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PubMed2004

Treatment of bioprosthetic heart valve tissue with long chain alcohol solution to lower calcification potential.

The use of glutaraldehyde-treated biological tissue in heart valve substitutes is an important option in the treatment of heart valve disease. These devices have limited durability, in part, because of tissue calcification and subsequent tearing of the valve leaflets. Components thought to induce calcification include lipids, cell remnants, and residual glutaraldehyde. We hypothesized that treatment of glutaraldehyde-treated bioprosthetic heart valve material using a short and long chain alcohol (LCA) combination, composed of 5% 1,2-octanediol in an ethanolic buffered solution, would reduce phospholipid content and subsequently lower the propensity of these tissues to calcify in vivo. Phospholipid content of glutaraldehyde-treated porcine valve leaflets and bovine pericardium was found to be 10.1 +/- 4.3 (n = 7) and 3.9 +/- 0.48 (n = 2) microg/mg dry tissue, respectively, which was reduced to 0.041 +/- 0.06 (n = 7) and 0.21 +/- 0.05 (n = 4) microg/mg dry tissue, respectively, after LCA treatment. Calcification potential of the treated tissues was assessed using a rat subcutaneous implant model. After 60 days of implantation, calcium levels were found to be 171 +/- 32 (n = 11) and 83 +/- 70 (n = 12) mg/g dry weight for glutaraldehyde-treated porcine leaflets and bovine pericardium, respectively, whereas prior LCA treatment resulted in reduced calcium levels of 1.1 +/- 0.6 (n = 12) and 0.82 +/- 0.1 (n = 12) mg/g dry weight, respectively. These data, taken together, support the notion that treatment of glutaraldehyde-treated tissue with a short and long chain alcohol combination will reduce both extractable phospholipids and the propensity for in vivo calcification.

Animals↗
PubMed2004

Prolonged ectopic calcification induced by BMP-2-derived synthetic peptide.

Bone morphogenetic protein-2 (BMP-2) promotes the formation and regeneration of bone and cartilage, and therefore constitutes the most promising candidate for a bone repair material. However, it also has a wide range of functions, such as in organogenesis and apoptosis. Therefore, we investigated a novel synthetic peptide corresponding to residues 73-92 of BMP-2. This peptide bound to a BMP-2-specific receptor and elevated both alkaline phosphatase activity and osteocalcin mRNA in the murine cell line, C3H10T1/2. The 73-92 peptide also induced ectopic calcification when conjugated to a covalently crosslinked alginate gel. Here we report that the 73-92 peptide-conjugated alginate gel showed prolonged ectopic calcification for up to 7 weeks in rat calf muscle. In contrast, rhBMP-2-impregnated collagen gel showed maximum ectopic calcification at 3 weeks, and the calcified products that had formed disappeared after 5 weeks. Histological examination showed that the 73-92 peptide-conjugated alginate gel induced many osteoblast-like cells and few osteoclasts. In contrast, rhBMP-2-impregnated collagen gel induced many osteoclasts. These results suggest that the 73-92 peptide on alginate gel remains active at the implanted site, continuously induces differentiation of osteoblast precursor cells into osteoblasts, and activates osteoblasts to promote ectopic calcification.

Alginates↗
PubMed2003

Glutaraldehyde-fixed kangaroo aortic wall tissue: histology, crosslink stability and calcification potential.

Stentless aortic heart valve substitutes, manufactured from biological tissues, are fixed with glutaraldehyde to cross-link collagen, reduce antigenicity, and sterilize the tissue. Despite improved cross linking, reduced antigenicity, and various anticalcification measures, the aortic wall tissue present in these prostheses tends to calcify. The aim of this study was to assess the morphology, collagen cross-link stability, and calcification potential of glutaraldehyde-preserved kangaroo aortic wall tissue as opposed to porcine aortic wall tissue. Porcine and kangaroo aortic wall tissues were fixed in 0.625% buffered glutaraldehyde. Histology and cross-link stability were examined. Calcification potential was determined in the subcutaneous rat model. Kangaroo aortic wall tissue was significantly (p < 0.01) less calcified than porcine aortic wall tissue (26.67 +/- 6.53 versus 41.959 +/- 2.75 microg/mg tissue) at 8 weeks. In conclusion, the histological differences between kangaroo and porcine aortic wall tissue correlate well with the reduced calcification potential of kangaroo aortic wall tissue. The reduced calcification potential could result in improved long-term durability of stentless kangaroo heart valves as bioprostheses.

Animals↗
PubMed1986

Ultrasound diagnosis of renal calcification in infants on chronic furosemide therapy.

We describe seven infants who developed renal calcification and bone demineralization following furosemide therapy with average daily doses of as little as 0.75 mg/kg per day. Renal calcifications were present in all seven cases and were more readily detected with ultrasonography than with plain films. Renal calculi were seen in four patients, sonographically demonstrated as echogenic foci in the dependent portion of the collecting system, usually accompanied by acoustic shadowing. One patient developed nephrocalcinosis, sonographically observed as echogenic medullary pyramids plus punctate, shadowing parenchymal calcifications. In two patients the location of the calcification could not be determined.

Bone Diseases↗
PubMed1988

Significance of scrotal calcifications detected by sonography.

A total of 468 patients were evaluated using a high-resolution scanner with a high-frequency transducer. Scrotal calcifications were diagnosed by sonographic criteria in 22 patients. Size, number, arrangement, and especially location (testicular or extratesticular) were precisely determined. Calcifications, located within testicular parenchyma, particularly if multiple and grouped, were considered highly suspicious for malignancy, and surgery was mandatory. Based on these sonographic features, 9 patients underwent surgery with pathological examination. In all, calcifications were confirmed and found in 4 necrotic germ-cell tumors, in a germ-cell tumor scar but with intratubular occult seminoma, in 1 epidermoid testicular cyst, in 1 tuberculous epididymo-orchitis, in 1 granulomatous orchitis, and at last, in 1 ruptured testis with an old hematoma. In the 13 remaining patients, calcification was usually defined as solitary, large, and extratesticular by sonography and considered benign. No changes were seen in follow-up examinations.

Adult↗
PubMed2006

Ex vivo identification of atherosclerotic plaque calcification by a 31P solid-state magnetic resonance imaging technique.

Calcified tissue is a common component of atherosclerotic plaques, and occurs most often in mature plaques. The process of calcification is a poorly understood risk factor that may contribute to a plaque's vulnerability to sudden rupture. In this study a solid-state imaging sequence, termed single-point imaging (SPI), was used to observe calcification directly in ex vivo atherosclerotic plaques. Standards were used to validate the ability of (31)P SPI to detect and differentiate calcification from crystalline cholesterol, phospholipids, and other plaque components. After suitable experimental parameters were found, human carotid specimens obtained by endarterectomy were imaged ex vivo by (31)P solid-state imaging and standard (1)H methods. In contrast to (1)H imaging methods, (31)P imaging detected only the calcification in the plaque.

Calcinosis↗
PubMed1975

Calcification in human breast carcinomas: ultrastructural observations.

Calcification in human breast carcinomas has been studied ultrastructurally. Multiple deposits of needle-shaped crystals intimately associated with electrondense material were observed among tumour cells. Similar deposits were present in intracytoplasmic lumina and the adjacent stroma. Cytoplasmic calcification was seen in membrane-bound vesicles and as partially membrane-bound clusters of crystals. It is suggested that the calcification is the result of an active secretory process rather than calcified necrotic or degenerate tumour cells. The possible mechanisms of calcification are discussed. Both electron diffraction and electron probe analysis show that the crystaline material is hydroxyapatite.

Breast Neoplasms↗
PubMed2005

Transdifferentiation of smooth muscle cells into chondrocytes in atherosclerotic arteries in situ: implications for diffuse intimal calcification.

Several hypotheses have been offered to explain the occurrence of arteriosclerotic calcification but the mechanisms involved are still not well understood. Using a combination of electron microscopy and immunohistochemistry, atherosclerotic plaques from human arteries as well as atherosclerotic-like lesions from aortas of apo-E-deficient mice were examined to identify cell type(s) associated with calcification. Electron microscopic analysis showed that, in human atherosclerotic plaques, chondrocyte-like cells were present in areas surrounding the necrotic cores. In these areas, some smooth muscle cells displayed features of their transdifferentiation into chondrocyte-like cells. Immunohistochemical analysis confirmed that smooth muscle cells with a reduced content of alpha-smooth muscle actin expressed Sox-9. Destruction of chondrocytes resulted in the accumulation of numerous membrane-bound vesicles in the extracellular space. Membrane-bound vesicles originating from chondrocytes were found to undergo calcification. Similar processes were found to occur in atherosclerotic-like lesions in apo-E-deficient mice. These observations suggest that transdifferentiation of smooth muscle cells into chondrocytes contributes to atherosclerotic calcification.

Adult↗
PubMed1998

Genetic analysis of dystrophic cardiac calcification in DBA/2 mice.

A DBA/2 x D2B6F1 backcross was produced in order to study the genetic background of pathological soft tissue calcification in the mouse. Calcification was assessed in the myocardium, kidney and tongue. Significant co-segregation was found with the genotype of microsatellite markers on the proximal end of Chromosome 7. This region contains a candidate gene, Hrc, coding for the histidine-rich calcium binding protein in the sarcoplasmatic reticulum. The results support the hypothesis that the gene previously reported to be responsible for DCC (dystrophic cardiac calcification) in C3H mice (1) causes generalized soft tissue calcification in DBA/2 mice.

Animals↗
PubMed1990

Case report 620. Progressive systemic sclerosis (PSS) with paraspinous and intraspinous calcifications.

Progressive systemic sclerosis (PSS) is a connective tissue disorder of unknown etiology and pathogenesis characterized by fibrosis of the skin (scleroderma) and variable involvement of several organ systems including the gastrointestinal tract, lungs, heart, and kidneys. Calcinosis cutis is a frequent finding, commonly seen in the soft tissues of the fingertips and over the knees and elbows. Calcifications may also occur in areas of muscle necrosis and have been reported in articular synovium. This report describes a patient with PSS in the form of subcutaneous calcifications and scleroderma who was noted to have extensive paraspinous and intraspinal calcific deposits, causing severe narrowing of the spinal canal. The radiographs of 66 patients with PSS seen at Northwestern Memorial Hospital of soft tissue calcifications.

Calcinosis↗
PubMed1993

Coexistence of calcific tendinitis and rotator cuff tear: an arthrographic study.

A prospective evaluation of the coexistence of calcific tendinitis and tear of the rotator cuff demonstrated by arthrography was made in patients presenting with shoulder pain. Patients were X-rayed using conventional views and impingement views. Eighty-one patients (mean age 61.2 years) with calcific tendinitis underwent arthrography. Arthrography showed 22 partial or complete tears of the rotator cuff. A small rather than a large amount of calcification was more likely to be associated with a rotator cuff tear (p = 0.005). The coexistence of calcific tendinitis with rotator cuff tear is not uncommon, especially in older age groups.

Calcinosis↗
PubMed1987

Cervical intervertebral disc calcification in children.

Intervertebral disc calcification in children is a rare occurrence. The clinical symptoms and signs are distinctively confined to the cervical area with pain, limitation of motion, and torticollis. Long tract signs or radicular involvement are extremely unusual. CT scan and cervical spinal X-ray films shown the calcification to be in the nucleus pulposus with anterior or posterior mild protrusion into the spinal canal. Recovery without neurological sequelae is the rule in most of the pediatric cases with conservative treatment. Intervertebral disc calcification does not necessarily disappear with the onset of clinical symptoms. A case with persistent and even denser calcification at the same level of intervertebral disc space at the second episode of recurrence is illustrated.

Calcinosis↗
PubMed1994

Coronary arterial calcification as an active process: a new perspective on an old problem.

The mechanism and purpose of coronary atherosclerotic calcification remain unknown. However, evidence reviewed here suggests that calcification is not passive precipitation or adsorption, but instead is organized and regulated. Gla containing proteins and other proteins normally associated with bone metabolism appear to play an important role in this process. A variety of studies are currently in progress in our laboratory which we hope will provide a more comprehensive understanding of processes leading to coronary calcification as well as prognostic data useful in clinical cardiologic practice. A clearer understanding of the nature and significance of coronary calcification may well pave the way toward new interventions to protect myocardium and minimize the morbidity and mortality associated with coronary artery disease.

Arteriosclerosis↗
PubMed1993

Portal vein calcification: a clinical review of the last 50 years and report of a case associated with dysplasminogenemia.

We report herein a case of a 68-year-old Japanese woman in whom calcification of the portal vein was recognized by plain abdominal X-ray radiograph and computed tomography (CT) scan when she presented with repeated thrombosis of the portal system. Following emergency small bowel resection for intestinal necrosis caused by superior mesenteric vein thrombosis, hematological studies revealed the association of dysplasminogenemia. A review of 21 cases of portal vein calcification reported between 1940 and 1990 revealed the average age to be 53.7 +/- 10.2 years and the male/female ratio 17:4. Although the majority of cases suffered from portal hypertension (81%), only 38% had any evidence of liver cirrhosis, while 52% had normal liver function, being comparable to idiopathic portal hypertension. The calcified lesions were located in the portal vein in 100% of cases, the splenic vein in 62%, the superior mesenteric vein in 33%, and the inferior mesenteric vein in 0%. The precise etiology of the calcification was not elucidated in any of the reviewed cases. The patient reported herein is the first reported case of portal vein calcification due to repeated thrombosis of the portal system caused by dysplasminogenemia, which could be accounted as a cause of idiopathic portal hypertension.

Aged↗
PubMed1983

Frontal lobe calcification in hypoparathyroid states.

Basal ganglion calcification is common in hypoparathyroid states. However, cerebral cortical calcification is rarely seen. Of the six cases previously recorded, five were in patients with idiopathic hypoparathyroidism and only one in a patient with pseudohypoparathyroidism. The present report is of a second case of pseudohypoparathyroidism with cerebral cortical calcification. It is stressed that cortical calcification occurs predominantly in the frontal lobes.

Adult↗
PubMed1980

Metastatic visceral calcification identified by bone scanning.

The scintigraphic abnormalities with radionuclide bone scanning observed in a patient with metastatic breast carcinoma associated with hypercalcaemia are described. Abnormal uptake of 99mTc-pyrophosphate was noted in the lungs, stomach, myocardium, kidneys, and thyroid, indicating metastatic visceral calcification. A scan performed 72 h later when she was normocalcaemic showed marked reduction in the accumulation in the myocardium and thyroid. In a further scan, 18 months later, no extraosseous uptake was present. A review of 26 reported cases of visceral metastatic calcification with scintigraphic abnormalities indicates that the changes in this patient were more widespread and that in only two of the previous cases similar total resolution had been observed. The reasons for the discrepancy between the incidence of visceral calcification on autopsy and on scintigraphic examination are discussed in relation to the aetiological factors. It is concluded that bone scanning offers a useful method for identifying visceral calcification, except when associated with uncomplicated renal failure, and is valuable in detecting this abnormality in patients with hypercalcaemia and in the assessment of response to therapy.

Bone and Bones↗
PubMed1995

Evaluation of four animal models of intrarenal calcium deposition and assessment of the influence of dietary supplementation with essential fatty acids on calcification.

Firstly, to determine a satisfactory animal model for induction of intrarenal calcification, a study of four previously described animal models of intrarenal calcification was carried out which showed that intraperitoneal injection of 10% calcium gluconate into female Sprague-Dawley rats was most effective. We then investigated the hypothesis that dietary supplementation with essential fatty acids could reduce the intrarenal calcification developing as a result of intraperitoneal calcium injection. Using a combination of fish oil and evening primrose oil, we demonstrated a significant difference in renal parenchymal calcification, which was 940 +/- 240 micrograms Ca/g dry weight renal parenchyma in unsupplemented animals and 320-370 +/- 55-65 micrograms Ca/g dry weight renal parenchyma in supplemented animals (means +/- SEM, P < 0.005). It was also demonstrated that there was synergism between eicosapentaenoic acid (EPA) and gamma-linolenic acid (GLA): dietary supplementation with a combined oil preparation containing 27 mg/ml EPA and 67 mg/ml GLA mixed as 2% with food was as effective as oils containing either 400 mg/ml EPA or 80 mg/ml GLA mixed as 4% of food.

Animals↗
PubMed1986

Generalized soft tissue calcification in children and adolescents with end stage renal failure.

Sixteen children and adolescents undergoing regular haemodialysis treatment were studied for the occurrence of metastatic calcifications. By the use of diphosphonate bone-scanning, roentgenography of the chest and skull and ocular slit lamp examination, generalized visceral calcification was diagnosed in two patients. No relationship between visceral calcification and biochemical, radiological or histological abnormalities of renal osteodystrophy was found. Our study demonstrates that visceral calcification also occurs in children with chronic renal failure and may be detected by scintigraphy.

Adolescent↗