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Dysfunction of myocardial sarcoplasmic reticulum in rats with myocardial calcification.

We investigated the relationship between cardiac dysfunction and Ca2+ transport in the myocardial sarcoplasmic reticulum (SR) during the pathogenesis of cardiovascular calcification in rats. The possible mechanism of SR dysfunction was explored by detecting the alteration of the nitric oxide/nitric oxide synthase (NO/NOS) pathway in the SR. Using the vitamin D plus nicotine (VDN treatment for 2 week and 6 week) experimental model of cardiac calcification, cardiac function and sarcoplasmic reticulum function were measured. Inhibition of cardiac functions in vivo (peak rate of contraction and peak rate of relaxation, P < 0.05 or P < 0.01) were observed in all calcification groups, simultaneously, Ca2+ release and uptake in the SR as well as the Ca2+ release channel and Ca2+ pump activity were inhibited. Myocardial Ca2+ concentration and cardiac and SR dysfunction were inversely related (P < 0.05). The specific NO/NOS pathway (NO production, NOS activity and nNOS expression in the SR) was upregulated in the SR and associated with calcification (both 2- and 6 week VDN groups). These results indicate that cardiac dysfunction associated with myocardial calcification might be mediated by SR dysfunction, which may result from an impaired SR-specific NO/NOS pathway.

Animals↗

Vitamin K intake and calcifications in breast arteries.

OBJECTIVES: Vitamin K is an important co-factor in the production of proteins that inhibit vascular calcification. A low dietary Vitamin K intake has been associated with aortic and coronary calcifications and an elevated cardiovascular risk. Calcifications in the arteries of the breasts have also been associated with cardiovascular risk, but whether there is a relation with a low Vitamin K intake has not yet been studied. METHODS: We conducted a cross-sectional study among 1689 women, aged 49-70 years. Dietary Vitamins K1 and K2 intake was calculated from a validated food frequency questionnaire. Breast arterial calcifications (BAC) were assessed on standard screening mammograms by two independent radiologists. With a general linear model mean Vitamins K1, K2 and Vitamin K2 subtypes were calculated for women with BAC and without, adjusted for age, smoking, diabetes, intake of saturated fat, mono-unsaturated fat, poly-unsaturated fat and protein- and calcium-intake. RESULTS: BAC was less common in the highest (9%) quartile of Vitamin K2 intake, compared to the lowest (13%) (OR 0.7, 95% CI 0.5-1.1) and not different across quartiles of Vitamin K1 intake. Mean Vitamin K2 levels and mean levels of Vitamin K2 subtypes MK-5 through MK-10 were lower in the participants with BAC (p=0.01) compared to participants without BAC. However, after adjustment for aging, smoking, diabetes and dietary factors the association of mean Vitamin K2 intake with BAC was no longer significant. CONCLUSION: Calcifications in breast arteries are not associated with a lower dietary intake of Vitamin K.

Aged↗

Calcific aortic valve disease should not be considered as a degenerative disease anymore.

Calcific aortic valve disease is common among the elderly. Until recently, the concept that calcific aortic valve disease is a degenerative and unmodifiable process basically induced by long-lasting mechanical stress was generally accepted. However calcific aortic valve disease is not merely related to age-associated "wear and tear". The development and progression of calcific aortic valve disease are based on an active process that shares a number of similarities with atherosclerosis. Statins and angiotensin-converting enzyme inhibitors have been shown to slow calcium accumulation in aortic valves. Thus, calcific aortic valve disease should not be considered as a degenerative disease anymore.

Aged↗

Arterial calcification in chronic kidney disease.

Hyperphosphatemia is associated with soft-tissue calcification and bone disease. Nephrologists prescribe phosphate binders to decrease dietary phosphate absorption, reduce serum phosphorus concentrations, and minimize the risk for soft-tissue calcification and bone disease. Recent data suggest that the dose of calcium used as a phosphate binder may contribute to the risk for cardiovascular calcification. Chronic positive calcium balance from diet, dialysis, and calcium-based phosphate binders or intermittent hypercalcemia may favor precipitation of calcium and phosphate into tissues. Calcium suppresses parathyroid hormone (PTH) secretion and bone turnover, limiting the ability of bone to incorporate calcium and phosphorus. Sevelamer, a non-absorbed polymer, allows physicians to bind dietary phosphate and decrease serum phosphorus without unwanted absorption of metals or calcium or over-suppression of PTH. In a comparative trial, calcium-based phosphate binders were associated with progressive coronary artery and aortic calcification that was attenuated by sevelamer. The optimal phosphate binder is one that controls hyperphosphatemia prevents soft-tissue calcification and preserves bone health.

Arteries↗

Correlation of cell necrosis and tissue calcification with ischemia/reperfusion injury after liver transplantation.

BACKGROUND: The cellular events following liver ischemia/reperfusion (I/R) during transplantation are largely unknown. The spectrum of I/R damage to the liver can be clinically revealed by the development of primary graft dysfunction or nonfunction. Because viral-induced liver necrosis has been associated with the development of calcifications in an animal model, we investigated the spectrum of I/R changes identified at an ultrastructural level among livers after liver transplant (LT). MATERIALS AND METHODS: Random liver biopsies from five recipients with different degrees of liver dysfunction (LD) were processed for light (LM) and electron (EM) microscopic examination. The degree of calcification was estimated as mild-moderate or severe. The degree of cell vacuolization, used as a surrogate marker of cell necrosis, was reported as mild-moderate or severe. RESULTS: Two patients with severe LD had obvious calcifications by LM and EM examinations. Both showed significant vacuole formation, suggesting a severe degree of cell necrosis, and both succumbed to the sequelae of their LD. One patient showed evidence of mild calcifications at EM (but not LM) examination, with mild vacuole formation. The remaining two patients displayed no microcalcifications. Both presented only mild vacuole formation. Both patients recovered from LD and are currently alive. CONCLUSION: In this preliminary report, we conclude that the clinically observed degree of LD after orthotopic liver transplant (OLT)correlates well with ultrastructural modifications. These include calcification and vacuole formation. We believe that both findings can be used as surrogate markers of a clinically significant hepatic I/R injury.

Biopsy↗

Can the presence of carotid artery calcification on panoramic radiographs predict the risk of vascular diseases among 80-year-olds?

OBJECTIVE: The purpose of this study was to evaluate whether subsequent vascular diseases and related death could be predicted by the presence of carotid artery calcification detected on panoramic radiographs among elderly persons. STUDY DESIGN: We evaluated 659 panoramic radiographs from 262 male and 397 female 80-year-old subjects and their general medical examination data to assess the relationship between the presence of carotid artery calcification and vascular disease risk at baseline examination. Of these subjects, the occurrence of vascular diseases within 5 years after baseline examination was examined in 191 subjects. Further, the causes of death were examined in 108 subjects who died within 5 years after baseline examination. RESULTS: There was a significant difference in the history of past vascular diseases among subjects with and without carotid artery calcifications; however, no significant difference in the occurrence of subsequent vascular diseases was found among them. Further, there was no significant difference in the occurrence of vascular disease-related death within 5 years after baseline examination among subjects with and without carotid artery calcifications (P = 0.719). CONCLUSION: Our results suggest that the presence of carotid artery calcifications on panoramic radiographs may be related to the history of past vascular diseases; however, this is not a useful marker for subsequent vascular diseases and related death among 80-year-olds.

Aged, 80 and over↗

Ureteroscopic laser papillotomy to treat papillary calcifications associated with chronic flank pain.

OBJECTIVES: To evaluate retrospectively the efficacy and durability of a novel approach using ureteroscopic laser papillotomy for the treatment of painful papillary calcifications. Chronic pain due to renal papillary calcifications has not been addressed by current techniques. METHODS: Ureteroscopic holmium laser lithotripsy and papillotomy were performed on patients with chronic pain and radiographically visible papillary calcifications without free collecting system calculi. The papillary urothelium overlying all cystic dilations and intraductal calcifications was vaporized. Treated patients answered a telephone survey to assess pain scores, duration of response, use of narcotics, and patient satisfaction. We reviewed the medical records to evaluate for procedure-related complications and serum creatinine measurements. RESULTS: Of 20 patients who underwent laser papillotomy and responded to the telephone survey, 7 had bilateral procedures, yielding 27 renal units available for analysis. "Much less pain" was reported after 85% of the procedures, with a durable improvement reported after 59% of the procedures, at a median follow-up of 14.5 months. Significant improvements in the median pain scores were seen at 1 month (1.0, P <0.001), 6 months (2.0, P <0.001), and 1 year (1.5, P <0.001) compared with a median preoperative pain score of 9.0. The mean serum creatinine was unchanged after the procedure. CONCLUSIONS: Ureteroscopic laser papillotomy appears to be an effective treatment option for the chronic pain associated with papillary calcifications. Laser papillotomy offers hope to patients who would otherwise have been denied an attempt at treatment because of a lack of free calculi within the collecting system.

Adult↗

Quantification of intramural calcification in coronary intravascular ultrasound images with automated image analysis.

BACKGROUND: Recent studies have documented the utility of intravascular ultrasonography in quantifying coronary morphologic characteristics and determining an appropriate intervention. Unfortunately, its potential for quantifying lesion calcification is limited by subjective evaluation and manual tracing. The aim of this study was to develop an objective automated method for quantifying calcification in intracoronary images with digital image analysis. METHODS: Images of human coronary arteries acquired with a 30 MHz intracoronary ultrasound catheter were evaluated with digital image analysis and compared with manual tracings. Calcifications were automatically identified as highly echogenic regions detected by global thresholding within sectors of acoustic shadowing defined as regions devoid of texture. RESULTS: The mean percentage agreement, sensitivity, and specificity of detecting calcification in 1-degree sectors of calcified vessels were 82%, 73%, and 87%, respectively. Similar results were obtained in noncalcified images. CONCLUSION: The accuracy of this automated technique was comparable to interoperator and intraoperator variability in manually tracing calcification.

Adult↗

Insights into the mechanism of vascular calcification.

Vascular calcification is common and clinically significant in atherosclerosis and heart failure. It was long believed to be an end-stage process of "passive" mineral precipitation. However, there is now a growing awareness that vascular calcification is a biologically regulated phenomenon. It has many similarities to bone formation, and ectopic bone is a well-documented part of vascular calcification. This implies that alterations in vascular cell differentiation, extensive or localized, are an integral part of vascular calcification. Matrix gamma-carboxylated glutamate (GLA) protein (MGP)-deficient mice develop extensive vascular calcification with replacement of the media by progressively calcifying cartilage. A potential mechanism that explains these findings is MGP interference with bone morphogenetic proteins-potent inducers of cartilage and bone.

Animals↗

Calcification in choroidal melanoma after transpupillary thermotherapy.

PURPOSE: To report the response of calcification in choroidal melanoma after transpupillary thermotherapy. METHODS: Interventional case report. A 66-year-old male with a posterior uveal melanoma measuring 10 x 8 x 4.4 mm underwent infrared diode laser transpupillary thermotherapy three times, each 12 weeks apart. For each treatment, a 3-mm spot size of 1-minute duration was used, and the power setting varied between 450 mW and 500 mW. RESULTS: Two months after the last transpupillary thermotherapy session, A- and B-mode echographic patterns strongly suggestive of intratumor calcification were observed. The tumor regressed to 2.8 mm in thickness, but calcification persisted. Local recurrence or distant metastasis was not detected during a follow-up of 14 months. CONCLUSION: Clinically detectable calcification is extremely rare in choroidal melanomas. Tumor regression with slowly progressive calcification may occur after transpupillary thermotherapy.

Aged↗

PC-1 nucleoside triphosphate pyrophosphohydrolase deficiency in idiopathic infantile arterial calcification.

Inogranic pyrophosphate (PPi) inhibits hydroxyapatite deposition, and mice deficient in the PPi-generating nucleoside triphosphate pyrophosphohydrolase (NTPPPH) Plasma cell membrane glycoprotein-1 (PC-1) develop peri-articular and arterial calcification in early life. In idiopathic infantile arterial calcification (IIAC), hydroxyapatite deposition and smooth muscle cell (SMC) proliferation occur, sometimes associated with peri-articular calcification. Thus, we assessed PC-1 expression and PPi metabolism in a 25-month-old boy with IIAC and peri-articular calcifications. Plasma PC-1 was <1 ng/ml by enzyme-linked immunosorbent assay in the proband, but 10 to 30 ng/ml in unaffected family members and controls. PC-1 functioned to raise extracellular PPi in cultured aortic SMCs. However, PC-1 was sparse in temporal artery lesion SMCs in the proband, unlike the case for SMCs in atherosclerotic carotid artery lesions of unrelated adults. Proband plasma and explant-cultured dermal fibroblast NTPPPH and PPi were markedly decreased. The proband was heterozygous at the PC-1 locus, and sizes of PC-1 mRNA and polypeptide, and the PC-1 mRNA-coding region sequence were normal in proband fibroblasts. However, immunoreactive PC-1 protein was relatively sparse in proband fibroblasts. In conclusion, deficient extracellular PPi and a deficiency of PC-1 NTPPPH activity can be associated with human infantile arterial and peri-articular calcification, and may help explain the sharing of certain phenotypic features between some IIAC patients and PC-1-deficient mice.

Arteriosclerosis↗

High glutaraldehyde concentrations mitigate bioprosthetic root calcification in the sheep model.

BACKGROUND: Fixation at high glutaraldehyde (GA) concentrations mitigated bioprosthetic calcification in the rat model. The present study intended to verify this observation in the circulatory sheep model. METHODS: Porcine aortic roots were either fixed in 0.2%, 1.0%, or 3.0% GA. Eight roots per group were implanted in the distal aortic arch of sheep. After six weeks and six months calcification and inflammation were quantitatively and qualitatively assessed. RESULTS: By increasing the GA concentration from 0.2% to 3.0%, aortic wall calcification could be reduced by 38% after 6 weeks and 34% after 6 months of implantation (p < 0.01). Mineralization coincided with the presence of elastin although calcium was predominantly found in cell nuclei and membranes. Leaflet calcification was absent in all groups after 6 weeks but in a few leaflets presented as heterogeneous, nodular spongiosa deposits after 6 months. Overall, differences between 0.2%-, 1.0%-, and 3.0%-fixed tissue were quantitative but not qualitative regarding distribution patterns. There was no significant difference in inflammatory host reaction between all groups. CONCLUSIONS: We have shown in the circulatory sheep model that the anticalcific effect of better cross-linking seems to outweigh the intrinsic pro-calcific effect of GA accumulation in bioprosthetic aortic wall tissue.

Animals↗

Extracorporeal shock wave therapy for chronic calcific tendinitis of the shoulders: a functional and sonographic study.

OBJECTIVES: To evaluate the therapeutic effect of extracorporeal shock wave therapy (ESWT) in shoulders with chronic calcific tendinitis, to compare the functional outcomes of ESWT and transcutaneous electric nerve stimulation (TENS) therapy, and to investigate which types of calcium deposit effectively respond to ESWT. DESIGN: Randomized controlled trial. SETTING: Outpatient clinics of the departments of physical medicine and rehabilitation and of orthopedics and traumatology of a veterans hospital in Taiwan. PARTICIPANTS: Sixty patients with continuous shoulder pain for 6 months or more and with radiographically and sonographically verified calcific tendinitis. Patients were randomly allocated to receive ESWT (33 shoulders) or TENS treatment (30 shoulders). INTERVENTIONS: ESWT was performed with 2000 shock waves at 2Hz and energy level between.26 and.32mJ/mm(2) per session. Treatment was given in 2 sessions, 14 days apart. TENS therapy was given 3 times a week for 4 weeks. MAIN OUTCOME MEASURES: Mean Constant score, visual analog scale (VAS), manual muscle test, and changes of sonographic size and shape of calcium deposits were calculated for 4 time points: at baseline, 2 weeks, 4 weeks, 12 weeks posttherapy. RESULTS: In both groups, Constant score and VAS improved significantly at 2-, 4-, and 12-week follow-ups (P<.05), and the size of calcium deposits decreased significantly at the 4- and 12-week follow-ups. Moreover, the arc-shaped calcific plaques of the rotator cuff were markedly meliorated with ESWT. CONCLUSIONS: ESWT is more effective in the treatment of chronic calcific tendinitis of the shoulder than is TENS therapy, especially for arc-type calcific plaque.

Activities of Daily Living↗

Aortic valve calcification on computed tomography predicts the severity of aortic stenosis.

AIM: Incidental aortic valve calcification is often detected during computed tomography. The aim was to compare the severity of valvular stenosis and calcification in patients with aortic stenosis. MATERIALS AND METHODS: One hundred and fifty-seven patients aged 68+/-11 years (range: 34-85) with aortic valve stenosis underwent multislice helical computed tomography and Doppler echocardiography performed by independent, blinded observers. The aortic valve calcium score was determined using automated computer software calibrated with a phantom. RESULTS: Doppler echocardiography demonstrated a post-valve velocity of 3.45+/-0.66 m/s and a peak gradient of 49+/-11 mmHg. Computed tomography showed excellent reproducibility and the median aortic valve calcium score was 5858 AU (interquartile range, 1555-14,596). The computed tomography aortic valve calcium score positively correlated with the Doppler post-valve velocity and peak gradient (r=0.54, p<0.0001 for both) of the aortic valve. All patients with severe aortic stenosis had a calcium score of >3700 AU. CONCLUSION: Calcification of the aortic valve is closely associated with the severity of aortic stenosis, and heavy calcification suggests the presence of severe aortic stenosis that requires urgent cardiological assessment. Patients with lesser degrees of aortic valve calcification should be screened for aortic stenosis and monitored for disease progression.

Adult↗

Interleukin-1 beta promotes matrix metalloproteinase expression and cell proliferation in calcific aortic valve stenosis.

Calcific aortic valve stenosis (AS), the main heart valve disease in the elderly, is characterized by extensive remodeling of the extracellular matrix. Matrix metalloproteinases (MMPs) are upregulated in calcific AS and might modulate matrix remodeling. The regulatory mechanisms are unclear. As recent studies have suggested that calcific AS might result from an inflammatory process involving leukocyte invasion and activation, the present study aimed to elucidate the role of the pro-inflammatory cytokine interleukin (IL)-1 beta on MMP expression and cell proliferation in human aortic valves. Immunohistochemistry for leukocytes, IL-1 beta and MMP-1 was performed on aortic valves with (n=6) and without (n=6) calcification obtained at valve replacement or autopsy. Stenotic valves showed marked leukocyte infiltration and associated expression of IL-1 beta and MMP-1. In control valves only scattered leukocytes, low staining for MMP-1 and no staining for IL-1 beta were present. Double-label immunostaining localized IL-1 beta expression mainly to leukocytes and MMP-1 expression to myofibroblasts. Stimulation of cultured human aortic valve myofibroblasts with IL-1 beta lead to a time-dependently increased expression of MMP-1 and MMP-2 by Western blotting and zymography, whereas MMP-9 remained unchanged. Cell proliferation was increased by IL-1 beta as determined by bromodesoxyuridine incorporation. Thus, IL-1 beta may regulate remodeling of the extracellular matrix in calcific AS.

Aortic Valve Stenosis↗

Renal calcification in preterm infants: pathophysiology and long-term sequelae.

We examined the clinical course of 17 preterm infants with chronic lung disease who received loop diuretics and developed nephrocalcinosis; nine of them were followed for up to 4.5 years. The mean gestational age was 26.8 weeks (SD 2.2 weeks), and mean birth weight was 830 gm (SD 276 gm). The diagnosis of renal calcification was made at a mean age of 12 weeks (SD 6.5 weeks) by abdominal x-ray examination, screening abdominal ultrasound studies or, both. Calcification was associated with both furosemide therapy and the presence of multiple potential risk factors. Renal calcification, length, and function were subsequently evaluated in nine patients at a mean age of 21.3 months (SD 15.3 months). Improvement in calcification occurred in five patients, with total resolution in four. Renal length, determined by ultrasound examination and corrected for body length, was normal in 17 of 18 kidneys. Serum creatinine values and calculated glomerular filtration rates were abnormal in four of nine patients. We conclude that renal calcification in preterm infants is associated with multiple risk factors, including furosemide usage, and tends to diminish during the first year of life. However, renal function may remain compromised in some patients.

Birth Weight↗

Calcifications in pituitary adenomas.

In a surgical series of 755 pituitary adenomas, 51 cases (6.75%) showed intratumoral calcifications on microscopic examination and 13 of these were visible on roentgenographic examination (1.72%). Thirty-eight of these 51 cases were prolactinomas, the highest incidence being in male patients. There was no correlation between age, sex, levels of hormone, size of the tumor, and the presence of calcifications. Four patterns of radiological calcifications were encountered. Histologically, the calcifications were most frequently found within the tumor masses. Their rare occurrence within fibrous or degenerative areas speaks against their dystrophic nature. Previously reported calcified bodies in fetal and newborn pituitaries and the recently described physiological hyperprolactinemia in early infancy suggest a possible hormonal influence in the genesis of calcifications in prolactinomas.

Adenoma↗

A computerized tank system for studying the effect of temperature on calcification of reef organisms.

Mediated by algal symbionts, calcification in reef building corals is one of the important processes, which enable coral's growth. In the present study, we used a buoyant weighing technique to study calcification of two coralline species, Stylophora pistillata and the hydrocoral Millepora dichotoma. The colonies were grown in a tank system, in which light, nutrition and water motion were kept constant and temperature was elevated by means of a computerized controlled apparatus. An almost constant rate of calcification was observed in the two species at 22-28 degrees C. Elevation of the temperature above this range to 29-31 degrees C caused a slow down in calcification in both species. A grater number of S. pistillata colonies became bleached at temperatures of >or=29 degrees C, whereas M. dichotoma colonies suffered from bleaching only after three days at 31 degrees C. For both species, control groups, remained viable during the experimental period. The differences in responses to changes in temperature of the two species may be as a consequence of different adaptive mechanisms or to different susceptibilities of the corals to elevated temperatures. We have shown that elevating temperatures above annual maximal ranges have a significant effect on coral calcification. We also demonstrated that sessile calcified marine organisms having ecological and biomedical significance could be cultured and manipulated under laboratory conditions.

Animals↗