ascorbic-acid and Calcinosis

A 50-year-old man presented with a complaint of low-back pain and widespread joint pain for the previous 20 years. Conventional radiography revealed wide areas of calcification in the intervertebral discs and degenerative changes in the peripheral joints. A diagnosis of ochronosis was made by the observation of bluish-brown pigmentation in the nose and ears, dark urine colors following alkalization, and high levels of homogentisic acid in the urine. Ochronosis should be considered in the differential diagnosis of patients with chronic low-back pain regarding features of widespread calcification in the intervertebral discs at radiography and bluish-brown pigmentation in the nose and ears.

Topics: Alkaptonuria; Anti-Inflammatory Agents, Non-Steroidal; Arthralgia; Ascorbic Acid; Back Pain; Calcinosis; Chronic Disease; Diagnosis, Differential; Diclofenac; Homogentisic Acid; Humans; Intervertebral Disc; Male; Middle Aged; Ochronosis; Radiography; Treatment Outcome; Vitamins

We sought to determine whether lipid-lowering therapy and antioxidants retard the progression of coronary calcification and prevent atherosclerotic cardiovascular disease (ASCVD) events.. The electron beam computed tomography-derived coronary calcium score predicts coronary disease events. Small, uncontrolled studies suggest that vigorous lipid-lowering therapy slows progression of coronary calcification and prevents coronary artery disease events, but controlled, scientific demonstration of these effects is lacking.. We conducted a double-blind, placebo-controlled randomized clinical trial of atorvastatin 20 mg daily, vitamin C 1 g daily, and vitamin E (alpha-tocopherol) 1,000 U daily, versus matching placebos in 1,005 asymptomatic, apparently healthy men and women age 50 to 70 years with coronary calcium scores at or above the 80th percentile for age and gender. All study participants also received aspirin 81 mg daily. Mean duration of treatment was 4.3 years.. Treatment reduced total cholesterol by 26.5% to 30.4% (p < 0.0001), low-density lipoprotein cholesterol by 39.1% to 43.4% (p < 0.0001), and triglycerides by 11.2% to 17.0% (p < or = 0.02) but had no effect (p = 0.80) on progression of coronary calcium score (Agatston method). Treatment also failed to significantly reduce the primary end point, a composite of all ASCVD events (6.9% vs. 9.9%, p = 0.08). Event rates were related to baseline calcium score (pre-specified analysis) and may have been reduced in a subgroup of participants with baseline calcium score >400 (8.7% vs. 15.0%, p = 0.046 [not a pre-specified analysis]).. Treatment with alpha-tocopherol, vitamin C, and low doses of atorvastatin (20 mg once daily) did not affect the progression of coronary calcification. Treatment may have reduced ASCVD events, especially in subjects with calcium scores >400, but these effects did not achieve conventional levels of statistical significance.

Topics: Aged; alpha-Tocopherol; Antioxidants; Ascorbic Acid; Aspirin; Atorvastatin; Calcinosis; Coronary Artery Disease; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Platelet Aggregation Inhibitors; Pyrroles; Tomography, X-Ray Computed

Chronic kidney disease (CKD) patients undergoing dialysis are at high risk of bone fractures. CKD-induced mineral and bone disorder is extended to periodontal disease due to changes in the ionic composition of saliva in CKD patients, dysregulating mineralization, hindering regeneration and thereby promoting the progression of dental complications. Despite the importance of cementum for overall oral health, the mechanisms that regulate its development and regeneration are not well comprehended, and a lack of sufficient in vitro experimental models has hindered research progress. In this study, the impact of experimental conditions on the calcification of cementoblasts was systematically investigated, aimed at establishing a standardized and validated model for the calcification of cementoblasts. The effects of phosphate, calcium, ascorbic acid, β-glycerolphosphate, dexamethasone, and fetal calf serum on the calcification process of cementoblasts were analyzed over a wide range of concentrations and time points by investigating calcium content, cell viability, gene expression and kinase activity. Cementoblasts calcified in a concentration- and time-dependent manner with higher concentrations of supplements cause a higher degree of calcification but decreased cell viability. Phosphate and calcium have a significantly stronger effect on cementoblast calcification processes compared to osteogenic supplements: ascorbic acid, β-glycerolphosphate, and dexamethasone induce calcification over a wide range of osteogenic signalling pathways, with osteopontin being a central target of gene regulation. Conversely, treatment with ascorbic acid, β-glycerolphosphate, and dexamethasone leads to activating only selected pathways, especially promoting bone sialoprotein expression. The developed and validated cementoblast calcification protocol, incubating up to 60% confluent cementoblasts with 1.9 mmol L

Topics: Ascorbic Acid; Calcinosis; Calcium; Calcium, Dietary; Dental Cementum; Dexamethasone; Glycerophosphates; Humans; Osteogenesis; Periodontium; Renal Dialysis

Comparative in vitro study examined the osteogenic potential of interstitial cells of aortic valve obtained from the patients with aortic stenosis and from control recipients of orthotopic heart transplantation with intact aortic valve. The osteogenic inductors augmented mineralization of aortic valve interstitial cells (AVIC) in patients with aortic stenosis in comparison with the control level. Native AVIC culture of aortic stenosis patients demonstrated overexpression of osteopontin gene (OPN) and underexpression of osteoprotegerin gene (OPG) in comparison with control levels. In both groups, AVIC differentiation was associated with overexpression of RUNX2 and SPRY1 genes. In AVIC of aortic stenosis patients, expression of BMP2 gene was significantly greater than the control level. The study revealed an enhanced sensitivity of AVIC to osteogenic inductors in aortic stenosis patients, which indicates probable implication of OPN, OPG, and BMP2 genes in pathogenesis of aortic valve calcification.

Topics: Aged; Aortic Valve; Aortic Valve Stenosis; Ascorbic Acid; Bone Morphogenetic Protein 2; Calcinosis; Cell Differentiation; Core Binding Factor Alpha 1 Subunit; Dexamethasone; Female; Gene Expression Regulation; Glycerophosphates; Heart Transplantation; Humans; Male; Membrane Proteins; Middle Aged; Osteoblasts; Osteogenesis; Osteopontin; Osteoprotegerin; Phosphoproteins; Primary Cell Culture; Stromal Cells; Tricuspid Valve

Vitamin D deficiency (hypovitaminosis D) causes osteomalacia and poor long bone mineralization. In apparent contrast, hypovitaminosis D has been reported in patients with primary brain calcifications ("Fahr's disease"). We evaluated the expression of two phosphate transporters which we have found to be associated with primary brain calcification (SLC20A2, whose promoter has a predicted vitamin D receptor binding site, and XPR1), and one unassociated (SLC20A1), in an in vitro model of calcification. Expression of all three genes was significantly decreased in calcifying human bone osteosarcoma (SaOs-2) cells. Further, we confirmed that vitamin D (calcitriol) reduced calcification as measured by Alizarin Red staining. Cells incubated with calcitriol under calcifying conditions specifically maintained expression of the phosphate transporter SLC20A2 at higher levels relative to controls, by RT-qPCR. Neither SLC20A1 nor XPR1 were affected by calcitriol treatment and remained suppressed. Critically, knockdown of SLC20A2 gene and protein with CRISPR technology in SaOs2 cells significantly ablated vitamin D mediated inhibition of calcification. This study elucidates the mechanistic importance of SLC20A2 in suppressing the calcification process. It also suggests that vitamin D might be used to regulate SLC20A2 gene expression, as well as reduce brain calcification which occurs in Fahr's disease and normal aging.

Topics: Ascorbic Acid; Calcinosis; Calcitriol; Cell Differentiation; Cell Line, Tumor; CRISPR-Cas Systems; Gene Knockdown Techniques; Glycerophosphates; Humans; Models, Biological; Phosphate Transport Proteins; Receptors, Calcitriol; Receptors, G-Protein-Coupled; Receptors, Virus; RNA, Messenger; Sodium-Phosphate Cotransporter Proteins, Type III; Up-Regulation; Xenotropic and Polytropic Retrovirus Receptor

To establish human heart valve interstitial cells calcification culture model in vitro, and observe the effect of bone morphogenetic protein-2 (BMP-2) on calcification of human heart valve interstitial cells.. Human heart valve interstitial cells were cultured in vitro, and divided into control group: cells were cultured in conventional media plus recombinant human BMP-2 treatment and experimental group: besides above treaments, calcification inducers ( recombinant human BMP-2, β-glycerophosphate, L-ascorbic acid, dexamethasone) were added to the culture media. The two group of cells were cultured for 14 days and were stained by Von Kossa, then the cell calcification was observed in this valvular interstitial cells calcification culture model in vitro. Protein expression of intercellular adhesion molecule 1 (ICAM-1), interleukin 8, BMP-2 and BMP-4 was determined by Western blot and BMP-2 secretion was measured by ELISA.. In the control group, the structure of human heart valve interstitial cells was clear, and the spindle and radial growth shaped cellular morphology was visible, and Von Kossa staining was negative. In the experimental group, the nuclei become darker in color, and granular sediment distribution was seen surrounding cells, and Von Kossa staining was positive, the cells were forming nodules of calcification. The protein expression of ICAM-1, interleukin 8, BMP-2 and BMP-4 in the experimental was significantly higher than that of the control group (all P < 0.05). The expression of BMP-2 in the experimental group was also significantly higher than that in control group ((92.5 ± 4.9) pg/ml vs. (22.2 ± 1.9) pg/ml, P < 0.05).. Human BMP-2, β-glycerophosphate, L-ascorbic acid, and dexamethasone can induce human heart valve interstitial cells calcification and enhance inflammation in vitro by stimulating the secretion of BMP-2.

Topics: Ascorbic Acid; Bone Morphogenetic Protein 2; Calcinosis; Cells, Cultured; Glycerophosphates; Heart Valve Diseases; Humans; Recombinant Proteins; Transforming Growth Factor beta

Cerebral malakoplakia is a very rare chronic inflammatory disease. We herein report the case of a 49-year-old female who presented with a slowly progressive speech disturbance and right hemiparesis. Computed tomography and magnetic resonance imaging showed irregular enhanced mass lesions with numerous scattered areas of calcification in the left insula, thalamus and basal ganglia. Histopathologically, the biopsy specimen showed basophilic laminated inclusion bodies and intracellular and extracellular calculospherules, usually with a typical targetoid appearance (Michaelis-Gutmann bodies). Treatment with antibiotics, bethanechol and ascorbic acid improved her symptoms in association with a decrease in the abnormal calcification and enhancement. The cerebral malakoplakia mimicked a brain tumor in terms of the patient's clinical course and neuroradiological image findings; however, it was successfully cured with medical treatment. This case provides evidence that the pathogenesis of cerebral malakoplakia is deeply tied to bacterial infection and that medical treatment is effective in cases of this disease.

Topics: Anti-Bacterial Agents; Ascorbic Acid; Bethanechol; Brain; Calcinosis; Female; Humans; Inclusion Bodies; Malacoplakia; Middle Aged; Muscarinic Agonists; Vitamins

Topics: Arthritis; Ascorbic Acid; Autistic Disorder; Calcinosis; Child; Gingival Hypertrophy; Humans; Knee Joint; Male; Radiography; Scurvy

Aortic valve calcification (AVC) is an active process characterized by osteoblastic differentiation of the aortic valve interstitial cells (AVICs). Taurine is a free β-amino acid and plays important physiological roles including protective effect of cardiovascular events. To evaluate the possible role of taurine in AVC, we isolated human AVICs from patients with type A dissection without leaflet disease. We demonstrated that the cultured AVICs express SM α-actin, vimentin and taurine transporter (TAUT), but not CD31, SM-myosin or desmin. We also established the osteoblastic differentiation model of the AVICs induced by pro-calcific medium (PCM) containing β-glycerophosphate disodium, dexamethasone and ascorbic acid in vitro. The results showed that taurine attenuated the PCM-induced osteoblastic differentiation of AVICs by decreasing the alkaline phosphate (ALP) activity/expression and the expression of the core binding factor α1 (Cbfα1) in a dose-dependent manner (reaching the maximum protective effect at 10 mM), and taurine (10 mM) inhibited the mineralization level of AVICs in the form of calcium content significantly. Furthermore, taurine activated the extracellular signal-regulated protein kinase (ERK) pathway via TAUT, and the inhibitor of ERK (PD98059) abolished the effect of taurine on both ALP activity/expression and Cbfα1 expression. These results suggested that taurine could inhibit osteoblastic differentiation of AVIC via the ERK pathway.

Topics: Adult; Alkaline Phosphatase; Aortic Valve; Ascorbic Acid; Bicuspid Aortic Valve Disease; Biomarkers; Calcinosis; Calcium; Cell Differentiation; Core Binding Factor Alpha 1 Subunit; Dexamethasone; Extracellular Signal-Regulated MAP Kinases; Fibroblasts; Gene Expression; Glycerophosphates; Heart Defects, Congenital; Heart Valve Diseases; Humans; MAP Kinase Signaling System; Membrane Glycoproteins; Membrane Transport Proteins; Myocytes, Smooth Muscle; Osteoblasts; Protein Kinase Inhibitors; Taurine

Matrix vesicles (MVs) are cell-derived membranous entities crucial for mineral formation in the extracellular matrix. One of the dominant groups of constitutive proteins present in MVs, recognised as regulators of mineralization in norm and pathology, are annexins. In this report, besides the annexins already described (AnxA2 and AnxA6), we identified AnxA1 and AnxA7, but not AnxA4, to become selectively enriched in MVs of Saos-2 cells upon stimulation for mineralization. Among them, AnxA6 was found to be almost EGTA-non extractable from matrix vesicles. Moreover, our report provides the first evidence of annexin-binding S100 proteins to be present in MVs of mineralizing cells. We observed that S100A10 and S100A6, but not S100A11, were selectively translocated to the MVs of Saos-2 cells upon mineralization. This observation provides the rationale for more detailed studies on the role of annexin-S100 interactions in MV-mediated mineralization.

Topics: Annexins; Ascorbic Acid; Bone Matrix; Calcification, Physiologic; Calcinosis; Cell Fractionation; Cell Line; Cell Line, Tumor; Cytoplasmic Vesicles; Cytoskeletal Proteins; Glycerophosphates; Humans; Protein Transport; S100 Proteins

Experimental and clinical data indicate that 3,4-methylenedioxy-N-methylamphetamine (MDMA) abuse can produce significant cardiovascular toxicity. A mechanism may be a direct toxic effect of redox active metabolites of MDMA. To evaluate the effect of a single MDMA dose on cellular antioxidant defence system and to investigate the morphology in male albino rats, total glutathione (GSH), oxidised glutathione (GSSG), ascorbic acid (AA), glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) and malondialdehyde (MDAL) were studied. The effects were evaluated at 3, 6, 16 and 24 h after MDMA administration. Antioxidant enzymes activity was significantly reduced: GPx (-24%) and SOD (-50%) after 3 h and GR (-19%) after 6 h from treatment. AA levels decrease (-37%) after 3 h and (-30%) after 6 h; MDAL level increased (+119%) after 3 h; GSH levels decreased after 3 (31.3%) and 6 h (37.9%) from MDMA treatment. GSSG content was not affected by ecstasy administration. Myocardial contraction band necrosis (CBN) was already visible in rats killed at 6 h. After 16 h, macrophagic monocytes around the necrotic myocardial cells were observed, and within 24 h, this infiltrate became more widespread with an early removal of the necrotic material. Calcium deposits were observed within ventricular cardiomyocytes with intact nuclei and sarcomeres. Single administration of MDMA can significantly alter the cellular antioxidant defence system and produce oxidative stress which may result in lipid peroxidation and disruption of Ca(2 +) homeostasis. The depression in Ca(2+) regulatory mechanism by reactive oxygen species ultimately results in intracellular Ca(2 +) overload, CBN and cell death.

Topics: Animals; Ascorbic Acid; Calcinosis; Forensic Toxicology; Glutathione; Glutathione Disulfide; Glutathione Peroxidase; Glutathione Reductase; Hallucinogens; Macrophages; Male; Malondialdehyde; Microscopy, Confocal; Models, Animal; Myocardium; Myocytes, Cardiac; Myoglobin; N-Methyl-3,4-methylenedioxyamphetamine; Necrosis; Oxidative Stress; Rats; Superoxide Dismutase; Time Factors; Troponin C; Troponin I

Vascular calcification is an organized process in which vascular smooth muscle cells (VSMCs) are implicated primarily. The purpose of the present study was to assess the effects of calcium antagonists and statins on VSMC calcification in vitro.. VSMC calcification was stimulated by incubation in growth medium supplemented with 10 mmol/l beta-glycerophosphate, 8 mmol/l CaCl(2), 10 mmol/l sodium pyruvate, 1 micromol/l insulin, 50 microg/ml ascorbic acid, and 100 nmol/l dexamethasone (calcification medium). Calcification, proliferation, and apoptosis of VSMCs were quantified.. Calcium deposition was stimulated dose-dependently by beta-glycerophosphate, CaCl(2), and ascorbic acid (all P < 0.01). Addition of amlodipine (0.01-1 micromol/l) to the calcification medium did not affect VSMC calcification. However, atorvastatin (2-50 micromol/l) stimulated calcium deposition dose-dependently. Combining treatments stimulated calcification to a degree similar to that observed with atorvastatin alone. Both atorvastatin and amlodipine inhibited VSMC proliferation at the highest concentration used. Only atorvastatin (50 micromol/l) induced considerable apoptosis of VSMCs.. In vitro calcification of VSMCs is not affected by amlodipine, but is stimulated by atorvastatin at concentrations > or =10 micromol/l, which could contribute to the plaque-stabilizing effect reported for statins.

Topics: Amlodipine; Animals; Animals, Newborn; Aorta; Apoptosis; Ascorbic Acid; Atorvastatin; Calcinosis; Calcium; Cell Proliferation; Cell Separation; Cells, Cultured; Dexamethasone; Dose-Response Relationship, Drug; Drug Synergism; Extracellular Space; Heptanoic Acids; Muscle, Smooth, Vascular; Phosphates; Pyrroles; Rats; Rats, Wistar

Topics: Antioxidants; Ascorbic Acid; Atorvastatin; Calcinosis; Cardiovascular Diseases; Coronary Disease; Drug Therapy, Combination; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pyrroles; Vitamin E

Numerous studies have evaluated the association between antioxidants and coronary atherosclerosis but have been limited by its study among individuals with advanced atherosclerosis. The authors studied 865 consecutive patients, 39-45 years of age, without known coronary artery disease and presenting for a periodic physical examination. Antioxidant intake was assessed with the Block Dietary Questionnaire, and coronary atherosclerosis was identified by measuring coronary artery calcification using electron beam computed tomography. The mean age was 42 (+/-2), 83% were male, and the prevalence of coronary artery calcification was 20%. Vitamin supplements were used by 56% of the participants, and the mean (+/-SD) daily intake (dietary plus supplemental) of vitamins A, C, and E were 1683 mg (+/-1245), 371 mg (+/-375), and 97 mg (+/-165), respectively. There was no significant correlation between coronary artery calcification score and individual vitamin or total antioxidant vitamin intake, even after adjusting for traditional cardiac risk factors. The highest quartile of vitamin E was positively associated with calcification (odds ratio=1.77; 95% confidence interval, 1.02-3.06). Antioxidant vitamin intake is not significantly related to coronary artery calcification, implying that there is no effect on the development of early coronary atherosclerosis. High doses of vitamin E may confer an increased risk of calcified atherosclerosis.

Topics: Adult; Antioxidants; Ascorbic Acid; Calcinosis; Case-Control Studies; Coronary Artery Disease; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Odds Ratio; Risk Factors; Surveys and Questionnaires; Tomography, X-Ray Computed; Vitamin A; Vitamin E; Vitamins

Ascorbic acid is an antioxidant nutrient possibly related to the development of atherosclerosis. To examine the relation between ascorbic acid and coronary artery calcium, an indicator of subclinical coronary disease, the authors analyzed data from 2,637 African-American and White men and women aged 18-30 years at baseline who were enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) Study (1985-2001). Participants completed diet histories at enrollment and year 7, and plasma ascorbic acid levels were obtained at year 10. Coronary artery computed tomography was performed at year 15. The authors calculated odds ratios in four biologically relevant plasma ascorbic acid categories, adjusting for possible confounding variables. When compared with men with high plasma ascorbic acid levels, men with low levels to marginally low levels had an increased prevalence of coronary artery calcium (multivariate odds ratio = 2.68, 95% confidence interval: 1.31, 5.48). Among women, the association was attenuated and nonsignificant (multivariate odds ratio = 1.50, 95% confidence interval: 0.58, 3.85). Ascorbic acid intakes from diet alone and diet plus supplements were not associated with coronary artery calcium. Low to marginally low plasma ascorbic acid levels were associated with a higher prevalence of coronary artery calcium among men but not among women.

Topics: Adolescent; Adult; Antioxidants; Ascorbic Acid; Black or African American; Calcinosis; Coronary Angiography; Coronary Artery Disease; Dietary Supplements; Feeding Behavior; Female; Humans; Male; Multivariate Analysis; Prevalence; Prospective Studies; Risk; Sex Distribution; United States; White People

The status of ascorbic acid (AA) in dialysis patients is the subject of debate. Some reports have found AA to be deficient in dialysis patients, while others have found that AA is not deficient. In an attempt to confirm AA serum concentrations in dialysis patients, we analyzed the concentrations of AA as well as its metabolites using the specific determination of AA with chemical derivatization and the HPLC method. We studied 131 patients under maintenance hemodialysis therapy (HD), 23 patients with chronic renal failure (CRF) and 48 healthy controls (C). Serum concentrations of AA and the AA metabolites dehydroascorbic acid (DHA) and 2, 3-diketogulonate (DKG) were measured by HPLC. Nine HD patients were taking AA supplements. Seventy-six (62.3%) of the 122 HD patients not taking AA supplements exhibited deficient levels of AA (< 20 microM), while 13 (56.5%) of the 23 CRF patients and 9 (18.8%) of the 48 C showed deficient levels of AA. Analysis of AA metabolites in the normal-range AA (20-80 microM) group revealed that the DHA/AA ratio in HD patients was significantly higher than in C (3.3 +/- 2.6% and 1.2 +/- 2.2%, respectively). The DKG/AA ratio in HD patients was higher than in CRF patients (3.6 +/- 5.2% vs. 0.9 +/- 1.9%), whereas DKG was not detected in C. When compared to serum levels before the start of dialysis, serum AA, DHA and DKG concentrations at the end of the dialysis session decreased by an average of 74.2, 84.0 and 78.8% respectively. In HD patients, serum levels of thiobarbituric reactive substances (TBARS) were significantly lower in the higher AA (> 80 microM) group than in the deficient and normal-range AA groups. In 12 AA-deficient patients, after 1 month of taking AA supplements (200 mg/day), serum AA levels rose to 79.9 microM, while serum TBARS level declined when compared with levels before supplementation. In conclusion, the frequency of AA deficiency in dialysis patients is extremely high. AA deficiency in HD patients may result in high TBARS levels, which reflect increased oxidative stress. Adequate AA supplementation should therefore be considered in such patients.

Topics: 2,3-Diketogulonic Acid; Administration, Oral; Aged; Aorta; Ascorbic Acid; Ascorbic Acid Deficiency; Calcinosis; Calcium Oxalate; Chromatography, High Pressure Liquid; Dehydroascorbic Acid; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Oxidative Stress; Renal Dialysis; Thiobarbituric Acid Reactive Substances

Topics: Adult; Anastomosis, Surgical; Ascorbic Acid; Calcinosis; Combined Modality Therapy; Female; Humans; Hydrogen-Ion Concentration; Ileum; Kidney Diseases; Kidney Pelvis; Kidney Transplantation; Postoperative Complications; Pyelitis

Topics: Adult; Antioxidants; Ascorbic Acid; Calcinosis; Diabetes Mellitus; Diabetes Mellitus, Type 2; DNA Damage; Erythrocytes; Humans; Nutrition Disorders; Oxidative Stress; Pancreatic Diseases; Vitamin A; Vitamin E

Cardiovascular calcification, the formation of calcium phosphate deposits in cardiovascular tissue, is a common endstage phenomenon affecting a wide variety of bioprostheses. The purpose of the present paper is to study the possibility that some antiplatelet drugs (aspirin and persantine) and certain vitamins (vitamin C, vitamin B6, and vitamin E) and their combinations might prevent the mineralization of glutaraldehyde treated bovine pericardium (GABP) by modifying the pericardial surface. In this experimental protocol, we used Golomb and Wagner's (1991) in vitro model for studying GABP calcification and a diffusion cell with 2 compartments for evaluating the diffusion of calcium across the GABP. The results showed that a combination of aspirin and vitamins (0.5 mg% aspirin, 1.5 mg% vitamin C, 4 mg% vitamin B6, and 2 mg% vitamin E) in a metastable calcium phosphate solution not only reduced the transport of calcium ions through GABP, but along with the combinations of 0.5 mg% aspirin and 5 mg% persantine also produced significant reductions in GABP calcification. The exact mechanism of these changes in the calcification of GABP are still unknown. From these in vitro findings, it appears that a combined vitamin therapy with low doses of aspirin may be beneficial for platelet suppression and thereby prevent thrombosis. In addition, the vitamins may modify calcium transport and interfere with the adsorption at the surface, thus reducing GABP calcification. However, an important question that remains unanswered is whether this inhibitory effect would continue if the antiplatelet drugs and vitamins were discontinued. For the answer, more in vivo studies are needed to develop applications.

Topics: Animals; Ascorbic Acid; Aspirin; Biological Transport; Bioprosthesis; Calcinosis; Calcium; Calcium Phosphates; Cattle; Dipyridamole; Drug Combinations; Fixatives; Glutaral; Microscopy, Electron, Scanning; Pericardium; Platelet Aggregation Inhibitors; Pyridoxine; Vitamin E; Vitamins

Calcification is a common feature of advanced atherosclerotic lesions and is being reemphasized as a clinically significant element of vascular disease. However, the scarcity of in vitro models of vascular calcification preclude studying its molecular and cellular mechanism. In the present study, we describe an in vitro calcification in which diffuse calcification can be induced by culturing bovine vascular smooth muscle cells (BVSMC) in the presence of beta-glycerophosphate, ascorbic acid, and insulin in a manner analogous to in vitro mineralization by osteoblasts. Calcification was confirmed by von Kossa staining and 45Ca accumulation. Factor analysis revealed that beta-glycerophosphate is the most important factor for this calcification process, suggesting that alkaline phosphatase (ALP) may be involved. As predicted, high levels of ALP expression were detected by ALP assay and Northern blot analysis. Functional significance of ALP was confirmed by demonstrating that levamisole, a specific inhibitor of ALP, inhibited BVSMC calcification in a dose-dependent manner. Bisphosphonates such as etidronate and pamidronate potently inhibited BVSMC calcification, suggesting that hydroxyapatite formation may be involved. Importantly, expression of osteopontin mRNA was dramatically increased in calcified BVSMC compared with uncalcified control cells. These data suggest that beta-glycerophosphate can induce diffuse calcification by an ALP-dependent mechanism and that this in vitro calcification system is useful for analyzing the molecular and cellular mechanisms of vascular calcification.

Topics: Alkaline Phosphatase; Animals; Ascorbic Acid; Calcinosis; Calcium; Calcium Radioisotopes; Cattle; Cells, Cultured; Glycerophosphates; Insulin; Muscle, Smooth, Vascular

Secondary oxalosis in chronic hemodialyzed patients is caused by impaired renal excretion and inadequate removal of oxalic acid during hemodialysis. Ascorbic acid is a precursor of oxalic acid. We report a parathyroidectomized patient with chronic renal failure, on hemodialysis, who received over a period of several months a total dose of 91.0 g ascorbic acid i.v. The plasma oxalic acid level in this patient was 14-fold higher than in healthy persons. Increased oxalic acid synthesis from its precursor ascorbic acid may be responsible for hyperoxalemia, high content of oxalic acid in myocardium, aorta and lung, and calcium oxalate deposition in soft tissues. Application of high doses of ascorbic acid should be avoided in hemodialysed patients with chronic renal failure.

Topics: Adult; Aorta; Ascorbic Acid; Calcinosis; Calcium Oxalate; Cardiomyopathies; Humans; Hyperparathyroidism, Secondary; Lung; Male; Nephritis, Interstitial; Parathyroid Glands; Renal Dialysis; Uremia

Topics: Adult; Ascorbic Acid; Calcinosis; Calcium Oxalate; Cardiomyopathies; Humans; Kidney Failure, Chronic; Male; Oxalates; Oxalic Acid; Renal Dialysis

Topics: Adult; Ascorbic Acid; Calcinosis; Humans; Kidney Diseases; Male; Oxalates

Topics: Alkaline Phosphatase; Animals; Ascorbic Acid; Body Weight; Bone and Bones; Bone Development; Calcinosis; Calcium; Calcium, Dietary; Dietary Proteins; Disease Models, Animal; Fluoride Poisoning; Fluorides; Haplorhini; Macaca; Phosphorus; Radiography; Statistics as Topic

Topics: Ascorbic Acid; Bone Diseases; Calcinosis; Diagnosis, Differential; Ergocalciferols; Fractures, Bone; Humans; Infant; Osteoporosis; Radiography; Rickets; Scurvy; Streptomycin; Vitamin A

Topics: Ascorbic Acid; Calcification, Physiologic; Calcinosis; Humans; Scurvy; Vitamins