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Long-term effects of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate and 6-nitro-7-sulphamoylbenzo(f)quinoxaline-2,3-dione in the rat basal ganglia: calcification, changes in glutamate receptors and glial reactions.

Previous data from our laboratory indicate that 25 mM ibotenic acid induces intracellular calcifications in the rat basal forebrain. Because of the lack of specificity of ibotenic acid for a glutamate receptor subtype, a dose-response study with alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate was undertaken and calcified areas (identified with Alizarin Red staining) as well as astro- and microglial reactions (by autoradiography with [3H]lazabemide and [3H]Ro 5-4864) were quantified at one month post-lesion. alpha-Amino-3-hydroxy-5-methyl-4-isoxazole propionate administered into the globus pallidus induced, in a dose-dependent manner, the formation of calcium deposits and the activation of both glial cells, the microglial reaction being particularly robust. From this study, a dose of 5.4 mM alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate was selected for further experiments. [3H]alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate, [3H]dizocilpine maleate and [3H]PN 200-110 binding in vitro were performed to assess autoradiographically whether the tissue damage was associated with changes in glutamate receptors and calcium channel binding sites. In the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate-treated animals, the specific binding of [3H]alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate was significantly reduced by 28% in the lesioned ventral pallidum, whereas it was unchanged in the globus pallidus and substantia innominata. In these three nuclei, calcifications developed and an increase in both glial markers was measured. In contrast, the binding of [3H]PN 200-110 and [3H]dizocilpine maleate were unaffected. Co-injection of 15 mM 6-nitro-7-sulphamoylbenzo(f)quinoxaline-2,3-dione, a selective alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate/kainate receptor antagonist, prevented the formation of calcium concretions, the microglial reaction and the decrease in [3H]alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate binding but it failed to inhibit totally the astroglial reaction induced by alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate. This may suggest that the microglial reaction and calcification take place through different mechanisms from the astrogliosis associated with the neuronal loss. In conclusion, acute administration of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate in the rat globus pallidus elicits a dose-dependent calcification process associated with a chronic reaction of astrocytes and microglia. alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate-induced injury is accompanied by a slight reduction of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors in the ventral pallidum, whereas the binding of N-methyl-D-aspartate and L-type calcium channels receptors remains unchanged in any lesioned nucleus.

Animals↗

[Calcification following intradiscal injection, a continuing problem?].

INTRODUCTION: Intradiscal injection of triamcinolone hexacetonide, used to treat sciatica caused by herniated discs was discontinued after discovery that it was followed in some cases by epidural calcification. OBSERVATION: Ten years after an intradiscal injection at L4-L5, a 40 year-old man developed voluminous perivertebral, bilateral foraminal and intraductal calcifications that compressed the dural sheath. After preliminary excision, these calcifications recurred and required further excision, followed by posterior lateral grafting and osteosynthesis. DISCUSSION: Calcifications following intradiscal injections are symptomatic in 14 to 68% of cases. They require radical surgical treatment to avoid recurrence.

Adult↗

Transesophageal echocardiography in the presence of left atrial calcification.

Calcification of left atrial walls is a rare finding that has been reported to hamper visibility of intracardiac structures during transesophageal echocardiography because of the posterior location of the left atrium. We report a case of severe mitral stenosis associated with heavy left atrial calcification in which we could obtain good quality transesophageal imaging in spite of such a calcification. We conclude that calcification of left atrial walls does not necessarily imply a limitation of transesophageal echocardiography.

Adolescent↗

Pan-valvular annular calcification in Takayasu's arteritis: report of 3 cases.

Takayasu's arteritis is a chronic inflammatory arteriopathy. It mainly affects the aortic arch and its main branches. The aortic valve annulus and coronary and pulmonary arteries are rarely affected. Mitral and tricuspid annular calcification were not reported previously. We identified mitral annular calcification by using transthoracic echocardiography in 3 patients with Takayasu's arteritis, in whom none had any of the reported causes of mitral annular calcification. Two of them had concomitant tricuspid and aortic annular calcification.

Adult↗

CT features of calcifications in abdominal malignant fibrous histiocytoma.

The purpose of this study was to describe the computed tomographic (CT) features of intralesional calcifications in abdominal malignant fibrous histiocytomas (MFH). Forty-three pathologically proven abdominal MFH with preoperative CT were retrospectively reviewed, of which seven tumors with intralesional calcifications were studied with pathohistologic correlation. All seven calcified abdominal MFH belonged to the storiform-pleomorphic subtype with peripherally located calcifications that appeared as either lumpy (three cases) or ringlike (four cases), which were due to the presence of variable amounts of osseous (six cases) and chondroid metaplasia (two cases). About 16% of abdominal MFH, especially the storiform-pleomorphic subtype, exhibited metaplastic calcifications which were characteristically located at the periphery of the tumor and appeared as either lumpy or ringlike on CT.

Abdominal Neoplasms↗

Inhibition of calcification in vivo by acyl azide cross-linking of a collagen-glycosaminoglycan sponge.

A collagen-glycosaminoglycan sponge composed of collagen (80%), chondroitin-4-sulfate (13.3%) and heparan sulfate (6.6%) was cross-linked using the acyl azide method or glutaraldehyde (0.0075%). Under optimal conditions, the denaturation temperature (Td) was raised to 69 degrees C (+23 degrees C) for the sponge treated by the acyl azide method and to 68 degrees C (+22 degrees C) for that treated with glutaraldehyde. The biocompatibility of the treated and control sponges was studied up to 3 months after subcutaneous implantation in rats by analysing cellular responses and calcification by histological and ultrastructural methods. A control collagen-glycosaminoglycan sponge was rapidly invaded by mononuclear cells (8 days), with the formation of granulation tissue. Calcification was observed at the periphery of the implant after 8 days, and the implant was entirely calcified after 15 days; it was degraded progressively after 30 days. Acyl azide treatment increased the persistence of the sponge in vivo up to 90 days and inhibited its calcification. A glutaraldehyde-treated sponge was completely calcified after 15 days, and calcified nodules persisted after 90 days. Thus, acyl azide method efficiently cross-linked a collagen-glycosaminoglycan sponge and inhibited calcification after subcutaneous implantation in rats (at least up to 90 days after implantation).

Animals↗

Cutaneous ectopic breast calcification in a haemodialysis patient.

This case report details the unique breast calcification and swellings of a 61-year-old lady. The ectopic breast calcification was a result of chronic renal failure and hyperparathyroidism secondary to vesiculo-ureteric reflux nephropathy. Subcutaneous nodules were also noted around her ileostomy (from surgery due to Crohn's disease) and abdominal wall. Mammogram revealed calcified breast discs and lobules with extensive vascular calcification. Histological biopsies revealed extensive calcium deposition (benign). Cutaneous deposition of calcium oxalate has been described in 13 patients world wide, usually involving fingers, ears, or nose. Two of these report breast involvement, but this is described as less extensive and more focal calcification on clinical findings and mammography. This case report describes a rare condition with extraordinary mammographic images.

Breast↗

Association of Chlamydia IgG Titers with Laproscopic Findings of Dystrophic Calcification and Hydrosalpinges but not with Endosalpingiosis

Psammoma bodies are discrete forms of dystrophic calcification which represent cross-sections of calcified papillary formations. At laparoscopy, these have been confused with both endometriosis and cancer. A recent abstract (Khare et al: AAGL, 1993) reported the association of peritoneal psammoma bodies (grain-like inclusions) with positive IgG chlamydia titers (p=0.012). The purpose of this study is to investigate a possible correlation of chlamydia IgG titers with endosalpinges. Histologic slides and charts of 60 consecutive women were reviewed in a blinded fashion for calcification, hydrosalpinx, endosalpingiosis, and other significant changes. Although dystrophic calcification and hydrosalpinges were associated with positive chlamydia IgG titers (p<0.05), endosalpingiosis was found in only one patient. This study confirms previous studies in showing a relationship of chlamydia IgG titers with dystrophic calcification and hydrosalpinges but did not demonstrate a relationship with endosalpingiosis.

Journal Article↗

Simulation model of mammographic calcifications based on the American College of Radiology Breast Imaging Reporting and Data System, or BIRADS.

RATIONALE AND OBJECTIVES: The authors developed and evaluated a method for the simulation of calcification clusters based on the guidelines of the Breast Imaging Reporting and Data System of the American College of Radiology. They aimed to reproduce accurately the relative and absolute size, shape, location, number, and intensity of real calcifications associated with both benign and malignant disease. MATERIALS AND METHODS: Thirty calcification clusters were simulated by using the proposed model and were superimposed on real, negative mammograms digitized at 30 microns and 16 bits per pixel. The accuracy of the simulation was evaluated by three radiologists in a blinded study. RESULTS: No statistically significant difference was observed in the observers' evaluation of the simulated clusters and the real clusters. The observers' classification of the cluster types seemed to be a good approximation of the intended types from the simulation design. CONCLUSION: This model can provide simulated calcification clusters with well-defined morphologic, distributional, and contrast characteristics for a variety of applications in digital mammography.

Breast Neoplasms↗

Schizophrenia and familial idiopathic basal ganglia calcification: a case report.

BACKGROUND: Familial idiopathic basal ganglia calcification (FIBGC) is generally associated with neurological and psychiatric symptoms. An association between FIBGC and schizophrenia has been described but it remains uncertain. We studied the relationship between the presence and extent of basal ganglia calcification and schizophrenia in a multiply affected family. METHOD: Symmetrical basal ganglia calcifications (BGC) were detected on computerized tomography (CT) in a schizophrenic proband and led us to carry out CTs and standardized psychiatric evaluations (SADS--Endicott & Spitzer, 1978) in all available first-degree relatives (mother and six siblings). RESULTS: Five subjects had BGC, including three subjects diagnosed as schizophrenic. Three subjects had no BGC and none of them was diagnosed as schizophrenic. We subdivided the BGC into three groups: massive (pallidum, striatum and dentate nuclei affected); medium (pallidum and striatum); and mild (pallidum only). The two subjects with massive BGC and one of the two with medium BGC had schizophrenia. The subject with mild BGC had no psychotic symptoms. CONCLUSION: Our results are consistent with the hypothesis that BGC favours the occurrence of a schizophrenia-like syndrome and that the risk of occurrence of this syndrome is proportional to the extent of calcification. These findings support the hypothesis that schizophrenia is determined by a disruption of thalamo-cortico-striatal circuits.

Adult↗

Glutaraldehyde-fixed biological tissue calcification: effectiveness of mitigation by dimethylsulphoxide.

The conditions defining the extent of dimethylsulphoxide (DMSO) effectiveness in mitigating calcification of glutaraldehyde (GA)-fixed tissue have been evaluated. Exposure of GA-fixed tissue porcine aortic valve cusps to low concentrations of DMSO does not impart calcification inhibitory activity. Mitigation in calcification becomes evident only as the DMSO component nears 100% and is best when neat DMSO is used. In all instances, regardless of the DMSO concentration, exposure to DMSO resulted in an increase in the tissue shrinkage temperature, attributed to further cross-linking in the tissue. Histological examination of samples before implantation indicate some deleterious effects to the tissue, the degree dependent on concentration, time and temperature of DMSO exposure. The results of this study suggest that treatment of GA-fixed tissue with high concentrations of DMSO for a short duration at a lowered temperature could give a bioprosthesis that has good mitigating calcification properties with retention of tissue integrity.

Journal Article↗

Reproducibility of two coronary calcium quantification algorithms in patients with different degrees of calcification.

PURPOSE: To evaluate the reproducibility of coronary calcium quantification algorithms by electron beam CT (EBT) in patients with different amounts of calcified plaque using the conventional (Agatston) score and an area score and to demonstrate a potential application of these results for evaluation of follow-up scans. METHODS: In 50 consecutive patients. the conventional calcium score (CCS = Agatston score) and the area score (AS) were summed for each artery and patient. Data were analyzed in four groups according to degrees of calcification: 0 (absent-minimal): CCS 0-9, I (mild): CCS 10-99, II (moderate): CCS 100-399, III (severe): CCS > or = 400. We determined and compared the reproducibility for each algorithm within and among groups. RESULTS: Median percent reproducibility improved with increasing amounts of calcified plaque for the CCS and the AS (p = 0.002 and p = 0.004, respectively). We demonstrate how these reproducibility values can be used to evaluate long-term follow-up studies. The reduction of median reproducibility per patient using the AS vs. the CCS was 32% (13 vs. 19%, respectively). On a vessel-by-vessel basis, the reduction of median reproducibility was 7% (24.3 vs. 22.6%, CCS vs. AS, p < 0.02), which was attributable to a 45% reduction in reproducibility in arteries with mild scores (46.1 vs. 25.5%, CCS vs. AS, p < 0.005). CONCLUSION: The AS has an improved reproducibility compared with the CCS, especially in patients with small amounts of coronary calcifications which may prove clinically useful. Different reproducibility values in different degrees of calcification can be used for an individual assessment of changes in amounts of coronary calcification.

Adult↗

Calcification and identification of metalloproteinases in bovine pericardium after subcutaneous implantation in rats.

The purpose of this study was to evaluate the influence of two anticalcification pre-treatments (chloroform/methanol and ethanol) and serum conditioning of glutaraldehyde-crosslinked bovine pericardium on the calcification degree and the presence of gelatinase activities in a subcutaneous implantation model in rats. Regarding calcification of the implants, glutaraldehyde control treatments showed a significatively higher calcification degree than pericardium treated with anticalcification reagents. Serum conditioning of glutaraldehyde treated tissues did not influence the calcification degree; moreover, no differences were found in these samples with the time of implantation (30 and 90 days). On the other hand, anticalcification treatments resulted in a very significant decrease in the calcium content in the implanted membranes. Gelatinase activities were detected by gelatin zymography in almost all the implanted samples. However, control tissues with and without serum conditioning showed less gelatinase activities than those samples pre-treated with anticalcification treatments. Metalloproteinase (MMP-2) activity was detected in all the samples analyzed but a higher expression of MMP-9 was detected in those implants treated with chloroform/methanol and ethanol. Additional gelatinase activities showing lower molecular weight than MMP-2 were also detected in both anticalcification treated samples. The presence of these gelatinase activities is probably due to host cellular infiltrates and could contribute to the biomaterial degradation.

Journal Article↗

Intratubular calcification in a post-renal transplanted patient with secondary hyperparathyroidism.

In this article, we present a case in which marked intratubular calcification occurred in the transplanted kidney. The patient received living renal transplantation without control of severe secondary hyperparathyroidism, and the tacrolimus hydrate was used as an immunosuppressive agent, the adverse effects of which can induce intratubular calcification. Biopsy of the renal allograft revealed many intratubular calcifications in the cortex region of the specimen, although the histological grade was borderline for the Banff classification. The pathogenic causes of intratubular calcification were difficult to distinguish from the adverse effects of tacrolimus and the uncontrolled hyperparathyroidism.

Biopsy↗

Reduced calcification of marine plankton in response to increased atmospheric CO2.

The formation of calcareous skeletons by marine planktonic organisms and their subsequent sinking to depth generates a continuous rain of calcium carbonate to the deep ocean and underlying sediments. This is important in regulating marine carbon cycling and ocean-atmosphere CO2 exchange. The present rise in atmospheric CO2 levels causes significant changes in surface ocean pH and carbonate chemistry. Such changes have been shown to slow down calcification in corals and coralline macroalgae, but the majority of marine calcification occurs in planktonic organisms. Here we report reduced calcite production at increased CO2 concentrations in monospecific cultures of two dominant marine calcifying phytoplankton species, the coccolithophorids Emiliania huxleyi and Gephyrocapsa oceanica. This was accompanied by an increased proportion of malformed coccoliths and incomplete coccospheres. Diminished calcification led to a reduction in the ratio of calcite precipitation to organic matter production. Similar results were obtained in incubations of natural plankton assemblages from the north Pacific ocean when exposed to experimentally elevated CO2 levels. We suggest that the progressive increase in atmospheric CO2 concentrations may therefore slow down the production of calcium carbonate in the surface ocean. As the process of calcification releases CO2 to the atmosphere, the response observed here could potentially act as a negative feedback on atmospheric CO2 levels.

Atmosphere↗

Pulmonary calcification in hemodialyzed patients detected by technetium-99m diphosphonate scanning.

Metastatic pulmonary calcification, a well-known complication in patients with chronic disease, has been demonstrated postmortem in patients with a negative chest X-ray. Recently, scintigrams with bone-seeking radionuclides have been used to detect such subclinical pulmonary calcium deposits. We describe 23 patients on maintenance hemodialysis with no evidence of pulmonary calcification on chest X-ray who were prospectively studied by lung scanning with a bone-seeking radionuclide and pulmonary function testing. Of the 23 patients, 14 (61%) had a positive technetium-99m diphosphonate (99mTc-DP) scan (group 1). These patients were on dialysis 38 +/- 5 months compared with 12 +/- 4 months in 9 patients with a negative scan (group 2) (P less than 0.01). Age, sex, blood pressure, hematocrit, serum calcium, phosphorous, bicarbonate, magnesium, and calcium X phosphorus product, as well as parathyroid hormone level did not differ between the two groups. Of 10 group-1 patients tested, 7 had abnormal pulmonary diffusion capacity compared with non in 5 group-2 patients tested (P = 0.014). Histologic examination of the lung in 1 group-1 patients who expired revealed calcification (amorphous on X-ray diffraction), whereas none was found in 1 group-2 patients autopsied. These observations suggest that in patients on maintenance hemodialysis, pulmonary scanning with 99mTc-DP is a sensitive method for detecting pulmonary metastatic calcification, which may be associated with an abnormality in pulmonary diffusion capacity.

Adult↗

Carminerin contributes to chondrocyte calcification during endochondral ossification.

Endochondral ossification is an essential process not only for physiological skeletal development and growth, but also for pathological disorders. We recently identified a novel cartilage-specific molecule, carminerin (also known as cystatin 10 and encoded by Cst10), which is upregulated in synchrony with cartilage maturation and stimulates the later differentiation of cultured chondrocytes. Although carminerin-deficient (Cst10-/-) mice developed and grew normally, they had a microscopic decrease in the calcification of hypertrophic chondrocytes at the growth plate. When we created experimental models of pathological endochondral ossification, we observed suppression of chondrocyte calcification during formation of osteoarthritic osteophytes, age-related ectopic ossification and healing of bone fractures in Cst10-/- mice. Cultured Cst10-/- chondrocytes showed a reduction in calcification with activation of an SRY site in the promoter of the gene encoding nucleotide pyrophosphatase phosphodiesterase 1 (NPP1, encoded by Enpp1). Functional NPP1 is required for carminerin deficiency to suppress the pathological endochondral ossifications listed above. Carminerin is the first cartilage-specific protein that contributes to chondrocyte calcification during endochondral ossification under physiological and pathological conditions through the transcriptional inhibition of NPP1.

Animals↗

Oxidative stress, advanced glycation end product, and coronary artery calcification in hemodialysis patients.

Coronary artery calcification is an index of the severity of atherosclerotic vascular disease, and may predict future adverse cardiovascular events in uremic patients undergoing hemodialysis (HD). HD patients are exposed to oxidative stress, and show high plasma levels of advanced glycation end products (AGEs). The association between oxidative stress, AGEs, established cardiovascular risk factors, and coronary artery calcification score (CACS) was studied in 225 HD patients (123 male, 102 female patients). CACS was measured by using multi-detector row computed tomography. Age, systolic blood pressure, calcium, calcium x phosphate, malondialdehyde, lipid peroxides, and pentosidine were significantly and positively correlated with CACS. Duration on HD tended to be positively correlated with CACS. From the independent variables included in the forward stepwise multiple linear regression analysis, only age, systolic blood pressure, lipid peroxides, calcium, and pentosidine were independently associated with CACS. The odds ratios for past history of coronary artery disease and the presence of diabetes mellitus for high CACS (> or =100) were 6.25 (95% confidence interval; 1.83-21.4) and 2.03 (95% confidence interval; 1.02-4.05), respectively. The plasma pentosidine was significantly and positively correlated with indoxyl sulfate. In conclusion, in addition to such traditional cardiovascular risk factors as past history, diabetes mellitus, aging, systolic blood pressure and calcium overload, oxidative stress (lipid peroxides), and AGE (pentosidine) are associated with extensive coronary artery calcification in HD patients. Lipid peroxidation and glycoxidation may be involved in the pathogenesis of coronary artery calcification.

Aged↗