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Sample records for calcific uremic arteriolopathy

  1. Calcific uremic arteriolopathy

    PubMed Central

    Sowers, Kurt M

    2010-01-01

    Calcific uremic arteriolopathy (CUA)/calciphylaxis is an important cause of morbidity and mortality in patients with chronic kidney disease requiring renal replacement. Once thought to be rare, it is being increasingly recognized and reported on a global scale. The uremic milieu predisposes to multiple metabolic toxicities including increased levels of reactive oxygen species and inflammation. Increased oxidative stress and inflammation promote this arteriolopathy by adversely affecting endothelial function resulting in a prothrombotic milieu and significant remodeling effects on vascular smooth muscle cells. These arteriolar pathological effects include intimal hyperplasia, inflammation, endovascular fibrosis and vascular smooth muscle cell apoptosis and differentiation into bone forming osteoblast-like cells resulting in medial calcification. Systemic factors promoting this vascular condition include elevated calcium, parathyroid hormone and hyperphosphatemia with consequent increases in the calcium × phosphate product. The uremic milieu contributes to a marked increased in upstream reactive oxygen species—oxidative stress and subsequent downstream increased inflammation, in part, via activation of the nuclear transcription factor NFκB and associated downstream cytokine pathways. Consitutive anti-calcification proteins such as Fetuin-A and matrix GLA proteins and their signaling pathways may be decreased, which further contributes to medial vascular calcification. The resulting clinical entity is painful, debilitating and contributes to the excess morbidity and mortality associated with chronic kidney disease and end stage renal disease. These same histopathologic conditions also occur in patients without uremia and therefore, the term calcific obliterative arteriolopathy could be utilized in these conditions. PMID:20716935

  2. Unexpectedly severe metabolic acidosis associated with sodium thiosulfate therapy in a patient with calcific uremic arteriolopathy.

    PubMed

    Selk, Natalie; Rodby, Roger A

    2011-01-01

    Calcific uremic arteriolopathy, formerly known as calciphylaxis is a devastating condition that primarily affects patients with end-stage renal disease. The lesions can progress to massive ulcerations of the subcutaneous tissue that are associated with a high degree of morbidity and mortality, usually related to sepsis. Although the pathophysiology of this condition is poorly understood, it appears to be related to a derangement in calcium-phosphate metabolism. Thus, treatments have focused on the treatment of hyperparathyroidism albeit with poor results. More recently, sodium thiosulfate (STS) has emerged as a promising therapy following multiple case reports of marked disease regression following its use. As STS is a strong acid, metabolic acidosis has been described following its administration, although relatively mild in degree. We report a case of a patient with calciphylaxis who repeatedly developed a severe anion gap metabolic acidosis following each dose of STS requiring a significant reduction in the dose.

  3. Successfully treated calcific uremic arteriolopathy: two cases of a high anion gap metabolic acidosis with intravenous sodium thiosulfate.

    PubMed

    Rein, Joshua L; Miyata, Kana N; Dadzie, Kobena A; Gruber, Steven J; Sulica, Roxana; Winchester, James F

    2014-01-01

    Calcific uremic arteriolopathy (CUA) is a rare and potentially fatal disorder of calcification involving subcutaneous small vessels and fat in patients with renal insufficiency. We describe the successful use of intravenous sodium thiosulfate (STS) for the treatment of CUA in two patients. The first case was complicated by the development of a severe anion gap metabolic acidosis, which was accompanied by a seizure. Both patients had complete wound healing within five months. Although STS should be considered in the treatment of CUA, little is known about pharmacokinetics and additional studies are required to determine dosing strategies to minimize severe potential side effects.

  4. The Effect of Cinacalcet on Calcific Uremic Arteriolopathy Events in Patients Receiving Hemodialysis: The EVOLVE Trial

    PubMed Central

    Kubo, Yumi; Floege, Anna; Chertow, Glenn M.; Parfrey, Patrick S.

    2015-01-01

    Background and objectives Uncontrolled secondary hyperparathyroidism (sHPT) in patients with ESRD is a risk factor for calcific uremic arteriolopathy (CUA; calciphylaxis). Design, setting, participants, & measurements Adverse event reports collected during the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events trial were used to determine the frequency of CUA in patients receiving hemodialysis who had moderate to severe sHPT, as well as the effects of cinacalcet versus placebo. CUA events were collected while patients were receiving the study drug. Results Among the 3861 trial patients who received at least one dose of the study drug, 18 patients randomly assigned to placebo and six assigned to cinacalcet developed CUA (unadjusted relative hazard, 0.31; 95% confidence interval [95% CI], 0.13 to 0.79; P=0.014). Corresponding cumulative event rates (95% CI) at year 4 were 0.011% (0.006% to 0.018%) and 0.005% (0.002% to 0.010%). By multivariable analysis, other factors associated with CUA included female sex, higher body mass index, higher diastolic BP, and history of dyslipidemia or parathyroidectomy. Median (10%, 90% percentile) plasma parathyroid hormone concentrations proximal to the report of CUA were 796 (225, 2093) pg/ml and 410 (71, 4957) pg/ml in patients randomly assigned to placebo and cinacalcet, respectively. Active use of vitamin K antagonists was recorded in 11 of 24 patients with CUA, nine randomly assigned to placebo, and two to cinacalcet, in contrast to 5%–7% at any one time point in patients in whom CUA was not reported. Conclusion Cinacalcet appeared to reduce the incidence of CUA in hemodialysis recipients who have moderate to severe sHPT. PMID:25887067

  5. Maximal conservative therapy of calcific uremic ateriolopathy.

    PubMed

    Van Noten, Charlotte; Janssen van Doorn, Karin; Vermander, Evert; Vlayen, Sonja; Verpooten, Gert A; Couttenye, Marie-Madeleine

    2012-07-01

    We present the case of a 61-year- old female patient in long-term hemodialysis who developed calcific uremic arteriolopathy (CUA) upon administration of the oral calcimimetic agent cinacalcet for treatment of secondary hyperparathyroidism. In May 2009, the baseline serum values were parathormone (PTH) 310 pg/ml, calcium 9.1 mg/dl and phosphorous 6.9 mg/dl. Necrotic wounds in the suprapubic fat tissue were successfully treated first, by correcting the calcium phosphorous product; second, through treatment with sodium thiosulfate and third, through intensive wound care with hyperbaric oxygen therapy and vacuum-assisted closure therapy, with no need for parathyroidectomy. Multiple factors have been described to play a role in the development of CUA. Based on the findings of this case, the treatment of CUA should be aimed at correcting different causes simultaneously.

  6. Acid-Base Balance in Uremic Rats with Vascular Calcification

    PubMed Central

    Peralta-Ramírez, Alan; Raya, Ana Isabel; Pineda, Carmen; Rodríguez, Mariano; Aguilera-Tejero, Escolástico; López, Ignacio

    2014-01-01

    Background/Aims Vascular calcification (VC), a major complication in humans and animals with chronic kidney disease (CKD), is influenced by changes in acid-base balance. The purpose of this study was to describe the acid-base balance in uremic rats with VC and to correlate the parameters that define acid-base equilibrium with VC. Methods Twenty-two rats with CKD induced by 5/6 nephrectomy (5/6 Nx) and 10 nonuremic control rats were studied. Results The 5/6 Nx rats showed extensive VC as evidenced by a high aortic calcium (9.2 ± 1.7 mg/g of tissue) and phosphorus (20.6 ± 4.9 mg/g of tissue) content. Uremic rats had an increased pH level (7.57 ± 0.03) as a consequence of both respiratory (PaCO2 = 28.4 ± 2.1 mm Hg) and, to a lesser degree, metabolic (base excess = 4.1 ± 1 mmol/l) derangements. A high positive correlation between both anion gap (AG) and strong ion difference (SID) with aortic calcium (AG: r = 0.604, p = 0.02; SID: r = 0.647, p = 0.01) and with aortic phosphorus (AG: r = 0.684, p = 0.007; SID: r = 0.785, p = 0.01) was detected. Conclusions In an experimental model of uremic rats, VC showed high positive correlation with AG and SID. PMID:25177336

  7. Restoration of bone mineralization by cinacalcet is associated with a significant reduction in calcitriol-induced vascular calcification in uremic rats.

    PubMed

    De Schutter, Tineke M; Behets, Geert J; Jung, Susanne; Neven, Ellen; D'Haese, Patrick C; Querfeld, Uwe

    2012-11-01

    The present study investigated to what extent normalization of bone turnover goes along with a reduction of high-dose calcitriol-induced vascular calcifications in uremic rats. Five groups of male Sprague-Dawley rats were studied: sham-operated controls (n = 7), subtotally nephrectomized (SNX) uremic (CRF) animals (n = 12), CRF + calcitriol (vitD) (0.25 μg/kg/day) (n = 12), CRF + vitD + cinacalcet (CIN) (10 mg/kg/day) (n = 12), and CRF + vitD + parathyroidectomy (PTX) (n = 12). Treatment started 2 weeks after SNX and continued for the next 14 weeks. High-dose calcitriol treatment in hyperparathyroid rats went along with the development of distinct vascular calcification, which was significantly reduced by >50 %, in both CIN-treated and PTX animals. Compared to control animals and those of the CRF group, calcitriol treatment either in combination with CIN or PTX or not was associated with a significant increase in bone area comprising ±50 % of the total tissue area. However, whereas excessive woven bone accompanied by a dramatically increased osteoid width/area was seen in the CRF + vitD group, CIN treatment and PTX resulted in significantly reduced serum PTH level, which was accompanied by a distinct reduction of both the bone formation rate and the amount of osteoid. These data indicate that less efficient calcium and phosphorus incorporation in bone inherent to the severe hyperparathyroidism in vitamin D-treated uremic rats goes along with excessive vascular calcification, a process which is partially reversed by CIN treatment in combination with a more efficacious bone mineralization, thus restricting the availability of calcium and phosphate for being deposited in the vessel wall.

  8. Mammogram - calcifications

    MedlinePlus

    Microcalcifications or macrocalcifications; Breast cancer - calcifications; Mammography - calcifications ... or take in as medicine does not cause calcifications in the breast. Most calcifications are not a ...

  9. [Ectopic calcification].

    PubMed

    Fukumoto, Seiji

    2014-02-01

    Calcium deposition can be observed in many tissues in addition to bones and teeth which physiologically calcify. This unphysiological calcification can damage several organs. It has been shown that vascular calcification which is a risk factor for cardiovascular events develops through similar mechanisms to physiological calcification. Further studies to clarify detailed mechanisms of calcification are necessary to develop measures that inhibit unphysiological ectopic calcification without affecting physiological calcification in bones and teeth.

  10. Uremic Itch Management.

    PubMed

    Mettang, Thomas

    2016-01-01

    Uremic itch is a frequent and sometimes very tormenting symptom in patients with advanced or end-stage renal failure, with a strong negative impact on the quality of life. According to a representative study, the point prevalence of chronic itch is 25% in hemodialysis patients but may reach more than 50% in single cohorts depending on the country and dialysis efficacy. Not much is known regarding the pathogenesis of uremic itch. Besides parathyroid hormone, histamine, tryptase, and alteration of the calcium-phosphate metabolism have been suspected. More recently, derangements in the opioid system and an inflammatory condition have been investigated as suspected players in the pathogenesis of uremic itch, but remain unproven so far. Treatment of chronic itch in dialysis patients remains difficult. Besides topical application of rehydrating or immunomodulating compounds, such as γ-linolenic acid or tacrolimus treatment with nalfurafine may be helpful. Apart from that, gabapentin and pregabalin are promising drugs to alleviate uremic itch. In many cases, UVB phototherapy is effective in reducing the intensity of itch. When treating patients, one should take into account that most of the drugs available are not licensed for the treatment of itch. Therefore, a deliberate use of therapeutic options aiming for a good risk-benefit relation should be adopted. In very severe and refractory cases, patients suitable for renal transplantation might be switched to 'high urgency' status, as successful renal transplantation cures uremic pruritus in most of the cases. PMID:27578082

  11. Prevention of vascular calcification with bisphosphonates without affecting bone mineralization: a new challenge?

    PubMed

    Neven, Ellen G; De Broe, Marc E; D'Haese, Patrick C

    2009-03-01

    Arterial calcification has been found to coexist with bone loss. Bisphosphonates, used as standard therapy for osteoporosis, inhibit experimentally induced vascular calcification, offering perspectives for the treatment of vascular calcification in renal failure patients. However, Lomashvili et al. report that the doses of etidronate and pamidronate that are effective in attenuating aortic calcification also decrease bone formation and mineralization in uremic rats, limiting their therapeutic use as anticalcifying agents.

  12. Uremic leontiasis ossea.

    PubMed

    Haroyan, Harut; Bos, Aron; Ginat, Daniel Thomas

    2015-01-01

    Uremic leontiasis ossea is a rare manifestation of renal osteodystrophy clinically characterized by jaw enlargement, widening of the nares, flattening of the nasal bridge, and increased interdental spacing. Computed tomography (CT) findings are particular characteristic and include serpiginous tunneling within the maxillofacial bones and cortical bone resorption. Nuclear medicine scans are also useful for demonstrating hyperplasia of the parathyroid glands. Ultimately, the diagnosis of uremic leontiasis ossea can be made non-invasively through a combination of clinical parameters and imaging findings, as described in this article. PMID:25224511

  13. Hemolytic uremic syndrome

    PubMed Central

    Canpolat, Nur

    2015-01-01

    Hemolytic uremic syndrome (HUS) is a clinical syndrome characterized by the triad of thrombotic microangiopathy, thrombocytopenia, and acute kidney injury. Hemolytic uremic syndrome represents a heterogeneous group of disorders with variable etiologies that result in differences in presentation, management and outcome. In recent years, better understanding of the HUS, especially those due to genetic mutations in the alternative complement pathway have provided an update on the terminology, classification, and treatment of the disease. This review will provide the updated classification of the disease and the current diagnostic and therapeutic approaches on the complement-mediated HUS in addition to STEC-HUS which is the most common cause of the HUS in childhood. PMID:26265890

  14. Encephalopathy, deafness and blindness in young women: a distinct retinocochleocerebral arteriolopathy?

    PubMed Central

    Bogousslavsky, J; Gaio, J M; Caplan, L R; Regli, F; Hommel, M; Hedges, T R; Ferrazzini, M; Pollak, P

    1989-01-01

    Three young women (aged 18 years, 19 years and 19 years) who developed progressive neuropsychic and neurologic disturbances with hearing loss and multifocal retinal artery branch occlusions are reported. This retinocochleocerebral syndrome has been reported previously only in 12 young North American women. Its pathogenesis is unknown, but an atypical viral infection of the vessel walls has been suggested. Abnormalities of T lymphocytes subsets in blood in one of the patients suggested an immunological dysfunction, but all other tests, including immunological reactions on brain and skin biopsies, were negative or non-specific. Steroids and immunosuppressive agents have been advocated on an empirical basis, but the second patient showed a substantial recovery without any therapy and the third gradually deteriorated despite azathioprine, cyclophosphamide, prednisone and plasma exchanges. This retinocochleocerebral syndrome probably corresponds to an arteriolopathy of unknown nature. Images PMID:2709035

  15. Atypical Hemolytic Uremic Syndrome

    PubMed Central

    Kavanagh, David; Goodship, Tim H.; Richards, Anna

    2013-01-01

    Summary Hemolytic uremic syndrome (HUS) is a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. The atypical form of HUS is a disease characterized by complement overactivation. Inherited defects in complement genes and acquired autoantibodies against complement regulatory proteins have been described. Incomplete penetrance of mutations in all predisposing genes is reported, suggesting that a precipitating event or trigger is required to unmask the complement regulatory deficiency. The underlying genetic defect predicts the prognosis both in native kidneys and after renal transplantation. The successful trials of the complement inhibitor eculizumab in the treatment of atypical HUS will revolutionize disease management. PMID:24161037

  16. [Atypical hemolytic uremic syndrome].

    PubMed

    Blasco Pelicano, Miquel; Rodríguez de Córdoba, Santiago; Campistol Plana, Josep M

    2015-11-20

    The hemolytic uremic syndrome (HUS) is a clinical entity characterized by thrombocytopenia, non-immune hemolytic anemia and renal impairment. Kidney pathology shows thrombotic microangiopathy (TMA) with endothelial cell injury leading to thrombotic occlusion of arterioles and capillaries. Traditionally, HUS was classified in 2 forms: Typical HUS, most frequently occurring in children and caused by Shiga-toxin-producing bacteria, and atypical HUS (aHUS). aHUS is associated with mutations in complement genes in 50-60% of patients and has worse prognosis, with the majority of patients developing end stage renal disease. After kidney transplantation HUS may develop as a recurrence of aHUS or as de novo disease. Over the last years, many studies have demonstrated that complement dysregulation underlies the endothelial damage that triggers the development of TMA in most of these patients. Advances in our understanding of the pathogenic mechanisms of aHUS, together with the availability of novel therapeutic options, will enable better strategies for the early diagnosis and etiological treatment, which are changing the natural history of aHUS. This review summarizes the aHUS clinical entity and describes the role of complement dysregulation in the pathogenesis of aHUS. Finally, we review the differential diagnosis and the therapeutic options available to patients with aHUS.

  17. Mitochondrial dysfunction in uremic cardiomyopathy

    PubMed Central

    Taylor, David; Bhandari, Sunil

    2015-01-01

    Uremic cardiomyopathy (UCM) is characterized by metabolic remodelling, compromised energetics, and loss of insulin-mediated cardioprotection, which result in unsustainable adaptations and heart failure. However, the role of mitochondria and the susceptibility of mitochondrial permeability transition pore (mPTP) formation in ischemia-reperfusion injury (IRI) in UCM are unknown. Using a rat model of chronic uremia, we investigated the oxidative capacity of mitochondria in UCM and their sensitivity to ischemia-reperfusion mimetic oxidant and calcium stressors to assess the susceptibility to mPTP formation. Uremic animals exhibited a 45% reduction in creatinine clearance (P < 0.01), and cardiac mitochondria demonstrated uncoupling with increased state 4 respiration. Following IRI, uremic mitochondria exhibited a 58% increase in state 4 respiration (P < 0.05), with an overall reduction in respiratory control ratio (P < 0.01). Cardiomyocytes from uremic animals displayed a 30% greater vulnerability to oxidant-induced cell death determined by FAD autofluorescence (P < 0.05) and reduced mitochondrial redox state on exposure to 200 μM H2O2 (P < 0.01). The susceptibility to calcium-induced permeability transition showed that maximum rates of depolarization were enhanced in uremia by 79%. These results demonstrate that mitochondrial respiration in the uremic heart is chronically uncoupled. Cardiomyocytes in UCM are characterized by a more oxidized mitochondrial network, with greater susceptibility to oxidant-induced cell death and enhanced vulnerability to calcium-induced mPTP formation. Collectively, these findings indicate that mitochondrial function is compromised in UCM with increased vulnerability to calcium and oxidant-induced stressors, which may underpin the enhanced predisposition to IRI in the uremic heart. PMID:25587120

  18. BMP-7 is an efficacious treatment of vascular calcification in a murine model of atherosclerosis and chronic renal failure.

    PubMed

    Davies, Matthew R; Lund, Richard J; Hruska, Keith A

    2003-06-01

    Chronic renal failure is complicated by high cardiovascular mortality. One key contributor to this mortality is vascular calcification, for which no therapy currently exists. Bone morphogenetic protein 7 is an essential renal morphogen that maintains renal tubular differentiation in the adult and is downregulated in renal failure. Several studies have demonstrated its efficacy in treating various renal diseases in rodents, and it was hypothesized that it would also be an effective treatment of vascular calcification in this setting. Uremia was imposed on LDL receptor null mice (a model of atherosclerosis), which were then treated with bone morphogenetic protein 7 for 15 wk. Uremic animals had increased vascular calcification by histology and chemical analysis. Calcification in treated animals was similar to or less than non-uremic control animals. Cells exhibiting an osteoblast-like phenotype in the vessel wall may be important in the etiology of vascular calcification. Expression of osteocalcin was assessed as a marker of osteoblastic function, and it is shown that it is increased in untreated uremic animals but downregulated to levels similar to non-uremic control animals with treatment. The data are compatible with bone morphogenetic protein 7 deficiency as a pathophysiologic factor in chronic renal failure, and they demonstrate its efficacy as a potential treatment of vascular calcification. PMID:12761256

  19. Atypical hemolytic uremic syndrome

    PubMed Central

    2011-01-01

    Hemolytic uremic syndrome (HUS) is defined by the triad of mechanical hemolytic anemia, thrombocytopenia and renal impairment. Atypical HUS (aHUS) defines non Shiga-toxin-HUS and even if some authors include secondary aHUS due to Streptococcus pneumoniae or other causes, aHUS designates a primary disease due to a disorder in complement alternative pathway regulation. Atypical HUS represents 5 -10% of HUS in children, but the majority of HUS in adults. The incidence of complement-aHUS is not known precisely. However, more than 1000 aHUS patients investigated for complement abnormalities have been reported. Onset is from the neonatal period to the adult age. Most patients present with hemolytic anemia, thrombocytopenia and renal failure and 20% have extra renal manifestations. Two to 10% die and one third progress to end-stage renal failure at first episode. Half of patients have relapses. Mutations in the genes encoding complement regulatory proteins factor H, membrane cofactor protein (MCP), factor I or thrombomodulin have been demonstrated in 20-30%, 5-15%, 4-10% and 3-5% of patients respectively, and mutations in the genes of C3 convertase proteins, C3 and factor B, in 2-10% and 1-4%. In addition, 6-10% of patients have anti-factor H antibodies. Diagnosis of aHUS relies on 1) No associated disease 2) No criteria for Shigatoxin-HUS (stool culture and PCR for Shiga-toxins; serology for anti-lipopolysaccharides antibodies) 3) No criteria for thrombotic thrombocytopenic purpura (serum ADAMTS 13 activity > 10%). Investigation of the complement system is required (C3, C4, factor H and factor I plasma concentration, MCP expression on leukocytes and anti-factor H antibodies; genetic screening to identify risk factors). The disease is familial in approximately 20% of pedigrees, with an autosomal recessive or dominant mode of transmission. As penetrance of the disease is 50%, genetic counseling is difficult. Plasmatherapy has been first line treatment until presently

  20. Molecular Mechanisms of Vascular Calcification in Chronic Kidney Disease: The Link between Bone and the Vasculature

    PubMed Central

    Byon, Chang Hyun

    2015-01-01

    Vascular calcification is highly prevalent in patients with chronic kidney disease (CKD) and increases mortality in those patients. Impaired calcium and phosphate homeostasis, increased oxidative stress, and loss of calcification inhibitors have been linked to vascular calcification in CKD. Additionally, impaired bone may perturb serum calcium/phosphate and their key regulator, parathyroid hormone, thus contributing to increased vascular calcification in CKD. Therapeutic approaches for CKD, such as phosphate binders and bisphosphonates, have been shown to ameliorate bone loss as well as vascular calcification. The precise mechanisms responsible for vascular calcification in CKD and the contribution of bone metabolism to vascular calcification have not been elucidated. This review discusses the role of systemic uremic factors and impaired bone metabolism in the pathogenesis of vascular calcification in CKD. The regulation of the key osteogenic transcription factor Runt-related transcription factor 2 (Runx2) and the emerging role of Runx2-dependent receptor activator of nuclear factor kappa-B ligand (RANKL) in vascular calcification of CKD are emphasized. PMID:25947259

  1. An Enlarged Profile of Uremic Solutes

    PubMed Central

    Tanaka, Hisae; Sirich, Tammy L.; Plummer, Natalie S.; Weaver, Daniel S.; Meyer, Timothy W.

    2015-01-01

    Better knowledge of the uremic solutes that accumulate when the kidneys fail could lead to improved renal replacement therapy. This study employed the largest widely available metabolomic platform to identify such solutes. Plasma and plasma ultrafiltrate from 6 maintenance hemodialysis (HD) patients and 6 normal controls were first compared using a platform combining gas and liquid chromatography with mass spectrometry. Further studies compared plasma from 6 HD patients who had undergone total colectomy and 9 with intact colons. We identified 120 solutes as uremic including 48 that had not been previously reported to accumulate in renal failure. Combination of the 48 newly identified solutes with those identified in previous reports yielded an extended list of more than 270 uremic solutes. Among the solutes identified as uremic in the current study, 9 were shown to be colon-derived, including 6 not previously identified as such. Literature search revealed that many uremic phenyl and indole solutes, including most of those shown to be colon-derived, come from plant foods. Some of these compounds can be absorbed directly from plant foods and others are produced by colon microbial metabolism of plant polyphenols that escape digestion in the small intestine. A limitation of the metabolomic method was that it underestimated the elevation in concentration of uremic solutes which were measured using more quantitative assays. PMID:26317986

  2. Protein-bound uremic toxins: new culprits of cardiovascular events in chronic kidney disease patients.

    PubMed

    Ito, Shunsuke; Yoshida, Masayuki

    2014-02-20

    Chronic kidney disease (CKD) has been considered a major risk factor for cardiovascular diseases. Although great advances have recently been made in the pathophysiology and treatment of cardiovascular diseases, CKD remains a major global health problem. Moreover, the occurrence rates of cardiovascular events among CKD patients increase even in cases in which patients undergo hemodialysis, and the mechanisms underlying the so-called "cardiorenal syndrome" are not clearly understood. Recently, small-molecule uremic toxins have been associated with cardiovascular mortality in CKD and/or dialysis patients. These toxins range from small uncharged solutes to large protein-bound structures. In this review, we focused on protein-bound uremic toxins, such as indoxyl sulfate and p-cresyl sulfate, which are poorly removed by current dialysis techniques. Several studies have demonstrated that protein-bound uremic toxins, especially indoxyl sulfate, induce vascular inflammation, endothelial dysfunction, and vascular calcification, which may explain the relatively poor prognosis of CKD and dialysis patients. The aim of this review is to provide novel insights into the effects of indoxyl sulfate and p-cresyl sulfate on the pathogenesis of atherosclerosis.

  3. MicroRNAs 29b, 133b, and 211 Regulate Vascular Smooth Muscle Calcification Mediated by High Phosphorus.

    PubMed

    Panizo, Sara; Naves-Díaz, Manuel; Carrillo-López, Natalia; Martínez-Arias, Laura; Fernández-Martín, José Luis; Ruiz-Torres, María Piedad; Cannata-Andía, Jorge B; Rodríguez, Isabel

    2016-03-01

    Vascular calcification is a frequent cause of morbidity and mortality in patients with CKD and the general population. The common association between vascular calcification and osteoporosis suggests a link between bone and vascular disorders. Because microRNAs (miRs) are involved in the transdifferentiation of vascular smooth muscle cells into osteoblast-like cells, we investigated whether miRs implicated in osteoblast differentiation and bone formation are involved in vascular calcification. Different levels of uremia, hyperphosphatemia, and aortic calcification were induced by feeding nephrectomized rats a normal or high-phosphorus diet for 12 or 20 weeks, at which times the levels of eight miRs (miR-29b, miR-125, miR-133b, miR-135, miR-141, miR-200a, miR-204, and miR-211) in the aorta were analyzed. Compared with controls and uremic rats fed a normal diet, uremic rats fed a high-phosphorous diet had lower levels of miR-133b and miR-211 and higher levels of miR-29b that correlated respectively with greater expression of osteogenic RUNX2 and with lower expression of several inhibitors of osteoblastic differentiation. Uremia per se mildly reduced miR-133b levels only. Similar results were obtained in two in vitro models of vascular calcification (uremic serum and high-calcium and -phosphorus medium), and experiments using antagomirs and mimics to modify miR-29b, miR-133b, and miR-211 expression levels in these models confirmed that these miRs regulate the calcification process. We conclude that miR-29b, miR-133b, and miR-211 have direct roles in the vascular smooth muscle calcification induced by high phosphorus and may be new therapeutic targets in the management of vascular calcification.

  4. Future Avenues to Decrease Uremic Toxin Concentration.

    PubMed

    Vanholder, Raymond C; Eloot, Sunny; Glorieux, Griet L R L

    2016-04-01

    In this article, we review approaches for decreasing uremic solute concentrations in chronic kidney disease and in particular, in end-stage renal disease (ESRD). The rationale to do so is the straightforward relation between concentration and biological (toxic) effect for most toxins. The first section is devoted to extracorporeal strategies (kidney replacement therapy). In the context of high-flux hemodialysis and hemodiafiltration, we discuss increasing dialyzer blood and dialysate flows, frequent and/or extended dialysis, adsorption, bioartificial kidney, and changing physical conditions within the dialyzer (especially for protein-bound toxins). The next section focuses on the intestinal generation of uremic toxins, which in return is stimulated by uremic conditions. Therapeutic options are probiotics, prebiotics, synbiotics, and intestinal sorbents. Current data are conflicting, and these issues need further study before useful therapeutic concepts are developed. The following section is devoted to preservation of (residual) kidney function. Although many therapeutic options may overlap with therapies provided before ESRD, we focus on specific aspects of ESRD treatment, such as the risks of too-strict blood pressure and glycemic regulation and hemodynamic changes during dialysis. Finally, some recommendations are given on how research might be organized with regard to uremic toxins and their effects, removal, and impact on outcomes of uremic patients. PMID:26500179

  5. Calcium-sensing receptor, calcimimetics, and cardiovascular calcifications in chronic kidney disease.

    PubMed

    Torres, Pablo A Ureña; De Broe, Marc

    2012-07-01

    Renal function impairment goes along with a disturbed calcium, phosphate, and vitamin D metabolism, resulting in secondary hyperparathyroidism (sHPT). These mineral metabolism disturbances are associated with soft tissue calcifications, particularly arteries, cardiac valves, and myocardium, ultimately associated with increased risk of mortality in patients with chronic kidney disease (CKD). sHPT may lead to cardiovascular calcifications by other mechanisms including an impaired effect of parathyroid hormone (PTH), and a decreased calcium-sensing receptor (CaR) expression on cardiovascular structures. PTH may play a direct role on vascular calcifications through activation of a receptor, the type-1 PTH/PTHrP receptor, normally attributed to PTH-related peptide (PTHrP). The CaR in vascular cells may also play a role on vascular mineralization as suggested by its extremely reduced expression in atherosclerotic calcified human arteries. Calcimimetic compounds increasing the CaR sensitivity to extracellular calcium efficiently reduce serum PTH, calcium, and phosphate in dialysis patients with sHPT. They upregulate the CaR in vascular cells and attenuate vascular mineralization in uremic states. In this article, the pathophysiological mechanisms associated with cardiovascular calcifications in case of sHPT, the impact of medical and surgical correction of sHPT, the biology of the CaR in vascular structures and its function in CKD state, and finally the role played by the CaR and its modulation by the calcimimetics on uremic-related cardiovascular calcifications are reviewed.

  6. Middle Cerebral Artery Calcification

    PubMed Central

    Kao, Hung-Wen; Liou, Michelle; Chung, Hsiao-Wen; Liu, Hua-Shan; Tsai, Ping-Huei; Chiang, Shih-Wei; Chou, Ming-Chung; Peng, Giia-Sheun; Huang, Guo-Shu; Hsu, Hsian-He; Chen, Cheng-Yu

    2015-01-01

    Abstract Calcification of the middle cerebral artery (MCA) is uncommon in the healthy elderly. Whether calcification of the MCA is associated with cerebral ischemic stroke remains undetermined. We intended to investigate the association using Agatston calcium scoring of the MCA. This study retrospectively included 354 subjects with ischemic stroke in the MCA territory and 1518 control subjects who underwent computed tomography (CT) of the brain. We recorded major known risk factors for ischemic stroke, including age, gender, hypertension, diabetes mellitus, smoking, hyperlipidemia, and obesity, along with the MCA calcium burden, measured with the Agatston calcium scoring method. Univariate and modified logistic regression analyses were performed to examine the association between the MCA calcification and ischemic stroke. The univariate analyses showed significant associations of ischemic stroke with age, hypertension, diabetes mellitus, smoking, total MCA Agatston score, and the presence of calcification on both or either side of the MCA. Subjects with the presence of MCA calcification on both or either side of the MCA were 8.46 times (95% confidence interval, 4.93–14.53; P < 0.001) more likely to have a cerebral infarct than subjects without MCA calcification after adjustment for the major known risk factors, including age, hypertension, diabetes mellitus, and smoking. However, a higher degree of MCA calcification reflected by the Agatston score was not associated with higher risk of MCA ischemic stroke after adjustment for the confounding factors and presence of MCA calcification. These results suggest that MCA calcification is associated with ischemic stroke in the MCA territory. Further prospective studies are required to verify the clinical implications of the MCA calcification. PMID:26683969

  7. [Diabetes mellitus and vascular calcification].

    PubMed

    Okuno, Yasuhisa; Sato, Kyoko

    2002-08-01

    Two types of arterial calcification are well recognized:intimal (atherosclerotic) and medial (Monckeberg type). These two calcifications are considered different in pathogenesis. Arterial calcification has recently been reported to be an organized, regulated process similar to bone formation. The relation of calcification to diabetes mellitus remains still unclear. EBCT can noninvasively and accurately detect coronary artery calcification. Diabetic patients seem to have increased prevalence of coronary calcification when compared with non-diabetic patients. Medial artery calcification is an independent predictor of cardiovascular mortality in diabetic patients. PMID:15775402

  8. Calcific Metamorphosis: A Review

    PubMed Central

    Siddiqui, Shoaib Haider; Mohamed, Ahmed Nabil

    2016-01-01

    Dental trauma to the permanent dentition can lead to clinical complications and its management may considerably challenge a practitioner. The incidence of pulp canal obliteration following dental trauma has been reported to be approximately 4 – 24%. Attempting to locate canals following calcific metamorphosis and negotiating it to full working length may lead to iatrogenic errors such as fractured instrument and perforation. This review article describes the possible etiology of Calcific Metamorphosis, its clinical and radiographic features as well as its management.

  9. Calcific Metamorphosis: A Review.

    PubMed

    Siddiqui, Shoaib Haider; Mohamed, Ahmed Nabil

    2016-07-01

    Dental trauma to the permanent dentition can lead to clinical complications and its management may considerably challenge a practitioner. The incidence of pulp canal obliteration following dental trauma has been reported to be approximately 4 - 24%. Attempting to locate canals following calcific metamorphosis and negotiating it to full working length may lead to iatrogenic errors such as fractured instrument and perforation. This review article describes the possible etiology of Calcific Metamorphosis, its clinical and radiographic features as well as its management. PMID:27610067

  10. Myocardial fibre calcification.

    PubMed Central

    McClure, J; Pieterse, A S; Pounder, D J; Smith, P S

    1981-01-01

    Three cases of myocardial fibre calcification found at post-mortem examination are described. In one case there was antemortem hypercalcaemia and hyperphosphataemia and the case was clearly an example of metastatic calcification. In the other two cases there was ischaemic myocardial necrosis and calcification was seen in fibres which were not overtly necrotic, but which were both in proximity to (the majority) and remote from the necrotic zones. Since renal failure with hyperphosphataemia was present in both cases, these were considered to be examples of augmented (by the hyperphosphataemia) dystrophic calcification. The histological, histochemical and ultrastructural features were identical in the three cases. Hydroxyapatite formation was observed initially in mitochondria, followed by spillage of crystals into the cytosol and ultimately into the interstitium. It is suggested that the fundamental lesion is a dysfunction of the fibre membrane; the similarity of this reaction with the calcification seen in skeletal muscle fibres in various myopathies is noted and a unifying hypothesis of the mechanism of skeletal and cardiac muscle fibre calcification is thereby suggested. Images PMID:7309897

  11. Skin problems in chronic kidney disease.

    PubMed

    Kuypers, Dirk R J

    2009-03-01

    Skin disorders associated with chronic kidney disease (CKD) can markedly affect a patient's quality of life and can negatively impact their mental and physical health. Uremic pruritus, which is frequently encountered in patients with CKD, is considered to be an inflammatory systemic disease rather than a local skin disorder. Biomarkers of inflammation are increased in patients with uremic pruritus and an imbalance of the endogenous opioidergic system might be involved in the complex pathogenesis of the disease. Treatment options for uremic pruritus include emollients, topical capsaicin cream, ultraviolet B phototherapy, gabapentin, oral activated charcoal and nalfurafine, a kappa-opioid-receptor agonist. Calcific uremic arteriolopathy is triggered by an imbalance of promoters and inhibitors of vascular calcification, caused by the inflammatory changes that occur in uremia. Promising therapeutic strategies for calcific uremic arteriolopathy include bisphosphonates and intravenous sodium thiosulfate. Nephrogenic systemic fibrosis is a devastating condition associated with the use of gadolinium-based contrast agents in patients with CKD. At present, no therapies are available for this complication. Preventive measures include use of iodine-based contrast agents, particularly in patients with CKD stage 4 and 5. If gadolinium contrast is necessary, administration of low volumes of the more stable macrocyclic ionic types of gadolinium-based contrast agent is advocated. Hemodialysis following gadolinium exposure might offer benefits but evidence is lacking. PMID:19190625

  12. Does the uremic milieu affect the epigenotype?

    PubMed

    Stenvinkel, Peter; Ekström, Tomas J

    2009-01-01

    Epigenetics is a discipline that for many years has languished in the shadow of its genomic big brother. Because our understanding of the role played by epigenetics in chronic kidney disease remains in its infancy, further studies are needed to understand the associations, for instance, of aberrant DNA methylation in relation to uremic dysmetabolism, and its presumably very complex interactions in the development of premature uremic vascular disease. Further research is also needed to study the association between aberrant global DNA-methylation, gene-level methylation status, and the silencing (or activation) of candidate genes associated with atherosclerosis. Insofar as it seems possible to manipulate the epigenome, the effects of various epigenetic-targeted and pathway-targeted therapeutic approaches on unbalanced DNA methylation, gene silencing, and vascular health and outcomes should be explored further in uremia.

  13. Managing atypical hemolytic uremic syndrome: chapter 2.

    PubMed

    Nester, Carla M

    2015-05-01

    Licht et al. present the 2-year follow-up data of the landmark trials studying the efficacy of eculizumab in the treatment of atypical hemolytic uremic syndrome (aHUS). They report sustained improvements in hematologic parameters, continued safety, and additional improvements in kidney function with extended treatment. This report adds a layer of comfort to our care of patients with this rare disease; however, it is unlikely to be the final chapter in the treatment of aHUS.

  14. Bioengineered kidney tubules efficiently excrete uremic toxins

    PubMed Central

    Jansen, J.; Fedecostante, M.; Wilmer, M. J.; Peters, J. G.; Kreuser, U. M.; van den Broek, P. H.; Mensink, R. A.; Boltje, T. J.; Stamatialis, D.; Wetzels, J. F.; van den Heuvel, L. P.; Hoenderop, J. G.; Masereeuw, R.

    2016-01-01

    The development of a biotechnological platform for the removal of waste products (e.g. uremic toxins), often bound to proteins in plasma, is a prerequisite to improve current treatment modalities for patients suffering from end stage renal disease (ESRD). Here, we present a newly designed bioengineered renal tubule capable of active uremic toxin secretion through the concerted action of essential renal transporters, viz. organic anion transporter-1 (OAT1), breast cancer resistance protein (BCRP) and multidrug resistance protein-4 (MRP4). Three-dimensional cell monolayer formation of human conditionally immortalized proximal tubule epithelial cells (ciPTEC) on biofunctionalized hollow fibers with maintained barrier function was demonstrated. Using a tailor made flow system, the secretory clearance of human serum albumin-bound uremic toxins, indoxyl sulfate and kynurenic acid, as well as albumin reabsorption across the renal tubule was confirmed. These functional bioengineered renal tubules are promising entities in renal replacement therapies and regenerative medicine, as well as in drug development programs. PMID:27242131

  15. Calcific Metamorphosis: A Review

    PubMed Central

    Siddiqui, Shoaib Haider; Mohamed, Ahmed Nabil

    2016-01-01

    Dental trauma to the permanent dentition can lead to clinical complications and its management may considerably challenge a practitioner. The incidence of pulp canal obliteration following dental trauma has been reported to be approximately 4 – 24%. Attempting to locate canals following calcific metamorphosis and negotiating it to full working length may lead to iatrogenic errors such as fractured instrument and perforation. This review article describes the possible etiology of Calcific Metamorphosis, its clinical and radiographic features as well as its management. PMID:27610067

  16. Familial idiopathic cerebral calcifications.

    PubMed Central

    Boller, F; Boller, M; Gilbert, J

    1977-01-01

    Nine members of a family spanning three generations showed bilateral calcifications of the basal ganglia with autosomal dominant inheritance. Two members developed chorea, dementia, and a characteristic speech disturbance (palialalia) in the third or fourth decade. A third member possibly shows the initial stage of a similar syndrome. Six members with calcifications but without neurological signs are younger than 25 years. All nine patients had normal calcium and phosphorus, and no evidence of endocrinological or somatic abnormalities. Thie 'isiopathic' picture must be differentiated from hypoparathyroidism and pseudohypoparathyroidism. Images PMID:886353

  17. Shiga toxin associated hemolytic uremic syndrome.

    PubMed

    Keir, Lindsay Susan

    2015-06-01

    Shiga toxin associated hemolytic uremic syndrome (Stx HUS), a thrombotic microangiopathy, is the most common cause of pediatric acute kidney injury but has no direct treatment. A better understanding of disease pathogenesis may help identify new therapeutic targets. For this reason, the role of complement is being actively studied while eculizumab, the C5 monoclonal antibody, is being used to treat Stx HUS but with conflicting results. A randomized controlled trial would help properly evaluate its use in Stx HUS while more research is required to fully evaluate the role complement plays in the disease pathogenesis.

  18. 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

  19. Pineal calcification among black patients.

    PubMed

    Fan, K J

    1983-08-01

    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.

  20. Uremic toxins originating from colonic microbial metabolism.

    PubMed

    Evenepoel, Pieter; Meijers, Bjorn K I; Bammens, Bert R M; Verbeke, Kristin

    2009-12-01

    Numerous molecules, which are either excreted or metabolized by the kidney, accumulate in patients with chronic kidney disease (CKD). These uremic retention molecules (URMs), contributing to the syndrome of uremia, may be classified according to their site of origin, that is, endogenous metabolism, microbial metabolism, or exogenous intake. It is increasingly recognized that bacterial metabolites, such as phenols, indoles, and amines, may contribute to uremic toxicity. In vitro studies have implicated bacterial URMs in CKD progression, cardiovascular disease, and bone and mineral disorders. Furthermore, several observational studies have demonstrated a link between serum levels of bacterial URMs and clinical outcomes. Bacterial metabolism may therefore be an important therapeutic target in CKD. There is evidence that besides reduced renal clearance, increased colonic generation and absorption explain the high levels of bacterial URMs in CKD. Factors promoting URM generation and absorption include an increased ratio of dietary protein to carbohydrate due to insufficient intake of fiber and/or reduced intestinal protein assimilation, as well as prolonged colonic transit time. Two main strategies exist to reduce bacterial URM levels: interventions that modulate intestinal bacterial growth (e.g., probiotics, prebiotics, dietary modification) and adsorbent therapies that bind bacterial URMs in the intestines to reduce their absorption (e.g., AST-120, sevelamer). The efficacy and clinical benefit of these strategies are currently an active area of interest. PMID:19946322

  1. Uremic pruritus. Clinical and experimental studies.

    PubMed

    Ståhle-Bäckdahl, M

    1989-01-01

    The aim of the study was to investigate clinical aspects of pruritus in maintenance hemodialysis patients and to evaluate factors of putative pathogenic importance. 60-65% of the patients in a maintenance hemodialysis program during a two-year period suffered from itching. Patients with pruritus tended to have been on dialysis treatment longer than those without pruritus (p = 0.05), otherwise there was no difference in clinical data or routine laboratory tests. Measurement of itch intensity continuously over one week in 28 patients using a computerized method showed that itching peaked at night after two days without dialysis, was relatively high during treatment and lowest during the day following dialysis. Our results suggest that the accumulation of pruritogens between dialysis sessions influences the intensity of itching. Most patients had "dry" skin. Recording of the stratum corneum water content by measurement of electrical capacitance, in 31 patients (19 with pruritus) and 12 controls, disclosed no significant difference between dialysis patients and controls, but a tendency that pruritic patients had a lower water content than the other subjects. In different body areas, there was a positive correlation in all groups between the clinical estimation of xerosis and hydration. Serum concentrations of parathyroid hormone (PTH) were significantly higher in dialysis patients with pruritus than in those without, but there was no correlation between the degree of symptoms and the PTH level. Indirect immunohistochemistry revealed no immunoreactivity for different parts of the PTH molecule in skin biopsies from uremic patients. Intradermal injections of PTH fragments did not evoke itching or other cutaneous reactions in patients or controls. Our results do not support PTH as a peripheral mediator of uremic itching. Flare reactions induced by intradermal histamine injections were significantly smaller in 26 dialysis patients (18 with pruritus) than in 9 healthy

  2. Effects of Sucroferric Oxyhydroxide Compared to Lanthanum Carbonate and Sevelamer Carbonate on Phosphate Homeostasis and Vascular Calcifications in a Rat Model of Chronic Kidney Failure

    PubMed Central

    Phan, Olivier; Maillard, Marc; Malluche, Hartmut H.; Stehle, Jean-Christophe; Funk, Felix; Burnier, Michel

    2015-01-01

    Elevated serum phosphorus, calcium, and fibroblast growth factor 23 (FGF23) levels are associated with cardiovascular disease in chronic renal disease. This study evaluated the effects of sucroferric oxyhydroxide (PA21), a new iron-based phosphate binder, versus lanthanum carbonate (La) and sevelamer carbonate (Se), on serum FGF23, phosphorus, calcium, and intact parathyroid hormone (iPTH) concentrations, and the development of vascular calcification in adenine-induced chronic renal failure (CRF) rats. After induction of CRF, renal function was significantly impaired in all groups: uremic rats developed severe hyperphosphatemia, and serum iPTH increased significantly. All uremic rats (except controls) then received phosphate binders for 4 weeks. Hyperphosphatemia and increased serum iPTH were controlled to a similar extent in all phosphate binder-treatment groups. Only sucroferric oxyhydroxide was associated with significantly decreased FGF23. Vascular calcifications of the thoracic aorta were decreased by all three phosphate binders. Calcifications were better prevented at the superior part of the thoracic and abdominal aorta in the PA21 treated rats. In adenine-induced CRF rats, sucroferric oxyhydroxide was as effective as La and Se in controlling hyperphosphatemia, secondary hyperparathyroidism, and vascular calcifications. The role of FGF23 in calcification remains to be confirmed. PMID:26221597

  3. Effects of Sucroferric Oxyhydroxide Compared to Lanthanum Carbonate and Sevelamer Carbonate on Phosphate Homeostasis and Vascular Calcifications in a Rat Model of Chronic Kidney Failure.

    PubMed

    Phan, Olivier; Maillard, Marc; Malluche, Hartmut H; Stehle, Jean-Christophe; Funk, Felix; Burnier, Michel

    2015-01-01

    Elevated serum phosphorus, calcium, and fibroblast growth factor 23 (FGF23) levels are associated with cardiovascular disease in chronic renal disease. This study evaluated the effects of sucroferric oxyhydroxide (PA21), a new iron-based phosphate binder, versus lanthanum carbonate (La) and sevelamer carbonate (Se), on serum FGF23, phosphorus, calcium, and intact parathyroid hormone (iPTH) concentrations, and the development of vascular calcification in adenine-induced chronic renal failure (CRF) rats. After induction of CRF, renal function was significantly impaired in all groups: uremic rats developed severe hyperphosphatemia, and serum iPTH increased significantly. All uremic rats (except controls) then received phosphate binders for 4 weeks. Hyperphosphatemia and increased serum iPTH were controlled to a similar extent in all phosphate binder-treatment groups. Only sucroferric oxyhydroxide was associated with significantly decreased FGF23. Vascular calcifications of the thoracic aorta were decreased by all three phosphate binders. Calcifications were better prevented at the superior part of the thoracic and abdominal aorta in the PA21 treated rats. In adenine-induced CRF rats, sucroferric oxyhydroxide was as effective as La and Se in controlling hyperphosphatemia, secondary hyperparathyroidism, and vascular calcifications. The role of FGF23 in calcification remains to be confirmed.

  4. Arterial calcification: Conscripted by collagen

    NASA Astrophysics Data System (ADS)

    Miller, Jordan D.

    2016-03-01

    In atherosclerotic plaques, patterns of calcification -- which have profound implications for plaque stability and vulnerability to rupture -- are determined by the collagen's content and patterning throughout the plaque.

  5. [Hemolytic uremic syndrome. Treatment of secondary glomerulopathy].

    PubMed

    Caletti, María G; Gallo, Guillermo

    2005-01-01

    Chronic renal failure (CRF) is the most severe complication of hemolytic uremic syndrome (HUS). In 1996, the histological sequence of changes in patients with long lasting oligoanuric periods was clarified. In the last years different therapeutic schemes have been proposed in order to slacken the development of terminal CRF in different renal conditions secondary to diabetes and other diseases. Some of these cases can suffer the onset of renal failure at adolescence. In this review, response to two treatment schemes in different patients with HUS and proteinuria with or without hypertension or renal failure is commented. Early indication of poor sodium diet and strict control of protein intake at the very moment of hospital discharge is strongly recommended, as well as angiotensin II conversion inhibiting enzymes (iACE) at the appearance of proteinuria.

  6. Thrombosis in the uremic milieu--emerging role of "thrombolome".

    PubMed

    Shashar, Moshe; Francis, Jean; Chitalia, Vipul

    2015-01-01

    Chronic kidney disease (CKD) is characterized by retention of a number of toxins, which unleash cellular damage. CKD environment with these toxins and a host of metabolic abnormalities (collectively termed as uremic milieu) is highly thrombogenic. CKD represents a strong and independent risk factor for both spontaneous venous and arterial (postvascular injury) thrombosis. Emerging evidence points to a previously unrecognized role of some of the prothrombotic uremic toxins. Here, we provide an overview of thrombosis in CKD and an update on indolic uremic toxins, which robustly increase tissue factor, a potent procoagulant, in several vascular cell types enhancing thrombosis. This panel of uremic toxins, which we term "thrombolome" (thrombosis and metabolome), represents a novel risk factor for thrombosis and can be further explored as biomarker for postvascular interventional thrombosis in patients with CKD.

  7. Uremic frost: a harbinger of impending renal failure.

    PubMed

    Saardi, Karl M; Schwartz, Robert A

    2016-01-01

    Uremic frost is a striking cutaneous finding seen in patients with severe kidney disease. Familiarity with this condition can be a life-saving signal to initiate urgent dialysis. Uremic frost generally occurs at blood urea nitrogen levels of approximately 200 mg/dl, although it may arise with less severe uremia. Recently confirmed urea transporters in the skin may play a role in the development of uremic frost. Alternatively, damage to the cutaneous microvasculature and pilosebaceous units, as seen in chronic kidney disease, could account for the high levels of urea deposited outside the skin. The treatment of uremic frost is largely aimed at correcting the underlying cause of uremia and the other life-threatening conditions associated with renal failure.

  8. Vascular calcification: Mechanisms of vascular smooth muscle cell calcification.

    PubMed

    Leopold, Jane A

    2015-05-01

    Vascular calcification is highly prevalent and, when present, is associated with major adverse cardiovascular events. Vascular smooth muscle cells play an integral role in mediating vessel calcification by undergoing differentiation to osteoblast-like cells and generating matrix vesicles that serve as a nidus for calcium-phosphate deposition in the vessel wall. Once believed to be a passive process, it is now recognized that vascular calcification is a complex and highly regulated process that involves activation of cellular signaling pathways, circulating inhibitors of calcification, genetic factors, and hormones. This review will examine several of the key mechanisms linking vascular smooth muscle cells to vessel calcification that may be targeted to reduce vessel wall mineralization and, thereby, reduce cardiovascular risk.

  9. Quality of life in predialytic uremic patients.

    PubMed

    Klang, B; Björvell, H; Clyne, N

    1996-02-01

    This study describes and analyses how 38 predialytic uremic patients perceived their sense of well-being, functional ability, level of anxiety and sense of coherence. The patients in this study reported decreased sense of well-being, considerable functional disabilities, and a high level of anxiety when compared to a healthy reference group. These observations were independent of laboratory data with the exception of hemoglobin concentration which showed a significant negative correlation to the SIP scale work. There was a significant negative correlation between the scores of sense of coherence and anxiety. Patients with a weak sense of coherence and a high level of anxiety perceived their well-being as being worse than those with higher scores in the sense of coherence test and lower scores in the level of anxiety test. Sense of well-being in turn influenced functional ability in daily life. Social and marital status also affected the results. These results indicate that the investigated group of predialytic patients have a decrease in quality of life. The results obtained provide a useful instrument showing in which areas care should be concentrated and in what way patients' own resources need to be strengthened while preparing for dialysis treatment.

  10. Thyroid calcifications: a pictorial essay.

    PubMed

    Lacout, Alexis; Chevenet, Carole; Thariat, Juliette; Marcy, Pierre Yves

    2016-05-01

    Incidental diagnosis of thyroid nodules is very common on adult neck ultrasonography examination. Thyroid calcifications are encountered in benign thyroid nodules and goiters as well as in thyroid malignancy. Depiction and characterization of such calcifications within a thyroid nodule may be a key element in the thyroid nodule diagnosis algorithm. The goal of this paper is to display typical radio-pathological correlations of various thyroid pathologies of benign and malignant conditions in which the calcification type diagnosis can play a key role in the final diagnosis of the thyroid nodule. PMID:26891122

  11. Cardiorenal syndrome: role of protein-bound uremic toxins.

    PubMed

    Lekawanvijit, Suree; Krum, Henry

    2015-03-01

    Renal impairment is a strong independent risk factor associated with poor prognosis in cardiovascular disease patients. Renal dysfunction is likely contributed by progressive renal structural damage. Accurate detection of kidney injury in a timely manner as well as increased knowledge of the pathophysiology and mechanisms underlying this injury is of great importance in developing therapeutic interventions for combating renal complications at an early stage. Regarding the role of uremic solutes in the pathophysiology of cardiorenal syndrome, a number of further studies are warranted. There may be uremic solutes discovered from proteomics not yet chemically identified or tested for biological activity. Beyond Protein-bound uremic toxins, uremic solutes in other classes (according to the European Uraemic Toxin Work Group classification) may have adverse cardiorenal effects. Although most small water-soluble solutes and middle molecules can be satisfactorily removed by either conventional or newly developed dialysis strategies, targeting uremic toxins with cardiorenal toxicity at predialysis stage of chronic kidney disease may retard or prevent incident dialysis as well as the initiation/progression of cardiorenal syndrome. PMID:25556308

  12. Extracorporeal removal of uremic toxins: can we still do better?

    PubMed

    Eloot, Sunny; Ledebo, Ingrid; Ward, Richard A

    2014-03-01

    Improving outcomes by manipulating the prescription of renal replacement therapy to increase the removal of uremic toxins has had limited success. Failure to achieve better outcomes can be attributed to the heterogenic nature of uremic toxins, the complex distribution of some toxins in the body, and the predominant regimen of thee times weekly, in-center hemodialysis. This review summarizes the various mechanisms and kinetics of removal for the three major classes of uremic toxin-small water-soluble solutes, middle molecules, and protein-bound solutes-from both a theoretical and an experimental perspective. Taken together, the available data suggest that contemporary dialyzers are not a significant impediment to the removal of water-soluble uremic toxins, particularly when combined with commonly used blood and dialysis fluid flow rates and in online convective therapies. Enhancing the removal of those solutes will require a change in paradigm to longer and more frequent treatment sessions. Whether or not such a strategy also would improve the removal of protein-bound uremic toxins is less clear; that goal might require the development of different, more complex devices than those currently used for renal replacement therapy.

  13. Vascular calcification inhibitors in relation to cardiovascular disease with special emphasis on fetuin-A in chronic kidney disease.

    PubMed

    Suliman, Mohamed E; García-López, Elvia; Anderstam, Björn; Lindholm, Bengt; Stenvinkel, Peter

    2008-01-01

    The mortality rate is extremely high in chronic kidney disease (CKD), primarily due to the high prevalence of cardiovascular disease (CVD) in this patient group. Apart from traditional Framingham risk factors, evidences suggest that nontraditional risk factors, such as inflammation, oxidative stress, endothelial dysfunction, and vascular calcification also contribute to this extremely high risk of CVD. Disturbance in the mineral metabolism, especially in the ions of Ca and PO4, are linked to enhanced calcification of blood vessels. Although the mechanism(s) of this enhanced calcification process are not fully understood, current knowledge suggests that a large number (and an imbalance between them) of circulating promoters and inhibitors of the calcification process, that is, fetuin-A (or alpha 2-Heremans-Schmid glycoprotein, AHSG), matrix-Gla protein (MGP), osteoprotegerin (OPG), osteopontin (OPN), bone morphogenetic proteins (BMPs), and inorganic pyrophosphate (PPi), are involved in the deterioration of vascular tissue. Thus, an imbalance in these factors may contribute to the high prevalence of vascular complications in CKD patients. Among these mediators, studies on fetuin-A deserve further attention as clinical studies consistently show that fetuin-A deficiency is associated with vascular calcification, all-cause and cardiovascular mortality in CKD patients. Both chronic inflammation and the uremic milieu per se may contribute to fetuin-A depletion, as well as specific mutations in the AHSG gene. Recent experimental and clinical studies also suggest an intriguing link between fetuin-A, insulin resistance, and the metabolic syndrome.

  14. Metabolic bone disease in chronic renal failure. I. Dialyzed uremics.

    PubMed Central

    Huffer, W. E.; Kuzela, D.; Popovtzer, M. M.

    1975-01-01

    Garner and ball's point counting technic was used to compare metabolic bone disease in dialyzed and nondialyzed uremic patients. Histologic measurements of bone from dialyzed and nondialyzed uremic patients dying between 1966 and 1971 showed that dialyzed patients have quantitatively more severe bone resorption, distortion of trabecular architecture and mineralization defects. Mineralization defects become more severe as the duration of dialysis increases but are not related to serum calcium and phosphorus levels. Bone volume in both groups is normal or increased and in dialysis patients increases in proportion to the elevation of serum phosphorus. Mean serum phosphorus and calcium levels, bone volume, and volume: surface ratios all decreased in dialysis patients between 1966 and 1971, while bone resorption and mineralization defects did not change. These results suggest that lowering of serum phosphorus without increasing serum calcium may aggrevate the uremic bone disease by reducing bone volume without improvement of mineralization and resorption defects. Images Fig 1 PMID:1119535

  15. Hemolytic uremic syndrome in an infant following Bordetella pertussis infection.

    PubMed

    Pela, I; Seracini, D; Caprioli, A; Castelletti, F; Giammanco, A

    2006-08-01

    Reported here is the case of a 6-week-old female infant with a severe Bordetella pertussis infection requiring supportive pressure-positive ventilation in the intensive care unit. After being discharged from the intensive care unit, she developed hemolytic anemia, thrombocytopenia and acute renal failure, which suggested a diagnosis of hemolytic uremic syndrome. The clinical outcome was favorable with no renal consequences. This case suggests there may be a direct cause-effect relationship between B. pertussis infection and hemolytic uremic syndrome. PMID:16871374

  16. Calcification prevention tablets

    NASA Technical Reports Server (NTRS)

    Lindsay, Geoffrey A.; Hasting, Michael A.; Gustavson, Michael A.

    1991-01-01

    Citric acid tablets, which slowly release citric acid when flushed with water, are under development by the Navy for calcification prevention. The citric acid dissolves calcium carbonate deposits and chelates the calcium. For use in urinals, a dispenser is not required because the tablets are non-toxic and safe to handle. The tablets are placed in the bottom of the urinal, and are consumed in several hundred flushes (the release rate can be tailored by adjusting the formulation). All of the ingredients are environmentally biodegradable. Mass production of the tablets on commercial tableting machines was demonstrated. The tablets are inexpensive (about 75 cents apiece). Incidences of clogged pipes and urinals were greatly decreased in long term shipboard tests. The corrosion rate of sewage collection pipe (90/10 Cu/Ni) in citric acid solution in the laboratory is several mils per year at conditions typically found in traps under the urinals. The only shipboard corrosion seen to date is of the yellow brass urinal tail pieces. While this is acceptable, the search for a nontoxic corrosion inhibitor is underway. The shelf life of the tablets is at least one year if stored at 50 percent relative humidity, and longer if stored in sealed plastic buckets.

  17. Should dialysis modalities be designed to remove specific uremic toxins?

    PubMed

    Baurmeister, Ulrich; Vienken, Joerg; Ward, Richard A

    2009-01-01

    The definition of optimal dialysis therapy remains elusive. Randomized clinical trials have neither supported using urea as a surrogate marker for uremic toxicity nor provided clear cut evidence in favor of larger solutes. Thus, where to focus resources in the development of new membranes, and therapies remains unclear. Three basic questions remain unanswered: (i) what solute(s) should be used as a marker for optimal dialysis; (ii) should dialytic therapies be designed to remove a specific solute; and (iii) how can current therapies be modified to provide better control of uremic toxicity? Identification of a single, well-defined uremic toxin appears to be unlikely as new analytical tools reveal an increasingly complex uremic milieu. As a result, it is probable that membranes and therapies should be designed for the nonspecific removal of a wide variety of solutes retained in uremia. Removal of the widest range of solutes can best be achieved using existing therapies that incorporate convection in conjunction with longer treatment times and more frequent treatments. Membranes capable of removing solutes over an expanded effective molecular size range can already be fabricated; however, their use will require novel approaches to conserve proteins, such as albumin.

  18. Adult hemolytic-uremic syndrome and bone marrow necrosis

    SciTech Connect

    Hicks, C.B.; Redmond, J. III

    1984-11-01

    A case is reported of adult hemolytic-uremic syndrome in which massive bone marrow necrosis developed, a previously undescribed complication. Technetium-99m minicolloid scanning and indium-111 bone marrow scans were used to demonstrate lack of bone marrow activity in the patient. 11 references, 2 figures.

  19. Calcification Transformation of Diasporic Bauxite

    NASA Astrophysics Data System (ADS)

    Zhao, Qiuyue; Zhu, Xiaofeng; Lv, Guozhi; Zhang, Zimu; Yin, Zhengnan; Zhang, Tingan

    2016-06-01

    The disposal of red mud, which is a solid waste that is generated during the extraction of alumina from bauxite, is one of major problems faced by the aluminum industry. Alkali in red mud seeping under the soil may pollute land and water. The Northeastern University, China, has proposed a calcification-carbonation method to deal with low-grade bauxite or red mud. Its main purpose is to change the equilibrium phase of red mud to 2CaO·SiO2 and CaCO3 hydrometallurgically, so that recomposed alkali-free red mud can be widely used. We conducted calcification transformation experiments using diasporic bauxite sampled from Wenshan, and investigated the effects of parameters such as diasporic bauxite grain size, temperature and treatment time on the calcification transformation digestion rate, which is also termed the calcification transformation rate (CTR). The main phase in the calcification transformation slag (CTS) is hydrogarnet with different grain sizes. The CTR increases with decrease in diasporic bauxite grain size, or increase in temperature or reaction time. The CTR reaches a maximum of 87% after 120 min reaction at 240°C. The Na2O/Al2O3 ratio decreases with increase in temperature and reaches 1.5. The sodium content in the CTS decreases with increasing reaction time and is lower than that in the red mud treated using the Bayer process (4-12%).

  20. Experimental Calcification of the Myocardium

    PubMed Central

    Bonucci, Ermanno; Sadun, Raffaele

    1973-01-01

    Focal areas of calcification are frequent in rat myocardium 30 and 60 days after administration of dihydrotachysterol. These areas are PAS-positive, stain deeply with alcian blue and show high affinity for colloidal iron. Calcification is almost completely confined to intracellular structures. Small clusters of needle-shaped crystals are first found in apparently undamaged mitochondria in undamaged myocardial cells. When all the mitochondria are calcified, the cell degenerates, and inorganic crystals are laid down in relationship with its myofilaments. In other myocardial cells, clusters of amorphous or finely granular inorganic substance are found in both mitochondria and myofibrils. Both structures show signs of advanced degeneration. Inorganic substance has only occasionally been found within the structures of the sarcoplasmic reticulum. These structures do not seem to be involved in myocardial calcification under the present experimental conditions. Calcification of myocardial cells gives rise to a cellular reaction. Many macrophagic cells surround the calcified areas, which are rapidly reabsorbed. The present results show that myocardial mitochondria are actively engaged in controlling the intracellular concentration and movement of calcium ions. Their role in the myocardial contraction-relaxation cycle and the possible mechanism of myocardial calcification are discussed. ImagesFig 14Fig 1Fig 2Fig 3Fig 4Fig 5Fig 6Fig 7Fig 8Fig 9Fig 10Fig 11Fig 12Fig 13 PMID:4197422

  1. CT of schistosomal calcification of the intestine

    SciTech Connect

    Fataar, S.; Bassiony, H.; Satyanath, S.; Rudwan, M.; Hebbar, G.; Khalifa, A.; Cherian, M.J.

    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.

  2. 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.

  3. Genetics and molecular biology of brain calcification.

    PubMed

    Deng, Hao; Zheng, Wen; Jankovic, Joseph

    2015-07-01

    Brain calcification is a common neuroimaging finding in patients with neurological, metabolic, or developmental disorders, mitochondrial diseases, infectious diseases, traumatic or toxic history, as well as in otherwise normal older people. Patients with brain calcification may exhibit movement disorders, seizures, cognitive impairment, and a variety of other neurologic and psychiatric symptoms. Brain calcification may also present as a single, isolated neuroimaging finding. When no specific cause is evident, a genetic etiology should be considered. The aim of the review is to highlight clinical disorders associated with brain calcification and provide summary of current knowledge of diagnosis, genetics, and pathogenesis of brain calcification.

  4. [Pharmacokinetics of defibrotide in uremic patients undergoing hemodialysis].

    PubMed

    Rossi, R; Farma, A; Maggi, G C; Marelli, A

    1991-12-01

    Defibrotide pharmacokinetics were studied in 6 voluntary healthy subjects and in 10 uremic patients undergoing dialysis during which (instead of heparin) defibrotide was administered to prevent fibrino-formation in the circuit. Blood concentrations of the drug were assessed (expressed with reference to the residual glycidic deoxyribose) during a standard dialysis using defibrotide, 3.5, 15, 30, 45, 60 and 90 minutes after the defibrotide bolus (200 mg) had been injected into the arterial channel. The half-lives of the alpha and beta plasmatic phases were found to be equal at 3.79 and 41.4 min in dialysed subjects and at 1.13 and 16.54 in healthy volunteers. These results indicate that in uremic patients undergoing dialysis at intervals using defibrotide, a longer time is required to eliminate the drug from the circulation. This variation does not however appear to be significant in terms of the therapeutic use of the drug during dialysis.

  5. Critical appraisal of eculizumab for atypical hemolytic uremic syndrome

    PubMed Central

    Palma, Lilian M Pereira; Langman, Craig B

    2016-01-01

    The biology of atypical hemolytic uremic syndrome has been shown to involve inability to limit activation of the alternative complement pathway, with subsequent damage to systemic endothelial beds and the vasculature, resulting in the prototypic findings of a thrombotic microangiopathy. Central to this process is the formation of the terminal membrane attack complex C5b-9. Recently, application of a monoclonal antibody that specifically binds to C5, eculizumab, became available to treat patients with atypical hemolytic uremic syndrome, replacing plasma exchange or infusion as primary therapy. This review focuses on the evidence, based on published clinical trials, case series, and case reports, on the efficacy and safety of this approach. PMID:27110144

  6. Distribution of purine nucleotides in uremic fluids and tissues.

    PubMed

    Rutkowski, Bolesław; Rutkowski, Przemysław; Słomińska, Ewa; Swierczyński, Julian

    2010-09-01

    There are almost 100 different substances called uremic toxins. In this study, we analyze all findings concerning the new family of uremic compounds--nicotinamide end products: N-methyl-2-pyridone-5-carboxamide (Met2PY), N-methyl-4-pyridone-5-carboxamide, newly described 4-pyridone-3-carboxamide-1-beta-D-ribonucleoside (4PYR) and 4-pyridone-3-carboxamide-1-beta-D-ribonucleoside triphosphate (4PYTP). After few years of studies, we have found that these substances have higher plasma concentration in patients with chronic renal failure (CRF) in comparison with the healthy population. We noted a 40-fold increase in plasma 4PYR concentration in patients with CRF. This increment correlates significantly with the decline of kidney function measured as an increase of serum creatinine concentration and decrease of estimated glomerular filtration rate. Tested compounds are present and measurable in physiological fluids and tissues. We found higher saliva Met2PY concentration in patients with CRF in comparison with controls. Saliva Met2PY correlated negatively with estimated glomerular filtration rate and positively with serum creatinine concentration. One-third of studied group had higher concentration of Met2PY in the saliva than in plasma, and this segment of patients may be called as "good excretors." In rats with experimental CRF, we found that both Met2PY and N-methyl-4-pyridone-5-carboxamide accumulated in selected tissues. We also demonstrated formation of 4PYTP in intact human erythrocytes during incubation with the precursor 4PYR. Incubation with 4PYR leads to lowering concentration of adenosine-5'-triphosphate. 4PYTP formation may be a way to remove 4PYR from the circulation and save adenosine-5'-triphosphate depletion. Summarizing, end products of the nicotinamide family are members of uremic toxins; however, exact pathophysiological role of these compounds in the development of uremic syndrome needs further studies. PMID:20797575

  7. 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. PMID:26363090

  8. 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.

  9. Neutrophil function in an experimental model of hemolytic uremic syndrome.

    PubMed

    Vedanarayanan, V V; Kaplan, B S; Fong, J S

    1987-03-01

    To understand the role of neutrophil leukocytosis in hemolytic uremic syndrome, we studied the changes in neutrophil function in the modified generalized Shwartzman reaction in rabbits. This model resembles hemolytic uremic syndrome associated with endotoxemia. At the end of an endotoxin infusion, we observed leukopenia, thrombocytopenia, and a decrease in hematocrit associated with schistocytosis. Plasma B-glucuronidase levels increased and this was associated with a decrease in neutrophil content of the enzyme. The chemotactic index and neutrophil aggregation to zymosan-activated serum were impaired compared to controls. The neutrophil procoagulant content increased after endotoxin infusion. The serum creatinine concentration and proteinuria increased in the endotoxin-treated animals. The changes returned to normal by 48 h. Renal cortical malondialdehyde, a reflection of lipid peroxidation, was higher in the endotoxin-treated animals than in the controls. We have shown enzyme release by neutrophils, impairment of chemotaxis and aggregation, increased procoagulant content in neutrophils, and evidence of lipid peroxidation in renal cortical tissue in this model. These observations raise the possibility that leukocytes may have a role in the pathogenesis of the hemolytic uremic syndrome. PMID:3550673

  10. Epigenetics and the uremic phenotype: a matter of balance.

    PubMed

    Stenvinkel, Peter; Ekström, Tomas J

    2008-01-01

    Epigenetics, which is the study of changes in gene expression that occur without changes in DNA sequence, is a novel discipline that has languished in the shadow of its genomic big brother. So far, studies of the epigenome have attracted little interest in nephrology. Chronic kidney disease is an example of complex disease in which the phenotype arises from a combination of environmental and heritable factors. Evidence suggests that the contribution made by the environment may be mediated via modifications of the epigenome. In the uremic milieu, several features such as inflammation, dyslipidemia, hyperhomocysteinema, oxidative stress as well as vitamin and nutritional deficiencies may affect aberrant global DNA methylation. However, as hyperhomocysteinemia seems to promote global DNA hypomethylation and persistent inflammation DNA hypermethylation, the effects of the uremic milieu on aberrant global DNA methylation may be complex and context-sensitive. It should be emphasized that in analogy to the unspecific nature of fever, aberrant global DNA methylation is only a sign of a generalized epigenetic dysregulation. Thus, to provide better understanding of the effects of aberrant DNA methylation on the uremic phenotype, further studies evaluating site-specific information on methylation in various candidate genes are needed. The science of epigenetics may not only uncover etiologic and pathogenic mechanisms in uremia, but may also be of help to develop novel treatment strategies targeting the unacceptable high death risk in cardiovascular complications in this patient population.

  11. 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

  12. Calcific retropharyngeal tendinitis. [Radiological findings

    SciTech Connect

    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 density in the longus colli tendon anterior to the body of C2 and inferior to the anterior arch of C1.

  13. [Atherosclerotic calcification of coronary artery detected by electron beam CT: A new probation of calcific algorithm].

    PubMed

    Li, Wensheng; Song, Zhijian; Zhao, Shumin; Zuo, Huanchen

    2006-08-01

    Electron beam computed tomography (EBCT) can detect the atherosclerotic calcification of coronary artery qualitatively and quantitatively. It was also verified that the atherosclerotic calcification was directly related to the atherosclerotic extent and had a limited relation to the occurrence of coronary heart disease (CHD). So EBCT is one of the good non-invasive methods for predicting the risk of CHD. However, there are some problems in the calcification parameters (calcification area, calcification score) adopted by EBCT which have high variability and low reproducibility. As a result, these parameters have imperfection and need to be improved further. This research provides a new calcification parameter (calcification volume) which makes the use of three dimensional information of all calcific pixels in EBCT scanning images of coronary artery. After experiment in 11 human coronary artery specimens, it was testified that calcification volume had a lower variability than calcification area and calcification score in 25% percentile, median, 75% percentile, Mean, respectively. P value of t test in Mean variability is 0.027, and 0.058. These results suggest that calcification volume may be a new calcification parameter. PMID:17002127

  14. Pleural calcification in northwest Greece

    SciTech Connect

    Bazas, T.; Oakes, D.; Gilson, J.C.; Bazas, B.; McDonald, J.C.

    1985-12-01

    Mass miniature radiography in 1969 detected a high prevalence of pleural calcification in three villages in northwest Greece. In 1980 a survey of a 15% sample of the population over the age of 10 was carried out with a 80% response rate. Full-size radiographs, ventilatory capacity measurements, and a detailed questionnaire on respiratory symptoms, type of work, and residence were used. Independent classification of the 408 films by two readers using the ILO/UC scheme showed very few small opacities but a very high prevalence of pleural calcification first evident in young adults and rising to 70% in the elderly. The overall prevalence was 34.7% in men and 21.5% in women. A comparison with the 1969 survey showed a progression rate of 5% per annum. In neither sex was there a significant relation of pleural calcification to smoking, ventilatory capacity, nor type of work, though those classified as field croppers had a slightly higher prevalence. There was no obvious evidence of increased lung cancer or mesothelioma in the village. The agent responsible for this apparently benign condition was not identified.

  15. Incidental Anterior Cruciate Ligament Calcification: Case Report

    PubMed Central

    Hayashi, Hisami; Fischer, Hans

    2016-01-01

    The calcification of knee ligaments is a finding noted only in a handful of case reports. The finding of an anterior cruciate ligament calcification has been reported once in the literature. Comparable studies involving the posterior cruciate ligament, medial collateral ligament and an ossicle within the anterior cruciate ligament are likewise discussed in reports of symptomatic patients. We report a case of incidentally discovered anterior cruciate ligament calcification. We discuss the likely etiology and clinical implications of this finding. PMID:27200163

  16. Incidental Anterior Cruciate Ligament Calcification: Case Report.

    PubMed

    Hayashi, Hisami; Fischer, Hans

    2016-03-01

    The calcification of knee ligaments is a finding noted only in a handful of case reports. The finding of an anterior cruciate ligament calcification has been reported once in the literature. Comparable studies involving the posterior cruciate ligament, medial collateral ligament and an ossicle within the anterior cruciate ligament are likewise discussed in reports of symptomatic patients. We report a case of incidentally discovered anterior cruciate ligament calcification. We discuss the likely etiology and clinical implications of this finding.

  17. Uremic toxins enhance statin-induced cytotoxicity in differentiated human rhabdomyosarcoma cells.

    PubMed

    Uchiyama, Hitoshi; Tsujimoto, Masayuki; Shinmoto, Tadakazu; Ogino, Hitomi; Oda, Tomoko; Yoshida, Takuya; Furukubo, Taku; Izumi, Satoshi; Yamakawa, Tomoyuki; Tachiki, Hidehisa; Minegaki, Tetsuya; Nishiguchi, Kohshi

    2014-09-03

    The risk of myopathy and rhabdomyolysis is considerably increased in statin users with end-stage renal failure (ESRF). Uremic toxins, which accumulate in patients with ESRF, exert cytotoxic effects that are mediated by various mechanisms. Therefore, accumulation of uremic toxins might increase statin-induced cytotoxicity. The purpose of this study was to determine the effect of four uremic toxins-hippuric acid, 3-carboxy-4-methyl-5-propyl-2-furanpropionate, indole-3-acetic acid, and 3-indoxyl sulfate-on statin-induced myopathy. Differentiated rhabdomyosarcoma cells were pre-treated with the uremic toxins for seven days, and then the cells were treated with pravastatin or simvastatin. Cell viability and apoptosis were assessed by viability assays and flow cytometry. Pre-treatment with uremic toxins increased statin- but not cisplatin-induced cytotoxicity (p < 0.05 vs. untreated). In addition, the pre-treatment increased statin-induced apoptosis, which is one of the cytotoxic factors (p < 0.05 vs. untreated). However, mevalonate, farnesol, and geranylgeraniol reversed the effects of uremic toxins and lowered statin-induced cytotoxicity (p < 0.05 vs. untreated). These results demonstrate that uremic toxins enhance statin-induced apoptosis and cytotoxicity. The mechanism underlying this effect might be associated with small G-protein geranylgeranylation. In conclusion, the increased severity of statin-induced rhabdomyolysis in patients with ESRF is likely due to the accumulation of uremic toxins.

  18. Uremic toxins enhance statin-induced cytotoxicity in differentiated human rhabdomyosarcoma cells.

    PubMed

    Uchiyama, Hitoshi; Tsujimoto, Masayuki; Shinmoto, Tadakazu; Ogino, Hitomi; Oda, Tomoko; Yoshida, Takuya; Furukubo, Taku; Izumi, Satoshi; Yamakawa, Tomoyuki; Tachiki, Hidehisa; Minegaki, Tetsuya; Nishiguchi, Kohshi

    2014-09-01

    The risk of myopathy and rhabdomyolysis is considerably increased in statin users with end-stage renal failure (ESRF). Uremic toxins, which accumulate in patients with ESRF, exert cytotoxic effects that are mediated by various mechanisms. Therefore, accumulation of uremic toxins might increase statin-induced cytotoxicity. The purpose of this study was to determine the effect of four uremic toxins-hippuric acid, 3-carboxy-4-methyl-5-propyl-2-furanpropionate, indole-3-acetic acid, and 3-indoxyl sulfate-on statin-induced myopathy. Differentiated rhabdomyosarcoma cells were pre-treated with the uremic toxins for seven days, and then the cells were treated with pravastatin or simvastatin. Cell viability and apoptosis were assessed by viability assays and flow cytometry. Pre-treatment with uremic toxins increased statin- but not cisplatin-induced cytotoxicity (p < 0.05 vs. untreated). In addition, the pre-treatment increased statin-induced apoptosis, which is one of the cytotoxic factors (p < 0.05 vs. untreated). However, mevalonate, farnesol, and geranylgeraniol reversed the effects of uremic toxins and lowered statin-induced cytotoxicity (p < 0.05 vs. untreated). These results demonstrate that uremic toxins enhance statin-induced apoptosis and cytotoxicity. The mechanism underlying this effect might be associated with small G-protein geranylgeranylation. In conclusion, the increased severity of statin-induced rhabdomyolysis in patients with ESRF is likely due to the accumulation of uremic toxins. PMID:25192420

  19. Cardiac effect of vitamin D receptor modulators in uremic rats.

    PubMed

    Mizobuchi, Masahide; Ogata, Hiroaki; Yamazaki-Nakazawa, Ai; Hosaka, Nozomu; Kondo, Fumiko; Koiwa, Fumihiko; Kinugasa, Eriko; Shibata, Takanori

    2016-10-01

    Vitamin D receptor (VDR) modulators (VDRMs) are commonly used to control secondary hyperparathyroidism (SHPT) associated with chronic kidney disease, and are associated with beneficial outcomes in cardiovascular disease. In this study, we compared the cardiac effect of VS-105, a novel VDRM, with that of paricalcitol in 5/6 nephrectomized uremic rats. Male Sprague-Dawley rats were 5/6 nephrectomized, fed a standard diet for 4 weeks to establish uremia, and then treated (intraperitoneally, 3 times/week) with vehicle (propylene glycol), paricalcitol (0.025 and 0.15μg/kg), or VS-105 (0.05 and 0.3μg/kg) for 4 weeks. In uremic rats, neither VDRM (low and high doses) altered serum creatinine and phosphorus levels. Serum calcium was significantly higher with high dose paricalcitol compared to sham rats. PTH levels were significantly decreased with low dose paricalcitol and VS-105, and were further reduced in the high dose groups. Interestingly, serum FGF23 was significantly higher with high dose paricalcitol compared to sham rats, whereas VS-105 had no significant effect on FGF23 levels. Left ventricle (LV) weight and LV mass index determined by echocardiography were significantly suppressed in both high dose VDRM groups. This suppression was more evident with VS-105. Western blotting showed significant decreases in a fibrosis marker TGF-β1 in both high dose VDRM groups (vs. vehicle) and Masson trichrome staining showed significant decreases in cardiac fibrosis in these groups. These results suggest that VS-105 is less hypercalcemic than paricalcitol and has favorable effects on SHPT and cardiac parameters that are similar to those of paricalcitol in uremic rats. The cardioprotective effect is a noteworthy characteristic of VS-105.

  20. Thrombotic Thrombocytopenic Purpura-Haemolytic Uremic Syndrome and pregnancy

    PubMed Central

    Mwita, Julius Chacha; Vento, Sandro; Benti, Tadele

    2014-01-01

    Thrombotic Thrombocytopenic Purpura-Haemolytic Uremic Syndrome (TTP-HUS) is a rare pregnancy and postpartum complication that may simulate the more common obstetric complications, preeclampsia and the syndrome of haemolysis, elevated liver functions tests, low platelets (HELLP). We describe a 26 years old patient who presented with peri-partum TTP-HUSand was initially treated as a case of HELLP syndrome without any improvement. A brief review of the current TTP-HUS treatment options in pregnancy is also presented. PMID:25309655

  1. Uremic pruritus treated successfully with the Goeckerman Program.

    PubMed

    Nakamura, Mio; Koo, John; Bhutani, Tina

    2016-01-01

    Uremic pruritus (UP) is a common condition among patients with chronic kidney disease (CKD) on hemodialysis (HD). We report 19 a case of severe UP recalcitrant to conventional therapy including topical corticosteroids, anti-histamines, and phototherapy, 20 which was treated successfully with the Goeckerman regimen consisting of topical coal tar, topical corticosteroids, and broadband 21 UVB (BB-UVB). Little is known about the pathophysiology of UP, and there is currently no consensus or evidence-based 22 treatments for UP. Although further studies are necessary, Goeckerman therapy may be a promising treatment option when 23 available for severe UP intractable to conventional therapies. PMID:27617950

  2. Pneumococcal hemolytic uremic syndrome and steroid resistant nephrotic syndrome

    PubMed Central

    Groves, Andrew P.; Reich, Patrick; Sigdel, Binayak; Davis, T. Keefe

    2016-01-01

    Pneumococcal-associated hemolytic uremic syndrome (pHUS) is a rare but severe complication of invasive Streptococcus pneumoniae infection. We report the case of a 12-year-old female with steroid-resistant nephrotic syndrome treated with adrenocorticotrophic hormone (H.P. Acthar® Gel), who developed pneumococcal pneumonia and subsequent pHUS. While nephrotic syndrome is a well-known risk factor for invasive pneumococcal disease, this is the first reported case of pHUS in an adolescent patient with nephrotic syndrome, and reveals novel challenges in the diagnosis, treatment and potential prevention of this complication. PMID:27478599

  3. Uremic pruritus treated successfully with the Goeckerman Program.

    PubMed

    Nakamura, Mio; Koo, John; Bhutani, Tina

    2016-01-01

    Uremic pruritus (UP) is a common condition among patients with chronic kidney disease (CKD) on hemodialysis (HD). We report 19 a case of severe UP recalcitrant to conventional therapy including topical corticosteroids, anti-histamines, and phototherapy, 20 which was treated successfully with the Goeckerman regimen consisting of topical coal tar, topical corticosteroids, and broadband 21 UVB (BB-UVB). Little is known about the pathophysiology of UP, and there is currently no consensus or evidence-based 22 treatments for UP. Although further studies are necessary, Goeckerman therapy may be a promising treatment option when 23 available for severe UP intractable to conventional therapies.

  4. Clinical guides for atypical hemolytic uremic syndrome in Japan.

    PubMed

    Kato, Hideki; Nangaku, Masaomi; Hataya, Hiroshi; Sawai, Toshihiro; Ashida, Akira; Fujimaru, Rika; Hidaka, Yoshihiko; Kaname, Shinya; Maruyama, Shoichi; Yasuda, Takashi; Yoshida, Yoko; Ito, Shuichi; Hattori, Motoshi; Miyakawa, Yoshitaka; Fujimura, Yoshihiro; Okada, Hirokazu; Kagami, Shoji

    2016-07-01

    Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. In 2013, we developed diagnostic criteria to enable early diagnosis and timely initiation of appropriate treatment for aHUS. Recent clinical and molecular findings have resulted in several proposed classifications and definitions of thrombotic microangiopathy and aHUS. Based on recent advances in this field and the emerging international consensus to exclude secondary TMAs from the definition of aHUS, we have redefined aHUS and proposed diagnostic algorithms, differential diagnosis, and therapeutic strategies for aHUS. PMID:27460397

  5. Clinical guides for atypical hemolytic uremic syndrome in Japan.

    PubMed

    Kato, Hideki; Nangaku, Masaomi; Hataya, Hiroshi; Sawai, Toshihiro; Ashida, Akira; Fujimaru, Rika; Hidaka, Yoshihiko; Kaname, Shinya; Maruyama, Shoichi; Yasuda, Takashi; Yoshida, Yoko; Ito, Shuichi; Hattori, Motoshi; Miyakawa, Yoshitaka; Fujimura, Yoshihiro; Okada, Hirokazu; Kagami, Shoji

    2016-08-01

    Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. In 2013, we developed diagnostic criteria to enable early diagnosis and timely initiation of appropriate treatment for aHUS. Recent clinical and molecular findings have resulted in several proposed classifications and definitions of thrombotic microangiopathy and aHUS. Based on recent advances in this field and the emerging international consensus to exclude secondary TMAs from the definition of aHUS, we have redefined aHUS and proposed diagnostic algorithms, differential diagnosis, and therapeutic strategies for aHUS. PMID:27422619

  6. Recurrent Hemolytic and Uremic Syndrome Induced by Escherichia Coli

    PubMed Central

    Commereuc, Morgane; Weill, Francois-Xavier; Loukiadis, Estelle; Gouali, Malika; Gleizal, Audrey; Kormann, Raphaël; Ridel, Christophe; Frémeaux-Bacchi, Véronique; Rondeau, Eric; Hertig, Alexandre

    2016-01-01

    Abstract A widespread belief is that typical hemolytic and uremic syndrome (HUS) does not recur. We report the case of a patient infected twice with raw milk taken from his own cow and containing a Shiga toxin–producing Escherichia coli O174:H21 that induced recurrent HUS causing severe renal and cerebral disorders. A genomic comparison of the human and bovine Shiga toxin–producing Escherichia coli O174:H21 isolates revealed that they were identical. Typical HUS may recur. Since milk from this animal was occasionally distributed locally, thereby posing a serious threat for the whole village, this particular cow was destroyed. PMID:26735524

  7. Penile calciphylaxis: a life-threatening condition successfully treated with sodium thiosulfate.

    PubMed

    Sandhu, Gagangeet; Gini, Marcelo Barrios; Ranade, Aditi; Djebali, David; Smith, Steven

    2012-01-01

    Calciphylaxis or calcific uremic arteriolopathy is a life-threatening condition that predominantly affects patients with end-stage renal disease on hemodialysis. A prevalence of up to 4% and a 6-month mortality rate of up to 80% have been reported in those with proximal disease (thighs, abdomen wall, and buttocks). Penile calciphylaxis is very rare but has a mortality rate of 69% within 6 months. Its treatment is controversial. For small lesions, conservative treatment with local wound care and debridement may suffice. Partial or complete penectomy may be needed for more extensive lesions, and especially those associated with signs of local infection. In addition to surgical intervention, as with any other case of calcific uremic arteriolopathy, the cornerstones of therapy should be to keep serum phosphorus <6 mg/dL, and a Ca × P product <55 mg²/dL². We report here the first case of penile calciphylaxis whereby intravenous sodium thiosulfate was used in addition to the standard medical and surgical therapy. Two months after surgery, the patient's wound completely healed and he has experienced no new lesions over the past 11 months.

  8. [Multiple calcifications and ossifications of tendons].

    PubMed

    Gaucher, A; Péré, P; Gillet, P

    1991-06-21

    Multiple calcifications and ossifications of tendons are, as a rule, associated with similar lesions of other articular and/or periarticular structures. The nature and multiplicity of these lesions gives them an unquestionable diagnostic and nosological value. Multiple calcifications are part of the apatite arthritis or of diffuse articular chondrocalcinosis. Multiple ossifications of tendons often suggest Forestier's disease and ankylosing spondylitis.

  9. Calcific tendinitis of the shoulder

    PubMed Central

    DE CARLI, ANGELO; PULCINELLI, FERDINANDO; ROSE, GIACOMO DELLE; PITINO, DARIO; FERRETTI, ANDREA

    2014-01-01

    Calcific tendinitis is a common disease that predominantly affects individuals aged between 40 and 60 years. Women seem to be more affected than men. Various factors have been suggested to play a role in this condition, such as abnormal activity of the thyroid gland, metabolic diseases (e.g. diabetes), and genetic predisposition. Various etiological hypotheses have been advanced: the degenerative and multiphasic theories are the two most accredited ones. Clinically, calcific tendinitis is characterized by severe, disabling pain which occurs spontaneously, usually in the morning. There can be concomitant stiffness, giving rise to a frozen shoulder-like clinical picture. Conventional radiography of the shoulder is the most appropriate imaging approach. Most cases resolve spontaneously. Many conservative treatments have been reported in the literature, showing varying levels of evidence of efficacy. Arthroscopic surgery is the orthopedic specialist’s last option. It is to be noted that post-surgical pain can persist for many weeks after the operation. Finally, it is important not to forget the variant characterized by osteolytic involvement of the greater tuberosity, which has been associated with a worse clinical outcome, both after conservative treatment and after surgery. PMID:25606556

  10. Physiopathology of intratendinous calcific deposition

    PubMed Central

    2012-01-01

    In calcific tendinopathy (CT), calcium deposits in the substance of the tendon, with chronic activity-related pain, tenderness, localized edema and various degrees of decreased range of motion. CT is particularly common in the rotator cuff, and supraspinatus, Achilles and patellar tendons. The presence of calcific deposits may worsen the clinical manifestations of tendinopathy with an increase in rupture rate, slower recovery times and a higher frequency of post-operative complications. The aetiopathogenesis of CT is still controversial, but seems to be the result of an active cell-mediated process and a localized attempt of the tendon to compensate the original decreased stiffness. Tendon healing includes many sequential processes, and disturbances at different stages of healing may lead to different combinations of histopathological changes, diverting the normal healing processes to an abnormal pathway. In this review, we discuss the theories of pathogenesis behind CT. Better understanding of the pathogenesis is essential for development of effective treatment modalities and for improvement of clinical outcomes. PMID:22917025

  11. Mechanisms and Clinical Consequences of Vascular Calcification

    PubMed Central

    Zhu, Dongxing; Mackenzie, Neil C. W.; Farquharson, Colin; MacRae, Vicky E.

    2012-01-01

    Vascular calcification has severe clinical consequences and is considered an accurate predictor of future adverse cardiovascular events, including myocardial infarction and stroke. Previously vascular calcification was thought to be a passive process which involved the deposition of calcium and phosphate in arteries and cardiac valves. However, recent studies have shown that vascular calcification is a highly regulated, cell-mediated process similar to bone formation. In this article, we outline the current understanding of key mechanisms governing vascular calcification and highlight the clinical consequences. By understanding better the molecular pathways and genetic circuitry responsible for the pathological mineralization process novel drug targets may be identified and exploited to combat and reduce the detrimental effects of vascular calcification on human health. PMID:22888324

  12. MicroRNAs Regulate Vascular Medial Calcification.

    PubMed

    Leopold, Jane A

    2014-01-01

    Vascular calcification is highly prevalent in patients with coronary artery disease and, when present, is associated with major adverse cardiovascular events, including an increased risk of cardiovascular mortality. The pathogenesis of vascular calcification is complex and is now recognized to recapitulate skeletal bone formation. Vascular smooth muscle cells (SMC) play an integral role in this process by undergoing transdifferentiation to osteoblast-like cells, elaborating calcifying matrix vesicles and secreting factors that diminish the activity of osteoclast-like cells with mineral resorbing capacity. Recent advances have identified microRNAs (miRs) as key regulators of this process by directing the complex genetic reprogramming of SMCs and the functional responses of other relevant cell types relevant for vascular calcification. This review will detail SMC and bone biology as it relates to vascular calcification and relate what is known to date regarding the regulatory role of miRs in SMC-mediated vascular calcification.

  13. Diagnosis and differential diagnosis of breast calcifications

    SciTech Connect

    Lanyi, M.

    1987-01-01

    This book is the result of more than 10 years' intensive research into the phenomena of breast calcifications. The author, himself a decisive figure in the development of mammography, demonstrates that a careful, detailed analysis of X-rays can lead to a high degree of diagnostic certainty. Indeed, Lanyi's descriptions make one ask why mammography, which originally awakened such high hopes, is given so little attention today. Contents: historical review; critical analysis of the literature; statement of problems and goals; instruments used in the evaluation of breast microcalcifications; remarks on the pathogenesis, pathophysiology, and composition of breast calcifications; calcifications within the lobular and ductal system of the breast; calcifications in intra- and pericanalicular fibroadenomas; calcifications outside the lobular and ductal systems of the breast; differential diagnosis of microcalcifications; clinically occult, mammographically suspicious microcalcification cluster: Pre-, intra-, and postoperative measures; references, and index.

  14. Calcification inhibitors in human ligamentum flavum.

    PubMed

    Maruta, K; Ichimura, K; Matsui, H; Yamagami, T; Sano, A; Tsuji, H

    1993-01-01

    To examine the presence of substances which inhibit calcification in human ligamentum flavum, the inhibitory effect of an Na2HPO4 extract of the flavum was determined in terms of the in vitro calcium uptake of the ligamentum flavum matrix. Additionally, grafts of extracted and non-extracted dry ligamentum flavum matrices were transplanted into the dorsal muscles of rats, and calcification in the grafts was examined radiologically and histochemically. In order to determine if component cells of human ligamentum flavum produce calcification inhibitors, ligamentum flavum cells were cultured, and the crystal inhibitor activity of the culture medium was measured by a seed test which used hydroxyapatite as the nucleus of precipitation. The calcification reaction system demonstrated that the ligamentum flavum extract contains an inhibitory factor for calcium uptake by the ligamentum flavum matrix. The seed test revealed that human ligamentum flavum cells produce calcification inhibitor activity.

  15. Mechanisms of vascular calcification and associated diseases.

    PubMed

    Marulanda, Juliana; Alqarni, Saleh; Murshed, Monzur

    2014-01-01

    Mineralization of bone and tooth extracellular matrix (ECM) is a physiologic process, while soft tissue mineralization, also known as ectopic mineralization (calcification), is a pathologic condition. Vascular calcification is common in aging and also in a number of genetic and metabolic disorders. The calcific deposits in arteries complicate the prognosis and increase the morbidity in diseases such as atherosclerosis, diabetes and chronic kidney disease (CKD). To completely understand the pathophysiology of these lifethreatening diseases, it is critical to elucidate the molecular mechanisms underlying vascular calcification. Unveiling these mechanisms will eventually identify new therapeutic targets and also improve the management of the associated complications. In the current review, we discussed the common determinants of ECM mineralization, the mechanism of vascular calcification associated with several human diseases and outlined the most common therapeutic approaches to prevent its progression.

  16. Abdominal calcifications in infants and children.

    PubMed

    Pintér, A B; Weisenbach, J; Szemlédy, F

    1984-12-01

    Abdominal and pelvic calcifications are usually incidental findings and require further measures to determine their origin. Most laboratory investigations are of little help. Plain anteroposterior and lateral x-rays are essential. The time of appearance and localisation of a calcification is of diagnostic importance. Amorphous, granular and irregular calcification can be an early sign of malignancy. Mobility of a calcification also helps to clarify its origin. Over the past 15 years abdominal and pelvic calcifications, excluding urological radiodensities, have been found in 63 patients up to fourteen years of age at our institute. A migrating deposit in the omentum, a spontaneously amputated calcified ovary mimicking a vesical calculus and a congenital retroperitoneal xanthofibroma caused the greatest difficulty in establishing a preoperative diagnosis.

  17. Bone disease in uremic patients: advances in PTH suppression.

    PubMed

    Brancaccio, Diego; Cozzolino, Mario; Gorio, Alfredo; Di Giulio, Anna Maria; Gallieni, Maurizio

    2002-01-01

    Chronic renal failure is often complicated by altered calcium and phosphate omeostasis. Many patients develop secondary hyperparathyroidism during the course of the disease. Therefore, both prevention and treatment of secondary hyperparathyroidism are central issues in the treatment of uremic patients. Active vitamin D metabolites are important agents in uremic patients, who have a defective activity of the renal 1alpha-hydroxylase responsible for calcitriol synthesis. Howewer, treatment with calcitriol has some limitations, namely an increase in intestinal phosphate absorption, a possible calcium overload and therefore an increase in CaxP ion product. These limitations stimulated an active research on the development of vitamin D analogs with reduced effects on intestinal transport as well as on bone mobilization of calcium and phosphate. Three vitamin D analogs, which have been used in humans, are reviewed in this article: 22-oxacalcitriol (Maxacalcitol), 19-nor-1alpha,25(OH)2 vitamin D2 (Paricalcitol), and 1alpha(OH) Vitamin D2 (Doxercalciferol). In addition, a new pharmacologic approach to the treatment of secondary hyperparathyroidism has been developed: the use of agonists for the parathyroid calcium sensing receptor, or calcimimetics. AMG O73, a second generation agent, is now under clinical evaluation in phase 3 studies, and it will soon be available in clinical practice. Given the different mechanism of action, it will be possible to use it along with vitamin D analogs and non calcemic phosphate binders. A broader spectrum of therapeutic approaches will enable the nephrologist to individually tailor the treatment of secondary hyperparathyroidism. PMID:12515379

  18. Serum Amyloid A in Uremic HDL Promotes Inflammation

    PubMed Central

    Kopecky, Chantal; Kubicek, Markus; Haidinger, Michael; Döller, Dominik; Katholnig, Karl; Suarna, Cacang; Eller, Philipp; Tölle, Markus; Gerner, Christopher; Zlabinger, Gerhard J.; van der Giet, Markus; Hörl, Walter H.; Stocker, Roland

    2012-01-01

    Uremia impairs the atheroprotective properties of HDL, but the mechanisms underlying why this occurs are unknown. Here, we observed that HDL isolated from healthy individuals inhibited the production of inflammatory cytokines by peripheral monocytes stimulated with a Toll-like receptor 2 agonist. In contrast, HDL isolated from the majority of patients with ESRD did not show this anti-inflammatory property; many HDL samples even promoted the production of inflammatory cytokines. To investigate this difference, we used shotgun proteomics to identify 49 HDL-associated proteins in a uremia-specific pattern. Proteins enriched in HDL from patients with ESRD (ESRD-HDL) included surfactant protein B (SP-B), apolipoprotein C-II, serum amyloid A (SAA), and α-1-microglobulin/bikunin precursor. In addition, we detected some ESRD-enriched proteins in earlier stages of CKD. We did not detect a difference in oxidation status between HDL isolated from uremic and healthy patients. Regarding function of these uremia-specific proteins, only SAA mimicked ESRD-HDL by promoting inflammatory cytokine production. Furthermore, SAA levels in ESRD-HDL inversely correlated with its anti-inflammatory potency. In conclusion, HDL has anti-inflammatory activities that are defective in uremic patients as a result of specific changes in its molecular composition. These data suggest a potential link between the high levels of inflammation and cardiovascular mortality in uremia. PMID:22282592

  19. Calcification

    MedlinePlus

    ... soft tissue tumors. In: Kumar V, Abbas AK, Aster JC, eds. Robbins and Cotran Pathologic Basis of ... Saunders; 2015:chap 26. Kumar V, Abbas AK, Aster JC. Cellular responses to stress and toxic insults: ...

  20. Indolic uremic solutes enhance procoagulant activity of red blood cells through phosphatidylserine exposure and microparticle release.

    PubMed

    Gao, Chunyan; Ji, Shuting; Dong, Weijun; Qi, Yushan; Song, Wen; Cui, Debin; Shi, Jialan

    2015-11-01

    Increased accumulation of indolic uremic solutes in the blood of uremic patients contributes to the risk of thrombotic events. Red blood cells (RBCs), the most abundant blood cells in circulation, may be a privileged target of these solutes. However, the effect of uremic solutes indoxyl sulfate (IS) and indole-3-acetic acid (IAA) on procoagulant activity (PCA) of erythrocyte is unclear. Here, RBCs from healthy adults were treated with IS and IAA (mean and maximal concentrations reported in uremic patients). Phosphatidylserine (PS) exposure of RBCs and their microparticles (MPs) release were labeled with Alexa Fluor 488-lactadherin and detected by flow cytometer. Cytosolic Ca(2+) ([Ca(2+)]) with Fluo 3/AM was analyzed by flow cytometer. PCA was assessed by clotting time and purified coagulation complex assays. We found that PS exposure, MPs generation, and consequent PCA of RBCs at mean concentrations of IS and IAA enhanced and peaked in maximal uremic concentrations. Moreover, 128 nM lactadherin, a PS inhibitor, inhibited over 90% PCA of RBCs and RMPs. Eryptosis or damage, by indolic uremic solutes was due to, at least partially, the increase of cytosolic [Ca(2+)]. Our results suggest that RBC eryptosis in uremic solutes IS and IAA plays an important role in thrombus formation through releasing RMPs and exposing PS. Lactadherin acts as an efficient anticoagulant in this process. PMID:26516916

  1. A Zebrafish Model for Uremic Toxicity: Role of the Complement Pathway

    PubMed Central

    Thurman, Josh; Reinecke, James; Raff, Amanda C.; Melamed, Michal L.; Reinecke, James; Quan, Zhe; Evans, Todd; Meyer, Timothy W.; Hostetter, Thomas H

    2016-01-01

    Many organic solutes accumulate in ESRD and some are poorly removed removed with urea based prescriptions for hemodialysis. However, their toxicities have been difficult to assess. We have employed an animal model, the zebrafish embryo, to test the toxicity of uremic serum compared to control. Serum was obtained from stable ESRD patients pre-dialysis or from normal subjects. Zebrafish embryos 24 hours post fertilization were exposed to experimental media at a ratio of 3:1 water:human serum. Those exposed to serum from uremic subjects had significantly reduced survival at 8 hours (19% +/− 18% vs. 94% +/− 6%; p < 0.05, uremic serum vs control, respectively). Embryos exposed to serum from ESRD subjects fractionated at 50kD showed significantly greater toxicity with the larger molecular weight fraction (83% +/− 11% vs 7% +/−17% survival, p < 0.05, <50kD vs >50 kD, respectively). Heating serum abrogated its toxicity. EDTA, a potent inhibitor of complement by virtue of calcium chelation, reduced the toxicity of uremic serum compared to untreated uremic serum (96%+/− 5% vs 28%+/− 20% survival, p < 0.016, chelated vs non chelated serum respectively). Anti- factor B, a specific inhibitor of the alternative complement pathway, reduced the toxicity of uremic serum, compared to untreated uremic serum (98% +/− 6% vs. 3% +/− 9% survival, p < 0.016, anti- factor B treated vs non treated, respectively).Uremic serum is thus more toxic to zebrafish embryos than normal serum. Furthermore, this toxicity is associated with a fraction of large size, is inactivated by heat, and is reduced by both specific and non-specific inhibitors of complement activation. Together these data lend support to the hypothesis that at least some uremic toxicities may be mediated by complement. PMID:23689420

  2. A zebrafish model for uremic toxicity: role of the complement pathway.

    PubMed

    Berman, Nathaniel; Lectura, Melisa; Thurman, Joshua M; Reinecke, James; Raff, Amanda C; Melamed, Michal L; Quan, Zhe; Evans, Todd; Meyer, Timothy W; Hostetter, Thomas H

    2013-01-01

    Many organic solutes accumulate in end-stage renal disease (ESRD) and some are poorly removed with urea-based prescriptions for hemodialysis. However, their toxicities have been difficult to assess. We have employed an animal model, the zebrafish embryo, to test the toxicity of uremic serum compared to control. Serum was obtained from stable ESRD patients predialysis or from normal subjects. Zebrafish embryos 24 h postfertilization were exposed to experimental media at a water:human serum ratio of 3:1. Those exposed to serum from uremic subjects had significantly reduced survival at 8 h (19 ± 18 vs. 94 ± 6%, p < 0.05, uremic serum vs. control, respectively). Embryos exposed to serum from ESRD subjects fractionated at 50 kDa showed significantly greater toxicity with the larger molecular weight fraction (83 ± 11 vs. 7 ± 17% survival, p < 0.05, <50 vs. >50 kDa, respectively). Heating serum abrogated its toxicity. EDTA, a potent inhibitor of complement by virtue of calcium chelation, reduced the toxicity of uremic serum compared to untreated uremic serum (96 ± 5 vs. 28 ± 20% survival, p < 0.016, chelated vs. nonchelated serum, respectively). Anti-factor B, a specific inhibitor of the alternative complement pathway, reduced the toxicity of uremic serum, compared to untreated uremic serum (98 ± 6 vs. 3 ± 9% survival, p < 0.016, anti-factor B treated vs. nontreated, respectively). Uremic serum is thus more toxic to zebrafish embryos than normal serum. Furthermore, this toxicity is associated with a fraction of large size, is inactivated by heat, and is reduced by both specific and nonspecific inhibitors of complement activation. Together these data lend support to the hypothesis that at least some uremic toxicities may be mediated by complement.

  3. A zebrafish model for uremic toxicity: role of the complement pathway.

    PubMed

    Berman, Nathaniel; Lectura, Melisa; Thurman, Joshua M; Reinecke, James; Raff, Amanda C; Melamed, Michal L; Quan, Zhe; Evans, Todd; Meyer, Timothy W; Hostetter, Thomas H

    2013-01-01

    Many organic solutes accumulate in end-stage renal disease (ESRD) and some are poorly removed with urea-based prescriptions for hemodialysis. However, their toxicities have been difficult to assess. We have employed an animal model, the zebrafish embryo, to test the toxicity of uremic serum compared to control. Serum was obtained from stable ESRD patients predialysis or from normal subjects. Zebrafish embryos 24 h postfertilization were exposed to experimental media at a water:human serum ratio of 3:1. Those exposed to serum from uremic subjects had significantly reduced survival at 8 h (19 ± 18 vs. 94 ± 6%, p < 0.05, uremic serum vs. control, respectively). Embryos exposed to serum from ESRD subjects fractionated at 50 kDa showed significantly greater toxicity with the larger molecular weight fraction (83 ± 11 vs. 7 ± 17% survival, p < 0.05, <50 vs. >50 kDa, respectively). Heating serum abrogated its toxicity. EDTA, a potent inhibitor of complement by virtue of calcium chelation, reduced the toxicity of uremic serum compared to untreated uremic serum (96 ± 5 vs. 28 ± 20% survival, p < 0.016, chelated vs. nonchelated serum, respectively). Anti-factor B, a specific inhibitor of the alternative complement pathway, reduced the toxicity of uremic serum, compared to untreated uremic serum (98 ± 6 vs. 3 ± 9% survival, p < 0.016, anti-factor B treated vs. nontreated, respectively). Uremic serum is thus more toxic to zebrafish embryos than normal serum. Furthermore, this toxicity is associated with a fraction of large size, is inactivated by heat, and is reduced by both specific and nonspecific inhibitors of complement activation. Together these data lend support to the hypothesis that at least some uremic toxicities may be mediated by complement. PMID:23689420

  4. Calciphylaxis in Patients With Preserved Kidney Function.

    PubMed

    Maroz, Natallia; Mohandes, Samer; Field, Halle; Kabakov, Zlata; Simman, Richard

    2014-04-01

    Calcific uremic arteriolopathy (CUA), also known as calciphylaxis, is a devastating disease typically seen in patients with end stage renal disease. It manifests as extremely painful symmetrical wounds resistant to surgical and medical interventions. The prevalence of CUA among hemodialysis dependent patients was found to be as high as 4.1%. The management of patients with CUA requires a multidisciplinary approach by the medical team, yet often results in a low rate of successful outcomes. Recently, non-uremic calciphylaxis (NUC) has been described in the absence of kidney disease. Limited knowledge exists on the management of NUC and the outcomes of this condition. Herein we describe three clinical scenarios of patients diagnosed with NUC in the absence of permanent or prolonged acute renal pathology. The reporting of successful and fruitless therapeutic interventions for wound management in NUC is important for compiling the evidence of effective therapeutic strategies.

  5. Calciphylaxis in Patients With Preserved Kidney Function

    PubMed Central

    Maroz, Natallia; Mohandes, Samer; Field, Halle; Kabakov, Zlata; Simman, Richard

    2015-01-01

    Calcific uremic arteriolopathy (CUA), also known as calciphylaxis, is a devastating disease typically seen in patients with end stage renal disease. It manifests as extremely painful symmetrical wounds resistant to surgical and medical interventions. The prevalence of CUA among hemodialysis dependent patients was found to be as high as 4.1%. The management of patients with CUA requires a multidisciplinary approach by the medical team, yet often results in a low rate of successful outcomes. Recently, non-uremic calciphylaxis (NUC) has been described in the absence of kidney disease. Limited knowledge exists on the management of NUC and the outcomes of this condition. Herein we describe three clinical scenarios of patients diagnosed with NUC in the absence of permanent or prolonged acute renal pathology. The reporting of successful and fruitless therapeutic interventions for wound management in NUC is important for compiling the evidence of effective therapeutic strategies. PMID:26442208

  6. Notch signaling in cardiovascular disease and calcification.

    PubMed

    Rusanescu, Gabriel; Weissleder, Ralph; Aikawa, Elena

    2008-08-01

    Recent increase in human lifespan has shifted the spectrum of aging-related disorders to an unprecedented upsurge in cardiovascular diseases, especially calcific aortic valve stenosis, which has an 80% risk of progression to heart failure and death. A current therapeutic option for calcified valves is surgical replacement, which provides only temporary relief. Recent progress in cardiovascular research has suggested that arterial and valve calcification are the result of an active process of osteogenic differentiation, induced by a pro-atherogenic inflammatory response. At molecular level, the calcification process is regulated by a network of signaling pathways, including Notch, Wnt and TGFbeta/BMP pathways, which control the master regulator of osteogenesis Cbfa1/Runx2. Genetic and in vitro studies have implicated Notch signaling in the regulation of macrophage activation and cardiovascular calcification. Individuals with inactivating Notch1 mutations have a high rate of cardiovascular disorders, including valve stenosis and calcification. This article reviews recent progress in the mechanism of cardiovascular calcification and discusses potential molecular mechanisms involved, focusing on Notch receptors. We propose a calcification model where extreme increases in vascular wall cell density due to inflammation-induced cell proliferation can trigger an osteogenic differentiation program mediated by Notch receptors. PMID:19936191

  7. Dystrophic calcification: A rare pediatric parotid mass.

    PubMed

    Chislett, Sean P; Liming, Bryan J; Rogers, Derek J

    2016-02-01

    Dystrophic calcification, the ectopic deposition of calcium in previously damaged or inflamed tissues, is an uncommon finding in the head and neck. Only a few cases have been reported in the parotidomasseteric region, and all of them have been located within and adjacent to the masseter. We present a case of dystrophic calcification occurring entirely within the parotid gland in a 7-year-old girl without apparent inciting inflammation, infection, or trauma. Our patient's presentation highlights the diagnostic challenge associated with parotid masses in the pediatric population. To our knowledge, this is the first reported case of dystrophic calcification occurring entirely within the parotid gland in a child. PMID:26810287

  8. Hemolytic uremic syndrome: pathogenesis and update of interventions.

    PubMed

    Palermo, Marina S; Exeni, Ramón A; Fernández, Gabriela C

    2009-08-01

    The typical form of hemolytic uremic syndrome (HUS) is the major complication of Shiga toxin-producing Escherichia coli infections. HUS is a critical health problem in Argentina since it is the main cause of acute renal failure in children and the second cause of chronic renal failure, accounting for 20% of renal transplants in children and adolescents in Argentina. Despite extensive research in the field, the mainstay of treatment for patients with HUS is supportive therapy, and there are no specific therapies preventing or ameliorating the disease course. In this review, we present the current knowledge about pathogenic mechanisms and discuss traditional and innovative therapeutic approaches, with special focus in Argentinean contribution. The hope that a better understanding of transmission dynamics and pathogenesis of this disease will produce better therapies to prevent the acute mortality and the long-term morbidity of HUS is the driving force for intensified research.

  9. Reversible visual evoked potential abnormalities in uremic children.

    PubMed

    Ethier, Audrey-Anne; Lippé, Sarah; Mérouani, Aicha; Lassonde, Maryse; Saint-Amour, Dave

    2012-06-01

    In this case study, two cystinosis-related uremic children were followed at the Department of Nephrology, University of Montreal Hospital Center Sainte-Justine. Pattern-reversal visual evoked potentials were recorded at two time points, during dialysis treatment (time 1) and after renal transplant (time 2). Data were compared with those obtained from a control group (n = 6). The P1 component was selected and analyzed as the electrophysiologic marker of interest. At time 1, P1 latency was delayed, and P1 amplitude was reduced compared with control subjects. Both responses fell within normal range after kidney transplantation. These results indicate that renal failure and dialysis are associated with abnormal visual evoked potentials in children with chronic renal failure, but such alterations of visual processing are reversible after kidney transplant. PMID:22633636

  10. 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.

  11. Nanobacteria-associated calcific aortic valve stenosis.

    PubMed

    Jelic, Tomislav M; Chang, Ho-Huang; Roque, Rod; Malas, Amer M; Warren, Stafford G; Sommer, Andrei P

    2007-01-01

    Calcific aortic valve stenosis is the most common valvular disease in developed countries, and the major reason for operative valve replacement. In the US, the current annual cost of this surgery is approximately 1 billion dollars. Despite increasing morbidity and mortality, little is known of the cellular basis of the calcifications, which occur in high-perfusion zones of the heart. The case is presented of a patient with calcific aortic valve stenosis and colonies of progressively mineralized nanobacteria in the fibrocalcific nodules of the aortic cusps, as revealed by transmission electron microscopy. Consistent with their outstanding bioadhesivity, nanobacteria might serve as causative agents in the development of calcific aortic valve stenosis. PMID:17315391

  12. The relationship between pulp calcifications and salivary gland calcifications

    PubMed Central

    Kaswan, Sumita; Maheshwari, Sneha; Rahman, Farzan; Khandelwal, Suneet

    2014-01-01

    Aim: Pulp stones are discrete calcified bodies found in the dental pulp. Sialolithasis is the most common salivary gland disease. The aim of the present study was to determine the relationship between the pulp stones and salivary gland stones. Material and Methods: 196 patients were randomly selected from the out patient department for the study. The periapical radiographs for all patients were evaluated for the presence or absence of the narrowing of dental pulp chambers and pulp canals. The intra oral occlusal radiographs were also evaluated to determine the presence or absence of salivary stones. The results were compared and analyzed using the Chi-square test (p<0.001). Results: Salivary gland calcifications were detected in 5 patients. 191 patients had pulp narrowing and 118 patients had pulp stones. There was no statistical correlation between pulp narrowing and salivary stones (p>0.001) and also between pulp stones and salivary gland stones (p>0.001). Conclusions: However, the incidental findings of salivary gland stones on intra oral occlusal radiographs can provide useful information in the early diagnosis of the condition, but in the present study no significant relationship was found between the presence of pulp stones and salivary gland stones. Key words:Pulp stone, salivary gland stone, periapical radiograph, occlusal radiograph. PMID:25674311

  13. Impact of the Uremic Milieu on the Osteogenic Potential of Mesenchymal Stem Cells

    PubMed Central

    Lanza, Diana; Perna, Alessandra F.; Oliva, Adriana; Vanholder, Raymond; Pletinck, Anneleen; Guastafierro, Salvatore; Di Nunzio, Annarita; Vigorito, Carmela; Capasso, Giovambattista; Jankowski, Vera; Jankowski, Joachim; Ingrosso, Diego

    2015-01-01

    Human mesenchymal stem cells (hMSCs), the precursors of osteoblasts during osteogenesis, play a role in the balance of bone formation and resorption, but their functioning in uremia has not been well defined. To study the effects of the uremic milieu on osteogenic properties, we applied an in vitro assay culturing hMSCs in osteogenic medium supplemented with serum from healthy donors and from uremic patients on hemodialysis. Compared to control, serum from uremic patients induces, in hMSC cultures, a modification of several key regulators of bone remodeling, in particular a reduction of the ratio Receptor Activator of Nuclear factor Kappa B Receptor (RANKL) over osteoprotegerin, indicating an adaptive response of the system to favor osteogenesis over osteoclastosis. However, the levels of osteopontin, osteocalcin, and collagen type I, are increased in cell medium, while BMP-2, and alizarin red staining were decreased, pointing to a reduction of bone formation favoring resorption. Selected uremic toxins, such as p-cresylsulfate, p-cresylglucuronide, parathyroid hormone, indoxyl sulfate, asymmetric dimethylarginine, homocysteine, were able to mimic some of the effects of whole serum from uremic patients. Serum from cinacalcet-treated patients antagonizes these effects. Hydrogen sulfide (H2S) donors as well as hemodialysis treatment are able to induce beneficial effects. In conclusion, bone modifications in uremia are influenced by the capability of the uremic milieu to alter hMSC osteogenic differentiation. Cinacalcet, H2S donors and a hemodialysis session can ameliorate the hampered calcium deposition. PMID:25635832

  14. Comparative histology of pineal calcification.

    PubMed

    Vígh, B; Szél, A; Debreceni, K; Fejér, Z; Manzano e Silva, M J; Vígh-Teichmann, I

    1998-07-01

    The pineal organ (pineal gland, epiphysis cerebri) contains several calcified concretions called "brain sand" or acervuli (corpora arenacea). These concretions are conspicuous with imaging techniques and provide a useful landmark for orientation in the diagnosis of intracranial diseases. Predominantly composed of calcium and magnesium salts, corpora arenacea are numerous in old patients. In smaller number they can be present in children as well. The degree of calcification was associated to various diseases. However, the presence of calcified concretions seems not to reflect a specific pathological state. Corpora arenacea occur not only in the actual pineal tissue but also in the leptomeninges, in the habenular commissure and in the choroid plexus. Studies with the potassium pyroantimonate (PPA) method on the ultrastructural localization of free calcium ions in the human pineal, revealed the presence of calcium alongside the cell membranes, a finding that underlines the importance of membrane functions in the production of calcium deposits. Intrapineal corpora arenacea are characterized by a surface with globular structures. Meningeal acervuli that are present in the arachnoid cover of the organ, differ in structure from intrapineal ones and show a prominent concentric lamination of alternating dark and light lines. The electron-lucent lines contain more calcium than the dark ones. There is a correlation between the age of the subject and the number of layers in the largest acervuli. This suggests that the formation of these layers is connected to circannual changes in the calcium level of the organ. The histological organization of the human pineal is basically the same as that of mammalian experimental animals. Pineal concretions present in mammalian animal species are mainly of the meningeal type. Meningeal cells around acervuli contain active cytoplasmic organelles and exhibit alkaline phosphatase reaction in the rat and mink, an indication of a presumable

  15. Gastrointestinal stromal tumor presenting with prominent calcification

    PubMed Central

    Izawa, Naoki; Sawada, Takeshi; Abiko, Ryuichi; Kumon, Daisuke; Hirakawa, Mami; Kobayashi, Mika; Obinata, Nobuyuki; Nomoto, Masahito; Maehata, Tadateru; Yamauchi, Shun-ichi; Kouro, Takefumi; Tsuda, Takashi; Kitajima, Satoshi; Yasuda, Hiroshi; Tanaka, Keiichi; Tanaka, Ichiro; Hoshikawa, Masahiro; Takagi, Masayuki; Itoh, Fumio

    2012-01-01

    We present a rare case of a gastrointestinal stromal tumor (GIST) in the stomach with prominent calcification at presentation. A 61-year-old woman visited our hospital because of epigastric discomfort. A spherical calcified lesion with a diameter of about 30 mm was incidentally shown in the left upper quadrant on an abdominal X-ray. Computed tomography demonstrated that the tumor was growing from the upper gastric body, with calcification in the peripheral ring area. A laparoscopic partial gastrectomy was performed, and the resected specimen revealed a well-circumscribed tumor with exophytic growth from the gastric muscularis propria. Microscopic examination revealed spindle-shaped tumor cells with calcification and hemorrhage. Additionally, positive immunoreactivity of the tumor to KIT and CD34 and a low mitotic index resulted in the diagnosis of very low risk GIST. There are a few case reports of heavily calcified GIST, although solitary or punctate calcification of primary GIST has been reported in several case series. Dystrophic calcification of necrotic or degenerative tissue is the supposed cause of primary calcified GISTs. In contrast, appearance of calcification after administration of imatinib mesylate, which may be one indicator of disease response, is possibly caused by a different mechanism. PMID:23112561

  16. Acute Renal Infarction Secondary to Calcific Embolus from Mitral Annular Calcification

    SciTech Connect

    Bande, Dinesh; Abbara, Suhny; Kalva, Sanjeeva P.

    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.

  17. Acute renal infarction secondary to calcific embolus from mitral annular calcification.

    PubMed

    Bande, Dinesh; Abbara, Suhny; Kalva, Sanjeeva P

    2011-06-01

    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.

  18. Eculizumab in Typical Hemolytic Uremic Syndrome (HUS) With Neurological Involvement

    PubMed Central

    Pape, Lars; Hartmann, Hans; Bange, Franz Christoph; Suerbaum, Sebastian; Bueltmann, Eva; Ahlenstiel-Grunow, Thurid

    2015-01-01

    Abstract In typical hemolytic uremic syndrome (HUS) approximately 25% of patients show central nervous system (CNS) involvement often leading to serious long-term disabilities. We used the C5-complement inhibitor Eculizumab as rescue therapy. From 2011 to 2014, 11 children (median age 22 months, range 11–175) with enterohemorrhagic Escherichia coli-positive HUS requiring dialysis who had seizures (11/11) and/or were in a stupor or coma (10/11) were treated with Eculizumab. Two patients enrolled on the Safety and Efficacy Study of Eculizumab in Shiga-Toxin Producing E coli Hemolytic-Uremic Syndrome (STEC-HUS) each received 6 doses of Eculizumab, 3 patients 2 doses, and 6 patients 1 dose. Laboratory diagnostics of blood samples and magnetic resonance imaging (MRI) were performed as per center practice. Data were analyzed retrospectively. Cranial MRI was abnormal in 8 of 10 patients with findings in the basal ganglia and/or white matter. A 2-year-old boy with severe cardiac involvement and status epilepticus needed repeated cardio-pulmonary resuscitation and extracorporeal membrane oxygenation. He died 8 days after start of Eculizumab treatment. Two patients with hemorrhagic colitis and repeated seizures required artificial ventilation for 6 and 16 days, respectively. At the time of discharge, 1 patient showed severe neurological impairment and 1 mild neurological impairment. The 8 surviving patients experienced no further seizures after the first dose of Eculizumab. Three patients showed mild neurological impairment at discharge, whilst the remaining 5 showed no impairment. The platelets normalized 4 days (median) after the first dose of Eculizumab (range 0–20 days). The mean duration of dialysis after the first dose of Eculizumab was 14.1 ± 6.1 days. In children with typical HUS and CNS involvement early use of Eculizumab appears to improve neurological outcome. In severe HUS cases which progress rapidly with multiple organ involvement, late treatment with

  19. Idiopathic Arterial Calcification of Infancy: Case Report.

    PubMed

    Attia, Tarek Hamed; Abd Alhamed, Mohamed Maisara; Selim, Mohamed Fouad; Haggag, Mohamed Salah; Fathalla, Diaa

    2015-11-01

    Idiopathic arterial calcification of infancy is a rare autosomal recessive disease, characterized by deposition of calcium along the internal elastic membrane of arteries, accompanied by fibrous thickening of the intima which causes luminal narrowing. Here we are reporting a case of idiopathic arterial calcification of infancy in a Saudi female newborn of non-consanguineous pregnant woman who had polyhydramnios. The newborn baby had severe respiratory distress, systemic hypertension and persistent pulmonary hypertension of newborn. She was admitted to Neonatal Intensive Care Unit, where she was ventilated and proper treatment was provided. Molecular genetic testing was positive for mutations of ectonucleotide pyrophosphatase/phosphodiesterase1 gene which is reported in 80% of cases of Idiopathic arterial calcification of infancy. The baby died at about 5 month of age because of myocardial ischemia and cardiorespiratory arrest. Idiopathic Arterial Calcification of Infancy should be considered in any newborn who presented with persistent pulmonary hypertension of newborn, severe systemic hypertension and echogenic vessels on any radiological study. Calcifications of large and medium-sized arteries are important diagnostic finding.

  20. Atypical Hemolytic Uremic Syndrome Recurrence after Renal Transplantation

    PubMed Central

    Bouatou, Yassine; Bacchi, Véronique Frémeaux; Villard, Jean; Moll, Solange; Martin, Pierre-Yves; Hadaya, Karine

    2015-01-01

    Abstract Risk for atypical hemolytic uremic syndrome (aHUS) recurrence after renal transplantation is low with an isolated membrane cofactor protein mutation (MCP). We report the case of a 32-year-old woman with a MCP who underwent kidney transplantation with a good evolution at 12 months. At 15 and 35 months, 2 episodes of thrombotic microangiopathy (TMA), after a miscarriage and a preeclampsia, were misinterpreted as triggered by tacrolimus. After each episode however serum creatinine returned to baseline. Five years after transplantation, she had a self-limited rhinosinusitis followed 3 weeks later by an oliguric renal failure. Her complement profile was normal. Graft biopsy showed C3 glomerulonephritis with no “humps” on electron microscopy. No significant renal function improvement followed methylprednisolone pulsing. A second biopsy showed severe acute TMA lesions with C3 glomerular deposits. Despite weekly eculizumab for 1 month, dialysis was resumed. A new workup identified the “at-risk” complement factor H haplotype. Thus, aHUS recurrence should be ruled out in aHUS patients considered at low recurrence risk when a TMA is found in graft biopsy. Prompt eculizumab therapy should be considered to avoid graft loss as aHUS recurrence can first present as a C3 glomerulonephritis. PMID:27500215

  1. Recessive mutations in DGKE cause atypical hemolytic-uremic syndrome

    PubMed Central

    Lemaire, Mathieu; Frémeaux-Bacchi, Véronique; Schaefer, Franz; Choi, Murim; Tang, Wai Ho; Le Quintrec, Moglie; Fakhouri, Fadi; Taque, Sophie; Nobili, François; Martinez, Frank; Ji, Weizhen; Overton, John D.; Mane, Shrikant M.; Nürnberg, Gudrun; Altmüller, Janine; Thiele, Holger; Morin, Denis; Deschenes, Georges; Baudouin, Véronique; Llanas, Brigitte; Collard, Laure; Majid, Mohammed A.; Simkova, Eva; Nürnberg, Peter; Rioux-Leclerc, Nathalie; Moeckel, Gilbert W.; Gubler, Marie Claire; Hwa, John; Loirat, Chantal; Lifton, Richard P.

    2013-01-01

    Pathologic thrombosis is a major cause of mortality. Hemolytic-uremic syndrome (HUS) features episodes of small vessel thrombosis resulting in microangiopathic hemolytic anemia, thrombocytopenia and renal failure1. Atypical HUS (aHUS) can result from genetic or autoimmune factors2 that lead to pathologic complement cascade activation3. By exome sequencing we identify recessive mutations in DGKE (diacylglycerol kinase epsilon) that co-segregate with aHUS in 9 unrelated kindreds, defining a distinctive Mendelian disease. Affected patients present with aHUS before age 1, have persistent hypertension, hematuria and proteinuria (sometimes nephrotic range), and develop chronic kidney disease with age. DGKE is found in endothelium, platelets, and podocytes. Arachidonic acid-containing diacylglycerols (DAG) activate protein kinase C, which promotes thrombosis. DGKE normally inactivates DAG signaling. We infer that loss of DGKE function results in a pro-thrombotic state. These findings identify a new mechanism of pathologic thrombosis and kidney failure and have immediate implications for treatment of aHUS patients. PMID:23542698

  2. Acute Neurological Involvement in Diarrhea-Associated Hemolytic Uremic Syndrome

    PubMed Central

    Kwon, Thérésa; Elmaleh, Monique; Charbit, Marina; Launay, Emma Allain; Harambat, Jérôme; Brun, Muriel; Ranchin, Bruno; Bandin, Flavio; Cloarec, Sylvie; Bourdat-Michel, Guylhene; Piètrement, Christine; Champion, Gérard; Ulinski, Tim; Deschênes, Georges

    2010-01-01

    Background and objectives: Neurologic involvement is the most threatening complication of diarrhea-associated hemolytic uremic syndrome (D+HUS). Design, setting, participants, & measurements: We report a retrospective multicenter series of 52 patients with severe initial neurologic involvement that occurred in the course of D+HUS. Results: Verotoxigenic Escherichia coli infection was documented in 24. All except two patients had acute renal failure that required peritoneal dialysis, hemodialysis, or both techniques. A first group of eight patients remained with normal consciousness; five of them had protracted seizures. A second group of 23 patients had stuporous coma; five of these had protracted severe seizures, and 18 had a neurologic defect including pyramidal syndrome, hemiplegia or hemiparesia, and extrapyramidal syndrome. A third group of 21 patients had severe coma. Plasma exchanges were undertaken in 25 patients, 11 of whom were treated within 24 hours after the first neurologic sign; four died, two survived with severe sequelae, and five were alive without neurologic defect. Magnetic resonance imaging (MRI) for 29 patients showed that (1) every structure of the central nervous system was susceptible to involvement; (2) no correlation seemed to exist between special profile of localization on early MRI and the final prognosis; and (3) MRI did not exhibit any focal lesions in three patients. The overall prognosis of the series was marked by the death of nine patients and severe sequelae in 13. Conclusions: Neurologic involvement is associated with a severe renal disease but does not lead systematically to death or severe disability. PMID:20498239

  3. A Comparison of Uremic Pruritus in Patients Receiving Peritoneal Dialysis and Hemodialysis.

    PubMed

    Wu, Hon-Yen; Peng, Yu-Sen; Chen, Hung-Yuan; Tsai, Wan-Chuan; Yang, Ju-Yeh; Hsu, Shih-Ping; Pai, Mei-Fen; Lu, Hui-Min; Chiang, Ju-Fen; Ko, Mei-Ju; Wen, Su-Ying; Chiu, Hsien-Ching

    2016-03-01

    Uremic pruritus is common and bothersome in patients receiving either peritoneal dialysis (PD) or hemodialysis (HD). To date, the preferred dialysis modality regarding the alleviation of uremic pruritus remains controversial. We conducted this cross-sectional study to compare the prevalence, intensity, and characteristics of uremic pruritus between PD and HD patients. Patients receiving maintenance dialysis at a referral medical center in Taiwan were recruited. Dialysis modality, patient demographic, clinical characteristics, and laboratory data were recorded. The intensity of uremic pruritus was measured using visual analogue scale (VAS) scores. Multivariate linear regression analysis was conducted to compare the severity of uremic pruritus between PD and HD patients. Generalized additive models were applied to detect nonlinear effects between pruritus intensity and continuous covariates. A total of 380 patients completed this study, with a mean age of 60.3 years and 49.2% being female. Uremic pruritus was presented in 24 (28.6%) of the 84 PD patients and 113 (38.2%) of the 296 HD patients (P = .12). The VAS score of pruritus intensity was significantly lower among the PD patients than the HD patients (1.32 ± 2.46 vs 2.26 ± 3.30, P = .04). Multivariate linear regression analysis showed that PD was an independent predictor for lower VAS scores of pruritus intensity compared with HD (β-value -0.88, 95% confidence interval -1.62 to -0.13). The use of active vitamin D was also an independent predictor for a lower intensity of uremic pruritus, whereas hyperphosphatemia and higher serum levels of triglyceride and aspartate transaminase were significantly associated with higher pruritus intensity. There was a trend toward a less affected body surface area of uremic pruritus in the PD patients than in the HD patients, but the difference did not reach statistical significance (P = .13).In conclusion, the severity of uremic pruritus was lower among PD

  4. A Comparison of Uremic Pruritus in Patients Receiving Peritoneal Dialysis and Hemodialysis

    PubMed Central

    Wu, Hon-Yen; Peng, Yu-Sen; Chen, Hung-Yuan; Tsai, Wan-Chuan; Yang, Ju-Yeh; Hsu, Shih-Ping; Pai, Mei-Fen; Lu, Hui-Min; Chiang, Ju-Fen; Ko, Mei-Ju; Wen, Su-Ying; Chiu, Hsien-Ching

    2016-01-01

    Abstract Uremic pruritus is common and bothersome in patients receiving either peritoneal dialysis (PD) or hemodialysis (HD). To date, the preferred dialysis modality regarding the alleviation of uremic pruritus remains controversial. We conducted this cross-sectional study to compare the prevalence, intensity, and characteristics of uremic pruritus between PD and HD patients. Patients receiving maintenance dialysis at a referral medical center in Taiwan were recruited. Dialysis modality, patient demographic, clinical characteristics, and laboratory data were recorded. The intensity of uremic pruritus was measured using visual analogue scale (VAS) scores. Multivariate linear regression analysis was conducted to compare the severity of uremic pruritus between PD and HD patients. Generalized additive models were applied to detect nonlinear effects between pruritus intensity and continuous covariates. A total of 380 patients completed this study, with a mean age of 60.3 years and 49.2% being female. Uremic pruritus was presented in 24 (28.6%) of the 84 PD patients and 113 (38.2%) of the 296 HD patients (P = .12). The VAS score of pruritus intensity was significantly lower among the PD patients than the HD patients (1.32 ± 2.46 vs 2.26 ± 3.30, P = .04). Multivariate linear regression analysis showed that PD was an independent predictor for lower VAS scores of pruritus intensity compared with HD (β-value −0.88, 95% confidence interval −1.62 to −0.13). The use of active vitamin D was also an independent predictor for a lower intensity of uremic pruritus, whereas hyperphosphatemia and higher serum levels of triglyceride and aspartate transaminase were significantly associated with higher pruritus intensity. There was a trend toward a less affected body surface area of uremic pruritus in the PD patients than in the HD patients, but the difference did not reach statistical significance (P = .13). In conclusion, the severity of uremic pruritus

  5. High-Dose Menaquinone-7 Supplementation Reduces Cardiovascular Calcification in a Murine Model of Extraosseous Calcification

    PubMed Central

    Scheiber, Daniel; Veulemans, Verena; Horn, Patrick; Chatrou, Martijn L.; Potthoff, Sebastian A.; Kelm, Malte; Schurgers, Leon J.; Westenfeld, Ralf

    2015-01-01

    Cardiovascular calcification is prevalent in the aging population and in patients with chronic kidney disease (CKD) and diabetes mellitus, giving rise to substantial morbidity and mortality. Vitamin K-dependent matrix Gla-protein (MGP) is an important inhibitor of calcification. The aim of this study was to evaluate the impact of high-dose menaquinone-7 (MK-7) supplementation (100 µg/g diet) on the development of extraosseous calcification in a murine model. Calcification was induced by 5/6 nephrectomy combined with high phosphate diet in rats. Sham operated animals served as controls. Animals received high or low MK-7 diets for 12 weeks. We assessed vital parameters, serum chemistry, creatinine clearance, and cardiac function. CKD provoked increased aortic (1.3 fold; p < 0.05) and myocardial (2.4 fold; p < 0.05) calcification in line with increased alkaline phosphatase levels (2.2 fold; p < 0.01). MK-7 supplementation inhibited cardiovascular calcification and decreased aortic alkaline phosphatase tissue concentrations. Furthermore, MK-7 supplementation increased aortic MGP messenger ribonucleic acid (mRNA) expression (10-fold; p < 0.05). CKD-induced arterial hypertension with secondary myocardial hypertrophy and increased elastic fiber breaking points in the arterial tunica media did not change with MK-7 supplementation. Our results show that high-dose MK-7 supplementation inhibits the development of cardiovascular calcification. The protective effect of MK-7 may be related to the inhibition of secondary mineralization of damaged vascular structures. PMID:26295257

  6. High-Dose Menaquinone-7 Supplementation Reduces Cardiovascular Calcification in a Murine Model of Extraosseous Calcification.

    PubMed

    Scheiber, Daniel; Veulemans, Verena; Horn, Patrick; Chatrou, Martijn L; Potthoff, Sebastian A; Kelm, Malte; Schurgers, Leon J; Westenfeld, Ralf

    2015-08-01

    Cardiovascular calcification is prevalent in the aging population and in patients with chronic kidney disease (CKD) and diabetes mellitus, giving rise to substantial morbidity and mortality. Vitamin K-dependent matrix Gla-protein (MGP) is an important inhibitor of calcification. The aim of this study was to evaluate the impact of high-dose menaquinone-7 (MK-7) supplementation (100 µg/g diet) on the development of extraosseous calcification in a murine model. Calcification was induced by 5/6 nephrectomy combined with high phosphate diet in rats. Sham operated animals served as controls. Animals received high or low MK-7 diets for 12 weeks. We assessed vital parameters, serum chemistry, creatinine clearance, and cardiac function. CKD provoked increased aortic (1.3 fold; p < 0.05) and myocardial (2.4 fold; p < 0.05) calcification in line with increased alkaline phosphatase levels (2.2 fold; p < 0.01). MK-7 supplementation inhibited cardiovascular calcification and decreased aortic alkaline phosphatase tissue concentrations. Furthermore, MK-7 supplementation increased aortic MGP messenger ribonucleic acid (mRNA) expression (10-fold; p < 0.05). CKD-induced arterial hypertension with secondary myocardial hypertrophy and increased elastic fiber breaking points in the arterial tunica media did not change with MK-7 supplementation. Our results show that high-dose MK-7 supplementation inhibits the development of cardiovascular calcification. The protective effect of MK-7 may be related to the inhibition of secondary mineralization of damaged vascular structures. PMID:26295257

  7. Dark calcification and the daily rhythm of calcification in the scleractinian coral, Galaxea fascicularis

    NASA Astrophysics Data System (ADS)

    Al-Horani, F. A.; Tambutté, É.; Allemand, D.

    2007-09-01

    The rate of calcification in the scleractinian coral Galaxea fascicularis was followed during the daytime using 45Ca tracer. The coral began the day with a low calcification rate, which increased over time to a maximum in the afternoon. Since the experiments were carried out under a fixed light intensity, these results suggest that an intrinsic rhythm exists in the coral such that the calcification rate is regulated during the daytime. When corals were incubated for an extended period in the dark, the calcification rate was constant for the first 4 h of incubation and then declined, until after one day of dark incubation, calcification ceased, possibly as a result of the depletion of coral energy reserves. The addition of glucose and Artemia reduced the dark calcification rate for the short duration of the experiment, indicating an expenditure of oxygen in respiration. Artificial hypoxia reduced the rate of dark calcification to about 25% compared to aerated coral samples. It is suggested that G. fascicularis obtains its oxygen needs from the surrounding seawater during the nighttime, whereas during the day time the coral exports oxygen to the seawater.

  8. Regulatory Circuits Controlling Vascular Cell Calcification

    PubMed Central

    Sallam, Tamer; Cheng, Henry; Demer, Linda L.; Tintut, Yin

    2013-01-01

    Vascular calcification is a common feature of chronic kidney disease, cardiovascular disease, and aging. Such abnormal calcium deposition occurs in medial and/or intimal layers of blood vessels as well as in cardiac valves. Once considered a passive and inconsequential finding, the presence of calcium deposits in the vasculature is widely accepted as a predictor of increased morbidity and mortality. Recognition of the importance of vascular calcification in health is driving research into mechanisms that govern its development, progression, and regression. Diverse, but highly interconnected factors, have been implicated, including disturbances in lipid metabolism, oxidative stress, inflammatory cytokines, and mineral and hormonal balances, which can lead to formation of osteoblast-like cells in the artery wall. A tight balance of procalcific and anticalcific regulators dictates the extent of disease. In this review, we focus on the main regulatory circuits modulating vascular cell calcification. PMID:23269436

  9. [The uremic toxin, indoxyl sulfate, signifies cardio-renal risk and intestinal-renal relationship].

    PubMed

    Kiss, István

    2011-10-23

    Uremic syndrome and condition is primarily a result of kidney failure in which uremic toxins are accumulated. More and more attention is paid to possibilities for removal of uremic toxins, which not only means dialysis, but also takes into account special dietary considerations and treatments, which aim to absorb the toxins or reduce their production. These uremic toxins, which also increase the cardiovascular risks, play a major part in morbidity and mortality of patients suffering from chronic renal failure and those receiving renal replacement therapy. One of them is a member of the indol group, the indoxyl sulfate. This toxin is difficult to remove with dialysis and is an endogenous protein-bound uremic toxin. Today we know that indoxyl sulfate is a vascular-nephrotoxic agent, which is able to enhance progression of cardiovascular and renal diseases. It is of particular importance that because of its redox potency, this toxin causes oxidative stress and antioxidant effects at the same time and, on top of that, it is formed in the intestinal system. Its serum concentration depends on the nutrition and the tubular function and, therefore, it can also signal the progression of chronic renal failure independently of glomerular filtration rate. Successful removal of indoxyl sulfate reduces the morbidity and mortality and improves survival. Therefore, it could be a possible target or area to facilitate the reduction of uremia in chronic renal failure. The use of probiotics and prebiotics with oral adsorbents may prove to be a promising opportunity to reduce indoxyl sulfate accumulation. PMID:21983398

  10. Different protein expression in normal and dysfunctional platelets from uremic patients.

    PubMed

    Marques, María; Sacristán, Daniel; Mateos-Cáceres, Petra J; Herrero, José; Arribas, María J; González-Armengol, Juan J; Villegas, Ana; Macaya, Carlos; Barrientos, Alberto; López-Farré, Antonio J

    2010-01-01

    Although many uremic patients show platelet dysfunctionality, there are others with normal platelet functionality and even with thrombotic tendencies. Our aim was to evaluate changes in the expression of proteins in functional and dysfunctional uremic platelets. Using the platelet function analyzer (PFA-100) assay, uremic patients were divided according to their platelet functionality into normal (n=7) and dysfunctional (n=8). There were no significant differences in the number of circulating platelets and hematocrit and hemoglobin levels. Two-dimensional electrophoresis and mass spectrometry were used to determine and identify changes in protein expression. The closure time (CT) in the PFA-100 assay was significantly prolonged in the dysfunctional uremic platelets. In the dysfunctional platelets, actin-interacting protein-1 isotype 1 was down-regulated, while integrin IIb was up-regulated. Glutathione-S-transferase isotypes 1 and 2 and peroxiredoxin VI were up-regulated in the dysfunctional platelets. Pearson analysis showed a negative correlation between the platelet expression of integrin IIb and creatinine clearance. A positive correlation was found between creatinine clearance and glutathione-S-transferase isotype 2. Serum uric acid concentration was positively correlated with CT values and glutathione-S-transferase isotype 1. In conclusion, the analysis of the protein expression in uremic platelets with normal and dysfunctional activity revealed differences which may occur at the megakaryocyte level.

  11. 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.

  12. 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.

  13. Effect of manganese on calcification of bone

    PubMed Central

    Tal, E.; Guggenheim, K.

    1965-01-01

    1. Young mice were maintained on a basal diet composed of meat, which is poor in both manganese and calcium. 2. The addition of small amounts (2·5–5·0mg./kg. of meat) of manganese improved weight gain and calcification of bone and decreased incorporation of injected radiocalcium into bone. 3. Prolonged treatment with larger amounts (10·0–25·0mg./kg. of meat) of manganese depressed growth, induced defective calcification of bone and increased incorporation of radiocalcium into bone. PMID:14333572

  14. Vascular Calcification in Uremia: New-Age Concepts about an Old-Age Problem.

    PubMed

    Smith, Edward R

    2016-01-01

    A hallmark of aging, and major contributor to the increased prevalence of cardiovascular disease in patients with chronic kidney disease (CKD), is the progressive structural and functional deterioration of the arteries and concomitant accrual of mineral. Vascular calcification (VC) was long viewed as a degenerative age-related pathology that resulted from the passive deposition of mineral in the extracellular matrix; however, since the discovery of "bone-related" protein expression in calcified atherosclerotic plaques over 20 years ago, a plethora of studies have evoked the now widely accepted view that VC is a highly regulated and principally cell-mediated phenomenon that recapitulates many features of physiologic ossification. Central to this theory are changes in vascular smooth muscle cell (VSMC) phenotype and viability, thought to be driven by chronic exposure to a number of dystrophic stimuli characteristics of the uremic state. Here, dedifferentiated synthetic VSMCs are seen to spawn calcifying matrix vesicles that actively seed mineralization of the arterial matrix. This review provides an overview of the major epidemiological, histological, and molecular aspects of VC in the context of CKD, and a counterpoint to the prevailing paradigm that emphasizes the primacy of VSMC-mediated mechanisms. Particular focus is given to the import of protein and small molecule inhibitors in regulating physiologic and pathological mineralization and the emerging role of mineral nanoparticles and their interplay with proinflammatory processes.

  15. Vascular Calcification in Uremia: New-Age Concepts about an Old-Age Problem.

    PubMed

    Smith, Edward R

    2016-01-01

    A hallmark of aging, and major contributor to the increased prevalence of cardiovascular disease in patients with chronic kidney disease (CKD), is the progressive structural and functional deterioration of the arteries and concomitant accrual of mineral. Vascular calcification (VC) was long viewed as a degenerative age-related pathology that resulted from the passive deposition of mineral in the extracellular matrix; however, since the discovery of "bone-related" protein expression in calcified atherosclerotic plaques over 20 years ago, a plethora of studies have evoked the now widely accepted view that VC is a highly regulated and principally cell-mediated phenomenon that recapitulates many features of physiologic ossification. Central to this theory are changes in vascular smooth muscle cell (VSMC) phenotype and viability, thought to be driven by chronic exposure to a number of dystrophic stimuli characteristics of the uremic state. Here, dedifferentiated synthetic VSMCs are seen to spawn calcifying matrix vesicles that actively seed mineralization of the arterial matrix. This review provides an overview of the major epidemiological, histological, and molecular aspects of VC in the context of CKD, and a counterpoint to the prevailing paradigm that emphasizes the primacy of VSMC-mediated mechanisms. Particular focus is given to the import of protein and small molecule inhibitors in regulating physiologic and pathological mineralization and the emerging role of mineral nanoparticles and their interplay with proinflammatory processes. PMID:26676134

  16. Thyroid hormone receptor binding to DNA and T3-dependent transcriptional activation are inhibited by uremic toxins

    PubMed Central

    Santos, Guilherme M; Pantoja, Carlos J; Costa e Silva, Aluízio; Rodrigues, Maria C; Ribeiro, Ralff C; Simeoni, Luiz A; Lomri, Noureddine; Neves, Francisco AR

    2005-01-01

    Background There is a substantial clinical overlap between chronic renal failure (CRF) and hypothyroidism, suggesting the presence of hypothyroidism in uremic patients. Although CRF patients have low T3 and T4 levels with normal thyroid-stimulating hormone (TSH), they show a higher prevalence of goiter and evidence for blunted tissue responsiveness to T3 action. However, there are no studies examining whether thyroid hormone receptors (TRs) play a role in thyroid hormone dysfunction in CRF patients. To evaluate the effects of an uremic environment on TR function, we investigated the effect of uremic plasma on TRβ1 binding to DNA as heterodimers with the retinoid X receptor alpha (RXRα) and on T3-dependent transcriptional activity. Results We demonstrated that uremic plasma collected prior to hemodialysis (Pre-HD) significantly reduced TRβ1-RXRα binding to DNA. Such inhibition was also observed with a vitamin D receptor (VDR) but not with a peroxisome proliferator-activated receptor gamma (PPARγ). A cell-based assay confirmed this effect where uremic pre-HD ultrafiltrate inhibited the transcriptional activation induced by T3 in U937 cells. In both cases, the inhibitory effects were reversed when the uremic plasma and the uremic ultrafiltrate were collected and used after hemodialysis (Post-HD). Conclusion These results suggest that dialyzable toxins in uremic plasma selectively block the binding of TRβ1-RXRα to DNA and impair T3 transcriptional activity. These findings may explain some features of hypothyroidism and thyroid hormone resistance observed in CRF patients. PMID:15807894

  17. A Case of Microangiopathic Hemolytic Anemia after Myxoma Excision and Mitral Valve Repair Presenting as Hemolytic Uremic Syndrome

    PubMed Central

    Park, Young Joo; Kim, Sang Pil; Shin, Ho-Jin

    2016-01-01

    Microangiopathic hemolytic anemia occurs in a diverse group of disorders, including thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, and prosthetic cardiac valves. Hemolytic anemia also occurs as a rare complication after mitral valve repair. In this report, we describe a case of microangiopathic hemolytic anemia following myxoma excision and mitral valve repair, which was presented as hemolytic uremic syndrome. PMID:27081450

  18. A Case of Microangiopathic Hemolytic Anemia after Myxoma Excision and Mitral Valve Repair Presenting as Hemolytic Uremic Syndrome.

    PubMed

    Park, Young Joo; Kim, Sang Pil; Shin, Ho-Jin; Choi, Jung Hyun

    2016-03-01

    Microangiopathic hemolytic anemia occurs in a diverse group of disorders, including thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, and prosthetic cardiac valves. Hemolytic anemia also occurs as a rare complication after mitral valve repair. In this report, we describe a case of microangiopathic hemolytic anemia following myxoma excision and mitral valve repair, which was presented as hemolytic uremic syndrome. PMID:27081450

  19. How Does Calcification Influence Plaque Vulnerability? Insights from Fatigue Analysis

    PubMed Central

    Wu, Baijian; Pei, Xuan; Li, Zhi-Yong

    2014-01-01

    Background. Calcification is commonly believed to be associated with cardiovascular disease burden. But whether or not the calcifications have a negative effect on plaque vulnerability is still under debate. Methods and Results. Fatigue rupture analysis and the fatigue life were used to evaluate the rupture risk. An idealized baseline model containing no calcification was first built. Based on the baseline model, we investigated the influence of calcification on rupture path and fatigue life by adding a circular calcification and changing its location within the fibrous cap area. Results show that 84.0% of calcified cases increase the fatigue life up to 11.4%. For rupture paths 10D far from the calcification, the life change is negligible. Calcifications close to lumen increase more fatigue life than those close to the lipid pool. Also, calcifications in the middle area of fibrous cap increase more fatigue life than those in the shoulder area. Conclusion. Calcifications may play a positive role in the plaque stability. The influence of the calcification only exists in a local area. Calcifications close to lumen may be influenced more than those close to lipid pool. And calcifications in the middle area of fibrous cap are seemly influenced more than those in the shoulder area. PMID:24955401

  20. [Hemolytic uremic syndrome (HUS): medical and social costs of treatment].

    PubMed

    Caletti, María Gracia; Petetta, Daniel; Jaitt, Marisa; Casaliba, Silvia; Gimenez, Alberto

    2006-01-01

    Hemolytic Uremic Syndrome (HUS) is the most frequent cause of renal failure in children, and the second cause of renal transplant. Argentina has the highest incidence of the world. Direct and indirect costs of HUS in its different clinical phases were studied. A retrospective review of all clinical notes of patients attending the hospital during the period 1987-2003 was carried out. Cost of every medical intervention, including diagnostic and therapeutic actions were calculated by the Hospital Department of Costs, according to two criteria: cost per process and cost per patient (considering total processes received each). Indirect costs were estimated according to guidelines established by the National Institute of Statistics and Census (INDEC): 1) family costs 2) social expenses afforded by the state, 3) cost of health services. Out of a total sample size of 525 patients, 231 clinical notes of children were selected and studied. The direct cost per patient in the acute period was US dollar 1 500, the total direct cost of care for each patient per year was US dollar 15 399,53; indirect costs per patient and for all year were US dollar 3 004,33 and US dollar 7 354,98 respectively. Total costs during 2005 per patient and per year was US dollar 17 553,39 and US dollar 2 170 477,37 respectively. Our study provides valuable information not only for purposes of health care planning, but also for helping authorities to set priorities in health, and to support the idea of developing preventive actions in a totally preventable condition in Argentina.

  1. Association of mitral annulus calcification, aortic valve calcification with carotid intima media thickness

    PubMed Central

    Sgorbini, Luca; Scuteri, Angelo; Leggio, Massimo; Leggio, Francesco

    2004-01-01

    Background Mitral annular calcification (MAC) and aortic annular calcification (AVC) may represent a manifestation of generalized atherosclerosis in the elederly. Alterations in vascular structure, as indexed by the intima media thickness (IMT), are also recognized as independent predictors of adverse cardiovascular outcomes. Aim To examine the relationship between the degree of calcification at mitral and/or aortic valve annulus and large artery structure (thickness). Methods We evaluated 102 consecutive patients who underwent transthoracic echocardiography and carotid artery echoDoppler for various indications; variables measured were: systemic blood pressure (BP), pulse pressure (PP=SBP-DBP), body mass index (BMI), fasting glucose, total, HDL, LDL chlolesterol, triglycerides, cIMT. The patients were divided according to a grading of valvular/annular lesions independent scores based on acoustic densitometry: 1 = annular/valvular sclerosis/calcification absence; 2 = annular/valvular sclerosis; 3 = annular calcification; 4 = annular-valvular calcification; 5 = valvular calcification with no recognition of the leaflets. Results Patient score was the highest observed for either valvular/annulus. Mean cIMT increased linearly with increasing valvular calcification score, ranging from 3.9 ± 0.48 mm in controls to 12.9 ± 1.8 mm in those subjects scored 5 (p < 0.0001). In the first to fourth quartile of cIMT values the respective maximal percentual of score were: score 1: 76.1%, score 2: 70.1%, score 4: 54.3% and score 5: 69.5% (p > 0.0001). Conclusion MAC and AVC score can identify subgroups of patients with different cIMT values which indicate different incidence and prevalence of systemic artery diseases. This data may confirm MAC-AVC as a useful important diagnostic parameter of systemic atherosclerotic disease. PMID:15471552

  2. Associations between Thyroid Hormones, Calcification Inhibitor Levels and Vascular Calcification in End-Stage Renal Disease

    PubMed Central

    Meuwese, Christiaan Lucas; Olauson, Hannes; Qureshi, Abdul Rashid; Ripsweden, Jonaz; Barany, Peter; Vermeer, Cees; Drummen, Nadja; Stenvinkel, Peter

    2015-01-01

    Introduction Vascular calcification is a common, serious and elusive complication of end-stage renal disease (ESRD). As a pro-calcifying risk factor, non-thyroidal illness may promote vascular calcification through a systemic lowering of vascular calcification inhibitors such as matrix-gla protein (MGP) and Klotho. Methods and Material In 97 ESRD patients eligible for living donor kidney transplantation, blood levels of thyroid hormones (fT3, fT4 and TSH), total uncarboxylated MGP (t-ucMGP), desphospho-uncarboxylated MGP (dp-ucMGP), descarboxyprothrombin (PIVKA-II), and soluble Klotho (sKlotho) were measured. The degree of coronary calcification and arterial stiffness were assessed by means of cardiac CT-scans and applanation tonometry, respectively. Results fT3 levels were inversely associated with coronary artery calcification (CAC) scores and measures of arterial stiffness, and positively with dp-ucMGP and sKlotho concentrations. Subfractions of MGP, PIVKA-II and sKlotho did not associate with CAC scores and arterial stiffness. fT4 and TSH levels were both inversely associated with CAC scores, but not with arterial stiffness. Discussion The positive associations between fT3 and dp-ucMGP and sKlotho suggest that synthesis of MGP and Klotho is influenced by thyroid hormones, and supports a link between non-thyroidal illness and alterations in calcification inhibitor levels. However, the absence of an association between serum calcification inhibitor levels and coronary calcification/arterial stiffness and the fact that MGP and Klotho undergo post-translational modifications underscore the complexity of this association. Further studies, measuring total levels of MGP and membrane bound Klotho, should examine this proposed pathway in further detail. PMID:26147960

  3. Aneurysm strength can decrease under calcification.

    PubMed

    Volokh, Konstantin Y; Aboudi, Jacob

    2016-04-01

    Aneurysms are abnormal dilatations of vessels in the vascular system that are prone to rupture. Prediction of the aneurysm rupture is a challenging and unsolved problem. Various factors can lead to the aneurysm rupture and, in the present study, we examine the effect of calcification on the aneurysm strength by using micromechanical modeling. The calcified tissue is considered as a composite material in which hard calcium particles are embedded in a hyperelastic soft matrix. Three experimentally calibrated constitutive models incorporating a failure description are used for the matrix representation. Two constitutive models describe the aneurysmal arterial wall and the third one - the intraluminal thrombus. The stiffness and strength of the calcified tissue are simulated in uniaxial tension under the varying amount of calcification, i.e. the relative volume of the hard inclusion within the periodic unit cell. In addition, the triaxiality of the stress state, which can be a trigger for the cavitation instability, is tracked. Results of the micromechanical simulation show an increase of the stiffness and a possible decrease of the strength of the calcified tissue as compared to the non-calcified one. The obtained results suggest that calcification (i.e. the presence of hard particles) can significantly affect the stiffness and strength of soft tissue. The development of refined experimental techniques that will allow for the accurate quantitative assessment of calcification is desirable. PMID:26717251

  4. Use of Eculizumab in Atypical Hemolytic Uremic Syndrome, Complicating Systemic Lupus Erythematosus.

    PubMed

    Bermea, Rene S; Sharma, Niharika; Cohen, Kenneth; Liarski, Vladimir M

    2016-09-01

    Atypical hemolytic uremic syndrome is characterized by the presence of thrombocytopenia, microangiopathic hemolytic anemia, and end-organ injury. In this report, we describe two patients with systemic lupus erythematosus who presented with findings compatible with atypical hemolytic uremic syndrome, complicated by acute kidney injury that was refractory to conventional therapies. Both patients exhibited a response to eculizumab, a monoclonal antibody to complement protein C5, with stabilization of their platelet count. On 1-year follow-up from their initial presentation, their hematologic disease remained in remission without recurrence. PMID:27556240

  5. Shigatoxin-associated hemolytic uremic syndrome: current molecular mechanisms and future therapies

    PubMed Central

    Keir, Lindsay S; Marks, Stephen D; Kim, Jon Jin

    2012-01-01

    Hemolytic uremic syndrome is the leading cause of acute kidney injury in childhood. Ninety percent of cases are secondary to gastrointestinal infection with shigatoxin-producing bacteria. In this review, we discuss the molecular mechanisms of shigatoxin leading to hemolytic uremic syndrome and the emerging role of the complement system and vascular endothelial growth factor in its pathogenesis. We also review the evidence for treatment options to date, in particular antibiotics, plasma exchange, and immunoadsorption, and link this to the molecular pathology. Finally, we discuss future avenues of treatment, including shigatoxin-binding agents and complement inhibitors, such as eculizumab. PMID:22888220

  6. Characteristics of rib cartilage calcification in Asian patients.

    PubMed

    Sunwoo, Woong Sang; Choi, Hyo Geun; Kim, Dae Woo; Jin, Hong-Ryul

    2014-01-01

    IMPORTANCE Rib cartilage from the sixth, seventh, and eighth ribs offers a long cartilaginous curvature, making the material reliable for grafting. Calcification of cartilage causes unexpected absorption, difficult manipulation, and donor site morbidity. Most studies of calcification were performed in Western countries. OBJECTIVE To investigate the incidence, degree, and pattern of rib cartilage calcification in Asian patients. DESIGN, SETTING, AND PARTICIPANTS Retrospective study of computed tomographic scans of the chest in 120 patients (60 male and 60 female). The incidence, degree, and pattern of cartilage calcification of the sixth through eighth ribs were noted. The patients were stratified into 6 age groups, and 20 patients (10 male and 10 female) were selected for each group. The degree of calcification was assessed as 0%, 1% to 25%, 26% to 50%, 51% to 75%, and 76% to 100%. Meaningful calcification was defined as 26% or greater. The pattern of calcification was classified as marginal, granular, and central. EXPOSURE Computed tomographic scans of the chest. MAIN OUTCOMES AND MEASURES Degree of calcification, presence of meaningful calcification, and calcification pattern. RESULTS Overall, 50.8% of cartilage was calcified, and female patients showed more frequent calcification than male patients (59.4% vs 42.2% [P < .001]). Calcification rates of the sixth and seventh rib cartilage were higher than those of the eighth rib cartilage in all age groups except teenagers, who had a similar rate for all 3 ribs. Calcification of the sixth and seventh rib cartilage significantly increased with age. A meaningful calcification rate was very low in males younger than 60 years, whereas the rate was relatively higher in females than males for all age groups. Males predominantly had the marginal type of calcification, whereas females predominantly had a granular type. The rate and pattern of calcification had no relationship to age. CONCLUSIONS AND RELEVANCE In Asian

  7. 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. PMID:26902864

  8. Adipocyte induced arterial calcification is prevented with sodium thiosulfate

    SciTech Connect

    Chen, Neal X.; O’Neill, Kalisha; Akl, Nader Kassis; Moe, Sharon M.

    2014-06-20

    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. 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, and

  9. 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

  10. [Enterohemorrhagic Escherichia coli and hemolytic-uremic syndrome].

    PubMed

    Allerberger, F; Sölder, B; Caprioli, A; Karch, H

    1997-09-19

    Enterohemorrhagic Escherichia coli (EHEC) are increasingly identified as the cause of diarrhea and hemorrhagic colitis in countries with highly developed livestock. In 5-10% of patients, full-blown hemolytic uremic syndrome (HUS) occurs as a postinfectious life-threatening complication. Up to 1996, 5 out of 39 patients (12.8%) with EHEC O157 infections in Austria developed HUS. Acute complications of HUS such as brain edema may also lead to death; one fatal outcome has been observed so far in Austrian patients. Aside from the cytotoxic Shiga toxins, other different pathogenic factors are often found in clinical EHEC isolates. These include a cytolysin termed EHEC-hemolysin and a low molecular heat-stabile enterotoxin. Furthermore, most EHEC strains express an important surface protein, intimin, which is important for adherence to intestinal epithelial cells. EHEC are heterogeneous in their antigenic structure (O-, H-antigens). In Austria O157:H7 and O157:H- are the dominating serogroups; in 1997 the first Austrian case of HUS due to EHEC O26:H11 was documented. Because there are no known reliable phenotypical markers for EHEC, diagnostic strategies should focus on the demonstration of Shiga toxins or Shiga toxin genes. For epidemiological purposes it is also important to attempt to isolate the causative agent. Cows and other ruminants are reservoirs for EHEC. In the Tyrol 3% of unpasteurised milk samples, up to 10% of minced beef samples, and 6% of calves yield EHEC O157. Aside from transmission via contaminated food, direct transmission from person to person also plays a major role in the chain of EHEC infection. In contrast to Italy and Bavaria, Austria has not experienced a major outbreak due to this organism so far. A nationwide surveillance system of HUS has shown an incidence of 0.37 HUS cases per 100,000 residents in the age group 0-14 years for 1995 (Italy: 0.2 cases per 100,000; Bavaria: approx. 1.5 cases per 100,000). PMID:9381722

  11. Separation of uremic toxins from urine with resorcinarene-based ion chromatography columns.

    PubMed

    Panahi, Tayyebeh; Weaver, Douglas J; Lamb, John D; Harrison, Roger G

    2015-01-01

    People with chronic kidney disease suffer from uremic toxins which accumulate in their bodies. Detection and quantification of uremic toxins help diagnose kidney problems and start patient care. The aim of this research was to seek a new method to assist this diagnosis by trace level detection and separation of guanidine containing uremic toxins in water and urine. To detect and quantify the uremic toxins, new stationary phases for ion chromatography (IC) columns based on glutamic acid functionalized resorcinarenes bound to divinylbenzene macroporous resin were prepared. The new column packing material afforded separation of the five compounds: guanidinoacetic acid, guanidine, methylguanidine, creatinine, and guanidinobenzoic acid in 30min. Peak resolutions ranged from 7.6 to 1.3. Gradient elutions at ambient temperature with methanesulfonic acid (MSA) solution as eluent resulted in detection levels in water from 10 to 47ppb and in synthetic urine from 28 to 180ppb. Limits of quantification for the analytes using pulsed amperometric detection were 30-160ppb in water and 93-590ppb in urine. Trace levels of creatinine (1ppm) were detected in the urine of a healthy individual using the columns.

  12. Escherichia coli O 157:H7-associated hemolytic-uremic syndrome after ingestion of contaminated hamburgers.

    PubMed

    Brandt, J R; Fouser, L S; Watkins, S L; Zelikovic, I; Tarr, P I; Nazar-Stewart, V; Avner, E D

    1994-10-01

    We conducted a retrospective analysis of 37 children with Escherichia coli O157:H7-associated hemolytic-uremic syndrome. The infection was traced to contaminated hamburgers at a fast-food restaurant chain. Within 5 days of the first confirmed case, the Washington State Department of Health identified the source and interrupted transmission of infection. Ninety-five percent of the children initially had severe hemorrhagic colitis. Nineteen patients (51%) had significant extrarenal abnormalities, including pancreatitis, colonic necrosis, glucose intolerance, coma, stroke, seizures, myocardial dysfunction, pericardial effusions, adult respiratory disease syndrome, and pleural effusions. Three deaths occurred, each in children with severe multisystem disease. At follow-up two children have significant impairment of renal function (glomerular filtration rate < 80 ml/min/per 1.73 Hm2); both of these children have a normal serum creatinine concentration. Hemolytic-uremic syndrome is the most common cause of acute renal failure in children, and this experience emphasizes the systemic nature of this disease. Clinicians should anticipate that multisystem involvement may occur in these patients, necessitating acute intervention or chronic follow-up. This outbreak of Hemolytic-uremic syndrome also highlights the microbiologic hazards of inadequately prepared food and emphasizes the importance of public health intervention in controlling Hemolytic-uremic syndrome.

  13. Deficiency of Soluble α-Klotho as an Independent Cause of Uremic Cardiomyopathy.

    PubMed

    Xie, J; Wu, Y-L; Huang, C-L

    2016-01-01

    Cardiovascular disease (CVD) is the major cause of mortality for patients with chronic kidney disease (CKD). Cardiac hypertrophy, occurring in up to 95% patients with CKD (also known as uremic cardiomyopathy), increases their risk for cardiovascular death. Many CKD-specific risk factors of uremic cardiomyopathy have been recognized, such as secondary hyperparathyroidism, indoxyl sulfate (IS)/p-cresyl, and vitamin D deficiency. However, several randomized controlled trials have recently shown that these risk factors have little impact on the mortality of CVD. Klotho is a type 1 membrane protein predominantly produced in the kidney, and CKD is known to be a Klotho-deficient state. Because of its important role in FGF23 and phosphate metabolism, Klotho is believed to affect cardiac growth and function indirectly through FGF23 and phosphate. Recent studies showed that soluble Klotho protects the heart against stress-induced cardiac hypertrophy by inhibiting TRPC6 channel-mediated abnormal Ca(2+) signaling in the heart, and the decreased level of circulating soluble Klotho in CKD is an important cause of uremic cardiomyopathy independent of FGF23 and phosphate. These new evidence suggested that Klotho is an independent contributing factor for uremic cardiomyopathy and a possible new target for treatment of this disease. PMID:27125747

  14. Insulin resistance in uremia: Insulin receptor kinase activity in liver and muscle from chronic uremic rats

    SciTech Connect

    Cecchin, F.; Ittoop, O.; Sinha, M.K.; Caro, J.F. )

    1988-04-01

    The authors have studied the structure and function of the partially purified insulin receptors from liver and skeletal muscle in a rat model of severe chronic uremia. {sup 125}I-insulin binding was higher in the liver from uremic rats when compared with ad libitum- and pair-fed controls. Furthermore, the ability of insulin to stimulate the autophosphorylation of the {beta}-subunit and insulin receptor kinase activity using Glu{sup 80}, Tyr{sup 20} as exogenous phosphoacceptor was increased in the liver of the uremic animals. The structural characteristics of the receptors, as determined by electrophoretic mobilities of affinity labeled {alpha}-subunit and the phosphorylated {beta}-subunit, were normal in uremia. {sup 125}I-insulin binding and insulin receptor kinase activity were similar in the skeletal muscle from uremic and pair- and ad libitum-fed animals. Thus the data are supportive of the hypothesis that in liver and muscle of chronic uremic rats, insulin resistance is due to a defect(s) distal to the insulin receptor kinase.

  15. Diarrhea, Urosepsis and Hemolytic Uremic Syndrome Caused by the Same Heteropathogenic Escherichia coli Strain.

    PubMed

    Ang, C Wim; Bouts, Antonia H M; Rossen, John W A; Van der Kuip, Martijn; Van Heerde, Marc; Bökenkamp, Arend

    2016-09-01

    We describe an 8-month-old girl with diarrhea, urosepsis and hemolytic uremic syndrome caused by Escherichia coli. Typing of cultured E. coli strains from urine and blood revealed the presence of virulence factors from multiple pathotypes of E. coli. This case exemplifies the genome plasticity of E. coli and the resulting heteropathogenic strains.

  16. Cerebro-renal interactions: impact of uremic toxins on cognitive function.

    PubMed

    Watanabe, Kimio; Watanabe, Tsuyoshi; Nakayama, Masaaki

    2014-09-01

    Cognitive impairment (CI) associated with chronic kidney disease (CKD) has received attention as an important problem in recent years. Causes of CI with CKD are multifactorial, and include cerebrovascular disease, renal anemia, secondary hyperparathyroidism, dialysis disequilibrium, and uremic toxins (UTs). Among these causes, little is known about the role of UTs. We therefore selected 21 uremic compounds, and summarized reports of cerebro-renal interactions associated with UTs. Among the compounds, uric acid, indoxyl sulfate, p-cresyl sulfate, interleukin 1-β, interleukin 6, TNF-α, and PTH were most likely to affect the cerebro-renal interaction dysfunction; however, sufficient data have not been obtained for other UTs. Notably, most of the data were not obtained under uremic conditions; therefore, the impact and mechanism of each UT on cognition and central nervous system in uremic state remains unknown. At present, impacts and mechanisms of UT effects on cognition are poorly understood. Clarifying the mechanisms and establishing novel therapeutic strategies for cerebro-renal interaction dysfunction is expected to be subject of future research.

  17. Localised pulmonary metastatic calcification associated with pulmonary artery obstruction.

    PubMed Central

    Bloodworth, J; Tomashefski, J F

    1992-01-01

    BACKGROUND: Metastatic pulmonary calcification, a complication of uraemia and disordered calcium metabolism, may be diffuse or localised. The factors that determine calcium precipitation are complex, but tissue alkalosis is thought to be important. As obstruction of the pulmonary artery theoretically causes local alkalosis a retrospective necropsy study was carried out to examine the relation between metastatic pulmonary calcification and vascular obstruction. METHODS: Five patients with focal and two with diffuse metastatic calcification in the lungs were identified over eight years. Lungs were studied macroscopically and by light microscopy, haematoxylin and eosin and histochemical stains being used for calcium. RESULTS: Underlying risk factors for calcification in these patients included renal failure in six and disseminated malignancy in five. In the five patients with localised calcification obstruction of the pulmonary artery by thrombus or tumour was found proximal or adjacent to areas of calcium deposition. In two patients metastatic calcification was confined to a lung with unilateral pulmonary artery thromboembolic occlusion. Calcification was not specifically associated with infarction, pneumonia, or diffuse alveolar damage. Lesions of the pulmonary artery were not seen in the two patients with diffuse bilateral metastatic calcification. CONCLUSION: In this small series there was a spatial association between pulmonary artery obstruction and localised metastatic calcification. It is proposed that pulmonary artery obstruction alters the microchemical environment of the lung, favouring tissue alkalosis and thereby enhancing parenchymal calcification in patients predisposed to this condition. Images PMID:1519194

  18. The role of inflammation in coronary artery calcification.

    PubMed

    Li, Jian-Jun; Zhu, Chen-Gang; Yu, Bing; Liu, Ya-Xin; Yu, Meng-Yue

    2007-12-01

    Vascular calcification is an age-dependent, common finding in human coronary arteries and begins as early as the second decade of life, just after fatty streak formation. Previous studies have showed that the severity of coronary calcification is closely related to atherosclerotic plaque burden and cardiac event rate. In the past few decades, coronary calcification has been considered passive and degenerative. With recent clinical and basic research, however, there is increasing recognition that coronary calcification is an active, regulated process. Current diagnostic methods for coronary artery calcification (CAC) are usually traditional coronary angiography, intravascular ultrasound (IVUS), electron beam computed tomography (EBCT) and multi-slice computed tomography (MSCT) while treatment for patients with calcified coronary arteries is troublesome. Several lines of evidence suggest that inflammation plays a major role in the development of atherosclerosis as well as its clinical manifestations. Recent study showed that inflammatory process might be also involved in coronary calcification. Accordingly, measurements of inflammatory markers such as C-reactive protein (CRP) may in part reflect indices of atherosclerosis, such as coronary calcification, and are likely to provide distinct information regarding cardiovascular risk. In this article, we review the current evidence of relationship between coronary calcification and inflammation for purpose of drawing the more attention on the inflammatory mechanism of coronary calcification, which may change our research as well as therapeutic strategies for coronary calcification in the future. PMID:17964226

  19. Unusual ganglioglioma with extensive calcification and ossification.

    PubMed

    Kavishwar, Vikas Shashikant; Chadha, Kirti G; Barodawala, Shaikhali Moiz; Murthy, Anuradha Krishna

    2016-01-01

    Ganglioglioma is a slow-growing relatively low-grade mixed glioneuronal tumor with most cases corresponding to the WHO Grade I category. It frequently presents with seizures. The temporal lobe is the most common location followed by frontal, parietal, and occipital lobes. These generally behave in a benign fashion and have a favorable prognosis. We describe a case of a 24-year-old male presenting with convulsions and a calcified parieto-occipital mass. This mass removed from the parietal lobe showed neoplastic glial and dysplastic neuronal tissue amidst extensive areas of calcification and foci of ossification. On immunohistochemistry, the glial component expressed glial fibrillary acidic protein whereas the dysplastic neuronal component expressed synaptophysin and CD34. Epithelial membrane antigen was negative and Ki-67 showed a low proliferative index. After the surgery, the patient is free of neurological symptoms. Widespread calcification and ossification are very unusual in ganglioglioma, which prompted us to report this case. PMID:27510688

  20. Computed tomographic evaluation of pineal calcification.

    PubMed

    Kohli, N; Rastogi, H; Bhadury, S; Tandon, V K

    1992-04-01

    A prospective study to ascertain the incidence of normally calcified pineal gland, was carried out in 1000 consecutive patients from different parts of Uttar Pradesh (India), undergoing cranial computed tomography for reasons other than a pineal or parapineal pathology. A total of 167 (16.70%) patients were found to have calcified pineals. Of these 128 were males and 39 females. The incidence rose from 1.16 per cent in the first decade to 31.88 per cent above the age of 50 yr. The percentage incidence of normal pineal calcification was lower than that seen in the Western population. No significant difference was found between men and women in any age group. Although calcification appeared as early as the first decade, this percentage was significantly lower than in the higher age groups. Significantly higher incidence rates were seen in the second decade, third decade and sixth decade onwards. PMID:1428055

  1. Vascular calcification in diabetes: mechanisms and implications.

    PubMed

    Snell-Bergeon, Janet K; Budoff, Matthew J; Hokanson, John E

    2013-06-01

    Cardiovascular disease (CVD) remains the leading cause of death among adults with diabetes, and CVD prevention remains a major challenge. Coronary artery calcium (CAC) score measured by electron beam tomography (EBT) or multi-slice detector computed tomography correlates closely with plaque burden and coronary angiography, and predicts coronary events independently of other risk factors. Further, progression of CAC over several years has been shown to predict increased mortality. Coronary calcification is an active process strongly associated with atherosclerotic plaque evolution and is an accepted surrogate endpoint in studies of patients with diabetes older than 30. In this review, recent findings regarding the mechanisms and implications of vascular calcification in diabetes will be discussed. PMID:23526400

  2. Dystrophic Calcification of the Prostate after Cryotherapy

    PubMed Central

    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. PMID:25548712

  3. Speckle tracking echocardiography detects uremic cardiomyopathy early and predicts cardiovascular mortality in ESRD.

    PubMed

    Kramann, Rafael; Erpenbeck, Johanna; Schneider, Rebekka K; Röhl, Anna B; Hein, Marc; Brandenburg, Vincent M; van Diepen, Merel; Dekker, Friedo; Marx, Nicolaus; Floege, Jürgen; Becker, Michael; Schlieper, Georg

    2014-10-01

    Cardiovascular mortality is high in ESRD, partly driven by sudden cardiac death and recurrent heart failure due to uremic cardiomyopathy. We investigated whether speckle-tracking echocardiography is superior to routine echocardiography in early detection of uremic cardiomyopathy in animal models and whether it predicts cardiovascular mortality in patients undergoing dialysis. Using speckle-tracking echocardiography in two rat models of uremic cardiomyopathy soon (4-6 weeks) after induction of kidney disease, we observed that global radial and circumferential strain parameters decreased significantly in both models compared with controls, whereas standard echocardiographic readouts, including fractional shortening and cardiac output, remained unchanged. Furthermore, strain parameters showed better correlations with histologic hallmarks of uremic cardiomyopathy. We then assessed echocardiographic and clinical characteristics in 171 dialysis patients. During the 2.5-year follow-up period, ejection fraction and various strain parameters were significant risk factors for cardiovascular mortality (primary end point) in a multivariate Cox model (ejection fraction hazard ratio [HR], 0.97 [95% confidence interval (95% CI), 0.95 to 0.99; P=0.012]; peak global longitudinal strain HR, 1.17 [95% CI, 1.07 to 1.28; P<0.001]; peak systolic and late diastolic longitudinal strain rates HRs, 4.7 [95% CI, 1.23 to 17.64; P=0.023] and 0.25 [95% CI, 0.08 to 0.79; P=0.02], respectively). Multivariate Cox regression analysis revealed circumferential early diastolic strain rate, among others, as an independent risk factor for all-cause mortality (secondary end point; HR, 0.43; 95% CI, 0.25 to 0.74; P=0.002). Together, these data support speckle tracking as a postprocessing echocardiographic technique to detect uremic cardiomyopathy and predict cardiovascular mortality in ESRD.

  4. Enlarging mediastinal/hilar lymphadenopathy with calcification.

    PubMed

    Adachi, Takashi; Nakahata, Masashi; Moritani, Suzuko; Iida, Hiroatsu; Ogawa, Kenji

    2016-02-01

    A 77-year-old man was referred to our hospital due to enlarging mediastinal/hilar lymphadenopathy with calcification. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and bone marrow aspiration were performed. Subsequently, monoclonal gammopathy of undetermined significance (MGUS) associated with mediastinal amyloidosis was diagnosed. We hereby report a case in which EBUS-TBNA led to a successful diagnosis of amyloidosis. PMID:26862422

  5. 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.

  6. Corals concentrate dissolved inorganic carbon to facilitate calcification.

    PubMed

    Allison, Nicola; Cohen, Itay; Finch, Adrian A; Erez, Jonathan; Tudhope, Alexander W

    2014-12-22

    The sources of dissolved inorganic carbon (DIC) used to produce scleractinian coral skeletons are not understood. Yet this knowledge is essential for understanding coral biomineralization and assessing the potential impacts of ocean acidification on coral reefs. Here we use skeletal boron geochemistry to reconstruct the DIC chemistry of the fluid used for coral calcification. We show that corals concentrate DIC at the calcification site substantially above seawater values and that bicarbonate contributes a significant amount of the DIC pool used to build the skeleton. Corals actively increase the pH of the calcification fluid, decreasing the proportion of DIC present as CO2 and creating a diffusion gradient favouring the transport of molecular CO2 from the overlying coral tissue into the calcification site. Coupling the increases in calcification fluid pH and [DIC] yields high calcification fluid [CO3(2-)] and induces high aragonite saturation states, favourable to the precipitation of the skeleton.

  7. Dystrophic calcifications after autologous fat injection on face.

    PubMed

    Kim, Dai Hyun; Jang, Hee Won; Kim, Hee Joo; Son, Sang Wook

    2014-06-01

    Autologous fat injection is widely used procedure for various functional and aesthetic purposes. However, it could result in many immediate or delayed complications including dystrophic calcifications. Almost all of the case reports about dystrophic calcification after autologous fat injection were result from the iatrogenic tissue trauma of breast augmentation. This is a report of a 30-year-old patient who developed pathologically proven multiple dystrophic calcifications on the face after autologous fat injection. PMID:24131074

  8. Atraumatic quadriceps tendon tear associated with calcific tendonitis.

    PubMed

    Abram, Simon G F; Sharma, Akash D; Arvind, Chinnakonda

    2012-11-27

    Calcific tendonitis of the quadriceps tendon is an uncommon condition. We present the first case of a quadriceps tendon tear associated with calcific tendonitis. In this case, the patient presented with symptoms mimicking a rupture of the quadriceps tendon. This case illustrates that although calcific tendonitis of the quadriceps is a rare condition it is not benign and should be considered when investigating acute symptoms associated with the extensor mechanism of the knee.

  9. Effects of Uremic Toxins from the Gut Microbiota on Bone: A Brief Look at Chronic Kidney Disease.

    PubMed

    Black, Ana Paula; Cardozo, Ludmila F M F; Mafra, Denise

    2015-10-01

    Patients with chronic kidney disease (CKD) frequently have mineral and bone disorders (CKD-MBD) that are caused by several mechanisms. Recent research has suggested that uremic toxins from the gut such as p-cresyl sulfate (PCS) and indoxyl sulfate (IS) could also be involved in the development of bone disease in patients with CKD. IS and PCS are produced by microbiota in the gut, carried into the plasma bound to serum albumin, and are normally excreted into the urine. However, in patients with CKD, there is an accumulation of high levels of these uremic toxins. The exact mechanisms of action of uremic toxins in bone disease remain unclear. The purpose of this brief review is to discuss the link between uremic toxins (IS and PCS) and bone mineral disease in chronic kidney disease.

  10. Attenuation of Na/K-ATPase Mediated Oxidant Amplification with pNaKtide Ameliorates Experimental Uremic Cardiomyopathy

    PubMed Central

    Liu, Jiang; Tian, Jiang; Chaudhry, Muhammad; Maxwell, Kyle; Yan, Yanling; Wang, Xiaoliang; Shah, Preeya T.; Khawaja, Asad A.; Martin, Rebecca; Robinette, Tylor J.; El-Hamdani, Adee; Dodrill, Michael W.; Sodhi, Komal; Drummond, Christopher A.; Haller, Steven T.; Kennedy, David J.; Abraham, Nader G.; Xie, Zijian; Shapiro, Joseph I.

    2016-01-01

    We have previously reported that the sodium potassium adenosine triphosphatase (Na/K-ATPase) can effect the amplification of reactive oxygen species. In this study, we examined whether attenuation of oxidant stress by antagonism of Na/K-ATPase oxidant amplification might ameliorate experimental uremic cardiomyopathy induced by partial nephrectomy (PNx). PNx induced the development of cardiac morphological and biochemical changes consistent with human uremic cardiomyopathy. Both inhibition of Na/K-ATPase oxidant amplification with pNaKtide and induction of heme oxygenase-1 (HO-1) with cobalt protoporphyrin (CoPP) markedly attenuated the development of phenotypical features of uremic cardiomyopathy. In a reversal study, administration of pNaKtide after the induction of uremic cardiomyopathy reversed many of the phenotypical features. Attenuation of Na/K-ATPase oxidant amplification may be a potential strategy for clinical therapy of this disorder. PMID:27698370

  11. Sortilin mediates vascular calcification via its recruitment into extracellular vesicles

    PubMed Central

    Goettsch, Claudia; Hutcheson, Joshua D.; Aikawa, Masanori; Iwata, Hiroshi; Pham, Tan; Nykjaer, Anders; Kjolby, Mads; Rogers, Maximillian; Michel, Thomas; Shibasaki, Manabu; Hagita, Sumihiko; Kramann, Rafael; Singh, Sasha A.

    2016-01-01

    Vascular calcification is a common feature of major cardiovascular diseases. Extracellular vesicles participate in the formation of microcalcifications that are implicated in atherosclerotic plaque rupture; however, the mechanisms that regulate formation of calcifying extracellular vesicles remain obscure. Here, we have demonstrated that sortilin is a key regulator of smooth muscle cell (SMC) calcification via its recruitment to extracellular vesicles. Sortilin localized to calcifying vessels in human and mouse atheromata and participated in formation of microcalcifications in SMC culture. Sortilin regulated the loading of the calcification protein tissue nonspecific alkaline phosphatase (TNAP) into extracellular vesicles, thereby conferring its calcification potential. Furthermore, SMC calcification required Rab11-dependent trafficking and FAM20C/casein kinase 2–dependent C-terminal phosphorylation of sortilin. In a murine model, Sort1-deficiency reduced arterial calcification but did not affect bone mineralization. Additionally, transfer of sortilin-deficient BM cells to irradiated atherosclerotic mice did not affect vascular calcification, indicating a primary role of SMC-derived sortilin. Together, the results of this study identify sortilin phosphorylation as a potential therapeutic target for ectopic calcification/microcalcification and may clarify the mechanism that underlies the genetic association between the SORT1 gene locus and coronary artery calcification. PMID:26950419

  12. Inhibitory Role of Notch1 in Calcific Aortic Valve Disease

    PubMed Central

    Koenig, Sara N.; Nichols, Haley A.; Galindo, Cristi L.; Garner, Harold R.; Merrill, Walter H.; Hinton, Robert B.; Garg, Vidu

    2011-01-01

    Aortic valve calcification is the most common form of valvular heart disease, but the mechanisms of calcific aortic valve disease (CAVD) are unknown. NOTCH1 mutations are associated with aortic valve malformations and adult-onset calcification in families with inherited disease. The Notch signaling pathway is critical for multiple cell differentiation processes, but its role in the development of CAVD is not well understood. The aim of this study was to investigate the molecular changes that occur with inhibition of Notch signaling in the aortic valve. Notch signaling pathway members are expressed in adult aortic valve cusps, and examination of diseased human aortic valves revealed decreased expression of NOTCH1 in areas of calcium deposition. To identify downstream mediators of Notch1, we examined gene expression changes that occur with chemical inhibition of Notch signaling in rat aortic valve interstitial cells (AVICs). We found significant downregulation of Sox9 along with several cartilage-specific genes that were direct targets of the transcription factor, Sox9. Loss of Sox9 expression has been published to be associated with aortic valve calcification. Utilizing an in vitro porcine aortic valve calcification model system, inhibition of Notch activity resulted in accelerated calcification while stimulation of Notch signaling attenuated the calcific process. Finally, the addition of Sox9 was able to prevent the calcification of porcine AVICs that occurs with Notch inhibition. In conclusion, loss of Notch signaling contributes to aortic valve calcification via a Sox9-dependent mechanism. PMID:22110751

  13. Sortilin mediates vascular calcification via its recruitment into extracellular vesicles.

    PubMed

    Goettsch, Claudia; Hutcheson, Joshua D; Aikawa, Masanori; Iwata, Hiroshi; Pham, Tan; Nykjaer, Anders; Kjolby, Mads; Rogers, Maximillian; Michel, Thomas; Shibasaki, Manabu; Hagita, Sumihiko; Kramann, Rafael; Rader, Daniel J; Libby, Peter; Singh, Sasha A; Aikawa, Elena

    2016-04-01

    Vascular calcification is a common feature of major cardiovascular diseases. Extracellular vesicles participate in the formation of microcalcifications that are implicated in atherosclerotic plaque rupture; however, the mechanisms that regulate formation of calcifying extracellular vesicles remain obscure. Here, we have demonstrated that sortilin is a key regulator of smooth muscle cell (SMC) calcification via its recruitment to extracellular vesicles. Sortilin localized to calcifying vessels in human and mouse atheromata and participated in formation of microcalcifications in SMC culture. Sortilin regulated the loading of the calcification protein tissue nonspecific alkaline phosphatase (TNAP) into extracellular vesicles, thereby conferring its calcification potential. Furthermore, SMC calcification required Rab11-dependent trafficking and FAM20C/casein kinase 2-dependent C-terminal phosphorylation of sortilin. In a murine model, Sort1-deficiency reduced arterial calcification but did not affect bone mineralization. Additionally, transfer of sortilin-deficient BM cells to irradiated atherosclerotic mice did not affect vascular calcification, indicating a primary role of SMC-derived sortilin. Together, the results of this study identify sortilin phosphorylation as a potential therapeutic target for ectopic calcification/microcalcification and may clarify the mechanism that underlies the genetic association between the SORT1 gene locus and coronary artery calcification. PMID:26950419

  14. Acupressure and Transcutaneous Electrical Acupoint Stimulation for Improving Uremic Pruritus: A Randomized, Controlled Trial.

    PubMed

    Kılıç Akça, Nazan; Taşcı, Sultan

    2016-03-01

    Context • Uremic pruritus, a frequent and compromising symptom for patients with advanced or end-stage renal disease (ESRD), strongly reduces the patient's quality of life. Pruritus may be extremely difficult to control because therapeutic options are limited. Topical products are frequently used for easing pruritus, but their effects are generally temporary and marginal. Although acupressure and electrical-stimulation methods for the application of acupressure have been evaluated separately in terms of pruritus efficiency in different studies, the existence of any difference between the efficacies of the 2 methods has not been assessed yet. Objective • The study intended to test the effectiveness of acupressure and transcutaneous electrical acupoint stimulation (TEAS) on uremic pruritus in patients who were receiving the routine hemodialysis treatment. Design • The study was a randomized, controlled trial. Setting • The study took place in hemodialysis units located in hemodialysis centers in Turkey. Participants • Participants were patients in the hemodialysis units who were under hemodialysis treatment and had experienced uremic pruritus. Intervention • Participants were randomly assigned to the acupressure group (intervention group), the TEAS group (intervention group), or the control group. For the 2 intervention groups, the treatment was applied 3 ×/wk during the 4 wk of the study on the large intestine (LI-11) acupuncture points in the arm, for a total of 12 sessions. Outcome Measures • The study measured the severity of participants' pruritus using a patient information form and a visual analogue scale (VAS). The data were collected at baseline and posttreatment. Results • A total of 75 patients participated in the study. The results indicated that patients in the acupressure and TEAS groups had significant reductions from baseline to posttreatment in their levels of discomfort from uremic pruritus compared with patients in the control

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  16. 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.

  17. 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.

  18. 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.

  19. Calcific tendinitis of the rotator cuff

    PubMed Central

    ElShewy, Mohamed Taha

    2016-01-01

    Calcific tendinitis within the rotator cuff tendon is a common shoulder disorder that should be differentiated from dystrophic calcification as the pathogenesis and natural history of both is totally different. Calcific tendinitis usually occurs in the fifth and sixth decades of life among sedentary workers. It is classified into formative and resorptive phases. The chronic formative phase results from transient hypoxia that is commonly associated with repeated microtrauma causing calcium deposition into the matrix vesicles within the chondrocytes forming bone foci that later coalesce. This phase may extend from 1 to 6 years, and is usually asymptomatic. The resorptive phase extends from 3 wk up to 6 mo with vascularization at the periphery of the calcium deposits causing macrophage and mononuclear giant cell infiltration, together with fibroblast formation leading to an aggressive inflammatory reaction with inflammatory cell accumulation, excessive edema and rise of the intra-tendineous pressure. This results in a severely painful shoulder. Radiological investigations confirm the diagnosis and suggest the phase of the condition and are used to follow its progression. Although routine conventional X-ray allows detection of the deposits, magnetic resonance imaging studies allow better evaluation of any coexisting pathology. Various methods of treatment have been suggested. The appropriate method should be individualized for each patient. Conservative treatment includes pain killers and physiotherapy, or “minimally invasive” techniques as needling or puncture and aspiration. It is almost always successful since the natural history of the condition ends with resorption of the deposits and complete relief of pain. Due to the intolerable pain of the acute and severely painful resorptive stage, the patient often demands any sort of operative intervention. In such case arthroscopic removal is the best option as complete removal of the deposits is unnecessary. PMID

  20. Association between calcifying nanoparticles and placental calcification

    PubMed Central

    Guo, Yanan; Zhang, Dechun; Lu, He; Luo, Shuang; Shen, Xuecheng

    2012-01-01

    Background The purpose of this study was to examine the possible contribution of calcifying nanoparticles to the pathogenesis of placental calcification. Methods Calcified placental tissues and distal tissue samples were collected from 36 confirmed placental calcification cases. In addition, 20 normal placental tissue samples were obtained as a control group. All the tissue samples were cultured using special nanobacterial culture methods. The cultured calcifying nanoparticles were examined by transmission electron microscopy (TEM), and their growth was monitored by optical density (OD) at a wavelength of 650 nm. 16S rRNA gene expression of the cultured calcifying nanoparticles was also isolated and sequenced. Results Novel calcifying nanoparticles wrapped with electron-dense shells between 50 nm to 500 nm in diameter were observed in the extracellular matrix of calcified placental tissues. They were detected in placental villi and hydroxyapatite crystals, and contained “nucleic acid-like materials”. After isolation and four weeks of culture, 28 of 36 calcified placental tissue samples showed white granular precipitates attached to the bottom of the culture tubes. OD650 measurements indicated that the precipitates from the calcified placental tissues were able to grow in culture, whereas no such precipitates from the control tissues were observed. The 16S rRNA genes were isolated from the cultured calcifying nanoparticles and calcified placental tissues, and their gene sequencing results implied that calcifying nanoparticles were novel nanobacteria (GenBank JF823648). Conclusion Our results suggest that these novel calcifying nanoparticles may play a role in placental calcification. PMID:22615531

  1. Medial vascular calcification revisited: review and perspectives

    PubMed Central

    Lanzer, Peter; Boehm, Manfred; Sorribas, Victor; Thiriet, Marc; Janzen, Jan; Zeller, Thomas; St Hilaire, Cynthia; Shanahan, Catherine

    2014-01-01

    Vascular calcifications (VCs) are actively regulated biological processes associated with crystallization of hydroxyapatite in the extracellular matrix and in cells of the media (VCm) or intima (VCi) of the arterial wall. Both patterns of VC often coincide and occur in patients with type II diabetes, chronic kidney disease, and other less frequent disorders; VCs are also typical in senile degeneration. In this article, we review the current state of knowledge about the pathology, molecular biology, and nosology of VCm, expand on potential mechanisms responsible for poor prognosis, and expose some of the directions for future research in this area. PMID:24740885

  2. Bone morphogenic protein-4 expression in vascular lesions of calciphylaxis.

    PubMed

    Griethe, Wanja; Schmitt, Roland; Jurgensen, Jan Steffen; Bachmann, Sebastian; Eckardt, Kai-Uwe; Schindler, Ralf

    2003-01-01

    Calciphylaxis is characterized by an extensive media-calcification of cutaneous and subcutaneous arterioles and capillaries. Recent studies have provided evidence that vascular calcification is a process with similarities to bone metabolism. Bone morphogenic protein-4 (BMP-4) is physiologically involved in bone development and repair. The presence of BMP-4 in atherosclerosis and in sclerotic heart valves led us to suggest that BMP-4 is also involved in calciphylaxis. A 47-year-old male patient developed end-stage renal failure due to chronic glomerulonephritis. He has had two kidney transplants with an immunosuppressive regimen consisting of cyclosporine A and steroids. He was admitted to our hospital because of an increase in serum creatinine (Cr) and he subsequently developed progressive dermal ulcerations. A skin biopsy led to the diagnosis of calciphylaxis. Immunohistochemistry for BMP-4 of a skin specimen from our patient showed strong cytoplasmic immunoreactivity of intradermal cells with clear spatial association to arterioles and hair follicles. Whereas there are identified inhibitors and promoters of vascular calcification, the presence of BMP-4 has not been demonstrated in calcific uremic arteriolopathy. In contrast to atherosclerosis, BMP-4 in calciphylaxis cannot be found in vascular media, but in intradermal cells at the border of arterioles and hair follicles. Therefore, in calciphylaxis BMP-4 can play the role of a cytokine, a growth factor or a media-calcification promoter. PMID:14733421

  3. Randomized, Double-blind Study with Glycerol and Paraffin in Uremic Xerosis

    PubMed Central

    Balaskas, Elias; Szepietowski, Jacek C.; Bessis, Didier; Ioannides, Dimitrios; Ponticelli, Claudio; Ghienne, Corinne; Taberly, Alain

    2011-01-01

    Summary Background and objectives Uremic xerosis is a bothersome condition that is poorly responsive to moisturizing and emollient therapy. Design, setting, participants, & measurements A randomized, double-blind, intraindividual (left versus right comparison), multicentric clinical study was performed on 100 patients with moderate to severe uremic xerosis for 7 days, during which the patients applied twice daily an emulsion combining glycerol and paraffin (test product) on one allocated lower leg, and the emulsion alone (comparator) on the other lower leg. This was followed by an open-labeled use of the test product on all of the xerotic areas for 49 days. The main efficacy parameter was treatment response on each lower leg, as defined by a reduction from baseline of at least two grades in a five-point clinical score on day 7. Results Among the 99 patients analyzed, the test product was highly effective with a treatment response in 72 patients (73%), whereas 44 patients (44%) responded to the comparator (P < 0.0001, intergroup analysis). This was associated with an objective reduction in the density and thickness of the scales on day 7 (P < 0.0001 compared with the comparator) and a substantial improvement of the uremic pruritus (75%) and quality of life of the patients at study end (P < 0.001, intragroup analysis). The test product was very well tolerated, with product-related local intolerance (exacerbated pruritus, local burning, or erythema) occurring in only five patients (5%). Conclusions Uremic xerosis can be managed successfully when an appropriate emollient therapy is used. PMID:21258039

  4. [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.

  5. Extracellular vesicles in cardiovascular calcification: expanding current paradigms.

    PubMed

    Krohn, Jona B; Hutcheson, Joshua D; Martínez-Martínez, Eduardo; Aikawa, Elena

    2016-06-01

    Vascular calcification is a major contributor to the progression of cardiovascular disease, one of the leading causes of death in industrialized countries. New evidence on the mechanisms of mineralization identified calcification-competent extracellular vesicles (EVs) derived from smooth muscle cells, valvular interstitial cells and macrophages as the mediators of calcification in diseased heart valves and atherosclerotic plaques. However, the regulation of EV release and the mechanisms of interaction between EVs and the extracellular matrix leading to the formation of destabilizing microcalcifications remain unclear. This review focuses on current limits in our understanding of EVs in cardiovascular disease and opens up new perspectives on calcific EV biogenesis, release and functions within and beyond vascular calcification. We propose that, unlike bone-derived matrix vesicles, a large population of EVs implicated in cardiovascular calcification are of exosomal origin. Moreover, the milieu-dependent loading of EVs with microRNA and calcification inhibitors fetuin-A and matrix Gla protein suggests a novel role for EVs in intercellular communication, adding a new mechanism to the pathogenesis of vascular mineralization. Similarly, the cell type-dependent enrichment of annexins 2, 5 or 6 in calcifying EVs posits one of several emerging factors implicated in the regulation of EV release and calcifying potential. This review aims to emphasize the role of EVs as essential mediators of calcification, a major determinant of cardiovascular mortality. Based on recent findings, we pinpoint potential targets for novel therapies to slow down the progression and promote the stability of atherosclerotic plaques. PMID:26824781

  6. Matrix Gla Protein polymorphisms are associated with coronary artery calcification

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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). We examined the cross-sectional association between MGP SNPs [rs1800802 (T-138C), rs1800801 (G-7A),and rs4236 (Ala102Thr)...

  7. Liposarcoma of the thigh with mixed calcification and ossification.

    PubMed

    Child, Jeremy R; Young, Colin R; Amini, Behrang

    2016-09-01

    Liposarcoma is one of the most common soft-tissue sarcomas. Calcification and ossification can occur in liposarcoma; however, the presence of both ossification and calcification is a very rare entity. We present a case of a partially calcified and ossified dedifferentiated liposarcoma of the thigh in a 76-year-old woman, which contained heterologous elements of chondrosarcoma and rhabdomyosarcoma. PMID:27594953

  8. Activation of Nrf2 by dimethyl fumarate improves vascular calcification.

    PubMed

    Ha, Chae-Myeong; Park, Sungmi; Choi, Young-Keun; Jeong, Ji-Yun; Oh, Chang Joo; Bae, Kwi-Hyun; Lee, Sun Joo; Kim, Ji-Hyun; Park, Keun-Gyu; Jun, Do Youn; Lee, In-Kyu

    2014-10-01

    Dimethyl fumarate (DMF) has several pharmacological benefits including immunomodulation and prevention of fibrosis, which are dependent on the NF-E2-related factor 2 (Nrf2) antioxidant pathways. Therefore, we hypothesized that DMF could attenuate vascular calcification via Nrf2 activation. Vascular calcification induced by hyperphosphataemia was significantly inhibited by DMF in vascular smooth muscle cells (VSMCs) in a dose-dependent manner. DMF-mediated Nrf2 upregulation was accompanied by the reduced expressions of genes related with osteoblast-like phenotype based on promoter activity, mRNA and protein expression, and von Kossa staining. Likewise, Nrf2 overexpression significantly decreased the formation of calcium deposit similar to the level of osteogenic staining in VSMCs, and DMF with Nrf2 knockdown failed to attenuate hyperphosphatemia induced vascular calcification. Furthermore, DMF significantly attenuated the calcification of ex vivo ring culture from both rat common carotid artery and mouse thoracic aorta as well as in vivo mouse model of Vitamin D3-induced calcification consistent with the increased Nrf2 protein levels in early stage of calcification by DMF. In conclusion, our data support that DMF stimulates Nrf2 activity to attenuate hyperphosphatamia in vitro or Vitamin D3-induced in vivo vascular calcification, which would be a beneficial effect on vascular diseases induced by oxidative stress such as vascular calcification. PMID:25135648

  9. Gender differences in the development of uremic cardiomyopathy following partial nephrectomy: Role of progesterone.

    PubMed

    Drummond, Christopher A; Buddny, George; Haller, Steven T; Liu, Jiang; Yan, Yanling; Xie, Zijian; Malhotra, Deepak; Shapiro, Joseph I; Tian, Jiang

    2013-01-31

    Gender difference has been suggested as a risk factor for developing cardiovascular and renal diseases in humans and experimental animals. As a major sex hormone, progesterone was reported to compete with cardiotonic steroid binding to Na/K-ATPase. Our previous publication demonstrated that cardiotonic steroids (e.g., marinobufagenin) play an important role in the development of experimental uremic cardiomyopathy. We also observed that the putative mineralocorticoid antagonists, spironolactone and its major metabolite canrenone, antagonize binding of cardiotonic steroids to Na/K-ATPase in a competitive manner and also ameliorate experimental uremic cardiomyopathy induced by partial nephrectomy. In the following studies, we noted that progesterone displayed competitive inhibition of cardiotonic steroid binding to Na/K-ATPase and partially inhibited collagen synthesis induced by marinobufagenin in cultured cardiac fibroblasts. Therefore, we sought to examine whether female rats displayed less uremic cardiomyopathy than male rats when subjected to partial nephrectomy. Although partial nephrectomy caused the induction of smaller increases in blood pressure of female rats, they appeared to be similarly susceptible to cardiac remodeling induced by partial nephrectomy in terms of hypertrophy and fibrosis as age-matched male rats. The possible explanations for our findings are therefore discussed. PMID:24404431

  10. Gender differences in the development of uremic cardiomyopathy following partial nephrectomy: Role of progesterone

    PubMed Central

    Drummond, Christopher A; Buddny, George; Haller, Steven T; Liu, Jiang; Yan, Yanling; Xie, Zijian; Malhotra, Deepak; Shapiro, Joseph I; Tian, Jiang

    2013-01-01

    Gender difference has been suggested as a risk factor for developing cardiovascular and renal diseases in humans and experimental animals. As a major sex hormone, progesterone was reported to compete with cardiotonic steroid binding to Na/K-ATPase. Our previous publication demonstrated that cardiotonic steroids (e.g., marinobufagenin) play an important role in the development of experimental uremic cardiomyopathy. We also observed that the putative mineralocorticoid antagonists, spironolactone and its major metabolite canrenone, antagonize binding of cardiotonic steroids to Na/K-ATPase in a competitive manner and also ameliorate experimental uremic cardiomyopathy induced by partial nephrectomy. In the following studies, we noted that progesterone displayed competitive inhibition of cardiotonic steroid binding to Na/K-ATPase and partially inhibited collagen synthesis induced by marinobufagenin in cultured cardiac fibroblasts. Therefore, we sought to examine whether female rats displayed less uremic cardiomyopathy than male rats when subjected to partial nephrectomy. Although partial nephrectomy caused the induction of smaller increases in blood pressure of female rats, they appeared to be similarly susceptible to cardiac remodeling induced by partial nephrectomy in terms of hypertrophy and fibrosis as age-matched male rats. The possible explanations for our findings are therefore discussed. PMID:24404431

  11. Alterations in trace elements and oxidative stress in uremic patients with dementia.

    PubMed

    Guo, Chih-Hung; Ko, Wang-Sheng; Chen, Pei-Chung; Hsu, Guoo-Shyng W; Lin, Chia-Yeh; Wang, Chia-Liang

    2009-10-01

    The present study was conducted to compare the trace elements and oxidative status between uremic patients with and without dementia. Chronic hemodialysis patients with dementia (n = 20) and without dementia (n = 25), and age-matched healthy volunteers (n = 20) were enrolled. The nutritional status, blood levels of trace elements aluminum (Al), zinc (Zn), copper (Cu), magnesium (Mg) and iron (Fe), malondialdehyde (MDA), and protein carbonyl production, antioxidant enzymes glutathione peroxidase (GPx), and glutathione reductase (GR) activities were measured. No significant difference in nutritional status or clinical characteristics was observed between nondementia and dementia patients. However, uremic patients with dementia have significantly higher Al, Cu, and Mg and lower Zn concentrations, as well as increased Cu/Zn ratio in comparison to nondementia patients. There were statistically significant increased MDA and carbonyl production and decreased GPx and GR activities in dementia patients. Furthermore, the significant associations of Al, Mg, and Cu/Zn ratio with oxidative status in patients with dementia were noted. The dementia may initially worsen with abnormal metabolism of trace elements and oxidative stress occurrence. Our results suggest that abnormalities in trace element levels are associated with oxidative stress and may be a major risk factor in the dementia development of uremic patients.

  12. Uremic toxins and lipases in haemodialysis: a process of repeated metabolic starvation.

    PubMed

    Stegmayr, Bernd

    2014-04-30

    Severe kidney disease results in retention of uremic toxins that inhibit key enzymes for lipid breakdown such as lipoprotein lipase (LPL) and hepatic lipase (HL). For patients in haemodialysis (HD) and peritoneal dialysis (PD) the LPL activity is only about half of that of age and gender matched controls. Angiopoietin, like protein 3 and 4, accumulate in the uremic patients. These factors, therefore, can be considered as uremic toxins. In animal experiments it has been shown that these factors inhibit the LPL activity. To avoid clotting of the dialysis circuit during HD, anticoagulation such as heparin or low molecular weight heparin are added to the patient. Such administration will cause a prompt release of the LPL and HL from its binding sites at the endothelial surface. The liver rapidly degrades the release plasma compound of LPL and HL. This results in a lack of enzyme to degrade triglycerides during the later part of the HD and for another 3-4 h. PD patients have a similar baseline level of lipases but are not exposed to the negative effect of anticoagulation.

  13. TBS Predict Coronary Artery Calcification in Adults

    PubMed Central

    Chuang, Tzyy-Ling; Hsiao, Fu-Tsung; Li, Yi-Da

    2016-01-01

    Purpose. This study analyzes the association between the bony microarchitecture score (trabecular bone score, TBS) and coronary artery calcification (CAC) in adults undergoing health exams. Materials and Methods. We retrospectively collected subjects (N = 81) who underwent coronary computed tomography and bone mineral density studies simultaneously. CAC was categorized to three levels (Group 0, G0, no CAC, score = 0, N = 45; Group 1, G1, moderate CAC, score = 1–100, N = 17; Group 2, G2, high CAC, score ≧ 101, N = 19). Multinomial logistic regression was used to study the association between TBS and CAC levels. Results. CAC is present in 44.4% of the population. Mean TBS ± SD was 1.399 ± 0.090. Per 1 SD increase in TBS, the unadjusted odds ratio (2.393) of moderate CAC compared with no CAC was significantly increased (95% CI, 1.219–4.696, p = 0.011). However, there has been no association of TBS with high CAC (OR: 1.026, 95% CI: 0.586–1.797, p = 0.928). These relationships also existed when individually adjusted for age, sex, and multiple other covariates. Conclusions. Higher TBS was related to moderate CAC, but not high CAC; a possible explanation may be that bone microarchitecture remodeling becomes more active when early coronary artery calcification occurs. However, further researches are needed to clarify this pathophysiology. PMID:27042671

  14. Mechanisms of ectopic calcification: implications for diabetic vasculopathy

    PubMed Central

    Fadini, Gian Paolo

    2015-01-01

    Vascular calcification (VC) is the deposition of calcium/phosphate in the vasculature, which portends a worse clinical outcome and predicts major adverse cardiovascular events. VC is an active process initiated and regulated via a variety of molecular signalling pathways. There are mainly two types of calcifications: the media VC and the intima VC. All major risk factors for cardiovascular disease (CVD) have been linked to the presence/development of VC. Besides the risk factors, a genetic component is also operative to determine arterial calcification. Several events take place before VC is established, including inflammation, trans-differentiation of vascular cells and homing of circulating pro-calcific cells. Diabetes is an important predisposing factor for VC. Compared with non-diabetic subjects, patients with diabetes show increased VC and higher expression of bone-related proteins in the medial layer of the vessels. In this review we will highlight the mechanisms underlying vascular calcification in diabetic patients. PMID:26543821

  15. 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

  16. ENPP1-Fc prevents mortality and vascular calcifications in rodent model of generalized arterial calcification of infancy

    PubMed Central

    Albright, Ronald A.; Stabach, Paul; Cao, Wenxiang; Kavanagh, Dillon; Mullen, Isabelle; Braddock, Alexander A.; Covo, Mariel S.; Tehan, Martin; Yang, Guangxiao; Cheng, Zhiliang; Bouchard, Keith; Yu, Zhao-Xue; Thorn, Stephanie; Wang, Xiangning; Folta-Stogniew, Ewa J.; Negrete, Alejandro; Sinusas, Albert J.; Shiloach, Joseph; Zubal, George; Madri, Joseph A.; De La Cruz, Enrique M.; Braddock, Demetrios T.

    2015-01-01

    Diseases of ectopic calcification of the vascular wall range from lethal orphan diseases such as generalized arterial calcification of infancy (GACI), to common diseases such as hardening of the arteries associated with aging and calciphylaxis of chronic kidney disease (CKD). GACI is a lethal orphan disease in which infants calcify the internal elastic lamina of their medium and large arteries and expire of cardiac failure as neonates, while calciphylaxis of CKD is a ubiquitous vascular calcification in patients with renal failure. Both disorders are characterized by vascular Mönckeburg's sclerosis accompanied by decreased concentrations of plasma inorganic pyrophosphate (PPi). Here we demonstrate that subcutaneous administration of an ENPP1-Fc fusion protein prevents the mortality, vascular calcifications and sequela of disease in animal models of GACI, and is accompanied by a complete clinical and biomarker response. Our findings have implications for the treatment of rare and common diseases of ectopic vascular calcification. PMID:26624227

  17. Functional Genomic Analysis Identifies Indoxyl Sulfate as a Major, Poorly Dialyzable Uremic Toxin in End-Stage Renal Disease

    PubMed Central

    Jhawar, Sachin; Singh, Prabhjot; Torres, Daniel; Ramirez-Valle, Francisco; Kassem, Hania; Banerjee, Trina; Dolgalev, Igor; Heguy, Adriana; Zavadil, Jiri; Lowenstein, Jerome

    2015-01-01

    Background Chronic renal failure is characterized by progressive renal scarring and accelerated arteriosclerotic cardiovascular disease despite what is considered to be adequate hemodialysis or peritoneal dialysis. In rodents with reduced renal mass, renal scarring has been attributed to poorly filtered, small protein-bound molecules. The best studied of these is indoxyl sulfate (IS). Methods We have attempted to establish whether there are uremic toxins that are not effectively removed by hemodialysis. We examined plasma from patients undergoing hemodialysis, employing global gene expression in normal human renal cortical cells incubated in pre- and post- dialysis plasma as a reporter system. Responses in cells incubated with pre- and post-dialysis uremic plasma (n = 10) were compared with responses elicited by plasma from control subjects (n = 5). The effects of adding IS to control plasma and of adding probenecid to uremic plasma were examined. Plasma concentrations of IS were measured by HPLC (high pressure liquid chromatography). Results Gene expression in our reporter system revealed dysregulation of 1912 genes in cells incubated with pre-dialysis uremic plasma. In cells incubated in post-dialysis plasma, the expression of 537 of those genes returned to baseline but the majority of them (1375) remained dysregulated. IS concentration was markedly elevated in pre- and post-dialysis plasma. Addition of IS to control plasma simulated more than 80% of the effects of uremic plasma on gene expression; the addition of probenecid, an organic anion transport (OAT) inhibitor, to uremic plasma reversed the changes in gene expression. Conclusion These findings provide evidence that hemodialysis fails to effectively clear one or more solutes that effect gene expression, in our reporter system, from the plasma of patients with uremia. The finding that gene dysregulation was simulated by the addition of IS to control plasma and inhibited by addition of an OAT inhibitor to

  18. Aortic calcification produced by vitamin D3 plus nicotine.

    PubMed

    Niederhoffer, N; Bobryshev, Y V; Lartaud-Idjouadiene, I; Giummelly, P; Atkinson, J

    1997-01-01

    Calcification of the elastic arteries of the young rat by treatment with vitamin D and nicotine (VDN) has been proposed as an animal model of arterial calcification associated with age and age-related vascular pathology in man. The calcium-binding protein, S-100, which is found in human atherosclerotic lesions was associated with medial calcification of the aorta in VDN rats, especially in cases of severe calcification. Calcification (total calcium content: 366 +/- 87, n = 12 in VDN vs. 24 +/- 2 micromol g(-1) aortic dry weight in controls, n = 13) involved elastocalcinosis leading to elastolysis as revealed by a fall in the amount of desmosine and isodesmosine in the aortic wall (266 +/- 17 and 254 +/- 15 in VDN vs. 655 +/- 56 and 588 +/- 30 microg g(-1) aortic dry weight in controls). The decrease in elastin was associated with an increase in the stiffness of the aortic wall (elastic modulus: 15.1 +/- 1.8 in VDN vs. 6.7 +/- 0.5 10(6) dyn cm(-2) in controls), an increase in end-systolic stress (central systolic aortic pressure: 152 +/- 6 in VDN vs. 136 +/- 2 mm Hg in controls) (at a normotensive mean pressure level) and left ventricular hypertrophy (heart weight/body weight 2.51 +/- 0.10 in VDN vs. 2.24 +/- 0.07 g kg(-1) in controls). In conclusion, the mechanisms and consequences of aortic calcification in VDN show several similarities with calcification occurring in human athero- and arteriosclerosis.

  19. Observer study to evaluate the simulation of mammographic calcification clusters

    NASA Astrophysics Data System (ADS)

    Sousa, Maria A. Z.; Marcomini, Karem D.; Bakic, Predrag R.; Maidment, Andrew D. A.; Schiabel, Homero

    2016-03-01

    Numerous breast phantoms have been developed to be as realistic as possible to ensure the accuracy of image quality analysis, covering a greater range of applications. In this study, we simulated three different densities of the breast parenchyma using paraffin gel, acrylic plates and PVC films. Hydroxyapatite was used to simulate calcification clusters. From the images acquired with a GE Senographe DR 2000D mammography system, we selected 68 regions of interest (ROIs) with and 68 without a simulated calcification cluster. To validate the phantom simulation, we selected 136 ROIs from the University of South Florida's Digital Database for Screening Mammography (DDSM). Seven trained observers performed two observer experiments by using a high-resolution monitor Barco mod. E-3620. In the first experiment, the observers had to distinguish between real or phantom ROIs (with and without calcification). In the second one, the observers had to indicate the ROI with calcifications between a pair of ROIs. Results from our study show that the hydroxyapatite calcifications had poor contrast in the simulated breast parenchyma, thus observers had more difficulty in identifying the presence of calcification clusters in phantom images. Preliminary analysis of the power spectrum was conducted to investigate the radiographic density and the contrast thresholds for calcification detection. The values obtained for the power spectrum exponent (β) were comparable with those found in the literature.

  20. In-vitro calcification study of polyurethane heart valves.

    PubMed

    Boloori Zadeh, Parnian; Corbett, Scott C; Nayeb-Hashemi, Hamid

    2014-02-01

    Tri-leaflet polyurethane heart valves have been considered as a potential candidate in heart valve replacement surgeries. In this study, polyurethane (Angioflex(®)) heart valve prostheses were fabricated using a solvent-casting method to evaluate their calcification resistance. These valves were subjected to accelerated life testing (continuous opening and closing of the leaflets) in a synthetic calcification solution. Results showed that Angioflex(®) could be considered as a potential material for fabricating prosthetic heart valves with possibly a higher calcification resistance compared to tissue valves. In addition, calcification resistance of bisphosphonate-modified Angioflex(®) valves was also evaluated. Bisphosphonates are considered to enhance the calcification resistance of polymers once covalently bonded to the bulk of the material. However, our in-vitro results showed that bisphosphonate-modified Angioflex(®) valves did not improve the calcification resistance of Angioflex(®) compared to its untreated counterparts. The results also showed that cyclic loading of the valves' leaflets resulted in formation of numerous cracks on the calcified surface, which were not present when calcification study did not involve mechanical loading. Further study of these cracks did not result in enough evidence to conclude whether these cracks have penetrated to the polymeric surface.

  1. Preliminary Study on Composition and Microstructure of Calcification in Craniopharyngiomas

    PubMed Central

    Peng, Junxiang; Qi, Songtao; Pan, Jun; Zhang, Xi’an; Huang, Guanglong; Li, Danling

    2016-01-01

    Abstract To analyze the element composition and microstructure of calcification in craniopharyngiomas and to explore the differences among differing degrees of calcification, 50 consecutive patients with craniopharyngioma were selected. X-ray diffraction analysis and energy-dispersive X-ray spectroscopy analysis were performed on the calcified plaques isolated from the tumor specimens. All calcified plaques were constituted of hydroxyapatite crystals and some amorphous materials. The main elements for the analysis were calcium, phosphate, carbon, and oxygen. There were significant differences among groups of differing degrees of calcification in the percentage composition of calcium, phosphorus, and carbon (P < 0.05), in which the element content of calcium and phosphorus had a positive correlation with the extent of calcification (rp = 0.745 and 0.778, respectively, P < 0.01), while the element content of carbon had a negative correlation with the extent of calcification (rp =−0.526, P <0.01). The calcium, phosphorus, and carbon content are different in calcified plaques with different extents of calcification. The element content of calcium, phosphorus, and carbon influences the degree of calcification. PMID:27213742

  2. [Vascular Calcification - Pathological Mechanism and Clinical Application - . Role of vascular smooth muscle cells in vascular calcification].

    PubMed

    Kurabayashi, Masahiko

    2015-05-01

    Vascular calcification is commonly seen with aging, chronic kidney disese (CKD), diabetes, and atherosclerosis, and is closely associated with cardiovascular morbidity and mortality. Vascular calcification has long been regarded as the final stage of degeneration and necrosis of arterial wall and a passive, unregulated process. However, it is now known to be an active and tightly regulated process involved with phenotypic transition of vascular smooth muscle cells (VSMC) that resembles bone mineralization. Briefly, calcium deposits of atherosclerotic plaque consist of hydroxyapatite and may appear identical to fully formed lamellar bone. By using a genetic fate mapping strategy, VSMC of the vascular media give rise to the majority of the osteochondrogenic precursor- and chondrocyte-like cells observed in the calcified arterial media of MGP (- / -) mice. Osteogenic differentiation of VSMC is characterized by the expression of bone-related molecules including bone morphogenetic protein (BMP) -2, Msx2 and osteopontin, which are produced by osteoblasts and chondrocytes. Our recent findings are that (i) Runx2 and Notch1 induce osteogenic differentiation, and (ii) advanced glycation end-product (AGE) /receptor for AGE (RAGE) and palmitic acid promote osteogenic differentiation of VSMC. To understand of the molecular mechanisms of vascular calcification is now under intensive research area. PMID:25926569

  3. [Vascular Calcification - Pathological Mechanism and Clinical Application - . Role of vascular smooth muscle cells in vascular calcification].

    PubMed

    Kurabayashi, Masahiko

    2015-05-01

    Vascular calcification is commonly seen with aging, chronic kidney disese (CKD), diabetes, and atherosclerosis, and is closely associated with cardiovascular morbidity and mortality. Vascular calcification has long been regarded as the final stage of degeneration and necrosis of arterial wall and a passive, unregulated process. However, it is now known to be an active and tightly regulated process involved with phenotypic transition of vascular smooth muscle cells (VSMC) that resembles bone mineralization. Briefly, calcium deposits of atherosclerotic plaque consist of hydroxyapatite and may appear identical to fully formed lamellar bone. By using a genetic fate mapping strategy, VSMC of the vascular media give rise to the majority of the osteochondrogenic precursor- and chondrocyte-like cells observed in the calcified arterial media of MGP (- / -) mice. Osteogenic differentiation of VSMC is characterized by the expression of bone-related molecules including bone morphogenetic protein (BMP) -2, Msx2 and osteopontin, which are produced by osteoblasts and chondrocytes. Our recent findings are that (i) Runx2 and Notch1 induce osteogenic differentiation, and (ii) advanced glycation end-product (AGE) /receptor for AGE (RAGE) and palmitic acid promote osteogenic differentiation of VSMC. To understand of the molecular mechanisms of vascular calcification is now under intensive research area.

  4. Humoral inhibitors of the immune response in uremia. V. Induction of suppressor cells in vitro by uremic serum.

    PubMed Central

    Raskova, J.; Raska, K.

    1983-01-01

    The mechanism of inhibition of mixed lymphocyte reaction (MLR) by serum of chronically uremic rats has been studied. The inhibitory activity of the serum has been associated with a discrete subset of very low density lipoproteins (VLDL) of Sf 100-400. The degree of the inhibitory activity of uremic serum correlates with the severity of uremia. Spleen cells from normal rats incubated for 20 hours with uremic serum or its VLDL fraction suppress the response of control syngeneic cells in the MLR. Induction of such suppressor activity does not require cell proliferation because it is not inhibited by mitomycin C. although the exact identity of the induced suppressor cells has not been established, they may be macrophages. The suppressor activity of induced spleen cells can be markedly reduced by filtration of spleen cells on glass wool or on nylon wool columns. Reconstruction experiments show that the adherent cell fraction of spleen cells exposed to uremic serum suppresses the response of the nonadherent fraction of control spleen cells. These results indicate that the immunosuppressive effects of rat uremic serum in vitro involve the induction of suppressor cells. PMID:6221666

  5. Effects of Uremic Toxins on Transport and Metabolism of Different Biopharmaceutics Drug Disposition Classification System (BDDCS) Xenobiotics

    PubMed Central

    Reyes, Maribel; Benet, Leslie Z.

    2013-01-01

    Chronic kidney disease (CKD) is recognized to cause pharmacokinetic changes in renally excreted drugs; however, pharmacokinetic changes are also reported for drugs that are non-renally eliminated. Few studies have investigated how uremic toxins may affect drug transporters and metabolizing enzymes and how these may result in pharmacokinetic/metabolic changes in CKD. Here, we investigated the effects of uremic toxins and human uremic serum on the transport of the prototypical transporter substrate [3H]-estrone sulfate and three BDDCS drugs, propranolol, losartan, and eprosartan. We observed a significant decrease in [3H]-estrone sulfate, losartan, and eprosartan uptake with some uremic toxins in both transfected cells and rat hepatocytes. The uptake of losartan was decreased in rat and human hepatocytes (28%, and 48% respectively) in the presence of hemodialysis (HD) serum. Time-course studies of losartan showed a 27%, 65% and 68% increase in AUC in the presence of HD serum, rifampin, and sulfaphenazole respectively. Intracellular losartan AUC decreased significantly in the treatment groups and the metabolite AUC decreased by 41% and 26% in rifampin and sulfaphenazole treated group. The intracellular AUC of eprosartan increased 190% in the presence of HD serum. These studies indicate that the uremic toxins contained in HD serum play an important role in drug disposition through drug transporters, and that there would be differential effects depending on the BDDCS classification of the drug. PMID:21618544

  6. Calcification of in vitro developed hypertrophic cartilage

    SciTech Connect

    Tacchetti, C.; Quarto, R.; Campanile, G.; Cancedda, R.

    1989-04-01

    We have recently reported that dedifferentiated cells derived from stage 28-30 chick embryo tibiae, when transferred in suspension culture in the presence of ascorbic acid, develop in a tissue closely resembling hypertrophic cartilage. Ultrastructural examination of this in vitro formed cartilage showed numerous matrix vesicles associated with the extracellular matrix. In the present article we report that the in vitro developed hypertrophic cartilage undergoes calcification. We indicate a correlation between the levels of alkaline phosphatase activity and calcium deposition at different times of development. Following the transfer of cells into suspension culture and an initial lag phase, the level of alkaline phosphatase activity rapidly increased. In most experiments the maximum of activity was reached after 5 days of culture. When alkaline phosphatase activity and /sup 45/Ca deposition were measured in the same experiment, we observed that the increase in alkaline phosphatase preceded the deposition of nonwashable calcium deposits in the cartilage.

  7. Intracranial Artery Calcification and Its Clinical Significance

    PubMed Central

    Wu, Xiao Hong; Wang, Li Juan; Wong, Ka Sing

    2016-01-01

    Intracranial arterial calcification (IAC) is an easily identifiable entity on plain head computed tomography scans. Recent studies have found high prevalence rates for IAC worldwide, and this may be associated with ischemic stroke and cognitive decline. Aging, traditional cardiovascular risk factors, and chronic kidney disease have been found to be associated with IAC. The severity of IAC can be assessed using different visual grading scales or various quantitative methods (by measuring volume or intensity). An objective method for assessing IAC using consistent criteria is urgently required to facilitate comparisons between multiple studies involving diverse populations. There is accumulating evidence from clinical studies that IAC could be utilized as an indicator of intracranial atherosclerosis. However, the pathophysiology underlying the potential correlation between IAC and ischemic stroke—through direct arterial stenosis or plaque stability—remains to be determined. More well-designed clinical studies are needed to explore the predictive values of IAC in vascular events and the underlying pathophysiological mechanisms. PMID:27165425

  8. Calcification of multipotent prostate tumor endothelium.

    PubMed

    Dudley, Andrew C; Khan, Zia A; Shih, Shou-Ching; Kang, Soo-Young; Zwaans, Bernadette M M; Bischoff, Joyce; Klagsbrun, Michael

    2008-09-01

    Solid tumors require new blood vessels for growth and metastasis, yet the biology of tumor-specific endothelial cells is poorly understood. We have isolated tumor endothelial cells from mice that spontaneously develop prostate tumors. Clonal populations of tumor endothelial cells expressed hematopoietic and mesenchymal stem cell markers and differentiated to form cartilage- and bone-like tissues. Chondrogenic differentiation was accompanied by an upregulation of cartilage-specific col2a1 and sox9, whereas osteocalcin and the metastasis marker osteopontin were upregulated during osteogenic differentiation. In human and mouse prostate tumors, ectopic vascular calcification was predominately luminal and colocalized with the endothelial marker CD31. Thus, prostate tumor endothelial cells are atypically multipotent and can undergo a mesenchymal-like transition.

  9. Pathological calcifications studied with micro-CT

    NASA Astrophysics Data System (ADS)

    Stock, Stuart R.; Rajamannan, Nalini M.; Brooks, Ellen R.; Langman, Craig B.; Pachman, Lauren M.

    2004-10-01

    The microstructure of pathological biomineral deposits has received relatively little attention, perhaps, in part because of the difficulty preparing samples for microscopy. MicroCT avoids these difficulties, and laboratory microCT results are reviewed for aortic valve calcification (human as well as a rabbit model), for human renal calculi (stones) and for calcinoses formed in juvenile dermatomyositis (JDM). In calcified aortic valves of rabbits, numerical analysis of the data shows statistically significant correlation with diet. In a large kidney stone the pattern of mineralization is clearly revealed and may provide a temporal blueprint for stone growth. In JDM calcified deposits, very different microstructures are observed and may be related to processes unique to this disease.

  10. Pineal and habenula calcification in schizophrenia.

    PubMed

    Sandyk, R

    1992-01-01

    Animal data indicate that melatonin secretion is stimulated by the paraventricular nucleus (PVN) of the hypothalamus and that lesions of the PVN mimic the endocrine effects of pinealectomy. Since the PVN lies adjacent to the third ventricle, I propose that periventricular damage, which is found in schizophrenia and may account for the third ventricular dilatation seen on computed tomographic (CT), may disrupt PVN-pineal interactions and ultimately enhance the process of pineal calcification (PC). To investigate this hypothesis, I conducted CT study on the relationship of PC size to third ventricular width (TVW) in 12 chronic schizophrenic patients (mean age: 33.7 years; SD = 7.3). For comparison, I also studied the relationship of PC size to the ventricular brain ratio and prefrontal cortical atrophy. As predicted, there was a significant correlation between PC size and TVW (r pbi = .61, p < .05), whereas PC was unrelated to the control neuroradiological measures. The findings support the hypothesis that periventricular damage may be involved in the process of PC in schizophrenia and may indirectly implicate damage to the PVN in the mechanisms underlying dysfunction of the pineal gland in schizophrenia. In a second study, I investigated the prevalence of habenular calcification (HAC) on CT in a cohort of 23 chronic schizophrenic-patients (mean age: 31.2 years; SD = 5.95). In this sample HAC was present in 20 patients (87%). Since the prevalence of HAC in a control population of similar age is only 15% these data reveal an almost 6-fold higher prevalence of HAC (X2 = 84.01, p < .0001) in chronic schizophrenia as compared to normal controls. The implications of HAC for the pathophysiology of schizophrenia are discussed in light of the central role of the habenula in the regulation of limbic functions.

  11. Pineal and habenula calcification in schizophrenia.

    PubMed

    Sandyk, R

    1992-01-01

    Animal data indicate that melatonin secretion is stimulated by the paraventricular nucleus (PVN) of the hypothalamus and that lesions of the PVN mimic the endocrine effects of pinealectomy. Since the PVN lies adjacent to the third ventricle, I propose that periventricular damage, which is found in schizophrenia and may account for the third ventricular dilatation seen on computed tomographic (CT), may disrupt PVN-pineal interactions and ultimately enhance the process of pineal calcification (PC). To investigate this hypothesis, I conducted CT study on the relationship of PC size to third ventricular width (TVW) in 12 chronic schizophrenic patients (mean age: 33.7 years; SD = 7.3). For comparison, I also studied the relationship of PC size to the ventricular brain ratio and prefrontal cortical atrophy. As predicted, there was a significant correlation between PC size and TVW (r pbi = .61, p < .05), whereas PC was unrelated to the control neuroradiological measures. The findings support the hypothesis that periventricular damage may be involved in the process of PC in schizophrenia and may indirectly implicate damage to the PVN in the mechanisms underlying dysfunction of the pineal gland in schizophrenia. In a second study, I investigated the prevalence of habenular calcification (HAC) on CT in a cohort of 23 chronic schizophrenic-patients (mean age: 31.2 years; SD = 5.95). In this sample HAC was present in 20 patients (87%). Since the prevalence of HAC in a control population of similar age is only 15% these data reveal an almost 6-fold higher prevalence of HAC (X2 = 84.01, p < .0001) in chronic schizophrenia as compared to normal controls. The implications of HAC for the pathophysiology of schizophrenia are discussed in light of the central role of the habenula in the regulation of limbic functions. PMID:1305634

  12. Screening of Cyanobacterial Species for Calcification

    SciTech Connect

    Brady D. Lee; William A. Apel; Michelle R. Walton

    2004-07-01

    Species of cyanobacteria in the genera Synechococcus and Synechocystis are known to be the catalysts of a phenomenon called "whitings", which is the formation and precipitation of fine-grained CaCO3 particles. Whitings occur when the cyanobacteria fix atmospheric CO2 through the formation of CaCO3 on their cell surfaces, which leads to precipitation to the ocean floor and subsequent entombment in mud. Whitings represent one potential mechanism for CO2 sequestration. Research was performed to determine the ability of various strains of Synechocystis and Synechococcus to calcify when grown in microcosms amended with 2.5 mM HCO3- and 3.4 mM Ca2+. Results indicated that although all strains tested have the ability to calcify, only two Synechococcus species, strains PCC 8806 and PCC 8807, were able to calcify to the extent that a CaCO3 precipitate was formed. Enumeration of the cyanobacterial cultures during testing indicated that cell density did not appear to have a direct effect on calcification. Factors that had the greatest effect on calcification were CO2 removal and subsequent generation of alkaline pH. Whereas cell density was similar for all strains tested, differences in maximum pH were demonstrated. As CO2 was removed, growth medium pH increased and soluble Ca2+ was removed from solution. The largest increases in growth medium pH occurred when CO2 levels dropped below 400 ppmv. Research presented demonstrates that, under the conditions tested, many species of cyanobacteria in the genera Synechocystis and Synechococcus are able to calcify but only two species of Synechococcus were able to calcify to an extent that led to the precipitation of calcium carbonate.

  13. Idiopathic calcification of the seminal vesicles: a rare cause for prostate cancer overstaging.

    PubMed

    Pannek, J; Senge, T

    2001-01-01

    Calcification of the seminal vesicles is a rare phenomenon. We present 2 cases in whom calcification of the seminal vesicles led to preoperative overstaging of prostate cancer. Although idiopathic calcifications are extremely rare, calcifications appear more frequently in diabetic patients. Therefore, knowledge of these formations is essential to prevent overstaging, namely infiltration of the seminal vesicles.

  14. Soft-tissue calcification after subcutaneus emphysema in a neonate

    SciTech Connect

    Naidech, H.J.; Chawla, H.S.

    1982-08-01

    Bilateral, almost symmetric, calcifications of the soft tissues after subcutaneous emphysema have not, to our knowledge, been described. Because of the close clinical and radiographic evaluation in our case, the finding of calcinosis was not a diagnostic problem. Several 1.5 mm computed tomographic (CT) sections of the thorax were scanned and they were confirmatory in showing the distribution of the calcifications. Since subcutaneous emphysema is commonplace, and calcification after it is apparently unknown, the literature was reviewed and an additional cause of soft-tissue calcinosis is presented.

  15. Role of Gut-Derived Protein-Bound Uremic Toxins in Cardiorenal Syndrome and Potential Treatment Modalities.

    PubMed

    Lekawanvijit, Suree

    2015-01-01

    Uremic toxins have been increasingly recognized as a crucial missing link in the cardiorenal syndrome. Advances in dialysis technologies have contributed to an enormous improvement in uremic toxin removal, but removal of protein-bound uremic toxins (PBUTs) by current conventional dialysis remains problematic because of their protein-binding capacity. Most PBUTs that have been implicated in cardiorenal toxicity have been demonstrated to be derived from a colonic microbiota metabolism pathway using dietary amino acids as a substrate. Currently, indoxyl sulfate and p-cresyl sulfate are the most extensively investigated gut-derived PBUTs. Strong evidence of adverse clinical outcomes, as well as biological toxicity on the kidney and cardiovascular system attributable to these toxins, has been increasingly reported. Regarding their site of origin, the colon has become a potential target for treatment of cardiorenal syndrome induced by gut-derived PBUTs.

  16. Genetics Home Reference: generalized arterial calcification of infancy

    MedlinePlus

    ... It is characterized by abnormal accumulation of the mineral calcium (calcification) in the walls of the blood ... characterized by the accumulation of calcium and other minerals (mineralization) in elastic fibers, which are a component ...

  17. Genetics Home Reference: familial idiopathic basal ganglia calcification

    MedlinePlus

    ... in regulating phosphate levels within the body (phosphate homeostasis) by transporting phosphate across cell membranes. The SLC20A2 ... link familial idiopathic basal ganglia calcification with phosphate homeostasis. Nat Genet. 2012 Feb 12;44(3):254- ...

  18. Calcification of vestibular schwannoma: a case report and literature review.

    PubMed

    Zhang, Yang; Yu, Jinlu; Qu, Limei; Li, Yunqian

    2012-10-02

    Calcification rarely occurs in vestibular schwannoma (VS), and only seven cases of calcified VS have been reported in the literature. Here, we report a 48-year-old man with VS, who had a history of progressive left-sided hearing loss for 3 years. Neurological examination revealed that he had left-sided hearing loss and left cerebellar ataxia. Magnetic resonance imaging and computerized tomography angiography showed a mass with calcification in the left cerebellopontine angle (CPA). The tumor was successfully removed via suboccipital craniotomy, and postoperative histopathology showed that the tumor was a schwannoma. We reviewed seven cases of calcified VS that were previously reported in the literature, and we analyzed and summarized the characteristics of these tumors, including the calcification, texture, and blood supply. We conclude that calcification in VS is associated with its texture and blood supply, and these characteristics affect the surgical removal of the tumor.

  19. Placental calcification: ultrastructural and X-ray microanalytic studies.

    PubMed

    Varma, V A; Kim, K M

    1985-01-01

    Calcification is common in human placentas and is widely recognized as a normal part of maturation and aging of this organ. Eleven human placentas were studied by light and electron microscopy to elucidate the mechanism of placental calcification. Earliest mineral deposits were seen along the trophoblastic basement membrane of the chorionic villi undergoing fibrinoid degeneration. Transmission electron microscopic examination revealed crystalline deposits within small membrane-bound vesicles; the latter appear to be derived from degenerating cells and were particularly numerous within the basement membrane. X-ray microanalysis of these deposits revealed calcium and phosphorus peaks and the pattern of calcium hydroxyapatite was noted by electron diffraction. This pattern of calcification, i.e., precipitation of calcium hydroxyapatite in association with extracellular membrane bound vesicles, is similar to that seen in physiologic and pathologic calcifications of other tissues.

  20. [Calcifications of the prostate: a transrectal echographic study].

    PubMed

    Bock, E; Calugi, V; Stolfi, V; Rossi, P; D'Ascenzo, R; Solivetti, F M

    1989-05-01

    Prostatic lithiasis is a well know phenomenon. It has little clinical significance and is not easily shown by conventional radiography, which has poor sensitivity and specificity. The authors have studied 612 patients with both suprapubic and transrectal US in order to 1) assess US sensitivity and specificity and 2) report the frequency, spatial distribution, number and features of prostatic calcifications with special emphasis on differential diagnosis between prostatic neoplasms and chronic prostatitis. The authors have also studied the relationship between morphology and symptoms and the results agree with those reported in the scanty literature. The authors conclude that the parameters studied are directly related to age, except for a younger group with clear evidence of genital inflammation. The authors emphasize the impossibility to correlate morphology of prostatic calcifications with pathologic conditions: there are no specific symptoms clearly connected with calcification even though the inflammation is often associated with calcifications.

  1. Calcification generates protons for nutrient and bicarbonate uptake

    NASA Astrophysics Data System (ADS)

    McConnaughey, T. A.; Whelan, J. F.

    1997-03-01

    The biosphere's great carbonate deposits, from caliche soils to deep-sea carbonate oozes, precipitate largely as by-products of autotrophic nutrient acquisition physiologies. Protons constitute the critical link: Calcification generates protons, which plants and photosynthetic symbioses use to assimilate bicarbonate and nutrients. A calcium ATPase-based "trans" mechanism underlies most biological calcification. This permits high calcium carbonate supersaturations and rapid carbonate precipitation. The competitive advantages of calcification become especially apparent in light and nutrient-deficient alkaline environments. Calcareous plants often dominate the lower euphotic zone in both the benthos and the plankton. Geographically and seasonally, massive calcification concentrates in nutrient-deficient environments including alkaline soils, coral reefs, cyanobacterial mats and coccolithophorid blooms. Structural and defensive uses for calcareous skeletons are sometimes overrated.

  2. Case report of atypical hemolytic uremic syndrome with retinal arterial and venous occlusion treated with eculizumab

    PubMed Central

    Greenwood, Gregory T

    2015-01-01

    Atypical hemolytic uremic syndrome (aHUS) is a rare disease caused by chronic, uncontrolled activation of the alternative complement pathway, leading to thrombotic microangiopathy. Renal impairment and progression to end-stage renal disease are common in untreated patients with aHUS, and extrarenal manifestations are being increasingly characterized in the literature. Ocular involvement remains rare in aHUS. This report describes a patient with aHUS with bilateral central retinal artery and vein occlusion, vitreous hemorrhage, and blindness in addition to renal impairment. The patient’s hematologic and renal parameters and ocular manifestation improved following initiation of eculizumab therapy. PMID:26508891

  3. Advances in the pathogenesis, diagnosis and treatment of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome.

    PubMed

    Franchini, Massimo; Zaffanello, Marco; Veneri, Dino

    2006-01-01

    The thrombotic microangiopathies are microvascular occlusive disorders characterized by hemolytic anemia caused by fragmentation of erythrocytes and thrombocytopenia due to increased platelet aggregation and thrombus formation, eventually leading to disturbed microcirculation with reduced organ perfusion. Depending on whether brain or renal lesions prevail, two different entities have been described: thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). However, not rarely the clinical distinctions between these two conditions remain questionable. Recent studies have contributed greatly to our current understanding of the molecular mechanisms leading to TTP and HUS. In this review, we briefly focus on the most important advances in the pathophysiology, diagnosis and treatment of these two thrombotic microangiopathies.

  4. Complement contributes to the pathogenesis of Shiga toxin-associated hemolytic uremic syndrome.

    PubMed

    Karpman, Diana; Tati, Ramesh

    2016-10-01

    Complement is activated during Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS). There is evidence of complement activation via the alternative pathway in STEC-HUS patients as well as from in vivo and in vitro models. Ozaki et al. demonstrate activation of the mannose-binding lectin (MBL) pathway in Shiga toxin-treated mice expressing human MBL2, but lacking murine Mbls. Treatment with anti-human MBL2 antibody was protective, suggesting that MBL pathway activation also contributes to Shiga toxin-mediated renal injury. PMID:27633864

  5. Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome

    PubMed Central

    Miller, Elizabeth C.; Liszewski, M. Kathryn; Strain, Lisa; Blouin, Jacques; Brown, Alison L.; Moghal, Nadeem; Kaplan, Bernard S.; Weiss, Robert A.; Lhotta, Karl; Kapur, Gaurav; Mattoo, Tej; Nivet, Hubert; Wong, William; Gie, Sophie; de Ligny, Bruno Hurault; Fischbach, Michel; Gupta, Ritu; Hauhart, Richard; Meunier, Vincent; Loirat, Chantal; Dragon-Durey, Marie-Agnès; Fridman, Wolf H.; Janssen, Bert J. C.

    2008-01-01

    Atypical hemolytic uremic syndrome (aHUS) is a disease of complement dysregulation. In approximately 50% of patients, mutations have been described in the genes encoding the complement regulators factor H, MCP, and factor I or the activator factor B. We report here mutations in the central component of the complement cascade, C3, in association with aHUS. We describe 9 novel C3 mutations in 14 aHUS patients with a persistently low serum C3 level. We have demonstrated that 5 of these mutations are gain-of-function and 2 are inactivating. This establishes C3 as a susceptibility factor for aHUS. PMID:18796626

  6. Atypical haemolytic uremic syndrome complicated by microangiopathic antiphospholipid-associated syndrome.

    PubMed

    Meglic, A; Grosek, S; Benedik-Dolnicar, M; Avcin, T

    2008-09-01

    A 4-year-old boy with an atypical course of haemolytic uremic syndrome (HUS), who developed microangiopathic antiphospholipid-associated syndrome (MAPS) with signs of multiple organ failure during the course of his disease, is reported. Early and aggressive treatment with intravenous gammaglobulin, pulse methylprednisolone and plasmapheresis resulted in an excellent clinical recovery. Our patient showed a concomitant presence of multiple factors that could precipitate atypical HUS, including positive antiphospholipid antibodies, decreased level of factor H and positive anti-ADAMTS-13 antibodies. We suggest that, along with infections, autoimmune conditions or defined genetic abnormalities of complement regulatory genes, MAPS should be considered among the pathogenic mechanisms in patients with atypical HUS.

  7. A Review of the Effect of Diet on Cardiovascular Calcification

    PubMed Central

    Nicoll, Rachel; Howard, John McLaren; Henein, Michael Y.

    2015-01-01

    Cardiovascular (CV) calcification is known as sub-clinical atherosclerosis and is recognised as a predictor of CV events and mortality. As yet there is no treatment for CV calcification and conventional CV risk factors are not consistently correlated, leaving clinicians uncertain as to optimum management for these patients. For this reason, a review of studies investigating diet and serum levels of macro- and micronutrients was carried out. Although there were few human studies of macronutrients, nevertheless transfats and simple sugars should be avoided, while long chain ω-3 fats from oily fish may be protective. Among the micronutrients, an intake of 800 μg/day calcium was beneficial in those without renal disease or hyperparathyroidism, while inorganic phosphorus from food preservatives and colas may induce calcification. A high intake of magnesium (≥380 mg/day) and phylloquinone (500 μg/day) proved protective, as did a serum 25(OH)D concentration of ≥75 nmol/L. Although oxidative damage appears to be a cause of CV calcification, the antioxidant vitamins proved to be largely ineffective, while supplementation of α-tocopherol may induce calcification. Nevertheless other antioxidant compounds (epigallocatechin gallate from green tea and resveratrol from red wine) were protective. Finally, a homocysteine concentration >12 µmol/L was predictive of CV calcification, although a plasma folate concentration of >39.4 nmol/L could both lower homocysteine and protect against calcification. In terms of a dietary programme, these recommendations indicate avoiding sugar and the transfats and preservatives found in processed foods and drinks and adopting a diet high in oily fish and vegetables. The micronutrients magnesium and vitamin K may be worthy of further investigation as a treatment option for CV calcification. PMID:25906474

  8. [Neuroimaging findings in cerebroretinal microangiopathy with calcifications and cysts].

    PubMed

    Herrera, Diego Alberto; Vargas, Sergio Alberto; Montoya, Claudia

    2014-01-01

    Cerebroretinal microangiopathy with calcifications and cysts is a rare condition characterized by brain, retinal and bone anomalies, as well as a predisposition to gastrointestinal bleeding. There are few reported cases of this condition in adults, among whom the incidence is low. Neuroimaging findings are characteristic, with bilateral calcifications, leukoencephalopathy and intracranial cysts. The purpose of this article was to do a literature survey and illustrate two cases diagnosed with the aid of neuroimaging. PMID:24967922

  9. Dense calcification in a GH-secreting pituitary macroadenoma

    PubMed Central

    Ibrahim, Ramez; Kalhan, Atul; Lammie, Alistair; Kotonya, Christine; Nannapanenni, Ravindra; Rees, Aled

    2014-01-01

    Summary A 30-year-old female presented with a history of secondary amenorrhoea, acromegalic features and progressive visual deterioration. She had elevated serum IGF1 levels and unsuppressed GH levels after an oral glucose tolerance test. Magnetic resonance imaging revealed a heterogeneously enhancing space-occupying lesion with atypical extensive calcification within the sellar and suprasellar areas. Owing to the extent of calcification, the tumour was a surgical challenge. Postoperatively, there was clinical, radiological and biochemical evidence of residual disease, which required treatment with a somatostatin analogue and radiotherapy. Mutational analysis of the aryl hydrocarbon receptor-interacting protein (AIP) gene was negative. This case confirms the relatively rare occurrence of calcification within a pituitary macroadenoma and its associated management problems. The presentation, biochemical, radiological and pathological findings are discussed in the context of the relevant literature. Learning points Calcification of pituitary tumours is relatively rare.Recognising calcification in pituitary adenomas on preoperative imaging is important in surgical decision-making.Gross total resection can be difficult to achieve in the presence of extensive calcification and dictates further management and follow-up to achieve disease control. PMID:24683483

  10. Computed tomography study of pineal calcification in schizophrenia.

    PubMed

    Bersani, G; Garavini, A; Taddei, I; Tanfani, G; Nordio, M; Pancheri, P

    1999-06-01

    Computed tomography studies concerning pineal calcification (PC) in schizophrenia have been conducted mainly by one author who correlated this calcification with several aspects of the illness. On the basis of these findings the aim of the present study was to analyze size and incidence of pineal gland calcification by CT in schizophrenics and healthy controls, and to verify the relationship between pineal calcification and age, and the possible correlation with psychopathologic variables. Pineal calcification was measured on CT scans of 87 schizophrenics and 46 controls divided into seven age subgroups of five years each. No significant differences in PC incidence and mean size between patients and controls were observed as far as the entire group was considered. PC size correlated with age both in schizophrenics and controls. We found a higher incidence of PC in schizophrenics in the age subgroup of 21-25 years, and a negative correlation with positive symptoms of schizophrenia in the overall group. These findings could suggest a premature calcific process in schizophrenics and a probable association with 'non-paranoid' aspects of the illness. Nevertheless the potential role of this process possibly related to some aspects of the altered neurodevelopment in schizophrenia is still unclear. PMID:10572342

  11. Ocean acidification reduces growth and calcification in a marine dinoflagellate.

    PubMed

    Van de Waal, Dedmer B; John, Uwe; Ziveri, Patrizia; Reichart, Gert-Jan; Hoins, Mirja; Sluijs, Appy; Rost, Björn

    2013-01-01

    Ocean acidification is considered a major threat to marine ecosystems and may particularly affect calcifying organisms such as corals, foraminifera and coccolithophores. Here we investigate the impact of elevated pCO2 and lowered pH on growth and calcification in the common calcareous dinoflagellate Thoracosphaera heimii. We observe a substantial reduction in growth rate, calcification and cyst stability of T. heimii under elevated pCO2. Furthermore, transcriptomic analyses reveal CO2 sensitive regulation of many genes, particularly those being associated to inorganic carbon acquisition and calcification. Stable carbon isotope fractionation for organic carbon production increased with increasing pCO2 whereas it decreased for calcification, which suggests interdependence between both processes. We also found a strong effect of pCO2 on the stable oxygen isotopic composition of calcite, in line with earlier observations concerning another T. heimii strain. The observed changes in stable oxygen and carbon isotope composition of T. heimii cysts may provide an ideal tool for reconstructing past seawater carbonate chemistry, and ultimately past pCO2. Although the function of calcification in T. heimii remains unresolved, this trait likely plays an important role in the ecological and evolutionary success of this species. Acting on calcification as well as growth, ocean acidification may therefore impose a great threat for T. heimii.

  12. 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

  13. Coronary artery calcification in renal transplant recipients.

    PubMed

    Rosas, Sylvia E; Mensah, Korlei; Weinstein, Rachel B; Bellamy, Scarlett L; Rader, Daniel J

    2005-08-01

    Cardiovascular disease is the leading cause of mortality in renal transplant recipients. Although renal transplant recipients frequently undergo cardiac functional tests prior to surgery, coronary atherosclerosis can remain undetected. Coronary artery calcification (CAC), an early marker of atherosclerosis can be quantified using EBCT. The purpose of this study was to determine the extent and characteristics of CAC at the time of renal transplantation. We evaluated 79 consecutive incident asymptomatic renal transplant recipients. Patients were mostly White (62%), male (54%) and had a deceased donor renal transplant (61%). The mean age was 47 (12.1) years. Sixty-five percentage of subjects had CAC. The mean CAC score was 331.5 (562.4) with a median of 43.3. Older age, presence of diabetes, not having a preemptive transplant, deceased donor transplantation and hypercholesterolemia were significantly associated with presence of CAC univariately. Median CAC scores were significantly increased in subjects with diabetes (127.8 vs. 28.9, p=0.05), exposed to dialysis (102.9 vs. 3.7, p<0.001) and deceased donor recipients (169.7 vs. 7.5, p=0.02). Using multiple logistic regression, age and time on dialysis were significantly associated with the presence of CAC at the time of transplant. In summary, CAC is prevalent in patients undergoing kidney transplant. CAC may be a method to identify renal transplant recipients at increased risk for future cardiovascular events. PMID:15996243

  14. Vascular calcification and renal bone disorders.

    PubMed

    Lu, Kuo-Cheng; Wu, Chia-Chao; Yen, Jen-Fen; Liu, Wen-Chih

    2014-01-01

    At the early stage of chronic kidney disease (CKD), the systemic mineral metabolism and bone composition start to change. This alteration is known as chronic kidney disease-mineral bone disorder (CKD-MBD). It is well known that the bone turnover disorder is the most common complication of CKD-MBD. Besides, CKD patients usually suffer from vascular calcification (VC), which is highly associated with mortality. Many factors regulate the VC mechanism, which include imbalances in serum calcium and phosphate, systemic inflammation, RANK/RANKL/OPG triad, aldosterone, microRNAs, osteogenic transdifferentiation, and effects of vitamins. These factors have roles in both promoting and inhibiting VC. Patients with CKD usually have bone turnover problems. Patients with high bone turnover have increase of calcium and phosphate release from the bone. By contrast, when bone turnover is low, serum calcium and phosphate levels are frequently maintained at high levels because the reservoir functions of bone decrease. Both of these conditions will increase the possibility of VC. In addition, the calcified vessel may secrete FGF23 and Wnt inhibitors such as sclerostin, DKK-1, and secreted frizzled-related protein to prevent further VC. However, all of them may fight back the inhibition of bone formation resulting in fragile bone. There are several ways to treat VC depending on the bone turnover status of the individual. The main goals of therapy are to maintain normal bone turnover and protect against VC. PMID:25136676

  15. Intracranial Calcifications and Hemorrhages: Characterization with Quantitative Susceptibility Mapping

    PubMed Central

    Chen, Weiwei; Zhu, Wenzhen; Kovanlikaya, IIhami; Kovanlikaya, Arzu; Liu, Tian; Wang, Shuai; Salustri, Carlo

    2014-01-01

    Purpose To compare gradient-echo (GRE) phase magnetic resonance (MR) imaging and quantitative susceptibility mapping (QSM) in the detection of intracranial calcifications and hemorrhages. Materials and Methods This retrospective study was approved by the institutional review board. Thirty-eight patients (24 male, 14 female; mean age, 33 years ± 16 [standard deviation]) with intracranial calcifications and/or hemorrhages diagnosed on the basis of computed tomography (CT), MR imaging (interval between examinations, 1.78 days ± 1.31), and clinical information were selected. GRE and QSM images were reconstructed from the same GRE data. Two experienced neuroradiologists independently identified the calcifications and hemorrhages on the QSM and GRE phase images in two randomized sessions. Sensitivity, specificity, and interobserver agreement were computed and compared with the McNemar test and k coefficients. Calcification loads and volumes were measured to gauge intermodality correlations with CT. Results A total of 156 lesions were detected: 62 hemorrhages, 89 calcifications, and five mixed lesions containing both hemorrhage and calcification. Most of these lesions (146 of 151 lesions, 96.7%) had a dominant sign on QSM images suggestive of a specific diagnosis of hemorrhage or calcium, whereas half of these lesions (76 of 151, 50.3%) were heterogeneous on GRE phase images and thus were difficult to characterize. Averaged over the two independent observers for detecting hemorrhages, QSM achieved a sensitivity of 89.5% and a specificity of 94.5%, which were significantly higher than those at GRE phase imaging (71% and 80%, respectively; P < .05 for both readers). In the identification of calcifications, QSM achieved a sensitivity of 80.5%, which was marginally higher than that with GRE phase imaging (71%; P = .08 and .10 for the two readers), and a specificity of 93.5%, which was significantly higher than that with GRE phase imaging (76.5%; P < .05 for both readers

  16. Computer aided breast calcification auto-detection in cone beam breast CT

    NASA Astrophysics Data System (ADS)

    Zhang, Xiaohua; Ning, Ruola; Liu, Jiangkun

    2010-03-01

    In Cone Beam Breast CT (CBBCT), breast calcifications have higher intensities than the surrounding tissues. Without the superposition of breast structures, the three-dimensional distribution of the calcifications can be revealed. In this research, based on the fact that calcifications have higher contrast, a local thresholding and a histogram thresholding were used to select candidate calcification areas. Six features were extracted from each candidate calcification: average foreground CT number value, foreground CT number standard deviation, average background CT number value, background CT number standard deviation, foreground-background contrast, and average edge gradient. To reduce the false positive candidate calcifications, a feed-forward back propagation artificial neural network was designed. The artificial neural network was trained with the radiologists confirmed calcifications and used as classifier in the calcification auto-detection task. In the preliminary experiments, 90% of the calcifications in the testing data sets were detected correctly with an average of 10 false positives per data set.

  17. Environmental NO2 and CO Exposure: Ignored Factors Associated with Uremic Pruritus in Patients Undergoing Hemodialysis.

    PubMed

    Huang, Wen-Hung; Lin, Jui-Hsiang; Weng, Cheng-Hao; Hsu, Ching-Wei; Yen, Tzung-Hai

    2016-01-01

    Uremic pruritus (UP), also known as chronic kidney disease-associated pruritus, is a common and disabling symptom in patients undergoing maintenance hemodialysis (MHD). The pathogenesis of UP is multifactorial and poorly understood. Outdoor air pollution has well-known effects on the health of patients with allergic diseases through an inflammatory process. Air pollution-induced inflammation could occur in the skin and aggravate skin symptoms such as pruritus or impair epidermal barrier function. To assess the role of air pollutants, and other clinical variables on uremic pruritus (UP) in HD patients, we recruited 866 patients on maintenance HD. We analyzed the following variables for association with UP: average previous 12-month and 24-month background concentrations for nitrogen dioxide (NO2) and carbon monoxide (CO), and suspended particulate matter of <2.5 μm (PM2.5). In a multivariate logistic regression, hemodialysis duration, serum ferritin levels, low-density lipoprotein levels, and environmental NO2/CO levels were positively associated with UP, and serum albumin levels were negatively associated with UP. This cross-sectional study showed that air pollutants such as NO2 and CO might be associated with UP in patients with MHD. PMID:27507591

  18. The effect of oral aluminium salts on the bone of non-dialysed uremic patients.

    PubMed

    Heaf, J G; Pødenphant, J; Joffe, P; Andersen, J R; Fugleberg, S; Braendstrup, O

    1987-01-01

    12 patients with conservatively treated uremia were investigated using bone histomorphometry, bone aluminium concentration determination and total body bone mineral content (TBBM). The bone aluminum was raised in 10 patients and was significantly related to oral aluminium salt consumption (p less than 0.01). Two of four patients who had not received aluminium also had raised levels but the difference was not significant from nonuremic patients. The two patients with the highest levels had a mineralisation defect despite normal levels of 1,25-dihydroxyvitamin D. Three patients had significant bone loss of whom one had osteomalacia (OM) while two had secondary hyperparathyroidism (2HP). It is concluded that 1) aluminium salt consumption results in bone aluminium accumulation, and may contribute to the mineralisation defect; 2) uremic patients not treated ith aluminium salts may have slightly raised levels, but this seems not to be clinically important; 3) secondary hyperparathyroidism causes greater destruction of bone mass than other uremic bone diseases; 4) atomic absorption spectrometry is a more sensitive method for detecting aluminium bone deposition than histochemical methods. PMID:3433024

  19. Detergent-resistant globotriaosyl ceramide may define verotoxin/glomeruli-restricted hemolytic uremic syndrome pathology.

    PubMed

    Khan, Fahima; Proulx, François; Lingwood, Clifford A

    2009-06-01

    Verotoxin binding to its receptor, globotriaosyl ceramide(Gb(3)) mediates the glomerular pathology of hemolytic uremic syndrome, but Gb(3) is expressed in both tubular and glomerular cells. Gb(3) within detergent-resistant membranes, an index of glycolipid-cholesterol enriched lipid rafts, is required for in vitro cytotoxicity. We found that verotoxin 1 and 2 binding to human adult renal glomeruli is detergent resistant, whereas the strong verotoxin binding to renal tubules is detergent sensitive. Verotoxin binding to pediatric glomeruli was detergent resistant but binding to adult glomeruli was enhanced, remarkably for some samples, by detergent extraction. Detergent-sensitive glomerular components may provide age-related protection against verotoxin glomerular binding. Mouse glomeruli remained verotoxin unreactive after detergent extraction, whereas tubular binding was lost. Cholesterol extraction induced strong verotoxin binding in poorly reactive adult glomeruli, suggesting cholesterol can mask Gb(3) in glomerular lipid rafts. Binding of the human immunodeficiency virus (HIV) adhesin, gp120 (another Gb(3) ligand) was detergent sensitive, tubule-restricted, and inhibited by verotoxin B subunit pretreatment, and may relate to HIV nephropathy. Our study shows that differential membrane Gb(3) organization in glomeruli and tubules provides a basis for the age- and glomerular-restricted pathology of hemolytic uremic syndrome.

  20. Studies on Erythropoiesis in Uremic and Post-Transplant (Renal) Patients Utilizing Radioactive Iron and Chromium

    PubMed Central

    Farooki, M. S.; Kimber, R. W.

    1971-01-01

    The association of anemia with chronic renal disease is well known. The striking hematologic improvement following a successful renal allotransplantation led to the present study. Using radioactive 59Fe, ferrokinetic measurements were carried out in nine uremic patients (seven with and two without anemia), four post-allotransplant cases, three patients with iron deficiency anemia and a group of five normal subjects. Erythrocyte life-span was calculated by 51Cr-labelled, autotransfused red cells in all patients who had had transplants and in three patients with renal anemia. The results showed that in patients with renal anemia the plasma radioiron clearance was slightly delayed but the 59Fe incorporation into the circulating erythrocytes was significantly decreased. Red cell life-span was moderately shortened in two out of three uremic patients investigated. The findings constitute evidence of ineffective erythropoiesis in patients with renal anemia. By comparison, the four transplant patients showed normal 59Fe plasma clearance and red cell incorporation; the 51Cr erythrocyte survival was normal in all four patients. PMID:4931770

  1. Handling of Drugs, Metabolites, and Uremic Toxins by Kidney Proximal Tubule Drug Transporters.

    PubMed

    Nigam, Sanjay K; Wu, Wei; Bush, Kevin T; Hoenig, Melanie P; Blantz, Roland C; Bhatnagar, Vibha

    2015-11-01

    The proximal tubule of the kidney plays a crucial role in the renal handling of drugs (e.g., diuretics), uremic toxins (e.g., indoxyl sulfate), environmental toxins (e.g., mercury, aristolochic acid), metabolites (e.g., uric acid), dietary compounds, and signaling molecules. This process is dependent on many multispecific transporters of the solute carrier (SLC) superfamily, including organic anion transporter (OAT) and organic cation transporter (OCT) subfamilies, and the ATP-binding cassette (ABC) superfamily. We review the basic physiology of these SLC and ABC transporters, many of which are often called drug transporters. With an emphasis on OAT1 (SLC22A6), the closely related OAT3 (SLC22A8), and OCT2 (SLC22A2), we explore the implications of recent in vitro, in vivo, and clinical data pertinent to the kidney. The analysis of murine knockouts has revealed a key role for these transporters in the renal handling not only of drugs and toxins but also of gut microbiome products, as well as liver-derived phase 1 and phase 2 metabolites, including putative uremic toxins (among other molecules of metabolic and clinical importance). Functional activity of these transporters (and polymorphisms affecting it) plays a key role in drug handling and nephrotoxicity. These transporters may also play a role in remote sensing and signaling, as part of a versatile small molecule communication network operative throughout the body in normal and diseased states, such as AKI and CKD.

  2. Involvement of the fractalkine pathway in the pathogenesis of childhood hemolytic uremic syndrome.

    PubMed

    Ramos, María Victoria; Fernández, Gabriela C; Patey, Natasha; Schierloh, Pablo; Exeni, Ramón; Grimoldi, Irene; Vallejo, Graciela; Elías-Costa, Christian; Del Carmen Sasiain, Maria; Trachtman, Howard; Combadière, Christophe; Proulx, François; Palermo, Marina S

    2007-03-15

    Thrombotic microangiopathy and acute renal failure are cardinal features of postdiarrheal hemolytic uremic syndrome (HUS). These conditions are related to endothelial and epithelial cell damage induced by Shiga toxin (Stx) through the interaction with its globotriaosyl ceramide receptor. However, inflammatory processes contribute to the pathogenesis of HUS by sensitizing cells to Stx fractalkine (FKN), a CX(3)C transmembrane chemokine expressed on epithelial and endothelial cells upon activation, is involved in the selective migration and adhesion of specific leukocyte subsets to tissues. Here, we demonstrated a selective depletion of circulating mononuclear leukocytes expressing the receptor for FKN (CX(3)CR1) in patients with HUS. We found a unique phenotype in children with HUS distinct from that seen in healthy, uremic, or infected controls, in which monocytes lost CX(3)CR1, down-modulated CD62L, and increased CD16. In addition, the CD56(dim) natural killer (NK) subpopulation was decreased, leading to an altered peripheral CD56(dim)/CD56(bright) ratio from 10.0 to 4.5. It is noteworthy that a negative correlation existed between the percentage of circulating CX(3)CR1(+) leukocytes and the severity of renal failure. Finally, CX(3)CR1(+) leukocytes were observed in renal biopsies from patients with HUS. We suggest that the interaction of CX(3)CR1(+) cells with FKN present on activated endothelial cells may contribute to renal injury in HUS.

  3. Impaired neutrophils in children with the typical form of hemolytic uremic syndrome.

    PubMed

    Fernández, Gabriela C; Gómez, Sonia A; Rubel, Carolina J; Bentancor, Leticia V; Barrionuevo, Paula; Alduncín, Marta; Grimoldi, Irene; Exeni, Ramón; Isturiz, Martín A; Palermo, Marina S

    2005-09-01

    Experimental and clinical evidence suggest that activated neutrophils (PMN) could contribute to endothelial damage in Hemolytic Uremic Syndrome (D+HUS). Additionally, while PMN-activating cytokines and PMN-derived products have been found in D+HUS sera, we have demonstrated phenotypic alterations in D+HUS PMN compatible with a deactivation state. Here, we investigated whether D+HUS PMN were actually hyporesponsive, and explored some of the mechanisms probably involved in their derangement. Twenty-two D+HUS children were bled in the acute period, and blood samples from healthy, acute uremic and neutrophilic children were obtained as controls. We evaluated degranulation markers in response to cytokines, intracellular granule content, and reactive oxygen species (ROS) generation in circulating D+HUS and control PMN. The influence of D+HUS-derived plasma and the direct effects of Stx in vitro were evaluated on healthy donors' PMN. We found that D+HUS PMN presented reduced degranulatory capacity in response to cytokines and intracellular granule content, and decreased ROS generation. D+HUS plasma or Stx did not affect the phenotype and function of healthy donors' PMN. These results suggest that upon hospitalization D+HUS PMN are functionally impaired and show features of previous degranulation, indicating a preceding process of activation with release of ROS and proteases involved in endothelial damage.

  4. [Effect of growth hormone and calcitriol on the growth plate in uremic rats].

    PubMed

    Amil, B; Fernández-Fuente, M; Santos, F; Rodríguez, J; Díaz-Tejón, L; García, E; Carbajo, E

    2003-01-01

    This study analyzed the modifications induced by growth hormone (GH) and/or calcitriol treatments in the growth plate of growth retarded uremic rats. Four groups of 5/6 nephrectomized rats were studied: untreated (U), treated with GH (U + GH), treated with calcitriol (U + D), treated with GH and calcitriol (U + GH + D). Treatments were given intraperitoneally during the second week of renal failure. Uremic groups were compared with sham-operated rats fed ad libitum (C) or pair-fed with U (CP). In comparison with C and CP, histomorphometric analysis of tibial proximal ends of U group showed decreased bone formation, as estimated by osseous front advance (OFA), elongation of growth cartilage and its hypertrophic zone, and decreased size of most distal chondrocytes. The U + D group tended to normalize growth cartilage height, and that of its hypertrophic zone, as well as the size of chondrocytes. In U + GH group OFA improved and chondrocyte size became normal, but growth cartilage remained elongated. Similar results were found in the U + GH + D group. These findings indicate that, in chronic renal insufficiency, the beneficial effect of GH on growth is not associated with normalization of growth cartilage morphology and that calcitriol facilitates chondrocyte maturation. When given together the effect of GH prevails.

  5. Environmental NO2 and CO Exposure: Ignored Factors Associated with Uremic Pruritus in Patients Undergoing Hemodialysis

    PubMed Central

    Huang, Wen-Hung; Lin, Jui-Hsiang; Weng, Cheng-Hao; Hsu, Ching-Wei; Yen, Tzung-Hai

    2016-01-01

    Uremic pruritus (UP), also known as chronic kidney disease–associated pruritus, is a common and disabling symptom in patients undergoing maintenance hemodialysis (MHD). The pathogenesis of UP is multifactorial and poorly understood. Outdoor air pollution has well-known effects on the health of patients with allergic diseases through an inflammatory process. Air pollution–induced inflammation could occur in the skin and aggravate skin symptoms such as pruritus or impair epidermal barrier function. To assess the role of air pollutants, and other clinical variables on uremic pruritus (UP) in HD patients, we recruited 866 patients on maintenance HD. We analyzed the following variables for association with UP: average previous 12-month and 24-month background concentrations for nitrogen dioxide (NO2) and carbon monoxide (CO), and suspended particulate matter of <2.5 μm (PM2.5). In a multivariate logistic regression, hemodialysis duration, serum ferritin levels, low-density lipoprotein levels, and environmental NO2/CO levels were positively associated with UP, and serum albumin levels were negatively associated with UP. This cross-sectional study showed that air pollutants such as NO2 and CO might be associated with UP in patients with MHD. PMID:27507591

  6. Direct evidence of complement activation in HELLP syndrome: A link to atypical hemolytic uremic syndrome.

    PubMed

    Vaught, Arthur J; Gavriilaki, Eleni; Hueppchen, Nancy; Blakemore, Karin; Yuan, Xuan; Seifert, Sara M; York, Sarah; Brodsky, Robert A

    2016-05-01

    HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) is a severe variant of pre-eclampsia whose pathogenesis remains unclear. Recent evidence and clinical similarities suggest a link to atypical hemolytic uremic syndrome, a disease of excessive activation of the alternative complement pathway effectively treated with a complement inhibitor, eculizumab. Therefore, we used a functional complement assay, the modified Ham test, to analyze sera of women with classic or atypical HELLP syndrome, pre-eclampsia with severe features, normal pregnancies, and healthy nonpregnant women. Sera were also evaluated using levels of the terminal product of complement activation (C5b-9). We tested the in vitro ability of eculizumab to inhibit complement activation in HELLP serum. Increased complement activation was observed in participants with classic or atypical HELLP compared with those with normal pregnancies and nonpregnant controls. Mixing HELLP serum with eculizumab-containing serum resulted in a significant decrease in cell killing compared with HELLP serum alone. We found that HELLP syndrome is associated with increased complement activation as assessed with the modified Ham test. This assay may aid in the diagnosis of HELLP syndrome and could confirm that its pathophysiology is related to that of atypical hemolytic uremic syndrome.

  7. Environmental NO2 and CO Exposure: Ignored Factors Associated with Uremic Pruritus in Patients Undergoing Hemodialysis

    NASA Astrophysics Data System (ADS)

    Huang, Wen-Hung; Lin, Jui-Hsiang; Weng, Cheng-Hao; Hsu, Ching-Wei; Yen, Tzung-Hai

    2016-08-01

    Uremic pruritus (UP), also known as chronic kidney disease–associated pruritus, is a common and disabling symptom in patients undergoing maintenance hemodialysis (MHD). The pathogenesis of UP is multifactorial and poorly understood. Outdoor air pollution has well-known effects on the health of patients with allergic diseases through an inflammatory process. Air pollution–induced inflammation could occur in the skin and aggravate skin symptoms such as pruritus or impair epidermal barrier function. To assess the role of air pollutants, and other clinical variables on uremic pruritus (UP) in HD patients, we recruited 866 patients on maintenance HD. We analyzed the following variables for association with UP: average previous 12-month and 24-month background concentrations for nitrogen dioxide (NO2) and carbon monoxide (CO), and suspended particulate matter of <2.5 μm (PM2.5). In a multivariate logistic regression, hemodialysis duration, serum ferritin levels, low-density lipoprotein levels, and environmental NO2/CO levels were positively associated with UP, and serum albumin levels were negatively associated with UP. This cross-sectional study showed that air pollutants such as NO2 and CO might be associated with UP in patients with MHD.

  8. Sclerostin levels in uremic patients: a link between bone and vascular disease.

    PubMed

    Bruzzese, Annamaria; Lacquaniti, Antonio; Cernaro, Valeria; Ricciardi, Carlo Alberto; Loddo, Saverio; Romeo, Adolfo; Montalto, Gaetano; Costantino, Giuseppe; Torre, Francesco; Pettinato, Giuseppina; Salamone, Ignazio; Aloisi, Carmela; Santoro, Domenico; Buemi, Michele

    2016-06-01

    Sclerostin is a marker of low-turnover bone disease in end stage renal disease patients. The aim of this study was to evaluate serum sclerostin in uremic patients, analyzing its behavior during a single hemodialysis session. Twenty-one adult patients on intermittent hemodialysis treatment were enrolled. Acetate Free Bio-filtration (AFB) was the technique employed. Uremic patients were characterized by higher levels of serum sclerostin when compared with values observed in healthy subjects. Sclerostin assessed in pre-dialysis samples was 1.4 ± 1.02 ng/mL, whereas, in post dialysis samples, a reduction of sclerostin values was observed (0.8 ± 0.6 ng/mL; p: 0.008). Sclerostin correlated with parameters of dialysis adequacy, such as creatinine levels and Kt/V values, and it was significantly associated with atherosclerotic disease. Receiver operating characteristics analysis revealed a good diagnostic profile in identifying atherosclerotic disease. Sclerostin, a full dialyzable substance during AFB dialysis, is closely associated with atherosclerotic disease. Its reduction obtained through AFB could represent a defensive mechanism, improving vascular disease and renal osteodystrophy. PMID:27001371

  9. Uremic Pruritus Is Not Associated with Endocannabinoid Receptor 1 Gene Polymorphisms

    PubMed Central

    Heisig, Monika; Łaczmański, Łukasz; Reich, Adam; Lwow, Felicja

    2016-01-01

    Uremic pruritus (UP) is a frequent and bothersome symptom in hemodialysis patients. Its etiology is not fully understood and that is why there is no specific treatment. The endocannabinoid system plays a role in many pathological conditions. There is reliable evidence on the association between cannabinoid system and pruritus. In our study, we aimed to evaluate whether genetic variations in the endocannabinoid receptor 1 (CNR1) gene can affect UP. The rs12720071, rs806368, rs1049353, rs806381, rs10485170, rs6454674, and rs2023239 polymorphisms of the CNR1 gene were genotyped in 159 hemodialysis patients and 150 healthy controls using two multiplex polymerase chain reactions and the minisequencing technique. No statistically significant relationship was found in any of the evaluated genotypes between patients with and without UP, even after excluding patients with diabetes and dyslipidemia. There were no differences between patients with UP and the control group. However, in the group of all HD patients, a significantly higher incidence of GA genotype and lower incidence in GG genotype in the polymorphism rs806381s were revealed versus the control group (p = 0.04). It seems that polymorphisms of the CNR1 gene are not associated with uremic pruritus. PMID:27034934

  10. The aryl hydrocarbon receptor-activating effect of uremic toxins from tryptophan metabolism: a new concept to understand cardiovascular complications of chronic kidney disease.

    PubMed

    Sallée, Marion; Dou, Laetitia; Cerini, Claire; Poitevin, Stéphane; Brunet, Philippe; Burtey, Stéphane

    2014-03-04

    Patients with chronic kidney disease (CKD) have a higher risk of cardiovascular diseases and suffer from accelerated atherosclerosis. CKD patients are permanently exposed to uremic toxins, making them good candidates as pathogenic agents. We focus here on uremic toxins from tryptophan metabolism because of their potential involvement in cardiovascular toxicity: indolic uremic toxins (indoxyl sulfate, indole-3 acetic acid, and indoxyl-β-d-glucuronide) and uremic toxins from the kynurenine pathway (kynurenine, kynurenic acid, anthranilic acid, 3-hydroxykynurenine, 3-hydroxyanthranilic acid, and quinolinic acid). Uremic toxins derived from tryptophan are endogenous ligands of the transcription factor aryl hydrocarbon receptor (AhR). AhR, also known as the dioxin receptor, interacts with various regulatory and signaling proteins, including protein kinases and phosphatases, and Nuclear Factor-Kappa-B. AhR activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin and some polychlorinated biphenyls is associated with an increase in cardiovascular disease in humans and in mice. In addition, this AhR activation mediates cardiotoxicity, vascular inflammation, and a procoagulant and prooxidant phenotype of vascular cells. Uremic toxins derived from tryptophan have prooxidant, proinflammatory, procoagulant, and pro-apoptotic effects on cells involved in the cardiovascular system, and some of them are related with cardiovascular complications in CKD. We discuss here how the cardiovascular effects of these uremic toxins could be mediated by AhR activation, in a "dioxin-like" effect.

  11. [Vascular Calcification - Pathological Mechanism and Clinical Application - . Extracellular matrix tenascin-X in calcific aortic valves].

    PubMed

    Matsumoto, Ken-ichi

    2015-05-01

    We previously disclosed a novel extracellular matrix tenascin-X (TNX) , the largest member of the tenascin family. So far, we have made efforts to elucidate the roles of TNX. TNX is involved in collagen deposition, collagen fibrillogenesis, and modulation of collagen stiffness. Homozygous mutations in TNXB, the gene encoding TNX, cause a classic-type Ehlers-Danlos syndrome (EDS) , a heritable connective tissue disorder, whereas haploinsufficiency of TNXB and heterozygous mutations in TNXB are associated with hypermobility-type EDS. Recently, we performed proteomic analyses of calcific aortic valves (CAVs) compared with relatively adjacent normal tissues to understand the underlying molecular mechanisms of dystrophic valvular calcification. Interestingly, we found that TNX was the protein with the greatest decrease in expression among the differentially expressed proteins and that expression levels of proteins modulating collagen structure and function, such as type I collagen and decorin, were also decreased in CAVs. In this review, I will discuss about the decreased level of collagen due to the reduction of expression levels of proteins that play regulatory roles in collagen functions such as fibril organization and fibrillogenesis in CAVs. PMID:25926574

  12. Shunt tube calcification as a late complication of ventriculoperitoneal shunting

    PubMed Central

    Salim, Abubakr Darrag; Elzain, Mohammed Awad; Mohamed, Haddab Ahmed; Ibrahim Zayan, Baha Eldin Mohamed

    2015-01-01

    Shunt calcification is a rare complication of ventriculoperitoneal shunting that occurs years later after the initial operation this condition is rarely reported in literature. Two patients with shunt calcifications were described. The first patient was 17-year-old lady who had congenital hydrocephalus and shunted in the early infancy, she was presented recently complaining of itching of the skin along the shunt track and limitation of neck movement. The patient was then operated with removal of the old peritoneal catheter and replacing it with a new one. The second patient was 17-year-old boy originally was a case of posterior fossa pilocytic astrocytoma associated with obstructive hydrocephalus, he was operated with both shunting for the hydrocephalus and tumor removal, 6 years later he presented with shunt exposure. Calcification of the shunt tube was discovered intraoperatively upon shunt removal. Shunt calcification has been observed mainly in barium-impregnated catheters. Introducing plain silicone-coated shunt tubing may reduce the rate of this condition. The usual complaints of the patients suffering from this condition are pain in the neck and chest wall along the shunt pathway and limitation of the neck movement due to shunt tube tethering, but features of shunt dysfunction and skin irritation above the shunt may be present. In this review, plain X-ray and operative findings showed that the most extensive calcification is present in the neck, where the catheters were subject to heavy mechanical stress. Disturbed calcium and phosphate metabolisms may be involved in this condition. Shunt calcification is a rare condition that occurs due to material aging presenting with features of shunt tethering, dysfunction or overlying skin irritation. Plain X-ray is needed to detect calcification while shunt removal, replacement or endoscopic third ventriculostomy may carry solution for this condition. PMID:26396620

  13. The association between abdominal body composition and vascular calcification.

    PubMed

    Jensky, Nicole E; Criqui, Michael H; Wright, C Michael; Wassel, Christina L; Alcaraz, John E; Allison, Matthew A

    2011-12-01

    Subclinical cardiovascular disease (CVD) may be associated with both adipose and skeletal muscle tissues in the abdomen. Accordingly, we examined whether subcutaneous, intermuscular, and visceral adipose tissue, as well as abdominal lean muscle, were associated with the presence and extent of vascular calcification in multiple vascular beds. Three hundred and ninety four patients (58.1% men) underwent electron beam computed tomography (EBCT) scans as part of routine health maintenance screening. The coronary and carotid calcium scores were analyzed at the time of the scan, whereas the other calcium scores, as well as the body composition analyses, were analyzed retrospectively. Mean age was 55.2 ± 11.1 years and BMI was 26.9 ± 4.2. The prevalence of any calcification in the carotids, coronaries, thoracic aorta, abdominal aorta, and iliacs was 30.1, 60.1, 39.8, 55.7, and 56.8%, respectively. Compared to those with calcification in different vascular beds, those without vascular calcification generally had significantly more lean muscle and less adipose tissue. In separate multivariable logistic models, a 1 s.d. increment in the ratio of abdominal and visceral fat to total area of each corresponding compartments was significantly associated with an increased odds for the presence of thoracic aortic calcium (odds ratio (OR) = 1.6, 1.5, respectively; P = 0.01 for both). Conversely, increases in abdominal lean muscle were associated with significantly decreased odds of thoracic aortic calcification (OR = 0.34; P ≤ 0.01). A similar pattern of associations existed among the other vascular beds. Also, the association between lean muscle and vascular calcification was independent of visceral adipose tissue. In conclusion, adipose tissue was positively and lean body mass inversely associated with prevalent aortic calcification. PMID:21475146

  14. The dark and bright side of atherosclerotic calcification.

    PubMed

    Pugliese, Giuseppe; Iacobini, Carla; Blasetti Fantauzzi, Claudia; Menini, Stefano

    2015-02-01

    Vascular calcification is an unfavorable event in the natural history of atherosclerosis that predicts cardiovascular morbidity and mortality. However, increasing evidence suggests that different calcification patterns are associated with different or even opposite histopathological and clinical features, reflecting the dual relationship between inflammation and calcification. In fact, initial calcium deposition in response to pro-inflammatory stimuli results in the formation of spotty or granular calcification ("microcalcification"), which induces further inflammation. This vicious cycle favors plaque rupture, unless an adaptive response prevails, with blunting of inflammation and survival of vascular smooth muscle cells (VSMCs). VSMCs promote fibrosis and also undergo osteogenic transdifferentiation, with formation of homogeneous or sheet-like calcification ("macrocalcification"), that stabilizes the plaque by serving as a barrier towards inflammation. Unfortunately, little is known about the molecular mechanisms regulating this adaptive response. The advanced glycation/lipoxidation endproducts (AGEs/ALEs) have been shown to promote vascular calcification and atherosclerosis. Recent evidence suggests that two AGE/ALE receptors, RAGE and galectin-3, modulate in divergent ways, not only inflammation, but also vascular osteogenesis, by favoring "microcalcification" and "macrocalcification", respectively. Galectin-3 seems essential for VSMC transdifferentiation into osteoblast-like cells via direct modulation of the WNT-β-catenin signaling, thus driving formation of "macrocalcification", whereas RAGE favors deposition of "microcalcification" by promoting and perpetuating inflammation and by counteracting the osteoblastogenic effect of galectin-3. Further studies are required to understand the molecular mechanisms regulating transition from "microcalcification" to "macrocalcification", thus allowing to design therapeutic strategies which favor this adaptive process

  15. Maintenance eculizumab dose adjustment in the treatment of atypical hemolytic uremic syndrome: a case report and review of the literature.

    PubMed

    Thomson, Nick; Ulrickson, Matthew

    2016-08-01

    Atypical hemolytic uremic syndrome (aHUS) patients treated with eculizumab may require higher doses to achieve and maintain optimal clinical response. Further studies are warranted to elucidate optimal dosing regimens of eculizumab in aHUS patients, and whether dosing regimens can be predicted based on mutational status, eculizumab levels, or other testing. PMID:27525082

  16. Serum Shiga toxin 2 values in patients during the acute phase of post-diarrheal hemolytic uremic syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Shiga toxins (Stxs) produced by Shiga toxin-producing Escherichia coli (STEC) are considered as the main causative agent, leading to the development of the hemolytic uremic syndrome (HUS); these toxins injure endothelial cells mainly the glomeruli. After passing through the intestinal wall, Stxs hav...

  17. Evidence of infection with organisms producing Shiga-like toxins in household contacts of children with the hemolytic uremic syndrome.

    PubMed

    Lopez, E L; Diaz, M; Devoto, S; Grinstein, S; Woloj, M; Murray, B E; Rubeglio, E; Mendilaharzu, F; Turco, M; Vasquez, M

    1991-01-01

    We conducted a prospective study in 87 household contacts of 51 children with hemolytic uremic syndrome to determine the frequency of infection with Shiga-like toxin-producing bacteria. Gastrointestinal tract symptoms occurred in only 1 of 87 contacts. Free fecal toxin was detected in 25 of 64 (39%) of the household members. Neutralization with specific antisera to Shiga-like toxins I and II (SLT-I, SLT-II) revealed that in 6 of these household contacts only SLT-I was present in stool, in 10 only SLT-II was present and in 9 both toxins were found. Thirty-three percent of the hemolytic uremic syndrome families in which 2 or more members were studied had more than 1 household member with free fecal toxin in stool. None of the household contacts was found to have E. coli O157:H7 in feces. Serum samples were available in 77 household contacts; 75% (58 of 77) had serum neutralizing titers of greater than or equal to 1:4 to 1 or both toxins. In those contacts for whom paired sera were available, seroconversion was found in 10 of 24 (42%). These data show that household contacts of children with hemolytic uremic syndrome are commonly colonized with Shiga-like toxin-producing E. coli and seroconversion to Shiga-like toxins occurs frequently in family members of children with hemolytic uremic syndrome.

  18. Proteomics and metabolomics as tools to unravel novel culprits and mechanisms of uremic toxicity: instrument or hype?

    PubMed

    Mullen, William; Saigusa, Daisuke; Abe, Takaaki; Adamski, Jerzy; Mischak, Harald

    2014-03-01

    The development of proteomic and metabolomic technologies holds the promise to significantly impact patient management by improving diagnosis, unraveling more appropriate therapeutic targets, and enabling more precise prognosis of disease development. Proteomics and metabolomics have been applied with the aim of improving dialysis, defining uremic toxins, and unraveling their origin. Ideally, these technologies should inform us which proteomic or metabolomic compounds are subject to significant alterations of concentration or structure as a result of failing kidney function, and thus can be considered as potential uremic toxins. After a few years of applying these technologies in the area of uremic toxicity studies we are now in a position where we can estimate how and what they can contribute to the field. In this review we critically examine the current literature on the application of proteomics and metabolomics in the context of dialysis and uremic toxins. We highlight the most promising findings, indicate where we see the current need, and which future developments consequently are to be expected, given the technological constraints that undoubtedly exist.

  19. The mechanism of vascular calcification – a systematic review

    PubMed Central

    Karwowski, Wojciech; Naumnik, Beata; Szczepański, Marek; Myśliwiec, Michał

    2012-01-01

    Summary Calcification of vessels reduces their elasticity, affecting hemodynamic parameters of the cardiovascular system. The development of arterial hypertension, cardiac hypertrophy, ischemic heart disease or peripheral arterial disease significantly increases mortality in patients over 60 years of age. Stage of advancement and the extent of accumulation of calcium deposits in vessel walls are key risk factors of ischemic events. Vascular calcification is an active and complex process that involves numerous mechanisms responsible for calcium depositions in arterial walls. They lead to increase in arterial stiffness and in pulse wave velocity, which in turn increases cardiovascular disease morbidity and mortality. In-depth study and thorough understanding of vascular calcification mechanisms may be crucial for establishing an effective vasculoprotective therapy. The aim of this study was to present a comprehensive survey of current state-of-the-art research into the impact of metabolic and hormonal disorders on development of vascular calcification. Due to strong resemblance to the processes occurring in bone tissue, drugs used for osteoporosis treatment (calcitriol, estradiol, bisphosphonates) may interfere with the processes occurring in the vessel wall. On the other hand, drugs used to treat cardiovascular problems (statins, angiotensin convertase inhibitors, warfarin, heparins) may have an effect on bone tissue metabolism. Efforts to optimally control calcium and phosphate concentrations are also beneficial for patients with end-stage renal disease, for whom vessel calcification remains a major problem. PMID:22207127

  20. Gaussian weighted projection for visualization of cardiac calcification

    NASA Astrophysics Data System (ADS)

    Chen, Xiang; Li, Ke; Gilkeson, Robert; Fei, Baowei

    2008-03-01

    At our institution, we are using dual-energy digital radiography (DEDR) as a cost-effective screening tool for the detection of cardiac calcification. We are evaluating DEDR using CT as the gold standard. We are developing image projection methods for the generation of digitally reconstructed radiography (DRR) from CT image volumes. Traditional visualization methods include maximum intensity projection (MIP) and average-based projection (AVG) that have difficulty to show cardiac calcification. Furthermore, MIP can over estimate the calcified lesion as it displays the maximum intensity along the projection rays regardless of tissue types. For AVG projection, the calcified tissue is usually overlapped with bone, lung and mediastinum. In order to improve the visualization of calcification on DRR images, we developed a Gaussian-weighted projection method for this particular application. We assume that the CT intensity values of calcified tissues have a Gaussian distribution. We then use multiple Gaussian functions to fit the intensity histogram. Based on the mean and standard deviation parameters, we incorporate a Gaussian weighted function into the perspective projection and display the calcification exclusively. Our digital and physical phantom studies show that the new projection method can display tissues selectively. In addition, clinical images show that the Gaussian-weighted projection method better visualizes cardiac calcification than either the AVG or MIP method and can be used to evaluate DEDR as a screening tool for the detection of coronary artery diseases.

  1. Epilepsy, occipital calcifications, and oligosymptomatic celiac disease in childhood.

    PubMed

    Arroyo, Hugo A; De Rosa, Susana; Ruggieri, Victor; de Dávila, María T G; Fejerman, Natalio

    2002-11-01

    The association of epilepsy, occipital calcifications, and celiac disease has been recognized as a distinct syndrome. The objective of this study was to present the clinical, electrophysiologic, and neuroradiologic features in a series of patients with this syndrome. Thirty-two patients with the constellation of epilepsy, occipital calcifications, and celiac disease were identified in our epilepsy clinic. The mean age was 11 years and the mean length of follow-up was 7.4 years. The 1990 criteria of the European Society of Pediatric Gastroenterology and Nutrition were used to diagnose celiac disease. The Kruskal-Wallis statistics test was employed with a signficance of P < .05. Thirty-one patients had partial seizures, 21 of them with symptoms related to the occipital lobe. In most patients, the epilepsy was controlled or the seizures were sporadic. Three developed severe epilepsy. Occipital calcifications were present in all cases. Computed tomography in 7 patients showed hypodense areas in the white matter around calcifications, which decreased or disappeared after a period of gluten-free diet in 3 patients. A favorable outcome of epilepsy was detected in patients with the earliest dietary therapy. This study presents the largest series of children with this syndrome outside Italy. White-matter hypodensities surrounding calcifications are rarely reported. A prompt diagnosis of celiac disease might improve the evolution of the epilepsy and may improve cognitive status. PMID:12585717

  2. Effect of calcium carbonate saturation of seawater on coral calcification

    USGS Publications Warehouse

    Gattuso, J.-P.; Frankignoulle, M.; Bourge, I.; Romaine, S.; Buddemeier, R.W.

    1998-01-01

    The carbonate chemistry of seawater is usually not considered to be an important factor influencing calcium-carbonate-precipitation by corals because surface seawater is supersaturated with respect to aragonite. Recent reports, however, suggest that it could play a major role in the evolution and biogeography of recent corals. We investigated the calcification rates of five colonies of the zooxanthellate coral Stylophora pistillata in synthetic seawater using the alkalinity anomaly technique. Changes in aragonite saturation from 98% to 585% were obtained by manipulating the calcium concentration. The results show a nonlinear increase in calcification rate as a function of aragonite saturation level. Calcification increases nearly 3-fold when aragonite saturation increases from 98% to 390%, i.e., close to the typical present saturation state of tropical seawater. There is no further increase of calcification at saturation values above this threshold. Preliminary data suggest that another coral species, Acropora sp., displays a similar behaviour. These experimental results suggest: (l) that the rate of calcification does not change significantly within the range of saturation levels corresponding to the last glacial-interglacial cycle, and (2) that it may decrease significantly in the future as a result of the decrease in the saturation level due to anthropogenic release of CO2 into the atmosphere. Experimental studies that control environmental conditions and seawater composition provide unique opportunities to unravel the response of corals to global environmental changes.

  3. Inflammatory, metabolic, and genetic mechanisms of vascular calcification.

    PubMed

    Demer, Linda L; Tintut, Yin

    2014-04-01

    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. Although 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 versus 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 γ-carboxyglutamic acid protein, 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 matrix γ-carboxyglutamic acid protein, 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. Until recently, vascular calcification was considered a purely degenerative, unregulated process. Since then, investigative groups around the world have identified a wide range of causative mechanisms and regulatory pathways, and some of the recent developments are highlighted in this review.

  4. Intracranial Cortical Calcifications in a Focal Epilepsy Patient with Pseudohypoparathyroidism.

    PubMed

    Kim, Ye Sel; Park, Jihyung; Park, Yoonkyung; Hwang, KyoungJin; Koo, Dae Lim; Kim, Daeyoung; Seo, Dae-Won

    2016-06-01

    Patients with chronic parathyroid dysfunction often have intracranial calcification in deep gray matter (GM) and subcortical white matter (WM) of their brain. Some of them are also epilepsy patients. Although cortical etiologies are main cause of epileptic seizure, cortical calcification has not been reported in these patients. We report a newly diagnosed focal epilepsy patient whose brain magnetic resonance imaging revealed intracranial calcifications in cortical as well as subcortical areas. Blood lab revealed that he had hypocalcemia due to pseudohypoparathyroidism. Video EEG monitoring revealed the ictal EEG mainly consist of polymorphic delta to theta waves with maximum at right temporal area followed by background attenuation and muscle artifacts. The interictal EEG showed multiple focal spike-wave discharges. After given oral calcium and calcitriol supplement, his calcium and phosphorous level normalized and he remains seizure free. This is the first case to show cortical calcification in a patient with pseudohypoparathyroidism. Cortical calcification could be an important measure of seizure burden in these patients and thus sophisticated imaging protocols should be used to visualize the extent of calcium deposits. PMID:27390678

  5. Intracranial Cortical Calcifications in a Focal Epilepsy Patient with Pseudohypoparathyroidism

    PubMed Central

    Kim, Ye Sel; Park, Jihyung; Park, Yoonkyung; Hwang, KyoungJin; Koo, Dae Lim; Kim, Daeyoung; Seo, Dae-Won

    2016-01-01

    Patients with chronic parathyroid dysfunction often have intracranial calcification in deep gray matter (GM) and subcortical white matter (WM) of their brain. Some of them are also epilepsy patients. Although cortical etiologies are main cause of epileptic seizure, cortical calcification has not been reported in these patients. We report a newly diagnosed focal epilepsy patient whose brain magnetic resonance imaging revealed intracranial calcifications in cortical as well as subcortical areas. Blood lab revealed that he had hypocalcemia due to pseudohypoparathyroidism. Video EEG monitoring revealed the ictal EEG mainly consist of polymorphic delta to theta waves with maximum at right temporal area followed by background attenuation and muscle artifacts. The interictal EEG showed multiple focal spike-wave discharges. After given oral calcium and calcitriol supplement, his calcium and phosphorous level normalized and he remains seizure free. This is the first case to show cortical calcification in a patient with pseudohypoparathyroidism. Cortical calcification could be an important measure of seizure burden in these patients and thus sophisticated imaging protocols should be used to visualize the extent of calcium deposits. PMID:27390678

  6. Local influence of calcifications on the wall mechanics of abdominal aortic aneurysm

    NASA Astrophysics Data System (ADS)

    de Putter, Sander; van de Vosse, Frans N.; Breeuwer, Marcel; Gerritsen, Frans A.

    2006-03-01

    Finite element wall stress simulations on patient-specific models of abdominal aortic aneurysm (AAA) may provide a better rupture risk predictor than the currently used maximum transverse diameter. Calcifications in the wall of AAA lead to a higher maximum wall stress and thus may lead to an elevated rupture risk. The reported material properties for calcifications and the material properties actually used for simulations show great variation. Previous studies have focused on simplified modelling of the calcification shapes within a realistic aneurysm shape. In this study we use an accurate representation of the calcification geometry and a simplified model for the AAA. The objective of this approach is to investigate the influence of the calcification geometry, the material properties and the modelling approach for the computed peak wall stress. For four realistic calcification shapes from standard clinical CT images of AAA, we performed simulations with three distinct modelling approaches, at five distinct elasticity settings. The results show how peak wall stress is sensitive to the material properties of the calcifications. For relatively elastic calcifications, the results from the different modelling approaches agree. Also, for relatively elastic calcifications the computed wall stress in the tissue surrounding the calcifications shows to be insensitive to the exact calcification geometry. For stiffer calcifications the different modelling approaches and the different geometries lead to significantly different results. We conclude that an important challenge for future research is accurately estimating the material properties and the rupture potential of the AAA wall including calcifications.

  7. 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.

  8. 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

  9. Declining coral calcification on the Great Barrier Reef.

    PubMed

    De'ath, Glenn; Lough, Janice M; Fabricius, Katharina E

    2009-01-01

    Reef-building corals are under increasing physiological stress from a changing climate and ocean absorption of increasing atmospheric carbon dioxide. We investigated 328 colonies of massive Porites corals from 69 reefs of the Great Barrier Reef (GBR) in Australia. Their skeletal records show that throughout the GBR, calcification has declined by 14.2% since 1990, predominantly because extension (linear growth) has declined by 13.3%. The data suggest that such a severe and sudden decline in calcification is unprecedented in at least the past 400 years. Calcification increases linearly with increasing large-scale sea surface temperature but responds nonlinearly to annual temperature anomalies. The causes of the decline remain unknown; however, this study suggests that increasing temperature stress and a declining saturation state of seawater aragonite may be diminishing the ability of GBR corals to deposit calcium carbonate.

  10. 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

  11. 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.

  12. Idiopathic Basal Ganglia Calcification Presented with Impulse Control Disorder

    PubMed Central

    Sahin, Cem; Levent, Mustafa; Akbaba, Gulhan; Kara, Bilge; Yeniceri, Emine Nese; Inanc, Betul Battaloglu

    2015-01-01

    Primary familial brain calcification (PFBC), also referred to as Idiopathic Basal Ganglia Calcification (IBGC) or “Fahr's disease,” is a clinical condition characterized by symmetric and bilateral calcification of globus pallidus and also basal ganglions, cerebellar nuclei, and other deep cortical structures. It could be accompanied by parathyroid disorder and other metabolic disturbances. The clinical features are dysfunction of the calcified anatomic localization. IBGC most commonly presents with mental damage, convulsion, parkinson-like clinical picture, and neuropsychiatric behavior disorders; however, presentation with impulse control disorder is not a frequent presentation. In the current report, a 43-year-old male patient who has been admitted to psychiatry policlinic with the complaints of aggressive behavior episodes and who has been diagnosed with impulse control disorder and IBGC was evaluated in the light of the literature. PMID:26246920

  13. A Premature Infant with Fetal Myocardial and Abdominal Calcifications and Factor V Leiden Homozygosity

    PubMed Central

    Parker, Margaret G.K.; Webster, Gregory; Insoft, Robert M.

    2014-01-01

    We present a premature male neonate with confirmed Factor V Leiden deficiency diagnosed prenatally with cardiac and abdominal calcifications. Our patient’s findings suggest that clinicians consider thromboembolic conditions when multiple fetal calcifications are visualized. PMID:19861970

  14. Alkalinity Enrichment Enhances Net Calcification of a Coral Reef Flat

    NASA Astrophysics Data System (ADS)

    Albright, R.; Caldeira, K.

    2015-12-01

    Ocean acidification is projected to shift reefs from a state of net accretion to one of net dissolution sometime this century. While retrospective studies show large-scale changes in coral calcification over the last several decades, it is not possible to unequivocally link these results to ocean acidification due to confounding factors of temperature and other environmental parameters. Here, we quantified the calcification response of a coral reef flat to alkalinity enrichment to test whether reef calcification increases when ocean chemistry is restored to near pre-industrial conditions. We used sodium hydroxide (NaOH) to increase the total alkalinity of seawater flowing over a reef flat, with the aim of increasing carbonate ion concentrations [CO32-] and the aragonite saturation state (Ωarag) to values that would have been attained under pre-industrial atmospheric pCO2 levels. We developed a dual tracer regression method to estimate alkalinity uptake (i.e., calcification) in response to alkalinity enrichment. This approach uses the change in ratios between a non-conservative tracer (alkalinity) and a conservative tracer (a non-reactive dye, Rhodamine WT) to assess the fraction of added alkalinity that is taken up by the reef as a result of an induced increase in calcification rate. Using this method, we estimate that an average of 17.3% ± 2.3% of the added alkalinity was taken up by the reef community. In providing results from the first seawater chemistry manipulation experiment performed on a natural coral reef community (without artificial confinement), we demonstrate that, upon increase of [CO32-] and Ωarag to near pre-industrial values, reef calcification increases. Thus, we conclude that, the impacts of ocean acidification are already being felt by coral reefs. This work is the culmination of years of work in the Caldeira lab at the Carnegie Institution for Science, involving many people including Jack Silverman, Kenny Schneider, and Jana Maclaren.

  15. 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. PMID:26909578

  16. 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.

  17. The association of bone and osteoclasts with vascular calcification.

    PubMed

    Han, Kum Hyun; Hennigar, Randolph A; O'Neill, W Charles

    2015-12-01

    The presence of bone tissue in calcified arteries may provide insights into the pathophysiology and potential reversibility of calcification, but the prevalence, distribution, and determinants of bone and osteoclasts in calcified arteries are unknown. Specimens of 386 arteries from lower limb amputations in 108 patients were examined retrospectively. Calcification was present in 282 arteries from 89 patients, which was medial in 64%, intimal in 9%, and both in 27%. Bone was present in 6% of arteries, essentially all of which were heavily calcified. Multiple sampling revealed that the true prevalence of bone in heavily calcified arteries was 25%. Bone was more common in medial rather than intimal calcifications (10% vs 3%, p=0.03) but did not vary with artery location (above vs below the knee). Heavily calcified arteries with bone were more likely to come from patients who were older (p=0.04), had diabetes (p=0.06), or were receiving warfarin (p=0.06), but there was no association with gender or renal failure. Bone was almost always adjacent to calcifications, along the periphery, but never within. Staining for the bone-specific proteins osteocalcin and osterix was noted in 20% and 45% of heavily calcified arteries without visible bone. Osteoclasts were present in 4.9% of arteries, all of which were heavily calcified and most of which contained bone. The frequent absence of bone in heavily calcified vessels and the histologic pattern strongly suggests a secondary rather than primary event. Recruitment of osteoclasts to vascular calcifications can occur but is rare, suggesting a limited capacity to reverse calcifications.

  18. Early detection of ocean acidification effects on marine calcification

    SciTech Connect

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

    2009-02-19

    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 TA 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.

  19. 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.

  20. [Mechanism of losartan suppressing vascular calcification in rat aortic artery].

    PubMed

    Shao, Juan; Wu, Panfeng; Wu, Jiliang; Li, Mincai

    2016-08-01

    Objective To investigate the effect of the angiotensin II receptor 1 (AT1R) blocker losartan on vascular calcification in rat aortic artery and explore the underlying mechanisms. Methods SD rats were divided randomly into control group, vascular calcification model group and treatment group. Vascular calcification models were made by subcutaneous injection of warfarin plus vitamin K1 for two weeks. Rats in the treatment group were subcutaneously injected with losartan (10 mg/kg) at the end of the first week and consecutively for one week. We observed the morphological changes by HE staining and the calcium deposition by Alizarin red staining in the artery vascular wall. The mRNA expressions of bone morphogenetic protein 2 (BMP2) and Runt-related transcription factor 2 (RUNX2) were analyzed by reverse transcription PCR. The BMP2 and RUNX2 protein expressions were determined by Western blotting. The apoptosis of smooth muscle cells (SMCs) were detected by TUNEL. The AT1R expression was tested by fluorescent immunohistochemistry. Results The aortic vascular calcification was induced by warfarin and vitamin K1. Compared with the vascular calcification model group, the mRNA and protein expressions of BMP2 and RUNX2 were significantly downregulated in the aorta in the losartan treatment group. Furthermore, the apoptosis of SMCs and the AT1R expression obviously decreased. Conclusion AT1R blocker losartan inhibits the apoptosis of SMCs and reduces AT1R expression; it downregulates the BMP2 and RUNX2 expressions in the vascular calcification process. PMID:27412937

  1. Clinical Practice Guidelines for the Management of Atypical Hemolytic Uremic Syndrome in Korea

    PubMed Central

    2016-01-01

    Atypical hemolytic uremic syndrome (aHUS) is a rare syndrome characterized by micro-angiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. The major pathogenesis of aHUS involves dysregulation of the complement system. Eculizumab, which blocks complement C5 activation, has recently been proven as an effective agent. Delayed diagnosis and treatment of aHUS can cause death or end-stage renal disease. Therefore, a diagnosis that differentiates aHUS from other forms of thrombotic microangiopathy is very important for appropriate management. These guidelines aim to offer recommendations for the diagnosis and treatment of patients with aHUS in Korea. The guidelines have largely been adopted from the current guidelines due to the lack of evidence concerning the Korean population. PMID:27550478

  2. Hemolytic uremic syndrome due to gemcitabine in a young woman with cholangiocarcinoma.

    PubMed

    Nieto-Ríos, John Fredy; Zuluaga-Quintero, Mónica; Higuita, Lina Maria Serna; Rincón, Cristian Ivan García; Galvez-Cárdenas, Kenny Mauricio; Ocampo-Kohn, Catalina; Aristizabal-Alzate, Arbey; Florez-Vargas, Adriana Alejandra; Zuluaga-Valencia, Gustavo Adolfo

    2016-06-01

    Gemcitabine is a medication used to treat various types of malignant neoplasms. Its association with hemolytic uremic syndrome (HUS) has been described in few cases, although these cases have resulted in mortality rates of at least 50%. We report on the case of a 25-year-old patient with cholangiocarcinoma in remission who developed microangiopathic hemolytic anemia with acute anuric renal failure after receiving 5 cycles of gemcitabine chemotherapy; this condition was consistent with HUS caused by the side effects of this drug. The administration of gemcitabine was stopped, and hemodialysis, blood transfusions, plasma exchanges, steroids, doxycycline, and rituximab were used to treat the patient. A favorable outcome was achieved; in particular, hemolysis was controlled, and renal function was completely recovered. PMID:27438981

  3. Role of polymorphonuclear leukocytes in the pathophysiology of typical hemolytic uremic syndrome.

    PubMed

    Exeni, Ramón A; Fernández, Gabriela C; Palermo, Marina S

    2007-08-10

    Thrombotic microangiopathy and acute renal failure are cardinal features of post-diarrheal hemolytic uremic syndrome (HUS). These conditions are related to endothelial and epithelial cell damage induced by Shiga toxin (Stx), through an interaction with its globotriaosylceramide (Gb3) receptor. Although, Stx is the main pathogenic factor and necessary for HUS development, clinical and experimental evidence suggest that the inflammatory response is able to potentiate Stx toxicity. Lipopolysaccharides (LPS) and neutrophils (PMN) represent two central components of inflammation during a Gram-negative infection. In this regard, patients with high peripheral PMN counts at presentation have a poor prognosis. In the present review, we discuss the contribution of experimental models and patient's studies in an attempt to elucidate the pathogenic mechanisms of HUS.

  4. Impaired antioxidant defense mechanisms in two children with hemolytic-uremic syndrome.

    PubMed

    Li Volti, S; Di Giacomo, C; Garozzo, R; Campisi, A; Mollica, F; Vanella, A

    1993-01-01

    In the present study we have assayed antioxidant enzymatic activities of SOD, CAT, GSH-Px, GSH-Red, and G6PD in erythrocytes from two children with hemolytic-uremic syndrome (HUS) during the acute phase of the disease and after their recovery; in addition, we have tested the percentage of hemolysis after 24-h incubation in PBS containing glucose (1 g/1000 mL) or in the presence of their own plasma. Endogenous plasmatic MDA levels were also evaluated as lipid peroxidation marker. A significant decrease in SOD activity was found in erythrocytes from HUS patients, and the addition of their own plasma further decreased SOD activity. Elevated percentage of hemolysis was found in HUS patients when RBCs were incubated in their own plasma; this last effect was less evident in PBS + glucose.

  5. Incomplete hemolytic-uremic syndrome in Argentinean children with bloody diarrhea.

    PubMed

    López, E L; Contrini, M M; Devoto, S; de Rosa, M F; Graña, M G; Aversa, L; Gómez, H F; Genero, M H; Cleary, T G

    1995-09-01

    Argentina has an exceptionally high frequency of hemolytic-uremic syndrome (HUS). We sought to define prospectively the role of verocytotoxins (Shiga-like toxins [SLTs]) in 254 Argentinean children with grossly bloody diarrhea during spring and summer. Free fecal SLTs (I/II) and/or DNA probe-positive isolates were found in 99 (39%) of the children. During the follow-up period, HUS developed in 6 patients (4 with evidence of recent SLT infection based on stool studies); another 14 patients had some, but not all, of the abnormalities seen in typical HUS. The development of HUS or incomplete HUS in these children was significantly associated with recent SLT-Escherichia coli infection (p = 0.024). The high incidence of SLT-associated bloody diarrhea in Argentina explains, at least partially, the unusually high frequency of HUS. Our data indicate that incomplete forms of HUS may be common in patients with SLT-associated bloody diarrhea.

  6. Clinical Practice Guidelines for the Management of Atypical Hemolytic Uremic Syndrome in Korea.

    PubMed

    Cheong, Hae Il; Jo, Sang Kyung; Yoon, Sung Soo; Cho, Heeyeon; Kim, Jin Seok; Kim, Young Ok; Koo, Ja Ryong; Park, Yong; Park, Young Seo; Shin, Jae Il; Yoo, Kee Hwan; Oh, Doyeun

    2016-10-01

    Atypical hemolytic uremic syndrome (aHUS) is a rare syndrome characterized by micro-angiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. The major pathogenesis of aHUS involves dysregulation of the complement system. Eculizumab, which blocks complement C5 activation, has recently been proven as an effective agent. Delayed diagnosis and treatment of aHUS can cause death or end-stage renal disease. Therefore, a diagnosis that differentiates aHUS from other forms of thrombotic microangiopathy is very important for appropriate management. These guidelines aim to offer recommendations for the diagnosis and treatment of patients with aHUS in Korea. The guidelines have largely been adopted from the current guidelines due to the lack of evidence concerning the Korean population. PMID:27550478

  7. Vero cytotoxin binding to polymorphonuclear leukocytes among households with children with hemolytic uremic syndrome.

    PubMed

    te Loo, D M; Heuvelink, A E; de Boer, E; Nauta, J; van der Walle, J; Schröder, C; van Hinsbergh, V W; Chart, H; van de Kar, N C; van den Heuvel, L P

    2001-08-15

    Hemolytic uremic syndrome (HUS), the leading cause of acute renal failure in childhood, can be caused by different serotypes of vero cytotoxin (VT; i.e., Shiga toxin)-producing Escherichia coli (VTEC). Recently, VT was shown to bind to polymorphonuclear leukocytes (PMNL) in the systemic circulation of patients with HUS. This study investigated whether VT bound to PMNL could be detected in persons in households with patients with HUS. Serum antibodies against E. coli O157 and, when available, fecal samples from patients with HUS and household members were studied for the presence of VTEC infection. The circulating PMNL of 82% of the household members were positive for VT, whereas stool and/or serum examination showed only 21% positivity. Thus, current methods underestimate the number of infected persons in households with patients with HUS.

  8. Dexmedetomidine controls twitch-convulsive syndrome in the course of uremic encephalopathy.

    PubMed

    Nomoto, Koichi; Scurlock, Corey; Bronster, David

    2011-12-01

    An 85 year old man with a history of chronic renal insufficiency was admitted to the cardiothoracic intensive care unit after aortic valve replacement. His postoperative course was marked by acute oliguric renal failure for high blood urea nitrogen (BUN) and acute hyperactive delirium. At this time he also developed tremors with muscle twitching; he received no other form of sedatives. A neurology consult made the diagnosis of twitch-convulsive syndrome associated with uremic encephalopathy. While the patient was receiving the dexmedetomidine infusion, the signs of the twitch-convulsive syndrome, particularly the twitching and tremors, disappeared. Within 30 minutes of the end of the dexmedetomidine infusion, symptoms of the twitch-convulsive syndrome returned, manifesting as acute tremulousness. After several dialysis treatments, his BUN decreased and the dexmedetomidine was weaned, without return of the symptoms of twitch-convulsive syndrome. PMID:22137518

  9. Symmetrical infantile thalamic degeneration with focal cytoplasmic calcification.

    PubMed

    Ambler, M; O'Neil, W

    1975-10-27

    Infantile thalamic degeneration is a rare clinico-pathological entity. Restricted location of the lesion and peculiar cytopathological changes serve to distinguish this disorder from other common encephalopathies. Optical and ultrastructural studies demonstrate cytoplasmic calcopherules in previously viable cells. According to current concepts of acute cellular reactions to injury and mechanism of intracellular calcification, the cytological changes cannot be attributed to either hypoxic ischemic cell change or dystrophic calcification. By analogy to other human and pathological material, the most likely basis for nondystrophic calcopherule formation is toxic or infectious injury with local synthesis, or autophagic or phagolysosomal degradation of cellular debris of specific chemical composition favoring calcium deposition.

  10. 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.

  11. Is Fluorescence Valid to Monitor Removal of Protein Bound Uremic Solutes in Dialysis?

    PubMed Central

    Luman, Merike; Uhlin, Fredrik; Tanner, Risto; Fridolin, Ivo

    2016-01-01

    The aim of this study was to evaluate the contribution and removal dynamics of the main fluorophores during dialysis by analyzing the spent dialysate samples to prove the hypothesis whether the fluorescence of spent dialysate can be utilized for monitoring removal of any of the protein bound uremic solute. A high performance liquid chromatography system was used to separate and quantify fluorophoric solutes in the spent dialysate sampled at the start and the end of 99 dialysis sessions, including 57 hemodialysis and 42 hemodiafiltration treatments. Fluorescence was acquired at excitation 280 nm and emission 360 nm. The main fluorophores found in samples were identified as indole derivatives: tryptophan, indoxyl glucuronide, indoxyl sulfate, 5-hydroxy-indoleacetic acid, indoleacetyl glutamine, and indoleacetic acid. The highest contribution (35 ± 11%) was found to arise from indoxyl sulfate. Strong correlation between contribution values at the start and end of dialysis (R2 = 0.90) indicated to the stable contribution during the course of the dialysis. The reduction ratio of indoxyl sulfate was very close to the decrease of the total fluorescence signal of the spent dialysate (49 ± 14% vs 51 ± 13% respectively, P = 0.30, N = 99) and there was strong correlation between these reduction ratio values (R2 = 0.86). On-line fluorescence measurements were carried out to illustrate the technological possibility for real-time dialysis fluorescence monitoring reflecting the removal of the main fluorophores from blood into spent dialysate. In summary, since a predominant part of the fluorescence signal at excitation 280 nm and emission 360 nm in the spent dialysate originates from protein bound derivatives of indoles, metabolites of tryptophan and indole, the fluorescence signal at this wavelength region has high potential to be utilized for monitoring the removal of slowly dialyzed uremic toxin indoxyl sulfate. PMID:27228162

  12. Trabecular bone volume and osteoprotegerin expression in uremic rats given high calcium.

    PubMed

    Rianthavorn, Pornpimol; Ettenger, Robert B; Salusky, Isidro B; Kuizon, Beatriz D

    2010-11-01

    Calcium (Ca)-containing phosphate binders have been recommended for the treatment of hyperphosphatemia in children with chronic kidney disease. To study the effects of high Ca levels on trabecular bone volume (BV) and osteoprotegerin (OPG) expression in uremic young rats, a model of marked overcorrection of secondary hyperparathyroidism was created by providing a diet of high Ca to 5/6 nephrectomized young rats (Nx-Ca) for 4 weeks. The results of chondrocyte proliferation and apoptosis, osteoclastic activity, OPG expression and BV were compared among intact rats given the control diet, intact rats given a high Ca diet and 5/6 nephrectomized rats given the control diet (Nx-Control) and the high Ca diet (Nx-Ca). Ionized Ca levels were higher and parathyroid hormone levels were lower in Nx-Ca rats than in the other groups. Final weight, final length and final tibial length of Nx-Ca rats were significantly less than those of the other groups, although the length gain did not differ among the groups. The hypertrophic zone width was markedly enlarged in Nx-Ca rats. Chondrocyte proliferation rates did not differ among the groups, whereas osteoclastic activity was decreased in Nx-Ca rats compared with the Nx-Control animals. The OPG expression and BV were increased in Nx-Ca rats compared with the Nx-Control rats. Increased BV should improve bone strength, whereas disturbance of osteoclastogenesis interferes with bone remodeling. Bone quality has yet to be determined in high Ca-fed uremic young rats.

  13. Depletion of reactive advanced glycation endproducts from diabetic uremic sera using a lysozyme-linked matrix.

    PubMed Central

    Mitsuhashi, T; Li, Y M; Fishbane, S; Vlassara, H

    1997-01-01

    Diabetic uremic sera contain excessive amounts of reactive advanced glycation endproducts (AGEs), which accelerate the vasculopathy of diabetes and end-stage renal disease. To capture in vivo-derived toxic AGEs, high affinity AGE-binding protein lysozyme (LZ) was linked to a Sepharose 4B matrix. Initial studies showed that > 80% of 125I-AGE-BSA was retained by the LZ matrix, compared with < 10% retained by a control matrix. More than 60% of AGE-lysine was captured by the LZ matrix, and the LZ-bound fraction retained immunoreactivity and cross-linking activity, but had little intrinsic fluorescence (370/440 nm). After passage through the LZ matrix, AGE levels in diabetic sera (0.37+/-0.04 U/mg) were significantly reduced to a level (0.09+/-0.01 U/mg; n = 10; P < 0. 0001) comparable with the level of normal human serum, whereas total protein absorption was < 3%. The AGE-enriched serum fraction exhibited cross-linking activity, which was completely prevented by aminoguanidine. Among numerous LZ-bound proteins in diabetic uremic sera, three major proteins "susceptible" to AGE modification were identified: the immunoglobulin G light chain, apolipoprotein J (clusterin/SP-40,40), and the complement 3b beta chain. These findings indicate that the LZ-linked AGE affinity column may serve as an efficient method for the depletion of toxic AGEs from sera, including specific AGE-modified proteins that may be linked to altered immunity, lipoprotein metabolism, and accelerated vasculopathy in renal failure patients with or without diabetes. PMID:9259584

  14. Neonatal hemolytic uremic syndrome after mother-to-child transmission of a low-pathogenic stx2b harboring shiga toxin-producing Escherichia coli.

    PubMed

    Stritt, Andrea; Tschumi, Sibylle; Kottanattu, Lisa; Bucher, Barbara S; Steinmann, Markus; von Steiger, Niklaus; Stephan, Roger; Hächler, Herbert; Simonetti, Giacomo D

    2013-01-01

    This case describes evidence for a Shiga toxin-producing Escherichia coli (STEC) O146:H28 infection leading to hemolytic uremic syndrome in a neonate. STEC O146:H28 was linked hitherto with asymptomatic carriage in humans. Based on strain characteristics and genotyping data, the mother is a healthy carrier who transmitted the STEC during delivery. STEC strains belonging to the low-pathogenic STEC group must also be considered in the workup of neonatal hemolytic uremic syndrome.

  15. Intracranial physiological calcifications in adults on computed tomography in Tabriz, Iran.

    PubMed

    Daghighi, M H; Rezaei, V; Zarrintan, S; Pourfathi, H

    2007-05-01

    Intracranial physiological calcifications are unaccompanied by any evidence of disease and have no demonstrable pathological cause. They are often due to calcium and sometimes iron deposition in the blood vessels of different structures of the brain. Computed tomography (CT) is the most sensitive means of detection of these calcifications. The aim of this study was the assessment of intracranial physiological calcifications in adults. We studied 1569 cases ranging in age from 15 to 85 in Tabriz Imam Khomeini Hospital, Iran. These patients had a history of head trauma and their CT scan did not show any evidence of pathological findings. The structures evaluated consisted of (A) the pineal gland, (B) the choroid plexus, (C) the habenula, (D) the basal ganglia, (E) the tentorium cerebelli, sagittal sinus and falx cerebri, (F) vessels and (G) lens and other structures which could be calcified. Of the 1569 subjects, 71.0% had pineal calcification, 66.2% had choroid plexus calcification, 20.1% had habenular calcification, 7.3% had tentorium cerebelli, sagittal sinus or falx cerebri calcifications, 6.6% had vascular calcification, 0.8% had basal ganglia calcification and 0.9% had lens and other non-defined calcifications. In general, the frequency of intracranial physiological calcifications was greater in men than in women. All types of calcification increased at older ages except for lens and other non-defined calcifications. We evaluated all the cranial structures and determined percentages for all types of intracranial physiological calcification. These statistics can be used for comparing physiological and pathological intracranial calcifications. Moreover, these statistics may be of interest from the clinical perspective and are potentially of clinical use. PMID:17594669

  16. Intracerebral metaplastic meningioma with prominent ossification and extensive calcification

    PubMed Central

    Huang, Jingxiang; Petersson, Fredrik

    2011-01-01

    We present a patient (male 26 years) with a short history of recurrent seizures induced by a largely intracerebrally located frontal lobe meningioma. The tumor displayed a heretofore unpublished combination of extensive metaplastic bone formation and prominent non-psammomatous calcifications with focal chicken-wire pattern. PMID:21769319

  17. 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

  18. 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

  19. [Vascular calcifications, the hidden side effects of vitamin K antagonists].

    PubMed

    Bennis, Youssef; Vengadessane, Subashini; Bodeau, Sandra; Gras, Valérie; Bricca, Giampiero; Kamel, Saïd; Liabeuf, Sophie

    2016-09-01

    Despite the availability of new oral anticoagulants, vitamin K antagonists (VKA, such as fluindione, acenocoumarol or warfarin) remain currently the goal standard medicines for oral prevention or treatment of thromboembolic disorders. They inhibit the cycle of the vitamin K and its participation in the enzymatic gamma-carboxylation of many proteins. The VKA prevent the activation of the vitamin K-dependent blood clotting factors limiting thus the initiation of the coagulation cascade. But other proteins are vitamin K-dependent and also remain inactive in the presence of VKA. This is the case of matrix Gla-protein (MGP), a protein that plays a major inhibitory role in the development of vascular calcifications. Several experimental and epidemiological results suggest that the use of the VKA could promote the development of vascular calcifications increasing thus the cardiovascular risk. This risk seems to be higher in patients with chronic kidney disease or mellitus diabetes who are more likely to develop vascular calcifications, and may be due to a decrease of the MGP activity. This review aims at summarizing the data currently available making vascular calcifications the probably underestimated side effects of VKA.

  20. Endothelial microparticles mediate inflammation-induced vascular calcification.

    PubMed

    Buendía, Paula; Montes de Oca, Addy; Madueño, Juan Antonio; Merino, Ana; Martín-Malo, Alejandro; Aljama, Pedro; Ramírez, Rafael; Rodríguez, Mariano; Carracedo, Julia

    2015-01-01

    Stimulation of endothelial cells (ECs) with TNF-α causes an increase in the expression of bone morphogenetic protein-2 (BMP-2) and the production of endothelial microparticles (EMPs). BMP-2 is known to produce osteogenic differentiation of vascular smooth muscle cells (VSMCs). It was found that EMPs from TNF-α-stimulated endothelial cells (HUVECs) contained a significant amount of BMP-2 and were able to enhance VSMC osteogenesis and calcification. Calcium content was greater in VSMCs exposed to EMPs from TNF-α-treated HUVECs than EMPs from nontreated HUVECs (3.56 ± 0.57 vs. 1.48 ± 0.56 µg/mg protein; P < 0.05). The increase in calcification was accompanied by up-regulation of Cbfa1 (osteogenic transcription factor) and down-regulation of SM22α (VSMC lineage marker). Inhibition of BMP-2 by small interfering RNA reduced the VSMC calcification induced by EMPs from TNF-α-treated HUVECs. Similar osteogenic capability was observed in EMPs from both patients with chronic kidney disease and senescent cells, which also presented a high level of BMP-2 expression. Labeling of EMPs with CellTracker shows that EMPs are phagocytized by VSMCs under all conditions (with or without high phosphate, control, and EMPs from TNF-α-treated HUVECs). Our data suggest that EC damage results in the release of EMPs with a high content of calcium and BMP-2 that are able to induce calcification and osteogenic differentiation of VSMCs.

  1. Severe prostatic calcification after radiation therapy for cancer.

    PubMed

    Jones, W A; Miller, E V; Sullivan, L D; Chapman, W H

    1979-06-01

    Severe symptomatic prostatic calcification was seen in 3 patients who had carcinoma of the prostate treated initially with transurethral resection, followed in 2 to 4 weeks by definitive radiation therapy. This complication is probably preventable if an interval of 6 weeks is allowed between transurethral resection of the prostate and radiation therapy.

  2. 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.

  3. Vascular diseases: aortitis, aortic aneurysms, and vascular calcification.

    PubMed

    Ladich, Elena; Yahagi, Kazuyuki; Romero, Maria E; Virmani, Renu

    2016-01-01

    Inflammatory diseases of the aorta broadly include noninfectious and infectious aortitis, periaortitis, atherosclerosis, and inflammatory atherosclerotic aneurysms. Aortitis is uncommon but is increasingly recognized as an important cause of aortic aneurysms and dissections. Abdominal (AAA) and thoracic aortic aneurysms (TAA) have different pathologies and etiologies. AAAs are the most common type of aortic aneurysm, and the vast majority of these are atherosclerotic. The causes of TAA vary depending on the site of involvement, but medial degeneration is a common pathologic substrate, regardless of etiology, and genetic influences play a prominent role in TAA expression. Standardized classification schemes for inflammatory and degenerative diseases of the aorta have only recently been added to the pathology literature. A brief overview of the new histopathologic classifications for aortic inflammatory and degenerative diseases has recently been published by the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology as a consensus document on the surgical pathology of the aorta. Vascular calcification is a highly regulated biologic process, and the mechanisms leading to vascular calcification are under investigation. Calcification may occur in the intima (atherosclerotic) or in the media secondary to metabolic disease. Rarely, vascular calcification may be associated with genetic disorders. PMID:27526100

  4. Endothelial microparticles mediate inflammation-induced vascular calcification.

    PubMed

    Buendía, Paula; Montes de Oca, Addy; Madueño, Juan Antonio; Merino, Ana; Martín-Malo, Alejandro; Aljama, Pedro; Ramírez, Rafael; Rodríguez, Mariano; Carracedo, Julia

    2015-01-01

    Stimulation of endothelial cells (ECs) with TNF-α causes an increase in the expression of bone morphogenetic protein-2 (BMP-2) and the production of endothelial microparticles (EMPs). BMP-2 is known to produce osteogenic differentiation of vascular smooth muscle cells (VSMCs). It was found that EMPs from TNF-α-stimulated endothelial cells (HUVECs) contained a significant amount of BMP-2 and were able to enhance VSMC osteogenesis and calcification. Calcium content was greater in VSMCs exposed to EMPs from TNF-α-treated HUVECs than EMPs from nontreated HUVECs (3.56 ± 0.57 vs. 1.48 ± 0.56 µg/mg protein; P < 0.05). The increase in calcification was accompanied by up-regulation of Cbfa1 (osteogenic transcription factor) and down-regulation of SM22α (VSMC lineage marker). Inhibition of BMP-2 by small interfering RNA reduced the VSMC calcification induced by EMPs from TNF-α-treated HUVECs. Similar osteogenic capability was observed in EMPs from both patients with chronic kidney disease and senescent cells, which also presented a high level of BMP-2 expression. Labeling of EMPs with CellTracker shows that EMPs are phagocytized by VSMCs under all conditions (with or without high phosphate, control, and EMPs from TNF-α-treated HUVECs). Our data suggest that EC damage results in the release of EMPs with a high content of calcium and BMP-2 that are able to induce calcification and osteogenic differentiation of VSMCs. PMID:25342130

  5. Metastatic calcification of the stomach imaged on a bone scan

    SciTech Connect

    Goldstein, R.; Ryo, U.Y.; Pinsky, S.M.

    1984-10-01

    A whole body bone scan obtained on a 21-year-old woman with sickle cell disease and chronic renal failure showed localization of the radionuclide diffusely in the stomach. The localization of the radionuclide represented metastatic calcification of the stomach caused by secondary hyperparathyroidism.

  6. Familial idiopathic basal ganglia calcification (Fahr’s disease)

    PubMed Central

    Mufaddel, Amir A.; Al-Hassani, Ghanem A.

    2014-01-01

    Familial idiopathic basal ganglia calcification (Fahr’s disease) is a rare neurodegenerative disorder characterized by symmetrical and bilateral calcification of the basal ganglia. Calcifications may also occur in other brain regions such as dentate nucleus, thalamus, and cerebral cortex. Both familial and non-familial cases of Fahr’s disease have been reported, predominantly with autosomal-dominant fashion. The disease has a wide range of clinical presentations, predominantly with neuropsychiatric features and movement disorders. Psychiatric features reported in the literature include: cognitive impairment, depression, hallucinations, delusions, manic symptoms, anxiety, schizophrenia-like psychosis, and personality change. Other clinical features include: Parkinsonism, ataxia, headache, seizures, vertigo, stroke-like events, orthostatic hypotension, tremor, dysarthria, and paresis. Fahr’s disease should be considered in the differential diagnosis of psychiatric symptoms, particularly when associated with movement disorder. The disease should be differentiated from other conditions that can cause intracranial calcification. No specific treatment is currently available. Further research is needed to bridge the gap existing in our current knowledge of the prevalence, etiology, symptoms, and treatment of Fahr’s disease. PMID:24983277

  7. Familial idiopathic basal ganglia calcification (Fahr`s disease).

    PubMed

    Mufaddel, Amir A; Al-Hassani, Ghanem A

    2014-07-01

    Familial idiopathic basal ganglia calcification (Fahr`s disease) is a rare neurodegenerative disorder characterized by symmetrical and bilateral calcification of the basal ganglia. Calcifications may also occur in other brain regions such as dentate nucleus, thalamus, and cerebral cortex. Both familial and non-familial cases of Fahr`s disease have been reported, predominantly with autosomal-dominant fashion. The disease has a wide range of clinical presentations, predominantly with neuropsychiatric features and movement disorders. Psychiatric features reported in the literature include: cognitive impairment, depression, hallucinations, delusions, manic symptoms, anxiety, schizophrenia-like psychosis, and personality change. Other clinical features include: Parkinsonism, ataxia, headache, seizures, vertigo, stroke-like events, orthostatic hypotension, tremor, dysarthria, and paresis. Fahr`s disease should be considered in the differential diagnosis of psychiatric symptoms, particularly when associated with movement disorder. The disease should be differentiated from other conditions that can cause intracranial calcification. No specific treatment is currently available. Further research is needed to bridge the gap existing in our current knowledge of the prevalence, etiology, symptoms, and treatment of Fahr`s disease.

  8. Isolation and Culture of Aortic Smooth Muscle Cells and In Vitro Calcification Assay.

    PubMed

    Villa-Bellosta, Ricardo; Hamczyk, Magda R

    2015-01-01

    Elevated serum phosphorus is a major risk factor for vascular calcification, which is characterized by the presence of calcium phosphate deposits, mainly hydroxyapatite crystals. In vitro studies of phosphate-induced calcification show that vascular smooth muscle cells undergo calcification with features similar to those observed in pathological vascular calcification in vivo, including the presence of hydroxyapatite crystals. Here, we describe the double-collagenase digestion method for isolating vascular smooth muscle cells from aorta, and a method for inducing calcification in vitro using high phosphate concentration.

  9. Evaluation of regional cerebral blood flow in patient with atypical senile dementia with asymmetrical calcification.

    PubMed

    Shoyama, Masaru; Ukai, Satoshi; Shinosaki, Kazuhiro

    2015-12-01

    We report an 83-year-old woman with atypical senile dementia with Fahr-type calcification. Brain computed tomography demonstrated asymmetrical calcification predominant in the basal ganglia on the right side and pronounced diffuse cortical atrophy in the frontotemporal areas. The patient was clinically diagnosed with diffuse neurofibrillary tangles with calcification. Brain single photon emission computed tomography findings revealed that cerebral blood flow was reduced on the right side, as compared with the left side, in widespread areas. Hemispheric asymmetry in both calcification and cerebral blood flow suggests a relationship between calcification and vascular changes. PMID:25737312

  10. 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.

  11. Molecular determinants of vascular calcification: a bench to bedside view.

    PubMed

    Dellegrottaglie, S; Sanz, J; Rajagopalan, S

    2006-08-01

    Vascular calcification (VC) is an orchestrated event, evoking the programmed process of the osteogenesis and triggered by inflammatory cytokines active at vascular level. VC is a dynamic process in which the vessel wall intima, media and also cardiac valves may be involved. Intimal calcification is an endochondral ossification process in which type II collagen is mineralized by calcium deposition. In contrast, an intra-membranous ossification process leads to medial calcification, while a dystrophic calcification process is responsible for valvular calcification. Mechanisms involved in VC may be summarized as: 1. Activation of osteogenesis in the vessel wall, 2. Loss of inhibitory factors, 3. Enhanced bone turnover, and 4. Abnormalities in mineral metabolism. The signaling axis constituted by osteoprotegerin (OPG), receptor activator nuclear factor kB (RANK) and its ligand (RANKL), along with the monocyte colony stimulating factor (M-CSF) and the transcription factor core Binding protein (Cbfa-1), play a pivotal role in the control of VC. In contrast, fetuin-A, matrix G1a protein (MGP) and osteopontin (OPN) control the inhibition of VC. In addition, abnormal mineral metabolism with enhanced phosphates availability favors calcium deposition. The inflammatory cytokines interleukin (IL-1) and tumor necrosis factor (TNF)-alpha enhance OPG and RANKL function in the vessel wall leading to VC. VC is a controlled process, depending on the balance between osteoblastic and osteoclastic influences and further modulated by the influence of risk factors like diabetes, smoking, age, hypertension and dyslipidemia. Recent advances in diagnostic tools such as with multi-detector computed tomography (MDCT) and electron beam computed tomography (EBCT), may help diagnosis and delineation of VC in the clinical setting and aid in understanding its prognostic value. PMID:16918372

  12. The role of vitamin K in soft-tissue calcification.

    PubMed

    Theuwissen, Elke; Smit, Egbert; Vermeer, Cees

    2012-03-01

    Seventeen vitamin K-dependent proteins have been identified to date of which several are involved in regulating soft-tissue calcification. Osteocalcin, matrix Gla protein (MGP), and possibly Gla-rich protein are all inhibitors of soft-tissue calcification and need vitamin K-dependent carboxylation for activity. A common characteristic is their low molecular weight, and it has been postulated that their small size is essential for calcification inhibition within tissues. MGP is synthesized by vascular smooth muscle cells and is the most important inhibitor of arterial mineralization currently known. Remarkably, the extrahepatic Gla proteins mentioned are only partly carboxylated in the healthy adult population, suggesting vitamin K insufficiency. Because carboxylation of the most essential Gla proteins is localized in the liver and that of the less essential Gla proteins in the extrahepatic tissues, a transport system has evolved ensuring preferential distribution of dietary vitamin K to the liver when vitamin K is limiting. This is why the first signs of vitamin K insufficiency are seen as undercarboxylation of the extrahepatic Gla proteins. New conformation-specific assays for circulating uncarboxylated MGP were developed; an assay for desphospho-uncarboxylated matrix Gla protein and another assay for total uncarboxylated matrix Gla protein. Circulating desphospho-uncarboxylated matrix Gla protein was found to be predictive of cardiovascular risk and mortality, whereas circulating total uncarboxylated matrix Gla protein was associated with the extent of prevalent arterial calcification. Vitamin K intervention studies have shown that MGP carboxylation can be increased dose dependently, but thus far only 1 study with clinical endpoints has been completed. This study showed maintenance of vascular elasticity during a 3-y supplementation period, with a parallel 12% loss of elasticity in the placebo group. More studies, both in healthy subjects and in patients at risk

  13. Mammographic calcification cluster detection and threshold gold thickness measurements

    NASA Astrophysics Data System (ADS)

    Warren, L. M.; Mackenzie, A.; Cooke, J.; Given-Wilson, R.; Wallis, M. G.; Chakraborty, D. P.; Dance, D. R.; Young, K. C.

    2012-03-01

    European Guidelines for quality control in digital mammography specify acceptable and achievable standards of image quality (IQ) in terms of threshold gold thickness using the CDMAM test object. However, there is little evidence relating such measurements to cancer detection. This work investigated the relationship between calcification detection and threshold gold thickness. An observer study was performed using a set of 162 amorphous selenium direct digital (DR) detector images (81 no cancer and 81 with 1-3 inserted calcification clusters). From these images four additional IQs were simulated: different digital detectors (computed radiography (CR) and DR) and dose levels. Seven observers marked and rated the locations of suspicious regions. DBM analysis of variances was performed on the JAFROC figure of merit (FoM) yielding 95% confidence intervals for IQ pairs. Automated threshold gold thickness (Tg) analysis was performed for the 0.25mm gold disc diameter on CDMAM images at the same IQs (16 images per IQ). Tg was plotted against FoM and a power law fitted to the data. There was a significant reduction in FoM for calcification detection for CR images compared with DR; FoM decreased from 0.83 to 0.63 (p<=0.0001). Detection was also sensitive to dose. There was a good correlation between FoM and Tg (R2=0.80, p<0.05), consequently threshold gold thickness was a good predictor of calcification detection at the same IQ. Since the majority of threshold gold thicknesses for the various IQs were above the acceptable standard despite large variations in calcification detection by radiologists, current EU guidelines may need revising.

  14. 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.

  15. Acute encephalopathy associated with hemolytic uremic syndrome caused by Escherichia coli O157: H7 and rotavirus infection.

    PubMed

    Imataka, G; Wake, K; Suzuki, M; Yamanouchi, H; Arisaka, O

    2015-05-01

    We reported a case of a 22-months child with hemolytic uremic syndrome associated with encephalopathy. As the cause of this case, the involvements of verotoxin 1 and 2 caused by O157: the H7 strain of the enterohemorrhagic Escherichia coli and rotavirus were presumed. We administered brain hypothermic therapy and steroid pulse therapy in the intensive care unit, but we were not able to save his life and the child died on the 6th day from the onset.

  16. Detection of Calcifications In Vivo and Ex Vivo After Brain Injury in Rat Using SWIFT

    PubMed Central

    Lehto, Lauri Juhani; Sierra, Alejandra; Corum, Curtis Andrew; Zhang, Jinjin; Idiyatullin, Djaudat; Pitkänen, Asla; Garwood, Michael; Gröhn, Olli

    2012-01-01

    Calcifications represent one component of pathology in many brain diseases. With MRI, they are most often detected by exploiting negative contrast in magnitude images. Calcifications are more diamagnetic than tissue, leading to a magnetic field disturbance that can be seen in phase MR images. Most phase imaging studies use gradient recalled echo based pulse sequences. Here, the phase component of SWIFT, a virtually zero acquisition delay sequence, was used to detect calcifications ex vivo and in vivo in rat models of status epilepticus and traumatic brain injury. Calcifications were detected in phase and imaginary SWIFT images based on their dipole like magnetic field disturbances. In magnitude SWIFT images, calcifications were distinguished as hypointense and hyperintense. Hypointense calcifications showed large crystallized granules with few surrounding inflammatory cells, while hyperintense calcifications contained small granules with the presence of more inflammatory cells. The size of the calcifications in SWIFT magnitude images correlated with that in Alizarin stained histological sections. Our data indicate that SWIFT is likely to better preserve signal in the proximity of a calcification or other field perturber in comparison to gradient echo due to its short acquisition delay and broad excitation bandwidth. Furthermore, a quantitative description for the phase contrast near dipole magnetic field inhomogeneities for the SWIFT pulse sequence is given. In vivo detection of calcifications provides a tool to probe the progression of pathology in neurodegenerative diseases. In particular, it appears to provide a surrogate marker for inflammatory cells around the calcifications after brain injury. PMID:22425671

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

    NASA Astrophysics Data System (ADS)

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

    2013-04-01

    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.

  18. 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

    2013-04-01

    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.

  19. Impact of calcifications on patient-specific wall stress analysis of abdominal aortic aneurysms.

    PubMed

    Maier, A; Gee, M W; Reeps, C; Eckstein, H-H; Wall, W A

    2010-10-01

    As a degenerative and inflammatory desease of elderly patients, about 80% of abdominal aortic aneurysms (AAA) show considerable wall calcification. Effect of calcifications on computational wall stress analyses of AAAs has been rarely treated in literature so far. Calcifications are heterogeneously distributed, non-fibrous, stiff plaques which are most commonly found near the luminal surface in between the intima and the media layer of the vessel wall. In this study, we therefore investigate the influence of calcifications as separate AAA constituents on finite element simulation results. Thus, three AAAs are reconstructed with regard to intraluminal thrombus (ILT), calcifications and vessel wall. Each patient-specific AAA is simulated twice, once including all three AAA constituents and once neglecting calcifications as it is still common in literature. Parameters for constitutive modeling of calcifications are thereby taken from experiments performed by the authors, showing that calcifications exhibit an almost linear stress-strain behavior with a Young's modulus E ≥ 40 MPa. Simulation results show that calcifications exhibit significant load-bearing effects and reduce stress in adjacent vessel wall. Average stress within the vessel wall is reduced by 9.7 to 59.2%. For two out of three AAAs, peak wall stress decreases when taking calcifications into consideration (8.9 and 28.9%). For one AAA, simulated peak wall stress increases by 5.5% due to stress peaks near calcification borders. However, such stress singularities due to sudden stiffness jumps are physiologically doubtful. It can further be observed that large calcifications are mostly situated in concavely shaped regions of the AAA wall. We deduce that AAA shape is influenced by existent calcifications, thus crucial errors occur if they are neglected in computational wall stress analyses. A general increase in rupture risk for calcified AAAs is doubted.

  20. Impact of calcifications on patient-specific wall stress analysis of abdominal aortic aneurysms.

    PubMed

    Maier, A; Gee, M W; Reeps, C; Eckstein, H-H; Wall, W A

    2010-10-01

    As a degenerative and inflammatory desease of elderly patients, about 80% of abdominal aortic aneurysms (AAA) show considerable wall calcification. Effect of calcifications on computational wall stress analyses of AAAs has been rarely treated in literature so far. Calcifications are heterogeneously distributed, non-fibrous, stiff plaques which are most commonly found near the luminal surface in between the intima and the media layer of the vessel wall. In this study, we therefore investigate the influence of calcifications as separate AAA constituents on finite element simulation results. Thus, three AAAs are reconstructed with regard to intraluminal thrombus (ILT), calcifications and vessel wall. Each patient-specific AAA is simulated twice, once including all three AAA constituents and once neglecting calcifications as it is still common in literature. Parameters for constitutive modeling of calcifications are thereby taken from experiments performed by the authors, showing that calcifications exhibit an almost linear stress-strain behavior with a Young's modulus E ≥ 40 MPa. Simulation results show that calcifications exhibit significant load-bearing effects and reduce stress in adjacent vessel wall. Average stress within the vessel wall is reduced by 9.7 to 59.2%. For two out of three AAAs, peak wall stress decreases when taking calcifications into consideration (8.9 and 28.9%). For one AAA, simulated peak wall stress increases by 5.5% due to stress peaks near calcification borders. However, such stress singularities due to sudden stiffness jumps are physiologically doubtful. It can further be observed that large calcifications are mostly situated in concavely shaped regions of the AAA wall. We deduce that AAA shape is influenced by existent calcifications, thus crucial errors occur if they are neglected in computational wall stress analyses. A general increase in rupture risk for calcified AAAs is doubted. PMID:20143120

  1. Low Florida coral calcification rates in the Plio-Pleistocene

    NASA Astrophysics Data System (ADS)

    Brachert, Thomas C.; Reuter, Markus; Krüger, Stefan; Klaus, James S.; Helmle, Kevin; Lough, Janice M.

    2016-08-01

    In geological outcrops and drill cores from reef frameworks, the skeletons of scleractinian corals are usually leached and more or less completely transformed into sparry calcite because the highly porous skeletons formed of metastable aragonite (CaCO3) undergo rapid diagenetic alteration. Upon alteration, ghost structures of the distinct annual growth bands often allow for reconstructions of annual extension ( = growth) rates, but information on skeletal density needed for reconstructions of calcification rates is invariably lost. This report presents the bulk density, extension rates and calcification rates of fossil reef corals which underwent minor diagenetic alteration only. The corals derive from unlithified shallow water carbonates of the Florida platform (south-eastern USA), which formed during four interglacial sea level highstands dated approximately 3.2, 2.9, 1.8, and 1.2 Ma in the mid-Pliocene to early Pleistocene. With regard to the preservation, the coral skeletons display smooth growth surfaces with minor volumes of marine aragonite cement within intra-skeletal porosity. Within the skeletal structures, voids are commonly present along centres of calcification which lack secondary cements. Mean extension rates were 0.44 ± 0.19 cm yr-1 (range 0.16 to 0.86 cm yr-1), mean bulk density was 0.96 ± 0.36 g cm-3 (range 0.55 to 1.83 g cm-3) and calcification rates ranged from 0.18 to 0.82 g cm-2 yr-1 (mean 0.38 ± 0.16 g cm-2 yr-1), values which are 50 % of modern shallow-water reef corals. To understand the possible mechanisms behind these low calcification rates, we compared the fossil calcification rates with those of modern zooxanthellate corals (z corals) from the Western Atlantic (WA) and Indo-Pacific calibrated against sea surface temperature (SST). In the fossil data, we found a widely analogous relationship with SST in z corals from the WA, i.e. density increases and extension rate decreases with increasing SST, but over a significantly larger

  2. Hilar cholangiocarcinoma with intratumoral calcification: A case report

    PubMed Central

    Inoko, Kazuho; Tsuchikawa, Takahiro; Noji, Takehiro; Kurashima, Yo; Ebihara, Yuma; Tamoto, Eiji; Nakamura, Toru; Murakami, Soichi; Okamura, Keisuke; Shichinohe, Toshiaki; Hirano, Satoshi

    2015-01-01

    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. PMID:26478684

  3. Coccolithophore calcification response to past ocean acidification and climate change

    PubMed Central

    O’Dea, Sarah A.; Gibbs, Samantha J.; Bown, Paul R.; Young, Jeremy R.; Poulton, Alex J.; Newsam, Cherry; Wilson, Paul A.

    2014-01-01

    Anthropogenic carbon dioxide emissions are forcing rapid ocean chemistry changes and causing ocean acidification (OA), which is of particular significance for calcifying organisms, including planktonic coccolithophores. Detailed analysis of coccolithophore skeletons enables comparison of calcite production in modern and fossil cells in order to investigate biomineralization response of ancient coccolithophores to climate change. Here we show that the two dominant coccolithophore taxa across the Paleocene–Eocene Thermal Maximum (PETM) OA global warming event (~56 million years ago) exhibited morphological response to environmental change and both showed reduced calcification rates. However, only Coccolithus pelagicus exhibits a transient thinning of coccoliths, immediately before the PETM, that may have been OA-induced. Changing coccolith thickness may affect calcite production more significantly in the dominant modern species Emiliania huxleyi, but, overall, these PETM records indicate that the environmental factors that govern taxonomic composition and growth rate will most strongly influence coccolithophore calcification response to anthropogenic change. PMID:25399967

  4. Low Florida coral calcification rates in the Plio-Pleistocene

    NASA Astrophysics Data System (ADS)

    Brachert, T. C.; Reuter, M.; Krüger, S.; Klaus, J. S.; Helmle, K.; Lough, J. M.

    2015-12-01

    In geological outcrops and drill cores from reef frameworks, the skeletons of scleractinian corals are usually leached and more or less completely transformed into sparry calcite because the highly porous skeletons formed of metastable aragonite (CaCO3) undergo rapid diagenetic alteration. Upon alteration, ghost structures of the distinct annual growth bands may be retained allowing for reconstructions of annual extension (= growth) rates, but information on skeletal density needed for reconstructions of calcification rates is invariably lost. Here we report the first data of calcification rates of fossil reef corals which escaped diagenetic alteration. The corals derive from unlithified shallow water carbonates of the Florida platform (southeastern USA), which formed during four interglacial sea level highstands dated 3.2, 2.9, 1.8, and 1.2 Ma in the mid Pliocene to early Pleistocene. With regard to the preservation, the coral skeletons display smooth growth surfaces with minor volumes of marine aragonite cement within intra-skeletal porosity. Within the skeletal structures, dissolution is minor along centers of calcification. Mean extension rates were 0.44 ± 0.19 cm yr-1 (range 0.16 to 0.86 cm yr-1) and mean bulk density was 0.86 ± 0.36 g cm-3 (range 0.55 to 1.22 g cm-3). Correspondingly, calcification rates ranged from 0.18 to 0.82 g cm-2 yr-1 (mean 0.38 ± 0.16 g cm-2 yr-1), values which are 50 % of modern shallow-water reef corals. To understand the possible mechanisms behind these low calcification rates, we compared the fossil calcification with modern zooxanthellate-coral (z-coral) rates from the Western Atlantic (WA) and Indo-Pacific (IP) calibrated against sea surface temperature (SST). In the fossil data, we found an analogous relationship with SST in z-corals from the WA, i.e. density increases and extension rate decreases with increasing SST, but over a significantly larger temperature window during the Plio-Pleistocene. With regard to the

  5. Coccolithophore calcification response to past ocean acidification and climate change.

    PubMed

    O'Dea, Sarah A; Gibbs, Samantha J; Bown, Paul R; Young, Jeremy R; Poulton, Alex J; Newsam, Cherry; Wilson, Paul A

    2014-01-01

    Anthropogenic carbon dioxide emissions are forcing rapid ocean chemistry changes and causing ocean acidification (OA), which is of particular significance for calcifying organisms, including planktonic coccolithophores. Detailed analysis of coccolithophore skeletons enables comparison of calcite production in modern and fossil cells in order to investigate biomineralization response of ancient coccolithophores to climate change. Here we show that the two dominant coccolithophore taxa across the Paleocene-Eocene Thermal Maximum (PETM) OA global warming event (~56 million years ago) exhibited morphological response to environmental change and both showed reduced calcification rates. However, only Coccolithus pelagicus exhibits a transient thinning of coccoliths, immediately before the PETM, that may have been OA-induced. Changing coccolith thickness may affect calcite production more significantly in the dominant modern species Emiliania huxleyi, but, overall, these PETM records indicate that the environmental factors that govern taxonomic composition and growth rate will most strongly influence coccolithophore calcification response to anthropogenic change. PMID:25399967

  6. Coccolithophore calcification response to past ocean acidification and climate change.

    PubMed

    O'Dea, Sarah A; Gibbs, Samantha J; Bown, Paul R; Young, Jeremy R; Poulton, Alex J; Newsam, Cherry; Wilson, Paul A

    2014-11-17

    Anthropogenic carbon dioxide emissions are forcing rapid ocean chemistry changes and causing ocean acidification (OA), which is of particular significance for calcifying organisms, including planktonic coccolithophores. Detailed analysis of coccolithophore skeletons enables comparison of calcite production in modern and fossil cells in order to investigate biomineralization response of ancient coccolithophores to climate change. Here we show that the two dominant coccolithophore taxa across the Paleocene-Eocene Thermal Maximum (PETM) OA global warming event (~56 million years ago) exhibited morphological response to environmental change and both showed reduced calcification rates. However, only Coccolithus pelagicus exhibits a transient thinning of coccoliths, immediately before the PETM, that may have been OA-induced. Changing coccolith thickness may affect calcite production more significantly in the dominant modern species Emiliania huxleyi, but, overall, these PETM records indicate that the environmental factors that govern taxonomic composition and growth rate will most strongly influence coccolithophore calcification response to anthropogenic change.

  7. Metanephric adenoma with diffuse calcifications: A case report

    PubMed Central

    WU, JINGTAO; ZHU, QINGQIANG; ZHU, WENRONG; ZHANG, HONGYING

    2015-01-01

    Metanephric adenoma is a rare and benign renal neoplasm originating in the epithelial cells of the kidney. The tumor has a benign course and a characteristic histopathological appearance, typically exhibiting a solid and poorly-demarcated margin with rare cystic components or calcifications. However, it is often difficult to distinguish metanephric adenoma from malignant neoplasms prior to surgical resection. To the best of our knowledge, only one case of metastasis to the lymph nodes has been described in the literature thus far. The present study retrospectively analyzed one case of surgically and pathologically-confirmed atypical metanephric adenoma. Clinical and pathological analysis, as well as computed tomography scans, revealed a mass with a clearly defined margin and diffuse calcifications. The mass was subsequently resected and the patient recovered well following the procedure. PMID:26622757

  8. Serum prolactin levels in a uremic child: effects of bilateral nephrectomy and kidney transplantation.

    PubMed

    Rondeau, Geneviève; Merouani, Aïcha; Phan, Véronique; Deal, Cheri; Robitaille, Pierre

    2011-10-01

    Elevated levels of serum prolactin (PRL) are common and well described in patients with chronic renal failure. We report the case of a 4-year-old girl who also presented with premature thelarche and transient galactorrhea. Neither peritoneal dialysis nor hemodialysis reduced her extremely elevated levels of PRL, which fluctuated from time to time, probably reflecting variations in lactotroph secretion rate. Bilateral nephrectomy (BN) was eventually followed by a progressive and significant rise in PRL levels, suggesting that even uremic kidneys can eliminate PRL through tubular breakdown. Kidney transplantation was responsible for a very abrupt normalization of PRL serum levels, much faster than that observed for creatinine. This confirms animal studies suggesting that elimination of PRL occurs both through glomerular filtration and tubular breakdown. We hypothesized that the seemingly precocious puberty may have resulted from a combination of growth hormone therapy, elevated PRL and a rise in estrogens through the aromatization of adrenal androgens. This case illustrates the impact of dialysis, BN and kidney transplantation on PRL, providing new knowledge on renal PRL metabolism. PMID:25984175

  9. Efficacy of plasma therapy in atypical hemolytic uremic syndrome with complement factor H mutations.

    PubMed

    Lapeyraque, Anne-Laure; Wagner, Eric; Phan, Véronique; Clermont, Marie-José; Merouani, Aïcha; Frémeaux-Bacchi, Véronique; Goodship, Timothy H J; Robitaille, Pierre

    2008-08-01

    Atypical hemolytic uremic syndrome (aHUS) frequently results in end-stage renal failure and can be lethal. Several studies have established an association between quantitative or qualitative abnormalities in complement factor H and aHUS. Although plasma infusion and exchange are often advocated, guidelines have yet to be established. Long-term outcome for patients under treatment is still unknown. We describe a patient who, at 7 months of age, presented with aHUS associated with combined de novo complement factor H mutations (S1191L and V1197A) on the same allele. Laboratory investigations showed normal levels of complements C4, C3 and factor H. Plasma exchanges and large-dose infusion therapy resulted in a resolution of hemolysis and recovery of renal function. Three recurrences were successfully treated by intensification of the plasma infusion treatment to intervals of 2 or 3 days. This patient showed good response to large doses of plasma infusions and her condition remained stable for 30 months with weekly plasma infusions (30 ml/kg). Long-term tolerance and efficacy of such intensive plasma therapy are still unknown. Reported secondary failure of plasma therapy in factor H deficiency warrants the search for alternative therapeutic approaches. PMID:18425537

  10. Hemolytic Uremic Syndrome in Pediatric Intensive Care Units in São Paulo, Brazil

    PubMed Central

    de Souza, Renato Lopes; Abreu Carvalhaes, João Tomás; Sanae Nishimura, Lucilia; de Andrade, Maria Cristina; Cabilio Guth, Beatriz Ernestina

    2011-01-01

    The hemolytic uremic syndrome (HUS) caused by Shiga toxin-producing Escherichia coli (STEC) is one of the most frequent causes of pediatric acute renal failure. The aim of this study was to report the clinic and microbiologic features associated with 13 post-diarrheal HUS cases identified in pediatric intensive care units in the city of São Paulo, Brazil, from January 2001 to August 2005. Epidemiologic, clinic, and laboratorial information, along with fecal and serum samples, were collected for identifying the genetic sequences of Stx and for studying antibodies directed against LPS O26, O111 and O157. STEC was isolated from three patients, and serotypes O26:H11, O157:H7 and O165:H- were identified. In nine patients, high levels of IgM against LPS O111 (n=2) and O157 (n=7) were detected. Dialysis was required in 76.9% of the patients; arterial hypertension was present in 61.5%, neurological complications were observed in 30.7%, and only one patient died. During a 5–year follow-up period, one patient developed chronic kidney disease. The combined use of microbiologic and serologic techniques provided evidence of STEC infection in 92.3% of the HUS cases studied, and the importance of O157 STEC as agents of HUS in São Paulo has not been previously highlighted. PMID:21804902

  11. Hemolytic-Uremic Syndrome in Uberlândia, MG, Brazil

    PubMed Central

    Bonetti, V.; Mangia, C. M. F.; Zuza, J. M. F.; Barcelos, M. O.; Fonseca, M. M. S.; Nery, S. P.; Carvalhaes, J. T. A.; Andrade, M. C.

    2011-01-01

    Purpose. To analyze the epidemiological, clinical, and laboratory characteristics of hemolytic-uremic syndrome (HUS) in Uberlandia, MG, Brazil. Methods. A historical cohort study was performed encompassing a ten-year period from January 1994 to January 2004 in the Department of Pediatric Nephrology at a full-service hospital; demographic factors, triggering factors, time of hospitalization, supportive therapy, and disease progression were analyzed. Results. Twenty-seven children aged 5 to 99 months (median age of 14 months) were studied; 70.4% were male. Of the 27 patients, 77.8% were from urban areas and 18.5% were from rural areas. Eight of the patients (29.6%) were reported to drink raw milk, and clinical diarrhea was reported in 81.5% of cases. The most common signs and symptoms were fever and vomiting (85.1%), anuria (63.0%), seizure (33.0%), cardiac involvement (11.0%), and acute pulmonary edema (7.4%). Dialysis was performed on 20 patients (74%). The mean hospital stay was 24 days (range: 13 to 36 days). While monitoring the patients, 2 died (7.4%), 3 developed chronic kidney disease (11.0%), and 21 (77.8%) developed hypertension. Conclusion. Our results emphasize the possibility of diagnosing HUS as a cause of renal failure in childhood in both typical (postdiarrheal) and atypical forms and suggest that an investigation of the etiological agent should be made whenever possible. PMID:22389782

  12. Nitrosylation: an adverse factor in Uremic Hemolytic Syndrome. Antitoxin effect of Ziziphus mistol Griseb.

    PubMed

    Virginia, Aiassa; Claudia, Albrecht; Soledad, Bustos Pamela; Gabriela, Ortega; Jorge, Eraso Alberto; Albesa, Inés

    2013-06-01

    Toxins of Escherichia coli (STEC) causing Uremic Hemolytic Syndrome (UHS) generate oxidative stress in human blood with more production of nitric oxide (NO) than reactive oxygen species (ROS). Shiga toxin (Stx) together with the hemolysin (Hly) increased lipid oxidation, as evaluated by malondialdehyde MDA and oxidation of proteins. The addition of Ziziphus mistol Griseb extracts decreased NO, ROS, MDA and simultaneously caused an increase in the degradation of oxidized proteins to advanced oxidation protein products (AOPPs) in controls and samples with toxins. Furthermore, the nitrosylated proteins/AOPP ratio was reduced, due to the increase of AOPP. Z. mistol Griseb extracts exhibited a high proportion of polyphenols and flavonoids, with evident correlation with ferrous reduction antioxidant potential (FRAP). The plasma of eight children with UHS showed oxidative stress and NO stimulus, comparable to the effect of toxins during the assays in vitro. UHS children presented high levels of nitrosylated proteins respect to control children of similar age. Although the degradation of oxidized proteins to AOPP rose in UHS children, the nitrosylated proteins/AOPP rate increased as a consequence of the elevated nitrosative stress observed in these patients. PMID:23454150

  13. Atypical Hemolytic Uremic Syndrome Secondary to Lupus Nephritis, Responsive to Eculizumab

    PubMed Central

    Raufi, Alexander G.; Scott, Shruti; Darwish, Omar; Harley, Kevin; Kahlon, Kanwarpal; Desai, Sheetal; Lu, Yuxin; Tran, Minh-Ha

    2016-01-01

    Among the spectrum of disease manifestations associated with systemic lupus erythematosus, lupus nephritis is particularly concerning due to the potential for renal failure. This autoimmune attack may not, however, be limited to the kidney and is increasingly being recognized as a trigger for atypical Hemolytic Uremic Syndrome (aHUS). Atypical HUS falls under the spectrum of the thrombotic microangiopathies (TMAs) – a group of disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and end organ damage. Although plasma exchange is considered first-line therapy for thrombotic thrombocytopenic purpura – a TMA classically associated with autoimmune depletion of ADAMTS-13 – aHUS demonstrates less reliable responsiveness to this modality. Instead, use of the late complement inhibitor Eculizumab has emerged as an effective modality for the management of such patients. Diagnosis of aHUS, however, is largely clinically based, relying heavily upon a multidisciplinary approach. Herein we present the case of a patient with atypical HUS successfully treated with Eculizumab in the setting of Class IV-G (A) lupus nephritis and hypocomplementemia. PMID:27781079

  14. Quantitative characteristics of calcitonin-producing cells in the thyroid and lungs of uremic rats.

    PubMed

    Kasacka, Irena

    2008-01-01

    Uremia leads to a number of metabolic and hormonal disorders induced by renal failure with definite biological and clinical sequels. For this reason and the absence of reports on influence of CRF on calcitonin (CT)-producing cells of the thyroid glands and airways, the author decided to investigate the behavior of neuroendocrine cells in experimental uremia, taking CT-producing cells as an example. The aim of the present study was to examine the number and distribution of CT-producing cells in the thyroid glands and lungs of uremic rats. Fragments of the thyroids and lungs were collected one week after nephrectomy. Paraffin-embedded sections were stained with H+E and by silver impregnation. To identify neuroendocrine cells, immunohistochemical reaction was performed with the use of a specific antibody against calcitonin. It was revealed that the number of CT-immunoreactive cells decrease in the thyroid and considerable increase in the lungs of rats, when compared to the value in the control animals. The results can be regarded as the morphological manifestation of calcitonin-producing endocrine cells in the rat thyroid and lungs to disorders in the internal environment of the body induced by the impairment of renal parenchyma functioning. PMID:19141408

  15. Leptin as an uremic toxin: Deleterious role of leptin in chronic kidney disease.

    PubMed

    Alix, Pascaline M; Guebre-Egziabher, Fitsum; Soulage, Christophe O

    2014-10-01

    White adipose tissue secretes a large variety of compounds named adipokines amongst which, leptin exhibits pleiotropic metabolic actions. Leptin is an anorexigenic hormone, secreted in proportion of fat mass, with additional effects on the regulation of inflammation, cardiovascular system, immunity, hematopoiesis and bone metabolism. Chronic kidney disease (CKD) is characterized by an increase of plasma leptin concentration that may be explained by a lack of renal clearance. Hyperleptinemia plays a key role in the pathogenesis of complications associated with CKD such as cachexia, protein energy wasting, chronic inflammation, insulin resistance, cardiovascular damages and bone complications. Leptin is also involved in the progression of renal disease through its pro-fibrotic and pro-hypertensive actions. Most of the adverse effects of leptin have been documented both experimentally and clinically. Leptin may therefore be considered as an uremic toxin in CKD. The aim of this review is to summarize the pathophysiological and clinical role of leptin in in vitro studies, experimental models, as well as in patients suffering from CKD.

  16. Correlations between Plasma Levels of Anionic Uremic Toxins and Clinical Parameters in Hemodialysis Patients.

    PubMed

    Ichimura, Yuichi; Takamatsu, Hiroyuki; Ideuchi, Hideki; Oda, Masako; Takeda, Kiyotaka; Saitoh, Hiroshi

    2016-01-01

    When the kidney is seriously impaired, various uremic toxins (UTs) accumulate in the body, often exerting unfavorable effects on physiological functions and drug pharmacokinetics. To prevent this, it is important to determine plasma UT levels accurately in chronic kidney disease patients. Although attempts to predict plasma UT levels using biomarkers have been made, the correlation between UT levels and the markers is not yet fully understood. In this study, we assessed the correlations among plasma levels of indoxyl sulfate (IS), indoleacetic acid (IA), and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF) in 20 hemodialysis patients and evaluated the relationship between the plasma levels of UTs and clinical parameters, such as serum creatinine (Scr), blood urea nitrogen, and estimated glomerular filtration rate (eGFR), with special focus on IS. There were no correlations among the plasma levels of the three UTs before and immediately after hemodialysis. However, a significant correlation was observed between plasma IS levels and Scr before hemodialysis (r=0.643, p=0.002), with the correlation becoming much stronger when using the data obtained immediately after hemodialysis (r=0.744, p<0.001). Further, plasma IS levels showed a significant negative correlation with eGFR (r=-0.558, p=0.011). However, no correlations were observed for IA or CMPF. The results obtained from this study suggest that plasma IS levels can be predicted from Scr values, although the precise mechanism behind the correlation remains to be clarified. PMID:27477735

  17. Induction of Neutrophil Extracellular Traps in Shiga Toxin-Associated Hemolytic Uremic Syndrome.

    PubMed

    Ramos, Maria Victoria; Mejias, Maria Pilar; Sabbione, Florencia; Fernandez-Brando, Romina Jimena; Santiago, Adriana Patricia; Amaral, Maria Marta; Exeni, Ramon; Trevani, Analia Silvina; Palermo, Marina Sandra

    2016-01-01

    Hemolytic uremic syndrome (HUS), a vascular disease characterized by hemolytic anemia, thrombocytopenia, and acute renal failure, is caused by enterohemorrhagic Shiga toxin (Stx)-producing bacteria, which mainly affect children. Besides Stx, the inflammatory response mediated by neutrophils (PMN) is essential to HUS evolution. PMN can release neutrophil extracellular traps (NET) composed of DNA, histones, and other proteins. Since NET are involved in infectious and inflammatory diseases, the aim of this work was to investigate the contribution of NET to HUS. Plasma from HUS patients contained increased levels of circulating free-DNA and nucleosomes in comparison to plasma from healthy children. Neutrophils from HUS patients exhibited a greater capacity to undergo spontaneous NETosis. NET activated human glomerular endothelial cells, stimulating secretion of the proinflammatory cytokines IL-6 and IL-8. Stx induced PMN activation as judged by its ability to trigger reactive oxygen species production, increase CD11b and CD66b expression, and induce NETosis in PMN from healthy donors. During HUS, NET can contribute to the inflammatory response and thrombosis in the microvasculature and thus to renal failure. Intervention strategies to inhibit inflammatory mechanisms mediated by PMN, such as NETosis, could have a potential therapeutic impact towards amelioration of the severity of HUS.

  18. Low levels of serum erythropoietin in children with endemic hemolytic uremic syndrome.

    PubMed

    Exeni, R; Donato, H; Rendo, P; Antonuccio, M; Rapetti, M C; Grimoldi, I; Exeni, A; de Galvagni, A; Trepacka, E; Amore, A

    1998-04-01

    Serum erythropoietin (EPO) levels were measured in ten previously non-transfused children with hemolytic uremic syndrome (HUS). Complete blood cell count, serum EPO, and renal function tests were carried out upon admission and weekly thereafter. Blood samples were obtained: (1) prior to the first transfusion; (2) after the first transfusion but before recovery from renal failure; (3) during the recovery stage. All patients required transfusions (mean 1.8+/-0.8 per child). Absolute values of EPO correlated positively with the hematocrit during the three stages (r = 0.53, 0.36, and 0.12, respectively) which is opposite to expected results. The observed EPO logarithm/predicted EPO logarithm upon admission was low (0.70+/-0.08), falling further during stage 2 (0.57+/-0.03), but increasing thereafter (0.78+/-0.07) without reaching normal values. The reticulocyte production rate followed a parallel course (0.74+/-0.14, 0.54+/-0.11, and 0.60+/-0.10, respectively). On comparing the observed serum EPO levels with those expected, 9 of 11 pre-transfusion samples showed low values; in stage 2, all samples were below normal; in the recovery phase most (77.8%) were still low. Our results show an inadequate EPO synthesis in children with HUS, which could play an important pathogenic role, since it aggravates the severity of the existing hemolytic anemia; the secondary inhibitory effect of repeated transfusions exacerbates this inadequate synthesis.

  19. Differential expression of function-related antigens on blood monocytes in children with hemolytic uremic syndrome.

    PubMed

    Fernández, Gabriela C; Ramos, María V; Gómez, Sonia A; Dran, Graciela I; Exeni, Ramón; Alduncín, Marta; Grimoldi, Irene; Vallejo, Graciela; Elías-Costa, Christian; Isturiz, Martín A; Palermo, Marina S

    2005-10-01

    Monocytes (Mo) mediate central functions in inflammation and immunity. Different subpopulations of Mo with distinct phenotype and functional properties have been described. Here, we investigate the phenotype and function of peripheral Mo from children with hemolytic uremic syndrome (HUS). For this purpose, blood samples from patients in the acute period of HUS (HUS AP) were obtained on admission before dialysis and/or transfusion. The Mo phenotypic characterization was performed on whole blood by flow cytometry, and markers associated to biological functions were selected: CD14 accounting for lipopolysaccharide (LPS) responsiveness, CD11b for adhesion, Fc receptor for immunoglobulin G type I (FcgammaRI)/CD64 for phagocytosis and cytotoxicity, and human leukocyte antigen (HLA)-DR for antigen presentation. Some of these functions were also determined. Moreover, the percentage of CD14+ CD16+ Mo was evaluated. We found that the entire HUS AP Mo population exhibited reduced CD14, CD64, and CD11b expression and decreased LPS-induced tumor necrosis factor production and Fcgamma-dependent cytotoxicity. HUS AP showed an increased percentage of CD14+ CD16+ Mo with higher CD16 and lower CD14 levels compared with the same subset from healthy children. Moreover, the CD14++ CD16- Mo subpopulation of HUS AP had a decreased HLA-DR expression, which correlated with severity. In conclusion, the Mo population from HUS AP patients presents phenotypic and functional alterations. The contribution to the pathogenesis and the possible scenarios that led to these changes are discussed.

  20. Enterohemorrhagic Escherichia coli associated with hemolytic-uremic syndrome in Chilean children.

    PubMed Central

    Cordovéz, A; Prado, V; Maggi, L; Cordero, J; Martinez, J; Misraji, A; Rios, R; Soza, G; Ojeda, A; Levine, M M

    1992-01-01

    A clinicoepidemiological study was undertaken to determine if enterohemorrhagic Escherichia coli (EHEC) was associated with hemolytic-uremic syndrome (HUS) in children in Santiago, Valdivia, and Temuco, Chile. Prospective surveillance detected 20 hospitalized cases of HUS in children less than 4 years of age in these cities from March 1988 to March 1989. Each HUS patient was matched (by sex and age) with two control children (hospitalized elective-surgery patients). To detect EHEC, DNA from stool culture isolates of E. coli was detected by hybridization with biotin-labelled DNA probes specific for the EHEC virulence plasmid, Shiga-like toxin I (SLT-I) or SLT-II. Stool cultures from 6 of 20 cases (30%) and from 2 of 38 controls (5.3%) yielded EHEC (P = 0.0158). EHEC isolates from all HUS cases hybridized with the EHEC plasmid probe and with probes for SLT-I or -II (or both). The serogroups of the isolates included O157, O26, and O111. EHEC causes HUS in Chile, and the biotinylated gene probes are practical diagnostic tools for epidemiologic studies. PMID:1500525

  1. Clostridium sordellii as a Cause of Fatal Septic Shock in a Child with Hemolytic Uremic Syndrome

    PubMed Central

    Beyers, Rebekah; Baldwin, Michael

    2014-01-01

    Clostridium sordellii is a toxin producing ubiquitous gram-positive anaerobe, mainly associated with trauma, soft tissue skin infections, and gynecologic infection. We report a unique case of a new strain of Clostridium sordellii (not present in the Center for Disease Control (CDC) database) infection induced toxic shock syndrome in a previously healthy two-year-old male with colitis-related hemolytic uremic syndrome (HUS). The patient presented with dehydration, vomiting, and bloody diarrhea. He was transferred to the pediatric critical care unit (PICU) for initiation of peritoneal dialysis (PD). Due to increased edema and intolerance of PD, he was transitioned to hemodialysis through a femoral vascular catheter. He subsequently developed severe septic shock with persistent leukocytosis and hypotension, resulting in subsequent death. Stool culture confirmed Shiga toxin producing Escherichia coli 0157:H7. A blood culture was positively identified for Clostridium sordellii. Clostridium sordelli is rarely reported in children; to our knowledge this is the first case described in a pediatric patient with HUS. PMID:24891968

  2. Protein-bound uremic toxins: a long overlooked culprit in cardiorenal syndrome.

    PubMed

    Lekawanvijit, Suree; Kompa, Andrew R; Krum, Henry

    2016-07-01

    Protein-bound uremic toxins (PBUTs) accumulate once renal excretory function declines and are not cleared by dialysis. There is increasing evidence that PBUTs exert toxic effects on many vital organs, including the kidney, blood vessels, and heart. It has been suggested that PBUTs are likely to be a potential missing link in cardiorenal syndrome, based on the high incidence of cardiovascular events and mortality in the dialysis population, which are dramatically reduced in successful kidney transplant recipients. These data have led the call for more effective dialysis or additional adjunctive therapy to eradicate these toxins and their adverse biological effects. Indoxyl sulfate and p-cresyl sulfate are the two most problematic PBUTs, conferring renal and cardiovascular toxicity, and are derived from dietary amino acid metabolites by colonic microbial organisms. Therefore, targeting the colon where these toxins are initially produced appears to be a potential therapeutic alternative for patients with chronic kidney disease. This strategy, if approved, is likely to be applicable to predialysis patients, thereby potentially preventing progression of chronic kidney disease to end-stage renal disease as well as preventing the development of cardiorenal syndrome.

  3. Posterior Reversible Encephalopathy Syndrome in Henoch-Schonlein Purpura and Hemolytic Uremic Syndrome

    PubMed Central

    Fidan, Kibriya; Kandur, Yasar; Ucar, Murat; Gucuyener, Kivilcim; Soylemezoglu, Oguz

    2016-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiological syndrome, composed of symptoms such as headache, seizures, visual disturbances, lethargy, confusion, stupor, focal neurologic findings and radiological findings of bilateral gray and white matter abnormalities suggestive of edema in the posterior regions of the cerebral hemispheres. PRES is associated with significant morbidity and mortality if it is not expeditiously recognized. Magnetic resonance image (MRI) represents the most sensitive imaging technique for recognizing PRES. PRES has been seen in various clinical settings including renal disorders such as acute glomerulonephritis, lupus nephritis, nephrotic syndrome, and drug usage such as calcineurin inhibitors. We aimed to present two study cases for such clinical setting. In this report, we present two patients with PRES in whom the primary diagnosis was hemolytic uremic syndrome (HUS) and Henoch-Schonlein purpura (HSP). Both of them were treated with anticonvulsant and proper antihypertensive drugs. A repeated MRI scan of the head, an ophthalmologic assessment, and a follow-up electroencephalogram produced normal results with no sequelae. Early recognition of PRES as a complication during different diseases and therapies in childhood may facilitate the appropriate treatment, so that intensive treatment should be performed as soon as possible to avoid neurological sequelae. PMID:27298664

  4. Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome

    PubMed Central

    de Jorge, Elena Goicoechea; Harris, Claire L.; Esparza-Gordillo, Jorge; Carreras, Luis; Arranz, Elena Aller; Garrido, Cynthia Abarrategui; López-Trascasa, Margarita; Sánchez-Corral, Pilar; Morgan, B. Paul; de Córdoba, Santiago Rodríguez

    2007-01-01

    Hemolytic uremic syndrome (HUS) is an important cause of acute renal failure in children. Mutations in one or more genes encoding complement-regulatory proteins have been reported in approximately one-third of nondiarrheal, atypical HUS (aHUS) patients, suggesting a defect in the protection of cell surfaces against complement activation in susceptible individuals. Here, we identified a subgroup of aHUS patients showing persistent activation of the complement alternative pathway and found within this subgroup two families with mutations in the gene encoding factor B (BF), a zymogen that carries the catalytic site of the complement alternative pathway convertase (C3bBb). Functional analyses demonstrated that F286L and K323E aHUS-associated BF mutations are gain-of-function mutations that result in enhanced formation of the C3bBb convertase or increased resistance to inactivation by complement regulators. These data expand our understanding of the genetic factors conferring predisposition to aHUS, demonstrate the critical role of the alternative complement pathway in the pathogenesis of aHUS, and provide support for the use of complement-inhibition therapies to prevent or reduce tissue damage caused by dysregulated complement activation. PMID:17182750

  5. The endothelial glycocalyx as a potential modifier of the hemolytic uremic syndrome.

    PubMed

    Boels, Margien G S; Lee, Dae Hyun; van den Berg, Bernard M; Dane, Martijn J C; van der Vlag, Johan; Rabelink, Ton J

    2013-09-01

    Atypical hemolytic uremic syndrome (HUS) is a renal disease due to complement dysregulation. Many of the known causes of atypical HUS originate from genetic mutations of complement regulatory proteins, such as complement factor H (CFH) and thrombomodulin. However, atypical HUS has only a genetic penetrance of 40-50% of the cases and usually appears in adulthood. We introduce a novel factor that may be involved in the onset and development of atypical HUS, i.e. the endothelial surface glycocalyx. The glycocalyx is a highly interactive matrix covering the luminal side of vascular endothelial cells and consists of glycosaminoglycans, proteoglycans and glycoproteins, which has an important role in maintaining homeostasis of the vasculature. The surface-bound glycocalyx glycosaminoglycan constituent heparan sulfate is crucial for CFH binding and function, both in recognition of host tissue and prevention of spontaneous complement activation via the alternative pathway. Most of the clinically relevant genetic mutations in CFH result in incorrect binding to heparan sulfate. In addition, a role between proper function of thrombomodulin and the endothelial glycocalyx has also been observed. We suggest that not only changes in binding properties of the complement regulatory proteins play a role but also changes in the endothelial glycocalyx are involved in increased risk of clinical manifestation of atypical HUS. Finally, vascular glycocalyx heterogeneity in turn could dictate the specific vulnerability of the glomerular vascular bed in atypical HUS and may provide new therapeutic targets to intervene with endothelial cell activation and local complement pathway regulation.

  6. Effect of Auricular Acupressure on Uremic Pruritus in Patients Receiving Hemodialysis Treatment: A Randomized Controlled Trial

    PubMed Central

    Yan, Cui-na; Yao, Wei-guo; Bao, Yi-jie; Shi, Xiao-jing; Yu, Hui; Yin, Pei-hao; Liu, Gui-zhen

    2015-01-01

    Background. Uremic pruritus (UP) is a common symptom in patients undergoing maintenance hemodialysis for end-stage renal disease (ESRD). Objective. To determine the clinical efficacy of auricular acupressure therapy on pruritus in hemodialysis patients and to explore possible underlying mechanisms. Methods. Patients receiving maintenance hemodialysis at a referral medical center were recruited and assigned to intervention (n = 32) and control (n = 30) groups. The intervention group underwent auricular acupressure treatment three times a week for six weeks. Auricular acupressure was not applied to patients in the control group. However, tape without Vaccaria seeds was applied to the same six auricular acupoints as the intervention group. Pruritus scores were assessed using VAS scores, and enzyme-linked immunosorbent assays (ELISA) were used to measure levels of other possible contributory biochemical factors. Results. There was a significant difference in mean VAS scores between the postintervention and control groups during follow-up (3.844 ± 1.687 versus 5.567 ± 2.285, F = 22.32, P < 0.0001). Compared to the control group, serum histamine levels in the postintervention group at the six-week follow-up had decreased significantly (F = 5.01, P = 0.0290). Conclusion. Our findings suggest that auricular acupressure may be a useful treatment in the multidisciplinary management of UP in ESRD patients. PMID:26495017

  7. Discontinuation of eculizumab maintenance treatment for atypical hemolytic uremic syndrome: a report of 10 cases.

    PubMed

    Ardissino, Gianluigi; Testa, Sara; Possenti, Ilaria; Tel, Francesca; Paglialonga, Fabio; Salardi, Stefania; Tedeschi, Silvana; Belingheri, Mirco; Cugno, Massimo

    2014-10-01

    Atypical hemolytic uremic syndrome (aHUS) is a life-threatening thrombotic microangiopathy, and as many as 70% of patients with aHUS have mutations in the genes encoding complement regulatory proteins. Eculizumab, a humanized recombinant monoclonal antibody targeting C5, has been used successfully in patients with aHUS since 2009. The standard maintenance treatment requires life-long eculizumab therapy, but the possibility of discontinuation has not yet been tested systematically. We report the safety of discontinuing eculizumab treatment in 10 patients who stopped treatment with the aim of minimizing the risk of adverse reactions, reducing the risk of meningitis, and improving quality of life while also reducing the considerable treatment costs. Disease activity was monitored closely at home by means of urine dipstick testing for hemoglobin. During the cumulative observation period of 95 months, 3 of the 10 patients experienced relapse within 6 weeks of discontinuation, but then immediately resumed treatment and completely recovered. Our experience supports the possibility of discontinuing eculizumab therapy with strict home monitoring for early signs of relapse in patients with aHUS who achieve stable remission. PMID:24656451

  8. Mapping interactions between complement C3 and regulators using mutations in atypical hemolytic uremic syndrome

    PubMed Central

    Schramm, Elizabeth C.; Roumenina, Lubka T.; Rybkine, Tania; Chauvet, Sophie; Vieira-Martins, Paula; Hue, Christophe; Maga, Tara; Valoti, Elisabetta; Wilson, Valerie; Jokiranta, Sakari; Smith, Richard J. H.; Noris, Marina; Goodship, Tim; Atkinson, John P.

    2015-01-01

    The pathogenesis of atypical hemolytic uremic syndrome (aHUS) is strongly linked to dysregulation of the alternative pathway of the complement system. Mutations in complement genes have been identified in about two-thirds of cases, with 5% to 15% being in C3. In this study, 23 aHUS-associated genetic changes in C3 were characterized relative to their interaction with the control proteins factor H (FH), membrane cofactor protein (MCP; CD46), and complement receptor 1 (CR1; CD35). In surface plasmon resonance experiments, 17 mutant recombinant proteins demonstrated a defect in binding to FH and/or MCP, whereas 2 demonstrated reduced binding to CR1. In the majority of cases, decreased binding affinity translated to a decrease in proteolytic inactivation (known as cofactor activity) of C3b via FH and MCP. These results were used to map the putative binding regions of C3b involved in the interaction with MCP and CR1 and interrogated relative to known FH binding sites. Seventy-six percent of patients with C3 mutations had low C3 levels that correlated with disease severity. This study expands our knowledge of the functional consequences of aHUS-associated C3 mutations relative to the interaction of C3 with complement regulatory proteins mediating cofactor activity. PMID:25608561

  9. Complement Factor B Mutations in Atypical Hemolytic Uremic Syndrome—Disease-Relevant or Benign?

    PubMed Central

    Marinozzi, Maria Chiara; Vergoz, Laura; Rybkine, Tania; Ngo, Stephanie; Bettoni, Serena; Pashov, Anastas; Cayla, Mathieu; Tabarin, Fanny; Jablonski, Mathieu; Hue, Christophe; Smith, Richard J.; Noris, Marina; Halbwachs-Mecarelli, Lise; Donadelli, Roberta; Fremeaux-Bacchi, Veronique

    2014-01-01

    Atypical hemolytic uremic syndrome (aHUS) is a genetic ultrarare renal disease associated with overactivation of the alternative pathway of complement. Four gain-of-function mutations that form a hyperactive or deregulated C3 convertase have been identified in Factor B (FB) ligand binding sites. Here, we studied the functional consequences of 10 FB genetic changes recently identified from different aHUS cohorts. Using several tests for alternative C3 and C5 convertase formation and regulation, we identified two gain-of-function and potentially disease-relevant mutations that formed either an overactive convertase (M433I) or a convertase resistant to decay by FH (K298Q). One mutation (R178Q) produced a partially cleaved protein with no ligand binding or functional activity. Seven genetic changes led to near-normal or only slightly reduced ligand binding and functional activity compared with the most common polymorphism at position 7, R7. Notably, none of the algorithms used to predict the disease relevance of FB mutations agreed completely with the experimental data, suggesting that in silico approaches should be undertaken with caution. These data, combined with previously published results, suggest that 9 of 15 FB genetic changes identified in patients with aHUS are unrelated to disease pathogenesis. This study highlights that functional assessment of identified nucleotide changes in FB is mandatory to confirm disease association. PMID:24652797

  10. Acquired renal cysts in uremic patients--in vivo demonstration by computed tomography.

    PubMed

    Bommer, J; Waldherr, R; van Kaick, G; Strauss, L; Ritz, E

    1980-12-01

    The development of renal cysts appears to be a common feature of terminal renal failure in patients with diffuse renal parenchymal disease. In the present investigation, the kidneys of 13 patients with terminal renal failure but not receiving dialysis, of 14 patients on maintenance hemodialysis and of 4 patients after renal transplantation (patients' own kidneys) were studied by computed tomography. Cystic lesions in the contracted renal parenchyma could be demonstrated by computed tomography in 7/13 non-dialyzed patients with terminal renal failure, in 11/14 patients on maintenance hemodialysis as well as in 3/4 transplanted patients (patients' own kidneys). Both solitary cysts (10/21 patients) and multiple cysts (11/21 patients) were observed. The size varied from 0.5 cm (barely detectable) to 3 cm in diameter. Such cysts could also be demonstrated at autopsy. Possible clinical complications include spontaneous retroperitoneal hemorrhage, macrohematuria, matrix stone formation and formation of benign or malignant papilloma. The present study shows that computed tomography allows the detection of acquired renal cysts in uremic patients in vivo. The cysts appear prior to dialysis, seem to increase in frequency during dialysis and do not disappear after transplantation. The lesions can be distinguished from multicystic or polycystic disease.

  11. Phenotypic expression of factor H mutations in patients with atypical hemolytic uremic syndrome.

    PubMed

    Vaziri-Sani, F; Holmberg, L; Sjöholm, A G; Kristoffersson, A-C; Manea, M; Frémeaux-Bacchi, V; Fehrman-Ekholm, I; Raafat, R; Karpman, D

    2006-03-01

    We investigated the phenotypic expression of factor H mutations in two patients with atypical hemolytic uremic syndrome (HUS). Factor H in serum was assayed by rocket immunoelectrophoresis, immunoblotting, and double immunodiffusion and in tissue by immunohistochemistry. Functional activity was analyzed by hemolysis of sheep erythrocytes and binding to endothelial cells. A homozygous mutation in complement control protein (CCP) domain 10 of factor H was identified in an adult man who first developed membranoproliferative glomerulonephritis and later HUS. C3 levels were very low. The patient had undetectable factor H levels in serum and a weak factor H 150 kDa band. Double immunodiffusion showed partial antigenic identity with factor H in normal serum owing to the presence of factor H-like protein 1. Strong specific labeling for factor H was detected in glomerular endothelium, mesangium and in glomerular and tubular epithelium as well as in bone marrow cells. A heterozygous mutation in CCP 20 of factor H was found in a girl with HUS. C3 levels were moderately decreased at onset. Factor H levels were normal and a normal 150 kDa band was present. Double immunodiffusion showed antigenic identity with normal factor H. Factor H labeling was minimal in the renal cortex. Factor H dysfunction was demonstrated by increased sheep erythrocyte hemolysis and decreased binding to endothelial cells. In summary, two different factor H mutations associated with HUS were examined: in one, factor H accumulated in cells, and in the other, membrane binding was reduced.

  12. Recombinant human erythropoietin (rHuEPO): more than just the correction of uremic anemia.

    PubMed

    Buemi, Michele; Aloisi, Carmela; Cavallaro, Emanuela; Corica, Francesco; Floccari, Fulvio; Grasso, Giovanni; Lasco, Antonino; Pettinato, Giuseppina; Ruello, Antonella; Sturiale, Alessio; Frisina, Nicola

    2002-01-01

    Hematopoiesis is controlled by numerous interdependent humoral and endocrine factors. Erythropoietin (EPO), a hydrophobic sialoglycoproteic hormone, plays a crucial role in the regulation of hematopoiesis, and induces proliferation, maturation and differentiation of the erythroid cell line precursors. Thanks to recombinant DNA techniques, different recombinant hormones can now be produced at low cost and in large amounts. This has led to greater understanding of the pathophysiological factors regulating hematopoiesis. This in turn, hasprompted the search for new therapeutic approaches. EPO might also be used to treat patients with different types of anemia: uremics, newborns, patients with anemia from cancer or myeloproliferative disease, thalassemia, bone marrow transplants, chronic infectious diseases. Besides erythroid cells, EPO affects other blood cell lines, such as myeloid cells, lymphocytes and megakaryocytes. It can also enhance polymorphonuclear cell phagocytosis and reduce macrophage activation, thus modulating the inflammatory process. Hematopoietic and endothelial cells probably have the same origin, and the discovery of eyrthropoietin receptors also on mesangial, myocardial and smooth muscle cells has prompted research into the non-erythropoietic function of the hormone. EPO has an important, direct, hemodynamic and vasoactive effect, which does not depend only on an increase in hematocrit and viscosity. Moreover, EPO and its receptors have been found in the brain, suggesting a role in preventing neuronal death. Finally, the recently discovered interaction between EPO and vascular endothelial growth factor (VEGF), and the ability of EPO to stimulate endothelial cell mitosis and motility may be of importance in neovascularization and wound healing.

  13. Calcific Tendinitis of the Gluteus Maximus in a Golfer.

    PubMed

    Williams, Ariel A; Stang, Thomas S; Fritz, Jan; Papp, Derek F

    2016-09-01

    Calcific tendinitis is a relatively rare condition in which calcium is inappropriately deposited in tendons, resulting in a local inflammatory reaction that can cause severe symptoms in certain cases. The cause of this disease process is not completely understood, although repetitive microtrauma likely plays a role in its development. Although the disorder most often involves the rotator cuff, it can affect other structures throughout the body, such as the tendons about the ankle and hip-including the rectus femoris and gluteus maximus. Nonoperative management typically involves using an anti-inflammatory medication and activity modification and can be augmented with formal physical therapy and modalities. Although nonoperative management provides adequate relief for many patients, sometimes operative debridement of the calcific deposit with or without repair of the involved tendon is required. The authors report an unusual case of calcific tendinitis of the gluteus maximus insertion in a golfer. The patient had tried nonoperative treatment for approximately 2 years with no real relief, and a recent exacerbation of the pain was significantly delaying his return to sport. Although plain radiographs did not show abnormalities, magnetic resonance imaging showed a calcific deposit in the insertion of the gluteus maximus tendon. After discussing further treatment options with the patient, the decision was made to remove the deposit and repair the insertion. He recovered completely and was able to return to play. The frequency, pathogenesis, and treatment of this condition are discussed in this case report, as well as the possible link to golf in this patient. [Orthopedics.2016; 39(5):e997-e1000.]. PMID:27337668

  14. Stone formation and calcification by nanobacteria in the human body

    NASA Astrophysics Data System (ADS)

    Ciftcioglu, Neva; Bjorklund, Michael; Kajander, E. Olavi

    1998-07-01

    The formation of discrete and organized inorganic crystalline structures within macromolecular extracellular matrices is a widespread biological phenomenon generally referred to as biomineralization. Recently, bacteria have been implicated as factors in biogeochemical cycles for formation of many minerals in aqueous sediments. We have found nanobacterial culture systems that allow for reproducible production of apatite calcification in vitro. Depending on the culture conditions, tiny nanocolloid-sized particles covered with apatite, forming various size of aggregates and stones were observed. In this study, we detected the presence of nanobacteria in demineralized trilobit fossil, geode, apatite, and calcite stones by immunofluorescence staining. Amethyst and other quartz stones, and chalk gave negative results. Microorganisms are capable of depositing apatite outside the thermodynamic equilibrium in sea water. We bring now evidence that this occurs in the human body as well. Previously, only struvite kidney stones composed of magnesium ammonium phosphate and small amounts of apatite have been regarded as bacteria related. 90 percent of demineralized human kidney stones now screened, contained nanobacteria. At least three different distribution patterns of nanobacteria were conditions, and human kidney stones that are formed from small apatite units. Prerequisites for the formation of kidney stones are the supersaturation of urine and presence of nidi for crystallization. Nanobacteria are important nidi and their presence might be of special interest in space flights where supersaturation of urine is present due to the loss of bone. Furthermore, we bring evidence that nanobacteria may act as crystallization nidi for the formation of biogenic apatite structures in tissue calcification found in e.g., atherosclerotic plaques, extensive metastatic and tumoral calcification, acute periarthritis, malacoplakia, and malignant diseases. In nanaobacteria-infected fibroblasts

  15. Modelling coral polyp calcification in relation to ocean acidification

    NASA Astrophysics Data System (ADS)

    Hohn, S.; Merico, A.

    2012-11-01

    Rising atmospheric CO2 concentrations due to anthropogenic emissions induce changes in the carbonate chemistry of the oceans and, ultimately, a drop in ocean pH. This acidification process can harm calcifying organisms like coccolithophores, molluscs, echinoderms, and corals. It is expected that ocean acidification in combination with other anthropogenic stressors will cause a severe decline in coral abundance by the end of this century, with associated disastrous effects on reef ecosystems. Despite the growing importance of the topic, little progress has been made with respect to modelling the impact of acidification on coral calcification. Here we present a model for a coral polyp that simulates the carbonate system in four different compartments: the seawater, the polyp tissue, the coelenteron, and the calcifying fluid. Precipitation of calcium carbonate takes place in the metabolically controlled calcifying fluid beneath the polyp tissue. The model is adjusted to a state of activity as observed by direct microsensor measurements in the calcifying fluid. We find that a transport mechanism for bicarbonate is required to supplement carbon into the calcifying fluid because CO2 diffusion alone is not sufficient to sustain the observed calcification rates. Simulated CO2 perturbation experiments reveal decreasing calcification rates under elevated pCO2 despite the strong metabolic control of the calcifying fluid. Diffusion of CO2 through the tissue into the calcifying fluid increases with increasing seawater pCO2, leading to decreased aragonite saturation in the calcifying fluid. Our modelling study provides important insights into the complexity of the calcification process at the organism level and helps to quantify the effect of ocean acidification on corals.

  16. ARTHROSCOPY FOR TREATMENT OF REFRACTORY CALCIFIC TENDONITIS OF THE SHOULDER

    PubMed Central

    Fernandes, Marcos Rassi; Fernandes, Rui José

    2015-01-01

    Objective: To evaluate the results from arthroscopic treatment in patients with calcific tendonitis of the shoulder. Methods: Between September 2001 and June 2006, 55 patients with calcific tendonitis of the shoulder that was resistant to conservative treatment were evaluated, with follow-up of 12 to 70 months. The mean age was 42 years, ranging from 30 to 64 years; 44 patients were female (80%). There were 37 right shoulders, and 63.63% of the cases were on the dominant side. Pain was the main symptom, and the mean time between onset of symptoms and arthroscopy was 38 months (range: five to 120 months). The tendon affected was the supraspinatus in 42 cases, the infraspinatus in 11 cases and an association between these in two cases. Acromioplasty was carried out in 12 patients (21.82%) and subacromial bursectomy was performed in all cases. Results: According to the UCLA criteria, 46 cases were excellent and six were good, making a total of 52 satisfactory results (94.54%). Conclusion: Arthroscopic treatment of calcific tendonitis of the shoulder appears to be an effective method, with high rates of satisfactory results. Associated acromioplasty is not necessary. PMID:27019839

  17. Calcification provides mechanical reinforcement to whale baleen alpha-keratin.

    PubMed

    Szewciw, L J; de Kerckhove, D G; Grime, G W; Fudge, D S

    2010-09-01

    Hard alpha-keratins such as hair, nail, wool and horn are stiff epidermal appendages used by mammals in a variety of functions including thermoregulation, feeding and intraspecific competition. Hard alpha-keratins are fibre-reinforced structures consisting of cytoskeletal elements known as 'intermediate filaments' embedded in an amorphous protein matrix. Recent research has shown that intermediate filaments are soft and extensible in living keratinocytes but become far stiffer and less extensible in keratinized cells, and this stiffening may be mediated by air-drying. Baleen, the keratinous plates used by baleen whales during filter feeding, is an unusual mammalian keratin in that it never air dries, and in some species, it represents the most heavily calcified of all the hard alpha-keratins. We therefore tested the hypothesis that whale baleen is stiffened by calcification. Here, we provide, to our knowledge, the first comprehensive description of baleen material properties and show that calcification contributes to overcoming the shortcomings of stiffening this hard alpha-keratin without the benefit of air-drying. We also demonstrate striking interspecies differences in the calcification patterns among three species of baleen whales and provide novel insights into the function and evolution of this unusual biomaterial.

  18. Peripheral arterial calcification: Prevalence, mechanism, detection, and clinical implications

    PubMed Central

    Rocha-Singh, Krishna J; Zeller, Thomas; Jaff, Michael R

    2014-01-01

    Vascular calcification (VC), particularly medial (Mönckeberg's medial sclerosis) arterial calcification, is common in patients with diabetes mellitus and chronic kidney disease and is associated with increased cardiovascular morbidity and mortality. Although, the underlying pathophysiological mechanisms and genetic pathways of VC are not fully known, hypocalcemia, hyperphosphatemia, and the suppression of parathyroid hormone activity are central to the development of vessel mineralization and, consequently, bone demineralization. In addition to preventive measures, such as the modification of atherosclerotic cardiovascular risk factors, current treatment strategies include the use of calcium-free phosphate binders, vitamin D analogs, and calcium mimetics that have shown promising results, albeit in small patient cohorts. The impact of intimal and medial VC on the safety and effectiveness of endovascular devices to treat symptomatic peripheral arterial disease (PAD) remains poorly defined. The absence of a generally accepted, validated vascular calcium grading scale hampers clinical progress in assessing the safety and utility of various endovascular devices (e.g., atherectomy) in treating calcified vessels. Accordingly, we propose the peripheral arterial calcium scoring system (PACSS) and a method for its clinical validation. A better understanding of the pathogenesis of vascular calcification and the development of optimal medical and endovascular treatment strategies are crucial as the population ages and presents with more chronic comorbidities. PMID:24402839

  19. Osteoprotegerin and Vascular Calcification: Clinical and Prognostic Relevance.

    PubMed

    Makarović, Sandra; Makarović, Zorin; Steiner, Robert; Mihaljević, Ivan; Milas-Ahić, Jasminka

    2015-06-01

    Osteoprotegerin (OPG) is a key regulator in bone metabolism, that also has effect in vascular system. Studies suggest that osteoprotegerin is a critical arterial calcification inhibitor, and is released by endothelial cells as a protective mechanism for their survival in certain pathological conditions, such as diabetes mellitus, chronic kidney disease, and other metabolic disorders. That has been shown in studies in vitro and in animal models. The discovery that OPG deficient mice (OPG -/- mice) develop severe osteoporosis and arterial calcification, has led to conclusion that osteoprotegerin might be mulecule linking vascular and bone system. Paradoxically however, clinical trials have shown recently that OPG serum levels is increased in coronary artery disease and correlates with its severity, ischemic cardial decompensation, and future cardiovascular events. Therefore it is possible that osteoprotegerin could have a new function as a potential biomarker in early identification and monitoring patients with cardiovascular disease. Amongst that osteoprotegerin is in association with well known atherosclerosis risc factors: undoubtedly it is proven its relationship with age, smoking and diabetes mellitus. There is evidence regarding presence of hyperlipoproteinemia and increased serum levels of osteoprotegerin. Also the researches have been directed in genetic level, linking certain single nucleotid genetic polymorphisms of osteoprotegerin and vascular calcification appearance. This review emphasises multifactorial role of OPG, presenting numerous clinical and experimental studies regarding its role in vascular pathology, suggesting a novel biomarker in cardiovascular diseases, showing latest conclusions about this interesting topic that needs to be further explored. PMID:26753467

  20. In vitro models of aortic valve calcification: solidifying a system.

    PubMed

    Bowler, Meghan A; Merryman, W David

    2015-01-01

    Calcific aortic valve disease (CAVD) affects 25% of people over 65, and the late-stage stenotic state can only be treated with total valve replacement, requiring 85,000 surgeries annually in the US alone (University of Maryland Medical Center, 2013, http://umm.edu/programs/services/heart-center-programs/cardiothoracic-surgery/valve-surgery/facts). As CAVD is an age-related disease, many of the affected patients are unable to undergo the open-chest surgery that is its only current cure. This challenge motivates the elucidation of the mechanisms involved in calcification, with the eventual goal of alternative preventative and therapeutic strategies. There is no sufficient animal model of CAVD, so we turn to potential in vitro models. In general, in vitro models have the advantages of shortened experiment time and better control over multiple variables compared to in vivo models. As with all models, the hypothesis being tested dictates the most important characteristics of the in vivo physiology to recapitulate. Here, we collate the relevant pieces of designing and evaluating aortic valve calcification so that investigators can more effectively draw significant conclusions from their results. PMID:25249188

  1. Effect of trace metal availability on coccolithophorid calcification.

    PubMed

    Schulz, K G; Zondervan, I; Gerringa, L J A; Timmermans, K R; Veldhuis, M J W; Riebesell, U

    2004-08-01

    The deposition of atmospheric dust into the ocean has varied considerably over geological time. Because some of the trace metals contained in dust are essential plant nutrients which can limit phytoplankton growth in parts of the ocean, it has been suggested that variations in dust supply to the surface ocean might influence primary production. Whereas the role of trace metal availability in photosynthetic carbon fixation has received considerable attention, its effect on biogenic calcification is virtually unknown. The production of both particulate organic carbon and calcium carbonate (CaCO3) drives the ocean's biological carbon pump. The ratio of particulate organic carbon to CaCO3 export, the so-called rain ratio, is one of the factors determining CO2 sequestration in the deep ocean. Here we investigate the influence of the essential trace metals iron and zinc on the prominent CaCO3-producing microalga Emiliania huxleyi. We show that whereas at low iron concentrations growth and calcification are equally reduced, low zinc concentrations result in a de-coupling of the two processes. Despite the reduced growth rate of zinc-limited cells, CaCO3 production rates per cell remain unaffected, thus leading to highly calcified cells. These results suggest that changes in dust deposition can affect biogenic calcification in oceanic regions characterized by trace metal limitation, with possible consequences for CO2 partitioning between the atmosphere and the ocean.

  2. Consideration of coastal carbonate chemistry in understanding biological calcification

    NASA Astrophysics Data System (ADS)

    Fassbender, Andrea J.; Sabine, Christopher L.; Feifel, Kirsten M.

    2016-05-01

    Correlations between aragonite saturation state (ΩAr) and calcification have been identified in many laboratory manipulation experiments aiming to assess biological responses to ocean acidification (OA). These relationships have been used with projections of ΩAr under continued OA to evaluate potential impacts on marine calcifiers. Recent work suggests, however, that calcification in some species may be controlled by the ratio of bicarbonate to hydrogen ion, or the substrate-to-inhibitor ratio (SIR), rather than ΩAr. SIR and ΩAr are not always positively correlated in the natural environment, which means that ΩAr can be a poor indicator of the calcifying environment when ΩAr->1. Highly variable carbonate chemistry in the coastal zone challenges our ability to monitor fluctuations in ΩAr, SIR, and the ΩAr-SIR relationship making it difficult to assess biological OA exposures and vulnerability. Careful consideration of natural variability throughout ocean environments is required to accurately determine the influence of OA on biological calcification.

  3. In vitro Models of Aortic Valve Calcification: Solidifying a System

    PubMed Central

    Bowler, Meghan A.; Merryman, W. David

    2014-01-01

    Calcific aortic valve disease (CAVD) affects 25% of people over 65, and the late-stage stenotic state can only be treated with total valve replacement, requiring 85,000 surgeries annually in the US alone [1]. As CAVD is an age-related disease, many of the affected patients are unable to undergo the open-chest surgery that is its only current cure. This challenge motivates the elucidation of the mechanisms involved in calcification, with the eventual goal of alternative preventative and therapeutic strategies. There is no sufficient animal model of CAVD, so we turn to potential in vitro models. In general, in vitro models have the advantages of shortened experiment time and better control over multiple variables compared to in vivo models. As with all models, the hypothesis being tested dictates the most important characteristics of the in vivo physiology to recapitulate. Here, we collate the relevant pieces of designing and evaluating aortic valve calcification so that investigators can more effectively draw significant conclusions from their results. PMID:25249188

  4. The role of cellular senescence during vascular calcification: a key paradigm in aging research.

    PubMed

    Mackenzie, N C W; MacRae, V E

    2011-07-01

    Vascular calcification has severe clinical consequences and is considered an accurate predictor of future adverse cardiovascular events. Vascular calcification refers to the deposition of calcium phosphate mineral, most often hydroxyapatite, in arteries. Extensive calcification of the vascular system is a key characteristic of aging. In this article, we outline the mechanisms governing vascular calcification and highlight its association with cellular senescence. This review discusses the molecular mechanisms of cellular senescence and its affect on calcification of vascular cells, the relevance of phosphate regulation and the function of FGF23 and Klotho proteins. The association of vascular calcification and cellular senescence with the rare human aging disorder Hutchison-Gilford Progeria Syndrome (HGPS) is highlighted and the mouse models used to try to determine the underlying pathways are discussed. By understanding the pathways involved in these processes novel drug targets may be elucidated in an effort to reduce the effects of cellular aging as a risk factor in cardiovascular disease.

  5. Decrease in coccolithophore calcification and CO2 since the middle Miocene

    NASA Astrophysics Data System (ADS)

    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 εp 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.

  6. 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

    2016-01-01

    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

  7. 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.

  8. 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

  9. Effect of image quality on calcification detection in digital mammography

    PubMed Central

    Warren, Lucy M.; Mackenzie, Alistair; Cooke, Julie; Given-Wilson, Rosalind M.; Wallis, Matthew G.; Chakraborty, Dev P.; Dance, David R.; Bosmans, Hilde; Young, Kenneth C.

    2012-01-01

    Purpose: This study aims to investigate if microcalcification detection varies significantly when mammographic images are acquired using different image qualities, including: different detectors, dose levels, and different image processing algorithms. An additional aim was to determine how the standard European method of measuring image quality using threshold gold thickness measured with a CDMAM phantom and the associated limits in current EU guidelines relate to calcification detection. Methods: One hundred and sixty two normal breast images were acquired on an amorphous selenium direct digital (DR) system. Microcalcification clusters extracted from magnified images of slices of mastectomies were electronically inserted into half of the images. The calcification clusters had a subtle appearance. All images were adjusted using a validated mathematical method to simulate the appearance of images from a computed radiography (CR) imaging system at the same dose, from both systems at half this dose, and from the DR system at quarter this dose. The original 162 images were processed with both Hologic and Agfa (Musica-2) image processing. All other image qualities were processed with Agfa (Musica-2) image processing only. Seven experienced observers marked and rated any identified suspicious regions. Free response operating characteristic (FROC) and ROC analyses were performed on the data. The lesion sensitivity at a nonlesion localization fraction (NLF) of 0.1 was also calculated. Images of the CDMAM mammographic test phantom were acquired using the automatic setting on the DR system. These images were modified to the additional image qualities used in the observer study. The images were analyzed using automated software. In order to assess the relationship between threshold gold thickness and calcification detection a power law was fitted to the data. Results: There was a significant reduction in calcification detection using CR compared with DR: the alternative FROC

  10. Effect of image quality on calcification detection in digital mammography

    SciTech Connect

    Warren, Lucy M.; Mackenzie, Alistair; Cooke, Julie; Given-Wilson, Rosalind M.; Wallis, Matthew G.; Chakraborty, Dev P.; Dance, David R.; Bosmans, Hilde; Young, Kenneth C.

    2012-06-15

    Purpose: This study aims to investigate if microcalcification detection varies significantly when mammographic images are acquired using different image qualities, including: different detectors, dose levels, and different image processing algorithms. An additional aim was to determine how the standard European method of measuring image quality using threshold gold thickness measured with a CDMAM phantom and the associated limits in current EU guidelines relate to calcification detection. Methods: One hundred and sixty two normal breast images were acquired on an amorphous selenium direct digital (DR) system. Microcalcification clusters extracted from magnified images of slices of mastectomies were electronically inserted into half of the images. The calcification clusters had a subtle appearance. All images were adjusted using a validated mathematical method to simulate the appearance of images from a computed radiography (CR) imaging system at the same dose, from both systems at half this dose, and from the DR system at quarter this dose. The original 162 images were processed with both Hologic and Agfa (Musica-2) image processing. All other image qualities were processed with Agfa (Musica-2) image processing only. Seven experienced observers marked and rated any identified suspicious regions. Free response operating characteristic (FROC) and ROC analyses were performed on the data. The lesion sensitivity at a nonlesion localization fraction (NLF) of 0.1 was also calculated. Images of the CDMAM mammographic test phantom were acquired using the automatic setting on the DR system. These images were modified to the additional image qualities used in the observer study. The images were analyzed using automated software. In order to assess the relationship between threshold gold thickness and calcification detection a power law was fitted to the data. Results: There was a significant reduction in calcification detection using CR compared with DR: the alternative FROC

  11. Age-related incidence of pineal calcification detected by computed tomography

    SciTech Connect

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

    1982-03-01

    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.

  12. Progression to calcific mitral stenosis in end-stage renal disease.

    PubMed

    D'Cruz, I A; Madu, E C

    1995-12-01

    A 59-year-old man with end-stage renal disease and on hemodialysis had neither mitral stenosis nor mitral calcification on echo-Doppler examination in 1989, but had extensive mitral calcification and definite mitral stenosis on conventional and transesophageal echocardiography in 1994. The left ventricle had marked concentric hypertrophy. To our knowledge this is the first documentation of the development of calcific mitral stenosis in end-stage renal disease revealed by serial echo-Doppler studies.

  13. Calcification and airway stenosis in a child with chondrodysplasia calcificans punctata

    PubMed Central

    Goussard, Pierre; Andronikou, Savvas; Semakula-Katende, Namakula S; Gie, Robert

    2014-01-01

    Calcification of the airways is rarely seen in children. A male baby was born at 34 weeks with severe respiratory distress. Intubation was difficult with severe hypercarbia after intubation. Chest radiography demonstrated calcification in the tracheobronchial tree and this was confirmed with Chest CT scan. Flexible bronchoscopy confirmed long-segment funnel tracheal stenosis with visible calcifications in the trachea and bronchi. Chondrodysplasia punctata was diagnosed based on the clinical and radiological findings. PMID:25246461

  14. Globular adiponectin reduces vascular calcification via inhibition of ER-stress-mediated smooth muscle cell apoptosis

    PubMed Central

    Lu, Yan; Bian, Yunfei; Wang, Yueru; Bai, Rui; Wang, Jiapu; Xiao, Chuanshi

    2015-01-01

    Objective: This study aims to explore the mechanism of globular adiponectin inhibiting vascular calcification. Methods: We established drug-induced rat vascular calcification model, globular adiponectin was given to observe the effect of globular Adiponectin on the degree of calcification. The markers of vascular calcification and apoptosis were also investigated. Meanwhile, the in vitro effect of globular Adiponectin on vascular calcification was also evaluated using primary cultured rat vascular smooth muscle cells. Results: We found that globular adiponectin could inhibit drug-induced rat vascular calcification significantly in vivo. The apoptosis of vascular smooth muscle cells was also reduced. The possible mechanism could be the down-regulation of endoplasmic reticulum stress by globular adiponectin. Experiments in primary cultured vascular smooth muscle cells also confirmed that globular adiponectin could reduce cell apoptosis to suppress vascular calcification via inhibition of endoplasmic reticulum stress. Conclusions: This study confirmed that globular adiponectin could suppress vascular calcification; one of the mechanisms could be inhibition of endoplasmic reticulum stress to reduce cell apoptosis. It could provide an effective method in the therapy of vascular calcification-associated diseases. PMID:26045760

  15. [Biomarkers of vascular calcifications: the osteoprotegerin/RANK/RANK L axis].

    PubMed

    Bargnoux, Anne-Sophie; Morena, Marion; Arnaud, Josiane; Cavalier, Étienne; Zaoui, Philippe; Delanaye, Pierre; Cristol, Jean-Paul

    2015-01-01

    A better knowledge of physiopathologic phenomena responsible for vascular mineralization leads to emerging biological markers of vascular calcifications. In calcified arteries, the presence of bone matrix as well as osteoblast cells suggest that vascular calcification is an active and highly regulated process. The OPG/RANK/RANKL system is clearly of central significance in controlling vascular calcifications as in bone metabolism. Converging results suggest that circulating OPG determination should be a relevant marker of calcifications. The OPG/RANK/RANKL pathway also represents a potential therapeutic target in diseases associated with high bone resorption.

  16. Identification of Calcification with Magnetic Resonance Imaging Using Susceptibility-Weighted Imaging: A Case Study

    PubMed Central

    Wu, Zhen; Mittal, Sandeep; Kish, Karl; Yu, Yingjian; Hu, J.; Haacke, E. Mark

    2008-01-01

    Susceptibility weighted imaging (SWI) is a new MRI technique that can identify calcification by using phase images. We present a single case with a partially calcified oligodendroglioma, multiple calcified cysticercosis lesions, and multiple physiologic calcifications in the same patient. SWI phase images and computed tomography (CT) images are compared. SWI phase images showed the same calcified lesions as shown on CT and sometimes some new calcifications. Our conclusion is that SWI filtered phase images can identify calcifications as well as CT in this case. PMID:19097156

  17. Harnessing osteopontin and other natural inhibitors to mitigate ectopic calcification of bioprosthetic heart valve material

    NASA Astrophysics Data System (ADS)

    Ohri, Rachit

    Dystrophic calcification has been the long-standing major cause of bioprosthetic heart valve failure, and has been well studied in terms of the underlying causative mechanisms. Such understanding has yielded several anti-calcification strategies involving biomaterial modification at the preparation stage: chemical alteration, extraction of calcifiable components, or material modification with small-molecule anti-calcific agents. However, newer therapeutic opportunities are offered by the growing illustration of the pathology as a dynamic, actively regulated process involving several gene products, such as osteopontin (OPN), matrix-gla protein (MGP) and glycosaminoglycans (GAGs). Osteopontin, a multi-functional matricellular glycosylated phosphoprotein has emerged as a prime candidate for the role of an in vivo inhibitor of ectopic calcification with two putative mechanisms: crystal poisoning and mineral-dissolution. The full therapeutic realization of its potential necessitates a better understanding of the mechanisms of anti-calcification by osteopontin, as well as appropriate in vivo models in which to evaluate its efficacy, potency and molecular mechanisms. In this work, we pursued the development and characterization of a reliable in vivo model with the OPN-null mouse to simulate the calcification of bioprosthetic valve material, namely glutaraldehyde-fixed bovine pericardium (GFBP) tissue. Subsequently, we used the calcification model to evaluate hypotheses based on the anti-calcific potential of osteopontin. Several modes of administering exogenous OPN to the implant site in OPN-null mice were explored, including soluble injected OPN, OPN covalently immobilized on the biomaterial, and OPN adsorbed onto the biomaterial. An investigation of the structure-function aspects of the anti-calcific ability of OPN was also pursued in the in vivo model. The OPN-null mouse was also used as an in vivo test-bed to evaluate the anti-calcific potential of other biomolecules

  18. Role of extracellular vesicles in de novo mineralization: an additional novel mechanism of cardiovascular calcification.

    PubMed

    New, Sophie E P; Aikawa, Elena

    2013-08-01

    Extracellular vesicles are membrane micro/nanovesicles secreted by many cell types into the circulation and the extracellular milieu in physiological and pathological conditions. Evidence suggests that extracellular vesicles, known as matrix vesicles, play a role in the mineralization of skeletal tissue, but emerging ultrastructural and in vitro studies have demonstrated their contribution to cardiovascular calcification as well. Cells involved in the progression of cardiovascular calcification release active vesicles capable of nucleating hydroxyapatite on their membranes. This review discusses the role of extracellular vesicles in cardiovascular calcification and elaborates on this additional mechanism of calcification as an alternative pathway to the currently accepted mechanism of biomineralization via osteogenic differentiation.

  19. Regulation of the sodium-phosphate cotransporter Pit-1 and its role in vascular calcification.

    PubMed

    Gonzalez, Magdalena; Martínez, Rafael; Amador, Cristián; Michea, Luis

    2009-10-01

    Vascular calcification is caused by the deposition of basic calcium phosphate crystals in blood vessels, myocardium, and/or cardiac valves. Calcification decreases artery wall compliance, and arterial calcification is associated to mortality in hyperphosphatemic renal failure and diabetes mellitus. The calcification of the tunica media characterizes the arteriosclerosis observed with age, diabetes and end stage-renal disease, and it can develop independently from intima calcification. As part of the vascular calcification mechanism, vascular smooth muscle cells (VSMC) experience a transition from a contractile to an osteochondrogenic phenotype and a sequence of molecular events that are typical of endochondral ossification. The current evidence indicates a key role of increased phosphate uptake by VSMC for calcification, which supplies the substrate for hydroxyapatite formation and could trigger or potentiate VSMC transdiferentiation. The present review analyzes the sodium-phosphate cotransporter Pit-1, which is implicated in calcification. On the basis of the available data obtained in the study of vascular and osteoblastic experimental models, we discuss potential regulatory mechanisms that could lead to increased sodium-dependent phosphate uptake in vascular calcification. PMID:19485893

  20. High-phosphorus diet maximizes and low-dose calcitriol attenuates skeletal muscle changes in long-term uremic rats.

    PubMed

    Acevedo, Luz M; López, Ignacio; Peralta-Ramírez, Alan; Pineda, Carmen; Chamizo, Verónica E; Rodríguez, Mariano; Aguilera-Tejero, Escolástico; Rivero, José-Luis L

    2016-05-01

    Although disorders of mineral metabolism and skeletal muscle are common in chronic kidney disease (CKD), their potential relationship remains unexplored. Elevations in plasma phosphate, parathyroid hormone, and fibroblastic growth factor 23 together with decreased calcitriol levels are common features of CKD. High-phosphate intake is a major contributor to progression of CKD. This study was primarily aimed to determine the influence of high-phosphate intake on muscle and to investigate whether calcitriol supplementation counteracts negative skeletal muscle changes associated with long-term uremia. Proportions and metabolic and morphological features of myosin-based muscle fiber types were assessed in the slow-twitch soleus and the fast-twitch tibialis cranialis muscles of uremic rats (5/6 nephrectomy, Nx) and compared with sham-operated (So) controls. Three groups of Nx rats received either a standard diet (0.6% phosphorus, Nx-Sd), or a high-phosphorus diet (0.9% phosphorus, Nx-Pho), or a high-phosphorus diet plus calcitriol (10 ng/kg 3 day/wk ip, Nx-Pho + Cal) for 12 wk. Two groups of So rats received either a standard diet or a high-phosphorus diet (So-Pho) over the same period. A multivariate analysis encompassing all fiber-type characteristics indicated that Nx-Pho + Cal rats displayed skeletal muscle phenotypes intermediate between Nx-Pho and So-Pho rats and that uremia-induced skeletal muscle changes were of greater magnitude in Nx-Pho than in Nx-Sd rats. In uremic rats, treatment with calcitriol preserved fiber-type composition, cross-sectional size, myonuclear domain size, oxidative capacity, and capillarity of muscle fibers. These data demonstrate that a high-phosphorus diet potentiates and low-dose calcitriol attenuates adverse skeletal muscle changes in long-term uremic rats.

  1. High-phosphorus diet maximizes and low-dose calcitriol attenuates skeletal muscle changes in long-term uremic rats.

    PubMed

    Acevedo, Luz M; López, Ignacio; Peralta-Ramírez, Alan; Pineda, Carmen; Chamizo, Verónica E; Rodríguez, Mariano; Aguilera-Tejero, Escolástico; Rivero, José-Luis L

    2016-05-01

    Although disorders of mineral metabolism and skeletal muscle are common in chronic kidney disease (CKD), their potential relationship remains unexplored. Elevations in plasma phosphate, parathyroid hormone, and fibroblastic growth factor 23 together with decreased calcitriol levels are common features of CKD. High-phosphate intake is a major contributor to progression of CKD. This study was primarily aimed to determine the influence of high-phosphate intake on muscle and to investigate whether calcitriol supplementation counteracts negative skeletal muscle changes associated with long-term uremia. Proportions and metabolic and morphological features of myosin-based muscle fiber types were assessed in the slow-twitch soleus and the fast-twitch tibialis cranialis muscles of uremic rats (5/6 nephrectomy, Nx) and compared with sham-operated (So) controls. Three groups of Nx rats received either a standard diet (0.6% phosphorus, Nx-Sd), or a high-phosphorus diet (0.9% phosphorus, Nx-Pho), or a high-phosphorus diet plus calcitriol (10 ng/kg 3 day/wk ip, Nx-Pho + Cal) for 12 wk. Two groups of So rats received either a standard diet or a high-phosphorus diet (So-Pho) over the same period. A multivariate analysis encompassing all fiber-type characteristics indicated that Nx-Pho + Cal rats displayed skeletal muscle phenotypes intermediate between Nx-Pho and So-Pho rats and that uremia-induced skeletal muscle changes were of greater magnitude in Nx-Pho than in Nx-Sd rats. In uremic rats, treatment with calcitriol preserved fiber-type composition, cross-sectional size, myonuclear domain size, oxidative capacity, and capillarity of muscle fibers. These data demonstrate that a high-phosphorus diet potentiates and low-dose calcitriol attenuates adverse skeletal muscle changes in long-term uremic rats. PMID:26869708

  2. Uremic Toxins Induce ET-1 Release by Human Proximal Tubule Cells, which Regulates Organic Cation Uptake Time-Dependently.

    PubMed

    Schophuizen, Carolien M S; Hoenderop, Joost G J; Masereeuw, Rosalinde; Heuvel, Lambert P van den

    2015-06-26

    In renal failure, the systemic accumulation of uremic waste products is strongly associated with the development of a chronic inflammatory state. Here, the effect of cationic uremic toxins on the release of inflammatory cytokines and endothelin-1 (ET-1) was investigated in conditionally immortalized proximal tubule epithelial cells (ciPTEC). Additionally, we examined the effects of ET-1 on the cellular uptake mediated by organic cation transporters (OCTs). Exposure of ciPTEC to cationic uremic toxins initiated production of the inflammatory cytokines IL-6 (117 ± 3%, p < 0.001), IL-8 (122 ± 3%, p < 0.001), and ET-1 (134 ± 5%, p < 0.001). This was accompanied by a down-regulation of OCT mediated 4-(4-(dimethylamino)styryl)-N-methylpyridinium-iodide (ASP+) uptake in ciPTEC at 30 min (23 ± 4%, p < 0.001), which restored within 60 min of incubation. Exposure to ET-1 for 24 h increased the ASP+ uptake significantly (20 ± 5%, p < 0.001). These effects could be blocked by BQ-788, indicating activation of an ET-B-receptor-mediated signaling pathway. Downstream the receptor, iNOS inhibition by (N(G)-monomethyl-l-arginine) l-NMMA acetate or aminoguanidine, as well as protein kinase C activation, ameliorated the short-term effects. These results indicate that uremia results in the release of cytokines and ET-1 from human proximal tubule cells, in vitro. Furthermore, ET-1 exposure was found to regulate proximal tubular OCT transport activity in a differential, time-dependent, fashion.

  3. Hemolytic uremic syndrome: late renal injury and changing incidence-a single centre experience in Canada.

    PubMed

    Robitaille, Pierre; Clermont, Marie-José; Mérouani, Aïcha; Phan, Véronique; Lapeyraque, Anne-Laure

    2012-01-01

    Aims. To assess trends in the incidence of pediatric diarrhea-associated hemolytic uremic syndrome (D(+) HUS) and document long-term renal sequelae. Methods. We conducted a retrospective cohort study of children with D(+) HUS admitted to a tertiary care pediatric hospital in Montreal, Canada, from 1976 to 2010. In 2010, we recontacted patients admitted before 2000. Results. Of 337 cases, median age at presentation was 3.01 years (range 0.4-14). Yearly incidence peaked in 1988 and 1994-95, returning to near-1977 levels since 2003. Twelve patients (3.6%) died and 19 (5.6%) experienced long-term renal failure. Almost half (47%) The patients required dialysis. Need for dialysis was the best predictor of renal sequelae, accounting for 100% of severe complications. Of children followed ≥1 year (n = 199, mean follow-up 8.20 ± 6.78 years), 19 had severe and 18 mild-to-moderate kidney injury, a total sequelae rate, of 18.6%. Ten years or more after-HUS (n = 85, mean follow-up 15.4 ± 5.32 years), 8 (9.4%) patients demonstrated serious complications and 22 (25.9%) mild-to-moderate, including 14 (16%) microalbuminuria: total sequelae, 35.3%. Conclusions. Patients with D(+) HUS should be monitored at least 5 years, including microalbuminuria testing, especially if dialysis was required. The cause of the declining incidence of D(+)HUS is elusive. However, conceivably, improved public health education may have played an important role in the prevention of food-borne disease. PMID:24278685

  4. Hemolytic Uremic Syndrome: Late Renal Injury and Changing Incidence—A Single Centre Experience in Canada

    PubMed Central

    Robitaille, Pierre; Clermont, Marie-José; Mérouani, Aïcha; Phan, Véronique; Lapeyraque, Anne-Laure

    2012-01-01

    Aims. To assess trends in the incidence of pediatric diarrhea-associated hemolytic uremic syndrome (D+ HUS) and document long-term renal sequelae. Methods. We conducted a retrospective cohort study of children with D+ HUS admitted to a tertiary care pediatric hospital in Montreal, Canada, from 1976 to 2010. In 2010, we recontacted patients admitted before 2000. Results. Of 337 cases, median age at presentation was 3.01 years (range 0.4–14). Yearly incidence peaked in 1988 and 1994-95, returning to near-1977 levels since 2003. Twelve patients (3.6%) died and 19 (5.6%) experienced long-term renal failure. Almost half (47%) The patients required dialysis. Need for dialysis was the best predictor of renal sequelae, accounting for 100% of severe complications. Of children followed ≥1 year (n = 199, mean follow-up 8.20 ± 6.78 years), 19 had severe and 18 mild-to-moderate kidney injury, a total sequelae rate, of 18.6%. Ten years or more after-HUS (n = 85, mean follow-up 15.4 ± 5.32 years), 8 (9.4%) patients demonstrated serious complications and 22 (25.9%) mild-to-moderate, including 14 (16%) microalbuminuria: total sequelae, 35.3%. Conclusions. Patients with D+ HUS should be monitored at least 5 years, including microalbuminuria testing, especially if dialysis was required. The cause of the declining incidence of D+HUS is elusive. However, conceivably, improved public health education may have played an important role in the prevention of food-borne disease. PMID:24278685

  5. End-Stage Renal Disease from Hemolytic Uremic Syndrome in the United States, 1995 to 2010

    PubMed Central

    Sexton, Donal J.; Reule, Scott; Solid, Craig A.; Chen, Shu-Cheng; Collins, Allan J.; Foley, Robert N.

    2015-01-01

    Background Management of hemolytic uremic syndrome (HUS) has evolved rapidly, and optimal treatment strategies are controversial. However, it is unknown whether the burden of end-stage renal disease (ESRD) from HUS has changed, and outcomes on dialysis in the US are not well described. Methods We retrospectively examined data for patients initiating maintenance renal replacement therapy (RRT) (n = 1,557,117), 1995–2010, to define standardized incidence ratios (SIRs) and outcomes of ESRD from HUS) (n = 2241). Results Overall ESRD rates from HUS in 2001–2002 were 0.5 cases/million per year; and were higher for patients characterized by age 40–64 years (0.6), ≥ 65 years (0.7), female sex (0.6), and non-Hispanic African American race (0.7). SIRs remained unchanged (P ≥ 0.05) between 2001–2002 and 2009–2010 in the overall population. Compared with patients with ESRD from other causes, patients with HUS were more likely to be younger, female, white, and non-Hispanic. Over 5.4 years of follow-up, HUS patients differed from matched controls with ESRD from other causes by lower rates of death (8.3 per 100 person-years in cases vs. 10.4 in controls, P < 0.001), listing for renal transplant (7.6 vs. 8.6 per 100 person-years, P = 0.04), and undergoing transplant (6.9 vs. 9 per 100 person-years, P < 0.001). Conclusions The incidence of ESRD from HUS appears not to have risen substantially in the last decade. However, given that HUS subtypes could not be determined in this study, these findings should be interpreted with caution. PMID:25689876

  6. Erectile dysfunction in uremic dialysis patients: diagnostic evaluation in the sildenafil era.

    PubMed

    Bellinghieri, G; Santoro, D; Lo Forti, B; Mallamace, A; De Santo, R M; Savica, V

    2001-10-01

    The two words that mean sexual dysfunction, impotence and erectile dysfunction (ED), express two different concepts. Impotence is a general male sexual dysfunction that includes libidinal, orgasmic, and ejaculatory dysfunction. ED is the inability to achieve or maintain an erection sufficient to allow satisfactory sexual intercourse and is part of the general male sexual dysfunction termed impotence that includes libidinal, orgasmic, and ejaculatory dysfunction. Uremic men of different ages report a variety of sexual problems, including sexual hormonal pattern alterations, reduction in or loss of libido, infertility, and impotence, conditioning their well-being status. In evaluating and treating sexual dysfunction, a nephrologist must consider factors involved in its pathogenesis, such as hypothalamic-pituitary-gonadal axis alterations, psychological problems related to chronic disease, secondary hyperparathyroidism, anemia, autonomic neuropathy, derangements in arterial supply or venous outflow, and the normal structure of cavernous body smooth muscle cells. The introduction of sildenafil to treat impotent patients has completely changed the approach to evaluating these subjects because this drug is considered an effective well-tolerated treatment for men with ED. In the past, we proposed an algorithm that gave the opportunity to explore the previously mentioned factors using such instrumental interventions as the nocturnal penile tumescence test, penile echo color Doppler, nervous conduction velocity, and cavernous body biopsy, addressed to prescribe needed surgical or medical interventions. The complexity of the proposed algorithm requires many diagnostic procedures and much time and economic resources to localize the pathological lesions responsible for ED. Because of the new oral drug sildenafil, we propose a new algorithm to test the possibility of obtaining an erection and classify patients as responders or nonresponders to the sildenafil test.

  7. Hemorrhagic colitis in postdiarrheal hemolytic uremic syndrome: retrospective analysis of 54 children.

    PubMed

    Rahman, Ricardo C; Cobeñas, Carlos J; Drut, Ricardo; Amoreo, Oscar R; Ruscasso, Javier D; Spizzirri, Ana P; Suarez, Angela Del C; Zalba, Javier H; Ferrari, Celia; Gatti, Marcela C

    2012-02-01

    Hemorrhagic colitis (HC) is a severe manifestation of the hemolytic uremic syndrome (HUS). We performed a retrospective analysis of patients with HC with the following aims: (1) to characterize the clinicopathologic features; (2) to evaluate mortality rate; (3) to analyze severity of renal and central nervous system (CNS) disease. Patients with HC assisted between 1981-2009 were evaluated and compared with a control group of 137 patients without HC. Among 987 patients with diarrheal prodrome (D) + HUS, 54 (5.5%) presented HC. Clinical findings included abdominal pain (96%), distension (93%), hematochezia (44%), and abdominal mass (11%). Surgery was indicated in 35 patients (65%), and 17 (48.5%) required bowel resection. Transverse and ascending colon were most frequently affected. Macroscopic evaluation showed bowel necrosis (18) and perforation (12). Histologic evaluation (29) showed that 25 (86.2%) had necrosis of the affected segment (transmural in 21). A leukocyte count >20,000/mm(3) and hematocrit >30% were more common in HC patients than in controls (p < 0.001 and p < 0.0001, respectively). Mortality rate was higher in HC patients (33.3%) than in controls (1.4%; p < 0.0001). Dialysis >10 days, seizures, and coma were more frequent in HC patients than in controls (p < 0.0001). In summary, most patients had prominent abdominal findings, and almost 2/3 patients required surgery. Transverse/ascending colon was most affected, and the main histologic finding was transmural necrosis. Higher hematocrit and leukocytosis were frequent. Mortality rate was extremely high, and most had long-lasting anuria and severe neurologic involvement. PMID:21809003

  8. Effect of diet, enalapril, or losartan in post-diarrheal hemolytic uremic syndrome nephropathy.

    PubMed

    Caletti, Maria Gracia; Missoni, Mabel; Vezzani, Clarisa; Grignoli, María; Piantanida, Juan Jose; Repetto, Horacio A; Exeni, Ramon; Rasse, Stella Maris

    2011-08-01

    Proteinuria is the main indicator of renal disease progression in many chronic conditions. There is currently little information available on the efficacy, safety, and individual tolerance of patients with post-diarrheal hemolytic uremic syndrome (D+ HUS) nephropathy to therapies involving diet, enalapril, or losartan. A multicenter, double-blind, randomized controlled trail was conducted to evaluate the effect of a normosodic-normoproteic diet (Phase I) and the effect of normosodic-normoproteic diet plus enalapril (0.18-0.27 mg/kg/day) or losartan (0.89-1.34 mg/kg/day) (Phase II) on children with D+ HUS, normal renal function, and persistent, mild (5.1-49.9 mg/kg/day) proteinuria. Dietary intervention reduced the mean protein intake from 3.4 to 2.2 mg/kg/day. Of 137 children, proteinuria normalized in 91 (66.4 %) within 23-45 days; the remaining 46 patients were randomized to diet plus placebo (group 1, n = 16), plus losartan (group 2, n = 16), or enalapril (group 3, n = 14). In groups 1, 2, and 3, proteinuria was reduced by 30.0, 82.0, and 66.3%, respectively, and normalized in six (37.5%), three (81.3%), and 11 (78.6%) patients, respectively (χ(2)= 8.9, p = 0.015). These results suggest that: (1) a normosodic-normoproteic diet can normalize proteinuria in the majority of children with D+ HUS with mild sequelae, (2) the addition of enalapril or losartan to such dietary restrictions of protein further reduces proteinuria, and (3) these therapeutic interventions are safe and well tolerated. Whether these short-term effects can be extended to the long-term remains to be demonstrated.

  9. Troponin I levels in a hemolytic uremic syndrome patient with severe cardiac failure.

    PubMed

    Askiti, Varvara; Hendrickson, Kristine; Fish, Alfred J; Braunlin, Elizabeth; Sinaiko, Alan R

    2004-03-01

    Troponins are highly sensitive and specific biochemical markers of myocardial injury that are released into the circulation during myocardial ischemia. We describe changes in cardiac troponin I (cTnI) prior to and following clinical evidence of severe myocardial dysfunction in a child with hemolytic uremic syndrome (HUS). A previously healthy, 22-month-old girl presented with typical HUS and stool cultures positive for Escherichia coli O157:H7. She required dialysis, blood and platelet transfusions, and insulin for HUS-related diabetes mellitus. On the 6th hospital day she had sudden circulatory collapse with a blood pressure of 70/40 mmHg and an oxygen saturation of 88%. She responded rapidly to emergency resuscitation but had diminished left ventricular function (ejection fraction 18%). Four days after the acute event an echocardiogram showed normal ventricular size and contractility. She underwent hemodialysis for 22 days, and renal function was normal after 33 days. cTnI levels were measured with a microparticle enzyme immunoassay. cTnI was normal (>0.4 microg/l) 32 h prior to cardiac collapse, mildly increased (2.1 microg/l) 8 h before the cardiac collapse, severely elevated shortly after the cardiac event (43.1 microg/l), and peaked (140.6 microg/l) at 24 h. It then fell gradually and was normal at discharge. These results suggest that measurement of cTnI may be a useful predictor of cardiac involvement in severely affected children with HUS. PMID:14685841

  10. THE ROLE OF THE SKIN BIOPSY IN THE DIAGNOSIS OF ATYPICAL HEMOLYTIC UREMIC SYNDROME

    PubMed Central

    Magro, Cynthia M.; Momtahen, Shabnam; Mulvey, J. Justin; Yassin, Aminah H.; Kaplan, Robert B.; Laurence, Jeffrey C.

    2014-01-01

    Introduction Atypical hemolytic uremic syndrome (aHUS) is a prototypic thrombotic microangiopathy attributable to complement dysregulation. In the absence of complement inhibition, progressive clinical deterioration occurs. We postulated that a biopsy of normal skin could corroborate the diagnosis of aHUS via the demonstration of vascular deposits of C5b-9. Materials and methods Biopsies of normal skin from 22 patients with and without aHUS were processed for routine light microscopy as well as immunofluorescent studies. An assessment was made for vascular C5b-9 deposition immunohistochemically and by immunofluorescence. The biopsies were obtained primarily from the forearm and or deltoid. Results Patients with classic features of atypical HUS showed insidious microvascular changes including loose luminal platelet thrombi except in two patients in whom a striking thrombogenic vasculopathy was apparent in biopsied digital ulcers. Extensive microvascular deposits of the membrane attack complex (MAC)/ C5b-9 were identified excluding one patient in whom eculizumab was initiated prior to biopsy. In 5 of the 7 patients where follow-up was available, the patients exhibited an excellent treatment response to eculizumab. Patients without diagnostic clinical features of atypical HUS failed to show significant vascular deposits of complement except two patients with TTP including one in whom a Factor H mutation was identified. Conclusion In a clinical setting where aHUS is an important diagnostic consideration, extensive microvascular deposition of C5b-9 supports the diagnosis of either aHUS or a subset of TTP patients with concomitant complement dysregulation; significant vascular C5b-9 deposition predicts clinical responsiveness to eculizumab. PMID:25893747

  11. 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

  12. 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.

  13. 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

  14. Autophagy protects end plate chondrocytes from intermittent cyclic mechanical tension induced calcification.

    PubMed

    Xu, Hong-guang; Yu, Yun-fei; Zheng, Quan; Zhang, Wei; Wang, Chuang-dong; Zhao, Xiao-yn; Tong, Wen-xue; Wang, Hong; Liu, Ping; Zhang, Xiao-ling

    2014-09-01

    Calcification of end plate chondrocytes is a major cause of intervertebral disc (IVD) degeneration. However, the underlying molecular mechanism of end plate chondrocyte calcification is still unclear. The aim of this study was to clarify whether autophagy in end plate chondrocytes could protect the calcification of end plate chondrocytes. Previous studies showed that intermittent cyclic mechanical tension (ICMT) contributes to the calcification of end plate chondrocytes in vitro. While autophagy serves as a cell survival mechanism, the relationship of autophagy and induced end plate chondrocyte calcification by mechanical tension in vitro is unknown. Thus, we investigated autophagy, the expression of the autophagy genes, Beclin-1 and LC3, and rat end plate chondrocyte calcification by ICMT. The viability of end plate chondrocytes was examined using the LIVE/DEAD viability/cytotoxicity kit. The reverse transcription-polymerase chain reaction and western blotting were used to detect the expression of Beclin-1; LC3; type I, II and X collagen; aggrecan; and Sox-9 genes. Immunofluorescent and fluorescent microscopy showed decreased autophagy in the 10- and 20-day groups loaded with ICMT. Additionally, Alizarin red and alkaline phosphatase staining detected the palpable calcification of end plate chondrocytes after ICMT treatment. We found that increased autophagy induced by short-term ICMT treatment was accompanied by an insignificant calcification of end plate chondrocytes. To the contrary, the suppressive autophagy inhibited by long-term ICMT was accompanied by a more significant calcification. The process of calcification induced by ICMT was partially resisted by increased autophagy activity induced by rapamycin, implicating that autophagy may prevent end plate chondrocyte calcification.

  15. Sensitivity of calcification to thermal stress varies among genera of massive reef-building corals.

    PubMed

    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 (Ω(ar)) 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 Ω(ar) 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

  16. Linking calcification by exotic snails to stream inorganic carbon cycling.

    PubMed

    Hotchkiss, Erin R; Hall, Robert O

    2010-05-01

    Biotic calcification is rarely considered in freshwater C budgets, despite calculations suggesting that calcifying animals can alter inorganic C cycling. Most studies that have quantified biocalcification in aquatic ecosystems have not directly linked CO(2) fluxes from biocalcification with whole-ecosystem rates of inorganic C cycling. The freshwater snail, Melanoides tuberculata, has achieved a high abundance and 37.4 g biomass m(-2) after invading Kelly Warm Springs in Grand Teton National Park. This high biomass suggests that introduced populations of Melanoides may alter ecosystem processes. We measured Melanoides growth rates and biomass to calculate the production of biomass, shell mass, and CO(2). We compared Melanoides biomass and inorganic C production with ecosystem C pools and fluxes, as well as with published rates of CO(2) production by other calcifying organisms. Melanoides calcification in Kelly Warm Springs produced 12.1 mmol CO(2) m(-2) day(-1) during summer months. We measured high rates of gross primary productivity and respiration in Kelly Warm Springs (-378 and 533 mmol CO(2) m(-2) day(-1), respectively); CO(2) produced from biocalcification increased net CO(2) production in Kelly Warm Springs from 155 to 167 mmol CO(2) m(-2) day(-1). This rate of CO(2) production via biocalcification is within the published range of calcification by animals. But these CO(2) fluxes are small when compared to ecosystem C fluxes from stream metabolism. The influence of animals is relative to ecosystem processes, and should always be compared with ecosystem fluxes to quantify the importance of a specific animal in its environment.

  17. Effects of Hydrogen Peroxide on Coral Photosynthesis and Calcification

    NASA Astrophysics Data System (ADS)

    Higuchi, T.; Fujimura, H.; Arakaki, T.; Oomori, T.

    2007-12-01

    The widely-observed decline of coral reefs is considered to be caused by changes in the environment by natural and anthropogenic activities. As one important factor, the run-off of various matters from human activities to the coastal seawater poses stresses to the corals by degrading the quality of the seawater. In Okinawa, Japan, red- soil running off from the developed land has been a major environmental issue since 1980s. Hydrogen peroxide (HOOH), a strong active oxygen species, is one of the photochemically formed chemicals in the red-soil-polluted seawater. Recent photochemical studies of seawater showed that HOOH photo-formation was faster in the red- soil-polluted seawater than clean seawater. We studied the effects of HOOH on corals by studying the changes in coral carbon metabolisms such as photosynthesis and calcification, which are indicators of the physiological state of a coral colony. The corals were exposed to various concentrations of HOOH (0, 0.3, 3 μM). Two massive coral species of Porites sp. and Goniastrea aspera and one branch coral of Galaxea facicularis were used for the exposure experiments. The control experiments showed that when no HOOH was added, metabolisms of each coral colony were relatively stable. On the other hand, when HOOH was added to the seawater, we observed obvious changes in the coral metabolisms in all the coral species. When 0.3 μM HOOH was added, photosynthesis decreased by 14% and calcification decreased by 17% within 3 days, compared with the control. When 3 μM HOOH was added, photosynthesis decreased by 21% and calcification decreased by 41% within 3 days, compared with the control. Our study showed that higher concentrations of HOOH posed more stress to the coral colonies.

  18. [Brain calcifications: a case presentation of congenital toxoplasmosis].

    PubMed

    Ávila, Mauricio J; Rodríguez-Restrepo, Andrea

    2014-12-18

    Toxoplasmosis is a common disease in Latin America. The infection has a major impact on public health worldwide. Congenital toxoplasmosis is part of the spectrum of the disease and the consequences for the newborn are devastating. In this article, we present a case of brain calcifications and hydrocephalus secondary to infection with Toxoplasma gondii in a newborn, as well as the outcome during follow-up and long-term sequelae. It is of high importance for the clinician to think about this disease, due to its high prevalence in Latin America, and to adopt adequate measures for its prevention and timely management in order to reduce long-term sequelae.

  19. Exploring Protein Binding of Uremic Toxins in Patients with Different Stages of Chronic Kidney Disease and during Hemodialysis.

    PubMed

    Deltombe, Olivier; Van Biesen, Wim; Glorieux, Griet; Massy, Ziad; Dhondt, Annemieke; Eloot, Sunny

    2015-10-01

    As protein binding of uremic toxins is not well understood, neither in chronic kidney disease (CKD) progression, nor during a hemodialysis (HD) session, we studied protein binding in two cross-sectional studies. Ninety-five CKD 2 to 5 patients and ten stable hemodialysis patients were included. Blood samples were taken either during the routine ambulatory visit (CKD patients) or from blood inlet and outlet line during dialysis (HD patients). Total (CT) and free concentrations were determined of p-cresylglucuronide (pCG), hippuric acid (HA), indole-3-acetic acid (IAA), indoxyl sulfate (IS) and p-cresylsulfate (pCS), and their percentage protein binding (%PB) was calculated. In CKD patients, %PB/CT resulted in a positive correlation (all p < 0.001) with renal function for all five uremic toxins. In HD patients, %PB was increased after 120 min of dialysis for HA and at the dialysis end for the stronger (IAA) and the highly-bound (IS and pCS) solutes. During one passage through the dialyzer at 120 min, %PB was increased for HA (borderline), IAA, IS and pCS. These findings explain why protein-bound solutes are difficult to remove by dialysis: a combination of the fact that (i) only the free fraction can pass the filter and (ii) the equilibrium, as it was pre-dialysis, cannot be restored during the dialysis session, as it is continuously disturbed. PMID:26426048

  20. [The role of calcium ions in the pathomechanism of the artery calcification accompanying atherosclerosis].

    PubMed

    Małecki, Rafał; Adamiec, Rajmund

    2005-01-01

    Artery calcification occurring in atherosclerosis is connected with a high risk of cardiovascular events. Quantitative calcification evaluation using electron beam tomography indicated a correlation between artery calcification and well-known cardiovascular risk factors, i.e. smoking, obesity, and hyperlipidemia. Elevated calcium scores are especially observed in diabetic patients, which may even explain the higher mortality in this group. Calcification leads to increased blood vessel rigidity and, consequently, elevated arterial vascular resistance and left ventricular hypertrophy. An increased risk of plaque rupture in relation to calcium-rich atherosclerotic lesions was not proved. Plaque rupture and thromboembolitic complications are probably higher in the case of lipid-rich lesions. Atherosclerotic calcification is an active process in which many cells (monocytes/macrophages, vascular smooth muscle cells, and endothelial cells) participate. Many substances and transcription factors normally participating in the bone remodeling process are found in calcified atherosclerotic lesions (e.g. Cbfa-1, osteocalcin, alkaline phosphatase, BMP-2, osteopontin, osteoprotegrin, and RANKL). On monocytes, cells playing an important role in atherosclerosis progression, the presence of a calcium-sensing receptor (CaR) has been demonstrated. Increase in monocyte chemotaxis and increased interleukin 6 secretion in response to extracellular calcium were observed. Monocytes also directly and indirectly enhance vascular calcification. Immune cells and cytokines participating in vascular calcification are connected in one pathogenetic mechanism, i.e. atherosclerosis as an inflammatory disease and calcification. PMID:15761385

  1. Generalized arterial calcification of infancy--Findings at post-mortem computed tomography and autopsy.

    PubMed

    Bolster, Ferdia; Ali, Zabiullah; Southall, Pamela; Fowler, David

    2015-09-01

    Generalized arterial calcification in infancy is a rare genetic disorder characterized by abnormal calcification of large and medium sized arteries and marked myointimal proliferation resulting in arterial stenosis. The condition is often fatal secondary to complications of cardiac ischemia, hypertension and cardiac failure. In this report we describe the findings at post mortem computed tomography, histology and autopsy.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

  3. Endochondral bone formation in the heart: a possible mechanism of coronary calcification.

    PubMed

    Fitzpatrick, L A; Turner, R T; Ritman, E R

    2003-06-01

    During the atherosclerotic process, calcification occurs and is associated with a high likelihood of adverse events. Coronary calcification has been perceived as a passive precipitation of mineral. Recently, calcification associated with atherosclerosis has been found to be the result of an organized, regulated process that is similar to the process of calcification in bone. Mineralization in skeletal tissue can form by endochondral ossification in which mesenchymal cells differentiate into chondroblasts and produce a cartilage matrix which then degenerates and is remodeled to form bone. In this study, hearts from oophorectomized, aged female Sprague Dawley rats were found to contain areas of cartilage. Micro-computerized tomography radiogrammetry provided quantitative images of the architecture and confirmed the calcified tissue. Histological analysis revealed staining for several markers consistent with cartilage and bone tissue: acid phosphatase and bone matrix proteins, osteocalcin, osteopontin, osteonectin, and bone sialoprotein. In addition, cartilage types II, X, and procollagen type I were present. The presence of chondrocytes in the aged rat heart provides insights into the process of calcification in coronary arteries. Many proteins associated with calcification in bone are present in the cartilage that is present in vascular tissue, suggesting that endochondral calcification is another possible mechanism by which calcification of vascular tissue may occur.

  4. Hypothesis: Phytate is an important unrecognised nutrient and potential intravenous drug for preventing vascular calcification.

    PubMed

    Joubert, Pieter; Ketteler, Markus; Salcedo, Carolina; Perello, Joan

    2016-09-01

    Cardiovascular calcification (CVC) associated with conditions such as ageing, diabetes or renal impairment, results from the deposition of hydroxyapatite in the endothelium or media of blood vessels. Key medical management options are directed towards controlling plasma calcium and phosphate concentrations (e.g. parathormone inhibition, phosphate binders, dialysis), enhancing the effect of calcification inhibitors (e.g. fetuin-A, pyrophosphate, vitamin K, osteopontin, matrix Gla protein) and decreasing the effect of promoters of calcification (e.g. vitamin D, lipids, cytokines). Dietary phytate prevents the calcification of ageing in rats and epidemiological data suggest that phytate rich diets are associated with a lower incidence of CVC in the elderly. Intravenous phytate prevents aggressive CVC induced by vitamin D in rats. We propose that phytate should be added to the list of inhibitors of vascular calcification. We further suggest that adequate dietary phytate could prevent mild forms of calcification and that the low phytate content of diets for patients with renal disease can contribute to the increased risk of vascular calcification. It is also our contention that supra-physiological systemic phytate concentrations not achievable orally, might prevent aggressive vascular calcification. Appropriate epidemiological (to determine nutritional value) and clinical studies (evaluating safety and efficacy) are required to confirm, modify or reject our hypothesis. PMID:27515210

  5. Abdominal aortic calcification is not superior over other vascular calcification in predicting mortality in hemodialysis patients: a retrospective observational study

    PubMed Central

    2013-01-01

    Background KDIGO (Kidney Disease: Improving Global Outcomes) guidelines recommend that a lateral abdominal radiograph should be performed to assess vascular calcification (VC) in dialysis patients. However, abdominal aortic calcification is a prevalent finding, and it remains unclear whether other anatomical areas of VC can predict mortality more accurately. Methods A total of 217 maintenance hemodialysis patients were enrolled at the Sichuan Provincial People’s Hospital between July 2010 and March 2011. Radiographs of the abdomen, pelvis and hands were evaluated by a radiologist to evaluate the presence of VC. The correlation between different areas of VC and all-cause or cardiovascular mortality was analyzed using univariate and multivariate models. Results The prevalence of VC was 70.0% (152 patients), and most had abdominal aortic calcification (90.1%). During 26 ± 7 months of follow-up, 37 patients died. The VC score was independently associated with patient mortality. VC observed on abdominal radiographs (abdominal aortic calcification) was associated with all-cause mortality in models adjusted for cardiovascular risk factors (HR, 4.69; 95%CI, 1.60-13.69) and dialysis factors (HR, 3.38; 95%CI, 1.18-9.69). VC in the pelvis or hands was associated with all-cause mortality in the model adjusted for dialysis factors. When three combinations of VC in different radiographs were included in models, the presence of abdominal VC was only significantly associated with all-cause mortality in the integrated model. VC in the abdomen and pelvis was associated with all-cause mortality in the model adjusted for cardiovascular factors and the integrated model, but neither was significantly associated with cardiovascular mortality. VC in all radiographs was significantly associated with a more than 6-fold risk of all-cause mortality and a more than 5-fold risk of cardiovascular mortality compared to patients without VC. Conclusions VC in different arteries as shown on

  6. Choroid plexus calcification: clinical, neuroimaging and histopathological correlations in schizophrenia.

    PubMed

    Marinescu, Ileana; Udriştoiu, I; Marinescu, D

    2013-01-01

    Schizophrenia is recognized as a psychiatric disorder that causes the most pronounced disturbances of cognition and social integration. In the etiopathogenesis of the disease, genetic, neurobiological and vascular factors are involved. Functional integrity of the brain can be correlated with the integrity of the blood-brain barrier (BBB), and the dysfunction of this barrier is an indicator that suggests neurodevelopmental abnormalities, injuries of various etiologies and dysfunctions within the small vessels of the brain that disrupt the calcium homeostasis. Neuroimaging shows that in patients with poor evolution, cognitive dysfunction and therapeutic resistance, the presence of choroid plexus calcification associated with hippocampal, frontal, temporoparietal and cerebellar atrophies. Antipsychotics with high capacity to block D2 dopamine receptors (haloperidol model) can aggravate apoptotic mechanisms of the brain areas involved in cognition and disrupts the functional integrity of the BBB due to decreased of choroid plexus blood flow because of the narrowing of cerebral small vessels. Choroid plexus calcification may be a predictive indicator of poor evolution or of a neurodegenerative type. PMID:23771083

  7. Hemodynamic and cellular response feedback in calcific aortic valve disease.

    PubMed

    Gould, Sarah T; Srigunapalan, Suthan; Simmons, Craig A; Anseth, Kristi S

    2013-07-01

    This review highlights aspects of calcific aortic valve disease that encompass the entire range of aortic valve disease progression from initial cellular changes to aortic valve sclerosis and stenosis, which can be initiated by changes in blood flow (hemodynamics) and pressure across the aortic valve. Appropriate hemodynamics is important for normal valve function and maintenance, but pathological blood velocities and pressure can have profound consequences at the macroscopic to microscopic scales. At the macroscopic scale, hemodynamic forces impart shear stresses on the surface of the valve leaflets and cause deformation of the leaflet tissue. As discussed in this review, these macroscale forces are transduced to the microscale, where they influence the functions of the valvular endothelial cells that line the leaflet surface and the valvular interstitial cells that populate the valve extracellular matrix. For example, pathological changes in blood flow-induced shear stress can cause dysfunction, impairing their homeostatic functions, and pathological stretching of valve tissue caused by elevated transvalvular pressure can activate valvular interstitial cells and latent paracrine signaling cytokines (eg, transforming growth factor-β1) to promote maladaptive tissue remodeling. Collectively, these coordinated and complex interactions adversely impact bulk valve tissue properties, feeding back to further deteriorate valve function and propagate valve cell pathological responses. Here, we review the role of hemodynamic forces in calcific aortic valve disease initiation and progression, with focus on cellular responses and how they feed back to exacerbate aortic valve dysfunction.

  8. The role of coccolithophore calcification in bioengineering their environment.

    PubMed

    Flynn, Kevin J; Clark, Darren R; Wheeler, Glen

    2016-06-29

    Coccolithophorids are enigmatic plankton that produce calcium carbonate coccoliths, which over geological time have buried atmospheric CO2 into limestone, changing both the atmosphere and geology of the Earth. However, the role of coccoliths for the proliferation of these organisms remains unclear; suggestions include roles in anti-predation, enhanced photosynthesis and sun-screening. Here we test the hypothesis that calcification stabilizes the pH of the seawater proximate to the organisms, providing a level of acidification countering the detrimental basification that occurs during net photosynthesis. Such bioengineering provides a more stable pH environment for growth and fits the empirical evidence for changes in rates of calcification under different environmental conditions. Under this scenario, simulations suggest that the optimal production ratio of inorganic to organic particulate C (PIC : POCprod) will be lower (by approx. 20%) with ocean acidification and that overproduction of coccoliths in a future acidified ocean, where pH buffering is weaker, presents a risk to calcifying cells. PMID:27358373

  9. Artifactual Stratum Corneum Calcification of the Beagle Dog Tongue.

    PubMed

    Glover, Christiana; Ochoa, Ricardo

    2015-07-01

    Examination of H&E-stained tongue samples from a 26-week intravenous infusion study of Beagle dogs, utilizing a compound with no recognized effect on mineral metabolism, exhibited superficial stratum corneum calcification in both treated and control animals. This resulted in the search for possible causes of the finding to help clarify confounding issues. Retrospective examination of 11 studies performed before the signal case indicated that the problem existed in the testing facility but was not recognized. Prior to 2008, this finding was not observed, perhaps indicating the requirement for a change in procedures or suppliers. Based on the hypothesis that the calcium salts were deposited from bone during processing, a series of tests was performed by fixing tongue and femur along with different tissues, processed routinely to slide, and stained with H&E and von Kossa stains. We conclude that the presence of superficial stratum corneum calcification of the tongue in dogs demonstrated in toxicology studies is an artifactual change related to the processing of tissues, specifically the fixation of tongue in the same container as bone and stomach. This change should not be confused with compound-related effects, even when the incidence varies between controls and treated animals.

  10. Vascular calcification, bone and mineral metabolism after kidney transplantation

    PubMed Central

    D’Marco, Luis; Bellasi, Antonio; Mazzaferro, Sandro; Raggi, Paolo

    2015-01-01

    The development of end stage renal failure can be seen as a catastrophic health event and patients with this condition are considered at the highest risk of cardiovascular disease among any other patient groups and risk categories. Although kidney transplantation was hailed as an optimal solution to such devastating disease, many issues related to immune-suppressive drugs soon emerged and it became evident that cardiovascular disease would remain a vexing problem. Progression of chronic kidney disease is accompanied by profound alterations of mineral and bone metabolism that are believed to have an impact on the cardiovascular health of patients with advanced degrees of renal failure. Cardiovascular risk factors remain highly prevalent after kidney transplantation, some immune-suppression drugs worsen the risk profile of graft recipients and the alterations of mineral and bone metabolism seen in end stage renal failure are not completely resolved. Whether this complex situation promotes progression of vascular calcification, a hall-mark of advanced chronic kidney disease, and whether vascular calcifications contribute to the poor cardiovascular outcome of post-transplant patients is reviewed in this article. PMID:26722649

  11. Succes of foraminiferal calcification mechanisms depend on ocean chemistry

    NASA Astrophysics Data System (ADS)

    van Dijk, I. V.; de Nooijer, L. J.; Hart, M.; Reichart, G. J.

    2014-12-01

    Although the relationship between Phanerozoic changes in seawater Mg/Ca and the evolutionary history of many marine calcifyers has been analyzed, the response of foraminifera to changes in Mg/Casw is only sparsely investigated. Geological longevity, areal distribution and importance in the global carbon cycle, however, make foraminifera particularly suitable to study the interplay between seawater chemistry and biogenic mineralogy. We assess global foraminifera abundances in the geological record from fossil species occurrences in the Paleobiology DataBase (PaleoDB; www.paleodb.org). Here, we present an analysis of the distribution of major groups of foraminifera through the Phanerozoic by comparing dominance of taxa producing aragonite or (low- and high-Mg) calcite in relation to changes in Mg/Casw and mass marine extinction events (P/T, T/J and K/Pg). This allows relating the effect of ocean chemistry to the relative success of foraminifera with different calcification strategies. We show for the first time that the success of foraminifera with different calcification mechanisms (i.e. aragonite versus calcite producers) is governed by Mg/Casw, potentially making foraminifera with unfavored mineralogy more vulnerable to major environmental perturbations. Furthermore, we suggest that planktic foraminifera, which are currently calcifying in a period with unfavorable sea water chemistry, might be more sensitive to on-going ocean acidification and associated environmental perturbations than currently assumed.

  12. The role of coccolithophore calcification in bioengineering their environment

    PubMed Central

    Clark, Darren R.; Wheeler, Glen

    2016-01-01

    Coccolithophorids are enigmatic plankton that produce calcium carbonate coccoliths, which over geological time have buried atmospheric CO2 into limestone, changing both the atmosphere and geology of the Earth. However, the role of coccoliths for the proliferation of these organisms remains unclear; suggestions include roles in anti-predation, enhanced photosynthesis and sun-screening. Here we test the hypothesis that calcification stabilizes the pH of the seawater proximate to the organisms, providing a level of acidification countering the detrimental basification that occurs during net photosynthesis. Such bioengineering provides a more stable pH environment for growth and fits the empirical evidence for changes in rates of calcification under different environmental conditions. Under this scenario, simulations suggest that the optimal production ratio of inorganic to organic particulate C (PIC : POCprod) will be lower (by approx. 20%) with ocean acidification and that overproduction of coccoliths in a future acidified ocean, where pH buffering is weaker, presents a risk to calcifying cells. PMID:27358373

  13. Growth and calcification of marine bryozoans in a changing ocean.

    PubMed

    Smith, Abigail M

    2014-06-01

    Bryozoans are colonial benthic marine invertebrate calcifiers, important and especially abundant and diverse in southern hemisphere shelf environments. Large heavily calcified colonies can be up to 50 years old, but most longer-lived bryozoans are limited to 10-20 y. Many smaller species are annual. Radial extension in flat encrusting bryozoans is generally on the order of 1-5 mm/y. Erect calcified species generally grow vertically 2-15 mm/y, though articulated species such as Cellaria may reach rates of 40 mm/y. Corresponding calcification rates are generally 10(1)-10(2) mg/y, but there can be an order of magnitude variation in rate among years in high-latitude bryozoans. Multi-branched bryozoans produce up to 24 g of CaCO3/y. The carbonate produced by bryozoans varies from calcite to aragonite and mixtures of both. Skeletal carbonate mineralogy of bryozoans is complex and appears to be strongly genetically controlled. Global climate change, leading to increasing water temperatures, will generally increase marine bryozoan metabolic rates, and may increase Mg in calcite. On the other hand, decreasing pH (ocean acidification) causes corrosion, changes in mineralogy, and decreased survival. This review of bryozoan growth and calcification allows a general perspective, but also reveals gaps in our knowledge which need to be addressed.

  14. Confocal laser scanning microscopy in study of bone calcification

    NASA Astrophysics Data System (ADS)

    Nishikawa, Tetsunari; Kokubu, Mayu; Kato, Hirohito; Imai, Koichi; Tanaka, Akio

    2012-12-01

    Bone regeneration in mandible and maxillae after extraction of teeth or tumor resection and the use of rough surface implants in bone induction must be investigated to elucidate the mechanism of calcification. The calcified tissues are subjected to chemical decalcification or physical grinding to observe their microscopic features with light microscopy and transmission electron microscopy where the microscopic tissue morphology is significantly altered. We investigated the usefulness of confocal laser scanning microscopy (CLSM) for this purpose. After staggering the time of administration of calcein and alizarin red to experimental rats and dogs, rat alveolar bone and dog femur grafted with coral as scaffold or dental implants were observed with CLSM. In rat alveolar bone, the calcification of newly-formed bone and net-like canaliculi was observed at the mesial bone from the roots progressed at the rate of 15 μm/day. In dog femur grafted with coral, newly-formed bones along the space of coral were observed in an orderly manner. In dog femur with dental implants, after 8 weeks, newly-formed bone proceeded along the rough surface of the implants. CLSM produced high-magnification images of newly-formed bone and thin sections were not needed.

  15. Growth and calcification of marine bryozoans in a changing ocean.

    PubMed

    Smith, Abigail M

    2014-06-01

    Bryozoans are colonial benthic marine invertebrate calcifiers, important and especially abundant and diverse in southern hemisphere shelf environments. Large heavily calcified colonies can be up to 50 years old, but most longer-lived bryozoans are limited to 10-20 y. Many smaller species are annual. Radial extension in flat encrusting bryozoans is generally on the order of 1-5 mm/y. Erect calcified species generally grow vertically 2-15 mm/y, though articulated species such as Cellaria may reach rates of 40 mm/y. Corresponding calcification rates are generally 10(1)-10(2) mg/y, but there can be an order of magnitude variation in rate among years in high-latitude bryozoans. Multi-branched bryozoans produce up to 24 g of CaCO3/y. The carbonate produced by bryozoans varies from calcite to aragonite and mixtures of both. Skeletal carbonate mineralogy of bryozoans is complex and appears to be strongly genetically controlled. Global climate change, leading to increasing water temperatures, will generally increase marine bryozoan metabolic rates, and may increase Mg in calcite. On the other hand, decreasing pH (ocean acidification) causes corrosion, changes in mineralogy, and decreased survival. This review of bryozoan growth and calcification allows a general perspective, but also reveals gaps in our knowledge which need to be addressed. PMID:25070865

  16. Mineralization by inhibitor exclusion: the calcification of collagen with fetuin.

    PubMed

    Price, Paul A; Toroian, Damon; Lim, Joo Eun

    2009-06-19

    One of our goals is to understand the mechanisms that deposit mineral within collagen fibrils, and as a first step we recently determined the size exclusion characteristics of the fibril. This study revealed that apatite crystals up to 12 unit cells in size can access the water within the fibril, whereas molecules larger than a 40-kDa protein are excluded. Based on these observations, we proposed a novel mechanism for fibril mineralization: that macromolecular inhibitors of apatite growth favor fibril mineralization by selectively inhibiting crystal growth in the solution outside of the fibril. To test this mechanism, we developed a system in which crystal formation is driven by homogeneous nucleation at high calcium phosphate concentration and the only macromolecule in solution is fetuin, a 48-kDa inhibitor of apatite growth. Our experiments with this system demonstrated that fetuin determines the location of mineral growth; in the presence of fetuin mineral grows exclusively within the fibril, whereas in its absence mineral grows in solution outside the fibril. Additional experiments showed that fetuin is also able to localize calcification to the interior of synthetic matrices that have size exclusion characteristics similar to those of collagen and that it does so by selectively inhibiting mineral growth outside of these matrices. We termed this new calcification mechanism "mineralization by inhibitor exclusion," the selective mineralization of a matrix using a macromolecular inhibitor of mineral growth that is excluded from that matrix. Future studies will be needed to evaluate the possible role of this mechanism in bone mineralization.

  17. Mineral and bone disorder and vascular calcification in patients with chronic kidney disease.

    PubMed

    Peres, Luis Alberto Batista; Pércio, Pedro Paulo Verona

    2014-01-01

    Vascular calcifications has been associated with bone and mineral disorders. The alterations in the serum level of calcium concentrations and phosphate are importants factors implicated in the arterial calcification in chronic kidney disease. The pathogenesis of vascular calcification is a complex mechanism and not completely clear, being able to correspond to an active process of cellular transformation and heterotopic ossification. Beyond the hypercalcemia and hyperphosphatemia, they are involved in this process changes in the metabolism of inhibitors and promoters of calcification such as fetuin A, osteopontin, osteoprotegerin, and matrix gla protein. For the diagnosis of the calcified arterial injury are available several complementary methods, a method of estimate of the cardiovascular risk based on plain radiographs of the lumbar column and another method based on simple x-rays of the pelvis and hands. Below, we will present a review approching the link between vascular calcifications and mineral disorders. PMID:25055361

  18. Calcific tendonitis of the tibialis posterior tendon at the navicular attachment

    PubMed Central

    Harries, Luke; Kempson, Susan; Watura, Roland

    2011-01-01

    Calcific tendinosis (tendonosis/tendonitis) is a condition which results from the deposition of calcium hydroxyapatite crystals in any tendon of the body. Calcific tendonitis usually presents with pain, which can be exacerbated by prolonged use of the affected tendon. We report a case of calcific tendinosis in the posterior tibialis tendon at the navicular insertion. The pathology is rare in the foot, and extremely rare in the tibialis posterior tendon, indeed there are only 2 reported in the published literature. This case report highlights the need to consider calcific tendinosis in the foot despite its rarity. If this diagnosis is considered early, appropriate investigations can then be requested and unnecessary biopsies, use of antibiotics and surgery can be avoided. We also discuss possible causes of calcific tendinosis in the tibialis posterior tendon, the role of imaging modalities and review treatment methods. PMID:22470798

  19. 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.

  20. [Assessment of coronary calcification by computed tomography inclusive of 3DCT].

    PubMed

    Tsushima, Motoo; Tsushima, Kensuke

    2003-09-01

    Coronary artheroclerosis in diabetes patients can be divided into 2 phases, one is seen in the early phase of diabetes or insulin resistance syndrome as unstable plaque with lipid-rich core, thinner fibrous caps and small dose or a lack of calcification and the other in the late or advanced stage of diabetes is hard and stable plaque with much fibrous protein and calcification which extends from truncal to peripheral areas. In diabetic patients in the late stage, coronary accidents occur as the chronic multiple vessel diseases with a lot of calcification, while in the early stage of diabetes vasospastic angina and acute coronary syndrome with less calcification tends to occur. We can find out the coronary calcification by EBCT or 3DCT easily which is characteristic in patients of diabetes complicated with coronary artery disease and in the early stage the stenosis of left truncal artery or large vessels of LAD can be detectable by 3DCT. PMID:15775196

  1. [Mechanism, imaging technique and therapy for vascular calcification in patients of chronic kidney disease].

    PubMed

    Yoshida, Hiraku; Yokoyama, Keitaro

    2007-05-01

    Vascular calcification has been reported to influence mortality and complications of cardiovascular diseases in patients with chronic kidney disease. Once vascular calcification was thought to the result from passive precipitation of calcium and phosphate, it now appears that end result of phenotypic change of vascular smooth muscle cells (VSMC) into osteoblast-like cells. A variety of imaging technique are available to visualize vascular calcification, including X-ray, vascular ultrasound, electron beam computed tomography (EBCT) and multidetector-row computed tomography (MDCT) . Especially, MDCT with contrast medium that can detect not only coronary calcification but also stenosis is useful and noninvasive methods for screening of coronary artery disease. Through greater understanding of both the mechanism and clinical consequence of vascular calcification, future therapeutic strategies may be more effectively designed and applied. PMID:17471002

  2. [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. PMID:25682995

  3. The effect of calcification on the structural mechanics of the costal cartilage.

    PubMed

    Forman, Jason L; Kent, Richard W

    2014-01-01

    The costal cartilage often undergoes progressive calcification with age. This study sought to investigate the effects of calcification on the structural mechanics of whole costal cartilage segments. Models were developed for five costal cartilage specimens, including representations of the cartilage, the perichondrium, calcification, and segments of the rib and sternum. The material properties of the cartilage were determined through indentation testing; the properties of the perichondrium were determined through optimisation against structural experiments. The calcified regions were then expanded or shrunk to develop five different sensitivity analysis models for each. Increasing the relative volume of calcification from 0% to 24% of the cartilage volume increased the stiffness of the costal cartilage segments by a factor of 2.3-3.8. These results suggest that calcification may have a substantial effect on the stiffness of the costal cartilage which should be considered when modelling the chest, especially if age is a factor.

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

    PubMed

    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.

  5. [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.

  6. Vascular calcification in rheumatoid arthritis: prevalence, pathophysiological aspects and potential targets.

    PubMed

    Paccou, J; Brazier, M; Mentaverri, R; Kamel, S; Fardellone, P; Massy, Z A

    2012-10-01

    Individuals with rheumatoid arthritis (RA) are at increased risk for morbidity and mortality from cardiovascular disease. Excess cardiovascular mortality in RA patients cannot be fully explained by conventional cardiovascular risk factors. The purpose of this review is to discuss recent progress concerning the prevalence and pathophysiological aspects of vascular calcification in RA. RA patients have early-onset diffuse calcification involving multiple vascular beds compared to age and sex-matched controls. Pathogenesis of vascular calcification in RA patients is not fully understood, but specific mediators such as proinflammatory cytokines and not global inflammation could be involved. The possible link between osteoporosis and vascular calcification in RA will not be discussed. Finally, potential targets to reduce vascular calcification in RA will be discussed.

  7. Interventions for preventing diarrhea-associated hemolytic uremic syndrome: systematic review

    PubMed Central

    2013-01-01

    Background Hemolytic Uremic Syndrome (HUS) may follow infection with Shiga-toxin-producing organisms, principally E. coli O157: H7 (STEC), causing high morbidity and mortality. Our aim was to identify interventions to prevent diarrhea-associated HUS. Methods Systematic search of the literature for relevant systematic reviews (SRs), randomised controlled trials (RCTs) and public health guidelines. Results Of 1097 animal and 762 human studies, 18 animal studies (2 SRs, 2 reviews, plus 14 RCTs) and 6 human studies (3 SRs, plus 3 RCTs) met inclusion criteria. E. coli O157: H7 Type III secreted protein vaccination decreased fecal E. coli O157 shedding in cattle (P = 0.002). E. coli O157: H7 siderophore receptor and porin proteins (SRP) vaccines reduced fecal shedding in cows (OR 0.42 (95% CI 0.25 to 0.73) and increased anti-E. coli 0157: H7 SRP antibodies in their calves (P < 0.001). Bacterin vaccines had no effect. Probiotic or sodium chlorate additives in feeds reduced fecal E. coli O157 load as did improved farm hygiene (P < 0.05). Solarization of soil reduced E. coli O157: H7 contamination in the soil (P < 0.05). In an RCT examining the role of antibiotic treatment of E. coli O157: H7 diarrhea, HUS rates were similar in children treated with Trimethoprim-sulfamethoxazole and controls (RR 0.57; 95% CI 0.11 to 2.81). In another RCT, HUS rates were similar in children receiving Synsorb-Pk and placebo (RR 0.93; 95% CI 0.39 to 2.22). In one SR, hand washing reduced diarrhea by 39% in institutions (IRR 0.61; 95% CI 0.40 to 0.92) and 32% in community settings (IRR 0.68; 95% CI 0.52 to 0.90) compared to controls. Guidelines contained recommendations to prevent STEC transmission from animals and environments to humans, including appropriate food preparation, personal hygiene, community education, and control of environmental contamination, food and water quality. Conclusions Animal carriage of STEC is decreased by vaccination and improved farm practices

  8. BMP-2 promotes phosphate uptake, phenotypic modulation, and calcification of human vascular smooth muscle cells.

    PubMed

    Li, Xianwu; Yang, Hsueh-Ying; Giachelli, Cecilia M

    2008-08-01

    Vascular calcification is associated with increased risk of cardiovascular events that are the most common cause of death in patients with end-stage renal disease. Clinical and experimental studies indicate that hyperphosphatemia is a risk factor for vascular calcification and cardiovascular mortality in these patients. Our previous studies demonstrated that phosphate transport through the type III sodium-dependent phosphate cotransporter, Pit-1, was necessary for phosphate-induced calcification and osteochondrogenic phenotypic change in cultured human smooth muscle cells (SMC). BMP-2 is a potent osteogenic protein required for osteoblast differentiation and bone formation that has been implicated in vascular calcification. In the present study, we have examined the effects of BMP-2 on human SMC calcification in vitro. We found that treatment of SMC with BMP-2 enhanced elevated phosphate-induced calcification, but did not induce calcification under normal phosphate conditions. mRNAs for BMP receptors, including ALK2, ALK3, ALK6, BMPR-II, ActR-IIA and ActR-IIB were all detected in human SMCs. Mechanistically, BMP-2 dose-dependently stimulated phosphate uptake in SMC (200 ng/ml BMP-2 vs. vehicle: 13.94 vs. 7.09 nmol/30 min/mg protein, respectively). Real-time PCR and Western blot revealed the upregulation of Pit-1 mRNA and protein levels, respectively, by BMP-2. More importantly, inhibition of phosphate uptake by a competitive inhibitor of sodium-dependent phosphate cotransport, phosphonoformic acid, abrogated BMP-2-induced calcification. These results indicate that phosphate transport via Pit-1 is crucial in BMP-2-regulated SMC calcification. In addition, BMP-2-induced Runx2 and inhibited SM22 expression, indicating that it promotes osteogenic phenotype transition in these cells. Thus, BMP-2 may promote vascular calcification via increased phosphate uptake and induction of osteogenic phenotype modulation in SMC. PMID:18179800

  9. Calcifications Are Potential Surrogates for Prostate Localization in Image-Guided Radiotherapy

    SciTech Connect

    Zeng, Grace G. McGowan, Tom S.; Larsen, Tessa M.; Bruce, Lisa M.; Moran, Natasha K.; Tsao, Jonathan R.; MacPherson, Miller S.

    2008-11-15

    Purpose: To investigate the feasibility of using calcifications as surrogates for the prostate position during cone-beam computed tomography (CBCT) image-guided radiotherapy. Methods and Materials: The twice-weekly CBCT images taken during the treatment course of 4 patients were retrospectively studied for the stability of the calcifications. The geometric center of three fiducial markers was used as the reference. The planning CT images of 131 prostate patients recently treated with external beam radiotherapy at our center were reviewed to estimate the calcification occurrence rate. Analysis was conducted using the Varian Eclipse treatment planning system. Two patients were treated using prostate calcifications as the landmark in on-line registration. Both the Varian standard and the low-dose CBCT modes were used for imaging. Results: The calcifications were found to be stable during the treatment course. At the 95% confidence interval, the difference between the distance from an identified calcification to the fiducial markers on CBCT and the distance on the planning CT scans was 0.2 {+-} 2.0 mm, 0.8 {+-} 2.2 mm, and 0.4 {+-} 2.4 mm in the left-right, anteroposterior, and superoinferior direction, respectively. Of the 131 patients, 46 (35%) had well-defined calcifications either inside the prostate or near the borders. Our experience in treating the first 2 patients demonstrated that the calcifications are easily distinguished on low-dose scans and that calcification registration can be precisely performed. Conclusion: The results of our study have shown that calcifications can be reliable markers of prostate position and allow for precise image guidance with a low-imaging dose. With this approach, potentially about one-third of prostate patients could benefit from precise image guidance without the invasive use of markers.

  10. 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. PMID:27108945

  11. Tenosynovitis with psammomatous calcification: a poorly recognized pseudotumor related to repetitive tendinous injury.

    PubMed

    Shon, Wonwoo; Folpe, Andrew L

    2010-06-01

    Tenosynovitis with psammomatous calcification, described in 1983 by Gravanis and Gaffney, is a distinctive clinicopathologic variant of "idiopathic calcifying tenosynovitis" or "calcific tendonitis." However, tenosynovitis with psammomatous calcification is poorly recognized by pathologists and for this reason has not been adopted widely as a distinct entity. We present the clinicopathologic features of 6 cases of tenosynovitis with psammomatous calcification. Cases involved the tendons, peritendinous soft tissues, and adjacent synovium of the distal extremities (3 fingers, 2 feet, and 1 carpal tendon) of women who ranged in age from 16 to 83 years (mean 48 y). The lesions presented a painful mass. A history of occupational or sports-related repetitive motion and/or persistent mild trauma was noted in all patients. No patient had a history of hyperphosphatemia. All lesions were treated by surgical excision and described clinically as variably cystic nodules composed of amorphous "cheese-like" debris. Histologically, the lesions were centered in the tendon or peritendinous soft tissue and composed of a mixed (myo) fibroblastic and histiocytic proliferation in association with a degenerating tendinous tissue, which was undergoing dystrophic calcification, with the formation of distinctive psammoma body-like spheroidal bodies. The clinical and morphologic characteristics of tenosynovitis with psammomatous calcification (distal location, absent hyperphosphatemia, and psammomatous calcifications) differ from those of typical idiopathic calcifying tenosynovitis/calcific tendinitis (proximal location and dystrophic tendinous calcification) and tumoral calcinosis (hyperphosphatemia and amorphous soft tissue calcification), and it should be recognized as a distinct clinicopathologic entity. Improved recognition of these unique features by pathologists should allow ready diagnosis of this unusual pseudotumor in most instances.

  12. Role of osteoprotegerin and its ligands and competing receptors in atherosclerotic calcification.

    PubMed

    Tintut, Yin; Demer, Linda

    2006-11-01

    Vascular calcification significantly impairs cardiovascular physiology, and its mechanism is under investigation. Many of the same factors that modulate bone osteogenesis, including cytokines, hormones, and lipids, also modulate vascular calcification, acting through many of the same transcription factors. In some cases, such as for lipids and cytokines, the net effect on calcification is positive in the artery wall and negative in bone. The mechanism for this reciprocal relation is not established. A recent series of reports points to the possibility that two bone regulatory factors, receptor activator of NF-kappaB ligand (RANKL) and its soluble decoy receptor, osteoprotegerin (OPG), govern vascular calcification and may explain the phenomenon. Both RANKL and OPG are widely accepted as the final common pathway for most factors and processes affecting bone resorption. Binding of RANKL to its cognate receptor RANK induces NF-kappaB signaling, which stimulates osteoclastic differentiation in preosteoclasts and induces bone morphogenetic protein (BMP-2) expression in chondrocytes. A role for RANKL and its receptors in vascular calcification is spported by several findings: a vascular calcification phenotype in mice genetically deficient in OPG; an increase in expression of RANKL, and a decrease in expression of OPG, in calcified arteries; clinical associations between coronary disease and serum OPG and RANKL levels; and RANKL induction of calcification and osteoblastic differentiation in valvular myofibroblasts. PMID:17169261

  13. Simulated effect of calcification feedback on atmospheric CO2 and ocean acidification

    NASA Astrophysics Data System (ADS)

    Zhang, Han; Cao, Long

    2016-02-01

    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.

  14. The Role of AGE/RAGE Signaling in Diabetes-Mediated Vascular Calcification

    PubMed Central

    2016-01-01

    AGE/RAGE signaling has been a well-studied cascade in many different disease states, particularly diabetes. Due to the complex nature of the receptor and multiple intersecting pathways, the AGE/RAGE signaling mechanism is still not well understood. The purpose of this review is to highlight key areas of AGE/RAGE mediated vascular calcification as a complication of diabetes. AGE/RAGE signaling heavily influences both cellular and systemic responses to increase bone matrix proteins through PKC, p38 MAPK, fetuin-A, TGF-β, NFκB, and ERK1/2 signaling pathways in both hyperglycemic and calcification conditions. AGE/RAGE signaling has been shown to increase oxidative stress to promote diabetes-mediated vascular calcification through activation of Nox-1 and decreased expression of SOD-1. AGE/RAGE signaling in diabetes-mediated vascular calcification was also attributed to increased oxidative stress resulting in the phenotypic switch of VSMCs to osteoblast-like cells in AGEs-induced calcification. Researchers found that pharmacological agents and certain antioxidants decreased the level of calcium deposition in AGEs-induced diabetes-mediated vascular calcification. By understanding the role the AGE/RAGE signaling cascade plays diabetes-mediated vascular calcification will allow for pharmacological intervention to decrease the severity of this diabetic complication. PMID:27547766

  15. Simulated effect of calcification feedback on atmospheric CO2 and ocean acidification.

    PubMed

    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

  16. Famotidine suppresses osteogenic differentiation of tendon cells in vitro and pathological calcification of tendon in vivo.

    PubMed

    Yamamoto, Kenichi; Hojo, Hironori; Koshima, Isao; Chung, Ung-il; Ohba, Shinsuke

    2012-12-01

    Heterotopic ossification or calcification follows any type of musculoskeletal trauma and is known to occur after arthroplasties of hip, knee, shoulder, or elbow; fractures; joint dislocations; or tendon ruptures. Histamine receptor H2 (Hrh2) has been shown to be effective for reducing pain and decreasing calcification in patients with calcifying tendinitis, which suggested that H2 blockers were effective for the treatment of tendon ossification or calcification. However, the detailed mechanisms of its action on tendon remain to be clarified. We investigated the mechanisms underlying H2 blocker-mediated suppression of tendon calcification, with a focus on the direct action of the drug on tendon cells. Famotidine treatment suppressed the mRNA expressions of Col10a1 and osteocalcin, ossification markers, in a tendon-derived cell line TT-D6, as well as a preosteoblastic one MC3T3-E1. Both of the cell lines expressed Hrh2; histamine treatment induced osteocalcin expression in these cells. Famotidine administration suppressed calcification in the Achilles tendon of ttw mice, a mouse model of ectopic ossification. These data suggest that famotidine inhibits osteogenic differentiation of tendon cells in vitro, and this inhibition may underlie the anti-calcification effects of the drug in vivo. This study points to the use of H2 blockers as a promising strategy for treating heterotopic ossification or calcification in tendon, and provides evidence in support of the clinical use of famotidine.

  17. 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

    2016-01-01

    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

  18. 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

  19. On the effect of calcification volume and configuration on the mechanical behaviour of carotid plaque tissue.

    PubMed

    Barrett, H E; Cunnane, E M; Kavanagh, E G; Walsh, M T

    2016-03-01

    Vascular calcification is a complex molecular process that exhibits a number of relatively characteristic morphology patterns in atherosclerotic plaques. Treatment of arterial stenosis by endovascular intervention, involving forceful circumferential expansion of the plaque, can be unpredictable in calcified lesions. The aim of this study was to determine the mechanical stretching mechanisms and define the mechanical limits for circumferentially expanding carotid plaque lesions under the influence of distinct calcification patterns. Mechanical and structural characterisation was performed on 17 human carotid plaques acquired from patients undergoing endarterectomy procedures. The mechanical properties were determined using uniaxial extension tests that stretch the lesions to complete failure along their circumferential axis. Calcification morphology of mechanically ruptured plaque lesions was characterised using high resolution micro computed tomography imaging. Scanning electron microscopy was used to examine the mechanically induced failure sites and to identify the interface boundary conditions between calcified and non-calcified tissue. The mechanical tests produced four distinct trends in mechanical behaviour which corresponded to the calcification patterns that structurally defined each mechanical group. Each calcification pattern produced unique mechanical restraining effects on the plaque tissue stretching properties evidenced by the variation in degree of stretch to failure. Resistance to failure appears to rely on interactions between calcification and non-calcified tissue. Scanning electron microscopy examination revealed structural gradations at interface boundary conditions to facilitate the transfer of stress. This study emphasises the mechanical influence of distinct calcification configurations on plaque expansion properties and highlights the importance of pre-operative lesion characterisation to optimise treatment outcomes.

  20. Elastin haploinsufficiency impedes the progression of arterial calcification in MGP-deficient mice.

    PubMed

    Khavandgar, Zohreh; Roman, Hassem; Li, Jingjing; Lee, Sara; Vali, Hojatollah; Brinckmann, Juergen; Davis, Elaine C; Murshed, Monzur

    2014-02-01

    Matrix gla protein (MGP) is a potent inhibitor of extracellular matrix (ECM) mineralization. MGP-deficiency in humans leads to Keutel syndrome, a rare genetic disease hallmarked by abnormal soft tissue calcification. MGP-deficient (Mgp(-/-)) mice show progressive deposition of hydroxyapatite minerals in the arterial walls and die within 2 months of age. The mechanism of antimineralization function of MGP is not fully understood. We examined the progression of vascular calcification and expression of several chondrogenic/osteogenic markers in the thoracic aortas of Mgp(-/-) mice at various ages. Although cells with chondrocyte-like morphology have been reported in the calcified aorta, our gene expression data indicate that chondrogenic/osteogenic markers are not upregulated in the arteries prior to the initiation of calcification. Interestingly, arterial calcification in Mgp(-/-) mice appears first in the elastic laminae. Considering the known mineral scaffolding function of elastin (ELN), a major elastic lamina protein, we hypothesize that elastin content in the laminae is a critical determinant for arterial calcification in Mgp(-/-) mice. To investigate this, we performed micro-computed tomography (µCT) and histological analyses of the aortas of Mgp(-/-);Eln(+/-) mice and show that elastin haploinsufficiency significantly reduces arterial calcification in this strain. Our data suggest that MGP deficiency leads to alterations of vascular ECM that may in turn initiate arterial calcification.

  1. Simulated effect of calcification feedback on atmospheric CO2 and ocean acidification.

    PubMed

    Zhang, Han; Cao, Long

    2016-02-03

    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.

  2. Mechanisms of Vascular Calcification: The Pivotal Role of Pyruvate Dehydrogenase Kinase 4

    PubMed Central

    2016-01-01

    Vascular calcification, abnormal mineralization of the vessel wall, is frequently associated with aging, atherosclerosis, diabetes mellitus, and chronic kidney disease. Vascular calcification is a key risk factor for many adverse clinical outcomes, including ischemic cardiac events and subsequent cardiovascular mortality. Vascular calcification was long considered to be a passive degenerative process, but it is now recognized as an active and highly regulated process similar to bone formation. However, despite numerous studies on the pathogenesis of vascular calcification, the mechanisms driving this process remain poorly understood. Pyruvate dehydrogenase kinases (PDKs) play an important role in the regulation of cellular metabolism and mitochondrial function. Recent studies show that PDK4 is an attractive therapeutic target for the treatment of various metabolic diseases. In this review, we summarize our current knowledge regarding the mechanisms of vascular calcification and describe the role of PDK4 in the osteogenic differentiation of vascular smooth muscle cells and development of vascular calcification. Further studies aimed at understanding the molecular mechanisms of vascular calcification will be critical for the development of novel therapeutic strategies. PMID:26996423

  3. 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

  4. Diffuse Brain Hypoperfusion in Advanced Leukoencephalopathy with Calcifications and Cysts.

    PubMed

    Bartolini, Emanuele; Bianchi, Andrea; Bartolomei, Ilaria; Vella, Alessandra; Sali, Lapo; Ciccarone, Antonio; Salvi, Fabrizio; Mascalchi, Mario

    2016-08-01

    Leukoencephalopathy with calcifications and cysts (LCC) is an uncommon condition of unknown etiology occurring in children and adults. Pathological findings include obliterative hyalinosis of the small vessels, myelin loss, intense gliosis, Rosenthal fiber formation, microcalcifications, and hemosiderin deposits. Herein we report a 55-year-old man with LCC documented 10 years ago, in whom we examined brain perfusion by pseudocontinuous arterial spin labeling technique. We demonstrated diffused hypoperfusion of the affected white matter (WM) and of the subcortical gray matter (GM) and cortical GM in the patient in comparison to a group of healthy control subjects, using both qualitative evaluation and region of interest analysis. WM and subcortical GM hypoperfusion reflects the known distribution of LCC microangiopathy. We speculate that cortical hypoperfusion may be related to cerebral atrophy or may reflect deafferentation secondary to severe leukoencephalopathy, and may possibly contribute to severe motor and cognitive impairment. Further studies addressing cerebral blood flow in LCC are necessary. PMID:27212271

  5. Magnesium in CKD: more than a calcification inhibitor?

    PubMed

    Floege, Jürgen

    2015-06-01

    Magnesium fulfils important roles in multiple physiological processes. Accordingly, a tight regulation of magnesium homeostasis is essential. Dysregulated magnesium serum levels, in particular hypomagnesaemia, are common in patients with chronic kidney disease (CKD) and have been associated with poor clinical outcomes. In cell culture studies as well as in clinical situations magnesium levels were associated with vascular calcification, cardiovascular disease and altered bone-mineral metabolism. Magnesium has also been linked to diseases such as metabolic syndrome, diabetes, hypertension, fatigue and depression, all of which are common in CKD. The present review summarizes and discusses the latest clinical data on the impact of magnesium and possible effects of higher levels on the health status of patients with CKD, including an outlook on the use of magnesium-based phosphate-binding agents in this context.

  6. Typical nodal calcifications in the maxillofacial region: a case report

    PubMed Central

    Wu, Guomin; Sun, Xiumei; Ni, Shilei; Zhang, Zhimin

    2014-01-01

    Multiple nodal calcifications in the maxillofacial region are very rare. This case report described a 49-year-old female patient diagnosed with calcified lymph nodes due to chronic inflammation of the lymphatic nodes, including the parotid lymphatic nodes, the posterior auricular lymphatic nodes and submandibular lymphatic nodes in the right maxillofacial region. In clinical practice, we conducted ultrasonography, three-dimensional reconstruction of CT and sialography make a preliminary diagnosis. Then we took surgery, while removing the calcified blocks within the lymphatic node and cleaning the wound cavity. After surgery, we used anti-inflammatory therapy for one week. Six months follow-up indicated no evidence of other calcified lymph nodes infection. PMID:25356188

  7. Calcification-carbonation method for red mud processing.

    PubMed

    Li, Ruibing; Zhang, Tingan; Liu, Yan; Lv, Guozhi; Xie, Liqun

    2016-10-01

    Red mud, the Bayer process residue, is generated from alumina industry and causes environmental problem. In this paper, a novel calcification-carbonation method that utilized a large amount of the Bayer process residue is proposed. Using this method, the red mud was calcified with lime to transform the silicon phase into hydrogarnet, and the alkali in red mud was recovered. Then, the resulting hydrogarnet was decomposed by CO2 carbonation, affording calcium silicate, calcium carbonate, and aluminum hydroxide. Alumina was recovered using an alkaline solution at a low temperature. The effects of the new process were analyzed by thermodynamics analysis and experiments. The extraction efficiency of the alumina and soda obtained from the red mud reached 49.4% and 96.8%, respectively. The new red mud with <0.3% alkali can be used in cement production. Using a combination of this method and cement production, the Bayer process red mud can be completely utilized. PMID:27214002

  8. Calcification-carbonation method for red mud processing.

    PubMed

    Li, Ruibing; Zhang, Tingan; Liu, Yan; Lv, Guozhi; Xie, Liqun

    2016-10-01

    Red mud, the Bayer process residue, is generated from alumina industry and causes environmental problem. In this paper, a novel calcification-carbonation method that utilized a large amount of the Bayer process residue is proposed. Using this method, the red mud was calcified with lime to transform the silicon phase into hydrogarnet, and the alkali in red mud was recovered. Then, the resulting hydrogarnet was decomposed by CO2 carbonation, affording calcium silicate, calcium carbonate, and aluminum hydroxide. Alumina was recovered using an alkaline solution at a low temperature. The effects of the new process were analyzed by thermodynamics analysis and experiments. The extraction efficiency of the alumina and soda obtained from the red mud reached 49.4% and 96.8%, respectively. The new red mud with <0.3% alkali can be used in cement production. Using a combination of this method and cement production, the Bayer process red mud can be completely utilized.

  9. The role of light in mediating the effects of ocean acidification on coral calcification.

    PubMed

    Dufault, Aaron M; Ninokawa, Aaron; Bramanti, Lorenzo; Cumbo, Vivian R; Fan, Tung-Yung; Edmunds, Peter J

    2013-05-01

    We tested the effect of light and PCO2 on the calcification and survival of Pocillopora damicornis recruits settled from larvae released in southern Taiwan. In March 2011, recruits were incubated at 31, 41, 70, 122 and 226 μmol photons m(-2) s(-1) under ambient (493 μatm) and high PCO2 (878 μatm). After 5 days, calcification was measured gravimetrically and survivorship estimated as the number of living recruits. Calcification was affected by the interaction of PCO2 with light, and at 493 μatm PCO2 the response to light intensity resembled a positive parabola. At 878 μatm PCO2, the effect of light on calcification differed from that observed at 493 μatm PCO2, with the result that there were large differences in calcification between 493 μatm and 878 μatm PCO2 at intermediate light intensities (ca. 70 μmol photons m(-2) s(-1)), but similar rates of calcification at the highest and lowest light intensities. Survivorship was affected by light and PCO2, and was highest at 122 μmol photons m(-2) s(-1) in both PCO2 treatments, but was unrelated to calcification. In June 2012 the experiment was repeated, and again the results suggested that exposure to high PCO2 decreased calcification of P. damicornis recruits at intermediate light intensities, but not at lower or higher intensities. Together, our findings demonstrate that the effect of PCO2 on coral recruits can be light dependent, with inhibitory effects of high PCO2 on calcification at intermediate light intensities that disappear at both higher and lower light intensities.

  10. Calcification in bleached and unbleached Montastraea faveolata: evaluating the role of oxygen and glycerol

    NASA Astrophysics Data System (ADS)

    Colombo-Pallotta, M. F.; Rodríguez-Román, A.; Iglesias-Prieto, R.

    2010-12-01

    All reef-building corals are symbiotic with dinoflagellates of the genus Symbiodinium, which influences many aspects of the host’s physiology including calcification. Coral calcification is a biologically controlled process performed by the host that takes place several membranes away from the site of photosynthesis performed by the symbiont. Although it is well established that light accelerates CaCO3 deposition in reef-building corals (commonly referred to as light-enhanced calcification), the complete physiological mechanism behind the process is not fully understood. To better comprehend the coral calcification process, a series of laboratory experiments were conducted in the major Caribbean reef-building species Montastraea faveolata, to evaluate the effect of glycerol addition and/or the super-saturation of oxygen in the seawater. These manipulations were performed in bleached and unbleached corals, to separate the effect of photosynthesis from calcification. The results suggest that under normal physiological conditions, a 42% increase in seawater oxygen concentration promotes a twofold increase in dark-calcification rates relative to controls. On the other hand, the results obtained using bleached corals suggest that glycerol is required, as a metabolic fuel, in addition to an oxygenic environment in a symbiosis that has been disrupted. Also, respiration rates in symbiotic corals that were pre-incubated in light conditions showed a kinetic limitation, whereas corals that were pre-incubated in darkness were oxygen limited, clearly emphasizing the role of oxygen in this regard. These findings indicate that calcification in symbiotic corals is not strictly a “light-enhanced” or “dark-repressed” process, but rather, the products of photosynthesis have a critical role in calcification, which should be viewed as a “photosynthesis-driven” process. The results presented here are discussed in the context of the current knowledge of the coral

  11. [Multidetector row CT in assessment of coronary artery calcification on hemodialisis].

    PubMed

    Caro, P; Delgado, R; Dapena, F; Núñez, A

    2007-01-01

    Vascular calcification is a strong predictor of cardiovascular and all-cause mortality. Coronary artery calcification is more frequent, more extensive and progresses more rapidly in CKD than in general population. They are also considered a marker of coronary heart disease, with high prevalence and functional significance. It suggests that detection and surveillance may be worthwhile in general clinical practice. New non-invasive image techniques, like Multi-detector row CT, a type of spiral scanner, assess density and volume of calcification at multiple sites and allow quantitative scoring of vascular calcification using calcium scores analogous to those from electron-beam CT. We have assessed and quantified coronary artery calcification with 16 multidetector row CT in 44 patients on hemodialysis and their relationship with several cardiovascular risk factors. Coronary artery calcification prevalence was of 84 % with mean calcium score of 1580 +/- 2010 ( r 0-9844) with calcium score > 400 in 66% of patients. It was usually multiple, affecting more than two vessels in more than 50%. In all but one patient, left anterior descending artery was involved with higher calcium score level at right coronary artery. Advanced age, male, diabetes, smoking, more morbidity, cerebrovascular disease previous, and calcium-binders phosphate and analogous vitamin D treatment would seem to be associated with coronary artery calcification. Coronary artery calcification is very frequent and extensive, usually multiple and associated to modifiable risk factors in hemodialysis patients. Multi-detector-row CT seems an effective, suitable, readily applicable method to assess and quantify coronary artery calcification. PMID:18336102

  12. 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

  13. Association of Big Endothelin-1 with Coronary Artery Calcification

    PubMed Central

    Zhang, Yan; Li, Yi-Lin; Xu, Rui-Xia; Guo, Yuan-Lin; Li, Sha; Wu, Na-Qiong; Li, Jian-Jun

    2015-01-01

    Background The coronary artery calcification (CAC) is clinically considered as one of the important predictors of atherosclerosis. Several studies have confirmed that endothelin-1(ET-1) plays an important role in the process of atherosclerosis formation. The aim of this study was to investigate whether big ET-1 is associated with CAC. Methods and Results A total of 510 consecutively admitted patients from February 2011 to May 2012 in Fu Wai Hospital were analyzed. All patients had received coronary computed tomography angiography and then divided into two groups based on the results of coronary artery calcium score (CACS). The clinical characteristics including traditional and calcification-related risk factors were collected and plasma big ET-1 level was measured by ELISA. Patients with CAC had significantly elevated big ET-1 level compared with those without CAC (0.5±0.4 vs. 0.2±0.2, P<0.001). In the multivariate analysis, big ET-1 (Tertile 2, HR = 3.09, 95% CI 1.66–5.74, P <0.001, Tertile3 HR = 10.42, 95% CI 3.62–29.99, P<0.001) appeared as an independent predictive factor of the presence of CAC. There was a positive correlation of the big ET-1 level with CACS (r = 0.567, p<0.001). The 10-year Framingham risk (%) was higher in the group with CACS>0 and the highest tertile of big ET-1 (P<0.01). The area under the receiver operating characteristic curve for the big ET-1 level in predicting CAC was 0.83 (95% CI 0.79–0.87, p<0.001), with a sensitivity of 70.6% and specificity of 87.7%. Conclusions The data firstly demonstrated that the plasma big ET-1 level was a valuable independent predictor for CAC in our study. PMID:26565974

  14. The Effect of Micro-Gravity on in vitro Calcification

    NASA Technical Reports Server (NTRS)

    Boskey; Stiner; Binderman; Mendelsohn; Doty, S. B.

    1997-01-01

    The experiment focuses on mineral deposition or calcification of cartilage. The experiments were used to compare the mineral formed in the microgravity of space with that formed on earth. Results of these experiments were anticipated to provide direct insight into how calcification in cartridge and bone may be controlled in space. In the C-2 experiment (STS 66), we found that mineralization started later in the cartridges (both on the ground and in hypo-gravity) than in plastic, and that mineralization appeared to be retarded in hypo-gravity. The flight experiments also showed that the cells differentiated normally, but more slowly than the ground controls, and that the matrix produced was not different from that made on the ground. The purpose of the C-5 experiment was to confirm these findings. The C-5 experiment was flown on STS-72. Because of a computer problem, cells received no gases and no nutrition. The C-7 was flown on STS-77. Ground controls were repeated a week later, however, because there was a problem with the temperature control during the flight, the concurrent ground controls were performed at a different temperature. Despite these problems, the results of the C-2 experiment were confirmed. The cells in the flight cultures did not mature, formed few cartilage nodules, and showed no evidence of mineral deposition up to a culture age of 28 days. Ground controls showed the presence of mineral (based on chemical, spectroscopic, and histochemical analyses) by 21 days. The mineral in these cultures was analogous to that found in calcifying cartilage of young chicks.

  15. [Posterior reversible encephalopathy syndrome of the midbrain and hypothalamus - a case report of uremic encephalopathy presenting with hypersomnia].

    PubMed

    Shiga, Yuji; Kanaya, Yuhei; Kono, Ryuhei; Takeshima, Shinichi; Shimoe, Yutaka; Kuriyama, Masaru

    2016-01-01

    We report the case of a 73-year-old woman presenting with hypersomnia and loss of appetite. She suffered from diabetic nephropathy without receiving dialysis, in addition to hypertension, which was well controlled without marked fluctuation. There were no objective neurological findings. Her laboratory findings showed renal failure with 3.7 mg/dl of serum creatinine and decreased serum sodium and potassium. Brain magnetic resonance imaging (MRI) showed posterior reversible encephalopathy syndrome (PRES) with vasogenic edema, which was distributed in the dorsal midbrain, medial thalamus, and hypothalamus. After we addressed the electrolyte imbalance and dehydration, her symptoms and MRI findings gradually improved, but faint high signals on MRI were still present 3 months later. Orexin in the cerebrospinal fluid was decreased on admission, but improved 6 months later. We diagnosed uremic encephalopathy with atypical form PRES showing functional disturbance of the hypothalamus. PMID:26640128

  16. Hemolytic uremic syndrome with mild renal involvement due to Shiga toxin-producing Escherichia coli (STEC) O145 strain.

    PubMed

    Pérez, Lucía; Apezteguía, Lucía; Piñeyrúa, Cecilia; Dabezies, Agustín; Bianco, María N; Schelotto, Felipe; Varela, Gustavo

    2014-01-01

    Hemolytic uremic syndrome (HUS) is a disorder characterized by the presence of the classic triad: microangiopathic hemolytic anemia, thrombocytopenia and acute renal injury. HUS without acute renal failure can be confused with other hematologic diseases. An infantile HUS caused by a Shiga-toxin-producing Escherichia coli (STEC) O145 strain carrying genotype stx2, ehxA, eae subtype β1 is herein reported. The infant did not require dialysis during the acute stage of HUS, evolved favorably, maintained normal blood pressure and normal renal function and had no recurrence until the last control. This could be due to several factors, such as the characteristics of infecting STEC strain and a reduction in host susceptibility to renal injury. This report highlights the regional participation of non-O157 STEC in childhood diseases and the importance of performing active surveillance for all forms of HUS.

  17. Gemcitabine-induced hemolytic uremic syndrome mimicking scleroderma renal crisis presenting with Raynaud's phenomenon, positive antinuclear antibodies and hypertensive emergency.

    PubMed

    Yamada, Yuichiro; Suzuki, Keisuke; Nobata, Hironobu; Kawai, Hirohisa; Wakamatsu, Ryo; Miura, Naoto; Banno, Shogo; Imai, Hirokazu

    2014-01-01

    A 58-year-old woman who received gemcitabine for advanced gallbladder cancer developed an impaired renal function, thrombocytopenia, Raynaud's phenomenon, digital ischemic changes, a high antinuclear antibody titer and hypertensive emergency that mimicked a scleroderma renal crisis. A kidney biopsy specimen demonstrated onion-skin lesions in the arterioles and small arteries along with ischemic changes in the glomeruli, compatible with a diagnosis of hypertensive emergency (malignant hypertension). The intravenous administration of a calcium channel blocker, the oral administration of an angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker and the transfusion of fresh frozen plasma were effective for treating the thrombocytopenia and progressive kidney dysfunction. Gemcitabine induces hemolytic uremic syndrome with accelerated hypertension and Raynaud's phenomenon, mimicking scleroderma renal crisis.

  18. The middle-molecule hypothesis 30 years after: lost and rediscovered in the universe of uremic toxicity?

    PubMed

    Vanholder, Raymond; Van Laecke, Steven; Glorieux, Griet

    2008-01-01

    The present review gives an overview of the known and newly detected middle molecules and their biological potential. Since many middle molecules were shown to affect leukocyte, endothelial cell, smooth muscle cell and/or thrombocyte function, the likelihood of their role in cardiovascular damage related to renal failure is described. In addition, the middle-molecule behaviour during dialysis is commented. The impact of dialytic removal by diffusion or convection in clinical studies is extensively discussed reflecting the benefit on patient survival and/or clinical outcome. The continuing search for new culprits will result in therapeutic options including improved removal of uremic solutes and/or the search for pharmacological strategies blocking responsible pathophysiological pathways.

  19. Dysregulation of Angiopoietin 1 and 2 in Escherichia coli O157:H7 Infection and the Hemolytic-Uremic Syndrome

    PubMed Central

    Page, Andrea V.; Tarr, Phillip I.; Watkins, Sandra L.; Rajwans, Nimerta; Petruzziello-Pellegrini, Tania N.; Marsden, Philip A.; Kain, Kevin C.; Liles, W. Conrad

    2013-01-01

    Escherichia coli O157:H7-associated hemolytic-uremic syndrome (HUS) is characterized by profound prothrombotic abnormalities. Endothelial dysfunction, manifested as dysregulation of angiopoietins 1 and 2 (Ang-1/2), could underlie HUS pathophysiology. We measured Ang-1/2 in 77 children with E. coli O157:H7 infection. Ang-1, Ang-2, and the Ang-2/Ang-1 ratio were significantly different in HUS vs the pre-HUS phase of illness or uncomplicated infection. Angiopoietin dysregulation preceded HUS and worsened as HUS developed. In vitro exposure of human microvascular endothelial cells to Shiga toxin recapitulated the in vivo observations. Angiopoietin regulation is profoundly affected before and during HUS, reflecting that subclinical endothelial dysfunction precedes overt microangiopathy. PMID:23801605

  20. Comment on "Coral reef calcification and climate change: The effect of ocean warming"

    USGS Publications Warehouse

    Kleypas, J.A.; Buddemeier, R.W.; Eakin, C.M.; Gattuso, J.-P.; Guinotte, J.; Hoegh-Guldberg, O.; Iglesias-Prieto, R.; Jokiel, P.L.; Langdon, C.; Skirving, W.; Strong, A.E.

    2005-01-01

    McNeil et al. [2004] attempt to address an important question about the interactions of temperature and carbonate chemistry on calcification, but their projected values of reef calcification are based on assumptions that ignore critical observational and experimental literature. Certainly, more research is needed to better understand how changing temperatures and carbonate chemistry will affect not only coral reef calcification, but coral survival. As discussed above, the McNeil et al. [2004] analysis is based on assumptions that exclude potentially important factors and therefore needs to be viewed with caution. Copyright 2005 by the American Geophysical Union.

  1. 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

  2. The realm of vitamin K dependent proteins: shifting from coagulation toward calcification.

    PubMed

    Willems, Brecht A G; Vermeer, Cees; Reutelingsperger, Chris P M; Schurgers, Leon J

    2014-08-01

    In the past few decades vitamin K has emerged from a single-function "haemostasis vitamin" to a "multi-function vitamin." The use of vitamin K antagonists (VKA) inevitably showed that the inhibition was not restricted to vitamin K dependent coagulation factors but also synthesis of functional extrahepatic vitamin K dependent proteins (VKDPs), thereby eliciting undesired side effects. Vascular calcification is one of the recently revealed detrimental effects of VKA. The discovery that VKDPs are involved in vascular calcification has propelled our mechanistic understanding of this process and has opened novel avenues for diagnosis and treatment. This review addresses mechanisms of VKDPs and their significance for physiological and pathological calcification.

  3. Physiological controls on seawater uptake and calcification in the benthic foraminifer Ammonia tepida

    NASA Astrophysics Data System (ADS)

    de Nooijer, L. J.; Langer, G.; Nehrke, G.; Bijma, J.

    2009-11-01

    To analyze the relation between seawater uptake and calcification, we incubated juveniles of the benthic foraminifer Ammonia tepida with various fluorescent probes and visualised them afterwards with confocal laser scanning microscopy. Vesicle membranes, Ca ions and vacuole fluids were followed with various tracers and showed for the first time that endocytosis of seawater is part of the calcification process in Ammonia tepida. Data on the intracellular Ca ion cycling allowed for calculating a preliminary cellular Ca budget during foraminiferal calcification. This showed that the free calcium involved in the production of a new chamber cannot be sufficient and suggests that foraminifera may precipitate their calcite from an amorphous precursor.

  4. Protein-energy wasting and uremic failure to thrive in children with chronic kidney disease: they are not small adults.

    PubMed

    Nourbakhsh, Noureddin; Rhee, Connie M; Kalantar-Zadeh, Kamyar

    2014-12-01

    Protein-energy wasting (PEW), a condition of decreased body protein and fat mass, is highly prevalent in patients with chronic kidney disease (CKD) and a potent predictor of mortality in this population. In adults with CKD, PEW has typically been defined on the basis of (1) deranged biochemical parameters, (2) reduced body mass, (3) reduced muscle mass, and (4) decreased dietary protein intake. Emerging data suggest that PEW may also commonly afflict children with CKD and have a negative impact on growth and development ("uremic failure to thrive"), yet it remains comparatively understudied and less well characterized in these patients. Given the challenges of applying adult-defined PEW criteria to the pediatric population, the authors of a recent study entitled "Protein energy wasting in children with chronic kidney disease" [Abraham et al. (2014) Pediatr Nephrol 29:1231-1238] have sought to develop a scoring system and three alterative definitions for this condition using a combination of biochemical markers, clinical measurements, and subjective reporting in children in the CKiD cohort: (1) minimal PEW definition (≥2 adult-defined PEW criteria); (2) standard PEW definition (≥3 adult-defined PEW criteria); (3) modified PEW definition (≥3 adult-defined PEW criteria, plus short stature or poor growth). These authors observed that meeting the modified PEW definition was associated with a significantly increased risk of hospitalization in unadjusted analyses, i.e., a 2.2-fold higher risk, and trended towards increased risk in multivariable adjusted analyses, i.e., 2.0-fold higher risk. At the present time, future studies validating these findings and developing further refined definitions and/or scoring systems for the detection and management of PEW in children and uremic failure to thrive are urgently needed.

  5. Calcific aortic valve disease: A consensus summary from the Alliance of Investigators on Calcific Aortic Valve Disease

    PubMed Central

    Yutzey, Katherine E.; Demer, Linda L.; Body, Simon C.; Huggins, Gordon S.; Towler, Dwight A.; Giachelli, Cecilia M.; Hofmann-Bowman, Marion A.; Mortlock, Douglas P.; Rogers, Melissa B.; Sadeghi, Mehran M.; Aikawa, Elena

    2014-01-01

    Calcific Aortic Valve Disease (CAVD) is increasingly prevalent worldwide with significant morbidity and mortality. Therapeutic options beyond surgical valve replacement are currently limited. In 2011, the National Heart Lung and Blood Institute assembled a working group on aortic stenosis. This group identified CAVD as an actively regulated disease process in need of further study. As a result, the Alliance of Investigators on CAVD was formed to coordinate and promote CAVD research, with the goals of identifying individuals at risk, developing new therapeutic approaches, and improving diagnostic methods. The group is composed of cardiologists, geneticists, imaging specialists, and basic science researchers. This report reviews the current status of CAVD research and treatment strategies with identification of areas in need of additional investigation for optimal management of this patient population. PMID:25189570

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

    PubMed Central

    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.

    2016-01-01

    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. PMID:27251104

  7. 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.

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

    PubMed

    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

    2016-01-01

    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. PMID:27251104

  9. Distal arterial occlusive disease in diabetes is related to medial arterial calcification.

    PubMed

    Chantelau, E; Lee, K M; Jungblut, R

    1997-01-01

    In diabetes mellitus, peripheral arterial occlusive disease predominantly affects the lower leg (tibial and peroneal vessel disease). Our study suggests that this feature is related to the presence of forefoot medial arterial calcification.

  10. Light enhanced calcification in Stylophora pistillata: effects of glucose, glycerol and oxygen

    PubMed Central

    Tambutté, Eric; Allemand, Denis; Tambutté, Sylvie

    2014-01-01

    Zooxanthellate corals have long been known to calcify faster in the light than in the dark, however the mechanism underlying this process has been uncertain. Here we tested the effects of oxygen under controlled pCO2 conditions and fixed carbon sources on calcification in zooxanthellate and bleached microcolonies of the branching coral Stylophora pistillata. In zooxanthellate microcolonies, oxygen increased dark calcification rates to levels comparable to those measured in the light. However in bleached microcolonies oxygen alone did not enhance calcification, but when combined with a fixed carbon source (glucose or glycerol), calcification increased. Respiration rates increased in response to oxygen with greater increases when oxygen is combined with fixed carbon. ATP content was largely unaffected by treatments, with the exception of glycerol which decreased ATP levels. PMID:24883242

  11. [Significance of vascular calcification in diabetic patients with increased risks of cardiovascular disease and stroke].

    PubMed

    Shioi, Atsushi

    2003-09-01

    Patients with diabetes have greatly elevated risks of atherosclerotic diseases such as coronary artery disease (CAD) and stroke. Vascular calcification in advanced atherosclerosis is a common feature in diabetic patients. In vitro and in vivo studies suggest that apoptosis and chondro/osteogenic differentiation of vascular wall cells such as smooth muscle cells may play important roles in the progression of vascular calcification. Diabetes may promote vascular calcification through the action of various factors including hyperglycemia, oxidative stress, tumor necrosis factor-alpha, and advanced glycation end products. Detection of coronary calcium by electron-beam computed tomography (EBCT) revealed clinical significance of vascular calcification and this technique may be a useful method to identify diabetic patients with increased risks of cardiovascular disease and stroke. PMID:15775191

  12. Intracranial calcification in a neonate with the Sturge Weber syndrome and additional problems.

    PubMed

    Alonso, A; Taboada, D; Ceres, L; Beltran, J; Olague, R; Nogues, A

    1979-02-26

    The neonate in this report had severe encephalotrigeminal angiomatosis with intracranial calcification, cranial hemiatrophy, microcephaly and generalised severe cerebral atrophy. Such findings are not common in the newborn with this syndrome. PMID:431990

  13. 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.

  14. Dystrophic Cutaneous Calcification and Metaplastic Bone Formation due to Long Term Bisphosphonate Use in Breast Cancer

    PubMed Central

    Tatlı, Ali Murat; Göksu, Sema Sezgin; Arslan, Deniz; Başsorgun, Cumhur İbrahim; Coşkun, Hasan Şenol

    2013-01-01

    Bisphosphonates are widely used in the treatment of breast cancer with bone metastases. We report a case of a female with breast cancer presented with a rash around a previous mastectomy site and a discharge lesion on her right chest wall in August 2010. Biopsy of the lesion showed dystrophic calcification and metaplastic bone formation. The patient's history revealed a long term use of zoledronic acid for the treatment of breast cancer with bone metastasis. We stopped the treatment since we believed that the cutaneous dystrophic calcification could be associated with her long term bisphosphonate therapy. Adverse cutaneous events with bisphosphonates are very rare, and dystrophic calcification has not been reported previously. The dystrophic calcification and metaplastic bone formation in this patient are thought to be due to long term bisphosphonate usage. PMID:23956898

  15. The Association Between Serum Magnesium Concentrations and Coronary Artery Calcification Scores in Astronauts

    NASA Technical Reports Server (NTRS)

    Betcher, Jenna; Zwart, Sara; Smith, Scott M.

    2016-01-01

    Magnesium is a natural calcium antagonist, and is inversely associated with coronary heart disease, cardiovascular mortality rates, and vascular calcification. Coronary artery calcification score is a tool used to evaluate the prognosis of coronary artery disease in individuals. Higher magnesium intake is associated with lower coronary artery calcification scores (CACS), and recent studies have found a significant inverse relationship between serum magnesium concentrations and CACS in Korean and Mexican-mestizo populations. The correlation between serum magnesium concentrations and CACS is not well researched, so our aim was to examine this relationship in astronauts. We found that a higher serum magnesium concentration is significantly related to a higher coronary artery calcification score (p=.0217), and that there is a significant difference in magnesium concentrations of subjects who have a CACS greater than 100 and a CACS less than 100.

  16. Pathological calcification and replicating calcifying-nanoparticles: general approach and correlation.

    PubMed

    Ciftçioğlu, Neva; McKay, David S

    2010-05-01

    Calcification, a phenomenon often regarded by pathologists little more than evidence of cell death, is becoming recognized to be important in the dynamics of a variety of diseases from which millions of beings suffer in all ages. In calcification, all that is needed for crystal formation to start is nidi (nuclei) and an environment of available dissolved components at or near saturation concentrations, along with the absence of inhibitors for crystal formation. Calcifying nanoparticles (CNP) are the first calcium phosphate mineral containing particles isolated from human blood and were detected in numerous pathologic calcification related diseases. Controversy and critical role of CNP as nidi and triggering factor in human pathologic calcification are discussed. PMID:20094006

  17. 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

  18. Atrium of stone: A case of confined left atrial calcification without hemodynamic compromise.

    PubMed

    Jones, Christopher; Lodhi, Aadil Mubeen; Cao, Long Bao; Chagarlamudi, Arjun Kumar; Movahed, Assad

    2014-05-16

    Dystrophic cardiac calcification is often associated with conditions causing systemic inflammation and when present, is usually extensive, often encompassing multiple cardiac chambers and valves. We present an unusual case of dystrophic left atrial calcification in the setting of end stage renal disease on hemodialysis diagnosed by echocardiography and computed tomography. Significant calcium deposition is confined within the walls of the left atrium with no involvement of the mitral valve, and no hemodynamic effects. PMID:24868514

  19. Chondrocyte Apoptosis Is Not Essential for Cartilage Calcification: Evidence From an In Vitro Avian Model

    PubMed Central

    Pourmand, Eric P.; Binderman, Itzhak; Doty, Stephen B.; Kudryashov, Valery; Boskey, Adele L.

    2006-01-01

    The calcification of cartilage is an essential step in the process of normal bone growth through endochondral ossification. Chondrocyte apoptosis is generally observed prior to the transition of calcified cartilage to bone. There are, however, contradictory reports in the literature as to whether chondrocyte apoptosis is a precursor to cartilage calcification, a co-event, or occurs after calcification. The purpose of this study was to test the hypothesis that chondrocyte apoptosis is not a requirement for initial calcification using a cell culture system that mimics endochondral ossification. Mesenchymal stem cells harvested from Stages 21-23 chick limb buds were plated as micro-mass cultures in the presence of 4 mM inorganic phosphate (mineralizing conditions). The cultures were treated with either an apoptosis inhibitor or stimulator and compared to un-treated controls before the start of calcification on day 7. Inhibition of apoptosis with the caspase inhibitor Z-Val-Ala-Asp (O-Me)-fluoromethylketone (Z-VAD-fmk) caused no decreases in calcification as indicated by radioactive calcium uptake or Fourier transform infrared (FT-IR) analysis of mineral properties. When apoptosis was inhibited, the cultures showed more robust histological features (including more intense staining for proteoglycans, and more intact cells within the nodules as well as along the periphery of the cells as compared to untreated controls), more proliferation as noted by bromo-deoxyuridine (BrdU) labeling, decreases in terminal deoxynucleotidyl transferase (Tdt)-mediated dUTP nick-end labeling (TUNEL) staining, and fewer apoptotic bodies in electron microscopy. Stimulation of apoptosis with 40-120 nM staurosporine prior to the onset of calcification resulted in inhibition of calcium accretion, with the extent of total calcium uptake significantly decreased, the amount of matrix deposition impaired, and the formation of abnormal mineral crystals. These results indicate that chondrocyte

  20. Screen-detected breast carcinoma with macroscopic dystrophic calcification: A pictorial essay with radiolological pathological correlation.

    PubMed

    Ebrahim, Lamya; Dissanayake, Deepthi; Metcalf, Cecily; Wylie, Elizabeth

    2016-04-01

    Breast calcifications are among the most common abnormal radiographic findings detected at screening mammography. This essay illustrates the clinico-pathological features of nine screen-detected breast carcinomas, which had benign-appearing macrocalcifications, as a radiographically dominant presenting feature. We aimed to demonstrate that benign-appearing calcifications within a breast lesion are not diagnostic of a benign process if the other imaging characteristics of the lesion are suspicious of malignancy.

  1. 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.

  2. [Intracardiac mass: Why not a liquefaction necrosis of a mitral annulus calcification?].

    PubMed

    Leddet, P; Couppié, P; De Poli, F; Uhry, S; Hanssen, M

    2015-11-01

    We report the case of an asymptomatic 70-year-old woman with a liquefaction necrosis of mitral annulus calcification. This mass was discovered incidentally during an echocardiographic examination. Additional treatment was not performed because liquefaction necrosis of mitral calcification usually has a benign prognosic. A scheduled clinical review with an echocardiographic examination and cardiac MRI was planified. The patient is actually healthy without any complication.

  3. Medullary nephrocalcinosis and pancreatic calcifications demonstrated by ultrasound and CT in infants after treatment with ACTH

    SciTech Connect

    Rausch, H.P.; Hanefield, F.; Kaufmann, B.J.

    1984-10-01

    Thirteen patients who had undergone prolonged adrenocorticotropic hormone (ACTH) therapy for infantile spasms or encephalopathy were examined with sonography. Nine patients were seen to have appearances characteristic of medullary nephrocalcinosis. Five patients also showed a homogeneously increased echogenicity of the whole pancreas on sonography, and one of these showed increased density on computed tomography. Density measurements were in the range of calcific arterial within the papillae and pancreatic tissue. On abdominal survey radiographs, even in retrospect, no calcifications could be recognized.

  4. A coral polyp model of photosynthesis, respiration and calcification incorporating a transcellular ion transport mechanism

    NASA Astrophysics Data System (ADS)

    Nakamura, T.; Nadaoka, K.; Watanabe, A.

    2013-09-01

    A numerical simulation model of coral polyp photosynthesis, respiration and calcification was developed. The model is constructed with three components (ambient seawater, coelenteron and calcifying fluid), and incorporates photosynthesis, respiration and calcification processes with transcellular ion transport by Ca-ATPase activity and passive transmembrane CO2 transport and diffusion. The model calculates dissolved inorganic carbon and total alkalinity in the ambient seawater, coelenteron and calcifying fluid, dissolved oxygen (DO) in the seawater and coelenteron and stored organic carbon (CH2O). To reconstruct the drastic variation between light and dark respiration, respiration rate dependency on DO in the coelenteron is incorporated. The calcification rate depends on the aragonite saturation state in the calcifying fluid (Ω a cal). Our simulation result was a good approximation of "light-enhanced calcification." In our model, the mechanism is expressed as follows: (1) DO in the coelenteron is increased by photosynthesis, (2) respiration is stimulated by increased DO in the light (or respiration is limited by DO depletion in the dark), then (3) calcification increases due to Ca-ATPase, which is driven by the energy generated by respiration. The model simulation results were effective in reproducing the basic responses of the internal CO2 system and DO. The daily calcification rate, the gross photosynthetic rate and the respiration rate under a high-flow condition increased compared to those under the zero-flow condition, but the net photosynthetic rate decreased. The calculated calcification rate responses to variations in the ambient aragonite saturation state (Ω a amb) were nonlinear, and the responses agreed with experimental results of previous studies. Our model predicted that in response to ocean acidification (1) coral calcification will decrease, but will remain at a higher value until Ω a amb decreases to 1, by maintaining a higher Ω a cal due to

  5. Comparison of Therapeutic Effect of Extracorporeal Shock Wave in Calcific Versus Noncalcific Lateral Epicondylopathy

    PubMed Central

    Park, Jong Wook; Hwang, Ji Hye; Choi, Yoo Seong

    2016-01-01

    Objective To assess the therapeutic effect of extracorporeal shock wave therapy (ESWT) in lateral epicondylopathy with calcification, and compare it to the effect of ESWT in lateral epicondylopathy without calcification. Methods A retrospective study was conducted. Forty-three patients (19 with calcific and 24 with noncalcific lateral epicondylopathy in ultrasound imaging) were included. Clinical evaluations included the 100-point score, Nirschl Pain Phase scale before and after ESWT, and Roles and Maudsley (R&M) scores after ESWT. ESWT (2,000 impulses and 0.06–0.12 mJ/mm2) was performed once a week for 4 weeks. Results The 100-point score and Nirschl Pain Phase scale changed significantly over time (p<0.001), but there was no significant difference between groups (p=0.555). The R&M scores at 3 and 6 months after ESWT were not significantly different between groups. In the presence of a tendon tear, those in the calcific lateral epicondylopathy group showed poor improvement of 100-point scores compared to the noncalcific group (p=0.004). Conclusion This study demonstrated that the therapeutic effect of ESWT in calcific lateral epicondylopathy was not significantly different from that in noncalcific lateral epicondylopathy. When a tendon tear is present, patients with calcific lateral epicondylopathy might show poor prognosis after ESWT relative to patients with noncalcific lateral epicondylopathy. PMID:27152280

  6. 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

  7. Calcification, a physiological process to be considered in the context of the whole organism

    NASA Astrophysics Data System (ADS)

    Findlay, H. S.; Wood, H. L.; Kendall, M. A.; Spicer, J. I.; Twitchett, R. J.; Widdicombe, S.

    2009-02-01

    Marine organisms that produce calcium carbonate structures are predicted to be most vulnerable to a decline in oceanic pH (ocean acidification) based on the understanding that calcification rates will decrease as a result of changes in the seawater carbonate chemistry thereby reducing carbonate ion concentration (and associated saturation states). Coastal seas are critical components of the global carbon cycle yet little research has been conducted on acidification impacts on coastal benthic organisms. Here, a critical appraisal of calcification in six benthic species showed, contrary to popular predictions, calcification can increase, and not decrease, in acidified seawater. Measuring the changes in calcium in isolated calcium carbonate structure as well as structures from live animals exposed to acidified seawater allowed a comparison between a species' ability to calcify and the dissolution affects across decreasing levels of pH. Calcium carbonate production is dependant on the ability to increase calcification thus counteracting an increase in dissolution. Comparison with paleoecological studies of past high carbon dioxide (CO2) events presents a similar picture. This conclusion implies that calcification may not be the critical process impacted by ocean acidification; particularly as all species investigated displayed physiological trade offs including reduced metabolism, health, and behavioural responses, in association with this calcification upregulation, which possess as great a threat to survival as an inability to calcify.

  8. Current trends in the management of uremic restless legs syndrome: a systematic review on aspects related to quality of life, cardiovascular mortality and survival.

    PubMed

    Sakkas, Giorgos K; Giannaki, Christoforos D; Karatzaferi, Christina; Maridaki, Maria; Koutedakis, Yiannis; Hadjigeorgiou, Georgios M; Stefanidis, Ioannis

    2015-06-01

    Restless legs syndrome (RLS) affects almost one out of three end-stage renal disease patients. This review assesses the current treatment options for uremic RLS and the potential benefits of those treatments on quality of life parameters, cardiovascular mortality and survival. A systematic review was conducted searching PubMed and Scopus by using the Cochrane and PRISMA guidelines. Fourteen studies met the inclusion criteria in which the international RLS study group criteria were used as the primary diagnostic tool. Both pharmacological and non-pharmacological approaches were found to reduce the severity of uremic RLS symptoms. Only four studies reported changes on aspects related to quality of life while those changes were also associated with health benefits that resulted in reduced cardiovascular risk. The severity of uremic RLS symptoms can be ameliorated by using dopamine agonists and gabapentin, intravenous iron, exercise or supplementation with vitamins C and E, although some of those treatment benefits may be transient. There is a lack of strong evidence regarding the effects of the pharmacological approaches on quality of life and cardiovascular survival and mortality. In contrast exercise has been proven beneficial in both reducing the RLS symptoms' severity score and improving the quality of life.

  9. [Study of the binding characteristics of chlorophenoxyisobutyric acid to serum proteins in chronically uremic patients : influence of dialysis and heparine (author's transl)].

    PubMed

    Lacour, B; Di Giulio, S; Nicolaï, A; Drüeke, T; Debray, M; Boulu, R G

    1982-01-01

    The binding characteristics of chlorophenoxyisobutyric acid (CPIB) to serum proteins has been studied in 10 chronically uremic patients and 9 healthy subjects using the technique of equilibrium dialysis. Scatchard analysis of the results indicated a significant decrease in association constants for low as well as for high affinity sites. The number of binding sites however was not diminished thus suggesting the presence of competitive inhibitors. Such inhibitors were dializable, at least in part, as demonstrated by in vivo-hemodialysis and in vitro-dialysis experiments. The in vivo administration of 50 mg heparin intravenously led to a striking increase in the unbound fraction of serum CPIB whereas the addition of 10 IU/ml heparin in vitro induced no change of protein binding which is in favor of only an indirect effect of heparin. In conclusion, CPIB binding to serum proteins of chronically uremic patients as compared to normal volunteers was decreased leading to an increase of its unbound circulating fraction. The observed change of protein binding appeared to be due to the presence of competitive inhibitors in uremic serum. PMID:7088259

  10. Pineal calcification in relation to menopause in schizophrenia.

    PubMed

    Sandyk, R

    1992-01-01

    I have suggested that critical changes in melatonin secretion, as mediated by the pineal gland, may exert a crucial role in the onset and pathogenesis of schizophrenia. Since pineal calcification (PC) is thought to reflect the metabolic and secretory activity of the gland, I investigated in 29 randomly selected chronic institutionalized female schizophrenic patients the association of PC on CT scan with premenopausal (prior to age 40) versus menopausal (ages 40-55) onset of illness. The premenopausal patients were found to show a significantly higher prevalence of PC than the menopausal patients (55.5% vs. 18.1%; X2 = 3.93, df = 1, p < .05). Since PC was unrelated to historical, demographic, and treatment variables, these findings highlight the importance of the pineal gland for the timing of the onset of schizophrenia, particularly in relation to the female reproductive state. The results carry theoretical implications on the pathogenesis of schizophrenia and suggest that the pineal gland may exert a protective effect against its onset. PMID:1305625

  11. Abnormal EEG and calcification of the pineal gland in schizophrenia.

    PubMed

    Sandyk, R; Kay, S R

    1992-01-01

    Computed tomographic (CT) studies of the brain in schizophrenic patients have demonstrated a variety of structural abnormalities. We reported recently an association between pineal calcification (PC) and cortical and prefrontal cortical atrophy, and third ventricular size on CT scan in chronic schizophrenic patients. These findings indicate that in schizophrenia PC is associated with the morphological brain abnormalities associated with the disease. If PC is, indeed, related to organic cerebral pathology, then one would expect a higher prevalence of pineal gland pathology among patients with electroencephalographic (EEG) abnormalities by comparison to those with a normal EEG. To investigate this hypothesis, we studied the prevalence of PC on CT scan in a sample of 52 neuroleptic-treated schizophrenic patients (29 men, 23 women, mean age: 51.3 years SD = 9.1), of whom 10 (19.2%) had an abnormal EEG. The prevalence of PC in patients with EEG abnormalities was significantly greater by comparison to those with a normal EEG (90.0% vs. 54.8%, X2 = 4.24, p < .05). Since both groups did not differ on any of the historical and demographic data, and since PC was unrelated to neuroleptic exposure, these findings suggest that in schizophrenia PC may be related to the disease process and that it may be a marker of subcortical pathology. PMID:1342008

  12. Potential drug targets for calcific aortic valve disease

    PubMed Central

    Hutcheson, Joshua D.; Aikawa, Elena; Merryman, W. David

    2014-01-01

    Calcific aortic valve disease (CAVD) is a major contributor to cardiovascular morbidity and mortality and, given its association with age, the prevalence of CAVD is expected to continue to rise as global life expectancy increases. No drug strategies currently exist to prevent or treat CAVD. Given that valve replacement is the only available clinical option, patients often cope with a deteriorating quality of life until diminished valve function demands intervention. The recognition that CAVD results from active cellular mechanisms suggests that the underlying pathways might be targeted to treat the condition. However, no such therapeutic strategy has been successfully developed to date. One hope was that drugs already used to treat vascular complications might also improve CAVD outcomes, but the mechanisms of CAVD progression and the desired therapeutic outcomes are often different from those of vascular diseases. We, therefore, discuss the benchmarks that must be met by a CAVD treatment approach, and highlight advances in the understanding of CAVD mechanisms to identify potential novel therapeutic targets. PMID:24445487

  13. Role of proteoglycans in the onset of calcification

    SciTech Connect

    Tellone, C.I.

    1985-01-01

    The objective of this investigation was to inquire if the presence or absence of proteoglycans or their chemical subunits had a direct effect on the onset of calcification. High density spot cultures of limb bud mesenchyme obtained from mouse embryos on the 12th day of gestation were exposed to medium containing 30 mM phosphate. Calcium deposits observed after staining by the von Kossa method were confined to the non-cartilagenous intenodular areas. Electron microscopy illustrated that a large proportion of the calcium deposits were associated with collagen fibrils. A significant increase in the uptake of /sup 45/Ca was observed in cultures supplemented with 30 mM phosphate. Atomic absorption analysis of the cultures showed that they contained 2.00 ng calcium/ug DNA. Incorporation of /sup 3/H-glucosamine into glycosaminoglycans (GAG) was significantly reduced by phosphate and both extruded and cell associated GAG were affected. Exposure of mineralizing cultures to a biologically active anticalculus agent, ethane-1-hydroxy-1,1-diphosphonate, resulted in a significant reduction in /sup 45/Ca uptake, providing confidence that the culture did response as a biological system. These data suggest that under the conditions employed, proteoglycans in the extracellular environment of limb bud mesenchyme inhibit calcium deposition. The inhibitory effect was observed only when proteoglycans were added as polymeric aggregates. The culture system employed was unable to detect the inhibitory effects, if any, of proteoglycan monomers or the subunits of proteoglycans, hyaluronic acid or chondroitin sulfate.

  14. PVAL breast phantom for dual energy calcification detection

    NASA Astrophysics Data System (ADS)

    Koukou, V.; Martini, N.; Velissarakos, K.; Gkremos, D.; Fountzoula, C.; Bakas, A.; Michail, C.; Kandarakis, I.; Fountos, G.

    2015-09-01

    Microcalcifications are the main indicator for breast cancer. Dual energy imaging can enhance the detectability of calcifications by suppressing the tissue background. Two digital images are obtained using two different spectra, for the low- and high-energy respectively, and a weighted subtracted image is produced. In this study, a dual energy method for the detection of the minimum breast microcalcification thickness was developed. The used integrated prototype system consisted of a modified tungsten anode X-ray tube combined with a high resolution CMOS sensor. The breast equivalent phantom used was an elastically compressible gel of polyvinyl alcohol (PVAL). Hydroxyapatite was used to simulate microcalcifications with thicknesses ranging from 50 to 500 μm. The custom made phantom was irradiated with 40kVp and 70kVp. Tungsten (W) anode spectra filtered with 100μm Cadmium and 1000pm Copper, for the low- and high-energy, respectively. Microcalcifications with thicknesses 300μm or higher can be detected with mean glandular dose (MGD) of 1.62mGy.

  15. Review article: Getting the balance right: assessing causes and extent of vascular calcification in chronic kidney disease.

    PubMed

    Ketteler, Markus; Biggar, Patrick H

    2009-06-01

    Vascular calcification is part of the definition of chronic kidney disease-mineral and bone disorder (CKD-MBD). It is also a surrogate parameter of cardiovascular and all-cause mortality risk in the CKD population. However, vascular calcification is not a homogenous entity, but a rather complex manifestation influenced by derangements of calcium and phosphate homeostasis, by dysregulated calcification inhibitors and promoters, and by the type of arterial disease (atherosclerosis vs arteriosclerosis). Despite the clear-cut risk association between the presence of vascular calcification and mortality, it is currently not well defined, how this knowledge about calcification should be translated into active clinical management. Further, the choice of the appropriate imaging test is a matter of debate. This article attempts to provide an update on insights into the pathophysiology of vascular calcification processes and a subjective view of the clinical consequences of management of CKD patients at risk. PMID:19563380

  16. 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

  17. 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.

  18. Insulin resistance in uremia. Characterization of lipid metabolism in freshly isolated and primary cultures of hepatocytes from chronic uremic rats.

    PubMed Central

    Caro, J F; Lanza-Jacoby, S

    1983-01-01

    We have studied the mechanism(s) of hyperlipidemia and liver insulin sensitivity in a rat model of severe chronic uremia (U). Basal lipid synthesis was decreased in freshly isolated hepatocytes from U when compared with sham-operated ad lib.-fed controls (alfC). Basal lipid synthesis in pair-fed controls (pfC) was in between U and alfC. Similarly, the activity of liver acetyl CoA carboxylase, fatty acid synthetase, citrate cleavage enzyme, malate dehydrogenase, and glucose-6-phosphate dehydrogenase was diminished in U. Muscle and adipose tissue lipoprotein lipase was also decreased. Insulin stimulated lipid synthesis in freshly isolated hepatocytes from alfC. Hepatocytes from U and pfC were resistant to this effect of insulin. To ascertain if the insulin resistance in U was due to starvation (chow intake 50% of alfC) or to uremia itself, the U and pfC were intragastrically fed an isocaloric diet via a Holter pump the last week of the experimental period. Hepatocytes from orally fed U and pfC were also cultured for 24 h in serum-free medium. While freshly isolated and cultured U hepatocytes remained insulin resistant, those from pfC normalized, in vivo and in vitro, when they were provided with enough nutrients. Conclusions: (a) Hyperlipidemia in uremia is not due to increased synthesis, but to defect(s) in clearance. (b) Insulin does not stimulate lipid synthesis in uremia. This finding, along with our recent demonstration that insulin binding and internalization are not decreased in the uremic liver, suggests that a post-binding defect(s) in the liver plays an important role in the mechanism(s) of insulin resistance in uremia. (c) Cultured hepatocytes from uremic rats remain insulin resistant. This quality renders these cells useful in studying the postinsulin binding events responsible for the insulin-resistant state in the absence of complicating hormonal and substrate changes that occur in vivo. PMID:6350367

  19. TRAIL-deficiency accelerates vascular calcification in atherosclerosis via modulation of RANKL.

    PubMed

    Di Bartolo, Belinda A; Cartland, Siân P; Harith, Hanis H; Bobryshev, Yuri V; Schoppet, Michael; Kavurma, Mary M

    2013-01-01

    The osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) cytokine system, not only controls bone homeostasis, but has been implicated in regulating vascular calcification. TNF-related apoptosis-inducing ligand (TRAIL) is a second ligand for OPG, and although its effect in vascular calcification in vitro is controversial, its role in vivo is not yet established. This study aimed to investigate the role of TRAIL in vascular calcification in vitro using vascular smooth muscle cells (VSMCs) isolated from TRAIL(-/-) and wild-type mice, as well as in vivo, in advanced atherosclerotic lesions of TRAIL(-/-)ApoE(-/-) mice. The involvement of OPG and RANKL in this process was also examined. TRAIL dose-dependently inhibited calcium-induced calcification of human VSMCs, while TRAIL(-/-) VSMCs demonstrated accelerated calcification induced by multiple concentrations of calcium compared to wild-type cells. Consistent with this, RANKL mRNA was significantly elevated with 24 h calcium treatment, while OPG and TRAIL expression in human VSMCs was inhibited. Brachiocephalic arteries from TRAIL(-/-)ApoE(-/-) and ApoE(-/-) mice fed a high fat diet for 12 w demonstrated increased chondrocyte-like cells in atherosclerotic plaque, as well as increased aortic collagen II mRNA expression in TRAIL(-/-)ApoE(-/-) mice, with significant increases in calcification observed at 20 w. TRAIL(-/-)ApoE(-/-) aortas also had significantly elevated RANKL, BMP-2, IL-1β, and PPAR-γ expression at 12 w. Our data provides the first evidence that TRAIL deficiency results in accelerated cartilaginous metaplasia and calcification in atherosclerosis, and that TRAIL plays an important role in the regulation of RANKL and inflammatory markers mediating bone turn over in the vasculature. PMID:24040204

  20. Detection of coronary calcifications from computed tomography scans for automated risk assessment of coronary artery disease

    SciTech Connect

    Isgum, Ivana; Rutten, Annemarieke; Prokop, Mathias; Ginneken, Bram van

    2007-04-15

    A fully automated method for coronary calcification detection from non-contrast-enhanced, ECG-gated multi-slice computed tomography (CT) data is presented. Candidates for coronary calcifications are extracted by thresholding and component labeling. These candidates include coronary calcifications, calcifications in the aorta and in the heart, and other high-density structures such as noise and bone. A dedicated set of 64 features is calculated for each candidate object. They characterize the object's spatial position relative to the heart and the aorta, for which an automatic segmentation scheme was developed, its size and shape, and its appearance, which is described by a set of approximated Gaussian derivatives for which an efficient computational scheme is presented. Three classification strategies were designed. The first one tested direct classification without feature selection. The second approach also utilized direct classification, but with feature selection. Finally, the third scheme employed two-stage classification. In a computationally inexpensive first stage, the most easily recognizable false positives were discarded. The second stage discriminated between more difficult to separate coronary calcium and other candidates. Performance of linear, quadratic, nearest neighbor, and support vector machine classifiers was compared. The method was tested on 76 scans containing 275 calcifications in the coronary arteries and 335 calcifications in the heart and aorta. The best performance was obtained employing a two-stage classification system with a k-nearest neighbor (k-NN) classifier and a feature selection scheme. The method detected 73.8% of coronary calcifications at the expense of on average 0.1 false positives per scan. A calcium score was computed for each scan and subjects were assigned one of four risk categories based on this score. The method assigned the correct risk category to 93.4% of all scans.