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Sample records for calcific uremic arteriolopathy

  1. Calcific Uremic Arteriolopathy on Multimodal Combination Therapy: Still Unmet Goal

    PubMed Central

    Malabu, Usman Hammawa; Manickam, Valli; Kan, George; Doherty, Susan Lynette; Sangla, Kunwarjit Singh

    2012-01-01

    Background. Calcific uremic arteriolopathy (CUA) or calciphylaxis though generally noted for its high mortality, recent case reports have shown promising results using single agent therapies. However, it is not clear whether combination therapeutic agents will improve course of the disease. Objective. To determine clinical outcome in subjects with CUA on multimodal treatment. Methods. All patients with end-stage renal failure (ESRF) at The Townsville Hospital, Australia, from April 1, 2006, to March 31, 2011, with diagnosis of CUA were retrospectively studied. Results. Six subjects with CUA (4 females and 2 males) were on various combination therapeutic agents comprising sodium thiosulphate, hyperbaric oxygen, prednisolone, cinacalcet, and parathyroidectomy in addition to intensified haemodialysis, specialist local wound care, and antibiotics. The wounds failed to heal in 3 patients while 5 of the 6 subjects died; cause of death being sepsis in 3 and myocardial infarction in 2. Conclusion. Prognosis of CUA remains poor in spite of multimodal combination therapy. Further prospective studies on a larger population are needed to verify our findings. PMID:22518312

  2. 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

  3. Vascular ossification – calcification in metabolic syndrome, type 2 diabetes mellitus, chronic kidney disease, and calciphylaxis – calcific uremic arteriolopathy: the emerging role of sodium thiosulfate

    PubMed Central

    Hayden, Melvin R; Tyagi, Suresh C; Kolb, Lisa; Sowers, James R; Khanna, Ramesh

    2005-01-01

    Background Vascular calcification is associated with metabolic syndrome, diabetes, hypertension, atherosclerosis, chronic kidney disease, and end stage renal disease. Each of the above contributes to an accelerated and premature demise primarily due to cardiovascular disease. The above conditions are associated with multiple metabolic toxicities resulting in an increase in reactive oxygen species to the arterial vessel wall, which results in a response to injury wound healing (remodeling). The endothelium seems to be at the very center of these disease processes, acting as the first line of defense against these multiple metabolic toxicities and the first to encounter their damaging effects to the arterial vessel wall. Results The pathobiomolecular mechanisms of vascular calcification are presented in order to provide the clinician – researcher a database of knowledge to assist in the clinical management of these high-risk patients and examine newer therapies. Calciphylaxis is associated with medial arteriolar vascular calcification and results in ischemic subcutaneous necrosis with vulnerable skin ulcerations and high mortality. Recently, this clinical syndrome (once thought to be rare) is presenting with increasing frequency. Consequently, newer therapeutic modalities need to be explored. Intravenous sodium thiosulfate is currently used as an antidote for the treatment of cyanide poisioning and prevention of toxicities of cisplatin cancer therapies. It is used as a food and medicinal preservative and topically used as an antifungal medication. Conclusion A discussion of sodium thiosulfate's dual role as a potent antioxidant and chelator of calcium is presented in order to better understand its role as an emerging novel therapy for the clinical syndrome of calciphylaxis and its complications. PMID:15777477

  4. Medial artery calcification of uremic patients: a histological, histochemical and ultrastructural study.

    PubMed

    Ballanti, P; Silvestrini, G; Pisanò, S; De Paolis, P; Di Giulio, S; Mantella, D; Iappelli, M; Favarò, A; Bonucci, E; Coen, G

    2011-02-01

    Recent findings suggest that vascular calcification (VC) is an active process similar to bone mineralization, the vascular smooth muscle cells (VSMCs) undergoing phenotypic differentiation into osteoblastic cells and synthesizing calcification-regulating proteins found in bone. This study has investigated the VC process of uremic patients, with a morphologic approach. Epigastric artery samples from 49 uremic, non-diabetic patients were taken during kidney transplantation. Sections from paraffin-embedded samples were stained with hematoxylin/eosin and von Kossa. CD68 was immunohistochemically detected, and sections from frozen samples were stained with Oil Red O. Deeply calcified samples were stained with Picrosirius Red, PAS, and Alcian blue. Specimens from one patient with moderate and one with severe VC were examined under the electron microscope. None of the samples had atherosclerosis. Calcifications were found in the media of 38 patients. In 23, dot-like calcifications were irregularly scattered near the adventitia (light VC); in 11, granular calcifications formed concentric rings near the adventitia (moderate-advanced VC); in 4, zones of consolidated calcifications were found (severe VC). These zones were poor in collagen, glycoproteins and proteoglycans. In cases with moderate or severe VC, VSCMs showed necrotic changes. Matrix vesicles could be recognized in the extracellular spaces. In cases with severe VC, uncalcified or partially calcified membranous bodies were found, together with Liesegang rings. Patches of fibrin were also found. These findings point to a mainly degenerative mechanism of VC, which proceeds from the outer portion of the media. An active mechanism, however, cannot be excluded. A unifying hypothesis is suggested. PMID:21154233

  5. Fetuin-A decrease induced by a low-protein diet enhances vascular calcification in uremic rats with hyperphosphatemia.

    PubMed

    Yamada, Shunsuke; Tokumoto, Masanori; Tsuruya, Kazuhiko; Tatsumoto, Narihito; Noguchi, Hideko; Kitazono, Takanari; Ooboshi, Hiroaki

    2015-10-15

    Although dietary phosphate restriction is important for treating hyperphosphatemia in patients with chronic kidney disease, it remains unclear whether a low-protein diet (LPD), which contains low phosphate, has beneficial effects on malnutrition, inflammation, and vascular calcification. The effects of LPD on inflammation, malnutrition, and vascular calcification were therefore assessed in rats. Rats were fed a normal diet or diets containing 0.3% adenine and low/normal protein and low/high phosphate. After 6 wk, serum and urinary biochemical parameters, systemic inflammation, and vascular calcification were examined. The protective effect of fetuin-A and albumin were assessed in cultured vascular smooth muscle cells. Rats fed the diet containing 0.3% adenine developed severe azotemia. LPD in rats fed high phosphate induced malnutrition (decreases in body weight, food intake, serum albumin and fetuin-A levels, and urinary creatinine excretion) and systemic inflammation (increases in serum tumor necrosis factor-α and urinary oxidative stress marker). LPD decreased the serum fetuin-A level and fetuin-A synthesis in the liver and increased serum calcium-phosphate precipitates. A high-phosphate diet increased aortic calcium content, which was enhanced by LPD. Reduced fetal calf serum in the medium of cultured vascular smooth muscle cells enhanced phosphate-induced formation of calcium-phosphate precipitates in the media and calcification of vascular smooth muscle cells, both of which were prevented by fetuin-A administration. Our results suggest that phosphate restriction by restricting dietary protein promotes vascular calcification by lowering the systemic fetuin-A level and increasing serum calcium-phosphate precipitates and induces inflammation and malnutrition in uremic rats fed a high-phosphate diet. PMID:26180236

  6. Uremic pruritus.

    PubMed

    Mettang, Thomas; Kremer, Andreas E

    2015-04-01

    Uremic pruritus or chronic kidney disease-associated pruritus (CKD-aP) remains a frequent and compromising symptom in patients with advanced or end-stage renal disease, strongly reducing the patient's quality of life. More than 40% of patients undergoing hemodialysis suffer from chronic pruritus; half of them complain about generalized pruritus. The pathogenesis of CKD-aP remains obscure. Parathormone and histamine as well as calcium and magnesium salts have been suspected as pathogenetic factors. Newer hypotheses are focusing on opioid-receptor derangements and microinflammation as possible causes of CKD-aP, although until now this could not be proven. Pruritus may be extremely difficult to control, as therapeutic options are limited. The most consequential approaches to treatment are: topical treatment with or without anti-inflammatory compounds or systemic treatment with (a) gabapentin, (b) μ-opioid receptor antagonists and κ-agonists, (c) drugs with an anti-inflammatory action, (d) phototherapy, or (e) acupuncture. A stepwise approach is suggested starting with emollients and gabapentin or phototherapy as first-line treatments. In refractory cases, more experimental options as μ-opioid-receptor-antagonists (i.e., naltrexone) or κ-opioid-receptor agonist (nalfurafine) may be chosen. In desperate cases, patients suitable for transplantation might be set on 'high urgency'-status, as successful kidney transplantation will relieve patients from CKD-aP. PMID:24402092

  7. 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

  8. 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

  9. Soft tissue calcification in chronic dialysis patients.

    PubMed Central

    Kuzela, D. C.; Huffer, W. E.; Conger, J. D.; Winter, S. D.; Hammond, W. S.

    1977-01-01

    Autopsy protocols and microscopic slides of 56 dialyzed and 18 nondialyzed chronically uremic patients were reviewed to assess the presence, extent, and severity of extraosseous soft tissue calcification. Calcification was identified in 79% of the dialysis patients and 44% of the nondialysis patients (P iss less than .025). Soft tissue calcification most frequently involved the heart, lungs, stomach, and kidneys. Lesions were severe in 36% of the dialysis patients and, when strategically located within the myocardium, were life-threatening. The deaths of 6 dialysis patients were attributed to severe calcification of the cardiac conduction system and/or myocardium. The presence and severity of soft tissue calcification was not related to duration of dialysis, patients' age, degree of parathyroid gland hyperplasia, radiographic evidence of soft tissue calcification, serum calcium and phosphate levels, Ca X P products, or type or severity of metabolic bone disease. Images Figure 7 Figure 8 Figure 9 Figure 10 Figure 1 Figure 2 Figure 11 Figure 12 Figure 3 Figure 4 Figure 5 Figure 6 PMID:836675

  10. [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. PMID:25433773

  11. 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

  12. 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

  13. Normal and Pathologic Concentrations of Uremic Toxins

    PubMed Central

    Duranton, Flore; Cohen, Gerald; De Smet, Rita; Rodriguez, Mariano; Jankowski, Joachim; Vanholder, Raymond

    2012-01-01

    An updated review of the existing knowledge regarding uremic toxins facilitates the design of experimental studies. We performed a literature search and found 621 articles about uremic toxicity published after a 2003 review of this topic. Eighty-seven records provided serum or blood measurements of one or more solutes in patients with CKD. These records described 32 previously known uremic toxins and 56 newly reported solutes. The articles most frequently reported concentrations of β2-microglobulin, indoxyl sulfate, homocysteine, uric acid, and parathyroid hormone. We found most solutes (59%) in only one report. Compared with previous results, more recent articles reported higher uremic concentrations of many solutes, including carboxymethyllysine, cystatin C, and parathyroid hormone. However, five solutes had uremic concentrations less than 10% of the originally reported values. Furthermore, the uremic concentrations of four solutes did not exceed their respective normal concentrations, although they had been previously described as uremic retention solutes. In summary, this review extends the classification of uremic retention solutes and their normal and uremic concentrations, and it should aid the design of experiments to study the biologic effects of these solutes in CKD. PMID:22626821

  14. Uremic tumoral calcinosis in the cervical spine: case report.

    PubMed

    Fatehi, Mostafa; Ahuja, Christopher S; Wang, Shelly; Ginsberg, Howard J

    2016-07-01

    Tumoral calcinosis is an uncommon condition characterized by the calcification of periarticular soft tissue. In uremic patients the disease is secondary to metabolic disturbances in predisposed patients. The authors report the case of a 73-year-old woman who presented with a new painful cervical mass while undergoing continuous ambulatory peritoneal dialysis for long-standing end-stage renal disease (ESRD). A CT scan of the neck showed a lobulated, calcified mass in the left paraspinal soft tissue at C2-3. This mass affected the facet joint and also extended into the neural foramen but did not cause any neurological compromise. Due to the patient's significant medical comorbidities, resection was deferred and the patient was followed in the clinic. Subsequent repeat imaging has shown a significant decrease in the size of the mass. In the context of ESRD, a diagnosis of uremic tumoral calcinosis (UTC) was made. The authors conducted a search of the PubMed and EMBASE databases and identified 7 previously reported cases of UTC of the cervical spine. They present a summary of these cases and discuss the etiology, diagnosis, and management of the condition. Although the metabolic disturbances seen in patients undergoing dialysis can lead to tumoral calcinosis, most reported cases involve large joints such as the shoulder or the hip; however, the spine can also be affected and should be considered in the differential diagnosis of patients with uremia as it can mimic aggressive bone-forming neoplasms. PMID:26943247

  15. Uremic pleuritis in chronic hemodialysis patients.

    PubMed

    Rashid-Farokhi, Farin; Pourdowlat, Guitti; Nikoonia, Mohammad-Reza; Behzadnia, Neda; Kahkouee, Shahram; Nassiri, Amir-Ahmad; Masjedi, Mohammad-Reza

    2013-01-01

    Chronic hemodialysis (HD) patients are predisposed to several complications associated with pleural effusion. In addition, uremia can directly cause pleuritis. However, there are inadequate data about pathogenesis and natural course of uremic pleuritis. In this study, 76 chronic HD patients with pleural effusion admitted to the Respiratory Center of Masih Daneshvari Hospital, in Tehran, Iran between June 2005 and May 2011 were evaluated to figure out the etiology of their pleural disease. Among these patients, patients with uremic pleuritis were identified and studied. The rate of uremic pleuritis was 23.7%. Other frequent etiologies of pleural effusion were parapneumonic effusion (23.7%), cardiac failure (19.7%), tuberculosis (6.6%), volume overload, malignancy, and unknown. In patients with uremic pleuritis, dyspnea was the most common symptom, followed by cough, weight loss, anorexia, chest pain, and fever. Compared to patients with parapneumonic effusion, patients with uremic effusion had a significantly higher rate of dyspnea and lower rate of cough and fever. Pleural fluid analysis showed that these patients had a significantly lower pleural to serum lactic dehydrogenase ratio, total pleural leukocytes, and polymorphonuclear count compared to patients with parapneumonic effusion. Improvement was achieved in 94.1% of patients with uremic pleuritis by continuation of HD, chest tube insertion or pleural decortication; an outcome better than the previous reports. Despite the association with an exudative effusion, inflammatory pleural reactions in patients with uremic pleuritis may not be as severe as infection-induced effusions. Owing to the advancement in HD technology and other interventions, outcome of uremic pleuritis may be improved. PMID:22716271

  16. 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

  17. 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

  18. Warfarin and Vascular Calcification.

    PubMed

    Poterucha, Timothy J; Goldhaber, Samuel Z

    2016-06-01

    The vitamin K antagonist, warfarin, is the most commonly prescribed oral anticoagulant. Use of warfarin is associated with an increase in systemic calcification, including in the coronary and peripheral vasculature. This increase in vascular calcification is due to inhibition of the enzyme matrix gamma-carboxyglutamate Gla protein (MGP). MGP is a vitamin K-dependent protein that ordinarily prevents systemic calcification by scavenging calcium phosphate in the tissues. Warfarin-induced systemic calcification can result in adverse clinical effects. In this review article, we highlight some of the key translational and clinical studies that associate warfarin with vascular calcification. PMID:26714212

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

    PubMed

    Ito, Shunsuke; Yoshida, Masayuki

    2014-02-01

    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. PMID:24561478

  20. 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

  1. 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. PMID:26187577

  2. Mechanism of atherosclerotic calcification.

    PubMed

    Shioi, A; Mori, K; Jono, S; Wakikawa, T; Hiura, Y; Koyama, H; Okuno, Y; Nishizawa, Y; Morii, H

    2000-01-01

    Calcification is almost invariably associated with atherosclerotic plaque lesions. Recent data suggest that plaque calcification is an active, regulated process similar to osteogenesis. In order to clarify the mechanism of plaque calcification, we developed an in vitro model of vascular calcification by utilizing bovine vascular smooth muscle cells (BVSMCs). This model is useful in that diffuse and massive calcification can be induced within 2 weeks and thereby biochemical analyses of vascular calcification can be performed. We have analyzed several aspects of vascular calcification by using this model and demonstrated as follows: 1) in vitro calcification of BVSMCs is regulated by calciotropic hormones and BVSMCs are equipped with a unique autocrine and/or paracrine system regulating calcium metabolism. 2) Sodium-dependent phosphate cotransport plays a crucial role in BVSMC calcification as well as in mineralization of skeletal tissues. 3) BVSMCs acquire osteoblastic phenotype under certain conditions. Finally, we discuss the roles of macrophages in the development of atherosclerotic calcification. Interferon-gamma (IFN-gamma) induces gene expression of 25-hydrovitamin D-1 alpha-hydroxylase (1 alpha OHase) and its activity in macrophages. Since 1 alpha OHase can locally convert 25-hydroxyvitamin D into 1 alpha, 25-dihydroxyvitamin D (1,25(OH)2D), an active metabolite of vitamin D, it is suggested that local production of 1,25(OH)2D by macrophages may promote atherosclerotic calcification. Moreover, macrophages may be involved in the phenotypic changes of vascular smooth muscle cells (VSMCs) to acquire calcifying capacity. Therefore, the phenotypic changes of VSMCs in atherosclerotic plaque may contribute to the development of atherosclerotic calcification. PMID:10769407

  3. 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

  4. Genetics Home Reference: atypical hemolytic-uremic syndrome

    MedlinePlus

    ... uremic syndrome Additional NIH Resources (3 links) National Heart, Lung, and Blood Institute: Hemolytic Anemia National Heart, Lung, and Blood Institute: Thrombocytopenia National Institute of Diabetes ...

  5. 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

  6. [Disk calcifications in children].

    PubMed

    Schmit, P; Fauré, C; Denarnaud, L

    1985-05-01

    It is not unusual for intervertebral disk calcifications to be detected in pediatric practice, the 150 or so cases reported in the literature probably representing only a small proportion of lesions actually diagnosed. Case reports of 33 children with intervertebral disk calcifications were analyzed. In the majority of these patients (31 of 33) a diagnosis of "idiopathic" calcifications had been made, the cervical localization of the lesions being related to repeated ORL infections and/or trauma. A pre-existing pathologic factor was found in two cases (one child with juvenile rheumatoid arthritis treated by corticoids and one child with Williams and Van Beuren's syndrome). An uncomplicated course was noted in 31 cases, the symptomatology (pain, spinal stiffness and febricula) improving after several days. Complications developed in two cases: one child had very disabling dysphagia due to an anteriorly protruding cervical herniated disc and surgery was necessary; the other child developed cervicobrachial neuralgia due to herniated disc protrusion into the cervical spinal canal, but symptoms regressed within several days although calcifications persisted unaltered. These findings and the course of the rare complications documented in the literature suggest the need for the most conservative treatment possible in cases of disc calcifications in children. PMID:4032343

  7. Acute Prevertebral Calcific Tendinitis

    PubMed Central

    Tamm, Alexander; Jeffery, Caroline C; Ansari, Khalid; Naik, Sandeep

    2015-01-01

    We present a case of neck pain in a middle-aged woman, initially attributed to a retropharyngeal infection and treated with urgent intubation. With the help of computed tomography, the diagnosis was later revised to acute prevertebral calcific tendinitis, a self-limiting condition caused by abnormal calcium hydroxyapatite deposition in the longus colli muscles. It is critical to differentiate between these two disease entities due to dramatic differences in management. A discussion of acute prevertebral calcific tendinitis and its imaging findings is provided below. PMID:27252789

  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. PMID:27610067

  9. Calciphylaxis: Controversies in Pathogenesis, Diagnosis and Treatment.

    PubMed

    Jeong, Haneol S; Dominguez, Arturo R

    2016-02-01

    Calcific uremic arteriolopathy, otherwise known as calciphylaxis, is a rare disease characterized by skin ulceration and tissue necrosis, likely the result of vascular calcification with accompanying intimal hypertrophy and small vessel thrombosis. Although most often associated with end-stage renal disease, it has also been seen in a number of other disorders (collectively referred to as nonuremic calciphylaxis). The purpose of this review is to summarize and analyze the currently available literature regarding the pathophysiology, risk factors, clinical presentation, diagnostic features and treatment modalities for this exceptionally uncommon illness. A series of recommended treatments is proposed for optimal treatment of calciphylaxis lesions. PMID:26897281

  10. What is new in uremic toxicity?

    PubMed Central

    Van Laecke, Steven; Glorieux, Griet

    2008-01-01

    Uremic syndrome results from a malfunctioning of various organ systems due to the retention of compounds which, under normal conditions, would be excreted into the urine and/or metabolized by the kidneys. If these compounds are biologically active, they are called uremic toxins. One of the more important toxic effects of such compounds is cardio-vascular damage. A convenient classification based on the physico-chemical characteristics affecting the removal of such compounds by dialysis is: (1) small water-soluble compounds; (2) protein-bound compounds; (3) the larger “middle molecules”. Recent developments include the identification of several newly detected compounds linked to toxicity or the identification of as yet unidentified toxic effects of known compounds: the dinucleotide polyphosphates, structural variants of angiotensin II, interleukin-18, p-cresylsulfate and the guanidines. Toxic effects seem to be typically exerted by molecules which are “difficult to remove by dialysis”. Therefore, dialysis strategies have been adapted by applying membranes with larger pore size (high-flux membranes) and/or convection (on-line hemodiafiltration). The results of recent studies suggest that these strategies have better outcomes, thereby clinically corroborating the importance attributed in bench studies to these “difficult to remove” molecules. PMID:18324423

  11. Genetic Pathways of Vascular Calcification

    PubMed Central

    Bowman, Marion A. Hofmann; McNally, Elizabeth M.

    2012-01-01

    Vascular calcification is an independent risk factor for cardiovascular disease. Arterial calcification of the aorta, coronary, carotid and peripheral arteries becomes more prevalent with age. Genomewide association studies have identified regions of the genome linked to vascular calcification, and these same regions are linked to myocardial infarction risk. The 9p21 region linked to vascular disease and inflammation also associates with vascular calcification. In addition to these common variants, rare genetic defects can serve as primary triggers of accelerated and premature calcification. Infancy-associated calcific disorders are caused by loss of function mutations in ENPP1 an enzyme that produces extracellular pyrophosphate. Adult onset vascular calcification is linked to mutations NTE5, another enzyme that regulates extracellular phosphate metabolism. Common conditions that secondarily enhance vascular calcification include atherosclerosis, metabolic dysfunction, diabetes, and impaired renal clearance. Oxidative stress and vascular inflammation, along with biophysical properties, converge with these predisposing factors to promote soft tissue mineralization. Vascular calcification is accompanied by an osteogenic profile, and this osteogenic conversion is seen within the vascular smooth muscle itself as well as the matrix. Herein we will review the genetic causes of medial calcification in the smooth muscle layer, focusing on recent discoveries of gene mutations that regulate extracellular matrix phosphate production and the role of S100 proteins as promoters of vascular calcification. PMID:23040839

  12. 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

  13. 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.

  14. Chondrocalcinosis and other calcifications.

    PubMed

    Jensen, P S

    1988-11-01

    Less than 30 years ago, McCarty and others first described a syndrome which presented with gout-like attacks of arthritis but was due to CPPD crystals instead of urate crystals. They termed the condition "pseudogout." It was noted that this was often associated with chondrocalcinosis and it was commonly held that cartilage calcification had to be present if the diagnosis was to be suggested on the basis of the radiographic findings. Subsequently, a clinical and radiographic pattern has emerged in which the diagnosis of CPPD deposition disease can be suggested in the absence of chondrocalcinosis. This condition is termed pyrophosphate arthropathy and is differentiated from degenerative disease by the pattern and distribution of the joint disease. It is important to recognize CPPD deposition disease because of its association with other diseases, such as hemochromatosis and hyperparathyroidism. Although painful periarticular tendinous calcification (peritendinitis calcarea) resulting from the deposition of calcium HA crystals has long been recognized, it has only recently been discovered that intra-articular HA can be associated with an acute inflammatory synovitis. Additionally, patients are now being identified who have CPPD deposition at one anatomic location and HA deposition at another. Differentiation of these various types of crystal-induced arthropathies should lead to more effective therapy in the future. PMID:2845468

  15. Hemolytic Uremic Syndrome: Toxins, Vessels, and Inflammation

    PubMed Central

    Cheung, Victoria; Trachtman, Howard

    2014-01-01

    Hemolytic uremic syndrome (HUS) is characterized by thrombotic microangiopathy of the glomerular microcirculation and other vascular beds. Its defining clinical phenotype is acute kidney injury (AKI), microangiopathic anemia, and thrombocytopenia. There are many etiologies of HUS including infection by Shiga toxin-producing bacterial strains, medications, viral infections, malignancy, and mutations of genes coding for proteins involved in the alternative pathway of complement. In the aggregate, although HUS is a rare disease, it is one of the most common causes of AKI in previously healthy children and accounts for a sizable number of pediatric and adult patients who progress to end stage kidney disease. There has been great progress over the past 20 years in understanding the pathophysiology of HUS and its related disorders. There has been intense focus on vascular injury in HUS as the major mechanism of disease and target for effective therapies for this acute illness. In all forms of HUS, there is evidence of both systemic and intra-glomerular inflammation and perturbations in the immune system. Renewed investigation into these aspects of HUS may prove helpful in developing new interventions that can attenuate glomerular and tubular injury and improve clinical outcomes in patients with HUS. PMID:25593915

  16. Hemolytic uremic syndrome: toxins, vessels, and inflammation.

    PubMed

    Cheung, Victoria; Trachtman, Howard

    2014-01-01

    Hemolytic uremic syndrome (HUS) is characterized by thrombotic microangiopathy of the glomerular microcirculation and other vascular beds. Its defining clinical phenotype is acute kidney injury (AKI), microangiopathic anemia, and thrombocytopenia. There are many etiologies of HUS including infection by Shiga toxin-producing bacterial strains, medications, viral infections, malignancy, and mutations of genes coding for proteins involved in the alternative pathway of complement. In the aggregate, although HUS is a rare disease, it is one of the most common causes of AKI in previously healthy children and accounts for a sizable number of pediatric and adult patients who progress to end stage kidney disease. There has been great progress over the past 20 years in understanding the pathophysiology of HUS and its related disorders. There has been intense focus on vascular injury in HUS as the major mechanism of disease and target for effective therapies for this acute illness. In all forms of HUS, there is evidence of both systemic and intra-glomerular inflammation and perturbations in the immune system. Renewed investigation into these aspects of HUS may prove helpful in developing new interventions that can attenuate glomerular and tubular injury and improve clinical outcomes in patients with HUS. PMID:25593915

  17. 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

  18. Uremic toxins, oxidative stress, and renal fibrosis: an interwined complex.

    PubMed

    Chao, Chia-Ter; Chiang, Chih-Kang

    2015-03-01

    The prevalence of end-stage renal diseases is currently on the rise globally, and finding the way to curb this tide is urgently needed. Tubulointerstitial fibrosis is a common pathway for essentially all the nephropathy categories known to date, and the manifestations of renal fibrosis include excessive deposition of extracellular matrix with distortion of renal microstructures and functional deterioration. Uremic toxins have been gradually found to play an important role in the development of progressive renal fibrosis, with protein-bound indoxyl sulfate, p-cresol, and p-cresyl sulfate receiving the most attention. However, the contribution of oxidative stress among the pathogenesis of uremic toxins and renal fibrosis has not been evaluated much until recently. In this review, we will discuss about the nature and sources of oxidative stress in the kidney and how uremic toxins use oxidative stress to orchestrate the processes of renal fibrosis. PMID:25511523

  19. 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. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:245-251, 2016. PMID:26891122

  20. [Calcifications in the maxillofacial area].

    PubMed

    Németh Bertalan; Pataky, Levente; Arpád, Joób F; Koppany, Ferenc; Barabás, József

    2015-09-01

    Among patients presenting for dental treatment we could reveal various calcifications on panoramic x-rays or on cone beam computed tomography (CBCT) Calcifications is more likely to occur in vessels, ligaments, glandular tissues and is usually associated with chronic inflammation or scarring. The purpose of this article is to describe the imaging characteristics of commonly observed calcifications of the maxillofacial area with presenting our own cases such as: tonsilloliths, calcified lymph nodes, elongeated styloid process (calcified stylohyoid chain), phleboliths, carotid atheromas, calcified laryngeal cartilage. PMID:26731963

  1. Current treatment of atypical hemolytic uremic syndrome

    PubMed Central

    Kaplan, Bernard S.; Ruebner, Rebecca L.; Spinale, Joann M.; Copelovitch, Lawrence

    2014-01-01

    Summary Tremendous advances have been made in understanding the pathogenesis of atypical Hemolytic Uremic Syndrome (aHUS), an extremely rare disease. Insights into the molecular biology of aHUS resulted in rapid advances in treatment with eculizumab (Soliris®, Alexion Pharmaceuticals Inc.). Historically, aHUS was associated with very high rates of mortality and morbidity. Prior therapies included plasma therapy and/or liver transplantation. Although often life saving, these were imperfect and had many complications. We review the conditions included under the rubric of aHUS: S. pneumoniae HUS (SpHUS), inborn errors of metabolism, and disorders of complement regulation, emphasizing their differences and similarities. We focus on the clinical features, diagnosis, and pathogenesis, and treatment of aHUS that results from mutations in genes encoding alternative complement regulators, SpHUS and HUS associated with inborn errors of metabolism. Mutations in complement genes, or antibodies to their protein products, result in unregulated activity of the alternate complement pathway, endothelial injury, and thrombotic microangiopathy (TMA). Eculizumab is a humanized monoclonal antibody that inhibits the production of the terminal complement components C5a and the membrane attack complex (C5b-9) by binding to complement protein C5a. This blocks the proinflammatory and cytolytic effects of terminal complement activation. Eculizumab use has been reported in many case reports, and retrospective and prospective clinical trials in aHUS. There have been few serious side effects and no reports of tachphylaxis or drug resistance. The results are very encouraging and eculizumab is now recognized as the treatment of choice for aHUS. PMID:25343125

  2. Uremic parkinsonism with atypical phenotypes and radiologic features.

    PubMed

    Yoon, Jee-Eun; Kim, Ji Sun; Park, Jeong-Ho; Lee, Kyung-Bok; Roh, Hakjae; Park, Sung Tae; Cho, Jin Whan; Ahn, Moo-Young

    2016-04-01

    Uremic encephalopathy with bilateral basal ganglia lesions has been reported as an acute neurometabolic disease which shows reversible clinical course and brain imaging features. The exact nature and pathophysiology have not been well established. We encountered two patients who showed a relapsing and aggravating course and an atypical phenotype including parkinsonism with paroxysmal dystonic head tremor and acute onset monoparesis of the lower extremity. They also showed unusual radiological findings which revealed combined lesions in the basal ganglia and cortex, persistent hemorrhagic transformation, and focal ischemic lesion in the internal capsule. Herein, we present the unusual phenomenology with atypical radiologic findings and suggest the possible multifactorial pathogenesis of uremic encephalopathy. PMID:26631408

  3. 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.

  4. 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%).

  5. 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.

  6. 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

  7. 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

  8. Acute calcific tendinitis in children.

    PubMed

    Lassoued, S; Billey, T; Millet, J P; Henia, A O

    1999-01-01

    Acute calcific tendinitis is uncommon in children. Clinical manifestations are similar to those in adults. The abrupt onset, functional impairment, and frequent presence of fever suggest an infection. Radiographic findings establish the diagnosis, obviating the need for further investigations. PMID:10526384

  9. Hemolytic-Uremic Syndrome—An Outbreak in Sacramento, California

    PubMed Central

    Rogers, Martha F.; Schonberger, Lawrence B.; Budnick, Lawrence D.; Hurwitz, Eugene S.; Hatch, Milford H.; Gary, G. William; Bopp, Cheryl A.; Kirson, Ian; Karmali, Mohamed A.; Layne, Robert

    1986-01-01

    Between July and November 1982, 14 cases of the hemolytic-uremic syndrome occurred in the Sacramento, California, metropolitan area; 9 of the 14 patients lived within a 7.5-mile radius in northeast Sacramento, 10 were female, 12 were white non-Hispanic and 13 were children with a mean age of 3.6 years. Of the 14 patients, 13 were admitted to hospital; 7 required peritoneal dialysis. The 14th child, a 3-month-old white female infant, was found dead in her crib and had renal histopathologic findings consistent with the hemolytic-uremic syndrome. Of the 13 nonfatal cases, 12 patients had diarrhea before being admitted to hospital. A case-control study involving 11 cases and 22 controls did not show any significant differences in exposure to a variety of possible risk factors including restaurants, specific foods and water supply. Stool specimens were negative for enteric bacterial pathogens by culture and for viruses by tissue culture assay, suckling mouse inoculation and immune electron microscopy; no serologic evidence was found for infection due to enteroviruses, respiratory viruses or arenaviruses. Two of four children tested, however, showed serologic evidence of infection by Vero-cytotoxin-producing Escherichia coli. These 14 cases represent one of the largest reported outbreaks of the hemolytic-uremic syndrome in the United States. ImagesFigure 1. PMID:3953085

  10. Effect of Sertraline on Uremic Pruritus Improvement in ESRD Patients

    PubMed Central

    Shakiba, Mansor; Sanadgol, Hoshang; Azmoude, Hamid Reza; Mashhadi, Mohamad Ali; Sharifi, Hassan

    2012-01-01

    Background. Although uremic pruritus is a common and upsetting problem of chronic kidney disease, there is no approved treatment for it. This study was undertaken to find the efficiency of sertraline as a possible treatment for uremic pruritus. Methods. 19 ESRD patients under hemodialysis with severe chronic pruritus were randomly selected to participate in this before-after clinical trial. Before and after starting treatment with sertraline, a detailed pruritus history was obtained and pruritus graded by the 30-item inventory of pruritus that patients based on priorities grade allocated to 3 classes. Subjects were treated with sertraline 50 mg oral daily for four months, with monthly assessments of pruritus symptoms. Results. Before treatment with sertraline, the grade of pruritus in 9 (47.4%) patients was moderate and severe in 10 (52.6%) patients. After treatment, grade of pruritus in 11 (57.8%) patients was weak, 6 (31.5%) have moderate and only 2 (10.7%) patients have severe pruritus. Of 10 patients with severe pruritus, 5 (50%) patients experiencing weak pruritus, and 4 (40%) patients have moderate pruritus after treatment. Based on Wilcoxon signed-rank test, the difference between the grade of pruritus before and after treatment with sertraline was significant (P = 0.001). Conclusions. Although no definitive recommendation can be made regarding treatment of uremic pruritus, we found an increased antipruritic effect of sertraline in ESRD patients. PMID:22973512

  11. Pregnancy-Associated Atypical Hemolytic-Uremic Syndrome.

    PubMed

    Saad, Antonio F; Roman, Jorge; Wyble, Aaron; Pacheco, Luis D

    2016-03-01

    Introduction Early diagnosis of atypical uremic-hemolytic syndrome may be challenging during the puerperium period. Correct diagnosis and timely management are crucial to improve outcomes. Background Pregnancy-associated atypical hemolytic-uremic syndrome (p-aHUS) is a rare condition characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Triggered by pregnancy, genetically predisposed women develop the syndrome, leading to a disastrous hemolytic disease characterized by diffuse endothelial damage and platelet consumption. This disease is a life-threatening condition that requires prompt diagnosis and therapy. Case A 19-year-old G1P1 Caucasian female with suspicion of HELLP syndrome was treated at our facility for severe thrombocytopenia and acute kidney injury. A diagnosis of atypical uremic-hemolytic syndrome was later confirmed. The patient's condition improved with normalization of platelets and improvement in kidney function after 14 days of plasmapheresis. She was subsequently treated with eculizumab, a monoclonal antibody against C5. The patient tolerated well the therapy and is currently in remission. Conclusion Diagnosis of p-aHUS is challenging, as it can mimic various diseases found during pregnancy and the postpartum. Plasma exchange should be promptly initiated within 24 hours of diagnosis. Eculizumab has risen to become an important tool to improve long-term comorbidities and mortality in this group population. PMID:26989566

  12. 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. PMID:25906927

  13. 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

  14. Mineralization (calcification) of coronary arteries.

    PubMed

    Pawlikowski, M; Pfitzner, R; Wachowiak, J

    1994-01-01

    Mineralogical investigations of calcifications located in coronary vessels were performed on the material obtained from the endarterectomized arteries of 18 patients (15 M, 3 F, aged 36-65) during surgical revascularization procedures consisting in coronary artery bypass grafting. The samples were tested using scanning microscopy, X-ray diffractometry, infrared spectroscopy, atomic absorption spectroscopy, electron microprobe and neutron activation spectroscopy. The results of analyses were calculated with the use of computer programmes. Two types of mineralization were determined: 1. secret mineralization identified as higher than normal content of elements in biological tissues, not demonstrating any mineral grains, and 2. apparent mineralization, appearing micro- and macroscopically as grains composed mainly of hydroxyapatite containing admixture of carbonate groups, i.e. a mineral identical with apatite present in bones, or as calcification of other tissues (heart valves, lungs etc.). The authors suggest that the phenomenon of mineralization should be taken into consideration in the preventive treatment of coronary atheriosclerosis. PMID:7808039

  15. 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

  16. 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.

  17. Changes in gluconeogenesis and intracellular lipid accumulation characterize uremic human hepatocytes ex vivo.

    PubMed

    Li, Meng; Ellis, Ewa; Johansson, Helene; Nowak, Greg; Isaksson, Bengt; Gnocchi, Davide; Parini, Paolo; Axelsson, Jonas

    2016-06-01

    It is well known that reduced glomerular filtration rate (GFR) leads to an increased risk of dyslipidemia, insulin resistance, and cardiovascular mortality. The liver is a central organ for metabolism, but its function in the uremic setting is still poorly characterized. We used human primary hepatocytes isolated from livers of nine donors with normal renal function to investigate perturbations in key metabolic pathways following exposure to uremic (n = 8) or healthy (n = 8) sera, and to serum-free control medium. Both uremic and healthy elicited consistent responses from hepatocytes from multiple donors and compared with serum-free control. However, at physiological insulin concentrations, uremic cells accumulated 56% more intracellular lipids. Also, when comparing uremic with healthy medium after culture, it contained more very-low-density lipoprotein-triglyceride and glucose. These changes were accompanied by decreased phosphorylation of AktS473 mRNA levels of key regulators of gluconeogenesis in uremic sera-treated hepatocytes such as phosphoenolpyruvate carboxykinase 1 and glucose 6-phosphate were elevated. We also found increased expression of 11β-hydroxysteroid dehydrogenase mRNA in uremic cells, along with high phosphorylation of downstream p53 and phospholipase C-γ1Y783 Thus our ex vivo data suggest that the uremic hepatocytes rapidly develop a glycogenic and lipogenic condition accompanied by perturbations in a large number of signaling networks. PMID:27056725

  18. Uremic Toxins Enhance Statin-Induced Cytotoxicity in Differentiated Human Rhabdomyosarcoma Cells

    PubMed Central

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

    2014-01-01

    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. 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.

  20. Imaging Atherosclerotic Plaque Calcification: Translating Biology.

    PubMed

    Bailey, Grant; Meadows, Judith; Morrison, Alan R

    2016-08-01

    Calcification of atherosclerotic lesions was long thought to be an age - related, passive process, but increasingly data has revealed that atherosclerotic calcification is a more active process, involving complex signaling pathways and bone-like genetic programs. Initially, imaging of atherosclerotic calcification was limited to gross assessment of calcium burden, which is associated with total atherosclerotic burden and risk of cardiovascular mortality and of all cause mortality. More recently, sophisticated molecular imaging studies of the various processes involved in calcification have begun to elucidate information about plaque calcium composition and consequent vulnerability to rupture, leading to hard cardiovascular events like myocardial infarction. As such, there has been renewed interest in imaging calcification to advance risk assessment accuracy in an evolving era of precision medicine. Here we summarize recent advances in our understanding of the biologic process of atherosclerotic calcification as well as some of the molecular imaging tools used to assess it. PMID:27339750

  1. 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

  2. Pneumococcal hemolytic uremic syndrome and steroid resistant nephrotic syndrome.

    PubMed

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

    2016-08-01

    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. PMID:27617950

  4. 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

  5. Recurrent Hemolytic and Uremic Syndrome Induced by Escherichia Coli.

    PubMed

    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

    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

  6. 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

  7. 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

  8. Osmotic concentration of polypeptides from hemofiltrate of uremic patients.

    PubMed

    Ehrlich, K; Holland, F; Turnham, T; Klein, E

    1980-07-01

    Hemofiltrate from uremic patients was concentrated 15- to 40-fold by osmotic removal of water across a reverse osmosis membrane which retains salts and proteins. Salts and low molecular weight components were removed from the concentrate by partial dialysis using a highly impermeable cellulose membrane. Following this desalting step, 100- to 500-fold concentration could be achieved by evaporation at low pressure. The concentrate was fractionated on Sephadex G15 columns. Fractions were tested for their toxicity to human cells in culture. Fractions containing components with molecular weights greater than 700 daltons inhibited 3H-thymidine incorporation into the DNA of HeLa and skin fibroblast cells more than did low molecular weight peptides and an iso-osmolar control. Components eluting in the molecular weight range of angiotensin I and vitamin B-12 were most inhibitory. These studies show that hemofiltrate from uremic patients is a readily available source of toxic polypeptides. The osmotic concentration and gel chromatographic procedures described should make available large amounts of these molecules for further studies. PMID:7408253

  9. Isolated posterior cruciate ligament calcification.

    PubMed

    Koukoulias, Nikolaos E; Papastergiou, Stergios G

    2011-01-01

    The authors present a case of calcified posterior cruciate ligament (PCL). A 61-year-old female presented in our department reporting 12 months history of knee pain that was getting worse during the night. The patient was under medication for epileptic seizure, osteoporosis and hyperthyroidism. X-rays demonstrated calcification of the PCL. CT and MRI excluded any other intra-articular and extra-articular pathology. Arthroscopic debridement of the calcium deposits was performed and the symptoms resolved immediately, while the postoperative x-rays were normal. Histological examination confirmed the calcium nature of the lesion. Two years postoperatively the patient remains asymptomatic. PMID:22669889

  10. Isolated posterior cruciate ligament calcification

    PubMed Central

    Koukoulias, Nikolaos E; Papastergiou, Stergios G

    2011-01-01

    The authors present a case of calcified posterior cruciate ligament (PCL). A 61-year-old female presented in our department reporting 12 months history of knee pain that was getting worse during the night. The patient was under medication for epileptic seizure, osteoporosis and hyperthyroidism. X-rays demonstrated calcification of the PCL. CT and MRI excluded any other intra-articular and extra-articular pathology. Arthroscopic debridement of the calcium deposits was performed and the symptoms resolved immediately, while the postoperative x-rays were normal. Histological examination confirmed the calcium nature of the lesion. Two years postoperatively the patient remains asymptomatic. PMID:22669889

  11. 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

  12. Indolic Uremic Solutes Enhance Procoagulant Activity of Red Blood Cells through Phosphatidylserine Exposure and Microparticle Release

    PubMed Central

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

    2015-01-01

    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 Ca2+ ([Ca2+]) 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 [Ca2+]. 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

  13. Uremic Toxins – Novel Arrhythmogenic Factor in Chronic Kidney Disease – Related Atrial Fibrillation

    PubMed Central

    Huang, Shih-Yu; Chen, Yi-Ann; Chen, Shih-Ann; Chen, Yi-Jen; Lin, Yung-Kuo

    2016-01-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia. Chronic kidney disease (CKD) is associated with a high prevalence of AF, and uremic toxins are an important risk factor for cardiovascular diseases associated with CKD. Uremic toxins can produce pro-fibrotic, pro-hypertrophic, and pro-inflammatory effects on cardiac tissues and enhance oxidative stress or neurohormonal phenomena of cardiovascular injury, which are recognized as arrhythmogenic factors of AF. This article reviews the clinical, molecular, and electrophysiological data of uremic toxins in CKD considered to induce AF through multiple mechanisms on structural and electrical remodeling of the cardiovascular system. PMID:27274165

  14. 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: ...

  15. 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

  16. Corneal calcification after amniotic membrane transplantation

    PubMed Central

    Anderson, S B; de Souza, R Ferreira; Hofmann-Rummelt, C; Seitz, B

    2003-01-01

    Background/aims: Amniotic membrane transplantation (AMT) has become well established as a treatment for chronic epithelial defects, conjunctival reconstruction, and partial limbal cell deficiency. The aim of this study was to describe cases of corneal calcification following AMT and to search for risk factors that might predispose to this unusual finding. Methods: Details of 117 AMTs on 93 corneas of 91 patients with a follow up period of at least 1 month performed since 1999 were collected prospectively. In those with calcification clinical photographs were studied and the medical records retrospectively examined. Results: 15 calcifications in 117 AMTs (12.8%) were identified, occurring 3–17 (median 6.1) weeks after AMT, during a follow up period of 4–151 (median 25) weeks. Overall epithelial healing rate was 83%. Calcification covered a surface area between 0.7–40.5 mm2 maximum size with varied morphology. The primary diagnosis was diverse. Risk factors included the use of phosphate eye drops and pre-existing calcification in the operative or other eye. No patient with a “patch” AMT developed calcification. Conclusions: Corneal calcification occurs after some cases of AMT. A common risk factor was the postoperative use of phosphate containing eye drops. PMID:12714401

  17. 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

  18. Atypical hemolytic uremic syndrome: from diagnosis to treatment.

    PubMed

    Franchini, Massimo

    2015-10-01

    Thrombotic microangiopathy (TMA) is a relatively rare condition but a medical urgency requiring immediate intervention to avoid irreversible organ damage or death. Symptoms on presentation include microangiopathic haemolytic anaemia, thrombocytopenia and organ damage. The most frequent direct causes of TMA are thrombotic thrombocytopenic purpura (TTP) and haemolytic uremic syndrome (HUS). The most common form of HUS is related to Shiga toxin producing Escherichia coli (STEC) infection while approximately 10% of cases are due to dysregulation of the complement pathway (atypical haemolytic uremic syndrome, aHUS). Optimal treatment regimens differ depending on the underlying cause; however, differential diagnosis may be difficult. The most accurate method of diagnosis is based on exclusion and should consider, beyond the symptoms common to TMA, ADAMTS13 activity levels and STEC infection status. For the management of TTP, plasma exchange (PE) is the most important acute intervention and is associated with lower mortality and better outcomes than plasma infusion. In most patients with STEC-HUS, the course of disease is self-limiting although management of acute kidney injury is often required. Until recently, the management of aHUS consisted of early and intensive PE, although this was mostly ineffective in protecting from subsequent organ damage. Eculizumab, an inhibitor of the alternative complement pathway, produces a rapid and sustained inhibition of the TMA process, with significant improvements in long-term clinical outcomes. Due to the significant improvement achieved, eculizumab has subsequently been approved as first-line therapy when an unequivocal diagnosis of aHUS has been made. PMID:25803082

  19. Fluid Secretion in Isolated Proximal Straight Renal Tubules EFFECT OF HUMAN UREMIC SERUM

    PubMed Central

    Grantham, Jared J.; Irwin, Richard L.; Qualizza, Patti B.; Tucker, Donald R.; Whittier, Frederick C.

    1973-01-01

    We have examined the effect of normal and uremic human sera on the transtubular flow of fluid in isolated perfused segments of rabbit proximal convoluted and straight renal tubules. Proximal convoluted and straight tubules absorbed fluid from the lumen when the external bath was normal rabbit serum. Normal human sera in the bath depressed net fluid absorption in both tubular segments, but more importantly, uremic human serum caused proximal straight tubules to secrete fluid into the lumen. Fluid secretion was also demonstrated indirectly by observing in nonperfused proximal straight, but not proximal convoluted tubules, that the normally collapsed lumens opened widely in uremic serum. Nonperfused proximal straight tubules developed expanded lumens even after a 25-fold dilution of human uremic serum with normal rabbit serum, whereas lumen expansion occurred only in undiluted normal human serum, on the average. Serum from acutely uremic rabbits possessed secretory activity but normal rabbit serum did not. The secretory effect of uremic sera in proximal straight tubules was inhibited by cooling and ouabain and probenecid. The secretory activity of uremic sera was removed by dialysis, but not by freezing or boiling. Para-aminohippurate and benzoate caused fluid secretion in proximal straight tubules but urea, creatinine, guanidinosuccinate, and urate did not. On the basis of these results, we suggest that the secretory factor in serum may be a substance or group of substances possibly related to the hippurate class of organic molecules that are accumulated to relatively high concentrations in renal failure. The secretory material in the serum of uremic patients may significantly influence the transport of salt and water in relatively intact residual nephrons. Images PMID:4738063

  20. Radiographic spectrum of rectocolonic calcification from schistosomiasis.

    PubMed

    Fataar, S; Bassiony, H; Hamed, M S; Ghoneim, I; Satyanath, S; Hebbar, H G; Elgindy, N N; Hanna, R M

    1984-05-01

    Rectocolonic calcification was detected radiographically in 17 sites in 14 patients undergoing excretory urography for the assessment of urinary schistosomiasis. The right colon was involved in 11 sites, the rectum in four, and the left colon in two. The pattern of calcification varied according to the degree of bowel distension. A laminar pattern was common to all sites and occurred when the rectum or colon was distended with air, feces, or barium. A laminar or irregular amorphous density was found in the empty colon, whereas the calcified, empty rectum had a corrugated pattern. Rectocolonic calcification is probably the most common radiographic manifestation of schistosomal infestation of the gastrointestinal tract. PMID:6609576

  1. Costs and benefits of calcification in coccolithophorids

    NASA Astrophysics Data System (ADS)

    Anning, T.; Nimer, N.; Merrett, M. J.; Brownlee, C.

    1996-10-01

    Calcification in coccolithophorids requires major intracellular fluxes of inorganic carbon and calcium. This paper summarises the major cellular fluxes of substrates and products of calcification described in a simple four compartment model (cytosol, Golgi, coccolith vesicle and chloroplast). Measurements of the cytosolic and intra-coccolith vesicle pH and electrical potentials across the plasma membrane and coccolith vesicle membrane allow calculations of the proton electrochemical gradients across these membranes and estimates of the free carbonate and calcium concentrations in the coccolith vesicle. Calcification may provide a relatively low cost route for elevating the concentration of carbon dioxide in the chloroplast. This may have benefits in terms of the nutrient requirements for photosynthesis and growth. In particular, a close relationship appears to exist between calcification and the availability of phosphorus which may correlate with the occurrence of large scale blooms of Emiliania huxleyi in the North Atlantic.

  2. Alendronate conjugated nanoparticles for calcification targeting.

    PubMed

    Li, Nanying; Song, Juqing; Zhu, Guanglin; Shi, Xuetao; Wang, Yingjun

    2016-06-01

    In this article, the synthesis of a novel calcification-targeting nanoparticle (NP) is reported, which is realized through dopamine self-polymerization on the poly(lactic-co-glycolic acid) (PLGA) particle surface and subsequent alendronate conjugation. Cell viability and proliferation tests confirmed that such particle has low cytotoxicity and good biocompatibility. Experiments were designed to observe whether the synthesized NPs can pass through an obstructive hydrogel and directly bind themselves to hydroxyapatite (HA) NPs (mimicking calcified spots) and HA porous scaffolds (mimicking calcified tissues); and the result was positive, indicating ingenious targeting of NPs on calcifications. The calcification-targeting NPs are expected to be with promising applications on calcification-related disease diagnoses and therapies. PMID:26970822

  3. 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

  4. 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.

  5. 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

  6. 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

  7. The Role of Epigenetics in Arterial Calcification

    PubMed Central

    Wu, Shan-Shan; Lin, Xiao; Yuan, Ling-Qing; Liao, Er-Yuan

    2015-01-01

    Arterial calcification is highly prevalent and correlated with cardiovascular mortality, especially in patients with ESRD or diabetes. The pathogenesis of arterial calcification is multifactorial, with both genetic and environmental factors being implicated. In recent years, several mechanisms contributing to arterial calcification have been proposed. However, these can only explain a small proportion of the variability in arterial calcification, which is a major obstacle for its prevention and management. Epigenetics has emerged as one of the most promising areas that may fill in some of the gaps in our current knowledge of the interaction between the environmental insults with gene regulation in the development of diseases. Epigenetics refers to heritable and acquired changes in gene transcription that occur independently of the DNA sequence. Well-known components of epigenetic regulation include DNA methylation, histone modifications, and microRNAs. Epigenetics research in the regulation of arterial calcification has only recently been elucidated. In this review, we will summarise recent progress in epigenetic pathways involved in arterial calcification and discuss potential therapeutic interventions based on epigenetic mechanisms. PMID:26221588

  8. 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

  9. 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.

  10. Age-related penetrance of hereditary atypical hemolytic uremic syndrome.

    PubMed

    Sullivan, Maren; Rybicki, Lisa A; Winter, Aurelia; Hoffmann, Michael M; Reiermann, Stefanie; Linke, Hannah; Arbeiter, Klaus; Patzer, Ludwig; Budde, Klemens; Hoppe, Bernd; Zeier, Martin; Lhotta, Karl; Bock, Andreas; Wiech, Thorsten; Gaspert, Ariana; Fehr, Thomas; Woznowski, Magdalena; Berisha, Gani; Malinoc, Angelica; Goek, Oemer-Necmi; Eng, Charis; Neumann, Hartmut P H

    2011-11-01

    Hereditary atypical hemolytic uremic syndrome (aHUS), a dramatic disease frequently leading to dialysis, is associated with germline mutations of the CFH, CD46, or CFI genes. After identification of the mutation in an affected aHUS patient, single-site gene testing of relatives is the preventive care perspective. However, clinical data for family counselling are scarce. From the German-Speaking-Countries-aHUS-Registry, 33 index patients with mutations were approached for permission to offer relatives screening for their family-specific mutations and to obtain demographic and clinical data. Mutation screening was performed using direct sequencing. Age-adjusted penetrance of aHUS was calculated for each gene in index cases and in mutation-positive relatives. Sixty-one relatives comprising 41 parents and 20 other relatives were enrolled and mutations detected in 31/61. In total, 40 research participants had germline mutations in CFH, 19 in CD46 and in 6 CFI. Penetrance at age 40 was markedly reduced in mutation-positive relatives compared to index patients overall with 10% versus 67% (P < 0.001); 6% vs. 67% (P < 0.001) in CFH mutation carriers and 21% vs. 70% (P= 0.003) in CD46 mutation carriers. Age-adjusted penetrance for hereditary aHUS is important to understand the disease, and if replicated in the future, for genetic counselling. PMID:21906045

  11. Management of hemolytic-uremic syndrome in children

    PubMed Central

    Grisaru, Silviu

    2014-01-01

    Acute renal failure associated with a fulminant, life-threatening systemic disease is rare in previously healthy young children; however, when it occurs, the most common cause is hemolytic-uremic syndrome (HUS). In most cases (90%), this abrupt and devastating illness is a result of ingestion of food or drink contaminated with pathogens that produce very potent toxins. Currently, there are no proven treatment options that can directly inactivate the toxin or effectively interfere with the cascade of destructive events triggered by the toxin once it gains access to the bloodstream and binds its receptor. However, HUS is self-limited, and effective supportive management during the acute phase is proven to be a life saver for children affected by HUS. A minority of childhood HUS cases, approximately 5%, are caused by various genetic mutations causing uncontrolled activation of the complement system. These children, who used to have a poor prognosis leading to end-stage renal disease, now have access to exciting new treatment options that can preserve kidney function and avoid disease recurrences. This review provides a summary of the current knowledge on the epidemiology, pathophysiology, and clinical presentation of childhood HUS, focusing on a practical approach to best management measures. PMID:24966691

  12. Update on hemolytic uremic syndrome: Diagnostic and therapeutic recommendations

    PubMed Central

    Salvadori, Maurizio; Bertoni, Elisabetta

    2013-01-01

    Hemolytic uremic syndrome (HUS) is a rare disease. In this work the authors review the recent findings on HUS, considering the different etiologic and pathogenetic classifications. New findings in genetics and, in particular, mutations of genes that encode the complement-regulatory proteins have improved our understanding of atypical HUS. Similarly, the complement proteins are clearly involved in all types of thrombotic microangiopathy: typical HUS, atypical HUS and thrombotic thrombocytopenic purpura (TTP). Furthermore, several secondary HUS appear to be related to abnormalities in complement genes in predisposed patients. The authors highlight the therapeutic aspects of this rare disease, examining both “traditional therapy” (including plasma therapy, kidney and kidney-liver transplantation) and “new therapies”. The latter include anti-Shiga-toxin antibodies and anti-C5 monoclonal antibody “eculizumab”. Eculizumab has been recently launched for the treatment of the atypical HUS, but it appears to be effective in the treatment of typical HUS and in TTP. Future therapies are in phases I and II. They include anti-C5 antibodies, which are more purified, less immunogenic and absorbed orally and, anti-C3 antibodies, which are more powerful, but potentially less safe. Additionally, infusions of recombinant complement-regulatory proteins are a potential future therapy. PMID:24255888

  13. Erythropoietin treatment for non-uremic patients: a personal view.

    PubMed

    Biesma, D H

    1999-01-01

    The correction of anemia in patients with chronic renal failure (CRF) has become the most important application of recombinant human erythropoietin (rHuEpo). The merits of rHuEpo therapy in patients with CRF are overt. Firstly, patients with CRF have an absolute deficiency in endogenous erythropoietin production and a relatively low maintenance dose of rHuEpo (often less than 100 IU/kg body weight per week) is effective in avoiding regular transfusions in the majority of the patients with CRF. Secondly, rHuEpo is able to avoid long-term complications of frequent transfusions (hemochromatosis, transfusion-transmissible diseases). Thirdly, patients with uremia notice a considerable improvement in quality of life (QOL) after initiation of rHuEpo. These advantages justify administration of this costly drug in CRF patients. The use of rHuEpo outside the setting of uremia do, however, not cover the complete spectrum of beneficial effects as compared to its use in (pre)dialysis patients. The aim of this overview is to provide some annotations on recently approved (cisplatin-induced anemia, preoperative anemia, zidovudine-related anemia) and possibly future (several types of malignancy and inflammation) indications for rHuEpo in non-uremic patients, leaving out the correction of anemia due to relatively uncommon disorders in the Dutch population (such as sickle cell anemia and thalassemia). PMID:10048290

  14. Partial ADAMTS13 deficiency in atypical hemolytic uremic syndrome

    PubMed Central

    Feng, Shuju; Eyler, Stephen J.; Zhang, Yuzhou; Maga, Tara; Nester, Carla M.; Kroll, Michael H.

    2013-01-01

    Complement dysregulation leads to atypical hemolytic uremic syndrome (aHUS), while ADAMTS13 deficiency causes thrombotic thrombocytopenic purpura. We investigated whether genetic variations in the ADAMTS13 gene partially explain the reduced activity known to occur in some patients with aHUS. We measured complement activity and ADAMTS13 function, and completed mutation screening of multiple complement genes and ADAMTS13 in a large cohort of aHUS patients. In over 50% of patients we identified complement gene mutations. Surprisingly, 80% of patients also carried at least 1 nonsynonymous change in ADAMTS13, and in 38% of patients, multiple ADAMTS13 variations were found. Six of the 9 amino acid substitutions in ADAMTS13 were common single nucleotide polymorphisms; however, 3 variants—A747V, V832M, and R1096H— were rare, with minor allele frequencies of 0.0094%, 0.5%, and 0.32%, respectively. Reduced complement and ADAMTS13 activity (<60% of normal activity) were found in over 60% and 50% of patients, respectively. We concluded that partial ADAMTS13 deficiency is a common finding in aHUS patients and that genetic screening and functional tests of ADAMTS13 should be considered in these patients. PMID:23847193

  15. 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

  16. Pregnancy-Associated Atypical Hemolytic-Uremic Syndrome

    PubMed Central

    Saad, Antonio F.; Roman, Jorge; Wyble, Aaron; Pacheco, Luis D.

    2016-01-01

    Précis Introduction Early diagnosis of atypical uremic–hemolytic syndrome may be challenging during the puerperium period. Correct diagnosis and timely management are crucial to improve outcomes. Background Pregnancy-associated atypical hemolytic-uremic syndrome (p-aHUS) is a rare condition characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Triggered by pregnancy, genetically predisposed women develop the syndrome, leading to a disastrous hemolytic disease characterized by diffuse endothelial damage and platelet consumption. This disease is a life-threatening condition that requires prompt diagnosis and therapy. Case A 19-year-old G1P1 Caucasian female with suspicion of HELLP syndrome was treated at our facility for severe thrombocytopenia and acute kidney injury. A diagnosis of atypical uremic–hemolytic syndrome was later confirmed. The patient's condition improved with normalization of platelets and improvement in kidney function after 14 days of plasmapheresis. She was subsequently treated with eculizumab, a monoclonal antibody against C5. The patient tolerated well the therapy and is currently in remission. Conclusion Diagnosis of p-aHUS is challenging, as it can mimic various diseases found during pregnancy and the postpartum. Plasma exchange should be promptly initiated within 24 hours of diagnosis. Eculizumab has risen to become an important tool to improve long-term comorbidities and mortality in this group population. PMID:26989566

  17. 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

  18. Current understanding of coronary artery calcification

    PubMed Central

    Liu, Wei; Zhang, Yue; Yu, Cheuk-Man; Ji, Qing-Wei; Cai, Meng; Zhao, Ying-Xin; Zhou, Yu-Jie

    2015-01-01

    Coronary artery calcification (CAC) is highly prevalent in patients with coronary heart disease (CHD) and is associated with major adverse cardiovascular events. There are two recognized type of CAC—intimal and medial calcification, and each of them have specific risk factors. Several theories about the mechanism of vascular calcification have been put forward, and we currently believe that vascular calcification is an active, regulated process. CAC can usually be found in patients with severe CHD, and this asymptomatic phenomenon make early diagnosis of CAC important. Coronary computed tomographic angiography is the main noninvasive tool to detect calcified lesions. Measurement of coronary artery calcification by scoring is a reasonable metric for cardiovascular risk assessment in asymptomatic adults at intermediate risk. To date, effective medical treatment of CAC has not been identified. Several strategies of percutaneous coronary intervention have been applied to CHD patients with CAC, but with unsatisfactory results. Prognosis of CAC is still a major problem of CHD patients. Thus, more details about the mechanisms of CAC need to be elucidated in order to improve the understanding and treatment of CAC. PMID:26788045

  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. PMID:27252793

  20. Idiopathic Arterial Calcification of Infancy: Case Report

    PubMed Central

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

    2015-01-01

    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. PMID:27252793

  1. 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

  2. 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

  3. 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.

  4. 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

  5. Evaluation of Left Ventricular Function in Uremic Patients by Speckle Tracking Imaging.

    PubMed

    Ma, Wen; Liu, Nannan; Tong, Ming; Zhou, Hongli

    2015-11-01

    Here, we tested the suitability of two-dimensional speckle tracking imaging (STI) for assessment of left ventricular function in uremic patients. Forty-nine patients and 40 healthy individuals were enrolled for STI evaluation of common echocardiography measurements, as well as twist angles of apical and basal segment rotations. The E/A wave ratio, rotation angle, and twist angles of apical and basal segment rotations were significantly lower in uremic patients (p < 0.05 vs. healthy individuals), while left ventricular interior diameter and left ventricular wall thickness were significantly increased (p < 0.05 vs. healthy individuals). There was no significant difference in the left ventricular ejection fraction between patients and healthy individuals. Thus, two-dimensional STI is suitable for assessment of changes of left ventricular function in uremic patients. PMID:27352356

  6. 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

  7. Acute calcific periarthritis in a child.

    PubMed

    Mercer, N S; Newman, J H; Watt, I

    1984-10-01

    We wish to present an account of a child who developed acute calcification in his thenar eminence to highlight the difficulty in differentiation between calcific periarthritis, acute infection, on clinical grounds. Calcific periarthritis is due to hydroxyapatite crystal deposits in bursae, tendons and ligaments (Bonavita 1980) with characteristic radiographic appearances of opacities of variable density and shape around joints (Hitchcock 1959). The condition was first described in the shoulder, by Duplay in 1870 (Sandstrom 1938) and this remains the most commonly affected site. The hip, elbow, wrist, knee and ankle may also be involved but involvement of the hand is uncommon. Involvement in this site was first described in 1924 by Cohen (Carroll 1955). The previously reported age span ranged from thirteen years upwards, with an average of forty-five years, both sexes being equally affected (Currey 1970, Hitchcock 1959, Bonavita 1980). PMID:6512382

  8. Fibroblast involvement in soft connective tissue calcification

    PubMed Central

    Ronchetti, Ivonne; Boraldi, Federica; Annovi, Giulia; Cianciulli, Paolo; Quaglino, Daniela

    2013-01-01

    Soft connective tissue calcification is not a passive process, but the consequence of metabolic changes of local mesenchymal cells that, depending on both genetic and environmental factors, alter the balance between pro- and anti-calcifying pathways. While the role of smooth muscle cells and pericytes in ectopic calcifications has been widely investigated, the involvement of fibroblasts is still elusive. Fibroblasts isolated from the dermis of pseudoxanthoma elasticum (PXE) patients and of patients exhibiting PXE-like clinical and histopathological findings offer an attractive model to investigate the mechanisms leading to the precipitation of mineral deposits within elastic fibers and to explore the influence of the genetic background and of the extracellular environment on fibroblast-associated calcifications, thus improving the knowledge on the role of mesenchymal cells on pathologic mineralization. PMID:23467434

  9. 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

  10. [Cardiac valves calcifications in dialysis patients].

    PubMed

    Klarić, Dragan; Klarić, Vera; Kristić, Ivica

    2011-10-01

    Chronic kidney disease (CKD) patients, especially those with end-stage renal disease (ESRD), are at much higher risk of cardiovascular disease (CVD) than the general population. High serum phosphorus (P) level play important role in pathogenesis of cardiovascular calcifications and is a frequent and important cardiovascular risk factor in patients with CKD. We aimed to investigate the association of serum levels of C-reactive protein (CRP), parathyroid hormon (PTH). calcium phosphorus product (CaxP) with cardiac valves calcifications (VC) in patients on hemodialysis (HD). We investigated for VC using colour Doppler echocardiography. VC were considered present if mitral annular calcifications and/or aortic annular calcifications were visualized. We divided patients in two groups. VC negative group (VC-) were patients with absence of VC. Patients with presence of VC were VC positive (VC+). CRP mean levels in two samples were higher in VC+ group than in VC- group (17.0 vs 3.4mg/L) and (17.1 vs 4.0 mg/L) p<0.0001. CaxP mean level in both samples was higher in VC+ group than in VC- group, 4.8 vs 4.2 (p=0.0219) and 5.0 vs 4.3 (p=0.0078). We also made analysis of absolute highest levels of three samples of CRP (CRPmax) between groups. CRPmax was higher in VC+ group than in VC- group, 19.5 vs 9.7 mg/L, (p=0.0045). We made analysis of absolute higher levels of two samples of Ca x P (CaxPmax) between groups. CaxPmax was higher in VC+ group than in VC- group, 5.2 vs 4.4 (p=0.0014). We found cardiac valve calcifications in 40 percent of patients on hemodialysis. We found that patients with correlation between PTH level, CRP level, CaxP product and cardiac valve calcifications have higher serum levels of PTH and CRP. We also found that CaxP product is higher in patients with cardiac valve calcifications. We didn't find correlation between age, dialysis duration, BMI and cardiac valve calcifications. These findings support careful monitoring of calcium metabolisum in end stage

  11. Where do we stand on vascular calcification?

    PubMed

    Boström, Kristina I

    2016-09-01

    Vascular disease, such as atherosclerosis and diabetic vasculopathy, is frequently complicated by vascular calcification. Previously believed to be an end-stage process of unregulated mineral precipitation, it is now well established to be a multi-faceted disease influenced by the characteristics of its vascular location, the origins of calcifying cells and numerous regulatory pathways. It reflects the fundamental plasticity of the vasculature that is gradually being revealed by progress in vascular and stem cell biology. This review provides a brief overview of where we stand in our understanding of vascular calcification, facing the challenge of translating this knowledge into viable preventive and therapeutic strategies. PMID:27260939

  12. Leptin as a uremic toxin interferes with neutrophil chemotaxis.

    PubMed

    Ottonello, Luciano; Gnerre, Paola; Bertolotto, Maria; Mancini, Marina; Dapino, Patrizia; Russo, Rodolfo; Garibotto, Giacomo; Barreca, Tommaso; Dallegri, Franco

    2004-09-01

    Leptin is a pleiotropic molecule involved in energy homeostasis, hematopoiesis, inflammation, and immunity. Hypoleptinemia characterizing starvation has been strictly related to increased susceptibility to infection secondary to malnutrition. Nevertheless, ESRD is characterized by high susceptibility to bacterial infection despite hyperleptinemia. Defects in neutrophils play a crucial role in the infectious morbidity, and several uremic toxins that are capable of depressing neutrophil functions have been identified. Only a few and contrasting reports about leptin and neutrophils are available. This study provides evidence that leptin inhibits neutrophil migration in response to classical chemoattractants. Moreover, serum from patients with ESRD inhibits migration of normal neutrophils in response to N-formyl-methionyl-leucyl-phenylalanine with a strict correlation between serum leptin levels and serum ability to suppress neutrophil locomotion. Finally, the serum inhibitory activity can be effectively prevented by immune depletion of leptin. The results also show, however, that leptin by itself is endowed with chemotactic activity toward neutrophils. The two activities-inhibition of the cell response to chemokines and stimulation of neutrophil migration-could be detected at similar concentrations. On the contrary, neutrophils exposed to leptin did not display detectable [Ca(2+)](i) mobilization, oxidant production, or beta(2)-integrin upregulation. The results demonstrate that leptin is a pure chemoattractant devoid of secretagogue properties that are capable of inhibiting neutrophil chemotaxis to classical neutrophilic chemoattractants. Taking into account the crucial role of neutrophils in host defense, the leptin-mediated ability of ERSD serum to inhibit neutrophil chemotaxis appears as a potential mechanism that contributes to the establishment of infections in ERSD. PMID:15339985

  13. A Longitudinal Study of Uremic Pruritus in Hemodialysis Patients

    PubMed Central

    Mathur, Vandana S.; Lindberg, Jill; Germain, Michael; Block, Geoffrey; Tumlin, James; Smith, Mark; Grewal, Mandeep

    2010-01-01

    Background and objectives: Although uremic pruritus (UP) is a highly prevalent complication of chronic kidney disease, it remains poorly characterized. There have been no longitudinal studies of natural history, and no health-related quality of life (HR-QOL) instruments have been developed for UP. The objectives of this study were to describe the natural history of UP, to compare rating scales of itching intensity, and to assess usefulness and validity of HR-QOL instruments for UP. Design, setting, participants, & measurements: The intensity, severity, and effects of pathologic itching on HR-QOL were assessed prospectively in 103 patients with UP on chronic hemodialysis. Outcome measures were obtained at scheduled intervals over 3.5 months. Results: Itching daily or nearly daily was reported by 84% of patients and had been ongoing for >1 year in 59%. In 83%, pruritus involved large, nondermatomal areas with striking bilateral symmetry. Two thirds of the patients were using medications such as antihistamines, steroids, and various emollients without satisfactory relief of itching. Statistically significant associations were found among itching intensity, severity, and HR-QOL measures in domains such as mood, social relations, and sleep. Among patients with moderate-to-severe UP, changes in itching intensity of 20% or greater were associated with significant reductions in HR-QOL measures. Conclusions: This first longitudinal study of UP describes key features of UP and its effect on HR-QOL. The assessment instruments we have developed are easily used, are responsive to changes in UP intensity, and should facilitate clinical evaluation and research to meet the needs of afflicted patients. PMID:20558560

  14. Atypical Hemolytic-Uremic Syndrome: A Clinical Review.

    PubMed

    Nayer, Ali; Asif, Arif

    2016-01-01

    Atypical hemolytic-uremic syndrome (HUS) is a rare life-threatening disorder characterized by microangiopathic hemolytic anemia, thrombocytopenia, and ischemic injury to organs, especially the kidneys. Microvascular injury and thrombosis are the dominant histologic findings. Complement activation through the alternative pathway plays a critical role in the pathogenesis of atypical HUS. Genetic abnormalities involving complement regulatory proteins and complement components form the molecular basis for complement activation. Endothelial cell dysfunction, probably because of the effects of complement activation, is an intermediate stage in the pathophysiologic cascade. Atypical HUS has a grave prognosis. Although mortality approaches 25% during the acute phase, end-stage renal disease develops in nearly half of patients within a year. Atypical HUS has a high recurrence rate after renal transplantation, and recurrent disease often leads to graft loss. Plasma therapy in the form of plasma exchange or infusion has remained the standard treatment for atypical HUS. However, many patients do not respond to plasma therapy and some require prolonged treatment. Approved by the Food and Drug Administration in the treatment of atypical HUS, eculizumab is a humanized monoclonal antibody that blocks cleavage of complement C5 into biologically active mediators of inflammation and cytolysis. Although case reports have shown the efficacy of eculizumab, randomized clinical trials are lacking. Therapeutic strategies targeting endothelial cells have demonstrated promising results in experimental settings. Therefore, inhibitors of angiotensin-converting enzyme, HMG-CoA reductase, and xanthine oxidase as well as antioxidants, such as ascorbic acid, may have salutary effects in patients with atypical HUS. PMID:24681522

  15. Modified Ham test for atypical hemolytic uremic syndrome

    PubMed Central

    Gavriilaki, Eleni; Yuan, Xuan; Ye, Zhaohui; Ambinder, Alexander J.; Shanbhag, Satish P.; Streiff, Michael B.; Kickler, Thomas S.; Moliterno, Alison R.; Sperati, C. John

    2015-01-01

    Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA) characterized by excessive activation of the alternative pathway of complement (APC). Atypical HUS is frequently a diagnosis of exclusion. Differentiating aHUS from other TMAs, especially thrombotic thrombocytopenic purpura (TTP), is difficult due to overlapping clinical manifestations. We sought to develop a novel assay to distinguish aHUS from other TMAs based on the hypothesis that paroxysmal nocturnal hemoglobinuria cells are more sensitive to APC-activated serum due to deficiency of glycosylphosphatidylinositol- anchored complement regulatory proteins (GPI-AP). Here, we demonstrate that phosphatidylinositol-specific phospholipase C–treated EA.hy926 cells and PIGA-mutant TF-1 cells are more susceptible to serum from aHUS patients than parental EA.hy926 and TF-1 cells. We next studied 31 samples from 25 patients with TMAs, including 9 with aHUS and 12 with TTP. Increased C5b-9 deposition was evident by confocal microscopy and flow cytometry on GPI-AP–deficient cells incubated with aHUS serum compared with heat-inactivated control, TTP, and normal serum. Differences in cell viability were observed in biochemically GPI-AP–deficient cells and were further increased in PIGA-deficient cells. Serum from patients with aHUS resulted in a significant increase of nonviable PIGA-deficient TF-1 cells compared with serum from healthy controls (P < .001) and other TMAs (P < .001). The cell viability assay showed high reproducibility, sensitivity, and specificity in detecting aHUS. In conclusion, we developed a simple, rapid, and serum-based assay that helps to differentiate aHUS from other TMAs. PMID:25862562

  16. Fatal uremic leontiasis ossea in long-lasting uncontrolled hyperparathyroidism: a case report

    PubMed Central

    Dimkovic, N; Piscevic, V; Jankovic, A; Djuric, P

    2015-01-01

    Background Leontiasis ossea is a rare medical condition, with characteristic overgrowth of the facial and cranial bones. Reports about this uremic complication are less frequently reported, probably due to better dialysis and better medical control of secondary hyperparathyroidism. Description of case We report the case of a 36-year-old female patient who had been treated with chronic hemodialysis and who developed secondary hyperparathyroidism. Conclusion In noncompliant patients with uncontrolled secondary hyperparathyroidism uremic leontiasis may develop in which case the treatment is rarely successful or may even be contraindicated due to other comorbid conditions. Hippokratia 2015; 19 (3): 266-267.

  17. 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

  18. 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

  19. Calcific tendinitis of the gluteus maximus tendon (Gluteus maximus tendinitis)

    SciTech Connect

    Wepfer, J.F.; Reed, J.G.; Cullen, G.M.; McDevitt, W.P.

    1983-02-01

    Seven cases of calcific tendinitis of the gluteus maximus tendon are presented. Awareness of the precise anatomic location of the calcific deposit is essential for the accurate diagnosis of this uncommon site of tendinitis. Clinically, the presenting complaint is that of pain. In some instances, however, the patients are asymptomatic and the calcification is an incidental finding.

  20. 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

  1. 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

  2. Role of Vitamin K in Calcification

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Observational studies are promising in terms of associations between vitamin K (either diet or biochemical measures) and bone health and other conditions of normal calcification in the elderly. The level of evidence from randomized, double-blind, placebo-controlled trials with phylloquinone is very ...

  3. Reversible vascular calcifications associated with hypervitaminosis D.

    PubMed

    Cirillo, Massimo; Bilancio, Giancarlo; Cirillo, Chiara

    2016-02-01

    A 64-year-old man was hospitalized in 2002 with symptoms of stupor, weakness, and renal colic. The clinical examination indicated borderline hypertension, small masses in the glutei, and polyuria. Laboratory tests evidenced high serum concentrations of creatinine, calcium, and phosphate. Imaging assessments disclosed widespread vascular calcifications, gluteal calcifications, and pelvic ectasia. Subsequent lab tests indicated suppressed serum parathyroid hormone, extremely high serum 25-hydroxy vitamin D, and normal serum 1,25-dihydroxy vitamin D. Treatment was started with intravenous infusion of saline and furosemide due to the evidence of hypercalcemia. Prednisone and omeprazole were added given the evidence of hypervitaminosis D. The treatment improved serum calcium, kidney function, and consciousness. The medical history disclosed recent treatment with exceptionally high doses of slow-release intra-muscular cholecalciferol and the recent excretion of urinary stones. The patient was discharged when it was possible to stop the intravenous treatment. The post-discharge treatment included oral hydration, furosemide, prednisone and omeprazole for approximately 6 months up to complete resolution of the hypercalcemia. The patient came back 12 years later because of microhematuria. Lab tests were normal for calcium/phosphorus homeostasis and kidney function. Imaging tests indicated only minor vascular calcifications. This is the first evidence of reversible vascular calcifications secondary to hypervitaminosis D. PMID:26318020

  4. [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

  5. Skin Autofluorescence Is Associated with Endothelial Dysfunction in Uremic Subjects on Hemodialysis

    PubMed Central

    Wang, Chun-Cheng; Wang, Yao-Chang; Wang, Guei-Jane; Shen, Ming-Yi; Chang, Yen-Lin; Liou, Show-Yih; Chen, Hung-Chih; Chang, Chiz-Tzung

    2016-01-01

    Background Elevated levels of advanced glycation end products (AGEs) within tissues may contribute to endothelial dysfunction, an early indicator of atherosclerosis. We aimed to investigate whether levels of skin AGEs could be a useful marker to predict endothelial dysfunction in uremic subjects on hemodialysis. Methods and Results One hundred and nineteen uremic patients on hemodialysis and 57 control subjects with moderate-to-high cardiovascular risk factors and without chronic kidney disease (CKD) were enrolled. We used ultrasound to measure flow-mediated vasodilation (FMD). An AGE reader measured skin autoflurorescence (AF). We then compared differences in FMD and skin AF values between the two groups. The uremic subjects had significantly higher levels of skin AF (3.47±0.76 AU vs. 2.21±0.45 arbitrary units; P<0.01) and significantly lower levels of FMD (4.79%±1.88% vs. 7.19%±2.17%; P<0.01) than the non-CKD subjects. After adjusting for all potential covariates, we found that skin AF level independently predicted FMD in both the hemodialysis and the non-CKD groups. In the hemodialysis group, skin AF ≥ 3.05 arbitrary units predicted abnormal FMD at a sensitivity of 87.9% and a specificity of 78.6% (P<0.01). Conclusions Skin AF could be a useful marker to predict endothelial dysfunction in uremic subjects on hemodialysis. PMID:26809145

  6. 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. PMID:25537175

  7. Immunohistochemical screening for neurochemical markers in uremic patients on maintenance hemodialysis.

    PubMed

    Johansson, O; Hilliges, M; Han, S W; Ståhle-Bäckdahl, M; Hägermark, O

    1988-01-01

    The epidermis and dermis of 12 uremic patients on maintenance hemodialysis were investigated utilizing the indirect immunofluorescence technique as a tool to study the distribution of neurochemical markers, such as neuropeptides. No differences between controls and the patients were revealed. PMID:3078417

  8. Uremic Pericarditis: A Report of 30 Cases and Review of the Literature

    PubMed Central

    Sadjadi, Seyed-Ali; Mashhadian, Ardavan

    2015-01-01

    Case series Patient: Male, 71 • Male, 69 • Female, 49 Final Diagnosis: Uremic pericarditis Symptoms: — Medication: — Clinical Procedure: Hemodialysis Specialty: Nephrology Objective: Rare disease Background: Uremic pericarditis, common at one time among dialysis patients, has become a rare entity in recent years. Due to its low incidence, its recognition has gained importance among internists, cardiologists, and nephrologists. It can be seen in predialysis patients and in dialysis patients who are on hemodialysis or peritoneal dialysis. Case Report: We report 3 cases of uremic pericarditis and their presenting manifestations and review 30 cases we have treated. Among these patients, the traditional findings among patients with acute pericarditis such as chest pain, fever, electrocardiographic changes, and leukocytosis are uncommon. Pericardial friction rub has a relatively high incidence but its differentiation by an untrained ear, especially by a non-cardiologist, could be a major problem. Not infrequently, it is complicated by pre-tamponade or tamponade, requiring pericardiocentesis or pericardial surgery. Conclusions: Uremic pericarditis is a treatable, but not always a preventable, condition. Timely recognition of its presence and its efficient management are essential elements of successful treatment. PMID:25796283

  9. Depressed expression of Klotho and FGF receptor 1 in hyperplastic parathyroid glands from uremic patients.

    PubMed

    Komaba, Hirotaka; Goto, Shunsuke; Fujii, Hideki; Hamada, Yasuhiro; Kobayashi, Akira; Shibuya, Koji; Tominaga, Yoshihiro; Otsuki, Naoki; Nibu, Ken-Ichi; Nakagawa, Kimie; Tsugawa, Naoko; Okano, Toshio; Kitazawa, Riko; Fukagawa, Masafumi; Kita, Tomoyuki

    2010-02-01

    Fibroblast growth factor 23 (FGF23) exerts its effect by binding to its cognate FGF receptor 1 (FGFR1) in the presence of its co-receptor Klotho. Parathyroid glands express both FGFR1 and Klotho, and FGF23 decreases parathyroid hormone gene expression and hormone secretion directly. In uremic patients with secondary hyperparathyroidism (SHPT), however, parathyroid hormone secretion remains elevated despite extremely high FGF23 levels. To determine the mechanism of this resistance, we measured the expression of Klotho, FGFR1, and the proliferative marker Ki67 in 7 normal and 80 hyperplastic parathyroid glands from uremic patients by immunohistochemistry. All uremic patients had severe SHPT along with markedly high FGF23 levels. Quantitative real-time reverse transcription PCR showed that the mRNA levels for Klotho and FGFR1correlated significantly with their semi-quantitative immunohistochemical intensity. Compared with normal tissue, the immunohistochemical expression of Klotho and FGFR1 decreased, but Ki67 expression increased significantly in hyperplastic parathyroid glands, particularly in glands with nodular hyperplasia. These results suggest that the depressed expression of the Klotho-FGFR1 complex in hyperplastic glands underlies the pathogenesis of SHPT and its resistance to extremely high FGF23 levels in uremic patients. PMID:19890272

  10. 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

  11. 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

  12. Oxidative consumption of nitric oxide: a potential mediator of uremic vascular disease.

    PubMed

    Thuraisingham, R C; Yaqoob, M M

    2003-05-01

    Recent data has drawn our attention to the relationship between altered biomechanical properties of the vasculature and left ventricular hypertrophy (LVH) in uremia. We have been able to show that uremia causes functional changes in the conduit vessels of rats, predating structural changes and independent of blood pressure. As nitric oxide (NO) is a potent modulator of the cardiovascular system, we studied the NO pathway in uremia. The existing data are somewhat confusing, with some suggesting up-regulation of the NO system, and others the opposite. When examined critically, however, a pattern emerges, with studies examining NO release showing increased production, whereas those examining NO bioactivity show it to be attenuated. We hypothesized that there is increased NO release, but excess consumption in uremia. Our own data on NO metabolites (NOx) in the serum of healthy young male hemodialysis patients indicate higher concentrations both pre- and post-dialysis compared to controls. As the endothelium is a potential source of NO, we cultured endothelial cells in uremic plasma. These studies demonstrated increased basal NO release from cells cultured under uremic conditions compared to controls. Furthermore, alterations in arginine metabolism appear to play a role, as there is evidence for reduced arginase activity in these cells, thereby increasing arginine availability for the NO pathway. Given the in vivo data and clinical characteristics of the uremic syndrome suggesting reduced NO bioactivity, we examined the possibility that the excess NO generated is being consumed and rendered bio-inactive. Aortae from uremic and control rats were stained for the presence of nitrotyrosine. All uremic aortae stained positively, but nitrotyrosine was not present in any control aortae. PMID:12694303

  13. Calcification by reef-building sclerobionts.

    PubMed

    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

  14. 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

  15. COX2 Inhibition Reduces Aortic Valve Calcification In Vivo

    PubMed Central

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

    2016-01-01

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

  16. 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

  17. 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

  18. 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

  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. 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

  1. Calcification of intraocular implant lens surfaces.

    PubMed

    Wu, Wenju; Guan, Xiangying; Tang, Ruikang; Hook, Daniel; Yan, Wenyan; Grobe, George; Nancollas, George H

    2004-02-17

    Calcification of octacalcium phosphate [Ca8H2(PO4)6 x 5H2O, OCP] on differently packaged "Ultem" and "Surefold" intraocular implant lens surfaces has been studied in vitro in solutions supersaturated with respect to OCP at pH = 7.10 and 37 degrees C. No mineral deposition was observed on the lenses packaged in Ultem vials even after treatment with behenic acid, one of the fatty acids identified on explanted lenses. Following treatment with behenic acid, nucleation of OCP occurred on the lenses from Surefold vials, which incorporate silicone gaskets; induction periods preceding calcification were about 6 h. No mineralization was found on the lenses in vials with other gasket materials, including polytetrafluoroethylene, fluorocarbon elastomer, and polypropylene. The results of this study indicate that both silicone and fatty acids such as behenic acid play important roles in inducing the in vivo calcification of OCP on IOL lenses; all of the lens treatment steps were necessary for nucleation induction. PMID:15803719

  2. Aortic Stenosis and Vascular Calcifications in Alkaptonuria

    PubMed Central

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

    2011-01-01

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

  3. Klotho and phosphate are modulators of pathologic uremic cardiac remodeling.

    PubMed

    Hu, Ming Chang; Shi, Mingjun; Cho, Han Jun; Adams-Huet, Beverley; Paek, Jean; Hill, Kathy; Shelton, John; Amaral, Ansel P; Faul, Christian; Taniguchi, Masatomo; Wolf, Myles; Brand, Markus; Takahashi, Masaya; Kuro-O, Makoto; Hill, Joseph A; Moe, Orson W

    2015-06-01

    Cardiac dysfunction in CKD is characterized by aberrant cardiac remodeling with hypertrophy and fibrosis. CKD is a state of severe systemic Klotho deficiency, and restoration of Klotho attenuates vascular calcification associated with CKD. We examined the role of Klotho in cardiac remodeling in models of Klotho deficiency-genetic Klotho hypomorphism, high dietary phosphate intake, aging, and CKD. Klotho-deficient mice exhibited cardiac dysfunction and hypertrophy before 12 weeks of age followed by fibrosis. In wild-type mice, the induction of CKD led to severe cardiovascular changes not observed in control mice. Notably, non-CKD mice fed a high-phosphate diet had lower Klotho levels and greatly accelerated cardiac remodeling associated with normal aging compared with those on a normal diet. Chronic elevation of circulating Klotho because of global overexpression alleviated the cardiac remodeling induced by either high-phosphate diet or CKD. Regardless of the cause of Klotho deficiency, the extent of cardiac hypertrophy and fibrosis correlated tightly with plasma phosphate concentration and inversely with plasma Klotho concentration, even when adjusted for all other covariables. High-fibroblast growth factor-23 concentration positively correlated with cardiac remodeling in a Klotho-deficient state but not a Klotho-replete state. In vitro, Klotho inhibited TGF-β1-, angiotensin II-, or high phosphate-induced fibrosis and abolished TGF-β1- or angiotensin II-induced hypertrophy of cardiomyocytes. In conclusion, Klotho deficiency is a novel intermediate mediator of pathologic cardiac remodeling, and fibroblast growth factor-23 may contribute to cardiac remodeling in concert with Klotho deficiency in CKD, phosphotoxicity, and aging. PMID:25326585

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

    PubMed

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

    2016-05-01

    Patients with generalized arterial calcification of infancy (GACI) develop vascular calcifications early in life. About half of them die within the first 6 months despite optimal medical care. A subset of those who survive eventually develop hypophosphatemic rickets. Since hypophosphatemia and hyperphosphaturia have been previously associated with increased survival in GACI patients, physicians often avoid phosphate repletion as treatment for rickets. As a consequence, GACI patients develop severe rachitic complications such as short stature and skeletal deformities. It appears that the recognition of hypophosphatemia later in life in some GACI patients is a consequence of having survived the first few months of life, and not the cause of their survival per se. Here, we report the long-term follow-up of a GACI patient who was phosphate-repleted for his rickets for more than 7 years without worsening of vascular calcification. © 2016 Wiley Periodicals, Inc. PMID:26857895

  5. 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

  6. The role of apoptosis in the initiation of vascular calcification.

    PubMed

    Proudfoot, D; Skepper, J N; Hegyi, L; Farzaneh-Far, A; Shanahan, C M; Weissberg, P L

    2001-01-01

    The initiation sites for calcification in cartilage and bone are cellular products called matrix vesicles. Similar structures have been found in calcified arteries and recent studies suggest that these may be derived from apoptotic cells. It is well established that there is a link between cell death and calcification but the mechanism involved is not known. Since apoptotic cell death is known to occur in the vasculature, we set out to investigate the role of apoptosis in the initiation of vascular calcification. We used a human vascular calcification model in which postconfluent vascular smooth muscle cell (VSMC) cultures form nodules spontaneously and calcify after approximately 28 days. Our studies revealed that apoptosis occurred prior to the onset of calcification and that VSMC "blebs" or apoptotic bodies (ABs) could concentrate calcium in a crystallised form. These observations suggest that apoptosis is involved in the development of VSMC calcification and that VSMC-derived ABs have similarities with matrix vesicles. PMID:11374032

  7. Revisiting cardiovascular calcification: A multifaceted disease requiring a multidisciplinary approach.

    PubMed

    Hutcheson, Joshua D; Goettsch, Claudia; Rogers, Maximillian A; Aikawa, Elena

    2015-10-01

    The presence of cardiovascular calcification significantly predicts patients' morbidity and mortality. Calcific mineral deposition within the soft cardiovascular tissues disrupts the normal biomechanical function of these tissues, leading to complications such as heart failure, myocardial infarction, and stroke. The realization that calcification results from active cellular processes offers hope that therapeutic intervention may prevent or reverse the disease. To this point, however, no clinically viable therapies have emerged. This may be due to the lack of certainty that remains in the mechanisms by which mineral is deposited in cardiovascular tissues. Gaining new insight into this process requires a multidisciplinary approach. The pathological changes in cell phenotype that lead to the physicochemical deposition of mineral and the resultant effects on tissue biomechanics must all be considered when designing strategies to treat cardiovascular calcification. In this review, we overview the current cardiovascular calcification paradigm and discuss emerging techniques that are providing new insight into the mechanisms of ectopic calcification. PMID:26358815

  8. Corals concentrate dissolved inorganic carbon to facilitate calcification.

    PubMed

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

    2014-01-01

    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. PMID:25531981

  9. 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

  10. 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

  11. Apoptosis and calcification of vascular endothelial cell under hyperhomocysteinemia.

    PubMed

    Fang, Kuaifa; Chen, Zhujun; Liu, Meng; Peng, Jian; Wu, Pingsheng

    2015-01-01

    In recent years, it is found that increase in Hcy level in blood can directly or indirectly cause vascular endothelial cell injury and induce vascular calcification. However, the mechanism of vascular endothelial cell injury and vascular calcification has not been studied thoroughly. This paper carried out experiment for research aiming at discussing the effect and action mechanism of Hhcy on endothelial cells and vascular calcification. Firstly, human umbilical vein endothelial cells (HUVECs) were cultured and then intervened by Hcy of different concentrations (0, 0.01, 0.1, 1.0, 3.0, 5.0 mmol/L) and at different action time (3, 6, 12, 24 h). Then apoptosis rate and reactive oxygen were detected by flow cytometry. At the same time, the model for the culture of rat vascular calcification was set up and induced into Hhcy so as to detect the total plasma Hcy level and judge vascular calcification degree. The results showed that with the increase in Hcy concentration and extension of action period, the apoptosis rate and generation of reactive oxygen of HUVECs all significantly increased, and the differences were all statistically significant (P < 0.01). In animal calcification model, mass of black particle deposition was seen after Von Kossa staining of rat vessels in calcification group. Compared with the control group, the vascular calcium content, alkaline phosphatase activity and osteocalcin content in calcification group all increased (P < 0.01). The content of plasma lipid conjugated olefine from highest to lowest wasas follows: calcification plus homoetheionin, homoetheionin, and calcification group. There was no significant difference between the calcification group and control group. All these findings suggested that Hcy could induce the apoptosis of endothelial cells and its effect degree depended on its concentration and action period; Hhcy could promote the calcification of blood vessels, and its mechanism might relate with the strengthening of

  12. Vascular calcification is dependent on plasma levels of pyrophosphate.

    PubMed

    Lomashvili, Koba A; Narisawa, Sonoko; Millán, Jose L; O'Neill, W Charles

    2014-06-01

    Plasma levels of pyrophosphate, an endogenous inhibitor of vascular calcification, are reduced in end-stage renal disease and correlate inversely with arterial calcification. However, it is not known whether the low plasma levels are directly pathogenic or are merely a marker of reduced tissue levels. This was tested in an animal model in which aortas were transplanted between normal mice and Enpp1(-/-) mice lacking ectonucleotide pyrophosphatase phosphodiesterase, the enzyme that synthesizes extracellular pyrophosphate. Enpp1(-/-) mice had very low plasma pyrophosphate and developed aortic calcification by 2 months that was greatly accelerated with a high-phosphate diet. Aortas of Enpp1(-/-) mice showed no further calcification after transplantation into wild-type mice fed a high-phosphate diet. Aorta allografts of wild-type mice calcified in Enpp1(-/-) mice but less so than the adjacent recipient Enpp1(-/-) aorta. Donor and recipient aortic calcium contents did not differ in transplants between wild-type and Enpp1(-/-) mice, demonstrating that transplantation per se did not affect calcification. Histology revealed medial calcification with no signs of rejection. Thus, normal levels of extracellular pyrophosphate are sufficient to prevent vascular calcification, and systemic Enpp1 deficiency is sufficient to produce vascular calcification despite normal vascular extracellular pyrophosphate production. This establishes an important role for circulating extracellular pyrophosphate in preventing vascular calcification. PMID:24717293

  13. 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

  14. Role of Glutaraldehyde in Calcification of Porcine Aortic Valve Fibroblasts

    PubMed Central

    Kim, Kookmin M.; Herrera, Guillermo A.; Battarbee, Harold D.

    1999-01-01

    Glutaraldehyde-treated porcine aortic valve xenografts frequently fail due to calcification. Calcification in the prostheses begins intracellularly. In a previous study, various types of cell injury to canine valvular fibroblasts, including glutaraldehyde treatment, led to calcification. An influx of extracellular Ca2+ into the phosphate-rich cytosol was theorized to be the mechanism of calcification. To test the Ca2+ influx theory, cytosolic Ca2+ and Pi concentrations were assessed in glutaraldehyde-treated porcine aortic valve fibroblasts, and their relationship to a subsequent calcification was studied. Glutaraldehyde caused an immediate and sustained massive cytosolic Ca2+ increase that was dose dependent and a several-fold increase in Pi. Calcification of cells followed within a week. The earliest calcification was observed in blebs formed on glutaraldehyde-treated cells. Live control cells or cells fixed with glutaraldehyde in Ca2+-free solution did not calcify under the same conditions. Concomitant increases in Ca2+ and Pi in glutaraldehyde-treated cells appear to underlie the mechanism of calcification, and the presence of extracellular Ca2+ during glutaraldehyde fixation promotes calcification. PMID:10079262

  15. Uremic pruritus: skin divalent ion content and response to ultraviolet phototherapy.

    PubMed

    Blachley, J D; Blankenship, D M; Menter, A; Parker, T F; Knochel, J P

    1985-05-01

    Pruritus is a frequent and troublesome consequence of end-stage renal disease. We have surveyed 155 chronic dialysis patients and found pruritus to be a significant problem in approximately 70%. Seventeen patients reporting severe pruritus were treated thrice weekly with total body exposure to either UVA or UVB light. UVB light resulted in resolution of pruritus in all cases. UVA light was without significant effect. Skin biopsies obtained before and after UV phototherapy revealed elevated contents of calcium, magnesium, and phosphorus in all pruritic patients. The resolution of pruritus following UVB treatment was associated with a reduction of skin phosphorus to values comparable with nonpruritic uremics or healthy volunteers. Uremic pruritus may be due to increased skin divalent ion content resulting in microprecipitation of calcium or magnesium phosphate. PMID:4003393

  16. 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...

  17. 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.

  18. Release of uremic retention solutes from protein binding by hypertonic predilution hemodiafiltration.

    PubMed

    Böhringer, Falko; Jankowski, Vera; Gajjala, Prathibha R; Zidek, Walter; Jankowski, Joachim

    2015-01-01

    Protein-bound uremic retention solutes accumulate in patients suffering from chronic kidney disease, and the removal of these solutes by hemodialysis is hampered. Therefore, we developed a dialysis technique where the protein-bound uremic retention solutes are removed more efficiently under high ionic strength. Protein-bound uremic solutes such as phenylacetic acid, indoxyl sulfate, and p-cresyl sulfate were combined with plasma in the presence of increased ionic strength. The protein integrity of proteins and enzymatic activities were analyzed. In vitro dialysis of albumin solution was performed to investigate the clearance of the bound uremic retention solutes. In vitro hemodiafiltrations of human blood were performed to investigate the influence of increased ionic strength on blood cell survival. The protein-bound fraction of phenylacetic acid, indoxyl sulfate, and p-cresyl sulfate was significantly decreased from 59.4% ± 3.4%, 95.7% ± 0.6%, 96.9% ± 1.5% to 36.4% ± 3.7%, 87.8% ± 0.6%, and 90.8% ± 1.3%, respectively. The percentage of phenylacetic acid, indoxyl sulfate, and p-cresyl sulfate released from protein was 23.0% ± 5.7%, 7.9% ± 1.1%, and 6.1% ± 0.2%, respectively. The clearance during in vitro dialysis was increased by 13.1% ± 3.6%, 68.8% ± 15.1%, and 53.6% ± 10.2%, respectively. There was no difference in NaCl concentrations at the outlet of the dialyzer using isotonic and hypertonic solutions. In conclusion, this study forms the basis for establishing a novel therapeutic approach to remove protein-bound retention solutes. PMID:25419832

  19. 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

  20. The uremic toxicity of indoxyl sulfate and p-cresyl sulfate: a systematic review.

    PubMed

    Vanholder, Raymond; Schepers, Eva; Pletinck, Anneleen; Nagler, Evi V; Glorieux, Griet

    2014-09-01

    A growing number of publications supports a biologic effect of the protein-bound uremic retention solutes indoxyl sulfate and p-cresyl sulfate. However, the use of unrealistically high free concentrations of these compounds and/or inappropriately low albumin concentrations may blur the interpretation of these results. Here, we performed a systematic review, selecting only studies in which, depending on the albumin concentration, real or extrapolated free concentrations of indoxyl sulfate and p-cresyl sulfate remained in the uremic range. The 27 studies retrieved comprised in vitro and animal studies. A quality score was developed, giving 1 point for each of the following criteria: six or more experiments, confirmation by more than one experimental approach, neutralization of the biologic effect by counteractive reagents or antibodies, use of a real-life model, and use of dose-response analyses in vitro and/or animal studies. The overall average score was 3 of 5 points, with five studies scoring 5 of 5 points and six studies scoring 4 of 5 points, highlighting the superior quality of a substantial number of the retrieved studies. In the 11 highest scoring studies, most functional deteriorations were related to uremic cardiovascular disease and kidney damage. We conclude that our systematic approach allowed the retrieval of methodologically correct studies unbiased by erroneous conditions related to albumin binding. Our data seem to confirm the toxicity of indoxyl sulfate and p-cresyl sulfate and support their roles in vascular and renal disease progression. PMID:24812165

  1. The Extent of Blockade Following Axillary and Infraclavicular Approaches of Brachial Plexus Block in Uremic Patients

    PubMed Central

    Sariguney, Damla; Mahli, Ahmet; Coskun, Demet

    2012-01-01

    Introduction This study was aimed to compare the axillary approach performed through multiple injection method and vertical infraclavicular approach performed through single injection method in terms of the sensory and motor block onset, quality, and extent of blocks of brachial plexus in uremic patients who underwent arteriovenous fistula surgery. Methods Forty patients scheduled for creation of arteriovenous fistula with axillary brachial plexus block (group AX, n = 20) or infraclavicular brachial plexus block (IC group, n = 20) were examined. The median, radial, ulnar, and musculocutaneous nerves were selectively localized by nerve stimulation. The volume of the local anesthetics was calculated based on the height of each patient, and the volume determined was prepared by mixing 2% lidocaine and 0.5% bupivacaine in equal proportions. Sensory and motor block were assessed at 3, 6, 9, 12, 15, 18, and 30th min and their durations were measured. Results While the adequate sensory and motor block rate with axillary approach was 100% in musculocutaneous, median, radial, ulnar and medial antebrachial cutaneous nerves, it was 65% in axillary nerve, 80% in intercostobrachial nerve and 95% in medial brachial cutaneous nerve. This rate was found to be 100% for all the nerves with infraclavicular approach. Conclusion For arteriovenous fistula surgeries in uremic patients, both axillary approach performed through multiple injection method and vertical infraclavicular approach performed through single injection method can be used successfully; however, for the short performance of the procedure, infraclavicular block may be preferred. Keywords Brachial plexus block; Axillary; Infraclavicular; Uremic patients PMID:22383924

  2. Determination of the binding properties of the uremic toxin phenylacetic acid to human serum albumin.

    PubMed

    Saldanha, Juliana F; Yi, Dan; Stockler-Pinto, Milena B; Soula, Hédi A; Chambert, Stéphane; Fouque, Denis; Mafra, Denise; Soulage, Christophe O

    2016-06-01

    Uremic toxins are compounds normally excreted in urine that accumulate in patients with chronic kidney disease as a result of decreased renal clearance. Phenylacetic acid (PAA) has been identified as a new protein bound uremic toxin. The purpose of this study was to investigate in vitro the interaction between PAA and human serum albumin (HSA) at physiological and pathological concentrations. We used ultrafiltration to show that there is a single high-affinity binding site for PAA on HSA, with a binding constant on the order of 3.4 × 10(4) M(-1) and a maximal stoichiometry of 1.61 mol per mole. The PAA, at the concentration reported in end-stage renal patients, was 26% bound to albumin. Fluorescent probe competition experiments demonstrated that PAA did not bind to Sudlow's site I (in subdomain IIA) and only weakly bind to Sudlow's site II (in subdomain IIIA). The PAA showed no competition with other protein-bound uremic toxins such as p-cresyl-sulfate or indoxyl sulfate for binding to serum albumin. Our results provide evidence that human serum albumin can act as carrier protein for phenylacetic acid. PMID:26945842

  3. H-reflex latency in uremic neuropathy: correlation with NCV and clinical findings.

    PubMed

    Halar, E M; Brozovich, F V; Milutinovic, J; Inouye, V L; Becker, V M

    1979-04-01

    Sixty-two uremic patients on dialysis of varying durations were tested bilaterally for posterior tibial nerve H-reflex latency, at 3-month intervals. Bilateral nerve conduction velocities (NCVs) of the peroneal, tibial, and sural nerves were concomitantly determined in all subjects. Proprioception sense, vibration perception threshold at the great toes, and deep tendon reflexes at the knee and ankle were determined in all subjects on the day of electrodiagnostic testing. The sensitivity of the H-reflex latency in detection of the onset and severity of uremic neuropathy was assessed. H-reflex latency changes were compared to NCV and clinical test results. The following was found: (1) of the parameters studied, the H-reflex latency appeared to be the most sensitive indicator of early uremic polyneuropathies, (2) electrodiagnostic tests were more sensitive to the onset of neuropathies than the clinical testing parameters studied, and (3) the sural sensory nerve appeared to be involved earlier than peroneal and tibial motor nerves in neuropathies studied. PMID:224838

  4. Uremic Toxins and Lipases in Haemodialysis: A Process of Repeated Metabolic Starvation

    PubMed Central

    Stegmayr, Bernd

    2014-01-01

    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. PMID:24784324

  5. Atypical Hemolytic-Uremic Syndrome: A Case Report and Literature Review

    PubMed Central

    Rafiq, Arsalan; Tariq, Hassan; Abbas, Naeem; Shenoy, Roopalekha

    2015-01-01

    Patient: Female, 59 Final Diagnosis: Atyipcal hemolytic uremic syndrome Symptoms: Delirium • headache Medication: — Clinical Procedure: — Specialty: Hematology Objective: Rare disease Background: Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by hemolysis, thrombocytopenia, and renal dysfunction. It is a disease related to genetic mutations in the alternative complement pathway and has a distinct pathophysiology but is difficult to differentiate from other thrombotic microangiopathies. Case Report: We present a case of a 59-year-old female patient who presented with accelerated hypertension, acute renal failure, hemolysis, and encephalopathy. She was managed with antihypertensive medication, but her encephalopathy did not improve. Evaluation resulted in our impression of the disease being atypical hemolytic-uremic syndrome. The patient continued to be managed with good blood pressure control and later was started on eculizumab, but evaluation of response to therapy was hindered by the patient’s non-compliance with therapy and follow-up appointments. Conclusions: We have a very limited understanding of the genetics and epidemiology of atypical HUS, and the overlapping clinical features sometimes delay diagnosis and initiation of appropriate treatment of this rare disease. PMID:25708146

  6. The time of onset of abnormal calcification in spondylometaepiphyseal dysplasia, short limb-abnormal calcification type.

    PubMed

    Tüysüz, Beyhan; Gazioğlu, Nurperi; Ungür, Savaş; Aji, Dolly Yafet; Türkmen, Seval

    2009-01-01

    A 1-month-old boy with shortness of extremities on prenatal US was referred to our department with a provisional diagnosis of achondroplasia. His height was normal but he had short extremities and platyspondyly, premature carpal epiphyses on both hands, and short tubular bones with irregular metaphyses on radiographs. Re-evaluation of the patient at the age of 1 year revealed very short height and premature calcification of the costal cartilages and epiphyses. Spondylometaepiphyseal dysplasia (SMED), short limb-abnormal calcification type was diagnosed. This condition is a very rare autosomal recessively inherited disorder, and most of the patients die in early childhood due to neurological involvement. At the age of 2 years and 5 months, a CT scan showed narrowing of the cervical spinal canal. One month later he died suddenly because of spinal cord injury. In conclusion early diagnosis is very important because the recurrence risk is high and patients may die due to early neurological complications. The time of onset of abnormal calcifications, a diagnostic finding of the disease, is at the age of around 1 year in most patients. When abnormal calcifications are not yet present, but radiological changes associated with SMED are present, this rare disease must be considered. PMID:19002453

  7. Intracranial Carotid Calcification on Cranial Computed Tomography

    PubMed Central

    Subedi, Deepak; Zishan, Umme Sara; Chappell, Francesca; Gregoriades, Maria-Lena; Sudlow, Cathie; Sellar, Robin

    2015-01-01

    Background and Purpose— Intracranial internal carotid artery calcification is associated with cerebrovascular risk factors and stroke, but few quantification methods are available. We tested the reliability of visual scoring, semiautomated Agatston score, and calcium volume measurement in patients with recent stroke. Methods— We used scans from a prospective hospital stroke registry and included patients with anterior circulation ischemic stroke or transient ischemic stroke whose noncontrast cranial computed tomographic scans were available electronically. Two raters measured semiautomatic quantitative Agatston score, and calcium volume, and performed qualitative visual scoring using the original 4-point Woodcock score and a modified Woodcock score, where each image on which the internal carotid arteries appeared was scored and the slice scores summed. Results— Intra- and interobserver coefficient of variations were 8.8% and 16.5% for Agatston, 8.8% and 15.5% for calcium volume, and 5.7% and 5.4% for the modified Woodcock visual score, respectively. The modified Woodcock visual score correlated strongly with both Agatston and calcium volume quantitative measures (both R2=0.84; P<0.0001); calcium volume increased by 0.47-mm/point increase in modified Woodcock visual score. Intracranial internal carotid artery calcification increased with age by all measures (eg, visual score, Spearman ρ=0.4; P=0.005). Conclusions— Visual scores correlate highly with quantitative intracranial internal carotid artery calcification measures, with excellent observer agreements. Visual intracranial internal carotid artery scores could be a rapid and practical method for epidemiological studies. PMID:26251250

  8. 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

  9. Calcific tendinitis of the rotator cuff.

    PubMed

    ElShewy, Mohamed Taha

    2016-01-18

    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

  10. 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

  11. Calcification of the breasts due to loiasis.

    PubMed

    Lemmenmeier, Eva; Keller, Nicole; Chuck, Natalie

    2016-01-01

    A 53-year-old HIV-positive female from Cameroon was diagnosed with loiasis in 2013 due to symptoms of polyarthritis and laboratory confirmed eosinophilia. Because of high microfilaremia primary treatment was given with two courses of albendazol and ivermectin and completed with a course of diethylcarbamazine. Therapy was successful as symptoms, eosinophilia and microfilaremia disappeared. In 2015, she had a gynecology check-up where a screening mammography showed several round and linear, meandering calcifications in both breasts, the latter are typically seen in filariasis. PMID:27051574

  12. 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

  13. Chest xerotomography: evaluation of calcification within lung nodules.

    PubMed

    Penkrot, R J; Gordon, R

    1980-01-01

    Through the use of a chest phantom and beeswax nodules containing calcium, xerotomography is shown to be a valuable tool in the evaluation of calcifications within lung nodules. The technique gives superior definition of calcium, especially fine calcifications in the 1-2-mm, or less, range. Our results suggest that clinical trials should follow and clinicopathologic correlation be obtained. PMID:7203908

  14. Calcific Aortic Valve Disease: Molecular Mechanisms and Therapeutic Approaches

    PubMed Central

    Lerman, Daniel Alejandro; Prasad, Sai; Alotti, Nasri

    2016-01-01

    Calcification occurs in atherosclerotic vascular lesions and In the aortic valve. Calcific aortic valve disease (CAVD) is a slow, progressive disorder that ranges from mild valve thickening without obstruction of blood flow, termed aortic sclerosis, to severe calcification with impaired leaflet motion, termed aortic stenosis. In the past, this process was thought to be ‘degenerative’ because of time-dependent wear and tear of the leaflets, with passive calcium deposition. The presence of osteoblasts in atherosclerotic vascular lesions and in CAVD implies that calcification is an active, regulated process akin to atherosclerosis, with lipoprotein deposition and chronic inflammation. If calcification is active, via pro-osteogenic pathways, one might expect that development and progression of calcification could be inhibited. The overlap in the clinical factors associated with calcific valve disease and atherosclerosis provides further support for a shared disease mechanism. In our recent research we used an in vitro porcine valve interstitial cell model to study spontaneous calcification and potential promoters and inhibitors. Using this model, we found that denosumab, a human monoclonal antibody targeting the receptor activator of nuclear factor-κB ligand may, at a working concentration of 50 μg/mL, inhibit induced calcium deposition to basal levels.

  15. Elastin Degradation and Calcification in an Abdominal Aorta Injury Model

    PubMed Central

    Basalyga, Dina M.; Simionescu, Dan T.; Xiong, Wanfen; Timothy Baxter, B.; Starcher, Barry C.; Vyavahare, Narendra R.

    2005-01-01

    Background Elastin calcification is a widespread feature of vascular pathology, and circumstantial evidence exists for a correlation between elastin degradation and calcification. We hypothesized that matrix metalloproteinase (MMP)–mediated vascular remodeling plays a significant role in elastin calcification. Methods and Results In the present studies, we determined that short-term periadventitial treatment of the rat abdominal aorta with low concentrations of calcium chloride (CaCl2) induced chronic degeneration and calcification of vascular elastic fibers in the absence of aneurysm formation and inflammatory reactions. Furthermore, the rate of progression of calcification depended on the application method and concentration of CaCl2 applied periarterially. Initial calcium deposits, associated mainly with elastic fibers, were persistently accompanied by elastin degradation, disorganization of aortic extracellular matrix, and moderate levels of vascular cell apoptosis. Application of aluminum ions (known inhibitors of elastin degradation) before the CaCl2-mediated injury significantly reduced elastin calcification and abolished both extracellular matrix degradation and apoptosis. We also found that MMP-knockout mice were resistant to CaCl2-mediated aortic injury and did not develop elastin degeneration and calcification. Conclusion Collectively, these data strongly indicate a correlation between MMP-mediated elastin degradation and vascular calcification. PMID:15545515

  16. 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)...

  17. 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

  18. 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

  19. Medial Arterial Calcification: An Overlooked Player in Peripheral Arterial Disease.

    PubMed

    Ho, Chin Yee; Shanahan, Catherine M

    2016-08-01

    Peripheral arterial disease (PAD) is a global health issue that is becoming more prevalent in an aging world population. Diabetes mellitus and chronic kidney disease are also on the increase, and both are associated with accelerated vascular calcification and an unfavorable prognosis in PAD. These data challenge the traditional athero-centric view of PAD, instead pointing toward a disease process complicated by medial arterial calcification. Like atherosclerosis, aging is a potent risk factor for medial arterial calcification, and accelerated vascular aging may underpin the devastating manifestations of PAD, particularly in patients prone to calcification. Consequently, this review will attempt to dissect the relationship between medial arterial calcification and atherosclerosis in PAD and identify common as well as novel risk factors that may contribute to and accelerate progression of PAD. In this context, we focus on the complex interplay between oxidative stress, DNA damage, and vascular aging, as well as the unexplored role of neuropathy. PMID:27312224

  20. Late calcification and rupture: a rare complication of ventriculoperitoneal shunting.

    PubMed

    Kural, Cahit; Kirik, Alparslan; Pusat, Serhat; Senturk, Tolga; Izci, Yusuf

    2012-01-01

    A 10-year old boy who had undergone a ventriculoperitoneal (V/P) shunt because of hydrocephalus at 10 days of age was doing well until 20 days ago, when he began to experience headache and seizures. CT scan revealed dilated lateral ventricles and calcification at the shunt site. X-rays showed an unusual calcification pattern around the shunt tube and rupture of the tube between the mastoid bone and clavicle. The patient underwent surgery and the shunt was changed completely. The ventricles became small in the follow-up. Even though V/P shunts may induce fibrous tissue formation and calcification around the tube, there are a few cases of shunt rupture and calcification of shunts in the literature. Possible mechanisms of the rupture and calcification are discussed in this paper. PMID:23208915

  1. 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

  2. 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

  3. Mechanisms of ectopic calcification: implications for diabetic vasculopathy.

    PubMed

    Avogaro, Angelo; Fadini, Gian Paolo

    2015-10-01

    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

  4. 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

  5. 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

  6. 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

  7. Mechanisms and treatment of extraosseous calcification in chronic kidney disease.

    PubMed

    Ketteler, Markus; Rothe, Hansjörg; Krüger, Thilo; Biggar, Patrick H; Schlieper, Georg

    2011-09-01

    Strong and unidirectional associations exist between the severity of cardiovascular calcifications and mortality in patients with advanced chronic kidney disease. In the past 10 years, a wealth of experimental and clinical information has been published on the key pathophysiological events that contribute to the development and progression of vascular and soft-tissue calcifications. These processes involve a sensitive balance of calcification inhibition, induction and removal. The traditional view of regarding secondary hyperparathyroidism and elevated calcium × phosphate product as the pivotal risk factors for calcification has been challenged by data demonstrating a role for other, more subtle and complex pathomechanisms. These mechanisms include the loss of endogenous calcification inhibitors, deficient clearance of calcified debris, effects of vitamin K and vitamin D, and the action of calcification inducers as in osteogenic transdifferentiation. In this Review, we describe our current knowledge of the factors involved in the passive and active regulation of extraosseous calcification processes, with an assessment of their importance as targets for future diagnostic and therapeutic interventions. PMID:21769106

  8. 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

  9. Adaptation of Coccolith Calcification to Sea Water Carbonate Chemistry

    NASA Astrophysics Data System (ADS)

    Ziveri, P.; Langer, G.; Probert, I.; Young, J.

    2008-12-01

    Coccolithophores are major calcifiers and through calcification cause feedbacks to atmospheric CO2 cycling. The formation of CaCO3 in seawater, in fact, causes a shift of the carbonate system towards CO2, which in turn affects atmosphere / ocean CO2 exchange. A change in marine calcification provides a concomitant feedback in organic carbon export and would lead to a change in the drawdown of atmospheric CO2. Coccolithophore culture experiments and field observations showed controversial results regarding the response of calcification to high CO2. The three strains of Emiliania huxleyi (the most abundant living coccolithophore species) tested so far show both increased and decreased calcification at high CO2 levels (lower pH). Living E. huxleyi is known to have a large variability in both size and carbonate content. The hypothesis that we want to test in this work is the importance of adaptation of calcification to the seawater carbonate chemistry where coccolithophores calcify. We selected 4 strains of E. huxleyi maintained at the Roscoff culture collection, collected from different oceanographic settings with different carbon speciation. The selected strains are collected from environments with very different water carbonate chemistry and they have different carbonate mass. They have been experimentally grown at different CO2 levels to test the strain calcification response to sea water carbonate chemistry. . With these experiments we test the importance of the calcification strain adaptation to carbonate chemistry. Size and possibly different responses to carbonate chemistry variations will also be discussed.

  10. 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.

  11. Periodontal Disease Is an Independent Predictor of Intracardiac Calcification

    PubMed Central

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

    2013-01-01

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

  12. [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

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. Emodin via colonic irrigation modulates gut microbiota and reduces uremic toxins in rats with chronic kidney disease.

    PubMed

    Zeng, Yu-Qun; Dai, Zhenhua; Lu, Fuhua; Lu, Zhaoyu; Liu, Xusheng; Chen, Cha; Qu, Pinghua; Li, Dingcheng; Hua, Zhengshuang; Qu, Yanni; Zou, Chuan

    2016-04-01

    Gut microbiota plays a dual role in chronic kidney disease (CKD) and is closely linked to production of uremic toxins. Strategies of reducing uremic toxins by targeting gut microbiota are emerging. It is known that Chinese medicine rhubarb enema can reduce uremic toxins and improve renal function. However, it remains unknown which ingredient or mechanism mediates its effect. Here we utilized a rat CKD model of 5/6 nephrectomy to evaluate the effect of emodin, a main ingredient of rhubarb, on gut microbiota and uremic toxins in CKD. Emodin was administered via colonic irrigation at 5ml (1mg/day) for four weeks. We found that emodin via colonic irrigation (ECI) altered levels of two important uremic toxins, urea and indoxyl sulfate (IS), and changed gut microbiota in rats with CKD. ECI remarkably reduced urea and IS and improved renal function. Pyrosequencing and Real-Time qPCR analyses revealed that ECI resumed the microbial balance from an abnormal status in CKD. We also demonstrated that ten genera were positively correlated with Urea while four genera exhibited the negative correlation. Moreover, three genera were positively correlated with IS. Therefore, emodin altered the gut microbiota structure. It reduced the number of harmful bacteria, such as Clostridium spp. that is positively correlated with both urea and IS, but augmented the number of beneficial bacteria, including Lactobacillus spp. that is negatively correlated with urea. Thus, changes in gut microbiota induced by emodin via colonic irrigation are closely associated with reduction in uremic toxins and mitigation of renal injury. PMID:27003359

  18. Emodin via colonic irrigation modulates gut microbiota and reduces uremic toxins in rats with chronic kidney disease

    PubMed Central

    Lu, Fuhua; Lu, Zhaoyu; Liu, Xusheng; Chen, Cha; Qu, Pinghua; Li, Dingcheng; Hua, Zhengshuang; Qu, Yanni; Zou, Chuan

    2016-01-01

    Gut microbiota plays a dual role in chronic kidney disease (CKD) and is closely linked to production of uremic toxins. Strategies of reducing uremic toxins by targeting gut microbiota are emerging. It is known that Chinese medicine rhubarb enema can reduce uremic toxins and improve renal function. However, it remains unknown which ingredient or mechanism mediates its effect. Here we utilized a rat CKD model of 5/6 nephrectomy to evaluate the effect of emodin, a main ingredient of rhubarb, on gut microbiota and uremic toxins in CKD. Emodin was administered via colonic irrigation at 5ml (1mg/day) for four weeks. We found that emodin via colonic irrigation (ECI) altered levels of two important uremic toxins, urea and indoxyl sulfate (IS), and changed gut microbiota in rats with CKD. ECI remarkably reduced urea and IS and improved renal function. Pyrosequencing and Real-Time qPCR analyses revealed that ECI resumed the microbial balance from an abnormal status in CKD. We also demonstrated that ten genera were positively correlated with Urea while four genera exhibited the negative correlation. Moreover, three genera were positively correlated with IS. Therefore, emodin altered the gut microbiota structure. It reduced the number of harmful bacteria, such as Clostridium spp. that is positively correlated with both urea and IS, but augmented the number of beneficial bacteria, including Lactobacillus spp. that is negatively correlated with urea. Thus, changes in gut microbiota induced by emodin via colonic irrigation are closely associated with reduction in uremic toxins and mitigation of renal injury. PMID:27003359

  19. Study of Uremic Toxin Fluxes Across Nanofabricated Hemodialysis Membranes Using Irreversible Thermodynamics

    PubMed Central

    Hedayat, Assem; Peace, Rob; Elmoselhi, Hamdi; Shoker, Ahmed

    2013-01-01

    Introduction The flux of uremic toxin middle molecules through currently used hemodialysis membranes is suboptimal, mainly because of the membranes’ pore architecture. Aim Identifying the modifiable sieving parameters that can be improved by nanotechnology to enhance fluxes of uremic toxins across the walls of dialyzers’ capillaries. Methods We determined the maximal dimensions of endothelin, cystatin C, and interleukin – 6 using the macromolecular modeling software, COOT. We also applied the expanded Nernst-Plank equation to calculate the changes in the overall flux as a function of increased electro-migration and pH of the respective molecules. Results In a high flux hemodialyzer, the effective diffusivities of endothelin, cystatin C, and interleukin – 6 are 15.00 x 10-10 cm2/s, 7.7 x 10-10 cm2/s, and 5.4 x 10-10 cm2/s, respectively, through the capillaries’ walls. In a nanofabricated membrane, the effective diffusivities of endothelin, cystatin C, and interleukin – 6 are 13.87 x 10-7 cm2/s, 5.73 x 10-7 cm2/s, and 3.45 x 10-7 cm2/s, respectively, through a nanofabricated membrane. Theoretical modeling showed that a 96% reduction in the membrane's thickness and the application of an electric potential of 10 mV across the membrane could enhance the flux of endothelin, cystatin C, and interleukin - 6 by a factor of 25. A ΔpH of 0.07 altered the fluxes minimally. Conclusions Nanofabricated hemodialysis membranes with a reduced thickness and an applied electric potential can enhance the effective diffusivity and electro-migration flux of the respective uremic toxins by 3 orders of magnitude as compared to those passing through the high flux hemodialyzer. PMID:24688713

  20. Uremic Pruritus, Dialysis Adequacy, and Metabolic Profiles in Hemodialysis Patients: A Prospective 5-Year Cohort Study

    PubMed Central

    Chen, Hung-Yuan; Chiu, Yen-Ling; Hsu, Shih-Ping; Pai, Mei-Fen; Ju-YehYang; Lai, Chun-Fu; Lu, Hui-Min; Huang, Shu-Chen; Yang, Shao-Yu; Wen, Su-Yin; Chiu, Hsien-Ching; Hu, Fu-Chang; Peng, Yu-Sen; Jee, Shiou-Hwa

    2013-01-01

    Background Uremic pruritus is a common and intractable symptom in patients on chronic hemodialysis, but factors associated with the severity of pruritus remain unclear. This study aimed to explore the associations of metabolic factors and dialysis adequacy with the aggravation of pruritus. Methods We conducted a 5-year prospective cohort study on patients with maintenance hemodialysis. A visual analogue scale (VAS) was used to assess the intensity of pruritus. Patient demographic and clinical characteristics, laboratory parameters, dialysis adequacy (assessed by Kt/V), and pruritus intensity were recorded at baseline and follow-up. Change score analysis of the difference score of VAS between baseline and follow-up was performed using multiple linear regression models. The optimal threshold of Kt/V, which is associated with the aggravation of uremic pruritus, was determined by generalized additive models and receiver operating characteristic analysis. Results A total of 111 patients completed the study. Linear regression analysis showed that lower Kt/V and use of low-flux dialyzer were significantly associated with the aggravation of pruritus after adjusting for the baseline pruritus intensity and a variety of confounding factors. The optimal threshold value of Kt/V for pruritus was 1.5 suggested by both generalized additive models and receiver operating characteristic analysis. Conclusions Hemodialysis with the target of Kt/V ≥1.5 and use of high-flux dialyzer may reduce the intensity of pruritus in patients on chronic hemodialysis. Further clinical trials are required to determine the optimal dialysis dose and regimen for uremic pruritus. PMID:23940749

  1. 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.

  2. Reversible Acute Parkinsonism and Bilateral Basal Ganglia Lesions in a Diabetic Uremic Patient

    PubMed Central

    Nzwalo, Hipólito; Sá, Francisca; Capela, Carlos; Ferreira, Fátima; Basílio, Carlos

    2012-01-01

    The syndrome of bilateral basal ganglia lesions in diabetic uremic patients is a rare disorder mostly reported in Asians. There are few reports of the syndrome in Caucasians. It manifests as an acute hyperkinetic or hypokinetic extrapyramidal disorder in association with uniform neuroimaging findings of bilateral symmetrical basal ganglia changes in diabetics undergoing hemodialysis. Its pathophysiology remains largely unknown. Thus, we report a typical case of the syndrome in a Caucasian patient who developed an acute and reversible akinetic rigid parkinsonism secondary to bilateral basal ganglia lesions. PMID:23185167

  3. Optimized Metabolomic Approach to Identify Uremic Solutes in Plasma of Stage 3–4 Chronic Kidney Disease Patients

    PubMed Central

    Mutsaers, Henricus A. M.; Engelke, Udo F. H.; Wilmer, Martijn J. G.; Wetzels, Jack F. M.; Wevers, Ron A.; van den Heuvel, Lambertus P.; Hoenderop, Joost G.; Masereeuw, Rosalinde

    2013-01-01

    Background Chronic kidney disease (CKD) is characterized by the progressive accumulation of various potential toxic solutes. Furthermore, uremic plasma is a complex mixture hampering accurate determination of uremic toxin levels and the identification of novel uremic solutes. Methods In this study, we applied 1H-nuclear magnetic resonance (NMR) spectroscopy, following three distinct deproteinization strategies, to determine differences in the plasma metabolic status of stage 3–4 CKD patients and healthy controls. Moreover, the human renal proximal tubule cell line (ciPTEC) was used to study the influence of newly indentified uremic solutes on renal phenotype and functionality. Results Protein removal via ultrafiltration and acetonitrile precipitation are complementary techniques and both are required to obtain a clear metabolome profile. This new approach, revealed that a total of 14 metabolites were elevated in uremic plasma. In addition to confirming the retention of several previously identified uremic toxins, including p-cresyl sulphate, two novel uremic retentions solutes were detected, namely dimethyl sulphone (DMSO2) and 2-hydroxyisobutyric acid (2-HIBA). Our results show that these metabolites accumulate in non-dialysis CKD patients from 9±7 µM (control) to 51±29 µM and from 7 (0–9) µM (control) to 32±15 µM, respectively. Furthermore, exposure of ciPTEC to clinically relevant concentrations of both solutes resulted in an increased protein expression of the mesenchymal marker vimentin with more than 10% (p<0.05). Moreover, the loss of epithelial characteristics significantly correlated with a loss of glucuronidation activity (Pearson r = −0.63; p<0.05). In addition, both solutes did not affect cell viability nor mitochondrial activity. Conclusions This study demonstrates the importance of sample preparation techniques in the identification of uremic retention solutes using 1H-NMR spectroscopy, and provide insight into the negative impact of

  4. 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- ...

  5. Acute Calcific Tendinitis of the Rectus Femoris: A Case Series

    PubMed Central

    IKobayashi, Hideo; Kaneko, Haruka; Homma, Yasuhiro; Baba, Tomonori; Kaneko, Kazuo

    2015-01-01

    Introduction: Periarticular calcific tendinitis is a common cause of Orthopedic outpatient referral. Calcific tendinitis of the rectus femoris, however, is very rare and not well known. Due to its rarity, correct diagnosis and prompt treatment are not fully understood. Case Report: Two females (38 and 40 years old) of acute calcific tendinitis of the rectus femoris with the good clinical course without any operative treatment were presented. The pain was managed with oral non-steroidal antiinflammatory drugs and/or local steroid injection. Interval radiographic assessment showed complete resorption of the calcification. Conclusion: Establishing the correct diagnosis and initiating prompt treatment are shown to be important in achieving resolution of symptoms and in avoiding unnecessary investigations. PMID:27299063

  6. 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 ...

  7. 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.

  8. Effects of. gamma. irradiation on cartilage matrix calcification

    SciTech Connect

    Nijweide, P.J.; Burger, E.H.; van Delft, J.L.; Kawilarange-de Haas, E.W.M.; Wassenaar, A.M.; Mellink, J.H.

    1980-10-01

    The effect of ..gamma.. irradiation on cartilage matrix calcification was studied in vitro. Metatarsal bones of 14- to 17-day-old embryonic mice were dissected and cultured under various conditions. Prior to culture, half of the metatarsal bones received absorbed doses of 1.0 to 30.0 Gy ..gamma.. radiation. Their paired counterparts served as controls. Irradiation inhibited longitudinal growth and calcification of the cartilage matrix during culture. In addition, a number of histological changes were noted. The inhibition of matrix calcification appeared to be due to an inhibition of the intracellular calcium accumulation. The formation of extracellular calcification foci and the growth of the calcified area already present at the moment of explanation were not inhibited during culture.

  9. Non-progressive familial idiopathic intracranial calcification: a family report.

    PubMed Central

    Callender, J S

    1995-01-01

    The clinical features and long term outcome of familial idiopathic intracranial calcification in three members of one family are described. The illness presented as psychiatric disorder in all patients, and in one patient, epilepsy and intellectual deterioration were later manifestations. Skull radiographs and CT were performed sequentially, in one patient, over a 22 year period and, in another, CT was carried out eight years apart. In neither patient was there any evidence of progression of calcification. Images PMID:7561925

  10. 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

  11. A review of the effect of diet on cardiovascular calcification.

    PubMed

    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

  12. [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

  13. 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

  14. 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

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

    PubMed Central

    Wu, Wei; Bush, Kevin T.; Hoenig, Melanie P.; Blantz, Roland C.; Bhatnagar, Vibha

    2015-01-01

    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. PMID:26490509

  16. 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

  17. 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.

  18. HPLC fractions of human uremic plasma inhibit the RBC membrane calcium pump.

    PubMed

    Lindner, A; Vanholder, R; De Smet, R; Hinds, T R; Vogeleere, P; Sandra, P; Foxall, P; Ringoir, S

    1997-04-01

    We have reported that uremic plasma filtrates (UF) inhibit the red blood cell (RBC) membrane calcium pump. The inhibitor was dialyzable, smaller than 3,000 molecular weight, heat-stable, and protease-resistant. In the present study, we used reverse-phase preparative HPLC, analytical HPLC, and Sephadex G-25 elution to identify inhibitory fractions. Inhibition was confirmed in three different bioassays: (1) Sr2+ efflux in intact RBC, the primary bio-assay; (2) 45Ca efflux in intact RBC; and (3) calcium ATPase activity in isolated RBC membranes. Active fractions were analyzed by mass spectrometry, capillary electrophoresis, enzymatic analysis, gas chromatography-mass spectrometry, and nuclear magnetic resonance spectroscopy. These demonstrated a number of compounds, including: sugars, polyols, osmolytes like betaine and myoinositol, amino acids, and other metabolites, such as 3-D-hydroxybutyrate, dimethylglycine, trimethylamine-N-oxide, guanidinoacetic acid and glycine. Many individual compounds were then tested for an effect on the calcium pump. Thus, HPLC was able to separate a substantial number of compounds in inhibitory fractions. Efforts are under way for precise identification of the inhibitor, to advance our understanding of uremic toxicity and/or hypertension in CRF. PMID:9083269

  19. 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

  20. 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. PMID:26490509

  1. Reduced capillary density in the myocardium of uremic rats--a stereological study.

    PubMed

    Amann, K; Wiest, G; Zimmer, G; Gretz, N; Ritz, E; Mall, G

    1992-11-01

    Using stereological techniques capillaries, interstitium and myocardial fibers were analyzed in perfusion-fixed hearts of subtotally nephrectomized male Sprague-Dawley rats with uremia of 14 months duration (or their sham-operated controls). Uremic rats had higher systolic blood pressure (140 +/- 20.3 mm Hg vs. 119 +/- 6.61 mm Hg) and left ventricular weight/body weight ratio (3.37 +/- 0.09 mg/kg vs. 2.01 +/- 0.12 mg/kg) than controls, and had slight anemia (Hct 35.0 +/- 3.16% vs. 40.4 +/- 3.3%). Length density (Lv) of capillaries, that is, capillary length per unit myocardial volume, was significantly (P < 0.001) decreased in uremia (2485 +/- 264 mm/mm3 vs. 3329 +/- 194 mm/mm3) versus controls. In parallel, surface density and volume density of the capillary lumina were also reduced (7.95 +/- 1.69 cm3/cm3 vs. 11.4 +/- 1.8 cm3/cm3) in the uremic rats. We conclude that in experimental uremia, cardiac hypertrophy is not accompanied by a commensurate increase in capillaries. PMID:1453595

  2. 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

  3. 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

  4. Ocean Acidification Reduces Growth and Calcification in a Marine Dinoflagellate

    PubMed Central

    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. PMID:23776586

  5. 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

  6. Divergent behavior of hydrogen sulfide pools and of the sulfur metabolite lanthionine, a novel uremic toxin, in dialysis patients.

    PubMed

    Perna, Alessandra F; Di Nunzio, Annarita; Amoresano, Angela; Pane, Francesca; Fontanarosa, Carolina; Pucci, Piero; Vigorito, Carmela; Cirillo, Giovanni; Zacchia, Miriam; Trepiccione, Francesco; Ingrosso, Diego

    2016-07-01

    Dialysis patients display a high cardiovascular mortality, the causes of which are still not completely explained, but are related to uremic toxicity. Among uremic toxins, homocysteine and cysteine are both substrates of cystathionine β-synthase and cystathionine γ-lyase in hydrogen sulfide biosynthesis, leading to the formation of two sulfur metabolites, lanthionine and homolanthionine, considered stable indirect biomarkers of its production. Hydrogen sulfide is involved in the modulation of multiple pathophysiological responses. In uremia, we have demonstrated low plasma total hydrogen sulfide levels, due to reduced cystathionine γ-lyase expression. Plasma hydrogen sulfide levels were measured in hemodialysis patients and healthy controls with three different techniques in comparison, allowing to discern the different pools of this gas. The protein-bound (the one thought to be the most active) and acid-labile forms are significantly decreased, while homolanthionine, but especially lanthionine, accumulate in the blood of uremic patients. The hemodialysis regimen plays a role in determining sulfur compounds levels, and lanthionine is partially removed by a single dialysis session. Lanthionine inhibits hydrogen sulfide production in cell cultures under conditions comparable to in vivo ones. We therefore propose that lanthionine is a novel uremic toxin. The possible role of high lanthionine as a contributor to the genesis of hyperhomocysteinemia in uremia is discussed. PMID:27129884

  7. 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...

  8. Blood serum atherogenicity and coronary artery calcification.

    PubMed

    Sobenin, Igor A; Myasoedova, Veronica A; Anisimova, Elena V; Pavlova, Xenia N; Möhlenkamp, Stefan; Schmermund, Axel; Seibel, Rainer; Berenbein, Sina; Lehmann, Nils; Moebus, Susanne; Jöckel, KarlHeinz; Orekhov, Alexander N; Erbel, Raimund

    2014-01-01

    The phenomenon of blood serum atherogenicity was described as the ability of human serum to induce lipid accumulation in cultured cells. The results of recent two-year prospective study in asymptomatic men provided the evidence for association between the changes in serum atherogenicity and dynamics of carotid intima-media thickness progression. The present study was undertaken to test the hypothesis that blood serum atherogenicity and its changes in dynamics may be associated with accumulation of coronary calcium in subclinical atherosclerosis. It was performed in 782 CHD-free participants of The Heinz Nixdorf RECALL (Risk Factors, Evaluation of Coronary Calcium and Lifestyle) Study, in whom blood samples have been taken at the baseline and at the end of 5-year follow-up. Opposite to the previous findings, the changes in serum atherogenicity did not correlate neither with the extent of coronary artery calcification, nor with the changes in Agatston CAC score. There was a moderate but significant rise in serum atherogenicity after 5-year followup period, and the same dynamics was observed for Agatston CAC score, but not for convenient lipid-related risk factors. The absence of association of the changes in serum atherogenicity with the changes in Agatston CAC score, along with previous findings, provides a point of view that serum-induced intracellular cholesterol accumulation is not related to the processes of calcium deposition in arterial wall, since the last one reflects the progression of already existing subclinical atherosclerotic lesions. PMID:24533940

  9. 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

  10. Retropharyngeal calcific tendinitis mimicking a retropharyngeal phlegmon.

    PubMed

    Gabra, Nathalie; Belair, Manon; Ayad, Tareck

    2013-01-01

    Background. Acute retropharyngeal tendinitis is a little known but not an uncommon condition. It was first described by Hartley in 1964 as an inflammation of the longus colli muscle secondary to calcium crystals deposition on its insertion. The calcifications are mostly located on the oblique portion of the muscle at the level of C1-C2. Methods. We will describe this disease through 4 cases that presented in our institution. Results. The most common symptoms are severe neck pain, odynophagia, and a painful restriction of neck movement. It is associated with mild fever and inflammatory lab findings such as a slight elevation of white blood cell count, erythrocyte sedimentation rate, and C-reactive protein. CT scan is recommended as the first-line imaging modality to establish a diagnosis. Treatments consist of NSAIDs and analgesics to accelerate the healing process. If symptoms are severe, a course of corticosteroids is required. Conclusion. Since the clinical and laboratory findings of this condition and those of a retropharyngeal abscess overlap, it is important to establish the right diagnosis in order to prevent more invasive procedures. A good knowledge of this clinical entity by otolaryngologists would prevent delays in hospital discharge and unnecessary anxiety. PMID:23862089

  11. Retropharyngeal Calcific Tendinitis Mimicking a Retropharyngeal Phlegmon

    PubMed Central

    Belair, Manon; Ayad, Tareck

    2013-01-01

    Background. Acute retropharyngeal tendinitis is a little known but not an uncommon condition. It was first described by Hartley in 1964 as an inflammation of the longus colli muscle secondary to calcium crystals deposition on its insertion. The calcifications are mostly located on the oblique portion of the muscle at the level of C1-C2. Methods. We will describe this disease through 4 cases that presented in our institution. Results. The most common symptoms are severe neck pain, odynophagia, and a painful restriction of neck movement. It is associated with mild fever and inflammatory lab findings such as a slight elevation of white blood cell count, erythrocyte sedimentation rate, and C-reactive protein. CT scan is recommended as the first-line imaging modality to establish a diagnosis. Treatments consist of NSAIDs and analgesics to accelerate the healing process. If symptoms are severe, a course of corticosteroids is required. Conclusion. Since the clinical and laboratory findings of this condition and those of a retropharyngeal abscess overlap, it is important to establish the right diagnosis in order to prevent more invasive procedures. A good knowledge of this clinical entity by otolaryngologists would prevent delays in hospital discharge and unnecessary anxiety. PMID:23862089

  12. Vascular Calcification and Renal Bone Disorders

    PubMed Central

    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

  13. Elastin Calcification and its Prevention with Aluminum Chloride Pretreatment

    PubMed Central

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

    1999-01-01

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

  14. 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.

  15. [Vascular Calcification - Pathological Mechanism and Clinical Application - . The effect of cinacalcet on vascular calcification].

    PubMed

    Yokoyama, Keitaro

    2015-05-01

    Cinacalcet acts on calcium receptors (CaR) expressed on chief cells of the parathyroid gland to inhibit the secretion of parathyroid hormone (PTH) . This drug inhibits PTH secretion without causing an elevation of serum calcium and phosphorus, unlike active vitamin D. Several experimental studies demonstrated an inhibitory effect of calcimimetics on the progression of vascular calcification in animals with chronic kidney disease (CKD), in keeping with the expression of the calcium-sensing receptor (CaSR) in vascular tissue. The EVOLVE, evaluated in patients with CKD 5D the effects of the cinacalcet on the progression of vascular calcification and hard cardiovascular outcomes, respectively. The EVOLVE trials missed their respective primary end point by intent-to-treat analysis. However, recently, in order to define the frequency of fatal and nonfatal cardiovascular events attributable to atherosclerotic and nonatherosclerotic mechanisms, risk factors for these events, and the effects of cinacalcet, post hoc analysis using adjudicated data collected during the EVOLVE Trial were perfomed. In this trial, combining fatal and nonfatal cardiovascular events, randomization to cinacalcet reduced the rates of sudden death and heart failure. Patients randomized to cinacalcet experienced fewer nonatherosclerotic cardiovascular events, while the effect of cinacalcet on atherosclerotic events did not reach statistical significance. PMID:25926577

  16. [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

  17. 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

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

    PubMed

    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

  19. Tablet fluoridation influences the calcification of primary tooth pulp.

    PubMed

    Holtgrave, E A; Hopfenmüller, W; Ammar, S

    2001-01-01

    This study was conducted to determine the influence of long-term tablet fluoridation on primary pulp calcification by light microscopy. Twenty-four caries-free primary molars (after continuous postpartally initiated 1- to 10-year tablet fluoridation) were compared to 17 primary molars of children without fluoride prophylaxis. Pulp calcification in children with tablet fluoridation was significantly more frequent and more pronounced than in untreated children (p = 0.001). Besides the known pulp stones, the prophylaxis group evidenced a special form of calcification consisting of fibrodentin-like hard tissue not observed in the untreated children. These hard tissue bodies developed "intramurally" on the pulp floor and the inside of the dental roots with an irregular extramural spread into the coronal and radicular pulp by displacement and fibrotization of the pulp tissue. Moreover, some of the teeth had more or less extensive areas of interglobular dentin. The affected teeth were ankylosed in the area of the bi- and trifurcation and on the inside of the roots and were thus infra-occluded. Although the duration of tablet fluoridation has no statistically significant influence on pulp calcification, there is a correlation between extensive pulp calcification, postnatally initiated fluoride prophylaxis and the infraocclusion of primary molars. PMID:11227204

  20. Permanent tooth calcification in chimpanzees (Pan troglodytes): patterns and polymorphisms.

    PubMed

    Kuykendall, K L; Conroy, G C

    1996-01-01

    Tooth calcification is an important developmental marker for use in constructing models for early hominid life history, particularly for its application to the fossil record. As chimpanzees are commonly utilized in interspecific comparisons in such research, this study aims to improve available baseline data for tooth calcification patterns in chimpanzees (Pan troglodytes), and to quantify basic patterns and polymorphisms. We present an analysis of developmental patterns for the left mandibular dentition (I1-M3) based on intraoral radiographs obtained from a cross-sectional sample of chimpanzees (58 males, 60 females) housed at LEMSIP (NYU Medical Center) and Yerkes (Emory University). No significant differences with previous descriptions of the basic sequences of tooth calcification in chimpanzees were found, but variation in such patterns was documented for the first time. In the overall sequence, polymorphisms between the canine and the group (M2 P4 P3) reached significant levels. This is due to the relative delay in canine crown formation compared to other teeth. Differences in the basic sequence between males and females were recorded, but are due to minor shifts in the percentages of occurrence for polymorphic sequences which are common to both genders. Perhaps our most important findings are that a) different polymorphic sequences occur in tooth calcification and tooth emergence in chimpanzees, and b) developmental relationships among teeth fluctuate throughout tooth calcification. Thus, characterizations of dental developmental patterns based on particular stages of development cannot necessarily be extrapolated to other stages without supporting data. PMID:8928717

  1. 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.

  2. Molecular mechanisms mediating vascular calcification: role of matrix Gla protein.

    PubMed

    Proudfoot, Diane; Shanahan, Catherine M

    2006-10-01

    Patients with chronic kidney disease (CKD) have a higher incidence of vascular calcification and a greatly increased risk of cardiovascular death. The mechanisms involved in the accelerated vascular calcification observed in CKD have recently become clearer, leading to the hypothesis that a lack of natural inhibitors of calcification may trigger calcium deposition. One of these inhibitory factors, matrix Gla protein (MGP), is the focus of the present review. MGP, originally isolated from bone, is a vitamin K-dependent protein that is also highly expressed by vascular smooth muscle cells. MGP has been confirmed as a calcification-inhibitor in numerous studies; however, its mechanism of action is not completely understood. It potentially acts in several ways to regulate calcium deposition including: (i) binding calcium ions and crystals; (ii) antagonizing bone morphogenetic protein and altering cell differentiation; (iii) binding to extracellular matrix components; and (iv) regulating apoptosis. Its expression is regulated by several factors including retinoic acid, vitamin D and extracellular calcium ions, and a reduced form of vitamin K (KH2) is important in maintaining MGP in an active form. Therefore, strategies aimed at increasing its expression and activity may be beneficial in tipping the balance in favour of inhibition of calcification in CKD. PMID:17014561

  3. Efficacy of reversal of aortic calcification by chelating agents

    PubMed Central

    Lei, Yang; Sinha, Aditi; Vyavahare, Naren

    2013-01-01

    Elastin specific medial vascular calcification, termed Monckeberg’s sclerosis has been recognized as a major risk factor for various cardiovascular events. We hypothesize that chelating agents, such as disodium ethylene diamine tetraacetic acid (EDTA), diethylene triamine pentaacetic acid (DTPA) and sodium thiosulfate (STS) might reverse elastin calcification by directly removing calcium (Ca) from calcified tissues into soluble calcium complexes. We assessed the chelating ability of EDTA, DTPA, and STS on removal of calcium from hydroxyapatite (HA) powder, calcified porcine aortic elastin, and calcified human aorta in vitro. We show that both EDTA and DTPA could effectively remove calcium from HA and calcified tissues, while STS was not effective. The tissue architecture was not altered during chelation. In the animal model of aortic elastin-specific calcification, we further show that local periadventitial delivery of EDTA loaded in to poly (lactic-co-glycolic acid) (PLGA) nanoparticles regressed elastin specific calcification in the aorta. Collectively, the data indicate that elastin-specific medial vascular calcification could be reversed by chelating agents. PMID:23963635

  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. 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.

  6. 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

  7. 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

  8. Recent progress in the treatment of vascular calcification

    PubMed Central

    O’Neill, W. Charles; Lomashvili, Koba A.

    2011-01-01

    Vascular calcification is common in patients with advanced chronic kidney disease and is associated with poorer outcomes. Although the pathophysiology is not completely understood, it is clear that it is a multifactorial process involving altered mineral metabolism, as well as changes in systemic and local factors that can promote or inhibit vascular calcification, and all of these are potential therapeutic targets. Current therapy is closely linked to strategies for preventing disordered bone and mineral metabolism in advanced kidney disease and involves lowering the circulating levels of both phosphate and calcium. The efficacy of compounds that specifically target calcification, such as bisphosphonates and thiosulfate, has been shown in animals but only in small numbers of humans, and safety remains an issue. Additional therapies, such as pyrophosphate, vitamin K, and lowering of pH, are supported by animal studies, but are yet to be investigated clinically. As the mineral composition of vascular calcifications is the same as in bone, potential effects on bone must be addressed with any therapy for vascular calcification. PMID:20861819

  9. Analysis of breast tissue calcifications using FTIR spectroscopy

    NASA Astrophysics Data System (ADS)

    Baker, Rebecca N.; Rogers, Keith D.; Shepherd, Neil; Stone, Nicholas

    2007-07-01

    Microalcifications can be found in both benign and malignant breast lesions and their composition can indicate the disease state. Type I microcalcifications are composed of calcium oxalate dihydrate (COD) and are associated mainly with benign tissue, whereas hydroxyapatite (HAP) can be present in both tissue types. As current practices such as mammography and histopathology examine the morphology of the specimen, they can not reliably distinguish between the two types of calcification, which frequently are the only mammographic features that indicate the presence of a cancerous lesion. Analysis of tissue by Fourier transform infrared microspectroscopy (FTIR) allows biochemical information to be achieved from the sample. Spectral maps have been carried out on paraffinized sections of breast tissue from 9 patients of different pathology types containing calcification. The chemical composition of the calcifications and surrounding tissue has been analysed and correlated with tissue pathology. This preliminary study has demonstrated the ability to conduct FTIR in paraffinized sections of breast tissue, and initial observations show a correlation between HAP carbonate substitution and tissue pathology. It is hoped that this and further studies will give insight into how the calcifications are linked to the disease process and will give an increased understanding of the significance of calcifications in breast tissue. If type II microcalcifications can be differentiated in benign and malignant tissue by spectroscopic techniques, this may have positive implications in early diagnosis if the techniques can be applied in vivo and spectroscopy of paraffin sections enables biochemical information to accompany histopathology of the sample.

  10. [Severe course of typical hemolytic-uremic syndrome in a 14-year-old boy].

    PubMed

    Adamczuk, Dominika; Ziołkowska, Helena; Leszczyńska, Beata; Roszkowska-Blaim, Maria

    2009-04-01

    The authors present a 14-year old boy with acute renal failure in the course of hemolytic-uremic syndrome (HUS), preceded by bloody diarrhea of unknown origin. The course of HUS was complicated with hypertensive crisis, pleural effusion. Pleural puncture was complicated with massive hemorrhage which required thoracotomy. Additional risk factor were subendocardial perfusion disorders found in MRI scan of the heart and peripheral peroneal nerve palsy (in neuro-motorical conduction examination--severe neuropathy). Renal replacement therapy was necessary for 11 days (hemodialyses--3 days, continuous hemodiafiltration--9 days). Transfusions of: 3000 mL of packed erythrocyte mass, 2700 mL of fresh frozen plasma, 1000 mL of packed platelet mass were performed. Full parenteric nutrition was needed for 11 days. Full recovery of renal function, gradual improvement of heart muscle function, regression of lung abnormalities have been obtained. PMID:19580203