cholecalciferol and Calcinosis

Atherosclerosis is common in patients with chronic kidney disease (CKD), and cardiovascular disease (CVD) represents a major cause of death in these patients, especially, in patients with end-stage renal disease(ESRD). The pathological features in ESRD patients are intimal atherosclerosis and medial calcific sclerosis. The important risk factors for CVD in ESRD patients are hypertension, dyslipidemia and CKD bone and mineral disorder (CKD-MBD). Atherosclerosis has been evaluated by measurements of intima-media thickness and pulse-wave velocity. Although the target blood pressure still undetermined, hypertension would be treated with renin-angiotensin system inhibitors. In addition, treatment of dyslipidemia with statins may lead to favorable CVD outcome. Finally, inhibition of vascular calcification should be important by treatment with active vitamin D and sevelamer.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Atherosclerosis; Bone Diseases, Metabolic; Calcinosis; Cholecalciferol; Chronic Disease; Dyslipidemias; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Kidney Failure, Chronic; Polyamines; Risk Factors; Sevelamer; Tunica Intima; Vascular Diseases

Serum parathyroid hormone concentrations decrease progressively during the first 3 to 6 month after successful renal transplantation. However 1 year after transplantation, persistent hyperparathyroidism is common. Hypercalcemia due to persistent hyperparathyroidism cause graft dysfunction and cardiovascular calcification. Renal transplant recipients with persistent hyperparathyroidism need treatment with vitamin D and calcium, in some cases parathyroidectomy has to be considered.

Topics: Calcinosis; Calcium; Cardiovascular Diseases; Cholecalciferol; Humans; Hypercalcemia; Hyperparathyroidism, Secondary; Kidney Transplantation; Parathyroidectomy

Topics: Alkalosis; Benzothiadiazines; Calcinosis; Cholecalciferol; Diuretics; Humans; Hypercalcemia; Hyperparathyroidism; Isotretinoin; Lithium; Osteitis Deformans; Sarcoidosis; Sodium Chloride Symporter Inhibitors; Tamoxifen; Tretinoin; Vitamin A

Topics: Animals; Calcinosis; Calcium; Cholecalciferol; Plant Poisoning; Solanaceous Alkaloids

Topics: Animals; Bone and Bones; Calcinosis; Calcium; Calcium Radioisotopes; Cattle; Chickens; Cholecalciferol; Dihydroxycholecalciferols; Horses; Humans; Phosphorus; Plant Poisoning; Plants; Rabbits; Rats; Species Specificity

Topics: Adenylyl Cyclases; Amino Acids; Animals; Biological Transport; Brain; Calcinosis; Calcitonin; Calcium; Chick Embryo; Cholecalciferol; Dihydroxycholecalciferols; Egg Shell; Female; Intestinal Mucosa; Kidney; Parathyroid Hormone; Plants; Protein Binding; Protein Biosynthesis; Proteins; Species Specificity; Sterols; Vitamin D

Although high-dose vitamin D supplementation is common, effects on arterial calcification remain unexplored. Tibial artery calcification was identified and quantified over 3 years in participants randomized to 400, 4000, or 10,000 IU vitamin D. To determine whether vitamin D supplementation has a dose-dependent effect on development and progression of arterial calcification.. Of 311 randomized participants, 302 (400: 105, 4000: 96, 10,000: 101) were eligible for analysis of arterial calcification (54% male, mean (SD) age 62 (4) years, mean (SD) 25-hydroxyvitamin D 78.9 (19.9) nmol/L). At baseline, 85 (28%) had tibial artery calcification, and mean (95% CI) calcification quantity was 2.8 mgHA (95% CI 1.7-3.9). In these 85 participants, calcification quantity increased linearly by 0.020 mgHA/month (95% CI 0.012-0.029) throughout the study, with no evidence of a treatment-group effect (p = 0.645 for interaction). No participants developed new arterial calcifications during the study.. In this population of community-dwelling adults who were vitamin D replete at baseline, supplementation with vitamin D 400, 4000, or 10,000 IU/day did not have differential effects on the development or progression of arterial calcification over 3 years.. clinicaltrials.gov (NCT01900860).

Topics: Adult; Aged; Calcinosis; Canada; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Humans; Male; Middle Aged; Vitamin D; Vitamin D Deficiency; Vitamins

Vitamin D deficiency is prevalent in chronic pancreatitis (CP), but the optimal route and dose of vitamin D supplementation are unknown. We evaluated the relative efficacy of two different doses of intramuscular (i.m.) vitamin D(3) in patients with CP and vitamin D insufficiency. In a double-blind randomized study, 40 patients with tropical calcific pancreatitis with serum 25-hydroxyvitamin D (25OHD) <75 nmol/L (mean 27.0 ± 14.5 nmol/L, <50 nmol/L in 90 %) were divided into three groups. Groups 1 and 2 received 600,000 IU (15,000 μg) and 300,000 IU (7,500 μg) i.m. cholecalciferol, respectively, while group 3 received i.m. saline. All groups received 1 g calcium and 500 IU (12.5 μg) vitamin D(3) orally daily and were studied for 9 months. The primary outcome was the proportion of patients with vitamin D sufficiency (25OHD >75 nmol/L) at 6 months. Vitamin D sufficiency was significantly different in the three groups (85, 29, and 0 % in groups 1, 2, and 3, respectively; p < 0.001). Mean 25OHD remained >75 nmol/L in months 1-6 in group 1 but reached a lower level (50-75 nmol/L) at these time points in group 2. At 6 months, serum alkaline phosphatase decreased significantly only in group 1 (230 ± 73 vs 165 ± 39 IU/L, p = 0.004). No patient in any group developed hypervitaminosis D or hypercalcemia. In conclusion, in patients with CP, a single i.m. injection of 600,000 IU was more effective at achieving vitamin D sufficiency over 6 months compared with 300,000 IU vitamin D(3). (Clinical Trials.gov number NCT00956839).

Topics: Adult; Bone Density Conservation Agents; Calcinosis; Cholecalciferol; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Pancreatitis, Chronic; Prospective Studies; Vitamin D Deficiency

Coronary artery calcified plaque is a marker for atheromatous plaque burden and predicts future risk of cardiovascular events. The relationship between calcium plus vitamin D (calcium/D) supplementation and coronary artery calcium (CAC) has not been previously assessed in a randomized trial setting. We compared CAC scores after trial completion between women randomized to calcium/vitamin D supplementation and women randomized to placebo.. In an ancillary substudy of women randomized to calcium carbonate (1,000 mg of elemental calcium daily) plus vitamin D3 (400 IU daily) or placebo, nested within the Women's Health Initiative trial of estrogen among women who underwent hysterectomy, we measured CAC with cardiac CT in 754 women aged 50 to 59 years at randomization. Imaging for CAC was performed at 28 of 40 centers after a mean of 7 years of treatment, and scans were read centrally. CAC scores were measured by a central reading center with masking to randomization assignments.. Posttrial CAC measurements were similar in women randomized to calcium/D supplementation and those receiving placebo. The mean CAC score was 91.6 for women receiving calcium/D and 100.5 for women receiving placebo (rank test P value = 0.74). After adjustment for coronary risk factors, multivariate odds ratios for increasing CAC score cutpoints (CAC >0, > or =10, and > or =100) for calcium/D versus placebo were 0.92 (95% CI, 0.64-1.34), 1.29 (0.88-1.87), and 0.90 (0.56-1.44), respectively. Corresponding odds ratios among women with a 50% or higher adherence to study pills and for higher levels of CAC (>300) were similar.. Treatment with moderate doses of calcium plus vitamin D3 did not seem to alter coronary artery calcified plaque burden among postmenopausal women. Whether higher or lower doses would affect this outcome remains uncertain.

Topics: Bone Density Conservation Agents; Calcinosis; Calcium Carbonate; Cholecalciferol; Coronary Angiography; Coronary Artery Disease; Double-Blind Method; Female; Humans; Middle Aged; Postmenopause; Tomography, X-Ray Computed

Klotho is an aging-suppressor gene. The purpose of this study was to investigate whether Klotho deficiency affects arterial structure. We found that Klotho-deficient (kl/kl) mice developed severe arterial calcification and elastin fragmentation. Klotho-deficient mice demonstrated higher levels of bone morphogenetic proteins (BMP2, BMP4) and runt-related transcription factor 2 (RUNX2) in aortas, indicating that Klotho deficiency upregulates expression of BMP2 and RUNX2 (a key transcription factor in osteoblasts). To exclude the potential involvement of hyperphosphatemia in arterial calcification, Klotho-deficient mice were given a low phosphate diet (0.2%). The low phosphate diet normalized blood phosphate levels and abolished calcification in the lungs and kidneys, but it did not prevent calcification in the aortas in Klotho-deficient mice. Thus, Klotho deficiency per se might play a causal role in the pathogenesis of arterial calcification, which is independent of hyperphosphatemia. In cultured mouse aortic smooth muscle cells (ASMCs), Klotho-deficient serum-induced transition of ASMCs to osteoblasts. Klotho-deficient serum promoted BMP2/vitamin D3-induced protein expression of PIT2 and RUNX2, phosphorylation of SMAD1/5/8 and SMAD2/3, and extracellular matrix calcification. Interestingly, treatments with recombinant Klotho protein abolished BMP2/vitamin D3-induced osteoblastic transition and morphogenesis and calcification. Therefore, Klotho is a critical regulator in the maintenance of normal arterial homeostasis. Klotho deficiency-induced arterial calcification is an active process that involves the osteoblastic transition of SMCs and activation of the BMP2-RUNX2 signaling.

Topics: Animals; Calcinosis; Cells, Cultured; Cholecalciferol; Core Binding Factor Alpha 1 Subunit; Glucuronidase; Hyperphosphatemia; Klotho Proteins; Mice; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Phosphates

Metastatic calcinosis cutis results from abnormal calcium levels leading to the precipitation of insoluble calcium salts in the skin and subcutaneous tissue. Here, we present the case of a 67-year-old man with multiple sclerosis on chronic dexamethasone and concurrent supplementation of calcium and daily cholecalciferol presenting with painful calcified lesions. During initial presentation, corrected calcium was 13.8 mg/dL (reference range: 8.5-10.1 mg/dL), ionised calcium was 1.70 mg/dL (reference range: 1.13-1.32 mg/dL) and 25-hydroxyvitamin D was 41.6 ng/mL (reference range 30-100 ng/mL). Normocalcaemia was restored with the off-label use of denosumab, usually reserved for hypercalcaemia of malignancy and intractable osteoporosis. We discuss potential aetiologies of this patient's hypercalcaemia, calcinosis cutis diagnosis and management and the off-label use of denosumab.

Topics: Calcinosis; Calcium; Cholecalciferol; Denosumab; Dexamethasone; Humans; Hypercalcemia; Male; Middle Aged; Multiple Sclerosis; Off-Label Use; Skin Diseases; Treatment Outcome

Duchenne muscular dystrophy (DMD) is caused by a lack of dystrophin protein. Next to direct effects on the muscles, this has also metabolic consequences. The influence of nutrition on disease progression becomes more and more recognized. Protein intake by DMD patients may be insufficient to meet the increased demand of the constantly regenerating muscle fibers. This led to the hypothesis that improving protein uptake by the muscles could have therapeutic effects. The present study examined the effects of a modified diet, which composition might stimulate muscle growth, on disease pathology in the D2-mdx mouse model. D2-mdx males were fed with either a control diet or modified diet, containing high amounts of branched-chain amino acids, vitamin D3 and ursolic acid, for six weeks. Our study indicates that the modified diet could not ameliorate the muscle pathology. No effects on bodyweight or weight of individual muscles were observed. Neither did the diet affect severity of fibrosis or calcification of the muscles.

Topics: Amino Acids, Branched-Chain; Animals; Calcinosis; Cholecalciferol; Dietary Proteins; Disease Models, Animal; Dystrophin; Fibrosis; Humans; Male; Mice; Mice, Inbred DBA; Mice, Inbred mdx; Muscle, Skeletal; Muscular Dystrophy, Duchenne; Regeneration; Triterpenes; Ursolic Acid

Arterial calcification is a common feature of cardiovascular disease. Sortilin is involved in the development of atherosclerosis, but the specific mechanism is unclear. In this study, we established calcification models in vivo and in vitro by using vitamin D

Topics: Adaptor Proteins, Vesicular Transport; Animals; Atherosclerosis; Calcinosis; Cell Line; Cholecalciferol; Disease Models, Animal; Gene Expression Regulation; Glycerophosphates; Humans; MicroRNAs; Muscle, Smooth, Vascular; Rats; Transfection; Vascular Calcification

End-stage renal disease is strongly associated with progressive cardiovascular calcification (CVC) and there is currently no therapy targeted to treat CVC. SNF472 is an experimental formulation under development for treatment of soft tissue calcification. We have investigated the pharmacokinetics of SNF472 administration in rats and its inhibitory effects on CVC. SNF472 was studied in three rat models: (1) prevention of vitamin D3-induced CVC with an intravenous SNF472 bolus of 1 mg/kg SNF472, (2) inhibition of progression of vitamin D3-induced CVC with a subcutaneous SNF472 bolus of 10 or 60 mg/kg SNF472, starting after calcification induction, (3) CVC in adenine-induced uremic rats treated with 50 mg/kg SNF472 via i.v. 4h -infusion. Uremic rats presented lower plasma levels of SNF472 than control animals after i.v. infusion. CVC in non-uremic rats was inhibited by 60-70% after treatment with SNF472 and progression of cardiac calcification completely blocked. Development of CVC in uremic rats was inhibited by up to 80% following i.v. infusion of SNF472. SNF472 inhibits the development and progression of CVC in uremic and non-uremic rats in the same range of SNF472 plasma levels but using in each case the required dose to obtain those levels. These results collectively support the development of SNF472 as a novel therapeutic option for treatment of CVC in humans.

Topics: Animals; Calcinosis; Cardiovascular Diseases; Cholecalciferol; Disease Models, Animal; Disease Progression; Humans; Inositol; Kidney Failure, Chronic; Rats; Renal Insufficiency, Chronic; Uremia

Fahr's syndrome is a rare disorder characterized by abnormal deposits of calcium in areas of the brain that control movement, including the basal ganglia and the cerebral cortex associated with many neurological and psychiatric abnormalities such as a rigid hypokinetic syndrome, mood disorders and cognitive impairment. Fahr's syndrome is secondary to some disorders, such as hypoparathyroidism.. We report the case of a 56 year-old man, with a history of cataract, who was admitted to our psychiatric hospital for the first time in his life because of psychotic symptoms associated with irritability and aggressiveness. Since the age of 38 the patient had become nervous, 10 years later he developed tonic-clonic seizures. Two months ago, he began expressing delusions of persecution against his wife and sons and making fugues. According to his family during this period, he was agitated, aggressive, and suffered from insomnia and anorexia. The general and psychiatric examination showed an upright and bronzed patient with neglected hygiene. He was indifferent to his environment and expressed poor mimics and gestures. He was anxious, suspicious and not very talkative. He was conscious but his attention was slightly decreased. Moreover, he was not aware of his problems. The neurological examination showed extrapyramidal syndrome with postural tremor and cerebellar ataxia. A cranial computed tomography brain scan found bilateral, symmetric basal ganglia calcifications, in favour of Fahr's syndrome. Phosphocalcic investigations revealed low concentration of serum calcium at 1.01mmol/L (normal 2.15 to 2.57mmol/L) and hyperphosphoremia at 2.69mmol/L (normal 0.81 to 1.55mmol/L). He also had low concentrations of 25-OH vitamin as well as decreased urinary levels of phosphate and calcium. The blood level of parathyroid hormone was 0ng/L. The diagnosis of Fahr's syndrome, revealing a hypoparathyroidism was posed. He was supplemented with calcium and alpha cholecalciferol and treated with clozapine (100mg per day). After four weeks, psychotic symptoms responded well to this treatment without expressing any side effects, notably seizures.. Psychotic symptoms seen in Fahr's disease include auditory and visual hallucinations, complex perceptual distortions, delusions, and fugue state. Some of them were manifest in this patient. It is likely that the psychosis in both Fahr's disease and schizophrenia share a similar pathology. Positive psychotic symptoms, hallucinations, and paranoia are not necessarily generated by the classical hypothesis of dopamine-mediated attachment of salience to internally generated stimuli. Still, there is some evidence that disruption of the cortex involved in the pathophysiology of schizophrenia is also seen in Fahr's disease, particularly in areas of the limbic system.. Psychiatrists should consider Fahr's syndrome as a differential diagnosis in the evaluation of psychosis associated with seizures. This case, along with others in the literature, further emphasizes the importance of the role of neuro-imaging and the search for disrupted phosphocalcic metabolism in patients with atypical psychotic symptoms. Moreover, further research should focus on pharmacologic interventions. The efficacy and risks of neuropharmacologic and psychopharmacologic interventions in Fahr's syndrome, and correlates of good and poor outcome with these interventions remain to be defined.

Topics: Basal Ganglia; Basal Ganglia Diseases; Brain Diseases; Calcinosis; Calcium; Cholecalciferol; Clozapine; Humans; Hypoparathyroidism; Male; Middle Aged; Neurocognitive Disorders; Neurodegenerative Diseases; Tomography, X-Ray Computed

Cardiovascular diseases are more prevalent in patients with chronic kidney disease than in the general population and they are considered the leading cause of death in patients with end-stage renal disease. The discovery that vitamin D3 plays a considerable role in cardiovascular protection has led, in recent years, to an increase in the administration of therapies based on the use of this molecule; nevertheless, several studies warned that an excess of vitamin D3 may increase the risk of hypercalcemia and vascular calcifications. In this study we evaluated the effects of vitamin D3, and of its selective analog paricalcitol, on immature cardiomyocytes. Results show that vitamin D3 induces cAMP-mediated cell proliferation and significant intracellular calcification. Paricalcitol, however, induces cell differentiation, morphological modifications in cell shape and size, and no intracellular calcification. Furthermore, vitamin D3 and paricalcitol differently affect cardiomyoblasts responses to acetylcholine treatment. In conclusion, our results demonstrate that the effects of vitamin D3 and paricalcitol on cardiomyoblasts are different and, if these in vitro observations could be extrapolated in vivo, they suggest that paricalcitol has the potential for cardiovascular protection without the risk of inducing intracellular calcification.

Topics: Acetylcholine; Animals; Calcinosis; Cardiovascular Diseases; Cell Line; Cell Proliferation; Cell Survival; Cholecalciferol; Ergocalciferols; Myocytes, Cardiac; Rats; Renal Insufficiency, Chronic

Vitamin D₃ and nicotine (VDN) serve as an animal model of arterial calcification. The vascular calcification induced by the VDN model is always accompanied by compensatory left ventricular (LV) hypertrophy and impaired cardiac performance. To determine the possible mechanisms that are responsible for the effects of VDN on the LV, a 2-DE based proteomics approach was used to evaluate the changes in protein expression of the left ventricle in VDN rats, to our knowledge, for the first time. We identified sixteen proteins that were markedly altered and involved in mitochondrial function, heat shock protein activity, myocyte cytoskeleton composition and enzyme activity for energy metabolism. We describe, for the first time, a novel pathway (NDPK) that is involved in LV hypertrophy and enzyme activities of three of the sixteen clinical identified proteins: lactate dehydrogenase (LDH), SOD [Mn] and GST.

Topics: Animals; Blood Pressure; Calcinosis; Cardiomyopathies; Cholecalciferol; Disease Models, Animal; Electrophoresis, Gel, Two-Dimensional; Heart Ventricles; Hypertrophy, Left Ventricular; Male; Nicotine; Proteome; Rats; Rats, Sprague-Dawley; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Cardiovascular calcifications are frequently found in the aging population and are independent predictors of future cardiovascular events. Integrated backscatter (IB) of ultrasound reflectivity can easily quantify calcifications. For this purpose, 30 male Wistar rats received 25,000 IU/kg/day of vitamin D(3) (group 1, n = 8), 18,800 IU/kg/day (group 2, n = 8), or injections with the vehicle only (group 3, n = 14), for 10 weeks. Echocardiographic calibrated IB (cIB) was measured and calculated at baseline and after 10 weeks, followed by ex vivo micro-CT and histopathology of the aortic valve, ascending aorta, and myocardium. After 10 weeks, the mean cIB value of the aortic valve was significantly higher for vitamin D(3)-dosed animals compared to controls. The mean cIB value of the ascending aorta and the myocardium was also significantly higher in group 1 compared to group 3. In vivo IB results were confirmed by ex vivo micro-CT and histopathology. In conclusion, IB is a non-ionizing, feasible, and reproducible tool to quantify cardiovascular calcifications in an in vivo rat model. The integration of IB in the standard echocardiographic examination for the quantification of cardiovascular calcifications could be useful for serial evaluation of treatment efficacy and for prognosis assessment.

Topics: Animals; Aorta; Aortic Valve; Calcinosis; Cardiomyopathies; Cholecalciferol; Disease Models, Animal; Echocardiography, Doppler, Color; Feasibility Studies; Heart Ventricles; Image Interpretation, Computer-Assisted; Male; Myocardium; Predictive Value of Tests; Rats; Rats, Wistar; Time Factors; Ventricular Function, Left; X-Ray Microtomography

A 14-year-old girl with juvenile dermatomyositis developed extensive and debilitating calcinosis, unresponsive to colchicine, while muscle involvement subsided. Pamidronate (2mg/kg/year) produced dramatic improvement of pain and function within 2 months and calcinosis had completely resolved by 2 years. No new calcifications have been noted with a 5-year follow-up.

Topics: Adolescent; Bone Density Conservation Agents; Calcinosis; Calcium; Cholecalciferol; Dermatomyositis; Diphosphonates; Drug Therapy, Combination; Female; Humans; Methylprednisolone; Pamidronate; Radiography; Recovery of Function; Treatment Outcome

To explore the effect of age on vascular calcification induced by vitamin D3 and nicotine.. Vascular calcification in rats was induced by administration of vitamin D3 plus nicotine (VDN treatment). After six weeks, Von Kossa staining, calcium content, alkaline phosphatase activity, phosphorus and calcium content in plasma were assayed. Carotid blood pressure, cardiac function and the relative amounts of osteopontin (OPN), osteoprotegerin (OPG), matrix Gla protein (MGP), bone morphogenetic protein-2 (BMP2) mRNA level and smooth muscle actin-alpha (alpha-SMA)protein level were measured.. Compared with control group, the systolic blood pressure(SBP)of the rats of 2,8 and 16 months with vascular calcification respectively increased by 20.7%, 29.4% and 22.2% (P<0.05); the left ventricular systolic pressure (LVSP) respectively increased by 13.6%, 21.1% and 16.2% (P<0.05); + LVdP/dtmax respectively increased by 49.1% (P<0.01), 21.4% and 13.1% (P<0.05); -LVdP/dtmax respectively increased by 56.3% (P<0.01), 24.4% and 11.3% (P<0.05). Aortic calcium contents of the 2-, 8- and 16-month calcified rats were respectively 2.62-fold (P<0.05), 24.87-fold (P<0.01) and 10.01-fold (P<0.05) of the age-matched control group. As compared with the aortic calcium contents of calcified groups at different ages, the calcification group of 8 months had higher aortic calcium content than those of 2 and 16 months, which were respectively, 5.28-fold and 2.63-fold (P<0.05). Compared with the control groups, alkaline phosphatases activity (ALP) of calcification groups increased respectively by 126.6%, 115.2% and 227.9% (P<0.01) in the 2-, 8- and 16-month rats. As compared with the ALP activity of calcified groups at different ages, ALP activity of aortic calcification group of the 8-month-old rats was higher than that of the 2-month-old and 16-month-old rats, which increased by 176% and 75% respectively (all P<0.01). Von kossa staining for calcification showed positive staining as black/brown areas within the main, large, nodular structures as shown in extracellular matrix and cytoplasma in VDN groups at different ages, especially in the 8-month-old VDN group, with the most dispersed calcific nodules deposited and a few of the elastic fibers of the medial layer collapse. The mRNA expressions of OPN, OPG, MGP, BMP2 were up-regulated (P<0.01 or P<0.05) and protein levels of alpha-SMA were down-regulated in different calcification groups(P<0.05). The mRNA levels of OPN in 8-month-old calcification group increased by 3.41-fold (P<0.01) and 1.34-fold (P<0.05) respectively compared with the 2-month-old and 16-month-old calcification groups. And the alpha-SMA protein expression levels were lower at calcification groups in different ages, which were respectively equivalent to 17.6% of the 2-month-old control group (P<0.01), 11% of the 8-month-old control group (P<0.05) and 41.7% of 16-month-old control group (P<0.01).. SD rats of 2, 8 and 16 months can all be used to duplicate vascular calcification model induced by vitamin D3 plus nicotine and the 8-month-old rat has the most sensitivity to the calcification treatment, which means that the 8-month-old rat may be the most appropriate age for the study of vascular calcification.

Topics: Aging; Animals; Aorta, Thoracic; Aortic Diseases; Calcinosis; Cholecalciferol; Disease Models, Animal; Male; Nicotine; Rats; Rats, Sprague-Dawley

Topics: Bone Density Conservation Agents; Calcinosis; Calcium Carbonate; Cholecalciferol; Coronary Angiography; Coronary Artery Disease; Female; Humans; Postmenopause

Vascular calcification refers to the deposition of calcium phosphate in cardiovascular tissues, including arteries and myocardium. Vascular calcification is frequently associated with cardiovascular disease. Recently, bone morphgenetic protein-7 (BMP-7) has been proposed to play an inhibitory role in vascular calcification, but its inhibitory effect has not been fully elucidated. We therefore tested the hypothesis that BMP-7 inhibits vascular calcification by using two conditions, high levels of vitamin D and phosphate, each of which could enhance vascular calcification. C57BL/6 mice were treated for 3 days with high vitamin D (500,000 IU/kg/day) in the presence or absence of recombinant human BMP-7 (rhBMP-7). Expression levels of osteopontin and osteocalcin, markers of the osteoblastic phenotype, were assessed by immunohistochemical staining or Western blotting analysis. Vitamin D increased calcium staining in thoracic aortas and hearts and the expression levels of osteopontin and osteocalcin in mice. Importantly, pretreatment for 7 days and subsequent treatment for 3 days with rhBMP-7 (10 microg/kg/day) abolished the vitamin D-mediated increases in the above parameters. In addition, human aortic smooth muscle cells (HASMCs) were cultured with high beta-glycerophosphate, a phosphate donor, for 2 weeks in the presence or absence of rhBMP-7. High beta-glycerophosphate increased expression levels of osteopontin and osteocalcin as well as calcium staining in HASMCs, but these changes were attenuated by treatment with BMP-7. Thus, BMP-7 inhibits vascular calcification associated with high levels of vitamin D or phosphate. We propose that BMP-7 treatment may be helpful in reducing the risks of cardiovascular disease related to vascular calcification.

Topics: Animals; Aorta, Thoracic; Bone Morphogenetic Protein 7; Calcinosis; Cells, Cultured; Cholecalciferol; Dose-Response Relationship, Drug; Drug Antagonism; Drug Combinations; Glycerophosphates; Heart; Humans; Male; Mice; Mice, Inbred C57BL; Muscle, Smooth, Vascular; Myocardium; Osteoblasts; Osteocalcin; Osteopontin; Recombinant Proteins

To determine whether adrenomedullin (ADM) attenuates vascular calcification (VC) by inducing osteopontin (OPN) expression.. A VC model of rat aorta was induced with vitamin D3 plus nicotine (VDN), and vascular smooth muscle cell (VSMC) calcification was induced with beta-glycerophosphate. Von Kossa staining and alizarin red staining were assessed. Alkaline phosphatase (ALP) activity was measured. Immunohistochemical analysis was used to detect alpha-actin, while RT-PCR and Western blot analysis were used to quantify OPN expression.. Administration of ADM greatly reduced VC in VDN-treated aortas compared with controls, which was confirmed in calcified VSMCs. The decrease in alpha-actin expression was ameliorated by ADM both in vivo and in vitro. Moreover, mRNA and protein expression levels of OPN were significantly up-regulated in calcified aortas, and ADM increased OPN expression in calcified aortas. Furthermore, ADM up-regulated OPN expression in normal aortas and VSMCs. The ADM-mediated effects were similar to that of forskolin, which activates adenylyl cyclase; additionally, while the PKA inhibitor H89 and Ca²(+) chelator Fura-2 blocked the effect of ADM. However, the MEK/ERK inhibitor PD98509 had no effect on ADM induction of OPN mRNA expression. An OPN polyclonal antibody inhibited ADM-mediated attenuation of VC.. ADM up-regulates OPN expression and thus attenuates VC via PKA. ADM appears to be an endogenous cardiovascular protective peptide and may represent a new therapeutic target for VC treatment.

Topics: Actins; Adenylyl Cyclases; Adrenomedullin; Animals; Aorta, Thoracic; Calcinosis; Calcium; Cholecalciferol; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Enzyme Activators; Glycerophosphates; Male; Mitogen-Activated Protein Kinases; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Nicotine; Osteopontin; Rats; Rats, Sprague-Dawley; Signal Transduction; Up-Regulation

Nutritional metabolic bone disease (NMBD) is one of the most frequently observed pathological conditions in herpetoculture. To develop guidelines for NMBD prevention in growing veiled chameleons (Chamaeleo calyptratus), 56 hatchlings were divided into 6 groups [group UV, with UVB exposure; group No: no supplements; group CaAUV: with calcium (Ca), vitamin A, UVB; group CaA: with Ca, vitamin A; group CaADUV: with Ca, vitamin A, cholecalciferol, UVB; and group CaAD, with Ca, vitamin A, cholecalciferol] and reared for 6 mo on locust-based diets. The nutrient composition of the locusts' diet and the locust-based diet for the chameleons was determined. The diagnosis included the detailed description of clinical findings, histopathology, measurements of serum Ca, 25-hydroxycholecalciferol (25-OHD(3)), liver 25-OHD(3), vitamin A, bone mineral density, and bone mineral concentration. Chameleons that received no dietary supplementation of Ca, vitamin A, and cholecalciferol developed NMBD. When Ca and vitamin A were supplemented, the chameleons did not develop NMBD, independently of additional UVB and dietary cholecalciferol. The best prevention for NMBD was achieved by chameleons that received locusts gut-loaded with 12% Ca and dusted with 250,000 IU/kg (75 mg/kg) vitamin A and 25,000 IU/kg (0.625 mg/kg) cholecalciferol plus provision of long (10 h/d), low irradiation exposure (3-120 μW/cm(2)) to UVB. Chameleons that were fed diets low in vitamin A, cholecalciferol, and Ca were diagnosed with fibrous osteodystrophy. We noticed an interaction of vitamin A and cholecalciferol supplementation in the storage of vitamin A in the liver and formation of colon calcifications. From these findings, recommendations for the rearing of juvenile chameleons were derived.

Topics: Animal Husbandry; Animals; Behavior, Animal; Bone and Bones; Bone Density; Bone Diseases, Metabolic; Calcifediol; Calcinosis; Calcium; Cholecalciferol; Colon; Colonic Diseases; Diet; Grasshoppers; Liver; Lizards; Nymph; Ultraviolet Rays; Vitamin A

Various complications consequent on disordered calcium and phosphate homeostasis occur frequently in chronic kidney disease (CKD) patients. Particularly, vascular calcification has high morbidity and mortality rates. There is a clear need for a better CKD model to examine various aspects of this disordered homeostasis.. Oral dosing with adenine induced CKD in rats in only 10 days. Serum calcium, phosphate and parathyroid hormone were measured and calcification in aorta was assessed histologically. The effects of varying phosphorus content of diet or treatment with phosphate binders or active vitamin D(3) on these parameters were examined.. After adenine dosing, significant hyperphosphatemia, hypocalcemia and secondary hyperparathyroidism (2HPT) were observed during the experimental period of 15 weeks. Aortic calcification was detected in only some of the animals even at 15 weeks (approximately 40%). Treatment with vitamin D(3) for 18 days, even at a low dose (100 ng x kg(-1), 3-4 times week(-1), p.o), caused aortic calcification in all animals and increases in serum calcium levels up to the normal range. The vitamin D(3)-induced calcification was significantly inhibited by phosphate binders which lowered serum phosphate levels and the calcium x phosphate product, although serum calcium levels were elevated.. These data suggest that rats dosed orally with adenine provide a more useful model for analysing calcium/phosphate homeostasis in severe CKD. Controlling serum calcium/phosphate levels with phosphate binders may be better than vitamin D(3) treatment in hyperphosphatemia and 2HPT, to avoid vascular calcification.

Topics: Adenine; Animals; Aortic Diseases; Biomarkers; Blood Urea Nitrogen; Calcinosis; Calcium; Calcium Carbonate; Chelating Agents; Cholecalciferol; Chronic Disease; Creatinine; Disease Models, Animal; Disease Progression; Hyperparathyroidism, Secondary; Hyperphosphatemia; Hypocalcemia; Kidney Diseases; Male; Parathyroid Hormone; Phosphates; Polyamines; Rats; Rats, Wistar; Sevelamer; Severity of Illness Index; Time Factors

Lanthanum, a rare earth element, has been used to decrease serum phosphorus level in patients with chronic renal disease and hyperphosphatemia. We aimed to observe the effect and mechanism of two doses of lanthanum acetate (375 and 750 mg/kg/day) on vascular calcification induced by vitamin D3 plus nicotine treatment in rats for 4 weeks. As compared with control rats, rats with calcification showed widespread calcified nodules and irregular elastic fibers in calcified aorta on von Kossa calcium staining and increased aortic calcium and phosphorus contents, alkaline phosphatase (ALP) activity and bone-related protein expressions for osteopontin (OPN) and type III sodium dependent phosphate cotransporter Pit-1 (Pit-1). After treatment with either dose of lanthanum acetate, the calcified nodules and degree of irregular elastic fibers decreased in aortas. Lanthanum acetate at 750 mg/kg/day was more effective than 375 mg/kg/day in lessening vascular calcification by significantly reducing plasma phosphorus level, calcium x phosphorus product and ALP activity, by 30.3%, 28.6%, and 68.6%, respectively; reducing aortic phosphorus and calcium contents and ALP activity, by 48%, 53.1%, and 63.5% (all P < 0.01), respectively; reducing aortic mRNA level of OPN and Pit-1, by 55.8% (P < 0.01) and 38.8% (P < 0.05) and protein level of OPN and Pit-1, by 37.2% and 27.2% (both P < 0.01), respectively; and increasing carboxylated matrix Gla-protein (MGP) protein expression by 33.7% (P < 0.05), as compared with rats treated with vitamin D3 and nicotine alone. Lanthanum acetate could effectively inhibit the pathogenesis of vascular calcification.

Topics: Acetates; Animals; Aorta; Calcinosis; Calcium; Calcium-Binding Proteins; Cholecalciferol; Extracellular Matrix Proteins; Gene Expression Regulation; Lanthanum; Male; Matrix Gla Protein; Nicotine; Osteopontin; Phosphorus; Rats; Rats, Sprague-Dawley; RNA, Messenger; Sodium-Phosphate Cotransporter Proteins, Type III

Epidemiological studies have reported an association between arterial calcification and bone loss after menopause. However, the underlying mechanism of the association remains unclear. Therefore, to explore the possible mechanisms of the association, we tried to develop a new combined model rat of ovariectomy (OVX, an animal model of osteoporosis) and vitamin D(3) plus nicotine (VDN rat, an animal model of arterial calcification). We tested them by using sham-operated control rats (SC), OVX control rats (OC), and OVX plus VDN-treated rats (OVN). Dissections were performed twice at 4 (4SC, 4OC, and 4OVN) and 8 (8SC, 8OC, and 8OVN) weeks after treatment. 8OVN showed bone loss and arterial calcification, although 8OC showed only bone loss. Moreover, arterial calcium content was associated with indexes of bone loss at 8 weeks. Thus, the OVN rat is considered a good model to examine the relationship of the two disorders after menopause. Additionally, the arterial endothelin-1 (ET-1, a potent regulator of arterial calcification) levels increased in both 4OVN and 8OVN, and the level was associated with arterial calcium content at 8 weeks. Furthermore, the arterial endothelial nitric oxide synthase (eNOS) protein, which is an enzyme that produces nitric oxide (an antiatherosclerotic substance), was significantly reduced in only 8OVN. Estrogens affect the alterations of the eNOS and ET-1 proteins. Therefore, we suggest that impairment of the ET-1- and NO-producing system in arterial tissue during periods of rapid bone loss by estrogen deficiency might be a mechanism of the relationship between the two disorders seen in postmenopausal women.

Topics: Animals; Arteries; Calcinosis; Calcium; Cholecalciferol; Disease Models, Animal; Endothelin-1; Estradiol; Female; Femur; Nicotine; Nitric Oxide Synthase Type III; Osteoporosis; Ovariectomy; Rats; Rats, Sprague-Dawley; Receptors, Estrogen; Tibia

Abnormalities of bone mineral metabolism in patients with stage-5 chronic kidney disease may contribute to the high incidence of cardiovascular disease. Noninvasive imaging methods may help predict the simultaneous presence of vasculopathy and bone disease. Accordingly, we measured pulse wave velocity and bone mineral density (BMD), and T-scores (number of SDs below the BMD of a younger reference group) of the spine by both dual energy x-ray absorptiometry and quantitative computed tomography (QCT) in 110 maintenance hemodialysis patients. Older age, white race, diabetes mellitus, lower diastolic blood pressure, and lower albumin levels were associated with lower QCT-assessed T-scores (each P<0.05). After age and multivariable adjustment, pulse wave velocity (PWV) increased as QCT BMD decreased (the prevalence of PWV >or=9 m/s was 32.4%, 61.8%, and 76.5% for participants in the highest to the lowest tertile of QCT-assessed BMD; P<0.001). In contrast, there was no relationship between spine dual energy x-ray absorptiometry-BMD and PWV. In unadjusted models, thoracic spine QCT-assessed T-scores correlated significantly, albeit weakly, with aorta calcification (r=0.22; P=0.01) but not with coronary calcification. The odds ratio of PWV >or=9 m/s for patients taking vitamin D(3) or its analogs was 0.51 (95% CI: 0.19 to 1.39). In conclusion, low spine BMD is associated with increased PWV in stage-5 chronic kidney disease, supporting the notion of a close interaction of vascular and bone disease in this patient group. QCT and not dual energy x-ray absorptiometry should be used to assess spine BMD in dialysis patients.

Topics: Absorptiometry, Photon; Adult; Aged; Blood Pressure; Bone Density; Calcinosis; Cholecalciferol; Female; Humans; Kidney Diseases; Lumbar Vertebrae; Male; Middle Aged; Pulsatile Flow; Regional Blood Flow; Renal Dialysis; Tomography, X-Ray Computed; Vascular Diseases

To investigate the role of the endogenous cystathionine gamma-synthase (CSE)/hydrogen sulfide (H2S) pathway in vascular calcification in vivo.. A rat vascular calcification model was established by administration of vitamin D3 plus nicotine (VDN). The amount of CSE and osteopontin (OPN) mRNA was determined by using semi-quantitative reverse-transcription polymerase chain reaction. The calcium content, 45Ca2+ accumulation and alkaline phosphatase (ALP) activity were measured. H2S production and CSE activity were measured.. von Kossa staining produced strong positive black/brown staining in areas among the elastic fibers of the medial layer in the calcified aorta. The calcium content, 45Ca2+ accumulation and ALP activity in calcified arteries increased by 6.77-, 1.42-, and 1.87-fold, respectively, compared with controls. The expression of the OPN gene was upregulated (P<0.01). Expression of the CSE gene was downregulated. However, calcium content, 45Ca2+ uptake and ALP activity in the VDN plus NaHS group was lower than that in the VDN group. The content of calcium and 45Ca2+ accumulation and activity of ALP in the aorta were 34.8%, 40.75% and 63.5% lower in the low-dosage NaHS group than in the VDN group, respectively (P<0.01), and the calcium content and deposition of 45Ca2+ and activity of ALP was 83.9%, 37.8 % and 46.2% lower in the aorta in the high-dosage NaHS group than in the VDN group, respectively (P<0.01). The expression of the OPN gene was downregulated.. The production of H2S, and CSE activity were decreased and CSE gene expression was downregulated in rats with vascular calcification. H2S can ameliorate vascular calcification, suggesting that the H2S/CSE pathway plays a regulatory role in the pathogenesis of vascular calcification.

Topics: Animals; Aorta; Calcinosis; Calcium; Cholecalciferol; Cystathionine gamma-Lyase; Hydrogen Sulfide; Male; Muscle, Smooth, Vascular; Nicotine; Osteopontin; Rats; Rats, Sprague-Dawley; RNA, Messenger; Sialoglycoproteins; Signal Transduction; Sulfides

Arterial calcification has been associated with matrix metalloproteinase (MMP)-mediated elastin degradation. In this study, we investigated whether inhibiting MMP activity could reduce calcium accumulation in rodent models of aortic calcification.. Aortic calcification was first induced in male Sprague-Dawley rats by administration of vitamin D3. Treatment with doxycycline decreased aortic calcium and phosphorus accumulation, and it reduced aortic gelatinase levels; however, it also prevented the bone resorption associated with high doses of vitamin D3. Using an in vivo model of localized aortic calcification, systemic doxycycline treatment reduced aortic calcium accumulation without affecting serum calcium levels, suggesting a more specific effect of doxycycline in the arterial wall. In organ culture, doxycycline limited aortic calcification caused by exposure to alkaline phosphatase and inorganic phosphate. When GM6001, a synthetic and specific inhibitor of MMPs, was used instead of doxycycline, it had a similar effect. In vivo, periadventitial delivery of GM6001 to calcifying arteries significantly reduced calcification compared with controls.. These results suggest that MMPs are involved in aortic calcification, and inhibiting MMP activity could reduce calcium accumulation in the arterial wall.

Topics: Animals; Aorta; Aortic Diseases; Bone Density; Calcinosis; Calcium; Calcium Chloride; Cholecalciferol; Dipeptides; Doxycycline; Male; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Organ Culture Techniques; Protease Inhibitors; Rats; Rats, Sprague-Dawley

Hyperphosphatemia-hyperostosis syndrome (HHS) is a rare autosomal recessive metabolic disorder characterized by elevated serum phosphate levels and repeated attacks of acute, painful swellings of the long bones with radiological evidence of periosteal reaction and cortical hyperostosis. HHS shares several clinical and metabolic features with hyperphosphatemic familial tumoral calcinosis (HFTC), which is caused by mutations in GALNT3 encoding a glycosyltransferase responsible for initiating O-glycosylation. To determine whether GALNT3 is involved in the pathogenesis of HHS we screened two unrelated Arab-Israeli HHS families for pathogenic mutations in this gene. All affected individuals harbored a homozygous splice site mutation (1524+1G-->A) in GALNT3. This mutation was previously described in a large Druze HFTC kindred and has been shown to alter GALNT3 expression and result in ppGalNAc-T3 deficiency. Genotype analysis of six microsatellite markers across the GALNT3 region on 2q24-q31 revealed that the HHS and HFTC families share a common haplotype spanning approximately 0.14 Mb. Our results demonstrate that HHS and HFTC are allelic disorders despite their phenotypic differences and suggest a common origin of the 1524+1G-->A mutation in the Middle East (founder effect). The heterogeneous phenotypic expression of the identified splice site mutation implies the existence of inherited or epigenetic modifying factors of importance in the regulation of ppGalNAc-T3 activity.

Topics: Calcinosis; Calcium; Child; Cholecalciferol; Female; Haplotypes; Humans; Hyperostosis; Male; N-Acetylgalactosaminyltransferases; Neoplasm Proteins; Neoplasms; Osteomalacia; Parathyroid Hormone; Pedigree; Phosphates; Polypeptide N-acetylgalactosaminyltransferase; Sequence Analysis, DNA

Topics: Calcinosis; Calcium; Cholecalciferol; Humans; Hyperostosis; N-Acetylgalactosaminyltransferases; Neoplasm Proteins; Neoplasms; Osteomalacia; Parathyroid Hormone; Phosphates; Polypeptide N-acetylgalactosaminyltransferase

Adrenomedullin (ADM) has the vasodilatory properties and involves in the pathogenesis of vascular calcification. ADM could be degraded into more than six fragments in the body, including ADM(27-52), and we suppose the degrading fragments from ADM do the same bioactivities as derived peptides from pro-adrenomedullin. The present study carries forward by assessing the effects on vascular calcification of the systemic administration of ADM(27-52). The rat vascular calcific model was replicated with vitamin D3 and nicotine. ADM or/and ADM(27-52) were systemically administrated with mini-osmotic pump beginning at seventh day after the model replication for 25 days. Vascular calcific nodules histomorphometry, vascular calcium content, vascular calcium uptake, alkaline phosphatase activity, and osteopontin-mRNA quantification in aorta were assessed. ADM limited 40.2% vascular calcific nodules (P<0.01), did not effect on calcium content (P>0.05), reduced 44.4% calcium uptake (P<0.01), lowered 21.1% alkaline phosphatase activity (P<0.01), and regulated 40.9% downwards osteopontin-mRNA expression (P<0.01) in the aorta of rats with vascular calcification. ADM(27-52) receded 32.0% vascular calcific nodules (P<0.01), taken from 55.5% calcium content (P<0.01), did not affect calcium uptake (P>0.05), inhibited 22.5% alkaline phosphatase activity (P<0.01), and restrained 21.9% osteopontin-mRNA expression (P<0.01) in the aorta of rats with vascular calcification. Both of ADM and ADM(27-52) did interact on vascular calcification each other. ADM could partially antagonize the effects of ADM(27-52) in taking from calcium content (17.5%, P<0.01) and in receding vascular calcific nodules (18.6%, P<0.01). ADM could obviously enhance the action of ADM(27-52) in inhibiting alkaline phosphatase activity (14.4%, P<0.01) and in reducing calcium uptake (11.4%, P<0.01). ADM(27-52) could partially antagonize the effects of ADM on regulating downwards osteopontin-mRNA expression (17.0%, P<0.01). It is concluded that ADM(27-52) derived from ADM acts as an inhibitory agent on vascular calcification, with special mechanisms different from ADM derived from ADM progenitor molecule.

Topics: Adrenomedullin; Animals; Aorta, Thoracic; Calcinosis; Cholecalciferol; Male; Nicotine; Nicotinic Agonists; Peptide Fragments; Rats; Rats, Sprague-Dawley

Ghrelin is a new peptide with regulatory actions in growth hormone secretion in the anterior pituitary gland and in energy metabolism. Currently, ghrelin has potently protective effects in cardiovascular diseases. We used an in vivo model of rat vascular calcification induced by vitamin D3 and nicotine and one of cultured rat vascular smooth muscular cells (VSMCs) calcification induced by beta-glycerophosphate to study the possible mechanism in the regulatory action of ghrelin in vascular calcification. Calcification increased total Ca2+ content and 45Ca2+ deposition in aortas and VSMCs and alkaline phosphatase (ALP) activation in plasma, aortas and VSMCs. However, calcified aortas and VSMCs showed a significant decrease in osteopontin (OPN) mRNA expression and a marked reduction of ghrelin levels in plasma and its mRNA expression in aortas. The aortic calcification was significantly attenuated by subcutaneous administration of ghrelin 30 and 300 nmol kg(-1) day(-1) for 4 weeks, and the latter dosage was more potent than the former. Ghrelin treatment at the two dosages reduced the total aorta Ca2+ content by 24.4% and 28.1%, aortic 45Ca2+ deposition by 18.4% and 24.9%, plasma ALP activity by 36.6% and 76.7%, and aortic ALP activity by 10.3% and 47.6% (all P < 0.01 or 0.05), respectively. Ghrelin at 10(-8)-10(-6) mol/L attenuated the calcification in cultured VSMCs, with decreased total Ca2+ content, 45Ca2+ deposition and ALP activity and increased OPN mRNA expression, in a concentration-dependent manner. In addition, endothelin levels in plasma and aortas and its mRNA expression in aortas significantly increased with calcification, but ghrelin treatment significantly decreased endothelin levels and mRNA expression, with the high dosage being more potent than the lower dosage. These results indicate that local ghrelin in vascular was down-regulated during vascular calcification, whereas administration of ghrelin effectively attenuated vascular and VSMCs calcification.

Topics: Animals; Aorta; Calcinosis; Cells, Cultured; Cholecalciferol; Ghrelin; Male; Muscle, Smooth, Vascular; Nicotine; Nicotinic Agonists; Peptide Hormones; Rats

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.

Topics: Animals; Calcinosis; Calcium; Cardiomyopathies; Cholecalciferol; Disease Models, Animal; Heart; Male; Nicotine; Nitric Oxide; Nitric Oxide Synthase; Rats; Rats, Wistar; Ryanodine Receptor Calcium Release Channel; Sarcoplasmic Reticulum; Up-Regulation

1. In humans, two of the principal characteristics of vascular ageing are arterial wall calcification and decreased arterial distensibility, which induce organ damage. To amplify arterial calcium accumulation in laboratory animals, it is necessary to use an overdose of vitamin D(3). 2. The aim of the present study was to assess the impact of arterial calcium overload on renal function. 3. Adult male Wistar rats were randomly divided into two groups: control and treated rats. Treated rats were injected 10 days before the experiment with a single dose of vitamin D(3) (300 000 IU/kg, i.m.). 4. Treated rats showed a decrease in renal blood flow and glomerular filtration rate. Tubular parameters were not modified under basal conditions. In contrast, a statistically significant increase in the fractional excretion of Na, K, Ca and H(2)O were observed in treated rats after the acute increment of sodium distal delivery, suggesting that the reabsorptive capacity of the thick ascending limb may be altered in treated rats. 5. Thus, Na(+)/K(+)-ATPase activity was evaluated in homogenates from renal cortex and medulla. Rats with arterial calcinosis presented a diminished activity of Na(+)/K(+)-ATPase in medulla homogenates. 6. An increment in the abundance of the Na-K-2Cl cotransporter (NKCC2) was observed in renal medulla homogenates from treated rats. It is suggested that this may compensate for the inefficiency of Na(+)/K(+)-ATPase under basal conditions but, in the presence of acute distal sodium overload, the increment in NKCC2 abundance may not be sufficient to compensate for the decrease in Na(+)/K(+)-ATPase activity. 7. In summary, in our experimental model of arterial calcinosis, renal function is impaired, presenting a vascular compromise and altered function of the medullar thick ascending limb that becomes evident in the presence of acute high distal sodium delivery.

Topics: Animals; Aorta, Abdominal; Calcinosis; Cholecalciferol; Kidney Diseases; Kidney Tubules, Distal; Male; Rats; Rats, Wistar; Renal Artery

Adrenomedullin (ADM) is a potent vasodilatory peptide which regulates blood pressure, cell growth and bone formation. Our work was aimed to explore the production of ADM, changes and pathophysiological significance of ADM mRNA and ADM receptor components--calcitonin receptor like receptor (CRLR) and receptor activity modifying proteins (RAMPs) mRNA in calcified myocardium and aorta of rats induced by Vitamin D3 plus nicotine. Contents of ADM in plasma, myocardium and aorta were measured by radioimmunoassay (RIA). The amount of ADM, CRLR and RAMPs mRNA was determined by semi-quantitative RT-PCR. The calcium content and alkaline phosphatase activity in myocardium and aorta of rats were measured. The results showed that the contents of calcium in calcified myocardium and aorta were increased by 3.5- and 6-fold (all P < 0.01), respectively, and alkaline phosphatases activity in calcified myocardium and aorta were increased by 66.5 and 82.7% (all P < 0.01 ), respectively, compared with control. Contents of ADM in plasma, myocardium and aorta were increased by 58% (P < 0.01), 14.3% (P < 0.01) and 27.8% P < 0.05). Furthermore, it was found that the amount of ADM, CRLR and RAMP2 mRNA in calcified myocardium was elevated by 90.6, 157.5 and 119.6% (all P < 0.01), RAMP3 mRNA was decreased by 14.1% (P < 0.01), respectively, compared with control. The amount of ADM, CRLR, RAMP2 and RAMP3 mRNA in calcified aorta was elevated by 37.7% (P < 0.01), 41.4% (P < 0.01), 60.1% (P < 0.05) and 13% P < 0.01), respectively, compared with control. The elevated level of CRLR and RAMP2 mRNA were in positive correlation with that of ADM mRNA (r = 0.992 and 0.882, respectively, P < 0.01) in calcified myocardium. The elevated level of CRLR and RAMP3 mRNA were also in positive correlation with that of ADM mRNA (r = 0.727, P < 0.05 and 0.816, P < 0.01, respectively) in calcified aorta. These results demonstrated that calcified myocardium and aorta generated an increased amount of ADM, up-regulated gene expressions of ADM, CRLR and RAMP2 mRNA. While the alteration of RAMP3 mRNA in calcified myocardium and aorta was different. These suggested that ADM and its receptor system might involve in the regulation of calcification in heart and aorta.

Topics: Adrenomedullin; Animals; Aorta; Calcinosis; Calcitonin Receptor-Like Protein; Cardiomyopathies; Cholecalciferol; Gene Expression Regulation; Intracellular Signaling Peptides and Proteins; Male; Membrane Proteins; Myocardium; Nicotine; Nicotinic Agonists; Peptides; Rats; Rats, Sprague-Dawley; Receptor Activity-Modifying Protein 2; Receptor Activity-Modifying Protein 3; Receptor Activity-Modifying Proteins; Receptors, Adrenomedullin; Receptors, Calcitonin; Receptors, G-Protein-Coupled; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

Topics: Calcinosis; Calcium Gluconate; Cholecalciferol; Female; Fingers; Goiter; Hand Deformities, Acquired; Humans; Hypoparathyroidism; Hypothyroidism; Middle Aged; Thyroid Hormones; Thyroidectomy; Thyroxine

In vascular smooth muscle, calcium overload is a highly pathogenic event, which increases with advancing age. An increase in the calcium content of arterial wall may be produced in rats by treatment with vitamin D3. The aim of this study was to evaluate the renal clearance of sulfanilamide (a model organic anion, preferentially eliminated by the kidneys) and other parameters of global renal function in rats with arterial calcinosis. Arterial calcinosis was produced in adult rats by means of a single dose of vitamin D3 (300,000 UI/kg bw, i.m.) 5 days before the experiment. Treated rats showed a large increase in calcium content of aortic tissue and an increase in systolic arterial pressure. No modifications were observed in plasma calcium levels and in plasma lipid profiles. Statistically significant decrements were observed in renal clearance of sulfanilamide, in renal blood flow, in fractional excretion of sodium and potassium. A slight decrease, not statistically different, was observed in the glomerular filtration rate. Rats with arterial calcinosis also showed an increment of total calcium levels in renal tissue, in fractional excretion of calcium and in the expression of organic anion transporter 1 (OAT1). Histological studies revealed tubular alterations. In summary, modifications in hemodynamics and tubular parameters are early manifestations of nephropathy in rats with arterial calcinosis, some of which may account for the changes observed in organic anions renal depuration. It is important to mention that the decrease in clearance of organic anions were seen in spite of the increase in expression of OAT1.

Topics: Animals; Aorta, Abdominal; Aortic Diseases; Blood Pressure; Calcinosis; Calcium; Cholecalciferol; Disease Models, Animal; Glomerular Filtration Rate; Kidney Diseases; Kidney Function Tests; Male; Organic Anion Transport Protein 1; Randomized Controlled Trials as Topic; Rats; Rats, Wistar; Renal Circulation; Sulfanilamide; Sulfanilamides; Systole; Time Factors

A now 65-year-old man had undergone a subtotal thyroidectomy over 40 years ago, which postoperatively resulted in hypoparathyroidism. His doctor began daily intravenous injections of a calcium preparation (1880 mg to 3760 mg calcium per day, over 40000 injections during this period), a regimen continued subsequently by a total of more than 15 other doctors for over 40 years. On admission the patient complained of oral paresthesias and paresthesias of the limbs.. Low calcium and parathormone levels confirmed the diagnosis of hypoparathyroidism.. Normal levels of calcium were achieved after a short course of 1.25-dihydroxycalciferol. This was followed by the administration of cholecalciferol and calcium. The patient soon became symptom-free and calcium levels returned to normal. Late sequelae have been calcification of the basal ganglia, first signs of nephrocalcinosis and bilateral cataract.. This case demonstrates that appropriate treatment of hypoparathyroidism [corrected] might not be given in every case.

Topics: Aged; Basal Ganglia; Calcinosis; Calcitriol; Calcium; Cholecalciferol; Humans; Hypocalcemia; Hypoparathyroidism; Injections, Intravenous; Male; Parathyroid Hormone; Paresthesia; Thyroidectomy

Paroxysmal kinesigenic dyskinesia (PKD) is an uncommon neurological disorder characterised by abnormal episodic brief movements induced by sudden movements of the body. The recognition and understanding of this disorder has increased over the past few decades. While most cases are idiopathic, the association of PKD with various disorders, including metabolic abnormalities has also been reported. We report an interesting case of a 52 year old male who presented with PKD manifesting as subtle facio-brachial movements and apraxia of eyelid opening (ALO) secondary toidiopathic hypoparathyroidism.

Topics: Arm; Brain Diseases; Calcinosis; Calcium Carbonate; Cholecalciferol; Chorea; Epilepsy, Tonic-Clonic; Eyelids; Facial Muscles; Humans; Hypoparathyroidism; Male; Middle Aged; Movement; Shoulder

Several studies have demonstrated that excess of vitamin D3 is toxic particularly to vascular tissues. A notable pathological feature is arterial calcification. The nature of the toxic metabolite in hypervitaminosis D and the pathogenesis of arterial calcification are not clearly understood. The present study was undertaken to explore whether arterial calcification is a sequel of increased calcium uptake by arterial smooth muscle mediated by up regulation of vitamin D receptor in the cells in response to elevated circulating levels of vitamin D3 in serum. The experimental study was performed in 20 New Zealand white female rabbits aged 6 months. Animals in the test group were injected 10,000 IU of cholecalciferol intramuscularly twice a week for one month. Six control animals were given intra-muscular injections of plain cottonseed oil. Animals were sacrificed and aortas were examined for pathological lesions, 1,25-dihyroxyvitamin D3 (1,25(OH)2 D3) receptor levels and 45Ca uptake in smooth muscle cells. Serum samples collected at intervals were assayed for levels of 25-OH-D3 and calcium. The results showed that in animals given injections of cholecalciferol, serum levels of 25-OH-D3 were elevated. In four of these animals calcification and aneurysmal changes were seen in the aorta. Histological lesions comprised of fragmentation of elastic fibers as well as extensive loss of elastic layers. 1,25(OH)2 D3 receptor levels were up regulated and 45Ca uptake enhanced in aortas of animals which were given excessive vitamin D3. The evidences gathered suggest that excess vitamin D is arteriotoxic and that the vitamin induces arterial calcification through up regulation of 1,25(OH)2D3 receptor and increased calcium uptake in smooth muscle cells of the arteries.

Topics: Animals; Aorta, Abdominal; Aorta, Thoracic; Calcifediol; Calcinosis; Calcium; Cells, Cultured; Cholecalciferol; Female; Injections, Intramuscular; Muscle, Smooth, Vascular; Rabbits; Receptors, Calcitriol; Up-Regulation

Matrix Gla Protein (MGP) is a small protein which is thought to be an inhibitor of tissue calcification and a regulator of cell differentiation. In this study we have examined the transcriptional regulation of MGP within rat vascular smooth muscle cells (VSMCs). We found that MGP transcription is downregulated by retinoic acid and transforming growth factor beta (TGF beta) whereas it is upregulated by vitamin D3 and cyclic AMP.

Topics: Animals; Arteriosclerosis; Calcinosis; Calcium-Binding Proteins; Cholecalciferol; Cyclic AMP; Down-Regulation; Extracellular Matrix Proteins; Gene Expression Regulation; Humans; Matrix Gla Protein; Muscle, Smooth, Vascular; Rats; Transcription, Genetic; Transforming Growth Factor beta; Tretinoin; Up-Regulation

We report autopsy findings of a 69-year-old man on long-term CAPD therapy for 13 years who showed linear peritoneal calcification. Continuous ambulatory peritoneal dialysis (CAPD) was started in 1982. He has been administered excessive amounts of vitamin D(3) derivatives (VitD) (2.0 to 2.5 microg daily) and calcium carbonate (4 g daily) for secondary hyperparathyroidism since initiation of CAPD. In May 1995, his intact parathyroid hormone (PTH) level increased over 1,000 pg/mL. Immediately after VitD was changed from pill to liquid, the dose was increased to 5 microg daily. Although the serum calcium level remained between 4.5 and 4.9 mEq/L, and serum phosphate level was 5.0 to 7.2 mg/dL, plain abdominal radiography and computed tomography showed continuous calcification along the intestinal wall in October 1995. In spite of the continuation of CAPD therapy, he remained asymptomatic until he died of congestive heart failure in January 1997. He experienced eight episodes of peritonitis during his clinical course. Autopsy showed that numerous calcified plaques were present on the submucosal portion between the thickened serosa and the longitudinal layer of the muscularis externa. The remainder of the subserosa was fibrotic, and the small arteries had markedly thickened intima and severely narrowed lumina.

Topics: Abdominal Muscles; Calcinosis; Calcium; Calcium Carbonate; Cholecalciferol; Humans; Hyperparathyroidism, Secondary; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Phosphates; Time Factors; Tomography, X-Ray Computed

Over 650 pigs died within a couple hours in a fattening unit with approximately 3,000 fattening spaces. The pigs showed vomiting, dyspnea, kyphosis, sunken flanks, diarrhea, and polyuria. Another striking symptom of the pigs, besides the apathy, was the aphonia, due to the calcification of the vocal cords. An acute vitamin D3-intoxication was found to be the cause. The pathologic findings, especially the histologic detection of calcification processes of the soft tissues, lead to the suspect of an intoxication with a vitamin D-like substance. Between 39,000 and 196,000 IU/kg of vitamin D3 have been detected in a ready-to-use food mix. 8.8 million IU/kg of crystaline vitamin D3 were found in an open whey bag. An explanation how vitamin D came into the bag could not be clarified to this point.

Topics: Animal Feed; Animals; Calcinosis; Cholecalciferol; Poisoning; Swine; Swine Diseases; Vocal Cords

To clarify the prevalence and etiology of ectopic calcification in patients with systemic lupus erythematosus (SLE), especially under the active vitamin D3 administrations and to reveal the risk factors of ectopic calcification.. Sixty patients with SLE, excluding the patients on dialysis were studied. We examined radiographs of hands, forearms, upper and lower extremities, and pelvises of all patients to evaluate ectopic calcification.. The prevalence of ectopic calcification in SLE was 40% (24 out of 60 patients), found in 6.7% (4 patients) in peripheral arteries, 33.3% (20 patients) in periarticular area and 16.7% (10 patients) in other soft tissues. The incidence of lupus nephritis and nephrotic syndrome were significantly higher (respectively: P=0. 0144 and P=0.0348) in the calcification-positive than negative group. Total protein levels (7.04+/-0.6 g/dl) of patients in the calcification-positive group were decreased significantly (P=0.0056) compared with 7.48+/-0.55 g/dl in the negative group. However, other biochemical parameters were not significantly different between the two groups. Sixty-three percent of the SLE patients with ectopic calcification received alfacarcidol, which is significantly (P=0. 0007) higher than the 19% in patients without calcification.. It is suggested that the alfacarcidol therapy and lupus nephritis could increase the risk of ectopic calcification in SLE patients.

Topics: Adult; Aged; Calcinosis; Cholecalciferol; Connective Tissue Diseases; Female; Humans; Hydroxycholecalciferols; Lupus Erythematosus, Systemic; Male; Middle Aged; Prevalence; Renal Dialysis

Two cases of vitamin D3 intoxication in piglets are described. The dietary concentrations of vitamin D3 were 265 and 435 thousand IE/kg. Decreased feed intake, growth depression and polyuria or polydypsia were observed. In some animals hypercalcemia and symptoms of impaired renal function were found. Pathological findings included calcinosis of several tissues and degenerative damage.

Topics: Animal Feed; Animals; Calcinosis; Cholecalciferol; Feeding and Eating Disorders; Foodborne Diseases; Hypercalcemia; Kidney; Swine; Swine Diseases

The model of vitamin D3-induced calcinosis in rats makes it possible to follow important aspects of lipid and lipoprotein metabolism regulation not only in vessels, but also in the myocardium and in other organs of experimental animals. THE AIM of this paper is to follow the influence of isradipine on some lipid parameters in the serum, in aorta and myocardium.. D3 vitamin, isradipine, olive oil and the solvent for isradipine respectively were administered to experimental animals, males of Wistar rats. The animals of the control group (I) received olive oil in dose 0.5 ml/100 mg of bodyweight and the solvent for isradipine in dose 1 ml/100 mg of bodyweight. The second group (II) received D3 vitamin in dose 300000 i.u./kg of bodyweight. The third group (III) got pure isradipine in dose 0.25 mg/100 mg of weight and pure olive oil. The fourth group (IV) got D3 vitamin in the experimental same dose as the second group and a subsequent dose of 0.25 mg/100 mg of bodyweight.. The animals were divided into 4 groups. The first group (I) were the controls. The second group (II) received D3 vitamin. We detected a significant increase in triacylyglycerol values by 12.4 per cent and in total lipids by 30.3 per cent, respectively an increase in triacylgycerols in myocardium by 188.8 per cent. The serum level of total cholesterol increased by 123.6 per cent and the level of LDL by 263.6 per cent. In the third group (III) the animals received only isradipine. In this group, the value of triacylglycerols in aorta decreased by 52.5 per cent, respectively and so did the total lipids by 22.4 per cent. The values of triacylglycerols in myocardium were decreased by 17.2 per cent and the total lipids by 6.2 per cent in contrast to the second group, where vitamin D3 was applied. The changes in the values of serum cholesterol were not significant. In the fourth group (IV) the experimental animals received vitamin D3 with isradipine. The values of total lipids and triacylglycerols were higher than these in group III, but in any of them did not attain the values of the second group, where only vitamin D3 was applied.. The model of experimental calcinosis opens new possibilities of study of the pathomechanism of some manifestations of atherosclerosis, as well as the possibilities of their influence. Our results testify a positive influence of isradipine on the development of experimental calcinosis. (Fig. 4, Ref. 34.)

Topics: Animals; Calcinosis; Calcium Channel Blockers; Cholecalciferol; Isradipine; Lipid Metabolism; Male; Rats; Rats, Wistar

Valvular calcification in chronic haemodialysis patients has already been reported in the literature, particularly the abnormally high incidence of aortic stenosis. In this study, 112 haemodialysis patients were followed up by Doppler echocardiography for a period of 36 months. Sixteen patients developed aortic valvular calcification with aortic stenosis over an 18.7 +/- 7.5 months period. The indexed aortic valve surface area decreased from 1.24 +/- 0.9 cm2/m2 to 0.66 +/- 0.21 cm2/m2 with abnormally rapid progression. Eight patients with aortic stenosis died during the 3 year study period. These results reflect the abnormal extra-skeletal calcification of chronic haemodialysis patients. Several predisposing factors were demonstrated: age (68.5 +/- 11.1 years versus 57.1 +/- 16.3 years in patients without calcifications), male gender, a longer period of dialysis than the patients without aortic stenosis (8.1 +/- 5.3 versus 5.9 +/- 5.7 years), abnormalities of calcium and phosphate metabolism, increased of the phosphocalcic product by hyperphosphoraemia and not by hypercalcaemia, hypoparathyroidism in 62% and hyperparathyroidism in 38% an increase in vitamin D 3 (19.7 +/- 14 ng/ml versus 9.6 +/- 6.3 ng/ml) biological signs of adynamic osteodystrophy. Calcific aortic stenosis is a commonly observed valvular lesion in haemodialysis patients: its progression may be very rapid, associated with a poor prognosis. Old age, male gender, duration of haemodialysis, hyperphosphataemia associated with hypoparathyroidism and raised Vitamin D3 are predisposing factors.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Calcinosis; Calcium Metabolism Disorders; Cholecalciferol; Female; Follow-Up Studies; Humans; Kidney Failure, Chronic; Male; Middle Aged; Phosphorus Metabolism Disorders; Prognosis; Renal Dialysis; Risk Factors; Ultrasonography

Vitamin D3-induced mural calcification represents an animal model for investigating experimental calcium (Ca) overload and calcification of arterial walls. In this study, long-term progression of calcific degeneration in coronary arteries of rats after one intoxication with vitamin D3 was examined, as well as possible regression of preestablished mural Ca overload with the Ca antagonist verapamil. Sprague-Dawley rats were treated with one intramuscular (i.m.) overdose of vitamin D3 [300,000 IU/kg body weight (b.w.)]. Oral verapamil therapy (100 mg/kg/day b.w. for 24 weeks) was initiated 14 days after the vitamin D3 intoxication. Arteriosclerotic alterations were verified by microchemical analyses of tissue Ca and of cholesterol contents with atomic absorption spectroscopy (special graphite tube technique) and gas chromatography, respectively, and by standard histological techniques. Serum lipids were determined by sequential ultracentrifugation. Between week 3 and week 26 after the vitamin D3 injection, a progressive Ca incorporation from 448.8 +/- 110 to 1,310 +/- 166.3% of control values (i.e., coronary Ca content in 32-week-old untreated control rats = 100%) was observed, associated with calcific morphological lesions, and reactive intimal plaque formation. Verapamil prevented this progression and induced a regression of preestablished mural Ca overload. Therefore, the coronary Ca content after 24 weeks of verapamil treatment amounted to only 146.3 +/- 53.8% of controls. The data indicate that an initial calcific lesion of coronary arteries may serve as crystallization nucleus for advancing Ca overload and morphological alterations.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Arteriosclerosis; Calcinosis; Calcium; Calcium Channel Blockers; Cholecalciferol; Coronary Vessels; Lipids; Male; Rats; Rats, Sprague-Dawley; Verapamil

Naked mole-rats have no access to obvious sources of vitamin D and therefore have an impoverished vitamin D status. In an investigation into the effects of vitamin D supplementation, inadvertently supraphysiological doses of 130,000 times the normal dose of vitamin D were administered. Within 5 days animals appeared lethargic, with reduced food intake. All but one of the seven animals were killed and blood was collected. Plasma vitamin D metabolites 25(OH)D and 1,25(OH)2D and calcium were determined. Both vitamin D metabolite concentrations exceeded the upper limits of sensitivity of the assays (> 100 ng/ml 25(OH)D and > 210 pg/ml 1,25(OH)2D). Active calcium uptake in the intestine was evident along with concomitant increases in calcium concentration in plasma, bone, and teeth. The remaining animal survived, but showed scab-like formations in the skin around the lower jaw and along the nipple line. X-ray analyses revealed calcium deposition in these cornified regions, although there was no evidence of metastatic calcification in other tissues. Deposition of excess calcium in skin that is regularly sloughed off and in teeth that are continuously worn down and replaced may reduce the vitamin D-induced hypercalcaemia and thus alleviate the effects of vitamin D intoxication.

Topics: Animals; Calcinosis; Calcium; Cholecalciferol; Hypercalcemia; Rodent Diseases; Rodentia; Skin Diseases; Tooth

The effect of SR 33805, a novel calcium entry blocker, on calcium overload was studied in six vascular beds in rat. Fantofarone, a parent compound, and verapamil were used as reference calcium entry blockers. Calcium overload induced with a single dose (300,000 IU, i.m. of vitamin D3) was measured by means of atomic absorption and histological techniques. From the time-course of calcium overload, a treatment period of 3 days was selected to determine the effects of drug treatment. The compounds were given orally twice a day in the following dose ranges: SR 33805 2-100 mg/kg, fantofarone 10-300 mg/kg, verapamil 100 mg/kg. SR 33805 significantly decreased the calcium content beginning at the dose of 2 mg/kg in the thoracic aorta, 5 mg/kg in the mesenteric artery and 30 mg/kg in the heart. Fantofarone and verapamil had the same effect at the dose of 100 mg/kg. Histological assessment of the heart revealed that lesions appearing in the tissue adjacent to the arteries were significantly diminished by treatment with SR 33805 at a dose which produced a significant decrease in the arterial calcium content. Thus, SR 33805 can inhibit both calcium overload and its deleterious consequences and its actions are evident at doses as low as 2 mg/kg.

Topics: Animals; Aorta, Thoracic; Calcinosis; Calcium; Calcium Channel Blockers; Cardiovascular Diseases; Cholecalciferol; Dose-Response Relationship, Drug; Indoles; Indolizines; Male; Mesenteric Arteries; Myocardium; Phenethylamines; Rats; Rats, Sprague-Dawley; Staining and Labeling; Sulfones; Verapamil

Topics: Basal Ganglia Diseases; Calcinosis; Calcium; Cholecalciferol; Drug Therapy, Combination; Humans; Hypoparathyroidism; Male; Middle Aged; Syndrome

The mineralization process was investigated in the aortic wall of hypercalcemic rabbits. The elevated calcium level in serum was induced by intramuscular injection of vitamin D3. The animals were killed at different times of the experiment (max. 246 d). The freeze-dried tissue homogenates were used for elemental composition studies by means of proton induced X-ray emission (PIXE) and atomic absorption spectroscopy. The structural information was obtained from infrared (IR) and X-ray diffraction (XRD) spectra. Moreover, the ascending part of the aortic arch was separated and used for micro-PIXE (PIXE in combination with proton microprobe) and histochemical examinations. It was found that hypercalcemia (blood serum Ca content elevated by about 20%) induced calcification of the aortic wall. The mineral phase within the aortic wall consisted of Ca-P salts. The Ca/P ratio continuously increased during the experiment and approached 2 after 246 d of the vitamin D3 treatment. The IR and XRD studies made possible the identification of the complex phase composition of the samples. The hydroxyapatite crystals were detected after 196 days, however, in earlier phases of the experiment, amorphous calcium phosphate, dicalcium phosphate dihydrate and octacalcium phosphate were also observed. On the basis of the data obtained, the mechanism of the precipitation and growth of inorganic deposits in the tunica media of the aortic wall was discussed.

Topics: Animals; Aortic Diseases; Calcinosis; Calcium; Calcium Phosphates; Cholecalciferol; Hypercalcemia; Phosphorus; Rabbits; Spectrometry, X-Ray Emission

We studied the aortic elastic behavior in response to vitamin D3-induced accelerated calcinosis in conscious dogs chronically instrumented with a pressure microtransducer and a pair of ultrasonic diameter dimension gauges in the upper descending thoracic aorta. The two functional phases of the elastic segmental properties of the aorta in vivo were discriminated by computation on a beat-by-beat basis from the phasic pressure-diameter (P-D) hysteresis loops in basal conditions and during the transient state of a wide range of pressures obtained mechanically (aortic occlusion) or pharmacologically (angiotensin bolus). The overall P-D curve formed by all P-D hysteresis loops was comprised of two linear relations according to a model that assumes that only elastin is stretched at lower pressures, whereas both elastin and collagen are stretched at higher pressures. The slope of the first linear portion of the P-D curve was considered as the elastin P-D elastic modulus, and the slope of the curve obtained by subtraction between the P-D curve and the extrapolation of the elastin straight line was assumed to be the collagen P-D elastic modulus. After vitamin D3-induced calcinosis, the elastin elastic modulus was unaffected, whereas the collagen elastic modulus decreased significantly during occlusion maneuvers (58.6%, p less than 0.01) and during bolus injections of angiotensin (37.2%, p less than 0.05). The collagen elastic modulus correlated with the serum calcium concentration (r = -0.65, p less than 0.001) and with the aortic pulse pressure (r = 0.51, p less than 0.01), and this relation persisted at constant heart rate. Histopathologic analysis evidenced calcium-depositing elastic lamina, focal disappearance of collagen, and rupture of elastic fibers. The present study shows that accelerated, severe, experimental calcinosis-inducing calcium deposition inside the large artery walls is accompanied by a clear-cut paradoxical reduction in arterial rigidity that is mainly due to functional and structural modification of collagen elasticity.

Topics: Animals; Aorta; Calcinosis; Cholecalciferol; Dogs; Elasticity; Male; Models, Cardiovascular

A 4-month-old 2.5-kg sexually intact female domestic shorthair cat was referred to the teaching hospital because of suspected cholecalciferol intoxication after ingestion of a cholecalciferol-containing rodenticide. At referral, the cat was hypercalcemic, hyperkalemic, and acidotic. Despite management of hypercalcemia and preservation of renal function with physiologic saline solution, furosemide, dopamine, and calcitonin, the cat died, apparently as a result of extensive pulmonary mineralization.

Topics: Animals; Calcinosis; Cat Diseases; Cats; Cholecalciferol; Female; Kidney; Lung; Lung Diseases; Rodenticides

Because the pathogenesis of osteosclerosis in hypervitaminosis D is still not well elucidated, the authors experimentally studied hypervitaminosis D3 in 66 rabbits by injecting different doses of vitamin D3. Contact radiographs of bone specimens showed various signs of osteosclerosis, including dense epiphyses and metaphyses, thickened bony articular surfaces, dense metaphyseal bands, modeling defects at the metaphysis, and dense and thickened cortical bone. The corresponding pathologic sections showed that conspicuous metastatic calcification coated the trabeculae and filled bone marrow cavity and caverns in the original but porotic cortical and periosteal new bone. Rather than being resorbed, the metastatic calcifications were embedded in a thick layer of newly formed bone 6 to 14 weeks after vitamin D3 withdrawal. This study suggests that in hypervitaminosis D3, the osteoblasts and bone marrow undergo degeneration, leading to necrosis and calcification. After vitamin D3 withdrawal, osteoblasts reappear and become overactive, leading to overossification.

Topics: Animals; Bone Diseases; Calcinosis; Cholecalciferol; Osteosclerosis; Rabbits; Radiography

Effects of experimental calcinosis induced by daily overdose of 500.000 IU Vit D3 during 10 days were studied in 6 mongrel conscious dogs chronically instrumented with intra-aortic Konigsberg microtransducer and two ultrasonic piezo-electric crystals diametrically opposed in the adventitia of the descending thoracic aorta. Simultaneous recording of instantaneous aortic pressure and diameter waves in basal state and during transient acute hypertension induced by intravenous angiotensin bolus (0.1 microgram/kg) allowed to obtain the pressure (y) diameter (x) relationship of the aorta according to an exponential regression: P = expo (beta D + A), with a highly significant correlation coefficient in all animals (r greater than 0.99). (table; see text) Anatomopathological studies of aortas revealed abnormal calcium deposition, ruptures of elastic fibers and disorganization of collagen. Thus, a striking decrease in aortic rigidity is observed after calcinosis in relation with structural changes of elastic materials and responsible in part for a reduction in pulsatile pressure; moreover this unexpected phenomena might represent an initiative process of development of aortic aneurysms.

Topics: Animals; Aorta, Thoracic; Aortic Diseases; Calcinosis; Cholecalciferol; Consciousness; Dogs; Elasticity; Models, Biological; Viscosity

The effects of salmon calcitonin on calcium overload and its deposition in the rat aorta was studied. Calcitonin administered 4 days to rats i.p. in doses of 10 IU/kg body weight blocked the development of calcinosis induced by a single dose of vitamin D3 (300,000 IU/kg body weight, orally). This was demonstrated biochemically, histochemically and by electron microscopic methods.

Topics: Animals; Aorta; Aortic Diseases; Calcinosis; Calcitonin; Calcium; Cholecalciferol; Male; Rats; Rats, Inbred Strains

Vitamin D intoxication, which may result from zealous intake of health food supplements, may cause metastatic calcification. This is the first reported case of a patient with vitamin D intoxication who had massive gastric uptake of [99mTc]MDP, but no lung uptake, with histologic documentation of the metastatic calcification by gastric biopsy. It is probable that the metastatic calcification was a highly metabolic process in this patient since the gastric uptake resolved within 3 wk when serum calcium and phosphate had returned to normal.

Topics: Bone and Bones; Calcinosis; Cholecalciferol; Female; Gastric Mucosa; Humans; Hypercalcemia; Lung; Middle Aged; Radionuclide Imaging; Sodium Pertechnetate Tc 99m; Stomach; Stomach Diseases; Technetium Tc 99m Medronate

It is reported on cases of calcinosis during winter 1979/80 occurring on 42 farms and leading to 34 forced slaughters and on the control of this disease in a localized region of the Alpine foot-hills. Instruction of the farmers, ploughing up of the meadows with following new sowing of grass without golden oat (Trisetum flavescens) allowed to push back calcinosis in high situated especially endangered farms. The different calcinogenic activity of golden oat in the different stages of growing, pushing back the golden oat by repeated utilisation of the pastures and keeping the cattle in the stable were successful methods. Additionally it was possible to influence the quantity of golden oat in pastures and meadows by methods influencing the growing such as climate, altitude, quality and quantity of fertilizer, age of the meadows. The importance of the Alpine pastures for prevention of calcinosis in cattle is pointed out.

Topics: Animals; Austria; Calcinosis; Cardiovascular System; Cattle; Cattle Diseases; Cholecalciferol; Edible Grain

Combined administration of vitamin D3 and nicotine produced severe myocardial and aortic calcinosis in mice within 4 days. Treatment of these mice with taurine increased the survival rate of the mice and reduced the elevation of calcium content in both aorta and myocardium as did diltiazem treatment. The present study suggests that taurine which is capable of regulating calcium flux may also prevent the progression of arteriosclerosis.

Topics: Animals; Aorta; Arteries; Arteriosclerosis; Calcinosis; Calcium; Cholecalciferol; Diltiazem; Male; Mice; Myocardium; Taurine

A rat animal model was used to study the ultrastructure of submucosal calcifications induced in the middle ear following inoculation with Streptococcus pyogenes and high doses of parenteral vitamin D3. The morphological changes present in affected animals resembled the classical picture of tympanosclerosis. While calcification occurred about bacterial remnants and myelin structures, the most important calcification centers were lysosomal and non-lysosomal matrix vesicles in the extracellular spaces. These formed band-like calcifications close to the basal membrane without affecting the epithelial layer. This animal model offers the possibility of studying the effect of various therapeutic regimens in the treatment of the dynamic tympanosclerotic process.

Topics: Animals; Calcinosis; Cholecalciferol; Ear, Middle; Epithelium; Microscopy, Electron; Mucous Membrane; Otosclerosis; Rats; Rats, Inbred Strains; Streptococcal Infections; Streptococcus pyogenes

Twenty-four children with vitamin D intoxication and a follow-up of one to thirteen years old (means: four years and seven months) are reviewed. Over-dosage was prescribed by medical order in 66.6% of patients and by the mother herself in 16.6%. Intensity of clinical symptoms (renal, neurologic, digestive) were related with daily dose administered whilst final secuelae depends on duration of overdosage. Hipercalcemia was easily corrected by association of low calcium diet, corticoesteroids and/or furosemide in least than a month in 81% of cases. Two patients died during the acute fase and 22.7% remain with permanent damage (five in chronic renal failure, one in haemodialysis and three with low IC).

Topics: Bone Diseases, Metabolic; Calcinosis; Calcium; Child; Child, Preschool; Cholecalciferol; Female; Humans; Hypertension; Infant; Male; Nephrocalcinosis

The following mechanisms for inactivating excessive Ca++ are found in the vessel wall (e.g. in old age, arteriosclerosis, hypertension, or overdosage with Vitamin D3): 1. The production of Matrix Vesicles, which reduce biologically active extracellular Ca++ by precipitating it during the initial stage of calcification. 2. An increase in the number of muscle cells changed from the "k" to the "m" form. These also possess a mechanism for reducing the intracellular Ca++ level. If in spite of these mechanisms the extracellular Ca++ concentration remains raised, this can result in calcification of the interzellular substance, particularly the elastic material.

Topics: Aged; Animals; Aorta, Thoracic; Calcinosis; Calcium; Cholecalciferol; Coronary Disease; Coronary Vessels; Disease Models, Animal; Elastic Tissue; Humans; Lipids; Microscopy, Electron; Muscle, Smooth, Vascular; Rats; Risk

Topics: Animals; Bird Diseases; Calcinosis; Calcium; Cardiovascular Diseases; Cholecalciferol; Coturnix; Diet; Female; Kidney Diseases; Microscopy, Electron; Plants; Proteoglycans; Quail

Nonspecific calcinosis engendered by vitamin D3 is associated with extraosseous calcium deposits, in connection with which proteoglycans (PG) can be observed. After administration of vitamin D3 tissue samples from cardiac muscle and aorta of rats were taken and traced ultrahistochemically by means of the acriflavin-phosphotungstic acid contrast-method. The calcification began first with an increase in PG in the cell membranes of the sarcolemma, in the ground substance, and in the capillaries of the interstice. Subsequently circularly formed concentric layers of calcium encrustations appear in the above-mentioned locations. Large amounts of PG were also observed prior to the formation of crystalline fascicular calcium deposits in the ground substance and in the elastic fibers of the media of the aorta. This process began at the outer edges of the media and continued towards their interior, resulting in a loosening of the bond between the elastic fibers and the sarcoplasmic continuations of the smooth muscle cells. The extraosseous calcification resulting after the administration of vitamin D3 can therefore be considered not only as a result of hypercalcemia, but also as a result of stimulation of the production of ground substance through vitamin D3. This form of calcification represents a characteristic pathophysiological process which is differentiated from the dystrophic form in that it begins without previous cell damage.

Topics: Animals; Aorta; Calcinosis; Cholecalciferol; Female; Male; Microscopy, Electron; Myocardium; Proteoglycans; Rats

Topics: Animals; Calcinosis; Calcium-Binding Proteins; Cholecalciferol; Coturnix; Epithelium; Intestine, Small; Microscopy, Electron; Quail; S100 Calcium Binding Protein G

Topics: Animals; Calcinosis; Calcium-Binding Proteins; Cholecalciferol; Coturnix; Egg Shell; Female; Histocytochemistry; Microscopy, Electron; Pregnancy; Quail; Uterus; Vitamin D Deficiency

Topics: Animal Feed; Animals; Calcinosis; Cardiovascular Diseases; Cholecalciferol; Female; Male; Poaceae; Sheep; Sheep Diseases

Topics: Adult; Brain Diseases, Metabolic; Calcinosis; Cholecalciferol; Female; Humans; Hypoparathyroidism; Syndrome; Vitamin D Deficiency

Topics: Animals; Aorta; Calcinosis; Calcium; Cholecalciferol; Female; Kidney; Male; Myocardium; Proteoglycans; Rats; Rats, Inbred Strains; Rodent Diseases

Calcium is increasing in ovaries of adult female rats when D3 vitamin is given by stomach intubation for 7 and 15 days. Histochemical studies show the presence of spherular chalky deposits specially in granulosa of some follicles. In the same times atresia becomes evident and fecondation is reduced. Chemical determination of calcium content of ovary show calcium accumulation in this organ.

Topics: Animals; Calcinosis; Calcium; Cholecalciferol; Female; Fertility; Ovarian Diseases; Ovary; Rats

Experimental hypervitaminosis D was produced in rabbits by feeding 25,000 I.U. vitamin D3 or the corresponding amount of vitamin D3 palmitate per kg of diet. Hypercalcemia and hyperphosphatemia was accompanied by increased CaBP activity and reduced weight gain in the vitamin D3 group as well as in the vitamin D3 ester group. The degree of calcification in the aorta and in the kidney also was similar in both groups. Increasing the vitamin intake by giving 10,000 I.U. vitamin D3 or vitamin D3 palmitate per day resulted in earlier and more widespread calcific deposits. In rats, receiving 50,000 I.U. vitamins D3 or vitamin D3 palmitate per kg of diet, calcification in soft tissue was much less extensive than in rabbits. But again, no difference was seen between vitamin D3 and vitamin D3 palmitate. These results indicate, that vitamin D3 esters are not suitable as a less calcinogenic form of vitamin D3.

Topics: Animals; Aorta; Body Weight; Calcinosis; Calcium; Cholecalciferol; Intestinal Mucosa; Kidney; Male; Myocardium; Phosphates; Rabbits; Rats; S100 Calcium Binding Protein G

Coronary atherosclerosis developed in normolipemic swine fed a basal ration supplemented with 125,000 IU, 62,500 IU and 31,250 IU of vitamin D3/kg of diet for 3 months and subsequently only the basal ration for the following 3 months. Lesions consisted of intimal atheromata and calcified internal elastica and caused luminal narrowing. The incidence of atherosclerotic lesions was proportional to the vitamin D3 doses. The present experimentally induced lesions had many morphological features resembling those in coronary arteries from human subjects.

Topics: Adult; Aged; Animals; Arteries; Arteriosclerosis; Calcinosis; Calcium; Cholecalciferol; Cholesterol; Coronary Disease; Coronary Vessels; Disease Models, Animal; Humans; Middle Aged; Swine

Daily administration of vitamin D3 (75,000 IU/kg b. wt) for 7 days accelerated Trichinella spiralis cyst calcification in rats with a 14-week-old infection. When disodium ethane-1-hydroxy-1, 1-diphosphonate (EHDP) was administered (50 mg/kg b. wt) from 2 days before until 2 days after vitamin D3 treatment, cyst calcification was inhibited. Thus, the ability to inhibit E. spiralis calcification has demonstrated for the first time.

Topics: Animals; Calcinosis; Cholecalciferol; Etidronic Acid; Larva; Male; Rats; Trichinella; Trichinellosis

Topics: Animals; Blood Vessels; Calcinosis; Calcium; Cholecalciferol; Female; Hydroxycholecalciferols; Male; Sheep

Aortic, coronary and cardiac lesions were induced in swine by a hypervitaminosis D3 diet Lipid-free intimal plaques overlying focally calcified medial or internal elastica occured in the thoracic aorta, pulmonary trunk and coronary artery of swine fed a basal ration supplemented with 250,000 IU of vitamin D3/kg of diet for an induction period of 4 months. Cartilage formation with minimal calcification was initiated in the aortic valve during this period. When such animals were subsequently fed only the basal ration free of excessive vitamin D3 for 3 months, intimal plaques regressed in the aorta and pulmonary trunk but progressed in the coronary artery. The calcific deposits in the medial elastica and internal elastica of all three arteries decreased in size. Atherosclerotic intimal thickening occurred in the main coronary arteries. The most severe lesion occupied 75 p.100 of the lumen area. Multiple intimal plaques were noted in the left atrium and aortic and mitral valves. The thickened intima at these coronary and cardiac sites contained calcified elastica and collagen fibers.

Topics: Animals; Aorta, Thoracic; Aortic Diseases; Calcinosis; Cardiovascular Diseases; Cholecalciferol; Coronary Disease; Coronary Vessels; Heart Diseases; Microscopy, Electron; Myocardium

A review is given of the literature concerning the so-called plant induced calcinosis in animals (tabel I), i.e. diseases which in their patological-anatomical appearance show great similarities with vit. D-intoxication. The etiology of the diseases are discussed in view of the last 5--10 years rapid development of knowledge concerning vit. D3 metabolism. It is pointed out that the most recent results indicate that enzootic calcinosis is caused by a 1,25-dihydrocholecalciferol-glycoside, which is hydrolysed in the intestinal tract. By this reaction 1.25 (OH) 2 cholecalciferol--the biological active metabolite of vit. D3 -- is set free, and thus able to act directly on the intestinal absorption mechanism. By this reaction the point of calcium metabolism regulation is essentially by-passed and calcium and phosphate absorption proceeds essentially out of control, causing hypercalcaemia, hyperphosphataemia, hypersecretion of calcitonin and calcinosis.

Topics: Animals; Calcinosis; Cattle; Cattle Diseases; Cholecalciferol; Kidney; Plant Poisoning; Time Factors; Vitamin D

The relative toxicity and metabolic effectiveness of cholecalciferol (CC) and 25-hydroxycholecalciferol (25-HCC) in chicks were evaluated by feeding six graded levels of each and observing gross and microscopic pathology as well as several metabolic parameters of calcium metabolism. Renal tubular calcification was observed when CC was fed at the rate of 10.0 mg/kg of diet and when 25-HCC was fed at the rate of 0.1 mg/kg diet. Thus, 100-fold increase in toxicity results when the hydroxylated form of CC is fed. Both microscopic renal lesions and increased renal calcium and inorganic phosphate concentrations occurred in chicks with normal serum calcium concentrations.

Topics: Alkaline Phosphatase; Animals; Body Weight; Calcinosis; Calcium; Chickens; Cholecalciferol; Dose-Response Relationship, Drug; Hydroxycholecalciferols; Kidney; Kidney Diseases; Kidney Tubules; Phosphorus

The history, clinical signs and post mortem findings in a cow with metastatic pulmonary calcification and calcific arteriosclerosis after vitamin D3 treatment are described.

Topics: Animals; Arteriosclerosis; Calcinosis; Cattle; Cattle Diseases; Cholecalciferol; Female; Lung Diseases

Five groups of 4 weanling pigs were fed a diet with 1.2% calcium and 1.0% phosphorus for 8 weeks with vitamin D3 at 1, 5, 25, 125 and 625 times the recommended levels, respectively. Hypercalcemia and hypophosphatasemia developed rapidly and persisted in Group 5 and developed more slowly but steadily in Group 4. Increasing levels of vitamin D3 influenced progressively and negatively the activity of resorbing osteocytes with osteopetrosis in Groups 2 and 3 and with osteonecrosis in Group 5. Atrophy of osteoblasts further contributed to the osteopenia in Group 5. Cartilage growth activity was arrested in Group 5. The negative effect on the resorbing osteocytes, which finally lead to death of the cells, was ascribed directly to vitamin D3 toxicosis since hypoparathyroidism and hypercalcitonism, both resulting from hypercalcemia, are not known to induce osteonecrosis. Since hypercalemia was finally as severe in Group 4 as in Group 5 and since there was soft tissue calcinosis only in Group 5, the calcinosis was always considered dystrophic, an interpretation supported by the observation that degenerative histologic changes preceded soft tissue calcinosis.

Topics: Animals; Bone Diseases; Bone Resorption; Calcinosis; Calcium; Cartilage; Cholecalciferol; Female; Humerus; Male; Parathyroid Glands; Swine; Swine Diseases; Thyroid Gland

Topics: Animals; Anti-Bacterial Agents; Calcinosis; Cholecalciferol; Female; Iron; Male; Rats; Swine; Swine Diseases

Topics: Aged; Antineoplastic Agents; Bone Neoplasms; Calcinosis; Calcitonin; Cholecalciferol; Cyclophosphamide; Ergocalciferols; Fractures, Spontaneous; Humans; Hypercalcemia; Kidney Calculi; Lung Neoplasms; Male; Neoplasm Metastasis; Osteitis Deformans; Plicamycin; Podophyllin; Quinones; Sarcoma; Vitamin D

Topics: Animals; Calcinosis; Calciphylaxis; Cholecalciferol; Disease Models, Animal; Ear, Middle; Granulation Tissue; Guinea Pigs; Histocytochemistry; Male; Ossification, Heterotopic; Otosclerosis; Tympanic Membrane

Topics: Animals; Calcinosis; Calciphylaxis; Cholecalciferol; Disease Models, Animal; Ear, Middle; Guinea Pigs; Male; Mucous Membrane; Ossification, Heterotopic; Otosclerosis; Tympanic Membrane

Topics: Age Factors; Animals; Arteriosclerosis; Blood Vessels; Calcinosis; Calcium; Calcium Chloride; Cholecalciferol; Choline; Dihydrotachysterol; Female; Rats

Topics: Animals; Calcinosis; Cholecalciferol; Female; Maternal-Fetal Exchange; Placenta; Pregnancy; Pregnancy, Animal; Rats; Time Factors

Topics: Animals; Aortic Diseases; Calcinosis; Calcium Phosphates; Cholecalciferol; Crystallization; Female; Hypercalcemia; Nephrocalcinosis; Organophosphonates; Rats

Two diphosphonates containing the P-C-P bond, CH(3)C(OH)(PO(3)HNa)(2) and H(2)C(PO(3)HNa)(2), inhibit the crystallization of calcium phosphate in vitro and prevent aortic calcification of rats given large amounts of vitamin D(3). The diphosphonates therefore have effects similar to those described for compounds containing the P-O-P bond but are active when administered orally.

Topics: Animals; Aortic Diseases; Calcinosis; Cholecalciferol; Crystallization; Diphosphates; Hydrogen-Ion Concentration; Organophosphonates; Phosphates; Rats; X-Ray Diffraction

Topics: Animals; Aorta, Thoracic; Aortic Diseases; Calcinosis; Cholecalciferol; Diphosphates; Female; Hypercalcemia; Kidney; Phosphates; Rats

Topics: Animals; Aortic Diseases; Bone Resorption; Calcinosis; Calcium Phosphates; Chemical Phenomena; Chemical Precipitation; Chemistry; Cholecalciferol; Diphosphates; Hypercalcemia; Mice; Organophosphonates; Pyrophosphatases; Rats

Topics: Animals; Calcinosis; Cattle; Cattle Diseases; Cholecalciferol; Female; Injections, Intramuscular

Topics: Animals; Aortic Diseases; Calcinosis; Cholecalciferol; Osteogenesis; Phosphates; Rats; Rickets

Topics: Animals; Body Weight; Calcinosis; Cholecalciferol; Female; Kyphosis; Lordosis; Rats

Topics: Animals; Calcinosis; Calcium; Cholecalciferol; Dentin; Ergocalciferols; Male; Parathyroid Hormone; Rabbits; Rickets

Topics: Calcinosis; Calcium; Calcium, Dietary; Cholecalciferol; Parathyroid Hormone; Pharmacology; Rats; Research

Topics: Animals; Calcinosis; Calciphylaxis; Calcium; Cholecalciferol; Hair Removal; Keratins; Male; Microscopy, Electron; Phosphorus; Rats; Rickets; Skin Diseases

Topics: Adrenocorticotropic Hormone; Aging; Aluminum; Calcification, Physiologic; Calcinosis; Calciphylaxis; Cholecalciferol; Chromium; Dextrans; Dihydrotachysterol; Egg Yolk; Ergocalciferols; Iron-Dextran Complex; Methyltestosterone; Rats; Research; Skin; Toxicology; Vitamin E

Topics: Calcification, Physiologic; Calcinosis; Cholecalciferol; Dihydrotachysterol; Myocardium; Papain; Pathology; Potassium; Quinolines; Rats; Research; Stress, Physiological; Toxicology

Topics: Aorta; Calcinosis; Calcium Phosphates; Cholecalciferol; Pharmacology; Phosphates; Polyphosphates; Rats; Research; Toxicology; Vascular Diseases

Topics: Alloxan; Calcinosis; Cholecalciferol; Dihydrotachysterol; Ergocalciferols; Islands; Islets of Langerhans; Kidney Diseases; Kidney Tubules; Nephrocalcinosis; Pancreas; Pathology; Rats; Research

Topics: Calcification, Physiologic; Calcinosis; Chlortetracycline; Cholecalciferol; Connective Tissue; Dihydrotachysterol; Fluorescence; Gastric Mucosa; Kidney; Lung; Microradiography; Microscopy; Microscopy, Fluorescence; Muscle, Smooth; Parathyroid Hormone; Rats; Research; Stomach; Tetracycline; Toxicology