtengyu; Yu, Zhen; Walts, Avram; Davaine, Jean-Michel; Lee, Duck-Yeon; Donahue, Danielle; Hsu, Kevin S.; Chen, Jessica; Cheng, Tao; Gahl, William; Chen, Guibin; Boehm, Manfred

2017-01-01

ACDC (arterial calcification due to deficiency of CD73) is an autosomal recessive disease resulting from loss-of-function mutations in NT5E, which encodes CD73, a 5′-ectonucleotidase that converts extracellular adenosine monophosphate to adenosine. ACDC patients display progressive calcification of lower extremity arteries, causing limb ischemia. Tissue-nonspecific alkaline phosphatase (TNAP), which converts pyrophosphate (PPi) to inorganic phosphate (Pi), and extracellular purine metabolism play important roles in other inherited forms of vascular calcification. Compared to cells from healthy subjects, induced pluripotent stem cell–derived mesenchymal stromal cells (iMSCs) from ACDC patients displayed accelerated calcification and increased TNAP activity when cultured under conditions that promote osteogenesis. TNAP activity generated adenosine in iMSCs derived from ACDC patients but not in iMSCs from control subjects, which have CD73. In response to osteogenic stimulation, ACDC patient–derived iMSCs had decreased amounts of the TNAP substrate PPi, an inhibitor of extracellular matrix calcification, and exhibited increased activation of AKT, mechanistic target of rapamycin (mTOR), and the 70-kDa ribosomal protein S6 kinase (p70S6K), a pathway that promotes calcification. In vivo, teratomas derived from ACDC patient cells showed extensive calcification and increased TNAP activity. Treating mice bearing these teratomas with an A2b adenosine receptor agonist, the mTOR inhibitor rapamycin, or the bisphosphonate etidronate reduced calcification. These results show that an increase of TNAP activity in ACDC contributes to ectopic calcification by disrupting the extracellular balance of PPi and Pi and identify potential therapeutic targets for ACDC. PMID:27965423

Effects of lectins on calcification by vesicles isolated from aortas of cholesterol-fed rabbits.

PubMed

Hsu, H H; Tawfik, O; Sun, F

2000-04-05

Advanced vascular calcification in atherosclerosis weakens arterial walls, thereby imposing a serious rupturing effect. However, the mechanism of dystrophic calcification remains unknown. Although accumulating morphological and biochemical evidence reveals a role for calcifiable vesicles in plaque calcification, the mechanism of vesicle-mediated calcification has not been fully explored. To study whether vesicles' membrane components, such as carbohydrates, may have a role in vesicle-mediated calcification, the effect of sugar-binding lectins on calcification was investigated. Atherosclerosis was developed by feeding rabbits with a diet supplemented with 0.5% cholesterol and 2% peanut oil for 4 months. Calcifiable vesicles were then isolated from thoracic aortas by collagenase digestion. The histological examination of aortas with hematoxylin counter-staining indicated abnormal formation of large plaques enriched with macrophage-derived foam cells. Fourier transform spectroscopy revealed mild calcification in aortas indicating that advanced stages of heavy calcification have yet to be reached. However, vesicles isolated from the aortas were capable of calcification in the presence of physiological levels of Ca(2+), Pi, and ATP. Thus, at this stage of atherosclerosis, aortas may start to produce calcifiable vesicles, but at a level insufficient for substantial formation of mineral in aortas. The assessments by FT-IR analysis and Alizarin red staining indicated that concanavalin A (Con A) substantially increased mineral formation by isolated vesicles. Con A also exerted a marked stimulatory effect on (45)Ca and (32)Pi deposition in a dose-dependent fashion with a half-maximal effect at 6-10 microg/ml. Either alpha-methylmannoside or alpha-methylglucoside, but not mannitol, at 10 mM abolished the stimulation. Con A stimulation was abolished after Con A was removed from calcifying media, suggesting that covalent binding may not be involved in the effect. Galactosides

Eicosapentaenoic acid prevents arterial calcification in klotho mutant mice.

PubMed

Nakamura, Kazufumi; Miura, Daiji; Saito, Yukihiro; Yunoki, Kei; Koyama, Yasushi; Satoh, Minoru; Kondo, Megumi; Osawa, Kazuhiro; Hatipoglu, Omer F; Miyoshi, Toru; Yoshida, Masashi; Morita, Hiroshi; Ito, Hiroshi

2017-01-01

The klotho gene was identified as an "aging-suppressor" gene that accelerates arterial calcification when disrupted. Serum and vascular klotho levels are reduced in patients with chronic kidney disease, and the reduced levels are associated with arterial calcification. Intake of eicosapentaenoic acid (EPA), an n-3 fatty acid, reduces the risk of fatal coronary artery disease. However, the effects of EPA on arterial calcification have not been fully elucidated. The aim of this study was to determine the effect of EPA on arterial calcification in klotho mutant mice. Four-week-old klotho mutant mice and wild-type (WT) mice were given a diet containing 5% EPA (EPA food, klotho and WT: n = 12, each) or not containing EPA (control food, klotho and WT: n = 12, each) for 4 weeks. Calcium volume scores of thoracic and abdominal aortas assessed by computed tomography were significantly elevated in klotho mice after 4 weeks of control food, but they were not elevated in klotho mice after EPA food or in WT mice. Serum levels of EPA and resolvin E1, an active metabolite of EPA, in EPA food-fed mice were significantly increased compared to those in control food-fed mice. An oxidative stress PCR array followed by quantitative PCR revealed that NADPH oxidase-4 (NOX4), an enzyme that generates superoxide, gene expression was up-regulated in arterial smooth muscle cells (SMCs) of klotho mice. Activity of NOX was also significantly higher in SMCs of klotho mice than in those of WT mice. EPA decreased expression levels of the NOX4 gene and NOX activity. GPR120, a receptor of n-3 fatty acids, gene knockdown by siRNA canceled effects of EPA on NOX4 gene expression and NOX activity in arterial SMCs of klotho mice. EPA prevents arterial calcification together with reduction of NOX gene expression and activity via GPR120 in klotho mutant mice.

Calcification at orifices of aortic arch branches is a reliable and significant marker of stenosis at carotid bifurcation and intracranial arteries.

PubMed

Yamada, Shigeki; Hashimoto, Kenji; Ogata, Hideki; Watanabe, Yoshihiko; Oshima, Marie; Miyake, Hidenori

2014-02-01

Simple rating scale for calcification in the cervical arteries and the aortic arch on multi-detector computed tomography angiography (MDCTA) was evaluated its reliability and validity. Additionally, we investigated where is the most representative location for evaluating the calcification risk of carotid bifurcation stenosis and atherosclerotic infarction in the overall cervical arteries covering from the aortic arch to the carotid bifurcation. The aortic arch and cervical arteries among 518 patients (292 men, 226 women) were evaluated the extent of calcification using a 4-point grading scale for MDCTA. Reliability, validity and the concomitant risk with vascular stenosis and atherosclerotic infarction were assessed. Calcification was most frequently observed in the aortic arch itself, the orifices from the aortic arch, and the carotid bifurcation. Compared with the bilateral carotid bifurcations, the aortic arch itself had a stronger inter-observer agreement for the calcification score (Fleiss' kappa coefficients; 0.77), but weaker associations with stenosis and atherosclerotic infarction. Calcification at the orifices of the aortic arch branches had a stronger inter-observer agreement (0.74) and enough associations with carotid bifurcation stenosis and intracranial stenosis. In addition, the extensive calcification at the orifices from the aortic arch was significantly associated with atherosclerotic infarction, similar to the calcification at the bilateral carotid bifurcations. The orifices of the aortic arch branches were the novel representative location of the aortic arch and overall cervical arteries for evaluating the calcification extent. Thus, calcification at the aortic arch should be evaluated with focus on the orifices of 3 main branches. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Development of a Patient-Specific Multi-Scale Model to Understand Atherosclerosis and Calcification Locations: Comparison with In vivo Data in an Aortic Dissection

PubMed Central

Alimohammadi, Mona; Pichardo-Almarza, Cesar; Agu, Obiekezie; Díaz-Zuccarini, Vanessa

2016-01-01

Vascular calcification results in stiffening of the aorta and is associated with hypertension and atherosclerosis. Atherogenesis is a complex, multifactorial, and systemic process; the result of a number of factors, each operating simultaneously at several spatial and temporal scales. The ability to predict sites of atherogenesis would be of great use to clinicians in order to improve diagnostic and treatment planning. In this paper, we present a mathematical model as a tool to understand why atherosclerotic plaque and calcifications occur in specific locations. This model is then used to analyze vascular calcification and atherosclerotic areas in an aortic dissection patient using a mechanistic, multi-scale modeling approach, coupling patient-specific, fluid-structure interaction simulations with a model of endothelial mechanotransduction. A number of hemodynamic factors based on state-of-the-art literature are used as inputs to the endothelial permeability model, in order to investigate plaque and calcification distributions, which are compared with clinical imaging data. A significantly improved correlation between elevated hydraulic conductivity or volume flux and the presence of calcification and plaques was achieved by using a shear index comprising both mean and oscillatory shear components (HOLMES) and a non-Newtonian viscosity model as inputs, as compared to widely used hemodynamic indicators. The proposed approach shows promise as a predictive tool. The improvements obtained using the combined biomechanical/biochemical modeling approach highlight the benefits of mechanistic modeling as a powerful tool to understand complex phenomena and provides insight into the relative importance of key hemodynamic parameters. PMID:27445834

In vivo canine studies of a Sinkhole valve and vascular graft coated with biocompatible PU-PEO-SO3.

PubMed

Han, D K; Lee, K B; Park, K D; Kim, C S; Jeong, S Y; Kim, Y H; Kim, H M; Min, B G

1993-01-01

PU-PEO-SO3 was applied as a coating material over a newly designed Sinkhole bileaflet PU heart valve and a porous PU vascular graft. Performance and biocompatibility were evaluated using an in vivo canine shunt system between the right ventricle and pulmonary artery. The survival periods in three implantations were 14, 24, and 39 days, during which no mechanical failure occurred in any Sinkhole valve or vascular graft. Scanning electron microscopy (SEM) studies demonstrated much less platelet adhesion and thrombus formation on PU-PEO-SO3 grafts than on PU vascular grafts. Cracks in the valve leaflet were occasionally observed on PU surfaces, but not on PU-PEO-SO3. After a 39 day implantation, calcium deposition on vascular grafts was decreased as compared with valve leaflets, and calcification on PU-PEO-SO3 was much lower than on PU. These results suggest that Sinkhole valves and vascular grafts are promising, and PU-PEO-SO3 as a coating material is more blood compatible, biostable, and calcification resistant in vivo than in untreated PU.

Idiopathic dental pulp calcifications in a tertiary care setting in South India

PubMed Central

Satheeshkumar, PS; Mohan, Minu P; Saji, Sweta; Sadanandan, Sudheesh; George, Giju

2013-01-01

Background: Dental pulp calcifications are unique and represent the dental pulp regenerative process. Dental pulp calcifications are sometimes routine findings in oral radiographs and may later serve as an important diagnostic criterion for a hidden aspect of systemic illness. Objective: The purpose of this study was to assess the patterns and prevalence of idiopathic dental pulp calcifications in a tertiary care setting in South India. Materials and Methods: A total of 227 patients were included in the study fulfilling the inclusion criteria. Age range of the study population was from 15 to 70 years. Teeth were examined under digital panoramic radiograph. The presence or absence of pulp stones was recorded. The presence of pulp stone were categorized according to the types classified as Type I, Type IA, Type II, Type IIA, Type II B, and Type III. The frequency of occurrence of pulp stones with sex, tooth type, dental arches, and types were compared with the types of calcification. Results: Total no. of patients with pulpal calcification were 227 [females 133 (58.59%) and males 94 (41.40%)]. The most common type between both sexes was Type I (48%). Total no. of teeth with calcification was 697; maxilla (48%), mandible (52%). The prevalence of pulp stone was found to be higher in the molars in both the arches. Most no. of pulp stones are reported at the third and fourth decade of life. Conclusion: Idiopathic dental pulp calcifications are incidental radiographic findings of the pulp tissue and also may be an indicator of underlying disease. PMID:23349577

Acute Renal Infarction Secondary to Calcific Embolus from Mitral Annular Calcification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bande, Dinesh; Abbara, Suhny; Kalva, Sanjeeva P., E-mail: skalva@partners.org

2011-06-15

We report a case of a 62-year-old man who presented with right groin pain who subsequently was found to have a renal infarct secondary to calcific embolus from mitral annular calcification on CT and angiography. We briefly review the literature and discuss the importance of this entity in clinical practice.

Acute Calcific Bursitis After Ultrasound-Guided Percutaneous Barbotage of Rotator Cuff Calcific Tendinopathy: A Case Report.

PubMed

Kang, Bo-Sung; Lee, Seung Hak; Cho, Yung; Chung, Sun Gun

2016-08-01

Ultrasound-guided percutaneous barbotage is an effective treatment for rotator cuff calcific tendinopathy, providing rapid and substantial pain relief. We present the case of a 49-year-old woman with aggravated pain early after ultrasound-guided barbotage of a large calcific deposit in the supraspinatus tendon. Subsequent examination revealed a thick calcification spreading along the subacromial-subdeltoid bursa space, suggesting acute calcific bursitis complicated by barbotage. Additional barbotage alleviated her pain completely. Therefore, a high index of suspicion for acute calcific bursitis is required in patients with unresolved or aggravated pain after barbotage. Repeated barbotage could be effective for this condition. Copyright © 2016 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Metastatic pulmonary calcification in a dialysis patient: case report and a review.

PubMed

Eggert, Christoph H; Albright, Robert C

2006-10-01

A 19-year-old male presented with chest pain and dyspnea. He was anephric following nephrectomy for focal segmental glomerulosclerosis, had a subsequent failed transplant, and had been dialysis dependent for 3 years. Workup revealed hyperparathyroidism and an abnormal chest X-ray and computed tomography scan, significant for massive extra-skeletal pulmonary calcification. A markedly abnormal Technitium99 methylene diphosphonate (Tc99m-MDP) bone scan confirmed the clinical suspicion of metastatic pulmonary calcification. Metastatic pulmonary calcification (MPC) is common, occurring in 60% to 80% of dialysis patients on autopsy and bone scan series. It may lead to impaired oxygenation and restrictive lung disease. Typically, the calcium crystal is whitlockite rather than hydroxyapatite, which occurs in vascular calcification. Four major predisposing factors may contribute to MPC in dialysis patients. First, chronic acidosis leaches calcium from bone. Second, intermittent alkalosis favors deposition of calcium salts. Third, hyperparathyroidism tends to cause bone resorption and intracellular hypercalcemia. Finally, low glomerular filtration rate can cause hyperphosphatemia and an elevated calcium-phosphorus product. There may be other factors. Some authors suggest that the incidence of MPC in recent years may be lower due to improved dialysis techniques. The diagnosis is confirmed by biopsy, but can be suspected by typical findings on a Tc99m-MDP bone scan. Therapy is limited to ensuring adequate dialysis, correcting calcium-phosphorus product, and hyperparathyroidism; discontinuing vitamin D analogues may help. Conflicting reports show that transplantation may either improve or worsen the situation. MPC should be considered in dialysis patients who have characteristic abnormal chest radiography and/or pulmonary symptoms.

Metastatic pulmonary calcification: high-resolution computed tomography findings in 23 cases.

PubMed

Belém, Luciana Camara; Souza, Carolina A; Souza, Arthur Soares; Escuissato, Dante Luiz; Hochhegger, Bruno; Nobre, Luiz Felipe; Rodrigues, Rosana Souza; Gomes, Antônio Carlos Portugal; Silva, Claudio S; Guimarães, Marcos Duarte; Zanetti, Gláucia; Marchiori, Edson

2017-01-01

The aim of this study was to evaluate the high-resolution computed tomography (HRCT) findings in patients diagnosed with metastatic pulmonary calcification (MPC). We retrospectively reviewed the HRCT findings from 23 cases of MPC [14 men, 9 women; mean age, 54.3 (range, 26-89) years]. The patients were examined between 2000 and 2014 in nine tertiary hospitals in Brazil, Chile, and Canada. Diagnoses were established by histopathologic study in 18 patients and clinical-radiological correlation in 5 patients. Two chest radiologists analyzed the images and reached decisions by consensus. The predominant HRCT findings were centrilobular ground-glass nodules ( n = 14; 60.9%), consolidation with high attenuation ( n = 10; 43.5%), small dense nodules ( n = 9; 39.1%), peripheral reticular opacities associated with small calcified nodules ( n = 5; 21.7%), and ground-glass opacities without centrilobular ground-glass nodular opacity ( n = 5; 21.7%). Vascular calcification within the chest wall was found in four cases and pleural effusion was observed in five cases. The abnormalities were bilateral in 21 cases. MPC manifested with three main patterns on HRCT, most commonly centrilobular ground-glass nodules, often containing calcifications, followed by dense consolidation and small solid nodules, most of which were calcified. We also described another pattern of peripheral reticular opacities associated with small calcified nodules. These findings should suggest the diagnosis of MPC in the setting of hypercalcemia.

Circulating vitamin K is inversely associated with incident cardiovascular disease risk among those treated for hypertension in the Health, Aging, and Body Composition Study (Health ABC)

USDA-ARS?s Scientific Manuscript database

Background: A role for vitamin K in coronary artery calcification (CAC), a subclinical manifestation of cardiovascular disease (CVD), has been proposed because vitamin K-dependent proteins, including the calcification inhibitor matrix Gla protein (MGP), are present in vascular tissue. Observational ...

Preparation of decellularized vascular matrix by co-crosslinking of procyanidins and glutaraldehyde.

PubMed

Wang, Xiaotong; Ma, Bing; Chang, Jiang

2015-01-01

Vascular extracellular matrices (vECMs) have shown potential for small-diameter blood vessel tissue engineering applications. However, problems such as chemical instability and easy calcification are still remained. Chemical crosslinking using crosslinkers such as glutaraldehyde (GA) can improve mechanical properties and proteolysis resistance of vECMs, but leads to calcification and cytotoxicity. Procyanidins (PC) can crosslink ECMs with anti-calcification property and cytocompatibility, but the mechanical properties and chemical stability are unsatisfactory. A novel co-crosslinking technique using PC and GA was developed, which combines the advantages of both PC and GA for enhancing mechanical properties and stability of vECMs with reduced calcification and cytotoxicity. Fresh carotid were decellularized and then crosslinked by PC and subsequent GA for 6 h respectively. The mechanical properties, dynamic release of PC, enzymatic degradation, calcification and cytotoxicity of crosslinked samples were evaluated. The co-crosslinked vECMs showed enhanced tensile strength, chemical and biological stability, comparable anti-calcification property as compared to pure PC-crosslinked samples. Cytotoxicity assay showed that the co-crosslinked vECMs were cytocompatible for supporting the adhesion and proliferation of HUVECs. Co-crosslinking with PC and GA might be a useful method for preparation of vECM scaffolds with potential applications in small-diameter blood vessel tissue engineering.

Magnesium Inhibits Wnt/β-Catenin Activity and Reverses the Osteogenic Transformation of Vascular Smooth Muscle Cells

PubMed Central

Montes de Oca, Addy; Guerrero, Fatima; Martinez-Moreno, Julio M.; Madueño, Juan A.; Herencia, Carmen; Peralta, Alan; Almaden, Yolanda; Lopez, Ignacio; Aguilera-Tejero, Escolastico; Gundlach, Kristina; Büchel, Janine; Peter, Mirjam E.; Passlick-Deetjen, Jutta; Rodriguez, Mariano; Muñoz-Castañeda, Juan R.

2014-01-01

Magnesium reduces vascular smooth muscle cell (VSMC) calcification in vitro but the mechanism has not been revealed so far. This work used only slightly increased magnesium levels and aimed at determining: a) whether inhibition of magnesium transport into the cell influences VSMC calcification, b) whether Wnt/β-catenin signaling, a key mediator of osteogenic differentiation, is modified by magnesium and c) whether magnesium can influence already established vascular calcification. Human VSMC incubated with high phosphate (3.3 mM) and moderately elevated magnesium (1.4 mM) significantly reduced VSMC calcification and expression of the osteogenic transcription factors Cbfa-1 and osterix, and up-regulated expression of the natural calcification inhibitors matrix Gla protein (MGP) and osteoprotegerin (OPG). The protective effects of magnesium on calcification and expression of osteogenic markers were no longer observed in VSMC cultured with an inhibitor of cellular magnesium transport (2-aminoethoxy-diphenylborate [2-APB]). High phosphate induced activation of Wnt/β-catenin pathway as demonstrated by the translocation of β-catenin into the nucleus, increased expression of the frizzled-3 gene, and downregulation of Dkk-1 gene, a specific antagonist of the Wnt/β-catenin signaling pathway. The addition of magnesium however inhibited phosphate-induced activation of Wnt/β-catenin signaling pathway. Furthermore, TRPM7 silencing using siRNA resulted in activation of Wnt/β-catenin signaling pathway. Additional experiments were performed to test the ability of magnesium to halt the progression of already established VSMC calcification in vitro. The delayed addition of magnesium decreased calcium content, down-regulated Cbfa-1 and osterix and up-regulated MGP and OPG, when compared with a control group. This effect was not observed when 2-APB was added. In conclusion, magnesium transport through the cell membrane is important to inhibit VSMC calcification in vitro

Vascular calcification on plain radiographs is associated with carotid intima media thickness, malnutrition and cardiovascular events in dialysis patients: a prospective observational study

PubMed Central

2013-01-01

Background Vascular calcification (VC) and carotid intima media thickness (CIMT) are strongly associated with cardiovascular (CV) disease. We hypothesized that significant VC on plain radiographs is associated with CIMT and CV events in dialysis patients. In addition, we evaluated risk factors for VC progression on plain radiographs in dialysis patients. Methods In this 2-year observational, prospective study, 67 dialysis patients were included. We checked plain radiographs at baseline and after 2 years. Laboratory tests and malnutrition score were obtained at baseline, after 12 months, and after 24 months. Results The mean age of patients was 56.3 ± 10.3 years and duration of dialysis was 41.3 ± 34.5 months. The prevalence of significant VC was 61.2% and the prevalence of carotid artery atheromatous plaques was 55.6%. Mean CIMT, malnutrition scores, CRP level and prevalence of carotid atheromatous plaques were significantly higher in patients with significant VC. Serum albumin and total iron binding capacity were significantly lower in patients with significant VC compared to patients without significant VC. During a mean observational period of 22 months, patients without significant VC showed lower CV events by the Kaplan-Meyer method (p = 0.010). Progression of VC was found in 35.7% among 56 patients followed up. Hemoglobin after 24 months was an independent factor for progression of VC (Exp(B) = 0.344, 95% Confidence Interval = 0.13 – 0.96, p = 0.034). Conclusions Significant VC on plain radiograph was associated with CIMT, malnutrition, inflammation, and CV events in dialysis patients. Conditions which increase hemoglobin level may retard progression of VC in dialysis patients. PMID:23360132

Brain calcifications and PCDH12 variants

PubMed Central

Nicolas, Gaël; Sanchez-Contreras, Monica; Ramos, Eliana Marisa; Lemos, Roberta R.; Ferreira, Joana; Moura, Denis; Sobrido, Maria J.; Richard, Anne-Claire; Lopez, Alma Rosa; Legati, Andrea; Deleuze, Jean-François; Boland, Anne; Quenez, Olivier; Krystkowiak, Pierre; Favrole, Pascal; Geschwind, Daniel H.; Aran, Adi; Segel, Reeval; Levy-Lahad, Ephrat; Dickson, Dennis W.; Coppola, Giovanni; Rademakers, Rosa

2017-01-01

Objective: To assess the potential connection between PCDH12 and brain calcifications in a patient carrying a homozygous nonsense variant in PCDH12 and in adult patients with brain calcifications. Methods: We performed a CT scan in 1 child with a homozygous PCDH12 nonsense variant. We screened DNA samples from 53 patients with primary familial brain calcification (PFBC) and 26 patients with brain calcification of unknown cause (BCUC). Results: We identified brain calcifications in subcortical and perithalamic regions in the patient with a homozygous PCDH12 nonsense variant. The calcification pattern was different from what has been observed in PFBC and more similar to what is described in in utero infections. In patients with PFBC or BCUC, we found no protein-truncating variant and 3 rare (minor allele frequency <0.001) PCDH12 predicted damaging missense heterozygous variants in 3 unrelated patients, albeit with no segregation data available. Conclusions: Brain calcifications should be added to the phenotypic spectrum associated with PCDH12 biallelic loss of function, in the context of severe cerebral developmental abnormalities. A putative role for PCDH12 variants remains to be determined in PFBC. PMID:28804758

Tremolite whitewashing and pleural calcifications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Constantopoulos, S.H.; Saratzis, N.A.; Kontogiannis, D.

1987-10-01

Radiologic screening of 688 inhabitants of the Metsovo area in Northwest Greece revealed that 323 (46.9 percent) had pleural calcifications. The percentage of positive examinations rose with age. Calcifications were observed in all four villages of the area where a material (luto soil) had been extensively used for whitewashing until 1940 to 1950. In four other villages in the immediate vicinity, where luto had never been used, pleural calcifications were not observed. Results suggest that Metsovo tremolite may have caused pleural calcifications to all individuals born in Metsovo before 1940. This is the first study indicating that environmental asbestos exposuremore » can cause abnormalities in everyone exposed to it.« less

Magnesium Attenuates Phosphate-Induced Deregulation of a MicroRNA Signature and Prevents Modulation of Smad1 and Osterix during the Course of Vascular Calcification.

PubMed

Louvet, Loïc; Metzinger, Laurent; Büchel, Janine; Steppan, Sonja; Massy, Ziad A

2016-01-01

Vascular calcification (VC) is prevalent in patients suffering from chronic kidney disease (CKD). High phosphate levels promote VC by inducing abnormalities in mineral and bone metabolism. Previously, we demonstrated that magnesium (Mg(2+)) prevents inorganic phosphate- (Pi-) induced VC in human aortic vascular smooth muscle cells (HAVSMC). As microRNAs (miR) modulate gene expression, we investigated the role of miR-29b, -30b, -125b, -133a, -143, and -204 in the protective effect of Mg(2+) on VC. HAVSMC were cultured in the presence of 3 mM Pi with or without 2 mM Mg(2+) chloride. Total RNA was extracted after 4 h, 24 h, day 3, day 7, and day 10. miR-30b, -133a, and -143 were downregulated during the time course of Pi-induced VC, whereas the addition of Mg(2+) restored (miR-30b) or improved (miR-133a, miR-143) their expression. The expression of specific targets Smad1 and Osterix was significantly increased in the presence of Pi and restored by coincubation with Mg(2+). As miR-30b, miR-133a, and miR-143 are negatively regulated by Pi and restored by Mg(2+) with a congruent modulation of their known targets Runx2, Smad1, and Osterix, our results provide a potential mechanistic explanation of the observed upregulation of these master switches of osteogenesis during the course of VC.

Magnesium Attenuates Phosphate-Induced Deregulation of a MicroRNA Signature and Prevents Modulation of Smad1 and Osterix during the Course of Vascular Calcification

PubMed Central

Louvet, Loïc; Metzinger, Laurent; Büchel, Janine; Steppan, Sonja; Massy, Ziad A.

2016-01-01

Vascular calcification (VC) is prevalent in patients suffering from chronic kidney disease (CKD). High phosphate levels promote VC by inducing abnormalities in mineral and bone metabolism. Previously, we demonstrated that magnesium (Mg2+) prevents inorganic phosphate- (Pi-) induced VC in human aortic vascular smooth muscle cells (HAVSMC). As microRNAs (miR) modulate gene expression, we investigated the role of miR-29b, -30b, -125b, -133a, -143, and -204 in the protective effect of Mg2+ on VC. HAVSMC were cultured in the presence of 3 mM Pi with or without 2 mM Mg2+ chloride. Total RNA was extracted after 4 h, 24 h, day 3, day 7, and day 10. miR-30b, -133a, and -143 were downregulated during the time course of Pi-induced VC, whereas the addition of Mg2+ restored (miR-30b) or improved (miR-133a, miR-143) their expression. The expression of specific targets Smad1 and Osterix was significantly increased in the presence of Pi and restored by coincubation with Mg2+. As miR-30b, miR-133a, and miR-143 are negatively regulated by Pi and restored by Mg2+ with a congruent modulation of their known targets Runx2, Smad1, and Osterix, our results provide a potential mechanistic explanation of the observed upregulation of these master switches of osteogenesis during the course of VC. PMID:27419135

Beneficial Effects of Galectin-3 Blockade in Vascular and Aortic Valve Alterations in an Experimental Pressure Overload Model

PubMed Central

Ibarrola, Jaime; Martínez-Martínez, Ernesto; Sádaba, J. Rafael; Arrieta, Vanessa; García-Peña, Amaia; Álvarez, Virginia; Fernández-Celis, Amaya; Gainza, Alicia; Rossignol, Patrick; Cachofeiro Ramos, Victoria; López-Andrés, Natalia

2017-01-01

Galectin-3 (Gal-3) is involved in cardiovascular fibrosis and aortic valve (AV) calcification. We hypothesized that Gal-3 pharmacological inhibition with modified citrus pectin (MCP) could reduce aortic and AV remodeling in normotensive rats with pressure overload (PO). Six weeks after aortic constriction, vascular Gal-3 expression was up-regulated in male Wistar rats. Gal-3 overexpression was accompanied by an increase in the aortic media layer thickness, enhanced total collagen, and augmented expression of fibrotic mediators. Further, vascular inflammatory markers as well as inflammatory cells content were greater in aorta from PO rats. MCP treatment (100 mg/kg/day) prevented the increase in Gal-3, media thickness, fibrosis, and inflammation in the aorta of PO rats. Gal-3 levels were higher in AVs from PO rats. This paralleled enhanced AV fibrosis, inflammation, as well as greater expression of calcification markers. MCP treatment prevented the increase in Gal-3 as well as fibrosis, inflammation, and calcification in AVs. Overall, Gal-3 is overexpressed in aorta and AVs from PO rats. Gal-3 pharmacological inhibition blocks aortic and AV remodeling in experimental PO. Gal-3 could be a new therapeutic approach to delay the progression and the development of aortic remodeling and AV calcification in PO. PMID:28758988

Mineralization/Anti-Mineralization Networks in the Skin and Vascular Connective Tissues

PubMed Central

Li, Qiaoli; Uitto, Jouni

2014-01-01

Ectopic mineralization has been linked to several common clinical conditions with considerable morbidity and mortality. The mineralization processes, both metastatic and dystrophic, affect the skin and vascular connective tissues. There are several contributing metabolic and environmental factors that make uncovering of the precise pathomechanisms of these acquired disorders exceedingly difficult. Several relatively rare heritable disorders share phenotypic manifestations similar to those in common conditions, and, consequently, they serve as genetically controlled model systems to study the details of the mineralization process in peripheral tissues. This overview will highlight diseases with mineral deposition in the skin and vascular connective tissues, as exemplified by familial tumoral calcinosis, pseudoxanthoma elasticum, generalized arterial calcification of infancy, and arterial calcification due to CD73 deficiency. These diseases, and their corresponding mouse models, provide insight into the pathomechanisms of soft tissue mineralization and point to the existence of intricate mineralization/anti-mineralization networks in these tissues. This information is critical for understanding the pathomechanistic details of different mineralization disorders, and it has provided the perspective to develop pharmacological approaches to counteract the consequences of ectopic mineralization. PMID:23665350

Calcification detection of abdominal aorta in CT images and 3D visualization in VR devices.

PubMed

Garcia-Berna, Jose A; Sanchez-Gomez, Juan M; Hermanns, Judith; Garcia-Mateos, Gines; Fernandez-Aleman, Jose L

2016-08-01

Automatic calcification detection in abdominal aorta consists of a set of computer vision techniques to quantify the amount of calcium that is found around this artery. Knowing that information, it is possible to perform statistical studies that relate vascular diseases with the presence of calcium in these structures. To facilitate the detection in CT images, a contrast is usually injected into the circulatory system of the patients to distinguish the aorta from other body tissues and organs. This contrast increases the absorption of X-rays by human blood, making it easier the measurement of calcifications. Based on this idea, a new system capable of detecting and tracking the aorta artery has been developed with an estimation of the calcium found surrounding the aorta. Besides, the system is complemented with a 3D visualization mode of the image set which is designed for the new generation of immersive VR devices.

Coronary artery calcification correlates with the presence and severity of valve calcification.

PubMed

Koulaouzidis, G; Nicoll, R; MacArthur, T; Jenkins, P J; Henein, M Y

2013-10-15

To investigate the prevalence of coronary artery calcification (CAC) in symptomatic individuals with CT evidence for left heart valve calcification, aortic valve (AVC), mitral valve (MAC) or both. This is a retrospective study of 282 consecutive patients with calcification in either the aortic valve or mitral annulus. Calcium scoring of the coronary artery, aortic and mitral valve was measured using the Agatston score. AVC was more prevalent than MAC (64% vs. 2.5%, p < 0.001), with 34% having both. Absence of CAC was noted in 12.7% of the study population. AVC + CAC were observed in 53.5%, MAC and CAC in 2.1%, and combined AVC, MAC and CAC in 31.6%. The median CAC score was higher in individuals with combined AVC+MAC, followed by those with AVC and lowest was in the MAC group. The majority (40%) of individuals with AVC had CAC score >400, and only in 16% had CAC = 0. The same pattern was more evident in individuals with AVC + MAC, where 70% had CAC score >400 and only 6% had CAC score of 0. These results were irrespective of gender. There was no correlation between AVC and MAC but there was modest correlation between CAC score and AVC score (r = 0.28, p = 0.0001), MAC (r = 0.36, p = 0.0001) and with combined AVC + MAC (r = 0.5, p = 0.0001). AVC score of 262 had a sensitivity of 78% and specificity of 92% for the prediction of presence of CAC. The presence and extent of calcification in the aortic valve or/and mitral valves are associated with severe coronary artery calcification. © 2013.

CT of schistosomal calcification of the intestine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fataar, S.; Bassiony, H.; Satyanath, S.

1985-01-01

The spectrum of schistosomal colonic calcification on abdominal radiographs has been described. The appearance on computed tomography (CT) is equally distinctive and occurs with varying degrees of genitourinary calcification. The authors have experience in three cases with the appearance on CT of intestinal calcification due to schistosomiasis.

Endoplasmic Reticulum Stress in Arterial Smooth Muscle Cells: A Novel Regulator of Vascular Disease

PubMed Central

Furmanik, Malgorzata; Shanahan, Catherine M.

2017-01-01

Cardiovascular disease continues to be the leading cause of death in industrialised societies. The idea that the arterial smooth muscle cell (ASMC) plays a key role in regulating many vascular pathologies has been gaining importance, as has the realisation that not enough is known about the pathological cellular mechanisms regulating ASMC function in vascular remodelling. In the past decade endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) have been recognised as a stress response underlying many physiological and pathological processes in various vascular cell types. Here we summarise what is known about how ER stress signalling regulates phenotypic switching, trans/dedifferentiation and apoptosis of ASMCs and contributes to atherosclerosis, hypertension, aneurysms and vascular calcification.

Targeted Reduction of Vascular Msx1 and Msx2 Mitigates Arteriosclerotic Calcification and Aortic Stiffness in LDLR-Deficient Mice Fed Diabetogenic Diets

PubMed Central

Cheng, Su-Li; Behrmann, Abraham; Shao, Jian-Su; Ramachandran, Bindu; Krchma, Karen; Bello Arredondo, Yoanna; Kovacs, Attila; Mead, Megan; Maxson, Robert

2014-01-01

When fed high-fat diets, male LDLR−/− mice develop obesity, hyperlipidemia, hyperglycemia, and arteriosclerotic calcification. An osteogenic Msx-Wnt regulatory program is concomitantly upregulated in the vasculature. To better understand the mechanisms of diabetic arteriosclerosis, we generated SM22-Cre;Msx1(fl/fl);Msx2(fl/fl);LDLR−/− mice, assessing the impact of Msx1+Msx2 gene deletion in vascular myofibroblast and smooth muscle cells. Aortic Msx2 and Msx1 were decreased by 95% and 34% in SM22-Cre;Msx1(fl/fl);Msx2(fl/fl);LDLR−/− animals versus Msx1(fl/fl);Msx2(fl/fl);LDLR−/− controls, respectively. Aortic calcium was reduced by 31%, and pulse wave velocity, an index of stiffness, was decreased in SM22-Cre;Msx1(fl/fl);Msx2(fl/fl);LDLR−/− mice vs. controls. Fasting blood glucose and lipids did not differ, yet SM22-Cre;Msx1(fl/fl);Msx2(fl/fl);LDLR−/− siblings became more obese. Aortic adventitial myofibroblasts from SM22-Cre;Msx1(fl/fl);Msx2(fl/fl);LDLR−/− mice exhibited reduced osteogenic gene expression and mineralizing potential with concomitant reduction in multiple Wnt genes. Sonic hedgehog (Shh) and Sca1, markers of aortic osteogenic progenitors, were also reduced, paralleling a 78% reduction in alkaline phosphatase (TNAP)–positive adventitial myofibroblasts. RNA interference revealed that although Msx1+Msx2 supports TNAP and Wnt7b expression, Msx1 selectively maintains Shh and Msx2 sustains Wnt2, Wnt5a, and Sca1 expression in aortic adventitial myofibroblast cultures. Thus, Msx1 and Msx2 support vascular mineralization by directing the osteogenic programming of aortic progenitors in diabetic arteriosclerosis. PMID:25056439

MiR-133a modulates osteogenic differentiation of vascular smooth muscle cells.

PubMed

Liao, Xiao-Bo; Zhang, Zhi-Yuan; Yuan, Ke; Liu, Yuan; Feng, Xiang; Cui, Rong-Rong; Hu, Ye-Rong; Yuan, Zhao-Shun; Gu, Lu; Li, Shi-Jun; Mao, Ding-An; Lu, Qiong; Zhou, Xin-Ming; de Jesus Perez, Vinicio A; Yuan, Ling-Qing

2013-09-01

Arterial calcification is a key pathologic component of vascular diseases such as atherosclerosis, coronary artery disease, and peripheral vascular disease. A hallmark of this pathological process is the phenotypic transition of vascular smooth muscle cells (VSMCs) to osteoblast-like cells. Several studies have demonstrated that microRNAs (miRNAs) regulate osteoblast differentiation, but it is unclear whether miRNAs also regulate VSMC-mediated arterial calcification. In the present study, we sought to characterize the role of miR-133a in regulating VSMC-mediated arterial calcification. Northern blotting analysis of VSMCs treated with β-glycerophosphate demonstrated that miR-133a was significantly decreased during osteogenic differentiation. Overexpression of miR-133a inhibited VSMC transdifferentiation into osteoblast-like cells as evidenced by a decrease in alkaline phosphatase activity, osteocalcin secretion, Runx2 expression, and mineralized nodule formation. Conversely, the knockdown of miR-133a using an miR-133a inhibitor promoted osteogenic differentiation of VSMCs by increasing alkaline phosphatase activity, osteocalcin secretion, and Runx2 expression. Runx2 was identified as a direct target of miR-133a by a cotransfection experiment in VSMCs with luciferase reporter plasmids containing wild-type or mutant 3'-untranslated region sequences of Runx2. Furthermore, the pro-osteogenic effects of miR-133a inhibitor were abrogated in Runx2-knockdown cells, and the inhibition of osteogenic differentiation by pre-miR-133a was reversed by overexpression of Runx2, providing functional evidence that the effects of miR-133a in osteogenic differentiation were mediated by targeting Runx2. These results demonstrate that miR-133a is a key negative regulator of the osteogenic differentiation of VSMCs.

Oxidized low-density lipoprotein and upregulated expression of osteonectin and bone sialoprotein in vascular smooth muscle cells.

PubMed

Farrokhi, Effat; Samani, Keihan Ghatreh; Chaleshtori, Morteza Hashemzadeh

2014-01-01

Oxidative stress has been associated with the progression of atherosclerosis and activation of genes that lead to increased deposition of proteins in the extracellular matrix. Bone sialoprotein (BSP) and osteonectin are proteins involved in the initiation and progression of vascular calcification. To investigate the effect of oxidized low-density lipoprotein on osteonectin and BSP expression in human aorta vascular smooth muscle cells (HA/VSMCs). We treated HA/VSMCs with oxidized low-density lipoprotein (oxLDL) and measured the relative expression of osteonectin and BSP genes using the real-time polymerase chain reaction (PCR) method. We investigated the protein levels produced by each gene using the western blotting technique. oxLDL increased osteonectin and BSP levels (mean [SD], 9.1 [2.1]-fold and 4.2 [0.75]-fold, respectively) after 48 hours. The western blotting results also confirmed the increased levels of osteonectin and BSP. oxLDL may enhance vascular calcification by promoting the expression of osteonectin and BSP. Copyright© by the American Society for Clinical Pathology (ASCP).

Magnesium Intake Is Inversely Associated With Coronary Artery Calcification

PubMed Central

Hruby, Adela; O'Donnell, Christopher J.; Jacques, Paul F.; Meigs, James B.; Hoffmann, Udo; McKeown, Nicola M.

2014-01-01

OBJECTIVES The aim of this study was to examine whether magnesium intake is associated with coronary artery calcification (CAC) and abdominal aortic calcification (AAC). BACKGROUND Animal and cell studies suggest that magnesium may prevent calcification within atherosclerotic plaques underlying cardiovascular disease. Little is known about the association of magnesium intake and atherosclerotic calcification in humans. METHODS We examined cross-sectional associations of self-reported total (dietary and supplemental) magnesium intake estimated by food frequency questionnaire with CAC and AAC in participants of the Framingham Heart Study who were free of cardiovascular disease and underwent Multi-Detector Computed Tomography (MDCT) of the heart and abdomen (n = 2,695; age: 53 ± 11 years), using multivariate-adjusted Tobit regression. CAC and AAC were quantified using modified Agatston scores (AS). Models were adjusted for age, sex, body mass index, smoking status, systolic blood pressure, fasting insulin, total-to-high-density lipoprotein cholesterol ratio, use of hormone replacement therapy (women only), menopausal status (women only), treatment for hyperlipidemia, hypertension, cardiovascular disease prevention, or diabetes, as well as self-reported intake of calcium, vitamins D and K, saturated fat, fiber, alcohol, and energy. Secondary analyses included logistic regressions of CAC and AAC outcomes as cut-points (AS >0 and AS ≥90th percentile for age and sex), as well as sex-stratified analyses. RESULTS In fully adjusted models, a 50-mg/day increment in self-reported total magnesium intake was associated with 22% lower CAC (p < 0.001) and 12% lower AAC (p = 0.07). Consistent with these observations, the odds of having any CAC were 58% lower (p trend: <0.001) and any AAC were 34% lower (p trend: 0.01), in those with the highest compared to those with the lowest magnesium intake. Stronger inverse associations were observed in women than in men. CONCLUSIONS In

Arterial Calcification in Diabetes Mellitus: Preclinical Models and Translational Implications.

PubMed

Stabley, John N; Towler, Dwight A

2017-02-01

Diabetes mellitus increasingly afflicts our aging and dysmetabolic population. Type 2 diabetes mellitus and the antecedent metabolic syndrome represent the vast majority of the disease burden-increasingly prevalent in children and older adults. However, type 1 diabetes mellitus is also advancing in preadolescent children. As such, a crushing wave of cardiometabolic disease burden now faces our society. Arteriosclerotic calcification is increased in metabolic syndrome, type 2 diabetes mellitus, and type 1 diabetes mellitus-impairing conduit vessel compliance and function, thereby increasing the risk for dementia, stroke, heart attack, limb ischemia, renal insufficiency, and lower extremity amputation. Preclinical models of these dysmetabolic settings have provided insights into the pathobiology of arterial calcification. Osteochondrogenic morphogens in the BMP-Wnt signaling relay and transcriptional regulatory programs driven by Msx and Runx gene families are entrained to innate immune responses-responses activated by the dysmetabolic state-to direct arterial matrix deposition and mineralization. Recent studies implicate the endothelial-mesenchymal transition in contributing to the phenotypic drift of mineralizing vascular progenitors. In this brief overview, we discuss preclinical disease models that provide mechanistic insights-and point to challenges and opportunities to translate these insights into new therapeutic strategies for our patients afflicted with diabetes mellitus and its arteriosclerotic complications. © 2016 American Heart Association, Inc.

Manipulation of valve composition to elucidate the role of collagen in aortic valve calcification

PubMed Central

2014-01-01

Background Extracellular matrix (ECM) disarray is found in calcific aortic valvular disease (CAVD), yet much remains to be learned about the role of individual ECM components in valvular interstitial cell (VIC) function and dysfunction. Previous clinical analyses have shown that calcification is associated with decreased collagen content, while previous in vitro work has suggested that the presence of collagen attenuates the responsiveness of VICs to pro-calcific stimuli. The current study uses whole leaflet cultures to examine the contributions of endogenous collagen in regulating the phenotype and calcification of VICs. Methods A “top-down” approach was used to characterize changes in VIC phenotype in response to collagen alterations in the native 3D environment. Collagen-deficient leaflets were created via enzymatic treatment and cultured statically for six days in vitro. After culture, leaflets were harvested for analysis of DNA, proliferation, apoptosis, ECM composition, calcification, and gene/protein expression. Results In general, disruption of collagen was associated with increased expression of disease markers by VICs in whole organ leaflet culture. Compared to intact control leaflets, collagen-deficient leaflets demonstrated increased VIC proliferation and apoptosis, increased expression of disease-related markers such as alpha-smooth muscle actin, alkaline phosphatase, and osteocalcin, and an increase in calcification as evidenced by positive von Kossa staining. Conclusions These results indicate that disruption of the endogenous collagen structure in aortic valves is sufficient to stimulate pathological consequences in valve leaflet cultures, thereby highlighting the importance of collagen and the valve extracellular matrix in general in maintaining homeostasis of the valve phenotype. PMID:24581344

[Molecular mechanisms in vascular osteocartilaginous metaplasia: systematic review].

PubMed

Rosero Salazar, Doris Haydee

2016-01-01

The cartilage and bone metaplasia occurring in both the heart and blood vessels, are the result of risk factors or chronic diseases that gradually adversely affect the performance of a person in society; however, clinical signs are reversible in early and intermediate stages of alterations. To establish how the molecular mechanisms underlying the increased vascular metaplastic changes and possible aspects of treatment and prevention. A systematic review was performed by searching for articles indexed in PubMed, Scopus and Science Direct data from 1995 to 2015. The MeSH descriptors used were metaplasia and vascular calcification, which terms associated were molecular mechanisms, condrogenic and osteogenic. Multiple factors influence the metaplastic change, especially the pro-inflammatory associated with vascular oxidation and the presence of free radicals; this development is reversible by treatment with antioxidants and changes in lifestyle and secondary prevention as there is a diagnosis of chronic degenerative disease. The literature evidences that factors that reduce the tissue oxidative stress and promote the maintenance of vascular phenotype are protective and / or reducing the osteochondral metaplastic formations.

Bioengineered vascular scaffolds: the state of the art.

PubMed

Palumbo, Vincenzo D; Bruno, Antonio; Tomasello, Giovanni; Damiano, Giuseppe; Lo Monte, Attilio I

2014-07-31

To date, there is increasing clinical need for vascular substitutes due to accidents, malformations, and ischemic diseases. Over the years, many approaches have been developed to solve this problem, starting from autologous native vessels to artificial vascular grafts; unfortunately, none of these have provided the perfect vascular substitute. All have been burdened by various complications, including infection, thrombogenicity, calcification, foreign body reaction, lack of growth potential, late stenosis and occlusion from intimal hyperplasia, and pseudoaneurysm formation. In the last few years, vascular tissue engineering has emerged as one of the most promising approaches for producing mechanically competent vascular substitutes. Nanotechnologies have contributed their part, allowing extraordinarily biostable and biocompatible materials to be developed. Specifically, the use of electrospinning to manufacture conduits able to guarantee a stable flow of biological fluids and guide the formation of a new vessel has revolutionized the concept of the vascular substitute. The electrospinning technique allows extracellular matrix (ECM) to be mimicked with high fidelity, reproducing its porosity and complexity, and providing an environment suitable for cell growth. In the future, a better knowledge of ECM and the manufacture of new materials will allow us to "create" functional biological vessels - the base required to develop organ substitutes and eventually solve the problem of organ failure.

Basal Ganglia Calcification with Tetanic Seizure Suggest Mitochondrial Disorder.

PubMed

Finsterer, Josef; Enzelsberger, Barbara; Bastowansky, Adam

2017-04-09

BACKGROUND Basal ganglia calcification (BGC) is a rare sporadic or hereditary central nervous system (CNS) abnormality, characterized by symmetric or asymmetric calcification of the basal ganglia. CASE REPORT We report the case of a 65-year-old Gypsy female who was admitted for a tetanic seizure, and who had a history of polyneuropathy, restless-leg syndrome, retinopathy, diabetes, hyperlipidemia, osteoporosis with consecutive hyperkyphosis, cervicalgia, lumbalgia, struma nodosa requiring thyroidectomy and consecutive hypothyroidism, adipositas, resection of a vocal chord polyp, arterial hypertension, coronary heart disease, atheromatosis of the aorta, peripheral artery disease, chronic obstructive pulmonary disease, steatosis hepatis, mild renal insufficiency, long-term hypocalcemia, hyperphosphatemia, impingement syndrome, spondylarthrosis of the lumbar spine, and hysterectomy. History and clinical presentation suggested a mitochondrial defect which also manifested as hypoparathyroidism or Fanconi syndrome resulting in BGC. After substitution of calcium, no further tetanic seizures occurred. CONCLUSIONS Patients with BGC should be investigated for a mitochondrial disorder. A mitochondrial disorder may also manifest as tetanic seizure.

Breast Calcifications

MedlinePlus

... al. Diagnostic evaluation of women with suspected breast cancer. http://www.uptodate.com/home. Accessed Dec. 9, 2015. Lai KC, et al. Linear breast calcifications. American Journal of Roentgenology. 2012;199:W151. Demetri-Lewis A, ...

Cardiac calcification in renal patients: what we do and don't know.

PubMed

Hujairi, Nabil M A; Afzali, Behdad; Goldsmith, David J A

2004-02-01

Cardiovascular (CV) disease is one of the major causes of mortality in patients with renal diseases, with an increased odds ratio of mortality with risk factors as diverse as blood pressure (high or low), cholesterol level (high or low), left ventricular hypertrophy, vascular stiffness, chronic inflammation, and hyperhomocysteinemia. Mainly cross-sectional studies of renal patients showed excess CV calcification (CVC) compared with the general population, but a clear link between calcification and subsequent mortality is tenuous to date. Several factors have been incriminated to explain the increase in CVC in this particular population. Increased duration of dialysis therapy, dyslipidemia, altered calcium-phosphorus metabolism, and chronic inflammation have all been associated with increased CVC. However, with the shortage of large, observational, population-based, prospective studies tracking these potential risk factors and the pathogenesis of CVC in renal patients not yet sufficiently understood, it is difficult with the present state of knowledge to make robust recommendations about care strategies. The purpose of this review is to examine the 10 available studies of renal patients that have used modern CVC imaging and quantification techniques for clues to likely targets for future interventional studies.

Matrix Gla Protein Polymorphisms are Associated with Coronary Artery Calcification in Men

PubMed Central

Crosier, Michael D.; Booth, Sarah L.; Peter, Inga; Dawson-Hughes, Bess; Price, Paul A.; O’Donnell, Christopher J.; Hoffmann, Udo; Williamson, Matthew K.; Ordovas, Jose M.

2009-01-01

Summary Matrix Gla protein (MGP) is a key regulator of vascular calcification. Genetic variation at the MGP locus could modulate the development of coronary artery calcification (CAC). Our aim was to examine the cross-sectional association between MGP single nucleotide polymorphisms (SNPs) [rs1800802 (T-138C), rs1800801 (G-7A), and rs4236 (Ala102Thr)] and CAC. CAC was measured by multidetector computed tomography (MDCT), in older men and women of European descent, (n = 386; 60 to 80 y of age). Serum MGP was measured by radioimmunoassay. Linear, Tobit and Ordinal regression analyses all revealed that in men, homozygous carriers of the minor allele of rs1800802 , rs1800801 , or rs4236 (minor allele frequency: 21, 38, and 40%, respectively) were associated with a decreased quantity of CAC, relative to major allele carriers. This association was not found in women. Although genetic variation in MGP was associated with serum MGP concentrations, there were no associations between serum MGP and CAC. The results of this study suggest a role for MGP genetic variants in coronary atherosclerosis among men that is not reflected in serum MGP concentrations. PMID:19352064

COX2 Inhibition Reduces Aortic Valve Calcification In Vivo

PubMed Central

Wirrig, Elaine E.; Gomez, M. Victoria; Hinton, Robert B.; Yutzey, Katherine E.

2016-01-01

Objective Calcific aortic valve disease (CAVD) is a significant cause of morbidity and mortality, which affects approximately 1% of the US population and is characterized by calcific nodule formation and stenosis of the valve. Klotho-deficient mice were used to study the molecular mechanisms of CAVD as they develop robust aortic valve (AoV) calcification. Through microarray analysis of AoV tissues from klotho-deficient and wild type mice, increased expression of the gene encoding cyclooxygenase 2/COX2 (Ptgs2) was found. COX2 activity contributes to bone differentiation and homeostasis, thus the contribution of COX2 activity to AoV calcification was assessed. Approach and Results In klotho-deficient mice, COX2 expression is increased throughout regions of valve calcification and is induced in the valvular interstitial cells (VICs) prior to calcification formation. Similarly, COX2 expression is increased in human diseased AoVs. Treatment of cultured porcine aortic VICs with osteogenic media induces bone marker gene expression and calcification in vitro, which is blocked by inhibition of COX2 activity. In vivo, genetic loss of function of COX2 cyclooxygenase activity partially rescues AoV calcification in klotho-deficient mice. Moreover, pharmacologic inhibition of COX2 activity in klotho-deficient mice via celecoxib-containing diet reduces AoV calcification and blocks osteogenic gene expression. Conclusions COX2 expression is upregulated in CAVD and its activity contributes to osteogenic gene induction and valve calcification in vitro and in vivo. PMID:25722432

Energy-dense diets increase FGF23, lead to phosphorus retention and promote vascular calcifications in rats.

PubMed

Raya, Ana I; Rios, Rafael; Pineda, Carmen; Rodriguez-Ortiz, Maria E; Diez, Elisa; Almaden, Yolanda; Muñoz-Castañeda, Juan R; Rodriguez, Mariano; Aguilera-Tejero, Escolastico; Lopez, Ignacio

2016-11-14

Rats with normal renal function (Experiment 1, n = 12) and uninephrectomized (1/2Nx) rats (Experiment 2, n = 12) were fed diets with normal P (NP) and either normal (NF) or high fat (HF). Rats with intact renal function (Experiment 3, n = 12) were also fed NF or HF diets with high P (HP). Additionally, uremic (5/6Nx) rats (n = 16) were fed HP diets with NF or HF. Feeding the HF diets resulted in significant elevation of plasma FGF23 vs rats fed NF diets: Experiment 1, 593 ± 126 vs 157 ± 28 pg/ml (p < 0.01); Experiment 2, 538 ± 105 vs 250 ± 18 pg/ml (p < 0.05); Experiment 3, 971 ± 118 vs 534 ± 40 pg/ml (p < 0.01). Rats fed HF diets showed P retention and decreased renal klotho (ratio klotho/actin) vs rats fed NF diets: Experiment 1, 0.75 ± 0.06 vs 0.97 ± 0.02 (p < 0.01); Experiment 2, 0.69 ± 0.07 vs 1.12 ± 0.08 (p < 0.01); Experiment 3, 0.57 ± 0.19 vs 1.16 ± 0.15 (p < 0.05). Uremic rats fed HF diet showed more severe vascular calcification (VC) than rats fed NF diet (aortic Ca = 6.3 ± 1.4 vs 1.4 ± 0.1 mg/g tissue, p < 0.001). In conclusion, energy-rich diets increased plasma levels of FGF23, a known risk factor of cardiovascular morbidity and mortality. Even though FGF23 has major phosphaturic actions, feeding HF diets resulted in P retention, likely secondary to decreased renal klotho, and aggravated uremic VC.

Energy-dense diets increase FGF23, lead to phosphorus retention and promote vascular calcifications in rats

PubMed Central

Raya, Ana I.; Rios, Rafael; Pineda, Carmen; Rodriguez-Ortiz, Maria E.; Diez, Elisa; Almaden, Yolanda; Muñoz-Castañeda, Juan R.; Rodriguez, Mariano; Aguilera-Tejero, Escolastico; Lopez, Ignacio

2016-01-01

Rats with normal renal function (Experiment 1, n = 12) and uninephrectomized (1/2Nx) rats (Experiment 2, n = 12) were fed diets with normal P (NP) and either normal (NF) or high fat (HF). Rats with intact renal function (Experiment 3, n = 12) were also fed NF or HF diets with high P (HP). Additionally, uremic (5/6Nx) rats (n = 16) were fed HP diets with NF or HF. Feeding the HF diets resulted in significant elevation of plasma FGF23 vs rats fed NF diets: Experiment 1, 593 ± 126 vs 157 ± 28 pg/ml (p < 0.01); Experiment 2, 538 ± 105 vs 250 ± 18 pg/ml (p < 0.05); Experiment 3, 971 ± 118 vs 534 ± 40 pg/ml (p < 0.01). Rats fed HF diets showed P retention and decreased renal klotho (ratio klotho/actin) vs rats fed NF diets: Experiment 1, 0.75 ± 0.06 vs 0.97 ± 0.02 (p < 0.01); Experiment 2, 0.69 ± 0.07 vs 1.12 ± 0.08 (p < 0.01); Experiment 3, 0.57 ± 0.19 vs 1.16 ± 0.15 (p < 0.05). Uremic rats fed HF diet showed more severe vascular calcification (VC) than rats fed NF diet (aortic Ca = 6.3 ± 1.4 vs 1.4 ± 0.1 mg/g tissue, p < 0.001). In conclusion, energy-rich diets increased plasma levels of FGF23, a known risk factor of cardiovascular morbidity and mortality. Even though FGF23 has major phosphaturic actions, feeding HF diets resulted in P retention, likely secondary to decreased renal klotho, and aggravated uremic VC. PMID:27841294

Proton pumping accompanies calcification in foraminifera.

PubMed

Toyofuku, Takashi; Matsuo, Miki Y; de Nooijer, Lennart Jan; Nagai, Yukiko; Kawada, Sachiko; Fujita, Kazuhiko; Reichart, Gert-Jan; Nomaki, Hidetaka; Tsuchiya, Masashi; Sakaguchi, Hide; Kitazato, Hiroshi

2017-01-27

Ongoing ocean acidification is widely reported to reduce the ability of calcifying marine organisms to produce their shells and skeletons. Whereas increased dissolution due to acidification is a largely inorganic process, strong organismal control over biomineralization influences calcification and hence complicates predicting the response of marine calcifyers. Here we show that calcification is driven by rapid transformation of bicarbonate into carbonate inside the cytoplasm, achieved by active outward proton pumping. Moreover, this proton flux is maintained over a wide range of pCO 2 levels. We furthermore show that a V-type H + ATPase is responsible for the proton flux and thereby calcification. External transformation of bicarbonate into CO 2 due to the proton pumping implies that biomineralization does not rely on availability of carbonate ions, but total dissolved CO 2 may not reduce calcification, thereby potentially maintaining the current global marine carbonate production.

Proton pumping accompanies calcification in foraminifera

NASA Astrophysics Data System (ADS)

Toyofuku, Takashi; Matsuo, Miki Y.; de Nooijer, Lennart Jan; Nagai, Yukiko; Kawada, Sachiko; Fujita, Kazuhiko; Reichart, Gert-Jan; Nomaki, Hidetaka; Tsuchiya, Masashi; Sakaguchi, Hide; Kitazato, Hiroshi

2017-01-01

Ongoing ocean acidification is widely reported to reduce the ability of calcifying marine organisms to produce their shells and skeletons. Whereas increased dissolution due to acidification is a largely inorganic process, strong organismal control over biomineralization influences calcification and hence complicates predicting the response of marine calcifyers. Here we show that calcification is driven by rapid transformation of bicarbonate into carbonate inside the cytoplasm, achieved by active outward proton pumping. Moreover, this proton flux is maintained over a wide range of pCO2 levels. We furthermore show that a V-type H+ ATPase is responsible for the proton flux and thereby calcification. External transformation of bicarbonate into CO2 due to the proton pumping implies that biomineralization does not rely on availability of carbonate ions, but total dissolved CO2 may not reduce calcification, thereby potentially maintaining the current global marine carbonate production.

Effects of dietary calcium on atherosclerosis, aortic calcification, and icterus in rabbits fed a supplemental cholesterol diet.

PubMed

Hsu, Howard H T; Culley, Nathan C

2006-06-23

Vascular calcification is implicated in myocardial infarction, instability and rigidity of the aortic wall, and bioprosthetic failures. Although an increase in the calcium (Ca) content in atherogenic diets has been shown to decrease atherosclerosis in rabbits, whether Ca supplementation and deficiency can affect atherosclerosis-related aortic calcification remains unknown. New Zealand White male rabbit littermates were fed an atherogenic diet containing 0.5% cholesterol and 2% peanut oil. The Ca content of the diet, which normally contains 1%, was adjusted to 0.5 or 3%. Segments of thoracic aortas were dissected from rabbits for histological evaluations and Ca and Pi determinations. Rabbits with calcium supplementation were maintained for 4 months, whereas those with calcium deficiency were maintained for 2 1/2 months due to severe icterus beyond this stage. The ratios of intimal to medial areas and calcified to intimal areas were used to semi-quantify lesion accumulation and calcification, respectively. Icterus was estimated from the extent of yellowing of the skin, sclera, and mucous membranes along with gross evidence of hepatic lipidosis and/or biliary obstructions. Statistical analysis of 16 matched littermates shows that Ca supplementation significantly decreased the lesions by 41% (p < 0.05) and markedly inhibited calcification by 62% (p < 0.05). Statistical analysis of 11 matched littermates shows that Ca deficiency significantly increased the lesions by 2.7-fold (p < 0.05) and that the diet caused a small but significant calcification not seen in the sibling groups with normal dietary Ca. Ca supplementation caused a significant 30% decrease in serum cholesterol (p < 0.05). Calcium deficiency increased serum cholesterol by 57% (p < 0.001). Serum cholesterol and LDL-cholesterol levels in Ca deficient rabbits were 2-fold higher than those with high Ca diets. Ca supplementation decreased soluble Ca and Pi content in aortas, suggesting that this effect may

Effects of Phosphate Binder Therapy on Vascular Stiffness in Early Stage Chronic Kidney Disease

PubMed Central

Seifert, Michael E.; de las Fuentes, Lisa; Rothstein, Marcos; Dietzen, Dennis J.; Bierhals, Andrew J.; Cheng, Steven C.; Ross, Will; Windus, David; Dávila-Román, Víctor G.; Hruska, Keith A.

2013-01-01

Background/Aims Cardiovascular disease (CVD) is increased in chronic kidney disease (CKD), and contributed to by the CKD-mineral bone disorder (CKD-MBD). The CKD-MBD begins in early CKD and its vascular manifestations begin with vascular stiffness proceeding to increased carotid artery intima-media thickness (cIMT) and vascular calcification (VC). Phosphorus is associated with this progression and is considered a CVD risk factor in CKD. We hypothesized that modifying phosphorus balance with lanthanum carbonate (LaCO3) in early CKD would not produce hypophosphatemia and may affect vascular manifestations of the CKD-MBD. Methods We randomized 38 subjects with normophosphatemic stage 3 CKD to a fixed dose of LaCO3 or matching placebo without adjusting dietary phosphorus in a 12-month randomized, double-blind, pilot and feasibility study. The primary outcome was the change in serum phosphorus. Secondary outcomes were changes in measures of phosphate homeostasis and vascular stiffness assessed by carotid-femoral pulse wave velocity (PWV), cIMT and VC over 12 months. Results There were no statistically significant differences between LaCO3 and placebo with respect to the change in serum phosphorus, urinary phosphorus, tubular reabsorption of phosphorus, PWV, cIMT, or VC. Biomarkers of the early CKD-MBD such as plasma fibroblast growth factor-23 (FGF23), Dickkopf-related protein 1 (DKK1), and sclerostin were increased 2–3-fold at baseline but were not affected by LaCO3. Conclusion 12 months of LaCO3 had no effect on serum phosphorus and did not alter phosphate homeostasis, PWV, cIMT, VC, or biomarkers of the CKD-MBD. PMID:23941761

Vascularization of bioprosthetic valve material

NASA Astrophysics Data System (ADS)

Boughner, Derek R.; Dunmore-Buyze, Joy; Heenatigala, Dino; Lohmann, Tara; Ellis, Chris G.

1999-04-01

Cell membrane remnants represent a probable nucleation site for calcium deposition in bioprosthetic heart valves. Calcification is a primary failure mode of both bovine pericardial and porcine aortic heterograft bioprosthesis but the nonuniform pattern of calcium distribution within the tissue remains unexplained. Searching for a likely cellular source, we considered the possibility of a previously overlooked small blood vessel network. Using a videomicroscopy technique, we examined 5 matched pairs of porcine aortic and pulmonary valves and 14 samples from 6 bovine pericardia. Tissue was placed on a Leitz Metallux microscope and transilluminated with a 75 watt mercury lamp. Video images were obtained using a silicon intensified target camera equipped with a 431 nm interference filter to maximize contrast of red cells trapped in a capillary microvasculature. Video images were recorded for analysis on a Silicon Graphics Image Analysis work station equipped with a video frame grabber. For porcine valves, the technique demonstrated a vascular bed in the central spongiosa at cusp bases with vessel sizes from 6-80 micrometers . Bovine pericardium differed with a more uniform distribution of 7-100 micrometers vessels residing centrally. Thus, small blood vessel endothelial cells provide a potential explanation patterns of bioprosthetic calcification.

Calcification by Reef-Building Sclerobionts

PubMed Central

Mallela, Jennie

2013-01-01

It is widely accepted that deteriorating water quality associated with increased sediment stress has reduced calcification rates on coral reefs. However, there is limited information regarding the growth and development of reef building organisms, aside from the corals themselves. This study investigated encruster calcification on five fore-reefs in Tobago subjected to a range of sedimentation rates (1.2 to 15.9 mg cm−2 d−1). Experimental substrates were used to assess rates of calcification in sclerobionts (e.g. crustose coralline algae, bryozoans and barnacles) across key reef microhabitats: cryptic (low-light), exposed (open-horizontal) and vertical topographic settings. Sedimentation negatively impacted calcification by photosynthesising crustose coralline algae in exposed microhabitats and encrusting foram cover (%) in exposed and cryptic substrates. Heterotrophs were not affected by sedimentation. Fore-reef, turbid water encruster assemblages calcified at a mean rate of 757 (SD ±317) g m−2 y−1. Different microhabitats were characterised by distinct calcareous encruster assemblages with different rates of calcification. Taxa with rapid lateral growth dominated areal cover but were not responsible for the majority of CaCO3 production. Cryptobiont assemblages were composed of a suite of calcifying taxa which included sciaphilic cheilostome bryozoans and suspension feeding barnacles. These calcified at mean rates of 20.1 (SD ±27) and 4.0 (SD ±3.6) g m−2 y−1 respectively. Encruster cover (%) on exposed and vertical substrates was dominated by crustose coralline algae which calcified at rates of 105.3 (SD ±67.7) g m−2 y−1 and 56.3 (SD ±8.3) g m−2 y−1 respectively. Globally, encrusting organisms contribute significant amounts of carbonate to the reef framework. These results provide experimental evidence that calcification rates, and the importance of different encrusting organisms, vary significantly according to topography and sediment

Secondary calcification and dissolution respond differently to future ocean conditions

NASA Astrophysics Data System (ADS)

Silbiger, N. J.; Donahue, M. J.

2014-09-01

Climate change threatens both the accretion and erosion processes that sustain coral reefs. Secondary calcification, bioerosion, and reef dissolution are integral to the structural complexity and long-term persistence of coral reefs, yet these processes have received less research attention than reef accretion by corals. In this study, we use climate scenarios from RCP8.5 to examine the combined effects of rising ocean acidity and SST on both secondary calcification and dissolution rates of a natural coral rubble community using a flow-through aquarium system. We found that secondary reef calcification and dissolution responded differently to the combined effect of pCO2 and temperature. Calcification had a non-linear response to the combined effect of pCO2-temperature: the highest calcification rate occurred slightly above ambient conditions and the lowest calcification rate was in the highest pCO2-temperature condition. In contrast, dissolution increased linearly with pCO2-temperature. The rubble community switched from net calcification to net dissolution at +272 μatm pCO2 and 0.84 °C above ambient conditions, suggesting that rubble reefs may shift from net calcification to net dissolution before the end of the century. Our results indicate that dissolution may be more sensitive to climate change than calcification, and that calcification and dissolution have different functional responses to climate stressors, highlighting the need to study the effects of climate stressors on both calcification and dissolution to predict future changes in coral reefs.

Smoking and morphology of calcific deposits affect the outcome of needle aspiration of calcific deposits (NACD) for calcific tendinitis of the rotator cuff.

PubMed

Oudelaar, Bart W; Ooms, Edwin M; Huis In 't Veld, Rianne M H A; Schepers-Bok, Relinde; Vochteloo, Anne J

2015-11-01

Although NACD has proven to be an effective minimal invasive treatment for calcific tendinitis of the rotator cuff, little is known about the factors associated with treatment failure or the need for multiple procedures. Patients with symptomatic calcific tendinitis who were treated by NACD were evaluated in a retrospective cohort study. Demographic details, medical history, sonographic and radiographic findings were collected from patient files. Failure of NACD was defined as the persistence of symptoms after a follow-up of at least six months. NACD procedures performed within six months after a previous NACD procedure were considered repeated procedures. Multivariate logistic regression analysis was used to determine factors associated with treatment failure and multiple procedures. 431 patients (277 female; mean age 51.4±9.9 years) were included. Smoking (adjusted odds ratio (AOR): 1.7, 95% CI 1.0-2.7, p=0.04) was significantly associated with failure of NACD. Patients with Gärtner and Heyer (GH) type I calcific deposits were more likely to need multiple NACD procedures (AOR: 3.4, 95% CI 1.6-7.5, p<0.01) compared to patients with type III calcific deposits. Partial thickness rotator cuff tears were of no influence on the outcome of NACD or the number of treatments necessary. Smoking almost doubled the chance of failure of NACD and the presence of GH type I calcific deposits significantly increased the chance of multiple procedures. Partial thickness rotator cuff tears did not seem to affect the outcome of NACD. Based on the findings in this study, the importance of quitting smoking should be emphasized prior to NACD and partial thickness rotator cuff tears should not be a reason to withhold patients NACD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Calcification and photosynthesis of the coral acropora cervicornis under calcium limited conditions

NASA Technical Reports Server (NTRS)

Rathfon, Megan; Brewer, Debbie

1997-01-01

Differing hypothesis about the function of calcification are based on an interesting dilemma. Is the purpose of calcification mainly a structural and protective one or does calcification serve other functions? Does photosynthesis increase carbonate ion activity and cause calcification or does calcification increase CO2 levels and stimulate photsynthesis? It is proposed that calcification in corals is not dependent upon photosynthesis but upon calcium levels in the water. Under normal ocean conditions, corals convert a certain percentage of energy to photosynthesis and respiration and another percentage to calcification. As corals become nutrient stressed, particularly calcium limited, the ratio of photosynthesis to calcification shifts towards calcification in order to generate protons. The protons generated during calcification may stimulate photosynthesis and aid in the uptake of nutrients and biocarbonates. The results of the calcification experiment show a trend towards increased calcification and decreased photosynthesis when the coral Acropora cervicornis is calcium limited, but the data are inconclusive and further research is needed.

Targeted reduction of vascular Msx1 and Msx2 mitigates arteriosclerotic calcification and aortic stiffness in LDLR-deficient mice fed diabetogenic diets.

PubMed

Cheng, Su-Li; Behrmann, Abraham; Shao, Jian-Su; Ramachandran, Bindu; Krchma, Karen; Bello Arredondo, Yoanna; Kovacs, Attila; Mead, Megan; Maxson, Robert; Towler, Dwight A

2014-12-01

When fed high-fat diets, male LDLR(-/-) mice develop obesity, hyperlipidemia, hyperglycemia, and arteriosclerotic calcification. An osteogenic Msx-Wnt regulatory program is concomitantly upregulated in the vasculature. To better understand the mechanisms of diabetic arteriosclerosis, we generated SM22-Cre;Msx1(fl/fl);Msx2(fl/fl);LDLR(-/-) mice, assessing the impact of Msx1+Msx2 gene deletion in vascular myofibroblast and smooth muscle cells. Aortic Msx2 and Msx1 were decreased by 95% and 34% in SM22-Cre;Msx1(fl/fl);Msx2(fl/fl);LDLR(-/-) animals versus Msx1(fl/fl);Msx2(fl/fl);LDLR(-/-) controls, respectively. Aortic calcium was reduced by 31%, and pulse wave velocity, an index of stiffness, was decreased in SM22-Cre;Msx1(fl/fl);Msx2(fl/fl);LDLR(-/-) mice vs. controls. Fasting blood glucose and lipids did not differ, yet SM22-Cre;Msx1(fl/fl);Msx2(fl/fl);LDLR(-/-) siblings became more obese. Aortic adventitial myofibroblasts from SM22-Cre;Msx1(fl/fl);Msx2(fl/fl);LDLR(-/-) mice exhibited reduced osteogenic gene expression and mineralizing potential with concomitant reduction in multiple Wnt genes. Sonic hedgehog (Shh) and Sca1, markers of aortic osteogenic progenitors, were also reduced, paralleling a 78% reduction in alkaline phosphatase (TNAP)-positive adventitial myofibroblasts. RNA interference revealed that although Msx1+Msx2 supports TNAP and Wnt7b expression, Msx1 selectively maintains Shh and Msx2 sustains Wnt2, Wnt5a, and Sca1 expression in aortic adventitial myofibroblast cultures. Thus, Msx1 and Msx2 support vascular mineralization by directing the osteogenic programming of aortic progenitors in diabetic arteriosclerosis. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Risk factors associated with coronary artery calcification should be examined before kidney transplantation.

PubMed

Simic-Ogrizovic, Sanja; Bogavac-Stanojevic, Natasa; Vuckovic, Maja; Dopsaj, Violeta; Giga, Voja; Kravljaca, Milica; Stosovic, Milan; Lezaic, Visnja

2012-02-01

The best treatment for end stage renal disease (ESRD) patients is kidney transplantation, but the renal transplant recipients still have a higher incidence of cardiovascular events compared with general population. Cardiovascular risk factors were imposed long before ESRD, as the majority of patients starting dialysis or kidney transplantation already have signs of advanced atherosclerosis. Artery calcification is an organized, regulated process similar to bone formation. Coronary artery calcification (CAC) is found frequently in advanced atherosclerotic lesions and could be a useful marker of them. We evaluated the prevalence of CAC in 49 stable renal transplant recipients and in 48 age- and gender-matched patients with chronic kidney disease (CKD) in stages 2-5 not requiring dialysis to assess risk factors associated with CAC. Computed tomography was used for CAC detection and quantification (CAC score). The prevalence of CAC was 43.8% in transplant recipients and 16.7% in CKD patients (p < 0.001). Transplant recipients with CAC were significantly older and had longer duration of CKD and/or dialysis than recipients without CAC. In contrast, the serum levels of fetuin A (an inhibitor of vascular calcification) and albumin were significantly lower in CKD patients with CAC than those without CAC. During the observation period (30 months), 30 patients, including 23 CKD patients, began dialysis, and 4 transplant recipients and 2 CKD patients died. Independent predictors of mortality were age, serum amyloid A and the CAC score. In conclusion, the examination and prevention of risk factors associated with atherosclerosis should be started at the beginning of renal failure.

Secondary calcification and dissolution respond differently to future ocean conditions

NASA Astrophysics Data System (ADS)

Silbiger, N. J.; Donahue, M. J.

2015-01-01

Climate change threatens both the accretion and erosion processes that sustain coral reefs. Secondary calcification, bioerosion, and reef dissolution are integral to the structural complexity and long-term persistence of coral reefs, yet these processes have received less research attention than reef accretion by corals. In this study, we use climate scenarios from RCP 8.5 to examine the combined effects of rising ocean acidity and sea surface temperature (SST) on both secondary calcification and dissolution rates of a natural coral rubble community using a flow-through aquarium system. We found that secondary reef calcification and dissolution responded differently to the combined effect of pCO2 and temperature. Calcification had a non-linear response to the combined effect of pCO2 and temperature: the highest calcification rate occurred slightly above ambient conditions and the lowest calcification rate was in the highest temperature-pCO2 condition. In contrast, dissolution increased linearly with temperature-pCO2 . The rubble community switched from net calcification to net dissolution at +271 μatm pCO2 and 0.75 °C above ambient conditions, suggesting that rubble reefs may shift from net calcification to net dissolution before the end of the century. Our results indicate that (i) dissolution may be more sensitive to climate change than calcification and (ii) that calcification and dissolution have different functional responses to climate stressors; this highlights the need to study the effects of climate stressors on both calcification and dissolution to predict future changes in coral reefs.

Chronic parotitis with multiple calcifications: Clinical and sialendoscopic findings.

PubMed

Jáuregui, Emmanuel; Kiringoda, Ruwan; Ryan, William R; Eisele, David W; Chang, Jolie L

2017-07-01

To characterize clinical, imaging, and sialendoscopy findings in patients with chronic parotitis and multiple parotid calcifications. Retrospective review. Clinical history, radiographic images and reports, lab tests, and operative reports were reviewed for adult patients with chronic parotitis and multiple parotid calcifications who underwent parotid sialendoscopy. Thirteen of 133 (10%) patients undergoing parotid sialendoscopy for chronic sialadenitis had more than one calcification in the region of the parotid gland. Seven patients (54%) were diagnosed with immune-mediated disease from autoimmune parotitis (positive Sjögren's antibodies or antinuclear antibodies) or human immunodeficiency virus (HIV) disease. The six patients (46%) who did not have an immune-mediated disorder had most calcifications located anterior or along the masseter muscle. Eight of 13 patients (61%) had at least one calculus found in the parotid duct on sialendoscopy. Four patients (38%) had multiple punctate calcifications within the parotid gland, all of whom had either autoimmune parotitis or HIV. None of the proximal or punctate parotid calcifications posterior to the masseter were visualized on sialendoscopy. Chronic parotitis in conjunction with multiple parotid calcifications is uncommon and was identified in 10% of our cohort. We contrast two classifications of parotid calcifications: 1) intraductal stones that cause recurrent duct obstruction and are often located within the main parotid duct along or anterior to the masseter and 2) punctate intraparenchymal parotid gland calcifications that are not visualized on sialendoscopy and may represent underlying inflammatory disease. 4 Laryngoscope, 127:1565-1570, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

The incidence of renal calcification in preterm infants.

PubMed Central

Short, A; Cooke, R W

1991-01-01

A total of 79 infants born at less than 32 weeks' gestation were studied with serial renal ultrasound scans to assess the incidence of nephrocalcinosis. Twenty one infants developed renal calcification giving an overall incidence of 26.6% in the study group. Affected infants were significantly smaller (mean (SD) birth weight 940 (323) g) and significantly less mature (mean (SD) gestation 26.9 (1.9) weeks). In 17 patients the calcification was represented by hyperechogenic renal pyramids alone, and in four patients renal calculi were demonstrated. Factors associated with renal calcification included hypophosphataemia, hypercalcaemia, hypercreatininaemia, and prolonged oxygen requirement during the first month of life. Multivariate analysis showed that the strongest clinical indicator of calcification was duration of oxygen treatment. Infants who still required oxygen treatment at 28 days had a 62% chance of developing renal calcification. Images Figure 4 Figure 5 PMID:2025034

[Arterial media calcification in patients with type 2 diabetes mellitus].

PubMed

Belovici, Maria Isabela; Pandele, G I

2008-01-01

Arterial calcification was previously viewed as an inevitable, passive, and degenerative process that occurred at the end stages of atherosclerosis. Recent studies, however, have demonstrated that calcification of arteries is a complex and regulated process. It may occur in conjunction with atherosclerosis or in an isolated form that is commonly associated with diabetes and renal failure. Higher artery calcium scores are associated with increased cardiovascular events, and some aspects of arterial calcification are similar to the biology of forming bone. Arterial calcification can thus be viewed as a distinct inflammatory arteriopathy, much like atherosclerosis and aneurysms, with its own contribution to cardiovascular morbidity and mortality. Current research involves efforts to define the complex interactions between cellular and molecular mediators of arterial calcification and, in particular, the role of endogenous calcification inhibitors. This review discusses the clinical relevance, cellular events, and suspected molecular pathways that control arterial calcification.

Periodontal disease is an independent predictor of intracardiac calcification.

PubMed

Pressman, Gregg S; Qasim, Atif; Verma, Nitin; Miyamae, Masami; Arishiro, Kumiko; Notohara, Yasuhiro; Crudu, Vitalie; Figueredo, Vincent M

2013-01-01

Periodontitis is the most common chronic inflammatory condition worldwide and is associated with incident coronary disease. We hypothesized that periodontal disease would also be associated with cardiac calcification, a condition which shares many risk factors with atherosclerosis and is considered a marker of subclinical atherosclerosis. Cross-sectional study at two sites (USA and Japan) involving subjects with both clinical echocardiograms and detailed dental examinations. Semiquantitative scoring systems were used to assess severity of periodontal disease and echocardiographic calcification. Fifty-six of 73 subjects (77%) had cardiac calcifications, and 51% had moderate to severe periodontal disease (score > 2). In unadjusted analysis, a significant relationship between periodontal score and cardiac calcification (Spearman rho = 0.4, P = 0.001) was noted, with increases in mean calcification score seen across increasing levels of periodontal disease. On multivariate logistic regression, adjusted for age, gender, race, glomerular filtration rate, and traditional risk factors, this association remained significant (P = 0.024). There was no significant interaction by study site, race, or gender. In a multiracial population, we found a significant association between the degree of periodontal disease, a chronic inflammatory condition, and cardiac calcification. Further, higher periodontal scores were associated with greater degrees of calcification.

Skeletal maturity assessment using mandibular canine calcification stages.

PubMed

Džemidžić, Vildana; Tiro, Alisa; Zukanović, Amila; Redžić, Ismeta; Nakaš, Enita

2016-11-01

The aims of this study were: to investigate the relationship between mandibular canine calcification stages and skeletal maturity; and to evaluate whether the mandibular canine calcification stages may be used as a reliable diagnostic tool for skeletal maturity assessment. This study included 151 subjects: 81 females and 70 males, with ages ranging from 9 to 16 years (mean age: 12.29±1.86 years). The inclusion criteria for subjects were as follows: age between 9 and 16 years; good general health without any hormonal, nutritional, growth or dental development problems. Subjects who were undergoing or had previously received orthodontic treatment were not included in this study. The calcification stages of the left permanent mandibular canine were assessed according to the method of Demirjian, on panoramic radiographs. Assessment of skeletal maturity was carried out using the cervical vertebral maturation index (CVMI), as proposed by the Hassel-Farman method, on lateral cephalograms. The correlation between the calcification stages of mandibular canine and skeletal maturity was estimated separately for male and female subjects. Correlation coefficients between calcification stages of mandibular canine and skeletal maturity were 0.895 for male and 0.701 for female subjects. A significant correlation was found between the calcification stages of the mandibular canine and skeletal maturity. The calcification stages of the mandibular canine show a satisfactory diagnostic performance only for assessment of pre-pubertal growth phase. Copyright © 2016 by Academy of Sciences and Arts of Bosnia and Herzegovina.

Characterisation of Calcium Phosphate Crystals on Calcified Human Aortic Vascular Smooth Muscle Cells and Potential Role of Magnesium

PubMed Central

Louvet, Loïc; Bazin, Dominique; Büchel, Janine; Steppan, Sonja; Passlick-Deetjen, Jutta; Massy, Ziad A.

2015-01-01

Background Cardiovascular disease including vascular calcification (VC) remains the leading cause of death in patients suffering from chronic kidney disease (CKD). The process of VC seems likely to be a tightly regulated process where vascular smooth muscle cells are playing a key role rather than just a mere passive precipitation of calcium phosphate. Characterisation of the chemical and crystalline structure of VC was mainly led in patients or animal models with CKD. Likewise, Mg2+ was found to be protective in living cells although a potential role for Mg2+ could not be excluded on crystal formation and precipitation. In this study, the crystal formation and the role of Mg2+ were investigated in an in vitro model of primary human aortic vascular smooth muscle cells (HAVSMC) with physical techniques. Methodology/Principal Findings In HAVSMC incubated with increased Ca x Pi medium, only calcium phosphate apatite crystals (CPA) were detected by Micro-Fourier Transform InfraRed spectroscopy (µFTIR) and Field Effect Scanning Electron Microscope (FE — SEM) and Energy Dispersive X-ray spectrometry (EDX) at the cell layer level. Supplementation with Mg2+ did not alter the crystal composition or structure. The crystal deposition was preferentially positioned near or directly on cells as pictured by FE — SEM observations and EDX measurements. Large µFTIR maps revealed spots of CPA crystals that were associated to the cellular layout. This qualitative analysis suggests a potential beneficial effect of Mg2+ at 5 mM in noticeably reducing the number and intensities of CPA µFTIR spots. Conclusions/Significance For the first time in a model of HAVSMC, induced calcification led to the formation of the sole CPA crystals. Our data seems to exclude a physicochemical role of Mg2+ in altering the CPA crystal growth, composition or structure. Furthermore, Mg2+ beneficial role in attenuating VC should be linked to an active cellular role. PMID:25607936

Histopathological assessment of calcification and inflammation of calcific aortic valves from patients with and without diabetes mellitus.

PubMed

Mosch, Josephin; Gleissner, Christian A; Body, Simon; Aikawa, Elena

2017-03-01

Calcific aortic valve disease (CAVD) is the most common valvular heart disease and likely evolves from inflammatory pre-conditions in the valve. Type II diabetes mellitus (DMII) has been associated with pathogenesis of CAVD, however, the mechanism initiating CAVD in DMII is not well understood and the human valve pathology in DMII has not been described. We therefore performed quantitative histological analyses of aortic valves of CAVD patients with and without DMII. CAVD human aortic valves (n=45) obtained after surgical valve replacement were examined macroscopically with gross measurements of calcified areas. Inflammation and calcification were assessed by immunohistochemistry and immunofluorescence staining. Calcification was increased in diabetic patients according to gross measurements (p<0.01) and alizarin red staining (p=0.05). Early calcification markers, including Runx2 (p=0.02) and alkaline phosphatase (ALP, p=0.03) were significantly elevated in diabetic patients. Furthermore, in diabetic patients we found significantly increased expression of annexin II (p=0.04) and annexin V (p=0.04), both of which are thought to play a role in microcalcification formation via apoptosis or extracellular vesicle release. Macrophage numbers were comparable in both groups (p=0.41), while the expression of the pro-inflammatory protein S100A9 (p<0.01) was significantly decreased in diabetic individuals. Evaluation of lymphocytes revealed similar CD8 (p=0.45) and CD4 (p=0.92) T cell counts in diabetic and non-diabetic aortic valves. Aortic valves from diabetic patients show more calcification, while inflammation is similar in both patient populations. Considering the generally accepted theory of an inflammation-dependent mechanism of calcification, these data suggest that in patients with CAVD requiring valve replacement, diabetic patients could be molecularly in a more advanced disease stage with a higher grade of mineralization than non-diabetic patients.

Susceptibility weighted imaging: differentiating between calcification and hemosiderin*

PubMed Central

Barbosa, Jeam Haroldo Oliveira; Santos, Antonio Carlos; Salmon, Carlos Ernesto Garrido

2015-01-01

Objective To present a detailed explanation on the processing of magnetic susceptibility weighted imaging (SWI), demonstrating the effects of echo time and sensitive mask on the differentiation between calcification and hemosiderin. Materials and Methods Computed tomography and magnetic resonance (magnitude and phase) images of six patients (age range 41– 54 years; four men) were retrospectively selected. The SWI images processing was performed using the Matlab’s own routine. Results Four out of the six patients showed calcifications at computed tomography images and their SWI images demonstrated hyperintense signal at the calcification regions. The other patients did not show any calcifications at computed tomography, and SWI revealed the presence of hemosiderin deposits with hypointense signal. Conclusion The selection of echo time and of the mask may change all the information on SWI images, and compromise the diagnostic reliability. Amongst the possible masks, the authors highlight that the sigmoid mask allows for contrasting calcifications and hemosiderin on a single SWI image. PMID:25987750

Relationship of Estimated GFR and Coronary Artery Calcification in the (CRIC) Chronic Renal Insufficiency Cohort Study

PubMed Central

Budoff, Matthew J; Rader, Daniel J; Reilly, Muredach P.; Mohler, Emile R.; Lash, Jim; Yang, Wei; Rosen, Leigh; Glenn, Melanie; Teal, Valerie; Feldman, Harold I.

2011-01-01

Background Coronary artery calcification (CAC) is associated with increased mortality risk in the general population. Although individuals with chronic kidney disease (CKD) are at markedly increased mortality risk, the incidence, prevalence, and prognosis of CAC in CKD is not well-understood. Study Design Cross-sectional observational study. Setting and Participants Analysis of 1,908 participants who underwent coronary calcium scanning as part of the multi-ethnic CRIC (Chronic Renal Insufficiency Cohort) Study. Predictor Estimated glomerular filtration rate (eGFR) computed using the Modification of Diet in Renal Disease (MDRD) Study equation, stratified by race, sex and diabetic status. eGFR was treated as a continous variable and a categorical variable compared to the reference range of >60 ml/min/1.73 m2 Measurements CAC detected using CT scans using either an Imatron C-300 electron beam computed tomography scanner or multi-detector CT scanner. CAC was computed using the Agatston score, as a categorical variable. Analyses were performed using ordinal logistic regression. Results We found a strong and graded relationship between lower eGFR and increasing CAC. In unadjusted models, ORs increased from 1.68 (95% CI, 1.23–2.31) for eGFR from 50–59 to 2.82 (95% CI, 2.06–3.85) for eGFR of <30. Multivariable adjustment only partially attenuated the results (OR, 1.53; 95% CI, 1.07–2.20) for eGFR<30. Limitations Use of eGFR rather than measured GFR. Conclusions We demonstrated a graded relationship between severity of CKD and CAC, independent of traditional risk factors. These findings supports recent guidelines that state that if vascular calcification is present, it should be considered as a complementary component to be included in the decision making required for individualizing treatment of CKD. PMID:21783289

Low Magnesium Levels and FGF-23 Dysregulation Predict Mitral Valve Calcification as well as Intima Media Thickness in Predialysis Diabetic Patients

PubMed Central

Jerónimo, Teresa; Fragoso, André; Silva, Claudia; Guilherme, Patrícia; Santos, Nélio; Faísca, Marília; Neves, Pedro

2015-01-01

Background. Mitral valve calcification and intima media thickness (IMT) are common complications of chronic kidney disease (CKD) implicated with high cardiovascular mortality. Objective. To investigate the implication of magnesium and fibroblast growth factor-23 (FGF-23) levels with mitral valve calcification and IMT in CKD diabetic patients. Methods. Observational, prospective study involving 150 diabetic patients with mild to moderate CKD, divided according to Wilkins Score. Carotid-echodoppler and transthoracic echocardiography were used to assess calcification. Statistical tests used to establish comparisons between groups, to identify risk factors, and to establish cut-off points for prediction of mitral valve calcification. Results. FGF-23 values continually increased with higher values for both IMT and calcification whereas the opposite trend was observed for magnesium. FGF-23 and magnesium were found to independently predict mitral valve calcification and IMT (P < 0.05). Using Kaplan-Meier analysis, the number of deaths was higher in patients with lower magnesium levels and poorer Wilkins score. The mean cut-off value for FGF-23 was 117 RU/mL and for magnesium 1.7 mg/dL. Conclusions. Hypomagnesemia and high FGF-23 levels are independent predictors of mitral valve calcification and IMT and are risk factors for cardiovascular mortality in this population. They might be used as diagnostic/therapeutic targets in order to better manage the high cardiovascular risk in CKD patients. PMID:26089881

Nanobacteria may be linked to calcification in placenta.

PubMed

Lu, He; Guo, Ya-nan; Liu, Sheng-nan; Zhang, De-chun

2012-05-01

Placental calcification is a common pathologic condition in obstetrics. To detect the bacteria infection mechanisms for calcification, an experiment was performed to isolate, culture, and identify the nanobacteria in placental calcification. Sixteen cases of placental calcification of pregnant women were collected for the purpose of the isolation of nanobacteria, cultivation, and identification of 16S rDNA sequence. Under transmission electron microscope, novel oval-shape nanobacteria-like particles (NLP) in extracellular matrix of calcified placenta tissues were found with 50-500 nm in diameter, and among hydroxyapatite crystals aggregation existed. After about 4 weeks of culturing and isolating NLP from these calcified tissues, all calcified placental tissue samples and one adjacent tissue of calcified placental tissue samples showed white granular depositions, which were firmly attached to the bottom of the culture tubes and visible to the naked eyes. In the control group they could not be seen. After PCR was amplified a 1407-bp fragment was obtained and submitted to GenBank after sequencing with accession number JN029830. The 16S rDNA sequence homology between the isolation strain and strain nanobacteria (X98418) was 92% in GenBank. For the first time isolated, cultured, and identified nanobacteria in placental calcification indicated that nanobacteria infection is related to placental calcification.

Elastin Calcification and its Prevention with Aluminum Chloride Pretreatment

PubMed Central

Vyavahare, Narendra; Ogle, Matthew; Schoen, Frederick J.; Levy, Robert J.

1999-01-01

Elastin, an abundant structural protein present in the arterial wall, is prone to calcification in a number of disease processes including porcine bioprosthetic heart valve calcification and atherosclerosis. The mechanisms of elastin calcification are not completely elucidated. In the present work, we demonstrated calcification of purified elastin in rat subdermal implants (Ca2+ = 89.73 ± 9.84 μg/mg after 21 days versus control, unimplanted Ca2+ = 0.16 ± 0.04 μg/mg). X-ray diffraction analysis along with resolution enhanced FTIR spectroscopy demonstrated the mineral phase to be a poorly crystalline hydroxyapatite. We investigated the time course of calcification, the effect of glutaraldehyde crosslinking on calcification, and mechanisms of inhibition of elastin calcification by pretreatment with aluminum chloride (AlCl3). Glutaraldehyde pretreatment did not affect calcification (Ca2+ = 89.06 ± 17.93 μg/mg for glutaraldehyde crosslinked elastin versus Ca2+ = 89.73 ± 9.84 μg/mg for uncrosslinked elastin). This may be explained by radioactive (3H) glutaraldehyde studies showing very low reactivity between glutaraldehyde and elastin. Our results further demonstrated that AlCl3 pretreatment of elastin led to complete inhibition of elastin calcification using 21-day rat subdermal implants, irrespective of glutaraldehyde crosslinking (Ca2+ = 0.73–2.15 μg/mg for AlCl3 pretreated elastin versus 89.73 ± 9.84 for untreated elastin). The AlCl3 pretreatment caused irreversible binding of aluminum ions to elastin, as assessed by atomic emission spectroscopy. Moreover, aluminum ion binding altered the spatial configuration of elastin as shown by circular dichroism (CD), Fourier transform infrared (FTIR), and 13C nuclear magnetic resonance (NMR) spectroscopy studies, suggesting a net structural change including a reduction in the extent of β sheet structures and an increase in coil-turn conformations. Thus, it is concluded that purified elastin calcifies in rat

Computerized assessment of placental calcification post-ultrasound: a novel software tool.

PubMed

Moran, M; Higgins, M; Zombori, G; Ryan, J; McAuliffe, F M

2013-05-01

Placental calcification is associated with an increased risk of perinatal morbidity and mortality. The subjectivity of current ultrasound methods of assessment of placental calcification indicates that a more objective method is required. The aim of this study was to correlate the percentage of calcification defined by the clinician using a new software tool for calculating the extent of placental calcification with traditional ultrasound methods and with pregnancy outcome. Ninety placental images were individually assessed. An upper threshold was defined, based on high intensity, to quantify calcification within the placenta. Output metrics were then produced including the overall percentage of calcification with respect to the total number of pixels within the region of interest. The results were correlated with traditional ultrasound methods of assessment of placental calcification and with pregnancy outcome. The results demonstrate a significant correlation between placental calcification, as defined using the software, and traditional methods of Grannum grading of placental calcification. Whilst correlation with perinatal outcome and cord pH was not significant as a result of small numbers, patients with placental calcification assessed using the computerized software at the upper quartile had higher rates of poor perinatal outcome when compared with those at the lower quartile (8/22 (36%) vs 3/23 (13%); P = 0.069). These results suggest that this computerized software tool has the potential to become an alternative method of assessing placental calcification. Copyright © 2012 ISUOG. Published by John Wiley & Sons Ltd.

Bilateral intraocular calcification in necrotizing cytomegalovirus retinitis.

PubMed

Tuncer, Samuray; Oray, Merih; Yildirim, Yeliz; Camcioglu, Yildiz; Tugal-Tutkun, Ilknur

2014-10-01

We report a unique case of bilateral intraocular calcification due to necrotizing cytomegalovirus (CMV) retinitis associated with congenital CMV infection. A 7-month-old boy with a history of congenital CMV infection showed bilateral intraocular calcific plaques on computed tomography (CT) and ultrasonography. We reviewed the patient's medical files for the purpose of this report. The patient had a prior medical history of hospitalization for fever and swelling in the neck at 3 months of age. Systemic findings (anemia, neutropenia, hepatosplenomegaly, and reactive lymphadenomegaly) in association with a low CD4 count, high blood CMV viral load, and positivity for urine CMV DNA by polymerase chain reaction led to the diagnosis of bone marrow suppression and congenital CMV infection. At 7 months, he developed horizontal nystagmus and bilateral leukocoria over 20 days. Cranial CT and ultrasonography revealed bilateral intraocular calcific plaques and the patient was referred to rule out retinoblastoma. Fundoscopy was consistent with bilateral hemorrhagic, necrotizing CMV retinitis. Significant resolution of the retinal infiltrations occurred 2 weeks after initiation of systemic treatment with ganciclovir. Intraocular calcification may be a sign of active CMV retinitis. To our knowledge this is the first report of bilateral intraocular calcification serving as the presenting clinical manifestation of necrotizing CMV retinitis.

Popcorn calcification in osteogenesis imperfecta: incidence, progression, and molecular correlation.

PubMed

Obafemi, Abimbola A; Bulas, Dorothy I; Troendle, James; Marini, Joan C

2008-11-01

Osteogenesis imperfecta (OI) is a heritable disorder characterized by osteoporosis and increased susceptibility to fracture. All children with severe OI have extreme short stature and some have "popcorn" calcifications, areas of disorganized hyperdense lines in the metaphysis and epiphysis around the growth plate on lower limb radiographs. Popcorn calcifications were noted on radiographs of two children with non-lethal type VIII OI, a recessive form caused by P3H1 deficiency. To determine the incidence, progression, and molecular correlations of popcorn calcifications, we retrospectively examined serial lower limb radiographs of 45 children with type III or IV OI and known dominant mutations in type I collagen. Popcorn calcifications were present in 13 of 25 type III (52%), but only 2 of 20 type IV (10%), OI children. The mean age of onset was 7.0 years, with a range of 4-14 years. All children with popcorn calcifications had this finding in their distal femora, and most also had calcifications in proximal tibiae. While unilateral popcorn calcification contributes to femoral growth deficiency and leg length discrepancy, severe linear growth deficiency, and metaphyseal flare do not differ significantly between type III OI patients with and without popcorn calcifications. The type I collagen mutations associated with popcorn calcifications occur equally in both COL1A1 and COL1A2, and have no preferential location along the chains. These data demonstrate that popcorn calcifications are a frequent feature of severe OI, but do not distinguish cases with defects in collagen structure (primarily dominant type III OI) or modification (recessive type VIII OI). Copyright 2008 Wiley-Liss, Inc.

Cardiovascular calcifications in chronic kidney disease: Potential therapeutic implications.

PubMed

Bover, Jordi; Ureña-Torres, Pablo; Górriz, José Luis; Lloret, María Jesús; da Silva, Iara; Ruiz-García, César; Chang, Pamela; Rodríguez, Mariano; Ballarín, José

Cardiovascular (CV) calcification is a highly prevalent condition at all stages of chronic kidney disease (CKD) and is directly associated with increased CV and global morbidity and mortality. In the first part of this review, we have shown that CV calcifications represent an important part of the CKD-MBD complex and are a superior predictor of clinical outcomes in our patients. However, it is also necessary to demonstrate that CV calcification is a modifiable risk factor including the possibility of decreasing (or at least not aggravating) its progression with iatrogenic manoeuvres. Although, strictly speaking, only circumstantial evidence is available, it is known that certain drugs may modify the progression of CV calcifications, even though a direct causal link with improved survival has not been demonstrated. For example, non-calcium-based phosphate binders demonstrated the ability to attenuate the progression of CV calcification compared with the liberal use of calcium-based phosphate binders in several randomised clinical trials. Moreover, although only in experimental conditions, selective activators of the vitamin D receptor seem to have a wider therapeutic margin against CV calcification. Finally, calcimimetics seem to attenuate the progression of CV calcification in dialysis patients. While new therapeutic strategies are being developed (i.e. vitamin K, SNF472, etc.), we suggest that the evaluation of CV calcifications could be a diagnostic tool used by nephrologists to personalise their therapeutic decisions. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Impact of seawater carbonate variables on post-larval bivalve calcification

NASA Astrophysics Data System (ADS)

Li, Jiaqi; Mao, Yuze; Jiang, Zengjie; Zhang, Jihong; Bian, Dapeng; Fang, Jianguang

2017-05-01

Several studies have demonstrated that shellfish calcification rate has been impacted by ocean acidification. However, the carbonate system variables responsible for regulating calcification rate are controversial. To distinguish the key variables, we manipulated a seawater carbonate system by regulating seawater pH and dissolved inorganic carbon (DIC). Calcification rates of juvenile blue mussel (Mytilus edulis) and Zhikong scallop (Chlamys farreri) were measured in different carbonate systems. Our results demonstrated that neither [HCO{3/-}], DIC, or pH ([H+]) were determining factors for the shellfish calcification rate of blue mussel or Zhikong scallop. However, a significant correlation was detected between calcification rate and DIC/[H+] and [CO{3/2-}] in both species.

Aortic root, not valve, calcification correlates with coronary artery calcification in patients with severe aortic stenosis: A two-center study.

PubMed

Henein, Michael; Hällgren, Peter; Holmgren, Anders; Sörensen, Karen; Ibrahimi, Pranvera; Kofoed, Klaus Fuglsang; Larsen, Linnea Hornbech; Hassager, Christian

2015-12-01

The underlying pathology in aortic stenosis (AS) and coronary artery stenosis (CAS) is similar including atherosclerosis and calcification. We hypothesize that coronary artery calcification (CAC) is likely to correlate with aortic root calcification (ARC) rather than with aortic valve calcification (AVC), due to tissue similarity between the two types of vessel rather than with the valve leaflet tissue. We studied 212 consecutive patients (age 72.5 ± 7.9 years, 91 females) with AS requiring aortic valve replacement (AVR) in two Heart Centers, who underwent multidetector cardiac CT preoperatively. CAC, AVC and ARC were quantified using Agatston scoring. Correlations were tested by Spearman's test and Mann-Whitney U-test was used for comparing different subgroups; bicuspid (BAV) vs tricuspid (TAV) aortic valve. CAC was present in 92%, AVC in 100% and ARC in 82% of patients. CAC correlated with ARC (rho = 0.51, p < 0.001) but not with AVC. The number of calcified coronary arteries correlated with ARC (rho = 0.45, p < 0.001) but not with AVC. 29/152 patients had echocardiographic evidence of BAV and 123 TAV, who were older (p < 0.001) but CAC was associated with TAV even after adjusting for age (p = 0.01). AVC score was associated with BAV after adjusting for age (p = 0.03) but ARC was not. Of the total cohort, 82 patients (39%) had significant coronary stenosis (>50%), but these were not different in the pattern of calcification from those without CAS. CAC was consistently higher in patients with risk factors for atherosclerosis compared to those without. The observed relationship between coronary and aortic root calcification suggests a diffuse arterial disease. The lack of relationship between coronary and aortic valve calcification suggests a different pathology. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Coccolithophore growth and calcification in a changing ocean

NASA Astrophysics Data System (ADS)

Krumhardt, Kristen M.; Lovenduski, Nicole S.; Iglesias-Rodriguez, M. Debora; Kleypas, Joan A.

2017-12-01

Coccolithophores are the most abundant calcifying phytoplankton in the ocean. These tiny primary producers have an important role in the global carbon cycle, substantially contributing to global ocean calcification, ballasting organic matter to the deep sea, forming part of the marine food web base, and influencing ocean-atmosphere CO2 exchange. Despite these important impacts, coccolithophores are not explicitly simulated in most marine ecosystem models and, therefore, their impacts on carbon cycling are not represented in most Earth system models. Here, we compile field and laboratory data to synthesize overarching, across-species relationships between environmental conditions and coccolithophore growth rates and relative calcification (reported as a ratio of particulate inorganic carbon to particulate organic carbon in coccolithophore biomass, PIC/POC). We apply our relationships in a generalized coccolithophore model, estimating current surface ocean coccolithophore growth rates and relative calcification, and projecting how these may change over the 21st century using output from the Community Earth System Model large ensemble. We find that average increases in sea surface temperature of ∼ 2-3 ° C lead to faster coccolithophore growth rates globally (> 10% increase) and increased calcification at high latitudes. Roughly an ubiquitous doubling of surface ocean pCO2 by the end of the century has the potential to moderately stimulate coccolithophore growth rates, but leads to reduced calcification (∼ 25% decrease). Decreasing nutrient availability (from warming-induced increases in stratification) produces increases in relative calcification, but leads to ∼ 25% slower growth rates. With all drivers combined, we observe decreases in calcification and growth in most low and mid latitude regions, with possible increases in both of these responses in most high latitude regions. Major limitations of our coccolithophore model stem from a lack of conclusive

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Neal X., E-mail: xuechen@iupui.edu; O’Neill, Kalisha; Akl, Nader Kassis

Highlights: • High phosphorus can induce calcification of adipocytes, even when fully differentiated. • Adipocytes can induce vascular calcification in an autocrine manner. • Sodium thiosulfate inhibits adipocyte calcification. - Abstract: Background: Calcification can occur in fat in multiple clinical conditions including in the dermis, breasts and in the abdomen in calciphylaxis. All of these are more common in patients with advanced kidney disease. Clinically, hyperphosphatemia and obesity are risk factors. Thus we tested the hypothesis that adipocytes can calcify in the presence of elevated phosphorus and/or that adipocytes exposed to phosphorus can induce vascular smooth muscle cell (VSMC) calcification.more » Methods: 3T3-L1 preadipocytes were induced into mature adipocytes and then treated with media containing high phosphorus. Calcification was assessed biochemically and PCR performed to determine the expression of genes for osteoblast and adipocyte differentiation. Adipocytes were also co-cultured with bovine VSMC to determine paracrine effects, and the efficacy of sodium thiosulfate was determined. Results: The results demonstrated that high phosphorus induced the calcification of differentiated adipocytes with increased expression of osteopontin, the osteoblast transcription factor Runx2 and decreased expression of adipocyte transcription factors peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT-enhancer-binding protein α (CEBPα), indicating that high phosphorus led to a phenotypic switch of adipocytes to an osteoblast like phenotype. Sodium thiosulfate, dose dependently decreased adipocyte calcification and inhibited adipocyte induced increase of VSMC calcification. Co-culture studies demonstrated that adipocytes facilitated VSMC calcification partially mediated by changes of secretion of leptin and vascular endothelial growth factor (VEGF) from adipocytes. Conclusion: High phosphorus induced calcification of mature adipocytes

Pulp Calcification in Traumatized Primary Teeth - Classification, Clinical And Radiographic Aspects.

PubMed

Mello-Moura, Anna Carolina Volpi; Santos, Ana Maria Antunes; Bonini, Gabriela Azevedo Vasconcelos Cunha; Zardetto, Cristina Giovannetti Del Conte; Moura-Netto, Cacio; Wanderley, Marcia Turolla

The aim of this study was to standardize the nomenclature of pulp alteration to pulp calcification (PC) and to classify it according to type, quantity and location, as well as relate it to clinical and radiographic features. The dental records of 946 patients from the Research and Clinical Center for Dental Trauma in Primary Teeth were studied. Two hundred and fifty PC-traumatized upper deciduous incisors were detected. According to radiographic analysis of the records, 62.5% showed diffuse calcification, 36.3% tube-like calcification, and 1.2% concentric calcification. According to the extension of pulp calcification, the records showed: 80% partial calcification, 17.2% total coronal calcification and partial radicular calcification, and 2.8 % total coronal and radicular calcification. As for location, only 2.4% were on the coronal pulp, 5.2% on the radicular pulp and 92.4% on both radicular and coronal pulp. Regarding coronal discoloration, 54% were yellow and 2% gray. In relation to periradicular changes, 10% showed widened periodontal ligament space, 3.1% internal resorption, 10% external resorption, 10.4% periapical bone rarefaction. Since PC is a general term, it is important to classify it and correlate it to clinical and radiographic changes, in order to establish the correct diagnosis, treatment and prognosis of each case.

Impact of seawater carbonate variables on post-larval bivalve calcification

NASA Astrophysics Data System (ADS)

Li, Jiaqi; Mao, Yuze; Jiang, Zengjie; Zhang, Jihong; Bian, Dapeng; Fang, Jianguang

2018-03-01

Several studies have demonstrated that shellfish calcification rate has been impacted by ocean acidification. However, the carbonate system variables responsible for regulating calcification rate are controversial. To distinguish the key variables, we manipulated a seawater carbonate system by regulating seawater pH and dissolved inorganic carbon (DIC). Calcification rates of juvenile blue mussel ( Mytilus edulis) and Zhikong scallop ( Chlamys farreri) were measured in different carbonate systems. Our results demonstrated that neither [HCOˉ3], DIC, or pH ([H+]) were determining factors for the shellfish calcification rate of blue mussel or Zhikong scallop. However, a significant correlation was detected between calcification rate and DIC/[H+] and [CO3 2ˉ] in both species.

Complex nonlinear autonomic nervous system modulation link cardiac autonomic neuropathy and peripheral vascular disease.

PubMed

Khalaf, Kinda; Jelinek, Herbert F; Robinson, Caroline; Cornforth, David J; Tarvainen, Mika P; Al-Aubaidy, Hayder

2015-01-01

Physiological interactions are abundant within, and between, body systems. These interactions may evolve into discrete states during pathophysiological processes resulting from common mechanisms. An association between arterial stenosis, identified by low ankle-brachial pressure index (ABPI) and cardiovascular disease (CVD) as been reported. Whether an association between vascular calcification-characterized by high ABPI and a different pathophysiology-is similarly associated with CVD, has not been established. The current study aims to investigate the association between ABPI, and cardiac rhythm, as an indicator of cardiovascular health and functionality, utilizing heart rate variability (HRV). Two hundred and thirty six patients underwent ABPI assessment. Standard time and frequency domain, and non-linear HRV measures were determined from 5-min electrocardiogram. ABPI data were divided into normal (n = 101), low (n = 67) and high (n = 66) and compared to HRV measures.(DFAα1 and SampEn were significantly different between the low ABPI, high ABPI and control groups (p < 0.05). A possible coupling between arterial stenosis and vascular calcification with decreased and increased HRV respectively was observed. Our results suggest a model for interpreting the relationship between vascular pathophysiology and cardiac rhythm. The cardiovascular system may be viewed as a complex system comprising a number of interacting subsystems. These cardiac and vascular subsystems/networks may be coupled and undergo transitions in response to internal or external perturbations. From a clinical perspective, the significantly increased sample entropy compared to the normal ABPI group and the decreased and increased complex correlation properties measured by DFA for the low and high ABPI groups respectively, may be useful indicators that a more holistic treatment approach in line with this more complex clinical picture is required.

Acute Calcific Tendinitis of the Index Finger in a Child.

PubMed

Walocko, Frances M; Sando, Ian C; Haase, Steven C; Kozlow, Jeffrey H

2017-09-01

Calcific tendinitis is characterized by calcium hydroxyapatite crystal deposition within tendons and is a common cause of musculoskeletal pain in adults. Its clinical manifestations may be acute, chronic, or asymptomatic. Acute calcific tendinitis is self-resolving condition that is rarely reported in the pediatric population and may be overlooked for more common processes, leading to unnecessary treatment. A chart reivew was performed of a single case of acute calcific tendonitis of the index finger in a child. We describe a case of calcific tendinitis of the index finger in a 9-year-old boy who was referred to us for a second opinion after surgical exploration of an acutely inflamed digit was recommended based on his initial presentation. The calcifications and symptoms resolved over time without operative management. Although rare in children, acute calcific tendinitis can present similar to an infection. However, appropriate managment is non-operative as the symptoms and radiographic findings resolve over time.

Coral calcification and ocean acidification

USGS Publications Warehouse

Jokiel, Paul L.; Jury, Christopher P.; Kuffner, Ilsa B.

2016-01-01

Over 60 years ago, the discovery that light increased calcification in the coral plant-animal symbiosis triggered interest in explaining the phenomenon and understanding the mechanisms involved. Major findings along the way include the observation that carbon fixed by photosynthesis in the zooxanthellae is translocated to animal cells throughout the colony and that corals can therefore live as autotrophs in many situations. Recent research has focused on explaining the observed reduction in calcification rate with increasing ocean acidification (OA). Experiments have shown a direct correlation between declining ocean pH, declining aragonite saturation state (Ωarag), declining [CO32_] and coral calcification. Nearly all previous reports on OA identify Ωarag or its surrogate [CO32] as the factor driving coral calcification. However, the alternate “Proton Flux Hypothesis” stated that coral calcification is controlled by diffusion limitation of net H+ transport through the boundary layer in relation to availability of dissolved inorganic carbon (DIC). The “Two Compartment Proton Flux Model” expanded this explanation and synthesized diverse observations into a universal model that explains many paradoxes of coral metabolism, morphology and plasticity of growth form in addition to observed coral skeletal growth response to OA. It is now clear that irradiance is the main driver of net photosynthesis (Pnet), which in turn drives net calcification (Gnet), and alters pH in the bulk water surrounding the coral. Pnet controls [CO32] and thus Ωarag of the bulk water over the diel cycle. Changes in Ωarag and pH lag behind Gnet throughout the daily cycle by two or more hours. The flux rate Pnet, rather than concentration-based parameters (e.g., Ωarag, [CO3 2], pH and [DIC]:[H+] ratio) is the primary driver of Gnet. Daytime coral metabolism rapidly removes DIC from the bulk seawater. Photosynthesis increases the bulk seawater pH while providing the energy that drives

Differential Effects of Ocean Acidification on Coral Calcification: Insights from Geochemistry.

NASA Astrophysics Data System (ADS)

Holcomb, M.; Decarlo, T. M.; Venn, A.; Tambutte, E.; Gaetani, G. A.; Tambutte, S.; Allemand, D.; McCulloch, M. T.

2014-12-01

Although ocean acidification is expected to negatively impact calcifying animals due to the formation of CaCO3 becoming less favorable, experimental evidence is mixed. Corals have received considerable attention in this regard; laboratory culture experiments show there to be a wide array of calcification responses to acidification. Here we will show how relationships for the incorporation of various trace elements and boron isotopes into synthetic aragonite can be used to reconstruct carbonate chemistry at the site of calcification. In turn the chemistry at the site of calcification can be determined under different ocean acidification scenarios and differences in the chemistry at the site of calcification linked to different calcification responses to acidification. Importantly we will show that the pH of the calcifying fluid alone is insufficient to estimate calcification responses, thus a multi-proxy approach using multiple trace elements and isotopes is required to understand how the site of calcification is affected by ocean acidification.

Automated selection of BI-RADS lesion descriptors for reporting calcifications in mammograms

NASA Astrophysics Data System (ADS)

Paquerault, Sophie; Jiang, Yulei; Nishikawa, Robert M.; Schmidt, Robert A.; D'Orsi, Carl J.; Vyborny, Carl J.; Newstead, Gillian M.

2003-05-01

We are developing an automated computer technique to describe calcifications in mammograms according to the BI-RADS lexicon. We evaluated this technique by its agreement with radiologists' description of the same lesions. Three expert mammographers reviewed our database of 90 cases of digitized mammograms containing clustered microcalcifications and described the calcifications according to BI-RADS. In our study, the radiologists used only 4 of the 5 calcification distribution descriptors and 5 of the 14 calcification morphology descriptors contained in BI-RADS. Our computer technique was therefore designed specifically for these 4 calcification distribution descriptors and 5 calcification morphology descriptors. For calcification distribution, 4 linear discriminant analysis (LDA) classifiers were developed using 5 computer-extracted features to produce scores of how well each descriptor describes a cluster. Similarly, for calcification morphology, 5 LDAs were designed using 10 computer-extracted features. We trained the LDAs using only the BI-RADS data reported by the first radiologist and compared the computer output to the descriptor data reported by all 3 radiologists (for the first radiologist, the leave-one-out method was used). The computer output consisted of the best calcification distribution descriptor and the best 2 calcification morphology descriptors. The results of the comparison with the data from each radiologist, respectively, were: for calcification distribution, percent agreement, 74%, 66%, and 73%, kappa value, 0.44, 0.36, and 0.46; for calcification morphology, percent agreement, 83%, 77%, and 57%, kappa value, 0.78, 0.70, and 0.44. These results indicate that the proposed computer technique can select BI-RADS descriptors in good agreement with radiologists.

GRECOS project. The use of genetics to predict the vascular recurrence after stroke

PubMed Central

Fernández-Cadenas, Israel; Mendióroz, Maite; Giralt, Dolors; Nafria, Cristina; Garcia, Elena; Carrera, Caty; Gallego-Fabrega, Cristina; Domingues-Montanari, Sophie; Delgado, Pilar; Ribó, Marc; Castellanos, Mar; Martínez, Sergi; Freijo, Mari Mar; Jiménez-Conde, Jordi; Rubiera, Marta; Alvarez-Sabín, José; Molina, Carlos A.; Font, Maria Angels; Olivares, Marta Grau; Palomeras, Ernest; de la Ossa, Natalia Perez; Martinez-Zabaleta, Maite; Masjuan, Jaime; Moniche, Francisco; Canovas, David; Piñana, Carlos; Purroy, Francisco; Cocho, Dolores; Navas, Inma; Tejero, Carlos; Aymerich, Nuria; Cullell, Natalia; Muiño, Elena; Serena, Joaquín; Rubio, Francisco; Davalos, Antoni; Roquer, Jaume; Arenillas, Juan Francisco; Martí-Fábregas, Joan; Keene, Keith; Chen, Wei-Min; Worrall, Bradford; Sale, Michele; Arboix, Adrià; Krupinski, Jerzy; Montaner, Joan

2017-01-01

Background and Purpose Vascular recurrence occurs in 11% of patients during the first year after ischemic stroke (IS) or transient ischemic attack (TIA). Clinical scores do not predict the whole vascular recurrence risk, therefore we aimed to find genetic variants associated with recurrence that might improve the clinical predictive models in IS. Methods We analyzed 256 polymorphisms from 115 candidate genes in three patient cohorts comprising 4,482 IS or TIA patients. The discovery cohort was prospectively recruited and included 1,494 patients, 6.2% of them developed a new IS during the first year of follow-up. Replication analysis was performed in 2,988 patients using SNPlex or HumanOmni1-Quad technology. We generated a predictive model using Cox regression (GRECOS score), and generated risk groups using a classification tree method. Results The analyses revealed that rs1800801 in the MGP gene (HR: 1.33, p= 9×10−03), a gene related to artery calcification, was associated with new IS during the first year of follow-up. This polymorphism was replicated in a Spanish cohort (n=1.305), however it was not significantly associated in a North American cohort (n=1.683). The GRECOS score predicted new IS (p= 3.2×10−09) and could classify patients, from low risk of stroke recurrence (1.9%) to high risk (12.6%). Moreover, the addition of genetic risk factors to the GRECOS score improves the prediction compared to previous SPI-II score (p=0.03). Conclusions The use of genetics could be useful to estimate vascular recurrence risk after IS. Genetic variability in the MGP gene was associated with vascular recurrence in the Spanish population. PMID:28411264

Treatment of the calcific tendinopathy of the rotator cuff by ultrasound-guided percutaneous needle lavage. Two years prospective study

PubMed Central

Castillo-González, Federico Del; Ramos-Álvarez, Juan José; Rodríguez-Fabián, Guillermo; González-Pérez, José; Calderón-Montero, Javier

2014-01-01

Summary Background: to evaluate the short and long term effectiveness of ultrasonography (US)-guided percutaneous needle lavage in calcific tendinopathy of the rotator cuff. To study the evolution of the size of calcifications and pain in the two years after treatment. Methods: study design: A 2 year longitudinal prospective study is carried out after applying the UGPL technique on a number of patients diagnosed with calcific tendinitis of the rotator cuff. Clinical, ultrasound and radiology follow-up controls were performed, 3 months, 6 months, one year and two years after the treatment. The Visual Analog Scale (VAS) was used to assess the pain. The degree and point of pain is selected on a 10 cm line, arranged horizontally or vertically. The “0” represents no pain and “10” represents worst pain. The population studied was made up of 121 patients that required our service as a result of suffering from a painful shoulder. Results: the pain (VAS) and the size of the calcification significantly decreased with the application of the technique (p< 0,001 in both cases) and regardless of the sex (p: 0.384 for pain and p: 0.578 for the size of the calcification). This occurred from the first check-up (3 months) and was maintained for two year. Conclusions: we consider this technique to be a valid alternative as a first-choice treatment of calcific tendinitis of the shoulder. The intervention is simple, cost-effective, does not require hospitalization, involves no complications, rehabilitation treatment is not required and it shows very few side effects without sequelae, significantly reducing the size of the calcification and pain in the majority of patients. PMID:25332939

Renal papillary calcification and the development of calcium oxalate monohydrate papillary renal calculi: a case series study

PubMed Central

2013-01-01

Background The objective of this study is to determine in a case series (four patients) how calcified deposits in renal papillae are associated with the development of calcium oxalate monohydrate (COM) papillary calculi. Methods From the recently collected papillary calculi, we evaluated retrospectively patients, subjected to retrograde ureteroscopy, with COM papillary lithiasis. Results The COM papillary calculi were found to result from subepithelial injury. Many of these lesions underwent calcification by hydroxyapatite (HAP), with calculus morphology and the amount of HAP in the concave zone dependent on the location of the calcified injury. Most of these HAP deposits grew, eroding the epithelium covering the renal papillae, coming into contact with urine and starting the development of COM calculi. Subepithelial HAP plaques may alter the epithelium covering the papillae, resulting in the deposit of COM crystals directly onto the epithelium. Tissue calcification depends on a pre-existing injury, the continuation of this process is due to modulators and/or crystallization inhibitors deficiency. Conclusions Since calculus morphology and the amount of detected HAP are dependent on the location and widespread of calcified injury, all types of papillary COM calculi can be found in the same patient. All patients had subepithelial calcifications, with fewer papillary calculi, demonstrating that some subepithelial calcifications did not further evolve and were reabsorbed. A high number of subepithelial calcifications increases the likelihood that some will be transformed into COM papillary calculi. PMID:23497010

Impact of seawater carbonate chemistry on the calcification of marine bivalves

NASA Astrophysics Data System (ADS)

Thomsen, J.; Haynert, K.; Wegner, K. M.; Melzner, F.

2015-01-01

Bivalve calcification, particular of the early larval stages is highly sensitive to the change of ocean carbonate chemistry resulting from atmospheric CO2 uptake. Earlier studies suggested that declining seawater [CO32-] and thereby lowered carbonate saturation affect shell production. However, disturbances of physiological processes such as acid-base regulation by adverse seawater pCO2 and pH can affect calcification in a secondary fashion. In order to determine the exact carbonate system component by which growth and calcification are affected it is necessary to utilize more complex carbonate chemistry manipulations. As single factors, pCO2 had no and [HCO3-] and pH only limited effects on shell growth, while lowered [CO32-] strongly impacted calcification. Dissolved inorganic carbon (CT) limiting conditions led to strong reductions in calcification, despite high [CO32-], indicating that [HCO3-] rather than [CO32-] is the inorganic carbon source utilized for calcification by mytilid mussels. However, as the ratio [HCO3-] / [H+] is linearly correlated with [CO32-] it is not possible to differentiate between these under natural seawater conditions. Therefore, the availability of [HCO3-] combined with favorable environmental pH determines calcification rate and an equivalent of about 80 μmol kg-1 [CO32-] is required to saturate inorganic carbon supply for calcification in bivalves. Below this threshold biomineralization rates rapidly decline. A comparison of literature data available for larvae and juvenile mussels and oysters originating from habitats differing substantially with respect to prevailing carbonate chemistry conditions revealed similar response curves. This suggests that the mechanisms which determine sensitivity of calcification in this group are highly conserved. The higher sensitivity of larval calcification seems to primarily result from the much higher relative calcification rates in early life stages. In order to reveal and understand the

The Relationship between Serum Apelin Levels and the Severity of Calcific Aortic Stenosis

PubMed Central

Duman, Hakan; Bahçeci, Ilkay; Hamur, Hikmet; Demirelli, Selami; Ramazan Dilek, Aziz; Erdogan, Turan; Duman, Handan; Şatıroğlu, Ömer; Emre Durakoğlugil, Murtaza

2018-01-01

Background Apelin, an endogenous peptide, has recently gained attention due to its positive inotropic effects in heart failure physiopathology. We investigated the relationship between serum apelin levels and the severity of calcific aortic stenosis (AS). Methods A total of 68 consecutive patients diagnosed with calcific AS and a control group of 32 subjects were included in the study. The subjects were divided into three group as follows: the control group, the mild-moderate AS group and the severe AS group. Blood samples were obtained from all of the subjects, which were used for biochemical comparisons of apelin 36 and high-sensitive C-reactive protein (hsCRP) levels. Results Plasma apelin 36 levels were significantly lower in the patients with severe AS [490 (247-1074) pg/ml] compared to both the mild-moderate AS [209 (97-453) pg/ml] and control [660 (378-1200) pg/ml] groups (p < 0.001). Correlation analysis between the left ventricular mass index and apelin concentrations revealed a significant negative correlation between the two parameters (p < 0.001, r = -0.478). Conclusions Our study demonstrated decreased apelin levels and increased hsCRP concentrations in patients with severe calcific AS. Our findings may help to clarify the exact pathophysiologic role of apelin in cardiovascular diseases. PMID:29844647

Arterial calcification: friend or foe?

PubMed

Nicoll, Rachel; Henein, Michael Y

2013-07-31

There is a significant relationship between the presence, extent and progression of coronary artery calcification (CAC) and cardiovascular (CV) events and mortality in both CV and renal patients and CAC scoring can provide improved predictive ability over risk factor scoring alone. There is also a close relationship between CAC presence and atherosclerotic plaque burden, with angiography studies showing very high sensitivity but poor specificity of CAC score for predicting obstructive disease. Nevertheless, there are objections to CAC screening because of uncertainties and lack of studies showing improved outcome. Furthermore, histopathology studies indicate that heavily calcified plaque is unlikely to result in a CV event, while the vulnerable plaque tends to be uncalcified or 'mixed', suggesting that calcification may be protective. This scenario highlights a number of paradoxes, which may indicate that the association between CAC and CV events is spurious, following from the adoption of CAC as a surrogate for high plaque burden, which itself is a surrogate for the presence of vulnerable plaque. Since studies indicate that arterial calcification is a complex, organised and regulated process similar to bone formation, there is no particular reason why it should be a reliable indicator of either the plaque burden or the risk of a future CV event. We suggest that it is time to divorce arterial calcification from atherosclerosis and to view it as a distinct pathology in its own right, albeit one which frequently coexists with atherosclerosis and is related to it for reasons which are not yet fully understood. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Association between serum alkaline phosphatase and coronary artery calcification in a sample of primary cardiovascular prevention patients.

PubMed

Panh, Loïc; Ruidavets, Jean Bernard; Rousseau, Hervé; Petermann, Antoine; Bongard, Vanina; Bérard, Emilie; Taraszkiewicz, Dorota; Lairez, Olivier; Galinier, Michel; Carrié, Didier; Ferrières, Jean

2017-05-01

A high level of serum alkaline phosphatase (ALP) is associated with an increased risk of mortality and myocardial infarction. ALP hydrolyses inorganic pyrophosphate, which is a strong inhibitor of calcium phosphate deposition. The aim of this study was to determine whether ALP is associated with the coronary artery calcium score (CACS). We examined the association of CACS, assessed by computed tomography scanning, and ALP, in 500 patients consecutively recruited, free of cardiovascular disease. The CACS were categorized into two groups: no calcification (CACS = 0) (n = 187) and with calcification (CACS>0) (n = 313). ALP activity was divided into three tertile groups: low ALP level (<55 IU/L), intermediate (55-66 IU/L) and high ALP level (>66 IU/L). The mean age was 60.9 ± 10.8 years, 49.6% of the patients were women. ALP ranged from 22 to 164 IU/L (mean 62.6 IU/L, SD 19.3). In univariate analysis, traditional cardiovascular risk factors, statin use (p = 0.001), and ALP (p = 0.001) were significantly associated with CACS. After adjusting for cardiovascular risk factors, only age (p = 0.001) and sex (p = 0.001) were independently associated with CACS. Compared to the tertile group with low levels of ALP, the intermediate tertile group [OR 2.11, 95% CI (1.12; 3.96), p = 0.02], as well as the high tertile group [OR 3.89, 95% CI (2.01; 7.54), p = 0.001)], was independently associated with CACS. In patients free of cardiovascular disease, high ALP levels are positively and independently associated with coronary artery calcification. The metabolic pathway of ALP and inorganic pyrophosphate could be a target for new therapies against vascular calcification. Copyright © 2017 Elsevier B.V. All rights reserved.

A greater reduction in high-frequency heart rate variability to a psychological stressor is associated with subclinical coronary and aortic calcification in postmenopausal women.

PubMed

Gianaros, Peter J; Salomon, Kristen; Zhou, Fan; Owens, Jane F; Edmundowicz, Daniel; Kuller, Lewis H; Matthews, Karen A

2005-01-01

Reduced cardiac parasympathetic activity, as indicated by a reduced level of clinic or ambulatory high-frequency heart rate variability (HF-HRV), is associated with an increased risk for atherosclerosis and coronary artery disease. We tested whether the reduction in HF-HRV to a psychological stressor relative to a baseline level is also associated with subclinical coronary or aortic atherosclerosis, as assessed by calcification in these vascular regions. Spectral estimates of 0.15 to 0.40 Hz HF-HRV were obtained from 94 postmenopausal women (61-69 years) who engaged in a 3-minute speech-preparation stressor after a 6-minute resting baseline. A median of 282 days later, electron beam tomography (EBT) was used to measure the extent of coronary and aortic calcification. In univariate analyses, a greater reduction in HF-HRV from baseline to speech preparation was associated with having more extensive calcification in the coronary arteries (rho = -0.29, p = .03) and in the aorta (rho = -0.22, p = .06). In multivariate analyses that controlled for age, education level, smoking status, hormone therapy use, fasting glucose, high-density lipoproteins, baseline HF-HRV, and the stressor-induced change in respiration rate, a greater stressor-induced reduction in HF-HRV was associated with more calcification in the coronary arteries (B = -1.21, p < .05), and it was marginally associated with more calcification in the aorta (B = -0.92, p = .09). In postmenopausal women, a greater reduction in cardiac parasympathetic activity to a psychological stressor from baseline may be an independent correlate of subclinical atherosclerosis, particularly in the coronary arteries.

Computed tomographic pattern of physiological intracranial calcifications in a city in central Africa.

PubMed

Uduma, Felix Uduma; Pius, Fokam; Mathieu, Motah

2011-12-29

Intracranial calcifications underlie certain brain diseases which may be de novo or systemic. But calcifications un-connected to pathologies are classified physiological. To evaluate physiological intracranial calcifications in Douala with establishment of earliest age range of detection. Prospective study of brain computed tomograms was done from April to October 2009 using Schumadzu CT Scan machine. Axial, reconstructed and bone window images as well Hounsfield unit measurements were used for final evaluations. RESULTS were analysed with SSPS 3. 132 patients with 75 males and 57 females were studied and 163 separate calcifications were identified due to co-existent calcifications. The highest calcification was in choroid plexi, constituting 56.82% of the studied population. This was followed by pineal gland. Both were commonly co-existent with advancing age. These calcifications were first seen at 10-19 years. No type of physiological intracranial calcification was seen below age 10. The least calcification of 0.76% of population was in dentate nucleus. No intra-cranial physiological calcifications started earlier than 9 years in Douala, a city in Cameroon, Central Africa.

Prevalence of Soft Tissue Calcifications in CBCT Images of Mandibular Region.

PubMed

Khojastepour, Leila; Haghnegahdar, Abdolaziz; Sayar, Hamed

2017-06-01

Most of the soft tissue calcifications within the head and neck region might not be accompanied by clinical symptoms but may indicate some pathological conditions. The aim of this research was to determine the prevalence of soft tissue calcifications in cone beam computed tomography (CBCT) images of mandibular region. In this cross sectional study the CBCT images of 602 patients including 294 men and 308 women with mean age 41.38±15.18 years were evaluated regarding the presence, anatomical location; type (single or multiple) and size of soft tissue calcification in mandibular region. All CBCT images were acquired by NewTom VGi scanner. Odds ratio and chi-square tests were used for data analysis and p < 0.05 was considered to be statistically significant. 156 out of 602 patients had at least one soft tissue calcification in their mandibular region (25.9%. of studied population with mean age 51.7±18.03 years). Men showed significantly higher rate of soft tissue calcification than women (30.3% vs. 21.8%). Soft tissue calcification was predominantly seen at posterior region of the mandible (88%) and most of them were single (60.7%). The prevalence of soft tissue calcification increased with age. Most of the detected soft tissue calcifications were smaller than 3mm (90%). Soft tissue calcifications in mandibular area were a relatively common finding especially in posterior region and more likely to happen in men and in older age group.

Geochemical Evidence for Calcification from the Drake Passage Time-series

NASA Astrophysics Data System (ADS)

Munro, D. R.; Lovenduski, N. S.; Takahashi, T.; Stephens, B. B.; Newberger, T.; Dierssen, H. M.; Randolph, K. L.; Freeman, N. M.; Bushinsky, S. M.; Key, R. M.; Sarmiento, J. L.; Sweeney, C.

2016-12-01

Satellite imagery suggests high particulate inorganic carbon within a circumpolar region north of the Antarctic Polar Front (APF), but in situ evidence for calcification in this region is sparse. Given the geochemical relationship between calcification and total alkalinity (TA), seasonal changes in surface concentrations of potential alkalinity (PA), which accounts for changes in TA due to variability in salinity and nitrate, can be used as a means to evaluate satellite-based calcification algorithms. Here, we use surface carbonate system measurements collected from 2002 to 2016 for the Drake Passage Time-series (DPT) to quantify rates of calcification across the Antarctic Circumpolar Current. We also use vertical PA profiles collected during two cruises across the Drake Passage in March 2006 and September 2009 to estimate the calcium carbonate to organic carbon export ratio. We find geochemical evidence for calcification both north and south of the APF with the highest rates observed north of the APF. Calcification estimates from the DPT are compared to satellite-based estimates and estimates based on hydrographic data from other regions around the Southern Ocean.

SLC20A2 DEFICIENCY IN MICE LEADS TO ELEVATED PHOSPHATE LEVELS IN CEREBROSPINAL FLUID AND GLYMPHATIC PATHWAY-ASSOCIATED ARTERIOLAR CALCIFICATION, AND RECAPITULATES HUMAN IDIOPATHIC BASAL GANGLIA CALCIFICATION

PubMed Central

Wallingford, MC; Chia, J; Leaf, EM; Borgeia, S; Chavkin, NW; Sawangmake, C; Marro, K; Cox, TC; Speer, MY; Giachelli, CM

2016-01-01

Idiopathic basal ganglia calcification is a brain calcification disorder that has been genetically linked to autosomal dominant mutations in the sodium-dependent phosphate co-transporter, SLC20A2. The mechanisms whereby deficiency of Slc20a2 leads to basal ganglion calcification are unknown. In the mouse brain, we found that Slc20a2 was expressed in tissues that produce and/or regulate cerebrospinal fluid, including choroid plexus, ependyma and arteriolar smooth muscle cells. Haploinsufficient Slc20a2 +/− mice developed age-dependent basal ganglia calcification that formed in glymphatic pathway-associated arterioles. Slc20a2 deficiency uncovered phosphate homeostasis dysregulation characterized by abnormally high cerebrospinal fluid phosphate levels and hydrocephalus, in addition to basal ganglia calcification. Slc20a2 siRNA knockdown in smooth muscle cells revealed increased susceptibility to high phosphate-induced calcification. These data suggested that loss of Slc20a2 led to dysregulated phosphate homeostasis and enhanced susceptibility of arteriolar smooth muscle cells to elevated phosphate-induced calcification. Together, dysregulated cerebrospinal fluid phosphate and enhanced smooth muscle cell susceptibility may predispose to glymphatic pathway-associated arteriolar calcification. PMID:26822507

Calcification Remodeling Index Characterized by Cardiac CT as a Novel Parameter to Predict the Use of Rotational Atherectomy for Coronary Intervention of Lesions with Moderate to Severe Calcification

PubMed Central

Yu, Mengmeng; Li, Yuehua; Li, Wenbin; Lu, Zhigang; Wei, Meng

2017-01-01

Objective To assess the feasibility of calcification characterization by coronary computed tomography angiography (CCTA) to predict the use of rotational atherectomy (RA) for coronary intervention of lesions with moderate to severe calcification. Materials and Methods Patients with calcified lesions treated by percutaneous coronary intervention (PCI) who underwent both CCTA and invasive coronary angiography were retrospectively included in this study. Calcification remodeling index was calculated as the ratio of the smallest vessel cross-sectional area of the lesion to the proximal reference luminal area. Other parameters such as calcium volume, regional Agatston score, calcification length, and involved calcium arc quadrant were also recorded. Results A total of 223 patients with 241 calcified lesions were finally included. Lesions with RA tended to have larger calcium volume, higher regional Agatston score, more involved calcium arc quadrants, and significantly smaller calcification remodeling index than lesions without RA. Receiver operating characteristic curve analysis revealed that the best cutoff value of calcification remodeling index was 0.84 (area under curve = 0.847, p < 0.001). Calcification remodeling index ≤ 0.84 was the strongest independent predictor (odds ratio: 251.47, p < 0.001) for using RA. Conclusion Calcification remodeling index was significantly correlated with the incidence of using RA to aid PCI. Calcification remodeling index ≤ 0.84 was the strongest independent predictor for using RA prior to stent implantation. PMID:28860893

Impact of seawater carbonate chemistry on the calcification of marine bivalves

NASA Astrophysics Data System (ADS)

Thomsen, J.; Haynert, K.; Wegner, K. M.; Melzner, F.

2015-07-01

Bivalve calcification, particularly of the early larval stages, is highly sensitive to the change in ocean carbonate chemistry resulting from atmospheric CO2 uptake. Earlier studies suggested that declining seawater [CO32-] and thereby lowered carbonate saturation affect shell production. However, disturbances of physiological processes such as acid-base regulation by adverse seawater pCO2 and pH can affect calcification in a secondary fashion. In order to determine the exact carbonate system component by which growth and calcification are affected it is necessary to utilize more complex carbonate chemistry manipulations. As single factors, pCO2 had no effects and [HCO3-] and pH had only limited effects on shell growth, while lowered [CO32-] strongly impacted calcification. Dissolved inorganic carbon (CT) limiting conditions led to strong reductions in calcification, despite high [CO32-], indicating that [HCO3-] rather than [CO32-] is the inorganic carbon source utilized for calcification by mytilid mussels. However, as the ratio [HCO3-] / [H+] is linearly correlated with [CO32-] it is not possible to differentiate between these under natural seawater conditions. An equivalent of about 80 μmol kg-1 [CO32-] is required to saturate inorganic carbon supply for calcification in bivalves. Below this threshold biomineralization rates rapidly decline. A comparison of literature data available for larvae and juvenile mussels and oysters originating from habitats differing substantially with respect to prevailing carbonate chemistry conditions revealed similar response curves. This suggests that the mechanisms which determine sensitivity of calcification in this group are highly conserved. The higher sensitivity of larval calcification seems to primarily result from the much higher relative calcification rates in early life stages. In order to reveal and understand the mechanisms that limit or facilitate adaptation to future ocean acidification, it is necessary to better

Size-dependent response of foraminiferal calcification to seawater carbonate chemistry

NASA Astrophysics Data System (ADS)

Henehan, Michael J.; Evans, David; Shankle, Madison; Burke, Janet E.; Foster, Gavin L.; Anagnostou, Eleni; Chalk, Thomas B.; Stewart, Joseph A.; Alt, Claudia H. S.; Durrant, Joseph; Hull, Pincelli M.

2017-07-01

The response of the marine carbon cycle to changes in atmospheric CO2 concentrations will be determined, in part, by the relative response of calcifying and non-calcifying organisms to global change. Planktonic foraminifera are responsible for a quarter or more of global carbonate production, therefore understanding the sensitivity of calcification in these organisms to environmental change is critical. Despite this, there remains little consensus as to whether, or to what extent, chemical and physical factors affect foraminiferal calcification. To address this, we directly test the effect of multiple controls on calcification in culture experiments and core-top measurements of Globigerinoides ruber. We find that two factors, body size and the carbonate system, strongly influence calcification intensity in life, but that exposure to corrosive bottom waters can overprint this signal post mortem. Using a simple model for the addition of calcite through ontogeny, we show that variable body size between and within datasets could complicate studies that examine environmental controls on foraminiferal shell weight. In addition, we suggest that size could ultimately play a role in determining whether calcification will increase or decrease with acidification. Our models highlight that knowledge of the specific morphological and physiological mechanisms driving ontogenetic change in calcification in different species will be critical in predicting the response of foraminiferal calcification to future change in atmospheric pCO2.

Can dental pulp calcification predict the risk of ischemic cardiovascular disease?

PubMed

Khojastepour, Leila; Bronoosh, Pegah; Khosropanah, Shahdad; Rahimi, Elham

2013-09-01

To report the association of pulp calcification with that of cardiovascular disease (CVD) using digital panoramic dental radiographs. Digital panoramic radiographs of patients referred from the angiography department were included if the patient was under 55 years old and had non-restored or minimally restored molars and canines. An oral and maxillofacial radiologist evaluated the images for pulpal calcifications in the selected teeth. The sensitivity, specificity, positive predictive value and negative predictive value of panoramic radiography in predicting CVD were calculated. Out of 122 patients who met the criteria, 68.2% of the patients with CVD had pulp chamber calcifications. Pulp calcification in panoramic radiography had a sensitivity of 68.9% to predict CVD. This study demonstrates that patients with CVD show an increased incidence of pulp calcification compared with healthy patients. The findings suggest that pulp calcification on panoramic radiography may have possibilities for use in CVD screening.

Dietary L-lysine prevents arterial calcification in adenine-induced uremic rats.

PubMed

Shimomura, Akihiro; Matsui, Isao; Hamano, Takayuki; Ishimoto, Takuya; Katou, Yumiko; Takehana, Kenji; Inoue, Kazunori; Kusunoki, Yasuo; Mori, Daisuke; Nakano, Chikako; Obi, Yoshitsugu; Fujii, Naohiko; Takabatake, Yoshitsugu; Nakano, Takayoshi; Tsubakihara, Yoshiharu; Isaka, Yoshitaka; Rakugi, Hiromi

2014-09-01

Vascular calcification (VC) is a life-threatening complication of CKD. Severe protein restriction causes a shortage of essential amino acids, and exacerbates VC in rats. Therefore, we investigated the effects of dietary l-lysine, the first-limiting amino acid of cereal grains, on VC. Male Sprague-Dawley rats at age 13 weeks were divided randomly into four groups: low-protein (LP) diet (group LP), LP diet+adenine (group Ade), LP diet+adenine+glycine (group Gly) as a control amino acid group, and LP diet+adenine+l-lysine·HCl (group Lys). At age 18 weeks, group LP had no VC, whereas groups Ade and Gly had comparable levels of severe VC. l-Lysine supplementation almost completely ameliorated VC. Physical parameters and serum creatinine, urea nitrogen, and phosphate did not differ among groups Ade, Gly, and Lys. Notably, serum calcium in group Lys was slightly but significantly higher than in groups Ade and Gly. Dietary l-lysine strongly suppressed plasma intact parathyroid hormone in adenine rats and supported a proper bone-vascular axis. The conserved orientation of the femoral apatite in group Lys also evidenced the bone-protective effects of l-lysine. Dietary l-lysine elevated plasma alanine, proline, arginine, and homoarginine but not lysine. Analyses in vitro demonstrated that alanine and proline inhibit apoptosis of cultured vascular smooth muscle cells, and that arginine and homoarginine attenuate mineral precipitations in a supersaturated calcium/phosphate solution. In conclusion, dietary supplementation of l-lysine ameliorated VC by modifying key pathways that exacerbate VC. Copyright © 2014 by the American Society of Nephrology.

Dietary l-Lysine Prevents Arterial Calcification in Adenine-Induced Uremic Rats

PubMed Central

Shimomura, Akihiro; Matsui, Isao; Hamano, Takayuki; Ishimoto, Takuya; Katou, Yumiko; Takehana, Kenji; Inoue, Kazunori; Kusunoki, Yasuo; Mori, Daisuke; Nakano, Chikako; Obi, Yoshitsugu; Fujii, Naohiko; Takabatake, Yoshitsugu; Nakano, Takayoshi; Tsubakihara, Yoshiharu; Rakugi, Hiromi

2014-01-01

Vascular calcification (VC) is a life-threatening complication of CKD. Severe protein restriction causes a shortage of essential amino acids, and exacerbates VC in rats. Therefore, we investigated the effects of dietary l-lysine, the first-limiting amino acid of cereal grains, on VC. Male Sprague-Dawley rats at age 13 weeks were divided randomly into four groups: low-protein (LP) diet (group LP), LP diet+adenine (group Ade), LP diet+adenine+glycine (group Gly) as a control amino acid group, and LP diet+adenine+l-lysine·HCl (group Lys). At age 18 weeks, group LP had no VC, whereas groups Ade and Gly had comparable levels of severe VC. l-Lysine supplementation almost completely ameliorated VC. Physical parameters and serum creatinine, urea nitrogen, and phosphate did not differ among groups Ade, Gly, and Lys. Notably, serum calcium in group Lys was slightly but significantly higher than in groups Ade and Gly. Dietary l-lysine strongly suppressed plasma intact parathyroid hormone in adenine rats and supported a proper bone-vascular axis. The conserved orientation of the femoral apatite in group Lys also evidenced the bone-protective effects of l-lysine. Dietary l-lysine elevated plasma alanine, proline, arginine, and homoarginine but not lysine. Analyses in vitro demonstrated that alanine and proline inhibit apoptosis of cultured vascular smooth muscle cells, and that arginine and homoarginine attenuate mineral precipitations in a supersaturated calcium/phosphate solution. In conclusion, dietary supplementation of l-lysine ameliorated VC by modifying key pathways that exacerbate VC. PMID:24652795

Pyrophosphate Supplementation Prevents Chronic and Acute Calcification in ABCC6-Deficient Mice.

PubMed

Pomozi, Viola; Brampton, Christopher; van de Wetering, Koen; Zoll, Janna; Calio, Bianca; Pham, Kevin; Owens, Jesse B; Marh, Joel; Moisyadi, Stefan; Váradi, András; Martin, Ludovic; Bauer, Carolin; Erdmann, Jeanette; Aherrahrou, Zouhair; Le Saux, Olivier

2017-06-01

Soft tissue calcification occurs in several common acquired pathologies, such as diabetes and hypercholesterolemia, or can result from genetic disorders. ABCC6, a transmembrane transporter primarily expressed in liver and kidneys, initiates a molecular pathway inhibiting ectopic calcification. ABCC6 facilitates the cellular efflux of ATP, which is rapidly converted into pyrophosphate (PPi), a major calcification inhibitor. Heritable mutations in ABCC6 underlie the incurable calcification disorder pseudoxanthoma elasticum and some cases of generalized arterial calcification of infancy. Herein, we determined that the administration of PPi and the bisphosphonate etidronate to Abcc6 -/- mice fully inhibited the acute dystrophic cardiac calcification phenotype, whereas alendronate had no significant effect. We also found that daily injection of PPi to Abcc6 -/- mice over several months prevented the development of pseudoxanthoma elasticum-like spontaneous calcification, but failed to reverse already established lesions. Furthermore, we found that the expression of low amounts of the human ABCC6 in liver of transgenic Abcc6 -/- mice, resulting in only a 27% increase in plasma PPi levels, led to a major reduction in acute and chronic calcification phenotypes. This proof-of-concept study shows that the development of both acute and chronic calcification associated with ABCC6 deficiency can be prevented by compensating PPi deficits, even partially. Our work indicates that PPi substitution represents a promising strategy to treat ABCC6-dependent calcification disorders. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Prevalence of Soft Tissue Calcifications in CBCT Images of Mandibular Region

PubMed Central

Khojastepour, Leila; Haghnegahdar, Abdolaziz; Sayar, Hamed

2017-01-01

Statement of the Problem: Most of the soft tissue calcifications within the head and neck region might not be accompanied by clinical symptoms but may indicate some pathological conditions. Purpose: The aim of this research was to determine the prevalence of soft tissue calcifications in cone beam computed tomography (CBCT) images of mandibular region. Materials and Method: In this cross sectional study the CBCT images of 602 patients including 294 men and 308 women with mean age 41.38±15.18 years were evaluated regarding the presence, anatomical location; type (single or multiple) and size of soft tissue calcification in mandibular region. All CBCT images were acquired by NewTom VGi scanner. Odds ratio and chi-square tests were used for data analysis and p< 0.05 was considered to be statistically significant. Results: 156 out of 602 patients had at least one soft tissue calcification in their mandibular region (25.9%. of studied population with mean age 51.7±18.03 years). Men showed significantly higher rate of soft tissue calcification than women (30.3% vs. 21.8%). Soft tissue calcification was predominantly seen at posterior region of the mandible (88%) and most of them were single (60.7%). The prevalence of soft tissue calcification increased with age. Most of the detected soft tissue calcifications were smaller than 3mm (90%). Conclusion: Soft tissue calcifications in mandibular area were a relatively common finding especially in posterior region and more likely to happen in men and in older age group. PMID:28620632

Relationship between dental calcification and skeletal maturation in a Peruvian sample.

PubMed

Lecca-Morales, Rocío M; Carruitero, Marcos J

2017-01-01

the objective of the study was to determine the relationship between dental calcification stages and skeletal maturation in a Peruvian sample. panoramic, cephalometric and carpal radiographs of 78 patients (34 girls and 44 boys) between 7 and 17 years old (9.90 ± 2.5 years) were evaluated. Stages of tooth calcification of the mandibular canine, first premolar, second premolar, and second molar and the skeletal maturation with a hand-wrist and a cervical vertebrae method were assessed. The relationships between the stages were assessed using Spearman's correlation coefficient. Additionally, the associations of mandibular and pubertal growth peak stages with tooth calcification were evaluated by Fisher's exact test. all teeth showed positive and statistically significant correlations, the highest correlation was between the mandibular second molar calcification stages with hand-wrist maturation stages (r = 0.758, p < 0.001) and with vertebrae cervical maturation stages (r = 0.605, p < 0.001). The pubertal growth spurt was found in the G stage of calcification of the second mandibular molar, and the mandibular growth peak was found in the F stage of calcification of the second molar. there was a positive relationship between dental calcification stages and skeletal maturation stages by hand-wrist and cervical vertebrae methods in the sample studied. Dental calcification stages of the second mandibular molar showed the highest positive correlation with the hand-wrist and cervical vertebrae stages.

Foraminiferal calcification and CO2

NASA Astrophysics Data System (ADS)

Nooijer, L. D.; Toyofuku, T.; Reichart, G. J.

2017-12-01

Ongoing burning of fossil fuels increases atmospheric CO2, elevates marine dissolved CO2 and decreases pH and the saturation state with respect to calcium carbonate. Intuitively this should decrease the ability of CaCO3-producing organisms to build their skeletons and shells. Whereas on geological time scales weathering and carbonate deposition removes carbon from the geo-biosphere, on time scales up to thousands of years, carbonate precipitation increases pCO2 because of the associated shift in seawater carbon speciation. Hence reduced calcification provides a potentially important negative feedback on increased pCO2 levels. Here we show that foraminifera form their calcium carbonate by active proton pumping. This elevates the internal pH and acidifies the direct foraminiferal surrounding. This also creates a strong pCO2 gradient and facilitates the uptake of DIC in the form of carbon dioxide. This finding uncouples saturation state from calcification and predicts that the added carbon due to ocean acidification will promote calcification by these organisms. This unknown effect could add substantially to atmospheric pCO2 levels, and might need to be accounted for in future mitigation strategies.

Decrease in coccolithophore calcification and CO2 since the middle Miocene.

PubMed

Bolton, Clara T; Hernández-Sánchez, María T; Fuertes, Miguel-Ángel; González-Lemos, Saúl; Abrevaya, Lorena; Mendez-Vicente, Ana; Flores, José-Abel; Probert, Ian; Giosan, Liviu; Johnson, Joel; Stoll, Heather M

2016-01-14

Marine algae are instrumental in carbon cycling and atmospheric carbon dioxide (CO2) regulation. One group, coccolithophores, uses carbon to photosynthesize and to calcify, covering their cells with chalk platelets (coccoliths). How ocean acidification influences coccolithophore calcification is strongly debated, and the effects of carbonate chemistry changes in the geological past are poorly understood. This paper relates degree of coccolith calcification to cellular calcification, and presents the first records of size-normalized coccolith thickness spanning the last 14 Myr from tropical oceans. Degree of calcification was highest in the low-pH, high-CO2 Miocene ocean, but decreased significantly between 6 and 4 Myr ago. Based on this and concurrent trends in a new alkenone ɛp record, we propose that decreasing CO2 partly drove the observed trend via reduced cellular bicarbonate allocation to calcification. This trend reversed in the late Pleistocene despite low CO2, suggesting an additional regulator of calcification such as alkalinity.

Decrease in coccolithophore calcification and CO2 since the middle Miocene

PubMed Central

Bolton, Clara T.; Hernández-Sánchez, María T.; Fuertes, Miguel-Ángel; González-Lemos, Saúl; Abrevaya, Lorena; Mendez-Vicente, Ana; Flores, José-Abel; Probert, Ian; Giosan, Liviu; Johnson, Joel; Stoll, Heather M.

2016-01-01

Marine algae are instrumental in carbon cycling and atmospheric carbon dioxide (CO2) regulation. One group, coccolithophores, uses carbon to photosynthesize and to calcify, covering their cells with chalk platelets (coccoliths). How ocean acidification influences coccolithophore calcification is strongly debated, and the effects of carbonate chemistry changes in the geological past are poorly understood. This paper relates degree of coccolith calcification to cellular calcification, and presents the first records of size-normalized coccolith thickness spanning the last 14 Myr from tropical oceans. Degree of calcification was highest in the low-pH, high-CO2 Miocene ocean, but decreased significantly between 6 and 4 Myr ago. Based on this and concurrent trends in a new alkenone ɛp record, we propose that decreasing CO2 partly drove the observed trend via reduced cellular bicarbonate allocation to calcification. This trend reversed in the late Pleistocene despite low CO2, suggesting an additional regulator of calcification such as alkalinity. PMID:26762469

Relationship between intracranial internal carotid artery calcification and enlarged cerebral perivascular space.

PubMed

Tao, Xiao-Xiao; Li, Ge-Fei; Wu, Yi-Lan; Liu, Yi-Sheng; Zhao, Ying; Shi, Yan-Hui; Zhuang, Mei-Ting; Hou, Tian-Yu; Zhao, Rong; Liu, Feng-Di; Wang, Xue-Mei; Shen, Ying; Cui, Guo-Hong; Su, Jing-Jing; Chen, Wei; Tang, Xue-Mei; Sun, Ji; Liu, Jian-Ren

2017-06-01

The association between intracranial internal carotid artery (IICA) calcification and lacunes, white matter hyperintensity (WMH), and cerebral microbleeds (CMBs) has been well researched. However, enlarged cerebral perivascular space (PVS) has not yet been reported to correlate with intracranial internal carotid artery calcification. Therefore, the primary aim of this study was to investigate the relationship between IICA calcification and enlarged PVS. A total of 189 patients with ischemic stroke in the middle cerebral artery territory who presented within 7 days of ictus from 2012 to 2015 were enrolled respectively. All patients were required to have undergone head computed tomography, magnetic resonance imaging, susceptibility-weighted magnetic resonance imaging, magnetic resonance angiography, or computed tomography angiography. Clinical characteristics were recorded. IICA calcification and enlarged PVS were semi-quantitatively evaluated, and the presence of lacunes, WMH, and CMBs was recorded. Of the 189 patients, 63.5% were male. Mean age of the patients was 68.6 ± 12.2 years. There were 104 patients with IICA calcification. Age, diabetes mellitus, lacunes, and white matter hyperintensity were significantly associated with IICA calcification (P < 0.05). Multivariate logistic regression analysis showed that age, diabetes mellitus, and lacunes were independent predictors of IICA calcification (P < 0.05). A lower risk of IICA calcification was found in patients with a higher enlarged PVS score (P = 0.004). Higher enlarged PVS scores were associated with a lesser degree of IICA calcification. There appears to be a relationship between reduced risk of IICA calcification and enlarged PVS.

Relationship between dental calcification and skeletal maturation in a Peruvian sample

PubMed Central

Lecca-Morales, Rocío M.; Carruitero, Marcos J.

2017-01-01

ABSTRACT Objective: the objective of the study was to determine the relationship between dental calcification stages and skeletal maturation in a Peruvian sample. Methods: panoramic, cephalometric and carpal radiographs of 78 patients (34 girls and 44 boys) between 7 and 17 years old (9.90 ± 2.5 years) were evaluated. Stages of tooth calcification of the mandibular canine, first premolar, second premolar, and second molar and the skeletal maturation with a hand-wrist and a cervical vertebrae method were assessed. The relationships between the stages were assessed using Spearman’s correlation coefficient. Additionally, the associations of mandibular and pubertal growth peak stages with tooth calcification were evaluated by Fisher’s exact test. Results: all teeth showed positive and statistically significant correlations, the highest correlation was between the mandibular second molar calcification stages with hand-wrist maturation stages (r = 0.758, p < 0.001) and with vertebrae cervical maturation stages (r = 0.605, p < 0.001). The pubertal growth spurt was found in the G stage of calcification of the second mandibular molar, and the mandibular growth peak was found in the F stage of calcification of the second molar. Conclusion: there was a positive relationship between dental calcification stages and skeletal maturation stages by hand-wrist and cervical vertebrae methods in the sample studied. Dental calcification stages of the second mandibular molar showed the highest positive correlation with the hand-wrist and cervical vertebrae stages. PMID:28746492

Genetics in arterial calcification: pieces of a puzzle and cogs in a wheel.

PubMed

Rutsch, Frank; Nitschke, Yvonne; Terkeltaub, Robert

2011-08-19

Artery calcification reflects an admixture of factors such as ectopic osteochondral differentiation with primary host pathological conditions. We review how genetic factors, as identified by human genome-wide association studies, and incomplete correlations with various mouse studies, including knockout and strain analyses, fit into "pieces of the puzzle" in intimal calcification in human atherosclerosis, and artery tunica media calcification in aging, diabetes mellitus, and chronic kidney disease. We also describe in sharp contrast how ENPP1, CD73, and ABCC6 serve as "cogs in a wheel" of arterial calcification. Specifically, each is a minor component in the function of a much larger network of factors that exert balanced effects to promote and suppress arterial calcification. For the network to normally suppress spontaneous arterial calcification, the "cogs" ENPP1, CD73, and ABCC6 must be present and in working order. Monogenic ENPP1, CD73, and ABCC6 deficiencies each drive a molecular pathophysiology of closely related but phenotypically different diseases (generalized arterial calcification of infancy (GACI), pseudoxanthoma elasticum (PXE) and arterial calcification caused by CD73 deficiency (ACDC)), in which premature onset arterial calcification is a prominent but not the sole feature.

Computed Tomographic Pattern of Physiological Intracranial Calcifications in a City in Central Africa

PubMed Central

Uduma, Uduma Felix; Pius, Fokam; Mathieu, Motah

2012-01-01

Objective: Intracranial calcifications underlie certain brain diseases which may be de novo or systemic. But calclfications un-connected to pathologies are classified physiological. Aim: To evaluate physiological intracranial calcifications in Douala with establishment of earliest age range of detection. Materials and Methods: Prospective study of brain computed tomograms was done from April to October 2009 using Schumadzu CT Scan machine. Axial, reconstructed and bone window images as well Hounsfield unit measurements were used for final evaluations. Results were analysed with SSPS 3. Results: 132 patients with 75 males and 57 females were studied and 163 separate calcifications were identified due to co-existent calcifications. The highest calcification was in choroid plexi, constituiting 56.82% of the studied population. This was followed by pineal gland. Both were commonly co-existent with advancing age. These calcifications were first seen at 10-19years. No type of physiological intracranial calcification was seen below age 10. The least calcification of 0.76% of population was in dentate nucleus. Conclusion: No intra-cranial physiological calcifications started earlier than 9years in Douala, a city in Cameroon, Central Africa. PMID:22980109

Effect of Calcifications on Breast Ultrasound Shear Wave Elastography: An Investigational Study

PubMed Central

Gregory, Adriana; Mehrmohammadi, Mohammad; Denis, Max; Bayat, Mahdi; Stan, Daniela L.; Fatemi, Mostafa; Alizad, Azra

2015-01-01

Purpose To investigate the effects of macrocalcifications and clustered microcalcifications associated with benign breast masses on shear wave elastography (SWE). Methods SuperSonic Imagine (SSI) and comb-push ultrasound shear elastography (CUSE) were performed on three sets of phantoms to investigate how calcifications of different sizes and distributions influence measured elasticity. To demonstrate the effect in vivo, three female patients with benign breast masses associated with mammographically-identified calcifications were evaluated by CUSE. Results Apparent maximum elasticity (Emax) estimates resulting from individual macrocalcifications (with diameters of 2mm, 3mm, 5mm, 6mm, 9mm, 11mm, and 15mm) showed values over 50 kPa for all cases, which represents more than 100% increase over background (~21kPa). We considered a 2cm-diameter circular region of interest for all phantom experiments. Mean elasticity (Emean) values varied from 26 kPa to 73 kPa, depending on the macrocalcification size. Highly dense clusters of microcalcifications showed higher Emax values than clusters of microcalcification with low concentrations, but the difference in Emean values was not significant. Conclusions Our results demonstrate that the presence of large isolated macrocalcifications and highly concentrated clusters of microcalcifications can introduce areas with apparent high elasticity in SWE. Considering that benign breast masses normally have significantly lower elasticity values than malignant tumors, such areas with high elasticity appearing due to presence of calcification in benign breast masses may lead to misdiagnosis. PMID:26368939

Effect of Calcifications on Breast Ultrasound Shear Wave Elastography: An Investigational Study.

PubMed

Gregory, Adriana; Mehrmohammadi, Mohammad; Denis, Max; Bayat, Mahdi; Stan, Daniela L; Fatemi, Mostafa; Alizad, Azra

2015-01-01

To investigate the effects of macrocalcifications and clustered microcalcifications associated with benign breast masses on shear wave elastography (SWE). SuperSonic Imagine (SSI) and comb-push ultrasound shear elastography (CUSE) were performed on three sets of phantoms to investigate how calcifications of different sizes and distributions influence measured elasticity. To demonstrate the effect in vivo, three female patients with benign breast masses associated with mammographically-identified calcifications were evaluated by CUSE. Apparent maximum elasticity (Emax) estimates resulting from individual macrocalcifications (with diameters of 2mm, 3mm, 5mm, 6mm, 9mm, 11mm, and 15mm) showed values over 50 kPa for all cases, which represents more than 100% increase over background (~21kPa). We considered a 2cm-diameter circular region of interest for all phantom experiments. Mean elasticity (Emean) values varied from 26 kPa to 73 kPa, depending on the macrocalcification size. Highly dense clusters of microcalcifications showed higher Emax values than clusters of microcalcification with low concentrations, but the difference in Emean values was not significant. Our results demonstrate that the presence of large isolated macrocalcifications and highly concentrated clusters of microcalcifications can introduce areas with apparent high elasticity in SWE. Considering that benign breast masses normally have significantly lower elasticity values than malignant tumors, such areas with high elasticity appearing due to presence of calcification in benign breast masses may lead to misdiagnosis.

Comparative characterization of stromal vascular cells derived from three types of vascular wall and adipose tissue.

PubMed

Yang, Santsun; Eto, Hitomi; Kato, Harunosuke; Doi, Kentaro; Kuno, Shinichiro; Kinoshita, Kahori; Ma, Hsu; Tsai, Chi-Han; Chou, Wan-Ting; Yoshimura, Kotaro

2013-12-01

Multipotent stem/progenitor cells localize perivascularly in many organs and vessel walls. These tissue-resident stem/progenitor cells differentiate into vascular endothelial cells, pericytes, and other mesenchymal lineages, and participate in physiological maintenance and repair of vasculatures. In this study, we characterized stromal vascular cells obtained through the explant culture method from three different vessel walls in humans: arterial wall (ART; >500 μm in diameter), venous wall (VN; >500 μm in diameter), and small vessels in adipose tissue (SV; arterioles and venules, <100 μm in diameter). These were examined for functionality and compared with adipose-derived stem/stromal cells (ASCs). All stromal vascular cells of different origins presented fibroblast-like morphology and we could not visually discriminate one population from another. Flow cytometry showed that the cultured population heterogeneously expressed a variety of surface antigens associated with stem/progenitor cells, but CD105 was expressed by most cells in all groups, suggesting that the cells generally shared the characteristics of mesenchymal stem cells. Our histological and flow cytometric data suggested that the main population of vessel wall-derived stromal vascular cells were CD34(+)/CD31(-) and came from the tunica adventitia and areola tissue surrounding the adventitia. CD271 (p75NTR) was expressed by the vasa vasorum in the VN adventitia and by a limited population in the adventitia of SV. All three populations differentiated into multiple lineages as did ASCs. ART cells induced the largest quantity of calcium formation in the osteogenic medium, whereas ASCs showed the greatest adipogenic differentiation. SV and VN stromal cells had greater potency for network formation than did ART stromal cells. In conclusion, the three stromal vascular populations exhibited differential functional properties. Our results have clinical implications for vascular diseases such as

Calcific Aortic Valve Stenosis: Methods, Models, and Mechanisms

PubMed Central

Miller, Jordan D.; Weiss, Robert M.; Heistad, Donald D.

2011-01-01

Calcific aortic valve stenosis (CAVS) is a major health problem facing aging societies. The identification of osteoblast-like and osteoclast-like cells in human tissue has led to a major paradigm shift in the field. CAVS was thought to be a passive, degenerative process, whereas now the progression of calcification in CAVS is considered to be actively regulated. Mechanistic studies examining the contributions of true ectopic osteogenesis, non-osseous calcification, and ectopic osteoblast-like cells (that appear to function differently from skeletal osteoblasts) to valvular dysfunction have been facilitated by the development of mouse models of CAVS. Recent studies also suggest that valvular fibrosis, as well as calcification, may play an important role in restricting cusp movement, and CAVS may be more appropriately viewed as a fibrocalcific disease. High resolution echocardiography and magnetic resonance imaging have emerged as useful tools for testing the efficacy of pharmacological and genetic interventions in vivo. Key studies in humans and animals are reviewed that have shaped current paradigms in the field of CAVS, and suggest promising future areas for research. PMID:21617136

Is there a correlation between the pineal gland calcification and migraine?

PubMed

Ozlece, H K; Akyuz, O; Ilik, F; Huseyinoglu, N; Aydin, S; Can, S; Serim, V A

2015-10-01

The pineal gland calcifications have been associated with some diseases such as cerebral infarction, Alzheimer's disease and intracerebral hemorrhage while most cases are considered idiopathic and physiologic. However, there are limited data in the current literature about the association of pineal calcification and migraine. Our aim was to evaluate this association between migraine and pineal calcification by computed tomography of the brain. In our study, we assessed the computed tomography images of patients, who referred to the neurology outpatient clinic with the complaint of headache and were diagnosed with migraine without aura based according to 2004 criteria of the International Headache Society. 503 migraine patients and 500 control subjects without migraine diagnosis were included in this study. When migraine and control groups were compared by pineal calcification, the rates were determined as 80, 6% and 55% in migraine and control group, respectively. The difference was statistically significant (p < 0.001). In addition, it was seen that pineal calcifications, detected in migraine patients, did not show age-related increase. According to our data, we can point that pineal calcification may be associated with migraine.

[Severe generalized dystonia due to postradiotherapy cerebral calcifications].

PubMed

Chanson, J-B; Anheim, M; Lagha-Boukbiza, O; Fleury, M; Sellal, F; Tranchant, C

2008-05-01

Cerebral calcifications are a cause of secondary dystonia and may be an uncommon complication of radiotherapy. We report a very severe case of generalized dystonia due to postradiotherapy basal ganglia calcifications. An 8-year-old girl received 53 grays radiotherapy after surgery for craniopharyngioma. One year later she developed generalized dystonia. Computed tomography showed bilateral basal ganglia calcifications, especially of the lenticular nuclei. Pharmacological treatment with tetrabenazine, clonazepam and trihexiphenydile allowed a very limited improvement of dystonia; the course was complicated by dystonic storms and decompensations resulting from the iatrogenous panhypopituitarism. This case illustrates a severe complication of cranial irradiation which should be considered in the indications of this treatment, especially for children.

SNF472, a novel inhibitor of vascular calcification, could be administered during hemodialysis to attain potentially therapeutic phytate levels.

PubMed

Perelló, Joan; Gómez, M; Ferrer, M D; Rodríguez, N Y; Salcedo, C; Buades, J M; Pérez, M M; Torregrosa, J V; Martín, E; Maduell, F

2018-04-01

Cardiovascular calcification (CVC) is a major concern in hemodialysis (HD) and the loss of endogenous modulators of calcification seems involved in the process. Phytate is an endogenous crystallization inhibitor and its low molecular mass and high water solubility make it potentially dialyzable. SNF472 (the hexasodium salt of phytate) is being developed for the treatment of calciphylaxis and CVC in HD patients. We aimed to verify if phytate is lost during dialysis, and evaluate SNF472's behaviour during dialysis. Dialyzability was assessed in vitro using online-hemodiafiltration and high-flux HD systems in blood and saline. SNF472 was infused for 20 min and quantified at different time points. Phytate completely dialyzed in 1 h at low concentrations (10 mg/l) but not when added at 30 or 66.67 mg/l SNF472. In bypass conditions, calcium was slightly chelated during SNF472 infusion but when the system was switched to dialysis mode the calcium in the bath compensated this chelation. Phytate dialyses with a low clearance. The administration of SNF472 as an exogenous source of phytate allows to attain supra-physiological levels required for its potential therapeutic properties. As SNF472 is infused during the whole dialysis session, the low clearance would not affect the drug's systemic exposure.

History of hot flashes and aortic calcification among postmenopausal women.

PubMed

Thurston, Rebecca C; Kuller, Lewis H; Edmundowicz, Daniel; Matthews, Karen A

2010-03-01

Menopausal hot flashes are considered largely a quality-of-life issue. However, emerging research also links hot flashes to cardiovascular risk. In some investigations, this risk is particularly apparent among women using hormone therapy. The aim of this study was to determine whether a longer history of reported hot flashes over the study period was associated with greater aortic and coronary artery calcification. Interactions with hormone therapy use were examined in an exploratory fashion. Participants included 302 women participating in the Healthy Women Study, a longitudinal study of cardiovascular risk during perimenopause and postmenopause, which was initiated in 1983. Hot flashes (any/none) were assessed when women were 1, 2, 5, and 8 years postmenopausal. Electron beam tomography measures of coronary artery calcification and aortic calcification were completed in 1997-2004. Associations between the number of visits with report of hot flashes, divided by the number of visits attended, and aortic or coronary artery calcification (transformed) were examined in linear regression models. Interactions by hormone therapy use were evaluated. Among women using hormone therapy, a longer history of reported hot flashes was associated with increased aortic calcification, controlling for traditional cardiovascular risk factors (b = 2.87, SE = 1.21, P < 0.05). There were no significant associations between history of hot flashes and coronary artery calcification. Among postmenopausal women using hormone therapy, a longer history of reported hot flashes measured prospectively was associated with increased aortic calcification, controlling for traditional cardiovascular risk factors. Hot flashes may signal adverse cardiovascular changes among certain postmenopausal women.

Clinical response to dorsal duct drainage via the minor papilla in refractory obstructing chronic calcific pancreatitis

PubMed Central

Kwon, Chang-Il; Gromski, Mark A.; Sherman, Stuart; El Hajj, Ihab I.; Easler, Jeffrey J.; Watkins, James; McHenry, Lee; Lehman, Glen A.; Fogel, Evan L.

2017-01-01

Background and study aims Complete stone removal from the main pancreatic duct might not be achieved in all patients with obstructive chronic calcific pancreatitis. We report our results for endoscopic dorsal pancreatic duct (DPD) bypass of obstructing stones in the ventral pancreatic duct (VPD). Patients and methods 16 patients with obstructive chronic calcific pancreatitis were treated with a DPD bypass. Clinical success was defined as significant pain relief and no hospital admissions for pain management during the ongoing treatment period. Results Among 16 patients meeting entry criteria, 10 (62.5%) had a history of unsuccessful endoscopic therapy, and 8 had failed extracorporeal shockwave lithotripsy (ESWL). Clinical success was achieved in 12 patients (75 %). Among these responders, 10 patients (83.3 %) had markedly improved or complete pain relief after the first stent placement, which persisted throughout the follow-up period; 11 patients (91.7 %) were able to discontinue their daily analgesics. Conclusions In selected patients with obstructive chronic calcific pancreatitis, the DPD bypass may be considered as a rescue endoscopic therapy, potentially obviating the need for surgery when standard endoscopic methods and ESWL fail. PMID:28201840

Reversal of ocean acidification enhances net coral reef calcification.

PubMed

Albright, Rebecca; Caldeira, Lilian; Hosfelt, Jessica; Kwiatkowski, Lester; Maclaren, Jana K; Mason, Benjamin M; Nebuchina, Yana; Ninokawa, Aaron; Pongratz, Julia; Ricke, Katharine L; Rivlin, Tanya; Schneider, Kenneth; Sesboüé, Marine; Shamberger, Kathryn; Silverman, Jacob; Wolfe, Kennedy; Zhu, Kai; Caldeira, Ken

2016-03-17

Approximately one-quarter of the anthropogenic carbon dioxide released into the atmosphere each year is absorbed by the global oceans, causing measurable declines in surface ocean pH, carbonate ion concentration ([CO3(2-)]), and saturation state of carbonate minerals (Ω). This process, referred to as ocean acidification, represents a major threat to marine ecosystems, in particular marine calcifiers such as oysters, crabs, and corals. Laboratory and field studies have shown that calcification rates of many organisms decrease with declining pH, [CO3(2-)], and Ω. Coral reefs are widely regarded as one of the most vulnerable marine ecosystems to ocean acidification, in part because the very architecture of the ecosystem is reliant on carbonate-secreting organisms. Acidification-induced reductions in calcification are projected to shift coral reefs from a state of net accretion to one of net dissolution this century. While retrospective studies show large-scale declines in coral, and community, calcification over recent decades, determining the contribution of ocean acidification to these changes is difficult, if not impossible, owing to the confounding effects of other environmental factors such as temperature. Here we quantify the net calcification response of a coral reef flat to alkalinity enrichment, and show that, when ocean chemistry is restored closer to pre-industrial conditions, net community calcification increases. In providing results from the first seawater chemistry manipulation experiment of a natural coral reef community, we provide evidence that net community calcification is depressed compared with values expected for pre-industrial conditions, indicating that ocean acidification may already be impairing coral reef growth.

Reversal of ocean acidification enhances net coral reef calcification

NASA Astrophysics Data System (ADS)

Albright, Rebecca; Caldeira, Lilian; Hosfelt, Jessica; Kwiatkowski, Lester; MacLaren, Jana K.; Mason, Benjamin M.; Nebuchina, Yana; Ninokawa, Aaron; Pongratz, Julia; Ricke, Katharine L.; Rivlin, Tanya; Schneider, Kenneth; Sesboüé, Marine; Shamberger, Kathryn; Silverman, Jacob; Wolfe, Kennedy; Zhu, Kai; Caldeira, Ken

2016-03-01

Approximately one-quarter of the anthropogenic carbon dioxide released into the atmosphere each year is absorbed by the global oceans, causing measurable declines in surface ocean pH, carbonate ion concentration ([CO32-]), and saturation state of carbonate minerals (Ω). This process, referred to as ocean acidification, represents a major threat to marine ecosystems, in particular marine calcifiers such as oysters, crabs, and corals. Laboratory and field studies have shown that calcification rates of many organisms decrease with declining pH, [CO32-], and Ω. Coral reefs are widely regarded as one of the most vulnerable marine ecosystems to ocean acidification, in part because the very architecture of the ecosystem is reliant on carbonate-secreting organisms. Acidification-induced reductions in calcification are projected to shift coral reefs from a state of net accretion to one of net dissolution this century. While retrospective studies show large-scale declines in coral, and community, calcification over recent decades, determining the contribution of ocean acidification to these changes is difficult, if not impossible, owing to the confounding effects of other environmental factors such as temperature. Here we quantify the net calcification response of a coral reef flat to alkalinity enrichment, and show that, when ocean chemistry is restored closer to pre-industrial conditions, net community calcification increases. In providing results from the first seawater chemistry manipulation experiment of a natural coral reef community, we provide evidence that net community calcification is depressed compared with values expected for pre-industrial conditions, indicating that ocean acidification may already be impairing coral reef growth.

Abdominal calcifications and diagnostic imaging decision making: a topic review

PubMed Central

Bassano, John M.

2006-01-01

Abstract Objective To review commonly encountered calcifications found within the abdomen as seen on the lumbar spine radiograph and to determine which advanced imaging modality is best to thoroughly assess the patient. Methods Searches of electronic databases and textbooks were conducted to construct this narrative overview. Discussion By categorizing the type of calcification and localizing it anatomically, most often a definitive diagnosis can be reached. Two commonly encountered conditions, abdominal aortic aneurysms and urinary calculi, are used to compare the main advanced imaging modalities (diagnostic ultrasound and computed tomography) used to further assess abdominal calcifications. Conclusion In most circumstances, either diagnostic ultrasound or computed tomography will establish a definitive diagnosis and offer thorough imaging assessment for abdominal calcifications. PMID:19674671

Model-based iterative reconstruction and adaptive statistical iterative reconstruction: dose-reduced CT for detecting pancreatic calcification

PubMed Central

Katsura, Masaki; Akahane, Masaaki; Sato, Jiro; Matsuda, Izuru; Ohtomo, Kuni

2016-01-01

Background Iterative reconstruction methods have attracted attention for reducing radiation doses in computed tomography (CT). Purpose To investigate the detectability of pancreatic calcification using dose-reduced CT reconstructed with model-based iterative construction (MBIR) and adaptive statistical iterative reconstruction (ASIR). Material and Methods This prospective study approved by Institutional Review Board included 85 patients (57 men, 28 women; mean age, 69.9 years; mean body weight, 61.2 kg). Unenhanced CT was performed three times with different radiation doses (reference-dose CT [RDCT], low-dose CT [LDCT], ultralow-dose CT [ULDCT]). From RDCT, LDCT, and ULDCT, images were reconstructed with filtered-back projection (R-FBP, used for establishing reference standard), ASIR (L-ASIR), and MBIR and ASIR (UL-MBIR and UL-ASIR), respectively. A lesion (pancreatic calcification) detection test was performed by two blinded radiologists with a five-point certainty level scale. Results Dose-length products of RDCT, LDCT, and ULDCT were 410, 97, and 36 mGy-cm, respectively. Nine patients had pancreatic calcification. The sensitivity for detecting pancreatic calcification with UL-MBIR was high (0.67–0.89) compared to L-ASIR or UL-ASIR (0.11–0.44), and a significant difference was seen between UL-MBIR and UL-ASIR for one reader (P = 0.014). The area under the receiver-operating characteristic curve for UL-MBIR (0.818–0.860) was comparable to that for L-ASIR (0.696–0.844). The specificity was lower with UL-MBIR (0.79–0.92) than with L-ASIR or UL-ASIR (0.96–0.99), and a significant difference was seen for one reader (P < 0.01). Conclusion In UL-MBIR, pancreatic calcification can be detected with high sensitivity, however, we should pay attention to the slightly lower specificity. PMID:27110389

Study of calcification formation and disease diagnostics utilising advanced vibrational spectroscopy

NASA Astrophysics Data System (ADS)

Kerssens, Marleen Maartje

The accurate and safe diagnosis of breast cancer is a significant societal issue, with annual disease incidence of 48,000 women and around 370 men in the UK. Early diagnosis of the disease allows more conservative treatments and better patient outcomes. Microcalcifications in breast tissue are an important indicator for breast cancers, and often the only sign of their presence. Several studies have suggested that the type of calcification formed may act as a marker for malignancy and its presence may be of biological significance. In this work, breast calcifications are studied with FTIR, synchrotron FTIR, ATR FTIR, and Raman mapping to explore their disease specific composition. From a comparison between vibrational spectroscopy and routine staining procedures it becomes clear that calcium builds up prior to calcification formation. Raman and FTIR indicate the same size for calcifications and are in agreement with routine staining techniques. From the synchrotron FTIR measurements it can be proven that amide is present in the centre of the calcifications and the intensity of the bands depends on the pathology. Special attention is paid to the type of carbonate substitution in the calcifications relating to different pathology grades. In contrast to mammography, Raman spectroscopy has the capability to distinguish calcifications based on their chemical composition. The ultimate goal is to turn the acquired knowledge from the mapping studies into a clinical tool based on deep Raman spectroscopy. Deep Raman techniques have a considerable potential to reduce large numbers of normal biopsies, reduce the time delay between screening and diagnosis and therefore diminish patient anxiety. In order to achieve this, a deep Raman system is designed and after evaluation of its performance tested on buried calcification standards in porcine soft tissue and human mammary tissue. It is shown that, when the calcification is probed through tissue, the strong 960 cm-1 phosphate band

Intramural location and size of arterial calcification are associated with stenosis at carotid bifurcation.

PubMed

Yamada, Shigeki; Oshima, Marie; Watanabe, Yoshihiko; Ogata, Hideki; Hashimoto, Kenji; Miyake, Hidenori

2014-06-01

The purpose of this study was to investigate the association between internal carotid artery (ICA) stenosis and intramural location and size of calcification at the ICA origins and the origins of the cervical arteries proximal to the ICA. A total of 1139 ICAs were evaluated stenosis and calcification on the multi-detector row CT angiography. The intramural location was categorized into none, outside and inside location. The calcification size was evaluated on the 4-point grading scale. The multivariate analyses were adjusted for age, serum creatinine level, hypertension, hyperlipidemia, diabetes mellitus, smoking and alcohol habits. Outside calcification at the ICA origins showed the highest multivariate odds ratio (OR) for the presence of ICA stenosis (30.0) and severe calcification (a semicircle or more of calcification at the arterial cross-sectional surfaces) did the second (14.3). In the subgroups of >70% ICA stenosis, the multivariate OR of outside location increased to 44.8 and that of severe calcification also increased to 32.7. Four of 5 calcified carotid plaque specimens extracted by carotid endarterectomy were histologically confirmed to be calcified burdens located outside the internal elastic lamia which were defined as arterial medial calcification. ICA stenosis was strongly associated with severe calcification located mainly outside the carotid plaque. Outside calcification at the ICA origins should be evaluated separately from inside calcification, as a marker for the ICA stenosis. Additionally, we found that calcification at the origins of the cervical arteries proximal to the ICA was significantly associated with the ICA stenosis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The relationship between inhibitors of the Wnt signalling pathway (Dickkopf-1(DKK1) and sclerostin), bone mineral density, vascular calcification and arterial stiffness in post-menopausal women.

PubMed

Hampson, Geeta; Edwards, Sylvie; Conroy, Soraya; Blake, Glen M; Fogelman, Ignac; Frost, Michelle L

2013-09-01

Epidemiological studies have shown an association between bone loss/osteoporosis and vascular calcification (VC). Recent studies have implicated the Wnt signalling pathway in the pathogenesis of VC. We investigated the association between circulating concentrations of Wnt inhibitors; DKK1 and sclerostin with bone mineral density (BMD), abdominal aortic calcification (AAC) and arterial stiffness in post-menopausal women. One hundred and forty six post-menopausal women aged (mean [SD]) 61.5[6.5] years were studied. Sclerostin and DKK1 were measured in serum. BMD was measured at the lumbar spine (LS), femoral neck (FN), total hip (TH). AAC was detected by Vertebral Fracture Assessment (VFA) imaging and quantified using an 8- and 24- point scoring methods. Arterial stiffness was determined by aortic pulse wave velocity (PWV). A significant positive correlation was observed between sclerostin and BMD at the FN (r = 0.166, p = 0.043) and TH (r = 0.165, p = 0.044). The association remained significant at the FN (p = 0.045) and TH (p = 0.026) following adjustment for confounders. No significant correlation was observed between DKK1 and BMD. In contrast, there was a significant negative correlation between log DKK1 and AAC (24-point score: r = -0.25, p = 0.008 and 8-point score: r = -0.21, p = 0.024). Subjects with AAC score of 1 or less had significantly higher DKK1 (p = 0.01). The association between DKK1 and AAC remained significant following correction for age, blood pressure, cholesterol (24-point score: p = 0.017, 8-point score: p = 0.044). In adjusted linear regression analysis, sclerostin was positively associated with AAC (24-point score: p = 0.048, 8-point score: p = 0.031). Subjects with a PWV>9 m/s had significantly higher sclerostin than those with PWV <9 m/s: 23.8[12.3], vs 29.7 [14] pmol/l, p = 0.03). No association was observed between DKK1 and PWV. The opposite association between AAC and the 2 Wnt signaling inhibitors is of interest and merits further

Association between arterial calcifications and nonlacunar and lacunar ischemic strokes.

PubMed

van Dijk, Anouk C; Fonville, Susanne; Zadi, Taihra; van Hattem, Antonius M G; Saiedie, Ghesrouw; Koudstaal, Peter J; van der Lugt, Aad

2014-03-01

Nonlacunar cerebral infarcts are presumed to be caused by thromboembolism from the heart or extracranial arteries, whereas lacunar infarcts are thought to be caused by small vessel disease. We investigated to what extent arterial calcifications differ between nonlacunar and lacunar ischemic strokes. We studied 820 consecutive patients with transient ischemic attack or ischemic stroke in the anterior circulation who underwent multidetector computed tomography angiography and had no rare cause of stroke. The presence of likely cardioembolic pathogenesis was determined according to the Trial of Org 10172 in Acute Stroke Treatment criteria. The remaining 708 patients were categorized as nonlacunar or lacunar strokes, either transient ischemic attacks or strokes, based on clinical symptoms corrected by brain imaging results. We measured volume of calcifications in the aortic arch, symptomatic extracranial and intracranial carotid artery using multidetector computed tomography angiography. The difference in calcifications between nonlacunar and lacunar strokes was assessed with a multivariable logistic regression analysis. We adjusted for degree of symptomatic carotid artery stenosis and cardiovascular risk factors. We found an independent association between volume of aortic arch calcifications and nonlacunar ischemic strokes (adjusted odds ratio [95% confidence interval], 1.11 [1.02-1.21]). No independent associations between extracranial and intracranial carotid artery calcifications and nonlacunar strokes were present. The only difference we found between nonlacunar and lacunar strokes was a higher calcification volume in the aortic arch in nonlacunar strokes. Our findings only partially confirm the notion of distinct etiologies and suggest that the potential role of other plaque components, plaque morphology, and aortic arch calcifications in ischemic stroke subtypes awaits further evaluation.

Age-related incidence of pineal calcification detected by computed tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zimmerman, R.A.; Bilaniuk, L.T.

The age-related incidence of detectable pineal calcification in 725 patients (age range, newborn-20 yrs) suggests that there is a relationship between calcification and the hormonal role played by the pineal gland in the regulation of sexual development. Pineal calcification (demonstrated by computed tomography (CT) on 8-mm-thick sections) in patients less than 6 years old should be looked upon with suspicion, and follow-up CT should be considered to exclude the possible development of a pineal neoplasm.

Early detection of ocean acidification effects on marine calcification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ilyina, T.; Zeebe, R. E.; E. Maier-Reimer

Ocean acidification is likely to impact calcification rates in many pelagic organisms, which may in turn cause significant changes in marine ecosystem structure. We examine effects of changes in marine CaCO3 production on total alkalinity (TA) in the ocean using the global biogeochemical ocean model HAMOCC. We test a variety of future calcification scenarios because experimental studies with different organisms have revealed a wide range of calcification sensitivities to CaCO3 saturation state. The model integrations start at a preindustrial steady state in the year 1800 and run until the year 2300 forced with anthropogenic CO2 emissions. Calculated trends in TAmore » are evaluated taking into account the natural variability in ocean carbonate chemistry, as derived from repeat hydrographic transects. We conclude that the data currently available does not allow discerning significant trends in TA due to changes in pelagic calcification caused by ocean acidification. Given different calcification scenarios, our model calculations indicate that the TA increase over time will start being detectable by the year 2040, increasing by 5–30 umol/kg compared to the present-day values. In a scenario of extreme reductions in calcification, large TA changes relative to preindustrial conditions would have occurred at present, which we consider very unlikely. However, the time interval of reliable TA observations is too short to disregard this scenario. The largest increase in surface ocean TA is predicted for the tropical and subtropical regions. In order to monitor and quantify possible early signs of acidification effects, we suggest to specifically target those regions during future ocean chemistry surveys.« less

Metal Ion-Loaded Nanofibre Matrices for Calcification Inhibition in Polyurethane Implants

PubMed Central

Singh, Charanpreet; Wang, Xungai

2017-01-01

Pathologic calcification leads to structural deterioration of implant materials via stiffening, stress cracking, and other structural disintegration mechanisms, and the effect can be critical for implants intended for long-term or permanent implantation. This study demonstrates the potential of using specific metal ions (MI)s for inhibiting pathological calcification in polyurethane (PU) implants. The hypothesis of using MIs as anti-calcification agents was based on the natural calcium-antagonist role of Mg2+ ions in human body, and the anti-calcification effect of Fe3+ ions in bio-prosthetic heart valves has previously been confirmed. In vitro calcification results indicated that a protective covering mesh of MI-doped PU can prevent calcification by preventing hydroxyapatite crystal growth. However, microstructure and mechanical characterisation revealed oxidative degradation effects from Fe3+ ions on the mechanical properties of the PU matrix. Therefore, from both a mechanical and anti-calcification effects point of view, Mg2+ ions are more promising candidates than Fe3+ ions. The in vitro MI release experiments demonstrated that PU microphase separation and the structural design of PU-MI matrices were important determinants of release kinetics. Increased phase separation in doped PU assisted in consistent long-term release of dissolved MIs from both hard and soft segments of the PU. The use of a composite-sandwich mesh design prevented an initial burst release which improved the late (>20 days) release rate of MIs from the matrix. PMID:28644382

Bulbous epiphysis and popcorn calcification as related to growth plate differentiation in osteogenesis imperfecta

PubMed Central

Brizola, Evelise; McCarthy, Edward; Shapiro, Jay Robert

2015-01-01

Summary Background Osteogenesis Imperfecta (OI) is an heritable systemic disorder of connective tissue due to different sequence variants in genes affecting both the synthesis of type I collagen and osteoblast function. Dominant and recessive inheritance is recognized. Approximately 90% of the OI cases are due to mutations in COL1A1/A2 genes. We clinically and radiologically describes an adult male with type III osteogenesis imperfecta who presents a rare bone dysplasia termed bulbous epiphyseal deformity in association with popcorn calcifications. Popcorn calcifications may occur with bulbous epiphyseal deformity or independently. Methods Molecular analysis was performed for COL1A1, COL1A2, LEPRE1 and WNT1 genes. Results An uncommon COL1A1 mutation was identified. Clinical and radiological exams confirmed a distinctive bulbous epiphyseal deformity with popcorn calcifications in distal femurs. We have identified four additional OI patients reported in current literature, whose X-rays show bulbous epiphyseal deformity related to mutations in CR-TAP, LEPRE1 and WNT1 genes. Conclusion The mutation identified here had been previously described twice in OI patients and no previous correlation with bulbous epiphyseal deformity was described. The occurrence of this bone dysplasia focuses attention on alterations in normal growth plate differentiation and the subsequent effect on endochondral bone formation in OI. PMID:26604951

Rare finding of Eustachian tube calcifications with cone-beam computed tomography.

PubMed

Syed, Ali Z; Hawkins, Anna; Alluri, Leela Subashini; Jadallah, Buthainah; Shahid, Kiran; Landers, Michael; Assaf, Hussein M

2017-12-01

Soft tissue calcification is a pathological condition in which calcium and phosphate salts are deposited in the soft tissue organic matrix. This study presents an unusual calcification noted in the cartilaginous portion of the Eustachian tube. A 67-year-old woman presented for dental treatment, specifically for implant placement, and cone-beam computed tomography (CBCT) was performed. The CBCT scan was reviewed by a board-certified oral and maxillofacial radiologist and revealed incidental findings of 2 distinct calcifications in the cartilaginous portion of the Eustachian tube. To the authors' knowledge, no previous study has reported the diagnosis of Eustachian tube calcification using CBCT. This report describes an uncommon variant of Eustachian tube calcification, which has a significant didactic value because such cases are seldom illustrated either in textbooks or in the literature. This case once again underscores the importance of having CBCT scans evaluated by a board-certified oral and maxillofacial radiologist.

Increased dietary intake of vitamin A promotes aortic valve calcification in vivo.

PubMed

Huk, Danielle J; Hammond, Harriet L; Kegechika, Hiroyuki; Lincoln, Joy

2013-02-01

Calcific aortic valve disease (CAVD) is a major public health problem with no effective treatment available other than surgery. We previously showed that mature heart valves calcify in response to retinoic acid (RA) treatment through downregulation of the SRY transcription factor Sox9. In this study, we investigated the effects of excess vitamin A and its metabolite RA on heart valve structure and function in vivo and examined the molecular mechanisms of RA signaling during the calcification process in vitro. Using a combination of approaches, we defined calcific aortic valve disease pathogenesis in mice fed 200 IU/g and 20 IU/g of retinyl palmitate for 12 months at molecular, cellular, and functional levels. We show that mice fed excess vitamin A develop aortic valve stenosis and leaflet calcification associated with increased expression of osteogenic genes and decreased expression of cartilaginous markers. Using a pharmacological approach, we show that RA-mediated Sox9 repression and calcification is regulated by classical RA signaling and requires both RA and retinoid X receptors. Our studies demonstrate that excess vitamin A dietary intake promotes heart valve calcification in vivo. Therefore suggesting that hypervitaminosis A could serve as a new risk factor of calcific aortic valve disease in the human population.

A Genomics-Based Model for Prediction of Severe Bioprosthetic Mitral Valve Calcification.

PubMed

Ponasenko, Anastasia V; Khutornaya, Maria V; Kutikhin, Anton G; Rutkovskaya, Natalia V; Tsepokina, Anna V; Kondyukova, Natalia V; Yuzhalin, Arseniy E; Barbarash, Leonid S

2016-08-31

Severe bioprosthetic mitral valve calcification is a significant problem in cardiovascular surgery. Unfortunately, clinical markers did not demonstrate efficacy in prediction of severe bioprosthetic mitral valve calcification. Here, we examined whether a genomics-based approach is efficient in predicting the risk of severe bioprosthetic mitral valve calcification. A total of 124 consecutive Russian patients who underwent mitral valve replacement surgery were recruited. We investigated the associations of the inherited variation in innate immunity, lipid metabolism and calcium metabolism genes with severe bioprosthetic mitral valve calcification. Genotyping was conducted utilizing the TaqMan assay. Eight gene polymorphisms were significantly associated with severe bioprosthetic mitral valve calcification and were therefore included into stepwise logistic regression which identified male gender, the T/T genotype of the rs3775073 polymorphism within the TLR6 gene, the C/T genotype of the rs2229238 polymorphism within the IL6R gene, and the A/A genotype of the rs10455872 polymorphism within the LPA gene as independent predictors of severe bioprosthetic mitral valve calcification. The developed genomics-based model had fair predictive value with area under the receiver operating characteristic (ROC) curve of 0.73. In conclusion, our genomics-based approach is efficient for the prediction of severe bioprosthetic mitral valve calcification.

A Genomics-Based Model for Prediction of Severe Bioprosthetic Mitral Valve Calcification

PubMed Central

Ponasenko, Anastasia V.; Khutornaya, Maria V.; Kutikhin, Anton G.; Rutkovskaya, Natalia V.; Tsepokina, Anna V.; Kondyukova, Natalia V.; Yuzhalin, Arseniy E.; Barbarash, Leonid S.

2016-01-01

Severe bioprosthetic mitral valve calcification is a significant problem in cardiovascular surgery. Unfortunately, clinical markers did not demonstrate efficacy in prediction of severe bioprosthetic mitral valve calcification. Here, we examined whether a genomics-based approach is efficient in predicting the risk of severe bioprosthetic mitral valve calcification. A total of 124 consecutive Russian patients who underwent mitral valve replacement surgery were recruited. We investigated the associations of the inherited variation in innate immunity, lipid metabolism and calcium metabolism genes with severe bioprosthetic mitral valve calcification. Genotyping was conducted utilizing the TaqMan assay. Eight gene polymorphisms were significantly associated with severe bioprosthetic mitral valve calcification and were therefore included into stepwise logistic regression which identified male gender, the T/T genotype of the rs3775073 polymorphism within the TLR6 gene, the C/T genotype of the rs2229238 polymorphism within the IL6R gene, and the A/A genotype of the rs10455872 polymorphism within the LPA gene as independent predictors of severe bioprosthetic mitral valve calcification. The developed genomics-based model had fair predictive value with area under the receiver operating characteristic (ROC) curve of 0.73. In conclusion, our genomics-based approach is efficient for the prediction of severe bioprosthetic mitral valve calcification. PMID:27589735

Serum calcification propensity is independently associated with disease activity in systemic lupus erythematosus

PubMed Central

Chalikias, George; Tziakas, Dimitrios; Chizzolini, Carlo; Ribi, Camillo; Trendelenburg, Marten; Eisenberger, Ute; Hauser, Thomas; Pasch, Andreas; Huynh-Do, Uyen; Arampatzis, Spyridon

2018-01-01

Background Systemic lupus erythematosus (SLE) is associated with severe cardiovascular complications. The T50 score is a novel functional blood test quantifying calcification propensity in serum. High calcification propensity (or low T50) is a strong and independent determinant of all-cause mortality in various patient populations. Methods A total of 168 patients with ≥ 4 American College of Rheumatology (ACR) diagnostic criteria from the Swiss Systemic lupus erythematosus Cohort Study (SSCS) were included in this analysis. Serum calcification propensity was assessed using time-resolved nephelometry. Results The cohort mainly consisted of female (85%), middle-aged (43±14 years) Caucasians (77%). The major determinants of T50 levels included hemoglobin, serum creatinine and serum protein levels explaining 43% of the variation at baseline. Integrating disease activity (SELENA-SLEDAI) into this multivariate model revealed a significant association between disease activity and T50 levels. In a subgroup analysis considering only patients with active disease (SELENA-SLEDAI score ≥4) we found a negative association between T50 and SELENA-SLEDAI score at baseline (Spearman’s rho -0.233, P = 0.02). Conclusions Disease activity and T50 are closely associated. Moreover, T50 levels identify a subgroup of SLE patients with ongoing systemic inflammation as mirrored by increased disease activity. T50 could be a promising biomarker reflecting SLE disease activity and might offer an earlier detection tool for high-risk patients. PMID:29364894

Oral calcium supplements do not affect the progression of aortic valve calcification or coronary artery calcification.

PubMed

Bhakta, Mayurkumar; Bruce, Charles; Messika-Zeitoun, David; Bielak, Lawrence; Sheedy, Patrick F; Peyser, Patricia; Sarano, Maurice

2009-01-01

The use of oral calcium supplementation among the elderly for prevention and treatment of osteoporosis and osteopenia is increasing. The incidence of aortic valve disease and coronary artery disease also is increasing. No study thus far has been done to demonstrate whether this affects the progression of calcification in both the valves and vasculature. We sought to determine whether ingestion of oral calcium supplementation has an effect on aortic valve calcification (AVC) and coronary artery calcification (CAC). We performed an independent assessment of AVC, CAC, and calcium supplementation among patients enrolled in the Epidemiology of Coronary Artery Calcification study who were >60 years of age and had baseline and 4-year follow-up AVC data. In this population-based study of Olmsted County (Minnesota) residents, AVC and CAC scores were determined prospectively by electron beam computed tomography. We evaluated baseline demographic data and analyzed whether those patients using calcium supplementation had a higher rate of progression of both AVC and CAC. We identified 257 patients (mean age, 67.8+/-5.2 years), 144 of whom were women. Twenty-five patients (all women) reported using calcium supplements. Analysis of the 144 women (25 taking calcium supplementation) showed there was no difference in the progression of AVC (mean difference in baseline and follow-up AVC score; no supplement versus supplement, 30+/-9 vs 39+/-28; P=.73) or CAC (mean difference in baseline and follow-up CAC score; no supplement vs supplement, 47+/-15 vs 112+/-22; P=.154). There were no significant differences between the 2 groups with regard to baseline AVC, serum calcium, renal function, diabetes, hypertension, cholesterol, or body mass index. In this community-based observational study with a 4-year follow-up, no significant increased progression of AVC or CAC was found in women taking oral calcium supplementation. Larger prospective, randomized studies are needed to confirm these

Neoatherosclerosis development following bioresorbable vascular scaffold implantation in diabetic and non-diabetic swine

PubMed Central

van Ditzhuijzen, Nienke S.; Kurata, Mie; van den Heuvel, Mieke; Sorop, Oana; van Duin, Richard W. B.; Krabbendam-Peters, Ilona; Ligthart, Jurgen; Witberg, Karen; Murawska, Magdalena; Bouma, Brett; Villiger, Martin; Garcia-Garcia, Hector M.; Serruys, Patrick W.; Zijlstra, Felix; van Soest, Gijs; Duncker, Dirk-Jan; Regar, Evelyn; van Beusekom, Heleen M. M.

2017-01-01

Background DM remains a risk factor for poor outcome after stent-implantation, but little is known if and how DM affects the vascular response to BVS. Aim The aim of our study was to examine coronary responses to bioresorbable vascular scaffolds (BVS) in swine with and without diabetes mellitus fed a ‘fast-food’ diet (FF-DM and FF-NDM, respectively) by sequential optical coherence tomography (OCT)-imaging and histology. Methods Fifteen male swine were evaluated. Eight received streptozotocin-injection to induce DM. After 9 months (M), 32 single BVS were implanted in epicardial arteries with a stent to artery (S/A)-ratio of 1.1:1 under quantitative coronary angiography (QCA) and OCT guidance. Lumen, scaffold, neointimal coverage and composition were assessed by QCA, OCT and near-infrared spectroscopy (NIRS) pre- and/or post-procedure, at 3M and 6M. Additionally, polarization-sensitive (PS)-OCT was performed in 7 swine at 6M. After sacrifice at 3M and 6M, histology and polymer degradation analysis were performed. Results Late lumen loss was high (~60%) within the first 3M after BVS-implantation (P<0.01 FF-DM vs. FF-NDM) and stabilized between 3M and 6M (<5% change in FF-DM, ~10% in FF-NDM; P>0.20). Neointimal coverage was highly heterogeneous in all swine (DM vs. NDM P>0.05), with focal lipid accumulation, irregular collagen distribution and neointimal calcification. Likewise, polymer mass loss was low (~2% at 3M, ~5% at 6M;P>0.20) and not associated with DM or inflammation. Conclusion Scaffold coverage showed signs of neo-atherosclerosis in all FF-DM and FF-NDM swine, scaffold polymer was preserved and the vascular response to BVS was not influenced by diabetes. PMID:28898243

Vanishing calcification associated with a spontaneous ventral spinal cerebrospinal fluid leak.

PubMed

Schievink, Wouter I; Ross, Lindsey; Prasad, Ravi S; Maya, M Marcel

2016-12-01

Some patients with spontaneous intracranial hypotension have a ventral spinal cerebrospinal fluid (CSF) leak and these CSF leaks may be associated with calcified disk herniations. Identifying these calcifications is helpful in directing treatment. We report here the unusual case of a patient with a ventral CSF leak in whom the associated calcification absorbed over a five-month period. A 42-year-old woman developed orthostatic headaches and bilateral abducens nerve palsies. Magnetic resonance imaging of her brain showed typical findings of spontaneous intracranial hypotension. Magnetic resonance imaging of her spine showed an extensive cervicothoracic CSF leak. Computed tomographic myelography showed calcification at the Th1-2 disk space. Three epidural blood patches were performed, but her symptoms persisted. Digital subtraction myelography performed five months later showed an upper thoracic ventral CSF, but the calcification was no longer present. A dural tear, found at surgery at the Th1-2 level, was repaired and the patient made an uneventful recovery. The resorption of calcifications at the level of a ventral spinal CSF leak could explain the absence of any calcifications in at least some patients with such leaks and demonstrates the usefulness of reviewing previous imaging in patients with ventral CSF leaks if the exact site of the leak remains unknown. © International Headache Society 2016.

[Calcific tendinitis of the shoulder].

PubMed

Gärtner, J; Heyer, A

1995-06-01

Degenerative ossification is formed directly at the major tubercle. Like in any other gliding tendon, fibrocartilage cells lie on the articular side of the rotator tendon at the pivot of the humerus head. Typically, the calcific deposits of calcifying tendinitis are found between these two areas. At this site, hydroxyapatite is usually formed by fibrocartilage cells through an unknown stimulus. There is no ossification. This is a two-phase disease. During the chronic initial phase, a calcific deposit is formed in the tendon of the rotator cuff. In the X-ray, it is clearly circumscribed and has a dense appearance (type I). Pain is inconsistent and may exist for years. In the acute phase, the deposit undergoes spontaneous resolution. Now it takes on a translucent and cloudy appearance without clear circumscription (type III). Patients experience severe pain for 2-3 weeks. Finally, a normally functioning shoulder joint will result. The X-ray therefore allows a prognostic conclusion. In a study including 235 calcific deposits, it became clear that there are some cases where it is not possible to designate the specific X-ray morphology to a given deposit (type II). Irrespective of the phase of disease, the so-called calcific deposit is composed of poorly mineralized hydroxyapatite. For a diagnosis, we require: a typical history, clinical findings consistent with tendinitis of the rotator cuff, calcific deposits in the tendon associated with signs and symptoms of tendinitis. It is recommended that radiographs be taken at least in AP projections with the shoulder in internal and external rotation to demonstrate the deposits without super-imposition. Ultrasound shows concomitant bursitis and is useful for the differential diagnosis of rupture of the rotator cuff. Radiographic diagnosis is most difficult when there are small opacifications near the rotator attachment. In this case, allocation may become possible only later in the course of disease. Initial treatment should

Calcific retropharyngeal tendinitis. [Radiological findings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karasick, D.; Karasick, S.

1981-12-01

Calcific retropharyngeal tendinitis is an imflammation of the longus colli muscle tendon which is located on the anterior surface of the verterbral column extending from the atlas to the third thoracic vertebra. The acute inflammatory condition is selflimiting with symptoms consisting of a gradually increasing neck pain often associated with throat pain and difficulty swallowing. The pain is aggravated by head and neck movement. Clinically the condition can be confused with retropharyngeal absecess, meningitis, infectious spondylitis, and post-traumatic muscle spasm. The radiographic features of this condition consist of pre-vertebral soft tissue swelling from C1 to C4 and amorphous calcific densitymore » in the longus colli tendon anterior to the body of C2 and inferior to the anterior arch of C1.« less

Phosphate Uptake-Independent Signaling Functions of the Type III Sodium-Dependent Phosphate Transporter, PiT-1, in Vascular Smooth Muscle Cells

PubMed Central

Chavkin, Nicholas W.; Jun Chia, Jia; Crouthamel, Matthew H.; Giachelli, Cecilia M.

2015-01-01

Vascular calcification (VC) is prevalent in chronic kidney disease and elevated serum inorganic phosphate (Pi) is a recognized risk factor. The type III sodium-dependent phosphate transporter, PiT-1, is required for elevated Pi-induced osteochondrogenic differentiation and matrix mineralization in vascular smooth muscle cells (VSMCs). However, the molecular mechanism(s) by which PiT-1 promotes these processes is unclear. In the present study, we confirmed that the Pi concentration required to induce osteochondrogenic differentiation and matrix mineralization of mouse VSMCs was well above that required for maximal Pi uptake, suggesting a signaling function of PiT-1 that was independent of Pi transport. Elevated Pi-induced signaling via ERK1/2 phosphorylation was abrogated in PiT-1 deficient VSMCs, but could be rescued by wild-type (WT) and a Pi transport-deficient PiT-1 mutant. Furthermore, both WT and transport-deficient PiT-1 mutants promoted osteochondrogenic differentiation as measured by decreased SM22α and increased osteopontin mRNA expression. Finally, compared to vector alone, expression of transport-deficient PiT-1 mutants promoted VSMC matrix mineralization, but not to the extent observed with PiT-1 WT. These data suggest that both Pi uptake-dependent and -independent functions of PiT-1 are important for VSMC processes mediating vascular calcification. PMID:25684711

Idiopathic infantile arterial calcification in two siblings: failure of treatment with diphosphonate.

PubMed Central

Stuart, G; Wren, C; Bain, H

1990-01-01

Two siblings with idiopathic infantile arterial calcification are reported. The fetal and postnatal echocardiographic features were a large pericardial effusion, thickened pulmonary and aortic valves, poor pulsation of the descending aorta, and calcification of the great vessels. In one patient calcification was first detected at 33 weeks' gestation. Despite treatment with disodium etidronate both children died. Images PMID:2118367

Computed Tomographic Distinction of Intimal and Medial Calcification in the Intracranial Internal Carotid Artery.

PubMed

Kockelkoren, Remko; Vos, Annelotte; Van Hecke, Wim; Vink, Aryan; Bleys, Ronald L A W; Verdoorn, Daphne; Mali, Willem P Th M; Hendrikse, Jeroen; Koek, Huiberdina L; de Jong, Pim A; De Vis, Jill B

2017-01-01

Intracranial internal carotid artery (iICA) calcification is associated with stroke and is often seen as a proxy of atherosclerosis of the intima. However, it was recently shown that these calcifications are predominantly located in the tunica media and internal elastic lamina (medial calcification). Intimal and medial calcifications are thought to have a different pathogenesis and clinical consequences and can only be distinguished through ex vivo histological analysis. Therefore, our aim was to develop CT scoring method to distinguish intimal and medial iICA calcification in vivo. First, in both iICAs of 16 cerebral autopsy patients the intimal and/or medial calcification area was histologically assessed (142 slides). Brain CT images of these patients were matched to the corresponding histological slides to develop a CT score that determines intimal or medial calcification dominance. Second, performance of the CT score was assessed in these 16 patients. Third, reproducibility was tested in a separate cohort. First, CT features of the score were circularity (absent, dot(s), <90°, 90-270° or 270-360°), thickness (absent, ≥1.5mm, or <1.5mm), and morphology (indistinguishable, irregular/patchy or continuous). A high sum of features represented medial and a lower sum intimal calcifications. Second, in the 16 patients the concordance between the CT score and the dominant calcification type was reasonable. Third, the score showed good reproducibility (kappa: 0.72 proportion of agreement: 0.82) between the categories intimal, medial or absent/indistinguishable. The developed CT score shows good reproducibility and can differentiate reasonably well between intimal and medial calcification dominance in the iICA, allowing for further (epidemiological) studies on iICA calcification.

Comparison of the x-ray attenuation properties of breast calcifications, aluminium, hydroxyapatite and calcium oxalate.

PubMed

Warren, L M; Mackenzie, A; Dance, D R; Young, K C

2013-04-07

Aluminium is often used as a substitute material for calcifications in phantom measurements in mammography. Additionally, calcium oxalate, hydroxyapatite and aluminium are used in simulation studies. This assumes that these materials have similar attenuation properties to calcification, and this assumption is examined in this work. Sliced mastectomy samples containing calcification were imaged at ×5 magnification using a digital specimen cabinet. Images of the individual calcifications were extracted, and the diameter and contrast of each calculated. The thicknesses of aluminium required to achieve the same contrast as each calcification when imaged under the same conditions were calculated using measurements of the contrast of aluminium foils. As hydroxyapatite and calcium oxalate are also used to simulate calcifications, the equivalent aluminium thicknesses of these materials were also calculated using tabulated attenuation coefficients. On average the equivalent aluminium thickness was 0.85 times the calcification diameter. For calcium oxalate and hydroxyapatite, the equivalent aluminium thicknesses were 1.01 and 2.19 times the thickness of these materials respectively. Aluminium and calcium oxalate are suitable substitute materials for calcifications. Hydroxyapatite is much more attenuating than the calcifications and aluminium. Using solid hydroxyapatite as a substitute for calcification of the same size would lead to excessive contrast in the mammographic image.

Incidence of Deflux® calcification masquerading as distal ureteric calculi on ultrasound.

PubMed

Yankovic, Francisca; Swartz, Robert; Cuckow, Peter; Hiorns, Melanie; Marks, Stephen D; Cherian, Abraham; Mushtaq, Imran; Duffy, Patrick; Smeulders, Naima

2013-12-01

Dextranomer-hyaluronic acid (Deflux(®)), the most widely used compound in the endoscopic treatment of vesico-ureteric reflux (VUR) today, is believed to provoke only minimal inflammation. Reports of calcification of Deflux(®) are increasing. We ascertain the incidence of Deflux(®) calcification appearing as distal ureteric calculi on ultrasound. Three cases (2 external patients) of ureteroscopy for calcified submucosal Deflux(®) prompted a retrospective review of the notes and imaging of all children treated with Deflux(®) for VUR between December 2000 and January 2011 at Great Ormond Street Hospital. 232 children (M:F = 5:3) received Deflux(®) for VUR at median age 2 years (range 2 months-12 years). Follow-up annual ultrasound, performed in all, identified calcification in 2. The interval between Deflux(®) injection and presentation of its calcification was 4 years. 104 of the 232 children had been followed up for 4-10 years. Considering the observed lag-period, after 4 years the incidence of calcification of Deflux(®) on ultrasound was 2% (2/104). Patients should be warned that calcification of Deflux(®) can occur. Misinterpretation as ureteric stones is common and may lead to unnecessary ureteroscopy. In this series, the incidence of calcification of Deflux(®) on ultrasound after 4 years was 2%. Copyright © 2012 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Atypical localizations of calcific deposits in the shoulder

PubMed Central

Vinanti, G.B.; Pavan, D.; Rossato, A.; Biz, Carlo

2015-01-01

Introduction Calcific tendinopathies of the shoulder are due to inflammation around deposits of calcium within periarticular tendineal structures. Presentation of cases We present three cases of atypical localization of calcium deposits in the shoulder. All of the cases have been treated with arthroscopic excision, followed by post-operative rehabilitation, regaining excellent results. Patients were evaluated 6 months after surgery using the Visual Analogue Scale (VAS), the Simple Shoulder Test (SST) and the UCLA modified shoulder rating. Discussion Calcific tendinopathy is a self-limiting condition or is successfully treated with conservative therapy especially during the early phases of the pathology. If conservative measures fail, removal of calcium deposits is recommended. Arthroscopic management showed good results in our three cases. Conclusion We suggest that arthroscopic treatment of calcific tendonitis guarantees good results even when calcium deposits are in atypical locations. PMID:25884610

Cardiac Fibroblasts Adopt Osteogenic Fates and Can Be Targeted to Attenuate Pathological Heart Calcification.

PubMed

Pillai, Indulekha C L; Li, Shen; Romay, Milagros; Lam, Larry; Lu, Yan; Huang, Jie; Dillard, Nathaniel; Zemanova, Marketa; Rubbi, Liudmilla; Wang, Yibin; Lee, Jason; Xia, Ming; Liang, Owen; Xie, Ya-Hong; Pellegrini, Matteo; Lusis, Aldons J; Deb, Arjun

2017-02-02

Mammalian tissues calcify with age and injury. Analogous to bone formation, osteogenic cells are thought to be recruited to the affected tissue and induce mineralization. In the heart, calcification of cardiac muscle leads to conduction system disturbances and is one of the most common pathologies underlying heart blocks. However the cell identity and mechanisms contributing to pathological heart muscle calcification remain unknown. Using lineage tracing, murine models of heart calcification and in vivo transplantation assays, we show that cardiac fibroblasts (CFs) adopt an osteoblast cell-like fate and contribute directly to heart muscle calcification. Small-molecule inhibition of ENPP1, an enzyme that is induced upon injury and regulates bone mineralization, significantly attenuated cardiac calcification. Inhibitors of bone mineralization completely prevented ectopic cardiac calcification and improved post injury heart function. Taken together, these findings highlight the plasticity of fibroblasts in contributing to ectopic calcification and identify pharmacological targets for therapeutic development. Copyright © 2017 Elsevier Inc. All rights reserved.

[Endomyocardial fibrosis with massive calcification of the left ventricle].

PubMed

Trigo, Joana; Camacho, Ana; Gago, Paula; Candeias, Rui; Santos, Walter; Marques, Nuno; Matos, Pedro; Brandão, Victor; Gomes, Veloso

2010-03-01

Endomyocardial fibrosis is a rare disease, endemic in tropical countries. It is characterized by fibrosis of the endocardium that can extend to myocardium. Important calcification of the endocardium is rare with only a few cases reported in the literature. We report a case of endomyocardial fibrosis in a european caucasian patient, associated with massive calcification of left ventricle.

Chlamydia pneumoniae antibody titers and cardiac calcifications: a cross-sectional serological-echocardiographic correlative study.

PubMed

Atar, Shaul; Tolstrup, Kirsten; Cercek, Bojan; Siegel, Robert J

2007-07-01

Chlamydia pneumoniae has previously been associated with higher prevalence of valvular and cardiac calcifications. To investigate a possible association of seropositivity for C. pneumoniae and the presence of cardiac calcifications (mitral annular or aortic root calcification, and aortic valve sclerosis). We retrospectively analyzed serological data (immunoglobulin G TWAR antibodies) from the AZACS trial (Azithromycin in Acute Coronary Syndromes), and correlated the serological findings according to titer levels with the presence of cardiac calcifications as detected by transthoracic echocardiography. In 271 patients, age 69 +/- 13 years, who underwent both serological and echocardiographic evaluation, we found no significant association between the "calcification sum score" (on a scale of 0-3) in seropositive compared to seronegative patients (1.56 +/- 1.15 vs.1.35 +/- 1.15, respectively, P = 0.26). The median calcification sum score was 1 (interquartile range 0-3) for the seronegative group, and 2 (interquartile range 0-3) for the seropositive group (P = 0.2757). In addition, we did not find a significant correlation of any of the individual sites of cardiac calcification and C. pneumoniae seropositivity. Our findings suggest that past C. pneumoniae infection may not be associated with the pathogenesis of valvular and cardiac calcifications.

Editorial Commentary: Be on the Lookout for White Chalk! Hip Labrum Calcification.

PubMed

Konyves, Arpad

2018-04-01

Amorphous calcification of the hip labrum is a little known and relatively rare condition. Although patients with amorphous calcification have favorable post-arthroscopic surgery self-reported outcome, it is unclear how much of their improvement can be attributed to the debridement of the calcific lesion itself. Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Towards predicting coral calcification responses to ocean acidification: A combined modeling and experimental approach

NASA Astrophysics Data System (ADS)

Mollica, N. R.; Guo, W.; Cohen, A. L.; Foster, G. L.; Barkley, H.

2016-02-01

Experiments show that ocean acidification is detrimental to coral calcification. Nevertheless, coral sensitivities to OA vary and the mechanism(s) underlying these variable responses are not fully understood. One hypothesis is that ocean acidification affects the ability of coral's to regulate the pH of fluid at the site of calcification. We developed a numerical model of coral calcification that simulates corals' pH regulation based on physiochemical principles and predicts the rate of calcification [1]. Here we apply this model to Palauan corals, and seek to test the model's efficacy by comparing the predicted coral calcification responses with experimental measurements. Four coral cores were collected from two sites of different pH (7.84 and 8.04 respectively). Their bulk annual calcification rates, quantified from average density and extension rate measurements, vary from .83 to 1.39 g cm-2 year-1 for the low pH site and from 0.75 to 1.21 g cm-2 year-1for the high pH site. The higher bulk calcification rates observed in corals from the low pH site contrasts the expected general decrease in calcification in low pH seawater, and differs from our model prediction. We suspect this apparent discrepancy arises because fast-calcifying corals in low pH water are able to modulate the pH of fluid at the site of calcification. We test this hypothesis using boron isotope measurements from each coral. In addition, a more accurate measurement of instantaneous calcification, considering the number of corallites per measured area and the exact surface area of each polyp's 3-dimensional calcification site is applied. [1] Guo, W. (2014). AGU Fall Meeting, Abstract B41B-0033.

Sensitivity of Calcification to Thermal Stress Varies among Genera of Massive Reef-Building Corals

PubMed Central

Carricart-Ganivet, Juan P.; Cabanillas-Terán, Nancy; Cruz-Ortega, Israel; Blanchon, Paul

2012-01-01

Reductions in calcification in reef-building corals occur when thermal conditions are suboptimal, but it is unclear how they vary between genera in response to the same thermal stress event. Using densitometry techniques, we investigate reductions in the calcification rate of massive Porites spp. from the Great Barrier Reef (GBR), and P. astreoides, Montastraea faveolata, and M. franksi from the Mesoamerican Barrier Reef (MBR), and correlate them to thermal stress associated with ocean warming. Results show that Porites spp. are more sensitive to increasing temperature than Montastraea, with calcification rates decreasing by 0.40 g cm−2 year−1 in Porites spp. and 0.12 g cm−2 year−1 in Montastraea spp. for each 1°C increase. Under similar warming trends, the predicted calcification rates at 2100 are close to zero in Porites spp. and reduced by 40% in Montastraea spp. However, these predictions do not account for ocean acidification. Although yearly mean aragonite saturation (Ωar) at MBR sites has recently decreased, only P. astreoides at Chinchorro showed a reduction in calcification. In corals at the other sites calcification did not change, indicating there was no widespread effect of Ωar changes on coral calcification rate in the MBR. Even in the absence of ocean acidification, differential reductions in calcification between Porites spp. and Montastraea spp. associated with warming might be expected to have significant ecological repercussions. For instance, Porites spp. invest increased calcification in extension, and under warming scenarios it may reduce their ability to compete for space. As a consequence, shifts in taxonomic composition would be expected in Indo-Pacific reefs with uncertain repercussions for biodiversity. By contrast, Montastraea spp. use their increased calcification resources to construct denser skeletons. Reductions in calcification would therefore make them more susceptible to both physical and biological breakdown, seriously

Arthroscopic Removal and Tendon Repair for Refractory Rotator Cuff Calcific Tendinitis of the Shoulder.

PubMed

Hashiguchi, Hiroshi; Iwashita, Satoshi; Okubo, Atsushi; Takai, Shinro

2017-01-01

The purpose of this study was to evaluate clinical and radiological outcomes of arthroscopic treatment for refractory rotator cuff calcific tendinitis of the shoulder. Subjects were 37 patients (35 women and 2 men; mean age, 47.8 years; age range 34-61 years) who had undergone arthroscopic treatment for calcific tendinitis of the shoulder. Despite sufficient nonsurgical treatments, all patients had residual calcific deposit with persistent or recurrent pain. Before surgery, all patients underwent 3-directional radiographs of the shoulder and three-dimensional computed tomography to determine the location and size of calcific deposit. Arthroscopic surgery was performed with the patient under general anesthesia in the lateral decubitus position. A 2-cm single longitudinal incision was made with a radiofrequency hook blade on the tendon surface above calcific deposit. Calcific deposit was removed as much as possible with a curette and a motorized shaver. The incised tendon was repaired with a side-to-side suture with strong sutures. The Japanese Orthopaedic Association shoulder score was used to evaluate clinical outcomes. The extent of calcific deposit removal was evaluated with radiographs obtained before surgery, 1 week after the surgery and at the final follow-up examination. The mean follow-up duration was 30.4 (range, 13-72) months. The mean shoulder score significantly improved from 69.7 (range, 58-80) points before surgery to 97.8 (range, 89-100) points at the final follow-up examination. Postoperative radiographs in all patients, showed that the calcific deposit was resolved or reduced and those from 1 week after surgery to the final examination showed no evidence of recurrence or enlargement of calcific deposit. The calcific deposit had completely resolved in 34 patients but remained in 3 patients. When treating calcific tendinitis of the shoulder, it is important to accurately determine the size and location of calcific deposit by radiographs and 3

Improving the imaging of calcifications in CT by histogram-based selective deblurring

NASA Astrophysics Data System (ADS)

Rollano-Hijarrubia, Empar; van der Meer, Frits; van der Lugt, Add; Weinans, Harrie; Vrooman, Henry; Vossepoel, Albert; Stokking, Rik

2005-04-01

Imaging of small high-density structures, such as calcifications, with computed tomography (CT) is limited by the spatial resolution of the system. Blur causes small calcifications to be imaged with lower contrast and overestimated volume, thereby hampering the analysis of vessels. The aim of this work is to reduce the blur of calcifications by applying three-dimensional (3D) deconvolution. Unfortunately, the high-frequency amplification of the deconvolution produces edge-related ring artifacts and enhances noise and original artifacts, which degrades the imaging of low-density structures. A method, referred to as Histogram-based Selective Deblurring (HiSD), was implemented to avoid these negative effects. HiSD uses the histogram information to generate a restored image in which the low-intensity voxel information of the observed image is combined with the high-intensity voxel information of the deconvolved image. To evaluate HiSD we scanned four in-vitro atherosclerotic plaques of carotid arteries with a multislice spiral CT and with a microfocus CT (μCT), used as reference. Restored images were generated from the observed images, and qualitatively and quantitatively compared with their corresponding μCT images. Transverse views and maximum-intensity projections of restored images show the decrease of blur of the calcifications in 3D. Measurements of the areas of 27 calcifications and total volumes of calcification of 4 plaques show that the overestimation of calcification was smaller for restored images (mean-error: 90% for area; 92% for volume) than for observed images (143%; 213%, respectively). The qualitative and quantitative analyses show that the imaging of calcifications in CT can be improved considerably by applying HiSD.

Mineral metabolism disorders, vertebral fractures and aortic calcifications in stable kidney transplant recipients: The role of gender (EMITRAL study).

PubMed

Torres, Armando; Torregrosa, Vicens; Marcen, Roberto; Campistol, Josep María; Arias, Manuel; Hernández, Domingo; Fernández, Constantino; Esforzado, Nuria; Paschoalin, Raphael; Pérez, Nuria; García, Ana Isabel; Del Amo, Montserrat; Pomés, Jaume; González Rinne, Ana; Marrero, Domingo; Pérez, Estefanía; Henríquez, Fernando; Díaz, Juan Manuel; Silva, Irene; López, Verónica; Perello, Manuel; Ramos, David; Beneyto, Isabel; Cruzado, José María; Martínez Castelao, Alberto; Bravo, Juan; Rodríguez, Minerva; Díaz, Carmen; Crespo, Josep; Anaya, Fernando; Rodríguez, María Luisa; Cubero, Juan José; Pascual, Pilar; Romero, Rafael; Andrés Belmonte, Amado; Checa, María Dolores; Jiménez, Carlos; Escuin, Fernando; Crespo, Marta; Mir, Marisa; Gómez, Gonzalo; Bayes, Beatriz; González, María José; Gutiérrez, Alex; Cuberes, Marta; Rodríguez Benoit, Alberto; García, Teresa; Llamas, Francisco; Ortega, Agustín; Conde, José Luis; Gómez Alamillo, Carlos

2016-01-01

The relationship between mineral metabolism disorders, bone fractures and vascular calcifications in kidney transplant recipients has not been established. We performed a cross-sectional study in 727 stable recipients from 28 Spanish transplant clinics. Mineral metabolism parameters, the semi-quantification of vertebral fractures and abdominal aortic calcifications were determined centrally. Vitamin D deficiency (25OHD3<15ng/ml) was more common in female recipients at CKD-T stages I-III (29.6% vs 44.4%; p=0.003). The inverse and significant correlation between 25OHD3 and PTH was gender-specific and women exhibited a steeper slope than men (p=0.01). Vertebral fractures (VFx) with deformity grade ≥2 were observed in 15% of recipients. Factors related to VFx differed by gender; in males, age (OR 1.04; 95% CI 1.01-1.06) and CsA treatment (OR: 3.2; 95% CI: 1.6-6.3); in females, age (OR 1.07; 95% CI: 1.03-1.12) and PTH levels (OR per 100pg/ml increase: 1.27; 95% CI: 1.043-1.542). Abdominal aortic calcifications were common (67.2%) and related to classical risk factors but not to mineral metabolism parameters. Vitamin D deficiency is more common among female kidney transplant recipients at earlier CKD-T stages, and it contributes to secondary hyperparathyroidism. Prevalent vertebral fractures are only related to high serum PTH levels in female recipients. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

[Clinical peculiarities of atherosclerosis of peripheral arteries in patients with abdominal aortic calcification].

PubMed

Mel'nikov, M V; Zelinskiĭ, V A

The authors analysed clinical peculiarities of atherosclerosis of peripheral arteries (hereinafter referred to as APA) in patients presenting with abdominal aortic calcification (AAC). In order to determine the incidence rate of AAC in the population of patients with APA we analysed medical records of a total of 1,800 patients. The study itself included a total of 193 patients with APA further subdivided into two groups: 108 patients with AAC (Study Group) and 85 patients without AAC. Beside general clinical examination all patients were subjected to transthoracic echocardiography, duplex scanning of the aorta and lower-limb arteries, extended lipidogram and coagulogram. AAC was verified by means of computed tomography. It was determined that in one third of cases AAC was combined with abdominal aortic calcification, with APA on the background of AAC having certain peculiarities, i.e., high incidence of multisegmental lesions (68%) with predominant localization of the process in the aortoiliac and femoropopliteal segments (43%); frequent involvement of the terminal portion of the aorta and pelvic arteries. Patients with AAC also were noted to have a series of peculiarities in the indices of lipid metabolism, as well as signs of procoagulant syndrome and alterations of the structural and functional characteristics of the myocardium. It was stated that peculiarities of APA on the background of AAC should be taken into consideration while working out the program of diagnosis, treatment (including surgical), and rehabilitation of patients.

Mussel larvae modify calcifying fluid carbonate chemistry to promote calcification.

PubMed

Ramesh, Kirti; Hu, Marian Y; Thomsen, Jörn; Bleich, Markus; Melzner, Frank

2017-11-22

Understanding mollusk calcification sensitivity to ocean acidification (OA) requires a better knowledge of calcification mechanisms. Especially in rapidly calcifying larval stages, mechanisms of shell formation are largely unexplored-yet these are the most vulnerable life stages. Here we find rapid generation of crystalline shell material in mussel larvae. We find no evidence for intracellular CaCO 3 formation, indicating that mineral formation could be constrained to the calcifying space beneath the shell. Using microelectrodes we show that larvae can increase pH and [CO 3 2- ] beneath the growing shell, leading to a ~1.5-fold elevation in calcium carbonate saturation state (Ω arag ). Larvae exposed to OA exhibit a drop in pH, [CO 3 2- ] and Ω arag at the site of calcification, which correlates with decreased shell growth, and, eventually, shell dissolution. Our findings help explain why bivalve larvae can form shells under moderate acidification scenarios and provide a direct link between ocean carbonate chemistry and larval calcification rate.

Impact of elevated CO2 on shellfish calcification

NASA Astrophysics Data System (ADS)

Gazeau, Frédéric; Quiblier, Christophe; Jansen, Jeroen M.; Gattuso, Jean-Pierre; Middelburg, Jack J.; Heip, Carlo H. R.

2007-04-01

Ocean acidification resulting from human emissions of carbon dioxide has already lowered and will further lower surface ocean pH. The consequent decrease in calcium carbonate saturation potentially threatens calcareous marine organisms. Here, we demonstrate that the calcification rates of the edible mussel (Mytilus edulis) and Pacific oyster (Crassostrea gigas) decline linearly with increasing pCO2. Mussel and oyster calcification may decrease by 25 and 10%, respectively, by the end of the century, following the IPCC IS92a scenario (~740 ppmv in 2100). Moreover, mussels dissolve at pCO2 values exceeding a threshold value of ~1800 ppmv. As these two species are important ecosystem engineers in coastal ecosystems and represent a large part of worldwide aquaculture production, the predicted decrease of calcification in response to ocean acidification will probably have an impact on coastal biodiversity and ecosystem functioning as well as potentially lead to significant economic loss.

Simulated effect of calcification feedback on atmospheric CO2 and ocean acidification

PubMed Central

Zhang, Han; Cao, Long

2016-01-01

Ocean uptake of anthropogenic CO2 reduces pH and saturation state of calcium carbonate materials of seawater, which could reduce the calcification rate of some marine organisms, triggering a negative feedback on the growth of atmospheric CO2. We quantify the effect of this CO2-calcification feedback by conducting a series of Earth system model simulations that incorporate different parameterization schemes describing the dependence of calcification rate on saturation state of CaCO3. In a scenario with SRES A2 CO2 emission until 2100 and zero emission afterwards, by year 3500, in the simulation without CO2-calcification feedback, model projects an accumulated ocean CO2 uptake of 1462 PgC, atmospheric CO2 of 612 ppm, and surface pH of 7.9. Inclusion of CO2-calcification feedback increases ocean CO2 uptake by 9 to 285 PgC, reduces atmospheric CO2 by 4 to 70 ppm, and mitigates the reduction in surface pH by 0.003 to 0.06, depending on the form of parameterization scheme used. It is also found that the effect of CO2-calcification feedback on ocean carbon uptake is comparable and could be much larger than the effect from CO2-induced warming. Our results highlight the potentially important role CO2-calcification feedback plays in ocean carbon cycle and projections of future atmospheric CO2 concentrations. PMID:26838480

SU-E-J-215: Towards MR-Only Image Guided Identification of Calcifications and Brachytherapy Seeds: Application to Prostate and Breast LDR Implant Dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Elzibak, A; Fatemi-Ardekani, A; Soliman, A

Purpose: To identify and analyze the appearance of calcifications and brachytherapy seeds on magnitude and phase MRI images and to investigate whether they can be distinguished from each other on corrected phase images for application to prostate and breast low dose rate (LDR) implant dosimetry. Methods: An agar-based gel phantom containing two LDR brachytherapy seeds (Advantage Pd-103, IsoAid, 0.8mm diameter, 4.5mm length) and two spherical calcifications (large: 7mm diameter and small: 4mm diameter) was constructed and imaged on a 3T Philips MR scanner using a 16-channel head coil and a susceptibility weighted imaging (SWI) sequence (2mm slices, 320mm FOV, TR/more » TE= 26.5/5.3ms, 15 degree flip angle). The phase images were unwrapped and corrected using a 32×32, 2D Hanning high pass filter to remove background phase noise. Appearance of the seeds and calcifications was assessed visually and quantitatively using Osirix (http://www.osirix-viewer.com/). Results: As expected, calcifications and brachytherapy seeds appeared dark (hypointense) relative to the surrounding gel on the magnitude MRI images. The diameter of each seed without the surrounding artifact was measured to be 0.1 cm on the magnitude image, while diameters of 0.79 and 0.37 cm were measured for the larger and smaller calcifications, respectively. On the corrected phase images, the brachytherapy seeds and the calcifications appeared bright (hyperintense). The diameter of the seeds was larger on the phase images (0.17 cm) likely due to the dipole effect. Conclusion: MRI has the best soft tissue contrast for accurate organ delineation leading to most accurate implant dosimetry. This work demonstrated that phase images can potentially be useful in identifying brachytherapy seeds and calcifications in the prostate and breast due to their bright appearance, which helps in their visualization and quantification for accurate dosimetry using MR-only. Future work includes optimizing phase filters to best

Vascular nanomedicine: Site specific delivery of elastin stabilizing therapeutics to damaged arteries

NASA Astrophysics Data System (ADS)

Sinha, Aditi

Elastin, a structural protein in the extra-cellular matrix, plays a critical role in the normal functioning of blood vessels. Apart from performing its primary function of providing resilience to arteries, it also plays major role in regulating cell-cell and cell-matrix interactions, response to injury, and morphogenesis. Medial arterial calcification (MAC) and abdominal aortic aneurysm (AAA) are two diseases where the structural and functional integrity of elastin is severely compromised. Although the clinical presentation of MAC and AAA differ, they have one common underlying causative mechanism---pathological degradation of elastin. Hence prevention of elastin degradation in the early stages of MAC and AAA can mitigate, partially if not wholly, the fatal consequences of both the diseases. The work presented here is motivated by the overwhelming statistics of people afflicted by elastin associated cardiovascular diseases and the unavailability of cure for the same. Overall goal of our research is to understand role of elastin degradation in cardiovascular diseases and to develop a targeted vascular drug delivery system that is minimally invasive, biodegradable, and non-toxic, that prevents elastin from degradation. Our hope is that such treatment will also help regenerate elastin, thereby providing a multi-fold treatment option for elasto-degenerative vascular diseases. For this purpose, we have first confirmed the combined role of degraded elastin and hyperglycemia in the pathogenesis of MAC. We have shown that in the absence of degraded elastin and TGF-beta1 (abundantly present in diabetic arteries) vascular smooth muscle cells maintain their homeostatic state, regardless of environmental glucose concentrations. However simultaneous exposure to glucose, elastin peptides and TGF-beta1 causes the pathological transgenesis of vascular cells to osteoblast-like cells. We show that plant derived polyphenols bind to vascular elastin with great affinity resulting in

Low calcification in corals in the Great Barrier Reef

NASA Astrophysics Data System (ADS)

Bhattacharya, Atreyee

2012-10-01

Reef-building coral communities in the Great Barrier Reef—the world's largest coral reef—may now be calcifying at only about half the rate that they did during the 1970s, even though live coral cover may not have changed over the past 40 years, a new study finds. In recent decades, coral reefs around the world, home to large numbers of fish and other marine species, have been threatened by such human activities as pollution, overfishing, global warming, and ocean acidification; the latter affects ambient water chemistry and availability of calcium ions, which are critical for coral communities to calcify, build, and maintain reefs. Comparing data from reef surveys during the 1970s, 1980s, and 1990s with present-day (2009) measurements of calcification rates in One Tree Island, a coral reef covering 13 square kilometers in the southern part of the Great Barrier Reef, Silverman et al. show that the total calcification rates (the rate of calcification minus the rate of dissolution) in these coral communities have decreased by 44% over the past 40 years; the decrease appears to stem from a threefold reduction in calcification rates during nighttime.

Nano-analytical electron microscopy reveals fundamental insights into human cardiovascular tissue calcification

NASA Astrophysics Data System (ADS)

Bertazzo, Sergio; Gentleman, Eileen; Cloyd, Kristy L.; Chester, Adrian H.; Yacoub, Magdi H.; Stevens, Molly M.

2013-06-01

The accumulation of calcified material in cardiovascular tissue is thought to involve cytochemical, extracellular matrix and systemic signals; however, its precise composition and nanoscale architecture remain largely unexplored. Using nano-analytical electron microscopy techniques, we examined valves, aortae and coronary arteries from patients with and without calcific cardiovascular disease and detected spherical calcium phosphate particles, regardless of the presence of calcific lesions. We also examined lesions after sectioning with a focused ion beam and found that the spherical particles are composed of highly crystalline hydroxyapatite that crystallographically and structurally differs from bone mineral. Taken together, these data suggest that mineralized spherical particles may play a fundamental role in calcific lesion formation. Their ubiquitous presence in varied cardiovascular tissues and from patients with a spectrum of diseases further suggests that lesion formation may follow a common process. Indeed, applying materials science techniques to ectopic and orthotopic calcification has great potential to lend critical insights into pathophysiological processes underlying calcific cardiovascular disease.

Prognostic factors for the outcome of extracorporeal shockwave therapy for calcific tendinitis of the shoulder.

PubMed

Chou, W-Y; Wang, C-J; Wu, K-T; Yang, Y-J; Ko, J-Y; Siu, K-K

2017-12-01

We conducted a study to identify factors that are prognostic of the outcome of extracorporeal shockwave therapy (ESWT) for calcific tendinitis of the shoulder. Since 1998, patients with symptomatic calcific tendinitis of the rotator cuff have been treated with ESWT using an electrohydraulic mode shockwave device. One year after ESWT, patients were grouped according to the level of resorption of calcification. Of 241 symptomatic shoulders, complete resorption (CR) of calcification occurred in 134 (CR group). The remaining 107 shoulders had incomplete resorption (ICR) (ICR group). Gartner type I calcification was most common (64.5%) in the ICR group. The mean duration of symptoms before ESWT was significantly longer in the ICR group. Overall, 81% of the CR group and 23.4% of the ICR group were symptom free. There was a strong relationship between subsidence of symptoms and remission of calcification. Poor prognosis was significantly related to Gartner type I calcification, calcification extent > 15 mm and duration of symptoms > 11 months. Patients with calcific tendinitis of the shoulder who have the factors identified for a poor outcome after ESWT should undergo a different procedure. Cite this article: Bone Joint J 2017;99-B:1643-50. ©2017 The British Editorial Society of Bone & Joint Surgery.

Nephrogenic diabetes insipidus with intracranial calcification in a child with thalassemia minor.

PubMed

Dimple, Jain; Alka, Jadhav; Mona, Gajre; Atul, Deshmukh

2013-09-01

There are numerous causes for intracranial calcification in children. We describe an unusual cause of intracranial calcification in a child, namely, nephrogenic diabetes insipidus (NDI). A 12-year-old boy presented with seizures and developmental delay. MRI of the brain revealed intracranial calcification. Evaluation showed findings suggestive of NDI. The lack of evidence of any other metabolic defect suggests that these calcifications were secondary to NDI. He also had anemia for which he was investigated and diagnosed as thalassemia minor. Detailed literature review failed to reveal any reported association between NDI and thalassemia minor. We report this case to emphasize the importance of early diagnosis and treatment of NDI to prevent organic brain damage.

Emiliania huxleyi increases calcification but not expression of calcification-related genes in long-term exposure to elevated temperature and pCO2.

PubMed

Benner, Ina; Diner, Rachel E; Lefebvre, Stephane C; Li, Dian; Komada, Tomoko; Carpenter, Edward J; Stillman, Jonathon H

2013-01-01

Increased atmospheric pCO2 is expected to render future oceans warmer and more acidic than they are at present. Calcifying organisms such as coccolithophores that fix and export carbon into the deep sea provide feedbacks to increasing atmospheric pCO2. Acclimation experiments suggest negative effects of warming and acidification on coccolithophore calcification, but the ability of these organisms to adapt to future environmental conditions is not well understood. Here, we tested the combined effect of pCO2 and temperature on the coccolithophore Emiliania huxleyi over more than 700 generations. Cells increased inorganic carbon content and calcification rate under warm and acidified conditions compared with ambient conditions, whereas organic carbon content and primary production did not show any change. In contrast to findings from short-term experiments, our results suggest that long-term acclimation or adaptation could change, or even reverse, negative calcification responses in E. huxleyi and its feedback to the global carbon cycle. Genome-wide profiles of gene expression using RNA-seq revealed that genes thought to be essential for calcification are not those that are most strongly differentially expressed under long-term exposure to future ocean conditions. Rather, differentially expressed genes observed here represent new targets to study responses to ocean acidification and warming.

Emiliania huxleyi increases calcification but not expression of calcification-related genes in long-term exposure to elevated temperature and pCO2

PubMed Central

Benner, Ina; Diner, Rachel E.; Lefebvre, Stephane C.; Li, Dian; Komada, Tomoko; Carpenter, Edward J.; Stillman, Jonathon H.

2013-01-01

Increased atmospheric pCO2 is expected to render future oceans warmer and more acidic than they are at present. Calcifying organisms such as coccolithophores that fix and export carbon into the deep sea provide feedbacks to increasing atmospheric pCO2. Acclimation experiments suggest negative effects of warming and acidification on coccolithophore calcification, but the ability of these organisms to adapt to future environmental conditions is not well understood. Here, we tested the combined effect of pCO2 and temperature on the coccolithophore Emiliania huxleyi over more than 700 generations. Cells increased inorganic carbon content and calcification rate under warm and acidified conditions compared with ambient conditions, whereas organic carbon content and primary production did not show any change. In contrast to findings from short-term experiments, our results suggest that long-term acclimation or adaptation could change, or even reverse, negative calcification responses in E. huxleyi and its feedback to the global carbon cycle. Genome-wide profiles of gene expression using RNA-seq revealed that genes thought to be essential for calcification are not those that are most strongly differentially expressed under long-term exposure to future ocean conditions. Rather, differentially expressed genes observed here represent new targets to study responses to ocean acidification and warming. PMID:23980248

Reduced calcification decreases photoprotective capability in the coccolithophorid Emiliania huxleyi.

PubMed

Xu, Kai; Gao, Kunshan

2012-07-01

Intracellular calcification of coccolithophores generates CO₂ and consumes additional energy for acquisition of calcium and bicarbonate ions; therefore, it may correlate with photoprotective processes by influencing the energetics. To address this hypothesis, a calcifying Emiliania huxleyi strain (CS-369) was grown semi-continuously at reduced (0.1 mM, LCa) and ambient Ca²⁺ concentrations (10 mM, HCa) for 150 d (>200 generations). The HCa-grown cells had higher photosynthetic and calcification rates and higher contents of Chl a and carotenoids compared with the naked (bearing no coccoliths) LCa-grown cells. When exposed to stressfull levels of photosynthetically active radiation (PAR), LCa-grown cells displayed lower photochemical yield and less efficient non-photochemical quenching (NPQ). When the LCa- or HCa-grown cells were inversely shifted to their counterpart medium, LCa to HCa transfer increased photosynthetic carbon fixation (P), calcification rate (C), the C/P ratio, NPQ and pigment contents, whereas those shifted from HCa to LCa exhibited the opposite effects. Increased NPQ, carotenoids and quantum yield were clearly linked with increased or sustained calcification in E. huxleyi. The calcification must have played a role in dissipating excessive energy or as an additional drainage of electrons absorbed by the photosynthetic antennae. This phenomenon was further supported by testing two non-calcifying strains, which showed insignificant changes in photosynthetic carbon fixation and NPQ when transferred to LCa conditions.

Apoptosis-mediated endothelial toxicity but not direct calcification or functional changes in anti-calcification proteins defines pathogenic effects of calcium phosphate bions

NASA Astrophysics Data System (ADS)

Kutikhin, Anton G.; Velikanova, Elena A.; Mukhamadiyarov, Rinat A.; Glushkova, Tatiana V.; Borisov, Vadim V.; Matveeva, Vera G.; Antonova, Larisa V.; Filip'Ev, Dmitriy E.; Golovkin, Alexey S.; Shishkova, Daria K.; Burago, Andrey Yu.; Frolov, Alexey V.; Dolgov, Viktor Yu.; Efimova, Olga S.; Popova, Anna N.; Malysheva, Valentina Yu.; Vladimirov, Alexandr A.; Sozinov, Sergey A.; Ismagilov, Zinfer R.; Russakov, Dmitriy M.; Lomzov, Alexander A.; Pyshnyi, Dmitriy V.; Gutakovsky, Anton K.; Zhivodkov, Yuriy A.; Demidov, Evgeniy A.; Peltek, Sergey E.; Dolganyuk, Viatcheslav F.; Babich, Olga O.; Grigoriev, Evgeniy V.; Brusina, Elena B.; Barbarash, Olga L.; Yuzhalin, Arseniy E.

2016-06-01

Calcium phosphate bions (CPB) are biomimetic mineralo-organic nanoparticles which represent a physiological mechanism regulating the function, transport and disposal of calcium and phosphorus in the human body. We hypothesised that CPB may be pathogenic entities and even a cause of cardiovascular calcification. Here we revealed that CPB isolated from calcified atherosclerotic plaques and artificially synthesised CPB are morphologically and chemically indistinguishable entities. Their formation is accelerated along with the increase in calcium salts-phosphates/serum concentration ratio. Experiments in vitro and in vivo showed that pathogenic effects of CPB are defined by apoptosis-mediated endothelial toxicity but not by direct tissue calcification or functional changes in anti-calcification proteins. Since the factors underlying the formation of CPB and their pathogenic mechanism closely resemble those responsible for atherosclerosis development, further research in this direction may help us to uncover triggers of this disease.

Vitamin K2 regression aortic calcification induced by warfarin via Gas6/Axl survival pathway in rats.

PubMed

Jiang, Xiaoyu; Tao, Huiren; Qiu, Cuiting; Ma, Xiaolei; Li, Shan; Guo, Xian; Lv, Anlin; Li, Huan

2016-09-05

The aim of this study was to investigate the effect of vitamin K2 on aortic calcification induced by warfarin via Gas6/Axl survival pathway in rats. A calcification model was established by administering 3mg/g warfarin to rats. Rats were divided into 9 groups: control group (0W, 4W, 6W and 12W groups), 4W calcification group, 6W calcification group, 12W calcification group, 6W calcification+6W normal group and 6W calcification+6W vitamin K2 group. Alizarin red S staining measured aortic calcium depositions; alkaline phosphatase activity in serum was measured by a kit; apoptosis was evaluated by TUNEL assay; protein expression levels of Gas6, Axl, phosphorylated Akt (p-Akt), and Bcl-2 were determined by western blotting. The calcium content, calcium depositions, ALP activity and apoptosis were significantly higher in the calcification groups than control group. Gas6, Axl, p-Akt and Bcl-2 expression was lower in the calcification group than control group. 100μg/g vitamin K2 treatment decreased calcium depositions, ALP activity and apoptosis significantly, but increased Gas6, Axl, p-Akt and Bcl-2 expression. 100μg/g vitamin K2 reversed 44% calcification. Pearson correlation analysis showed a positive correlation between formation calcification and apoptosis (R(2)=0.8853, P<0.0001). In conclusion, we established a warfarin-induced calcification model and showed vitamin K2 can inhibit warfarin-induced aortic calcification and apoptosis. The regression of aortic calcification by vitamin K2 involved the Gas6/Axl axis. This data may provide a theoretical basis for future clinical treatments for aortic calcification. Copyright © 2016 Elsevier B.V. All rights reserved.

Calcific tendinitis of the rotator cuff: management options.

PubMed

Suzuki, Kentaro; Potts, Aaron; Anakwenze, Oke; Singh, Anshu

2014-11-01

Calcific tendinitis of the rotator cuff tendons is a common cause of shoulder pain in adults and typically presents as activity-related shoulder pain. It is thought to be an active, cell-mediated process, although the exact pathophysiology remains unclear. Nonsurgical management continues to be the mainstay of treatment; most patients improve with modalities such as oral anti-inflammatory medication, physical therapy, and corticosteroid injections. Several options are available for patients who fail nonsurgical treatment, including extracorporeal shock wave therapy, ultrasound-guided needle lavage, and surgical débridement. These modalities alleviate pain by eliminating the calcific deposit, and several recent studies have demonstrated success with the use of these treatment options. Surgical management options include arthroscopic procedures to remove calcific deposits and subacromial decompression; however, the role of subacromial decompression and repair of rotator cuff defects created by removing these deposits remains controversial. Copyright 2014 by the American Academy of Orthopaedic Surgeons.

Gastroschisis, destructive brain lesions, and placental infarction in the second trimester suggest a vascular pathogenesis.

PubMed

Folkerth, Rebecca D; Habbe, Donald M; Boyd, Theonia K; McMillan, Kristin; Gromer, Jessica; Sens, Mary Ann; Elliott, Amy J

2013-01-01

The cause and pathogenesis of gastroschisis are uncertain. We report the autopsy and placental pathology of a stillbirth at 20 gestational weeks, in which gastroschisis was accompanied by destructive lesions in the cerebral cortex and brainstem, as well as cardiac calcification, consistent with ischemic injury during the 2nd trimester. An important potential underlying mechanism explaining the fetal abnormalities is the presence of infarcts in the placenta, indicative at this gestational age of maternal vascular underperfusion. The association of gastroschisis with ischemic lesions in the brain, heart, and placenta in this case supports the concept that gastroschisis, at least in some instances, may result from vascular event(s) causing disruption of the fetal abdominal wall and resulting in the extrusion of the abdominal organs, as well as hypoxic-ischemic brain and cardiac injury.

Correlation between calcification and bone sialoprotein and osteopontin in papillary thyroid carcinoma.

PubMed

Wu, Gang; Guo, Jing-Jing; Ma, Zhen-Yu; Wang, Jie; Zhou, Zhong-Wen; Wang, Yi

2015-01-01

The correlation between calcification and papillary thyroid carcinoma has received increasing attention. We investigated the ability of bone sialoprotein (BSP) and osteopontin (OPN) protein levels to diagnose papillary thyroid carcinoma (PTC), and explored the correlation between BSP and OPN protein levels and calcification in PTC. Archival PTC specimens from patients with PTC with calcification and lateral cervical lymph node metastasis (LNM) were included in this retrospective immunohistochemical study. The protein levels of BSP and OPN were analysed immunohistochemically using routinely prepared tissue sections. PTC specimens from 66 patients with PTC were reviewed retrospectively (25 patients with histological calcification seen in paraffin sections, 41 patients without calcification; 35 patients with lateral cervical LNM, 31 patients without LNM). The percentage of samples that had cells that demonstrated positive protein staining differed significantly between PTC specimens, benign thyroid nodules, and adjacent normal follicular epithelium (BSP: 87.88%, 55.00%, and 42.50%, respectively; OPN: 83.33%, 70.00% and 50.00%, respectively). There was a significant difference in the immunohistochemical score (IHS) for BSP and OPN protein staining between PTC specimens with and without calcification (P < 0.05). The level of BSP protein staining was found to be significantly correlated with the level of OPN protein staining in PTC specimens. We conclude that the strong correlation between BSP and OPN and PTC suggests a role for BSP and OPN in calcification and tumor progression of PTC. BSP and OPN might be useful tumour markers for the diagnosis of PTC with limited value, because both of them had low specificity.

Idiopathic dental pulp calcifications in a tertiary care setting in South India.

PubMed

Satheeshkumar, P S; Mohan, Minu P; Saji, Sweta; Sadanandan, Sudheesh; George, Giju

2013-01-01

Dental pulp calcifications are unique and represent the dental pulp regenerative process. Dental pulp calcifications are sometimes routine findings in oral radiographs and may later serve as an important diagnostic criterion for a hidden aspect of systemic illness. The purpose of this study was to assess the patterns and prevalence of idiopathic dental pulp calcifications in a tertiary care setting in South India. A total of 227 patients were included in the study fulfilling the inclusion criteria. Age range of the study population was from 15 to 70 years. Teeth were examined under digital panoramic radiograph. The presence or absence of pulp stones was recorded. The presence of pulp stone were categorized according to the types classified as Type I, Type IA, Type II, Type IIA, Type II B, and Type III. The frequency of occurrence of pulp stones with sex, tooth type, dental arches, and types were compared with the types of calcification. Total no. of patients with pulpal calcification were 227 [females 133 (58.59%) and males 94 (41.40%)]. The most common type between both sexes was Type I (48%). Total no. of teeth with calcification was 697; maxilla (48%), mandible (52%). The prevalence of pulp stone was found to be higher in the molars in both the arches. Most no. of pulp stones are reported at the third and fourth decade of life. Idiopathic dental pulp calcifications are incidental radiographic findings of the pulp tissue and also may be an indicator of underlying disease.

A Comparison of Coral and Mollusk Calcification Strategies Under Future Ocean Acidification Scenarios

NASA Astrophysics Data System (ADS)

Cameron, L.; Reymond, C.; Westfield, I. T.; Mueller-Lundin, F.; Fink, A.; Hardenberg, S.; Westphal, H.; de Beer, D.; Ries, J. B.

2016-12-01

Here, we contrast the calcification dynamics of the coral Stylophora pistillata and the scallop Pecten maximus under future ocean acidification scenarios. Specimens were cultured in fully crossed pCO2 (400, 1000, 3000 matm) and temperature (28, 31 °C for corals; 9, 12 °C for scallops) treatments. Net calcification rates were determined from changes in the organisms' buoyant weights between the beginning and end of the experiment. After one month of exposure, proton-sensitive microelectrodes were used to measure pH at the calcification site of both corals and scallops. Net calcification rates of S. pistillata increased linearly with increasing pCO2 at 28 °C, but were near zero in all pCO2 treatments at 31 °C. Under each pCO2 treatment, net calcification rates of S. pistillata were significantly greater at 28 °C than at 31 °C. Net calcification rates of P. maximus decreased linearly with increasing pCO2 at 12 °C, but showed no significant trend with pCO2 at 9 °C. Net calcification rates of P. maximus under each pCO2 were significantly greater at 12 °C than at 9 °C. Microelectrode measurements revealed that regulation of calcification site pH differed substantially between the investigated coral and scallop. The coral exhibited calcifying fluid pH that was elevated relative to seawater pH by 0.3 - 0.5 units under all pCO2 conditions at 28 °C, and by 0.1 - 0.3 under all pCO2 conditions at 31 °C. In contrast, the scallop exhibited extrapallial fluid pH fixed at 7.8 - 8.2 pH units under 400 and 1000 matm pCO2 at both 9 and 12 °C. At 3000 matm pCO2, extrapallial fluid pH decreased to between 7.1 and 7.3 under both temperatures. These results suggest that the investigated coral calcifies more quickly under higher pCO2 by elevating pH of its calcifying fluid, thereby converting the increased DIC to carbonate ions for calcification. However, this ability appears to be impaired under substantially elevated temperatures (31 °C), resulting in conditions

Does the calcification of adamantinomatous craniopharyngioma resemble the calcium deposition of osteogenesis/odontogenesis?

PubMed

Song-Tao, Qi; Xiao-Rong, Yan; Jun, Pan; Yong-Jian, Deng; Jin, Liang; Guang-Long, Huang; Yun-Tao, Lu; Jian, Ruan; Xiang-Zhao, Li; Jia-Ming, Xu

2014-02-01

Calcification in adamantinomatous craniopharyngioma (ACP) is troublesome for surgical intervention. The aim of this study was to examine the osteogenic proteins that play important roles in the calcium deposition of the odontogenic/osteogenic tissues in craniopharyngioma. Craniopharyngiomas (n = 89) were investigated for the presence and expression pattern of the osteoinductive/odontoinductive factor bone morphogenetic protein-2 (Bmp2) and two osteoblastic differentiation makers, Runt-related transcription factor-2 (Runx2) and Osterix, using immunohistochemistry and Western blotting. Our results showed that Bmp2, Runx2 and Osterix levels increased in cases with high calcification and correlated positively with the degree of calcification in ACP, whereas they showed little or no expression in squamous papillary craniopharyngioma. In ACP, Bmp2 was expressed primarily in the stellate reticulum and whorl-like array cells; Runx2 and Osterix tended to be expressed in calcification-related epithelia, including whorl-like array cells and epithelia in/around wet keratin and calcification lesions. Our study indicated, for the first time, that osteogenic factor Bmp2 may play an important role in the calcification of ACP via autocrine or paracrine mechanisms. Given the presence of osteogenic markers (Runx2 and Osterix), craniopharyngioma cells could differentiate into an osteoblast-like lineage, and the process of craniopharyngioma calcification resembles that which occurs in osteogenesis/odontogenesis. © 2014 John Wiley & Sons Ltd.

Spatial and seasonal reef calcification in corals and calcareous crusts in the central Red Sea

NASA Astrophysics Data System (ADS)

Roik, Anna; Roder, Cornelia; Röthig, Till; Voolstra, Christian R.

2016-06-01

The existence of coral reef ecosystems critically relies on the reef carbonate framework produced by scleractinian corals and calcareous crusts (i.e., crustose coralline algae). While the Red Sea harbors one of the longest connected reef systems in the world, detailed calcification data are only available from the northernmost part. To fill this knowledge gap, we measured in situ calcification rates of primary and secondary reef builders in the central Red Sea. We collected data on the major habitat-forming coral genera Porites, Acropora, and Pocillopora and also on calcareous crusts (CC) in a spatio-seasonal framework. The scope of the study comprised sheltered and exposed sites of three reefs along a cross-shelf gradient and over four seasons of the year. Calcification of all coral genera was consistent across the shelf and highest in spring. In addition, Pocillopora showed increased calcification at exposed reef sites. In contrast, CC calcification increased from nearshore, sheltered to offshore, exposed reef sites, but also varied over seasons. Comparing our data to other reef locations, calcification in the Red Sea was in the range of data collected from reefs in the Caribbean and Indo-Pacific; however, Acropora calcification estimates were at the lower end of worldwide rates. Our study shows that the increasing coral cover from nearshore to offshore environments aligned with CC calcification but not coral calcification, highlighting the potentially important role of CC in structuring reef cover and habitats. While coral calcification maxima have been typically observed during summer in many reef locations worldwide, calcification maxima during spring in the central Red Sea indicate that summer temperatures exceed the optima of reef calcifiers in this region. This study provides a foundation for comparative efforts and sets a baseline to quantify impact of future environmental change in the central Red Sea.

Validation of a Radiography-Based Quantification Designed to Longitudinally Monitor Soft Tissue Calcification in Skeletal Muscle.

PubMed

Moore, Stephanie N; Hawley, Gregory D; Smith, Emily N; Mignemi, Nicholas A; Ihejirika, Rivka C; Yuasa, Masato; Cates, Justin M M; Liu, Xulei; Schoenecker, Jonathan G

2016-01-01

Soft tissue calcification, including both dystrophic calcification and heterotopic ossification, may occur following injury. These lesions have variable fates as they are either resorbed or persist. Persistent soft tissue calcification may result in chronic inflammation and/or loss of function of that soft tissue. The molecular mechanisms that result in the development and maturation of calcifications are uncertain. As a result, directed therapies that prevent or resorb soft tissue calcifications remain largely unsuccessful. Animal models of post-traumatic soft tissue calcification that allow for cost-effective, serial analysis of an individual animal over time are necessary to derive and test novel therapies. We have determined that a cardiotoxin-induced injury of the muscles in the posterior compartment of the lower extremity represents a useful model in which soft tissue calcification develops remote from adjacent bones, thereby allowing for serial analysis by plain radiography. The purpose of the study was to design and validate a method for quantifying soft tissue calcifications in mice longitudinally using plain radiographic techniques and an ordinal scoring system. Muscle injury was induced by injecting cardiotoxin into the posterior compartment of the lower extremity in mice susceptible to developing soft tissue calcification. Seven days following injury, radiographs were obtained under anesthesia. Multiple researchers applied methods designed to standardize post-image processing of digital radiographs (N = 4) and quantify soft tissue calcification (N = 6) in these images using an ordinal scoring system. Inter- and intra-observer agreement for both post-image processing and the scoring system used was assessed using weighted kappa statistics. Soft tissue calcification quantifications by the ordinal scale were compared to mineral volume measurements (threshold 450.7mgHA/cm3) determined by μCT. Finally, sample-size calculations necessary to discriminate

Validation of a Radiography-Based Quantification Designed to Longitudinally Monitor Soft Tissue Calcification in Skeletal Muscle

PubMed Central

Moore, Stephanie N.; Hawley, Gregory D.; Smith, Emily N.; Mignemi, Nicholas A.; Ihejirika, Rivka C.; Yuasa, Masato; Cates, Justin M. M.; Liu, Xulei; Schoenecker, Jonathan G.

2016-01-01

Introduction Soft tissue calcification, including both dystrophic calcification and heterotopic ossification, may occur following injury. These lesions have variable fates as they are either resorbed or persist. Persistent soft tissue calcification may result in chronic inflammation and/or loss of function of that soft tissue. The molecular mechanisms that result in the development and maturation of calcifications are uncertain. As a result, directed therapies that prevent or resorb soft tissue calcifications remain largely unsuccessful. Animal models of post-traumatic soft tissue calcification that allow for cost-effective, serial analysis of an individual animal over time are necessary to derive and test novel therapies. We have determined that a cardiotoxin-induced injury of the muscles in the posterior compartment of the lower extremity represents a useful model in which soft tissue calcification develops remote from adjacent bones, thereby allowing for serial analysis by plain radiography. The purpose of the study was to design and validate a method for quantifying soft tissue calcifications in mice longitudinally using plain radiographic techniques and an ordinal scoring system. Methods Muscle injury was induced by injecting cardiotoxin into the posterior compartment of the lower extremity in mice susceptible to developing soft tissue calcification. Seven days following injury, radiographs were obtained under anesthesia. Multiple researchers applied methods designed to standardize post-image processing of digital radiographs (N = 4) and quantify soft tissue calcification (N = 6) in these images using an ordinal scoring system. Inter- and intra-observer agreement for both post-image processing and the scoring system used was assessed using weighted kappa statistics. Soft tissue calcification quantifications by the ordinal scale were compared to mineral volume measurements (threshold 450.7mgHA/cm3) determined by μCT. Finally, sample-size calculations necessary

Serum Phosphate is Associated with Aortic Valve Calcification in the Multi-Ethnic Study of Atherosclerosis (MESA)

PubMed Central

Linefsky, Jason P.; O’Brien, Kevin D.; Sachs, Michael; Katz, Ronit; Eng, John; Michos, Erin D.; Budoff, Matthew J.; de Boer, Ian; Kestenbaum, Bryan

2014-01-01

Objectives This study sought to investigate associations of phosphate metabolism biomarkers with aortic valve calcification (AVC). Background Calcific aortic valve disease (CAVD) is a common progressive condition that involves inflammatory and calcification mediators. Currently there are no effective medical treatments, but mineral metabolism pathways may be important in the development and progression of disease. Methods We examined associations of phosphate metabolism biomarkers, including serum phosphate, urine phosphate, parathyroid hormone (PTH) and serum fibroblast growth factor (FGF)-23, with CT-assessed AVC at study baseline and in short-term follow-up in 6,814 participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Results At baseline, AVC prevalence was 13.2%. Higher serum phosphate levels were associated with significantly greater AVC prevalence (relative risk 1.3 per 1mg/dL increment, 95% confidence incidence: 1.1 to 1.5, p < 0.001). Serum FGF-23, serum PTH, and urine phosphate were not associated with prevalent AVC. Average follow-up CT evaluation was 2.4 years (range 0.9–4.9 years) with an AVC incidence of 4.1%. Overall, phosphate metabolism biomarkers were not associated with incident AVC except in the top FGF-23 quartile. Conclusions Serum phosphate levels are significantly associated with AVC prevalence. Further study of phosphate metabolism as a modifiable risk factor for AVC is warranted. PMID:24530958

Detecting prostate cancer and prostatic calcifications using advanced magnetic resonance imaging.

PubMed

Dou, Shewei; Bai, Yan; Shandil, Ankit; Ding, Degang; Shi, Dapeng; Haacke, E Mark; Wang, Meiyun

2017-01-01

Prostate cancer and prostatic calcifications have a high incidence in elderly men. We aimed to investigate the diagnostic capabilities of susceptibility-weighted imaging in detecting prostate cancer and prostatic calcifications. A total number of 156 men, including 34 with prostate cancer and 122 with benign prostate were enrolled in this study. Computed tomography, conventional magnetic resonance imaging, diffusion-weighted imaging, and susceptibility-weighted imaging were performed on all the patients. One hundred and twelve prostatic calcifications were detected in 87 patients. The sensitivities and specificities of the conventional magnetic resonance imaging, apparent diffusion coefficient, and susceptibility-filtered phase images in detecting prostate cancer and prostatic calcifications were calculated. McNemar's Chi-square test was used to compare the differences in sensitivities and specificities between the techniques. The results showed that the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic cancer were greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient (P < 0.05). In addition, the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic calcifications were comparable to that of computed tomography and greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient (P < 0.05). Given the high incidence of susceptibility-weighted imaging (SWI) abnormality in prostate cancer, we conclude that susceptibility-weighted imaging is more sensitive and specific than conventional magnetic resonance imaging, diffusion-weighted imaging, and computed tomography in detecting prostate cancer. Furthermore, susceptibility-weighted imaging can identify prostatic calcifications similar to computed tomography, and it is much better than conventional magnetic resonance imaging and diffusion-weighted imaging.

Risk factors for coronary artery calcification in Japanese patients.

PubMed

Shikada, Tomoki; Washio, Masakazu; Nishizaki, Akiko; Kakino, Takamori; Ooe, Kensuke; Ishibashi, Yuuji; Sagara, Shuuichirou; Morishige, Kunio; Tashiro, Hideki

2015-07-01

Because the prevalence of coronary artery calcification is lower among Japanese than among Western individuals, aspects of the Japanese lifestyle might be related to the development of calcification. We aimed to clarify the relationship between coronary artery calcium scores in Japanese patients and various lifestyle factors among the Japanese population. Study subjects were patients aged ≥20 years who underwent multidetector-row computed tomography. A total of 201 patients agreed to take part in this study and answered a questionnaire regarding lifestyle, medical history, and other factors. Old age, current and former smoking, sedentary work, short sleep time, coronary artery stenosis, treatment with statins, medical history of cerebrovascular disease, medical history of angina pectoris, medical history of ischemic heart disease, and medical history of dyslipidemia were associated with higher odds ratios than the other factors examined, while the Japanese-style breakfast (e.g. boiled rice, miso soup, grilled fish) was associated with lower odds ratios. In this study, smoking, sedentary work, short sleep time, and the Japanese-style breakfast were lifestyle factors related to coronary artery calcification. The lifestyle of Japanese people may be related to coronary calcification. Copyright © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Coconut Atrium: Transmural Calcification of the Entire Left Atrium

PubMed Central

Campo, Carlos Del; Weinstein, Paul; Kunnelis, Constantine; DiStefano, Peter; Ebers, Gloria M.

2000-01-01

Massive calcification of the left atrium usually spares the interatrial septum, which provides a cleavage plane for surgical access to the mitral valve. Endoatriectomy with mitral valve replacement is the currently accepted corrective procedure because it affords maximum exposure while decreasing the risk of embolization and intraoperative hemorrhage. We describe a case in which the entire left atrium, including the septum, was thickly calcified and resembled a coconut shell. This condition prevented surgical correction of severe mitral stenosis. To our knowledge, this is the most severe case of left atrial calcification yet reported in the literature. Although it is not possible to establish preoperatively that the atrium is completely calcified and impossible to incise, when predisposing factors and evidence of complete transmural calcification are present, the surgeon should be aware of this possibility and should weigh carefully the decision to operate. PMID:10830629

Detection of vessel wall calcifications in vertebral arteries using susceptibility weighted imaging.

PubMed

Adams, Lisa C; Böker, Sarah M; Bender, Yvonne Y; Fallenberg, Eva M; Wagner, Moritz; Liebig, Thomas; Hamm, Bernd; Makowski, Marcus R

2017-09-01

Calcification of the brain supplying arteries has been linked to an increased risk for cerebrovascular disease. The purpose of this study was to test the potential of susceptibility weighted MR imaging (SWMR) for the detection of vertebral artery calcifications, based on CT as a reference standard. Four hundred seventy-four patients, who had received head CT and 1.5 T MR scans with SWMR, including the distal vertebral artery, between January 2014 and December 2016, were retrospectively evaluated and 389 patients were included. Sensitivity and specificity for the detection of focal calcifications and intra- and interobserver agreement were calculated for SWMR and standard MRI, using CT as a standard of reference. The diameter of vertebral artery calcifications was used to assess correlations between imaging modalities. Furthermore, the degree of vessel stenosis was determined in 30 patients, who had received an additional angiography. On CT scans, 40 patients showed a total of 52 vertebral artery calcifications. While SWMR reached a sensitivity of 94% (95% CI 84-99%) and a specificity of 97% (95% CI 94-98%), standard MRI yielded a sensitivity of 33% (95% CI 20-46%), and a specificity of 93% (95% CI 90-96%). Linear regression analysis of size measurements confirmed a close correlation between SWMR and CT measurements (R 2  = 0.74, p < 0.001). Compared to standard MRI (ICC = 0.52; CI 0.45-0.59), SWMR showed a higher interobserver agreement for calcification measurements (ICC = 0.84; CI 0.81-0.87). For detection of distal vertebral artery calcifications, SWMR demonstrates a performance comparable to CT and considerably higher than conventional MRI.

Kangaroo vs. porcine aortic valves: calcification potential after glutaraldehyde fixation.

PubMed

Narine, K; Chéry, Cyrille C; Goetghebeur, Els; Forsyth, R; Claeys, E; Cornelissen, Maria; Moens, L; Van Nooten, G

2005-01-01

The aim of this study was to evaluate and compare the calcification potential of kangaroo and porcine aortic valves after glutaraldehyde fixation at both low (0.6%) and high (2.0%) concentrations of glutaraldehyde in the rat subcutaneous model. To our knowledge this is the first report comparing the time-related, progressive calcification of these two species in the rat subcutaneous model. Twenty-two Sprague-Dawley rats were each implanted with two aortic valve leaflets (porcine and kangaroo) after fixation in 0.6% glutaraldehyde and two aortic valve leaflets (porcine and kangaroo) after fixation in 2% glutaraldehyde respectively. Animals were sacrificed after 24 h and thereafter weekly for up to 10 weeks after implantation. Calcium content was determined using inductively coupled plasma-mass spectrometry and confirmed histologically. Mean calcium content per milligram of tissue (dry weight) treated with 0.6 and 2% glutaraldehyde was 116.2 and 110.4 microg/mg tissue for kangaroo and 95.0 and 106.8 microg/mg tissue for porcine valves. Calcium content increased significantly over time (8.8 microg/mg tissue per week) and was not significantly different between groups. Regression analysis of calcification over time showed no significant difference in calcification of valves treated with 0.6 or 2% glutaraldehyde within and between the two species. Using the subcutaneous model, we did not detect a difference in calcification potential between kangaroo and porcine aortic valves treated with either high or low concentrations of glutaraldehyde. Copyright 2005 S. Karger AG, Basel.

Hypophosphatemia, Hyperphosphaturia, and Bisphosphonate Treatment Are Associated With Survival Beyond Infancy in Generalized Arterial Calcification of Infancy

PubMed Central

Rutsch, Frank; Böyer, Petra; Nitschke, Yvonne; Ruf, Nico; Lorenz-Depierieux, Bettina; Wittkampf, Tanja; Weissen-Plenz, Gabriele; Fischer, Rudolf-Josef; Mughal, Zulf; Gregory, John W.; Davies, Justin H.; Loirat, Chantal; Strom, Tim M.; Schnabel, Dirk; Nürnberg, Peter; Terkeltaub, Robert

2009-01-01

Background Generalized arterial calcification of infancy has been reported to be frequently lethal, and the efficiency of any therapy, including bisphosphonates, is unknown. A phosphate-poor diet markedly increases survival of NPP1 null mice, a model of generalized arterial calcification of infancy. Methods and Results We performed a multicenter genetic study and retrospective observational analysis of 55 subjects affected by generalized arterial calcification of infancy to identify prognostic factors. Nineteen (34%) patients survived the critical period of infancy. In all 8 surviving patients tested, hypophosphatemia due to reduced renal tubular phosphate reabsorption developed during childhood. Eleven of 17 (65%) patients treated with bisphosphonates survived. Of 26 patients who survived their first day of life and were not treated with bisphosphonates only 8 (31%) patients survived beyond infancy. Forty different homozygous or compound heterozygous mutations, including 16 novel mutations in ENPP1, were found in 41 (75%) of the 55 patients. Twenty-nine (71%) of these 41 patients died in infancy (median, 30 days). Seven of the 14 (50%) patients without ENPP1 mutations died in infancy (median, 9 days). When present on both alleles, the mutation p.P305T was associated with death in infancy in all 5 cases; otherwise, no clear genotype-phenotype correlation was seen. Conclusion ENPP1 coding region mutations are associated with generalized arterial calcification of infancy in ≈75% of subjects. Except for the p.P305T mutation, which was universally lethal when present on both alleles, the identified ENPP1 mutations per se have no discernable effect on survival. However, survival seems to be associated with hypophosphatemia linked with hyperphosphaturia and also with bisphosphonate treatment. PMID:20016754

Evidence for Rhythmicity Pacemaker in the Calcification Process of Scleractinian Coral

NASA Astrophysics Data System (ADS)

Gutner-Hoch, Eldad; Schneider, Kenneth; Stolarski, Jaroslaw; Domart-Coulon, Isabelle; Yam, Ruth; Meibom, Anders; Shemesh, Aldo; Levy, Oren

2016-02-01

Reef-building scleractinian (stony) corals are among the most efficient bio-mineralizing organisms in nature. The calcification rate of scleractinian corals oscillates under ambient light conditions, with a cyclic, diurnal pattern. A fundamental question is whether this cyclic pattern is controlled by exogenous signals or by an endogenous ‘biological-clock’ mechanism, or both. To address this problem, we have studied calcification patterns of the Red Sea scleractinian coral Acropora eurystoma with frequent measurements of total alkalinity (AT) under different light conditions. Additionally, skeletal extension and ultra-structure of newly deposited calcium carbonate were elucidated with 86Sr isotope labeling analysis, combined with NanoSIMS ion microprobe and scanning electron microscope imaging. Our results show that the calcification process persists with its cyclic pattern under constant light conditions while dissolution takes place within one day of constant dark conditions, indicating that an intrinsic, light-entrained mechanism may be involved in controlling the calcification process in photosymbiotic corals.

Effects of ocean acidification on calcification of symbiont-bearing reef foraminifers

NASA Astrophysics Data System (ADS)

Fujita, K.; Hikami, M.; Suzuki, A.; Kuroyanagi, A.; Kawahata, H.

2011-02-01

Ocean acidification (decreases in carbonate ion concentration and pH) in response to rising atmospheric pCO2 is generally expected to reduce rates of calcification by reef calcifying organisms, with potentially severe implications for coral reef ecosystems. Large, algal symbiont-bearing benthic foraminifers, which are important primary and carbonate producers in coral reefs, produce high-Mg calcite shells, whose solubility can exceed that of aragonite produced by corals, making them the "first responder" in coral reefs to the decreasing carbonate saturation state of seawater. Here we report results of culture experiments performed to assess the effects of ongoing ocean acidification on the calcification of symbiont-bearing reef foraminifers using a high-precision pCO2 control system. Living clone individuals of three foraminiferal species (Baculogypsina sphaerulata, Calcarina gaudichaudii, and Amphisorus hemprichii) were subjected to seawater at five pCO2 levels from 260 to 970 μatm. Cultured individuals were maintained for about 12 weeks in an indoor flow-through system under constant water temperature, light intensity, and photoperiod. After the experiments, the shell diameter and weight of each cultured specimen were measured. Net calcification of Baculogypsina and Calcarina, which secrete a hyaline shell and host diatom symbionts, increased under intermediate levels of pCO2 (580 and/or 770 μatm) and decreased at a higher pCO2 level (970 μatm). Net calcification of Amphisorus, which secretes a porcelaneous shell and hosts dinoflagellate symbionts, tended to decrease at elevated pCO2. These different responses among the three species are possibly due to differences in calcification mechanisms (in particular, the specific carbonate species used for calcification) between hyaline and porcelaneous taxa, and to links between calcification by the foraminiferal hosts and photosynthesis by the algal endosymbionts. Our findings suggest that ongoing ocean acidification

Coral calcification in a changing ocean

USGS Publications Warehouse

Kuffner, Ilsa B.

2010-01-01

One of the goals of the Coral Reef Ecosystem Studies (CREST) project is to examine how calcification rates in reef-building corals and encrusting coralline algae are changing in response to changes in the ocean environment.

Reversal of mineral ion homeostasis and soft-tissue calcification of klotho knockout mice by deletion of vitamin D 1α-hydroxylase

PubMed Central

Ohnishi, Mutsuko; Nakatani, Teruyo; Lanske, Beate; Razzaque, M. Shawkat

2011-01-01

Changes in the expression of klotho, a β-glucuronidase, contribute to the development of features that resemble those of premature aging, as well as chronic renal failure. Klotho knockout mice have increased expression of the sodium/phosphate cotransporter (NaPi2a) and 1α-hydroxylase in their kidneys, along with increased serum levels of phosphate and 1,25-dihydroxyvitamin D. These changes are associated with widespread soft-tissue calcifications, generalized tissue atrophy, and a shorter lifespan in the knockout mice. To determine the role of the increased vitamin D activities in klotho knockout animals, we generated klotho and 1α-hydroxylase double-knockout mice. These double mutants regained body weight and developed hypophosphatemia with a complete elimination of the soft-tissue and vascular calcifications that were routinely found in klotho knockout mice. The markedly increased serum fibroblast growth factor 23 and the abnormally low serum parathyroid hormone levels, typical of klotho knockout mice, were significantly reversed in the double-knockout animals. These in vivo studies suggest that vitamin D has a pathologic role in regulating abnormal mineral ion metabolism and soft-tissue anomalies of klotho-deficient mice. PMID:19225558

Methods for monitoring corals and crustose coralline algae to quantify in-situ calcification rates

USGS Publications Warehouse

Morrison, Jennifer M.; Kuffner, Ilsa B.; Hickey, T. Don

2013-01-01

The potential effect of global climate change on calcifying marine organisms, such as scleractinian (reef-building) corals, is becoming increasingly evident. Understanding the process of coral calcification and establishing baseline calcification rates are necessary to detect future changes in growth resulting from climate change or other stressors. Here we describe the methods used to establish a network of calcification-monitoring stations along the outer Florida Keys Reef Tract in 2009. In addition to detailing the initial setup and periodic monitoring of calcification stations, we discuss the utility and success of our design and offer suggestions for future deployments. Stations were designed such that whole coral colonies were securely attached to fixed apparati (n = 10 at each site) on the seafloor but also could be easily removed and reattached as needed for periodic weighing. Corals were weighed every 6 months, using the buoyant weight technique, to determine calcification rates in situ. Sites were visited in May and November to obtain winter and summer rates, respectively, and identify seasonal patterns in calcification. Calcification rates of the crustose coralline algal community also were measured by affixing commercially available plastic tiles, deployed vertically, at each station. Colonization by invertebrates and fleshy algae on the tiles was low, indicating relative specificity for the crustose coralline algal community. We also describe a new, nonlethal technique for sampling the corals, used following the completion of the monitoring period, in which two slabs were obtained from the center of each colony. Sampled corals were reattached to the seafloor, and most corals had completely recovered within 6 months. The station design and sampling methods described herein provide an effective approach to assessing coral and crustose coralline algal calcification rates across time and space, offering the ability to quantify the potential effects of

Detecting prostate cancer and prostatic calcifications using advanced magnetic resonance imaging

PubMed Central

Dou, Shewei; Bai, Yan; Shandil, Ankit; Ding, Degang; Shi, Dapeng; Haacke, E Mark; Wang, Meiyun

2017-01-01

Prostate cancer and prostatic calcifications have a high incidence in elderly men. We aimed to investigate the diagnostic capabilities of susceptibility-weighted imaging in detecting prostate cancer and prostatic calcifications. A total number of 156 men, including 34 with prostate cancer and 122 with benign prostate were enrolled in this study. Computed tomography, conventional magnetic resonance imaging, diffusion-weighted imaging, and susceptibility-weighted imaging were performed on all the patients. One hundred and twelve prostatic calcifications were detected in 87 patients. The sensitivities and specificities of the conventional magnetic resonance imaging, apparent diffusion coefficient, and susceptibility-filtered phase images in detecting prostate cancer and prostatic calcifications were calculated. McNemar's Chi-square test was used to compare the differences in sensitivities and specificities between the techniques. The results showed that the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic cancer were greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient (P < 0.05). In addition, the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic calcifications were comparable to that of computed tomography and greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient (P < 0.05). Given the high incidence of susceptibility-weighted imaging (SWI) abnormality in prostate cancer, we conclude that susceptibility-weighted imaging is more sensitive and specific than conventional magnetic resonance imaging, diffusion-weighted imaging, and computed tomography in detecting prostate cancer. Furthermore, susceptibility-weighted imaging can identify prostatic calcifications similar to computed tomography, and it is much better than conventional magnetic resonance imaging and diffusion-weighted imaging. PMID:27004542

Management of acute calcific tendinitis around the hip joint.

PubMed

Park, Sang-Min; Baek, Ji-Hoon; Ko, Young-Bong; Lee, Han-Jun; Park, Ki Jeong; Ha, Yong-Chan

2014-11-01

Although the natural history of calcific tendinitis within the rotator cuff of the shoulder is established, the natural history of calcific tendinitis around the hip joint remains unknown. To examine the duration of symptoms including pain, the location of calcific tendinitis around the hip joint, the radiologic course of calcium phosphate crystals, and the proportion of patients who required surgical treatment. Case series; Level of evidence, 4. Thirty hips (29 patients) with acute calcific tendinitis were treated between January 2010 and December 2012. Level of subjective hip pain using the visual analog scale pain score, radiologic type, and the location and size of calcium deposits were measured during a follow-up period of 12 to 32 months. The 29 patients included 7 men (24%) and 22 women (76%) with a mean age of 51.5 years (range, 28-78 years). All visual analog scale pain scores significantly improved from a mean of 7.1 to 0.8 at the latest follow-up (P < .001). The most common site of calcium deposition was the tendon of the gluteus medius. During follow-up, calcium deposition completely resolved in 5 of 20 hips. Symptoms in 23 patients (24 hips) responded to nonoperative treatment. Two patients (2 hips) were treated with ultrasound-guided local anesthetic and steroid injection. Four patients (4 hips) with long duration (>3 months) of severe pain, solid type, and large size (range, 96-416 mm(2)) were treated with arthroscopic excision. Nonoperative treatment in patients with acute calcific tendinitis of the hip joint might be successful in most patients. Surgical treatment is of value for patients experiencing prolonged severe pain, solid type, and large size. © 2014 The Author(s).

Coral Calcification Across a Natural Gradient in Ocean Acidification

NASA Astrophysics Data System (ADS)

Cohen, A. L.; Brainard, R. E.; Young, C.; Shamberger, K. E.; McCorkle, D. C.; Feely, R. A.; Mcleod, E.; Cantin, N.; Rose, K.; Lohmann, G. P.

2011-12-01

Much of our understanding of the impact of ocean acidification on coral calcification comes from laboratory manipulation experiments in which corals are reared under a range of seawater pH and aragonite saturation states (μar) equivalent to those projected for the next hundred years. In general, experiments show a consistently negative impact of acidification on coral calcification, leading to predictions of mass coral reef extinctions by dissolution as natural rates of carbonate erosion exceed the rates at which corals and other reef calcifiers can replace it. The tropical oceans provide a natural laboratory within which to test hypotheses about the longer term impact and adaptive potential of corals to acidification of the reef environment. Here we report results of a study in which 3-D CT scan and imaging techniques were used to quantify annual rates of calcification by conspecifics at 12 reefs sites spanning a natural gradient in ocean acidification. In situ μar calculated from alkalinity and DIC measurements of reef seawater ranged from less than 2.7 on an eastern Pacific Reef to greater than 4.0 in the central Red Sea. No correlation between μar and calcification was observed across this range. Corals living on low μar reefs appear to be calcifying as fast, sometimes faster than conspecifics living on high μar reefs. We used total lipid and tissue thickness to index the energetic status of colonies collected at each of our study sites. Our results support the hypothesis that energetics plays a key role in the coral calcification response to ocean acidification. Indeed, the true impact of acidification on coral reefs will likely be felt as temperatures rise and the ocean becomes more stratified, depleting coral energetic reserves through bleaching and reduced nutrient delivery to oceanic reefs.

Dystrophic calcification of the prostate after cryotherapy.

PubMed

Dru, Christopher; Bender, Leon

2014-01-01

We present a previously undocumented complication of dystrophic calcification of the prostate after cryotherapy. An 87-year-old male presented with recurrent lower urinary tract infections and was found to have an obstructing large calcified mass in the right lobe of the prostate. Subsequently, he underwent transurethral resection of the prostate (TURP) and bladder neck with laser lithotripsy to remove the calculus. We propose that chronic inflammation and necrosis of the prostate from cryotherapy resulted in dystrophic calcification of the prostate. As the use of cryotherapy for the treatment of localized prostate cancer continues to increase, it is important that clinicians be aware of this scenario and the technical challenges it poses.

Environmental controls on modern scleractinian coral and reef-scale calcification.

PubMed

Courtney, Travis A; Lebrato, Mario; Bates, Nicholas R; Collins, Andrew; de Putron, Samantha J; Garley, Rebecca; Johnson, Rod; Molinero, Juan-Carlos; Noyes, Timothy J; Sabine, Christopher L; Andersson, Andreas J

2017-11-01

Modern reef-building corals sustain a wide range of ecosystem services because of their ability to build calcium carbonate reef systems. The influence of environmental variables on coral calcification rates has been extensively studied, but our understanding of their relative importance is limited by the absence of in situ observations and the ability to decouple the interactions between different properties. We show that temperature is the primary driver of coral colony ( Porites astreoides and Diploria labyrinthiformis ) and reef-scale calcification rates over a 2-year monitoring period from the Bermuda coral reef. On the basis of multimodel climate simulations (Coupled Model Intercomparison Project Phase 5) and assuming sufficient coral nutrition, our results suggest that P. astreoides and D. labyrinthiformis coral calcification rates in Bermuda could increase throughout the 21st century as a result of gradual warming predicted under a minimum CO 2 emissions pathway [representative concentration pathway (RCP) 2.6] with positive 21st-century calcification rates potentially maintained under a reduced CO 2 emissions pathway (RCP 4.5). These results highlight the potential benefits of rapid reductions in global anthropogenic CO 2 emissions for 21st-century Bermuda coral reefs and the ecosystem services they provide.

Spatial and Seasonal Calcification in Corals and Calcareous Crusts in a Naturally Warm Coral Reef Region

NASA Astrophysics Data System (ADS)

Roik, A.; Roder, C.; Roethig, T.; Voolstra, C. R.

2016-02-01

The Red Sea harbors highly diverse and structurally complex coral reefs and is of interest for ocean warming studies. In the central and southern part, water temperatures rise above 30°C during summer, constituting one of the warmest coral reef environments worldwide. Additionally, seasonal variability of temperatures allows studying changes of environmental conditions and their effects on coral reef processes. To explore the influence of these warm and seasonally variable habitats on reef calcification, we measured in situ calcification of primary and secondary reef-builders in the central Red Sea. We collected calcification rates on the major habitat-forming coral genera Porites, Acropora, and Pocillopora, and also on calcareous crusts (CC). The study comprised forereef and backreef environments of three reefs along a cross-shelf gradient assessed over four seasons of the year. Calcification patterns of all coral genera were consistent across the shelf and highest in spring. In contrast to the corals, CC calcification strongly increased with distance from shore, but varied to a lesser extend over the seasons demonstrating lower calcification rates during spring and summer. Interestingly, reef calcification rates in the central Red Sea were on average in the range of data reported from the Caribbean and Indo-Pacific. For Acropora, annual average calcification rates were even at the lower end in comparison to studies from other locations. While coral calcification maxima typically have been observed during summer in many reef locations worldwide, we observed calcification maxima during spring in the central Red Sea indicating that summer temperatures may exceed the optima of reef calcifiers. Our study provides a baseline of calcification data for the region and serves as a foundation for comparative efforts to quantify the impact of future environmental change.

CIRSE Vascular Closure Device Registry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reekers, Jim A., E-mail: j.a.reekers@amc.uva.nl; Mueller-Huelsbeck, Stefan; Libicher, Martin

2011-02-15

Purpose: Vascular closure devices are routinely used after many vascular interventional radiology procedures. However, there have been no major multicenter studies to assess the safety and effectiveness of the routine use of closure devices in interventional radiology. Methods: The CIRSE registry of closure devices with an anchor and a plug started in January 2009 and ended in August 2009. A total of 1,107 patients were included in the registry. Results: Deployment success was 97.2%. Deployment failure specified to access type was 8.8% [95% confidence interval (95% CI) 5.0-14.5] for antegrade access and 1.8% (95% CI 1.1-2.9) for retrograde access (Pmore » = 0.001). There was no difference in deployment failure related to local PVD at the access site. Calcification was a reason for deployment failure in only <0.5% of patients. Postdeployment bleeding occurred in 6.4%, and most these (51.5%) could be managed with light manual compression. During follow-up, other device-related complications were reported in 1.3%: seven false aneurysms, three hematoma >5.9 cm, and two vessel occlusions. Conclusion: The conclusion of this registry of closure devices with an anchor and a plug is that the use of this device in interventional radiology procedures is safe, with a low incidence of serious access site complications. There seems to be no difference in complications between antegrade and retrograde access and other parameters.« less

CIRSE Vascular Closure Device Registry

PubMed Central

Müller-Hülsbeck, Stefan; Libicher, Martin; Atar, Eli; Trentmann, Jens; Goffette, Pierre; Borggrefe, Jan; Zeleňák, Kamil; Hooijboer, Pieter; Belli, Anna-Maria

2010-01-01

Purpose Vascular closure devices are routinely used after many vascular interventional radiology procedures. However, there have been no major multicenter studies to assess the safety and effectiveness of the routine use of closure devices in interventional radiology. Methods The CIRSE registry of closure devices with an anchor and a plug started in January 2009 and ended in August 2009. A total of 1,107 patients were included in the registry. Results Deployment success was 97.2%. Deployment failure specified to access type was 8.8% [95% confidence interval (95% CI) 5.0–14.5] for antegrade access and 1.8% (95% CI 1.1–2.9) for retrograde access (P = 0.001). There was no difference in deployment failure related to local PVD at the access site. Calcification was a reason for deployment failure in only <0.5% of patients. Postdeployment bleeding occurred in 6.4%, and most these (51.5%) could be managed with light manual compression. During follow-up, other device-related complications were reported in 1.3%: seven false aneurysms, three hematoma >5.9 cm, and two vessel occlusions. Conclusion The conclusion of this registry of closure devices with an anchor and a plug is that the use of this device in interventional radiology procedures is safe, with a low incidence of serious access site complications. There seems to be no difference in complications between antegrade and retrograde access and other parameters. PMID:20981425

Calcifications valvulaires chez l'hémodialysé au Maroc

PubMed Central

Noto-Kadou-Kaza, Béfa; Abouamrane, Lalla Meryam; Mtiou, Naoufal; El Khaya, Selma; Zamd, Mohamed; Medkouri, Ghislaine; Bengahanem, Mohamed Gharbi; Ramdani, Benyounes

2016-01-01

Introduction Les calcifications valvulaires constituent une des complications cardiovasculaires majeures de l'hémodialysé de par sa prévalence et son caractère prédictif de morbidité et de mortalité. De nombreux facteurs de risque sont à l'origine de ces calcifications. Le but de notre étude est d’évaluer à la fois la prévalence des calcifications valvulaires chez nos patients hémodialysés ainsi que leurs facteurs de risque. Méthodes Il s'agissait d'une étude transversale monocentrique, descriptive et analytique, ayant inclus 111 patients adultes hémodialysés depuis plus de 6 mois au centre d'hémodialyse du CHU Ibn Rochd de Casablanca et qui ont eu à bénéficier d'une ETT durant l'année 2013. Résultats L’âge moyen de nos patients était de 44 ± 14 ans. L'ancienneté moyenne en hémodialyse était de 146 ± 80 mois. La pression artérielle moyenne était de 123 ± 23 mmHg pour la systolique et de 72 ± 13 mmHg pour la diastolique, la PTHi moyenne de 529±460 pg/ml, la calcémie moyenne de 86±10 mg/l et la phosphatémie moyenne de 40±15 mg/l. La CRP moyenne était de 11±19,8 mg/L. Sur le plan thérapeutique, 96% des patients étaient sous carbonate de calcium, 11% sous 25 OH vitamine D, 55,5% sous 1 hydroxy-vitamine D3. La prévalence des calcifications valvulaires était de 15% avec une localisation valvulaire aortique dans 41,2% et valvulaire mitrale dans 41,2%. En analyse univariée, seule la durée d'hémodialyse semble être associée à la survenue des calcifications avec p = 0,09 proche du seuil de significativité. Conclusion La prévalence des calcifications valvulaires chez nos patients hémodialysés reste élevée même si elle parait relativement moindre comparée aux données de la littérature. Aucun facteur de risque connu n'est apparu significativement associé à ces calcifications. PMID:27642453

Is the response of coral calcification to seawater acidification related to nutrient loading?

NASA Astrophysics Data System (ADS)

Chauvin, Anne; Denis, Vianney; Cuet, Pascale

2011-12-01

The effect of decreasing aragonite saturation state (ΩArag) of seawater (elevated pCO2) on calcification rates of Acropora muricata was studied using nubbins prepared from parent colonies located at two sites of La Saline reef (La Réunion Island, western Indian Ocean): a back-reef site (BR) affected by nutrient-enriched groundwater discharge (mainly nitrate), and a reef flat site (RF) with low terrigenous inputs. Protein and chlorophyll a content of the nubbins, as well as zooxanthellae abundance, were lower at RF than BR. Nubbins were incubated at ~27°C over 2 h under sunlight, in filtered seawater manipulated to get differing initial pCO2 (1,440-340 μatm), ΩArag (1.4-4.0), and dissolved inorganic carbon (DIC) concentrations (2,100-1,850 μmol kg-1). Increasing DIC concentrations at constant total alkalinity (AT) resulted in a decrease in ΩArag and an increase in pCO2. AT at the beginning of the incubations was kept at a natural level of 2,193 ± 6 μmol kg-1 (mean ± SD). Net photosynthesis (NP) and calcification were calculated from changes in pH and AT during the incubations. Calcification decrease in response to doubling pCO2 relative to preindustrial level was 22% for RF nubbins. When normalized to surface area of the nubbins, (1) NP and calcification were higher at BR than RF, (2) NP increased in high pCO2 treatments at BR compared to low pCO2 treatments, and (3) calcification was not related to ΩArag at BR. When normalized to NP, calcification was linearly related to ΩArag at both sites, and the slopes of the relationships were not significantly different. The increase in NP at BR in the high pCO2 treatments may have increased calcification and thus masked the negative effect of low ΩArag on calcification. Removing the effect of NP variations at BR showed that calcification declined in a similar manner with decreased ΩArag (increased pCO2) whatever the nutrient loading.

Perioperative ultrasound-guided wire marking of calcific deposits in calcifying tendinitis of the rotator cuff.

PubMed

Sigg, Andreas; Draws, Detlev; Stamm, Axel; Pfeiffer, Michael

2011-03-01

The identification of a calcific deposit in the rotator cuff can often cause difficulties. A new technique is described to identify the calcific deposit perioperatively with a ultrasound-guided wire. The technique allows a safe direct marking of calcific deposits making the procedure faster especially in difficult cases.

[Diagnosis and treatment of adipsic diabetes insipidus accompanied with intracranial calcification].

PubMed

Hu, Ming-ming; Liu, Min; Liu, Wei

2013-04-01

To summarize our experience in the management of adipsic central diabetes insipidus(ADI) accompanied with intracranial calcification. The clinical data of one ADI patient accompanied with intracranial calcification who was treated in our hospital since December 2011 were retrospectively summarized. The 24-hour urine volume was 800 ml. She didn't feel thirsty even with increased plasma sodium concentration(153 mmol/L) and blood osmotic pressure(333 mmol/L) . Combined water deprivation and vasopressin test revealed the diagnosis of central diabetes insipidus. The high intensity signal(on T1-weighted magnetic resonance imaging) in the posterior lobe of pituitary gland was found. Computed tomography showed calcifications in the bilateral basal ganglia.Serum cytomegalovirus IgG was positive. She was treated with desmopressin and asked for regular water intake regardless of the adipsia. The plasma sodium concentration was still below 150 mmol/L during the 4-month follow-up. Routine adipsia evaluation and combined water deprivation and vasopressin test are critical for the diagnosis and treatment of ADI. Past insidious intracranial cytomegalovirus infection may explain the cause of ADI and calcification.

Oxidized low-density lipoprotein acts synergistically with beta-glycerophosphate to induce osteoblast differentiation in primary cultures of vascular smooth muscle cells.

PubMed

Bear, Mackenzie; Butcher, Martin; Shaughnessy, Stephen G

2008-09-01

Previous studies have localized osteoblast specific markers to sites of calcified atherosclerotic lesions. We therefore decided to use an established in vitro model of vascular calcification in order to confirm earlier reports of oxidized low-density lipoprotein (oxLDL) promoting the osteogenic differentiation of vascular smooth muscle cells. Treatment of primary bovine aortic smooth muscle cells (BASMCs) with beta-glycerophosphate was found to induce a time-dependent increase in osteoblast differentiation. In contrast, no effect was seen when BASMCs were cultured in the presence of oxLDL alone. However, when the BASMCs were cultured in the presence of both beta-glycerophosphate and oxLDL, beta-glycerophosphate's ability to induce osteoblast differentiation was significantly enhanced. In an attempt to resolve the mechanism by which this effect was occurring, we examined the effect of beta-glycerophosphate and oxLDL on several pathways known to be critical to the differentiation of osteoblasts. Surprisingly, beta-glycerophosphate alone was found to enhance Osterix (Osx) expression by inducing both Smad 1/5/8 activation and Runx2 expression. In contrast, oxLDL did not affect either Smad 1/5/8 activation or Runx2 activation but rather, it enhanced both beta-glycerophosphate-induced Osx expression and osteoblast differentiation in an extracellular signal-regulated kinase 1 and 2 (Erk 1 and 2) -dependent manner. When taken together, these findings suggest a plausible mechanism by which oxLDL may promote osteogenic differentiation and vascular calcification in vivo. J. Cell. Biochem. 105: 185-193, 2008. (c) 2008 Wiley-Liss, Inc. (c) 2008 Wiley-Liss, Inc.

Pulmonary metastatic calcification with respiratory insufficiency in patients on maintenance haemodialysis.

PubMed Central

Justrabo, E; Genin, R; Rifle, G

1979-01-01

A uraemic patient undergoing chronic haemodialysis developed diffuse metastatic pulmonary calcification and died from acute respiratory insufficiency after renal transplantation. Thirteen similar cases previously published are reviewed, with emphasis on the clinical and anatomical features of such calcinosis. The pathogenesis of this calcification in patients on maintenance haemodialysis and some rules for its prevention are discussed. Images PMID:483215

Increased dietary intake of vitamin A promotes aortic valve calcification in vivo

PubMed Central

Huk, Danielle J.; Hammond, Harriet L.; Kegechika, Hiroyuki; Lincoln, Joy

2013-01-01

Objective Calcific aortic valve disease (CAVD) is a major public health problem with no effective treatment available other than surgery. We previously showed that mature heart valves calcify in response to retinoic acid (RA) treatment through downregulation of the SRY-transcription factor Sox9. In this study, we investigated the effects of excess vitamin A and its metabolite RA on heart valve structure and function in vivo, and examined the molecular mechanisms of RA signaling during the calcification process in vitro. Methods and Results Using a combination of approaches, we defined CAVD pathogenesis in mice fed 200 IU/g and 20 IU/g of retinyl palmitate for 12 months at molecular, cellular and functional levels. We show that mice fed excess vitamin A develop aortic valve stenosis and leaflet calcification associated with increased expression of osteogenic genes and decreased expression of cartilaginous markers. Using a pharmacological approach, we show that RA-mediated Sox9 repression and calcification is regulated by classical RA signaling and requires both RAR and RXR receptors. Conclusions Our studies demonstrate that excess vitamin A dietary intake promotes heart valve calcification in vivo. Therefore suggesting that hypervitaminosis A could serve as a new risk factor of CAVD in the human population. PMID:23202364

Electrocardiogram Abnormalities and Coronary Calcification in Postmenopausal Women

PubMed Central

Sabour, Siamak; Grobbee, Diederick; Rutten, Annemarieke; Prokop, Mathias; Bartelink, Marie-Louise; van der Schouw, Yvonne; Bots, Michiel

2010-01-01

Background: An electrocardiogram (ECG) can provide information on subclinical myocardial damage. The presence, and more importantly, the quantity of coronary artery calcification (CAC), relates well with the overall severity of the atherosclerotic process. A strong relation has been demonstrated between coronary calcium burden and the incidence of myocardial infarction, a relation independent of age. The aim of this study was to assess the relation of left ventricular hypertrophy (LVH) and ECG abnormalities with CAC. Methods: The study population comprised 566 postmenopausal women selected from a population-based cohort study. Information on LVH and repolarization abnormalities (T-axis and QRS-T angle) was obtained using electrocardiography. Modular ECG Analysis System (MEANS) was used to assess ECG abnormalities. The women underwent a multi detector-row computed tomography (MDCT) scan (Philips Mx 8000 IDT 16) to assess CAC. The Agatston score was used to quantify CAC; scores greater than zero were considered as the presence of coronary calcium. Logistic regression was used to assess the relation of ECG abnormality with coronary calcification. Results: LVH was found in 2.7% (n = 15) of the women. The prevalence of T-axis abnormality was 6% (n = 34), whereas 8.5% (n = 48) had a QRS-T angle abnormality. CAC was found in 62% of the women. Compared to women with a normal T-axis, women with borderline or abnormal T-axes were 3.8 fold more likely to have CAC (95% CI: 1.4–10.2). Similarly, compared to women with a normal QRS-T angle, in women with borderline or abnormal QRS-T angle, CAC was 2.0 fold more likely to be present (95% CI: 1.0–4.1). Conclusion: Among women with ECG abnormalities reflecting subclinical ischemia, CAC is commonly found and may in part explain the increased coronary heart disease risk associated with these ECG abnormalities. PMID:23074563

Calcification by juvenile corals under heterotrophy and elevated CO2

NASA Astrophysics Data System (ADS)

Drenkard, E. J.; Cohen, A. L.; McCorkle, D. C.; de Putron, S. J.; Starczak, V. R.; Zicht, A. E.

2013-09-01

Ocean acidification (OA) threatens the existence of coral reefs by slowing the rate of calcium carbonate (CaCO3) production of framework-building corals thus reducing the amount of CaCO3 the reef can produce to counteract natural dissolution. Some evidence exists to suggest that elevated levels of dissolved inorganic nutrients can reduce the impact of OA on coral calcification. Here, we investigated the potential for enhanced energetic status of juvenile corals, achieved via heterotrophic feeding, to modulate the negative impact of OA on calcification. Larvae of the common Atlantic golf ball coral, Favia fragum, were collected and reared for 3 weeks under ambient (421 μatm) or significantly elevated (1,311 μatm) CO2 conditions. The metamorphosed, zooxanthellate spat were either fed brine shrimp (i.e., received nutrition from photosynthesis plus heterotrophy) or not fed (i.e., primarily autotrophic). Regardless of CO2 condition, the skeletons of fed corals exhibited accelerated development of septal cycles and were larger than those of unfed corals. At each CO2 level, fed corals accreted more CaCO3 than unfed corals, and fed corals reared under 1,311 μatm CO2 accreted as much CaCO3 as unfed corals reared under ambient CO2. However, feeding did not alter the sensitivity of calcification to increased CO2; ∆ calcification/∆Ω was comparable for fed and unfed corals. Our results suggest that calcification rates of nutritionally replete juvenile corals will decline as OA intensifies over the course of this century. Critically, however, such corals could maintain higher rates of skeletal growth and CaCO3 production under OA than those in nutritionally limited environments.

Environmental controls on modern scleractinian coral and reef-scale calcification

PubMed Central

Courtney, Travis A.; Lebrato, Mario; Bates, Nicholas R.; Collins, Andrew; de Putron, Samantha J.; Garley, Rebecca; Johnson, Rod; Molinero, Juan-Carlos; Noyes, Timothy J.; Sabine, Christopher L.; Andersson, Andreas J.

2017-01-01

Modern reef-building corals sustain a wide range of ecosystem services because of their ability to build calcium carbonate reef systems. The influence of environmental variables on coral calcification rates has been extensively studied, but our understanding of their relative importance is limited by the absence of in situ observations and the ability to decouple the interactions between different properties. We show that temperature is the primary driver of coral colony (Porites astreoides and Diploria labyrinthiformis) and reef-scale calcification rates over a 2-year monitoring period from the Bermuda coral reef. On the basis of multimodel climate simulations (Coupled Model Intercomparison Project Phase 5) and assuming sufficient coral nutrition, our results suggest that P. astreoides and D. labyrinthiformis coral calcification rates in Bermuda could increase throughout the 21st century as a result of gradual warming predicted under a minimum CO2 emissions pathway [representative concentration pathway (RCP) 2.6] with positive 21st-century calcification rates potentially maintained under a reduced CO2 emissions pathway (RCP 4.5). These results highlight the potential benefits of rapid reductions in global anthropogenic CO2 emissions for 21st-century Bermuda coral reefs and the ecosystem services they provide. PMID:29134196

Causation and management of calcific tendonitis and periarthritis.

PubMed

Carcia, Christopher R; Scibek, Jason S

2013-03-01

The purpose of this review is to update the reader on contemporary theory related to the cause of calcific periarthritis and provide the latest evidence associated with treating recalcitrant cases. Contemporary theory suggests calcific periarthritis is the result of a cellular-mediated process in which calcium is deposited and resorbed via a multiple phase process. Resorption is associated with an acute inflammatory response and is often the factor that prompts one to seek medical care. The majority of cases require nothing more than a combination of symptomatic care and benign neglect. A small percentage of cases require intervention to further stimulate deposit resorption. Moderate evidence exists for extracorporeal shock wave therapy in the treatment of chronic cases related to deposits about the shoulder. Numerous case studies support the use of NSAIDs as an effective intervention for retropharyngeal periarthritis. If conservative interventions fail, surgery appears to be a viable option for symptom relief associated with rotator cuff calcific deposits. Periarthritis is typically a symptom-limiting condition that resolves spontaneously. Numerous conservative treatment modalities each with varying levels of evidence exist for use in refractory cases. Future study is necessary to further refine the efficacy and parameters associated with available interventions.

The association between mammographic calcifications and breast cancer prognostic factors in a population-based registry cohort.

PubMed

Nyante, Sarah J; Lee, Sheila S; Benefield, Thad S; Hoots, Tiffany N; Henderson, Louise M

2017-01-01

Mammographic calcifications can be a marker of malignancy, but their association with prognosis is less well established. In the current study, the authors examined the relationship between calcifications and breast cancer prognostic factors in the population-based Carolina Mammography Registry. The current study included 8472 invasive breast cancers diagnosed in the Carolina Mammography Registry between 1996 and 2011 for which information regarding calcifications occurring within 2 years of diagnosis was reported. Calcification-specific Breast Imaging Reporting and Data System (BI-RADS) assessments were reported prospectively by a radiologist. Tumor characteristic data were obtained from the North Carolina Central Cancer Registry and/or pathology reports. Multivariable-adjusted associations between the presence of calcifications in the breast affected by cancer and tumor characteristics were estimated using logistic regression. Statistical tests were 2-sided. The presence of calcifications was found to be positively associated with tumors that were high grade (vs low grade: odds ratio [OR], 1.43; 95% confidence interval [95% CI], 1.10-1.88) or had an in situ component (vs without: OR, 2.15; 95% CI, 1.81-2.55). Calcifications were found to be inversely associated with hormone receptor-negative status (vs positive status: OR, 0.73; 95% CI, 0.57-0.93), size >35 mm (vs ≤8 mm: OR, 0.47; 95% CI, 0.37-0.61), and lobular tumors (vs ductal: OR, 0.39; 95% CI, 0.22-0.69). The association between the presence of calcifications and an in situ component was limited to BI-RADS category 4 and 5 calcifications and was absent for BI-RADS category 2 or 3 calcifications (P for heterogeneity <.01). The association with tumor size was found to be strongest for BI-RADS categories 3 and 4 (P for heterogeneity <.01). Calcifications were found to be associated with both unfavorable (high grade) and favorable (small size, hormone receptor positivity) prognostic factors

Relationship between sclerostin and cardiovascular calcification in hemodialysis patients: a cross-sectional study

PubMed Central

2013-01-01

Background Sclerostin is a Wnt pathway antagonist regulating osteoblast activity and bone turnover. Here, we assessed the potential association of sclerostin with the development of coronary artery (CAC) and aortic valve calcifications (AVC) in haemodialysis (HD) patients. Methods We conducted a cross-sectional multi-slice computed tomography (MS-CT) scanning study in 67 chronic HD patients (59.4 ± 14.8 yrs) for measurement of CAC and AVC. We tested established biomarkers as well as serum sclerostin (ELISA) regarding their association to the presence of calcification. Fifty-four adults without relevant renal disease served as controls for serum sclerostin levels. Additionally, sclerostin expression in explanted aortic valves from 15 dialysis patients was analysed ex vivo by immunohistochemistry and mRNA quantification (Qt-RT-PCR). Results CAC (Agatston score > 100) and any AVC were present in 65% and in 40% of the MS-CT patient group, respectively. Serum sclerostin levels (1.53 ± 0.81 vs 0.76 ± 0.31 ng/mL, p < 0.001) were significantly elevated in HD compared to controls and more so in HD patients with AVC versus those without AVC (1.78 ± 0.84 vs 1.35 ± 0.73 ng/mL, p = 0.02). Multivariable regression analysis for AVC revealed significant associations with higher serum sclerostin. Ex vivo analysis of uraemic calcified aortic valves (n = 10) revealed a strong sclerostin expression very close to calcified regions (no sclerostin staining in non-calcified valves). Correspondingly, we observed a highly significant upregulation of sclerostin mRNA in calcified valves compared to non-calcified control valves. Conclusion We found a strong association of sclerostin with calcifying aortic heart valve disease in haemodialysis patients. Sclerostin is locally produced in aortic valve tissue adjacent to areas of calcification. PMID:24112318

Relationship between valve calcification and long-term results of percutaneous mitral commissurotomy for rheumatic mitral stenosis.

PubMed

Bouleti, Claire; Iung, Bernard; Himbert, Dominique; Messika-Zeitoun, David; Brochet, Eric; Garbarz, Eric; Cormier, Bertrand; Vahanian, Alec

2014-06-01

Indications of percutaneous mitral commissurotomy (PMC) remain debated in calcific mitral stenosis. We analyzed long-term results of PMC for calcific mitral stenosis and the factors associated with late functional results. We compared the characteristics and outcome of 314 patients undergoing PMC for calcific mitral stenosis with 710 patients with noncalcified valves followed up to 20 years. Calcification was defined by fluoroscopy, and its extent was graded from 1 to 4. Good immediate results (valve area ≥ 1.5 cm(2) with mitral regurgitation ≤ 2/4) were obtained in 251 patients (80%) with calcified valves and 661 (93%) with noncalcified valves (P < 0.001). The hazard ratio for good functional results (survival without cardiovascular death, without mitral reintervention, and in New York Heart Association class I or II) was 2.5 (95% confidence interval [2.1-2.9]; P < 0.0001) in patients with calcified valves (12 ± 3% at 20 years) relative to the noncalcified group (38 ± 2% at 20 years). In the 251 patients with calcified valves who had good immediate results, 15-year rates of good functional results were 35 ± 4% for minor (grade 1) calcification, 24 ± 6% for grade 2, and 10 ± 6% for severe (grades 3-4) calcification. Factors associated with poor late functional results on multivariable analysis were calcification extent, older age, higher New York Heart Association class, atrial fibrillation, and higher mean gradient after PMC. Although late results of PMC are less satisfying in calcific mitral stenosis, long-term functional outcome depends on calcification extent, patient characteristics, and immediate results of PMC. These findings support the use of PMC as first-line treatment in selected patients with calcific mitral stenosis. © 2014 American Heart Association, Inc.

Calcification responses to diurnal variation in seawater carbonate chemistry by the coral Acropora formosa

NASA Astrophysics Data System (ADS)

Chan, W. Y.; Eggins, S. M.

2017-09-01

Significant diurnal variation in seawater carbonate chemistry occurs naturally in many coral reef environments, yet little is known of its effect on coral calcification. Laboratory studies on the response of corals to ocean acidification have manipulated the carbonate chemistry of experimental seawater to compare calcification rate changes under present-day and predicted future mean pH/Ωarag conditions. These experiments, however, have focused exclusively on differences in mean chemistry and have not considered diurnal variation. The aim of this study was to compare calcification responses of branching coral Acropora formosa under conditions with and without diurnal variation in seawater carbonate chemistry. To achieve this aim, we explored (1) a method to recreate natural diurnal variation in a laboratory experiment using the biological activities of a coral-reef mesocosm, and (2) a multi-laser 3D scanning method to accurately measure coral surface areas, essential to normalize their calcification rates. We present a cost- and time-efficient method of coral surface area estimation that is reproducible within 2% of the mean of triplicate measurements. Calcification rates were compared among corals subjected to a diurnal range in pH (total scale) from 7.8 to 8.2, relative to those at constant pH values of 7.8, 8.0 or 8.2. Mean calcification rates of the corals at the pH 7.8-8.2 (diurnal variation) treatment were not statistically different from the pH 8.2 treatment and were 34% higher than the pH 8.0 treatment despite similar mean seawater pH and Ωarag. Our results suggest that calcification of adult coral colonies may benefit from diurnal variation in seawater carbonate chemistry. Experiments that compare calcification rates at different constant pH without considering diurnal variation may have limitations.

Prevalence of pineal gland calcification as an incidental finding in patients referred for implant dental therapy.

PubMed

Mutalik, Sunil; Tadinada, Aditya

2017-09-01

Pineal gland calcification has been proposed to play a role in the pathogenesis of Alzheimer disease. This study evaluated the prevalence and extent of pineal gland calcification in cone-beam computed tomography (CBCT) scans of patients referred for dental implant therapy who could possibly be a vulnerable group for this condition. A retrospective evaluation of 500 CBCT scans was conducted. Scans that showed the area where the pineal gland was located were included. The scans were initially screened by a single observer to record the prevalence and extent of calcification. Six weeks following the completion of the study, another investigator randomly reviewed and selected 50 scans to investigate inter-observer variation, which was evaluated using reliability analysis statistics. The prevalence and measurements of the calcifications were reported using descriptive statistics. The chi-square test was used to compare the prevalence between males and females. The prevalence of pineal gland calcification was 58.8%. There was no statistically significant correlation between age and the extent of the calcification. The prevalence of calcification was 58.6% in females and 59.0% in males. The average anteroposterior measurement was 3.73±1.63 mm, while the average mediolateral measurement was 3.47±1.31 mm. The average total calcified area was 9.79±7.59 mm 2 . The prevalence of pineal gland calcification was high in patients undergoing implant therapy. While not all pineal gland calcifications lead to neurodegenerative disorders, they should be strongly considered in the presence of any symptoms as a reason to initiate further investigations.

Raman spectroscopy imaging reveals interplay between atherosclerosis and medial calcification in the human aorta

PubMed Central

You, Amanda Y. F.; Bergholt, Mads S.; St-Pierre, Jean-Philippe; Kit-Anan, Worrapong; Pence, Isaac J.; Chester, Adrian H.; Yacoub, Magdi H.; Bertazzo, Sergio; Stevens, Molly M.

2017-01-01

Medial calcification in the human aorta accumulates during aging and is known to be aggravated in several diseases. Atherosclerosis, another major cause of cardiovascular calcification, shares some common aggravators. However, the mechanisms of cardiovascular calcification remain poorly understood. To elucidate the relationship between medial aortic calcification and atherosclerosis, we characterized the cross-sectional distributions of the predominant minerals in aortic tissue, apatite and whitlockite, and the associated extracellular matrix. We also compared the cellular changes between atherosclerotic and nonatherosclerotic human aortic tissues. This was achieved through the development of Raman spectroscopy imaging methods that adapted algorithms to distinguish between the major biomolecules present within these tissues. We present a relationship between apatite, cholesterol, and triglyceride in atherosclerosis, with the relative amount of all molecules concurrently increased in the atherosclerotic plaque. Further, the increase in apatite was disproportionately large in relation to whitlockite in the aortic media directly underlying a plaque, indicating that apatite is more pathologically significant in atherosclerosis-aggravated medial calcification. We also discovered a reduction of β-carotene in the whole aortic intima, including a plaque in atherosclerotic aortic tissues compared to nonatherosclerotic tissues. This unprecedented biomolecular characterization of the aortic tissue furthers our understanding of pathological and physiological cardiovascular calcification events in humans. PMID:29226241

Molecular evolution of calcification genes in morphologically similar but phylogenetically unrelated scleractinian corals.

PubMed

Wirshing, Herman H; Baker, Andrew C

2014-08-01

Molecular phylogenies of scleractinian corals often fail to agree with traditional phylogenies derived from morphological characters. These discrepancies are generally attributed to non-homologous or morphologically plastic characters used in taxonomic descriptions. Consequently, morphological convergence of coral skeletons among phylogenetically unrelated groups is considered to be the major evolutionary process confounding molecular and morphological hypotheses. A strategy that may help identify cases of convergence and/or diversification in coral morphology is to compare phylogenies of existing "neutral" genetic markers used to estimate genealogic phylogenetic history with phylogenies generated from non-neutral genes involved in calcification (biomineralization). We tested the hypothesis that differences among calcification gene phylogenies with respect to the "neutral" trees may represent convergent or divergent functional strategies among calcification gene proteins that may correlate to aspects of coral skeletal morphology. Partial sequences of two nuclear genes previously determined to be involved in the calcification process in corals, "Cnidaria-III" membrane-bound/secreted α-carbonic anhydrase (CIII-MBSα-CA) and bone morphogenic protein (BMP) 2/4, were PCR-amplified, cloned and sequenced from 31 scleractinian coral species in 26 genera and 9 families. For comparison, "neutral" gene phylogenies were generated from sequences from two protein-coding "non-calcification" genes, one nuclear (β-tubulin) and one mitochondrial (cytochrome b), from the same individuals. Cloned CIII-MBSα-CA sequences were found to be non-neutral, and phylogenetic analyses revealed CIII-MBSα-CAs to exhibit a complex evolutionary history with clones distributed between at least 2 putative gene copies. However, for several coral taxa only one gene copy was recovered. With CIII-MBSα-CA, several recovered clades grouped taxa that differed from the "non-calcification" loci. In some

[Serpiginous calcifications in breast filariasis: A descriptor not included in the BI-RADS classification system].

PubMed

Mora-Encinas, J P; Martín-Martín, B; Martín-Martín, L; Mora-Monago, R

2015-01-01

Filariasis is a parasitic disease with a benign course caused by nematodes. Filariasis is endemic in some tropical regions, and immigration has made it increasingly common in some centers in Spain. The death of the parasites can lead to calcifications that are visible in mammograms; these calcifications have specific characteristics and should not be confused with those arising in other diseases. However, the appearance of calcifications due to filariasis is not included in the most common systems used for the classification of calcifications on mammograms (BI-RADS), and this can lead to confusion. In this article, we discuss the need to update classification systems and warn radiologists about the appearance of these calcifications to ensure their correct diagnosis and avoid confusion with other diseases. Copyright © 2014 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Unexpected severe calcification after transplantation of bone marrow cells in acute myocardial infarction.

PubMed

Yoon, Young-Sup; Park, Jong-Seon; Tkebuchava, Tengiz; Luedeman, Corinne; Losordo, Douglas W

2004-06-29

There has been a rapid increase in the number of clinical trials using unselected bone marrow (BM) cells or the mononuclear fraction of BM cells for treating ischemic heart diseases. Thus far, no significant deleterious effects or complications have been reported in any studies using BM-derived cells for treatment of various cardiac diseases. Seven-week-old female Fisher-344 rats underwent surgery to induce acute myocardial infarction and were randomized into 3 groups of 16 rats, each receiving intramyocardial injection of either 7x10(5) DiI-labeled total BM cells (TBMCs), the same number of DiI-labeled, clonally expanded BM multipotent stem cells, or the same volume of phosphate-buffered saline in the peri-infarct area. Echocardiography 2 weeks after cell transplantation indicated intramyocardial calcification in 4 of 14 surviving rats (28.5%) in the TBMC group. Histological examination with hematoxylin and eosin staining and von Kossa staining confirmed the presence of extensive intramyocardial calcification. Alkaline phosphatase staining revealed strong positivity surrounding the calcified area suggestive of ongoing osteogenic activity. Fluorescent microscopic examination revealed that acellular calcific areas were surrounded by DiI-labeled TBMCs, suggesting the direct involvement of transplanted TBMCs in myocardial calcification. In contrast, in hearts receiving equal volumes of saline or BM multipotent stem cells delivered in the same manner, there was no evidence of calcification. These results demonstrate that direct transplantation of unselected BM cells into the acutely infarcted myocardium may induce significant intramyocardial calcification.

Ultrasound imaging-guided percutaneous treatment of rotator cuff calcific tendinitis: success in short-term outcome.

PubMed

Bazzocchi, Alberto; Pelotti, Patrizia; Serraino, Salvatore; Battaglia, Milva; Bettelli, Graziano; Fusaro, Isabella; Guglielmi, Giuseppe; Rotini, Roberto; Albisinni, Ugo

2016-01-01

Rotator cuff calcific tendinitis (RCCT) is a common cause of shoulder pain in adults and typically presents as activity-related shoulder pain. Between non-surgical and surgical treatment options, today a few minimal invasive techniques are available to remove the calcific deposit, and they represent a cornerstone in the management of this painful clinical condition. The aim of the work was a retrospective evaluation of double-needle ultrasound-guided percutaneous fragmentation and lavage (DNL), focused on understanding the factors which are of major importance in determining a quick and good response at 1 month. A series of 147 patients affected by RCCT and suitable for DNL were evaluated. A systematic review of anamnestic, clinical and imaging data was performed in 144 shoulders treated in a single-centre setting. Clinical reports and imaging examinations were revisited. The inclusion criteria were submission to DNL, therefore fitness for the percutaneous procedure, and following 1-month follow-up. There was no exclusion owing to risk of bias. The treatment was defined as successful for constant shoulder modified score (CSS) improvement of >50% at 1 month. In 70% of shoulders, the treatment resulted in a quick and significant reduction of symptoms (successful). On the whole, CSS increase at 1 month was estimated at 91.5 ± 69.1%. CSS variations were significantly related to age of patients (better results between 30 and 40 years old), calcification size (more relevant improvement for middle-sized calcifications, 12-17 mm), sonographic and radiographic features of calcific deposits (softer calcifications) and thickening of subacromial/subdeltoid bursa walls. In the final model of stepwise regression for CSS variation, ultrasound score pre-treatment and post-treatment, the distance between bursa and calcification before treatment and the size of post-treatment calcification area were shown to be independently correlated to success. Numeric rating scale score

Calcific periarthritis of the elbow presenting as acute tennis elbow.

PubMed

Jawad, F; Jawad, A S M

2014-01-01

A 28-year-old woman presented with sudden acute lateral epicondylitis. There was no history of preceding trauma or repetitive use of the arm. Because of the acute onset and signs of acute inflammation, an X-ray was arranged. The X-ray showed a hyperdense calcified elongated globule distal to the lateral epicondyle. A diagnosis of calcific periarthritis (calcium apatite) of the elbow was made. Calcific periarthritis has rarely been reported as a cause of acute elbow pain.

Reef-scale modeling of coral calcification responses to ocean acidification and sea-level rise

NASA Astrophysics Data System (ADS)

Nakamura, Takashi; Nadaoka, Kazuo; Watanabe, Atsushi; Yamamoto, Takahiro; Miyajima, Toshihiro; Blanco, Ariel C.

2018-03-01

To predict coral responses to future environmental changes at the reef scale, the coral polyp model (Nakamura et al. in Coral Reefs 32:779-794, 2013), which reconstructs coral responses to ocean acidification, flow conditions and other factors, was incorporated into a reef-scale three-dimensional hydrodynamic-biogeochemical model. This coupled reef-scale model was compared to observations from the Shiraho fringing reef, Ishigaki Island, Japan, where the model accurately reconstructed spatiotemporal variation in reef hydrodynamic and geochemical parameters. The simulated coral calcification rate exhibited high spatial variation, with lower calcification rates in the nearshore and stagnant water areas due to isolation of the inner reef at low tide, and higher rates on the offshore side of the inner reef flat. When water is stagnant, bottom shear stress is low at night and thus oxygen diffusion rate from ambient water to the inside of the coral polyp limits respiration rate. Thus, calcification decreases because of the link between respiration and calcification. A scenario analysis was conducted using the reef-scale model with several pCO2 and sea-level conditions based on IPCC (Climate change 2013: the physical science basis. Contribution of working group I to the fifth assessment report of the intergovernmental panel on climate change, Cambridge University Press, Cambridge, 2013) scenarios. The simulation indicated that the coral calcification rate decreases with increasing pCO2. On the other hand, sea-level rise increases the calcification rate, particularly in the nearshore and the areas where water is stagnant at low tide under present conditions, as mass exchange, especially oxygen exchange at night, is enhanced between the corals and their ambient seawater due to the reduced stagnant period. When both pCO2 increase and sea-level rise occur concurrently, the calcification rate generally decreases due to the effects of ocean acidification. However, the

Characterisation of calcium phosphate crystals on calcified human aortic vascular smooth muscle cells and potential role of magnesium.

PubMed

Louvet, Loïc; Bazin, Dominique; Büchel, Janine; Steppan, Sonja; Passlick-Deetjen, Jutta; Massy, Ziad A

2015-01-01

Cardiovascular disease including vascular calcification (VC) remains the leading cause of death in patients suffering from chronic kidney disease (CKD). The process of VC seems likely to be a tightly regulated process where vascular smooth muscle cells are playing a key role rather than just a mere passive precipitation of calcium phosphate. Characterisation of the chemical and crystalline structure of VC was mainly led in patients or animal models with CKD. Likewise, Mg2+ was found to be protective in living cells although a potential role for Mg2+ could not be excluded on crystal formation and precipitation. In this study, the crystal formation and the role of Mg2+ were investigated in an in vitro model of primary human aortic vascular smooth muscle cells (HAVSMC) with physical techniques. In HAVSMC incubated with increased Ca x Pi medium, only calcium phosphate apatite crystals (CPA) were detected by Micro-Fourier Transform InfraRed spectroscopy (µFTIR) and Field Effect Scanning Electron Microscope (FE-SEM) and Energy Dispersive X-ray spectrometry (EDX) at the cell layer level. Supplementation with Mg2+ did not alter the crystal composition or structure. The crystal deposition was preferentially positioned near or directly on cells as pictured by FE-SEM observations and EDX measurements. Large µFTIR maps revealed spots of CPA crystals that were associated to the cellular layout. This qualitative analysis suggests a potential beneficial effect of Mg2+ at 5 mM in noticeably reducing the number and intensities of CPA µFTIR spots. For the first time in a model of HAVSMC, induced calcification led to the formation of the sole CPA crystals. Our data seems to exclude a physicochemical role of Mg2+ in altering the CPA crystal growth, composition or structure. Furthermore, Mg2+ beneficial role in attenuating VC should be linked to an active cellular role.

Factors associated with early atherosclerosis and arterial calcifications in young subjects with a benign phenotype of obesity.

PubMed

Gilardini, Luisa; Pasqualinotto, Lucia; Di Matteo, Silvia; Caffetto, Katherine; Croci, Marina; Girola, Andrea; Invitti, Cecilia

2011-08-01

We assessed (i) the association between early arterial disease and factors linked to adiposity, dietary habits, and family in a young cohort of 151 obese children and adolescents with less than or equal to one cardiovascular (CV) risk factor, (ii) whether in subjects with carotid calcifications there was an imbalance of calcium-phosphorus homeostasis. Measurement included: carotid ultrasound, oral glucose tolerance test, anthropometry, body composition, dietary history, white blood cells count, lipids, uric acid, adiponectin, insulin, C-reactive protein, plasminogen activator inhibitor 1 (PAI-1), 25-hydroxyvitamin D, parathyroid hormone (PTH), calcium and phosphorus. Obese children with carotid artery intima media thickness (cIMT) values >75° percentile (0.55 mm), compared to those with lower cIMT, were more obese, more often pubertal and had higher prevalence of family history of CV disease (CVD) (P < 0.05), higher plasma PAI-1 and uric acid (P < 0.001) and lower adiponectin (P < 0.05) and high-density lipoprotein (HDL) cholesterol levels (P < 0.05). After adjustment for sex, age, puberty, obesity, and insulin levels, only PAI-I remained significantly different between the two groups (10.9 (7.2-29.8) vs. 6.2 (4.3-10.6) ng/ml, P < 0.001). Dietary intake did not affect cIMT values. Eight percent of subjects showed nonatherosclerotic carotid calcifications with patchy pattern. These children had a worse lipid profile (P < 0.05) and higher plasma PTH levels (48.6 ± 21.5 vs 38.5 ± 16.9 pg/ml, P < 0.05) that were inversely associated with 25-hydroxyvitamin D levels (r = 0.245, P < 0.01). Present results suggest that (i) several adiposity-related factors may play a role in promoting the development of early arterial diseases in young subjects with a benign phenotype of obesity, (ii) a PTH rise resulting from a subclinical imbalance in calcium-phosphorus homeostasis may affect the biological process of vascular calcifications.

Assessment of Growth Using Mandibular Canine Calcification Stages and Its Correlation with Modified MP3 Stages

PubMed Central

Nayak, US Krishna; Hegde, Gautam

2010-01-01

Background and objectives Orthodontic diagnosis and treatment planning for growing children must involve growth prediction, especially in the treatment of skeletal problems. Studies have shown that a strong association exists between skeletal maturity and dental calcification stages. The present study was therefore taken up to provide a simple and practical method for assessing skeletal maturity using a dental periapical film and standard dental X-ray machine, to compare the developmental stages of the mandibular canine with that of developmental stages of modified MP3 and to find out if any correlation exists, to determine if the developmental stages of the mandibular canine alone can be used as a reliable indicator for assessment of skeletal maturity. Methods A total of 160 periapical radiographs (80 males and 80 females), of the mandibular right canine and the MP3 region was taken and assessed according to the Dermirjian’s stages of dental calcification and the modified MP3 stages. Results The correlation between the developmental stages of MP3 and the mandibular right canine in male and female groups, is of high statistical significance (p = 0.001). The correlation coefficient between MP3 stages and developmental stages of mandibular canine and chronological age in male and females was found to be not significant. Conclusions The correlation between the mandibular canine calcification stages and MP3 stages was found to be significant. The developmental stages of the mandibular canine could be used very reliably as a sole indicator for assessment of skeletal maturity. PMID:27625553

Chorioretinal dysplasia, hydranencephaly, and intracranial calcifications: pseudo-TORCH or a new syndrome?

PubMed

Watts, P; Kumar, N; Ganesh, A; Sastry, P; Pilz, D; Levin, A V; Chitayat, D

2008-05-01

To report the association of severe chorioretinal dysplasia, hydranencephaly, microcephaly, and intracranial calcification in children with no evidence of intrauterine infections. Two unrelated female infants with visually inattentive behaviour, hydranencephaly, and intracranial calcification were referred for an ophthalmological opinion. The fundus examination and computerised tomograms (CT scans) of head were similar in both children. There was bilateral extensive chorioretinal dysplasia, intracranial calcifications, and hydranencephaly. Serology was negative for acquired intrauterine congenital infections. We report two cases that may represent a new syndrome or the more severe end of the spectrum of the pseudo-TORCH (toxoplasma, rubella, cytomegalovirus, and herpes simplex) syndrome. The association of chorioretinal dysplasia with the pseudo-TORCH syndrome has not been reported previously.

Pulp calcification in traumatized primary teeth: prevalence and associated factors.

PubMed

Mello-Moura, A C V; Bonini, G A V C; Zardetto, C G D C; Rodrigues, C R M D; Wanderley, M T

2011-01-01

To establish the prevalence of pulp calcifications in 946 patients at the Research and Clinical Center of Dental Trauma in Primary Teeth. The clinical and radiographic records of l675 traumatized primary teeth were evaluated. Statistical analysis was performed using chi-square and univariate logistic regression. 197 (20.8%) patients showed pulp calcification (PC). A total of 250 (14.9%) calcified teeth were observed In most teeth, PC appeared within the first 12 months following trauma. PC prevalence was higher in cases of repeated trauma (29.6%) than in single trauma (16.4%), p < 0.05, with a 2.14 chance of showing pulp calcification when a child suffered recurrent trauma. Most teeth showing calcified pulp, suffered trauma to the supportive tissue (67.4%), being statistically significant in relation to the trauma to dental tissue (p < 0.05). PC is a sequelae in cases of trauma to the primary dentition; teeth that suffered recurrent traumatic injuries show higher risk of presenting.

Decreased calcification in the Southern Ocean over the satellite record

NASA Astrophysics Data System (ADS)

Freeman, Natalie M.; Lovenduski, Nicole S.

2015-03-01

Widespread ocean acidification is occurring as the ocean absorbs anthropogenic carbon dioxide from the atmosphere, threatening marine ecosystems, particularly the calcifying plankton that provide the base of the marine food chain and play a key role within the global carbon cycle. We use satellite estimates of particulate inorganic carbon (PIC), surface chlorophyll, and sea surface temperature to provide a first estimate of changing calcification rates throughout the Southern Ocean. From 1998 to 2014 we observe a 4% basin-wide reduction in summer calcification, with ˜9% reductions in large regions (˜1 × 106 km2) of the Pacific and Indian sectors. Southern Ocean trends are spatially heterogeneous and primarily driven by changes in PIC concentration (suspended calcite), which has declined by ˜24% in these regions. The observed decline in Southern Ocean calcification and PIC is suggestive of large-scale changes in the carbon cycle and provides insight into organism vulnerability in a changing environment.

Combined presence of aortic valve calcification and mitral annular calcification as a marker of the extent and vulnerable characteristics of coronary artery plaque assessed by 64-multidetector computed tomography.

PubMed

Utsunomiya, Hiroto; Yamamoto, Hideya; Kunita, Eiji; Kitagawa, Toshiro; Ohashi, Norihiko; Oka, Toshiharu; Yamazato, Ryo; Horiguchi, Jun; Kihara, Yasuki

2010-11-01

We examined the association of aortic valve calcification (AVC) and mitral annular calcification (MAC) to coronary atherosclerosis using 64-multidetector computed tomography (MDCT). Valvular calcification is considered a manifestation of atherosclerosis. The impact of multiple heart valve calcium deposits on the distribution and characteristics of coronary plaque is unknown. We evaluated 322 patients referred for 64-MDCT, and assessed valvular calcification and the extent of calcified (CAP), mixed (MCAP), and noncalcified coronary atherosclerotic plaque (NCAP) in accordance with the 17-coronary segments model. We assessed the vulnerable characteristics of coronary plaque with positive remodeling, low-density plaque (CT density ≤38 Hounsfield units), and the presence of adjacent spotty calcification. In 49 patients with both AVC and MAC, the segment numbers of CAP and MCAP were larger than in those with a lack of valvular calcification and an isolated AVC (p<0.001 for both). Multivariate analyses revealed that a combined presence of AVC and MAC was independently associated with the presence (odds ratio [OR] 9.36, 95% confidence interval [95%CI] 1.55-56.53, p=0.015) and extent (β-estimate 1.86, p<0.001) of overall coronary plaque. When stratified by plaque composition, it was associated with the extent of CAP (β-estimate 1.77, p<0.001) and MCAP (β-estimate 1.04, p<0.001), but not with NCAP. Moreover, it was also related to the presence of coronary plaque with all three vulnerable characteristics (OR 4.87, 95%CI 1.85-12.83, p=0.001). The combined presence of AVC and MAC is highly associated with the presence, extent, and vulnerable characteristics of coronary plaque identified by 64-MDCT. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Calcification of the planktonic foraminifera Globigerina bulloides and carbonate ion concentration: Results from the Santa Barbara Basin

NASA Astrophysics Data System (ADS)

Osborne, Emily B.; Thunell, Robert C.; Marshall, Brittney J.; Holm, Jessica A.; Tappa, Eric J.; Benitez-Nelson, Claudia; Cai, Wei-Jun; Chen, Baoshan

2016-08-01

Planktonic foraminiferal calcification intensity, reflected by shell wall thickness, has been hypothesized to covary with the carbonate chemistry of seawater. Here we use both sediment trap and box core samples from the Santa Barbara Basin to evaluate the relationship between the calcification intensity of the planktonic foraminifera species Globigerina bulloides, measured by area density (µg/µm2), and the carbonate ion concentration of seawater ([CO32-]). We also evaluate the influence of both temperature and nutrient concentration ([PO43-]) on foraminiferal calcification and growth. The presence of two G. bulloides morphospecies with systematically different calcification properties and offset stable isotopic compositions was identified within sampling populations using distinguishing morphometric characteristics. The calcification temperature and by extension calcification depth of the more abundant "normal" G. bulloides morphospecies was determined using δ18O temperature estimates. Calcification depths vary seasonally with upwelling and were used to select the appropriate [CO32-], temperature, and [PO43-] depth measurements for comparison with area density. Seasonal upwelling in the study region also results in collinearity between independent variables complicating a straightforward statistical analysis. To address this issue, we use additional statistical diagnostics and a down core record to disentangle the respective roles of each parameter on G. bulloides calcification. Our results indicate that [CO32-] is the primary variable controlling calcification intensity while temperature influences shell size. We report a modern calibration for the normal G. bulloides morphospecies that can be used in down core studies of well-preserved sediments to estimate past [CO32-].

Exposure to Cigarette Smoke and the Carotid Arteries Calcification Index in Patients with Essential Hypertension.

PubMed

Gać, Paweł; Jaźwiec, Przemysław; Mazur, Grzegorz; Poręba, Rafał

2017-07-01

The arteries calcification index is a quantitative, mathematically estimated parameter characterizing the total amount of calcium within atherosclerotic plaques in the walls of arteries. The objective is to determine a relationship between exposure to cigarette smoke and the carotid arteries calcification index in patients with essential hypertension. The tested group included 66 patients with essential hypertension: 19 active smokers (subgroup A), 20 non-smokers, environmentally exposed to cigarette smoke (subgroup B) and 27 persons without exposure to cigarette smoke (subgroup C). The tested group was subjected to computed tomography angiography of carotid arteries. Evaluation of the carotid arteries calcification indexes was conducted. The average value of the total calcification index of the carotid arteries (CAci) amounted to 368.28 ± 384.21. In subgroup A and B in relation to subgroup C, CAci was significantly higher. In summary, active and passive smoking in patients with essential hypertension may be associated with a higher calcification index of carotid arteries.

[Clinical and pathological significance of carotid siphon calcification observed on bone condition of brain CT].

PubMed

Matsumoto, Hideyuki; Hamaguchi, Hirotoshi; Nakayama, Takahiro; Oda, Tetsuya; Ikagawa, Takashi; Imafuku, Ichiro

2008-02-01

On plain brain computed tomography (CT), it is difficult to evaluate stenosis of internal carotid artery (ICA) because ICA is surrounded by structures, even though we can observe calcification of carotid siphon in some patients by using bone condition. However the pathologic significance has not been well known. We studied the pathologic significance of carotid siphon calcification observed on bone condition of brain CT. A total of 112 patients who were diagnosed or suspected as cerebrovascular diseases were registered. We classified the calcification into four levels (none, mild, moderate, severe) based on the degree of calcification. Then we compared it with the degree of stenosis of carotid siphon seen on brain magnetic resonance angiography (MRA) and with max intima-medial thickness (IMT) from common carotid artery (CCA) to ICA on carotid ultrasonography. The mean +/- standard deviation of max IMT to none, mild, moderate and severe in the degree of calcification were 1.03 +/- 0.64 (0.4-2.8), 1.65 +/- 0.83 (0.5-4.1), 2.03 +/- 0.83 (0.8-4.1) and 2.81 +/- 1.15 (0.7-6.5) mm, respectively. The calcification on brain CT significantly correlated with the degree of stenosis on brain MRA and with max IMT on carotid ultrasonography. The calcification of carotid siphon on bone condition of brain CT correlated with stenosis of the same portion and atherosclerosis of CCA bifurcation. Recently, on DICOM viewer, clinicians can convert plain condition into bone condition on brain CT due to popularization of PACS. We should pay attention to calcification of carotid siphon in patients with ischemic cerebrovascular diseases because we can estimate the atherosclerosis of both carotid siphon and CCA bifurcation easily and immediately.

High-energy extracorporeal shock-wave therapy for treating chronic calcific tendinitis of the shoulder: a systematic review.

PubMed

Bannuru, Raveendhara R; Flavin, Nina E; Vaysbrot, Elizaveta; Harvey, William; McAlindon, Timothy

2014-04-15

Calcific and noncalcific tendinitis of the shoulder can be unresponsive to conventional therapies. Extracorporeal shock-wave therapy (ESWT) has been suggested as an alternative treatment. To assess the efficacy of ESWT in patients with calcific and noncalcific tendinitis. MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, Web of Science, and Google Scholar were searched up to 1 November 2013. Randomized, controlled trials (RCTs) comparing high-energy versus low-energy ESWT or placebo for treatment of calcific or noncalcific tendinitis of the shoulder. Outcome measures included pain (visual analogue scale score), functional assessment (Constant-Murley score), and resolution of calcifications. Three independent reviewers abstracted data and determined eligibility and quality by consensus. Twenty-eight RCTs met the inclusion criteria. Studies were heterogeneous. Twenty RCTs compared ESWT energy levels and placebo and consistently showed that high-energy ESWT was significantly better than placebo in decreasing pain and improving function and resorption of calcifications in calcific tendinitis. No significant difference was found between ESWT and placebo in treatment of noncalcific tendinitis. The number of RCTs was small, and the studies were heterogeneous. High-energy ESWT is effective for improving pain and shoulder function in chronic calcific shoulder tendinitis and can result in complete resolution of calcifications. This therapy may be underutilized for a condition that can be difficult to manage. None.

Ultrasound imaging-guided percutaneous treatment of rotator cuff calcific tendinitis: success in short-term outcome

PubMed Central

Pelotti, Patrizia; Serraino, Salvatore; Battaglia, Milva; Bettelli, Graziano; Fusaro, Isabella; Guglielmi, Giuseppe; Rotini, Roberto; Albisinni, Ugo

2016-01-01

Objective: Rotator cuff calcific tendinitis (RCCT) is a common cause of shoulder pain in adults and typically presents as activity-related shoulder pain. Between non-surgical and surgical treatment options, today a few minimal invasive techniques are available to remove the calcific deposit, and they represent a cornerstone in the management of this painful clinical condition. The aim of the work was a retrospective evaluation of double-needle ultrasound-guided percutaneous fragmentation and lavage (DNL), focused on understanding the factors which are of major importance in determining a quick and good response at 1 month. Methods: A series of 147 patients affected by RCCT and suitable for DNL were evaluated. A systematic review of anamnestic, clinical and imaging data was performed in 144 shoulders treated in a single-centre setting. Clinical reports and imaging examinations were revisited. The inclusion criteria were submission to DNL, therefore fitness for the percutaneous procedure, and following 1-month follow-up. There was no exclusion owing to risk of bias. The treatment was defined as successful for constant shoulder modified score (CSS) improvement of >50% at 1 month. Results: In 70% of shoulders, the treatment resulted in a quick and significant reduction of symptoms (successful). On the whole, CSS increase at 1 month was estimated at 91.5 ± 69.1%. CSS variations were significantly related to age of patients (better results between 30 and 40 years old), calcification size (more relevant improvement for middle-sized calcifications, 12–17 mm), sonographic and radiographic features of calcific deposits (softer calcifications) and thickening of subacromial/subdeltoid bursa walls. In the final model of stepwise regression for CSS variation, ultrasound score pre-treatment and post-treatment, the distance between bursa and calcification before treatment and the size of post-treatment calcification area were shown to be independently correlated to

Association of inflammatory, lipid and mineral markers with cardiac calcification in older adults.

PubMed

Bortnick, Anna E; Bartz, Traci M; Ix, Joachim H; Chonchol, Michel; Reiner, Alexander; Cushman, Mary; Owens, David; Barasch, Eddy; Siscovick, David S; Gottdiener, John S; Kizer, Jorge R

2016-07-13

Calcification of the aortic valve and adjacent structures involves inflammatory, lipid and mineral metabolism pathways. We hypothesised that circulating biomarkers reflecting these pathways are associated with cardiac calcification in older adults. We investigated the associations of various biomarkers with valvular and annular calcification in the Cardiovascular Health Study. Of the 5888 participants, up to 3585 were eligible after exclusions for missing biomarker, covariate or echocardiographic data. We evaluated analytes reflecting lipid (lipoprotein (Lp) (a), Lp-associated phospholipase A 2 (LpPLA 2 ) mass and activity), inflammatory (interleukin-6, soluble (s) CD14) and mineral metabolism (fetuin-A, fibroblast growth factor (FGF)-23) pathways that were measured within 5 years of echocardiography. The relationships of plasma biomarkers with aortic valve calcification (AVC), aortic annular calcification (AAC) and mitral annular calcification (MAC) were assessed with relative risk (RR) regression. Calcification was prevalent: AVC 59%, AAC 45% and MAC 41%. After adjustment, Lp(a), LpPLA 2 mass and activity and sCD14 were positively associated with AVC. RRs for AVC per SD (95% CI) were as follows: Lp(a), 1.051 (1.022 to 1.081); LpPLA 2 mass, 1.036 (1.006 to 1.066) and LpPLA 2 activity, 1.037 (1.004 to 1.071); sCD14, 1.039 (1.005 to 1.073). FGF-23 was positively associated with MAC, 1.040 (1.004 to 1.078) and fetuin-A was negatively associated, 0.949 (0.911 to 0.989). No biomarkers were significantly associated with AAC. This study shows novel associations of circulating FGF-23 and fetuin-A with MAC, and LpPLA 2 and sCD14 with AVC, confirming that previously reported for Lp(a). Further investigation of Lp and inflammatory pathways may provide added insight into the aetiology of AVC, while study of phosphate regulation may illuminate the pathogenesis of MAC. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a

Variation in calcification rate of Acropora downingi relative to seasonal changes in environmental conditions in the northeastern Persian Gulf

NASA Astrophysics Data System (ADS)

Vajed Samiei, Jahangir; Saleh, Abolfazl; Shirvani, Arash; Sheijooni Fumani, Neda; Hashtroudi, Mehri; Pratchett, Morgan Stuart

2016-12-01

There is a strong interest in understanding how coral calcification varies with changing environmental conditions, especially given the projected changes in temperature and aragonite saturation due to climate change. This study explores in situ variation in calcification rates of Acropora downingi in the northeastern Persian Gulf relative to seasonal changes in temperature, irradiance and aragonite saturation state ( Ω arag). Calcification rates of A. downingi were highest in the spring and lowest in the winter, and intra-annual variation in calcification rate was significantly related to temperature ( r 2 = 0.30) and irradiance ( r 2 = 0.36), but not Ω arag ( r 2 = 0.02). Seasonal differences in temperature are obviously confounded by differences in other environmental conditions and vice versa. Therefore, we used published relationships from experimental studies to establish which environmental parameter(s) (temperature, irradiance, and/or Ω arag) placed greatest constraints on calcification rate (relative to the maximum spring rate) in each season. Variation in calcification rates was largely attributable to seasonal changes in irradiance and temperature (possibly 57.4 and 39.7% respectively). Therefore, we predict that ocean warming may lead to increased rates of calcification during winter, but decelerate calcification during spring, fall and especially summer, resulting in net deceleration of calcification for A. downingi in the Persian Gulf.

Serum gamma-glutamyltransferase activity is increased in patients with calcific aortic valve stenosis.

PubMed

Bozbas, Huseyin; Yildirir, Aylin; Demir, Ozlem; Cakmak, Abdulkadir; Karacaglar, Emir; Yilmaz, Mustafa; Eroglu, Serpil; Pirat, Bahar; Ozin, Bulent; Muderrisoglu, Haldun

2008-07-01

A growing body of data indicates an independent association between serum gamma-glutamyltransferase (GGT) activity, a marker of increased oxidative stress, and cardiovascular diseases. The process of calcific aortic valve disease has been shown to present characteristics of atherosclerosis. The study aim was to evaluate the possible role of serum GGT in patients with calcific aortic valve disease. The results of patients' echocardiography studies from 2005 for the presence of calcific aortic valve disease in the forms of aortic stenosis (AS) and aortic valve calcification (AVC) without significant valve stenosis, were retrospectively evaluated. Age-and gender-matched patients with normal aortic valve morphology were selected at random as a control group. A total of 383 patients was enrolled into the study (126 with AS, 133 with AVC, 124 controls). Serum GGT activity, along with other liver enzyme analyses and laboratory results, were determined and compared among the groups. Age, gender and clinical and laboratory results were similar among the three groups. Median serum GGT levels in the AS, AVC and control groups were 23.0 U/1 (mean 31.5 +/- 24.9 U/1), 22.0 U/1 (mean 27.6 +/- 18.6 U/) and 18.0 U/l (mean 22.4 +/- 16.4 U/l), respectively. Compared to controls, AS patients had significantly higher serum GGT and C-reactive protein levels, while the differences between AVC patients and controls for these parameters were not significant. The study results suggest that serum GGT activity is increased in patients with calcific AS. These increases seem to occur in advanced rather than milder forms of calcific aortic valve disease.

Pineal Calcification, Melatonin Production, Aging, Associated Health Consequences and Rejuvenation of the Pineal Gland.

PubMed

Tan, Dun Xian; Xu, Bing; Zhou, Xinjia; Reiter, Russel J

2018-01-31

The pineal gland is a unique organ that synthesizes melatonin as the signaling molecule of natural photoperiodic environment and as a potent neuronal protective antioxidant. An intact and functional pineal gland is necessary for preserving optimal human health. Unfortunately, this gland has the highest calcification rate among all organs and tissues of the human body. Pineal calcification jeopardizes melatonin's synthetic capacity and is associated with a variety of neuronal diseases. In the current review, we summarized the potential mechanisms of how this process may occur under pathological conditions or during aging. We hypothesized that pineal calcification is an active process and resembles in some respects of bone formation. The mesenchymal stem cells and melatonin participate in this process. Finally, we suggest that preservation of pineal health can be achieved by retarding its premature calcification or even rejuvenating the calcified gland.

Calcific tendinopathy of the rotator cuff: the correlation between pain and imaging features in symptomatic and asymptomatic female shoulders.

PubMed

Sansone, Valerio; Consonni, Olmo; Maiorano, Emanuele; Meroni, Roberto; Goddi, Alfredo

2016-01-01

To provide new epidemiological data regarding the prevalence, distribution and macroscopic features of shoulder rotator cuff calcific tendinopathy (calcific tendinopathy), and to identify the characteristics of calcific deposits associated with shoulder pain. Three hundred and two female volunteers (604 shoulders) who had been referred to a gynaecological clinic participated in the study. The subjects underwent a high-resolution ultrasonography of both shoulders, and those with a diagnosis of calcific tendinopathy compiled a standardized questionnaire relating to shoulder symptoms. We determined the prevalence of symptomatic and asymptomatic rotator cuff calcific tendinopathy, and compared differences in distribution and macroscopic features of the symptomatic and asymptomatic calcifications. The prevalence of calcific tendinopathy was 17.8% (103 shoulders). Ninety-five shoulders (15.7%) were symptomatic; of these, calcific tendinopathy was found in 34 shoulders (33%) on imaging. Of the 509 asymptomatic (84.3%) shoulders, calcific tendinopathy was observed in 69 cases (67%). Among tendons, supraspinatus (53.4%) and infraspinatus (54.6%) were the most frequently involved. The majority of calcific deposits were of maximum diameter between 2 and 5 mm (77.9%), and were linear in form (69.9%). The involvement of multiple tendons and a location in the supraspinatus tendon were found to be significantly correlated with pain (p = 0.023, p = 0.043 respectively), as were age (p = 0.041) and an excessive body mass index (p = 0.024). In this sample from the general population of working age females, both intrinsic factors (location in supraspinatus, multiple tendon involvement) and extrinsic variables (age, abnormally high BMI) were correlated with pain in calcific tendinopathy. Level III, cross-sectional study, prevalence study.

Media calcification, low erythrocyte magnesium, altered plasma magnesium, and calcium homeostasis following grafting of the thoracic aorta to the infrarenal aorta in the rat--differential preventive effects of long-term oral magnesium supplementation alone and in combination with alkali.

PubMed

Schwille, P O; Schmiedl, A; Schwille, R; Brunner, P; Kissler, H; Cesnjevar, R; Gepp, H

2003-03-01

Calcifications in arterial media are clinically well documented, but the role played by magnesium in pathophysiology and therapy is uncertain. To clarify this, an animal model in which the juxtacardial aorta was grafted to the infrarenal aorta, and the subsequent calcifications in the media of the graft and their response to oral supplementation with three magnesium-containing and alkalinizing preparations was investigated. Groups of highly inbred rats were formed as follows: sham-operation (Sham, n = 12), aorta transplantation (ATx, n = 12), ATx + magnesium citrate (MgC, n = 12), ATx + MgC + potassium citrate (MgCPC, n = 12), ATx + MgC + MgCPC (MgCPCSB, n = 12). At 84 (+/-2) days after ATx with or without treatment the following observations were made: (1) weight gain and general status were normal; (2) ATx rats developed massive media calcification, mineral accumulation in the graft, decreased erythrocyte magnesium and plasma parathyroid hormone, and increased plasma ionized magnesium and calcium, and uric acid; (3) Mg-treated rats developed variable degrees of metabolic alkalosis, but only MgCPCSB supplementation prevented calcifications. Additional findings after ATx alone were: imbalance in endothelin and nitric oxide production, the mineral deposited in media was poorly crystallized calcium phosphate, calcium exchange between plasma and graft, and bone resorption were unchanged. The superior anti-calcification effect of MgCPCSB was characterized by complete restoration of normal extracellular mineral homeostasis and uric acid, but sub-optimal normalization of erythrocyte magnesium. It was concluded that in the rat: (1) ATx causes loss of cellular magnesium, excess of extracellular magnesium and calcium in the presence of apparently unchanged bone resorption, and increased uricemia; (2) ATx facilitates enhanced influx of calcium into vascular tissue, leading to calcium phosphate deposition in the media; (3) ATx-induced calcification is prevented by dietary

Outcomes of truncal vascular injuries in children

PubMed Central

Allison, Nathan D.; Anderson, Christopher M.; Shah, Shinil K.; Lally, Kevin P.; Hayes-Jordan, Andrea; Tsao, Kuo-Jen; Andrassy, Richard J.; Cox, Charles S.

2011-01-01

Background Pediatric truncal vascular injuries occur infrequently and have a reported mortality rate of 30% to 50%. This report examines the demographics, mechanisms of injury, associated trauma, and outcome of patients presenting for the past 10 years at a single institution with truncal vascular injuries. Methods A retrospective review (1997-2006) of a pediatric trauma registry at a single institution was undertaken. Results Seventy-five truncal vascular injuries occurred in 57 patients (age, 12 ± 3 years); the injury mechanisms were penetrating in 37%. Concomitant injuries occurred with 76%, 62%, and 43% of abdominal, thoracic, and neck vascular injuries, respectively. Nonvascular complications occurred more frequently in patients with abdominal vascular injuries who were hemodynamically unstable on presentation. All patients with thoracic vascular injuries presenting with hemodynamic instability died. In patients with neck vascular injuries, 1 of 2 patients who were hemodynamically unstable died, compared to 1 of 12 patients who died in those who presented hemodynamically stable. Overall survival was 75%. Conclusions Survival and complications of pediatric truncal vascular injury are related to hemodynamic status at the time of presentation. Associated injuries are higher with trauma involving the abdomen. PMID:19853755

Evaluation and nonsurgical management of rotator cuff calcific tendinopathy.

PubMed

Greis, Ari C; Derrington, Stephen M; McAuliffe, Matthew

2015-04-01

Rotator cuff calcific tendinopathy is a common finding that accounts for about 7% of patients with shoulder pain. There are numerous theories on the pathogenesis of rotator cuff calcific tendinopathy. The diagnosis is confirmed with radiography, MRI or ultrasound. There are numerous conservative treatment options available and most patients can be managed successfully without surgical intervention. Nonsteroidal anti-inflammatory drugs and multiple modalities are often used to manage pain and inflammation; physical therapy can help improve scapular mechanics and decrease dynamic impingement; ultrasound-guided needle aspiration and lavage techniques can provide long-term improvement in pain and function in these patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Efficacy of ultrasound-guided percutaneous needle treatment of calcific tendinitis.

PubMed

Vignesh, K Nithin; McDowall, Adam; Simunovic, Nicole; Bhandari, Mohit; Choudur, Hema N

2015-01-01

The purpose of this study was to conduct a systematic review of the efficacy of ultrasound-guided needle lavage in treating calcific tendinitis. Two independent assessors searched medical databases and screened studies for eligibility. Eleven articles were included. Heterogeneity among included studies precluded meta-analysis. Results of randomized controlled trials suggested no difference in pain relief between needle lavage and other interventions, but the studies were of low quality. Additional high-quality evidence is required to determine the relative efficacy of ultrasound-guided needle lavage in the management of calcific tendinitis of the rotator cuff.

[Calcificated necrotic inflammatory granuloma after intradiscal injection of triamcinolone hexacetonide].

PubMed

Menei, P; Fournier, D; Alhayek, G; Mercier, P; François, H; Audran, M; Guy, G

1991-10-01

Recently, it has been demonstrated that symptomatic epidural calcifications represent a complication of intradiscal injection of triamcinolone hexacetonide (Hexatrione). Out of our three cases, pathological examination showed lesions of necrosis with granulomatous inflammatory reaction and bone metaplasia. Necrosis seems to be the primary cause of calcifications so we propose to call the lesion inflammatory and necrotic granuloma. The incidence of these granulomas is unknown. They are unpredictable and appear with a mean range of a year following the intradiscal injection. The treatment is surgery if they become symptomatic.

Using Na3PO4 to Enhance In vitro Animal Models of Aortic Valve Calcification.

PubMed

Lerman, Daniel Alejandro; Prasad, Sai; Alotti, Nasri

2016-01-07

The pathogenesis of calcific aortic valvular disease (CAVD) involves an active inflammatory process of valvular interstitial cells (VICs) characterized by the activation of specific osteogenic signaling pathways and apoptosis. This process can be studied by analyzing certain molecular markers and gene expression pathways of spontaneous calcification. The purpose of our study is to investigate the role of sodium phosphate (Na3PO4) as a calcification promoter, with the aim of improving in vitro animal models for testing potential calcification inhibitors. VICs were extracted from 6 healthy 6-month-old fresh porcine hearts by serial collagenase digestion. Quantitative polymerase chain reaction (qPCR) was used to quantify trans-differentiation of genes of interest during spontaneous calcification of VICs. Spontaneous calcification of VICs was increased by adding Na 3 PO 4 (3 mM, pH 7.4). The degree of calcification was estimated by Alizarin Red staining for calcium deposition, and Sirius Red staining for collagen. Colorimetric techniques were used to determine calcium and collagen deposition quantitatively. Additionally, the enzymatic activity of alkaline phosphatase (ALP) was measured by a kinetic assay. For statistical analysis we used SPSS and Microsoft Office Excel 2013. Porcine VICs calcify spontaneously with demonstrable calcium and collagen deposition. In this study we observed an increase of calcium and collagen deposition from day 0 to day 14 (calcium: 376%; P<0.001, collagen: 3553%; P<0.001). qPCR analysis of mRNA by day 14 showed the following results: α-actin, a marker of myoblast phenotype, was increased to 1.6-fold; P<0.001. Runx2, an osteoblast marker, rose to 1.3 fold; P<0.05, TGF-β, a promoter of osteogenesis, increased to 3.2-fold; P<0.001, and RhoA, a regulator of nodular formation in myoblasts, increased to 4.5-fold; P<0.001, compared to their levels at day 0. RANKL mRNA and calponin did not change significantly. Treatment of porcine VICs with Na3

Impact of chocolate liquor on vascular lesions in apoE-knockout mice.

PubMed

Yazdekhasti, Narges; Brandsch, Corinna; Hirche, Frank; Kühn, Julia; Schloesser, Anke; Esatbeyoglu, Tuba; Huebbe, Patricia; Wolffram, Siegfried; Rimbach, Gerald; Stangl, Gabriele I

2017-10-15

Cocoa polyphenols are thought to reduce the risk of cardiovascular diseases. Thus, cocoa-containing foods may have significant health benefits. Here, we studied the impact of chocolate liquor on vascular lesion development and plaque composition in a mouse model of atherosclerosis. Apolipoprotein E (apoE)-knockout mice were assigned to two groups and fed a Western diet that contained 250 g/kg of either chocolate liquor or a polyphenol-free isoenergetic control paste for 16 weeks. In addition to fat, protein, and fibers, the chocolate liquor contained 2 g/kg of polyphenols. Compared with the control group, mice fed the chocolate liquor had larger plaque areas in the descending aorta and aortic root, which were attributed to a higher mass of vascular smooth muscle cells (VSMCs) and collagen. Vascular lipid deposits and calcification areas did not differ between the two groups. The aortic tissue level of interleukin-6 (IL-6) mRNA was 5-fold higher in the mice fed chocolate liquor than in the control mice. Chocolate-fed mice exhibited an increased hepatic saturated to polyunsaturated fatty acid ratio than the controls. Although the chocolate liquor contained 14 µg/kg of vitamin D 2 , the chocolate liquor-fed mice did not have measurable 25-hydroxyvitamin D 2 in the serum. These mice even showed a 25% reduction in the level of 25-hydroxyvitamin D 3 compared with the control mice. Overall, present data may contribute to our understanding how chocolate constituents can impact vascular lesion development. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Environmental control on Emiliania huxleyi coccolithophore calcification in the Mediterranean Sea

NASA Astrophysics Data System (ADS)

D'Amario, Barbara; Grelaud, Michael; Ziveri, Patrizia

2016-04-01

The Mediterranean Sea, a "natural laboratory" characterized by strong environmental gradients, is likely to undergo serious alterations due to climate change and ocean acidification. These processes are expected to affect also phytoplankton distribution. Coccolithophores are the only phytoplankton calcifying group and laboratory studies on E. huxleyi, the most abundant and widely distributed species of coccolithophores worldwide, yield strain-specific results. Culture experiments must be integrated with observations in the natural environment to understand existing interactions between drivers, and to verify population structures in different areas. Two transects spanning the south-western and south-eastern basins have been investigated, combining data from April 2011 (Meteor cruise M84/3) and May 2013 (MedSeA cruise). E. huxleyi coccolith morphometry was analyzed to determine average mass and length. These results were then compared with morphological observations performed on the largely dominant E. huxleyi Type A through scanning electron microscope (SEM). We distinguished four main calcification morphologies within E. huxleyi Type A: low-calcified (A1), medium-calcified (A2), high-calcified with closed central area (A3a), and open central area (A3b). E. huxleyi coccolith mass was strongly and positively correlated with the relative abundance of a particular morphology. Moreover, the calcification morphologies were preferentially distributed in the Mediterranean according to specific combinations of environmental variables, which included the carbonate chemistry system. The distribution of E. huxleyi Type A calcification morphologies in the Mediterranean is likely to be influenced by climate changes. Coccolithophore calcification degree is connected to the carbon cycle through photosynthesis / calcification ratio and sedimentation (particulate inorganic and organic carbon reaching the seafloor). This study aims to provide a basis for future investigations on the

Decoupling between the response of coral calcifying fluid pH and calcification to ocean acidification.

PubMed

Comeau, S; Cornwall, C E; McCulloch, M T

2017-08-08

Evaluating the factors responsible for differing species-specific sensitivities to declining seawater pH is central to understanding the mechanisms via which ocean acidification (OA) affects coral calcification. We report here the results of an experiment comparing the responses of the coral Acropora yongei and Pocillopora damicornis to differing pH levels (8.09, 7.81, and 7.63) over an 8-week period. Calcification of A. youngei was reduced by 35% at pH 7.63, while calcification of P. damicornis was unaffected. The pH in the calcifying fluid (pH cf ) was determined using δ 11 B systematics, and for both species pH cf declined slightly with seawater pH, with the decrease being more pronounced in P. damicornis. The dissolved inorganic carbon concentration at the site of calcification (DIC cf ) was estimated using geochemical proxies (B/Ca and δ 11 B) and found to be double that of seawater DIC, and increased in both species as seawater pH decreased. As a consequence, the decline of the saturation state at the site of calcification (Ω cf ) with OA was partially moderated by the DIC cf increase. These results highlight that while pH cf , DIC cf and Ω cf are important in the mineralization process, some corals are able to maintain their calcification rates despite shifts in their calcifying fluid carbonate chemistry.

Association between asymptomatic inflammatory prostatitis NIH category IV and prostatic calcification in patients with obstructive benign prostatic hyperplasia.

PubMed

Engelhardt, Paul F; Seklehner, Stephan; Brustmann, Herman; Riedl, Claus R; Lusuardi, Lukas

2016-06-01

The aim of this study was to evaluate the incidence of prostatic calcification and prostatitis NIH category IV in patients with obstructive BPH. Ninety-six patients with obstructive BPH who had undergone transurethral electroresection of the prostate gland were evaluated. In accordance with a preoperative transrectal ultrasound examination, patients were divided into one group with prostatic calcification (N.=31) and one without (N.=65). Prostatitis NIH category IV was classified according to the grading system by Irani. Correlations between the incidence of prostatic calcification, histological prostatitis, PSA, uric acid, cholesterol, triglycerides, CRP, IPSS, IIEF-25, and NIC-CPSI were analyzed. A stone analysis of prostatic calcification was performed using X-ray powder diffraction. Sixty-nine (71.9%) patients had NIH category IV prostatitis, accounting for 83.9% of those with prostatic calcification versus 66.1% of those without (P<0.04). Significant correlations were found between prostatic calcification and the severity of inflammation (P<0.02) as well as the NIH-CPSI subdomain of urinary symptoms (P<0.02). The only predictor for prostatic calcifications were elevated levels of uric acid. Such patients were 1.4times more likely of having calcifications in the prostate gland (OR=1.4, P<0.047). Stone analysis revealed the following: apatite in 41.7%, whewellite in 29.2%, weddellite and brushite in 8.7% each, whitlockite, apatite/whewellite and organic substances in 4.2%. On ultrasound examination, one third of patients who were treated with TURP for obstructive BPH had prostatic calcification. These were significantly more common in patients with NIH category IV prostatitis.

Impact of calcification state on the inherent optical properties of Emiliania huxleyi coccoliths and coccolithophores

NASA Astrophysics Data System (ADS)

Bi, Lei; Yang, Ping

2015-04-01

Understanding the inherent optical properties (IOPs) of coccoliths and coccolithophores is important in oceanic radiative transfer simulations and remote sensing implementations. In this study, the invariant imbedding T-matrix method (II-TM) is employed to investigate the IOPs of coccoliths and coccolithophores. The Emiliania huxleyi (Ehux) coccolith and coccolithophore models are built based on observed biometric parameters including the eccentricity, the number of slits, and the rim width of detached coccoliths. The calcification state that specifies the amount of calcium of a single coccolith is critical in the determination of the size-volume/mass relationship (note, the volume/mass of coccoltihs at different calcification states are different although the diameters are the same). The present results show that the calcification state, namely, under-calcification, normal-calcification, or over-calcification, significantly influences the backscattering cross section and the phase matrix. Furthermore, the linear depolarization ratio of the light scattered by coccoliths is sensitive to the degree of calcification, and provides a potentially valuable parameter for interpreting oceanic remote sensing data. The phase function of an ensemble of randomly oriented coccolithophores has a similar pattern to that of individual coccoliths, but the forward scattering is dominant in the coccolithophores due to the large geometric cross sections. The linear depolarization ratio associated with coccolithophores is found to be larger than that for coccoliths as polarization is more sensitive to multiple scattering than the phase function. The simulated coccolithophore phase matrix numerical results are compared with laboratory measurements. For scattering angles larger than 100°, an increase of the phase function with respect to the scattering angle is confirmed based on the present coccolithophore model while the spherical approximation fails.

Correlation of inflammation assessed by 18F-FDG PET, active mineral deposition assessed by 18F-fluoride PET, and vascular calcification in atherosclerotic plaque: a dual-tracer PET/CT study.

PubMed

Derlin, Thorsten; Tóth, Zoltán; Papp, László; Wisotzki, Christian; Apostolova, Ivayla; Habermann, Christian R; Mester, Janos; Klutmann, Susanne

2011-07-01

Formation and progression of atherosclerotic plaque is a dynamic and complex process involving various pathophysiologic steps including inflammation and calcification. The purpose of this study was to compare macrophage activity as determined by (18)F-FDG PET and ongoing mineral deposition as measured by (18)F-sodium fluoride PET in atherosclerotic plaque and to correlate these findings with calcified plaque burden as assessed by CT. Forty-five patients were examined by whole-body (18)F-FDG PET, (18)F-sodium fluoride PET, and CT. Tracer uptake in various arterial segments was analyzed both qualitatively and semiquantitatively by measuring the blood-pool-corrected standardized uptake value (target-to-background ratio [TBR]). The pattern of tracer uptake in atherosclerotic lesions was compared after color-coded multistudy image fusion of PET and CT studies. The Fisher exact test and the Spearman correlation coefficient r(s) were used for statistical analysis of image-based results and cardiovascular risk factors. Intra- and interrater reproducibility were evaluated using the Cohen κ. (18)F-sodium fluoride uptake was observed at 105 sites in 27 (60%) of the 45 study patients, and mean TBR was 2.3 ± 0.7. (18)F-FDG uptake was seen at 124 sites in 34 (75.6%) patients, and mean TBR was 1.5 ± 0.3. Calcified atherosclerotic lesions were observed at 503 sites in 34 (75.6%) patients. Eighty-one (77.1%) of the 105 lesions with marked (18)F-sodium fluoride uptake and only 18 (14.5%) of the 124 lesions with (18)F-FDG accumulation were colocalized with arterial calcification. Coincident uptake of both (18)F-sodium fluoride and (18)F-FDG was observed in only 14 (6.5%) of the 215 arterial lesions with radiotracer accumulation. PET/CT with (18)F-FDG and (18)F-sodium fluoride may allow evaluation of distinct pathophysiologic processes in atherosclerotic lesions and might provide information on the complex interactions involved in formation and progression of atherosclerotic plaque.

Genome-wide association study of coronary and aortic calcification in lung cancer screening CT

NASA Astrophysics Data System (ADS)

de Vos, Bob D.; van Setten, Jessica; de Jong, Pim A.; Mali, Willem P.; Oudkerk, Matthijs; Viergever, Max A.; Išgum, Ivana

2016-03-01

Arterial calcification has been related to cardiovascular disease (CVD) and osteoporosis. However, little is known about the role of genetics and exact pathways leading to arterial calcification and its relation to bone density changes indicating osteoporosis. In this study, we conducted a genome-wide association study of arterial calcification burden, followed by a look-up of known single nucleotide polymorphisms (SNPs) for coronary artery disease (CAD) and myocardial infarction (MI), and bone mineral density (BMD) to test for a shared genetic basis between the traits. The study included a subcohort of the Dutch-Belgian lung cancer screening trial comprised of 2,561 participants. Participants underwent baseline CT screening in one of two hospitals participating in the trial. Low-dose chest CT images were acquired without contrast enhancement and without ECG-synchronization. In these images coronary and aortic calcifications were identified automatically. Subsequently, the detected calcifications were quantified using coronary artery calcium Agatston and volume scores. Genotype data was available for these participants. A genome-wide association study was conducted on 10,220,814 SNPs using a linear regression model. To reduce multiple testing burden, known CAD/MI and BMD SNPs were specifically tested (45 SNPs from the CARDIoGRAMplusC4D consortium and 60 SNPS from the GEFOS consortium). No novel significant SNPs were found. Significant enrichment for CAD/MI SNPs was observed in testing Agatston and coronary artery calcium volume scores. Moreover, a significant enrichment of BMD SNPs was shown in aortic calcium volume scores. This may indicate genetic relation of BMD SNPs and arterial calcification burden.

Hilar cholangiocarcinoma with intratumoral calcification: A case report.

PubMed

Inoko, Kazuho; Tsuchikawa, Takahiro; Noji, Takehiro; Kurashima, Yo; Ebihara, Yuma; Tamoto, Eiji; Nakamura, Toru; Murakami, Soichi; Okamura, Keisuke; Shichinohe, Toshiaki; Hirano, Satoshi

2015-10-14

This report describes a rare case of hilar cholangiocarcinoma with intratumoral calcification that mimicked hepatolithiasis. A 73-year-old man presented to a local hospital with a calcified lesion in the hepatic hilum. At first, hepatolithiasis was diagnosed, and he underwent endoscopic stone extraction via the trans-papillary route. This treatment strategy failed due to biliary stricture. He was referred to our hospital, and further examination suggested the existence of cholangiocarcinoma. He underwent left hepatectomy with caudate lobectomy and extrahepatic bile duct resection. Pathological examination revealed hilar cholangiocarcinoma with intratumoral calcification, while no stones were found. To the best of our knowledge, only one case of calcified hilar cholangiocarcinoma has been previously reported in the literature. Here, we report a rare case of calcified hilar cholangiocarcinoma and reveal its clinicopathologic features.

Diagnostic value of contrast-enhanced ultrasound in thyroid nodules with calcification.

PubMed

Jiang, Jue; Shang, Xu; Wang, Hua; Xu, Yong-Bo; Gao, Ya; Zhou, Qi

2015-03-01

The aim of this study was to investigate the diagnostic values of conventional ultrasound and contrast-enhanced ultrasound (CEUS) in benign and malignant thyroid nodules with calcification. Conventional ultrasound and CEUS were performed in 122 patients with thyroid nodules with calcification. The thyroid nodules were characterized as benign or malignant by pathological diagnosis. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accordance rate of the two imaging methods were determined. The area under the receiver operating characteristics curve (AUC) was used to assess the diagnostic values of the two imaging methods. In 122 cases of thyroid nodules with calcification, 73 benign nodules and 49 malignant nodules were verified by pathological diagnosis. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accordance rate of conventional ultrasound were 50%, 77%, 59%, 69%, and 66%, respectively, and those of CEUS were 90%, 92%, 88%, 93%, and 91%, respectively. There were significant differences between the two imaging methods. AUCs of conventional ultrasound and CEUS were 0.628 ± 0.052 and 0.908 ± 0.031, suggesting low and high diagnostic values, respectively. CEUS has high diagnostic values, being significantly greater than those of conventional ultrasound, in differential diagnosis of benign and malignant thyroid nodules with calcification. Copyright © 2014. Published by Elsevier Taiwan.

Coralline algae elevate pH at the site of calcification under ocean acidification.

PubMed

Cornwall, Christopher E; Comeau, Steeve; McCulloch, Malcolm T

2017-10-01

Coralline algae provide important ecosystem services but are susceptible to the impacts of ocean acidification. However, the mechanisms are uncertain, and the magnitude is species specific. Here, we assess whether species-specific responses to ocean acidification of coralline algae are related to differences in pH at the site of calcification within the calcifying fluid/medium (pH cf ) using δ 11 B as a proxy. Declines in δ 11 B for all three species are consistent with shifts in δ 11 B expected if B(OH) 4 - was incorporated during precipitation. In particular, the δ 11 B ratio in Amphiroa anceps was too low to allow for reasonable pH cf values if B(OH) 3 rather than B(OH) 4 - was directly incorporated from the calcifying fluid. This points towards δ 11 B being a reliable proxy for pH cf for coralline algal calcite and that if B(OH) 3 is present in detectable proportions, it can be attributed to secondary postincorporation transformation of B(OH) 4 - . We thus show that pH cf is elevated during calcification and that the extent is species specific. The net calcification of two species of coralline algae (Sporolithon durum, and Amphiroa anceps) declined under elevated CO 2 , as did their pH cf . Neogoniolithon sp. had the highest pH cf , and most constant calcification rates, with the decrease in pH cf being ¼ that of seawater pH in the treatments, demonstrating a control of coralline algae on carbonate chemistry at their site of calcification. The discovery that coralline algae upregulate pH cf under ocean acidification is physiologically important and should be included in future models involving calcification. © 2017 John Wiley & Sons Ltd.

Denosumab could be a Potential Inhibitor of Valvular Interstitial Cells Calcification in vitro.

PubMed

Lerman, Daniel Alejandro; Prasad, Sai; Alotti, Nasri

2016-01-03

Denosumab is a fully human monoclonal antibody and novel antiresorptive agent that works by binding receptor activator of nuclear factor kappa-β ligand (RANKL) and inhibiting the signaling cascade that causes osteoclast maturation, activity, and survival. We aimed to elucidate the effect of Denosumab in the process of spontaneous and induced calcification in an in vitro porcine valvular interstitial cells (VICs) model. VICs were extracted from fresh porcine hearts by serial collagenase digestion. Spontaneous calcification of VICs was increased in vitro by adding Na 3 PO 4 (3 mM, pH 7.4) and different concentrations (0.1, 1 and 10 ng/ml) of transforming growth factor beta (TGFß). The degree of calcification before and after treatment with Denosumab was estimated by Alizarin Red staining for calcium deposition, and Sirius Red staining for collagen. Colorimetric techniques were used to determine calcium and collagen deposition quantitatively. For statistical analysis we used SPSS and Microsoft Office Excel 2013. Porcine aortic VICs in vitro were induced to calcify by the addition of either 3 mM Na 3 PO 4 , showing a 5.2 fold increase by 14 days (P<0.001), or 3 mM Na 3 PO 4 + 10 ng/ml of TGFβ, showing a 7 fold increase by Day 14 (P<0.001). Denosumab inhibited induced calcification by 3 mM Na 3 PO 4 and 3 mM Na 3 PO 4 with the addition of TGFß at either 0.1, 1 or 10 ng/ml to basal levels only at a concentration of 50 μg/ml (P<0.001). This study has proved that Denosumab could be a potential inhibitor of the calcification of VICs in vitro . A fuller understanding of the actions of Denosumab may identify a novel therapeutic strategy for clinical intervention against aortic valve calcification and aortic stenosis.

Calcification rates of the massive coral Siderastrea siderea and crustose coralline algae along the Florida Keys (USA) outer-reef tract

USGS Publications Warehouse

Kuffner, I.B.; Hickey, T.D.; Morrison, J.M.

2013-01-01

Coral reefs are degrading on a global scale, and rates of reef-organism calcification are predicted to decline due to ocean warming and acidification. Systematic measurements of calcification over space and time are necessary to detect change resulting from environmental stressors. We established a network of calcification monitoring stations at four managed reefs along the outer Florida Keys Reef Tract (FKRT) from Miami to the Dry Tortugas. Eighty colonies (in two sequential sets of 40) of the reef-building coral, Siderastrea siderea, were transplanted to fixed apparatus that allowed repetitive detachment for buoyant weighing every 6 months. Algal-recruitment tiles were also deployed during each weighing interval to measure net calcification of the crustose coralline algal (CCA) community. Coral-calcification rates were an order of magnitude greater than those of CCA. Rates of coral calcification were seasonal (summer calcification was 53% greater than winter), and corals in the Dry Tortugas calcified 48% faster than those at the other three sites. Linear extension rates were also highest in the Dry Tortugas, whereas percent area of the coral skeletons excavated by bioeroding fauna was lowest. The spatial patterns in net coral calcification revealed here correlate well with Holocene reef thickness along the FKRT and, in part, support the “inimical waters hypothesis” proposed by Ginsburg, Hudson, and Shinn almost 50 yrs ago to explain reef development in this region. Due to the homogeneity in coral-calcification rates among the three main Keys sites, we recommend refinement of this hypothesis and suggest that water-quality variables (e.g., carbonate mineral saturation state, dissolved and particulate organic matter, light attenuation) be monitored alongside calcification in future studies. Our results demonstrate that our calcification monitoring network presents a feasible and worthwhile approach to quantifying potential impacts of ocean acidification

Calcification rates of the massive coral Siderastrea siderea and crustose coralline algae along the Florida Keys (USA) outer-reef tract

NASA Astrophysics Data System (ADS)

Kuffner, I. B.; Hickey, T. D.; Morrison, J. M.

2013-12-01

Coral reefs are degrading on a global scale, and rates of reef-organism calcification are predicted to decline due to ocean warming and acidification. Systematic measurements of calcification over space and time are necessary to detect change resulting from environmental stressors. We established a network of calcification monitoring stations at four managed reefs along the outer Florida Keys Reef Tract (FKRT) from Miami to the Dry Tortugas. Eighty colonies (in two sequential sets of 40) of the reef-building coral, Siderastrea siderea, were transplanted to fixed apparatus that allowed repetitive detachment for buoyant weighing every 6 months. Algal-recruitment tiles were also deployed during each weighing interval to measure net calcification of the crustose coralline algal (CCA) community. Coral-calcification rates were an order of magnitude greater than those of CCA. Rates of coral calcification were seasonal (summer calcification was 53 % greater than winter), and corals in the Dry Tortugas calcified 48 % faster than those at the other three sites. Linear extension rates were also highest in the Dry Tortugas, whereas percent area of the coral skeletons excavated by bioeroding fauna was lowest. The spatial patterns in net coral calcification revealed here correlate well with Holocene reef thickness along the FKRT and, in part, support the "inimical waters hypothesis" proposed by Ginsburg, Hudson, and Shinn almost 50 yrs ago to explain reef development in this region. Due to the homogeneity in coral-calcification rates among the three main Keys sites, we recommend refinement of this hypothesis and suggest that water-quality variables (e.g., carbonate mineral saturation state, dissolved and particulate organic matter, light attenuation) be monitored alongside calcification in future studies. Our results demonstrate that our calcification monitoring network presents a feasible and worthwhile approach to quantifying potential impacts of ocean acidification, warming

Cerebroretinal microangiopathy with calcifications and cysts associated with CTC1 and NDP mutations.

PubMed

Romaniello, Romina; Arrigoni, Filippo; Citterio, Andrea; Tonelli, Alessandra; Sforzini, Cinzia; Rizzari, Carmelo; Pessina, Marco; Triulzi, Fabio; Bassi, Maria Teresa; Borgatti, Renato

2013-12-01

Mutations in the conserved telomere maintenance component 1 (CTC1) gene were recently described in Coats plus syndrome and in cerebroretinal microangiopathy with calcifications and cysts. Norrie disease protein (NDP) gene was found mutated in Norrie disease, in Familial Exudative Vitreoretinopathy, and in Coats syndrome. Here we describe a boy affected by Norrie disease who developed typical features of cerebroretinal microangiopathy with calcifications and cysts. Direct sequencing of the CTC1 and NDP genes in this patient shows the presence of compound heterozygosity for 2 mutations in CTC1 (c.775G>A, pV259M and a novel microdeletion c.1213delG) and a missense mutation in the NDP gene (c.182T>C, p.L61P). Based on these genetic findings and on the expression of both genes in endothelial cells, we postulate that microangiopathy might be a primary underlying pathologic abnormality in cerebroretinal microangiopathy with calcifications and cysts. This hypothesis is further supported by magnetic resonance imaging (MRI) data showing multiple minute calcifications in the deep gray nuclei and in terminal arteriolar zones.

A Possible Role for Vitamin C in Coral Calcification

NASA Astrophysics Data System (ADS)

Rosenthal, J. J.; Roberson, L.; Vazquez, N.

2016-02-01

Despite the importance of coral reefs to tropical, marine ecosystems, the biological components of the calcification process are poorly understood. Because calcification must involve the delivery of organic and inorganic components across cell membranes, we postulate that it has similar features to epithelial and neuronal transport mechanisms in vertebrates. Accordingly, we are interested in identifying the specific membrane transporters underlying skeleton formation. As a model, we are using larvae from the ubiquitous Caribbean species Porites astreoides, a rapidly growing stony coral that is resistant to anthropogenic stressors. Using Illumina RNAseq, we assembled a larval transcriptome and compared gene expression between swimming larvae and recently settled ones that had just commenced the process of calcification. As expected, we identified many ion transporter, pump and channel transcripts that were upregulated in settled larvae. It was surprising, however, to find that the most upregulated transcript appeared to encode a Na-dependent Vitamin C transporter (SLC23A). In vertebrates, SLC23A transporters play a vital role in bone morphogenesis where Vitamin C is an essential cofactor for enzymes that condition collagen precursors for assembly into mature molecules. In corals, collagen has been identified as a component of the skeleton's extracellular matrix. Using in situ hybridization, we showed that the P. astreoides SLC23A messages were expressed in regions adjacent to rapid skeleton formation, on the aboral surface and septa of settled larvae. To confirm that the coral clone is indeed a Vitamin C transporter, we expressed it in Xenopus oocytes and studied its activity using voltage-clamp. Preliminary data demonstrate that it induces a current that is activated by Na and Vitamin C. This approach will help us better understand the molecular mechanisms underlying calcification and how they might respond to environmental change.

Progressive renal papillary calcification and ureteral stone formation in mice deficient for Tamm-Horsfall protein

PubMed Central

Liu, Yan; Mo, Lan; Goldfarb, David S.; Evan, Andrew P.; Liang, Fengxia; Khan, Saeed R.; Lieske, John C.

2010-01-01

Mammalian urine contains a range of macromolecule proteins that play critical roles in renal stone formation, among which Tamm-Horsfall protein (THP) is by far the most abundant. While THP is a potent inhibitor of crystal aggregation in vitro and its ablation in vivo predisposes one of the two existing mouse models to spontaneous intrarenal calcium crystallization, key controversies remain regarding the role of THP in nephrolithiasis. By carrying out a long-range follow-up of more than 250 THP-null mice and their wild-type controls, we demonstrate here that renal calcification is a highly consistent phenotype of the THP-null mice that is age and partially gene dosage dependent, but is gender and genetic background independent. Renal calcification in THP-null mice is progressive, and by 15 mo over 85% of all the THP-null mice develop spontaneous intrarenal crystals. The crystals consist primarily of calcium phosphate in the form of hydroxyapatite, are located more frequently in the interstitial space of the renal papillae than intratubularly, particularly in older animals, and lack accompanying inflammatory cell infiltration. The interstitial deposits of hydroxyapatite observed in THP-null mice bear strong resemblances to the renal crystals found in human kidneys bearing idiopathic calcium oxalate stones. Compared with 24-h urine from the wild-type mice, that of THP-null mice is supersaturated with brushite (calcium phosphate), a stone precursor, and has reduced urinary excretion of citrate, a stone inhibitor. While less frequent than renal calcinosis, renal pelvic and ureteral stones and hydronephrosis occur in the aged THP-null mice. These results provide direct in vivo evidence indicating that normal THP plays an important role in defending the urinary system against calcification and suggest that reduced expression and/or decreased function of THP could contribute to nephrolithiasis. PMID:20591941

Coral reef calcification: carbonate, bicarbonate and proton flux under conditions of increasing ocean acidification.

PubMed

Jokiel, P L

2013-08-07

Data on calcification rate of coral and crustose coralline algae were used to test the proton flux model of calcification. There was a significant correlation between calcification (G) and the ratio of dissolved inorganic carbon (DIC) to proton concentration ([DIC] : [H(+)] ratio). The ratio is tightly correlated with [CO3(2-)] and with aragonite saturation state (Ωa). An argument is presented that correlation does not prove cause and effect, and that Ωa and [CO3(2-)] have no basic physiological meaning on coral reefs other than a correlation with [DIC] : [H(+)] ratio, which is the driver of G.

Dystrophic Calcification in the Epidural and Extraforaminal Space Caused by Repetitive Triamcinolone Acetonide Injections

PubMed Central

Chung, Sang-Bong; Kim, Ki-Jeong; Kim, Hyun-Jib

2011-01-01

The authors report a case of epidural and extraforaminal calcification caused by repetitive triamcinolone acetonide injections. A 66-year-old woman was admitted presenting with lower extremity weakness and radiating pain in her left leg. Ten months before admission, the patient was diagnosed as having an L4-5 spinal stenosis and underwent anterior lumbar interbody fusion followed by posterior fixation. Her symptoms had been sustained and she did not respond to transforaminal steroid injections. Repetitive injections (10 times) had been performed on the L4-5 level for six months. She had been taking bisphosphonate as an antiresorptive agent for ten months after surgery. Calcification in the ventral epidural and extraforaminal space was detected. The gritty particles were removed during decompressive surgery and these were proven to be a dystrophic calcification. The patient recovered from weakness and radiating leg pain. Repetitive triamcinolone acetonide injections after discectomy may be the cause of dystrophic calcification not only in the degenerated residual disc, but also in the posterior longitudinal ligament. Possible mechanisms may include the toxicity of preservatives and the insolubility of triamcinolone acetonide. We should consider that repetitive triamcinolone injections in the postdisectomy state may cause intraspinal ossification and calcification. PMID:22053235

Effects of Disturbed Flow on Vascular Endothelium: Pathophysiological Basis and Clinical Perspectives

PubMed Central

Chiu, Jeng-Jiann; Chien, Shu

2013-01-01

Vascular endothelial cells (ECs) are exposed to hemodynamic forces, which modulate EC functions and vascular biology/pathobiology in health and disease. The flow patterns and hemodynamic forces are not uniform in the vascular system. In straight parts of the arterial tree, blood flow is generally laminar and wall shear stress is high and directed; in branches and curvatures, blood flow is disturbed with nonuniform and irregular distribution of low wall shear stress. Sustained laminar flow with high shear stress upregulates expressions of EC genes and proteins that are protective against atherosclerosis, whereas disturbed flow with associated reciprocating, low shear stress generally upregulates the EC genes and proteins that promote atherogenesis. These findings have led to the concept that the disturbed flow pattern in branch points and curvatures causes the preferential localization of atherosclerotic lesions. Disturbed flow also results in postsurgical neointimal hyperplasia and contributes to pathophysiology of clinical conditions such as in-stent restenosis, vein bypass graft failure, and transplant vasculopathy, as well as aortic valve calcification. In the venous system, disturbed flow resulting from reflux, outflow obstruction, and/or stasis leads to venous inflammation and thrombosis, and hence the development of chronic venous diseases. Understanding of the effects of disturbed flow on ECs can provide mechanistic insights into the role of complex flow patterns in pathogenesis of vascular diseases and can help to elucidate the phenotypic and functional differences between quiescent (nonatherogenic/nonthrombogenic) and activated (atherogenic/thrombogenic) ECs. This review summarizes the current knowledge on the role of disturbed flow in EC physiology and pathophysiology, as well as its clinical implications. Such information can contribute to our understanding of the etiology of lesion development in vascular niches with disturbed flow and help to generate

Detection of Asymptomatic Renal Calcifications in Astronauts Using a Novel Ultrasound Protocol

NASA Technical Reports Server (NTRS)

Garcia, Kathleen; Sargsyan, Ashot; Reyes, David; Locke, James

2017-01-01

Ultrasound (US) specifically looking for asymptomatic renal calcifications that may be renal stones is typically not done in the terrestrial setting. Standard abdominal US without a renal focus may discover incidental, mineralized renal material (MRM); however punctate solid areas of MRM is less than 3 mm are usually considered subclinical. Detecting these early calcifications before they become symptomatic renal stones is critical to prevent adverse medical and mission outcomes during spaceflight.

Impact of different aortic valve calcification patterns on the outcome of transcatheter aortic valve implantation: A finite element study.

PubMed

Sturla, Francesco; Ronzoni, Mattia; Vitali, Mattia; Dimasi, Annalisa; Vismara, Riccardo; Preston-Maher, Georgia; Burriesci, Gaetano; Votta, Emiliano; Redaelli, Alberto

2016-08-16

Transcatheter aortic valve implantation (TAVI) can treat symptomatic patients with calcific aortic stenosis. However, the severity and distribution of the calcification of valve leaflets can impair the TAVI efficacy. Here we tackle this issue from a biomechanical standpoint, by finite element simulation of a widely adopted balloon-expandable TAVI in three models representing the aortic root with different scenarios of calcific aortic stenosis. We developed a modeling approach realistically accounting for aortic root pressurization and complex anatomy, detailed calcification patterns, and for the actual stent deployment through balloon-expansion. Numerical results highlighted the dependency on the specific calcification pattern of the "dog-boning" of the stent. Also, local stent distortions were associated with leaflet calcifications, and led to localized gaps between the TAVI stent and the aortic tissues, with potential implications in terms of paravalvular leakage. High stresses were found on calcium deposits, which may be a risk factor for stroke; their magnitude and the extent of the affected regions substantially increased for the case of an "arc-shaped" calcification, running from commissure to commissure. Moreover, high stresses due to the interaction between the aortic wall and the leaflet calcifications were computed in the annular region, suggesting an increased risk for annular damage. Our analyses suggest a relation between the alteration of the stresses in the native anatomical components and prosthetic implant with the presence and distribution of relevant calcifications. This alteration is dependent on the patient-specific features of the calcific aortic stenosis and may be a relevant indicator of suboptimal TAVI results. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Symmetrical and bilateral basal ganglia calcification. Case series and literature review.

PubMed

Jiménez-Ruiz, Amado; Cárdenas-Sáenz, Omar; Ruiz-Sandoval, José Luis

2018-01-01

Symmetric, bilateral basal ganglia calcification is rare finding that sometimes occurs asymptomatically. Its prevalence increases with age, and the most affected site is the globus pallidus. A series of seven cases with clinical and imaging diagnosis of basal ganglia calcification, recorded during the 2012 to 2016 period at the Department of Internal Medicine of the Hospital Civil de Guadalajara "Fray Antonio Alcalde, is presented. Most common clinical presentation was with altered alertness, headache and seizures. There was one case with movement disorders; there were no cases identified with dementia or tetany. Ganglia calcification can be associated with age-related neurodegenerative changes, but it can be an initial manifestation of a variety of systemic pathologies, including disorders of the calcium metabolism, intoxication by different agents, and autoimmune and genetic diseases. Correlation of typical imaging findings with clinical manifestations and laboratory results should be established to reach a definitive judgment. Copyright: © 2018 SecretarÍa de Salud.

Calcification rates and the effect of ocean acidification on Mediterranean cold-water corals

PubMed Central

Maier, C.; Watremez, P.; Taviani, M.; Weinbauer, M. G.; Gattuso, J. P.

2012-01-01

Global environmental changes, including ocean acidification, have been identified as a major threat to scleractinian corals. General predictions are that ocean acidification will be detrimental to reef growth and that 40 to more than 80 per cent of present-day reefs will decline during the next 50 years. Cold-water corals (CWCs) are thought to be strongly affected by changes in ocean acidification owing to their distribution in deep and/or cold waters, which naturally exhibit a CaCO3 saturation state lower than in shallow/warm waters. Calcification was measured in three species of Mediterranean cold-water scleractinian corals (Lophelia pertusa, Madrepora oculata and Desmophyllum dianthus) on-board research vessels and soon after collection. Incubations were performed in ambient sea water. The species M. oculata was additionally incubated in sea water reduced or enriched in CO2. At ambient conditions, calcification rates ranged between −0.01 and 0.23% d−1. Calcification rates of M. oculata under variable partial pressure of CO2 (pCO2) were the same for ambient and elevated pCO2 (404 and 867 µatm) with 0.06 ± 0.06% d−1, while calcification was 0.12 ± 0.06% d−1 when pCO2 was reduced to its pre-industrial level (285 µatm). This suggests that present-day CWC calcification in the Mediterranean Sea has already drastically declined (by 50%) as a consequence of anthropogenic-induced ocean acidification. PMID:22130603

Sea Hare Aplysia punctata (Mollusca: Gastropoda) Can Maintain Shell Calcification under Extreme Ocean Acidification.

PubMed

Carey, Nicholas; Dupont, Sam; Sigwart, Julia D

2016-10-01

Ocean acidification is expected to cause energetic constraints upon marine calcifying organisms such as molluscs and echinoderms, because of the increased costs of building or maintaining shell material in lower pH. We examined metabolic rate, shell morphometry, and calcification in the sea hare Aplysia punctata under short-term exposure (19 days) to an extreme ocean acidification scenario (pH 7.3, ∼2800 μatm pCO 2 ), along with a group held in control conditions (pH 8.1, ∼344 μatm pCO 2 ). This gastropod and its congeners are broadly distributed and locally abundant grazers, and have an internal shell that protects the internal organs. Specimens were examined for metabolic rate via closed-chamber respirometry, followed by removal and examination of the shell under confocal microscopy. Staining using calcein determined the amount of new calcification that occurred over 6 days at the end of the acclimation period. The width of new, pre-calcified shell on the distal shell margin was also quantified as a proxy for overall shell growth. Aplysia punctata showed a 30% reduction in metabolic rate under low pH, but calcification was not affected. This species is apparently able to maintain calcification rate even under extreme low pH, and even when under the energetic constraints of lower metabolism. This finding adds to the evidence that calcification is a largely autonomous process of crystallization that occurs as long as suitable haeomocoel conditions are preserved. There was, however, evidence that the accretion of new, noncalcified shell material may have been reduced, which would lead to overall reduced shell growth under longer-term exposures to low pH independent of calcification. Our findings highlight that the chief impact of ocean acidification upon the ability of marine invertebrates to maintain their shell under low pH may be energetic constraints that hinder growth of supporting structure, rather than maintenance of calcification.

Mechanisms and seasonal drivers of calcification in the temperate coral Turbinaria reniformis at its latitudinal limits.

PubMed

Ross, Claire L; Schoepf, Verena; DeCarlo, Thomas M; McCulloch, Malcolm T

2018-05-30

High-latitude coral reefs provide natural laboratories for investigating the mechanisms and limits of coral calcification. While the calcification processes of tropical corals have been studied intensively, little is known about how their temperate counterparts grow under much lower temperature and light conditions. Here, we report the results of a long-term (2-year) study of seasonal changes in calcification rates, photo-physiology and calcifying fluid (cf) chemistry (using boron isotope systematics and Raman spectroscopy) for the coral Turbinaria reniformis growing near its latitudinal limits (34.5° S) along the southern coast of Western Australia. In contrast with tropical corals, calcification rates were found to be threefold higher during winter (16 to 17° C) compared with summer (approx. 21° C), and negatively correlated with light, but lacking any correlation with temperature. These unexpected findings are attributed to a combination of higher chlorophyll a, and hence increased heterotrophy during winter compared with summer, together with the corals' ability to seasonally modulate pH cf , with carbonate ion concentration [Formula: see text] being the main controller of calcification rates. Conversely, calcium ion concentration [Ca 2+ ] cf declined with increasing calcification rates, resulting in aragonite saturation states Ω cf that were stable yet elevated fourfold above seawater values. Our results show that corals growing near their latitudinal limits exert strong physiological control over their cf in order to maintain year-round calcification rates that are insensitive to the unfavourable temperature regimes typical of high-latitude reefs. © 2018 The Author(s).

Calcification and associated physiological parameters during a stress event in the scleractinian coral Stylophora pistillata.

PubMed

Moya, Aurélie; Ferrier-Pagès, Christine; Furla, Paola; Richier, Sophie; Tambutté, Eric; Allemand, Denis; Tambutté, Sylvie

2008-09-01

High calcification rates observed in reef coral organisms are due to the symbiotic relationship established between scleractinian corals and their photosynthetic dinoflagellates, commonly called zooxanthellae. Zooxanthellae are known to enhance calcification in the light, a process referred as "light-enhanced calcification". The disruption of the relationship between corals and their zooxanthellae leads to bleaching. Bleaching is one of the major causes of the present decline of coral reefs related to climate change and anthropogenic activities. In our aquaria, corals experienced a chemical pollution leading to bleaching and ending with the death of corals. During the time course of this bleaching event, we measured multiple parameters and could evidence four major consecutive steps: 1) at month 1 (January 2005), the stress affected primarily the photosystem II machinery of zooxanthellae resulting in an immediate decrease of photosystem II efficiency, 2) at month 2, the stress affected the photosynthetic production of O2 by zooxanthellae and the rate of light calcification, 3) at month 3, there was a decrease in both light and dark calcification rates, the appearance of the first oxidative damage in the zooxanthellae, the disruption of symbiosis, 4) and finally the death of corals at month 6.

Atherosclerosis in ancient and modern Egyptians: the Horus study.

PubMed

Allam, Adel H; Mandour Ali, Mohamed A; Wann, L Samuel; Thompson, Randall C; Sutherland, M Linda; Sutherland, James D; Frohlich, Bruno; Michalik, David E; Zink, Albert; Lombardi, Guido P; Watson, Lucia; Cox, Samantha L; Finch, Caleb E; Miyamoto, Michael I; Sallam, Sallam L; Narula, Jagat; Thomas, Gregory S

2014-06-01

Although atherosclerosis is usually thought of as a disease of modernity, the Horus Team has previously reported atherosclerotic vascular calcifications on computed tomographic (CT) scans in ancient Egyptians. The purpose of this study was to compare patterns and demographic characteristics of this disease among Egyptians from ancient and modern eras. We compared the presence and extent of vascular calcifications from whole-body CT scans performed on 178 modern Egyptians from Cairo undergoing positron emission tomography (PET)/CT for cancer staging to CT scans of 76 Egyptian mummies (3100 bce to 364 ce). The mean age of the modern Egyptian group was 52.3 ± 15 years (range 14 to 84) versus estimated age at death of ancient Egyptian mummies 36.5 ± 13 years (range 4 to 60); p < 0.0001. Vascular calcification was detected in 108 of 178 (60.7%) of modern patients versus 26 of 76 (38.2%) of mummies, p < 0.001. Vascular calcifications on CT strongly correlated to age in both groups. In addition, the severity of disease by number of involved arterial beds also correlated to age, and there was a very similar pattern between the 2 groups. Calcifications in both modern and ancient Egyptians were seen peripherally in aortoiliac beds almost a decade earlier than in event-related beds (coronary and carotid). The presence and severity of atherosclerotic vascular disease correlates strongly to age in both ancient and modern Egyptians. There is a striking correlation in the distribution of the number of vascular beds involved. Atherosclerotic calcifications are seen in the aortoiliac beds almost a decade earlier than in the coronary and carotid beds. Copyright © 2014. Published by Elsevier B.V.