Effect of heat shock on ultrastructure and calcium distribution in Lavandula pinnata L. glandular trichomes.

PubMed

Huang, S S; Kirchoff, B K; Liao, J P

2013-02-01

The effects of heat shock (HS) on the ultrastructure and calcium distribution of Lavandula pinnata secretory trichomes are examined using transmission electron microscopy and potassium antimonate precipitation. After 48-h HS at 40°C, plastids become distorted and lack stroma and osmiophilic deposits, the cristae of the mitochondria become indistinct, the endoplasmic reticulum acquires a chain-like appearance with ribosomes prominently attached to the lamellae, and the plasma and organelle membranes become distorted. Heat shock is associated with a decrease in calcium precipitates in the trichomes, while the number of precipitates increases in the mesophyll cells. Prolonged exposure to elevated calcium levels may be toxic to the mesophyll cells, while the lack of calcium in the glands cell may deprive them of the normal protective advantages of elevated calcium levels. The inequality in calcium distribution may result not only from uptake from the transpiration stream, but also from redistribution of calcium from the trichomes to the mesophyll cells.

Relationship between serum calcium and CA 19-9 levels in colorectal cancer

PubMed Central

Fuszek, Peter; Lakatos, Peter; Tabak, Adam; Papp, Janos; Nagy, Zsolt; Takacs, Istvan; Horvath, Henrik Csaba; Lakatos, Peter Laszlo; Speer, Gabor

2004-01-01

AIM: To examine the calcium metabolism of colorectal cancer (CRC) in patients with colorectal cancer and control patients. METHODS: Seventy newly diagnosed CRC patients were included. The healthy control group was age and gender matched (n = 32). Particular attention was devoted to the relationship between serum calcium of patients, and levels of AFP, CEA, carbohydrate antigen 19-9 (CA 19-9) (that could be considered as prognostic factors). Furthermore, the Ca-sensing receptor (CaSR) gene A986S polymorphism was investigated in these patients, as well as the relationship between different CaSR genotypes and the data stated above. RESULTS: A lower level of ionized calcium (also corrected for albumin) was found in the serum of CRC patients with normal 25 (OH) vitamin D levels. The ionized calcium concentration was inversely correlated with the serum level of CA 19-9. There was no difference in the distribution of CaSR genotypes, between CRC patients and general population. The genotypes did not correlate with other data examined. CONCLUSION: Based on these results, lower levels of serum calcium might be a pathogenic and prognostic factor in colorectal cancer. PMID:15222030

Relationship between blood calcium level and ST peak interval of electrocardiographic variables in peripartum Holstein cows

PubMed Central

ITOH, Megumi; SAKURAI, Yoshie; NAKAJIMA, Yasuhiro; KAWAMOTO, Satoshi

2015-01-01

The association between blood calcium levels and electrocardiographic variables was compared in 137 normal parturient and 36 peripartum recumbent Holstein cows to determine whether hypocalcemia in peripartum dairy cows can be rapidly diagnosed using electrocardiograph. Inverse of STc (ST peak interval/SS interval0.5) and blood ionized calcium or serum calcium concentrations were strongly correlated, and both correlation coefficients were 0.81 (P<0.001). The 95% prediction interval indicated that cows with STc >0.385 ± 0.001 sec are very likely to be hypocalcemic (blood ionized or serum calcium concentrations of <0.9 mmol/l or <7.5 mg/dl, respectively). These findings indicate that hypocalcemia in parturient cows can be non-invasively estimated using the STc. PMID:26118411

Hyperthyroidism-associated hypercalcemic crisis: A case report and review of the literature.

PubMed

Chen, Ke; Xie, Yanhong; Zhao, Liling; Mo, Zhaohui

2017-01-01

Hyperthyroidism is one of the major clinical causes of hypercalcaemia, however, hyperthyroidism-related hypercalcemic crisis is rare, only 1 case have been reported. The potential mechanisms are still not too clear. It may be related that thyroid hormone stimulate bone turnover, elevate serum calcium, increase urinary and fecal calcium excretion. A 58-year-old female patient was found to have Graves' disease, a marked elevated serum calcium level (adjusted serum calcium: 3.74 mmol/L), and reduced parathyroid hormone level. She was diagnosed as hyperthyroidism-associated hypercalcemic crisis. Treatment with methimazole to correct the hyperthyroidism and treatment of the patient's hypercalcaemia was achieved by physiological saline, salmon calcitonin and furosemide. After treatment for hypercalcaemia and hyperthyroidism, her symptoms and serum calcium levels quickly returned to normal. hyperthyroid-associated hypercalcaemia crisis is rare, however, the diagnosis should pay attention to screening for other diseases caused by hypercalcemia. Timely treatment of hypercalcaemia is a critical step for rapidly control of symptoms, and treatment of hyperthyroidism is beneficial to relief the symptoms and maintain the blood calcium level.

Biochemical Response of Late Rickets and Osteomalacia to a Chupatty-free Diet

PubMed Central

Ford, J. A.; Colhoun, E. M.; McIntosh, W. B.; Dunnigan, M. G.

1972-01-01

Eight Pakistani children with late rickets and two Pakistani women with osteomalacia were given a chupatty-free diet for seven weeks, substituting leavened bread of lower extraction. On this diet serum calcium levels rose to normal or near normal, levels of serum inorganic phosphorus rose slightly but significantly, and serum alkaline phosphatase levels showed a definite rise indicative of healing bone disease. It is concluded that the high phytate content of unleavened bread is the major cause of late rickets and osteomalacia in Pakistani and Indian communities in the United Kingdom. The simplest prophylactic measure seems to be the additional fortification with calcium carbonate of the high extraction flour used in preparing unleavened bread. PMID:5069221

Hypercalcemia in hyperthyroidism: patterns of serum calcium, parathyroid hormone, and 1,25-dihydroxyvitamin D3 levels during management of thyrotoxicosis.

PubMed

Iqbal, Ayesha A; Burgess, Elizabeth H; Gallina, Daniel L; Nanes, Mark S; Cook, Curtiss B

2003-01-01

To present two cases of hypercalcemia associated with thyrotoxicosis and to describe serial biochemical findings during the course of treatment of hyperthyroidism. We report two cases, illustrate the changes in serum calcium, parathyroid hormone, and 1,25-dihydroxyvitamin D3 levels during management of thyrotoxicosis, and compare our findings with those in previous studies. Hypercalcemia attributable to thyrotoxicosis is well documented, but the mechanism for the hypercalcemia is incompletely understood. Our first patient had a complicated medical history and several potential causes of hypercalcemia, including recurrent hyperparathyroidism, metastatic breast cancer, and relapse of previously treated thyrotoxicosis. A suppressed parathyroid hormone level and negative bone and computed tomographic scans excluded the first two factors. After thyroid ablation with 131I, the serum calcium and thyroxine levels decreased, and the parathyroid hormone and 1,25-dihydroxyvitamin D3 levels normalized. Our second patient, who was referred to our institution with a preliminary diagnosis of hypercalcemia associated with malignant disease and who had no symptoms of hyperthyroidism, was found to have a high free thyroxine level, diffuse enlargement of the thyroid, and high uptake (58%) of 123I on a thyroid scan. After thyroid ablation, the serum calcium, 1,25-dihydroxyvitamin D3, and intact parathyroid hormone levels normalized, and the free thyroxine level declined. The probable pathogenesis of hypercalcemia in thyrotoxicosis is reviewed with respect to thyroid hormone and its effect on bone turnover. Physicians should consider thyrotoxicosis in the differential diagnosis of hypercalcemia.

Studying dyadic structure-function relationships: a review of current modeling approaches and new insights into Ca2+ (mis)handling.

PubMed

Maleckar, Mary M; Edwards, Andrew G; Louch, William E; Lines, Glenn T

2017-01-01

Excitation-contraction coupling in cardiac myocytes requires calcium influx through L-type calcium channels in the sarcolemma, which gates calcium release through sarcoplasmic reticulum ryanodine receptors in a process known as calcium-induced calcium release, producing a myoplasmic calcium transient and enabling cardiomyocyte contraction. The spatio-temporal dynamics of calcium release, buffering, and reuptake into the sarcoplasmic reticulum play a central role in excitation-contraction coupling in both normal and diseased cardiac myocytes. However, further quantitative understanding of these cells' calcium machinery and the study of mechanisms that underlie both normal cardiac function and calcium-dependent etiologies in heart disease requires accurate knowledge of cardiac ultrastructure, protein distribution and subcellular function. As current imaging techniques are limited in spatial resolution, limiting insight into changes in calcium handling, computational models of excitation-contraction coupling have been increasingly employed to probe these structure-function relationships. This review will focus on the development of structural models of cardiac calcium dynamics at the subcellular level, orienting the reader broadly towards the development of models of subcellular calcium handling in cardiomyocytes. Specific focus will be given to progress in recent years in terms of multi-scale modeling employing resolved spatial models of subcellular calcium machinery. A review of the state-of-the-art will be followed by a review of emergent insights into calcium-dependent etiologies in heart disease and, finally, we will offer a perspective on future directions for related computational modeling and simulation efforts.

Kit W-sh Mutation Prevents Cancellous Bone Loss during Calcium Deprivation.

PubMed

Lotinun, Sutada; Suwanwela, Jaijam; Poolthong, Suchit; Baron, Roland

2018-01-01

Calcium is essential for normal bone growth and development. Inadequate calcium intake increases the risk of osteoporosis and fractures. Kit ligand/c-Kit signaling plays an important role in regulating bone homeostasis. Mice with c-Kit mutations are osteopenic. The present study aimed to investigate whether impairment of or reduction in c-Kit signaling affects bone turnover during calcium deprivation. Three-week-old male WBB6F1/J-Kit W /Kit W-v /J (W/W v ) mice with c-Kit point mutation, Kit W-sh /HNihrJaeBsmJ (W sh /W sh ) mice with an inversion mutation in the regulatory elements upstream of the c-Kit promoter region, and their wild-type controls (WT) were fed either a normal (0.6% calcium) or a low calcium diet (0.02% calcium) for 3 weeks. μCT analysis indicated that both mutants fed normal calcium diet had significantly decreased cortical thickness and cancellous bone volume compared to WT. The low calcium diet resulted in a comparable reduction in cortical bone volume and cortical thickness in the W/W v and W sh /W sh mice, and their corresponding controls. As expected, the low calcium diet induced cancellous bone loss in the W/W v mice. In contrast, W sh /W sh cancellous bone did not respond to this diet. This c-Kit mutation prevented cancellous bone loss by antagonizing the low calcium diet-induced increase in osteoblast and osteoclast numbers in the W sh /W sh mice. Gene expression profiling showed that calcium deficiency increased Osx, Ocn, Alp, type I collagen, c-Fms, M-CSF, and RANKL/OPG mRNA expression in controls; however, the W sh mutation suppressed these effects. Our findings indicate that although calcium restriction increased bone turnover, leading to osteopenia, the decreased c-Kit expression levels in the W sh /W sh mice prevented the low calcium diet-induced increase in cancellous bone turnover and bone loss but not the cortical bone loss.

Levels of Serum Calcium and Magnesium in Pre-eclamptic and Normal Pregnancy: A Study from Coastal India.

PubMed

Kanagal, Deepa V; Rajesh, Aparna; Rao, Kavyarashmi; Devi, Ullal Harshini; Shetty, Harish; Kumari, Sucheta; Shetty, Prasanna Kumar

2014-07-01

Pre-eclampsia is one of the major causes of maternal and fetal morbidity and mortality. Though the aetiology is obscure, recent studies indicate that serum levels of calcium and magnesium may have a role in pre-eclampsia. The aim of this study was to find out the relationship of serum levels of calcium and magnesium in pre-eclamptic pregnancies compared to normal pregnancies in women from southern coastal India. This study was done in a medical college hospital in southern coastal India. The blood samples from 60 pre-eclamptic women and an equal number of controls were analysed for calcium and magnesium levels. Data on Body Mass Index, maternal and gestational ages, serum calcium and magnesium were compared between the two groups. Outcome of pregnancy was analysed in both the groups and compared. Data was expressed as Mean ± Standard Deviation. Data analysis was done by SPSS version 20. Comparison of serum levels of the elements between the two groups was performed by Independent t-test and Chi-square test and P-value of < 0.05 was considered as statistically significant. The serum calcium concentration was significantly lower in the pre-eclamptic group compared to normotensives (7.84 ± 0.87 mg/dl Vs 8.97± 0.69 mg/dl, p<0.001) whereas the levels of serum magnesium showed a marginal difference in both the groups. (1.43± 0.55 mg/dl Vs, 1.57 ± 0.72 mg/dl P 0.257) The study also showed that pre-eclamptic women were older, their BMI was higher and birth weight of babies lower compared to normotensives. According to the results of our research, intake of supplements, mainly calcium may help in the reduction of incidence of pre-eclampsia especially in a population of a developing country like ours where the nutrition is poor. Not many studies have been done in developing countries to assess the role of these elements in pre-eclampsia. The actual role of magnesium and calcium supplements needs further investigation.

The beneficial effect of the sap of Acer mono in an animal with low-calcium diet-induced osteoporosis-like symptoms.

PubMed

Lee, Geun-Shik; Byun, Hyuk-Soo; Kim, Man-Hee; Lee, Bo-Mi; Ko, Sang-Hwan; Jung, Eui-Man; Gwak, Ki-Seob; Choi, In-Gyu; Kang, Ha-Young; Jo, Hyun-Jin; Lee, Hak-Ju; Jeung, Eui-Bae

2008-11-01

The sap of Acer mono has been called 'bone-benefit-water' in Korea because of its mineral and sugar content. In particular, the calcium concentration of the sap of A. mono is 37.5 times higher than commercial spring water. In the current study, we examined whether A. mono sap could improve or prevent osteoporosis-like symptoms in a mouse model. Male mice (3 weeks old) were fed a low-calcium diet supplemented with 25, 50 or 100 % A. mono sap, commercial spring water or a high calcium-containing solution as a beverage for 7 weeks. There were no differences in weekly weight gain and food intake among all the groups. Mice that were given a low-calcium diet supplemented with commercial spring water developed osteoporosis-like symptoms. To assess the effect of sap on osteoporosis-like symptoms, we examined serum calcium concentration, and femur density and length, and carried out a histological examination. Serum calcium levels were significantly lower in mice that received a low-calcium diet supplemented with commercial spring water (the negative control group), and in the 25 % sap group compared to mice fed a normal diet, but were normal in the 50 and 100 % sap and high-calcium solution groups. Femur density and length were significantly reduced in the negative control and 25 % sap groups. These results indicate that a 50 % sap solution can mitigate osteoporosis-like symptoms induced by a low-calcium diet. We also examined the regulation of expression of calcium-processing genes in the duodenum and kidney. Duodenal TRPV6 and renal calbindin-D9k were up-regulated dose-dependently by sap, and the levels of these factors were higher than those attained in the spring water-treated control. The results demonstrate that the sap of A. mono ameliorates the low bone density induced by a low-calcium diet, most likely by increasing calcium ion absorption.

High-dose calcium stimulation test in a case of insulinoma masquerading as hysteria.

PubMed

Nakamura, Yoshio; Doi, Ryuichiro; Kohno, Yasuhiro; Shimono, Dai; Kuwamura, Naomitsu; Inoue, Koichi; Koshiyama, Hiroyuki; Imamura, Masayuki

2002-11-01

It is reported that some cases with insulinoma present with neuropsychiatric symptoms and are often misdiagnosed as psychosis. Here we report a case of insulinoma masquerading as hysteria, whose final diagnosis could be made using high-dose calcium stimulation test. A 28-yr-old woman was referred presenting with substupor, mutism, mannerism, restlessness, and incoherence. Laboratory examinations revealed hypoglycemia (33 mg/dL) and detectable insulin levels (9.7 microU/mL), suggesting the diagnosis of insulinoma. However, neither imaging studies nor selective arterial calcium injection (SACI) test with a conventional dose of calcium (0.025 mEq/kg) indicated the tumor. High-dose calcium injection (0.05 mEq/kg) evoked insulin secretion when injected into superior mesenteric artery. A solitary tumor in the head of the pancreas was resected, and her plasma glucose returned to normal. Postoperatively, iv injection of secretin resulted in a normal response of insulin, which was not found preoperatively. This case suggests the usefulness of the SACI test with high-dose of calcium in the case of insulinoma when the standard dose fails to detect such a tumor.

A study of water hardness and the prevalence of hypomagnesaemia and hypocalcaemia in healthy subjects of Surat district (Gujarat).

PubMed

Kanadhia, Kirti C; Ramavataram, Divvi Venkata Subrahmanya Shri; Nilakhe, Shreeyas Prasad Dhanpal; Patel, Swati

2014-01-01

Various sources of drinking water, with varying levels of total hardness, and calcium and magnesium concentrations, are used by populations in different regions. The use of water purifiers can compound the problem of maintaining the desired levels of hardness. An inverse relationship between various conditions, including cardiovascular disease, and hard water has been reported. Until this study, investigation of the hardness of drinking water from different sources, and serum magnesium and calcium in normal subjects from the Surat district, had not been undertaken. This study was performed to assess the concentrations of calcium and magnesium, and total hardness in filtered and non-filtered water and the relationship with serum magnesium and calcium levels in normal subjects consuming such water. Three water samples were collected, at 15-day intervals, from 12 urban and rural areas of Surat; and also 10 different brands of bottled water. Samples were analyzed for total hardness and calcium by complexometric and EDTA methods respectively. Magnesium concentrations were obtained by subtraction of the calcium concentration from total hardness. Serum samples from healthy individuals were analyzed for magnesium and calcium using calmagite and arsenazo methods respectively. The independent t-test was used to establish significance at a level of 95%. A p-value <0.05 was considered significant. Mean total hardness, and calcium and magnesium concentrations in non-filtered, rural tube-well water were much higher than in filtered water from the same area, and the magnesium concentrations were significantly higher (p = 0.038). Filtered urban municipal had lower hardness and concentrations of calcium and magnesium (p = 0.01) compared to corresponding non-filtered water. Significantly lower levels were observed in bottled water compared to rural and urban sources of water. Serum magnesium was significantly lower in the population who were consuming filtered water compared to those drinking non-filtered water (p<0.05). No such difference was observed for serum calcium. Hypomagnesemia correlates with lower magnesium concentrations in drinking water (both rural tube-well and urban municipal waters), which can be attributed to the use of water purifiers. Assuming that a person consumes two liters of drinking water per day, it is estimated that there is an average loss of 160 mg (79%) of magnesium from total waterborne magnesium levels as a result of the filtration of both rural and urban water supplies. Bottled water is too hardness as in calcium and magnesium concentrations.

Outcome of hypocalcaemia after thyroidectomy treated only in symptomatic patients.

PubMed

Järhult, J; Landerholm, K

2016-05-01

Calcium supplementation has been proposed after bilateral thyroid surgery, either to all patients or to those with biochemical hypocalcaemia. It has also been suggested that supplementation aids parathyroid recovery and prevents permanent hypoparathyroidism. This single-centre study investigated the feasibility of a restrictive management of post-thyroidectomy hypocalcaemia. Serum calcium was checked before surgery, on postoperative day 1 (POD) 1, at a follow-up visit 6-8 weeks after surgery and after a minimum of 12 months in all patients. Regardless of serum calcium levels, patients with symptoms of hypocalcaemia were prescribed oral calcium supplementation (0·5-1·0 g twice daily) and asymptomatic patients were not. Asymptomatic patients were informed about hypocalcaemic symptoms and instructed to contact the surgical ward should symptoms appear. Some 640 patients underwent bilateral thyroid surgery without previous or intentional simultaneous parathyroidectomy. A subnormal serum calcium level (below 2·15 mmol/l) was observed in 412 patients (64·4 per cent) on POD 1. By comparison, only 63 patients (9·8 per cent) experienced symptoms of hypocalcaemia in the postoperative period, all but one with a corresponding biochemical hypocalcaemia on POD 1. Calcium levels in all patients with asymptomatic postoperative hypocalcaemia recovered to normal without supplementation. Serum calcium was also normalized during follow-up in all symptomatic patients, except 22 (3·4 per cent) who became permanently hypoparathyroid. No patient without early hypocalcaemic symptoms developed permanent hypoparathyroidism. The proposed restrictive management of postoperative hypocalcaemia after bilateral thyroid surgery avoids unnecessary supplementation for most patients. © 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.

Structural evidence that botulinum toxin blocks neuromuscular transmission by impairing the calcium influx that normally accompanies nerve depolarization

PubMed Central

1981-01-01

Taking advantage of the fact that nerve terminal mitochondria swell and sequester calcium during repetitive nerve stimulation, we here confirm that this change is caused by calcium influx into the nerve and use this fact to show that botulinum toxin abolishes such calcium influx. The optimal paradigm for producing the mitochondrial changes in normal nerves worked out to be 5 min of stimulation at 25 Hz in frog Ringer's solution containing five time more calcium than normal. Applying this same stimulation paradigm to botulinum-intoxicated nerves produced no mitochondrial changes at all. Only when intoxicated nerves were stimulated in 4-aminopyridine (which grossly exaggerates calcium currents in normal nerves) or when they were soaked in black widow spider venom (which is a nerve-specific calcium ionophore) could nerve mitochondria be induced to swell and accumulate calcium. These results indicate that nerve mitochondria are not damaged directly by the toxin and point instead to a primary inhibition of the normal depolarization- evoked calcium currents that accompany nerve activity. Because these currents normally provide the calcium that triggers transmitter secretion from the nerve, this demonstration of their inhibition helps to explain how botulinum toxin paralyzes. PMID:6259176

Influence of calcium depletion on iron-binding properties of milk.

PubMed

Mittal, V A; Ellis, A; Ye, A; Das, S; Singh, H

2015-04-01

We investigated the effects of calcium depletion on the binding of iron in milk. A weakly acidic cation-exchange resin was used to remove 3 different levels (18-22, 50-55, and 68-72%) of calcium from milk. Five levels of iron (5, 10, 15, 20, and 25 mM) were added to each of these calcium-depleted milks (CDM) and the resultant milks were analyzed for particle size, microstructure, and the distribution of protein and minerals between the colloidal and soluble phases. The depletion of calcium affected the distribution of protein and minerals in normal milk. Iron added to normal milk and low-CDM (~20% calcium depletion) bound mainly to the colloidal phase (material sedimented at 100,000 × g for 1 h at 20 °C), with little effect on the integrity of the casein micelles. Depletion of ~70% of the calcium from milk resulted in almost complete disintegration of the casein micelles, as indicated by all the protein remaining in the soluble phase upon ultracentrifugation. Addition of up to ~20 mM iron to high CDM resulted in the formation of small fibrous structures that remained in the soluble phase of milk. It appeared that the iron bound to soluble (nonsedimentable) caseins in high-CDM. We observed a decrease in the aqueous phosphorus content of all milks upon iron addition, irrespective of their calcium content. We considered the interaction between aqueous phosphorus and added iron to be responsible for the high iron-binding capacity of the proteins in milk. The soluble protein-iron complexes formed in high-CDM (~70% calcium depletion) could be used as an effective iron fortificant for a range of food products because of their good solubility characteristics. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Ionised calcium levels in major trauma patients who received blood en route to a military medical treatment facility.

PubMed

Kyle, Tony; Greaves, Ian; Beynon, Anthony; Whittaker, Vicky; Brewer, Mike; Smith, Jason

2018-03-01

Hypocalcaemia is a common metabolic derangement in critically ill patients. Blood transfusion can also contribute to depleted calcium levels. The aims of this study were to identify the incidence of hypocalcaemia in military trauma patients receiving blood products en route to a deployed hospital facility and to determine if intravenous calcium, given during the prehospital phase, has an effect on admission calcium levels. This was a retrospective review of patients transported by the UK Medical Emergency Response Team in Afghanistan between January 2010 and December 2014 who were treated with blood products in the prehospital setting. Total units of blood products administered, basic demographics, Injury Severity Score and trauma type were collected. Ionised serum calcium levels on admission to hospital were compared between those who received blood products without prehospital intravenous calcium supplemental therapy (non-treatment) and patients who were treated with 10 mL of intravenous calcium chloride (10%) concurrently with blood products (treatment). The study included 297 patients; 237 did not receive calcium and 60 did. The incidence of hypocalcaemia in the non-treatment group was 70.0% (n=166) compared with 28.3% (n=17) in the treatment group. Serum calcium levels were significantly different between the groups (1.03 mmol/L vs 1.25 mmol/L, difference 0.22 mmol/L, 95% CI 0.15 to 0.27). In the non-treatment group, 26.6% (n=63) had calcium levels within the normal range compared with 41.7% (n=25) in those who received calcium. There was a dose response of calcium level to blood products with a significant decrease in calcium levels as the volume of blood products increased. Trauma patients who received blood products were at high risk of hypocalcaemia. Aggressive management of these patients with intravenous calcium during transfusion may be required. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Idiopathic hypercalciuria with bilateral macular colobomata: a new variant of oculo-renal syndrome.

PubMed

Meier, W; Blumberg, A; Imahorn, W; De Luca, F; Wildberger, H; Oetliker, O

1979-01-01

Two siblings from a consanguineous family, suffering from nephrocalcinosis and nephrolithiasis caused by idiopathic hypercalciuria are described. The condition is associated with bilateral macular colobomata and tapeto-retinal degeneration. It is known that the latter can occur together with different nephropathies; however, until now it has never been described in combination with idiopathic hypercalciuria. Blood calcium levels were found to be normal, calcium excretion rates were, with one exception, more than 6 mg/kg/24 h corrected for 100 ml GFR. Hypomagnesemia of 1.5 and 1.2 mg/dl and hyermagnesuria of 1.9 and 2.5 mg/kg/24 h corrected for 100 ml GFR were found in both patients. Tubular phosphate reabsorption reached 87% and 84% at serum parathormone levels of 0.34 microgram/l and 0.31 microgram/l in the two patients, respectively. Under calcium and magnesium loading the clearance rates of calcium and magnesium were raised whilst there was only a small insignificant increase in the blood levels of these cations. Acid-base titrations showed normal excretion rates of acid and base in one patient and a mild proximal tubular acidosis in the other. Quantitative investigation of the renal concentrating and diluting capacity established a decrease in the formation of the medullary concentrating gradient in both patients.

Hypervitaminosis D and Metastatic Calcification in a Colony of Inbred Strain 13 Guinea Pigs, Cavia porcellus.

PubMed

Holcombe, H; Parry, N M; Rick, M; Brown, D E; Albers, T M; Refsal, K R; Morris, J; Kelly, R; Marko, S T

2015-07-01

A commercial diet fed to a colony of inbred strain 13 guinea pigs for approximately 6 weeks was subsequently recalled for excessive levels of vitamin D. Twenty-one of 62 animals exhibited clinical signs, including anorexia, lethargy, and poor body condition. Nine affected and 4 clinically normal animals were euthanized for further evaluation, including serum chemistry, urinalysis, and gross and/or histopathology. Macroscopic findings included white discoloration in multiple organs in 8 animals, and microscopic evaluation confirmed multiorgan mineralization in tissues from 7 animals. Serum 25-hydroxyvitamin D levels were elevated in 10 animals. Serum inorganic phosphorus and alkaline phosphatase levels were increased in all exposed animals; however, total calcium and ionized calcium levels were not significantly higher in exposed animals than in control strain 13 guinea pigs from a different institution. The data support a diagnosis of hypervitaminosis D with metastatic calcification. Following the diet recall, the remaining guinea pigs increased their food intake and regained body condition. Diagnostic testing of 8 animals euthanized approximately 3 months after returning to a normal diet demonstrated that serum parathyroid hormone remained significantly lower, and ionized calcium and ionized magnesium were significantly higher, in recovered animals compared to controls and exposed animals. These results indicate that diagnostic tests other than serum calcium are necessary for a diagnosis of hypervitaminosis D in guinea pigs. © The Author(s) 2014.

Vitamin D: the light side of sunshine.

PubMed

Mason, R S; Sequeira, V B; Gordon-Thomson, C

2011-09-01

Under normal circumstances, vitamin D is mainly obtained from skin through the action of ultraviolet B irradiation on 7-dehydrocholesterol. It is further metabolized to 25-hydroxyvitamin D (25OHD), the major circulating vitamin D compound, and then to 1,25-dihydroxyvitamin D, the hormonal form. The major function of vitamin D compounds is to enhance active absorption of ingested calcium (and phosphate). This assists in building bone at younger ages and ensures that despite obligatory urinary losses, bone does not need to be resorbed to maintain blood calcium concentrations. Vitamin D compounds appear to have direct effects to improve bone and muscle function, and there is good, although not entirely consistent, evidence that supplemental vitamin D and calcium together reduce falls and fractures in older individuals. On the basis of calcium control and musculoskeletal function, target levels for 25OHD in blood are at least 50-60 nmol/l and there may be a case for higher targets of 75-80 nmol/l. There are vitamin D receptors in most nucleated cells and some evidence, although not consistent, that adequate vitamin D levels may be important in reducing the incidence of, or mortality from, some cancers and in reducing autoimmune disease. Adequate vitamin D may also allow for a normal innate immune response to pathogens, improve cardiovascular function and mortality and increase insulin responsiveness. Vitamin D levels are maintained better in the presence of adequate calcium intakes, more exercise and less obesity. Genetic variation may have an effect on vitamin D blood levels and response to treatment with vitamin D.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Recker, R.R.

Defective absorption of calcium has been thought to exist in patients with achlorhydria. The author compared absorption of calcium in its carbonate form with that in a pH-adjusted citrate form in a group of 11 fasting patients with achlorhydria and in 9 fasting normal subjects. Fractional calcium absorption was measured by a modified double-isotope procedure with 0.25 g of calcium used as the carrier. Mean calcium absorption (+/- S.D.) in the patients with achlorhydria was 0.452 +/- 0.125 for citrate and 0.042 +/- 0.021 for carbonate (P less than 0.0001). Fractional calcium absorption in the normal subjects was 0.243 +/-more » 0.049 for citrate and 0.225 +/- 0.108 for carbonate (not significant). Absorption of calcium from carbonate in patients with achlorhydria was significantly lower than in the normal subjects and was lower than absorption from citrate in either group; absorption from citrate in those with achlorhydria was significantly higher than in the normal subjects, as well as higher than absorption from carbonate in either group. Administration of calcium carbonate as part of a normal breakfast resulted in completely normal absorption in the achlorhydric subjects. These results indicate that calcium absorption from carbonate is impaired in achlorhydria under fasting conditions. Since achlorhydria is common in older persons, calcium carbonate may not be the ideal dietary supplement.« less

[Vitamin-resistant rickets cured by removal of a bone tumor. Review of the literature].

PubMed

François, S; Lefort, G; Poli-Merol, M L; Gaillard, D; Roussel, B; Sulmont, V; Daoud, S

1997-01-01

Rickets secondary to bone or soft tissue tumors are rare in children. Majority of the reported cases occurred in adults older than thirty. This entity can be cured after tumor removal. The authors present a case in a ten year boy and literature review. A ten year boy complained of diffuse bone and muscle weakness for two years. A diagnosis of arthritis was made but the patient continued to complain. Serum calcium level was normal (2.33 mmol/l), phosphorus was very low (0.43 mmol/l), serum alkaline phosphatase was high, parathyroid hormone and vitamin D level were normal. Urinalysis showed abnormal phosphate excretion. The absence of malabsorption, no family history of rickets or hypophosphatermy presence of a marked excess of urinary phosphate, very low serum phosphate and normal serum calcium, vitamin D and parathyroid hormone levels led us to consider a diagnosis of tumor induced osteomalacia. Radiographs showed a large round radiolucent lesion in the left superior pubic ramus and generalized demineralisation. We performed a complete tumor resection and the space was filled with bone graft. On histopathologic examination it was a benign mesenchymal tumor. Rapid reversal of biochemical anomalies, radiographs anomalies and clinical manifestation were observed after complete tumor resection. The authors have described the tumor, the osteomalacia and the pathogenesis of tumor rickets. Histologically the most common causative tumors were vascular tumors, mesenchymal tumors and non ossifying tumors. The tumor were of bone or soft tissue origin. Clinical symptoms were muscular weakness, bone and muscle pain. Biochemically there is a very low phosphate level, a normal serum calcium level as well as a normal vitamin D and PTH level. There is a significant high level of urinal phosphate. The mechanism proposed to explain oncogenic osteomalacia includes tumor secretion of phosphaturic substance other than PTH and calcitonin. Another hypothesis is a substance interfering with normal vitamin D metabolism. The pathogenesis is not clearly defined. Regardless to the mechanism of osteomalacia, complete removal of the tumor will cure the patient. A diligent search for tumors should be done in patients with vitamin D resistant rickets.

Postoperative Calcium Management in Same-Day Discharge Thyroid and Parathyroid Surgery.

PubMed

Nelson, Kurt L; Hinson, Andrew M; Lawson, Bradley R; Middleton, Derek; Bodenner, Donald L; Stack, Brendan C

2016-05-01

To describe a safe and effective postoperative prophylactic calcium regimen for same-day discharge thyroid and parathyroid surgery. Case series with chart review. Tertiary referral academic institution. In total, 162 adult patients who underwent total thyroidectomy, completion thyroidectomy, unilateral parathyroidectomy, parathyroidectomy with bilateral neck exploration, or revision parathyroidectomy were identified preoperatively to be candidates for same-day discharge. All patients in this study were successfully discharged the same day on our standard prophylactic calcium regimen. Less than 1% (1/162) of patients re-presented to the hospital within 30 days of surgery, and that patient was successfully discharged from the emergency department after negative workup for hypocalcemia. There was no significant difference between preoperative and postoperative calcium levels in the total/completion thyroidectomy groups (9.3 vs 9.2 mg/dL, respectively; P = .14). The average postoperative calcium level in the parathyroid group was well within normal limits (9.5 mg/dL), and the difference in postoperative calcium levels between revision and primary parathyroidectomy cases was not significantly different (P = .34). The reported calcium regimen demonstrates a safe, effective, and objective means of postoperative calcium management in outpatient thyroid and parathyroid surgery in appropriately selected patients. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

Reduced expression of the Ca(2+) transporter protein PMCA2 slows Ca(2+) dynamics in mouse cerebellar Purkinje neurones and alters the precision of motor coordination.

PubMed

Empson, Ruth M; Turner, Paul R; Nagaraja, Raghavendra Y; Beesley, Philip W; Knöpfel, Thomas

2010-03-15

Cerebellar Purkinje neurones (PNs) express high levels of the plasma membrane calcium ATPase, PMCA2, a transporter protein critical for the clearance of calcium from excitable cells. Genetic deletion of one PMCA2 encoding gene in heterozygous PMCA2 knock-out (PMCA2(+/-) mice enabled us to determine how PMCA2 influences PN calcium regulation without the complication of the severe morphological changes associated with complete PMCA2 knock-out (PMCA2(-/-) in these cells. The PMCA2(+/-) cerebellum expressed half the normal levels of PMCA2 and this nearly doubled the time taken for PN dendritic calcium transients to recover (mean fast and slow recovery times increased from 70 ms to 110 ms and from 600 ms to 1100 ms). The slower calcium recovery had distinct consequences for PMCA2(+/-) PN physiology. The PNs exhibited weaker climbing fibre responses, prolonged outward Ca(2+)-dependent K(+) current (mean fast and slow recovery times increased from 136 ms to 192 ms and from 595 ms to 1423 ms) and a slower mean frequency of action potential firing (7.4 Hz compared with 15.8 Hz). Our findings were consistent with prolonged calcium accumulation in the cytosol of PMCA2(+/-) Purkinje neurones. Although PMCA2(+/-) mice exhibited outwardly normal behaviour and little change in their gait pattern, when challenged to run on a narrow beam they exhibited clear deficits in hindlimb coordination. Training improved the motor performance of both PMCA2(+/-) and wild-type mice, although PMCA2(+/-) mice were always impaired. We conclude that reduced calcium clearance perturbs calcium dynamics in PN dendrites and that this is sufficient to disrupt the accuracy of cerebellar processing and motor coordination.

Circulating parathyroid hormone and calcitonin in rats after spaceflight

NASA Technical Reports Server (NTRS)

Arnaud, Sara B.; Fung, Paul; Popova, Irina A.; Morey-Holton, Emily R.; Grindeland, Richard E.

1992-01-01

Parathyroid hormone and calcithonin, two major calcium-regulating hormones, were measured in the plasma of five experimental groups of rats to evaluate postflight calcium homeostasis after the 14-day Cosmos 2044 flight. Parathyroid hormone values were slightly higher in the flight animals (F) than in the appropriate cage and diet controls (S) (44 +/- 21 vs 21 +/- 4 pg/ml, P less than 0.05), but they were the same as in the vivarium controls (V), which had different housing and feeding schedules. The difference in F and V (22 +/- 11 vs 49 +/- 16 pg/ml, P less than 0.05) was most likely due to failure of circulating calcitonin in F to show the normal age-dependent increase which was demonstrated in age-matched controls in a separate experiment. Basal values for parathyroid hormone and calcitonin were unchanged after 2 wk of hindlimb suspension, a flight simulation model, in age-matched and younger rats. From a time course experiment serum calcium was higher and parathyroid hormone lower after 4 wk than in ambulatory controls. Postflight circulating levels of parathyroid hormone appear to reflect disturbances in calcium homeostasis from impaired renal function of undetermined cause, whereas levels of calcitonin reflect depression of a normal growth process.

High calcium to phosphorus ratio impairs growth and bone mineralization in Pekin ducklings.

PubMed

Zhu, Y W; Wen, J; Jiang, X X; Wang, W C; Yang, L

2018-04-01

Two experiments were conducted to investigate the effect of high dietary calcium (Ca) level on growth performance, Ca and phosphorus (P) metabolism, and nutrient utilization in ducklings subjected to normal and low P levels in diets. A completely randomized design was used with a factorial arrangement of 2 total dietary P levels [normal-P (0.60%) and low-P (0.45%) groups] × 4 dietary Ca levels [low-Ca (0.55%), normal-Ca (0.75%), medium-Ca (0.95%) and high-Ca (1.15%) groups)]. Compared to normal-P group, low-P group had lower (P < 0.05) final body weight (BW), average daily gain (ADG), and average daily feed intake (ADFI) and reduced (P < 0.05) serum Ca and P levels, bone Ca, P, and ash content, and bone mineral density in ducklings during the starter period. Under the low-P group, birds from high-Ca group had lower (P < 0.05) final BW, ADG, ADFI, bone ash content, bone mineral density, and the utilization of energy, Ca, and P than those from low-Ca, normal-Ca, and medium-Ca groups. Our results indicate that high-Ca diet induced greater growth suppression and bone mineralization loss in ducklings fed a low-P diet. The aggravated negative effect of high dietary Ca level with a low P level might be related to the elevated serum alkaline phosphatase activity and the reduced utilization of energy, Ca, and P.

Perioperative indicators of hypocalcemia in total thyroidectomy: the role of vitamin D and parathyroid hormone.

PubMed

Salinger, Eric M; Moore, John T

2013-12-01

Hypocalcemia is a common complication of thyroidectomy. The aim of this study was to identify risk factors for this problem. This prospective analysis included 111 patients undergoing total or completion thyroidectomy. Preoperative vitamin D levels and postoperative day 1 parathyroid hormone levels were analyzed for their predictive effects on postoperative hypocalcemia. Patients with ionized calcium <4.4 mg/dL had significantly lower mean parathyroid hormone levels than normocalcemic patients (13.0 vs 28.4 pg/mL, P < .001). Parathyroid hormone levels were also significantly lower in symptomatic patients (11.0 vs 28.4 pg/mL, P < .001). Preoperative vitamin D level, body mass index, gender, and pathologic findings were not associated with low calcium levels or symptoms of hypocalcemia. Younger age and low postoperative parathyroid hormone levels are predictive of symptomatic hypocalcemia. A parathyroid hormone level outside of the reference range may indicate a need for more aggressive postoperative calcium supplementation and treatment with activated vitamin D. Older patients with normal postoperative parathyroid hormone levels may be safely discharged with appropriate calcium supplementation. Copyright © 2013 Elsevier Inc. All rights reserved.

Electrolyte status in birth asphyxia.

PubMed

Basu, Pallab; Som, Sabyasachi; Das, Harendranath; Choudhuri, Nabendu

2010-03-01

To study electrolyte status in asphyxiated newborns of different severity in early neonatal period and compare with controls. Sodium, potassium and total calcium levels were estimated in the serum samples of asphyxiated newborns of different severity and control group immediately after birth. Mean serum sodium level was significantly lower (122.1 +/- 6.0 mEq/L vs 138.8 +/- 2.7 mEq/L; P < 0.001), mean serum potassium was higher (5.05 +/- 0.63 mEq/L vs 4.19 +/- 0.40 mEq/L; P < 0.001) and mean serum calcium level was found lower (6.85 +/- 0.95 mg/dl vs 9.50 +/- 0.51 mg/dl; P < 0.001) in cases than controls. Among cases, a strong positive linear correlation was found between the serum sodium, serum calcium levels and their Apgar scores, between sodium levels and total calcium levels and significant negative linear correlation between Apgar scores and serum potassium level. Among cases, hyponatremia and hypocalcemia developed early and simultaneously and the decrease in their serum levels was directly proportional to each other and to the degree of asphyxia. Though, mean potassium level was within the normal limit, the value was higher among cases than controls and directly proportional to asphyxia.

Experiment K-310: The effect of spaceflight on osteogenesis and dentinogenesis in the mandibles of rats

NASA Technical Reports Server (NTRS)

Simmons, D. J.; Russell, J. E.; Winter, F.; Rosenberg, G. D.; Walker, W. V.

1981-01-01

Normal rates of dentinogenesis and osteogenesis in the body of the mandible were observed. The total calcium, inorganic phosphorus and hydroxyproline levels in the jaws and incisors of the flight rats were normal. Gravity density fractionation studies suggested, however, that spaceflight caused a delay in the normal maturation of bone mineral and matrix; normal values were reestablished by 6 days postflight. The teeth were spared. The circadian and ultradian patterns of dentin calcification were normal during spaceflight and recovery periods, but the enamel rhythms displayed a greater amplitude of sulfur concentrations and this abnormal calcium to sulfur ratios only during exposure to zero gravity. The rat mandible and teeth do not suffer the deficits of bone formation common to weight bearing parts of the skeleton during spaceflight. The only derangements detected were in the quality of the matrix and mineral moieties.

Calcium and vitamin D intake and biochemical tests in short-stature children and adolescents.

PubMed

Bueno, A L; Czepielewski, M A; Raimundo, F V

2010-11-01

Growth is highly dependent on the absorption of nutrients. Inadequate calcium and vitamin D intake may compromise bone mineralization and growth. There is a great deal of concern regarding calcium and vitamin D intake, as well as biochemical changes in children and adolescents, which led us to investigate calcium and vitamin D levels during growth. Fifty-eight children and adolescents with short stature (z-score <3 s.d.) were evaluated from September 2005 to February 2007. Blood biochemical analyses and 24-h urine tests were performed and were used to evaluate calcium, phosphorus, creatinine, sodium, alkaline phosphatase, parathyroid hormone (PTH) and 25(OH)D levels. Dietary inquiries, repeated three times, were used to estimate the actual intake of these substances. A reduced calcium (608.6 mg/day) and vitamin D (72.5 IU/day) intake was observed. Calcium excretion in 24-h urine (56 mg/24 h) and calcium excretion by weight (2.0 mg/24 h/kg) showed scores that were below normal. A negative correlation between PTH and both dietary vitamin D (r=-0.46; P<0.01) and calcium intake (r =-0.41; P<0.001) was observed. The low calcium and vitamin D intake observed in short-stature children and adolescents was associated with biochemical results, and suggested that PTH and calcium excretion may be useful screening tests for evaluating dietary calcium and vitamin D.

Lipid body accumulation alters calcium signaling dynamics in immune cells

PubMed Central

Greineisen, William E.; Speck, Mark; Shimoda, Lori M.N.; Sung, Carl; Phan, Nolwenn; Maaetoft-Udsen, Kristina; Stokes, Alexander J.; Turner, Helen

2014-01-01

Summary There is well-established variability in the numbers of lipid bodies (LB) in macrophages, eosinophils, and neutrophils. Similarly to the steatosis observed in adipocytes and hepatocytes during hyperinsulinemia and nutrient overload, immune cell LB hyper-accumulate in response to bacterial and parasitic infection and inflammatory presentations. Recently we described that hyperinsulinemia, both in vitro and in vivo, drives steatosis and phenotypic changes in primary and transformed mast cells and basophils. LB reach high numbers in these steatotic cytosols, and here we propose that they could dramatically impact the transcytoplasmic signaling pathways. We compared calcium release and influx responses at the population and single cell level in normal and steatotic model mast cells. At the population level, all aspects of FcεRI-dependent calcium mobilization, as well as activation of calcium-dependent downstream signalling targets such as NFATC1 phosphorylation are suppressed. At the single cell level, we demonstrate that LB are both sources and sinks of calcium following FcεRI cross-linking. Unbiased analysis of the impact of the presence of LB on the rate of trans-cytoplasmic calcium signals suggest that LB enrichment accelerates calcium propagation, which may reflect a Bernoulli effect. LB abundance thus impacts this fundamental signalling pathway and its downstream targets. PMID:25016314

Serum tumour necrosis factor alpha in osteopenic and osteoporotic postmenopausal females: A cross-sectional study in Pakistan.

PubMed

Murad, Rafat; Shezad, Zahra; Ahmed, Saara; Ashraf, Mussarat; Qadir, Murad; Rehman, Rehana

2018-03-01

To compare biochemical parameters serum tumour necrosis factor alpha, calcium, magnesium, bone-specific alkaline phosphatase and vitamin D in postmenopausal women. This cross-sectional study was carried out from June 2015 to July 2016 at Jinnah Medical and Dental College, Karachi, and comprised postmenopausal women. Bone mineral density done by dual energy X-ray absorptiometryscan categorised subjects by World Health Organisation classification into normal (T score > -1) osteopenic (T score between -1 and -2.5) and osteoporotic (T score < -2.5). Biochemical parameters like tumour necrosis alpha, calcium, magnesium, bone-specific alkaline phosphatase and vitamin D were measured by solid phase enzyme amplified sensitivity immunoassay method. SPSS 16 was used to analyse the data. Of the 146 women, 34(23%) were normal, 93(67%) were osteopenic and 19(13%) were osteoporotic. There was significant difference in mean body mass index, serum tumour necrosis factor alpha and calcium in all the three groups (p<0.01). Significant mean difference was observed in serum calcium levels between normal and osteopenic, and between normal and osteoporotic group (p<0.05 each) without any significant mean difference between osteopenic and osteoporotic groups (p>0.05). A significant difference was observed for mean tumour necrosis factor alpha values between normal and osteoporotic groups (p<0.05). Tumour necrosis factor alpha showed negative correlation with bone mineral density in osteopenic and osteoporotic groups (p>0.05). Increased bone turnover in postmenopausal osteopenic women can be predicted by increased serum cytokine.

Aromatase Deficient Female Mice Demonstrate Altered Expression of Molecules Critical for Renal Calcium Reabsorption

NASA Astrophysics Data System (ADS)

Öz, Orhan K.; Hajibeigi, Asghar; Cummins, Carolyn; van Abel, Monique; Bindels, René J.; Kuro-o, Makoto; Pak, Charles Y. C.; Zerwekh, Joseph E.

2007-04-01

The incidence of kidney stones increases in women after the menopause, suggesting a role for estrogen deficiency. In order to determine if estrogen may be exerting an effect on renal calcium reabsorption, we measured urinary calcium excretion in the aromatase-deficient female mouse (ArKO) before and following estrogen therapy. ArKO mice had hypercalciuria that corrected during estrogen administration. To evaluate the mechanism by which estrogen deficiency leads to hypercalciuria, we examined the expression of several proteins involved in distal tubule renal calcium reabsorption, both at the message and protein levels. Messenger RNA levels of TRPV5, TRPV6, calbindin-D28K, the Na+/Ca++ exchanger (NCX1), and the plasma membrane calcium ATPase (PMCA1b) were significantly decreased in kidneys of ArKO mice. On the other hand, klotho mRNA levels were elevated in kidneys of ArKO mice. ArKO renal protein extracts had lower levels of calbindin-D28K but higher levels of the klotho protein. Immunochemistry demonstrated increased klotho expression in ArKO kidneys. Estradiol therapy normalized the expression of TRPV5, calbindin-D28K, PMCA1b and klotho. Taken together, these results demonstrate that estrogen deficiency produced by aromatase inactivation is sufficient to produce a renal leak of calcium and consequent hypercalciuria. This may represent one mechanism leading to the increased incidence of kidney stones following the menopause in women.

Effect of animal and vegetable protein intake on oxalate excretion in idiopathic calcium stone disease.

PubMed

Marangella, M; Bianco, O; Martini, C; Petrarulo, M; Vitale, C; Linari, F

1989-04-01

Oxalate excretion was measured in healthy subjects and idiopathic calcium stone-formers on dietary regimens which differed in the type and amount of protein allowed; 24-h urine collections were obtained from 41 practising vegetarians and 40 normal persons on a free, mixed, "mediterranean" diet. Twenty idiopathic calcium stone-formers were also studied while on two low calcium, low oxalate diets which differed in that animal protein was high in one and restricted in the other. Vegetarians had higher urinary oxalate levels than controls and although the calcium levels were markedly lower, urinary saturation with calcium/oxalate was significantly higher. This mild hypercalciuria was interpreted as being secondary to both a higher intake and increased fractional intestinal absorption of oxalate. Changing calcium stone-formers from a high to a low animal protein intake produced a significant decrease in calcium excretion but there was no variation in urinary oxalate. As a result, the decrease in calcium oxalate saturation was only marginal and not significant. It was concluded that dietary animal protein has a minimal effect on oxalate excretion. Mild hyperoxaluria of idiopathic calcium stone disease is likely to be intestinal in origin. Calcium stone-formers should be advised to avoid an excess of animal protein but the risks of a vegetable-rich diet should also be borne in mind.

Regulation of Cellular Calcium in Vestibular Supporting Cells by Otopetrin 1

PubMed Central

Kim, Euysoo; Hyrc, Krzysztof L.; Speck, Judith; Lundberg, Yunxia W.; Salles, Felipe T.; Kachar, Bechara; Goldberg, Mark P.; Warchol, Mark E.

2010-01-01

Otopetrin 1 (OTOP1) is a multitransmembrane domain protein, which is essential for mineralization of otoconia, the calcium carbonate biominerals required for vestibular function, and the normal sensation of gravity. The mechanism driving mineralization of otoconia is poorly understood, but it has been proposed that supporting cells and a mechanism to maintain high concentrations of calcium are critical. Using Otop1 knockout mice and a utricular epithelial organ culture system, we show that OTOP1 is expressed at the apex of supporting cells and functions to increase cytosolic calcium in response to purinergic agonists, such as adenosine 5′-triphosphate (ATP). This is achieved by blocking mobilization of calcium from intracellular stores in an extracellular calcium-dependent manner and by mediating influx of extracellular calcium. These data support a model in which OTOP1 acts as a sensor of the extracellular calcium concentration near supporting cells and responds to ATP in the endolymph to increase intracellular calcium levels during otoconia mineralization. PMID:20554841

Calcitonin: discovery, development, and clinical application.

PubMed

Copp, D H

1994-06-01

In 1954, when I gave a talk on calcium homeostasis at the first Gordon Conference on Bones and Teeth, it was recognized that the level of ionic calcium in the plasma and body fluids must be maintained with precision, since it is critically important for a number of vital processes. However, very little was known of the mechanisms involved and I decided to make this the focus of my research career. With the assistance of a number of first-year medical students working during the summer, we developed a precise method for measuring calcium, demonstrated the remarkable constancy of plasma calcium in normal human subjects, and found that normal calcium levels were restored quickly after being artificially raised or lowered. We focussed on parathyroid hormone (PTH), which plays a key role in controlling hypocalcemia by stimulating osteolysis. While studying the control of its secretion in 1961, we discovered a second calcium-regulating hormone (calcitonin) which was released by hypercalcemia and lowered plasma calcium by inhibiting osteolysis. It is a straight-chain peptide with 32 amino acids and a 7-membered disulfide ring at the N terminal. It is produced by C cells which arise from the neural crest and is considered a neuropeptide hormone. It is produced in the thyroid of mammals and the ultimobranchial glands of lower vertebrates. We were involved in the isolation of salmon calcitonin, which is the form most widely used in therapy because of its high potency. In addition to inhibiting bone resorption, it is a powerful analgesic agent with a potency in certain circumstances which is 30-50 times that of morphine. It is widely used clinically for the treatment of Paget's disease, hypercalcemia, osteoporosis, and relief of bone pain. World sales in 1992 exceeded US$900 million, of which 85% was for osteoporosis.

Calcium blood test

MedlinePlus

... may be found in nutritional supplements or antacids) Lithium Thiazide diuretics (water pills) Thyroxine Vitamin D Drinking ... like substance. Use of certain medicines such as lithium, tamoxifen, and thiazides. A lower than normal levels ...

Calcium citrate without aluminum antacids does not cause aluminum retention in patients with functioning kidneys

NASA Technical Reports Server (NTRS)

Sakhaee, K.; Wabner, C. L.; Zerwekh, J. E.; Copley, J. B.; Pak, L.; Poindexter, J. R.; Pak, C. Y.

1993-01-01

It has been suggested that calcium citrate might enhance aluminum absorption from food, posing a threat of aluminum toxicity even in patients with normal renal function. We therefore measured serum and urinary aluminum before and following calcium citrate therapy in patients with moderate renal failure and in normal subjects maintained on constant metabolic diets with known aluminum content (967-1034 mumol/day, or 26.1-27.9 mg/day, in patients and either 834 or 1579 mumol/day, or 22.5 and 42.6 mg/day, in normal subjects). Seven patients with moderate renal failure (endogenous creatinine clearance of 43 ml/min) took 50 mmol (2 g) calcium/day as effervescent calcium citrate with meals for 17 days. Eight normal women received 25 mmol (1 g) calcium/day as tricalcium dicitrate tablets with meals for 7 days. In patients with moderate renal failure, serum and urinary aluminum were normal before treatment at 489 +/- 293 SD nmol/l (13.2 +/- 7.9 micrograms/l) and 767 +/- 497 nmol/day (20.7 +/- 13.4 micrograms/day), respectively. They remained within normal limits and did not change significantly during calcium citrate treatment (400 +/- 148 nmol/l and 600 +/- 441 nmol/day, respectively). Similarly, no significant change in serum and urinary aluminum was detected in normal women during calcium citrate administration (271 +/- 59 vs 293 +/- 85 nmol/l and 515 +/- 138 vs 615 +/- 170 nmol/day, respectively). In addition, skeletal bone aluminum content did not change significantly in 14 osteoporotic patients (endogenous creatinine clearance of 68.5 ml/min) treated for 24 months with calcium citrate, 10 mmol calcium twice/day separately from meals (29.3 +/- 13.9 ng/mg ash bone to 27.9 +/0- 10.4, P = 0.727). In them, histomorphometric examination did not show any evidence of mineralization defect. Thus, calcium citrate given alone without aluminum-containing drugs does not pose a risk of aluminum toxicity in subjects with normal or functioning kidneys, when it is administered on an empty stomach at a recommended dose of 20 mmol calcium/day.

Management and surgical treatment of parathyroid crisis secondary to parathyroid tumors: report of four cases.

PubMed

Ameerudden, Shakil; He, Xianghui

2011-01-01

Parathyroid crisis, also known as a parathyroid storm, is a rare and serious complication of primary hyperparathyroidism. Four cases are reported here in which patients presented to hospital with general complaints due to hypercalcemia secondary to hyperparathyroidism. Blood test results upon admission showed high levels of serum calcium and parathyroid hormone, and medical treatment initiated to lower the calcium level was ineffective. After relevant investigations, each patient underwent surgical exploration of the parathyroid glands, followed by excision of a pathological parathyroid tumor. There was a prompt decrease in parathyroid hormone level immediately after surgery. Histology reports revealed that patients had parathyroid adenoma. All patients recovered after surgery, with serum calcium levels restored back to normal and with resolution of all symptoms of hypercalcemia. This report illustrates how often this disease is initially misdiagnosed, and how prompt appropriate surgical treatment provides the best outcome for the patient.

Effects of liver function on ionized hypocalcaemia following rapid blood transfusion.

PubMed

Chung, H S; Cho, S J; Park, C S

2012-01-01

Hypocalcaemia detrimentally affects the cardiovascular system and massive transfusion-related hypocalcaemia is particularly severe in end-stage liver disease patients undergoing liver transplantation (LT). This study, therefore, compared the severity and duration of ionized hypocalcaemia between patients with normal and impaired liver function. Patients (n = 26 per group) were transfused at a rate of 10 ml/kg within 10 min with packed red blood cells (PRBCs) during LT (group LP) or spinal surgery (group SP), or were infused with 0.9% normal saline during spinal surgery (group SN). Serum levels of ionized calcium were assessed before (T(0)), just after (T(1)), and at 20 (T(2)) and 60 min (T(3)) after transfusion. Transfusion with PRBCs caused more severe ionized hypocalcaemia than 0.9% normal saline at T(1). In contrast to the faster (20 min) normalization in group SP, ionized hypocalcaemia in group LP persisted at T(3). Serum ionized calcium levels at T(3) showed correlations with vital signs, blood glucose, serum potassium, base deficit and lactate. Rapid blood transfusion caused more severe and prolonged ionized hypo calcaemia in patients with liver dysfunction than in those with normal liver function.

Vitamin D and intestinal calcium transport after bariatric surgery.

PubMed

Schafer, Anne L

2017-10-01

Bariatric surgery is a highly effective treatment for obesity, but it may have detrimental effects on the skeleton. Skeletal effects are multifactorial but mediated in part by nutrient malabsorption. While there is increasing interest in non-nutritional mechanisms such as changes in fat-derived and gut-derived hormones, nutritional factors are modifiable and thus represent potential opportunities to prevent and treat skeletal complications. This review begins with a discussion of normal intestinal calcium transport, including recent advances in our understanding of its regulation by vitamin D, and areas of continued uncertainty. Human and animal studies of vitamin D and intestinal calcium transport after bariatric surgery are then summarized. In humans, even with optimized 25-hydroxyvitamin D levels and recommended calcium intake, fractional calcium absorption decreased dramatically after Roux-en-Y gastric bypass (RYGB). In rats, intestinal calcium absorption was lower after RYGB than after sham surgery, despite elevated 1,25-dihyroxyvitamin D levels and intestinal gene expression evidence of vitamin D responsiveness. Such studies have the potential to shed new light on the physiology of vitamin D and intestinal calcium transport. Moreover, understanding the effects of bariatric surgery on these processes may improve the clinical care of bariatric surgery patients. Published by Elsevier Ltd.

Clinical and biochemical presentation of sarcoidosis with high and normal serum angiotensin-converting enzyme.

PubMed

Sejdic, A; Graudal, N; Baslund, B

2018-06-22

The presentation of sarcoidosis can involve symptoms from all organs and the diagnosis is therefore often difficult. A raised serum level of serum angiotensin-converting enzyme (sACE) can be detected in 41-58% of patients. However, whether the sACE level per se reflects the severity of the sarcoid inflammation at the onset of the disease is not well described. The purpose of this study was to investigate the clinical and laboratory significance of high versus normal sACE levels in sarcoidosis. Journal data were retrospectively extracted from 101 patients from our clinic. Clinical and biochemical data were compared between patients with high sACE levels (> 115 U/L) on at least one occasion and normal sACE levels (< 115 U/L). In total, 48% (n = 48) of the patients had high ACE and 52% (n = 53) had normal ACE. The most common extrapulmonary manifestation for both groups was arthritis, followed by skin and eye involvement, but none of these differed between the two groups. Serum ionized calcium was significantly higher in the high sACE group, with a correlation coefficient of 0.112 (p = 0.460). Our study demonstrates that serum ionized calcium is significantly higher in the high sACE group but there was no statistical correlation to sACE. No other clinical or biochemical differences were observed.

Deterioration of teeth and alveolar bone loss due to chronic environmental high-level fluoride and low calcium exposure.

PubMed

Simon, Maciej J K; Beil, Frank Timo; Riedel, Christoph; Lau, Grace; Tomsia, Antoni; Zimmermann, Elizabeth A; Koehne, Till; Ueblacker, Peter; Rüther, Wolfgang; Pogoda, Pia; Ignatius, Anita; Amling, Michael; Oheim, Ralf

2016-12-01

Health risks due to chronic exposure to highly fluoridated groundwater could be underestimated because fluoride might not only influence the teeth in an aesthetic manner but also seems to led to dentoalveolar structure changes. Therefore, we studied the tooth and alveolar bone structures of Dorper sheep chronically exposed to very highly fluoridated and low calcium groundwater in the Kalahari Desert in comparison to controls consuming groundwater with low fluoride and normal calcium levels within the World Health Organization (WHO) recommended range. Two flocks of Dorper ewes in Namibia were studied. Chemical analyses of water, blood and urine were performed. Mineralized tissue investigations included radiography, HR-pQCT analyses, histomorphometry, energy-dispersive X-ray spectroscopy and X-ray diffraction-analyses. Fluoride levels were significantly elevated in water, blood and urine samples in the Kalahari group compared to the low fluoride control samples. In addition to high fluoride, low calcium levels were detected in the Kalahari water. Tooth height and mandibular bone quality were significantly decreased in sheep, exposed to very high levels of fluoride and low levels of calcium in drinking water. Particularly, bone volume and cortical thickness of the mandibular bone were significantly reduced in these sheep. The current study suggests that chronic environmental fluoride exposure with levels above the recommended limits in combination with low calcium uptake can cause significant attrition of teeth and a significant impaired mandibular bone quality. In the presence of high fluoride and low calcium-associated dental changes, deterioration of the mandibular bone and a potential alveolar bone loss needs to be considered regardless whether other signs of systemic skeletal fluorosis are observed or not.

Uraemic hyperparathyroidism causes a reversible inflammatory process of aortic valve calcification in rats

PubMed Central

Shuvy, Mony; Abedat, Suzan; Beeri, Ronen; Danenberg, Haim D.; Planer, David; Ben-Dov, Iddo Z.; Meir, Karen; Sosna, Jacob; Lotan, Chaim

2008-01-01

Aims Renal failure is associated with aortic valve calcification (AVC). Our aim was to develop an animal model for exploring the pathophysiology and reversibility of AVC, utilizing rats with diet-induced kidney disease. Methods and results Sprague–Dawley rats (n = 23) were fed a phosphate-enriched, uraemia-inducing diet for 7 weeks followed by a normal diet for 2 weeks (‘diet group’). These rats were compared with normal controls (n = 10) and with uraemic controls fed with phosphate-depleted diet (‘low-phosphate group’, n = 10). Clinical investigations included serum creatinine, phosphate and parathyroid hormone (PTH) levels, echocardiography, and multislice computed tomography. Pathological examinations of the valves included histological characterization, Von Kossa staining, and antigen and gene expression analyses. Eight diet group rats were further assessed for reversibility of valve calcification following normalization of their kidney function. At 4 weeks, all diet group rats developed renal failure and hyperparathyroidism. At week 9, renal failure resolved with improvement in the hyperparathyroid state. Echocardiography demonstrated valve calcifications only in diet group rats. Tomographic calcium scores were significantly higher in the diet group compared with controls. Von Kossa stain in diet group valves revealed calcium deposits, positive staining for osteopontin, and CD68. Gene expression analyses revealed overexpression of osteoblast genes and nuclear factor κB activation. Valve calcification resolved after diet cessation in parallel with normalization of PTH levels. Resolution was associated with down-regulation of inflammation and osteoblastic features. Low-phosphate group rats developed kidney dysfunction similar to that of the diet group but with normal levels of PTH. Calcium scores and histology showed only minimal valve calcification. Conclusion We developed an animal model for AVC. The process is related to disturbed mineral metabolism. It is associated with inflammation and osteoblastic features. Furthermore, the process is reversible upon normalization of the mineral homeostasis. Thus, our model constitutes a convenient platform for studying AVC and potential remedies. PMID:18390899

Uraemic hyperparathyroidism causes a reversible inflammatory process of aortic valve calcification in rats.

PubMed

Shuvy, Mony; Abedat, Suzan; Beeri, Ronen; Danenberg, Haim D; Planer, David; Ben-Dov, Iddo Z; Meir, Karen; Sosna, Jacob; Lotan, Chaim

2008-08-01

Renal failure is associated with aortic valve calcification (AVC). Our aim was to develop an animal model for exploring the pathophysiology and reversibility of AVC, utilizing rats with diet-induced kidney disease. Sprague-Dawley rats (n = 23) were fed a phosphate-enriched, uraemia-inducing diet for 7 weeks followed by a normal diet for 2 weeks ('diet group'). These rats were compared with normal controls (n = 10) and with uraemic controls fed with phosphate-depleted diet ('low-phosphate group', n = 10). Clinical investigations included serum creatinine, phosphate and parathyroid hormone (PTH) levels, echocardiography, and multislice computed tomography. Pathological examinations of the valves included histological characterization, Von Kossa staining, and antigen and gene expression analyses. Eight diet group rats were further assessed for reversibility of valve calcification following normalization of their kidney function. At 4 weeks, all diet group rats developed renal failure and hyperparathyroidism. At week 9, renal failure resolved with improvement in the hyperparathyroid state. Echocardiography demonstrated valve calcifications only in diet group rats. Tomographic calcium scores were significantly higher in the diet group compared with controls. Von Kossa stain in diet group valves revealed calcium deposits, positive staining for osteopontin, and CD68. Gene expression analyses revealed overexpression of osteoblast genes and nuclear factor kappaB activation. Valve calcification resolved after diet cessation in parallel with normalization of PTH levels. Resolution was associated with down-regulation of inflammation and osteoblastic features. Low-phosphate group rats developed kidney dysfunction similar to that of the diet group but with normal levels of PTH. Calcium scores and histology showed only minimal valve calcification. We developed an animal model for AVC. The process is related to disturbed mineral metabolism. It is associated with inflammation and osteoblastic features. Furthermore, the process is reversible upon normalization of the mineral homeostasis. Thus, our model constitutes a convenient platform for studying AVC and potential remedies.

Calcitonin secretion in congenital nongoitrous cretinism.

PubMed

Carey, D E; Jones, K L; Parthemore, J G; Deftos, L J

1980-04-01

Plasma calcitonin (CT) was measured in the basal state and/or during provocative tests of hormone secretion in 11 children with congenital non-goitrous cretinism (CNC), in 1 girl with a lingual thyroid, and in 11 normal children. Basal and stimulated CT concentrations were significantly lower in the patients with CNC than in the normal subjects. Mean basal CT (+/- SE) was 41 +/- 4 pg/ml in the normal children, 24 +/- 3 pg/ml in the children with CNC, and 20 +/- 2 pg/ml in the patient with the lingual thyroid. The mean incremental CT responses to calcium infusion were 7.0 +/- 2 pg/ml in the children with CNC, 6.0 pg/ml in the patient with the lingual thyroid, and 146 +/- 47 pg/ml in the normal children. The children with CNC also demonstrated a significant delay in the return of the total serum calcium to basal level after the calcium infusion. The mean incremental CT response after infusion of pentagastrin was 7.6 +/- 2 pg/ml in the children with CNC, 10.0 pg/ml in the child with the lingual thyroid, and 34.4 +/- 11 pg/ml in the normal children. These data indicate that CT deficiency is present in children with CNC and suggest that the deficiency is a consequence of the defective embryologic development of the thyroid gland.

Maternal hypervitaminosis D reduces fetal bone mass and mineral acquisition and leads to neonatal lethality.

PubMed

Lieben, L; Stockmans, I; Moermans, K; Carmeliet, G

2013-11-01

Pregnancy challenges maternal calcium handling because sufficient calcium has to be transferred to the fetus to ensure fetal bone mass acquisition. 1,25(OH)2 vitamin D [1,25(OH)2D] is an important regulator of calcium homeostasis during adulthood, yet its role seems redundant for the maternal adaptations to pregnancy as well as during fetal development. However, not only deficiency but also excess of 1,25(OH)2D can be harmful and we therefore questioned whether high maternal 1,25(OH)2D levels may injure fetal development or neonatal outcome, as maternal-fetal transport of 1,25(OH)2D has been largely disputed. To this end, vitamin D receptor (VDR) null (Vdr(-/-)) females, displaying high 1,25(OH)2D levels, were mated with Vdr(+/-) males to obtain pregnancies with fetuses that are responsive (Vdr(+/-)) or resistant (Vdr(-/-)) to 1,25(OH)2D. Surprisingly, most of the Vdr(+/-) neonates died shortly after birth, whereas none of the Vdr(-/-). Mechanistically, we noticed that in Vdr(+/-) embryos, serum calcium levels were normal, but that skeletal calcium storage was reduced as evidenced by decreased mineralized bone mass as well as bone mineral content. More precisely, bone formation was decreased and the level of bone mineralization inhibitors was increased. This decreased fetal skeletal calcium storage may severely compromise calcium balance and survival at birth. In conclusion, these data indicate that high maternal 1,25(OH)2D levels are transferred across the placental barrier and adversely affect the total amount of calcium stored in fetal bones which is accompanied by neonatal death. © 2013 Elsevier Inc. All rights reserved.

Acute hypocalcemia following kidney transplantation may depend on the type of remote parathyroidectomy: a retrospective cohort study
.

PubMed

Simons, Malorie; Bautista, Josef; Occhiogrosso, Rachel; Scott-Sheldon, Lori Aj; Gohh, Reginald

2017-06-01

Secondary hyperparathyroidism is a common complication of chronic kidney disease. When medical management fails, parathyroidectomy (PTX) is a treatment option. The two most common types are subtotal PTX and total PTX with autotransplantation (AT). To date, there is no consensus as to which procedure is preferable, especially in patients who are candidates for future kidney transplantation. The aim of this study was to identify if the type of PTX is a risk factor for acute postrenal transplant (postRTX) hypocalcemia and a concern for problems with long-term calcium homeostasis. Renal transplant recipients at Rhode Island Hospital from 2005 to 2014 were screened for prior PTX. Out of 297 participants, 11 patients met the criteria. They were further divided into subtotal PTX (n = 5) vs. total PTX+AT (n = 6). Immediate postoperative (14 days) and long-term (1 year) calcium levels were followed and analyzed. Linear growth models were used to determine the effects of type of parathyroidectomy (subtotal PTX, total PTX+AT) alone on hypocalcemia over time. In these models, pretransplant levels of calcium and PTH were included as covariates. Baseline characteristics showed that prerenal transplant (preRTX) parathyroid hormone (PTH) levels were lower in total PTX+AT vs. subtotal PTX (3.5 vs. 247.2 mg/dL, p < 0.005). PreRTX calcium levels were slightly lower in subtotal PTX (9.5 vs. 8.25 mg/dL, p < 0.01), but were within normal limits for both groups. No significant differences were noted between total vitamin D levels and time between PTX and RTX. Within 14 days postRTX, the total PTX+AT group had lower average calcium levels (5.8 vs 8.8 mg/dL, p < 0.001); however, both groups had normal and stable calcium levels from 1 month to 1 year after transplant. This was further supported after adjusting for preRTX levels of calcium and PTH, showing a significant interaction between treatment and time such that patients had lower calcium levels if they underwent total PTX+AT vs. subtotal PTX within 14 days postRTX (β = -0.204, SE = 0.039, p < 0.001) (Figure 1) but not at 1 year postRTX (β = 0.035, SE = 0.075, p = 0.640). This study suggests that total PTX+AT increases the risk for acute postRTX hypocalcemia but has no effect on long-term calcium homeostasis. We speculate that the acuity of the hypocalcemia may be compounded by high-dose glucocorticoids required for induction, in addition to the preoperative undetectable PTH. Thus, prior to RTX, physicians should take into account the type of remote PTX. If a patient had a total PTX+AT, then postRTX hypocalcemia is likely to occur.
.

Hypercalcemia caused by iatrogenic hypervitaminosis A.

PubMed

Bhalla, Karan; Ennis, David M; Ennis, Elizabeth D

2005-01-01

Vitamin A toxicity produces protean clinical manifestations involving a wide variety of tissues and systems. Hypercalcemia can occasionally be associated with high vitamin A levels, but is rare. In this report we describe a patient who was receiving a commercially prepared enteral feeding formula for 2 years. He developed asymptomatic hypercalcemia and had serum vitamin A levels several fold above normal. Subsequently, a custom-made enteral feed was used which contained negligible amounts of vitamin A. Several months later, vitamin A levels diminished substantially and serum calcium levels returned to normal.

Vitamin D status did not related to calcium status in active tuberculosis patients in North Sumatera, Indonesia

NASA Astrophysics Data System (ADS)

Keumala Sari, Dina; Khairina Arrasyid, Nurfida

2018-03-01

Background: Tuberculosis is one of the highest mortality caused in a tropical country with abundant sunlight such Indonesia. Vitamin D and calcium plays important roles in tuberculosis pathogenesis. Objective:We sought to determine whether there is an association between vitamin D status and calcium status in tuberculosis patients. Design: We conducted a cross-sectional study of 32 man and women aged 18-60 years with active tuberculosis in North Sumatera, Indonesia. Parameters were 25(OH)D and calcium serum level, body mass index, fat mass, and others lifestyles factors also assessed. The association was analysis using chi-square or fischer test. Results: the mean of study subjects age were 37.2±14.9 years old and BMI were 20.8±4.4 kg/m2 There were 81.2% subjects categorized into vitamin D deficiency-insufficiency and 18.8% categorized into vitamin D sufficiency. There were 29% subjects categorized into normal calcium level, and 3% were hypocalcemia. Based on food recall analysis, there were found lower vitamin D and calcium intake. There is no association between vitamin D and calcium classification. Conclusions: based on this result, although there is no association between vitamin D and calcium, but there could be altered by lower food intake and tuberculosis progression.

Concentrations of cadmium and selected essential elements in malignant large intestine tissue

PubMed Central

Dziki, Adam; Kilanowicz, Anna; Sapota, Andrzej; Duda-Szymańska, Joanna; Daragó, Adam

2015-01-01

Introduction Colorectal cancer is one of the most common cancers worldwide. Incidence rates of large intestine cancer indicate a role of environmental and occupational factors. The role of essential elements and their interaction with toxic metals can contribute to the explanation of a complex mechanism by which large intestine cancer develops. Bearing this in mind, determining the levels of essential and toxic elements in tissues (organs), as well as in body fluids, seems to shed light on their role in the mode of action in malignant disease. Aim Determination of the levels of cadmium, zinc, copper, selenium, calcium, magnesium, and iron in large intestine malignant tissue. Material and methods Two intraoperative intestine sections were investigated: one from the malignant tissue and the other one from the normal tissue, collected from each person with diagnosed large intestine cancer. Cadmium, zinc, copper, calcium, magnesium, and iron levels were determined with atomic absorption spectrometry, and selenium levels by spectrofluorimetric method. Results The levels of copper, selenium, and magnesium were higher in the malignant than in normal tissues. In addition, the zinc/copper and calcium/magnesium relationship was altered in malignant tissue, where correlations were lower compared to non-malignant tissue. Conclusions The results seems to demonstrate disturbed homeostasis of some essential elements. However, it is hard to confirm their involvement in the aetiology of colorectal cancer. PMID:27110307

The pmr gene, encoding a Ca2+-ATPase, is required for calcium and manganese homeostasis and normal development of hyphae and conidia in Neurospora crassa.

PubMed

Bowman, Barry J; Abreu, Stephen; Johl, Jessica K; Bowman, Emma Jean

2012-11-01

The pmr gene is predicted to encode a Ca(2+)-ATPase in the secretory pathway. We examined two strains of Neurospora crassa that lacked PMR: the Δpmr strain, in which pmr was completely deleted, and pmr(RIP), in which the gene was extensively mutated. Both strains had identical, complex phenotypes. Compared to the wild type, these strains required high concentrations of calcium or manganese for optimal growth and had highly branched, slow-growing hyphae. They conidiated poorly, and the shape and size of the conidia were abnormal. Calcium accumulated in the Δpmr strains to only 20% of the wild-type level. High concentrations of MnCl(2) (1 to 5 mM) in growth medium partially suppressed the morphological defects but did not alter the defect in calcium accumulation. The Δpmr Δnca-2 double mutant (nca-2 encodes a Ca(2+)-ATPase in the plasma membrane) accumulated 8-fold more calcium than the wild type, and the morphology of the hyphae was more similar to that of wild-type hyphae. Previous experiments failed to show a function for nca-1, which encodes a SERCA-type Ca(2+)-ATPase in the endoplasmic reticulum (B. J. Bowman, S. Abreu, E. Margolles-Clark, M. Draskovic, and E. J. Bowman, Eukaryot. Cell 10:654-661, 2011). The pmr(RIP) Δnca-1 double mutant accumulated small amounts of calcium, like the Δpmr strain, but exhibited even more extreme morphological defects. Thus, PMR can apparently replace NCA-1 in the endoplasmic reticulum, but NCA-1 cannot replace PMR. The morphological defects in the Δpmr strain are likely caused, in part, by insufficient concentrations of calcium and manganese in the Golgi compartment; however, PMR is also needed to accumulate normal levels of calcium in the whole cell.

Biochemical Predictors of Low Bone Mineral Density and Fracture Susceptibility in Maltese Postmenopausal Women.

PubMed

Formosa, Melissa M; Xuereb-Anastasi, Angela

2016-01-01

Osteoporosis and fractures are complex conditions influenced by an interplay of genetic and environmental factors. The aim of the study was to investigate three biochemical parameters including total serum calcium, total serum alkaline phosphatase (sALP) and albumin in relation to bone mineral density (BMD) at the lumbar spine and femoral neck (FN), and with all-type of low-trauma fractures in Maltese postmenopausal women. Levels were also correlated with age and physical activity. A case-control study of 1045 women was performed. Women who suffered a fracture were classified as cases whereas women without a fracture history were included as controls subdivided into normal, osteopenic, or osteoporotic according to their BMD measurements. Blood specimens were collected following good standard practice and testing was performed by spectrophotometry. Calcium and sALP levels were weakly correlated with FN BMD levels (calcium: r = -0.111, p = 0.002; sALP: r = 0.089, p = 0.013). Fracture cases had the lowest serum levels of calcium, sALP and albumin relative to all other control groups, which decreased with increasing age, possibly increasing fracture risk. Biochemical levels were lowest in women who sustained a hip fracture and more than one fracture. Biochemical parameters decreased with reduced physical activity; however, this was most evident for fracture cases. Reduced physical activity was associated with lower BMD levels at the hip, and to a lower extent at the spine. In conclusion, results suggest that levels of serum calcium and albumin could be indicative of fracture risk, whereas calcium levels and to lower extent sALP levels could be indicators of hip BMD.

[The French clinician's guide to the Kidney disease: Improving global outcomes (KDIGO) for chronic kidney disease-mineral and bone disorders (CKD-MBD)].

PubMed

Jean, G; Chazot, C

2010-06-01

The new recommendations of "Kidney disease: improving global outcomes" for the definition and classification of chronic kidney disease and mineral and bone disorders were released in August 2009. We report the most important of these recommendations and a brief comment from a clinician's point of view. The main points to be noted with regard to the new recommendations are as follows: serum calcium should be in the normal range; phosphorus concentration should be lowered toward the normal range and serum parathyroid hormone (PTH) levels should be two to nine times the upper limit of the normal range; bone remodelling can be assessed using alkaline phosphatase; the use of calcium-phosphorus (Ca x P) product as an index is not recommended anymore; at any stage of CKD, vitamin D deficiency and insufficiency must be corrected; vascular calcification should be detected in a simple way using lateral abdominal radiography and echocardiography; a bone biopsy should be performed before therapy with bisphosphonates; the prescription of dialysate calcium should be individualized within the range of 1.25-1.5 mmol/l; the phosphate binder (calcium- or non-calcium-based) and the other treatments for secondary hyperparathyroidism should be individualized based on a global strategy. A majority of these recommendations are not based on evidence and their feasibility and relevance need to be assessed. Copyright 2010 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Renal Control of Calcium, Phosphate, and Magnesium Homeostasis

PubMed Central

Chonchol, Michel; Levi, Moshe

2015-01-01

Calcium, phosphate, and magnesium are multivalent cations that are important for many biologic and cellular functions. The kidneys play a central role in the homeostasis of these ions. Gastrointestinal absorption is balanced by renal excretion. When body stores of these ions decline significantly, gastrointestinal absorption, bone resorption, and renal tubular reabsorption increase to normalize their levels. Renal regulation of these ions occurs through glomerular filtration and tubular reabsorption and/or secretion and is therefore an important determinant of plasma ion concentration. Under physiologic conditions, the whole body balance of calcium, phosphate, and magnesium is maintained by fine adjustments of urinary excretion to equal the net intake. This review discusses how calcium, phosphate, and magnesium are handled by the kidneys. PMID:25287933

Effect of limestone reactivity and percent on production by dairy cows in early lactation.

PubMed

Nocek, J E; Braund, D G; English, J E

1983-12-01

Seventy-two Holstein cows (16 first lactation) were assigned to four treatments: A) normal-grind limestone (800 to 1000 mu) added to provide .77% calcium (total ration dry basis); B) fine-grind limestone (less than 150 mu) at .77% calcium; C) normal-grind at 1.15% calcium; and D) fine-grind limestone at 1.15% calcium. Cows fed diets containing .77% calcium had higher percent milk fat and fat yield than those fed 1.15% calcium diets, and cows fed fine-grind limestone had greater percent fat and fat yield than those fed normal-grind limestone. Four percent fat-corrected milk was higher for cows fed .77% calcium diets. Trends were similar for heifers in first lactation. Dry matter intake was higher for cows fed .77% calcium diets, and nutrient efficiency for milk synthesis favored cows fed fine-grind 1.15% calcium. Fecal pH was higher during wk 4 on treatment for cows fed high calcium diets; however, 8 wk were not different. Fecal starch and calcium and phosphorus in plasma were not different between treatments: however, heifers fed fine-grind 1.15% calcium showed a decrease of fecal starch with time.

Influence of calcium on glucose biosensor response and on hydrogen peroxide detection.

PubMed

Labat-Allietta, N; Thévenot, D R

1998-01-01

Of small species capable of reaching a platinum working electrode from biological samples, calcium cations have been found to inhibit significantly glucose biosensor responses. The sensitivities to glucose of sensors immersed in carbonate buffer saline solutions decreased when 0.5 mM calcium chloride was added. The degree of inhibition was proportional to the glucose response in the absence of calcium (0-17% of the normalized current). Likewise, sensor sensitivities to hydrogen peroxide decreased, in the 5-90% range, in the presence of 0.5 mM calcium. Bare Pt-lr wires show a reversible inhibition of hydrogen peroxide sensitivity. This reversible inhibition is directly related to the decrease of hydrogen peroxide oxidation rate at the platinum anode: this has been evidenced, using rotating disk electrodes, by plotting Koutecky-Levich plots. Such inhibition has been found both for free and chelated calcium cations at levels below 1 mM. Several hypotheses for possible reactions between platinum, hydrogen peroxide and calcium are discussed.

Therapeutic effects of calcium dobesilate on diabetic nephropathy mediated through reduction of expression of PAI-1

PubMed Central

ZHANG, XIAOQIAN

2013-01-01

The aim of this study was to investigate whether calcium dobesilate (calcium dihydroxy-2,5-benzenesulfonate) may be used to treat diabetic nephropathy. A total of 121 patients with type 2 diabetic nephropathy received calcium dobesilate (500 mg, 3 times a day) for 3 months. The levels of glycated hemoglobin, fasting serum C peptide, triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, alanine aminotransferase, γ-glutamyl transferase, urea nitrogen, creatinine, hematocrit, plasma viscosity, whole blood reduced viscosity, high, medium and low shear rate whole blood viscosity, fibrinogen, plasminogen activator inhibitor-1 (PAI-1) and endothelin were determined. The urinary albumin excretion rate (UAER) was also determined once a month during the study. The UAER and medium and low shear rate whole blood viscosity were significantly lower in the treated patients. The rate of microalbuminuria normalization was 90%. During the treatment, the UAERs decreased. The results revealed that calcium dobesilate has therapeutic effects on type 2 diabetes patients with microalbuminuria. In addition, the benefit was positively correlated with the calcium dobesilate treatment time. The therapeutic effect may be due to decreases in the levels of PAI-1. PMID:23251286

Involvement of TRPV2 and SOCE in calcium influx disorder in DMD primary human myotubes with a specific contribution of α1-syntrophin and PLC/PKC in SOCE regulation.

PubMed

Harisseh, Rania; Chatelier, Aurélien; Magaud, Christophe; Déliot, Nadine; Constantin, Bruno

2013-05-01

Calcium homeostasis is critical for several vital functions in excitable and nonexcitable cells and has been shown to be impaired in many pathologies including Duchenne muscular dystrophy (DMD). Various studies using murine models showed the implication of calcium entry in the dystrophic phenotype. However, alteration of store-operated calcium entry (SOCE) and transient receptor potential vanilloid 2 (TRPV2)-dependant cation entry has not been investigated yet in human skeletal muscle cells. We pharmacologically characterized basal and store-operated cation entries in primary cultures of myotubes prepared from muscle of normal and DMD patients and found, for the first time, an increased SOCE in DMD myotubes. Moreover, this increase cannot be explained by an over expression of the well-known SOCE actors: TRPC1/4, Orai1, and stromal interaction molecule 1 (STIM1) mRNA and proteins. Thus we investigated the modes of regulation of this cation entry. We firstly demonstrated the important role of the scaffolding protein α1-syntrophin, which regulates SOCE in primary human myotubes through its PDZ domain. We also studied the implication of phospholipase C (PLC) and protein kinase C (PKC) in SOCE and showed that their inhibition restores normal levels of SOCE in DMD human myotubes. In addition, the involvement of TRPV2 in calcium deregulation in DMD human myotubes was explored. We showed an abnormal elevation of TRPV2-dependant cation entry in dystrophic primary human myotubes compared with normal ones. These findings show that calcium homeostasis mishandling in DMD myotubes depends on SOCE under the influence of Ca(2+)/PLC/PKC pathway and α1-syntrophin regulation as well as on TRPV2-dependant cation influx.

Aging-associated changes in L-type calcium channels in the left atria of dogs.

PubMed

Gan, Tian-Yi; Qiao, Weiwei; Xu, Guo-Jun; Zhou, Xian-Hui; Tang, Bao-Peng; Song, Jian-Guo; Li, Yao-Dong; Zhang, Jian; Li, Fa-Peng; Mao, Ting; Jiang, Tao

2013-10-01

Action potential (AP) contours vary considerably between the fibers of normal adult and aged left atria. The underlying ionic and molecular mechanisms that mediate these differences remain unknown. The aim of the present study was to investigate whether the L-type calcium current (I Ca.L ) and the L-type Ca 2+ channel of the left atria may be altered with age to contribute to atrial fibrillation (AF). Two groups of mongrel dogs (normal adults, 2-2.5 years old and older dogs, >8 years old) were used in this study. The inducibility of AF was quantitated using the cumulative window of vulnerability (WOV). A whole-cell patch-clamp was used to record APs and I Ca.L in left atrial (LA) cells obtained from the two groups of dogs. Protein and mRNA expression levels of the a1C (Cav1.2) subunit of the L-type calcium channel were assessed using western blotting and quantitative PCR (qPCR), respectively. Although the resting potential, AP amplitude and did not differ with age, the plateau potential was more negative and the APD 90 was longer in the aged cells compared with that in normal adult cells. Aged LA cells exhibited lower peak I Ca.L current densities than normal adult LA cells (P<0.05). In addition, the Cav1.2 mRNA and protein expression levels in LA cells were decreased in the aged group compared with those in the normal adult group. The lower AP plateau potential and the decreased I Ca.L of LA cells in aged dogs may contribute to the slow and discontinuous conduction of the left atria. Furthermore, the reduction of the expression levels of Cav1.2 with age may be the molecular mechanism that mediates the decline in I Ca.L with increasing age.

Proton pump inhibitor use for 12 months is not associated with changes in serum magnesium levels: a prospective open label comparative study.

PubMed

Bahtiri, Elton; Islami, Hilmi; Hoxha, Rexhep; Gashi, Afrim; Thaçi, Kujtim; Karakulak, Çağla; Thaçi, Shpetim; Qorraj Bytyqi, Hasime

2017-03-01

Proton pump inhibitors (PPIs) are a widely used class of drugs because of a generally acceptable safety profile. Among recently raised safety issues of the long-term use of PPIs is the increased risk of developing hypomagnesemia. As there have been very few prospective studies measuring serum magnesium levels before and after PPI therapy, we aimed to prospectively assess the potential association between PPI therapy for 12 months and the risk of hypomagnesemia as well as the incidence of new-onset hypomagnesemia during the study. In addition, the association of PPI therapy with the risk of hypocalcemia was assessed. The study included 250 patients with normal serum magnesium and total calcium levels, who underwent a long-term PPI treatment. Serum magnesium, total calcium, and parathormone (PTH) levels were measured at baseline and after 12 months. Of the 250 study participants, 209 completed 12 months of treatment and were included in the statistical analysis. The Wilcoxon signed rank test showed no statistically significant differences in serum magnesium levels between measurements at two different time points. However, there were statistically significant differences in serum total calcium and PTH levels in PPI users. Stable serum magnesium levels were demonstrated after 12 months and no association between PPI use and risk of hypomagnesemia was shown in the general population. Significant reductions of serum total calcium levels were demonstrated among PPI users; nevertheless, further research is required before recommending any serum calcium and PTH level monitoring in patients initiated on long-term PPI therapy.

Use of two calcium concentrations in hemodialysis--report of a 20-year clinical experience.

PubMed

Seyffart, G; Schulz, T; Stiller, S

2009-03-01

Over the past almost 50 years several calcium concentrations in the dialysate (CaD) have been used to balance calcium in hemodialysis (HD) patients but a consensus as to which is most appropriate has not been established. Moreover, since the late 1980s, further confusion has been caused following the use of calcium salts as intestinal phosphate binders. This paper reports results of 387 chronic HD patients with respect to secondary hyperparathyroidism (sHPT) and renal osteodystrophy (ROD) of a single center over 20 years. The most important therapeutic measures applied were use of only 2 CaD, 1.5 and 1.75 mmol/l, with very few exceptions, administration of either calcium-containing or calcium-magnesium-containing and/or calcium-free phosphate binders, no dietary restrictions and continuous compensation of uremic acidosis via dialysate and oral supplements of bicarbonate. Using one of the two CaD and selective administration of different phosphate binders for fine adjustment of serum calcium through this combination, we were able to maintain in the long term almost physiological conditions. With exception of the phosphate metabolism, most physiological functions with regard to sHPT and ROD returned close to normal. As a result, the incidence of hypercalcemia, hypocalcemia, extraosseous, extravascular calcification, bone pain and spontaneous bone fractures was extremely low. We conclude that the clinical advantages of the therapeutic measures, above all precise balance of calcium homeostasis, in our investigation were demonstrated by high survival rates (92% after the first year on HD, 82% after 2, and 55% after 5 years), low incidence of cardiovascular fatalities (about 25%), and very low incidence of sHPT (mostly normal parathyroid hormone levels, 1 parathyrdoidectomy within 20 years).

The salutary effect of dietary calcium on bone mass in a rat model of simulated weightlessness

NASA Technical Reports Server (NTRS)

Bikle, D. D.; Globus, R.; Halloran, B. P.; Morey-Holton, E.

1985-01-01

Whether supplementation of dietary calcium reduces the differences in bone mass of unweighed limbs and normally weighted limbs, and whether parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (1,25(OH)2D) respond differently to dietary calcium in unweighted animals in comparison with pair-fed controls was studied. The hind limbs of rats were unweighted by a tail suspension method and diets containing 0.1% to 2.4% calcium. After 2 weeks serum calcium, phosphorus, PTH and 1,25(OH)2D intestinal calcium transport were determined and bone mass, ash weight, and calcium in the tibia, L-1 vertebra, and humerus were measured. No significant differences in body weights were observed among the various groups. Suspended rats maintained constant levels of serum calcium and phosphate over the wide range of dietary calcium. Serum PTH and 1,25(OH)2D and intestinal calcium transport fell as dietary calcium was increased. Bone calcium in the tibia and vertebra from suspended rats remained less than that from pair-fed control. It is suggested that although no striking difference between suspended and control animals was observed in response to dieteary calcium, increasing dietary calcium may reduce the negative impact of unloading on the calcium content of the unweighted bones. The salutary effect of high dietary calcium appears to be due to inhibition of bone resorption rather than to stimulation of bone formation.

Assessment of bone turnover markers and bone mineral density in normal short boys.

PubMed

Gayretli Aydin, Zeynep Gökçe; Bideci, Aysun; Emeksiz, Hamdi C; Çelik, Nurullah; Döğer, Esra; Bukan, Neslihan; Yildiz, Ummügülsüm; Camurdan, Orhun M; Cinaz, Peyami

2015-11-01

To investigate whether there is a change in bone turnover-related biochemical markers and bone mineral density of children with constitutional delay of growth and puberty (CDGP) in the prepubertal period. We measured serum calcium, phosphorus, alkaline phosphatase, parathormone, 25-OH vitamin D, osteocalcin, osteoprotogerin and urinary deoxypyridinoline levels (D-pyd), and bone mineral density (BMD) in 31 prepubertal boys with CDGP. These children were compared with 22 prepubertal boys with familial short stature (FSS) and 27 normal prepubertal boys. Urinary D-pyd was significantly high in CDGP group as compared to control group (p=0.010). Volumetric BMD did not significantly differ between CDGP, FSS, and control groups (p=0.450). Volumetric BMD and urinary D-pyd levels of FSS and control groups were similar. Mean or median levels of calcium, phosphorus, alkaline phosphatase, parathormone, and osteoprotegerin did not significantly differ between CDGP, FSS, and control groups. Our data suggest that prepubertal boys with CDPG have normal bone turnover. However, their significantly higher urinary D-pyd levels relative to those of FSS and control groups might be an indicator of later development of osteoporosis. Therefore, long-term follow-up studies monitoring bone mineral status of prepubertal boys with CDPG from prepuberty to adulthood are needed to better understand bone metabolism of these patients.

Intake of dehydrated nopal (Opuntia ficus indica) improves bone mineral density and calciuria in adult Mexican women.

PubMed

Aguilera-Barreiro, María de Los Angeles; Rivera-Márquez, José Alberto; Trujillo-Arriaga, Héctor Miguel; Tamayo Y Orozco, Juan Alfredo; Barreira-Mercado, Eduardo; Rodríguez-García, Mario E

2013-01-01

The intake of dehydrated nopal (DN) at a high stage of maturity along with high calcium content could improve bone mineral density (BMD) and calciuria and thus prevent osteoporosis. To evaluate the effect of calcium intake from a vegetable source (DN) on BMD and calciuria covering a 2-year period in menopausal and non-menopausal women with low bone mass (LBM). The study was quasi-experimental, blinded, and randomized, and included 131 Mexican women aged 35-55. Urinary calcium/creatinine index (CCI) was determined; BMD was analyzed on lumbar spine and total hip regions. Four groups were studied: Control group (CG), women with normocalciuria and a minimum dose of DN; experimental group 1 (EG1), women with hypercalciuria and a minimum dose of DN; experimental group 2 (EG2), women with hypercalciuria, and a maximum dose of DN; and normal group (NG) for reference in BMD. After the first semester of treatment, calciuria levels in women from both experimental groups returned to normal, remaining constant for the rest of the treatment. The percentage difference in BMD increased in the total hip region in the CG (pre 4.5% and post 2.1%) and EG2 (pre 1.8% and post 2.5%) groups significantly in comparison to NG and EG1, which exhibited a significant decrease in their BMD. BMD increased only for the lumbar region in the EG2 group (premenopausal). The use of a vegetable calcium source such as nopal improves BMD in women with LBM in the total hip and lumbar spine regions principally in the premenopausal women, maintaining constant and normal calciuria levels.

Intake of dehydrated nopal (Opuntia ficus indica) improves bone mineral density and calciuria in adult Mexican women

PubMed Central

Aguilera-Barreiro, María de los Angeles; Rivera-Márquez, José Alberto; Trujillo-Arriaga, Héctor Miguel; Tamayo y Orozco, Juan Alfredo; Barreira-Mercado, Eduardo; Rodríguez-García, Mario E

2013-01-01

Background The intake of dehydrated nopal (DN) at a high stage of maturity along with high calcium content could improve bone mineral density (BMD) and calciuria and thus prevent osteoporosis. Objective To evaluate the effect of calcium intake from a vegetable source (DN) on BMD and calciuria covering a 2-year period in menopausal and non-menopausal women with low bone mass (LBM). Methods The study was quasi-experimental, blinded, and randomized, and included 131 Mexican women aged 35–55. Urinary calcium/creatinine index (CCI) was determined; BMD was analyzed on lumbar spine and total hip regions. Four groups were studied: Control group (CG), women with normocalciuria and a minimum dose of DN; experimental group 1 (EG1), women with hypercalciuria and a minimum dose of DN; experimental group 2 (EG2), women with hypercalciuria, and a maximum dose of DN; and normal group (NG) for reference in BMD. Results After the first semester of treatment, calciuria levels in women from both experimental groups returned to normal, remaining constant for the rest of the treatment. The percentage difference in BMD increased in the total hip region in the CG (pre 4.5% and post 2.1%) and EG2 (pre 1.8% and post 2.5%) groups significantly in comparison to NG and EG1, which exhibited a significant decrease in their BMD. BMD increased only for the lumbar region in the EG2 group (premenopausal). Conclusion The use of a vegetable calcium source such as nopal improves BMD in women with LBM in the total hip and lumbar spine regions principally in the premenopausal women, maintaining constant and normal calciuria levels. PMID:23704856

Binding and release of brain calcium by low-level electromagnetic fields: A review

NASA Astrophysics Data System (ADS)

Adey, W. R.; Bawin, S. M.

Evidence has accumulated that sensitivity of brain tissue to specific weak oscillating electromagnetic fields occurs in the absence of significant tissue heating (less than 0.1°C). This review focuses on the ‘windowed’ character of sensitivities of calcium binding and electrical activity in brain tissue to low-frequency modulation and intensity characteristics of impressed RF fields. ELF fields decrease calcium efflux from isolated chick and cat cerebral tissue by about 15% only in narrow amplitude and frequency ‘windows,’ between 6 and 20 Hz and between 10 and 100 V/m (approximate tissue gradient, 10-7 V/cm). VHF (147 MHz) and UHF (450 MHz) fields increase calcium efflux from isolated chick brain by about 15% when amplitude modulated between 6 and 20 Hz, but only for incident fields in the vicinity of 1.0 mW/cm2. We have now shown that this increased efflux in response to 16-Hz amplitude-modulated 450-MHz, 0.75-mW/cm2 field exposure is insensitive to variations in calcium concentration from 0 to 4.16 mM in the testing solution but is enhanced by addition of hydrogen ions (0.108 mM 0.1 N HCl) and inhibited in the absence of normal bicarbonate ion levels (2.4 mM). In the presence of lanthanum ions (2.0 mM), which block transmembrane movement of calcium, exposure to these EM fields decreases the 45Ca2 + efflux. Low-frequency gradients may be transduced in a specific class of extracellular binding sites, normally occupied by calcium ions and susceptible to competitive hydrogen ion binding. Transductive coupling may involve coherent charge states between anionic sites on membrane surface glycoproteins, with longrange cooperative interactions triggered by weak extracellular electric fields. Proton ‘tunneling’ may occur at boundaries between coherent and noncoherent charge zones.

[Results of a dynamic study on the status of health and nutrition of a Siberian vegan settlement].

PubMed

Medkova, I L; Mosiakina, L I; Biriukova, L S

2001-01-01

In 1996 for the first time a study of state of health, living conditions and nutrition status of 84 persons from the Siberian settlement of the rigorous vegetarians--vegans and 26 aboriginal inhabitants who feed on a traditional mixed diet was carried out. The clinical and laboratory investigations are kept. The positive influencing vegan ration on a serum lipids, body weight, state of cardiovascular system was showed. The contents of vitamin B12 and serum iron in vegans was in normal physiological range. The level of blood calcium was reduced in comparison with control. Increased contents of copper and zinc in blood was marked both in vegans and in control group. The repeated examination of 77 vegans of the same settlement in 1999 has revealed positive alterations in serum lipids: augmentation of cholesterol of high density lipoproteins on the average on 54.3%, that result in a reliable decrease of atherogenicity coefficient. The decrease to normal amounts of blood copper and zinc, and also increase of blood calcium on the average on 16% was marked. However level of calcium remained below than physiological values.

Calcification and photosynthesis of the coral acropora cervicornis under calcium limited conditions

NASA Technical Reports Server (NTRS)

Rathfon, Megan; Brewer, Debbie

1997-01-01

Differing hypothesis about the function of calcification are based on an interesting dilemma. Is the purpose of calcification mainly a structural and protective one or does calcification serve other functions? Does photosynthesis increase carbonate ion activity and cause calcification or does calcification increase CO2 levels and stimulate photsynthesis? It is proposed that calcification in corals is not dependent upon photosynthesis but upon calcium levels in the water. Under normal ocean conditions, corals convert a certain percentage of energy to photosynthesis and respiration and another percentage to calcification. As corals become nutrient stressed, particularly calcium limited, the ratio of photosynthesis to calcification shifts towards calcification in order to generate protons. The protons generated during calcification may stimulate photosynthesis and aid in the uptake of nutrients and biocarbonates. The results of the calcification experiment show a trend towards increased calcification and decreased photosynthesis when the coral Acropora cervicornis is calcium limited, but the data are inconclusive and further research is needed.

Symptomatic Hypercalcemia in a Patient with B-cell Chronic Lymphocytic Leukemia - A Case Report and Review of the Literature.

PubMed

Koutroumpakis, Efstratios; Lobe, Montgomery; McCarthy, Lezah; Mehdi, Syed

Hypercalcemia due to malignancy is well described in the literature and a common paraneoplastic finding in certain solid tumors. Hematologic malignancies, however, are less frequently associated with hypercalcemia with the exception of myelomas and T-cell lymphomas. This case report describes a patient with B-cell chronic lymphocytic leukemia (B-CLL) who developed symptomatic hypercalcemia. None of the pathogenetic mechanisms of malignancy-associated hypercalcemia already described in the literature could explain the pathogenesis of hypercalcemia in our patient. Calcium levels were normalized after initial treatment and remained within normal limits following treatment of the underlying B-CLL. The follow-up period was 26 months. The normalization of calcium levels was closely associated with the drop in the absolute lymphocyte count. Symptomatic hypercalcemia in B-CLL is exceedingly rare and only documented a few times in the literature. Hypercalcemia, in the present case, was not caused by any of the mechanisms already described in the literature and responded well to treatment of the underlying B-CLL. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

[Diet, nutrition and bone health].

PubMed

Miggiano, G A D; Gagliardi, L

2005-01-01

Nutrition is an important "modifiable" factor in the development and maintenance of bone mass and in the prevention of osteoporosis. The improvement of calcium intake in prepuberal age translates to gain in bone mass and, with genetic factor, to achievement of Peak Bone Mass (PBM), the higher level of bone mass reached at the completion of physiological growth. Individuals with higher PBM achieved in early adulthood will be at lower risk for developing osteoporosis later in life. Achieved the PBM, it is important maintain the bone mass gained and reduce the loss. This is possible adopting a correct behaviour eating associated to regular physical activity and correct life style. The diet is nutritionally balanced with caloric intake adequate to requirement of individual. This is moderate in protein (1 g/kg/die), normal in fat and the carbohydrates provide 55-60% of the caloric intake. A moderate intake of proteins is associated with normal calcium metabolism and presumably does'nt alter bone turnover. An adequate intake of alkali-rich foods may help promote a favorable effect of dietary protein on the skeleton. Lactose intolerance may determinate calcium malabsorption or may decrease calcium intake by elimination of milk and dairy products. Omega3 fatty acids may "down-regulate" pro-inflammatory cytokines and protect against bone loss by decreasing osteoclast activation and bone reabsorption. The diet is characterized by food containing high amount of calcium, potassium, magnesium and low amount of sodium. If it is impossible to reach the requirement with only diet, it is need the supplement of calcium and vitamin D. Other vitamins (Vit. A, C, E, K) and mineral (phosphorus, fluoride, iron, zinc, copper and boron) are required for normal bone metabolism, thus it is need adequate intake of these dietary components. It is advisable reduce ethanol, caffeine, fibers, phytic and ossalic acid intake. The efficacy of phytoestrogens is actually under investigation. Some drugs may interfere with calcium and other nutrients and produce an unfavourable effect on bone health.

Renal control of calcium, phosphate, and magnesium homeostasis.

PubMed

Blaine, Judith; Chonchol, Michel; Levi, Moshe

2015-07-07

Calcium, phosphate, and magnesium are multivalent cations that are important for many biologic and cellular functions. The kidneys play a central role in the homeostasis of these ions. Gastrointestinal absorption is balanced by renal excretion. When body stores of these ions decline significantly, gastrointestinal absorption, bone resorption, and renal tubular reabsorption increase to normalize their levels. Renal regulation of these ions occurs through glomerular filtration and tubular reabsorption and/or secretion and is therefore an important determinant of plasma ion concentration. Under physiologic conditions, the whole body balance of calcium, phosphate, and magnesium is maintained by fine adjustments of urinary excretion to equal the net intake. This review discusses how calcium, phosphate, and magnesium are handled by the kidneys. Copyright © 2015 by the American Society of Nephrology.

Pharmacological and clinical properties of calcimimetics: calcium receptor activators that afford an innovative approach to controlling hyperparathyroidism.

PubMed

Nagano, Nobuo

2006-03-01

Circulating levels of calcium ion (Ca2+) are maintained within a narrow physiological range mainly by the action of parathyroid hormone (PTH) secreted from parathyroid gland (PTG) cells. PTG cells can sense small fluctuations in plasma Ca2+ levels by virtue of a cell surface Ca2+ receptor (CaR) that belongs to the superfamily of G protein-coupled receptors (GPCR). Compounds that activate the CaR and inhibit PTH secretion are termed 'calcimimetics' because they mimic or potentiate the effects of extracellular Ca2+ on PTG cell function. Preclinical studies with NPS R-568, a first generation calcimimetic compound that acts as a positive allosteric modulator of the CaR, have demonstrated that oral administration decreases serum levels of PTH and calcium, with a leftward shift in the set-point for calcium-regulated PTH secretion in normal rats. NPS R-568 also suppresses the elevation of serum PTH levels and PTG hyperplasia and can improve bone mineral density (BMD) and strength in rats with chronic renal insufficiency (CRI). Clinical trials with cinacalcet hydrochloride (cinacalcet), a compound with an improved metabolic profile, have shown that long-term treatment continues to suppress the elevation of serum levels of calcium and PTH in patients with primary hyperparathyroidism (1HPT). Furthermore, clinical trials in patients with uncontrolled secondary hyperparathyroidism (2HPT) have demonstrated that cinacalcet not only lowers serum PTH levels, but also the serum phosphorus and calcium x phosphorus product; these are a hallmark of an increased risk of cardiovascular disease and mortality in dialysis patients with end-stage renal disease. Indeed, cinacalcet has already been approved for marketing in several countries. Calcimimetic compounds like cinacalcet have great potential as an innovative medical approach to manage 1HPT and 2HPT.

Influence of parathyroid state on calcium uptake in bone

PubMed Central

LEMON, GERARD J.; BASSINGTHWAIGHTE, JAMES B.; KELLY, PATRICK J.

2010-01-01

The exchange of calcium and strontium ions in bone was studied in control dogs, dogs made hypocalcemic by parathyroidectomy, and dogs rendered hypercalcemic by injection of parathyroid hormone. After injections of tracer into the tibial nutrient artery, extraction of tracer during transcapillary passage was measured and expressed as a fraction of 1. Extraction over the first 3 min in normal dogs was 0.46 ± 0.09 (n = 6), in hypocalcemic dogs it was increased to 0.53 ± 0.07 (n = 6), and in hypercalcemic dogs it was decreased to 0.39 ± 0.07 (n = 5). Subsequent washout was less rapid than normal in hypoparathyroid dogs and more rapid than normal in hyperparathyroid dogs. We conclude from this that the immediate volume of distribution in bone (or the number of available binding sites) for strontium diminishes as the parathyroid hormone level increases. PMID:7065174

Management of nutritional rickets in Indian children: a randomized controlled trial.

PubMed

Aggarwal, Varun; Seth, Anju; Marwaha, Raman K; Sharma, Bhavna; Sonkar, Pitamber; Singh, Satveer; Aneja, Satinder

2013-04-01

Rickets is usually attributed to vitamin D deficiency. However, recent studies have implicated dietary calcium deficiency in its etiology. Information on relative efficacy of calcium, vitamin D or both together in healing of rickets is limited. To study effect of treatment with calcium, vitamin D or a combination of these two on healing of nutritional rickets in young children. Randomized controlled trial. Sixty-seven cases of nutritional rickets in the age group of 6 months to 5 years were randomly allocated to receive vitamin D (600 000 IU single intramuscular dose), calcium (75 mg/kg/day elemental calcium orally) or a combination of the above two for a period of 12 weeks. The demographic parameters, nutritional status, dietary calcium and phytate intake were assessed for all. Radiographs (wrist and knee) and biochemical parameters (serum calcium, inorganic phosphate, alkaline phosphatase, 25-hydroxycholecalciferol and parathyroid hormone) were evaluated at baseline, 6 and 12 weeks for evidence of healing. Mean dietary intake of calcium in all cases was low (204 ± 129 mg/day). Mean serum 25-hydroxycholecalciferol D level was 15.9 ± 12.4 ng/ml, and 82.1% of patients had serum vitamin D levels <20 ng/ml, indicative of vitamin D deficiency. After 6 and 12 weeks of treatment, radiological and biochemical evidence of healing rickets was observed in all treatment groups, albeit to a variable extent. The combined end point of normal serum alkaline phosphatase and complete radiological healing at 12 weeks was observed in 50% subjects on combination therapy as compared with 15.7% subjects on vitamin D alone and 11.7% on calcium alone. Children with rickets had a low serum vitamin D level and a low dietary calcium intake. The best therapeutic response was seen with a combination of vitamin D and calcium than either of them given alone. CTRI/2010/091/000448.

Defects in antioxidant defense and calcium transport in the epidermis of xeroderma pigmentosum patients.

PubMed

Schallreuter, K U; Pittelkow, M R; Wood, J M

1991-01-01

A comparative study of the antioxidant enzymes superoxide dismutase, catalase, glutathione reductase and thioredoxin reductase was undertaken in two families with xeroderma pigmentosum (XP) and in healthy controls of corresponding skin phototypes. Epidermal blister roofs obtained from the XP patients revealed significant decreases in catalase, thioredoxin reductase, and superoxide dismutase, but glutathione reductase was unaffected. In addition, keratinocytes established from XP patients contained a significantly higher than normal intracellular calcium concentration compared with control cells from a corresponding skin type. Keratinocytes established from an XP obligate heterozygote revealed intermediate levels of calcium between XP homozygotes and controls. Previously high intracellular calcium has been shown to compromise the redox status of keratinocytes by allosteric inhibition of the thioredoxin reductase/thioredoxin electron transfer system. In XP homozygous keratinocytes from sun-exposed epidermis, the intracellular concentration of reduced thioredoxin was decreased to 50% compared with these cells from unexposed skin. Taken together, the results from this study indicate that the epidermis in XP patients lacks effective defense against free radicals and peroxides. In addition to the well-established defect in the normal rates of unscheduled DNA repair, these findings provide an even better explanation for the multiple cutaneous neoplasms in these patients.

Diagram of Calcium Movement in the Human Body

NASA Technical Reports Server (NTRS)

2002-01-01

This diagram shows the normal pathways of calcium movement in the body and indicates changes (green arrows) seen during preliminary space flight experiments. Calcium plays a central role because 1) it gives strength and structure to bone and 2) all types of cells require it to function normally. To better understand how and why weightlessness induces bone loss, astronauts have participated in a study of calcium kinetics -- that is, the movement of calcium through the body, including absorption from food, and its role in the formation and breakdown of bone.

Handling of induced hypercalcaemia in hyperthyroidism

PubMed Central

Lim, P.; Jacob, E.; Khoo, O. T.

1969-01-01

The mean serum calcium of 13 hyperthyroid patients was found to be significantly higher than that of controls matched for sex and age, though none of the patients' values were outside the normal range. Nevertheless, these patients responded very promptly to hypercalcaemia (induced by an intravenous calcium load), and their serum calcium returned to normal much more rapidly compared with the matched controls. There was also increased retention of intravenous calcium load, possibly owing to increased calcitonin production. Calcium infusion may be useful in treating bone diseases in which increased bone resorption exceeds bone accretion. PMID:5354875

The Role of Nutrition in the Changes in Bone and Calcium Metabolism During Space Flight

NASA Technical Reports Server (NTRS)

Morey-Holton, Emily R.; Arnaud, Sara B.

1995-01-01

On Earth, the primary purpose of the skeleton is provide structural support for the body. In space, the support function of the skeleton is reduced since, without gravity, structures have only mass and no weight. The adaptation to space flight is manifested by shifts in mineral distribution, altered bone turnover, and regional mineral deficits in weight-bearing bones. The shifts in mineral distribution appear to be related to the cephalic fluid shift. The redistribution of mineral from one bone to another or to and from areas in the same bone in response to alterations in gravitational loads is more likely to affect skeletal function than quantitative whole body losses and gains. The changes in bone turnover appear dependent upon changes in body weight with weight loss tending to increase bone resorption as well as decrease bone formation. During bedrest, the bone response to unloading varies depending upon the routine activity level of the subjects with more active subjects showing a greater suppression of bone formation in the iliac crest with inactivity. Changes in body composition during space flight are predicted by bedrest studies on Earth which show loss of lean body mass and increase tn body fat in adult males after one month. In ambulatory studies on Earth, exercising adult males of the same age, height, g weight, body mass index, and shoe size show significantly higher whole body mineral and lean body mass. than non-exercising subjects. Nutritional preference appears to change with activity level. Diet histories in exercisers and nonexercisers who maintain identical body weights show no differences in nutrients except for slightly higher carbohydrate intake in the exercisers. The absence of differences in dietary calcium in men with higher total body calcium is noteworthy. In this situation, the increased bone mineral content was facilitated by the calcium endocrine system. This regulatory system can be by-passed by raising dietary calcium. Increased calcium intake can increase the calcium content in normally loaded bone. However, bone with a higher calcium content still decreases proportionally to normal bone during unloading. Nutritional requirements in space should be reevaluated with respect to these adaptive changes to loading and physical activity.

Prolonged Hypocalcemic Effect by Pulmonary Delivery of Calcitonin Loaded Poly(Methyl Vinyl Ether Maleic Acid) Bioadhesive Nanoparticles

PubMed Central

Varshosaz, J.; Minaiyan, M.; Forghanian, M.

2014-01-01

The purpose of the present study was to design a pulmonary controlled release system of salmon calcitonin (sCT). Therefore, poly(methyl vinyl ether maleic acid) [P(MVEMA)] nanoparticles were prepared by ionic cross-linking method using Fe2+ and Zn2+ ions. Physicochemical properties of nanoparticles were studied in vitro. The stability of sCT in the optimized nanoparticles was studied by electrophoretic gel method. Plasma calcium levels until 48 h were determined in rats as pulmonary-free sCT solution or nanoparticles (25 μg·kg−1), iv solution of sCT (5 μg·kg−1), and pulmonary blank nanoparticles. The drug remained stable during fabrication and tests on nanoparticles. The optimized nanoparticles showed proper physicochemical properties. Normalized reduction of plasma calcium levels was at least 2.76 times higher in pulmonary sCT nanoparticles compared to free solution. The duration of hypocalcemic effect of pulmonary sCT nanoparticles was 24 h, while it was just 1 h for the iv solution. There was not any significant difference between normalized blood calcium levels reduction in pulmonary drug solution and iv injection. Pharmacological activity of nanoparticles after pulmonary delivery was 65% of the iv route. Pulmonary delivery of P(MVEMA) nanoparticles of sCT enhanced and prolonged the hypocalcemic effect of the drug significantly. PMID:24701588

Thyroid C-Cell Biology and Oncogenic Transformation

PubMed Central

Cote, Gilbert J.; Grubbs, Elizabeth G.; Hofmann, Marie-Claude

2017-01-01

The thyroid parafollicular cell, or commonly named “C-cell,” functions in serum calcium homeostasis. Elevations in serum calcium trigger release of calcitonin from the C-cell, which in turn functions to inhibit absorption of calcium by the intestine, resorption of bone by the osteoclast, and reabsorption of calcium by renal tubular cells. Oncogenic transformation of the thyroid C-cell is thought to progress through a hyperplastic process prior to malignancy with increasing levels of serum calcitonin serving as a biomarker for tumor burden. The discovery that Multiple Endocrine Neoplasia, type 2 is caused by activating mutations of the RET gene serves to highlight the RET-RAS-MAPK signaling pathway in both initiation and progression of medullary thyroid carcinoma. Thyroid C-cells are known to express RET at high levels relative to most cell types, therefore aberrant activation of this receptor is targeted primarily to the C-cell, providing one possible cause of tissue-specific oncogenesis. The role of RET signaling in normal C-cell function is unknown though calcitonin gene transcription appears to be sensitive to RET activation. Beyond RET the modeling of oncogenesis in animals and screening of human tumors for candidate gene mutations has uncovered mutation of RAS family members and inactivation of Rb1 regulatory pathway as potential mediators of C-cell transformation. A growing understanding of how RET interacts with these pathways, both in normal C-cell function and during oncogenic transformation will help in the development of novel molecular targeted therapies. PMID:26494382

Refractory hypocalcemia precipitated by dual infection with typhoid fever and hepatitis A in a patient with congenital hypoparathyroidism.

PubMed

Karanth, Suman S; Bhat, Ram; Gupta, Anurag

2012-08-01

We present this rare occurrence of a 17 yr old boy, a known case of congenital hypoparathyroidism, who presented with fever and jaundice for 8 days and 2 episodes of generalised tonic-clonic seizures. Premorbidly patient was on regular oral calcium supplementations with normal serum calcium levels. Investigations revealed severe hypocalcaemia (3.2 mg/dL), low 25 hydroxyvitamin D levels and hypomagnesaemia. The marked elevation of serum bilirubin was accompanied by derangement of liver enzymes. Microbiological investigations were confirmatory for both hepatitis A and typhoid fever. In spite of the aggressive management with intravenous calcium gluconate infusion, refractory hypocalcaemia persisted with recovery only after gradual decline in the bilirubin levels. We inferred that the cholestatic process produced by both acute viral hepatitis A and typhoid fever precipitated this state of refractory hypocalcaemia in the previously well preserved patient. Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Lemon juice has protective activity in a rat urolithiasis model.

PubMed

Touhami, Mohammed; Laroubi, Amine; Elhabazi, Khadija; Loubna, Farouk; Zrara, Ibtissam; Eljahiri, Younes; Oussama, Abdelkhalek; Grases, Félix; Chait, Abderrahman

2007-10-05

The use of herbal medicines (medicinal plants or phytotherapy) has recently gained popularity in Europe and the United States. Nevertheless the exact mechanism of the preventive effects of these products is still far to be clearly established, being its knowledge necessary to successfully apply these therapies to avoid stone formation. The effect of oral lemon juice administration on calcium oxalate urolithiasis was studied in male Wistar rats. Rats were rendered nephrolithic by providing drinking water containing 0.75% ethylene glycol [v/v] (EG) and 2% ammonium chloride [w/v] (AC) for 10 days. In addition to EG/AC treatment, three groups of rats were also gavage-administered solutions containing 100%, 75% or 50% lemon juice [v/v] (6 microl solution/g body weight). Positive control rats were treated with EG/AC but not lemon juice. Negative control rats were provided with normal drinking water, and were administered normal water by gavage. Each group contained 6 rats. After 10 days, serum samples were collected for analysis, the left kidney was removed and assessed for calcium levels using flame spectroscopy, and the right kidney was sectioned for histopathological analysis using light microscopy. Analysis showed that the rats treated with EG/AC alone had higher amounts of calcium in the kidneys compared to negative control rats. This EG/AC-induced increase in kidney calcium levels was inhibited by the administration of lemon juice. Histology showed that rats treated with EG/AC alone had large deposits of calcium oxalate crystals in all parts of the kidney, and that such deposits were not present in rats also treated with either 100% or 75% lemon juice. These data suggest that lemon juice has a protective activity against urolithiasis.

Effect of zoledronic acid on serum calcium in Paget’s disease patients after educational strategies to improve calcium and vitamin D supplementation

PubMed Central

Bone, Henry G.; Su, Guoqin; Tan, Monique; Ozturk, Zafer E.; Aftring, Paul

2015-01-01

Objective: Bisphosphonates are the most effective therapeutic agents in patients with Paget’s disease of bone. As a result of their inhibition of osteoclastic activity, hypocalcemia of variable frequency and severity following intravenous bisphosphonate therapy has been reported. The present study assessed the effect of physician and patient education on adequate supplementation of calcium and vitamin D to reduce the potential risk of developing hypocalcemia following infusion of 5 mg zoledronic acid. Methods: This was an open-label, multicenter, controlled registry trial in which patients with Paget’s disease were treated with a single intravenous infusion of zoledronic acid. Physicians were provided with educational materials focusing on optimization of calcium and vitamin D supplementation following zoledronic infusion that they used to educate their patients. The primary safety variable was the percentage of patients with serum calcium level <2.07mmol/l 9–11 days after zoledronic acid infusion. Results: A total of 75 patients were evaluable in the post dose hypocalcemia safety analysis. Of these, only 1 patient had treatment-emergent hypocalcemia, with a serum calcium level of 1.92 mmol/l 4 days following therapy. Hypocalcemia-related symptoms were not reported in this patient and the serum calcium returned to normal range at 2.17 mmol/l within 1 week on oral calcium supplementation. Conclusions: These results suggest that, with optimization of calcium and vitamin D supplementation by physician and patient education, hypocalcemia is an infrequent occurrence following zoledronic acid infusion. PMID:26301065

INTRACELLULAR DISTRIBUTION OF CALCIUM IN DEVELOPING BREAST MUSCLE OF NORMAL AND DYSTROPHIC CHICKENS

PubMed Central

Cosmos, Ethel

1964-01-01

To follow the intracellular distribution of calcium in the breast muscles of developing chickens, Ca45 was injected into the albumen of predeveloped eggs. Since the embryos were grown in a radioactive medium, a complete exchange of the isotope for its non-radioactive counterpart in muscles was accomplished. Subcellular particulates of the muscle cells were separated by the method of differential centrifugation. Analysis of the separated fractions showed that in the muscles of the 13-day embryo, when the nuclear-myofibrillar ratio is high, 65 per cent of the muscle calcium is in the nuclei. With the increased synthesis of myofibrils, the nuclear-myofibrillar ratio decreases with a concomitant fall in radioactivity. Thus, calcium was not associated with the developing myofibrils. At the time of hatching, when myofibrils perform physiological work, the highest level of calcium is in the mitochondria. This suggests that the mitochondria play a key role in the physiological activities of calcium in the cell. The microsomal fraction reaches a maximal level of calcium when the adult composition of muscle is attained. Results of investigations on dystrophic muscles show changes in the calcium distribution of the fractions as early as the 3rd week of embryonic development, which are interpreted to indicate an alteration in the protein metabolism of the cell, or an early destruction of muscle tissue. Further, alterations in the calcium content of fractions which seem to regulate the movements of this ion in the cell are discussed. A new technique for homogenizing tissues from embryos of different ages is presented. PMID:14222812

Paclitaxel Induces Apoptosis in Breast Cancer Cells through Different Calcium—Regulating Mechanisms Depending on External Calcium Conditions

PubMed Central

Pan, Zhi; Avila, Andrew; Gollahon, Lauren

2014-01-01

Previously, we reported that endoplasmic reticulum calcium stores were a direct target for paclitaxel initiation of apoptosis. Furthermore, the actions of paclitaxel attenuated Bcl-2 resistance to apoptosis through endoplasmic reticulum-mediated calcium release. To better understand the calcium-regulated mechanisms of paclitaxel-induced apoptosis in breast cancer cells, we investigated the role of extracellular calcium, specifically; whether influx of extracellular calcium contributed to and/or was necessary for paclitaxel-induced apoptosis. Our results demonstrated that paclitaxel induced extracellular calcium influx. This mobilization of extracellular calcium contributed to subsequent cytosolic calcium elevation differently, depending on dosage. Under normal extracellular calcium conditions, high dose paclitaxel induced apoptosis-promoting calcium influx, which did not occur in calcium-free conditions. In the absence of extracellular calcium an “Enhanced Calcium Efflux” mechanism in which high dose paclitaxel stimulated calcium efflux immediately, leading to dramatic cytosolic calcium decrease, was observed. In the absence of extracellular calcium, high dose paclitaxel’s stimulatory effects on capacitative calcium entry and apoptosis could not be completely restored. Thus, normal extracellular calcium concentrations are critical for high dose paclitaxel-induced apoptosis. In contrast, low dose paclitaxel mirrored controls, indicating that it occurs independent of extracellular calcium. Thus, extracellular calcium conditions only affect efficacy of high dose paclitaxel-induced apoptosis. PMID:24549172

Endocrine effects of the tyrosine kinase inhibitor vandetanib in patients treated for thyroid cancer.

PubMed

Brassard, Maryse; Neraud, Barbara; Trabado, Séverine; Salenave, Sylvie; Brailly-Tabard, Sylvie; Borget, Isabelle; Baudin, Eric; Leboulleux, Sophie; Chanson, Philippe; Schlumberger, Martin; Young, Jacques

2011-09-01

The purpose of the study was to assess the endocrine effects of vandetanib, a multikinase inhibitor targeting RET, vascular endothelial growth factor receptor, and epidermal growth factor receptor, in 39 patients with progressive thyroid cancer included in two randomized placebo-controlled trials using vandetanib 300 mg/d. Endocrine samplings were performed at baseline and then every 6 months. We compared differences in endocrine parameters between baseline and on vandetanib therapy or placebo. During vandetanib treatment, several changes were observed. 1) Calcium (P = 0.0004) and vitamin D (P = 0.001) mean replacement doses were increased; calcium level remained unchanged, but serum 25(OH) vitamin D level decreased (P = 0.001); and serum PTH (P = 0.01) and 1,25(OH)(2) vitamin D (P = 0.01) levels increased, suggesting a decreased intestinal absorption of vitamin D or lack of sun exposure as a result of photosensitization. 2) l-T(4) doses were increased (P < 0.0001) to maintain serum TSH within the normal range. 3) In male patients, total testosterone (P = 0.048), bioavailable testosterone (P = 0.03), and SHBG (P = 0.02) levels increased. Serum inhibin B decreased (P = 0.02) and stimulated FSH increased (P = 0.006), suggesting a Sertoli cells insufficiency. 4) Cortisol level increased (P = 0.007) as well as ACTH level (P = 0.03) and cortisol-binding globulin (P = 0.02), but free urinary cortisol levels remained in the normal range. None of these changes were observed in patients randomized to the placebo arm. In patients with locally advanced or metastatic thyroid cancer, the tyrosine kinase inhibitor vandetanib has several endocrine effects. Thyroid hormone, calcium, and vitamin D analog requirements increased, but consequences of the biological alterations on phosphocalcic metabolism and gonadotrope and adrenal functions are unknown.

High bone turnover elevates the risk of denosumab-induced hypocalcemia in women with postmenopausal osteoporosis

PubMed Central

Ishikawa, Koji; Nagai, Takashi; Sakamoto, Keizo; Ohara, Kenji; Eguro, Takeshi; Ito, Hiroshi; Toyoshima, Yoichi; Kokaze, Akatsuki; Toyone, Tomoaki; Inagaki, Katsunori

2016-01-01

Hypocalcemia is the most common major adverse event in patients with osteoporosis receiving the bone resorption inhibitor denosumab; however, limited information is available regarding risk factors of hypocalcemia. Therefore, this study aimed to identify the risk factors of hypocalcemia induced by denosumab treatment for osteoporosis. We retrospectively reviewed the records of patients who had received initial denosumab supplemented with activated vitamin D for osteoporosis. Serum levels of the following bone turnover markers (BTMs) were measured at baseline: bone-specific alkaline phosphatase (BAP), total N-terminal propeptide of type 1 procollagen (P1NP), tartrate-resistant acid phosphatase 5b (TRACP-5b), and urinary cross-linked N-telopeptide of type 1 collagen (NTX). Of the 85 denosumab-treated patients with osteoporosis studied, 22 (25.9%) developed hypocalcemia. Baseline serum total P1NP, TRACP-5b, and urinary NTX were significantly higher in patients with hypocalcemia than in those with normocalcemia following denosumab administration (all P<0.01). Multivariate logistic regression analysis revealed that patients with total P1NP >76.5 μg/L, TRACP-5b >474 mU/dL, or urinary NTX >49.5 nmol bone collagen equivalent/mmol creatinine had a higher risk of hypocalcemia (P<0.01). Our study suggests that denosumab may have a greater impact on serum calcium levels in patients with postmenopausal osteoporosis with higher baseline bone turnover than in patients with postmenopausal osteoporosis with normal baseline bone turnover, because maintenance of normal serum calcium in this subgroup is more dependent on bone resorption. Close monitoring of serum calcium levels is strongly recommended for denosumab-treated patients with high bone turnover, despite supplementation with activated vitamin D and oral calcium. PMID:27980413

Towards bio monitoring of toxic (lead) and essential elements in whole blood from 1- to 72-month old children: a cross-sectional study.

PubMed

Kang-Sheng, Liu; Xiao-Dong, Mao; Juan, Shi; Chun-Fan, Dai; Pingqing, Gu

2015-06-01

Minerals such as zinc, copper, selenium, calcium, and magnesium are essential for normal human development and functioning of the body. They have been found to play important roles in immuno-physiologic functions. The study is to evaluate the distribution and correlation of nonessential (lead) and essential elements in whole blood from 1- to 72-month old children. The cross-sectional study was performed in 1551 children. Six element concentrations, including copper (Cu), zinc (Zn), calcium (Ca), magnesium (Mg), iron (Fe) and lead (Pb) in the blood were determined by atomic absorption spectrometry. Distributions and correlations of trace elements in different age groups were analyzed and compared. A Pearson correlation controlled for age and gender was used to assess the relationship of non essential (lead) and essential elements. Levels of copper and magnesium were 18.09 ± 4.42 µmol/L and 1.42 ± 0.12 mmol/L, respectively. 6.04% of all children showed copper levels below the normal threshold, the levels of Magnesium were stable in different age groups. Though the overall mean blood zinc and iron concentrations (61.19 ± 11.30 µmol/L and 8.24 ± 0.59 mmol/L, respectively) gradually increased with age and the overall deficiency levels (24.1% and 36.0%, respectively) decreased with age, zinc and iron deficiencies were still very stable. Controlling for gender and age, significant positive correlations were found when comparing copper to zinc, calcium, magnesium, and iron ((r = 0.333, 0.241, 0.417, 0.314 ,p < 0.01); zinc to magnesium and iron (r = 0.440, 0.497p < 0.01); and magnesium to Calcium and iron (r = 0.349, 0.645, p < 0.01). The overall mean blood lead levels (41.16 ± 16.10) were relatively unstable among different age groups. The prevalence of lead intoxication in all children was 1.3% .Calcium levels decreased gradually with age, with an overall concentration of 1.78 ± 0.13 mmol/L. Significant negative correlations were also noted between Pb and Zn, Fe (r = -0.179, -0.124.p < 0.01) .The importance of calcium deficiency and supplementation is well realized, but the severity of iron and zinc deficiency is not well recorded. The degree of lead intoxication in all the children studied was low; The established reference intervals for Cu, Zn, Ca and Mg provide an important guidance for the reasonable supplementation of essential elements during different age groups.

Cardiac basal metabolism: energetic cost of calcium withdrawal in the adult rat heart.

PubMed

Bonazzola, P; Takara, D

2010-07-01

Cardiac basal metabolism upon extracellular calcium removal and its relationship with intracellular sodium and calcium homeostasis was evaluated. A mechano-calorimetric technique was used that allowed the simultaneous and continuous measurement of both heat rate and resting pressure in arterially perfused quiescent adult rat hearts. Using pharmacological tools, the possible underlying mechanisms related to sodium and calcium movements were investigated. Resting heat rate (expressed in mW g(-1)(dry wt)) increased upon calcium withdrawal (+4.4 +/- 0.2). This response was: (1) unaffected by the presence of tetrodotoxin (+4.3 +/- 0.6), (2) fully blocked by both, the decrease in extracellular sodium concentration and the increase in extracellular magnesium concentration, (3) partially blocked by the presence of either nifedipine (+2.8 +/- 0.4), KB-R7943 (KBR; +2.5 +/- 0.2), clonazepam (CLO; +3.1 +/- 0.3) or EGTA (+1.9 +/- 0.3). The steady heat rate under Ca(2+)-free conditions was partially reduced by the addition of Ru360 (-1.1 +/- 0.2) but not CLO in the presence of EGTA, KBR or Ru360. Energy expenditure for resting state maintenance upon calcium withdrawal depends on the intracellular rise in both sodium and calcium. Our data are consistent with a mitochondrial Ca(2+) cycling, not detectable under normal calcium diastolic levels. The experimental condition here analysed, partially simulates findings reported under certain pathological situations including heart failure in which mildly increased levels of both diastolic sodium and calcium have also been found. Therefore, under such pathological conditions, hearts should distract chemical energy to fuel processes associated with sodium and calcium handling, making more expensive the maintenance of their functions.

Biotechnology

NASA Image and Video Library

2002-07-31

This diagram shows the normal pathways of calcium movement in the body and indicates changes (green arrows) seen during preliminary space flight experiments. Calcium plays a central role because 1) it gives strength and structure to bone and 2) all types of cells require it to function normally. To better understand how and why weightlessness induces bone loss, astronauts have participated in a study of calcium kinetics -- that is, the movement of calcium through the body, including absorption from food, and its role in the formation and breakdown of bone.

Effect of parathyroid hormone and uremic sera on the autoagglutination and sedimentation of human red blood cells.

PubMed

Earon, Y; Blum, M; Bogin, E

1983-12-30

Parathyroid hormone (PTH) caused a dramatic acceleration of erythrocyte sedimentation rate (ESR). This effect was calcium dependent and was partially reversed by verapamil. It was not mimicked by 5 mumol/l calcium ionophore A-23187. Following the removal of PTH from the cell suspension the ESR returned to normal. PTH also caused haemagglutination, the reaction was Ca2+ dependent, pH dependent and was partially reversed by verapamil. High levels of Ca2+ ionophore A-23187 mimicked this phenomenon. Magnesium ions even at concentrations of 5 mmol/l did not replace Ca2+, while Ca2+ at concentrations of 3 mmol/l and above caused haemagglutination. The glycolytic inhibitor NaF at levels of 1 mmol/l did not inhibit haemagglutination. The polyamines pertusin and spermidin, prostaglandins PGE2 and PGF, and the calcium hormone calcitonin, did not reproduce the PTH effect. Dialysate from serum of patients with chronic renal failure and hyperparathyroidism caused haemagglutination, while dialysate from patients with chronic renal failure following parathyroidectomy and normal individuals did not cause this phenomenon. It seems that abnormal erythrocyte behaviour seen in patients with chronic renal failure is caused by PTH which leads to modified Ca2+ metabolism in these cells.

Effects of calcium and vitamin D supplementation on crypt morphology in normal colon mucosa: A randomized clinical trial.

PubMed

Shen, Huafeng; Ahearn, Thomas U; Bostick, Roberd M

2015-03-01

Calcium and vitamin D modify the molecular phenotypic profiles of colon crypts in the normal colorectal mucosa of colorectal adenoma patients, but their effects on crypt morphology (length, perimeter, and area) are unknown. We analyzed data from a previously conducted pilot, randomized, double-blind, placebo-controlled 2 × 2 factorial chemoprevention clinical trial of supplemental calcium 2000 mg/d and vitamin D3 800 IU/d, alone and in combination, versus placebo over 6 mo. Colorectal crypt length, perimeter, and area in the normal-appearing rectal mucosa were quantified by image analysis. The mean crypt length increased by 1% (P=0.92) in the calcium group, and decreased by 2% (P=0.69) and 4% (P=0.40) in the vitamin D and calcium plus vitamin D groups, respectively, relative to the placebo group. The mean crypt perimeter decreased by 2% (P=0.70) and 4% (P=0.40) in the vitamin D and calcium plus vitamin D groups, respectively, relative to the placebo group, but did not change appreciably in the calcium group. The mean crypt area decreased by 2% (P=0.74), 5% (P=0.41) and 7% (P=0.30) in the calcium, vitamin D and calcium plus vitamin D groups, respectively, relative to the placebo group. Calcium and/or vitamin D3 supplementation do not appear to appreciably change crypt morphology in the normal colorectal mucosa of sporadic adenoma patients. These results, taken together with previous findings, support the use of molecular phenotypic over morphologic pre-neoplastic biomarkers of risk for colorectal neoplasms. © 2013 Wiley Periodicals, Inc.

Calcium leakage as a cause of the high resting tension in vascular smooth muscle from the spontaneously hypertensive rat.

PubMed

Noon, J P; Rice, P J; Baldessarini, R J

1978-03-01

Aortic strips from spontaneously hypertensive (SH) rats relax in calcium-free physiological medium and contract to approximately 60% of maximum when calcium is again restored to the medium. In vivid contrast, the resting tension of aortic strips from normal rats is unaffected by manipulation of the calcium concentration of the bathing medium. These findings, as well as the reduced sensitivity of aortic strips from SH rats to norepinephrine and the observation that aortic strips from SH rats relax at a faster rate in calcium-free medium in comparison with aortic strips from normal rats, are consistent with the hypothesis that vascular smooth muscle membranes from SH rats leak calcium at a rate that is only partially compensated by the calcium pump.

Brain aluminium accumulation and oxidative stress in the presence of calcium silicate dental cements.

PubMed

Demirkaya, K; Demirdöğen, B Can; Torun, Z Öncel; Erdem, O; Çırak, E; Tunca, Y M

2017-10-01

Mineral trioxide aggregate (MTA) is a calcium silicate dental cement used for various applications in dentistry. This study was undertaken to test whether the presence of three commercial brands of calcium silicate dental cements in the dental extraction socket of rats would affect the brain aluminium (Al) levels and oxidative stress parameters. Right upper incisor was extracted and polyethylene tubes filled with MTA Angelus, MTA Fillapex or Theracal LC, or left empty for the control group, were inserted into the extraction socket. Rats were killed 7, 30 or 60 days after operation. Brain tissues were obtained before killing. Al levels were measured by atomic absorption spectrometry. Thiobarbituric acid reactive substances (TBARS) levels, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were determined using spectrophotometry. A transient peak was observed in brain Al level of MTA Angelus group on day 7, while MTA Fillapex and Theracal LC groups reached highest brain Al level on day 60. Brain TBARS level, CAT, SOD and GPx activities transiently increased on day 7 and then returned to almost normal levels. This in vivo study for the first time indicated that initial washout may have occurred in MTA Angelus, while element leaching after the setting is complete may have taken place for MTA Fillapex and Theracal LC. Moreover, oxidative stress was induced and antioxidant enzymes were transiently upregulated. Further studies to search for oxidative neuronal damage should be done to completely understand the possible toxic effects of calcium silicate cements on the brain.

Sensitive methods for the titrimetric micro-determination of biological calcium and magnesium

PubMed Central

Beale, R. N.; Bostrom, J. O.

1963-01-01

New reagents containing high concentrations of urea are developed for micro-titration of calcium and magnesium, with ethylenediamine tetra-acetic acid (E.D.T.A.) as titrant and Corinth Ca (Plasmocorinth B) as indicator. Magnesium is determined as the difference between calcium plus magnesium and calcium. Quantitative aspects are studied, and accurate titration of untreated serum or urine is believed to be possible; precision is satisfactory. The methods are simple, robust, and suitable for routine use. Normal ranges are established for serum from blood donors of each sex. The mean serum calcium level for women is found to be lower than for men, while the mean magnesium contents are approximately the same. The latter appear to be somewhat lower than values found by flame emission spectrophotometry; in very good agreement with a mean value for plasma obtained by flame absorption spectrophotometry; and intermediate when compared with the values obtained by two other titrimetric procedures. PMID:13969919

The Efficacy of Calcium Hydroxide Powder mixed with 0.2% Chlorhexidine Digluconate or mixed with Normal Saline as Intracanal Medicament in the Treatment of Apical Periodontitis.

PubMed

Menakaya, Ifeoma N; Adegbulugbe, Ilemobade C; Oderinu, Olabisi H; Shaba, Olufemi P

2015-08-01

To compare the efficacy of calcium hydroxide powder mixed with 0.2% chlorhexidine digluconate or mixed with normal saline as intracanal medicament in the treatment of apical periodontitis. Subjects were 55 in number aged 17 to 60 years. Two-visit conventional root canal treatment was performed on 70 teeth. The teeth were divided by randomization (balloting) into two groups: control group and experimental group, each with 35 teeth treated with calcium hydroxide mixed with normal saline or with 0.2% chlorhexidine digluconate as intracanal medicament respectively. All treated teeth were evaluated clinically and radiographically for signs and symptom of periapical infection at specified periods postoperatively. Overall efficacy of medicament was rated based on quality guidelines for endodontic treatment by the European Society of Endodontology 2006. A postoperative favorable outcome of 97.1% in the control group and 94.3% in the experimental group was observed at 6-month review. This difference was not statistically significant (p > 0.05). The use of normal saline or 0.2% chlorhexidine digluconate to mix calcium hydroxide used as intracanal medicament during endodontic treatment resulted in high postoperative favorable outcomes. Efficacy of 0.2% chlorhexidine digluconate as a vehicle for mixing calcium hydroxide as an intracanal medicament in the treatment of apical periodontitis is comparable to the efficacy of calcium hydroxide mixed with normal saline.

Monitoring changes in the intracellular calcium concentration and synaptic efficacy in the mollusc Aplysia.

PubMed

Ludwar, Bjoern Ch; Evans, Colin G; Cropper, Elizabeth C

2012-07-15

It has been suggested that changes in intracellular calcium mediate the induction of a number of important forms of synaptic plasticity (e.g., homosynaptic facilitation). These hypotheses can be tested by simultaneously monitoring changes in intracellular calcium and alterations in synaptic efficacy. We demonstrate how this can be accomplished by combining calcium imaging with intracellular recording techniques. Our experiments are conducted in a buccal ganglion of the mollusc Aplysia californica. This preparation has a number of experimentally advantageous features: Ganglia can be easily removed from Aplysia and experiments use adult neurons that make normal synaptic connections and have a normal ion channel distribution. Due to the low metabolic rate of the animal and the relatively low temperatures (14-16 °C) that are natural for Aplysia, preparations are stable for long periods of time. To detect changes in intracellular free calcium we will use the cell impermeant version of Calcium Orange which is easily 'loaded' into a neuron via iontophoresis. When this long wavelength fluorescent dye binds to calcium, fluorescence intensity increases. Calcium Orange has fast kinetic properties and, unlike ratiometric dyes (e.g., Fura 2), requires no filter wheel for imaging. It is fairly photo stable and less phototoxic than other dyes (e.g., fluo-3). Like all non-ratiometric dyes, Calcium Orange indicates relative changes in calcium concentration. But, because it is not possible to account for changes in dye concentration due to loading and diffusion, it can not be calibrated to provide absolute calcium concentrations. An upright, fixed stage, compound microscope was used to image neurons with a CCD camera capable of recording around 30 frames per second. In Aplysia this temporal resolution is more than adequate to detect even a single spike induced alteration in the intracellular calcium concentration. Sharp electrodes are simultaneously used to induce and record synaptic transmission in identified pre- and postsynaptic neurons. At the conclusion of each trial, a custom script combines electrophysiology and imaging data. To ensure proper synchronization we use a light pulse from a LED mounted in the camera port of the microscope. Manipulation of presynaptic calcium levels (e.g. via intracellular EGTA injection) allows us to test specific hypotheses, concerning the role of intracellular calcium in mediating various forms of plasticity.

Hypercalcaemia and hypocalcaemia: finding the balance.

PubMed

Body, Jean-Jacques; Niepel, Daniela; Tonini, Giuseppe

2017-05-01

The balance between bone formation and resorption may be disrupted in patients with cancer, leading either to increased bone resorption, calcium release, and possibly hypercalcaemia, or to increased bone formation, sequestration of calcium, and possibly hypocalcaemia. In adults, hypercalcaemia of malignancy is most common in patients with tumours that produce factors that induce osteoclast activation and enhance bone resorption. Impaired renal function and increased renal tubular calcium resorption may further affect calcium levels. Inhibitors of bone resorption, first the bisphosphonates and, later, denosumab, have been shown to be effective in hypercalcaemia treatment. Bisphosphonates (which are administered intravenously) are approved for hypercalcaemia of malignancy and are the current mainstay of treatment, whereas denosumab (which is administered subcutaneously) may offer an option for patients who do not respond to bisphosphonates or suffer from renal insufficiency. TREATMENT AND PREVENTION: Hypocalcaemia is most common in patients with prostate cancer and osteoblastic bone metastases, but can occur in patients with a variety of tumour types who are receiving inhibitors of bone resorption. While patients often respond to calcium and vitamin D supplementation, prevention should be the aim; at-risk patients should be identified before starting treatment with inhibitors of bone resorption, be closely monitored during at least the first few months of treatment, and receive concomitant calcium and vitamin D supplementation unless hypercalcaemia is present. Both hypercalcaemia and hypocalcaemia can be serious if left untreated. It is therefore important that patients with cancer are closely monitored and receive adequate prevention and treatment measures to maintain normal blood calcium levels.

Responses to the lowering of magnesium and calcium concentrations in the cerebrospinal fluid of unanesthetized sheep.

PubMed

Allsop, T F; Pauli, J V

1975-12-01

A technique for ventriculolumbar perfusion of the cerebrospinal fluid space has been used to study the neuromuscular effects of low concentrations of magnesium and calcium in the cerebrospinal fluid of conscious sheep. Perfusion with synthetic cerebrospinal fluid solutions containing less than 0-6 mg magnesium/100 ml produced episodes of tetany which were abolished by perfusion with a solution of normal magnesium concentration. This suggests that the low cerebrospinal fluid magnesium concentrations reported in cases of hypomagneseamic tetany may result in changes within the central nervous system that could produce the nervous signs. Perfusates with a calcium concentration below 2-0 mg/100 ml caused hyperpnoea and continuous muscle tremors. Magnesium (0-6 mg/100 ml) and calcium (2-0 mg/100 ml) perfused simultaneously acted synergistically to produce signs characteristic of low levels of each of the ions.

Calcium-Induced Calcium Release during Action Potential Firing in Developing Inner Hair Cells

PubMed Central

Iosub, Radu; Avitabile, Daniele; Grant, Lisa; Tsaneva-Atanasova, Krasimira; Kennedy, Helen J.

2015-01-01

In the mature auditory system, inner hair cells (IHCs) convert sound-induced vibrations into electrical signals that are relayed to the central nervous system via auditory afferents. Before the cochlea can respond to normal sound levels, developing IHCs fire calcium-based action potentials that disappear close to the onset of hearing. Action potential firing triggers transmitter release from the immature IHC that in turn generates experience-independent firing in auditory neurons. These early signaling events are thought to be essential for the organization and development of the auditory system and hair cells. A critical component of the action potential is the rise in intracellular calcium that activates both small conductance potassium channels essential during membrane repolarization, and triggers transmitter release from the cell. Whether this calcium signal is generated by calcium influx or requires calcium-induced calcium release (CICR) is not yet known. IHCs can generate CICR, but to date its physiological role has remained unclear. Here, we used high and low concentrations of ryanodine to block or enhance CICR to determine whether calcium release from intracellular stores affected action potential waveform, interspike interval, or changes in membrane capacitance during development of mouse IHCs. Blocking CICR resulted in mixed action potential waveforms with both brief and prolonged oscillations in membrane potential and intracellular calcium. This mixed behavior is captured well by our mathematical model of IHC electrical activity. We perform two-parameter bifurcation analysis of the model that predicts the dependence of IHCs firing patterns on the level of activation of two parameters, the SK2 channels activation and CICR rate. Our data show that CICR forms an important component of the calcium signal that shapes action potentials and regulates firing patterns, but is not involved directly in triggering exocytosis. These data provide important insights into the calcium signaling mechanisms involved in early developmental processes. PMID:25762313

Calcium-Induced calcium release during action potential firing in developing inner hair cells.

PubMed

Iosub, Radu; Avitabile, Daniele; Grant, Lisa; Tsaneva-Atanasova, Krasimira; Kennedy, Helen J

2015-03-10

In the mature auditory system, inner hair cells (IHCs) convert sound-induced vibrations into electrical signals that are relayed to the central nervous system via auditory afferents. Before the cochlea can respond to normal sound levels, developing IHCs fire calcium-based action potentials that disappear close to the onset of hearing. Action potential firing triggers transmitter release from the immature IHC that in turn generates experience-independent firing in auditory neurons. These early signaling events are thought to be essential for the organization and development of the auditory system and hair cells. A critical component of the action potential is the rise in intracellular calcium that activates both small conductance potassium channels essential during membrane repolarization, and triggers transmitter release from the cell. Whether this calcium signal is generated by calcium influx or requires calcium-induced calcium release (CICR) is not yet known. IHCs can generate CICR, but to date its physiological role has remained unclear. Here, we used high and low concentrations of ryanodine to block or enhance CICR to determine whether calcium release from intracellular stores affected action potential waveform, interspike interval, or changes in membrane capacitance during development of mouse IHCs. Blocking CICR resulted in mixed action potential waveforms with both brief and prolonged oscillations in membrane potential and intracellular calcium. This mixed behavior is captured well by our mathematical model of IHC electrical activity. We perform two-parameter bifurcation analysis of the model that predicts the dependence of IHCs firing patterns on the level of activation of two parameters, the SK2 channels activation and CICR rate. Our data show that CICR forms an important component of the calcium signal that shapes action potentials and regulates firing patterns, but is not involved directly in triggering exocytosis. These data provide important insights into the calcium signaling mechanisms involved in early developmental processes. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Heterogeneity of the calcium-induced permeability transition in isolated non-synaptic brain mitochondria.

PubMed

Kristián, Tibor; Weatherby, Tina M; Bates, Timothy E; Fiskum, Gary

2002-12-01

Calcium overload of neural cell mitochondria plays a key role in excitotoxic and ischemic brain injury. This study tested the hypothesis that brain mitochondria consist of subpopulations with differential sensitivity to calcium-induced inner membrane permeability transition, and that this sensitivity is greatly reduced by physiological levels of adenine nucleotides. Isolated non-synaptosomal rat brain mitochondria were incubated in a potassium-based medium in the absence or presence of ATP or ADP. Measurements were made of medium and intramitochondrial free calcium, light scattering, mitochondrial ultrastructure, and the elemental composition of electron-opaque deposits within mitochondria treated with calcium. In the absence of adenine nucleotides, calcium induced a partial decrease in light scattering, accompanied by three distinct ultrastructural morphologies, including large-amplitude swelling, matrix vacuolization and a normal appearance. In the presence of ATP or ADP the mitochondrial calcium uptake capacity was greatly enhanced and calcium induced an increase rather than a decrease in mitochondrial light scattering. Approximately 10% of the mitochondria appeared damaged and the rest contained electron-dense precipitates that contained calcium, as determined by electron-energy loss spectroscopy. These results indicate that brain mitochondria are heterogeneous in their response to calcium. In the absence of adenine nucleotides, approximately 20% of the mitochondrial population exhibit morphological alterations consistent with activation of the permeability transition, but less than 10% exhibit evidence of osmotic swelling and membrane disruption in the presence of ATP or ADP.

Down-regulation of L-type calcium channel and sarcoplasmic reticular Ca(2+)-ATPase mRNA in human atrial fibrillation without significant change in the mRNA of ryanodine receptor, calsequestrin and phospholamban: an insight into the mechanism of atrial electrical remodeling.

PubMed

Lai, L P; Su, M J; Lin, J L; Lin, F Y; Tsai, C H; Chen, Y S; Huang, S K; Tseng, Y Z; Lien, W P

1999-04-01

We investigated the gene expression of calcium-handling genes including L-type calcium channel, sarcoplasmic reticular calcium adenosine triphosphatase (Ca(2+)-ATPase), ryanodine receptor, calsequestrin and phospholamban in human atrial fibrillation. Recent studies have demonstrated that atrial electrical remodeling in atrial fibrillation is associated with intracellular calcium overload. However, the changes of calcium-handling proteins remain unclear. A total of 34 patients undergoing open heart surgery were included. Atrial tissue was obtained from the right atrial free wall, right atrial appendage, left atrial free wall and left atrial appendage, respectively. The messenger ribonucleic acid (mRNA) amount of the genes was measured by reverse transcription-polymerase chain reaction and normalized to the mRNA levels of glyceraldehyde 3-phosphate dehydrogenase. The mRNA of L-type calcium channel and of Ca(2+)-ATPase was significantly decreased in patients with persistent atrial fibrillation for more than 3 months (0.36+/-0.26 vs. 0.90+/-0.88 for L-type calcium channel; 0.69+/-0.42 vs. 1.21+/-0.68 for Ca(2+)-ATPase; both p < 0.05, all data in arbitrary unit). We further demonstrated that there was no spatial dispersion of the gene expression among the four atrial tissue sampling sites. Age, gender and underlying cardiac disease had no significant effects on the gene expression. In contrast, the mRNA levels of ryanodine receptor, calsequestrin and phospholamban showed no significant change in atrial fibrillation. L-type calcium channel and the sarcoplasmic reticular Ca(2+)-ATPase gene were down-regulated in atrial fibrillation. These changes may be a consequence of, as well as a contributory factor for, atrial fibrillation.

A High-Calcium and Phosphate Rescue Diet and VDR-Expressing Transgenes Normalize Serum Vitamin D Metabolite Profiles and Renal Cyp27b1 and Cyp24a1 Expression in VDR Null Mice

PubMed Central

Kaufmann, Martin; Lee, Seong Min; Pike, J. Wesley

2015-01-01

Vitamin D receptor (VDR)-mediated 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)-dependent gene expression is compromised in the VDR null mouse. The biological consequences include: hypocalcemia, hypophosphatemia, elevated parathyroid hormone (PTH) and 1,25(OH)2D3, and consequential skeletal abnormalities. CYP24A1 is a cytochrome P450 enzyme that is involved in the side chain oxidation and destruction of both 1,25(OH)2D3 and 25-hydroxyvitamin D3 (25-OH-D3). In the current studies, we used liquid chromatography-tandem mass spectrometry technology to compare the metabolic profiles of VDR null mice fed either a normal or a calcium and phosphate-enriched rescue diet and to assess the consequence of transgenic expression of either mouse or human VDR genes in the same background. Serum 1,25(OH)2D3 levels in VDR null mice on normal chow were highly elevated (>3000 pg/mL) coincident with undetectable levels of catabolites such as 24,25-(OH)2D3 and 25-OH-D3-26,23-lactone normally observed in wild-type mice. The rescue diet corrected serum Ca++, PTH, and 1,25(OH)2D3 values and restored basal expression of Cyp24a1 as evidenced by both renal expression of Cyp24a1 and detection of 24,25-(OH)2D3 and the 25-OH-D3-26,23-lactone. Unexpectedly, this diet also resulted in supranormal levels of 3-epi-24,25-(OH)2D3 and 3-epi-25-OH-D3-26,23-lactone. The reappearance of serum 24,25-(OH)2D3 and renal Cyp24a1 expression after rescue suggests that basal levels of Cyp24a1 may be repressed by high PTH. Introduction of transgenes for either mouse or human VDR also normalized vitamin D metabolism in VDR null mice, whereas this metabolic pattern was unaffected by a transgene encoding a ligand binding-deficient mutant (L233S) human VDR. We conclude that liquid chromatography-tandem mass spectrometry-based metabolic profiling is an ideal analytical method to study mouse models with alterations in calcium/phosphate homeostasis. PMID:26441239

Roles of calcium and pH in activation of eggs of the medaka fish, Oryzias latipes

PubMed Central

1983-01-01

Unfertilized eggs of the medaka fish (Oryzias latipes) were injected with pH-buffered calcium buffers. Medaka egg activation is accompanied by a transient increase in cytoplasmic free calcium (Gilkey, J. C., L. F. Jaffe, E. B. Ridgway, and G. T. Reynolds, 1978, J. Cell Biol., 76:448-466). The calcium buffer injections demonstrated that (a) the threshold free calcium required to elicit the calcium transient and activate the egg is between 1.7 and 5.1 microM at pH 7.0, well below the 30 microM reached during the transient, and (b) buffers which hold free calcium below threshold prevent activation of the buffered region in subsequently fertilized eggs. Therefore an increase in free calcium is necessary and sufficient to elicit the calcium transient, and the calcium transient is necessary to activate the egg. Further, these results are additional proof that the calcium transient is initiated and propagated through the cytoplasm by a mechanism of calcium- stimulated calcium release. Finally, a normal calcium transient must propagate through the entire cytoplasm to ensure normal development. Unfertilized eggs were injected with pH buffers to produce short-term, localized changes in cytoplasmic pH. The eggs were then fertilized at various times after injection. In other experiments, unfertilized and fertilized eggs were exposed to media containing either NH4Cl or CO2 to produce longer term, global changes in cytoplasmic pH. These treatments neither activated the eggs nor interfered with the normal development of fertilized eggs, suggesting that even if a natural change in cytoplasmic pH is induced by activation, it has no role in medaka egg development. The injected pH buffers altered the rate of propagation of the calcium transient through the cytoplasm, suggesting that the threshold free calcium required to trigger calcium-stimulated calcium release might be pH dependent. The results of injection of pH-buffered calcium buffers support this conjecture: for a tenfold increase in hydrogen ion concentration, free calcium must also be raised tenfold to elicit the calcium transient. PMID:6411737

Comparative Analysis of Serum Mineral Levels and Parasite Load in Goats Naturally Infected with Gastrointestinal Nematodes.

PubMed

Ünübol Aypak, Serap; Aypak, Süleyman; Voyvoda, Hüseyin; Güven, Gülşen; Dereli Fidan, Evrim; Tosun, Gamze; Gültekin, Mehmet; Şimşek, Emrah; Gülçe Güler, Asude

2016-09-01

This study aimed to investigate the relationship between serum mineral levels and parasite load in Saanen (n=37) and Damascus (n=13) goats, which were all approximately 2 months pregnant and naturally infected with gastrointestinal nematodes. To determine parasite concentration individually, fecal samples were taken from each goat, and the eggs per gram (EPG) of feces was detected via a modified McMaster technique. To investigate the possible effects of parasite concentration on serum mineral levels, blood was drawn from the goats and serum calcium, phosphorus, magnesium, iron, copper, zinc, manganese, nickel, and cadmium levels were measured via the ICP-OES technique. In a correlation analysis of the individual EPG values and mineral levels performed on the basis of the species, it was seen that increased egg numbers did not cause a statistically significant increase or decrease in Saanens except for cadmium (significant moderate positive correlation, p<0.05) for both species. A comparison of the mineral element levels with the lower and upper normal limits in the published literature found that manganese and iron were below the normal range, while zinc and calcium levels were close to the lower limits. It is estimated that the effect of parasite load, which continuously increases with the progression of pregnancy and deliveries, on blood mineral levels would be much more significant.

Whole-Saliva Fluoride Levels and Saturation Indices in 65+ Elderly during Use of Four Different Toothpaste Regimens.

PubMed

Ekstrand, Kim Rud; Ekstrand, Mia Linding; Lykkeaa, Joan; Bardow, Allan; Twetman, Svante

2015-01-01

Elderly individuals suffering from subnormal saliva secretion combined with inadequate oral hygiene may develop rampant caries and caries in parts of the dentition not normally affected by caries if preventive measures are not undertaken. Such measures include elevating fluoride levels at the saliva/biofilm/tooth interface. To analyse whole-saliva fluoride levels and mineral saturation indices during different fluoride toothpaste regimens in home-living elderly. Whole saliva was collected from 27 subjects (7 males and 20 females, mean age 73.5±6.1 years) at ten time points covering the whole day during five 2-week periods. During the first period, participants used their normal toothpaste without instructions (baseline). This was followed by TP1: 1,450-ppm NaF toothpaste; TP2: 1,450-ppm monofluorophosphate (MFP) toothpaste with addition of calcium; TP3: 5,000-ppm NaF toothpaste, and TP4: the same toothpaste with additional 'smearing' of toothpaste on the teeth, twice daily. During TP1-TP4, the participants were instructed to brush 3 times per day using 1.5 g of toothpaste without rinsing. Salivary fluoride levels increased with toothpaste fluoride content (p<0.001), although major interindividual and intraindividual variations were observed. The highest fluoride values appeared in the morning and at night (p<0.001). Saturation indices for calcium fluoride were affected by the fluoride content in pastes (p<0.05). Concerning hydroxyapatite and fluorapatite, indices were highest with the MFP toothpaste and extra calcium (NS to p<0.05). Use of a high-fluoride toothpaste resulted in significantly increased fluoride levels in whole saliva and mineral saturation indices were indeed influenced by choice of toothpaste. © 2015 S. Karger AG, Basel.

Best time window for the use of calcium-modulating agents to improve functional recovery in injured peripheral nerves-An experiment in rats.

PubMed

Yan, Yuhui; Shen, Feng-Yi; Agresti, Michael; Zhang, Lin-Ling; Matloub, Hani S; LoGiudice, John A; Havlik, Robert; Li, Jifeng; Gu, Yu-Dong; Yan, Ji-Geng

2017-09-01

Peripheral nerve injury can have a devastating effect on daily life. Calcium concentrations in nerve fibers drastically increase after nerve injury, and this activates downstream processes leading to neuron death. Our previous studies showed that calcium-modulating agents decrease calcium accumulation, which aids in regeneration of injured peripheral nerves; however, the optimal therapeutic window for this application has not yet been identified. In this study, we show that calcium clearance after nerve injury is positively correlated with functional recovery in rats suffering from a crushed sciatic nerve injury. After the nerve injury, calcium accumulation increased. Peak volume is from 2 to 8 weeks post injury; calcium accumulation then gradually decreased over the following 24-week period. The compound muscle action potential (CMAP) measurement from the extensor digitorum longus muscle recovered to nearly normal levels in 24 weeks. Simultaneously, real-time polymerase chain reaction results showed that upregulation of calcium-ATPase (a membrane protein that transports calcium out of nerve fibers) mRNA peaked at 12 weeks. These results suggest that without intervention, the peak in calcium-ATPase mRNA expression in the injured nerve occurs after the peak in calcium accumulation, and CMAP recovery continues beyond 24 weeks. Immediately using calcium-modulating agents after crushed nerve injury improved functional recovery. These studies suggest that a crucial time frame in which to initiate effective clinical approaches to accelerate calcium clearance and nerve regeneration would be prior to 2 weeks post injury. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Calcium channel blockers and transmitter release at the normal human neuromuscular junction.

PubMed

Protti, D A; Reisin, R; Mackinley, T A; Uchitel, O D

1996-05-01

Transmitter release evoked by nerve stimulation is highly dependent on Ca2+ entry through voltage-activated plasma membrane channels. Calcium influx may be modified in some neuromuscular diseases like Lambert-Eaton syndrome and amyotrophic lateral sclerosis. We studied the pharmacologic sensitivity of the transmitter release process to different calcium channel blockers in normal human muscles and found that funnel web toxin and omega-Agatoxin-IVA, both P-type calcium channel blockers, blocked nerve-elicited muscle action potentials and inhibited evoked synaptic transmission. The transmitter release was not affected either by nitrendipine, an L-type channel blocker, or omega-Conotoxin-GVIA, an N-type channel blocker. The pharmacologic profile of neuromuscular transmission observed in normal human muscles indicates that P-like channels mediate transmitter release at the motor nerve terminals.

Calcium orthophosphates

PubMed Central

Dorozhkin, Sergey V.

2011-01-01

The present overview is intended to point the readers’ attention to the important subject of calcium orthophosphates. This type of materials is of special significance for human beings, because they represent the inorganic part of major normal (bones, teeth and antlers) and pathological (i.e., those appearing due to various diseases) calcified tissues of mammals. For example, atherosclerosis results in blood vessel blockage caused by a solid composite of cholesterol with calcium orthophosphates, while dental caries and osteoporosis mean a partial decalcification of teeth and bones, respectively, that results in replacement of a less soluble and harder biological apatite by more soluble and softer calcium hydrogenphosphates. Therefore, the processes of both normal and pathological calcifications are just an in vivo crystallization of calcium orthophosphates. Similarly, dental caries and osteoporosis might be considered an in vivo dissolution of calcium orthophosphates. Thus, calcium orthophosphates hold a great significance for humankind, and in this paper, an overview on the current knowledge on this subject is provided. PMID:23507744

Intracellular interaction of EBV/C3d receptor (CR2) with p68, a calcium-binding protein present in normal but not in transformed B lymphocytes.

PubMed

Barel, M; Gauffre, A; Lyamani, F; Fiandino, A; Hermann, J; Frade, R

1991-08-15

To analyze direct intracellular interactions of CR2 in normal human B lymphocytes, we used polyclonal anti-Id anti-CR2 antibodies (Ab2) prepared against the highly purified CR2 molecule (gp140) as original immunogen. We previously demonstrated that this Ab2 contained specificities that mimicked extracellular and intracellular domains of CR2 and was helpful for identifying CR2-specific ligands. Indeed, some Ab2 specificities recognized human C3d and EBV, two extracellular CR2 ligands. In addition, other Ab2 specificities interacted directly, as CR2, with the intracellular p53 antioncoprotein that is expressed in transformed cells and not in normal cells. We demonstrate herein that Ab2 detected in normal B lymphocytes a 68-kDa protein, p68, that was not expressed in transformed B cells. p68 was localized in purified plasma membranes and cytosol fractions. Direct interaction of purified CR2 with purified p68 was demonstrated. Competitive studies supported that CR2 and Ab2 interacted with identical sites on p68. These interactions were calcium dependent. p68 was identified as a calcium-binding protein by its ability to be solubilized from B lymphocyte membranes by EGTA, a calcium-chelating agent, to bind specifically on phenothiazine-Sepharose in a calcium-dependent interaction, and to be recognized by specific antibodies directed against human p68, a calcium-binding protein of the annexin VI family. Thus, demonstration of different intracellular interactions of CR2 with distinct regulatory proteins, such as p53, the antioncoprotein, and p68, a calcium-binding protein, supports involvement of two regulatory pathways of signal transduction through CR2, depending on the normal or transformed state of human B lymphocytes.

Hyperkalemia induced by the calcium channel blocker, benidipine.

PubMed

Imamura, Takuroh; Matsuura, Yunosuke; Nagoshi, Toshiro; Ishikawa, Tetsunori; Date, Haruhiko; Kita, Toshihiro; Matsuyama, Akihiko; Matsuo, Takeshi; Eto, Tanenao

2003-06-01

A 73-year-old hypertensive, non-diabetic woman without obvious renal dysfunction had frequently been hyperkalemic over four years after receiving antihypertensive drugs including the calcium channel blocker (CCB) benidipine. One week after all medications were accidentally discontinued, the serum potassium level returned to normal. After we obtained the informed consent of the patient, benidipine alone was administered again for over two weeks and hyperkalemia developed once more. This previously uncommon side effect of hyperkalemia induced by benidipine is not very serious but it is apt to be overlooked. Since CCBs are now widely prescribed, the development of hyperkalemia should be considered.

Calcium, phosphorus and protein levels as factors in the distribution of the pheasant

USGS Publications Warehouse

Dale, F.H.; DeWitt, J.B.

1958-01-01

Summary of work on pheasant nutrition conducted since 1949 at the Patuxent Research Refuge. Pheasant chicks fed experimental diets failed to develop normally on protein levels of 15 and 18%. With 22% protein they grew at a reduced rate as compared to those on 28%. Protein level of the reproductive diet was shown to be important; low production of eggs and young resulted from levels below 25%. Calcium was found to be even more critical than protein level for reproduction; birds on a winter diet that furnished 145 mg./kg. per day had poor reproductive success the following spring. About 600 mg./kg. of Ca per day was necessary in the reproduction diet. Birds on an intermediate level of Ca (about 0.5% of diet) showed evidence of cumulative deficiency. It was concluded that pheasants receiving levels of Ca no higher than 0.5% in nature might display 'straggling failure' such as has been observed in several midwestern areas.

Severe hypocalcemia following bisphosphonate treatment in a patient with Paget's disease of bone.

PubMed

Whitson, Heather E; Lobaugh, Bruce; Lyles, Kenneth W

2006-10-01

Bisphosphonate therapy is a common and effective treatment for Paget's disease of bone, osteoporosis, hypercalcemia of malignancy and cancer metastatic to bone. Clinically significant hypocalcemia has not been reported in patients with Paget's disease of bone and normal parathyroid function treated with an aminobisphosphonate. We treated a 52-year-old woman with polyostotic Paget's disease of bone (serum alkaline phosphatase level-1971 IU/L [normal 31-110 IU/L]), who had not previously received bisphosphonates, with daily oral 30 mg risedronate, oral 1000 mg elemental calcium and oral 400 IU cholecalciferol. After 10 days of treatment, she developed severe hypocalcemia (5.4 mg/dL [normal 8.7-10.2 mg/dL]), requiring hospitalization and support with 5 days of intravenous calcium gluconate. On the day risedronate treatment began, her PTH was low normal at 14 pg/mL (normal 12-72 pg/mL), consistent with a relatively suppressed PTH axis due to high bone turnover. Her vitamin D level was within normal limits (serum 25(OH)D 19 ng/mL [normal 8-38 ng/mL]), although possibly not optimally repleted. We hypothesize that this case represents an example of hungry bone syndrome in a patient with extensive Paget's disease of bone who received risedronate, causing acute suppression of bone resorption while elevated bone formation rates continued. In the year following her recovery, the patient was successfully treated with slowly titrated anti-resorptive therapy (subcutaneous calcitonin followed by titrated doses of risedronate), and is now clinically well. Physicians should be aware of the potential for hypocalcemia when patients with polyostotic Paget's disease and markedly elevated indicators of bone remodeling are initiated on powerful anti-resorptive therapy.

Seminal Plasma pH, Inorganic Phosphate, Total and Ionized Calcium Concentrations In The Assessment of Human Spermatozoa Function.

PubMed

Banjoko, S Olatunbosun; Adeseolu, Fasiu O

2013-11-01

Fertilization in humans is dependent on viability of the male spermatozoa among other factors and there have been conflicting reports on the role of pH, calcium and phosphate concentrations in sperm function. This study therefore aimed to investigate seminal plasma pH, inorganic phosphate, total and ionized calcium concentrations relative to spermatozoa function. Seminal plasma concentrations of pH, total calcium, ionized calcium (Ca(++)); inorganic phosphate, motility and spermatozoa count were determined in 80 males by standard methods. Forty-nine of the subjects had normal spermatozoa motility (> 60%) and 31 had hypomotility (< 60%). The hypomotility group exhibited lower calcium ion (Ca(2)+) concentrations; 0.19+0.01mmol/L compared with normal motility group; 0.24+0.01mmol/L (p<0.001) the latter also had significantly higher inorganic phosphate; 7.83+1.27 while the former had 5.64+1.62mmol/L (p= 0.004). The mean spermatozoa counts for hypomotility and normal motility group were 42.0 ± 13 x 106 , 72.35 + 20 x 106 respectively (p< 0.001). No significant differences were observed in pH, volume of ejaculate and total calcium concentration between the hypomotility and normal motility groups The mean concentrations of pH were 7.51 ± 0.02 and 7.54 ± 0.03 respectively (p= 0.21) and total calcium; 3.10 ± 0.12 and 3.36 ± 0.14mmol/L respectively (p= 0.16 ). There was a significant difference in percentage of abnormal forms in both groups with hypomotile group having 36% compared to mormal motility group with 5% (p< 0.05). Correlations were observed between seminal concentrations of calcium ions, inorganic phosphate, spermatozoa count and motility but not with total calcium concentrations and pH and therefore should be considered in understanding male infertility and preparation of media for sperm preservation for in vitro fertilization.

Vitamin D, calcium, and breast cancer risk: a review.

PubMed

Cui, Yan; Rohan, Thomas E

2006-08-01

Vitamin D and calcium are metabolically interrelated and highly correlated dietary factors. Experimental studies have shown their anticarcinogenic effects due to their participation in regulating cell proliferation, differentiation, and apoptosis in normal and malignant breast cells. Given the emerging interest in their potential roles in the etiology of breast cancer, we review the current epidemiologic literature on dietary and/or supplemental intakes of vitamin D, endogenous circulating levels of vitamin D, and dietary and/or supplemental intakes of calcium in relation to breast cancer risk. To place these studies in context, we also provide a brief review of other supporting epidemiologic evidence. Despite inconsistent results from the epidemiologic studies, several lines of evidence suggest that vitamin D and calcium may be involved in the development of breast cancer. Specifically, (a) there is some epidemiologic evidence for inverse associations between vitamin D and calcium intakes and breast cancer; (b) serum, plasma, and/or blood levels of vitamin D metabolites have been inversely associated with breast cancer risk in some studies; (c) high sunlight exposure, presumably reflecting vitamin D synthesis in the skin, has been associated with a reduced risk of breast cancer; (d) vitamin D and calcium intakes have been inversely related to breast density, an intermediate end point for breast cancer; (e) calcium has been associated with a reduced risk of benign proliferative epithelial disorders of the breast, putative precursors of breast cancer; and (f) certain polymorphisms of the vitamin D receptor might modify breast cancer susceptibility. To further confirm the potential protective effects of calcium and vitamin D on breast cancer, well-designed cohort studies and clinical trials are warranted.

Parasitoid wasp venom SERCA regulates Drosophila calcium levels and inhibits cellular immunity.

PubMed

Mortimer, Nathan T; Goecks, Jeremy; Kacsoh, Balint Z; Mobley, James A; Bowersock, Gregory J; Taylor, James; Schlenke, Todd A

2013-06-04

Because parasite virulence factors target host immune responses, identification and functional characterization of these factors can provide insight into poorly understood host immune mechanisms. The fruit fly Drosophila melanogaster is a model system for understanding humoral innate immunity, but Drosophila cellular innate immune responses remain incompletely characterized. Fruit flies are regularly infected by parasitoid wasps in nature and, following infection, flies mount a cellular immune response culminating in the cellular encapsulation of the wasp egg. The mechanistic basis of this response is largely unknown, but wasps use a mixture of virulence proteins derived from the venom gland to suppress cellular encapsulation. To gain insight into the mechanisms underlying wasp virulence and fly cellular immunity, we used a joint transcriptomic/proteomic approach to identify venom genes from Ganaspis sp.1 (G1), a previously uncharacterized Drosophila parasitoid species, and found that G1 venom contains a highly abundant sarco/endoplasmic reticulum calcium ATPase (SERCA) pump. Accordingly, we found that fly immune cells termed plasmatocytes normally undergo a cytoplasmic calcium burst following infection, and that this calcium burst is required for activation of the cellular immune response. We further found that the plasmatocyte calcium burst is suppressed by G1 venom in a SERCA-dependent manner, leading to the failure of plasmatocytes to become activated and migrate toward G1 eggs. Finally, by genetically manipulating plasmatocyte calcium levels, we were able to alter fly immune success against G1 and other parasitoid species. Our characterization of parasitoid wasp venom proteins led us to identify plasmatocyte cytoplasmic calcium bursts as an important aspect of fly cellular immunity.

The Use of Calcimimetics for the Treatment of Secondary Hyperparathyroidism: A 10 Year Evidence Review.

PubMed

Rodríguez, Mariano; Goodman, William G; Liakopoulos, Vassilios; Messa, Piergiorgio; Wiecek, Andrzej; Cunningham, John

2015-01-01

Until the discovery of calcimimetics, the management of secondary hyperparathyroidism (SHPT) relied exclusively on treatment with phosphate binders, vitamin D derivatives or surgical parathyroidectomy with limited success. The therapeutic use of calcimimetic agents, together with a better understanding of the pivotal role of the calcium-sensing receptor (CaSR) in the physiological regulation of parathyroid gland function, substantially advanced the management of hyperparathyroidism in dialysis practice. Calcimimetics bind selectively to the CaSR receptor in parathyroid tissue and enhance the inhibitory effect of extracellular calcium ions on parathyroid hormone (PTH) secretion, thereby reducing PTH levels even when serum calcium concentrations are normal or low. The availability of calcimimetic agents for clinical use has opened a new era in the management of patients with SHPT. Indeed, calcimimetic compounds have been shown to reduce PTH levels and to lower serum calcium concentrations in all forms of hyperparathyroidism, including primary hyperparathyroidism (PHPT) and parathyroid carcinoma. Such findings underscore the critical importance of the CaSR as a therapeutic target in this family of clinical disorders. New calcimimetic agents are being developed that have the potential to offer improved efficacy and safety compared with currently available calcimimetic compounds. © 2015 Wiley Periodicals, Inc.

Long-Term Oral Administration of Theaphenon-E Improves Cardiomyocyte Mechanics and Calcium Dynamics by Affecting Phospholamban Phosphorylation and ATP Production.

PubMed

Bocchi, Leonardo; Savi, Monia; Naponelli, Valeria; Vilella, Rocchina; Sgarbi, Gianluca; Baracca, Alessandra; Solaini, Giancarlo; Bettuzzi, Saverio; Rizzi, Federica; Stilli, Donatella

2018-06-15

Dietary polyphenols from green tea have been shown to possess cardio-protective activities in different experimental models of heart diseases and age-related ventricular dysfunction. The present study was aimed at evaluating whether long term in vivo administration of green tea extracts (GTE), can exert positive effects on the normal heart, with focus on the underlying mechanisms. The study population consisted of 20 male adult Wistar rats. Ten animals were given 40 mL/day tap water solution of GTE (concentration 0.3%) for 4 weeks (GTE group). The same volume of water was administered to the 10 remaining control rats (CTRL). Then, in vivo and ex vivo measurements of cardiac function were performed in the same animal, at the organ (hemodynamics) and cellular (cardiomyocyte mechanical properties and intracellular calcium dynamics) levels. On cardiomyocytes and myocardial tissue samples collected from the same in vivo studied animals, we evaluated: (1) the intracellular content of ATP, (2) the endogenous mitochondrial respiration, (3) the expression levels of the Sarcoplasmic Reticulum Ca2+-dependent ATPase 2a (SERCA2), the Phospholamban (PLB) and the phosphorylated form of PLB, the L-type Ca2+ channel, the Na+-Ca2+ exchanger, and the ryanodine receptor 2. GTE cardiomyocytes exhibited a hyperdynamic contractility compared with CTRL (the rate of shortening and re-lengthening, the fraction of shortening, the amplitude of calcium transient, and the rate of cytosolic calcium removal were significantly increased). A faster isovolumic relaxation was also observed at the organ level. Consistent with functional data, we measured a significant increase in the intracellular ATP content supported by enhanced endogenous mitochondrial respiration in GTE cardiomyocytes, as well as higher values of the ratios phosphorylated-PLB/PLB and SERCA2/PLB. Long-term in vivo administration of GTE improves cell mechanical properties and intracellular calcium dynamics in normal cardiomyocytes, by increasing energy availability and removing the inhibitory effect of PLB on SERCA2. © 2018 The Author(s). Published by S. Karger AG, Basel.

Subclinical hypocalcaemia in captive Asian elephants (Elephas maximus).

PubMed

van der Kolk, J H; van Leeuwen, J P T M; van den Belt, A J M; van Schaik, R H N; Schaftenaar, W

2008-04-12

The hypothesis that hypocalcaemia may play a role in dystocia in captive Asian elephants (Elephas maximus) was investigated. The objectives of the study were to measure the total calcium concentration in elephant plasma; assess the changes in parameters of calcium metabolism during a feeding trial; investigate a possible relationship between calcium metabolism and dystocia; and assess bone mineralisation in captive Asian elephants in vivo. The following parameters were measured: total and ionised calcium, inorganic phosphorous and magnesium, the fractional excretions of these minerals, intact parathyroid hormone, 25-OH-D(3) and 1,25-OH-D(3). Radiographs were taken from tail vertebrae for assessment of bone mineralisation. The mean (sd) heparinised plasma total calcium concentration was 2.7 (0.33) mmol/l (n=43) ranging from 0.84 to 3.08 mmol/l in 11 Asian elephants. There was no significant correlation between plasma total calcium concentration and age. Following feeding of a calcium rich ration to four captive Asian elephant cows, plasma total and ionised calcium peaked at 3.6 (0.24) mmol/l (range 3.4 to 3.9 mmol/l) and 1.25 (0.07) mmol/l (range 1.17 to 1.32 mmol/l), respectively. Plasma ionised calcium concentrations around parturition in four Asian elephant cows ranged from 0.37 to 1.1 mmol/l only. The present study indicates that captive Asian elephants might be hypocalcaemic, and that, in captive Asian elephants, the normal plasma concentration of total calcium should actually be around 3.6 mmol/l and normal plasma concentration of ionised calcium around 1.25 mmol/l. Given the fact that elephants absorb dietary calcium mainly from the intestine, it could be concluded that elephants should be fed calcium-rich diets at all times, and particularly around parturition. In addition, normal values for ionised calcium in captive Asian elephants should be reassessed.

(Z)3,4,5,4‧-trans-tetramethoxystilbene, a new analogue of resveratrol, inhibits gefitinb-resistant non-small cell lung cancer via selectively elevating intracellular calcium level

NASA Astrophysics Data System (ADS)

Fan, Xing-Xing; Yao, Xiao-Jun; Xu, Su Wei; Wong, Vincent Kam-Wai; He, Jian-Xing; Ding, Jian; Xue, Wei-Wei; Mujtaba, Tahira; Michelangeli, Francesco; Huang, Min; Huang, Jun; Xiao, Da-Kai; Jiang, Ze-Bo; Zhou, Yan-Ling; Kin-Ting Kam, Richard; Liu, Liang; Lai-Han Leung, Elaine

2015-11-01

Calcium is a second messenger which is required for regulation of many cellular processes. However, excessive elevation or prolonged activation of calcium signaling would lead to cell death. As such, selectively regulating calcium signaling could be an alternative approach for anti-cancer therapy. Recently, we have identified an effective analogue of resveratrol, (Z)3,4,5,4‧-trans-tetramethoxystilbene (TMS) which selectively elevated the intracellular calcium level in gefitinib-resistant (G-R) non-small-cell lung cancer (NSCLC) cells. TMS exhibited significant inhibitory effect on G-R NSCLC cells, but not other NSCLC cells and normal lung epithelial cells. The phosphorylation and activation of EGFR were inhibited by TMS in G-R cells. TMS induced caspase-independent apoptosis and autophagy by directly binding to SERCA and causing endoplasmic reticulum (ER) stress and AMPK activation. Proteomics analysis also further confirmed that mTOR pathway, which is the downstream of AMPK, was significantly suppressed by TMS. JNK, the cross-linker of ER stress and mTOR pathway was significantly activated by TMS. In addition, the inhibition of JNK activation can partially block the effect of TMS. Taken together, TMS showed promising anti-cancer activity by mediating calcium signaling pathway and inducing apoptosis as well as autophagy in G-R NSCLC cells, providing strategy in designing multi-targeting drug for treating G-R patients.

Calcium supplementation in osteoporosis: useful or harmful?

PubMed

Chiodini, Iacopo; Bolland, Mark J

2018-04-01

Osteoporosis and fragility fractures are important social and economic problems worldwide and are due to both the loss of bone mineral density and sarcopenia. Indeed, fragility fractures are associated with increased disability, morbidity and mortality. It is known that a normal calcium balance together with a normal vitamin D status is important for maintaining well-balanced bone metabolism, and for many years, calcium and vitamin D have been considered crucial in the prevention and treatment of osteoporosis. However, recently, the usefulness of calcium supplementation (alone or with concomitant vitamin D) has been questioned, since some studies reported only weak efficacy of these supplementations in reducing fragility fracture risk. On the other hand, besides the gastrointestinal side effects of calcium supplements and the risk of kidney stones related to use of co-administered calcium and vitamin D supplements, other recent data suggested potential adverse cardiovascular effects from calcium supplementation. This debate article is focused on the evidence regarding both the possible usefulness for bone health and the potential harmful effects of calcium and/or calcium with vitamin D supplementation. © 2018 European Society of Endocrinology.

Acid precipitation and food quality: Inhibition of growth and survival in black ducks and mallards by dietary aluminum, calcium and phosphorus

USGS Publications Warehouse

Robbins, C.S.

1990-01-01

In areas impacted by acid precipitation, water chemistry of acidic ponds and streams often changes, resulting in increased mobilization of aluminum and decreased concentration of calcium carbonate. Aluminum binds with phosphorus and inhibits its uptake by organisms. Thus, invertebrate food organisms used by waterfowl may have inadequate Ca and P or elevated Al for normal growth and development. Acid rain and its effects may be one of the factors negatively impacting American black ducks (Anas rubripes) in eastern North America. One-day old mallards (A. platyrhynchos) and black ducks were placed on one of three Ca:P regimens: low:low (LL), normal:normal (NN), and low:high (LH) with each regimen divided further into three or four Al levels for 10 weeks. Forty-five % of the black ducks died on nine different diets whereas only 28% of the mallards died on three different diets. Mortality was significantly related to diet in both species. Growth rates for body weight, culmens, wings, and tarsi of both species on control diets exceeded those on many treatment diets but the differences were less apparent for mallards than for black ducks. Differences among treatments were due to both Ca:P and Al levels.

Effects of supplemental vitamin D and calcium on oxidative DNA damage marker in normal colorectal mucosa: a randomized clinical trial.

PubMed

Fedirko, Veronika; Bostick, Roberd M; Long, Qi; Flanders, W Dana; McCullough, Marjorie L; Sidelnikov, Eduard; Daniel, Carrie R; Rutherford, Robin E; Shaukat, Aasma

2010-01-01

The exact antineoplastic effects of calcium and vitamin D(3) in the human colon are unclear. Animal and in vitro studies show that these two agents reduce oxidative stress; however, these findings have never been investigated in humans. To address this, we conducted a pilot, randomized, double-blind, placebo-controlled, 2 x 2 factorial clinical trial to test the effects of calcium and vitamin D(3) on a marker of oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine (8-OH-dG), in the normal colorectal mucosa. Patients (N = 92) with at least one pathology-confirmed colorectal adenoma were treated with 2 g/d calcium and/or 800 IU/d vitamin D(3) versus placebo over 6 months. Overall labeling and colorectal crypt distribution of 8-OH-dG in biopsies of normal-appearing rectal mucosa were detected by standardized automated immunohistochemistry and quantified by image analysis. After 6 months of treatment, 8-OH-dG labeling along the full lengths of colorectal crypts decreased by 22% (P = 0.15) and 25% (P = 0.10) in the calcium and vitamin D(3) groups, respectively, but not in the calcium plus vitamin D(3) group. The estimated treatment effects were strongest among participants with higher baseline colon crypt vitamin D receptor expression (P = 0.05). Overall, these preliminary results indicate that calcium and vitamin D(3) may decrease oxidative DNA damage in the normal human colorectal mucosa, support the hypothesis that 8-OH-dG labeling in colorectal crypts is a treatable oxidative DNA damage biomarker of risk for colorectal neoplasms, and provide support for further investigation of calcium and vitamin D(3) as chemopreventive agents against colorectal neoplasms.

Ionic regulation of the cardiac sodium-calcium exchanger.

PubMed

Reeves, John P; Condrescu, Madalina

2008-01-01

The Na(+)-Ca(2+) exchanger (NCX) links transmembrane movements of Ca(2+) ions to the reciprocal movement of Na(+) ions. It normally functions primarily as a Ca(2+) efflux mechanism in excitable tissues such as the heart, but it can also mediate Ca(2+) influx under certain conditions. Na(+) and Ca(2+) ions exert complex regulatory effects on NCX activity. Ca(2+) binds to two regulatory sites in the exchanger's central hydrophilic domain, and this interaction is normally essential for activation of exchange activity. High cytosolic Na(+) concentrations, however, can induce a constitutive activity that by-passes the need for allosteric Ca(2+) activation. Constitutive NCX activity can also be induced by high levels of phopshotidylinositol-4,5-bisphosphate (PIP₂) and by mutations affecting the regulatory calcium binding domains. In addition to promoting constitutive activity, high cytosolic Na(+) concentrations also induce an inactivated state of the exchanger (Na(+)-dependent inactivation) that becomes dominant when cytosolic pH and PIP₂ levels fall. Na(+)-dependent inactivation may provide a means of protecting cells from Ca(2+) overload due to NCX-mediated Ca(2+) influx during ischemia.

Effects of vitamin D supplementation on strength, physical function, and health perception in older, community-dwelling men.

PubMed

Kenny, Anne M; Biskup, Bradley; Robbins, Bertha; Marcella, Glenn; Burleson, Joseph A

2003-12-01

To study the effects of vitamin D supplementation in healthier populations of men. : Randomized, controlled trial. General clinical research center. Sixty-five healthy, community-dwelling men (mean age+/-standard deviation=76+/-4, range 65-87). Cholecalciferol (1,000 IU/d) or placebo supplementation for 6 months; all received 500 mg supplemental calcium. Upper and lower extremity muscle strength and power, physical performance and activity, health perception, calcium and vitamin D intake, and biochemical assessment, including 25-hydroxyvitamin D (25OHD), parathyroid hormone (PTH), and ionized calcium levels. The levels of 25OHD increased and PTH decreased in the cholecalciferol group, whereas there were no significant changes in the control group (P<.001). Baseline 25OHD levels correlated with baseline single-leg stance time and physical activity score. Baseline PTH levels correlated with baseline 8-foot walk time and physical activity score. No significant difference in strength, power, physical performance, or health perception was found between groups. The 25OHD or PTH levels correlated with physical activity and physical performance in older, community-dwelling men with normal 25OHD status. Vitamin D supplementation increased 25OHD levels and decreased PTH levels but did not increase muscle strength or improve physical performance or health perception in this group of healthy, older men. Further investigations of the effects of vitamin D supplementation should focus on individuals with low levels of vitamin D.

[Serum PTH levels as a predictive factor of hypocalcaemia after total thyroidectomy].

PubMed

Díez Alonso, Manuel; Sánchez López, José Daniel; Sánchez-Seco Peña, María Isabel; Ratia Jiménez, Tomás; Arribas Gómez, Ignacio; Rodríguez Pascual, Angel; Martín-Duce, Antonio; Guadalix Hidalgo, Gregorio; Hernández Domínguez, Sara; Granell Vicent, Javier

2009-02-01

Postoperative parathyroid hormone (PTH) levels as a predictor of hypocalcaemia in patients subjected to total thyroidectomy is analyzed. Prospective study involving 67 patients who underwent total thyroidectomy due to a benign disease. Serum PTH and ionised calcium were measured 20 h after surgery. Sensitivity, specificity and predictive values of PTH and ionised calcium levels were calculated to predict clinical and analytical hypocalcaemia. A total of 42 (62.7%) patients developed hypocalcaemia (ionised calcium<0.95 mmol/l), but only 20 (29.9%) presented with symptoms. PTH concentration the day after surgery was significantly lower in the group that developed symptomatic hypocalcaemia (5.57+/-6.4 pg/ml) than in the asymptomatic (21.5+/-15.3 pg/ml) or normocalcaemic (26.8+/-24.9 pg/ml) groups (p=0.001). Taking the value of 13 pg/ml as a cut-off point of PTH levels, sensitivity, specificity, positive predictive value and negative predictive value were 54%, 72%, 76% and 48%, respectively. On the other hand, sensitivity for predicting symptomatic hypocalcaemia was 95% and specificity was 76%. The test showed a high incidence of false positives (11/30, 36%). Negative predictive value was 97% and positive predictive value was 65%. In multivariate analysis, PTH and ionised calcium were the only perioperative factors that showed an independent predictive value as risk indicators of symptomatic hypocalcaemia. Normal PTH levels 20 h after surgery practically rule out the subsequent appearance of hypocalcaemia symptoms. On the other hand, low PTH levels are not necessarily associated to symptomatic hypocalcaemia due to the high number of false positives.

Measurement of intraoperative parathyroid hormone predicts long-term operative success.

PubMed

Westerdahl, Johan; Lindblom, Pia; Bergenfelz, Anders

2002-02-01

A decrease in the intraoperative parathyroid hormone (PTH) level predicts long-term operative success. A case series of consecutive patients undergoing parathyroidectomy with intraoperative PTH measurement. A university hospital. One hundred two patients with sporadic primary hyperparathyroidism underwent parathyroidectomy according to the principles of unilateral exploration with intraoperative PTH measurement. Longitudinal effects on levels of serum calcium and PTH. In 94 of 98 patients who underwent primary exploration because of a solitary adenoma, intraoperative PTH decreased at least 60% 15 minutes after gland excision. The 4 cases in which PTH fell to less than 60% were classified as false negatives. Patients examined for multiglandular disease (n = 4) were correctly predicted not to have an adenoma. Twenty-two patients (22%) were unavailable for 5-year follow-up. These patients were followed up for 2 months to 48 months (median, 24 months), and none developed recurrent primary hyperparathyroidism. Of the remaining 80 patients (78%), all but 1 patient had normal or slightly decreased serum calcium levels (mean +/- SD, 9.24 +/- 0.4 mg/dL [2.31 +/- 0.10 mmol/L]) at 5-year follow-up. One patient with hypercalcemia (10.6 mg/dL [2.65 mmol/L]) was interpreted to have developed renal failure with secondary hyperparathyroidism. Thirty-four patients had elevated serum PTH levels at least once during the postoperative study period, with normal or slightly decreased calcium concentrations. The prediction of late postoperative normocalcemia by means of intraoperative PTH measurement had an overall accuracy of 95%. The measurement of intraoperative PTH during surgery for primary hyperparathyroidism accurately differentiates between single- and multiple-gland disease and ensures good long-term results.

CaPTHUS scoring model in primary hyperparathyroidism: can it eliminate the need for ioPTH testing?

PubMed

Elfenbein, Dawn M; Weber, Sara; Schneider, David F; Sippel, Rebecca S; Chen, Herbert

2015-04-01

The CaPTHUS model was reported to have a positive predictive value of 100 % to correctly predict single-gland disease in patients with primary hyperparathyroidism, thus obviating the need for intraoperative parathyroid hormone (ioPTH) testing. We sought to apply the CaPTHUS scoring model in our patient population and assess its utility in predicting long-term biochemical cure. We retrospective reviewed all parathyroidectomies for primary hyperparathyroidism performed at our university hospital from 2003 to 2012. We routinely perform ioPTH testing. Biochemical cure was defined as a normal calcium level at 6 months. A total of 1,421 patients met the inclusion criteria: 78 % of patients had a single adenoma at the time of surgery, 98 % had a normal serum calcium at 1 week postoperatively, and 96 % had a normal serum calcium level 6 months postoperatively. Using the CaPTHUS scoring model, 307 patients (22.5 %) had a score of ≥ 3, with a positive predictive value of 91 % for single adenoma. A CaPTHUS score of ≥ 3 had a positive predictive value of 98 % for biochemical cure at 1 week as well as at 6 months. In our population, where ioPTH testing is used routinely to guide use of bilateral exploration, patients with a preoperative CaPTHUS score of ≥ 3 had good long-term biochemical cure rates. However, the model only predicted adenoma in 91 % of cases. If minimally invasive parathyroidectomy without ioPTH testing had been done for these patients, the cure rate would have dropped from 98 % to an unacceptable 89 %. Even in these patients with high CaPTHUS scores, multigland disease is present in almost 10 %, and ioPTH testing is necessary.

Evidence that low plasma 1,25-dihydroxyvitamin D causes intestinal malabsorption of calcium and phosphate in juvenile X-linked hypophosphatemic mice.

PubMed

Meyer, R A; Meyer, M H; Gray, R W; Bruns, M E

1987-02-01

X-linked hypophosphatemic (Hyp) mice are a model for human sex-linked vitamin D-resistant rickets. We have reported intestinal malabsorption of calcium in young Hyp mice, and in this report we have explored the mechanism for it. To test for resistance of the intestine to 1,25(OH)2 vitamin D3, this hormone was continually infused via osmotic minipumps into 4-week-old normal and Hyp mice at 0, 17, 50 or 150 ng/kg/day. After 3 days, 45Ca and inorganic 32P were administered by gavage, and the mice were sacrificed on the fifth day. The Hyp mice showed responses to the hormone equivalent to the normal mice in terms of increased intestinal absorption of both 45Ca and 32P, increased plasma isotope levels, increased femoral isotope content, and increased duodenal and renal 9 kD vitamin D-dependent calcium-binding protein (calbindin-D9K; CaBP). Plasma 1,25(OH)2D was measured in these mice. There were significant correlations of plasma 1,25(OH)2D to the intestinal absorption of 45Ca and 32P and to duodenal and renal CaBP. Plasma 1,25(OH)2D was also measured in stock normal and Hyp mice and was found to be lower in 4-week-old Hyp mice than in 4-week-old normal mice (113 +/- 10 pM (n = 18) vs. 67 +/- 10 (n = 20), normal vs. Hyp, p less than .01), but unchanged at 13 weeks of age (77 +/- 13 (n = 13) vs. 70 +/- 15 (n = 15), NS). This observed difference in plasma 1,25(OH)2D between normal and Hyp mice at 4 weeks of age was sufficient to explain the observed normal-to-Hyp differences in intestinal absorption of 45Ca and duodenal and renal CaBP. It also explained 72 +/- 18% of the observed difference in 32P absorption. We conclude that Hyp mouse intestine is not resistant to 1,25(OH)2D and that the lower plasma 1,25(OH)2D of 4-week-old Hyp mice causes intestinal malabsorption of calcium and phosphate.

Reversibility of electrophysiological changes induced by chronic high-altitude hypoxia in adult rat heart.

PubMed

Chouabe, C; Amsellem, J; Espinosa, L; Ribaux, P; Blaineau, S; Mégas, P; Bonvallet, R

2002-04-01

Recent studies indicate that regression of left ventricular hypertrophy normalizes membrane ionic current abnormalities. This work was designed to determine whether regression of right ventricular hypertrophy induced by permanent high-altitude exposure (4,500 m, 20 days) in adult rats also normalizes changes of ventricular myocyte electrophysiology. According to the current data, prolonged action potential, decreased transient outward current density, and increased inward sodium/calcium exchange current density normalized 20 days after the end of altitude exposure, whereas right ventricular hypertrophy evidenced by both the right ventricular weight-to-heart weight ratio and the right ventricular free wall thickness measurement normalized 40 days after the end of altitude exposure. This morphological normalization occurred at both the level of muscular tissue, as shown by the decrease toward control values of some myocyte parameters (perimeter, capacitance, and width), and the level of the interstitial collagenous connective tissue. In the chronic high-altitude hypoxia model, the regression of right ventricular hypertrophy would not be a prerequisite for normalization of ventricular electrophysiological abnormalities.

Serum ionized calcium, intact PTH and novel markers of bone turnover in bedridden elderly patients.

PubMed

Sorva, A; Välimäki, M; Risteli, J; Risteli, L; Elfving, S; Takkunen, H; Tilvis, R

1994-12-01

Chronic immobilization could markedly affect calcium and bone metabolism in elderly people. To investigate this, and to test the theory of 'type II' osteoporosis in bedridden elderly patients with low vitamin D status, 55 such subjects were examined. Serum concentrations of ionized calcium (Ca++), intact parathyrin (PTH) and two novel markers of bone collagen formation (carboxyterminal propeptide of type I procollagen; PICP) and resorption (carboxyterminal crosslinked telopeptide of type I collagen; ICTP) were measured. The effects on these parameters after 40 weeks of supplementation with vitamin D (1000 IU d-1) and/or calcium (1 g d-1) were subsequently prospectively evaluated. Despite low (mean 11.6 nmoll-1) serum 25-hydroxyvitamin D levels (25-OHD), those of 1,25-dihydroxy-vitamin D (1,25-(OH)2D) were mostly normal. Neither correlated with Ca++ or PTH. PTH correlated negatively not only with Ca++ (r = -0.328, P < 0.05) but also with ICTP (r = -0.306, P < 0.05). Mean PICP was normal but ICTP was elevated and tended to correlate positively with Ca++ (r = 0.268, P = 0.06). Vitamin D supplementation did not change PICP or ICTP considerably, despite slightly increased 1,25-(OH)2D and slightly decreased PTH. Ca++ values were normal and remained stable. In conclusion, Ca++ and PTH are poor indicators of vitamin D status in chronically immobilized elderly subjects. Furthermore, the results suggest that the increased bone resorption is not due to 'type II' secondary hyperparathyroidism; rather the resorption is primarily increased. Correction of vitamin D deficiency does not seem to benefit ageing bones unless adequate mechanical loading is provided.

Influence of the autonomic nervous system on calcium homeostasis in the rat.

PubMed

Stern, J E; Cardinali, D P

1994-01-01

The local surgical manipulation of sympathetic and parasympathetic nerves innervating the thyroid-parathyroid territory was employed to search for the existence of a peripheral neuroendocrine link controlling parathyroid hormone (PTH) and calcitonin (CT) release. From 8 to 24 h after superior cervical ganglionectomy (SCGx), at the time of wallerian degeneration of thyroid-parathyroid sympathetic nerve terminals, an alpha-adrenergic inhibition, together with a minor beta-adrenergic stimulation, of hypercalcemia-induced CT release, and an alpha-adrenoceptor inhibition of hypocalcemia-induced PTH release were found. In chronically SCGx rats PTH response to EDTA was slower, and after CaCl2 injection, serum calcium attained higher levels in face of normal CT levels. SCGx blocked the PTH increase found in sham-operated rats stressed by a subcutaneous injection of turpentine oil, but did not affect the greater response to EDTA. The higher hypocalcemia seen after turpentine oil was no longer observed in SCGx rats. The effects of turpentine oil stress on calcium and CT responses to a bolus injection of CaCl2 persisted in rats subjected to SCGx 14 days earlier. Interruption of thyroid-parathyroid parasympathetic input conveyed by the thyroid nerves (TN) and the inferior laryngeal nerves (ILN) caused a fall in total serum calcium, an increase of PTH levels and a decrease of CT levels, when measured 10 days after surgery. Greater responses of serum CT and PTH were detected in TN-sectioned, and in TN- or ILN-sectioned rats, respectively. Physiological concentrations of CT decreased, and those of PTH increased, in vitro cholinergic activity in rat SCG, measured as specific choline uptake, and acetylcholine synthesis and release. The results indicate that cervical autonomic nerves constitute a pathway through which the brain modulates calcium homeostasis.

Calcium and bones

MedlinePlus

... as you get older. This can result in brittle, fragile bones that can break easily, even without a fall or other injury. The digestive system is normally very bad at absorbing calcium. Most people absorb only 15% to 20% of the calcium ...

Protein tyrosine phosphatase 1B is a mediator of cyclic ADP ribose-induced Ca2+ signaling in ventricular myocytes.

PubMed

Park, Seon-Ah; Hong, Bing-Zhe; Ha, Ki-Chan; Kim, Uh-Hyun; Han, Myung-Kwan; Kwak, Yong-Geun

2017-06-02

Cyclic ADP-ribose (cADPR) releases Ca 2+ from ryanodine receptor (RyR)-sensitive calcium pools in various cell types. In cardiac myocytes, the physiological levels of cADPR transiently increase the amplitude and frequency of Ca 2+ (that is, a rapid increase and decrease of calcium within one second) during the cardiac action potential. In this study, we demonstrated that cADPR levels higher than physiological levels induce a slow and gradual increase in the resting intracellular Ca 2+ ([Ca 2+ ] i ) level over 10 min by inhibiting the sarcoendoplasmic reticulum Ca 2+ ATPase (SERCA). Higher cADPR levels mediate the tyrosine-dephosphorylation of α-actin by protein tyrosine phosphatase 1B (PTP1B) present in the endoplasmic reticulum. The tyrosine dephosphorylation of α-actin dissociates phospholamban, the key regulator of SERCA, from α-actin and results in SERCA inhibition. The disruption of the integrity of α-actin by cytochalasin B and the inhibition of α-actin tyrosine dephosphorylation by a PTP1B inhibitor block cADPR-mediated Ca 2+ increase. Our results suggest that levels of cADPR that are relatively higher than normal physiological levels modify calcium homeostasis through the dephosphorylation of α-actin by PTB1B and the subsequent inhibition of SERCA in cardiac myocytes.

Calcium orthophosphates: occurrence, properties, biomineralization, pathological calcification and biomimetic applications.

PubMed

Dorozhkin, Sergey V

2011-01-01

The present overview is intended to point the readers' attention to the important subject of calcium orthophosphates. This type of materials is of special significance for human beings, because they represent the inorganic part of major normal (bones, teeth and antlers) and pathological (i.e., those appearing due to various diseases) calcified tissues of mammals. For example, atherosclerosis results in blood vessel blockage caused by a solid composite of cholesterol with calcium orthophosphates, while dental caries and osteoporosis mean a partial decalcification of teeth and bones, respectively, that results in replacement of a less soluble and harder biological apatite by more soluble and softer calcium hydrogenphosphates. Therefore, the processes of both normal and pathological calcifications are just an in vivo crystallization of calcium orthophosphates. Similarly, dental caries and osteoporosis might be considered an in vivo dissolution of calcium orthophosphates. Thus, calcium orthophosphates hold a great significance for humankind, and in this paper, an overview on the current knowledge on this subject is provided.

Effects of atorvastatin and losartan on monocrotaline-induced pulmonary artery remodeling in rats.

PubMed

Xie, Liangdi; Lin, Peisen; Xie, Hong; Xu, Changsheng

2010-01-01

Structural remodeling of pulmonary artery plays an important role in maintaining sustained pulmonary arterial hypertension (PAH). The anti-remodeling effects of statins have been reported in systemic hypertension. In this study, we studied the effects of atovastatin (Ato) or losartan (Los) in monocrotaline (MCL)-induced pulmonary artery remodeling using a rat model. Forty Sprague-Dawley (SD) rats were randomly assigned into four groups (n = 10): normal control (Ctr), PAH, PAH treated with Los, and PAH treated with Ato. We found that in the Los- or Ato-treated group, the mean pulmonary arterial pressure, right heart hypertrophy index, ratio of wall/lumen thickness (WT%), as well as the wall/lumen area (WA%) were significantly reduced compared to the PAH group. Also in pulmonary arteries dissected from rats in the Ato- or Los-treated group, in both mRNA and protein levels, the expression of α1C subunit of voltage-gated calcium channel (Ca(v)α1c) was downregulated, while sarcoplasmic/endoplasmic reticulum calcium-ATPase (SERCA-2a) and inositol 1,4,5 triphosphate receptor 1 (IP3R-1) upregulated. However, the mRNA level of RyR-3 subunit of calcium regulating channel was increased, whereas its protein level was reduced in the treated groups. Our results suggest that atorvastatin or losartan may regress the remodeling of the pulmonary artery in pulmonary hypertensive rats, with differential expression of calcium regulating channels.

Clinical and laboratory characteristics of neonatal hypocalcemia

PubMed Central

Cho, Won Im; Yu, Hyeoh Won; Shin, Choong Ho; Yang, Sei Won; Choi, Chang Won; Kim, Beyong Il

2015-01-01

Purpose To describe the clinical characteristics of full-term neonates with hypocalcemia and to suggest factors associated with neonatal hypocalcemia Methods The medical records of full-term neonates with hypocalcemia were reviewed. Hypocalcemia was defined as an ionized calcium (iCa) concentration of <4 mg/dL. Parathyroid hormone (PTH) insufficiency was defined as a serum PTH level of <60 pg/mL or a serum phosphorus level higher than the serum calcium level in the presence of hypocalcemia. Results Fifty-three neonates were enrolled. The median age at diagnosis of hypocalcemia was 3 days. In all the neonates, formula feeding predominance was observed. Thirty-eight neonates (69.8%) were compatible with PTH insufficiency. The number of formula-fed neonates was significantly higher than that of breast-fed patients among neonates with PTH insufficiency (P=0.017). Intact PTH was negatively correlated with serum phosphorus levels. Twelve out of 14 neonates (85.7%) had 25-hydroxy vitamin D (25OHD) levels <20 ng/mL and 9 neonates (64.3%) had 25OHD levels <10 ng/mL. Twenty-one neonates had hypocalcemic tetany. The serum calcium and iCa concentrations of neonates with tetany were 4.2-8.3 mg/dL and 1.85-3.88 mg/dL, respectively. Three neonates showed symptomatic hypocalcemia with calcium levels over 7.5 mg/dL. Among the 16 neonates who underwent electroencephalography (EEG), 12 had abnormalities, which normalized after 1-2 months. Conclusion Formula milk feeding, PTH insufficiency and low serum vitamin D concentration are associated with the development of neonatal hypocalcemia. Symptoms such as tetany and QT interval prolongation can develop in relatively mild hypocalcemia. Moreover, transient neonatal hypocalcemia can cause transient EEG abnormalities. PMID:26191512

Parathyroid gland angiography with indocyanine green fluorescence to predict parathyroid function after thyroid surgery

PubMed Central

Vidal Fortuny, J.; Belfontali, V.; Sadowski, S. M.; Karenovics, W.; Guigard, S.

2016-01-01

Background Postoperative hypoparathyroidism remains the most common complication following thyroidectomy. The aim of this pilot study was to evaluate the use of intraoperative parathyroid gland angiography in predicting normal parathyroid gland function after thyroid surgery. Methods Angiography with the fluorescent dye indocyanine green (ICG) was performed in patients undergoing total thyroidectomy, to visualize vascularization of identified parathyroid glands. Results Some 36 patients underwent ICG angiography during thyroidectomy. All patients received standard calcium and vitamin D supplementation. At least one well vascularized parathyroid gland was demonstrated by ICG angiography in 30 patients. All 30 patients had parathyroid hormone (PTH) levels in the normal range on postoperative day (POD) 1 and 10, and only one patient exhibited asymptomatic hypocalcaemia on POD 1. Mean(s.d.) PTH and calcium levels in these patients were 3·3(1·4) pmol/l and 2·27(0·10) mmol/l respectively on POD 1, and 4·0(1.6) pmol/l and 2·32(0·08) mmol/l on POD 10. Two of the six patients in whom no well vascularized parathyroid gland could be demonstrated developed transient hypoparathyroidism. None of the 36 patients presented symptomatic hypocalcaemia, and none received treatment for hypoparathyroidism. Conclusion PTH levels on POD 1 were normal in all patients who had at least one well vascularized parathyroid gland demonstrated during surgery by ICG angiography, and none required treatment for hypoparathyroidism. PMID:26864909

Osteomalacia mimicking spondyloarthropathy: a case report.

PubMed

Garip, Y; Dedeoglu, M; Bodur, H

2014-07-01

Osteomalacia is a metabolic bone disorder characterized by impaired mineralization of bone matrix. Symptoms of osteomalacia can be confused with other conditions such as spondyloarthropathy, polymyalgia rheumatica, polymyositis, and fibromyalgia. In this case, we report a patient with axial osteomalacia who developed low back pain, morning stiffness, and "grade 3 sacroiliitis" in pelvis X-ray, leading to the misdiagnosis as seronegative spondyloarthropathy. Serum biochemical studies revealed low serum phosphorus, low 25-hydroxy vitamin D3, normal calcium, elevated parathyroid hormone, and alkaline phosphatase levels. Her symptoms were relieved with vitamin D and calcium therapy. The diagnosis of osteomalacia should be considered in case of sacroiliitis and spondylitis.

Effects of supplemental calcium and vitamin D on the APC/β-catenin pathway in the normal colorectal mucosa of colorectal adenoma patients.

PubMed

Liu, Siyu; Barry, Elizabeth L; Baron, John A; Rutherford, Robin E; Seabrook, March E; Bostick, Roberd M

2017-02-01

APC/β-catenin pathway malfunction is a common and early event in colorectal carcinogenesis. To assess calcium and vitamin D effects on the APC/β-catenin pathway in the normal-appearing colorectal mucosa of sporadic colorectal adenoma patients, nested within a larger randomized, double-blind, placebo-controlled, partial 2 × 2 factorial chemoprevention clinical trial of supplemental calcium (1200 mg daily) and vitamin D (1000 IU daily), alone and in combination versus placebo, we assessed APC, β-catenin, and E-cadherin expression in colon crypts in normal-appearing rectal mucosa biopsies from 104 participants at baseline and 1-yr follow up using standardized, automated immunohistochemistry and quantitative image analysis. For vitamin D versus no vitamin D, the ratio of APC expression to β-catenin expression in the upper 40% (differentiation zone) of crypts (APC/β-catenin score) increased by 28% (P = 0.02), for calcium versus no calcium it increased by 1% (P = 0.88), and for vitamin D + calcium versus calcium by 35% (P = 0.01). Total E-cadherin expression increased by 7% (P = 0.35) for vitamin D versus no vitamin D, 8% (P = 0.31) for calcium versus no calcium, and 12% (P = 0.21) for vitamin D + calcium versus calcium. These results support (i) that vitamin D, alone or in combination with calcium, may modify APC, β-catenin, and E-cadherin expression in humans in directions hypothesized to reduce risk for colorectal neoplasms; (ii) vitamin D as a potential chemopreventive agent against colorectal neoplasms; and (iii) the potential of APC, β-catenin, and E-cadherin expression as treatable, pre-neoplastic risk biomarkers for colorectal neoplasms. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

An unusual case of hyperthyroidism associated with jaundice and hypercalcaemia.

PubMed

Klangjareonchai, Theerawut

2012-05-08

A 51-year-old woman with rheumatoid arthritis presented with a 3 month history of painless jaundice and significant weight loss and constipation. Laboratory values were consistent with hyperthyroidism, cholestatic jaundice and parathyroid hormone-independent hypercalcaemia. Three months after beginning of methimazole, euthyroidism was achieved and serum adjusted calcium, total and direct bilirubin levels were normal.

Acidity of Lakes and Impoundments in North-Central Minnesota

Treesearch

Elon S. Verry

1981-01-01

Measurements of lake and impoundment pH for several years, intensive sampling within years, and pH-calcium plots verify normal pH levels and do not show evidence of changes due to acid precipitation. These data in comparison with general lake data narrow the northern Lake States area in which rain or snow may cause lake acidification.

Alkaline phosphatase as a screening test for osteomalacia.

PubMed

Chinoy, Muhammad Amin; Javed, Muhammad Imran; Khan, Alamzeb; Sadruddin, Nooruddin

2011-01-01

Vitamin D deficiency remains common in children and adults in Pakistan despite adequate sunlight exposure. Diagnosis in adults is usually delayed and is made following pathological fractures that result in significant morbidity. The objective of this study was to see whether Serum Alkaline Phosphatase levels could be used as a screening test for osteomalacia. The Study was conducted at Fatima Hospital, Baqai Medical University, Gadap, Karachi, between July 2002 and June 2005. Serum calcium levels are commonly used to screen patients suspected of osteomalacia, and raised serum alkaline phosphatase (SALP) is considered a diagnostic finding. We used SALP to screen patients who presented with back or non-specific aches and pain of more than six months duration. Three hundred thirty-four (334) patients were screened of which 116 (35%) had raised SALP. Osteomalacia was diagnosed in 92 (79.3%) of these 116 either by plain radiographs, bone biopsy or isotope bone scan. Fifty-four (53.4%) of the 101 cases had a normal level of serum calcium. Osteomalacia is likely to be missed if only serum calcium is used to screen patients. Serum Alkaline Phosphate should be used as the preferred method for screening these patients.

Urine risk factors in children with calcium kidney stones and their siblings

PubMed Central

Bergsland, Kristin J.; Coe, Fredric L.; White, Mark D.; Erhard, Michael J.; DeFoor, William R.; Mahan, John D.; Schwaderer, Andrew L.; Asplin, John R.

2012-01-01

Calcium nephrolithiasis in children is increasing in prevalence and tends to be recurrent. Although children have a lower incidence of nephrolithiasis than adults, its etiology in children is less well understood; hence treatments targeted for adults may not be optimal in children. To better understand metabolic abnormalities in stone forming children, we compared chemical measurements and the crystallization properties of 24-hour urine collections from 129 stone formers matched to 105 non-stone forming siblings and 183 normal, healthy children with no family history of stones; all aged 6 to 17 years. The principal risk factor for calcium stone formation was hypercalciuria. Stone formers have strikingly higher calcium excretion along with high supersaturation for calcium oxalate and calcium phosphate, and a reduced distance between the upper limit of metastability and supersaturation for calcium phosphate, indicating increased risk of calcium phosphate crystallization. Other differences in urine chemistry that exist between adult stone formers and normal individuals such as hyperoxaluria, hypocitraturia, abnormal urine pH and low urine volume were not found in these children. Hence, hypercalciuria and a reduction in the gap between calcium phosphate upper limit of metastability and supersaturation are crucial determinants of stone risk. This highlights the importance of managing hypercalciuria in children with calcium stones. PMID:22358148

Restricting calcium currents is required for correct fiber type specification in skeletal muscle

PubMed Central

Sultana, Nasreen; Dienes, Beatrix; Benedetti, Ariane; Tuluc, Petronel; Szentesi, Peter; Sztretye, Monika; Rainer, Johannes; Hess, Michael W.; Schwarzer, Christoph; Obermair, Gerald J.; Csernoch, Laszlo

2016-01-01

ABSTRACT Skeletal muscle excitation-contraction (EC) coupling is independent of calcium influx. In fact, alternative splicing of the voltage-gated calcium channel CaV1.1 actively suppresses calcium currents in mature muscle. Whether this is necessary for normal development and function of muscle is not known. However, splicing defects that cause aberrant expression of the calcium-conducting developmental CaV1.1e splice variant correlate with muscle weakness in myotonic dystrophy. Here, we deleted CaV1.1 (Cacna1s) exon 29 in mice. These mice displayed normal overall motor performance, although grip force and voluntary running were reduced. Continued expression of the developmental CaV1.1e splice variant in adult mice caused increased calcium influx during EC coupling, altered calcium homeostasis, and spontaneous calcium sparklets in isolated muscle fibers. Contractile force was reduced and endurance enhanced. Key regulators of fiber type specification were dysregulated and the fiber type composition was shifted toward slower fibers. However, oxidative enzyme activity and mitochondrial content declined. These findings indicate that limiting calcium influx during skeletal muscle EC coupling is important for the secondary function of the calcium signal in the activity-dependent regulation of fiber type composition and to prevent muscle disease. PMID:26965373

Urine risk factors in children with calcium kidney stones and their siblings.

PubMed

Bergsland, Kristin J; Coe, Fredric L; White, Mark D; Erhard, Michael J; DeFoor, William R; Mahan, John D; Schwaderer, Andrew L; Asplin, John R

2012-06-01

Calcium nephrolithiasis in children is increasing in prevalence and tends to be recurrent. Although children have a lower incidence of nephrolithiasis than adults, its etiology in children is less well understood; hence, treatments targeted for adults may not be optimal in children. To better understand metabolic abnormalities in stone-forming children, we compared chemical measurements and the crystallization properties of 24-h urine collections from 129 stone formers matched to 105 non-stone-forming siblings and 183 normal, healthy children with no family history of stones, all aged 6 to 17 years. The principal risk factor for calcium stone formation was hypercalciuria. Stone formers have strikingly higher calcium excretion along with high supersaturation for calcium oxalate and calcium phosphate, and a reduced distance between the upper limit of metastability and supersaturation for calcium phosphate, indicating increased risk of calcium phosphate crystallization. Other differences in urine chemistry that exist between adult stone formers and normal individuals such as hyperoxaluria, hypocitraturia, abnormal urine pH, and low urine volume were not found in these children. Hence, hypercalciuria and a reduction in the gap between calcium phosphate upper limit of metastability and supersaturation are crucial determinants of stone risk. This highlights the importance of managing hypercalciuria in children with calcium stones.

A case report: Giant cystic parathyroid adenoma presenting with parathyroid crisis after Vitamin D replacement.

PubMed

Asghar, Ali; Ikram, Mubasher; Islam, Najmul

2012-07-28

Parathyroid adenoma with cystic degeneration is a rare cause of primary hyperparathyroidism. The clinical and biochemical presentation may mimic parathyroid carcinoma. We report the case of a 55 year old lady, who had longstanding history of depression and acid peptic disease. Serum calcium eight months prior to presentation was slightly high, but she was never worked up. She was found to be Vitamin D deficient while being investigated for generalized body aches. A month after she was replaced with Vitamin D, she presented to us with parathyroid crisis. Her corrected serum calcium was 23.0 mg/dL. She had severe gastrointestinal symptoms and acute kidney injury. She had unexplained consistent hypokalemia until surgery. Neck ultrasound and CT scan revealed giant parathyroid cyst extending into the mediastinum. After initial medical management for parathyroid crisis, parathyroid cystic adenoma was surgically excised. Her serum calcium, intact parathyroid hormone, creatinine and potassium levels normalized after surgery. This case of parathyroid crisis, with very high serum calcium and parathyroid hormone levels, is a rare presentation of parathyroid adenoma with cystic degeneration. This case also highlights that Vitamin D replacement may unmask subclinical hyperparathyroidism. Consistent hypokalemia until surgery merits research into its association with hypercalcemia.

Vitamin D: a hormone for all seasons.

PubMed

Mason, R S

2011-04-01

Vitamin D is principally obtained from skin through the action of ultraviolet B irradiation on 7-dehydrocholesterol. It is further metabolized to 25-hydroxyvitamin D, the major circulating vitamin D compound, and then to 1,25-dihydroxyvitamin D, the hormonal form. The major function of vitamin D compounds is to enhance active absorption of calcium (and phosphate) from the gut, ensuring that bone does not need to be resorbed to maintain blood calcium concentrations despite obligatory urinary losses. Vitamin D compounds have direct effects to enhance bone and muscle function. Based on good evidence, target levels for 25-hydroxyvitamin D in blood are at least 50 nmol/l and there may be a case for higher targets of 75-80 nmol/l. Adequate calcium intakes help to reduce vitamin D degradation. Vitamin D and calcium together reduce the risk of falls and fractures in older people. There are vitamin D receptors in most nucleated cells and preliminary evidence that adequate vitamin D levels may be important in reducing the incidence of, or mortality from, some cancers, and in reducing autoimmune disease. Adequate vitamin D may also allow for a normal innate immune response to pathogens, improve cardiovascular function and mortality, and reduce type 2 diabetes. Supplemental vitamin D seems to work in a generally similar manner to skin-derived vitamin D.

Calcium sensitivity of dicarboxylate transport in cultured proximal tubule cells

PubMed Central

Schiro, Faith R.; Pajor, Ana M.; Hamm, L. Lee

2011-01-01

Urinary citrate is an important inhibitor of calcium nephrolithiasis and is primarily determined by proximal tubule reabsorption. The major transporter to reabsorb citrate is Na+-dicarboxylate cotransporter (NaDC1), which transports dicarboxylates, including the divalent form of citrate. We previously found that opossum kidney (OK) proximal tubule cells variably express either divalent or trivalent citrate transport, depending on extracellular calcium. The present studies were performed to delineate the mechanism of the effect of calcium on citrate and succinate transport in these cells. Transport was measured using isotope uptake assays. In some studies, NaDC1 transport was studied in Xenopus oocytes, expressing either the rabbit or opossum ortholog. In the OK cell culture model, lowering extracellular calcium increased both citrate and succinate transport by more than twofold; the effect was specific in that glucose transport was not altered. Citrate and succinate were found to reciprocally inhibit transport at low extracellular calcium (<60 μM), but not at normal calcium (1.2 mM); this mutual inhibition is consistent with dicarboxylate transport. The inhibition varied progressively at intermediate levels of extracellular calcium. In addition to changing the relative magnitude and interaction of citrate and succinate transport, decreasing calcium also increased the affinity of the transport process for various other dicarboxylates. Also, the affinity for succinate, at low concentrations of substrate, was increased by calcium removal. In contrast, in oocytes expressing NaDC1, calcium did not have a similar effect on transport, indicating that NaDC1 could not likely account for the findings in OK cells. In summary, extracellular calcium regulates constitutive citrate and succinate transport in OK proximal tubule cells, probably via a novel transport process that is not NaDC1. The calcium effect on citrate transport parallels in vivo studies that demonstrate the regulation of urinary citrate excretion with urinary calcium excretion, a process that may be important in decreasing urinary calcium stone formation. PMID:21123491

Inhibition of Glycolate Oxidase With Dicer-substrate siRNA Reduces Calcium Oxalate Deposition in a Mouse Model of Primary Hyperoxaluria Type 1

PubMed Central

Dutta, Chaitali; Avitahl-Curtis, Nicole; Pursell, Natalie; Larsson Cohen, Marita; Holmes, Benjamin; Diwanji, Rohan; Zhou, Wei; Apponi, Luciano; Koser, Martin; Ying, Bo; Chen, Dongyu; Shui, Xue; Saxena, Utsav; Cyr, Wendy A; Shah, Anee; Nazef, Naim; Wang, Weimin; Abrams, Marc; Dudek, Henryk; Salido, Eduardo; Brown, Bob D; Lai, Chengjung

2016-01-01

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive, metabolic disorder caused by mutations of alanine-glyoxylate aminotransferase (AGT), a key hepatic enzyme in the detoxification of glyoxylate arising from multiple normal metabolic pathways to glycine. Accumulation of glyoxylate, a precursor of oxalate, leads to the overproduction of oxalate in the liver, which accumulates to high levels in kidneys and urine. Crystalization of calcium oxalate (CaOx) in the kidney ultimately results in renal failure. Currently, the only treatment effective in reduction of oxalate production in patients who do not respond to high-dose vitamin B6 therapy is a combined liver/kidney transplant. We explored an alternative approach to prevent glyoxylate production using Dicer-substrate small interfering RNAs (DsiRNAs) targeting hydroxyacid oxidase 1 (HAO1) mRNA which encodes glycolate oxidase (GO), to reduce the hepatic conversion of glycolate to glyoxylate. This approach efficiently reduces GO mRNA and protein in the livers of mice and nonhuman primates. Reduction of hepatic GO leads to normalization of urine oxalate levels and reduces CaOx deposition in a preclinical mouse model of PH1. Our results support the use of DsiRNA to reduce liver GO levels as a potential therapeutic approach to treat PH1. PMID:26758691

Artefactual serum hyperkalaemia and hypercalcaemia in essential thrombocythaemia

PubMed Central

Howard, M; Ashwell, S; Bond, L; Holbrook, I

2000-01-01

Aim—To investigate possible abnormalities of serum potassium and calcium levels in patients with essential thrombocythaemia and significant thrombocytosis. Methods—24 cases of essential thrombocythaemia with significant thrombocytosis (platelet count > 700 x 109/litre) had serum potassium and calcium estimations performed at the time of maximum thrombocytosis before treatment, and at the time of low platelet count after treatment with cytoreductive drugs. Selected patients were further investigated with plasma sampling and estimation of ionised calcium and parathyroid hormone. Results—At the time of maximum thrombocytosis six patients had serum hyperkalaemia (> 5.5 mmol/litre) and five had serum hypercalcaemia (> 2.6 mmol/litre). Following treatment and reduction of the platelet count, hyperkalaemia resolved in all cases and hypercalcaemia in four of the five cases. Mean serum potassium and calcium concentrations were raised (p < 0.0001) at maximum thrombocytosis compared with the values when the platelet count was low. Serum potassium and calcium values were significantly correlated at all stages. Measurements on plasma consistently corrected the hyperkalaemia but not the hypercalcaemia. Serum hypercalcaemia was associated with raised ionised calcium and normal parathyroid hormone concentrations. Conclusions—Essential thrombocythaemia with significant thrombocytosis is associated with serum hyperkalaemia and hypercalcaemia. The probable mechanism of hypercalcaemia is the secretion of calcium in vitro from an excessive number of abnormally activated platelets. It is thus likely that the hypercalcaemia is an artefact, as is the hyperkalaemia. Key Words: thrombocythaemia • hypercalcaemia • hyperkalaemia PMID:10767824

[Dropped head syndrome as first manifestation of primary hyperparathyroid myopathy].

PubMed

Ota, Kiyobumi; Koseki, Sayo; Ikegami, Kenji; Onishi, Iichiroh; Tomimitsu, Hiyoryuki; Shintani, Shuzo

2018-03-28

75 years old woman presented with 6-month history of progressive dropped head syndrome. Neurological examination revealed moderate weakness of flexor and extensor of neck and mild weakness of proximal appendicular muscles with normal deep tendon reflexes. The needle electromyography showed short duration and low amplitude motor unit potential. No fibrillation potentials or positive sharp waves were seen. Biopsy of deltoid muscle was normal. Laboratory studies showed elevated levels of serum calcium (11.8 mg/dl, upper limit of normal 10.1) and intact parathyroid hormone (104 pg/ml, upper limit of normal 65), and decreased level of serum phosphorus (2.3 mg/dl, lower limit of normal 2.7). Ultrasonography and enhanced computed tomography revealed a parathyroid tumor. The tumor was removed surgically. Pathological examination proved tumor to be parathyroid adenoma. Dropped head and weakness of muscles were dramatically improved within a week after the operation. Although hyperparathyroidism is a rare cause of dropped head syndrome, neurologists must recognize hyperparathyroidism as a treatable cause of dropped head syndrome.

Calcium oxalate monohydrate aggregation induced by aggregation of desialylated Tamm-Horsfall protein

PubMed Central

Viswanathan, Pragasam; Rimer, Jeffrey D.; Kolbach, Ann M.; Kleinman, Jack G.

2011-01-01

Tamm-Horsfall protein (THP) is thought to protect against calcium oxalate monohydrate (COM) stone formation by inhibiting COM aggregation. Several studies reported that stone formers produce THP with reduced levels of glycosylation, particularly sialic acid levels, which leads to reduced negative charge. In this study, normal THP was treated with neuraminidase to remove sialic acid residues, confirmed by an isoelectric point shift to higher pH. COM aggregation assays revealed that desialylated THP (ds-THP) promoted COM aggregation, while normal THP inhibited aggregation. The appearance of protein aggregates in solutions at ds-THP concentrations ≥1 µg/mL in 150 mM NaCl correlated with COM aggregation promotion, implying that ds-THP aggregation induced COM aggregation. The aggregation-promoting effect of the ds-THP was independent of pH above its isoelectric point, but was substantially reduced at low ionic strength, where protein aggregation was much reduced. COM aggregation promotion was maximized at a ds-THP to COM mass ratio of ~0.025, which can be explained by a model wherein partial COM surface coverage by ds-THP aggregates promotes crystal aggregation by bridging opposing COM surfaces, whereas higher surface coverage leads to repulsion between adsorbed ds-THP aggregates. Thus, desialylation of THP apparently abrogates a normal defensive action of THP by inducing protein aggregation, and subsequently COM aggregation, a condition that favors kidney stone formation. PMID:21229239

Calcium antagonists modulate oxidative stress and acrosomal reaction in rat spermatozoa.

PubMed

Morakinyo, Ayodele; Iranloye, Bolanle; Adegoke, Olufeyisipe

2011-08-01

Calcium ions are vital in many biological processes and qualify as an almost ubiquitous intracellular second messenger. This indicates the multiplicity of the effects associated with drug actions aimed at interfering with calcium ions. To examine the cellular process involved in the induction of infertility in males by calcium antagonist (CA) even in the presence of normal semen parameters, we studied the effects of different CA namely; nifedipine, verapamil and diltiazem on oxidative balance and acrosome reaction in the sperm. For this purpose, lipid peroxidation, antioxidants such as superoxide dismutase, catalase and reduced glutathione, and acrosomal reaction were determined in sperm samples of rats. Calcium antagonist causes significant oxidative stress in the epididymal sperm with increased malondialdehyde level and a concomitant decrease in antioxidant activities of catalase and superoxide dismutase. The percentage value of acrosomal-reacted sperm in the nifedipine, verapamil and diltiazem-treated rats were 41 ±2.45, 39 ±2.92 and 42 ±1.22 respectively, compared with the control group value of 86 ±2.92. It appears CA oxidatively modify the sperm resulting in functional inhibition of acrosomal reaction. Suppression of the sperm acrosomal reaction is known to have serious adverse implications for fertilization.

Imbalanced Diet Deficient in Calcium and Vitamin D- Induced Juvenile Osteopenia in Rats; the Potential Therapeutic Effect of Egyptian Moghat Roots Water Extract (Glossostemon bruguieri).

PubMed

Ghareeb, Doaa A; El-Rashidy, Fatma H; El-Mallawany, Sherif

2014-01-01

This study aimed to explore and validate a new juvenile osteopenic (JO) rat model then examine the efficacy of moghat (Glossostemon bruguieri) as an alternative reversal therapy for JO. Phytochemical screening analysis showed that moghat contains 5.8% alkaloids, 1.5% flavonoids and 13.2% total phenols. Juvenile osteopenia was induced in 15 days old Sprague- Dawley female rats by feeding them free Ca and vitamin D synthetic diet for 21 days. Osteopenic rats were either treated with moghat (0.8 g dried plant tissue/Kg body weight, orally), or with a reference nutritional supplements of calcium chloride (14 mg Ca/Kg) and vitamin D3 (7 IU/Kg), for extra 21 days. Both untreated and treated groups were compared to a control group that fed a regular pelleted food. Our results showed that osteopenic rats lost normal bone tissue architecture, 30 % of body mass, 54 % of bone mass and finally 93% of bone calcium mass. Furthermore, these rats showed a markedly increase in serum phosphate, PTH, alkaline phosphatase, aspartate transaminase activities and creatinine level as compared to the control group. Moghat administration was successfully reversed osteopenia by normalizing body and bone masses to the reference ranges, increased the bone calcium mass by 17 fold without any detectable side effects on liver and kidney physiological performance. Therefore, moghat could be considered as potent safe -JO- reversal extract.

CA-45 AND Sr-85 METABOLISM IN MAN. Progress Report for June 15, 1959- May 20, 1960

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

1960-10-31

Bone formation rate in a normal, healthy, young adult was observed to be 0.521 g calcium/day. Calcium balance and bone formation and destruction rates were studied in patients with disuse osetoporosis associated with quadriplegia secondary to poliomyelitis and patients with senile and posmenopausal osteoporosis. Renal strontium/calcium discrimination, studied for nine cases, was given by a mean factor of 4.3. This factor means that, exposed to trace amounts of strontium and normal calcium loads, the human kidney will produce a urine containing 4.3 atoms of strontium per unit filtered strontium for each atom calcium per unit filtered calcium. The mean valuemore » for gastrointestinal discrimination between endogenously secreted Sr/sup 85/ and Ca/sup 45/ was 1.4. The ratio of strontium-determined pool to calcium- determined pool was 1.04 plus or minus 0.13 (1 S.D.) and the corresponding ratio for bone formation values was 1.04 plus or minus 0.32 (1 S.D.) for nine patients studied. (C.J.G.)« less

Efficacy of colestilan in the treatment of hyperphosphataemia in renal disease patients.

PubMed

Locatelli, Francesco; Dimkovic, Nada; Spasovski, Goce

2014-07-01

Hyperphosphataemia is common in chronic kidney disease (CKD), particularly in the late stages and is associated with secondary hyperparathyroidism, abnormal bone mineralisation and increased cardiovascular morbidity/mortality. At present, there is a range of phosphate binders designed to keep serum phosphate at normal or near normal levels. Colestilan is a new binder that offers additional actions that may afford further benefits over simply lowering phosphate. This paper reviews the pharmacology and clinical data currently available in the use of colestilan to treat hyperphosphataemia in CKD stage 5 patients on dialysis. Available phosphate binders lower serum phosphorus levels to a clinically relevant extent. The balance between the risks and the potential benefits associated with each agent must be considered when choosing a binder. Calcium-based binders can lead to hypercalcaemia and/or positive calcium balance and cardiovascular calcification. Like sevelamer, colestilan is not absorbed and there is no evidence of any risk of hypercalcaemia. In addition, a significant lowering of low-density lipoprotein-cholesterol, similar to simvastatin, a reduction in plasma uric acid and a reduction in high glycosylated haemoglobin values suggest additional beneficial actions that may convert to reductions in mortality.

High calcium diet improves the liver oxidative stress and microsteatosis in adult obese rats that were overfed during lactation.

PubMed

Conceição, E P S; Moura, E G; Soares, P N; Ai, X X; Figueiredo, M S; Oliveira, E; Lisboa, P C

2016-06-01

Obesity is related to diabetes, higher oxidative stress and nonalcoholic fatty liver disease, and dietetic therapies, for instance calcium-rich diet, can improve these dysfunctions. Rats raised in small litters (SL) had increased fat depots and insulin resistance at adulthood associated with higher liver oxidative stress and microsteatosis. Thus, we evaluated if dietary calcium can improve these changes. In PN3, litter size was adjusted to 3 pups (SL group) to induce overfeeding, while controls had 10 pups until weaning. At PN120, SL group was randomly divided into: rats fed with standard chow or fed with calcium supplementation (SL-Ca group, 10 g/kg chow) for 60 days. At PN180, dietary calcium normalized food consumption, visceral fat, plasma aspartate aminotransferase (AST) and glycaemia. Concerning oxidative balance, calcium restored both higher hepatic lipid peroxidation and protein carbonylation as well as higher plasma lipid peroxidation. Higher fatty acid synthase (FAS) content, steatosis and lower protein kinase B (Akt) in SL group were normalized by dietary calcium and SL-Ca rats had lower hepatic cholesterol. Thus, calcium supplementation improved the insulin sensitivity, redox balance and steatosis in the liver. Therefore, dietary calcium can be a promising therapy for liver disease in the metabolic syndrome. Copyright © 2016 Elsevier Ltd. All rights reserved.

Light adaption of the cyclic GMP phosphodiesterase of frog photoreceptor membranes mediated by ATP and calcium ions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kawamura, S.; Bownds, M.D.

1981-05-01

The light-activated guanosine 3',5'-cyclic monophosphate (cyclic GMP) phosphodiesterase (PDE) of frog photoreceptor membranes has been assayed by measuring the evolution of protons that accompanies cyclic GMP hydrolysis. The validity of this assay has been confirmed by comparison with an isotope assay used in previous studies (Robinson et al. 1980. J. Gen. Physiol. 76: 631-645). The PDE activity elicited by either flash or continuous dim illumination is reduced if ATP is added to outer segment suspensions. This desensitization is most pronounced at low calcium levels. In 10(-9) M Ca/sup + +/, with 0.5 mM ATP and 0.5 mM GTP present, PDEmore » activity remains almost constant as dim illumination and rhodopsin bleaching continue. At intermediate Ca/sup + +/ levels (10-7-10-5M) the activity slowly increases during illumination. Finally, in 10(-4) and PDE activity is more a reflection of the total number of rhodopsin molecules bleached than of the rate of the rhodopsin bleaching. At intermediate or low calcium levels a short-lived inhibitory process is revealed by observing a nonlinear summation of responses of the enzyme to closely spaced flashes of light. Each flash makes PDE activity less responsive to successive flashes, and a steady state is obtained in which activation and inactivation are balanced. It is suggested that calcium and ATP regulation of PDE play a role in the normal light adaption processes of frog photoreceptor membranes.« less

Changes in body temperature of the unanaesthetized monkey produced by sodium and calcium ions perfused through the cerebral ventricles

PubMed Central

Myers, R. D.; Veale, W. L.; Yaksh, T. L.

1971-01-01

1. In the unanaesthetized Rhesus monkey, solutions containing sodium, calcium, potassium or magnesium in excess of the normal concentration of extracellular fluid were perfused from a lateral to the fourth ventricle through chronically implanted cannulae. 2. Sodium (11·0-88·0 mM in excess of the physiological concentration) perfused through the ventricles, caused an immediate rise in body temperature which was accompanied by vasoconstriction, piloerection and shivering. The latency of the hyperthermia was related directly to the rate of perfusion and the concentration of sodium, whereas the magnitude of the response depended upon the concentration only. When the perfusion was terminated, shivering ceased and the temperature of the monkey returned to the base line level. 3. When calcium ions were perfused in concentrations 2·5-47·9 mM in excess of that of extracellular fluid, a fall in the temperature of the animal occurred. The magnitude of the decreases depended upon the concentration of calcium in the perfusion fluid. Vasodilatation, sedation and a reduction in withdrawal reflexes accompanied the calcium-induced hypothermia. After the perfusion ended, the temperature continued to fall until the monkey began to shiver and vasoconstriction was observed in many skin areas. 4. The perfusion through the cerebral ventricles with modified Krebs solution alone or with the Krebs solution which contained potassium or magnesium ions in concentrations five to ten times normal had virtually no effect on the temperature of the monkey. 5. Since the temperature of the monkey was unchanged as long as the physiological ratio of sodium to calcium in the perfusion fluid remained constant, we conclude that the balance between these two essential cations within the brain stem could determine the neural mechanism whereby the set-point for body temperature of the primate is established. PMID:4999638

Sarcoidosis mimicking toxoplasmosis with severe hypercalcaemia and normal 1,25-dihydroxy vitamin D.

PubMed

Levy, Y; Hayek, T; Finkelstein, R

1996-09-01

We report a case of a female patient with sarcoidosis who presented with a generalized lymphadenopathy and a strong IgG serological test of toxoplasmosis. Progressive lymphadenopathy with a rising plasma calcium (up to 15 mg dL-1) with a normal plasma 1,25-dihydroxy vitamin D concentration occurred later. Corticosteroid therapy resulted in prompt clinical and biochemical responses with normalization of plasma calcium and a significant reduction in 1,25-dihydroxy vitamin D concentration. This is an exceptional presentation of sarcoidosis with severe hypercalcaemia and normal vitamin D metabolites.

Tang Wang Ming Mu Granule Attenuates Diabetic Retinopathy in Type 2 Diabetes Rats.

PubMed

Chen, Mingxia; Lv, Haibo; Gan, Jiakuan; Ren, Junguo; Liu, Jianxun

2017-01-01

Aims: This study aimed to determine the influence of Tang Wang Ming Mu granule (TWMM) on the diabetic retinopathy of diabetic rats. Methods: Male Wistar rats were divided into seven groups: normal control, diabetes model(DM), diabetes with TWMM (3.6, 7.2, and 14.4 g/kg) treatment, the positive control treatment groups of Qi Ming granules and Calcium dobesilate capsules. All rats were treated for 8 weeks. The levels of body weight, fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) in blood were measured to evaluate the antihyperglycemic activity of TWMM. Furthermore, malondialdehyde (MDA), intracellular adhesion molecule-1 (ICAM-1) and vascular endothelial growth factor (VEGF) in serum were measured to study effects of TWMM on oxidative stress and inflammatory in DM2 rats. VEGF, JAK/STAT signaling pathway and SOCS3 in retina was detected by immunohistochemistry. Results: TWMM and the positive control drugs Qi Ming and Calcium dobesilate showed a remarkable suppression of retinal neovascularization and amelioration of retinal internal limiting membrane morphology. Moreover, TWMM significantly decreased HbA1c, MDA, ICAM-1, and VEGF levels in serum of diabetic rats. However, Qi Ming granules showed significantly reduced MDA and VEGF levels ( P < 0.01, and P < 0.05, respectively), Calcium dobesilate showed significantly reduced MDA and ICAM-1levels ( P < 0.01 and P < 0.05, respectively) in serum. All drug- treated DM2 rats showed significantly lower levels of VEGF, JAK2, P-JAK2, STAT3, and P-STAT3 in retina than DM group, while TWMM and Calcium dobesilate significantly increased SOCS3 in retina. Conclusion: Our data suggest that the diabetic retina protective effect of TWMM might be related to antiinflammatory, antioxidative, upregulation of SOCS3 expression, inhibition of the JAK/STAT/VEGF signaling pathway.

Urinary excretion values in 2-day food-deprived, unrestrained chimpanzees.

NASA Technical Reports Server (NTRS)

Mcnew, J. J.; Sabbot, I. M.; Hoshizaki, T.; Mandell, A. J.; Spooner, C. E.; Marcus, I.; Adey, W. R.

1972-01-01

A study was conducted to determine the baseline 24-hr urinary excretion values in the young, unrestrained chimpanzee, and also changes in urinary values, if any, induced by the two-day food deprivation stress. Urine was analyzed for volume, osmolarity, creatinine, creatine, urea nitrogen, 17-hydroxycorticosteroids (17-OHCS), 3-methoxy-4-hydroxymandelic acid (VMA), calcium, and inorganic phosphorus. Significant increases due to food deprivation stress were observed for volume, creatine, urea nitrogen, 17-OHCS, VMA, and phosphorus values, with significant decreases in osmolarity and calcium. All values approached normal levels by the second poststress day. No significant changes were observed in creatinine. A comparison is drawn between human and chimpanzee adaptation to stress.

Maternal Hypercalcemia Due to Failure of 1,25-Dihydroxyvitamin-D3 Catabolism in a Patient With CYP24A1 Mutations

PubMed Central

Hsiao, Edward C.; O'Donnell, Betsy; Salmeen, Kirsten; Nussbaum, Robert; Krebs, Michael; Baumgartner-Parzer, Sabina; Kaufmann, Martin; Jones, Glenville; Bikle, Daniel D.; Wang, YongMei; Mathew, Allen S.; Shoback, Dolores; Block-Kurbisch, Ingrid

2015-01-01

Context: Calcium metabolism changes in pregnancy and lactation to meet fetal needs, with increases in 1,25-dihydroxyvitamin D [1,25-(OH)2D] during pregnancy playing an important role. However, these changes rarely cause maternal hypercalcemia. When maternal hypercalcemia occurs, further investigation is essential, and disorders of 1,25-(OH)2D catabolism should be carefully considered in the differential diagnosis. Case: A patient with a childhood history of recurrent renal stone disease and hypercalciuria presented with recurrent hypercalcemia and elevated 1,25-(OH)2D levels during pregnancy. Laboratory tests in the fourth pregnancy showed suppressed PTH, elevated 1,25-(OH)2D, and high-normal 25-hydroxyvitamin D levels, suggesting disordered vitamin D metabolism. Analysis revealed low 24,25-dihydroxyvitamin D3 and high 25-hydroxyvitamin D3 levels, suggesting loss of function of CYP24A1 (25-hydroxyvitamin-D3-24-hydroxylase). Gene sequencing confirmed that she was a compound heterozygote with the E143del and R396W mutations in CYP24A1. Conclusions: This case broadens presentations of CYP24A1 mutations and hypercalcemia in pregnancy. Furthermore, it illustrates that patients with CYP24A1 mutations can maintain normal calcium levels during the steady state but can develop hypercalcemia when challenged, such as in pregnancy when 1,25-(OH)2D levels are physiologically elevated. PMID:26097993

Chemotherapy-induced hypocalcemia.

PubMed

Ajero, Pia Marie E; Belsky, Joseph L; Prawius, Herbert D; Rella, Vincent

2010-01-01

To present a unique case of transient, asymptomatic chemotherapy-induced hypocalcemia not attributable to hypomagnesemia or tumor lysis syndrome and review causes of hypocalcemia related to cancer with and without use of chemotherapy. We present a case detailing the clinical and laboratory findings of a patient who had severe hypocalcemia during chemotherapy and discuss causes of hypocalcemia with an extensive literature review of chemotherapeutic agents associated with this biochemical abnormality. In a 90-year-old man, hypocalcemia developed during 2 courses of chemotherapy for Hodgkin lymphoma, with partial recovery between courses and normal serum calcium 10 months after completion of treatment. Magnesium, vitamin D, and parathyroid hormone levels were low normal. There was no evidence of tumor lysis syndrome. Of the various agents administered, vinca alkaloids seemed the most likely cause. Serial testing suggested that the underlying mechanism may have been acquired, reversible hypoparathyroidism. No other similar case was found in the published literature. The severe hypocalcemia in our patient could not be attributed to hypomagnesemia or tumor lysis syndrome, and it was clearly associated with the timing of his chemotherapeutic regimen. Possibilities include direct parathyroid hormone suppression or alteration of calcium sensing by the chemotherapeutic drugs. Serum calcium surveillance before and during chemotherapeutic management of cancer patients may reveal more instances and provide insight into the exact mechanism of this lesser known yet striking complication.

Hereditary hypophosphatemic rickets with hypercalciuria and nephrolithiasis-identification of a novel SLC34A3/NaPi-IIc mutation.

PubMed

Phulwani, Priya; Bergwitz, Clemens; Jaureguiberry, Graciana; Rasoulpour, Majjid; Estrada, Elizabeth

2011-03-01

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is characterized by rickets, hyperphosphaturia, hypophosphatemia, elevated 1,25-dihydroxyvitamin-D, increased gastrointestinal calcium absorption and hypercalciuria. Serum calcium, 25-hydroxyvitamin-D and PTH levels are normal. Here we describe a boy with HHRH, nephrolithiasis, and compound heterozygosity for one previously described mutation (g.4225_50del) and a novel splice mutation (g.1226G>A) in SLC34A3, the gene encoding the renal sodium-phosphate co-transporter NaPi-IIc. The patient's mother and grandmother are carriers of g.4225_50del, and both have a history of nephrolithiasis associated with hypercalciuria and elevated 1,25-dihydroxyvitamin-D. His three siblings (2-6 years old), who are also carriers of g.4225_50del, have hypercalciuria but so far their renal ultrasounds are normal. Thus, SLC34A3/NaPi-IIc mutations appear to be associated with variable phenotypic changes at presentation, which can include recurrent nephrolithiasis. Copyright © 2011 Wiley-Liss, Inc.

Hereditary Hypophosphatemic Rickets With Hypercalciuria and Nephrolithiasis—Identification of a Novel SLC34A3/NaPi-IIc Mutation

PubMed Central

Phulwani, Priya; Bergwitz, Clemens; Jaureguiberry, Graciana; Rasoulpour, Majjid; Estrada, Elizabeth

2015-01-01

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is characterized by rickets, hyperphosphaturia, hypophosphatemia, elevated 1,25-dihydroxyvitamin-D, increased gastrointestinal calcium absorption and hypercalciuria. Serum calcium, 25-hydroxyvitamin-D and PTH levels are normal. Here we describe a boy with HHRH, nephrolithiasis, and compound heterozygosity for one previously described mutation (g.4225_50del) and a novel splice mutation (g.1226G>A) in SLC34A3, the gene encoding the renal sodium-phosphate co-transporter NaPi-IIc. The patient’s mother and grandmother are carriers of g.4225_50del, and both have a history of nephrolithiasis associated with hypercalciuria and elevated 1,25-dihydroxyvitamin-D. His three siblings (2–6 years old), who are also carriers of g.4225_50del, have hypercalciuria but so far their renal ultrasounds are normal. Thus, SLC34A3/NaPi-IIc mutations appear to be associated with variable phenotypic changes at presentation, which can include recurrent nephrolithiasis. PMID:21344632

Membrane properties involved in calcium-stimulated microparticle release from the plasma membranes of S49 lymphoma cells.

PubMed

Campbell, Lauryl E; Nelson, Jennifer; Gibbons, Elizabeth; Judd, Allan M; Bell, John D

2014-01-01

This study answered the question of whether biophysical mechanisms for microparticle shedding discovered in platelets and erythrocytes also apply to nucleated cells: cytoskeletal disruption, potassium efflux, transbilayer phospholipid migration, and membrane disordering. The calcium ionophore, ionomycin, disrupted the actin cytoskeleton of S49 lymphoma cells and produced rapid release of microparticles. This release was significantly inhibited by interventions that impaired calcium-activated potassium current. Microparticle release was also greatly reduced in a lymphocyte cell line deficient in the expression of scramblase, the enzyme responsible for calcium-stimulated dismantling of the normal phospholipid transbilayer asymmetry. Rescue of the scrambling function at high ionophore concentration also resulted in enhanced particle shedding. The effect of membrane physical properties was addressed by varying the experimental temperature (32-42°C). A significant positive trend in the rate of microparticle release as a function of temperature was observed. Fluorescence experiments with trimethylammonium diphenylhexatriene and Patman revealed significant decrease in the level of apparent membrane order along that temperature range. These results demonstrated that biophysical mechanisms involved in microparticle release from platelets and erythrocytes apply also to lymphocytes.

Measurement of urinary calcium using AT89C51RD2 microcontroller.

PubMed

Neelamegam, P; Jamaludeen, A; Rajendran, A; Raghunathan, R

2009-04-01

A simple and inexpensive absorption technique for determination of calcium ion in urine samples is developed, comprising a light emitting diode (650 nm) as the light source and photodiode as the detector with AT89C51RD2 microcontroller. The design of the system and details of interface, calibration, and procedure of operation are explained in this paper. Software is developed to monitor sample processing and to display the results in liquid crystal display screen. With 15 microl sample volume, a linear output is obtained in the range of 2.5-7.5 mM calcium with a detection limit of 0.06 mM. Interferences from other cations such as monovalent ion and divalent ion are investigated in the expected range, which are normally present in clinical samples, and absorption changes over the pH range of 3-12 are also determined. This system has been demonstrated successfully for the successive assay of calcium in urine samples, with the results comparing well to those achieved and in good agreement with values obtained with the current clinical spectrophotometric method at 95% of confidence level.

Early prediction of post-thyroidectomy hypocalcemia by early parathyroid hormone measurement.

PubMed

Yetkin, Gurkan; Citgez, Bulent; Yazici, Pinar; Mihmanli, Mehmet; Sit, Erhan; Uludag, Mehmet

2016-01-01

Hypoparathyroidism is the most common complication of total thyroidectomy (TT). Postthyroidectomy hypocalcemia occurs 24 to 48 hours after the operation. It prolongs the length of hospital stay, even though transient in most cases. The aim of this study was to predetermine the patients who may develop postthyroidectomy hypocalcemia by using early postoperative serum intact parathormone (iPTH) and calcium (Ca2+) measurements, and to investigate the effects of early initiated oral calcium and vitamin D treatments on the development of transient hypocalcemia. Patients who underwent TT after initiation of the early iPTH measurement protocol in January 2013 were included into the study group (Group 1, n=202). The control group (Group 2) was composed of 72 patients who underwent TT before the protocol. Prior to the initiation of the protocol, Ca2+ was measured instead of iPTH. In the study group, the serum Ca2+ and iPTH levels were measured before surgery, and 1 and 24-hours after. A calcium level below 8 mg/dL was accepted as biochemical hypocalcaemia, and a iPTH level under 15pg/mL was accepted as hypoparathyroidism. In the study group, patients with below normal iPTH levels were treated with prophylactic oral calcium and vitamin D. In Group 1, 15.8% (n=32) of the patients had hypoparathyroidism on the 1h and 24 h iPTH measurements. There was no statistically difference with regard to PTH levels measured in the postoperative 1st hour and at the 24th hour (p= 0.078). Biochemical hypocalcaemia developed in 16 (7.9%) and 13 (18%) patients in Groups 1 and 2, respectively, 24 hours after thyroidectomy (p<0.05). Mean length of hospital stay was 2.17 and 3.26 days in the study and control groups (p<0.001). We believe that the measurement of iPTH levels one hour after thyroidectomy, when compared to levels at 24 hours after procedure, is a safe, reliable, and adequate method for the effective management of plausible postthyroidectomic hypocalcemia. It yields significantly shorter hospital stay periods. Calcium, Hypoparathyroidism, Postoperative complication, Total thyroidectomy.

Calcium dynamics in cardiac excitatory and non-excitatory cells and the role of gap junction.

PubMed

Das, Phonindra Nath; Mehrotra, Parul; Mishra, Aseem; Bairagi, Nandadulal; Chatterjee, Samrat

2017-07-01

Calcium ions aid in the generation of action potential in myocytes and are responsible for the excitation-contraction coupling of heart. The heart muscle has specialized patches of cells, called excitatory cells (EC) such as the Sino-atrial node cells capable of auto-generation of action potential and cells which receive signals from the excitatory cells, called non-excitatory cells (NEC) such as cells of the ventricular and auricular walls. In order to understand cardiac calcium homeostasis, it is, therefore, important to study the calcium dynamics taking into account both types of cardiac cells. Here we have developed a model to capture the calcium dynamics in excitatory and non-excitatory cells taking into consideration the gap junction mediated calcium ion transfer from excitatory cell to non-excitatory cell. Our study revealed that the gap junctional coupling between excitatory and non-excitatory cells plays important role in the calcium dynamics. It is observed that any reduction in the functioning of gap junction may result in abnormal calcium oscillations in NEC, even when the calcium dynamics is normal in EC cell. Sensitivity of gap junction is observed to be independent of the pacing rate and hence a careful monitoring is required to maintain normal cardiomyocyte condition. It also highlights that sarcoplasmic reticulum may not be always able to control the amount of cytoplasmic calcium under the condition of calcium overload. Copyright © 2017 Elsevier Inc. All rights reserved.

Improving diagnostic recognition of primary hyperparathyroidism with machine learning.

PubMed

Somnay, Yash R; Craven, Mark; McCoy, Kelly L; Carty, Sally E; Wang, Tracy S; Greenberg, Caprice C; Schneider, David F

2017-04-01

Parathyroidectomy offers the only cure for primary hyperparathyroidism, but today only 50% of primary hyperparathyroidism patients are referred for operation, in large part, because the condition is widely under-recognized. The diagnosis of primary hyperparathyroidism can be especially challenging with mild biochemical indices. Machine learning is a collection of methods in which computers build predictive algorithms based on labeled examples. With the aim of facilitating diagnosis, we tested the ability of machine learning to distinguish primary hyperparathyroidism from normal physiology using clinical and laboratory data. This retrospective cohort study used a labeled training set and 10-fold cross-validation to evaluate accuracy of the algorithm. Measures of accuracy included area under the receiver operating characteristic curve, precision (sensitivity), and positive and negative predictive value. Several different algorithms and ensembles of algorithms were tested using the Weka platform. Among 11,830 patients managed operatively at 3 high-volume endocrine surgery programs from March 2001 to August 2013, 6,777 underwent parathyroidectomy for confirmed primary hyperparathyroidism, and 5,053 control patients without primary hyperparathyroidism underwent thyroidectomy. Test-set accuracies for machine learning models were determined using 10-fold cross-validation. Age, sex, and serum levels of preoperative calcium, phosphate, parathyroid hormone, vitamin D, and creatinine were defined as potential predictors of primary hyperparathyroidism. Mild primary hyperparathyroidism was defined as primary hyperparathyroidism with normal preoperative calcium or parathyroid hormone levels. After testing a variety of machine learning algorithms, Bayesian network models proved most accurate, classifying correctly 95.2% of all primary hyperparathyroidism patients (area under receiver operating characteristic = 0.989). Omitting parathyroid hormone from the model did not decrease the accuracy significantly (area under receiver operating characteristic = 0.985). In mild disease cases, however, the Bayesian network model classified correctly 71.1% of patients with normal calcium and 92.1% with normal parathyroid hormone levels preoperatively. Bayesian networking and AdaBoost improved the accuracy of all parathyroid hormone patients to 97.2% cases (area under receiver operating characteristic = 0.994), and 91.9% of primary hyperparathyroidism patients with mild disease. This was significantly improved relative to Bayesian networking alone (P < .0001). Machine learning can diagnose accurately primary hyperparathyroidism without human input even in mild disease. Incorporation of this tool into electronic medical record systems may aid in recognition of this under-diagnosed disorder. Copyright © 2016 Elsevier Inc. All rights reserved.

Simple test of intestinal calcium absorption measured by stable strontium.

PubMed Central

Milsom, S; Ibbertson, K; Hannan, S; Shaw, D; Pybus, J

1987-01-01

A clinical test of intestinal calcium absorption has been developed using non-radioactive stable strontium as a calcium tracer. In nine elderly subjects there was a close correlation between the fractional absorption of strontium and radioactive calcium (45Ca) during a five hour period after the simultaneous oral administration of the two tracers. Comparable precision was achieved with each tracer in six subjects in whom the test was repeated after two weeks. The effect of food on strontium absorption was examined in a further 33 normal subjects (age 21-60 years), and the administration of the strontium with a standard breakfast was shown to reduce the variance at individual time points. A simplified test in which serum strontium concentration was measured four hours after the oral dose given with a standard breakfast was adopted as the routine procedure. The normal range (mean (2 SD], established over 97 tests in 53 patients, was 7.0-18.0% of the dose in the extracellular fluid. A further 30 patients with possible disorders of calcium absorption (10 with primary hyperparathyroidism and 20 with coeliac disease) were studied by this standard test. In both groups of patients the mean four hour strontium values were significantly different from normal. This standard strontium absorption test allows assessment of calcium absorption with sufficient sensitivity and precision to have a wide application in clinical practice. PMID:3115389

Medical application of in vivo neutron activation analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cohn, S.H.; Ellis, K.J.; Vartsky, D.

1978-01-01

The clinical usefulness of total body neutron activation analysis (TBNAA) was clearly established at an IAEA panel meeting in Vienna in 1972. It is best demonstrated by the studies involving the measurement of total-body calcium. This measurement provides data useful for the diagnosis and management of metabolic bone disorders. It should be emphasized, however, that while most of the applications to date have involved calcium and phosphorus, the measurement of sodium, chlorine and nitrogen also appear to be useful clinically. Total-body calcium measurements utilizing TBNAA have been used in studies of osteoporosis to establish absolute and relative deficits of calciummore » in patients with this disease in comparison to a normal contrast population. Changes in total-body calcium (skeletal mass) have also been useful for quantitating the efficacy of various therapies in osteoporosis. Serial measurements over periods of years provide long-term balance data by direct measurement with a higher precision (+- 2%) than is possible by the use of any other technique. In the renal osteodystrophy observed in patients with renal failure, disorders of both calcium and phosphorus, as well as electrolyte disturbances, have been studied. The measure of total-body levels of these elements gives the clinician useful data upon which to design dialysis therapy. The measurement of bone changes in endocrine dysfunction has been studied, particularly in patients with thyroid and parathyroid disorders. In parathyroidectomy, the measurement of total-body calcium, post-operatively, can indicate the degree of bone resorption. Skeletal metabolism and body composition in acromegaly and Cushing's disease have also been investigated by TBNAA. Levels of cadmium in liver and kidney have also been measured in-vivo by prompt-gamma neutron activation and associated with hypertension, emphysema and cigarette smoking.« less

Immunological Development and Cardiovascular Function Are Normal in Annexin VI Null Mutant Mice

PubMed Central

Hawkins, Tim E.; Roes, Jürgen; Rees, Daryl; Monkhouse, Jayne; Moss, Stephen E.

1999-01-01

Annexins are calcium-binding proteins of unknown function but which are implicated in important cellular processes, including anticoagulation, ion flux regulation, calcium homeostasis, and endocytosis. To gain insight into the function of annexin VI, we performed targeted disruption of its gene in mice. Matings between heterozygous mice produced offspring with a normal Mendelian pattern of inheritance, indicating that the loss of annexin VI did not interfere with viability in utero. Mice lacking annexin VI reached sexual maturity at the same age as their normal littermates, and both males and females were fertile. Because of interest in the role of annexin VI in cardiovascular function, we examined heart rate and blood pressure in knockout and wild-type mice and found these to be identical in the two groups. Similarly, the cardiovascular responses of both sets of mice to septic shock were indistinguishable. We also examined components of the immune system and found no differences in thymic, splenic, or bone marrow lymphocyte levels between knockout and wild-type mice. This is the first study of annexin knockout mice, and the lack of a clear phenotype has broad implications for current views of annexin function. PMID:10567528

Regulatory effect of chrysin on expression of lenticular calcium transporters, calpains, and apoptotic-cascade components in selenite-induced cataract

PubMed Central

Sundararajan, Mahalingam; Thomas, Philip A.; Teresa, P. Archana; Anbukkarasi, Muniyandi

2016-01-01

Purpose Selenite-induced cataract is associated with oxidative stress, loss of calcium homeostasis, activation of calpain enzymes, and apoptotic cell death in the lens. An evaluation of naturally occurring antioxidants that also restrict calcium influx into the lens and calpain activation and thus prevent lenticular cell death may lead to the development of safe and effective anticataractogenic drugs. This study focuses on a naturally occurring flavone, chrysin, and its efficacy in preventing cataractogenic changes in in vitro cultured Wistar rat lenses. Methods Lenses from Wistar rats incubated for 24 h at 37 °C in Dulbecco’s modified Eagle’s medium (DMEM) were categorized into four main groups: Group I (control, incubated in DMEM alone); Group II (selenite-challenged and untreated, incubated in DMEM that contained 100 µM/ml of sodium selenite only); Group III (selenite-challenged and chrysin-treated, incubated in DMEM that contained sodium selenite [100 µM/ml of DMEM] and chrysin [200 µM/ml of DMEM]); and Group IV (chrysin-treated, incubated in DMEM that contained chrysin [200 µM/ml of DMEM] only). The Group III (selenite-challenged and chrysin-treated) lenses were further categorized into five sub-groups: Group IIIa (incubated for 24 h in DMEM that contained sodium selenite and chrysin added simultaneously), Group IIIb (first incubated for 2 h in DMEM that contained chrysin only and then for up to 24 h in fresh DMEM that contained sodium selenite only), Group IIIc (first incubated for 30 min in DMEM that contained sodium selenite only and subsequently for up to 24 h in DMEM that contained chrysin only), and Groups IIId and IIIe (first incubated for 1 h and 2 h, respectively, in DMEM that contained sodium selenite only and subsequently for up to 24 h in DMEM that contained chrysin only). Results Gross morphological assessment revealed dense opacification (Grade +++) in the selenite-challenged, untreated lenses (Group II); however, seven of the eight selenite-challenged and simultaneously chrysin-treated (Group IIIa) lenses showed no opacification (Grade 0) after 24 h incubation, while the remaining single lens exhibited only a slight degree of opacification (Grade +). In the Group IIIa lenses, the reduced glutathione, protein sulfhydryl, and malondialdehyde concentrations appeared to have been maintained at near-normal levels. The mean lenticular concentration of calcium was significantly lower in the Group IIIa lenses than that in the Group II lenses and approximated the values observed in the normal control (Group I) lenses. The Group IIIa lenses also exhibited significantly (p<0.05) higher mean lenticular activity of calpain, significantly higher mean mRNA transcript levels of genes that encode m-calpain and lenticular preferred calpain (Lp82), and significantly higher mean levels of the m-calpain and Lp82 proteins than the corresponding values in the Group II lenses. Casein zymography results suggested that chrysin prevented calpain activation and autolysis. Significantly (p<0.05) lower mean levels of mRNA transcripts of the genes that encode calcium transporter proteins (plasma membrane Ca2+-ATPase-1 and sarco/endoplasmic reticulum Ca2+-ATPase-2) and lenticular apoptotic-cascade proteins (early growth response protein-1, caspase-3, caspase-8, and caspase-9) and significantly (p<0.05) lower mean concentrations of the proteins themselves were seen in the Group IIIa rat lenses in comparison to the values noted in the Group II rat lenses. Conclusions Chrysin appears to prevent selenite-induced cataractogenesis in vitro by maintaining the redox system components at near-normal levels and by preventing the abnormal expression of several lenticular calcium transporters and apoptotic-cascade proteins, thus preventing accumulation of calcium and subsequent calpain activation and lenticular cell death in cultured Wistar rat lenses. PMID:27168717

Regulatory effect of chrysin on expression of lenticular calcium transporters, calpains, and apoptotic-cascade components in selenite-induced cataract.

PubMed

Sundararajan, Mahalingam; Thomas, Philip A; Teresa, P Archana; Anbukkarasi, Muniyandi; Geraldine, Pitchairaj

2016-01-01

Selenite-induced cataract is associated with oxidative stress, loss of calcium homeostasis, activation of calpain enzymes, and apoptotic cell death in the lens. An evaluation of naturally occurring antioxidants that also restrict calcium influx into the lens and calpain activation and thus prevent lenticular cell death may lead to the development of safe and effective anticataractogenic drugs. This study focuses on a naturally occurring flavone, chrysin, and its efficacy in preventing cataractogenic changes in in vitro cultured Wistar rat lenses. Lenses from Wistar rats incubated for 24 h at 37 °C in Dulbecco's modified Eagle's medium (DMEM) were categorized into four main groups: Group I (control, incubated in DMEM alone); Group II (selenite-challenged and untreated, incubated in DMEM that contained 100 µM/ml of sodium selenite only); Group III (selenite-challenged and chrysin-treated, incubated in DMEM that contained sodium selenite [100 µM/ml of DMEM] and chrysin [200 µM/ml of DMEM]); and Group IV (chrysin-treated, incubated in DMEM that contained chrysin [200 µM/ml of DMEM] only). The Group III (selenite-challenged and chrysin-treated) lenses were further categorized into five sub-groups: Group IIIa (incubated for 24 h in DMEM that contained sodium selenite and chrysin added simultaneously), Group IIIb (first incubated for 2 h in DMEM that contained chrysin only and then for up to 24 h in fresh DMEM that contained sodium selenite only), Group IIIc (first incubated for 30 min in DMEM that contained sodium selenite only and subsequently for up to 24 h in DMEM that contained chrysin only), and Groups IIId and IIIe (first incubated for 1 h and 2 h, respectively, in DMEM that contained sodium selenite only and subsequently for up to 24 h in DMEM that contained chrysin only). Gross morphological assessment revealed dense opacification (Grade +++) in the selenite-challenged, untreated lenses (Group II); however, seven of the eight selenite-challenged and simultaneously chrysin-treated (Group IIIa) lenses showed no opacification (Grade 0) after 24 h incubation, while the remaining single lens exhibited only a slight degree of opacification (Grade +). In the Group IIIa lenses, the reduced glutathione, protein sulfhydryl, and malondialdehyde concentrations appeared to have been maintained at near-normal levels. The mean lenticular concentration of calcium was significantly lower in the Group IIIa lenses than that in the Group II lenses and approximated the values observed in the normal control (Group I) lenses. The Group IIIa lenses also exhibited significantly (p<0.05) higher mean lenticular activity of calpain, significantly higher mean mRNA transcript levels of genes that encode m-calpain and lenticular preferred calpain (Lp82), and significantly higher mean levels of the m-calpain and Lp82 proteins than the corresponding values in the Group II lenses. Casein zymography results suggested that chrysin prevented calpain activation and autolysis. Significantly (p<0.05) lower mean levels of mRNA transcripts of the genes that encode calcium transporter proteins (plasma membrane Ca(2+)-ATPase-1 and sarco/endoplasmic reticulum Ca(2+)-ATPase-2) and lenticular apoptotic-cascade proteins (early growth response protein-1, caspase-3, caspase-8, and caspase-9) and significantly (p<0.05) lower mean concentrations of the proteins themselves were seen in the Group IIIa rat lenses in comparison to the values noted in the Group II rat lenses. Chrysin appears to prevent selenite-induced cataractogenesis in vitro by maintaining the redox system components at near-normal levels and by preventing the abnormal expression of several lenticular calcium transporters and apoptotic-cascade proteins, thus preventing accumulation of calcium and subsequent calpain activation and lenticular cell death in cultured Wistar rat lenses.

Post-thyroidectomy hypocalcemia is related to parathyroid dysfunction even in patients with normal parathyroid hormone concentrations early after surgery.

PubMed

Raffaelli, Marco; De Crea, Carmela; D'Amato, Gerardo; Moscato, Umberto; Bellantone, Chiara; Carrozza, Cinzia; Lombardi, Celestino Pio

2016-01-01

Hypocalcemia may develop even in the presence of normal postoperative parathyroid hormone (PTH) concentrations. We aimed to identify risk factors of hypocalcemia in patients with normal PTH concentration early after total thyroidectomy (TT). We included 1,504 consecutive patients who underwent TT between January 2012 and December 2013. Significant hypocalcemia was defined as serum calcium concentrations of <8.0 mg/dL. Overall, 333 patients had subnormal PTH 4 hours after surgery (4-hour PTH; <10 pg/mL) and received oral calcium (OC) and calcitriol supplementation. Among the 1,171 patients with normal 4-hour PTH (≥ 10 pg/mL; euparathyroid), 211 experienced hypocalcemia and required OC administration. Among the euparathyroid patients, no difference was found between normocalcemic and hypocalcemic patients in terms of age, hormonal status, preoperative PTH, 25-hydroxy vitamin D (25OH-VD), magnesium, and phosphate concentrations. On univariate analysis, euparathyroid hypocalcemic patients were more frequently females, had significantly lower preoperative serum calcium and 4-hour PTH concentrations, and greater decreases in PTH. Independent risk factors for hypocalcemia with normal 4-hour PTH were preoperative serum calcium concentration and PTH decline of ≥ 50%. Female sex, toxic goiter, and 25OH-VD deficiency are not risk factors for post-TT hypocalcemia. Relative parathyroid insufficiency seems to be the principal mechanism of post-thyroidectomy hypocalcemia, even in patients with normal postoperative PTH concentrations. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of the Administration of 25(OH) Vitamin D3 in an Experimental Model of Chronic Kidney Disease in Animals Null for 1-Alpha-Hydroxylase.

PubMed

Torremadé, Noelia; Bozic, Milica; Goltzman, David; Fernandez, Elvira; Valdivielso, José M

2017-01-01

The final step in vitamin D activation is catalyzed by 1-alpha-hydroxylase (CYP27B1). Chronic kidney disease (CKD) is characterized by low levels of both 25(OH)D3 and 1,25(OH)2D3 provoking secondary hyperparathyroidism (2HPT). Therefore, treatments with active or native vitamin D compounds are common in CKD to restore 25(OH)D3 levels and also to decrease PTH. This study evaluates the dose of 25(OH)D3 that restores parathyroid hormone (PTH) and calcium levels in a model of CKD in CYP27B1-/- mice. Furthermore, we compare the safety and efficacy of the same dose in CYP27B1+/+ animals. The dose needed to decrease PTH levels in CYP27B1-/- mice with CKD was 50 ng/g. That dose restored blood calcium levels without modifying phosphate levels, and increased the expression of genes responsible for calcium absorption (TRPV5 and calbindinD- 28K in the kidney, TRPV6 and calbindinD-9k in the intestine). The same dose of 25(OH)D3 did not modify PTH in CYP27B1+/+ animals with CKD. Blood calcium remained normal, while phosphate increased significantly. Blood levels of 25(OH)D3 in CYP27B1-/- mice were extremely high compared to those in CYP27B1+/+ animals. CYP27B1+/+ animals with CKD showed increases in TRPV5, TRPV6, calbindinD-28K and calbindinD-9K, which were not further elevated with the treatment. Furthermore, CYP27B1+/+ animals displayed an increase in vascular calcification. We conclude that the dose of 25(OH)D3 effective in decreasing PTH levels in CYP27B1-/- mice with CKD, has a potentially toxic effect in CYP27B1+/+ animals with CKD.

Effects of dietary calcium on atherosclerosis, aortic calcification, and icterus in rabbits fed a supplemental cholesterol diet.

PubMed

Hsu, Howard H T; Culley, Nathan C

2006-06-23

Vascular calcification is implicated in myocardial infarction, instability and rigidity of the aortic wall, and bioprosthetic failures. Although an increase in the calcium (Ca) content in atherogenic diets has been shown to decrease atherosclerosis in rabbits, whether Ca supplementation and deficiency can affect atherosclerosis-related aortic calcification remains unknown. New Zealand White male rabbit littermates were fed an atherogenic diet containing 0.5% cholesterol and 2% peanut oil. The Ca content of the diet, which normally contains 1%, was adjusted to 0.5 or 3%. Segments of thoracic aortas were dissected from rabbits for histological evaluations and Ca and Pi determinations. Rabbits with calcium supplementation were maintained for 4 months, whereas those with calcium deficiency were maintained for 2 1/2 months due to severe icterus beyond this stage. The ratios of intimal to medial areas and calcified to intimal areas were used to semi-quantify lesion accumulation and calcification, respectively. Icterus was estimated from the extent of yellowing of the skin, sclera, and mucous membranes along with gross evidence of hepatic lipidosis and/or biliary obstructions. Statistical analysis of 16 matched littermates shows that Ca supplementation significantly decreased the lesions by 41% (p < 0.05) and markedly inhibited calcification by 62% (p < 0.05). Statistical analysis of 11 matched littermates shows that Ca deficiency significantly increased the lesions by 2.7-fold (p < 0.05) and that the diet caused a small but significant calcification not seen in the sibling groups with normal dietary Ca. Ca supplementation caused a significant 30% decrease in serum cholesterol (p < 0.05). Calcium deficiency increased serum cholesterol by 57% (p < 0.001). Serum cholesterol and LDL-cholesterol levels in Ca deficient rabbits were 2-fold higher than those with high Ca diets. Ca supplementation decreased soluble Ca and Pi content in aortas, suggesting that this effect may underlie the effects of Ca supplementation on calcification. Calcium deficiency increased icterus by 33% (p < 0.05), which may affect hepatic clearance of cholesterol, while calcium supplementation decreased it by 43% (p < 0.001). Ca supplementation to an atherogenic diet inhibits atherosclerosis, aortic calcification, and icterus, whereas a Ca deficient-diet promotes them.

Vitamin D

MedlinePlus

... body needs to grow and develop normally. Vitamin D helps your body absorb calcium. Calcium is one ... building blocks of bone. A lack of vitamin D can lead to bone diseases such as osteoporosis ...

Ca 45 Uptake in Fracture Callus of Normal and Aminoacetonitrile-Treated Rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bolognani, L.; Ponseti, T. V.

1962-04-01

Calcium content and Ca 45 uptake were measured in the fracture callus of normal and AAN-treated rats. It appears that total calcium deposition and Ca 45 uptake are both higher in the young callus, 5 and 10 days after fracture, of the AAN-treated animals. By the 20th day, mineralization of the callus in both groups is similar.

Calcium Homeostatasis and Mitochondrial Dysfunction in Dopaminergic Neurons of the Substantia Nigra

DTIC Science & Technology

2010-03-01

discovery that calcium entry through L-type channels during normal pacemaking elevates the sensitivity of SNc dopaminergic neurons to toxins; • the...discovery that L-type calcium channels participate in but are not necessary for pacemaking; • the discovery that serum concentration of the...FDA approved doses; • the discovery that calcium entry through L-type channels during pacemaking elevates mitochondrial oxidant stress and leads

The Function of the Mitochondrial Calcium Uniporter in Neurodegenerative Disorders

PubMed Central

Liao, Yajin; Dong, Yuan; Cheng, Jinbo

2017-01-01

The mitochondrial calcium uniporter (MCU)—a calcium uniporter on the inner membrane of mitochondria—controls the mitochondrial calcium uptake in normal and abnormal situations. Mitochondrial calcium is essential for the production of adenosine triphosphate (ATP); however, excessive calcium will induce mitochondrial dysfunction. Calcium homeostasis disruption and mitochondrial dysfunction is observed in many neurodegenerative disorders. However, the role and regulatory mechanism of the MCU in the development of these diseases are obscure. In this review, we summarize the role of the MCU in controlling oxidative stress-elevated mitochondrial calcium and its function in neurodegenerative disorders. Inhibition of the MCU signaling pathway might be a new target for the treatment of neurodegenerative disorders. PMID:28208618

Expressed sequence tag analysis of adult human optic nerve for NEIBank: Identification of cell type and tissue markers

PubMed Central

Bernstein, Steven L; Guo, Yan; Peterson, Katherine; Wistow, Graeme

2009-01-01

Background The optic nerve is a pure white matter central nervous system (CNS) tract with an isolated blood supply, and is widely used in physiological studies of white matter response to various insults. We examined the gene expression profile of human optic nerve (ON) and, through the NEIBANK online resource, to provide a resource of sequenced verified cDNA clones. An un-normalized cDNA library was constructed from pooled human ON tissues and was used in expressed sequence tag (EST) analysis. Location of an abundant oligodendrocyte marker was examined by immunofluorescence. Quantitative real time polymerase chain reaction (qRT-PCR) and Western analysis were used to compare levels of expression for key calcium channel protein genes and protein product in primate and rodent ON. Results Our analyses revealed a profile similar in many respects to other white matter related tissues, but significantly different from previously available ON cDNA libraries. The previous libraries were found to include specific markers for other eye tissues, suggesting contamination. Immune/inflammatory markers were abundant in the new ON library. The oligodendrocyte marker QKI was abundant at the EST level. Immunofluorescence revealed that this protein is a useful oligodendrocyte cell-type marker in rodent and primate ONs. L-type calcium channel EST abundance was found to be particularly low. A qRT-PCR-based comparative mammalian species analysis reveals that L-type calcium channel expression levels are significantly lower in primate than in rodent ON, which may help account for the class-specific difference in responsiveness to calcium channel blocking agents. Several known eye disease genes are abundantly expressed in ON. Many genes associated with normal axonal function, mRNAs associated with axonal transport, inflammation and neuroprotection are observed. Conclusion We conclude that the new cDNA library is a faithful representation of human ON and EST data provide an initial overview of gene expression patterns in this tissue. The data provide clues for tissue-specific and species-specific properties of human ON that will help in design of therapeutic models. PMID:19778450

Aluminium and hydrogen ions inhibit a mechanosensory calcium-selective cation channel

NASA Technical Reports Server (NTRS)

Ding, J. P.; Pickard, B. G.

1993-01-01

The tension-dependent activity of mechanosensory calcium-selective cation channels in excised plasmalemmal patches from onion bulb scale epidermis is modulated by pH in the physiologically meaningful range between 4.5 and 7.2. It is rapidly lowered by lowering pH and rapidly raised by raising pH. Channel activity is effectively inhibited by low levels of aluminium ions and activity can be partially restored by washing for a few minutes. We suggest that under normal conditions the sensitivity of the mechanosensory channels to pH of the wall free space plays important roles in regulation of plant activities such as growth. We further suggest that, when levels of acid and aluminium ions in the soil solution are high, they might inhibit similar sensory channels in cells of the root tip, thus contributing critically to the acid soil syndrome.

Effects of 1,25-dihydroxycholecalciferol on intestinal calcium transport in cortisone-treated rats.

PubMed

Favus, M J; Walling, M W; Kimberg, D V

1973-07-01

The administration of glucocorticoids may decrease intestinal calcium absorption in vivo and the active transport of calcium in rat duodenum in vitro. It has been suggested that this apparent "anti-vitamin D-like" effect of steroid hormones may be related to alterations in vitamin D metabolism. In order to test this hypothesis, vitamin D-deficient control and cortisone-treated rats were given an intraperitoneal injection of 5.5 IU of 1,25-dihydroxycholecalciferol (1,25-DHCC), the probable end-organ active vitamin D metabolite in the intestine, and 16 h later studies of duodenal calcium transport were performed in modified Ussing chambers. In the vitamin D-deficient state, cortisone administration was associated with a diminution in J(MS), J(Net), and the flux ratio (J(MS)/J(SM)). While the magnitude of the increases in J(MS) and J(Net) that resulted from 1,25-DHCC treatment were approximately the same in control and cortisone-treated animals, 1,25-DHCC failed to restore these parameters to "normal levels" in the steroid-treated rats. Furthermore, contrary to the results obtained in the saline-treated controls, 1,25-DHCC failed to reduce J(SM) in the duodenum from cortisone-treated rats. The cortisone-related defect in calcium transport was due to alterations in both unidirectional calcium fluxes (decrease in J(MS) and increase in J(SM)), such that the J(Net) and the flux ratio (J(MS)/J(SM)) were only approximately 50% of the levels achieved in vitamin D-deficient control animals repleted with the same dose of 1,25-DHCC. The administration of 1,25-DHCC was accompanied by a marked increase in the serum calcium levels of control rats, but there was no such response in the cortisone-treated group. The results support the concept that under the conditions of these experiments in the rat the apparent antagonism between glucocorticoids and vitamin D may be due to steroid hormone-related alterations in end organ function that are independent of any direct interaction between the hormone and the vitamin and that cannot be reversed by the vitamin.

Effects of calcium dobesilate on Nrf2, Keap1 and HO-1 in the lenses of D-galactose-induced cataracts in rats

PubMed Central

Sun, Jinfeng; Wang, Bin; Hao, Youjuan; Yang, Xueli

2018-01-01

This study investigated the effects of calcium dobesilate on Nrf2, Keap1 and HO-1 in the lenses of D-galactose-induced cataracts in rats. Thirty Sprague-Dawley rats were randomly divided into three groups: a blank control group, a model control group and a model administration group. A normal diet was given to the rats in the blank control group and the rats with D-galactose-induced cataracts of the model control group. Calcium dobesilate was also given to the rats with D-galactose-induced cataracts of the model administration group. A slit lamp microscope was used to check the degree of lens opacity. RT-PCR and western blot analysis were used to detect the mRNA and protein expression of Nrf2, Keap1 and HO-1 in the lenses of the three groups. There was a significant difference in the degree of lens opacity among the three groups (P<0.05). The model control group was the most turbid of the three groups, followed by the model administration group. Moreover, the mRNA and protein expression of Nrf2, Keap1 and HO-1 in the lenses of the three groups were also significantly different (P<0.05). The mRNA levels of Nrf2 and HO-1 were the highest in the model control group, followed by the model administration group, and were the lowest in the blank control group. However, the mRNA expression level of Keap1 among the three groups had an opposite trend. In conclusion, calcium dobesilate can effectively increase the levels of Nrf2 and HO-1 in the lenses of diabetic cataract rats and inhibit the level of Keap1. Therefore, the therapeutic effect of calcium dobesilate against cataracts is related to the improvement of the Nrf2-Keap1 signaling pathway. PMID:29399076

Arterial Structure and Function in Mild Primary Hyperparathyroidism Is Not Directly Related to Parathyroid Hormone, Calcium, or Vitamin D

PubMed Central

Ring, Margareta; Farahnak, Parastou; Gustavsson, Tomas; Nilsson, Inga-Lena; Eriksson, Maria J.; Caidahl, Kenneth

2012-01-01

Objective Elevated levels of calcium and parathyroid hormone (PTH), characteristics of primary hyperparathyroidism (PHPT), may be associated with cardiovascular morbidity and mortality in the general population. We evaluated the possible vascular effects of these risk factors in patients with mild PHPT by using standard methods and new imaging techniques. Design A prospective case-control study. Subjects and Methods Forty-eight patients with mild PHPT without any known cardiovascular risk factors were studied at baseline and at one year after parathyroidectomy (PTX) in comparison with 48 healthy age- and gender-matched controls. We measured biochemical variables, augmentation index (AIx), aortic pulse wave velocity (PWVao), radial (IMTrad) and common carotid artery (IMTcca) intima media thicknesses, and the grayscale median (IM-GSM) of the latter. Results No significant differences were observed between PHPT patients and controls at baseline for AIx (28.6±12.2 vs. 27.7±12.8%), IMTrad (0.271±0.060 vs. 0.255±0.053 mm), IMTcca (0.688±0.113 vs. 0.680±0.135 mm), or IM-GSM (82.3±17.2 vs. 86.5±15.3), while PWVao was slightly higher in patients (8.68±1.50 vs. 8.13±1.55, p<0.05). Systolic blood pressure (SBP), calcium, and PTH were higher in patients compared with controls, and decreased after PTX, while vitamin D was lower in patients and increased after PTX. While AIx, PWVao, IMTrad, and IMTcca were related to SBP, neither correlated to vitamin D levels. Only PWVao correlated weakly to plasma PTH (r = 0.29, p<0.01) and ionized calcium (r = 0.22, p<0.05) but showed no relation when age and SBP were adjusted for. Conclusion We found normal arterial function despite high calcium, PTH, and low vitamin D levels, in patients with mild PHPT without cardiovascular risk factors. The cardiovascular risk associated with low vitamin D and/or high PTH and calcium levels may be explained by their coupling to blood pressure and other risk factors rather than direct effects on arterial structure. PMID:22815708

Kefir improves bone mass and microarchitecture in an ovariectomized rat model of postmenopausal osteoporosis.

PubMed

Chen, H-L; Tung, Y-T; Chuang, C-H; Tu, M-Y; Tsai, T-C; Chang, S-Y; Chen, C-M

2015-02-01

Kefir treatment in ovariectomized (OVX) rats could significantly decrease the levels of bone turnover markers and prevent OVX-induced bone loss, deterioration of trabecular microarchitecture, and biomechanical dysfunction that may be due to increase intracellular calcium uptake through the TRPV6 calcium channel. Osteoporosis is a disease characterized by low bone mass and structural deterioration of bone tissue, leading to an increased fracture risk. The incidence of osteoporosis increases with age and occurs most frequently in postmenopausal women due to estrogen deficiency, as the balance between bone resorption and bone formation shifts towards increased levels of bone resorption. Among various methods of prevention and treatment for osteoporosis, an increase in calcium intake is the most commonly recommended preventive measure. Kefir is a fermented milk product made with kefir grains that degrade milk proteins into various peptides with health-promoting effects, including immunomodulating-, antithrombotic-, antimicrobial-, and calcium-absorption-enhancing bioactivities. The aim of this study is to investigate the effect of kefir on osteoporosis prophylaxis in an ovariectomized rat model. A total of 56 16-week-old female Sprague-Dawley (SD) rats were divided into 7 experimental groups: sham (normal), OVX/Mock, OVX/1X kefir (164 mg/kg BW/day), OVX/2X kefir (328 mg/kg BW/day), OVX/4X kefir (656 mg/kg BW/day), OVX/ALN (2.5 mg/kg BW/day), and OVX/REBONE (800 mg/kg BW/day). After 12-week treatment with kefir, the bone physiology in the OVX rat model was investigated. Accordingly, the aim of this study was to investigate the possible transport mechanism involved in calcium absorption using the Caco-2 human cell line. A 12-week treatment with kefir on the OVX-induced osteoporosis model reduced the levels of C-terminal telopeptides of type I collagen (CTx), bone turnover markers, and trabecular separation (Tb. Sp.). Additionally, treatment with kefir increased trabecular bone mineral density (BMD), bone volume (BV/TV), trabecular thickness (Tb. Th), trabecular number (Tb. N), and the biomechanical properties (hardness and modulus) of the distal femur with a dose-dependent efficacy. In addition, in in vitro assay, we found that kefir increased intracellular calcium uptake in Caco-2 cell through TRPV6 calcium channels and not through L-type voltage-operated calcium channels. The protective effect of kefir in the OVX rat model may occur through increasing intracellular calcium uptake through the TRPV6 calcium channel.

A novel germline inactivating mutation in the CASR gene in an Italian kindred affected by familial hypocalciuric hypercalcemia.

PubMed

Falchetti, Alberto; Gozzini, Alessia; Terranegra, Annalisa; Soldati, Laura; Vezzoli, Giuseppe; Leoncini, Gigliola; Giusti, Francesca; Franceschelli, Francesco; Masi, Laura; Tanini, Annalisa; Cavalli, Loredana; Brandi, Maria Luisa

2012-05-01

Familial hypocalciuric hypercalcemia (FHH) syndrome is a rare benign condition, inherited as an autosomal dominant trait, in which inactivating mutations of the calcium-sensing receptor (CASR) gene affects the body's ability to regulate calcium homeostasis. Its outcome is featured by increased levels of serum calcium, moderate hypophosphatemia, and inadequately normal or elevated circulating parathyroid hormone levels. Affected patients are mostly asymptomatic and do not benefit from surgical resection of their mildly enlarged parathyroids. We evaluated for hypercalcemia an Italian family that was identified via a young adult male proband referred to our center for parathyroidectomy. The patients and the family members were evaluated both biochemically and genetically as suspected FHH subjects. An in vitro functional study was performed by site-directed mutagenesis, and CASR activity was monitored by measuring intracellular calcium ([Ca(2)(+)](i)). The patient had a novel germline heterozygous CASR mutation (c.361_364GATT; p.D121del/fsX122). The mutation caused a premature stop codon at codon 122, exiting a truncated protein. The biochemical phenotype of all family members carrying the heterozygous deletion was concordant with classic FHH syndrome. Our findings confirm the role of CASR gene mutational analysis to offer a valuable addition for the recognition of FHH in hypercalcemic patients not yet characterized for a positive familial history of hypercalcemia, the only condition that identifies CASR gene mutations in hypercalcemia.

Brain-state dependent astrocytic Ca2+ signals are coupled to both positive and negative BOLD-fMRI signals.

PubMed

Wang, Maosen; He, Yi; Sejnowski, Terrence J; Yu, Xin

2018-02-13

Astrocytic Ca 2+ -mediated gliovascular interactions regulate the neurovascular network in situ and in vivo. However, it is difficult to measure directly both the astrocytic activity and fMRI to relate the various forms of blood-oxygen-level-dependent (BOLD) signaling to brain states under normal and pathological conditions. In this study, fMRI and GCaMP-mediated Ca 2+ optical fiber recordings revealed distinct evoked astrocytic Ca 2+ signals that were coupled with positive BOLD signals and intrinsic astrocytic Ca 2+ signals that were coupled with negative BOLD signals. Both evoked and intrinsic astrocytic calcium signal could occur concurrently or respectively during stimulation. The intrinsic astrocytic calcium signal can be detected globally in multiple cortical sites in contrast to the evoked astrocytic calcium signal only detected at the activated cortical region. Unlike propagating Ca 2+ waves in spreading depolarization/depression, the intrinsic Ca 2+ spikes occurred simultaneously in both hemispheres and were initiated upon the activation of the central thalamus and midbrain reticular formation. The occurrence of the intrinsic astrocytic calcium signal is strongly coincident with an increased EEG power level of the brain resting-state fluctuation. These results demonstrate highly correlated astrocytic Ca 2+ spikes with bidirectional fMRI signals based on the thalamic regulation of cortical states, depicting a brain-state dependency of both astrocytic Ca 2+ and BOLD fMRI signals.

SIDT2 is involved in the NAADP-mediated release of calcium from insulin secretory granules.

PubMed

Chang, Guoying; Yang, Rui; Cao, Yanan; Nie, Aifang; Gu, Xuefan; Zhang, Huiwen

2016-04-01

The Sidt2 global knockout mouse (Sidt2(-/-)) has impaired insulin secretion. The aim of this study was to assess the role of SIDT2 protein in glucose-induced insulin secretion in primary cultured mouse β-cells. The major metabolic and electrophysiological steps of glucose-induced insulin secretion of primary cultured β-cells from Sidt2(-/-) mice were investigated. The β-cells from Sidt2(-/-) mice had normal NAD(P)H responses and KATP and KV currents. However, they exhibited a lower [Ca(2+)]i peak height when stimulated with 20mM glucose compared with those from WT mice. Furthermore, it took a longer time for the [Ca(2+)]i of β-cell from Sidt2(-/-) mice to reach the peak. Pretreatment with ryanodine or 2-aminoethoxydiphenyl borate (2-APB) did not change [Ca(2+)]i the response pattern to glucose in Sidt2(-/-) cells. Extraordinarily, pretreatment with bafilomycin A1(Baf-A1) led to a comparable [Ca(2+)]i increase pattern between these two groups, suggesting that calcium traffic from the intracellular acidic compartment is defective in Sidt2(-/-) β-cells. Bath-mediated application of 50nM nicotinic acid adenine dinucleotide phosphate (NAADP) normalized the [Ca(2+)]i response of Sidt2(-/-) β-cells. Finally, glucose-induced CD38 expression increased to a comparable level between Sidt2(-/-) and WT islets, suggesting that Sidt2(-/-) islets generated NAADP normally. We conclude that Sidt2 is involved in NAADP-mediated release of calcium from insulin secretory granules and thus regulates insulin secretion. © 2016 Society for Endocrinology.

Molecular imaging of in vivo calcium ion expression in area postrema of total sleep deprived rats: Implications for cardiovascular regulation by TOF-SIMS analysis

NASA Astrophysics Data System (ADS)

Mai, Fu-Der; Chen, Li-You; Ling, Yong-Chien; Chen, Bo-Jung; Wu, Un-In; Chang, Hung-Ming

2010-05-01

Excessive calcium influx in chemosensitive neurons of area postrema (AP) is detrimental for sympathetic activation and participates in the disruption of cardiovascular activities. Since total sleep deprivation (TSD) is a stressful condition known to harm the cardiovascular function, the present study is aimed to determine whether the in vivo calcium expression in AP would significantly alter following TSD by the use of time-of-flight secondary ion mass spectrometry (TOF-SIMS) and calretinin (a specific calcium sensor protein in AP neurons) immunohistochemistry. The results indicated that in normal rats, the calcium intensity was estimated to be 0.5 × 10 5 at m/ z 40.08. However, following TSD, the intensity for calcium ions was greatly increased to 1.2 × 10 5. Molecular imaging revealed that after TSD, various strongly expressed calcium signals were distributed throughout AP with clear identified profiles instead of randomly scattered within this region in normal rats. Immunohistochemical staining corresponded well with ionic image in which a majority of calcium-enriched gathering co-localized with calretinin positive neurons. The functional significance of TSD-induced calcium augmentation was demonstrated by increased heart rate and mean arterial pressure, clinical markers for cardiovascular dysfunction. Considering AP-mediated sympathetic activation is important for cardiovascular regulation, exaggerated calcium influx in AP would render this neurocircuitry more vulnerable to over-excitation, which might serve as the underlying mechanism for the development of TSD-relevant cardiovascular deficiency.

Cetuximab-induced hypomagnesaemia aggravates peripheral sensory neurotoxicity caused by oxaliplatin

PubMed Central

Satomi, Machiko; Asama, Toshiyuki; Ebisawa, Yoshiaki; Chisato, Naoyuki; Suno, Manabu; Karasaki, Hidenori; Furukawa, Hiroyuki; Matsubara, Kazuo

2010-01-01

Calcium and magnesium replacement is effective in reducing oxaliplatin-induced neurotoxicity. However, cetuximab treatment has been associated with severe hypomagnesaemia. Therefore, we retrospectively investigated whether cetuximab-induced hypomagnesaemia exacerbated oxaliplatin-induced neurotoxicity. Six patients with metastatic colorectal cancer who were previously treated with oxaliplatin-fluorouracil combination therapy were administered cetuximab in combination with irinotecan alone or irinotecan and fluorouracil as a second-line treatment. All patients had normal magnesium levels before receiving cetuximab. The Common Terminology Criteria for Adverse Events version 3.0 was used to evaluate the grade of neurotoxicity, hypomagnesaemia, hypocalcaemia, and hypokalemia every week. All six patients had grade 1 or higher hypomagnesaemia after starting cetuximab therapy. The serum calcium and potassium levels were within the normal range at the onset of hypomagnesaemia. Oxaliplatin-induced neurotoxicity occurred in all patients at the beginning of cetuximab therapy, with grade 1 neurotoxicity in five patients and grade 2 in one patient. After cetuximab administration, the neurotoxicity worsened in all six patients, and three progressed to grade 3. Among the three patients with grade 3 neurotoxicity, two required a dose reduction and one had to discontinue cetuximab therapy. A discontinuation or dose reduction in cetuximab therapy was associated with exacerbated oxaliplatin-induced neurotoxicity due to cetuximab-induced hypomagnesaemia in half of patients who had previously received oxaliplatin. Therefore, when administering cetuximab after oxaliplatin therapy, we suggest serially evaluating serum magnesium levels and neurotoxicity. PMID:22811813

Effects of AISI 316L corrosion products in in vitro bone formation.

PubMed

Morais, S; Sousa, J P; Fernandes, M H; Carvalho, G S; de Bruijn, J D; van Blitterswijk, C A

1998-06-01

Rat bone marrow cells were cultured in experimental conditions that favour the proliferation and differentiation of osteoblastic cells (i.e., 2.52 x 10(-4) mol l(-1) ascorbic acid, 10(-2) mol l(-1) beta-glycerophosphate and 10(-8) mol l(-1) dexamethasone) in the absence and in the presence of stainless-steel corrosion products, for a period of 18 days. An AISI 316L stainless-steel slurry (SS) was obtained by electrochemical means and the concentrations of the major metal ions, determined by atomic absorption spectrometry, were 8.78 x 10(-3) mol l(-1) of Fe, 4.31 x 10(-3) mol l(-1) of Cr and 2.56 x 10(-3) mol l(-1) of Ni. Bone marrow cells were exposed to 0.01, 0.1 and 1% of the SS and at the end of the incubation period, control and treated cultures were evaluated by histochemical assays for the identification of the presence of alkaline phosphatase and also calcium and phosphate deposition. Cultures were further observed by scanning electron microscopy. Levels of total and ionised calcium and phosphorus in the culture media collected from control and metal exposed cell cultures were also quantified. Histochemical staining showed that control cultures presented a strong reaction for the presence of alkaline phosphatase and exhibited formation of calcium and phosphates deposits. The presence of 0.01% SS caused no detectable biological effects in these cultures, 0.1% SS impaired osteoblastic behaviour and, 1% SS resulted in cell death. In the absence of bone cells, levels of total and ionised calcium and phosphorus in the control and metal added culture medium were similar throughout the incubation period. A significant decrease in the levels of ionised calcium and phosphorus were observed in the culture medium of control cultures and also in cultures exposed to 0.01% SS after two weeks of incubation, an event related with the formation of mineral calcium phosphate deposits in these cultures. In cultures grown in the presence of 0.1 and 1% SS corrosion products, levels of calcium and phosphorus were similar to those observed in the absence of cells. Results showed that stainless-steel corrosion products above certain concentrations may disturb the normal behaviour of osteoblast-like rat bone marrow cell cultures.

Physiological Role of Gap-Junctional Hemichannels

PubMed Central

Quist, Arjan Pieter; Rhee, Seung Keun; Lin, Hai; Lal, Ratneshwar

2000-01-01

Hemichannels in the overlapping regions of apposing cells plasma membranes join to form gap junctions and provide an intercellular communication pathway. Hemichannels are also present in the nonjunctional regions of individual cells and their activity is gated by several agents, including calcium. However, their physiological roles are unknown. Using techniques of atomic force microscopy (AFM), fluorescent dye uptake assay, and laser confocal immunofluorescence imaging, we have examined the extracellular calcium-dependent modulation of cell volume. In response to a change in the extracellular physiological calcium concentration (1.8 to ≤1.6 mM) in an otherwise isosmotic condition, real-time AFM imaging revealed a significant and reversible increase in the volume of cells expressing gap-junctional proteins (connexins). Volume change did not occur in cells that were not expressing connexins. However, after the transient or stable transfection of connexin43, volume change did occur. The volume increase was accompanied by cytochalasin D-sensitive higher cell stiffness, which helped maintain cell integrity. These cellular physical changes were prevented by gap-junctional blockers, oleamide and β-glycyrrhetinic acid, or were reversed by returning extracellular calcium to the normal level. We conclude that nongap-junctional hemichannels regulate cell volume in response to the change in extracellular physiological calcium in an otherwise isosmotic situation. PMID:10704454

Influence of the ionophore A23187 on the plastic behavior of normal erythrocytes.

PubMed

Kuettner, J F; Dreher, K L; Rao, G H; Eaton, J W; Blackshear, P L; White, J G

1977-07-01

Previous studies have demonstrated that A23187, an ionophore which selectively transports divalent cations across cell membranes, has profound effects on human erythrocytes: it causes red cells to take up calcium; lose potassium, water, and ATP; convert from biconcave discs to echinocytes and spheroechinocytes; and become more rigid. The present study has explored the influence of calcium uptake induced by the ionophore on the behavior of individual erythrocyte membranes by the micropipette aspiration technique. Exposure of erythrocytes to calcium and A23187 for intervals of up to 30 minutes resulted in marked changes in membrane viscoelastic properties, including the development of increased resistance to aspiration. The most striking manifestation of altered membrane mechanics was apparent after 10 minutes on incubation. Cells pulled into the pipette for a few seconds and the extruded back into the medium retained the deformity imposed by the pipette for several seconds to a few minutes before regaining the form they manifested prior to initial aspiration. The calcium-induced changes in erythrocyte behavior observed in this study strongly support the concept that extrinsic proteins located inside the membrane provide mechanical support to the cell wall, and that increased levels of calcium cause precipitation or cross-linking of the proteins responsible for the increased resistence to deformation and recoil observed after aspiration into micropipettes.

[Role of serum 25-hydroxyvitamin D in the diagnosis of vitamin D deficiency rickets].

PubMed

Wang, Xiao-Yan; Jin, Chun-Hua; Wu, Jian-Xin; Liu, Zhuo; Li, Mei; Li, Na

2012-10-01

To study the role of serum 25-hydroxyvitamin D in the early diagnosis of vitamin D deficiency rickets. Concentrations of serum 25(OH)D, calcium, phosphorus and alkaline phosphatase were measured in normal control (n=73), suspected rickets (n=45) and confirmed rickets groups (n=65). Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of serum 25(OH)D for rickets. Serum 25(OH)D levels in the suspected and confirmed rickets groups were 83±30 and 72±31 nmol/L respectively, which was lower than in the normal control group (112±37 nmol/L) (P<0.01). There was no significant difference between the suspected and confirmed rickets groups (P>0.05). Vitamin D deficiency rates in the suspected and confirmed rickets groups were higher than in the control group (P<0.01). The ROC curve area of serum 25(OH)D for the diagnosis of rickets was 0.760 (95%CI 0.692-0.820, P<0.01), and the optimal operating point was 90.70 nmol/L (sensitivity 68.49%, specificity 72.73%). There was no significant difference in levels of calcium, phosphorus and alkaline phosphatase between the three groups (P>0.05). Serum 25(OH)D levels in infants with suspected and confirmed rickets are significantly reduced and this may reflect vitamin D deficiency . Therefore, it may be useful to check serum 25(OH)D levels in screening for rickets.

Influence of hypergravity on fish inner ear otoliths: II. Incorporation of calcium and kinetotic behaviour.

PubMed

Beier, M; Anken, R H; Rahmann, H

2002-01-01

Larval siblings of cichlid fish (Oreochromis mossambicus) were subjected to hypergravity (hg; 3 g, 14 days) during development. Following the transfer to 1 g (i.e., stopping the centrifuge) they were separated into normally and kinetotically swimming individuals (the latter performed spinning movements). During hg, the animals were maintained in aquarium water containing alizarin-complexone (AC), a fluorescent calcium tracer. Densitometric measurements of AC uptake into inner ear otoliths (optical density of AC/micrometers2) revealed that the kinetotic individuals had incorporated significantly more AC/calcium than the normally behaving fish. Since the amount of otolithic calcium can be taken as an approximation for otolith weight, the present results indicate that the otoliths of kinetotically swimming samples were heavier than those of the normally behaving larvae, thus exhibiting a higher absolute weight asymmetry of the otoliths between the right vs. the left side of the body. This supports an earlier concept according to which otolith (or statolith) asymmetry is the cause for kinetoses such as human static space sickness. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

The control of calcium metabolism by parathyroid hormone, calcitonin and vitamin D

NASA Technical Reports Server (NTRS)

Potts, J. T., Jr.

1976-01-01

Advances in analysis of chemistry and physiology of parathyroid hormone, calcitonin, and Vitamin D are described along with development of techniques in radioassay methods. Emphasis is placed on assessment of normal and abnormal patterns of secretion of these hormones in specific relation to the physiological adaptations of weightlessness and space flight. Related diseases that involve perturbations in normal skeletal and calcium homeostasis are also considered.

Consequences of phosphorus interactions with calcium, phytase, and cholecalciferol on zootechnical performance and mineral retention in broiler chickens.

PubMed

Delezie, E; Maertens, L; Huyghebaert, G

2012-10-01

The objective was to determine the effect of calcium (Ca), total phosphorus (Ptot), cholecalciferol, and phytase level in the diet on the performance, tibia ash percentage, and Ca and P retention in broilers until slaughter age. Broilers were randomly assigned to 12 treatments, each with 6 replicates, comprising 3 diets differing in Ca and P level: 1) normal Ca and Ptot level (NN); 2) normal Ca and low Ptot level (NL), 3) low Ca and Ptot level (LL). Broilers were also given 2 levels of cholecalciferol and 2 levels of phytase. The normal levels of Ca and Ptot for the starter, grower, and finisher phases were 0.90, 0.82, 0.74% and 0.67, 0.62, 0.57%, respectively. The low Ca and Ptot levels for the 3 phases were 0.67, 0.60, 0.52% and 0.57, 0.51, 0.46%, respectively. Broilers of the NL treatment obtained the lowest BW, whereas BW of the NN and LL groups were comparable. Cholecalciferol significantly affected the BW, with differences up to 2.6 and 1.2% for the starter and grower phases, respectively. The highest cholecalciferol effect was found in combination with the NN treatment. The percentage of retained Ca increased from 33% to 41% and 48% when the imbalanced diet was replaced by the NN and LL balanced diets, respectively. P release from phytate was 64 and 67% for the NL and LL diets, respectively. Phytase and cholecalciferol had significantly favorable effects on retention values but these effects were dependent on Ca and Ptot levels and their ratio. In conclusion, both diets with the balanced Ca/Ptot ratio resulted in the best performance, highest tibia ash percentage and P release from phytate. A reduction of the Aviagen (2009) recommended P requirements by 25 to 30% and Ca by 15 to 20% over the various phases did not negatively affect performance, bone development, and improved Ca and Ptot retention. The effects of supplementing cholecalciferol and phytase were additive but not significant and no synergism between both was present.

Java project on periodontal diseases: effect of vitamin C/calcium threonate/citrus flavonoids supplementation on periodontal pathogens, CRP and HbA1c.

PubMed

Amaliya, Amaliya; Laine, Marja L; Loos, Bruno G; Van der Velden, Ubele

2015-12-01

To assess in a periodontally diseased rural population deprived from regular dental care and having poor dietary conditions, the effect of vitamin C/calcium threonate/citrus flavonoids (VitC/Ca/Fl) supplementation on subgingival microbiota and plasma levels of vitamin C, HbA1c and hsCRP. The study population consisted of 98 subjects who previously participated in a prospective study on the natural history of periodontitis. Participants were instructed to consume one tablet/day containing 200 mg Ester C(®) calcium ascorbate, 25 mg calcium threonate and 100 mg citrus flavonoids for 90 days. Following parameters were evaluated: prevalence/amount of seven traditional periodontal pathogens, cytomegalovirus, Epstein-Barr virus (EBV); and plasma levels of vitamin C, HbA1c and hsCRP. After VitC/Ca/Fl supplementation, 100% of subjects showed normal plasma vitamin C values compared to 55% before. At baseline, 48% of subjects harboured Aggregatibacter actinomycetemcomitans, >97% the other periodontal pathogens and 73% EBV. Supplementation with VitC/Ca/F reduced the subgingival load of all studied bacteria (p-values: 0.014-0.0001) and EBV (p < 0.0001) substantially in all initially positive subjects. Plasma levels of HbA1c and hsCRP dropped in all subjects (p < 0.0001). This uncontrolled study suggested that supplemental VitC/Ca/Fl may be helpful in reducing subgingival numbers of periodontal pathogens and EBV, and promoting systemic health. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dietary vitamin D intake is not associated with 25-hydroxyvitamin D3 or parathyroid hormone in elderly subjects, whereas the calcium-to-phosphate ratio affects parathyroid hormone.

PubMed

Jungert, Alexandra; Neuhäuser-Berthold, Monika

2013-08-01

This cross-sectional study investigates whether serum 25-hydroxyvitamin D3 [25(OH)D3] and intact parathyroid hormone (iPTH) are affected by vitamin D, calcium, or phosphate intake in 140 independently living elderly subjects from Germany (99 women and 41 men; age, 66-96 years). We hypothesized that habitual dietary intakes of vitamin D, calcium, and phosphate are not associated with 25(OH)D3 or iPTH and that body mass index confounds these associations. Serum 25(OH)D3 and iPTH were measured by an electrochemiluminescence immunoassay. Dietary intake was determined using a 3-day estimated dietary record. The median dietary intake levels of vitamin D, calcium, and phosphate were 3 μg/d, 999 mg/d, and 1250 mg/d, respectively. Multiple regression analyses confirmed that dietary vitamin D and calcium did not affect 25(OH)D3 or iPTH; however, supplemental intakes of vitamin D and calcium were associated with 25(OH)D3 after adjustment for age, sex, body composition, sun exposure, physical activity, and smoking. In addition, phosphate intake and the calcium-to-phosphate ratio were associated with iPTH after multiple adjustments. In a subgroup analysis, calcium and vitamin D supplements, as well as phosphate intake, were associated with 25(OH)D3 and/or iPTH in normal-weight subjects only. Our results indicate that habitual dietary vitamin D and calcium intakes have no independent effects on 25(OH)D3 or iPTH in elderly subjects without vitamin D deficiency, whereas phosphate intake and the calcium-to-phosphate ratio affect iPTH. However, vitamin D and calcium supplements may increase 25(OH)D3 and decrease iPTH, even during the summer, but the impact of supplements may depend on body mass index. Copyright © 2013. Published by Elsevier Inc.

[Effect of vitamin D deficiency on hypocalcaemia after total thyroidectomy due to benign goitre].

PubMed

Díez, Manuel; Vera, Cristina; Ratia, Tomás; Diego, Lucía; Mendoza, Fernando; Guillamot, Paloma; San Román, Rosario; Mugüerza, José M; Rodríguez, Angel; Medina, Carlos; Gómez, Beatriz; Granell, Javier

2013-04-01

The purpose of this study was to analyse the relationship between preoperative serum levels of vitamin D and postoperative hypocalcaemia after total thyroidectomy. A prospective observational study was conducted on 113 patients treated by total thyroidectomy due to benign disease. Preoperative vitamin D serum levels and postoperative albumin-corrected calcium and parathormone (PTH) levels were determined. Sensitivity, specificity, positive predictive value and negative predictive value of vitamin D and PTH levels, respectively, in the diagnosis of postoperative hypocalcaemia were calculated. Hypocalcaemia was diagnosed in 44 (38.9%) patients. Vitamin D levels were significantly higher in the group of patients with normal postoperative calcium (median: 25.4pg/mL; range: 4-60), compared to those who developed hypocalcaemia (median: 16.4pg/mL; range: 6.3-46.9) (P=.001). Postoperative hypocalcaemia was more frequent in patients with vitamin D < 30ng/mL (39/78) (50%), than among those with normal levels (5/35) (14.2%) (P=.001). Sensitivity, specificity, positive predictive value and negative predictive value were 88% and 68%, 43% and 82%, 50% and 71%, and 85% and 80% for vitamin D and PTH, respectively. Vitamin D and PTH showed independent prognostic values on the risk of hypocalcaemia. The OR associated with vitamin D < 30ng/mL was 4.25 (95% CI: 1.31-13.78) (P=.016), and the OR of PTH<13pg/mL was 15.4 (95% CI: 4.83-49.1) (P<.001). Vitamin D deficiency is a risk factor of hypocalcaemia after total thyroidectomy for benign goitre. The vitamin D level provides independent prognostic information, which is complementary to that given by PTH. Copyright © 2012 AEC. Published by Elsevier Espana. All rights reserved.

Subclinical nutritional rickets among adolescents in Kaghan Valley.

PubMed

Shah, Tanveer Hussain; Hassan, Mukhtiar; Siddiqui, Tahir Saeed

2014-09-01

To determine the occurrence of subclinical rickets and its causing factors among adolescent students of schools in Kaghan Valley, Pakistan. Observation cross-sectional study. Department of Biochemistry and Health Sciences, Hazara University, Mansehra, Ayub Medical College and Teaching Hospital, Abbottabad, from March to April 2012. Sixty seven students (34 boys and 33 girls) age between 11 - 16 years included in the study from different schools of Kaghan Valley, Pakistan. Characteristic, serum biochemical and nutritional status were measured for all the participants. On the basis of biochemical finding the boys and girls students were divided in to two groups, normal subjects and subclinical rickets (absent symptoms with altered biochemistry). Twenty six participants, 19 (73%) girls and 07 (27%) boys had biochemical abnormality but no clinical signs and symptoms of rickets. Low vitamin D and high alkaline phosphatase level were observed in 26 (100%), 21 (81%), low calcium in 17 (65%) and low phosphorus 7 (27%) subjects with subclinical rickets. None had high parathormone level above normal range. Nutritional intake of calcium, phosphorus and vitamin D was found less than the recommended daily intake in all the participants. Subclinical rickets is common problem among adolescent students especially in girls which is due to low nutritional intakes and avoidance of sunshine due to environmental and traditional impacts.

Ketone bodies protection against HIV-1 Tat-induced neurotoxicity.

PubMed

Hui, Liang; Chen, Xuesong; Bhatt, Dhaval; Geiger, Nicholas H; Rosenberger, Thad A; Haughey, Norman J; Masino, Susan A; Geiger, Jonathan D

2012-07-01

HIV-1-associated neurocognitive disorder (HAND) is a syndrome that ranges clinically from subtle neuropsychological impairments to profoundly disabling HIV-associated dementia. Not only is the pathogenesis of HAND unclear, but also effective treatments are unavailable. The HIV-1 transactivator of transcription protein (HIV-1 Tat) is strongly implicated in the pathogenesis of HAND, in part, because of its well-characterized ability to directly excite neurons and cause neurotoxicity. Consistent with previous findings from others, we demonstrate here that HIV-1 Tat induced neurotoxicity, increased intracellular calcium, and disrupted a variety of mitochondria functions, such as reducing mitochondrial membrane potential, increasing levels of reactive oxygen species, and decreasing bioenergetic efficiency. Of therapeutic importance, we show that treatment of cultured neurons with ketone bodies normalized HIV-1 Tat induced changes in levels of intracellular calcium, mitochondrial function, and neuronal cell death. Ketone bodies are normally produced in the body and serve as alternative energy substrates in tissues including brain and can cross the blood-brain barrier. Ketogenic strategies have been used clinically for treatment of neurological disorders and our current results suggest that similar strategies may also provide clinical benefits in the treatment of HAND. © 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.

Combined Therapy with Renin-Angiotensin System and Calcium Channel Blockers in Type 2 Diabetic Hypertensive Patients with Proteinuria: Effects on Soluble TWEAK, PTX3, and Flow-Mediated Dilation

PubMed Central

Yilmaz, Mahmut Ilker; Carrero, Juan Jesús; Martín-Ventura, Jose Luis; Sonmez, Alper; Saglam, Mutlu; Celik, Turgay; Yaman, Halil; Yenicesu, Mujdat; Eyileten, Tayfun; Moreno, Juan Antonio; Egido, Jesús

2010-01-01

Background and objectives: Soluble TNF-like weak inducer of apoptosis (sTWEAK) and long pentraxin-3 (PTX3) concentrations have been associated with endothelial function in patients with chronic kidney disease (CKD). This study tested the hypothesis that the improvement in endothelial function after initiation of angiotensin II receptor blocker (valsartan), calcium channel blocker (amlodipine) therapy, or a combination of both is directly linked to the normalization of sTWEAK and PTX3. Design, setting, participants, & measurements: One-hundred-eight diabetic CKD stage I patients with hypertension (56% men, 46.7 ± 5.3 years) were allocated to a 12-week intervention with amlodipine (10 mg/d), valsartan (160 mg/d), or their combination. Plasma levels of sTWEAK, PTX3, and flow-mediated dilation (FMD) were studied during the interventions. Results: All treatment strategies effectively increased FMD and reduced proteinuria, confirming a more prone reduction with the combined therapy. These improvements were followed by significant PTX3 reductions. Valsartan alone and in combination with amlodipine achieved significant incremental raises in sTWEAK plasma levels. More importantly, the changes observed in sTWEAK (β = 0.25, P = 0.006) or PTX3 (β = −0.24, P = 0.007) plasma levels were independently associated with the improvement in ultrasonographically measured FMD. Conclusions: This study shows that treatment with antihypertensive drugs improves FMD and normalizes proteinuria, PTX3, and sTWEAK in diabetic CKD stage I patients with hypertension. The improvement in FMD was independently associated with PTX3 and sTWEAK normalization. Two surrogate biomarkers of endothelial function are therefore identified with potential as therapeutic targets. The study was registered in clinicaltrials.gov as NCT00921570. PMID:20430947

[Determination of micro and macronutrients in the cattle of the Venezuelan plains and their influence on the origin of bovine paraplegic syndrome].

PubMed

Rojas, H; Serrano, J R; DiPolo, R

1994-01-01

We report a study carried out in three livestock-producing regions of Venezuela to determine the mineral status of grazing cattle and its relationship to the Síndrome Parpléjico del Bovino (SPB). Animal tissue samples from blood and liver were collected from a total of 17 farms within three regions: southwest (Apure), central (Guárico) and southeast (Bolívar) both during the dry and rainy seasons. In SPB free animals, the serum levels of sodium, potassium, chloride, magnesium, total and ionized calcium, phosphorus, and creatinine, were within the normal range. Glucose was found to be deficient in cattle from Bolívar and Guárico states and normal in Apure. With the exception of liver copper and serum zinc, all the other microelements analyzed (liver cobalt, and molybdenum, and serum iron) were found to be normal. Copper was found to be low in all regions studied with a mean value of 74.8 ppm indicating a moderate deficiency of this element. Similarly, in the central and southwest regions, zinc was found to be close to 0.34 ppm, significantly lower than the critical level of 0.7 ppm. In order to determine the effect of the dry and rainy seasons on the content of macro and microelements, controlled group of cattle from the three regions were followed in their contents of magnesium, calcium, copper and iron. In the dry season all of these elements tended to be much lower, showing a significant increase in the rainy season. This increase was much greater in cattle that received mineral supplementation and sanitary treatment. Bovines with diagnosis of SPB showed: low liver copper content, low serum magnesium and phosphorus levels significantly higher that control cattle.

Proteomics detection of S100A6 in tumor tissue interstitial fluid and evaluation of its potential as a biomarker of cholangiocarcinoma.

PubMed

Onsurathum, Sudarat; Haonon, Ornuma; Pinlaor, Porntip; Pairojkul, Chawalit; Khuntikeo, Narong; Thanan, Raynoo; Roytrakul, Sittiruk; Pinlaor, Somchai

2018-04-01

Tumor interstitial fluid contains tumor-specific proteins that may be useful biomarkers for cancers. In this study, we identified proteins present in cholangiocarcinoma interstitial fluid. Proteins derived from three samples of tumor interstitial fluid and paired samples of adjacent normal interstitial fluid from cholangiocarcinoma patients were subjected to two-dimensional liquid chromatography with tandem mass spectrometry. Candidate proteins were selected based on a greater than twofold change in expression levels between tumor interstitial fluid and normal interstitial fluid. Upregulation of six proteins in tumor interstitial fluid, including S100 calcium binding protein A6 (S100A6), S100 calcium binding protein A9, aldo-keto reductase family 1 member C4, neuropilin-1, 14-3-3 zeta/delta, and triosephosphate isomerase was assessed by western blot and immunohistochemistry. Their potential as markers was evaluated in human cholangiocarcinoma tissue arrays, and in serum using enzyme-linked immunosorbent assay. Expression of S100A6 was higher in tumor interstitial fluid than in normal interstitial fluid and showed the highest positive rate (98.96%) in cholangiocarcinoma tissues. Serum levels of S100A6 did not differ between cholangitis and cholangiocarcinoma patients, but were significantly higher than in healthy individuals ( p < 0.0001). In cholangiocarcinoma cases, S100A6 level was associated with vascular invasion ( p = 0.007) and could distinguish cholangiocarcinoma patients from healthy individuals as effectively as the carbohydrate antigen 19-9. In addition, potential for drug treatment targeting S100A6 and other candidate proteins was also demonstrated using STITCH analysis. In conclusion, proteomics analysis of tumor interstitial fluid could be a new approach for biomarker discovery, and S100A6 is a potential risk marker for screening of cholangiocarcinoma.

The effect of habitat geology on calcium intake and calcium status of wild rodents.

PubMed

Shore, R F; Balment, R J; Yalden, D W

1991-12-01

Calcium is essential for normal physiological function, reproduction and growth in mammals but its distribution in the natural environment is heterogeneous. Spatial variation in calcium soil content is especially marked in the Peak District, United Kingdom, where both calcium-rich limestone and calcium-poor gritstone rock types occur. Wood mice Apodemus sylvaticus (L) and bank voles Clethrionomys glareolus (Schreber 1780) from limestone areas had significantly higher calcium concentrations in stomach contents and in faeces compared with their counterparts from gritstone areas. Calcium status was assessed from serum calcium concentration, femur weight, ash content of the body, calcium concentration in the femur and body ash. There was no significant difference in serum calcium concentration, femur calcium concentration and body ash calcium concentration between animals from the limestone and the gritstone. However, on the limestone, bank voles, but not wood mice, had significantly heavier femora and a greater proportion of ash in the body compared with their gritstone counterparts.

[Traffic-related PM2.5 regulates IL-2 releasing in Jurkat T cells by calcium signaling pathway].

PubMed

Tong, Guoqiang; Zhang, Zhihong; Han, Jianbiao; Qiu, Yong; Xu, Jianjun

2013-09-01

To explore the effects of traffic-related PM2.5 on interleukin-2 (IL-2) in Jurkat T cells and the regulatory action of calcium signaling pathway. The cells were exposed to 100 microg/ml of PM2.5 for 3, 6 and 24 h. Normal saline group, blank filter group, calcium chelating agent EGTA group and the calcineurin antagonist cyclosporine A (CSA) group were as parallel control. The level of IL-2 was detected by ELISA kits, the mRNA expression of CaN, NFAT were determined by QRT-PCR. The nuclear distribution of NFAT was observed by immunofluorescence microscopy. The level of IL-2 in Jurkat T cells exposed to 100 microg/ml PM2.5 was significantly lower than parallel groups, but higher than PM2.5 + CSA group and PM2.5 + EGTA group (P < 0.05). With the increase of time, the releasing level of IL-2 appeared reducing trend in 100 microg/ml of PM2.5 group. The mRNA expression level of NFAT and CaN were higher than parallel groups, PM2.5 + CSA group and PM2.5 + EGTA group (P < 0.05). PM2.5 can induce NFAT protein with dephosphorylation and be activated, and NFAT protein can shift into nuclear. The level of IL-2 was negatively associated with the expression level of NFAT and CaN gene (P < 0.05). Traffic-related PM2.5 may inhibit the releasing of IL-2, Ca(2+)-CaN-NFAT signal pathway may involve in the regulation of IL-2.

Changes in 42K efflux produced by alterations in transmembrane calcium movements in turtle cardiac pace-maker tissue.

PubMed Central

Fleming, B P; Giles, W

1981-01-01

1. 42K efflux has been measured from small strips of turtle sinus venosus which were electrically paced. Three different procedures for altering transmembrane calcium influx have been utilized to test whether changes in 42K efflux may be modulated by changes in intracellular calcium levels. 2. No significant changes in the 42K fractional escape rate (FER) were observed when external calcium was reduced to O mM or increased to 4 x normal (10 mM). In these experiments extracellular divalent cation concentration was held constant by adding or removing magnesium ions. 3. Application of 10 mM-Ba2+ also failed to alter 42K FER consistently. In red blood cells and snail neurones addition of barium ions has been shown to reduce significantly the calcium-mediated potassium current. 4. A tenfold increase in pacing rate (0.5-5 Hz) resulted in an augmented 42K FER, but repetition of this rate change in O mM-Ca2+ indicated that this increase in 42K FER was not strongly dependent on the amount of calcium entry. 5. Attempts to load the pace-maker cells with calcium by using the ionophore A23187 (10 micrograms ml . -1 of 2.0 x 10(-5) M) consistently resulted in very large increases in 42K FER. However, this effect (i) was blocked by atropine and (ii) was markedly reduced by pretreating the tissues with hemicholinium, indicating that A23187-induced release of acetylcholine from the endogenous nerve terminals was responsible for the observed increase in 42K FER. 6. In summary, three different experimental tests indicate that the majority of the 42K efflux is not tightly linked to transmembrane calcium movement in sinus venosus pace-maker tissue. PMID:6796675

Estimating background-subtracted fluorescence transients in calcium imaging experiments: a quantitative approach.

PubMed

Joucla, Sébastien; Franconville, Romain; Pippow, Andreas; Kloppenburg, Peter; Pouzat, Christophe

2013-08-01

Calcium imaging has become a routine technique in neuroscience for subcellular to network level investigations. The fast progresses in the development of new indicators and imaging techniques call for dedicated reliable analysis methods. In particular, efficient and quantitative background fluorescence subtraction routines would be beneficial to most of the calcium imaging research field. A background-subtracted fluorescence transients estimation method that does not require any independent background measurement is therefore developed. This method is based on a fluorescence model fitted to single-trial data using a classical nonlinear regression approach. The model includes an appropriate probabilistic description of the acquisition system's noise leading to accurate confidence intervals on all quantities of interest (background fluorescence, normalized background-subtracted fluorescence time course) when background fluorescence is homogeneous. An automatic procedure detecting background inhomogeneities inside the region of interest is also developed and is shown to be efficient on simulated data. The implementation and performances of the proposed method on experimental recordings from the mouse hypothalamus are presented in details. This method, which applies to both single-cell and bulk-stained tissues recordings, should help improving the statistical comparison of fluorescence calcium signals between experiments and studies. Copyright © 2013 Elsevier Ltd. All rights reserved.

Elemental calcium intake associated with calcium acetate/calcium carbonate in the treatment of hyperphosphatemia

PubMed Central

Wilson, Rosamund J; Copley, J Brian

2017-01-01

Background Calcium-based and non-calcium-based phosphate binders have similar efficacy in the treatment of hyperphosphatemia; however, calcium-based binders may be associated with hypercalcemia, vascular calcification, and adynamic bone disease. Scope A post hoc analysis was carried out of data from a 16-week, Phase IV study of patients with end-stage renal disease (ESRD) who switched to lanthanum carbonate monotherapy from baseline calcium acetate/calcium carbonate monotherapy. Of the intent-to-treat population (N=2520), 752 patients with recorded dose data for calcium acetate (n=551)/calcium carbonate (n=201) at baseline and lanthanum carbonate at week 16 were studied. Elemental calcium intake, serum phosphate, corrected serum calcium, and serum intact parathyroid hormone levels were analyzed. Findings Of the 551 patients with calcium acetate dose data, 271 (49.2%) had an elemental calcium intake of at least 1.5 g/day at baseline, and 142 (25.8%) had an intake of at least 2.0 g/day. Mean (95% confidence interval [CI]) serum phosphate levels were 6.1 (5.89, 6.21) mg/dL at baseline and 6.2 (6.04, 6.38) mg/dL at 16 weeks; mean (95% CI) corrected serum calcium levels were 9.3 (9.16, 9.44) mg/dL and 9.2 (9.06, 9.34) mg/dL, respectively. Of the 201 patients with calcium carbonate dose data, 117 (58.2%) had an elemental calcium intake of at least 1.5 g/day, and 76 (37.8%) had an intake of at least 2.0 g/day. Mean (95% CI) serum phosphate levels were 5.8 (5.52, 6.06) mg/dL at baseline and 5.8 (5.53, 6.05) mg/dL at week 16; mean (95% CI) corrected serum calcium levels were 9.7 (9.15, 10.25) mg/dL and 9.2 (9.06, 9.34) mg/dL, respectively. Conclusion Calcium acetate/calcium carbonate phosphate binders, taken to control serum phosphate levels, may result in high levels of elemental calcium intake. This may lead to complications related to calcium balance. PMID:28182142

The Trypanosoma cruzi immunosuppressive factor (TIF) targets a lymphocyte activation event subsequent to increased intracellular calcium ion concentration and translocation of protein kinase C but previous to cyclin D2 and cdk4 mRNA accumulation.

PubMed

Kierszenbaum, F; Majumder, S; Paredes, P; Tanner, M K; Sztein, M B

1998-04-01

Many immunosuppressive effects of Trypanosoma cruzi can be reproduced in vitro by a preparation consisting of molecules spontaneously released by this protozoan (termed trypanosomal immunosuppressive factor (TIF)). In this work, we attempted to establish whether TIF-induced inhibition of lymphoproliferation results from preventing lymphocyte activation or impairing a post-activation process. Although [3H]thymidine uptake and expression of CD25 by normal human T lymphocytes stimulated with a phorbol ester were markedly reduced by T. cruzi or TIF, translocation of cytosolic protein kinase C (PKC) to the cell membrane was not affected. Lymphoproliferation induced by ionomycin was also inhibited by T. cruzi or TIF but the typical elevation of intracellular calcium ions [Ca2+]i caused by this calcium ionophore was not altered. The increase in [Ca2+]i induced with anti-CD3 antibody was also unaffected by TIF. TIF did not preclude lymphocytes stimulated with phytohemagglutinin from accumulating normal mRNA levels of NFAT1 (also known as NFATp) and NFATc. NFAT1 and NFATc are components of the NFAT complex that controls transcription of genes coding for several cytokines and whose translocation to the nucleus is dependent upon PKC activation and increased [Ca2+]i. In contrast, the mRNA levels of cyclin D2 and cdk4, which form a holoenzyme complex known to regulate cell progression through the G1 phase, were markedly reduced by TIF. These results indicated that TIF did not inhibit lymphocyte activation leading to early secondary signaling but curtailed a mechanism controlling cell progression through G1 and necessary for reaching S phase.

Sexual divergence in microtubule function: the novel intranasal microtubule targeting SKIP normalizes axonal transport and enhances memory.

PubMed

Amram, N; Hacohen-Kleiman, G; Sragovich, S; Malishkevich, A; Katz, J; Touloumi, O; Lagoudaki, R; Grigoriadis, N C; Giladi, E; Yeheskel, A; Pasmanik-Chor, M; Jouroukhin, Y; Gozes, I

2016-10-01

Activity-dependent neuroprotective protein (ADNP), essential for brain formation, is a frequent autism spectrum disorder (ASD)-mutated gene. ADNP associates with microtubule end-binding proteins (EBs) through its SxIP motif, to regulate dendritic spine formation and brain plasticity. Here, we reveal SKIP, a novel four-amino-acid peptide representing an EB-binding site, as a replacement therapy in an outbred Adnp-deficient mouse model. We discovered, for the first time, axonal transport deficits in Adnp(+/-) mice (measured by manganese-enhanced magnetic resonance imaging), with significant male-female differences. RNA sequencing evaluations showed major age, sex and genotype differences. Function enrichment and focus on major gene expression changes further implicated channel/transporter function and the cytoskeleton. In particular, a significant maturation change (1 month-five months) was observed in beta1 tubulin (Tubb1) mRNA, only in Adnp(+/+) males, and sex-dependent increase in calcium channel mRNA (Cacna1e) in Adnp(+/+) males compared with females. At the protein level, the Adnp(+/-) mice exhibited impaired hippocampal expression of the calcium channel (voltage-dependent calcium channel, Cacnb1) as well as other key ASD-linked genes including the serotonin transporter (Slc6a4), and the autophagy regulator, BECN1 (Beclin1), in a sex-dependent manner. Intranasal SKIP treatment normalized social memory in 8- to 9-month-old Adnp(+/-)-treated mice to placebo-control levels, while protecting axonal transport and ameliorating changes in ASD-like gene expression. The control, all d-amino analog D-SKIP, did not mimic SKIP activity. SKIP presents a novel prototype for potential ASD drug development, a prevalent unmet medical need.

Computational model based approach to analysis ventricular arrhythmias: Effects of dysfunction calcium channels

NASA Astrophysics Data System (ADS)

Gulothungan, G.; Malathi, R.

2018-04-01

Disturbed sodium (Na+) and calcium (Ca2+) handling is known to be a major predisposing factor for life-threatening cardiac arrhythmias. Cardiac contractility in ventricular tissue is prominent by Ca2+ channels like voltage dependent Ca2+ channels, sodium-calcium exchanger (Na+-Ca2+x) and sacroplasmicrecticulum (SR) Ca2+ pump and leakage channels. Experimental and clinical possibilities for studying cardiac arrhythmias in human ventricular myocardium are very limited. Therefore, the use of alternative methods such as computer simulations is of great importance. Our aim of this article is to study the impact on action potential (AP) generation and propagation in single ventricular myocyte and ventricular tissue under different dysfunction Ca2+ channels condition. In enhanced activity of Na+-Ca2+x, single myocyte produces AP duration (APD90) and APD50 is significantly smaller (266 ms and 235 ms). Its Na+-Ca2+x current at depolarization is increases 60% from its normal level and repolarization current goes more negative (nonfailing= -0.28 pA/pF and failing= -0.47 pA/pF). Similarly, same enhanced activity of Na+-Ca2+x in 10 mm region of ventricular sheet, raises the plateau potential abruptly, which ultimately affects the diastolic repolarization. Compare with normal ventricular sheet region of 10 mm, 10% of ventricular sheet resting state is reduces and ventricular sheet at time 250 ms is goes to resting state very early. In hypertrophy condition, single myocyte produces APD90 and APD50 is worthy of attention smaller (232 mS and 198 ms). Its sodium-potassium (Na+-K+) pump current is 75% reduces from its control conditions (0.13 pA/pF). Hypertrophy condition, 50% of ventricular sheet is reduces to minimum plateau potential state, that starts the repolarization process very early and reduces the APD. In a single failing SR Ca2+ channels myocyte, recovery of Ca2+ concentration level in SR reduces upto 15% from its control myocytes. At time 290 ms, 70% of ventricular sheet is in dysfunction resting potential state in the range -83 mV and ventricular sheet at time 295 ms is goes to 65% dysfunction resting state. Therefore we concluded that shorter APD, instability resting potential and affected calcium induced calcium release (CICR) due to dysfunction Ca2+ channels is potentially have a substantial effect on cardiac contractility and relaxation. Computational study on ventricular tissue AP and its underlying ionic channel currents could help to elucidate possible arrhythmogenic mechanism on a cellular level.

Effect of hydrocortisone on cell morphology in C6 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berliner, J.A.; Bennett, K.; de Vellis, J.

Hydrocortisone has been found to induce cell spreading in rat glial C6 cells by 24 hours after its addition. This spreading phenomenon is correlated with an increase in the fraction of the peripheral cytoplasm occupied by microfilaments. Cytochalasin B causes disorganization of microfilaments in the peripheral cytoplasm of the cells. Additionally, it also prevents cell spreading in response to hormonal stimulation. High levels of calcium prevent recovery of normal microfilament organization and cell spreading following removal of cytochalasin B, but have no effect on normal microfilament organization alone. Additionally both the hydrocortisone induced spreading of C6 cells and increases inmore » peripheral microfilaments are shown to be dependent on RNA and protein synthesis. The levels of protein co-electrophorescing with actin are not affected by hydrocortisone.« less

Magnesium and the Athlete.

PubMed

Volpe, Stella Lucia

2015-01-01

Magnesium is the fourth most abundant mineral and the second most abundant intracellular divalent cation in the body. It is a required mineral that is involved in more than 300 metabolic reactions in the body. Magnesium helps maintain normal nerve and muscle function, heart rhythm (cardiac excitability), vasomotor tone, blood pressure, immune system, bone integrity, and blood glucose levels and promotes calcium absorption. Because of magnesium's role in energy production and storage, normal muscle function, and maintenance of blood glucose levels, it has been studied as an ergogenic aid for athletes. This article will cover the general roles of magnesium, magnesium requirements, and assessment of magnesium status as well as the dietary intake of magnesium and its effects on exercise performance. The research articles cited were limited from those published in 2003 through 2014.

A randomized clinical trial of the effects of supplemental calcium and vitamin D3 on the APC/β-catenin pathway in the normal mucosa of colorectal adenoma patients.

PubMed

Ahearn, Thomas U; Shaukat, Aasma; Flanders, W Dana; Rutherford, Robin E; Bostick, Roberd M

2012-10-01

APC/β-catenin pathway perturbation is a common early event in colorectal carcinogenesis and is affected by calcium and vitamin D in basic science studies. To assess the effects of calcium and vitamin D on adenomatous polyposis coli (APC), β-catenin, and E-cadherin expression in the normal appearing colorectal mucosa of sporadic colorectal adenoma patients, we conducted a randomized, double-blinded, placebo-controlled 2 × 2 factorial clinical trial. Pathology-confirmed colorectal adenoma cases were treated with 2 g/day elemental calcium and/or 800 IU/day vitamin D(3) versus placebo over 6 months (N = 92; 23/group). Overall APC, β-catenin, and E-cadherin expression and distributions in colon crypts in normal-appearing rectal mucosa biopsies were detected by standardized automated immunohistochemistry and quantified by image analysis. In the vitamin D(3)-supplemented group relative to placebo, the proportion of APC in the upper 40% of crypts (Φh APC) increased 21% (P = 0.01), β-catenin decreased 12% (P = 0.18), E-cadherin increased 72% (P = 0.03), and the Φh APC/β-catenin ratio (APC/β-catenin score) increased 31% (P = 0.02). In the calcium-supplemented group Φh APC increased 10% (P = 0.12), β-catenin decreased 15% (P = 0.08), and the APC/β-catenin score increased 41% (P = 0.01). In the calcium/vitamin D(3)-supplemented group, β-catenin decreased 11% (P = 0.20), E-cadherin increased 51% (P = 0.08), and the APC/β-catenin score increased 16% (P = 0.26). These results support (i) that calcium and vitamin D modify APC, β-catenin, and E-cadherin expression in humans in directions hypothesized to reduce risk for colorectal neoplasms, (ii) calcium and vitamin D as potential chemopreventive agents against colorectal neoplasms, and (iii) the potential of APC, β-catenin, and E-cadherin expression as modifiable, preneoplastic risk biomarkers for colorectal neoplasms.

TMEM16A is associated with voltage-gated calcium channels in mouse retina and its function is disrupted upon mutation of the auxiliary α2δ4 subunit

PubMed Central

Caputo, Antonella; Piano, Ilaria; Demontis, Gian Carlo; Bacchi, Niccolò; Casarosa, Simona; Santina, Luca Della; Gargini, Claudia

2015-01-01

Photoreceptors rely upon highly specialized synapses to efficiently transmit signals to multiple postsynaptic targets. Calcium influx in the presynaptic terminal is mediated by voltage-gated calcium channels (VGCC). This event triggers neurotransmitter release, but also gates calcium-activated chloride channels (TMEM), which in turn regulate VGCC activity. In order to investigate the relationship between VGCC and TMEM channels, we analyzed the retina of wild type (WT) and Cacna2d4 mutant mice, in which the VGCC auxiliary α2δ4 subunit carries a nonsense mutation, disrupting the normal channel function. Synaptic terminals of mutant photoreceptors are disarranged and synaptic proteins as well as TMEM16A channels lose their characteristic localization. In parallel, calcium-activated chloride currents are impaired in rods, despite unaltered TMEM16A protein levels. Co-immunoprecipitation revealed the interaction between VGCC and TMEM16A channels in the retina. Heterologous expression of these channels in tsA-201 cells showed that TMEM16A associates with the CaV1.4 subunit, and the association persists upon expression of the mutant α2δ4 subunit. Collectively, our experiments show association between TMEM16A and the α1 subunit of VGCC. Close proximity of these channels allows optimal function of the photoreceptor synaptic terminal under physiological conditions, but also makes TMEM16A channels susceptible to changes occurring to calcium channels. PMID:26557056

Effects of Laparoscopic Sleeve Gastrectomy on Parathyroid Hormone, Vitamin D, Calcium, Phosphorus, and Albumin Levels.

PubMed

Mihmanli, Mehmet; Isil, Riza Gurhan; Isil, Canan Tulay; Omeroglu, Sinan; Sayin, Pinar; Oba, Sibel; Ozturk, Feyza Yener; Altuntas, Yuksel

2017-12-01

Laparoscopic sleeve gastrectomy (LSG) reduces obesity-related co-morbidities, such as diabetes, hypertension, and hyperlipidemia. Endocrinological abnormalities may occur as undesired side effects. Most centers routinely prescribe folic acid, cyanocobalamin (vitB12), and protein replacement in the postoperative period, but 25-OH-vitamin-D3 (vitD) and intact parathyroid hormone (iPTH) levels are not routinely followed up. The aim of this study was to identify the effects of LSG on iPTH, vitD, calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and albumin levels. Data of morbidly obese patients who underwent LSG between January and December 2014 were studied in this prospectively designed study. Serum levels of iPTH, vitD, Ca, P, folic acid, vitB12, ALP, and albumin were measured preoperatively and postoperatively at the 3rd, 6th, and 12th months. In total, 119 patients were analyzed. All patients had normal iPTH, vitD, Ca, P, folic acid, vitB12, ALP, and albumin values preoperatively, and 31.6% had received vitD supplementation during their nutritionist observation time before surgery. At the 3rd, 6th, and 12th postoperative months, 21 (17.6%), 17 (17.3%), and 1 (0.8%) patients, respectively, had increased iPTH and ALP and decreased vitD levels. A total of 39 (32.7%) patients needed high-dose vitD treatment during a 1 year follow-up. Approximately 37.5% of the patients who received vitD supplementation preoperatively needed vitD supplementation postoperatively. Hospital records of 101 of 119 patients who underwent LSG could be screened to determine their vitD supplementation requirements previously ordered by their nutritionist for a 1-year period before LSG. Thirty-two (31.6%) of the 101 patients had received vitD supplementation during the 1-year period preoperatively. Although serum levels of iPTH, vitD, Ca, P, vitB12, ALP, and albumin may be normal preoperatively, severe vitD insufficiency requiring high-dose vitD replacement may develop in morbidly obese patients postoperatively. Instead of iPTH and vitD, which are expensive to measure, ALP serum level, which is correlated with iPTH levels, can be a good indicator to monitor calcium metabolism.

Dietary pattern among schoolchildren with normal nutritional status in Navarre, Spain.

PubMed

Durá-Travé, Teodoro; Gallinas-Victoriano, Fidel

2014-04-11

A nutrition survey was carried out (food intake registration of three consecutive school days) in a randomly selected group of 353 schoolchildren (188 males and 165 females) with normal nutritional status. The average age of the surveyed students was 10.5 years (CI 95%: 10.3-11.7). There were no significant differences between both sexes in mean values for calorie intake (males: 2072.7 ± 261.7 and females: 2060.9 ± 250.6) and intake of macronutrients, minerals and vitamins. Cereals (34%), dairy products (19%) and meats (17%) were responsible for approximately 70% of total calorie intake. Protein accounted for 20.3% of energy intake, carbohydrates for 48.8%, total fat for 30.9%, and saturated fat for 12.6%. Cholesterol intake was excessive and over two-thirds of protein intake was from animal sources. The mean intakes of calcium, iodine and Vitamins A, D and E were below recommended levels. The dietary patterns of the schoolchildren with normal nutritional status differed from the Mediterranean diet. Intakes of meat were too high and dairy products and cereals consumption was relatively limited; while that of vegetables; legumes; fruits and fish were insufficient; leading to excessive protein and fat intake from animal sources and insufficient mineral (calcium and iodine) and Vitamins A; D and E intake.

Progress report on the ground-water resources of the Louisville area, Kentucky, 1949-55

USGS Publications Warehouse

Bell, Edwin A.; Kellogg, Robert W.; Kulp, Willis K.

1963-01-01

In the Louisville area, the principal water-bearing formations are the glacial-outwash sand and gravel and, in places, the underlying limestone. During the period 1949 through 1955 pumpage from the two aquifers averaged about 30 mgd (million gallons per day). The pumpage was approximately in balance with the normal net recharge to the area but was only about 8 percent of the estimated potential supply of ground water, including induced infiltration from the river. In the Louisville area, ground water is used chiefly for air conditioning and for industrial cooling. In the part of the area southwest of the city, ground water is used also for public supply. High ground-water levels in 1937 resulted from the greatest flood of record. Subsequently, water levels generally declined in the entire Louisville area. In downtown Louisville, where ground water is used for air conditioning, the water level fluctuates seasonally in response to variations in the rate of pumping. In the heavily pumped industrial areas, where ground water is used for cooling, water-level fluctuations correlate with changes in rates of pumping caused by variations in production schedules. Levels were lowest during the years of World War II. During the period 1952-55, relatively low levels throughout the area reflected the effects of less than normal rainfall, summer drought, and sustained pumping. Ground water in the Louisville area is very hard and generally of the calcium bicarbonate or calcium sulfate type. It is high in iron and sulfate content but is moderately low in chloride content. In water of the sand and gravel aquifer, the concentration of sulfate has increased gradually during the period 1949-54.

NADPH oxidase-2 inhibition restores contractility and intracellular calcium handling and reduces arrhythmogenicity in dystrophic cardiomyopathy

PubMed Central

Gonzalez, Daniel R.; Treuer, Adriana V.; Lamirault, Guillaume; Mayo, Vera; Cao, Yenong; Dulce, Raul A.

2014-01-01

Duchenne muscular dystrophy may affect cardiac muscle, producing a dystrophic cardiomyopathy in humans and the mdx mouse. We tested the hypothesis that oxidative stress participates in disrupting calcium handling and contractility in the mdx mouse with established cardiomyopathy. We found increased expression (fivefold) of the NADPH oxidase (NOX) 2 in the mdx hearts compared with wild type, along with increased superoxide production. Next, we tested the impact of NOX2 inhibition on contractility and calcium handling in isolated cardiomyocytes. Contractility was decreased in mdx myocytes compared with wild type, and this was restored toward normal by pretreating with apocynin. In addition, the amplitude of evoked intracellular Ca2+ concentration transients that was diminished in mdx myocytes was also restored with NOX2 inhibition. Total sarcoplasmic reticulum (SR) Ca2+ content was reduced in mdx hearts and normalized by apocynin treatment. Additionally, NOX2 inhibition decreased the production of spontaneous diastolic calcium release events and decreased the SR calcium leak in mdx myocytes. In addition, nitric oxide (NO) synthase 1 (NOS-1) expression was increased eightfold in mdx hearts compared with wild type. Nevertheless, cardiac NO production was reduced. To test whether this paradox implied NOS-1 uncoupling, we treated cardiac myocytes with exogenous tetrahydrobioterin, along with the NOX inhibitor VAS2870. These agents restored NO production and phospholamban phosphorylation in mdx toward normal. Together, these results demonstrate that, in mdx hearts, NOX2 inhibition improves the SR calcium handling and contractility, partially by recoupling NOS-1. These findings reveal a new layer of nitroso-redox imbalance in dystrophic cardiomyopathy. PMID:25015966

Effects of Supplemental Vitamin D and Calcium on Normal Colon Tissue and Circulating Biomarkers of Risk for Colorectal Neoplasms

PubMed Central

Bostick, Roberd M.

2015-01-01

This brief review, based on an invited presentation at the 17th Workshop on Vitamin D, is to summarize a line of the author’s research that has been directed at the intertwined missions of clarifying and/or developing vitamin D and calcium and as preventive agents against colorectal cancer in humans, understanding the mechanisms by which these agents may reduce risk for the disease, and developing ‘treatable’ biomarkers of risk for colorectal cancer. The biological plausibility and observational and clinical trial evidence for vitamin D and calcium in reducing risk for colorectal neoplasms, the development of pre-neoplastic biomarkers of risk for colorectal neoplasms, and the clinical trial findings from the author’s research group on the efficacy of vitamin D and calcium in modulating these biomarkers are summarized. Regarding the latter, we tested the efficacy of 800 IU (20 µg) of vitamin D3 and 2.0g of calcium daily, alone and combined vs. placebo over 6 months on modulating normal colon tissue and circulating hypothesis-based biomarkers of risk for colorectal neoplasms in a randomized, double-blind, placebo-controlled, 2×2 factorial design clinical trial (n = 92). The tissue-based biomarkers were measured in biopsies of normal-appearing rectal mucosa using immunohistochemistry with quantitative image analysis, and a panel of circulating inflammation markers was measured using enzyme-linked immunoassays (ELISA). Statistically significant proportional tissue increases in the vitamin D group relative to the placebo group were found in bax (51%), p21 (141%), APC (48%), E-cadherin (78%), MSH2 (179%), the CaSR (39%), and CYP27B1 (159%). In blood, there was a 77% statistically significant decrease in a summary inflammation z-score. The findings for calcium were similar to those for vitamin D. These findings indicate that supplemental vitamin D3 or calcium can favorably modulate multiple normal colon tissue and circulating hypothesis-based biomarkers of risk for colorectal neoplasms in sporadic colorectal adenoma patients. PMID:25597952

Effects of supplemental vitamin D and calcium on normal colon tissue and circulating biomarkers of risk for colorectal neoplasms.

PubMed

Bostick, Roberd M

2015-04-01

This brief review, based on an invited presentation at the 17th Workshop on Vitamin D, is to summarize a line of the author's research that has been directed at the intertwined missions of clarifying and/or developing vitamin D and calcium as preventive agents against colorectal cancer in humans, understanding the mechanisms by which these agents may reduce risk for the disease, and developing 'treatable' biomarkers of risk for colorectal cancer. The biological plausibility and observational and clinical trial evidence for vitamin D and calcium in reducing risk for colorectal neoplasms, the development of pre-neoplastic biomarkers of risk for colorectal neoplasms, and the clinical trial findings from the author's research group on the efficacy of vitamin D and calcium in modulating these biomarkers are summarized. Regarding the latter, we tested the efficacy of 800 IU (20μg) of vitamin D3 and 2.0g of calcium daily, alone and combined vs. placebo over 6 months on modulating normal colon tissue and circulating hypothesis-based biomarkers of risk for colorectal neoplasms in a randomized, double-blind, placebo-controlled, 2×2 factorial design clinical trial (n=92). The tissue-based biomarkers were measured in biopsies of normal-appearing rectal mucosa using immunohistochemistry with quantitative image analysis, and a panel of circulating inflammation markers was measured using enzyme-linked immunoassays (ELISA). Statistically significant proportional tissue increases in the vitamin D group relative to the placebo group were found in bax (51%), p21 (141%), APC (48%), E-cadherin (78%), MSH2 (179%), the CaSR (39%), and CYP27B1 (159%). In blood, there was a 77% statistically significant decrease in a summary inflammation z-score. The findings for calcium were similar to those for vitamin D. These findings indicate that supplemental vitamin D3 or calcium can favorably modulate multiple normal colon tissue and circulating hypothesis-based biomarkers of risk for colorectal neoplasms in sporadic colorectal adenoma patients. This article is part of a Special Issue entitled '17th Vitamin D Workshop'. Copyright © 2015 Elsevier Ltd. All rights reserved.

Treatment of mcf-7 breast cancer cells with a red grape wine polyphenol fraction results in disruption of calcium homeostasis and cell cycle arrest causing selective cytotoxicity.

PubMed

Hakimuddin, Fatima; Paliyath, Gopinadhan; Meckling, Kelly

2006-10-04

Food components influence the physiology by modulating gene expression and biochemical pathways within the human body. The disease-preventive roles of several fruit and vegetable components have been related to such properties. Polyphenolic components such as flavonoids are strong antioxidants and induce the expression of several xenobiotic-detoxifying enzymes. The mechanism of selective cytotoxicity induced by red grape wine polyphenols against MCF-7 breast cancer cells was investigated in relation to their interference with calcium homeostasis. MCF-7 cells showed an increase in cytosolic calcium levels within 10 min of treatment with the polyphenols. Immunohistochemical localization of calmodulin with secondary gold-labeled antibodies showed similar levels of gold labeling in both MCF-7 cells and the spontaneously immortalized, normal MCF-10A cell line. MCF-7 cells treated with the red wine polyphenol fraction (RWPF) showed swelling of endoplasmic reticulum, dissolution of the nucleus, and loss of plasma membrane integrity as well as reduced mitochondrial membrane potential. These cells were arrested at the G2/M interphase. By contrast, MCF-10A cells did not show such changes after RWPF treatment. The results suggest that polyphenol-induced calcium release may disrupt mitochondrial function and cause membrane damage, resulting in selective cytotoxicity toward MCF-7 cells. This property could further be developed toward breast cancer prevention strategies either independently or in conjunction with conventional prevention therapies where a positive drug-nutrient interaction can be demonstrated.

Relationship between nutritional habits and hair calcium levels in young women.

PubMed

Jeruszka-Bielak, Marta; Brzozowska, Anna

2011-12-01

The present study was conducted to investigate whether hair calcium levels are related to nutritional habits, selected status parameters, and life-style factors in young women. Eighty-five healthy female students neither pregnant nor lactating, using no hair dyes or permanents were recruited for the study. Food consumption data, including fortified products and dietary supplements were collected with 4-day records. The calcium levels in hair and serum were analyzed by atomic absorption spectroscopy. Serum osteocalcin and the C-terminal telopeptide of type I collagen were assayed by ELISA. The women were divided into four groups according to their total vitamin D and calcium intakes and hair calcium levels. At adequate calcium intake and comparable serum bone biomarker levels, supplemental vitamin D increased the hair calcium levels. On the other hand, at lower than estimated adequate requirement of vitamin D intake the hair calcium levels were comparable in women with low calcium intakes but consuming high amounts of meat products or those whose diets were rich in dairy products, possibly due to homeostatic mechanisms. Elevated hair calcium was seen in 25% of subjects and could not be related to nutritional or life-style factors. The results show that the hair calcium levels were weakly related to the quality of diet, with some synergistic interactions between nutrients, especially vitamin D and magnesium.

Autosomal dominant hypoparathyroidism caused by germline mutation in GNA11: phenotypic and molecular characterization.

PubMed

Li, Dong; Opas, Evan E; Tuluc, Florin; Metzger, Daniel L; Hou, Cuiping; Hakonarson, Hakon; Levine, Michael A

2014-09-01

Most cases of autosomal dominant hypoparathyroidism (ADH) are caused by gain-of-function mutations in CASR or dominant inhibitor mutations in GCM2 or PTH. Our objectives were to identify the genetic basis for ADH in a multigenerational family and define the underlying disease mechanism. Here we evaluated a multigenerational family with ADH in which affected subjects had normal sequences in these genes and were shorter than unaffected family members. We collected clinical and biochemical data from 6 of 11 affected subjects and performed whole-exome sequence analysis on DNA from two affected sisters and their affected father. Functional studies were performed after expression of wild-type and mutant Gα11 proteins in human embryonic kidney-293-CaR cells that stably express calcium-sensing receptors. Whole-exome-sequencing followed by Sanger sequencing revealed a heterozygous mutation, c.179G>T; p.R60L, in GNA11, which encodes the α-subunit of G11, the principal heterotrimeric G protein that couples calcium-sensing receptors to signal activation in parathyroid cells. Functional studies of Gα11 R60L showed increased accumulation of intracellular concentration of free calcium in response to extracellular concentration of free calcium with a significantly decreased EC50 compared with wild-type Gα11. By contrast, R60L was significantly less effective than the oncogenic Q209L form of Gα11 as an activator of the MAPK pathway. Compared to subjects with CASR mutations, patients with GNA11 mutations lacked hypercalciuria and had normal serum magnesium levels. Our findings indicate that the germline gain-of-function mutation of GNA11 is a cause of ADH and implicate a novel role for GNA11 in skeletal growth.

Autosomal Dominant Hypoparathyroidism Caused by Germline Mutation in GNA11: Phenotypic and Molecular Characterization

PubMed Central

Li, Dong; Opas, Evan E.; Tuluc, Florin; Metzger, Daniel L.; Hou, Cuiping; Hakonarson, Hakon

2014-01-01

Context: Most cases of autosomal dominant hypoparathyroidism (ADH) are caused by gain-of-function mutations in CASR or dominant inhibitor mutations in GCM2 or PTH. Objective: Our objectives were to identify the genetic basis for ADH in a multigenerational family and define the underlying disease mechanism. Subjects: Here we evaluated a multigenerational family with ADH in which affected subjects had normal sequences in these genes and were shorter than unaffected family members. Methods: We collected clinical and biochemical data from 6 of 11 affected subjects and performed whole-exome sequence analysis on DNA from two affected sisters and their affected father. Functional studies were performed after expression of wild-type and mutant Gα11 proteins in human embryonic kidney-293-CaR cells that stably express calcium-sensing receptors. Results: Whole-exome-sequencing followed by Sanger sequencing revealed a heterozygous mutation, c.179G>T; p.R60L, in GNA11, which encodes the α-subunit of G11, the principal heterotrimeric G protein that couples calcium-sensing receptors to signal activation in parathyroid cells. Functional studies of Gα11 R60L showed increased accumulation of intracellular concentration of free calcium in response to extracellular concentration of free calcium with a significantly decreased EC50 compared with wild-type Gα11. By contrast, R60L was significantly less effective than the oncogenic Q209L form of Gα11 as an activator of the MAPK pathway. Compared to subjects with CASR mutations, patients with GNA11 mutations lacked hypercalciuria and had normal serum magnesium levels. Conclusions: Our findings indicate that the germline gain-of-function mutation of GNA11 is a cause of ADH and implicate a novel role for GNA11 in skeletal growth. PMID:24823460

Modifiable Risk Factors for Increased Arterial Stiffness in Outpatient Nephrology

PubMed Central

Elewa, Usama; Fernandez-Fernandez, Beatriz; Alegre, Raquel; Sanchez-Niño, Maria D.; Mahillo-Fernández, Ignacio; Perez-Gomez, Maria Vanessa; El-Fishawy, Hussein; Belal, Dawlat; Ortiz, Alberto

2015-01-01

Arterial stiffness, as measured by pulse wave velocity (PWV), is an independent predictor of cardiovascular events and mortality. Arterial stiffness increases with age. However, modifiable risk factors such as smoking, BP and salt intake also impact on PWV. The finding of modifiable risk factors may lead to the identification of treatable factors, and, thus, is of interest to practicing nephrologist. We have now studied the prevalence and correlates of arterial stiffness, assessed by PWV, in 191 patients from nephrology outpatient clinics in order to identify modifiable risk factors for arterial stiffness that may in the future guide therapeutic decision-making. PWV was above normal levels for age in 85/191 (44.5%) patients. Multivariate analysis showed that advanced age, systolic BP, diabetes mellitus, serum uric acid and calcium polystyrene sulfonate therapy or calcium-containing medication were independent predictors of PWV. A new parameter, Delta above upper limit of normal PWV (Delta PWV) was defined to decrease the weight of age on PWV values. Delta PWV was calculated as (measured PWV) - (upper limit of the age-adjusted PWV values for the general population). Mean±SD Delta PWV was 0.76±1.60 m/sec. In multivariate analysis, systolic blood pressure, active smoking and calcium polystyrene sulfonate therapy remained independent predictors of higher delta PWV, while age, urinary potassium and beta blocker therapy were independent predictors of lower delta PWV. In conclusion, arterial stiffness was frequent in nephrology outpatients. Systolic blood pressure, smoking, serum uric acid, calcium-containing medications, potassium metabolism and non-use of beta blockers are modifiable factors associated with increased arterial stiffness in Nephrology outpatients. PMID:25880081

High doses of digoxin increase the myocardial nuclear factor-kB and CaV1.2 channels in healthy mice. A possible mechanism of digitalis toxicity.

PubMed

Farghaly, Hanan Sayed Mohamed; Ashry, Israa El-Sayed Mohamed; Hareedy, Mohammad Salem

2018-06-06

Toxic effects of digoxin may occur with normal therapeutic serum level. However, the underlying mechanisms are not fully understood. Nuclear factor kappa-B (NF-kB) is an important transcription factor in most organ systems and is often implicated in the harmful effects of cardiac injury. NF-kB promotes inflammatory responses, mediates adverse cardiac remodeling and has a function correlation with calcium. The voltage-gated L-type calcium channel CaV1.2 mediates the influx of Ca+2 into the cell in response to membrane depolarization. Our aim was to characterize the role of NF-kB during digoxin toxicity and to assess its correlation with Cav 1.2 in healthy mice in vivo. To address these questions, digoxin was administered in doses of 0.1, 1 or 5 mg/kg orally daily for seven days to the animals. Serum digoxin, serum calcium, atrial and ventricular calcium levels were measured. We, also, looked for NF-kB and CaV1.2 channel expression in cardiac muscle of mice. Digoxin at a dose of 0.1 mg/kg did not enhance serum, atrial, and ventricular Ca+2 levels, but were increased when digoxin dose of 1 and 5 mg/kg were administered. Histologically, myocardial necrosis and cellular infiltration on day 7 were significantly more severe in the 5 mg/kg/day digoxin group. Immunohistochemical studies showed more expression of both NF-kB and CaV1.2 in 1 and 5 mg/kg/day digoxin groups. These data suggest that NF-kB may be responsible for digoxin toxicity, at least partially via modulation of CaV1.2 and intracellular calcium homeostasis in the myocardium. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Women’s Health Initiative Clinical Trials: Interaction of calcium plus vitamin D and Hormone Therapy

PubMed Central

Robbins, John A; Aragaki, Aaron; Crandall, Carolyn J; Manson, Joann E; Carbone, Laura; Jackson, Rebecca; Lewis, Cora E.; Johnson, Karen C.; Sarto, Gloria; Stefanick, Marcia L; Wactawski-Wende, Jean

2013-01-01

Objective To test the added value of Calcium and vitamin D (CaD) for fracture prevention among women taking postmenopausal hormone therapy (HT). Methods A prospective, partial-factorial design, randomized controlled double blind trial amongst Women’s Health Initiative post-menopausal participants, ages 50–79, at 40 centers in the US, with 7.1 years average follow-up. 27,347 women were randomized to HT (conjugated estrogen 0.625 mg alone, or CEE 0.625 mg daily plus medroxyprogesterone acetate 2.5mg) and 36,282 women randomized to either 1000mg elemental calcium (carbonate) plus 400 IU of vitamin D3 daily each compared to placebo. A total of 16,089 women were in both arms. The predefined outcomes were adjudicated hip fractures and measured bone mineral density. Results Interaction between HT and CaD on hip fracture (P-interaction = 0.01) was shown. The effect of CaD was stronger among women assigned to HT (HR, 0.59; 95%CI, 0.38–0.93) than placebo (HR, 1.20; 95%CI, 0.85, 1.69). The effect of HT on hip fracture was stronger among women assigned to active CaD (HR, 0.43; 0.28–0.66) than placebo (HR, 0.87; 95%CI, 0.60–1.26). CaD supplementation enhanced the anti-fracture effect of the HT at all levels of personal calcium intake. There was no interaction of HT and CaD on change in hip or spine BMD. Conclusions Postmenopausal women at normal risk of hip fracture on HT, supplementation with CaD significantly reduced incident hip fracture beyond HT alone; at all levels of personal baseline total calcium intake. PMID:23799356

Therapeutic effects of aqueous extracts of Petroselinum sativum on ethylene glycol-induced kidney calculi in rats.

PubMed

Saeidi, Jafar; Bozorgi, Hadi; Zendehdel, Ahmad; Mehrzad, Jamshid

2012-01-01

To investigate the therapeutic effects of the aqueous extract of Petroselinum Sativum aerial parts and roots on kidney calculi. Thirty-six male Wistar rats were randomly assigned into 6 groups and treated for 30 days. Group A served as normal control and group B received 1% ethylene glycol in drinking water. Groups C, D, E, and F received 1% ethylene glycol from day 0 and were used as the treatment subjects. Rats in groups C and D received 200 and 600 mg/kg body weight of aerial parts aqueous extract, respectively, and those in groups E and F received 200 and 600 mg/kg body weight of root aqueous extract in drinking water, respectively, from the 14th day of the experiment. On the 14th and 30th days of the experiment, serum level of magnesium (1.71 ± 0.12 and 3.81 ± 0.25, respectively) decreased significantly while serum level of calcium (10.45 ± 0.26 and 11.33 ± 0.18, respectively) increased significantly in group B compared with the control group (14th day: magnesium = 2.87 ± 0.17 and calcium = 8.80 ± 0.00 and 30th day: magnesium = 6.01 ± 0.00 and calcium = 8.30 ± 0.22; P < .001). In the treatment groups of C, D, E, and F, the number of deposits decreased significantly compared with group B on the 30th day (P < .001). The weight of the kidneys increased significantly in group B (2.01 ± 0.17) compared with the control group (1.52 ± 0.07) and decreased significantly in treatment groups (P < .05). Petroselinum Sativum has a therapeutic effect on calcium oxalate stones in rats with nephrolithiasis and reduces the number of calcium oxalate deposits.

Recombinant γT305A fibrinogen indicates severely impaired fibrin polymerization due to the aberrant function of hole 'A' and calcium binding sites.

PubMed

Ikeda, Minami; Kobayashi, Tamaki; Arai, Shinpei; Mukai, Saki; Takezawa, Yuka; Terasawa, Fumiko; Okumura, Nobuo

2014-08-01

We examined a 6-month-old girl with inherited fibrinogen abnormality and no history of bleeding or thrombosis. Routine coagulation screening tests showed a markedly low level of plasma fibrinogen determined by functional measurement and also a low level by antigenic measurement (functional/antigenic ratio=0.295), suggesting hypodysfibrinogenemia. DNA sequence analysis was performed, and γT305A fibrinogen was synthesized in Chinese hamster ovary cells based on the results. We then functionally analyzed and compared with that of nearby recombinant γN308K fibrinogen. DNA sequence analysis revealed a heterozygous γT305A substitution (mature protein residue number). The γT305A fibrinogen indicated markedly impaired thrombin-catalyzed fibrin polymerization both in the presence or absence of 1mM calcium ion compared with that of γN308K fibrinogen. Protection of plasmin degradation in the presence of calcium ion or Gly-Pro-Arg-Pro peptide (analogue for so-called knob 'A') and factor XIIIa-catalyzed fibrinogen crosslinking demonstrated that the calcium binding sites, hole 'a' and D:D interaction sites were all markedly impaired, whereas γN308Kwas impaired at the latter two sites. Molecular modeling demonstrated that γT305 is localized at a shorter distance than γN308 from the high affinity calcium binding site and hole 'a'. Our findings suggest that γT305 might be important for construction of the overall structure of the γ module of fibrinogen. Substitution of γT305A leads to both dysfibrinogenemic and hypofibrinogenemic characterization, namely hypodysfibrinogenemia. We have already reported that recombinant γT305A fibrinogen was synthesized normally and secreted slightly, but was significantly reduced. Copyright © 2014 Elsevier Ltd. All rights reserved.

Tang Wang Ming Mu Granule Attenuates Diabetic Retinopathy in Type 2 Diabetes Rats

PubMed Central

Chen, Mingxia; Lv, Haibo; Gan, Jiakuan; Ren, Junguo; Liu, Jianxun

2017-01-01

Aims: This study aimed to determine the influence of Tang Wang Ming Mu granule (TWMM) on the diabetic retinopathy of diabetic rats. Methods: Male Wistar rats were divided into seven groups: normal control, diabetes model(DM), diabetes with TWMM (3.6, 7.2, and 14.4 g/kg) treatment, the positive control treatment groups of Qi Ming granules and Calcium dobesilate capsules. All rats were treated for 8 weeks. The levels of body weight, fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) in blood were measured to evaluate the antihyperglycemic activity of TWMM. Furthermore, malondialdehyde (MDA), intracellular adhesion molecule-1 (ICAM-1) and vascular endothelial growth factor (VEGF) in serum were measured to study effects of TWMM on oxidative stress and inflammatory in DM2 rats. VEGF, JAK/STAT signaling pathway and SOCS3 in retina was detected by immunohistochemistry. Results: TWMM and the positive control drugs Qi Ming and Calcium dobesilate showed a remarkable suppression of retinal neovascularization and amelioration of retinal internal limiting membrane morphology. Moreover, TWMM significantly decreased HbA1c, MDA, ICAM-1, and VEGF levels in serum of diabetic rats. However, Qi Ming granules showed significantly reduced MDA and VEGF levels (P < 0.01, and P < 0.05, respectively), Calcium dobesilate showed significantly reduced MDA and ICAM-1levels (P < 0.01 and P < 0.05, respectively) in serum. All drug- treated DM2 rats showed significantly lower levels of VEGF, JAK2, P-JAK2, STAT3, and P-STAT3 in retina than DM group, while TWMM and Calcium dobesilate significantly increased SOCS3 in retina. Conclusion: Our data suggest that the diabetic retina protective effect of TWMM might be related to antiinflammatory, antioxidative, upregulation of SOCS3 expression, inhibition of the JAK/STAT/VEGF signaling pathway. PMID:29311988

Effects of oral supplementation with stable strontium

PubMed Central

Skoryna, Stanley C.

1981-01-01

The biologic effects of stable strontium, a naturally occurring trace element in the diet and the body, have been little investigated. This paper discusses the effects of oral supplementation with stable strontium in laboratory studies and clinical investigations. The extent of intestinal absorption of various doses of orally administered strontium was estimated by determining serum and tissue levels with atomic absorption spectrophotometry. The central observation is that increased oral intake produces a direct increase in serum levels and intracellular uptake of strontium. The results of these studies, as well as those of other investigators, demonstrate that a moderate dosage of stable strontium does not adversely affect the level of calcium either in the serum or in soft tissues. In studies of patients receiving 1 to 1.5 g/d of strontium gluconate, a sustained increase in the serum level of strontium produced a 100-fold increase in the strontium:calcium ratio. In rats, studies indicate that an increase in intracellular strontium content following supplementation may exert a protective effect on mitochondrial structure, probably by means of a stabilizing effect of strontium on membranes. The strontium:calcium ratio in animals receiving a standard diet is higher in the cell than in the extracellular fluid; this may be of physiologic significance. An increase in density that corresponded to the deposition of stable strontium was observed in areas of bone lesions due to metastatic cancer in patients receiving stable strontium supplementation. This suggests the possibility of using strontium to mineralize osteophenic areas and to relieve bone pain. Also, because of reports of an inverse relation between the incidence of dental caries and a high strontium content in drinking water, the use of natural water containing relatively high levels of stable strontium should be considered. In each of these instances it is important to maintain a normal dietary intake of calcium. ImagesFIG. 1FIG. 3FIG. 4FIG. 5 PMID:6120036

Mutual independence of alkaline- and calcium-mediated signalling in Aspergillus fumigatus refutes the existence of a conserved druggable signalling nexus.

PubMed

Loss, Omar; Bertuzzi, Margherita; Yan, Yu; Fedorova, Natalie; McCann, Bethany L; Armstrong-James, Darius; Espeso, Eduardo A; Read, Nick D; Nierman, William C; Bignell, Elaine M

2017-12-01

Functional coupling of calcium- and alkaline responsive signalling occurs in multiple fungi to afford efficient cation homeostasis. Host microenvironments exert alkaline stress and potentially toxic concentrations of Ca 2+ , such that highly conserved regulators of both calcium- (Crz) and pH- (PacC/Rim101) responsive signalling are crucial for fungal pathogenicity. Drugs targeting calcineurin are potent antifungal agents but also perturb human immunity thereby negating their use as anti-infectives, abrogation of alkaline signalling has, therefore, been postulated as an adjunctive antifungal strategy. We examined the interdependency of pH- and calcium-mediated signalling in Aspergillus fumigatus and found that calcium chelation severely impedes hyphal growth indicating a critical requirement for this ion independently of ambient pH. Transcriptomic responses to alkaline pH or calcium excess exhibited minimal similarity. Mutants lacking calcineurin, or its client CrzA, displayed normal alkaline tolerance and nuclear translocation of CrzA was unaffected by ambient pH. Expression of a highly conserved, alkaline-regulated, sodium ATPase was tolerant of genetic or chemical perturbations of calcium-mediated signalling, but abolished in null mutants of the pH-responsive transcription factor PacC, and PacC proteolytic processing occurred normally during calcium excess. Taken together our data demonstrate that in A. fumigatus the regulatory hierarchy governing alkaline tolerance circumvents calcineurin signalling. © 2017 The Authors. Molecular Microbiology Published by John Wiley & Sons Ltd.

Reduced cortical BDNF expression and aberrant memory in Carf knockout mice

PubMed Central

McDowell, Kelli A.; Hutchinson, Ashley N.; Wong-Goodrich, Sarah J.E.; Presby, Matthew M.; Su, Dan; Rodriguiz, Ramona M.; Law, Krystal C.; Williams, Christina L.; Wetsel, William C.; West, Anne E.

2010-01-01

Transcription factors are a key point of convergence between the cell-intrinsic and extracellular signals that guide synaptic development and brain plasticity. Calcium-Response Factor (CaRF) is a unique transcription factor first identified as a binding protein for a calcium-response element in the gene encoding Brain-Derived Neurotrophic Factor (Bdnf). We have now generated Carf knockout (KO) mice to characterize the function of this factor in vivo. Intriguingly, Carf KO mice have selectively reduced expression of Bdnf exon IV-containing mRNA transcripts and BDNF protein in the cerebral cortex while BDNF levels in the hippocampus and striatum remain unchanged, implicating CaRF as a brain region-selective regulator of BDNF expression. At the cellular level, Carf KO mice show altered expression of GABAergic proteins at striatal synapses, raising the possibility that CaRF may contribute to aspects of inhibitory synapse development. Carf KO mice show normal spatial learning in the Morris water maze and normal context-dependent fear conditioning. However they have an enhanced ability to find a new platform location on the first day of reversal training in the water maze and they extinguish conditioned fear more slowly than their wildtype (WT) littermates. Finally, Carf KO mice show normal short-term and long-term memory in a novel object recognition task, but exhibit impairments during the remote memory phase of testing. Taken together these data reveal novel roles for CaRF in the organization and/or function of neural circuits that underlie essential aspects of learning and memory. PMID:20519520

Assessing the effect of dietary calcium intake and 25 OHD status on bone turnover in women in Pakistan.

PubMed

Khan, Aysha Habib; Naureen, Ghazala; Iqbal, Romaina; Dar, Farhan Javed

2013-01-01

Bone health assessed in three towns of Karachi, Pakistan in females showed poor calcium intake, vitamin D deficiency, secondary hyperparathyroidism, and high bone turnover. Correlates of high bone turnover included females residing in Saddar Town, underweight females less than 30 years of age from low socio-economic status, and secondary hyperparathyroidism. To assess bone health and association of dietary calcium and 25 hydroxy vitamin D with bone turnover in the community-dwelling females of Karachi. Bone health was assessed in three randomly selected towns of Karachi, Pakistan. One premenopausal female fulfilling the inclusion criteria from each household was included in the study. Dietary calcium was assessed through a food frequency questionnaire and biochemical markers including calcium, phosphates, albumin, magnesium, creatinine, and SGPT, intact parathyroid hormone, 25 hydroxy vitamin D, and N-telopeptide of type I collagen were measured to assess the bone health. Three hundred and five females were included from three towns. Overall, 90.5% of females had vitamin D deficiency with 42.6 and 23.3% having secondary hyperparathyroidism and high bone turn over respectively. Prevalence of vitamin D deficiency, secondary hyperparathyroidism, and high bone turnover was significantly different among towns. Mean vitamin D levels were significantly low and iPTH levels significantly high in females with high bone turnover. Calcium intake was not significantly different among females with normal, high, and low bone turnover. Correlates of high bone turnover included females residing in Saddar Town, underweight females less than 30 years of age belonging to low socio-economic status, and secondary hyperparathyroidism. Compromised bone health is seen in community-dwelling females of Karachi. There is a need to perform large-scale community-based studies in all age groups to understand the interplay of markers in our population to understand the impact of these variables translating into the risk of osteoporosis.

Cardiac voltage gated calcium channels and their regulation by β-adrenergic signaling.

PubMed

Kumari, Neema; Gaur, Himanshu; Bhargava, Anamika

2018-02-01

Voltage-gated calcium channels (VGCCs) are the predominant source of calcium influx in the heart leading to calcium-induced calcium release and ultimately excitation-contraction coupling. In the heart, VGCCs are modulated by the β-adrenergic signaling. Signaling through β-adrenergic receptors (βARs) and modulation of VGCCs by β-adrenergic signaling in the heart are critical signaling and changes to these have been significantly implicated in heart failure. However, data related to calcium channel dysfunction in heart failure is divergent and contradictory ranging from reduced function to no change in the calcium current. Many recent studies have highlighted the importance of functional and spatial microdomains in the heart and that may be the key to answer several puzzling questions. In this review, we have briefly discussed the types of VGCCs found in heart tissues, their structure, and significance in the normal and pathological condition of the heart. More importantly, we have reviewed the modulation of VGCCs by βARs in normal and pathological conditions incorporating functional and structural aspects. There are different types of βARs, each having their own significance in the functioning of the heart. Finally, we emphasize the importance of location of proteins as it relates to their function and modulation by co-signaling molecules. Its implication on the studies of heart failure is speculated. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of Oxcarbazepine and Levetiracetam on Calcium, Ionized Calcium, and 25-OH Vitamin-D3 Levels in Patients with Epilepsy.

PubMed

Aksoy, Duygu; Güveli, Betül Tekin; Ak, Pelin Doğan; Sarı, Hüseyin; Ataklı, Dilek; Arpacı, Baki

2016-02-29

The primary objective of the present study was to further elucidate the effects of oxcarbazepine (OXC) and levetiracetam (LEV) monotherapies on the bone health status of patients with epilepsy. This study included 48 patients who attended our epilepsy outpatient clinic, had a diagnosis of epilepsy, and were undergoing either OXC or LEV monotherapy and 42 healthy control subjects. The demographic and clinical features of the patients, including gender, age, onset of disease, daily drug dosage, and duration of disease, were noted. Additionally, the calcium, ionized calcium, and 25-OH vitamin-D3 levels of the participants were prospectively evaluated. The 25-OH vitamin-D3, calcium, and ionized calcium levels of the patients taking OXC were significantly lower than those of the control group. These levels did not significantly differ between the patients taking LEV and the control group, but there was a significant negative relationship between daily drug dose and ionized calcium levels in the LEV patients. In the present study, anti-epileptic drugs altered the calcium, ionized calcium, and 25-OH vitamin-D3 levels of epilepsy patients and resulted in bone loss, abnormal mineralization, and fractures. These findings suggest that the calcium, ionized calcium, and 25-OH vitamin-D3 levels of patients with epilepsy should be regularly assessed.

Pseudohypoparathyroidism: a rare but important cause of hypocalcaemia

PubMed Central

Chong, Pui Lin; Meeking, Darryl R

2013-01-01

We present a 46-year-old Caucasian lady with symptomatic hypocalcaemia. Investigations revealed markedly raised parathyroid hormone (PTH) levels with vitamin D deficiency. A number of conditions causing secondary hyperparathyroidism were ruled out from her medical history and initial investigations. The main differential diagnoses were vitamin D deficiency and PTH resistance (pseudohypoparathyroidism, PHP). With high-normal serum phosphate and normal alkaline phosphatase, and a lack of symptoms associated with osteomalacia, vitamin D deficiency alone was unlikely to be the cause of hypocalcaemia. Given a normal physical appearance, genetic testing was arranged and confirmed the diagnosis of PHP type Ib. She is currently taking activated vitamin D to maintain calcium homeostasis. PTH resistance is the hallmark of PHP, a rare complex genetic disorder, which can be easily missed resulting in potentially serious consequences. PMID:23345494

Analysis of Adequacy of 25-Hydroxi vitamin D3 Supplementation in Patients on Hemodialysis and Parathormone, Calcium and Phosphorus Level in the Blood of These Patients.

PubMed

Prnjavorac, Besim; Irejiz, Nedzada; Kurbasic, Zahid; Krajina, Katarina; Deljkic, Amina; Sinanovic, Albina; Fejzic, Jasmin

2015-04-01

Appropriate vitamin D turnover is essential for many physiological function. Knowledge of it's function was improved in last two decades with enlargement of scientific confirmation and understanding of overall importance. In addition to classical (skeletal) roles of vitamin D, many other function (no classical), out of bone and calcium-phosphate metabolism, are well defined today. To analyze vitamin D level in the blood in dialysis and pre dialysis patients and evaluate efficacy of supplementation therapy with vitamin D supplements. Vitamin D3 level in form of 25-hydroxivitamin D3 was measured in dialysis and pre dialysis patients, using combination of enzyme immunoassay competition method with final fluorescent detection (ELFA). Parathormone was measured by ELISA method. Other parameters were measured by colorimetric methods. Statistical analysis was done by nonparametric methods, because of dispersion of results of Vitamin D and parathormone. In group of dialysis patients 38 were analyzed. Among them 35 (92%) presented vitamin D deficiency, whether they took supplementation or not. In only 3 patients vitamin D deficiency was not so severe. Vitamin D form were evaluated in 42 pre dialysis patients. Out of all 19 patients (45 %) have satisfied level, more than 30 ng/ml. Moderate deficiency have 16 patients (38%), 5 of all (12%) have severe deficiency, and two patients (5%) have very severe deficiency, less than 5 ng/ml. Parathormone was within normal range (9.5-75 pg/mL) in 13 patients (34 %), below normal range (2 %) in one subject, and in above normal range in 24 (63 %). Vitamin D3 deficiency was registered in most hemodialysis patients; nevertheless supplemental therapy was given regularly or not. It is to be considered more appropriate supplementation of Vitamin D3 for dialyzed patients as well as for pre dialysis ones. In pre dialysis patient moderate deficiency is shown in half of patients but sever in only two.

[Changes induced by hypertonic solutions in the transportation of calcium by the cardiac reticular sarcoplasma].

PubMed

Sierra, M; Holguín, J A

1979-01-01

In the sarcoplasmic reticulum of the myocardium, celular organell which function is to regulate the cytoplasmic concentration of calcium in contraction and relaxation, we have studied the effect of hypertonic solutions of sucrose between 1 and 6.96 times the normal tonicity in order to observe the behavior of the internal linked or free calcium of this structure, as well as to prove the hypothesis that hypertonic solutions encourage the calcium exit of the sarcoplasmatic reticulum with the resulting signs of contractures. The following results were obtained: 1. The ATP hydrolisis and calcium transport rate are 14% and 90% respectively of the maximum speeds of 10(-5) M in calcium, while for concentrations of 10(-7) M or ess of the said cation, the transport rates and the ATPase do not reach 5% of the maximum values. 2. Between 1 and 2.54 times of the normal tonicity the calcium uptake remains between 400 and 500 nmoles of calcium/mg protein/min, the transported amount of calcium varies between 14 and 16 nmoles/mg protein and the rate of the ATP hydrolysis increases a 37% to 0.4 M in sucrose. 3. Between 0.4 and 1.2 M in sucrose of 2.54 to 6.96 times the isotonicity, the calcium transport rate velocity as well as the ATP hydrolisis are strongly inhibited. The vesicles volume minimizes and the amount of linked calcium remains within the control values, proving that the capacity of linking this cathion is independent from sarcoplasmic reticulum volume. These results show that the sarcoplasmic reticulum is involved in the contractures induced by hypertonic solutions in intact cells, since the osmolarity increase produces changes of volume which results in a decrease of the calcium transportation velocity or in an increase of the exit of said cathion.

Blood biochemistry reference values for wild juvenile loggerhead sea turtles (Caretta caretta) from Madeira archipelago.

PubMed

Delgado, Cláudia; Valente, Ana; Quaresma, Isabel; Costa, Margarida; Dellinger, Thomas

2011-07-01

Standard biochemical parameters were determined in wild juvenile loggerhead sea turtles Caretta caretta living offshore Madeira Island, northeast Atlantic. We analyzed the influence of age, sex, sea surface temperature, and body condition index on biochemical parameters including uric acid, total bilirubin, total cholesterol, creatinine kinase (CK), glucose, total protein, urea nitrogen, lactate dehydrogenase, aspartate aminotranspherase (AST), gamma-glutamyl transferase (GGT), albumin, alkaline phosphatase (ALP), sodium (NA), potassium (K), chloride, calcium, phosphorus, and magnesium. Significant positive correlations were found between turtle body size and total cholesterol, total protein, and albumin. Total protein and the enzymes AST and CK were lower than reported levels in adults. Calcium levels were lower than those reported in adult or captive turtles, but similar to wild juveniles from Australian waters, and were interpreted as normal for this age category. These data may be useful to evaluate the health status of stranded or injured animals and to improve veterinary care at rehabilitation centers.

Quantitative histochemistry of rat lumbar vertebrae following spaceflight

NASA Technical Reports Server (NTRS)

Eurell, J. A.; Kazarian, L. E.

1983-01-01

The histochemical effects of the return to gravity immediately and 6 and 29 days following spaceflight on the bone of rat vertebral bodies were investigated. No significant change in the calcium salt content of the vertebrae was found immediately postflight, although 6 days later it was significantly decreased. The calcium content was found to have returned to normal by 29 days postflight. While postflight collagen content was not significantly altered, keratosulfate was found to be significantly higher in trabecular bone of rats immediately postflight and 6 days postflight. In addition, chondroitin sulfate was found to be increased in vertebral bone on days 6 and 29 postflight. These findings indicate that bone turnover slows in vertebrae during spaceflight allowing bone aging, which support the contention that a form of osteolysis begins immediately upon return to gravity to remove components of old bone at which time mineral levels decrease and levels of chondroitin and keratkosulfates shift. It was found that the osteolysis phase was quickly followed by new bone replacement which was completed before 29 days postspaceflight.

Extending storage life of fresh-cut apples using natural products and their derivatives.

PubMed

Buta, J G; Moline, H E; Spaulding, D W; Wang, C Y

1999-01-01

Prevention of browning of apples slices has been difficult to achieve because of the rapidity of the enzymatic oxidation of phenolic substrates even under reduced atmospheric pressure storage. Combinations of enzymatic inhibitors, reducing agents, and antimicrobial compounds containing calcium to extend storage life were tested to decrease the browning of Red Delicious apple slices stored at 5 and 10 degrees C under normal atmospheric conditions. Treatments were devised to prevent browning for up to 5 weeks at 5 degrees C with no apparent microbial growth using dipping solutions of compounds derived from natural products consisting of 4-hexylresorcinol, isoascorbic acid, a sulfur-containing amino acid (N-acetylcysteine), and calcium propionate. Analyses of organic acids and the major sugars revealed that the slices treated with the combinations of antibrowning compounds retained higher levels of malic acid and had no deterioration in sugar levels at 5 and 10 degrees C, indicating that higher quality was maintained during storage.

Calcium and phosphorus regulatory hormones and risk of incident symptomatic kidney stones.

PubMed

Taylor, Eric N; Hoofnagle, Andrew N; Curhan, Gary C

2015-04-07

Calcium and phosphorus regulatory hormones may contribute to the pathogenesis of calcium nephrolithiasis. However, there has been no prospective study to date of plasma hormone levels and risk of kidney stones. This study aimed to examine independent associations between plasma levels of 1,25-dihydroxyvitamin D (1,25[OH]2D), 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, fibroblast growth factor 23 (FGF23), parathyroid hormone, calcium, phosphate, and creatinine and the subsequent risk of incident kidney stones. This study was a prospective, nested case-control study of men in the Health Professionals Follow-Up Study who were free of diagnosed nephrolithiasis at blood draw. During 12 years of follow-up, 356 men developed an incident symptomatic kidney stone. Using risk set sampling, controls were selected in a 2:1 ratio (n=712 controls) and matched for age, race, and year, month, and time of day of blood collection. Baseline plasma levels of 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, parathyroid hormone, calcium, phosphate, and creatinine were similar in cases and controls. Mean 1,25(OH)2D and median FGF23 levels were higher in cases than controls but differences were small and statistically nonsignificant (45.7 versus 44.2 pg/ml, P=0.07 for 1,25[OH]2D; 47.6 versus 45.1 pg/ml, P=0.08 for FGF23). However, after adjusting for body mass index, diet, plasma factors, and other covariates, the odds ratios of incident symptomatic kidney stones in the highest compared with lowest quartiles were 1.73 (95% confidence interval, 1.11 to 2.71; P for trend 0.01) for 1,25(OH)2D and 1.45 (95% confidence interval, 0.96 to 2.19; P for trend 0.03) for FGF23. There were no significant associations between other plasma factors and kidney stone risk. Higher plasma 1,25(OH)2D, even in ranges considered normal, is independently associated with higher risk of symptomatic kidney stones. Although of borderline statistical significance, these findings also suggest that higher FGF23 may be associated with risk. Copyright © 2015 by the American Society of Nephrology.

Steroid-induced hypocalcaemia with tetany in a patient with hypoparathyroidism.

PubMed

Oikonomou, Dimitrios; Laina, Ageliki; Xydaki, Aikaterini; Christopoulos, Constantinos

2014-11-18

Although glucocorticoids have a known negative effect on calcium balance, they do not normally cause clinically significant hypocalcaemia. A young woman with post-surgical hypoparathyroidism developed symptomatic hypocalcaemia on two occasions following treatment with intravenous hydrocortisone for allergic reactions. Oral calcium and vitamin D supplementation could not prevent the development of hypocalcaemia. She was treated successfully with intravenous calcium gluconate infusions and discontinuation of glucocorticoids. In patients with hypoparathyroidism, impaired parathyroid hormone response to steroid-induced negative calcium balance may result in severe symptomatic hypocalcaemia requiring hospitalisation. 2014 BMJ Publishing Group Ltd.

Steroid-induced hypocalcaemia with tetany in a patient with hypoparathyroidism

PubMed Central

Oikonomou, Dimitrios; Laina, Ageliki; Xydaki, Aikaterini; Christopoulos, Constantinos

2014-01-01

Although glucocorticoids have a known negative effect on calcium balance, they do not normally cause clinically significant hypocalcaemia. A young woman with post-surgical hypoparathyroidism developed symptomatic hypocalcaemia on two occasions following treatment with intravenous hydrocortisone for allergic reactions. Oral calcium and vitamin D supplementation could not prevent the development of hypocalcaemia. She was treated successfully with intravenous calcium gluconate infusions and discontinuation of glucocorticoids. In patients with hypoparathyroidism, impaired parathyroid hormone response to steroid-induced negative calcium balance may result in severe symptomatic hypocalcaemia requiring hospitalisation. PMID:25406219

Estimation of calcium and magnesium in serum and urine by atomic absorption spectrophotometry

PubMed Central

Thin, Christian G.; Thomson, Patricia A.

1967-01-01

A method has been described for the estimation of calcium and magnesium in serum and urine using atomic absorption spectrophotometry. The precision and accuracy of the techniques have been determined and were found to be acceptable. The range of values for calcium and magnesium in the sera of normal adults was found to be: serum calcium (corrected to a specific gravity of 1·026) 8·38-10·08 mg. per 100 ml.; serum magnesium 1·83-2·43 mg. per 100 ml. PMID:5602562

OligoG CF-5/20 normalizes cystic fibrosis mucus by chelating calcium.

PubMed

Ermund, Anna; Recktenwald, Christian V; Skjåk-Braek, Gudmund; Meiss, Lauren N; Onsøyen, Edvar; Rye, Philip D; Dessen, Arne; Myrset, Astrid Hilde; Hansson, Gunnar C

2017-06-01

The goal of this study was to determine whether the guluronate (G) rich alginate OligoG CF-5/20 (OligoG) could detach cystic fibrosis (CF) mucus by calcium chelation, which is also required for normal mucin unfolding. Since bicarbonate secretion is impaired in CF, leading to insufficient mucin unfolding and thereby attached mucus, and since bicarbonate has the ability to bind calcium, we hypothesized that the calcium chelating property of OligoG would lead to detachment of CF mucus. Indeed, OligoG could compete with the N-terminus of the MUC2 mucin for calcium binding as shown by microscale thermophoresis. Further, effects on mucus thickness and attachment induced by OligoG and other alginate fractions of different length and composition were evaluated in explants of CF mouse ileum mounted in horizontal Ussing-type chambers. OligoG at 1.5% caused effective detachment of CF mucus and the most potent alginate fraction tested, the poly-G fraction of about 12 residues, had similar potency compared to OligoG whereas mannuronate-rich (M) polymers had minimal effect. In conclusion, OligoG binds calcium with appropriate affinity without any overt harmful effect on the tissue and can be exploited for treating mucus stagnation. © 2017 John Wiley & Sons Australia, Ltd.

Expression of the high capacity calcium-binding domain of calreticulin increases bioavailable calcium stores in plants

NASA Technical Reports Server (NTRS)

Wyatt, Sarah E.; Tsou, Pei-Lan; Robertson, Dominique; Brown, C. S. (Principal Investigator)

2002-01-01

Modulation of cytosolic calcium levels in both plants and animals is achieved by a system of Ca2+-transport and storage pathways that include Ca2+ buffering proteins in the lumen of intracellular compartments. To date, most research has focused on the role of transporters in regulating cytosolic calcium. We used a reverse genetics approach to modulate calcium stores in the lumen of the endoplasmic reticulum. Our goals were two-fold: to use the low affinity, high capacity Ca2+ binding characteristics of the C-domain of calreticulin to selectively increase Ca2+ storage in the endoplasmic reticulum, and to determine if those alterations affected plant physiological responses to stress. The C-domain of calreticulin is a highly acidic region that binds 20-50 moles of Ca2+ per mole of protein and has been shown to be the major site of Ca2+ storage within the endoplasmic reticulum of plant cells. A 377-bp fragment encoding the C-domain and ER retention signal from the maize calreticulin gene was fused to a gene for the green fluorescent protein and expressed in Arabidopsis under the control of a heat shock promoter. Following induction on normal medium, the C-domain transformants showed delayed loss of chlorophyll after transfer to calcium depleted medium when compared to seedlings transformed with green fluorescent protein alone. Total calcium measurements showed a 9-35% increase for induced C-domain transformants compared to controls. The data suggest that ectopic expression of the calreticulin C-domain increases Ca2+ stores, and that this Ca2+ reserve can be used by the plant in times of stress.

Hypophosphatemia leads to rickets by impairing caspase-mediated apoptosis of hypertrophic chondrocytes.

PubMed

Sabbagh, Yves; Carpenter, Thomas O; Demay, Marie B

2005-07-05

Rickets is seen in association with vitamin D deficiency and in several genetic disorders associated with abnormal mineral ion homeostasis. Studies in vitamin D receptor (VDR)-null mice have demonstrated that expansion of the late hypertrophic chondrocyte layer, characteristic of rickets, is secondary to impaired apoptosis of these cells. The observation that normalization of mineral ion homeostasis in the VDR-null mice prevents rachitic changes suggests that rickets is secondary to hypocalcemia, hypophosphatemia, or hyperparathyroidism, rather than impaired VDR action. To determine which of these abnormalities is responsible for impaired chondrocyte apoptosis and subsequent rachitic changes, two additional models were examined: diet-induced hypophosphatemia/hypercalcemia and hypophosphatemia secondary to mutations in the Phex gene. The former model is associated with suppressed parathyroid hormone levels as a consequence of hypercalcemia. The latter model demonstrates normal calcium and parathyroid hormone levels, but 1,25-dihydroxyvitamin D levels that are inappropriately low for the degree of hypophosphatemia. Our studies demonstrate that normal phosphorus levels are required for growth plate maturation and implicate a critical role for phosphate-regulated apoptosis of hypertrophic chondrocytes via activation of the caspase-9-mediated mitochondrial pathway.

Ultrasound assisted immersion freezing of broccoli (Brassica oleracea L. var. botrytis L.).

PubMed

Xin, Ying; Zhang, Min; Adhikari, Benu

2014-09-01

The aim of this study was to research the ultrasound-assisted freezing (UAF) of broccoli. CaCl2 solution was used as freezing medium. The comparative advantage of using UAF over normal freezing on the freezing time, cell-wall bound calcium to total calcium ratio, textural properties, color, drip loss and L-ascorbic acid contents was evaluated. The application of UAF at selected acoustic intensity with a range of 0.250-0.412 W/cm(2) decreased the freezing time and the loss of cell-wall bound calcium content. Compared to normal freezing, the values of textural properties, color, L-ascorbic acid content were better preserved and the drip loss was significantly minimized by the application of UAF. However, when outside that range of acoustic intensity, the quality of the ultrasound-assisted frozen broccoli was inferior compared to that of the normally frozen samples. Selected the appropriate acoustic intensity was very important for the application of UAF. Copyright © 2014 Elsevier B.V. All rights reserved.

Hypocalcemia following surgical treatment of metastatic anal sac adenocarcinoma in a dog.

PubMed

Saba, Corey; Ellis, Angela; Cornell, Karen

2011-01-01

A 9 yr old neutered male mixed-breed dog was presented for an anal sac apocrine gland adenocarcinoma with regional nodal metastases. At presentation, ionized calcium was 1.91 mmol/L (NOVA Stat reference range, 1.1-1.3 mmol/L). Surgical excision of the primary tumor and metastatic lymph nodes was performed. Following surgery, symptomatic hypocalcemia was noted. Repeated ionized calcium measurements confirmed hypocalcemia, and hypercalcemia of malignancy panels suggested parathyroid gland suppression as the cause. The calcium normalized with parenteral calcium administration, but calcium later became elevated with tumor recurrence and an increase in the parathormone-related peptide. Disrupted calcium homeostasis is a potential complication following the treatment of long-standing humoral hypercalcemia of malignancy.

Calcium homeostasis in intraerythrocytic malaria parasites.

PubMed

Garcia, C R; Dluzewski, A R; Catalani, L H; Burting, R; Hoyland, J; Mason, W T

1996-12-01

The fluorescent indicator, fura-2, AM, was used to measure free calcium concentrations in the intraerythrocytic malaria parasites of Plasmodium chabaudi and Plasmodium falciparum. In both species the free cytosolic calcium concentration was maintained at low levels (between 40 and 100 nM throughout the maturation process. Digital image analysis of the indicator fluorescence was performed on parasites and evaluated with the aid of a calibration of the calcium response, based on permeabilized parasites, exposed to calcium buffers. This again revealed that free calcium concentrations in the intact parasite are maintained at a predetermined level, regardless of the free calcium in the surrounding milieu. Both species of parasites are thus capable of regulating their internal free calcium levels with high precision, presumably by means of calcium pump ATPases. A small but significant elevation of the cytosolic free calcium concentration by the tumor promoter, thapsigargin, may be taken to reflect the presence of calcium stores in the endoplasmic reticulum in P. falciparum.

Interaction between parathyroid hormone and endogenous estrogen in normal women.

PubMed

Buchanan, J R; Santen, R J; Cavaliere, A; Cauffman, S W; Greer, R B; Demers, L M

1986-06-01

It has been hypothesized that estrogens conserve bone substance by blocking the resorbing effect of parathyroid hormone (PTH). We evaluated this hypothesis by examining the relation of circulating PTH to endogenous estrogen fluctuation during four quarters of a single menstrual cycle in 20 normal women. The hypothesis predicts that PTH should vary directly with estrogen, since PTH should increase following estrogen elevation to satisfy physiologic demands for calcium. Contrary to the predicted direct variation, PTH remained constant throughout the menstrual cycle despite sharply fluctuating estrogen levels. Furthermore, PTH was negatively associated with estrone during the early follicular (r = -.65, P less than 0.005) and late follicular (r = -.84, P less than 0.0001) phases. We attempted to determine whether this unexpected relationship between estrone and PTH signified a direct physiologic link, by excluding factors which could have spuriously engendered the inverse correlation. Stepwise multiple regression and partial correlation showed that estrone contributed significantly to circulating PTH independent of the effects of dietary calcium, 25-hydroxyvitamin D, serum calcium, 1,25-dihydroxyvitamin D, phosphate, estradiol, progesterone, and body weight. Therefore, it is possible that the inverse correlation between estrone and PTH signified a direct physiologic link, as an artifactual cause for the relationship could not be identified. These data imply that estrone interacts with PTH, but not by blocking PTH-mediated bone resorption. We conclude that estrone is associated with reduced circulating PTH through an as yet undetermined mechanism.

Provocative tests of parathyroid and C cell function in adrenalectomized and chemically sympathectomized rats.

PubMed

Heath, H

1980-10-01

Recent in vitro and in vivo evidence shows that secretion of parathyroid hormone (PTH) and calcitonin (CT) is stimulated by beta-adrenergic agonists and inhibited by beta-adrenergic antagonists. To assess the possible roles of adrenal medullary or adrenergic nerve terminal catecholamines in calcium homeostasis, we have examined serum calcium (Ca), immunoreactive PTH (iPTH), and immunoreactive CT (iCT) in control, adrenalectomized (ADRX), and chemically sympathectomized [6-hydroxydopamine (6-OHDA)] rats. Animals were studied in the fed and fasted states, after ip injection of CA and after ip injection of EDTA. In comparison with fasted rats, fed control rats tended to have increased serum Ca and iCT, but decreased or unchanged iPTH. Neither adrenalectomy nor 6-OHDA treatment notably altered this pattern. Serum iCT concentrations rose markedly after ip Ca, and peak iCT responses remained normal in ADRX and 6-OHDA-treated rats. Similarly, rises of iPTH levels after EDTA-induced hypocalcemia were normal in ADRX and 6-OHDA-treated rats. The only possible abnormality concerned basal serum iCT levels after 6-OHDA treatment, which were lower than control in five of six experiments, albeit not always significantly. We conclude that deprivation of either adrenal medullary or adrenergic nerve terminal catecholamines does not interfere with plasma Ca regulation or the homeostatic responses of PTH and CT in the rat.

Thyroid hormone is required for pruning, functioning and long-term maintenance of afferent inner hair cell synapses

PubMed Central

Sundaresan, Srividya; Kong, Jee-Hyun; Fang, Qing; Salles, Felipe T.; Wangsawihardja, Felix; Ricci, Anthony J.; Mustapha, Mirna

2016-01-01

Functional maturation of afferent synaptic connections to inner hair cells (IHCs) involves pruning of excess synapses formed during development, as well as the strengthening and survival of the retained synapses. These events take place during the thyroid hormone (TH)-critical period of cochlear development, which is in the perinatal period for mice and in the third trimester for humans. Here, we used the hypothyroid Snell dwarf mouse (Pit1dw) as a model to study the role of TH in afferent type I synaptic refinement and functional maturation. We observed defects in afferent synaptic pruning and delays in calcium channel clustering in the IHCs of Pit1dw mice. Nevertheless, calcium currents and capacitance reached near normal levels in Pit1dw IHCs by the age of onset of hearing, despite the excess number of retained synapses. We restored normal synaptic pruning in Pit1dw IHCs by supplementing with TH from postnatal day (P)3 to P8, establishing this window as being critical for TH action on this process. Afferent terminals of older Pit1dw IHCs showed evidence of excitotoxic damage accompanied by a concomitant reduction in the levels of the glial glutamate transporter, GLAST. Our results indicate that a lack of TH during a critical period of inner ear development causes defects in pruning and long-term homeostatic maintenance of afferent synapses. PMID:26386265

Idiopathic hypercalciuria and formation of calcium renal stones

PubMed Central

Coe, Fredric L.; Worcester, Elaine M.; Evan, Andrew P.

2018-01-01

The most common presentation of nephrolithiasis is idiopathic calcium stones in patients without systemic disease. Most stones are primarily composed of calcium oxalate and form on a base of interstitial apatite deposits, known as Randall’s plaque. By contrast some stones are composed largely of calcium phosphate, as either hydroxyapatite or brushite (calcium monohydrogen phosphate), and are usually accompanied by deposits of calcium phosphate in the Bellini ducts. These deposits result in local tissue damage and might serve as a site of mineral overgrowth. Stone formation is driven by supersaturation of urine with calcium oxalate and brushite. The level of supersaturation is related to fluid intake as well as to the levels of urinary citrate and calcium. Risk of stone formation is increased when urine citrate excretion is <400 mg per day, and treatment with potassium citrate has been used to prevent stones. Urine calcium levels >200 mg per day also increase stone risk and often result in negative calcium balance. Reduced renal calcium reabsorption has a role in idiopathic hypercalciuria. Low sodium diets and thiazide-type diuretics lower urine calcium levels and potentially reduce the risk of stone recurrence and bone diseas PMID:27452364

Changes in force and calcium sensitivity in the developing avian heart.

PubMed

Godt, R E; Fogaça, R T; Nosek, T M

1991-11-01

The aim of this study was to characterize the development of the contractile properties of intact and chemically skinned muscle from chicken heart and to compare these characteristics with those of developing mammalian heart reported by others. Small trabeculae were dissected from left ventricles of Arbor Acre chickens between embryonic day 7 and young adulthood (7 weeks post-hatching). At all ages, increasing extracellular calcium (0.45-3.6 mM) progressively increased twitch force of electrically stimulated trabeculae. Twitch force at 1.8 mM extracellular calcium, normalized to cross-sectional area, increased to a maximum at 1 day post-hatching, remained constant through 3 weeks post-hatching, but then decreased at 7 weeks post-hatching. The maximal calcium-activated force of trabeculae chemically skinned with Triton X-100 detergent increased to a maximum 2 days before the time of hatching and was not significantly changed up to 7 weeks post-hatching. Over the ages studied, average twitch force in 1.8 mM calcium was between 26 and 66% of maximal calcium-activated force after skinning, suggesting that the contractile apparatus is not fully activated during the twitch in normal Ringer. In skinned trabeculae, the calcium sensitivity of the contractile apparatus was higher in the embryo than in the young adult. These age-dependent changes in calcium sensitivity are correlated with isoform switching in troponin T. A decrease in pH from 7.0 to 6.5 decreased the calcium sensitivity of the contractile apparatus to a greater degree in skinned trabeculae from young adult hearts than in those from embryonic hearts. This change in susceptibility to acidosis is temporally associated with isoform switching in troponin I.(ABSTRACT TRUNCATED AT 250 WORDS)

Vitamin D insufficiency in osteoporotic hip fracture patients: rapid substitution therapy with high dose oral cholecalciferol (vitamin D3).

PubMed

de Jong, Andy; Woods, Kate; Van Gestel, Lise; Suresh, Mohanraj; Porteous, Matthew

2013-10-01

Assessment and treatment of osteoporosis are recommended following hip fracture. Osteoporosis treatment assumes an adequate calcium intake and a normal vitamin D plasma level. The authors conducted a study in three phases. Phase I: circulating 25-hydroxyvitamin D levels were retrospectively recorded from in the case records of 381 consecutive patients with 387 hip fractures, between March 2010 and September 2011. Only 27 patients had sufficient (> 75 nmol/L) circulating vitamin D, and of these 22 were taking vitamin D supplements. The remainder, 354 patients, had abnormally low vitamin D levels, with a mean value of 26.4 nmol/L. These findings confirmed literature data, and gave rise to the prospective Phase II (October 2011): 14 consecutive patients with a hip fracture received rapid substitution therapy with 50,000 IU cholecalciferol (vitamin D3) daily for 3 days. Patients with corrected calcium level (calcium level based on the serum albumin level) > 2.60 mmol/L were excluded from phase II (and phase III), in order to avoid hypercalcemia. Substitution resulted in an increase in vitamin D plasma levels from +/- 29.6 nmol/L to +/- 81.4 nmol/L (p < 0.0001), after +/- 14 days. However, vitamin D level remained below the desired threshold of 75 nmol/L in 29%. Therefore it was decided to increase the treatment period from 3 days to 7 days in the next 54 patients with a hip fracture in a prospective phase III (October 2011-January 2012). This time rapid substitution resulted in an increase from +/-31.4 nmol/L to +/-131.1 nmol/L (p < 0.0001), after +/- 16 days, and 100% of treated patients achieved plasma levels above the desired threshold of 75 nmol/L. virtually all patients with a hip fracture have low vitamin D plasma levels; substitution with 50,000 IU oral cholecalciferol daily for 7 days increases vitamin D plasma levels rapidly, safely and consistently.

Vitamin D deficiency and low ionized calcium are linked with semen quality and sex steroid levels in infertile men.

PubMed

Blomberg Jensen, Martin; Gerner Lawaetz, Jacob; Andersson, Anna-Maria; Petersen, Jørgen Holm; Nordkap, Loa; Bang, Anne Kirstine; Ekbom, Pia; Joensen, Ulla Nordström; Prætorius, Lisbeth; Lundstrøm, Peter; Boujida, Vibeke Hartvig; Lanske, Beate; Juul, Anders; Jørgensen, Niels

2016-08-01

Are low vitamin D levels linked with semen quality and sex steroids in infertile men? Infertile men with vitamin D deficiency had lower sperm motility, total numbers of motile sperm, Inhibin B, sex-hormone-binding-globulin (SHBG) and testosterone/estradiol ratio, but higher levels of free sex steroids, than infertile men with normal vitamin D levels. Low vitamin D levels have been associated with decreased sperm motility in healthy men, but a relationship between vitamin D and calcium with semen quality and especially sex steroids has not been sufficiently described in infertile men. This study comprises baseline characteristics of 1427 infertile men screened from 2011 to 2014 for inclusion in a randomized clinical trial, the Copenhagen-Bone-Gonadal Study. In total 1427 infertile men, consecutively referred to our tertiary andrological centre for fertility workup, underwent a physical examination and had semen quality assessed based on two samples and blood analysed for serum testosterone, SHBG, estradiol, inhibin B, luteinizing hormone, follicle-stimulating hormone (FSH), 25-hydroxyvitamin D (25-OHD), ionized calcium (Ca(2+)) and karyotype. There were 179 men excluded due to serious comorbidities or anabolic steroid usage, leaving 1248 patients for analyses. Men with 25-OHD >75 nmol/l had higher sperm motility and 66 and 111% higher total numbers of motile spermatozoa after 45 and 262 min, respectively, than men with 25-OHD <25 nmol/l (all P < 0.05). SHBG levels and testosterone/estradiol ratios were 15 and 14% lower, respectively, while free testosterone and estradiol ratios were 6 and 13% higher, respectively, in men with 25-OHD <25 nmol/l (all P < 0.05). Men with lower Ca(2+) levels had higher progressive sperm motility and inhibin B/FSH ratio but lower testosterone/estradiol ratio (all P < 0.05). All outcomes presented are predefined end-points but inferral of causality is compromised by the descriptive study design. It remains to be shown whether the links between vitamin D, calcium, semen quality and sex steroids in infertile men are causal. The associations between vitamin D deficiency and low calcium with semen quality and sex steroids support the existence of a cross-link between regulators of calcium homeostasis and gonadal function in infertile men. This study was supported by the Danish Agency for Science, Technology and Innovation, Hørslev Fonden, Danish Cancer Society and Novo Nordisk Foundation. There are no conflicts of interest. NCT01304927. 25 February 2011. 8 March 2011. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Is ionized calcium a reliable predictor of hypocalcemia after total thyroidectomy? A before and after study

PubMed Central

TARTAGLIA, F.; GIULIANI, A.; SGUEGLIA, M.; PATRIZI, G.; DI ROCCO, G.; BLASI, S.; RUSSO, G.; TORTORELLI, G.; GIANNOTTI, D.; REDLER, A.

2014-01-01

Summary Wanting to find a way of identifying patients suitable for early discharge after thyroidectomy, we set out to establish whether ionized calcium concentration is a better predictor of post-surgical hypocalcemia than total serum calcium. Data were analyzed to establish whether serum ionized calcium concentrations are correlated with total serum calcium levels and symptomatic hypocalcemia after thyroidectomy. Sixty-two patients undergoing total thyroidectomy at the Department of Surgical Sciences of the “Sapienza” University of Rome, Italy, in 2010. Ionized calcium was measured before (day 0) and after surgery (days 1, 2 and 60) in all the patients. These measurements were compared with preoperative (day 0) and postoperative total serum calcium levels (days 1, 2 and 60). The preoperative ionized calcium levels differed from the ionized calcium levels recorded on days 1 and 2; this pattern was not observed for the total calcium concentrations. Conversely, total calcium on days I and II correlated significantly with the various ionized calcium measurements. The presence of parathyroid glands in the surgical specimen did not seem to affect suitability for discharge. The statistical analysis showed that ionized calcium measurements are more reliable than total calcium measurements in the immediate and long-term follow-up of total thyroidectomy patients. Applying a 95% confidence interval we established reference values for both total serum calcium and ionized calcium, below which all patients develop postoperative symptomatic hypocalcemia. In conclusion, measurement of ionized calcium, as opposed to total calcium, should be strongly recommended in the immediate and long-term follow-up of total thyroidectomy patients. PMID:24690338

Changes in urinary risk profile after short-term low sodium and low calcium diet in recurrent Swiss kidney stone formers.

PubMed

Seeger, Harald; Kaelin, Andrea; Ferraro, Pietro M; Weber, Damian; Jaeger, Philippe; Ambuehl, Patrice; Robertson, William G; Unwin, Robert; Wagner, Carsten A; Mohebbi, Nilufar

2017-12-04

Kidney stone disease is common in industrialized countries. Recently, it has attracted growing attention, because of its significant association with adverse renal outcomes, including end stage renal disease. Calcium-containing kidney stones are frequent with high recurrence rates. While hypercalciuria is a well-known risk factor, restricted intake of animal protein and sodium, combined with normal dietary calcium, has been shown to be more effective in stone prevention compared with a low-calcium diet. Notably, the average sodium intake in Switzerland is twice as high as the WHO recommendation, while the intake of milk and dairy products is low. We retrospectively analyzed Swiss recurrent kidney stone formers (rKSF) to test the impact of a low-sodium in combination with a low-calcium diet on the urinary risk profile. In patients with recurrent calcium oxalate containing stones, we investigated both, the consequence of a low-sodium diet on urinary volume and calcium excretion, and the influence of a low-sodium low-calcium diet on urinary oxalate excretion. Of the 169 patients with CaOx stones, 49 presented with hypercalciuria at baseline. The diet resulted in a highly significant reduction in 24-h urinary sodium and calcium excretion: from 201 ± 89 at baseline to 128 ± 88 mmol/d for sodium (p < 0.0001), and from 5.67 ± 3.01 to 4.06 ± 2.46 mmol/d (p < 0.0001) for calcium, respectively. Urine volume remained unchanged. Notably, no increase in oxalate excretion occurred on the restricted diet (0.39 ± 0.26 vs 0.39 ± 0.19 mmol/d, p = 0.277). Calculated Psf (probability of stone formation) values were only predictive for the risk of calcium phosphate stones. A diet low in sodium and calcium in recurrent calcium oxalate stone formers resulted in a significant reduction of urinary calcium excretion, but no change in urine volume. In this population with apparently low intake of dairy products, calcium restriction does not necessarily result in increased urinary oxalate excretion. However, based on previous studies, we recommend a normal dietary calcium intake to avoid a potential increase in urinary oxalate excretion and unfavorable effects on bone metabolism in hypercalciuric KSFs.

Quality of 4-hourly ejaculates--levels of calcium and magnesium.

PubMed

Valsa, J; Skandhan, K P; Gusani, P H; Sahab Khan, P; Amith, S

2013-02-01

A four-hourly ejaculation study was conducted in which eleven normal healthy subjects participated. Five of them discontinued after submitting three samples. One alone was present for submission at the end of 16 h (fifth ejaculate), which was his last submission. Physical exhaustion was the sole reason for all participants for their discontinuation from the study. The result showed a decrease in semen volume and sperm count from first to last ejaculate. The increase in motility was probably due to reduction in exposure time to sperm motility inhibitory factors. In general, total motile spermatozoa as well as actively motile spermatozoa progressively increased from first to last ejaculate at the cost of sluggish spermatozoa. A significant increase in seminal plasma calcium and magnesium was seen as well as a significant increase in magnesium inside the cell from the first to the fourth ejaculate. Considering the quality of semen, which was good in sperm count and excellent in motility, calcium and magnesium may be helpful in cleaning motility inhibitory factors of spermatozoa. © 2012 Blackwell Verlag GmbH.

Hypocalcaemia, Alcohol Drinking and Viroimmune Responses in ART Recipients

PubMed Central

Míguez, María José; Burbano-Levy, Ximena; Carmona, Talita; Quiros, Clery; Thompson, Michelle; Lewis, John; Asthana, Desharatan; Rodríguez, Allan; Valiathan, Ranjini; Malow, Robert

2013-01-01

Metabolic perturbations associated with HIV and antiretroviral therapies are widespread. Unfortunately, research has predominantly focused in cardiometabolic problems, neglecting other important areas. In fact, the immune-calcium-skeletal interface has been understudied despite its potential relevance in people living with HIV (PLWH). Using a case-control methodology, 200 PLWH receiving medical care were enrolled and stratified according to hazardous vs. non-hazardous alcohol intake (HAU vs. non-HAU) and calcium (Ca) levels by analyzing baseline data. The group was chosen to represent relatively "pure" HAU with minimal drug use and no psychiatric diagnoses. With these narrow parameters in place, we found evidence that HAU significantly increases TNF-α levels compared to Non-HAU (2.8±0.6 vs. 1.9±0.3 pg/ml, p=0.05) and decreases blood Ca levels (9±0.6 vs. 9.4 ±0.5, p=0.03). Our analyses also suggest that chronic inflammation, as indicated by increased TNF-α levels, is associated with hypocalcemia (hypoCa <8.6). Despite the limited prevalence of hypoCa, these findings are clinically significant given that hypoCA PLWH exhibited decreased CD4 (253±224 vs. 417.7±281, p=0.02), B cells (147±58 vs. 248±151 p=0.03) and NK cells (146.8±90 vs. 229±148, p=0.008) and elevated CD8 (902.5±438 vs. 699±510, p=0.09) compared to those with normal calcium. Furthermore, calcium effects on viral load were also evident with hypoCA exhibiting the highest loads (140,187±111 vs. 35622 ±7770 HIV copies, p=0.01). Multivariate analyses confirmed the significance of hypoCa in predicting viro-immune parameters. This paper provides the first evidence that hypoCa accounts for some of the variation in viroimmune measures in HAART recipients and suggests that hypoCa may be mediating alcohol’s deleterious effects. PMID:22857856

Normal Hematological, Biochemical, and Serum Electrolyte Values for a Colony of Rhesus Monkeys ’Macaca mulatta’,

DTIC Science & Technology

1976-10-28

ammonia quantitatively with alpha - ketoglutarate along with the oxidation of NADH to NAD. The resultant decrease in absorbence at 340 nm is directly...Sephrophore III membranes. 3. Serum Electrolytes a. Calcium - A manual fluorescent titration method was used to determine serum calcium concentration...The dye calcein fluoresces in the presence of calcium . This fluorescent complex is titrated with ethylenediamine tetra-acetic acid (EDTA), the end

Susceptibility to kinetotic Behaviour during Parabolic Aircraft Flights and otolithic Calcium Incorporation in Fish

NASA Astrophysics Data System (ADS)

Forster, A.; Anken, R.; Hilbig, R.

According to an earlier concept, otolith (or statolith) asymmetry is the cause for susceptibility to kinetoses (e.g., human static space sickness). Indeed, we could recently show that fish showing a kinetotic behaviour after development at hypergravity had incorporated significantly more otolithic calcium (and had an higher otolith asymmetry concerning calcium incorporation) as had normally swimming hyper-g specimens. In order to determine whether a (predispositioned) high asymmetry of otolithic calcium incorporation may also be the cause for kinetosis susceptibility in the microgravity environment (to be achived during parabolic aircraft flights, PFs), larval cichlid fish (Oreochromis mossambicus) were (prior to the PFs) maintained in aquarium water containing alizarin-complexone (AC), a fluorescent calcium tracer. Subsequently, the behaviour of the animals during the microgravity phases of the PF experiment was qualitatively assessed and the specimens were seperated into normally and kinetotically swimming individuals (the latter performed spinning movements). Finally, otolithic AC (and thus calzium) incorporation was densitometrically determined in the otoliths and correlated with the animals' behavior. The respective data will be communicated at the meeting. Acknowledgement: This work was financially supported by the German Aerospace Center (DLR) (FKZ: 50 WB 9997).

Dietary Calcium Intake, Serum Calcium Level, and their Association with Preeclampsia in Rural North India

PubMed Central

Gupta, Anant; Kant, Shashi; Pandav, Chandrakant S.; Gupta, Sanjeev K.; Rai, Sanjay K.; Misra, Puneet

2016-01-01

Background: Preeclampsia in pregnancy has been shown to be associated with low serum calcium level. Though the evidence is abundant, it is equivocal. Objectives: The study aimed to estimate the dietary calcium intake and serum calcium status among pregnant women, and to document the association of the dietary calcium intake and serum calcium status with incidence of preeclampsia in the 3rd trimester of pregnancy. Materials and Methods: A community-based cross-sectional study was conducted in the Health and Demographic Surveillance System (HDSS) site, Ballabgarh, Haryana, India. All pregnant women between 28 weeks and 36 weeks of gestation were interviewed. A semi-structured interview schedule and a 24-h dietary recall questionnaire were administered to assess the dietary calcium intake. AutoAnalyser (Biolis 24i) was used for measuring serum calcium. Results: We enrolled 217 pregnant women. The mean [standard deviation (SD)] dietary calcium intake was 858 (377) mg/day. The mean (SD) serum calcium level was 9.6 mg/dL (0.56). Incidence of preeclampsia was 13.4%. Preeclampsia was not associated with hypocalcemia [odds ratio (OR) = 1.2 95% confidence interval (CI); 0.27-3.98]. Conclusion: The majority of pregnant women had inadequate dietary calcium intake. The prevalence of hypocalcemia was low. Low serum calcium level was not associated with preeclampsia. Calcium supplementation may not reduce preeclampsia in this population. PMID:27385877

The Relationship between Serum Vitamin D Levels and Spinal Fusion Success: A Quantitative Analysis

PubMed Central

Metzger, Melodie F.; Kanim, Linda E.; Zhao, Li; Robinson, Samuel T.; Delamarter, Rick B.

2015-01-01

Study Design An in vivo dosing study of vitamin D in a rat posterolateral spinal fusion model with autogenous bone grafting. Rats randomized to four levels of Vitamin D adjusted rat chow, longitudinal serum validation, surgeons/observers blinded to dietary conditions, and rats followed prospectively for fusion endpoint. Objective To assess the impact of dietary and serum levels of Vitamin D on fusion success, consolidation of fusion mass, and biomechanical stiffness after posterolateral spinal fusion procedure. Summary of Background Data Metabolic risk factors, including vitamin D insufficiency, are often overlooked by spine surgeons. Currently there are no published data on the causal effect of insufficient or deficient vitamin D levels on the success of establishing solid bony union after a spinal fusion procedure. Methods 50 rats were randomized to four experimentally controlled rat chow diets: normal control, vitamin D-deficient, vitamin-D insufficient, and a non-toxic high dose of vitamin D, four weeks prior to surgery and maintained post-surgery until sacrifice. Serum levels of 25(OH)D were determined at surgery and sacrifice using radioimmunoassay. Posterolateral fusion surgery with tail autograft was performed. Rats were sacrificed 12 weeks post-operatively and fusion was evaluated via manual palpation, high resolution radiographs, μCT, and biomechanical testing. Results Serum 25(OH)D and calcium levels were significantly correlated with vitamin-D adjusted chow (p<0.001). There was a dose dependent relationship between vitamin D adjusted chow and manual palpation fusion with greatest differences found in measures of radiographic density between high and deficient vitamin D (p<0.05). Adequate levels of vitamin D (high and normal control) yielded stiffer fusion than inadequate levels (insufficient and deficient) (p<0.05). Conclusions Manual palpation fusion rates increased with supplementation of dietary vitamin D. Biomechanical stiffness, bone volume and density were also positively-related to vitamin D, and calcium. PMID:25627287

Anti-stress effects of cilnidipine and nimodipine in immobilization subjected mice.

PubMed

Kumar, Naresh; Singh, Nirmal; Jaggi, Amteshwar Singh

2012-03-20

The present study was designed to investigate the ameliorative role of cilnidipine and nimodipine in immobilization stress-induced behavioral alterations and memory defects in the mice. Acute stress was induced by immobilizing the mice for 150 min and stress-induced behavioral changes were assessed using actophotometer, hole board, open field and social interaction tests. The learning and memory was evaluated using elevated plus maze tests and biochemically, the corticosterone levels were measured in the blood serum. Acute immobilization stress resulted in decrease in locomotor activity, frequency of head dips and rearings in hole board; line crossing and rearing in the open field; increase in avoidance in social behavior along with development of memory deficits assessed by an increased transfer latency time and elevation of the corticosterone levels. Administration of cilnidipine (10 mg/kg), an L and N-type dual calcium channel blocker, and nimodipine (10 mg/kg), an L-type calcium channel blocker, significantly attenuated the immobilized stress-induced behavioral changes and restored memory deficits along with normalization of the corticosterone levels. Cilnidipine and nimodipine produced comparable beneficial effects in restoring immobilization stress subjected mice. It may be concluded that cilnidipine and nimodipine mediated attenuation of corticosterone release by blockage of calcium channels (both L and N-type) on the HPA-axis is responsible for beneficial effects in restoration of behavioral alterations and memory deficits in immobilization-induced acute stress in mice. Copyright © 2011 Elsevier Inc. All rights reserved.

Ameliorative effect of Vernonia cinerea in vincristine-induced painful neuropathy in rats.

PubMed

Thiagarajan, Venkata Rathina Kumar; Shanmugam, Palanichamy; Krishnan, Uma Maheswari; Muthuraman, Arunachalam

2014-10-01

The present study was designed to investigate the antinociceptive potential of Vernonia cinerea (VC) on vincristine-induced painful neuropathy in rats. A chemotherapeutic agent, vincristine (50 μg/kg intraperitoneally for 10 consecutive days), was administered for the induction of neuropathic pain in rats. The painful behavioral changes were assessed using hot plate, acetone drop, paw pressure, Von Frey hair and tail immersion tests to assess the degree of hyperalgesic and allodynic pain sensation in paw and tail. Tissue biomarker changes including thiobarbituric acid reactive substances (TBARSs), reduced glutathione (GSH) and total calcium levels were estimated in sciatic nerve tissue samples to assess the degree of oxidative stress. Histopathological changes were also observed in transverse sections of rat sciatic nerve tissue. Ethanolic extract of VC leaves and pregabalin were administered for 14 consecutive days from day 0 (day of surgery). Pregabalin served as a positive control in the present study. Vincristine administration resulted in a significant reduction in painful behavioral changes along with a rise in the levels of TBARS, total calcium and decrease in GSH levels when compared with the normal control group. Furthermore, significant histopathological changes were also observed. Pretreatment with VC significantly attenuated vincristine-induced development of painful behavioral, biochemical and histological changes in a dose-dependent manner, which is similar to that of pregabalin-pretreated group. The attenuating effect of VC in vincristine-induced nociceptive painful sensation may be due to its potential of antioxidative, neuroprotective and calcium channel inhibitory action. © The Author(s) 2012.

Ossification of the cervical ligamentum flavum and osseous brown tumor: late manifestations of primary hyperparathyroidism misdiagnosed in a case of parathyroid carcinoma

PubMed Central

Sampanis, Nikolaos; Gavriilaki, Eleni; Paschou, Eleni; Kalaitzoglou, Asterios; Vasileiou, Sotirios

2016-01-01

Summary Parathyroid carcinoma represents an extremely rare neoplasm with diverse clinical manifestations. Herein we aimed at presenting an unique case of a young patient with late manifestations of parathyroid cancer and reviewing the relevant literature. A 45-year-old male patient presented in the Outpatient Clinic with an episode of nephrolithiasis. His personal medical history includes: recurrent episodes of nephrolithiasis, laminectomy in the cervical spine due to ossification of the cervical ligamentum flavum and surgical resection of a giant cell tumor of the brain. Laboratory testing revealed findings of primary hyperparathyroidism (serum calcium 16,0 mmol/l phosphorus 1,46 mg/dl and parathyroid hormone/PTH 8560 pg/ml). Neck ultrasound and technetium-99 m sestamibi scan were performed showing a parathyroid tumor. Due to the persistently high serum calcium and PTH levels, the high alkaline phosphatase levels (440 IU/L) and the late manifestations of HPT, surgical excision of the tumor was performed. The tumor was identified as parathyroid carcinoma. Immediately after surgery serum calcium and phosphorus levels were normalized. The patient is on a regular follow-up program with no signs of recurrence or metastasis one year after the excision. We describe the coexistence of rare late manifestations of HPT, which had not been adequately investigated at their onset in this young patient. Therefore, increased awareness is needed in order to recognize and further investigate signs or symptoms of HPT. PMID:27252748

Ossification of the cervical ligamentum flavum and osseous brown tumor: late manifestations of primary hyperparathyroidism misdiagnosed in a case of parathyroid carcinoma.

PubMed

Sampanis, Nikolaos; Gavriilaki, Eleni; Paschou, Eleni; Kalaitzoglou, Asterios; Vasileiou, Sotirios

2016-01-01

Parathyroid carcinoma represents an extremely rare neoplasm with diverse clinical manifestations. Herein we aimed at presenting an unique case of a young patient with late manifestations of parathyroid cancer and reviewing the relevant literature. A 45-year-old male patient presented in the Outpatient Clinic with an episode of nephrolithiasis. His personal medical history includes: recurrent episodes of nephrolithiasis, laminectomy in the cervical spine due to ossification of the cervical ligamentum flavum and surgical resection of a giant cell tumor of the brain. Laboratory testing revealed findings of primary hyperparathyroidism (serum calcium 16,0 mmol/l phosphorus 1,46 mg/dl and parathyroid hormone/PTH 8560 pg/ml). Neck ultrasound and technetium-99 m sestamibi scan were performed showing a parathyroid tumor. Due to the persistently high serum calcium and PTH levels, the high alkaline phosphatase levels (440 IU/L) and the late manifestations of HPT, surgical excision of the tumor was performed. The tumor was identified as parathyroid carcinoma. Immediately after surgery serum calcium and phosphorus levels were normalized. The patient is on a regular follow-up program with no signs of recurrence or metastasis one year after the excision. We describe the coexistence of rare late manifestations of HPT, which had not been adequately investigated at their onset in this young patient. Therefore, increased awareness is needed in order to recognize and further investigate signs or symptoms of HPT.

Thymol, a dietary monoterpene phenol abrogates mitochondrial dysfunction in β-adrenergic agonist induced myocardial infarcted rats by inhibiting oxidative stress.

PubMed

Nagoor Meeran, M F; Jagadeesh, G S; Selvaraj, P

2016-01-25

Mitochondrial dysfunction has been suggested to be one of the important pathological events in isoproterenol (ISO), a synthetic catecholamine and β-adrenergic agonist induced myocardial infarction (MI). In this context, we have evaluated the impact of thymol against ISO induced oxidative stress and calcium uniporter malfunction involved in the pathology of mitochondrial dysfunction in rats. Male albino Wistar rats were pre and co-treated with thymol (7.5 mg/kg body weight) daily for 7 days. Isoproterenol (100 mg/kg body weight) was subcutaneously injected into rats on 6th and 7th day to induce MI. To explore the extent of cardiac mitochondrial damage, the activities/levels of cardiac marker enzymes, mitochondrial lipid peroxidation products, antioxidants, lipids, calcium, adenosine triphosphate and multi marker enzymes were evaluated. Isoproterenol induced myocardial infarcted rats showed a significant increase in the activities of cardiac diagnostic markers, heart mitochondrial lipid peroxidation, lipids, calcium, and a significant decrease in the activities/levels of heart mitochondrial superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, isocitrate, malate, α-ketoglutarate and NADH-dehydrogenases, cytochrome-C-oxidase, and adenosine triphosphate. Thymol pre and co-treatment showed near normalized effects on all the biochemical parameters studied. Transmission electron microscopic findings and mitochondrial swelling studies confirmed our biochemical findings. The in vitro study also revealed the potent free-radical scavenging activity of thymol. Thus, thymol attenuates the involvement of ISO against oxidative stress and calcium uniporter malfunction associated with mitochondrial dysfunction in rats. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[Effect of nerve growth factor on osteogenic potential of type 2 diabetic mice bone marrow stromal cell in vitro].

PubMed

Cui, G S; Zeng, J Y; Zhang, J; Lu, R

2018-02-09

Objective: To study the effects of nerve growth factor (NGF) on the proliferation, osteogenic differentiation and mineralization of type 2 diabetic mice bone marrow stromal cell (BMSC), providing basis for clinical application of NGF. Methods: Three 8-week-old male db/db mice and two 8-week-old male C57BL/6J mice were used in the study. BMSC derived from femur were cultured though adherence method. BMSC of C57BL/6J mice and db/db mice was divided into normal group and diabetic group to conduct the osteogenic potential experiment, named experiment one. In experiment two, diabetic BMSC was divided into 3 groups: diabetic control group, NGF group, and K252a+NGF group [K252a was the inhibitor of tyrosine kinase A (TrkA), which was the high affinity receptor of NGF], to investigate effect of NGF on osteogenic potential of diabetic mice BMSC. After seeding BMSC, K252a was added into K252a+NGF group, then NGF was added 30 min later. NGF was added into NGF group and K252a+NGF group, but not diabetic control group. The proliferation of BMSC at 1, 3, 5 and 7 d in experiment one and the proliferation of BMSC at 1, 2 and 3 d in experiment two were evaluated through methyl thiazolyl tetrazolium, and the level of alkaline phosphatase (ALP) at 3, 5 and 7 d in both experiments were measured. After being osteogenic induced for 14 d, mineralized nodules in both experiments were quantitated by alizarin red calcium stain. Five holes were set in every group, and all experiments were repeated 3 times. Results: The BMSC proliferation of diabetic group was significantly higher than that of the normal group at 3, 5 and 7 d ( P< 0.05). After being osteogenic inducted for 3, 5 and 7 d, ALP level of diabetic group were significantly lower than that of normal group ( P< 0.05). After being osteogenic inducted for 14 d, calcium nodule count of diabetic group [(23.1±6.4) nodule/field] were significantly lower than that of normal group [(36.9±7.9) nodule/field]( P< 0.05). At 1, 2 and 3 d, BMSC proliferations of diabetic control group, NGF group and K252a+NGF group were not statistically different ( P> 0.05). After being osteogenic inducted for 3 and 5 d, ALP level of NGF group was significantly higher than that of diabetic control group ( P< 0.05). After being osteogenic inducted for 3, 5, and 7 d, ALP level of K252a+NGF group was significantly lower than that of NGF group ( P< 0.05) and diabetic control group ( P< 0.05). After being osteogenic induced for 14 d, calcium nodule count of NGF group [(45.2±6.8) nodule/field] was significantly more than that of diabetic control group [(23.1±6.4) nodule/field]( P< 0.05); while calcium nodule count of K252a+NGF group [(18.0±4.5) nodule/field] was significantly less than that of NGF group ( P< 0.05) and diabetic control group ( P< 0.05). Conclusions: The differentiation and mineralization of type 2 diabetic mice BMSC was significantly reduced. NGF promoted the osteoblastic differentiation and mineralization of diabetic mice BMSC in viro though combining with TrkA.

Chronic alcohol feeding potentiates hormone-induced calcium signalling in hepatocytes.

PubMed

Bartlett, Paula J; Antony, Anil Noronha; Agarwal, Amit; Hilly, Mauricette; Prince, Victoria L; Combettes, Laurent; Hoek, Jan B; Gaspers, Lawrence D

2017-05-15

Chronic alcohol consumption causes a spectrum of liver diseases, but the pathogenic mechanisms driving the onset and progression of disease are not clearly defined. We show that chronic alcohol feeding sensitizes rat hepatocytes to Ca 2+ -mobilizing hormones resulting in a leftward shift in the concentration-response relationship and the transition from oscillatory to more sustained and prolonged Ca 2+ increases. Our data demonstrate that alcohol-dependent adaptation in the Ca 2+ signalling pathway occurs at the level of hormone-induced inositol 1,4,5 trisphosphate (IP 3 ) production and does not involve changes in the sensitivity of the IP 3 receptor or size of internal Ca 2+ stores. We suggest that prolonged and aberrant hormone-evoked Ca 2+ increases may stimulate the production of mitochondrial reactive oxygen species and contribute to alcohol-induced hepatocyte injury. ABSTRACT: 'Adaptive' responses of the liver to chronic alcohol consumption may underlie the development of cell and tissue injury. Alcohol administration can perturb multiple signalling pathways including phosphoinositide-dependent cytosolic calcium ([Ca 2+ ] i ) increases, which can adversely affect mitochondrial Ca 2+ levels, reactive oxygen species production and energy metabolism. Our data indicate that chronic alcohol feeding induces a leftward shift in the dose-response for Ca 2+ -mobilizing hormones resulting in more sustained and prolonged [Ca 2+ ] i increases in both cultured hepatocytes and hepatocytes within the intact perfused liver. Ca 2+ increases were initiated at lower hormone concentrations, and intercellular calcium wave propagation rates were faster in alcoholics compared to controls. Acute alcohol treatment (25 mm) completely inhibited hormone-induced calcium increases in control livers, but not after chronic alcohol-feeding, suggesting desensitization to the inhibitory actions of ethanol. Hormone-induced inositol 1,4,5 trisphosphate (IP 3 ) accumulation and phospholipase C (PLC) activity were significantly potentiated in hepatocytes from alcohol-fed rats compared to controls. Removal of extracellular calcium, or chelation of intracellular calcium did not normalize the differences in hormone-stimulated PLC activity, indicating calcium-dependent PLCs are not upregulated by alcohol. We propose that the liver 'adapts' to chronic alcohol exposure by increasing hormone-dependent IP 3 formation, leading to aberrant calcium increases, which may contribute to hepatocyte injury. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Quercetin Attenuates Vascular Calcification through Suppressed Oxidative Stress in Adenine-Induced Chronic Renal Failure Rats.

PubMed

Chang, Xue-Ying; Cui, Lei; Wang, Xing-Zhi; Zhang, Lei; Zhu, Dan; Zhou, Xiao-Rong; Hao, Li-Rong

2017-01-01

This study investigated whether quercetin could alleviate vascular calcification in experimental chronic renal failure rats induced by adenine. 32 adult male Wistar rats were randomly divided into 4 groups fed normal diet, normal diet with quercetin supplementation (25 mg/kg·BW/d), 0.75% adenine diet, or adenine diet with quercetin supplementation. All rats were sacrificed after 6 weeks of intervention. Serum renal functions biomarkers and oxidative stress biomarkers were measured and status of vascular calcification in aorta was assessed. Furthermore, the induced nitric oxide synthase (iNOS)/p38 mitogen activated protein kinase (p38MAPK) pathway was determined to explore the potential mechanism. Adenine successfully induced renal failure and vascular calcification in rat model. Quercetin supplementation reversed unfavorable changes of phosphorous, uric acid (UA) and creatinine levels, malonaldehyde (MDA) content, and superoxide dismutase (SOD) activity in serum and the increases of calcium and alkaline phosphatase (ALP) activity in the aorta ( P < 0.05) and attenuated calcification and calcium accumulation in the medial layer of vasculature in histopathology. Western blot analysis showed that iNOS/p38MAPK pathway was normalized by the quercetin supplementation. Quercetin exerted a protective effect on vascular calcification in adenine-induced chronic renal failure rats, possibly through the modulation of oxidative stress and iNOs/p38MAPK pathway.

Quercetin Attenuates Vascular Calcification through Suppressed Oxidative Stress in Adenine-Induced Chronic Renal Failure Rats

PubMed Central

Chang, Xue-ying; Cui, Lei; Wang, Xing-zhi; Zhang, Lei; Zhu, Dan

2017-01-01

Background This study investigated whether quercetin could alleviate vascular calcification in experimental chronic renal failure rats induced by adenine. Methods 32 adult male Wistar rats were randomly divided into 4 groups fed normal diet, normal diet with quercetin supplementation (25 mg/kg·BW/d), 0.75% adenine diet, or adenine diet with quercetin supplementation. All rats were sacrificed after 6 weeks of intervention. Serum renal functions biomarkers and oxidative stress biomarkers were measured and status of vascular calcification in aorta was assessed. Furthermore, the induced nitric oxide synthase (iNOS)/p38 mitogen activated protein kinase (p38MAPK) pathway was determined to explore the potential mechanism. Results Adenine successfully induced renal failure and vascular calcification in rat model. Quercetin supplementation reversed unfavorable changes of phosphorous, uric acid (UA) and creatinine levels, malonaldehyde (MDA) content, and superoxide dismutase (SOD) activity in serum and the increases of calcium and alkaline phosphatase (ALP) activity in the aorta (P < 0.05) and attenuated calcification and calcium accumulation in the medial layer of vasculature in histopathology. Western blot analysis showed that iNOS/p38MAPK pathway was normalized by the quercetin supplementation. Conclusions Quercetin exerted a protective effect on vascular calcification in adenine-induced chronic renal failure rats, possibly through the modulation of oxidative stress and iNOs/p38MAPK pathway. PMID:28691026

Effects of Human Mesenchymal Stem Cells Coculture on Calcium-Induced Differentiation of Normal Human Keratinocytes.

PubMed

Sah, Shyam Kishor; Kim, Hae Young; Lee, Ji Hae; Lee, Seong-Wook; Kim, Hyung-Sik; Kim, Yeon-Soo; Kang, Kyung-Sun; Kim, Tae-Yoon

2017-06-01

The influence of mesenchymal stem cells (MSCs) on keratinocytes in altered microenvironments is poorly understood. Here, we cocultured umbilical cord blood-derived MSCs with normal human epidermal keratinocytes to evaluate their paracrine effect in the presence of high extracellular calcium (Ca 2+ ) concentration. High Ca 2+ environment to keratinocytes can disrupt normal skin barrier function due to abnormal/premature differentiation of keratinocytes. Surprisingly, we found that MSCs suppress both proliferation and differentiation of keratinocytes under a high Ca 2+ environment in transforming growth factors β1 (TGFβ1)-dependent manner. Furthermore, we determined that MSCs can regulate the mitogen-activated protein kinases, phosphatidylinositol 3-kinase/protein kinase B, and protein kinase C pathways in Ca 2+ -induced differentiated keratinocytes. Knockdown of TGFβ1 from MSCs results in decreased suppression of differentiation with significantly increased proliferation of keratinocytes compared with control MSCs. MSCs-derived TGFβ1 further induced growth inhibition of keratinocyte in high extracellular Ca 2+ environment as analyzed by a decrease in DNA synthesis, accumulation of phosphorylated retinoblastoma protein, cdc2, and increased mRNA level of p21, and independent of TGFβ1/SMAD pathway. Taken together, we found that MSCs-derived TGFβ1 is a critical regulator of keratinocyte function, and involves multiple proximal signaling cascades. Stem Cells 2017;35:1592-1602. © 2017 AlphaMed Press.

Plasma concentrations of parathyroid hormone-related protein in dogs with potential disorders of calcium metabolism.

PubMed

Mellanby, R J; Craig, R; Evans, H; Herrtage, M E

2006-12-16

The plasma concentrations of total calcium, ionised calcium, albumin, parathyroid hormone and parathyroid hormone-related protein (PTHrp) were measured in 25 dogs with lymphoma, nine dogs with primary hyperparathyroidism and seven dogs with adenocarcinoma of the apocrine gland of the anal sac. Plasma total calcium, ionised calcium, albumin and parathyroid hormone-related protein were measured in 18 clinically normal control dogs. The concentration of PTHrp was high in 12 of the 14 dogs that were hypercalcaemic because of an underlying malignancy but was within the reference range in all the control dogs, in the 17 normocalcaemic dogs with lymphoma and in the seven dogs which were hypercalcaemic because of a parathyroid adenoma.

Association of Genetic Variants Related to Serum Calcium Levels With Coronary Artery Disease and Myocardial Infarction.

PubMed

Larsson, Susanna C; Burgess, Stephen; Michaëlsson, Karl

2017-07-25

Serum calcium has been associated with cardiovascular disease in observational studies and evidence from randomized clinical trials indicates that calcium supplementation, which raises serum calcium levels, may increase the risk of cardiovascular events, particularly myocardial infarction. To evaluate the potential causal association between genetic variants related to elevated serum calcium levels and risk of coronary artery disease (CAD) and myocardial infarction using mendelian randomization. The analyses were performed using summary statistics obtained for single-nucleotide polymorphisms (SNPs) identified from a genome-wide association meta-analysis of serum calcium levels (N = up to 61 079 individuals) and from the Coronary Artery Disease Genome-wide Replication and Meta-analysis Plus the Coronary Artery Disease Genetics (CardiogramplusC4D) consortium's 1000 genomes-based genome-wide association meta-analysis (N = up to 184 305 individuals) that included cases (individuals with CAD and myocardial infarction) and noncases, with baseline data collected from 1948 and populations derived from across the globe. The association of each SNP with CAD and myocardial infarction was weighted by its association with serum calcium, and estimates were combined using an inverse-variance weighted meta-analysis. Genetic risk score based on genetic variants related to elevated serum calcium levels. Co-primary outcomes were the odds of CAD and myocardial infarction. Among the mendelian randomized analytic sample of 184 305 individuals (60 801 CAD cases [approximately 70% with myocardial infarction] and 123 504 noncases), the 6 SNPs related to serum calcium levels and without pleiotropic associations with potential confounders were estimated to explain about 0.8% of the variation in serum calcium levels. In the inverse-variance weighted meta-analysis (combining the estimates of the 6 SNPs), the odds ratios per 0.5-mg/dL increase (about 1 SD) in genetically predicted serum calcium levels were 1.25 (95% CI, 1.08-1.45; P = .003) for CAD and 1.24 (95% CI, 1.05-1.46; P = .009) for myocardial infarction. A genetic predisposition to higher serum calcium levels was associated with increased risk of CAD and myocardial infarction. Whether the risk of CAD associated with lifelong genetic exposure to increased serum calcium levels can be translated to a risk associated with short-term to medium-term calcium supplementation is unknown.

Correlation of Salivary Statherin and Calcium Levels with Dental Calculus Formation: A Preliminary Study.

PubMed

Pateel, Deepak Gowda Sadashivappa; Gunjal, Shilpa; Math, Swarna Y; Murugeshappa, Devarasa Giriyapura; Nair, Sreejith Muraleedharan

2017-01-01

Salivary constituents have a wide range of functions including oral calcium homeostasis. Salivary proteins such as statherin inhibit crystal growth of calcium phosphate in supersaturated solutions and interact with several oral bacteria to adsorb on hydroxyapatite. Concurrently, saliva, which is supersaturated with respect to calcium phosphates, is the driving force for plaque mineralization and formation of calculus. Thus, the aim of the present study was to estimate and correlate salivary statherin and calcium concentration to the dental calculus formation. A cross-sectional study was conducted to assess the relationship between salivary statherin, calcium, and dental calculus among 70 subjects, aged 20-55 years. Subjects were divided into 3 groups based on the calculus scores as interpreted by Calculus Index which was followed by collection of whole saliva using Super•SAL™. Salivary calcium levels were assessed by calorimetric method using Calcium Assay kit (Cayman Chemical, Michigan, USA) and statherin levels by using ELISA Kit (Cusabio Biotech). Statherin levels showed a weak negative correlation with the calcium levels and with calculus formation. The mean salivary statherin and calcium concentration were found to be 0.96  μ g/ml and 3.87 mg/ml, respectively. Salivary statherin levels differed significantly among the three groups ( p < 0.05). Our preliminary data indicates that statherin could possibly play a role in the formation of dental calculus.

Loperamide: A positive modulator for store-operated calcium channels?

PubMed Central

Harper, Jacquie L.; Shin, Yangmee; Daly, John W.

1997-01-01

The depletion of inositol trisphosphate-sensitive intracellular pools of calcium causes activation of store-operated calcium (SOC) channels. Loperamide at 10–30 μM has no effect on intracellular calcium levels alone, but augments calcium levels in cultured cells when SOC channels have been activated. In HL-60 leukemic cells, the apparent positive modulatory effect of loperamide on SOC channels occurs when these channels have been activated after ATP, thapsigargin, or ionomycin-elicited depletion of calcium from intracellular storage sites. Loperamide has no effect when levels of intracellular calcium are elevated through a mechanism not involving SOC channels by using sphingosine. Loperamide caused augmentation of intracellular calcium levels after activation of SOC channels in NIH 3T3 fibroblasts, astrocytoma 1321N cells, smooth muscle DDT-MF2 cells, RBL-2H3 mast cells, and pituitary GH4C1 cells. Only in astrocytoma cells did loperamide cause an elevation in intracellular calcium in the absence of activation of SOC channels. The augmentation of intracellular calcium elicited by loperamide in cultured cells was dependent on extracellular calcium and was somewhat resistant to agents (SKF 96365, miconazole, clotrimazole, nitrendipine, and trifluoperazine) that in the absence of loperamide effectively blocked SOC channels. It appears that loperamide augments influx of calcium through activated SOC channels. PMID:9405713

Intestinal Calcium Absorption among Hypercalciuric Patients with or without Calcium Kidney Stones.

PubMed

Vezzoli, Giuseppe; Macrina, Lorenza; Rubinacci, Alessandro; Spotti, Donatella; Arcidiacono, Teresa

2016-08-08

Idiopathic hypercalciuria is a frequent defect in calcium kidney stone formers that is associated with high intestinal calcium absorption and osteopenia. Characteristics distinguishing hypercalciuric stone formers from hypercalciuric patients without kidney stone history (HNSFs) are unknown and were explored in our study. We compared 172 hypercalciuric stone formers with 36 HNSFs retrospectively selected from patients referred to outpatient clinics of the San Raffaele Hospital in Milan from 1998 to 2003. Calcium metabolism and lumbar bone mineral density were analyzed in these patients. A strontium oral load test was performed: strontium was measured in 240-minute urine and serum 30, 60, and 240 minutes after strontium ingestion; serum strontium concentration-time curve and renal strontium clearance were evaluated to estimate absorption and excretion of divalent cations. Serum strontium concentration-time curve (P<0.001) and strontium clearance (4.9±1.3 versus 3.5±2.7 ml/min; P<0.001) were higher in hypercalciuric stone formers than HNSFs, respectively. The serum strontium-time curve was also higher in hypercalciuric stone formers with low bone mineral density (n=42) than in hypercalciuric stone formers with normal bone mineral density (n=130; P=0.03) and HNSFs with low (n=22; P=0.01) or normal bone mineral density (n=14; P=0.02). Strontium clearance was greater in hypercalciuric stone formers with normal bone mineral density (5.3±3.4 ml/min) than in hypercalciuric stone formers and HNSFs with low bone mineral density (3.6±2.5 and 3.1±2.5 ml/min, respectively; P=0.03). Multivariate regression analyses displayed that strontium absorption at 30 minutes was positively associated calcium excretion (P=0.03) and negatively associated with lumbar bone mineral density z score (P=0.001) in hypercalciuric stone formers; furthermore, hypercalciuric patients in the highest quartile of strontium absorption had increased stone production risk (odds ratio, 5.06; 95% confidence interval, 1.2 to 20.9; P=0.03). High calcium absorption in duodenum and jejunum may expose hypercalciuric patients to the risk of stones because of increased postprandial calcium concentrations in urine and tubular fluid. High calcium absorption may identify patients at risk of bone loss among stone formers. Copyright © 2016 by the American Society of Nephrology.

Therapeutic role of calcium and vitamin K3 in chemically induced hepatocarcinogenesis - new tools for cancer treatment.

PubMed

Anwar, Firoz; Khan, Ruqaiyah; Sachan, Richa; Kazmi, Imran; Rawat, Alisha; Sabih, Abdullah; Singh, Rajbala; Afzal, Muhammad; Ahmad, Aftab; Al-Orab, Abdulaziz S; Al-Abbasi, F A; Bhatt, Prakash Chandra; Kumar, Vikas

2018-04-17

HCC has been reported to be immensely occurring carcinoma worldwide. Recent days the mortality occurred due to liver cancer has also been found to be increased at an alarming speed affecting mostly the young patients. The aim of the current study was to decipher the role of calcium and vitamin K3 in the treatment of chemically induced hepatocarcinogenesis in the male Wistar rats. Liver cancer was induced via a subnecrogenic dose of 160 mg/kg body weight, diethylnitrosamine (DENA) when associated with fasting/refeeding in male Wistar rats. It elevated the serum glutamate oxaloacetate (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), bilirubin, total cholesterol (CH), triglycerides (TG), alfa-fetoprotein (AFP) and reduced high-density lipoprotein (HDL). Histopathological examination of liver tissue showed marked carcinogenicity of the chemical carcinogen. Food, water intake and animal weights were also assessed, respectively. The animals exposed to DENA showed a significant decrease in the body weight. The elevated levels of serum SGOT, SGPT, ALP, AFP, TC and TG were restored by administration of calcium and Vit K (ad libitum) combination at higher dose than the normal dietary requirement (3 mg/kg) daily for 12 weeks p.o. Physiological and biochemical analysis showed the beneficial effects of calcium and vitamin K3 combination in the animals exposed to DENA. The results deciphered the beneficial effects of calcium and vitamin K3 in combination.

High sodium chloride intake is associated with low bone density in calcium stone-forming patients.

PubMed

Martini, L A; Cuppari, L; Colugnati, F A; Sigulem, D M; Szejnfeld, V L; Schor, N; Heilberg, I P

2000-08-01

Although renal stone disease has been associated with reduced bone mass, the impact of nutrient intake on bone loss is unknown. The present study was undertaken to investigate the influence of nutrient intake on bone density of 85 calcium stone-forming (CSF) patients (47 male and 38 premenopausal females) aged 41+/-11 years (X+/-SD). Bone mineral density (BMD) was measured using dual energy X-ray absorptiometry at the lumbar spine (L2-L4) and femoral neck sites, and low BMD was defined as a T score < -1 (WHO criteria). A 4-day dietary record and a 24-hour urine sample were obtained from each patient for the assessment of nutrient intake and urinary calcium (U(Ca)), sodium (U(Na)), phosphate and creatinine excretion. Forty-eight patients (56%) presented normal BMD and 37 (44%) low BMD. There were no statistical differences regarding age, weight, height, body mass index, protein, calcium and phosphorus intakes between both groups. The mean U(Ca), phosphorus and nitrogen appearance also did not differ between groups. However, there was a higher percentage of hypercalciuria among low vs normal BMD patients (62 vs 33%, p < 0.05). Low BMD patients presented a higher mean sodium chloride (NaCl) intake and excretion (UNa) than normal BMD (14+/-5 vs 12+/-4 g/day and 246+/-85 vs 204+/-68 mEq/day, respectively p < 0.05). The percentage of patients presenting NaCl intake > or = 16 g/day was also higher among low vs normal BMD patients (35 vs 12%, p < 0.05). After adjustment for calcium and protein intakes, age, weight, body mass index, urinary calcium, citrate and uric acid excretion, and duration of stone disease, multiple-regression analysis showed that a high NaCl intake (> or = 16 g/day) was the single variable that was predictive of risk of low bone density in CSF patients (odds ratio = 3.8). These data suggest that reducing salt intake should be recommended for CSF patients presenting hypercalciuria and osteopenia.

Plasma oxalic acid and calcium levels in oxalate poisoning

PubMed Central

Zarembski, P. M.; Hodgkinson, A.

1967-01-01

Observations are reported on five cases of suicide or attempted suicide by poisoning with oxalic acid or ethylene glycol. Elevated oxalic acid levels were observed in the plasma, stomach contents, and a number of tissues. Raised oxalic acid levels in plasma were associated with reduced total and ultrafilterable calcium levels. It is suggested that the reduction in plasma total calcium level is due mainly to the deposition of calcium oxalate in the soft tissues, but inhibition of the parathyroid glands may be a contributory factor. Microscopic examination of various tissues indicated that oxalic acid is deposited in the tissues in two forms: (1) crystalline calcium oxalate dihydrate in the kidney and (2) a non-crystalline complex of calcium oxalate and lipid in liver and other tissues. PMID:5602563

BIN1 is reduced and Cav1.2 trafficking is impaired in human failing cardiomyocytes.

PubMed

Hong, Ting-Ting; Smyth, James W; Chu, Kevin Y; Vogan, Jacob M; Fong, Tina S; Jensen, Brian C; Fang, Kun; Halushka, Marc K; Russell, Stuart D; Colecraft, Henry; Hoopes, Charles W; Ocorr, Karen; Chi, Neil C; Shaw, Robin M

2012-05-01

Heart failure is a growing epidemic, and a typical aspect of heart failure pathophysiology is altered calcium transients. Normal cardiac calcium transients are initiated by Cav1.2 channels at cardiac T tubules. Bridging integrator 1 (BIN1) is a membrane scaffolding protein that causes Cav1.2 to traffic to T tubules in healthy hearts. The mechanisms of Cav1.2 trafficking in heart failure are not known. To study BIN1 expression and its effect on Cav1.2 trafficking in failing hearts. Intact myocardium and freshly isolated cardiomyocytes from nonfailing and end-stage failing human hearts were used to study BIN1 expression and Cav1.2 localization. To confirm Cav1.2 surface expression dependence on BIN1, patch-clamp recordings were performed of Cav1.2 current in cell lines with and without trafficking-competent BIN1. Also, in adult mouse cardiomyocytes, surface Cav1.2 and calcium transients were studied after small hairpin RNA-mediated knockdown of BIN1. For a functional readout in intact heart, calcium transients and cardiac contractility were analyzed in a zebrafish model with morpholino-mediated knockdown of BIN1. BIN1 expression is significantly decreased in failing cardiomyocytes at both mRNA (30% down) and protein (36% down) levels. Peripheral Cav1.2 is reduced to 42% by imaging, and a biochemical T-tubule fraction of Cav1.2 is reduced to 68%. The total calcium current is reduced to 41% in a cell line expressing a nontrafficking BIN1 mutant. In mouse cardiomyocytes, BIN1 knockdown decreases surface Cav1.2 and impairs calcium transients. In zebrafish hearts, BIN1 knockdown causes a 75% reduction in calcium transients and severe ventricular contractile dysfunction. The data indicate that BIN1 is significantly reduced in human heart failure, and this reduction impairs Cav1.2 trafficking, calcium transients, and contractility. Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

BIN1 is Reduced and Cav1.2 Trafficking is Impaired in Human Failing Cardiomyocytes

PubMed Central

Hong, Ting-Ting; Smyth, James W.; Chu, Kevin Y.; Vogan, Jacob M.; Fong, Tina S.; Jensen, Brian C.; Fang, Kun; Halushka, Marc K.; Russell, Stuart D.; Colecraft, Henry; Hoopes, Charles W.; Ocorr, Karen; Chi, Neil C.; Shaw, Robin M.

2011-01-01

Background Heart failure is a growing epidemic and a typical aspect of heart failure pathophysiology is altered calcium transients. Normal cardiac calcium transients are initiated by Cav1.2 channels at cardiac T-tubules. BIN1 is a membrane scaffolding protein that causes Cav1.2 to traffic to T-tubules in healthy hearts. The mechanisms of Cav1.2 trafficking in heart failure are not known. Objective To study BIN1 expression and its effect on Cav1.2 trafficking in failing hearts. Methods Intact myocardium and freshly isolated cardiomyocytes from non-failing and end-stage failing human hearts were used to study BIN1 expression and Cav1.2 localization. To confirm Cav1.2 surface expression dependence on BIN1, patch clamp recordings were performed of Cav1.2 current in cell lines with and without trafficking competent BIN1. Also, in adult mouse cardiomyocytes, surface Cav1.2 and calcium transients were studied after shRNA mediated knockdown of BIN1. For a functional readout in intact heart, calcium transients and cardiac contractility were analyzed in a zebrafish model with morpholino mediated knockdown of BIN1. Results BIN1 expression is significantly decreased in failing cardiomyocytes at both mRNA (30% down) and protein (36% down) levels. Peripheral Cav1.2 is reduced 42% by imaging and biochemical T-tubule fraction of Cav1.2 is reduced 68%. Total calcium current is reduced 41% in a cell line expressing non-trafficking BIN1 mutant. In mouse cardiomyocytes, BIN1 knockdown decreases surface Cav1.2 and impairs calcium transients. In zebrafish hearts, BIN1 knockdown causes a 75% reduction in calcium transients and severe ventricular contractile dysfunction. Conclusions The data indicate that BIN1 is significantly reduced in human heart failure, and this reduction impairs Cav1.2 trafficking, calcium transients, and contractility. PMID:22138472

Alpha2delta-1 in SF1+ Neurons of the Ventromedial Hypothalamus Is an Essential Regulator of Glucose and Lipid Homeostasis.

PubMed

Felsted, Jennifer A; Chien, Cheng-Hao; Wang, Dongqing; Panessiti, Micaella; Ameroso, Dominique; Greenberg, Andrew; Feng, Guoping; Kong, Dong; Rios, Maribel

2017-12-05

The central mechanisms controlling glucose and lipid homeostasis are inadequately understood. We show that α2δ-1 is an essential regulator of glucose and lipid balance, acting in steroidogenic factor-1 (SF1) neurons of the ventromedial hypothalamus (VMH). These effects are body weight independent and involve regulation of SF1 + neuronal activity and sympathetic output to metabolic tissues. Accordingly, mice with α2δ-1 deletion in SF1 neurons exhibit glucose intolerance, altered lipolysis, and decreased cholesterol content in adipose tissue despite normal energy balance regulation. Profound reductions in the firing rate of SF1 neurons, decreased sympathetic output, and elevated circulating levels of serotonin are associated with these alterations. Normal calcium currents but reduced excitatory postsynaptic currents in mutant SF1 neurons implicate α2δ-1 in the promotion of excitatory synaptogenesis separate from its canonical role as a calcium channel subunit. Collectively, these findings identify an essential mechanism that regulates VMH neuronal activity and glycemic and lipid control and may be a target for tackling metabolic disease. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

The effect of physical activity on bone turnover in young adults.

PubMed

Franck, H; Beuker, F; Gurk, S

1991-01-01

Physical activity has been suggested as one of the determinants of bone turnover and to prevent the involutional age related bone loss. However, the degree to which physical exercise is necessary to induce changes in bone turnover and calciotropic hormones have been widely discussed (Williams et al., 1984; Cook et al., 1987; Smith et al., 1985). The aim of this study was to examine the rate of bone formation measured by osteocalcin in 56 healthy volunteers before and after 4 and 8 weeks of physical exercise (PE) and its dependence on various parameters of calcium and phosphate metabolism. The studied group consisting of 44 men and 12 women, mean age 24.8 and 24.3 years, respectively, performed a standardized physical training of 8 weeks. Mean serum osteocalcin levels were significantly (p less than 0.01) reduced after 4 weeks (men: 2.26 +/- 1.8 ng/ml; women: 0.94 +/- 1.6 ng/ml) compared to the values before PE (men: 4.01 +/- 2.18 ng/ml; women: 1.69 +/- 1.7 ng/ml) and returned to normal values after 8 weeks. Similarly, magnesium levels (0.82 mmol/l) decreased significantly (p less than 0.01) after 4 weeks of PE (0.79 mmol/l), returning to normal values after 8 weeks. Concomitantly, there was only a slight, but significant fall of serum calcium from 2.48 +/- 0.07 to 2.45 +/- 0.07 returning to initial values again. Furthermore, serum phosphate increased slightly in men from 1.01 mmol/l to 1.13 and 1.15 mmol/l after 4 and 8 weeks, respectively. In contrast, alkaline phosphatase and serum creatinine remained in the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypomagnesaemia and hypocalcaemia in a patient with ovarian carcinoma.

PubMed Central

Leese, G. P.; Jung, R. T.; Browning, M. C.

1993-01-01

A patient with disseminated ovarian carcinoma presented with symptoms of hypocalcaemia secondary to hypomagnesaemia. The low serum magnesium (0.4 mmol/l) appeared to be due to renal leakage with no evidence of ureteric obstruction or hydronephrosis on intravenous urogram. Parathyroid hormone activity (serum levels and cAMP response) was normal, despite hypomagnesaemia. The patient's complaints resolved after magnesium and calcium supplementation. Hypomagnesaemia of malignancy is a rare but important complication, and is both poorly recognized and understood. PMID:8415350

Seasonal patterns of nitrogen, phosphorus, potassium, calcium and magnesium in the leaves of the Massachusetts cranberry. [Vaccinium macrocarpon

DOE Office of Scientific and Technical Information (OSTI.GOV)

DeMoranville, C.J.; Deubert, K.H.

1986-01-01

Leaf samples from cranberry plants in Wareham, MA, were collected during the 1980-82 growing seasons and analyzed for N, P, K, Ca and Mg. The seasonal patterns which emerged allowed the proposal of normal ranges for the elements and optimum times for sampling. The foliar nutrient levels obtained were compared to those for cranberries grown in other areas as well as to those for crops which are grown under similar conditions.

The Endogenous Calcium Ions of Horseradish Peroxidase C Are Required to Maintain the Functional Nonplanarity of the Heme

PubMed Central

Laberge, Monique; Huang, Qing; Schweitzer-Stenner, Reinhard; Fidy, Judit

2003-01-01

Horseradish peroxidase C (HRPC) binds 2 mol calcium per mol of enzyme with binding sites located distal and proximal to the heme group. The effect of calcium depletion on the conformation of the heme was investigated by combining polarized resonance Raman dispersion spectroscopy with normal coordinate structural decomposition analysis of the hemes extracted from models of Ca2+-bound and Ca2+-depleted HRPC generated and equilibrated using molecular dynamics simulations. Results show that calcium removal causes reorientation of heme pocket residues. We propose that these rearrangements significantly affect both the in-plane and out-of-plane deformations of the heme. Analysis of the experimental depolarization ratios are clearly consistent with increased B1g- and B2g-type distortions in the Ca2+-depleted species while the normal coordinate structural decomposition results are indicative of increased planarity for the heme of Ca2+-depleted HRPC and of significant changes in the relative contributions of three of the six lowest frequency deformations. Most noteworthy is the decrease of the strong saddling deformation that is typical of all peroxidases, and an increase in ruffling. Our results confirm previous work proposing that calcium is required to maintain the structural integrity of the heme in that we show that the preferred geometry for catalysis is lost upon calcium depletion. PMID:12668462

Dwarfism in Alaskan malamutes: a disease resembling metaphyseal dysplasia in human beings.

PubMed Central

Sande, R. D.; Alexander, J. E.; Spencer, G. R.; Padgett, G. A.; Davis, W. C.

1982-01-01

In a study of 300 Alaskan Malamutes, dwarfism was shown to be an autosomal recessive inherited disease with complete penetrance that resulted in disturbed endochondral bone formation. Osseous growth disturbance was manifest at the metaphyses of tubular bones. Clinical and radiographic changes were very similar to those of rickets, although appositional bone formation rates were normal. Serum calcium, phosphorus, and alkaline phosphatase were within normal limits. Urinary excretion of calcium, phosphate, and amino acids were normal. Excess matrix was formed in the zone of cartilage cell proliferation, and the matrix persisted in the growth plate. Normal stresses resulted in microfractures in the metaphyses with subsequent interference of vascular penetration into the zone of degenerated cartilage cells. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:7065114

Intronic deletions in the SLC34A3 gene: A cautionary tale for mutation analysis of hereditary hypophosphatemic rickets with hypercalciuria

PubMed Central

Ichikawa, Shoji; Tuchman, Shamir; Padgett, Leah R.; Gray, Amie K.; Baluarte, H. Jorge; Econs, Michael J.

2013-01-01

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare metabolic disorder, characterized by hypophosphatemia, variable degrees of rickets/osteomalacia, and hypercalciuria secondary to increased serum 1,25-dihydroxyvitamin D [1,25(OH)2D] levels. HHRH is caused by mutations in the SLC34A3 gene, which encodes sodium-phosphate co-transporter type IIc. A 6 ½-year-old female presented with a history of nephrolithiasis. Her metabolic evaluation revealed increased 24- hour urine calcium excretion with high serum calcium, low intact parathyroid hormone (PTH) levels, and elevated 1,25(OH)2D level. In addition, the patient had low to low-normal serum phosphorus with high urine phosphorus. The patient had normal stature; without rachitic or boney deformities or a history of fractures. Genetic analysis of SLC34A3 revealed the patient to be a compound heterozygote for a novel single base pair deletion in exon 12 (c.1304delG) and 30-base pair deletion in intron 6 (g.1440–1469del). The single-base pair mutation causes a frameshift, which results in premature stop codon. The intronic deletion is likely caused by misalignment of the 4-basepair homologous repeats and results in the truncation of an already small intron to 63 bp, which would impair proper RNA splicing of the intron. This is the fourth unique intronic deletion identified in patients with HHRH, suggesting the frequent occurrence of sequence misalignments in SLC34A3 and the importance of screening introns in patients with HHRH. PMID:24176905

Effect of ethanolic fruit extract of Cucumis trigonus Roxb. on antioxidants and lipid peroxidation in urolithiasis induced wistar albino rats

PubMed Central

Balakrishnan, A.; Kokilavani, R; Gurusamy, K.; Teepa, K. S. Ananta; Sathya, M.

2011-01-01

Urolithiasis was induced using ethylene glycol in wistar albino rats, the formation of calcium stones in the kidney results with the damage of antioxidant system. Ethanolic extract of Cucumis trigonus Roxb fruit of family Curcurbitaceae was used to treat urolithiasis. On this course, the extract also repairs the changes that happened in the enzymatic, non enzymatic antioxidants and lipid peroxidation in liver and kidney of urolithiasis induced rats. The results obtained from the analysis were compared at 5% level of significance using one way ANOVA. The results show that the ethanolic fruit extract has repaired the levels of antioxidants and malondialdehyde to their normal levels. PMID:22736884

[Osteopenia of prematurity--prophylaxis, diagnostics and treatment].

PubMed

Hitrova, St; Slancheva, B; Popivanova, A; Vakrilova, L; Pramatarova, T; Emilova, Z; Yarakova, N

2012-01-01

Osteopenia of prematurity is a metabolic bone disease of premature infants with birth weight < 1500 g and gestational age < 32 weeks. Sub-optimal bone matrix, poor skeletal support and an increased risk of fractures characterized the disease. Its importance is determined by relatively high frequency--between 30-70% of infants at risk, multifactorial etiology and impact on early and late morbidity of the newborns. The prevention and treatment of bone disorders are important aspects of the care of preterm babies. To identify of the risk factors, to determine early diagnostic criteria and to create a prevention program for osteopenia in infants with very low and extremely low birth weight. The prospective study includes 39 preterm babies with birth weight below 1500 gr. and < 32 g. w who were admitted to the NICU from September 2011-January 2012. Bone metabolism was monitored by calcium, phosphate and alkaline phosphatise at 2-weeks intervals. Vitamin D levels of the neonates were registered at birth, and at 8th week. PTH was measured at the second and the 8th weeks. The following biochemical abnormalities were found. Hypophosphatemia in two weeks (P < 1,6 mmol/l), a gradual increase in phosphorus levels and normalization at eight weeks of age. There was a significant positive correlation between 25OHD/phosphorus at eight weeks/r = 0.353/. Significantly elevated levels of parathyroid hormone in eight weeks, correlating with low levels of vitamin D (negative correlation between 25OHD/parathormone r = -0.581). Blood levels of calcium and alkaline phosphatase were in normal limits. Risk factors for osteopenia are: the low gestational age and low levels of vitamin D at birth. Biochemical markers of osteopenia are: changes in levels of parathyroid hormone, phosphorus and vitamin D at eight weeks of age. Prevention includes: early supplementation of vitamin D in the risk neonates with individual dose adjustment. Upon biochemical evidence of osteopenia treatment should begin in the second week of life with supplementation of phosphorus, and vitamin D 1320 IU/daily and appropriate physiotherapy.

Serum magnesium and calcium levels in infertile women during a cycle of reproductive assistance.

PubMed

Grossi, Elena; Castiglioni, Sara; Moscheni, Claudia; Antonazzo, Patrizio; Cetin, Irene; Savasi, Valeria Maria

2017-05-01

Magnesium (Mg) and calcium (Ca) are essential cations for women's preconception health. It is well known that, in blood, the concentration of ionized form of these two cations is temporally altered during menstrual cycle, suggesting a correlation between sex steroid hormones and serum calcium and magnesium levels. Evidence from literature suggests that in assisted reproductive technology increasing estrogens during ovarian hyperstimulation may also modulate serum magnesium and calcium levels. Therefore, we first examined total serum magnesium and calcium levels during follicular phase in a large population of infertile patients who underwent intrauterine insemination (IUI). The results were compared to a group of fertile women. Successively, we studied the total serum magnesium and calcium concentrations in infertile patients before and after ovarian hyperstimulation for in vitro fertilization (IVF). Results highlight that total serum concentration of magnesium and calcium does not seem altered in infertile women. During stimulation with gonadotropins, the values of the two cations do not change significantly in ovarian-stimulated women. However, we found a downward trend in the total magnesium and calcium levels in relation to the rising estrogens.

Effect of zinc supplementation on the status of thyroid hormones and Na, K, And Ca levels in blood following ethanol feeding.

PubMed

Pathak, R; Dhawan, D; Pathak, A

2011-05-01

The influence of zinc (Zn) on the serum levels of triiodothyronine (T(3)), thyroxine (T(4)), thyroid-stimulating hormone (TSH) and sodium (Na), potassium (K), and calcium (Ca) was evaluated following ethanol toxicity to the rats. To achieve this, male Wistar rats (150-195 g) were given 3 ml of 30% ethanol orally, and zinc was given in the form of zinc sulfate (227 mg/l) in their drinking water daily for 8 weeks. Ethanol feeding resulted in a slight decrease in T(3) and T(4) levels and a significant increase in thyroid-stimulating hormone concentration, which may be due to the direct stimulatory effect of ethanol on thyroid. Interestingly, when zinc was given to these rats, all the above levels were brought quite close to their normal levels, thus indicating the positive role of zinc in thyroid hormone metabolism. Serum Zn and Ca levels were found to be reduced, but Na levels were raised upon ethanol feeding. Restoration of normal levels of these metals upon zinc supplementation to ethanol fed rats confirms that zinc has potential in alleviating some of the altered thyroid functions following ethanol administration.

Association of calcium sensing receptor polymorphisms at rs1801725 with circulating calcium in breast cancer patients.

PubMed

Wang, Li; Widatalla, Sarrah E; Whalen, Diva S; Ochieng, Josiah; Sakwe, Amos M

2017-08-02

Breast cancer (BC) patients with late-stage and/or rapidly growing tumors are prone to develop high serum calcium levels which have been shown to be associated with larger and aggressive breast tumors in post and premenopausal women respectively. Given the pivotal role of the calcium sensing receptor (CaSR) in calcium homeostasis, we evaluated whether polymorphisms of the CASR gene at rs1801725 and rs1801726 SNPs in exon 7, are associated with circulating calcium levels in African American and Caucasian control subjects and BC cases. In this retrospective case-control study, we assessed the mean circulating calcium levels, the distribution of two inactivating CaSR SNPs at rs1801725 and rs1801726 in 199 cases and 384 age-matched controls, and used multivariable regression analysis to determine whether these SNPs are associated with circulating calcium in control subjects and BC cases. We found that the mean circulating calcium levels in African American subjects were higher than those in Caucasian subjects (p < 0.001). As expected, the mean calcium levels were higher in BC cases compared to control subjects (p < 0.001), but the calcium levels in BC patients were independent of race. We also show that in BC cases and control subjects, the major alleles at rs1801725 (G/T, A986S) and at rs1801726 (C/G, Q1011E) were common among Caucasians and African Americans respectively. Compared to the wild type alleles, polymorphisms at the rs1801725 SNP were associated with higher calcium levels (p = 0.006) while those at rs1801726 were not. Using multivariable linear mixed-effects models and adjusting for age and race, we show that circulating calcium levels in BC cases were associated with tumor grade (p = 0.009), clinical stage (p = 0.003) and more importantly, with inactivating mutations of the CASR at the rs1801725 SNP (p = 0.038). These data suggest that decreased sensitivity of the CaSR to calcium due to inactivating polymorphisms at rs1801725, may predispose up to 20% of BC cases to high circulating calcium-associated larger and/or aggressive breast tumors.

Iron promotes protein insolubility and aging in C. elegans.

PubMed

Klang, Ida M; Schilling, Birgit; Sorensen, Dylan J; Sahu, Alexandria K; Kapahi, Pankaj; Andersen, Julie K; Swoboda, Peter; Killilea, David W; Gibson, Bradford W; Lithgow, Gordon J

2014-11-01

Many late-onset proteotoxic diseases are accompanied by a disruption in homeostasis of metals (metallostasis) including iron, copper and zinc. Although aging is the most prominent risk factor for these disorders, the impact of aging on metallostasis and its role in proteotoxic disease remain poorly understood. Moreover, it is not clear whether a loss of metallostasis influences normal aging. We have investigated the role of metallostasis in longevity ofCaenorhabditis elegans. We found that calcium, copper, iron, and manganese levels increase as a function of age, while potassium and phosphorus levels tend to decrease. Increased dietary iron significantly accelerated the age-related accumulation of insoluble protein, a molecular pathology of aging. Proteomic analysis revealed widespread effects of dietary iron in multiple organelles and tissues. Pharmacological interventions to block accumulation of specific metals attenuated many models of proteotoxicity and extended normal lifespan. Collectively, these results suggest that a loss of metallostasis with aging contributes to age-related protein aggregation.

Quadriplegia due to lead-contaminated opium--case report.

PubMed

Beigmohammadi, Mohammad Taghi; Aghdashi, Moosa; Najafi, Atabak; Mojtahedzadeh, Mojtaba; Karvandian, Kassra

2008-10-01

Utilization of lead-contaminated opium may lead to severe motor neuron impairment and quadriplegia. Forty years oriented old male, opium addict, was admitted to the ICU, with headache, nausea and abdominal pain, and weakness in his lower and upper extremities without definitive diagnosis. The past medical and occupational history was negative. Laboratory investigation showed; anemia (Hb 7.7 g/dl), slightly elevated liver function tests, elevated total bilirubin, and ESR. Abdominal sonography and brain CT scan were normal. EMG and NCV results and neurologic examination were suggestive for Guillain-Barre. He underwent five sessions of plasmapheresis. Blood lead level was > 200 microg/dl. He received dimercaprol (BAL) and calcium disodium edetate (CaEDTA) for two five days session. Upon discharge from ICU all laboratory tests were normal and blood lead level was reduced, but he was quadriplegic. The delayed treatment of lead poisoning may lead to irreversible motor neuron defect.

Current concepts regarding calcium metabolism and bone health in sarcoidosis.

PubMed

Baughman, Robert P; Papanikolaou, Ilias

2017-09-01

Vitamin D supplementation is widespread used in the general population. In sarcoidosis, up to 50% of patients, especially postmenopausal women and those taking corticosteroids, show evidence of increased bone fragility. The purpose of this review is to provide an evidence-based rationale on how to treat sarcoidosis patients with bone health issues. Evidence from observational studies show that decreased 25-hydroxy vitamin D is common in sarcoidosis. However, the great majority of sarcoidosis patents have normal or often elevated levels of 1,25-dihydroxy vitamin D (calcitriol), a marker associated with disease activity. High calcitriol levels may often be associated with hypercalcemia and hypercalcuria. The few interventional randomized controlled studies in the field, suggest that vitamin D supplementation may not be well tolerated because of hypercalcemia, moreover without substantial benefit on bone health and risk for fractures in these patients. Vitamin D supplementation may be withheld in sarcoidosis patients with bone fragility, unless calcitriol levels are below normal limits. A treating scheme is proposed.

Effect of supplemental vitamin D and calcium on serum sclerostin levels.

PubMed

Dawson-Hughes, Bess; Harris, Susan S; Ceglia, Lisa; Palermo, Nancy J

2014-04-01

Serum sclerostin levels have been reported to be inversely associated with serum 25OHD levels, but the effect of vitamin D and calcium supplementation on serum sclerostin levels is unknown. This study was carried out to determine whether vitamin D and calcium supplementation altered serum sclerostin levels in healthy older adults. We measured serum sclerostin levels at baseline and after 2 years in 279 men and women who participated in a placebo-controlled vitamin D (700 IU/day) and calcium (500 mg/day) intervention trial carried out in men and women aged ≥65 years. Serum sclerostin levels were measured using the MesoScale Discovery chemiluminescence assay. In the men, sclerostin levels increased over 2 years by 4.11±1.81 ng/l (13.1%) in the vitamin D plus calcium-supplemented group and decreased by 3.16±1.78 ng/l (10.9%) in the placebo group (P=0.005 for difference in change). Adjustments for the season of measurement, baseline physical activity levels, baseline serum sclerostin levels, and total body bone mineral content did not substantially alter the changes. In the women, there was no significant group difference in change in serum sclerostin levels either before or after the above-mentioned adjustments. In both the sexes, vitamin D and calcium supplementation significantly increased serum ionized calcium levels and decreased parathyroid hormone levels. Men and women appear to have different serum sclerostin responses to vitamin D and calcium supplementation. The reason for this difference remains to be determined.

Malnutrition-inflammation-coronary calcification in pediatric patients receiving chronic hemodialysis.

PubMed

Srivaths, Poyyapakkam R; Silverstein, Douglas M; Leung, Jocelyn; Krishnamurthy, Rajesh; Goldstein, Stuart L

2010-07-01

Malnutrition, inflammation, and renal osteodystrophy parameters with resultant coronary calcification (CC) are associated with increased cardiovascular mortality in adults. Previous pediatric studies demonstrated CC in children but none assessed for an association between inflammation, malnutrition, renal osteodystrophy, and CC. To assess CC, ultrafast computerized tomogram was obtained for 16 pediatric patients (6 females; median age 17.2 years; range 9.1-21.2 years) receiving hemodialysis for >/=2 months. Inflammation was assessed by serum IL-6, IL-8, and C-reactive protein levels on the day of the computerized tomogram scan; nutrition parameters included serum albumin, cholesterol, the body mass index standard deviation score, and normalized protein catabolic rate. Renal osteodystrophy parameters included time-averaged serum calcium, phosphorus, total PTH, and calcitriol/calcium dose. Patients received hemodialysis thrice-weekly; mean single pool Kt/V 1.48+/-0.13; and mean normalized protein catabolic rate 1.27+/-0.17 g/kg/day. Five of 16 patients had CC. Patients with CC were older (19.1+/-2.1 vs. 15.4+/-3.1 months; P=0.03), had longer dialysis vintage (49.4+/-15.3 vs. 17.2+/-10.5 months, P=0.0002), lower serum cholesterol (122+/-17.7 vs. 160.4+/-10.6 mg/dL, P=0.02), and higher phosphorus (9.05+/-1.2 vs. 6.1+/-0.96 mg/dL, P=0.0001). Mean serum albumin and normalized protein catabolic rate did not differ for patients with CC. All patients had elevated IL-6 and IL-8 levels compared with healthy norms; the mean IL-6, IL-8, and C-reactive protein levels were not different in patients with CC. Coronary calcification was prevalent in older children receiving maintenance hemodialysis with a longer dialysis vintage. Worse renal osteodystrophy control and malnutrition (low cholesterol) may contribute to CC development.

Metabolic responses to high protein diet in Korean elite bodybuilders with high-intensity resistance exercise.

PubMed

Kim, Hyerang; Lee, Saningun; Choue, Ryowon

2011-07-04

High protein diet has been known to cause metabolic acidosis, which is manifested by increased urinary excretion of nitrogen and calcium. Bodybuilders habitually consumed excessive dietary protein over the amounts recommended for them to promote muscle mass accretion. This study investigated the metabolic response to high protein consumption in the elite bodybuilders. Eight elite Korean bodybuilders within the age from 18 to 25, mean age 21.5 ± 2.6. For data collection, anthropometry, blood and urinary analysis, and dietary assessment were conducted. They consumed large amounts of protein (4.3 ± 1.2 g/kg BW/day) and calories (5,621.7 ± 1,354.7 kcal/day), as well as more than the recommended amounts of vitamins and minerals, including potassium and calcium. Serum creatinine (1.3 ± 0.1 mg/dl) and potassium (5.9 ± 0.8 mmol/L), and urinary urea nitrogen (24.7 ± 9.5 mg/dl) and creatinine (2.3 ± 0.7 mg/dl) were observed to be higher than the normal reference ranges. Urinary calcium (0.3 ± 0.1 mg/dl), and phosphorus (1.3 ± 0.4 mg/dl) were on the border of upper limit of the reference range and the urine pH was in normal range. Increased urinary excretion of urea nitrogen and creatinine might be due to the high rates of protein metabolism that follow high protein intake and muscle turnover. The obvious evidence of metabolic acidosis in response to high protein diet in the subjects with high potassium intake and intensive resistance exercise were not shown in this study results. However, this study implied that resistance exercise with adequate mineral supplementation, such as potassium and calcium, could reduce or offset the negative effects of protein-generated metabolic changes. This study provides preliminary information of metabolic response to high protein intake in bodybuilders who engaged in high-intensity resistance exercise. Further studies will be needed to determine the effects of the intensity of exercise and the level of mineral intakes, especially potassium and calcium, which have a role to maintain acid-base homeostasis, on protein metabolism in large population of bodybuilders.

Natural radioactivity in geothermal waters, Alhambra Hot Springs and nearby areas, Jefferson County, Montana

USGS Publications Warehouse

Leonard, Robert B.; Janzer, Victor J.

1978-01-01

Radioactive hot springs issue from a fault zone in crystalline rock of the Boulder batholith at Alhambra, Jefferson County, in southwestern Montana. The discharge contains high concentrations of radon, and the gross alpha activity and the concentration of adium-226 exceed maximum levels recommended by the Environmental Protection Agency for drinking water. Part of the discharge is diverted for space heating, bathing, and domestic use. The radioactive thermal waters at measured temperatures of about 60°C are of the sodium bicarbonate type and saturated with respect to calcium carbonate. Radium-226 in the rock and on fractured surfaces or coprecipitated with calcium carbonate probably is the principal source of radon that is dissolved in the thermal water and discharged with other gases from some wells and springs. Local surface water and shallow ground water are of the calcium bicarbonate type and exhibit low background activity. The temperature, percent sodium, and radioactivity of mixed waters adjacent to the fault zone increase with depth. Samples from most of the major hot springs in southwestern Montana have been analyzed for gross alpha and beta activity. The high level of radioactivity at Alhambra appears to be related to leaching of radioactive material from siliceous veins by ascending thermal waters and is not a normal characteristic of hot springs issuing from fractured crystalline rock in Montana.

Structural changes of casein micelles in a calcium gradient film.

PubMed

Gebhardt, Ronald; Burghammer, Manfred; Riekel, Christian; Roth, Stephan Volkher; Müller-Buschbaum, Peter

2008-04-09

Calcium gradients are prepared by sequentially filling a micropipette with casein solutions of varying calcium concentration and spreading them on glass slides. The casein film is formed by a solution casting process, which results in a macroscopically rough surface. Microbeam grazing incidence small-angle X-ray scattering (microGISAXS) is used to investigate the lateral size distribution of three main components in casein films: casein micelles, casein mini-micelles, and micellar calcium phosphate. At length scales within the beam size the film surface is flat and detection of size distribution in a macroscopic casein gradient becomes accessible. The model used to analyze the data is based on a set of three log-normal distributed particle sizes. Increasing calcium concentration causes a decrease in casein micelle diameter while the size of casein mini-micelles increases and micellar calcium phosphate particles remain unchanged.

Calcium distribution in Amoeba proteus

PubMed Central

1979-01-01

A preliminary investigation of the distribution of cellular calcium in Amoeba proteus was undertaken. Total cellular calcium under control conditions was found to be 4.59 mmol/kg of cells. When the external Ca++ concentration is increased from the control level of 0.03 to 20 mM, a net Ca++ influx results with a new steady-state cellular calcium level being achieved in integral of 3 h. At steady state the amount of calcium per unit weight of cells is higher than the amount of calcium per unit weight of external solution when the external concentration of Ca++ is below 10 mM. At external Ca++ concentrations above this level, total cellular calcium approaches the medium level of Ca++. Steady- state calcium exchange in Amoeba proteus was determined with 45Ca. There is an immediate and rapid exchange of integral of 0.84 mmol/kg of cells or 18% of the total cellular calcium with the labelled Ca++. Following this initial exchange, there was very little if any further exchange observed. Most of this exchanged calcium could be eliminated from the cell with 1 mM La+++, suggesting that the exchanged calcium is associated with the surface of the cell. Increase in either the external Ca++ concentration of pH raise the amount of exchangeable calcium associated with the cell. Calcium may be associated with the cell surface as a co-ion in the diffuse double layer or bound to fixed negative sites on the surface of the cell. If Ca++-binding sites do exist on the cell surface, there may be more than one type and they may have different dissociation constants. The cytoplasmic Ca++ ion activity is probably maintained at very low levels. PMID:512628

NCKX3 was compensated by calcium transporting genes and bone resorption in a NCKX3 KO mouse model.

PubMed

Yang, Hyun; Ahn, Changhwan; Shin, Eun-Kyeong; Lee, Ji-Sun; An, Beum-Soo; Jeung, Eui-Bae

2017-10-15

Gene knockout is the most powerful tool for determination of gene function or permanent modification of the phenotypic characteristics of an animal. Existing methods for gene disruption are limited by their efficiency, time required for completion and potential for confounding off-target effects. In this study, a rapid single-step approach to knockout of a targeted gene in mice using zinc-finger nucleases (ZFNs) was demonstrated for generation of mutant (knockout; KO) alleles. Specifically, ZFNs to target the sodium/calcium/potassium exchanger3 (NCKX3) gene in C57bl/6j were designed using the concept of this approach. NCKX3 KO mice were generated and the phenotypic characterization and molecular regulation of active calcium transporting genes was assessed when mice were fed different calcium diets during growth. General phenotypes such as body weight and plasma ion level showed no distinct abnormalities. Thus, the potassium/sodium/calcium exchanger of NCKX3 KO mice proceeded normally in this study. As a result, the compensatory molecular regulation of this mechanism was elucidated. Renal TRPV5 mRNA of NCKX3 KO mice increased in both male and female mice. Expression of TRPV6 mRNA was only down-regulated in the duodenum of male KO mice. Renal- and duodenal expression of PTHR and VDR were not changed; however, GR mRNA expression was increased in the kidney of NCKX3 KO mice. Depletion of the NCKX3 gene in a KO mouse model showed loss of bone mineral contents and increased plasma parathyroid hormone, suggesting that NCKX3 may play a role in regulating calcium homeostasis. Copyright © 2017 Elsevier B.V. All rights reserved.

Calcium Orthophosphates in Nature, Biology and Medicine

PubMed Central

Dorozhkin, Sergey V.

2009-01-01

The present overview is intended to point the readers’ attention to the important subject of calcium orthophosphates. These materials are of the special significance because they represent the inorganic part of major normal (bones, teeth and dear antlers) and pathological (i.e. those appearing due to various diseases) calcified tissues of mammals. Due to a great chemical similarity with the biological calcified tissues, many calcium orthophosphates possess remarkable biocompatibility and bioactivity. Materials scientists use this property extensively to construct artificial bone grafts that are either entirely made of or only surface-coated with the biologically relevant calcium ortho-phosphates. For example, self-setting hydraulic cements made of calcium orthophosphates are helpful in bone repair, while titanium substitutes covered by a surface layer of calcium orthophosphates are used for hip joint endoprostheses and as tooth substitutes. Porous scaffolds made of calcium orthophosphates are very promising tools for tissue engineering applications. In addition, technical grade calcium orthophosphates are very popular mineral fertilizers. Thus ere calcium orthophosphates are of great significance for humankind and, in this paper, an overview on the current knowledge on this subject is provided.

A Multidisciplinary Evaluation of the Effectiveness of Cyclosporine A in Dystrophic Mdx Mice

PubMed Central

De Luca, Annamaria; Nico, Beatrice; Liantonio, Antonella; Paola Didonna, Maria; Fraysse, Bodvael; Pierno, Sabata; Burdi, Rosa; Mangieri, Domenica; Rolland, Jean-François; Camerino, Claudia; Zallone, Alberta; Confalonieri, Paolo; Andreetta, Francesca; Arnoldi, Elisa; Courdier-Fruh, Isabelle; Magyar, Josef P.; Frigeri, Antonio; Pisoni, Michela; Svelto, Maria; Conte-Camerino, Diana

2005-01-01

Chronic inflammation is a secondary reaction of Duchenne muscular dystrophy and may contribute to disease progression. To examine whether immunosuppressant therapies could benefit dystrophic patients, we analyzed the effects of cyclosporine A (CsA) on a dystrophic mouse model. Mdx mice were treated with 10 mg/kg of CsA for 4 to 8 weeks throughout a period of exercise on treadmill, a protocol that worsens the dystrophic condition. The CsA treatment fully prevented the 60% drop of forelimb strength induced by exercise. A significant amelioration (P < 0.05) was observed in histological profile of CsA-treated gastrocnemius muscle with reductions of nonmuscle area (20%), centronucleated fibers (12%), and degenerating area (50%) compared to untreated exercised mdx mice. Consequently, the percentage of normal fibers increased from 26 to 35% in CsA-treated mice. Decreases in creatine kinase and markers of fibrosis were also observed. By electrophysiological recordings ex vivo, we found that CsA counteracted the decrease in chloride conductance (gCl), a functional index of degeneration in diaphragm and extensor digitorum longus muscle fibers. However, electrophysiology and fura-2 calcium imaging did not show any amelioration of calcium homeostasis in extensor digitorum longus muscle fibers. No significant effect was observed on utrophin levels in diaphragm muscle. Our data show that the CsA treatment significantly normalized many functional, histological, and biochemical endpoints by acting on events that are independent or downstream of calcium homeostasis. The beneficial effect of CsA may involve different targets, reinforcing the usefulness of immunosuppressant drugs in muscular dystrophy. PMID:15681831

Presence of a deletion mutation (c.716delA) in the ligand binding domain of the vitamin D receptor in an Indian patient with vitamin D-dependent rickets type II.

PubMed

Kanakamani, Jeyaraman; Tomar, Neeraj; Kaushal, Esha; Tandon, Nikhil; Goswami, Ravinder

2010-01-01

Vitamin D-dependent rickets type II (VDDR-type II) is a rare disorder caused by mutations in the vitamin D receptor (VDR) gene. Here, we describe a patient with VDDR-type II with severe alopecia and rickets. She had hypocalcemia, hypophosphatemia, secondary hyperparathyroidism, and elevated serum alkaline phosphatase and 1,25-dihydroxyvitamin D(3). Sequence analysis of the lymphocyte VDR cDNA revealed deletion mutation c.716delA. Sequence analysis of her genomic DNA fragment amplified from exon 6 of the VDR gene incorporating this mutation confirmed the presence of the mutation in homozygous form. This frameshift mutation in the ligand binding domain (LBD) resulted in premature termination (p.Lys240Argfs) of the VDR protein. The mutant protein contained 246 amino acids, with 239 normal amino acids at the N terminus, followed by seven changed amino acids resulting in complete loss of its LBD. The mutant VDR protein showed evidence of 50% reduced binding with VDR response elements on electrophoretic mobility assay in comparison to the wild-type VDR protein. She was treated with high-dose calcium infusion and oral phosphate. After 18 months of treatment, she gained 6 cm of height, serum calcium and phosphorus improved, alkaline phosphatase levels decreased, and intact PTH normalized. Radiologically, there were signs of healing of rickets. Her parents and one of her siblings had the same c.716delA mutation in heterozygous form. Despite the complete absence of LBD, the rickets showed signs of healing with intravenous calcium.

Densitometric and biochemical values of broiler tibias at different ages.

PubMed

Barreiro, F R; Sagula, A L; Junqueira, O M; Pereira, G T; Baraldi-Artoni, S M

2009-12-01

The objective of this experiment was to determine the normal values of bone radiographic density (BRD) by using the optical densitometry in radiographic images and the biochemical values represented by serum calcium, ash percentage, and minerals (calcium, phosphorus, and magnesium) from tibia ash of Cobb broilers at 8, 22, and 43 d of age. A total of 14 broilers were used for densitometric analysis, and 15 were used for biochemical dosages. The BRD values increased (P < 0.05) with age and in all tibia regions (proximal epiphysis, diaphysis, and distal epiphysis), concluding that growth was a determinative factor for bone performance, demanding a higher BRD during broiler development. Tibia proximal epiphysis presented higher BRD values in relation to the other bone regions (P < 0.05), as a result of a possible biomechanical adaptation to ligaments and tension of the muscle tendons at this region, allowing the support of the muscle mass increase. The serum calcium values were kept constant, as a result of the appropriate nutritional levels of the diet that supported the animal homeostasis. The bone ash and mineral percentage increased (P < 0.05) at 22 d of age, due to the higher mineral requirement in this age. The correlation between bone densitometry and the invasive techniques showed that the bone densitometry can substitute the determination of mineral percentage in the ash. This experiment presented normal values of the noninvasive and invasive methods more used in aviculture, allowing us to compare, subsequently, pathological and physiological values or results of broilers fed with different diets.

Protective effect of protopine on the focal cerebral ischaemic injury in rats.

PubMed

Xiao, Xianghua; Liu, Juntian; Hu, Jingwen; Li, Tianxia; Zhang, Yuanhui

2007-08-01

Protopine, an isoquinoline alkaloidis, is known to produce many effects such as vasodilation, down-regulation of glutamate levels in brain and decrease of intracellular calcium. However, so far there is no report on the effect of protopine in cerebral ischaemia. In this study, the effect of protopine on the focal cerebral ischaemia was investigated in rats. Male Sprague-Dawley rats were divided into five groups: sham-operated group, vehicle-treated group and three doses of protopine-treated groups (0.98, 1.96 and 3.92 mg/kg). Protopine was intraperitoneally administered to rats once daily for 3 days prior to the ischaemia and 0.9% normal saline to rats in the vehicle-treated group in the same pattern. Rats in the sham-operated group were given 0.9% normal saline without the ischaemia. The focal cerebral ischaemia was induced by the middle cerebral artery occlusion for 24 hr via the intraluminal filament technique. The results showed that pre-treatment with protopine reduced the cerebral infarction ratio and serum lactate dehydrogenase activity, and improved the ischaemia-induced neurological deficit score and histological changes of brain in a dose-dependent manner. The further studies demonstrated that protopine increased superoxide dismutase activity in serum, and decreased total calcium and terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL)-positive cells in the ischaemic brain tissue in the middle cerebral artery occlusion rats. The results indicate that protopine is able to produce an effective protection on the injury caused by the focal cerebral ischaemia in rats possibly through the multiple effects of calcium antagonism, antioxidation and depression of cell apoptosis.

Bilirubin induces a calcium-dependent inhibition of multifunctional Ca2+/calmodulin-dependent kinase II activity in vitro.

PubMed

Churn, S B; DeLorenzo, R J; Shapiro, S M

1995-12-01

Excessive bilirubin levels in newborn infants result in long-term neurologic deficits that remain after bilirubin levels return to normal. Much of the observed neurologic deficits can be attributed to bilirubin-induced, delayed neuronal cell death. Inhibition of calcium/calmodulin-dependent kinase II (CaM kinase II) activity that precedes cell death is observed in conditions such as seizure activity, stroke, and glutamate excitotoxicity. Because neonatal bilirubin exposure results in neuronal loss in developing brain systems, we tested whether bilirubin exposure would induce an immediate inhibition of CaM activity, in vitro. P-81 filtration assay of basal and calcium-stimulated kinase activity was performed under standard kinase assay conditions. Bilirubin and/or albumin was added to the reaction vessels to determine the effect of these agents on kinase activity. Bilirubin exposure resulted in a concentration-dependent inhibition of CaM kinase II activity (IC50 = 16.78 microM). At concentrations above 50 microM, bilirubin exposure resulted in a 71 +/- 8% (mean +/- SD) inhibition of kinase activity (p < 0.001, t test, n = 10). Bilirubin exposure did not result in kinase inhibition if excessive bilirubin was removed by albumin binding before stimulation of kinase activity (106.9 +/- 9.6% control activity, n = 5). However, removal of bilirubin by binding with albumin after calcium addition did not restore kinase activity. (36.1 +/- 3.8% control activity, n = 5). Thus, once inhibition was observed, the activity could not be restored by addition of albumin. The data suggest that bilirubin exposure resulted in a calcium-dependent inhibition of CaM kinase II activity that, once induced, was not reversible by removing bilirubin by the addition of albumin. Because inhibition of CaM kinase II activity has been correlated with delayed neuronal cell death in many neuropathologic conditions, bilirubin-induced inhibition of this enzyme may be a cellular mechanism by which bilirubin exposure results in delayed neuronal cell death in developing brain.

Bioelements in hair of children with selected neurological disorders.

PubMed

Józefczuk, Jan; Kasprzycka, Wiktoria; Czarnecki, Rafał; Graczyk, Alfreda; Józefczuk, Paweł; Krzysztof, Magda; Lampart, Urszula; Mrozowska-Ząbek, Ewa; Surdy, Weronika; Kwiatkowska-Graczyk, Róża

2017-01-01

We have analyzed concentrations of magnesium (Mg), calcium (Ca), copper (Cu), zinc (Zn) and iron (Fe) in hair of a group of 82 children with mental retardation, in which 9 patients suffered from epilepsy, 18 from the Down's syndrome and 55 from cerebral palsy. Girls comprised little over 50% of the patients. In the group of boys with epilepsy, we found Mg, Ca, Cu and Fe deficiency, and normal level of Zn. In the group of girls with epilepsy, apart from low Fe concentration, a high level of Ca, Mg, Zn, and Cu was noted. For girls with the Down's syndrome, a high or normal level of Ca, Mg, Zn and Cu was found, whereas the Fe concentration varied and presented itself in a non-characteristic way. Both groups of children with cerebral palsy, i.e. boys and girls, displayed low Fe concentration in their hair; low Cu level was found in older patients as well. In this group of patients, we also noted high concentrations of Ca, Mg and Zn in girls and normal in boys. A high concentration of Ca in girls with cerebral palsy requires separate analysis. The obtained results could be useful as guidance in the direction and determination of the amount of possible patient nutritional supplementation.

Hypocalcaemia after treatment with [177Lu-DOTA 0,Tyr3]octreotate.

PubMed

van Vliet, Esther I; de Herder, Wouter W; de Rijke, Yolanda B; Zillikens, M Carola; Kam, Boen L R; Teunissen, Jaap J M; Peeters, Robin P; Krenning, Eric P; Kwekkeboom, Dik J

2013-12-01

The aim of this study was to explore the possible mechanisms involved in an observed decline in serum calcium levels in patients with a neuroendocrine tumour (NET) treated with [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-octreotate). In 47 patients with NET who were normocalcaemic at baseline, serum calcium, albumin, creatinine, alkaline phosphatase, gamma glutamyl transpeptidase, magnesium, phosphate and 25-hydroxyvitamin D were prospectively analysed at baseline and up to 6 months after treatment. Parathyroid hormone (PTH), 1,25-dihydroxyvitamin D3, type 1 aminoterminal propeptide of procollagen, bone-specific alkaline phosphatase, carboxyterminal crosslinking telopeptide of bone collagen, collagen type I crosslinked N-telopeptide, and creatinine and calcium in 24-h urine samples, were evaluated at baseline and at 3 and 6 months. Another 153 patients with NET were included in a retrospective study to estimate the occurrence of hypocalcaemia in a larger patient group. In the prospectively included patients, the mean serum calcium level decreased significantly after treatment (2.31 ± 0.01 to 2.26 ± 0.02 mmol/l, p = 0.02). Eight patients (17%) showed a marked decrease in serum calcium levels with a nadir of ≤ 2.10 mmol/l. In five patients (11%), calcium substitution therapy was prescribed. PTH increased significantly (5.9 ± 0.6 to 6.7 ± 0.8 pmol/l, p = 0.02), presumably in response to the decreasing serum calcium levels. 25-Hydroxyvitamin D remained stable after treatment. Creatinine levels increased significantly (73 ± 3 to 77 ± 3 μmol/l, p = 0.01), but not enough to explain the hypocalcaemia. Phosphate levels remained unaffected. In the retrospectively analysed patients, the mean serum calcium level decreased significantly from 2.33 ± 0.01 at baseline to a nadir of 2.24 ± 0.01 mmol/l at 18 months after treatment (p < 0.001). Of the 153 patients, 33 (22%) showed a serum calcium nadir of ≤ 2.10 mmol/l, and 11 (7%) received calcium substitution therapy. The mean serum calcium level decreased significantly after treatment with (177)Lu-octreotate, resulting in mild hypocalcaemia in about 20% of patients. We excluded several potential causes of this hypocalcaemia, so the cause remains unknown. Serum calcium levels should be monitored after peptide receptor radionuclide therapy, and calcium substitution therapy should be initiated if appropriate.

Chemical and physical compatibility of an intravenous solution of epinephrine with calcium chloride.

PubMed

Weeks, Phillip A; Teng, Yang; Wu, Lei; Sun, Mary; Yang, Zhen; Chow, Diana S-L

2014-01-01

An infusion of epinephrine combined with calcium chloride has been used historically as an intravenous inotropic solution to support critically ill heart failure patients with severe cardiogenic shock. There is no reliable data on the stability of this solution beyond three hours. This study was conducted to evaluate the chemical and physical compatibility of epinephrine (0.032 mg/mL) combined with calcium chloride (4 mg/mL) in a solution for intravenous administration up to 26 hours at room temperature. The chemical stability of epinephrine was monitored by measuring epinephrine concentrations using high-performance liquid chromatography. The physical compatibility of the mixture was determined by measuring spectrophotometric absorbance between 400 to 700 nm. Absorbance greater than 0.010 AU was considered an indicator of the presence of precipitation. The results showed epinephrine with calcium chloride was stable together in normal saline up to 26 hours at room temperature, irrespective of exposure to light. The absorbance of epinephrine throughout the study was less than 0.010 AU, indicating no significant precipitation. Conclusions indicate that epinephrine (0.032 mg/mL) combined with calcium chloride (4 mg/mL) in normal saline at room temperature is acceptably stable up to 26 hours for intravenous administration.

Human water, sodium, and calcium regulation during space flight and exercise

NASA Astrophysics Data System (ADS)

Doty, S. E.; Seagrave, R. C.

When one is exposed to microgravity, fluid which is normally pooled in the lower extremities is redistributed headward and weight bearing bones begin to demineralize due to reduced mechanical stresses. The kidney, which is the primary regulator of body fluid volume and composition, responds to the fluid shift and bone demineralization by increasing the urinary output of water, sodium, and calcium. This research involves developing a mathematical description of how water and electrolytes are internally redistributed and exchanged with the environment during space flight. This model consequently involves kidney function and the associated endocrine system. The model agrees well with actual data, including that a low sodium diet can prevent bone demineralization. Therefore, assumptions made to develop the model are most likely valid. Additionally, various levels of activity are also considered in the model since exercise may help to eliminate some of the undesired effects of space flight such as muscle atrophy and bone demineralization.

Human water, sodium, and calcium regulation during space flight and exercise

NASA Astrophysics Data System (ADS)

Doty, S. E.; Seagrave, R. C.

2000-05-01

When one is exposed to microgravity, fluid which is normally pooled in the lower extremities is redistributed headward and weight bearing bones begin to demineralize due to reduced mechanical stresses. The kidney, which is the primary regulator of body fluid volume and composition, responds to the fluid shift and bone demineralization by increasing the urinary output of water, sodium, and calcium. This research involves developing a mathematical description of how water and electrolytes are internally redistributed and exchanged with the environment during space flight. This model consequently involves kidney function and the associated endocrine system. The model agrees well with actual data, including that a low sodium diet can prevent bone demineralization. Therefore, assumptions made to develop the model are most likely valid. Additionally, various levels of activity are also considered in the model since exercise may help to eliminate some of the undesired effects of space flight such as muscle atrophy and bone demineralization.

Resolution of hypercalcemia and acute kidney injury after treatment for pulmonary tuberculosis without the use of corticosteroids.

PubMed

Araujo, Constance A A; Araujo, Nicole A A; Daher, Elizabeth F; Oliveira, José Daniel B; Kubrusly, Marcos; Duarte, Pastora M A; Silva, Sonia L; Araujo, Sonia M H A

2013-03-01

Abstract. Hypercalcemia caused by tuberculosis is rare and it is usually asymptomatic. Tuberculosis (TB) -related hypercalcemia associated with acute kidney injury (AKI) is rarely reported. We report a case of a 22-year-old immunocompetent man with 1-month history of daily fever, asthenia and weight loss. Laboratory findings on admission included serum calcium 14.9 mg/dL, urinary Ca(2+) 569.6 mg/24 hours, low level of parathyroid hormone, serum creatinine = 2.2 mg/dL and sodium fractional excretion (FeNa) 2.73%. The result of the tuberculin skin test was 17 mm. A chest X-ray revealed micronodular pulmonary infiltrate in the apex of the right lung, which was confirmed by computed tomography scan. The patient was diagnosed with hypercalcemia associated with pulmonary TB and AKI. A general improvement of the hypercalcemia and renal function was observed in the first 2 weeks after effective hydration and treatment of TB without corticosteroids. The patient was discharged with normal calcium levels and renal function.

Calcium Balance in Chronic Kidney Disease.

PubMed

Hill Gallant, Kathleen M; Spiegel, David M

2017-06-01

The kidneys play a critical role in the balance between the internal milieu and external environment. Kidney failure is known to disrupt a number of homeostatic mechanisms that control serum calcium and normal bone metabolism. However, our understanding of calcium balance throughout the stages of chronic kidney disease is limited and the concept of balance itself, especially with a cation as complex as calcium, is often misunderstood. Both negative and positive calcium balance have important implications in patients with chronic kidney disease, where negative balance may increase risk of osteoporosis and fracture and positive balance may increase risk of vascular calcification and cardiovascular events. Here, we examine the state of current knowledge about calcium balance in adults throughout the stages of chronic kidney disease and discuss recommendations for clinical strategies to maintain balance as well as future research needs in this area. Recent calcium balance studies in adult patients with chronic kidney disease show that neutral calcium balance is achieved with calcium intake near the recommended daily allowance. Increases in calcium through diet or supplements cause high positive calcium balance, which may put patients at risk for vascular calcification. However, heterogeneity in calcium balance exists among these patients. Given the available calcium balance data in this population, it appears clinically prudent to aim for recommended calcium intakes around 1000 mg/day to achieve neutral calcium balance and avoid adverse effects of either negative or positive calcium balance. Assessment of patients' dietary calcium intake could further equip clinicians to make individualized recommendations for meeting recommended intakes.

Low physiological levels of prostaglandins E2 and F2α improve human sperm functions.

PubMed

Rios, Mariana; Carreño, Daniela V; Oses, Carolina; Barrera, Nelson; Kerr, Bredford; Villalón, Manuel

2016-03-01

Prostaglandins (PGs) have been reported to be present in the seminal fluid and cervical mucus, affecting different stages of sperm maturation from spermatogenesis to the acrosome reaction. This study assessed the effects of low physiological PGE2 and PGF2α concentrations on human sperm motility and on the ability of the spermatozoa to bind to the zona pellucida (ZP). Human spermatozoa were isolated from seminal samples with normal concentration and motility parameters and incubated with 1μM PGE2, 1μM PGF2α or control solution to determine sperm motility and the ability to bind to human ZP. The effects of both PGs on intracellular calcium levels were determined. Incubation for 2 or 18h with PGE2 or PGF2α resulted in a significant (P<0.05) increase in the percentage of spermatozoa with progressive motility. In contrast with PGF2α, PGE2 alone induced an increase in sperm intracellular calcium levels; however, the percentage of sperm bound to the human ZP was doubled for both PGs. These results indicate that incubation of human spermatozoa with low physiological levels of PGE2 or PGF2α increases sperm functions and could improve conditions for assisted reproduction protocols.

NADPH Oxidase 5 Is a Pro-Contractile Nox Isoform and a Point of Cross-Talk for Calcium and Redox Signaling-Implications in Vascular Function.

PubMed

Montezano, Augusto C; De Lucca Camargo, Livia; Persson, Patrik; Rios, Francisco J; Harvey, Adam P; Anagnostopoulou, Aikaterini; Palacios, Roberto; Gandara, Ana Caroline P; Alves-Lopes, Rheure; Neves, Karla B; Dulak-Lis, Maria; Holterman, Chet E; de Oliveira, Pedro Lagerblad; Graham, Delyth; Kennedy, Christopher; Touyz, Rhian M

2018-06-15

NADPH Oxidase 5 (Nox5) is a calcium-sensitive superoxide-generating Nox. It is present in lower forms and higher mammals, but not in rodents. Nox5 is expressed in vascular cells, but the functional significance remains elusive. Given that contraction is controlled by calcium and reactive oxygen species, both associated with Nox5, we questioned the role of Nox5 in pro-contractile signaling and vascular function. Transgenic mice expressing human Nox5 in a vascular smooth muscle cell-specific manner (Nox5 mice) and Rhodnius prolixus , an arthropod model that expresses Nox5 endogenoulsy, were studied. Reactive oxygen species generation was increased systemically and in the vasculature and heart in Nox5 mice. In Nox5-expressing mice, agonist-induced vasoconstriction was exaggerated and endothelium-dependent vasorelaxation was impaired. Vascular structural and mechanical properties were not influenced by Nox5. Vascular contractile responses in Nox5 mice were normalized by N -acetylcysteine and inhibitors of calcium channels, calmodulin, and endoplasmic reticulum ryanodine receptors, but not by GKT137831 (Nox1/4 inhibitor). At the cellular level, vascular changes in Nox5 mice were associated with increased vascular smooth muscle cell [Ca 2+ ] i , increased reactive oxygen species and nitrotyrosine levels, and hyperphosphorylation of pro-contractile signaling molecules MLC20 (myosin light chain 20) and MYPT1 (myosin phosphatase target subunit 1). Blood pressure was similar in wild-type and Nox5 mice. Nox5 did not amplify angiotensin II effects. In R. prolixus , gastrointestinal smooth muscle contraction was blunted by Nox5 silencing, but not by VAS2870 (Nox1/2/4 inhibitor). Nox5 is a pro-contractile Nox isoform important in redox-sensitive contraction. This involves calcium-calmodulin and endoplasmic reticulum-regulated mechanisms. Our findings define a novel function for vascular Nox5, linking calcium and reactive oxygen species to the pro-contractile molecular machinery in vascular smooth muscle cells. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Actin dynamics mediates the changes of calcium level during the pulvinus movement of Mimosa pudica

PubMed Central

Yao, Heng; Xu, Qiangyi

2008-01-01

The bending movement of the pulvinus of Mimosa pudica is caused by a rapid change in volume of the abaxial motor cells, in response to various environmental stimuli. We investigated the relationship between the actin cytoskeleton and changes in the level of calcium during rapid contractile movement of the motor cells that was induced by electrical stimulation. The bending of the pulvinus was retarded by treatments with actin-affecting reagents and calcium channel inhibitors. The actin filaments in the motor cells were fragmented in response to electrical stimulation. Further investigations were performed using protoplasts from the motor cells of M. pudica pulvini. Calcium-channel inhibitors and EGTA had an inhibitory effect on contractile movement of the protoplasts. The level of calcium increased and became concentrated in the tannin vacuole after electrical stimulation. Ruthenium Red inhibited the increase in the level of calcium in the tannin vacuole and the contractile movement of the protoplasts. However, treatment with latrunculin A abolished the inhibitory effect of Ruthenium Red. Phalloidin inhibited the contractile movement and the increase in the level of calcium in the protoplasts. Our study demonstrates that depolymerization of the actin cytoskeleton in pulvinus motor cells in response to electrical signals results in increased levels of calcium. PMID:19513198

Supplementation with bio-calcium from shells Pinctada maxima in postmenopausal women with decreased mineral bone density--pilot study.

PubMed

Vujasinović-Stupar, Nada; Novković, Snezana; Jezdić, Ivana

2009-01-01

Treatment of osteoporosis, in addition to a specific antiresorptive or anabolic treatment, requires supplementation with calcium and vitamin D. Widespread cultivation of pearl shells has made pearls available for commercial use for a very reasonable price. The main chemical compound of pearls from shells Pinctada maxima is calcium-carbonate (CaCO3). Recently developed technologies applied in a micronisation process have provided increased gastrointestinal resorption of calcium, estimated at over 90% of calcium intake. The paper is aimed at monitoring of efficacy and tolerance of six-month bio-calcium supplementation in postmenopausal women with reduced bone mineral density. Group 1 (30 patients) received, three times a day, capsules of pearl powder from shells Pinctada maxima (it is equal to 260 mg of elementary calcium); group II (20 patients) received a daily dose of 500 mg inorganic CaCO3. Both groups received 666 IU of cholecalciferol per day. In all patients, bone mineral density (BMD) of the spine or hip, serum blood and urine levels of Ca, phosphates and alkaline phosphatase, were measured before and after six months of the treatment. Group I/Group II: average age 61.7/61.7 years; beginning of menopause: 48.32 /48 years; menopause duration 13.4/13.7 years; average body mass index 27.2/27 kg/m2. These two groups did not different significantly before supplementation. Six-month supplementation with CaCO3 of the biological origin led to the increase of BMD from 0.901 g/cm2 to 0.948 g/cm2 (p = 0.067), while BMD remained the same in the group supplemented with inorganic CaCO3 Gastrointestinal tolerability of bio-calcium was excellent, without any adverse events. These data could not strongly support the hypothesis of better efficacy of bio-calcium taking into account a small number of patients and a short follow-up period in this pilot study. Tolerance of CaCO3 of the biological origin was excellent and free of any adverse events. The results of laboratory values were within normal range.

Effects of Lowering Dialysate Calcium Concentration on Mineral and Bone Disorders in Chronic Hemodialysis Patients: Conversion from 3.0 mEq/L to 2.75 mEq/L.

PubMed

Yamada, Shunsuke; Ueki, Kenji; Tokumoto, Masanori; Suehiro, Takaichi; Kimura, Hiroshi; Taniguchi, Masatomo; Fujimi, Satoru; Kitazono, Takanari; Tsuruya, Kazuhiko

2016-02-01

Selection of a lower dialysate calcium concentration (DCa) can reduce calcium burden and prevent vascular calcification in hemodialysis patients. However, decreased DCa can worsen mineral and bone disorders. This 1-year retrospective observational study evaluated 121 hemodialysis patients at Fukuoka Renal Clinic who underwent conversion of DCa from 3.0 mEq/L to 2.75 mEq/L. The primary outcomes were changes in serum levels of calcium, phosphate, and parathyroid hormone (PTH). The effects of baseline serum calcium and PTH levels on changes in biochemical parameters were also determined. One year after DCa conversion, mean serum calcium level decreased, while serum phosphate, alkaline phosphatase, and PTH concentrations increased. The rate of achievement of target PTH was higher in patients with lower serum PTH level at baseline, while patients with higher baseline serum PTH level tended to exceed the upper limit of the PTH target range. Patients with higher baseline serum calcium concentration showed a greater decrease in serum calcium level and a greater increase in serum PTH level at 1 year. Patients with a lower baseline serum PTH level can benefit from optimal PTH control following conversion of DCa from 3.0 mEq/L to 2.75 mEq/L. However, secondary hyperparathyroidism may be exacerbated in some patients with higher baseline serum calcium (Ca) and PTH levels. These results indicate that an individualized approach can maximize the benefits of Ca unloading after conversion to lower DCa. © 2015 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

Absence of the ER Cation Channel TMEM38B/TRIC-B Disrupts Intracellular Calcium Homeostasis and Dysregulates Collagen Synthesis in Recessive Osteogenesis Imperfecta

PubMed Central

Cabral, Wayne A.; Ishikawa, Masaki; Garten, Matthias; Makareeva, Elena N.; Sargent, Brandi M.; Weis, MaryAnn; Barnes, Aileen M.; Webb, Emma A.; Shaw, Nicholas J.; Ala-Kokko, Leena; Lacbawan, Felicitas L.; Högler, Wolfgang; Leikin, Sergey; Blank, Paul S.; Zimmerberg, Joshua; Eyre, David R.; Yamada, Yoshihiko; Marini, Joan C.

2016-01-01

Recessive osteogenesis imperfecta (OI) is caused by defects in proteins involved in post-translational interactions with type I collagen. Recently, a novel form of moderately severe OI caused by null mutations in TMEM38B was identified. TMEM38B encodes the ER membrane monovalent cation channel, TRIC-B, proposed to counterbalance IP3R-mediated Ca2+ release from intracellular stores. The molecular mechanisms by which TMEM38B mutations cause OI are unknown. We identified 3 probands with recessive defects in TMEM38B. TRIC-B protein is undetectable in proband fibroblasts and osteoblasts, although reduced TMEM38B transcripts are present. TRIC-B deficiency causes impaired release of ER luminal Ca2+, associated with deficient store-operated calcium entry, although SERCA and IP3R have normal stability. Notably, steady state ER Ca2+ is unchanged in TRIC-B deficiency, supporting a role for TRIC-B in the kinetics of ER calcium depletion and recovery. The disturbed Ca2+ flux causes ER stress and increased BiP, and dysregulates synthesis of proband type I collagen at multiple steps. Collagen helical lysine hydroxylation is reduced, while telopeptide hydroxylation is increased, despite increased LH1 and decreased Ca2+-dependent FKBP65, respectively. Although PDI levels are maintained, procollagen chain assembly is delayed in proband cells. The resulting misfolded collagen is substantially retained in TRIC-B null cells, consistent with a 50–70% reduction in secreted collagen. Lower-stability forms of collagen that elude proteasomal degradation are not incorporated into extracellular matrix, which contains only normal stability collagen, resulting in matrix insufficiency. These data support a role for TRIC-B in intracellular Ca2+ homeostasis, and demonstrate that absence of TMEM38B causes OI by dysregulation of calcium flux kinetics in the ER, impacting multiple collagen-specific chaperones and modifying enzymes. PMID:27441836

Chronic production of angiotensin IV in the brain leads to hypertension that is reversible with an angiotensin II AT1 receptor antagonist.

PubMed

Lochard, Nadheige; Thibault, Gaétan; Silversides, David W; Touyz, Rhian M; Reudelhuber, Timothy L

2004-06-11

Angiotensin IV (Ang IV) is a metabolite of the potent vasoconstrictor angiotensin II (Ang II). Because specific binding sites for this peptide have been reported in numerous tissues including the brain, it has been suggested that a specific Ang IV receptor (AT4) might exist. Bolus injection of Ang IV in brain ventricles has been implicated in learning, memory, and localized vasodilatation. However, the functions of Ang IV in a physiological context are still unknown. In this study, we generated a transgenic (TG) mouse model that chronically releases Ang IV peptide specifically in the brain. TG mice were found to be hypertensive by the tail-cuff method as compared with control littermates. Treatment with the angiotensin-converting enzyme inhibitor captopril had no effect on blood pressure, but surprisingly treatment with the Ang II AT1 receptor antagonist candesartan normalized the blood pressure despite the fact that the levels of Ang IV in the brains of TG mice were only 4-fold elevated over the normal endogenous level of Ang peptides. Calcium mobilization assays performed on cultured CHO cells chronically transfected with the AT1 receptor confirm that low-dose Ang IV can mobilize calcium via the AT1 receptor only in the presence of Ang II, consistent with an allosteric mechanism. These results suggest that chronic elevation of Ang IV in the brain can induce hypertension that can be treated with angiotensin II AT1 receptor antagonists.

The Androgen-Regulated Calcium-Activated Nucleotidase 1 (CANT1) Is Commonly Overexpressed in Prostate Cancer and Is Tumor-Biologically Relevant in Vitro

PubMed Central

Gerhardt, Josefine; Steinbrech, Corinna; Büchi, Oralea; Behnke, Silvia; Bohnert, Annette; Fritzsche, Florian; Liewen, Heike; Stenner, Frank; Wild, Peter; Hermanns, Thomas; Müntener, Michael; Dietel, Manfred; Jung, Klaus; Stephan, Carsten; Kristiansen, Glen

2011-01-01

Previously, we identified the calcium-activated nucleotidase 1 (CANT1) transcript as up-regulated in prostate cancer. Now, we studied CANT1 protein expression in a large cohort of nearly 1000 prostatic tissue samples including normal tissue, prostatic intraepithelial neoplasia (PIN), primary carcinomas, metastases, and castrate-resistant carcinomas, and further investigated its functional relevance. CANT1 displayed predominantly a Golgi-type immunoreactivity with additional and variable cytoplasmic staining. In comparison to normal tissues, the staining intensity was significantly increased in PIN lesions and cancer. In cancer, high CANT1 levels were associated with a better prognosis, and castrate-resistant carcinomas commonly showed lower CANT1 levels than primary carcinomas. The functional role of CANT1 was investigated using RNA interference in two prostate cancer cell lines with abundant endogenous CANT1 protein. On CANT1 knockdown, a significantly diminished cell number and DNA synthesis rate, a cell cycle arrest in G1 phase, and a strong decrease of cell transmigration rate and wound healing capacity of CANT1 knockdown cells was found. However, on forced CANT1 overexpression, cell proliferation and migration remained unchanged. In summary, CANT1 is commonly overexpressed in the vast majority of primary prostate carcinomas and in the precursor lesion PIN and may represent a novel prognostic biomarker. Moreover, this is the first study to demonstrate a functional involvement of CANT1 in tumor biology. PMID:21435463

Effects of calcium and vitamin D3 on transforming growth factors in rectal mucosa of sporadic colorectal adenoma patients: a randomized controlled trial.

PubMed

Tu, Huakang; Flanders, W Dana; Ahearn, Thomas U; Daniel, Carrie R; Gonzalez-Feliciano, Amparo G; Long, Qi; Rutherford, Robin E; Bostick, Roberd M

2015-04-01

Transforming growth factor alpha (TGFα) and TGFβ1 are growth-promoting and -inhibiting autocrine/paracrine growth factors, respectively, that may (1) affect risk for colorectal cancer and (2) be modifiable by anti-proliferative exposures. The effects of supplemental calcium and vitamin D3 on these two markers in the normal-appearing colorectal mucosa in humans are unknown. We conducted a pilot, randomized, double-blind, placebo-controlled, 2 × 2 factorial clinical trial (n = 92; 23/treatment group) of calcium 2 g and/or vitamin D3 800 IU/d versus placebo over 6 mo. TGFα and TGFβ1 expression was measured in biopsies of normal-appearing rectal mucosa using automated immunohistochemistry and quantitative image analysis at baseline and 6-mo follow-up. In the calcium, vitamin D3 , and calcium plus vitamin D3 groups relative to the placebo group (1) the mean overall expression of TGFβ1 increased by 14% (P= 0.25), 19% (P = 0.17), and 22% (P = 0.09); (2) the ratio of TGFα expression in the upper 40% (differentiation zone) to that in the lower 60 (proliferation zone) of the crypts decreased by 34% (P = 0.11), 31% (P = 0.22), and 26% (P = 0.33); and (3) the TGFα/TGFβ1 ratio in the upper 40% of the crypts decreased by 28% (P = 0.09), 14% (P = 0.41), and 22% (P = 0.24), respectively. These preliminary results, although not statistically significant, suggest that supplemental calcium and vitamin D3 may increase TGFβ1 expression and shift TGFα expression downward from the differentiation to the proliferation zone in the crypts in the normal-appearing colorectal mucosa of sporadic colorectal adenoma patients, and support further investigation in a larger clinical trial. © 2013 Wiley Periodicals, Inc.

Efficacy of a Calcium Sucrose Phosphate Based Toothpaste in Elevating the Level of Calcium, Phosphate Ions in Saliva and Reducing Plaque: A Clinical Trial

PubMed Central

Menon, Leena Unnikrishnan; Varma, R. Balagopal; Kumaran, Parvathy; Xavier, Arun Mamachan; Govinda, Bhat Sangeetha; Kumar, J. Suresh

2018-01-01

Aim: To evaluate and compare the efficacy of “calcium sucrose phosphate” (CaSP) toothpaste (Enafix 5%) with ordinarily used calcium, phosphate-containing toothpaste in elevating the level of calcium, phosphate ions in saliva. Secondary aims were to evaluate substantivity and plaque-reducing ability of CaSP toothpaste. Materials and Methods: Thirty study participants of age group 6–13 years were divided into two groups: Group X (Control group) was made to continue brushing with their regularly used calcium, phosphate-containing toothpaste and Group Y (Test group) was allotted CaSP toothpaste. 1 ml of unstimulated saliva was periodically collected from both groups to determine any alteration in the salivary calcium, phosphate level. Parameters such as substantivity and plaque-reducing ability of CaSP toothpaste were also evaluated. Salivary mineral's intergroup comparison was evaluated by Student's t-test while its intragroup comparison along with the plaque amount variation in Group Y was evaluated by ANOVA and Tukey's post hoc test. Results: Group Y showed an increase in the salivary calcium level though not statistically significant. The increase was pronounced in samples collected on day 1. Group Y showed a consistent level of calcium, phosphate in samples collected immediately and 6 h postbrushing, indicating its substantivity. In addition, Group Y had an impact in reducing the plaque level when the 1st-month plaque score was compared with the 12th-month score. Conclusion: CaSP leads to an increase in the salivary calcium level though it was not statistically significant. Supervised brushing and dietary habits showed a positive effect on both the groups. CaSP toothpaste also showed substantivity and plaque-reducing ability.

Characterisation of mineralisation of bone and cartilage: X-ray diffraction and Ca and Sr K α X-ray fluorescence microscopy

NASA Astrophysics Data System (ADS)

Bradley, D. A.; Muthuvelu, P.; Ellis, R. E.; Green, E. M.; Attenburrow, D.; Barrett, R.; Arkill, K.; Colridge, D. B.; Winlove, C. P.

2007-10-01

Bone is a dynamic structure, constantly remodelling in response to changing mechanical and environmental factors. This is particularly evident in the mineral component encrusting the collagenous framework. The mineral is principally in the form of calcium apatite, but calcium can exchange with strontium, both during the cellular processes of mineralisation and resorption and by passive exchange with the deposited crystals. Mineralisation is generally characterized by densitometry, but because of the differences in absorption cross sections of calcium and strontium it can be misleading in studies of composition. In this work we have used X-ray diffraction to identify calcium and strontium apatite and X-ray fluorescence to quantify strontium and calcium distribution. With the beam characteristics available from synchrotron radiation, this has enabled us to obtain microscopic resolution on thin sections of bone and cartilage from the equine metacarpophalangeal joint. Two issues have been investigated; the first is the distribution of mineral in the bone-cartilage interface and within individual trabeculae. In trabecular bone the ratio of strontium to calcium concentration was typically 0.0035 ± 0.0020, and higher by a factor of ∼3 at the periphery than in the centre of a trabeculum (possibly reflecting the more rapid turnover of mineral in the surface layer). In the dense subchondral bone the ratio was similar, approximately doubling in the calcified cartilage. The second objective was to explore the changes in mineralisation associated with development of osteoarthrosis. We analysed lesions showing cartilage thinning and changes in the trabecular organization and density of the underlying bone. At the centre of the lesion the ratio of strontium to calcium was much lower than that in normal tissue, although the calcified cartilage still showed a higher ratio than the underlying bone. In the superficially normal tissue around the lesion the calcified cartilage returned to a normal ratio much more rapidly than the underlying bone. These data demonstrate the complex relationship between changes in cartilage and the underlying bone.

Media calcification, low erythrocyte magnesium, altered plasma magnesium, and calcium homeostasis following grafting of the thoracic aorta to the infrarenal aorta in the rat--differential preventive effects of long-term oral magnesium supplementation alone and in combination with alkali.

PubMed

Schwille, P O; Schmiedl, A; Schwille, R; Brunner, P; Kissler, H; Cesnjevar, R; Gepp, H

2003-03-01

Calcifications in arterial media are clinically well documented, but the role played by magnesium in pathophysiology and therapy is uncertain. To clarify this, an animal model in which the juxtacardial aorta was grafted to the infrarenal aorta, and the subsequent calcifications in the media of the graft and their response to oral supplementation with three magnesium-containing and alkalinizing preparations was investigated. Groups of highly inbred rats were formed as follows: sham-operation (Sham, n = 12), aorta transplantation (ATx, n = 12), ATx + magnesium citrate (MgC, n = 12), ATx + MgC + potassium citrate (MgCPC, n = 12), ATx + MgC + MgCPC (MgCPCSB, n = 12). At 84 (+/-2) days after ATx with or without treatment the following observations were made: (1) weight gain and general status were normal; (2) ATx rats developed massive media calcification, mineral accumulation in the graft, decreased erythrocyte magnesium and plasma parathyroid hormone, and increased plasma ionized magnesium and calcium, and uric acid; (3) Mg-treated rats developed variable degrees of metabolic alkalosis, but only MgCPCSB supplementation prevented calcifications. Additional findings after ATx alone were: imbalance in endothelin and nitric oxide production, the mineral deposited in media was poorly crystallized calcium phosphate, calcium exchange between plasma and graft, and bone resorption were unchanged. The superior anti-calcification effect of MgCPCSB was characterized by complete restoration of normal extracellular mineral homeostasis and uric acid, but sub-optimal normalization of erythrocyte magnesium. It was concluded that in the rat: (1) ATx causes loss of cellular magnesium, excess of extracellular magnesium and calcium in the presence of apparently unchanged bone resorption, and increased uricemia; (2) ATx facilitates enhanced influx of calcium into vascular tissue, leading to calcium phosphate deposition in the media; (3) ATx-induced calcification is prevented by dietary supplementation with a combination of magnesium, alkali citrate and bases. Although the described circulatory model of media calcification in the rat requires further investigation, the data allow ascribing a fundamental role to magnesium and acid-base metabolism.

Effects of muscarinic, alpha-adrenergic, and substance P agonists and ionomycin on ion transport mechanisms in the rat parotid acinar cell. The dependence of ion transport on intracellular calcium

PubMed Central

1989-01-01

The relationship between receptor-mediated increases in the intracellular free calcium concentration [( Ca]i) and the stimulation of ion fluxes involved in fluid secretion was examined in the rat parotid acinar cell. Agonist-induced increases in [Ca]i caused the rapid net loss of up to 50-60% of the total content of intracellular chloride (Cli) and potassium (Ki), which is consistent with the activation of calcium-sensitive chloride and potassium channels. These ion movements were accompanied by a 25% reduction in the intracellular volume. The relative magnitudes of the losses of Ki and the net potassium fluxes promoted by carbachol (a muscarinic agonist), phenylephrine (an alpha-adrenergic agonist), and substance P were very similar to their characteristic effects on elevating [Ca]i. Carbachol stimulated the loss of Ki through multiple efflux pathways, including the large-conductance Ca-activated K channel. Carbachol and substance P increased the levels of intracellular sodium (Nai) to more than 2.5 times the normal level by stimulating the net uptake of sodium through multiple pathways; Na-K-2Cl cotransport accounted for greater than 50% of the influx, and approximately 20% was via Na-H exchange, which led to a net alkalinization of the cells. Ionomycin stimulated similar fluxes through these two pathways, but also promoted sodium influx through an additional pathway which was nearly equivalent in magnitude to the combined uptake through the other two pathways. The carbachol- induced increase in Nai and decrease in Ki stimulated the activity of the sodium pump, measured by the ouabain-sensitive rate of oxygen consumption, to nearly maximal levels. In the absence of extracellular calcium or in cells loaded with the calcium chelator BAPTA (bis[o- aminophenoxy]ethane-N,N,N',N'-tetraacetic acid) the magnitudes of agonist- or ionomycin-stimulated ion fluxes were greatly reduced. The parotid cells displayed a marked desensitization to substance P; within 10 min the elevation of [Ca]i and alterations in Ki, Nai, and cell volume spontaneously returned to near baseline levels. In addition to quantitating the activation of various ion flux pathways in the rat parotid acinar cell, these results demonstrate that the activation of ion transport systems responsible for fluid secretion in this tissue is closely linked to the elevation of [Ca]i. PMID:2467962

Evaluation of calcium ion, hydroxyl ion release and pH levels in various calcium hydroxide based intracanal medicaments: An in vitro study

PubMed Central

Fulzele, Punit; Baliga, Sudhindra; Thosar, Nilima; Pradhan, Debaprya

2011-01-01

Aims: Evaluation of calcium ion and hydroxyl ion release and pH levels in various calcium hydroxide based intracanal medicaments. Objective: The purpose of this study was to evaluate calcium and hydroxyl ion release and pH levels of calcium hydroxide based products, namely, RC Cal, Metapex, calcium hydroxide with distilled water, along with the new gutta-percha points with calcium hydroxide. Materials and Methods: The materials were inserted in polyethylene tubes and immersed in deionized water. The pH variation, Ca++ and OH- release were monitored periodically for 1 week. Statistical Analysis Used: Statistical analysis was carried out using one-way analysis of variance and Tukey's post hoc tests with PASW Statistics version 18 software to compare the statistical difference. Results: After 1 week, calcium hydroxide with distilled water and RC Cal raised the pH to 12.7 and 11.8, respectively, while a small change was observed for Metapex, calcium hydroxide gutta-percha points. The calcium released after 1 week was 15.36 mg/dL from RC Cal, followed by 13.04, 1.296, 3.064 mg/dL from calcium hydroxide with sterile water, Metapex and calcium hydroxide gutta-percha points, respectively. Conclusions: Calcium hydroxide with sterile water and RC Cal pastes liberate significantly more calcium and hydroxyl ions and raise the pH higher than Metapex and calcium hydroxidegutta-percha points. PMID:22346155

Aluminum, iron, lead, cadmium, copper, zinc, chromium, magnesium, strontium, and calcium content in bone of end-stage renal failure patients.

PubMed

D'Haese, P C; Couttenye, M M; Lamberts, L V; Elseviers, M M; Goodman, W G; Schrooten, I; Cabrera, W E; De Broe, M E

1999-09-01

Little is known about trace metal alterations in the bones of dialysis patients or whether particular types of renal osteodystrophy are associated with either increased or decreased skeletal concentrations of trace elements. Because these patients are at risk for alterations of trace elements as well as for morbidity from skeletal disorders, we measured trace elements in bone of patients with end-stage renal disease. We analyzed bone biopsies of 100 end-stage renal failure patients enrolled in a hemodialysis program. The trace metal contents of bone biopsies with histological features of either osteomalacia, adynamic bone disease, mixed lesion, normal histology, or hyperparathyroidism were compared with each other and with the trace metal contents of bone of subjects with normal renal function. Trace metals were measured by atomic absorption spectrometry. The concentrations of aluminum, chromium, and cadmium were increased in bone of end-stage renal failure patients. Comparing the trace metal/calcium ratio, significantly higher values were found for the bone chromium/calcium, aluminum/calcium, zinc/calcium, magnesium/calcium, and strontium/calcium ratios. Among types of renal osteodystrophy, increased bone aluminum, lead, and strontium concentrations and strontium/calcium and aluminum/calcium ratios were found in dialysis patients with osteomalacia vs the other types of renal osteodystrophy considered as one group. Moreover, the concentrations of several trace elements in bone were significantly correlated with each other. Bone aluminum was correlated with the time on dialysis, whereas bone iron, aluminum, magnesium, and strontium tended to be associated with patient age. Bone trace metal concentrations did not depend on vitamin D intake nor on the patients' gender. The concentration of several trace elements in bone of end-stage renal failure patients is disturbed, and some of the trace metals under study might share pathways of absorption, distribution, and accumulation. The clinical significance of the increased/decreased concentrations of several trace elements other than aluminum in bone of dialysis patients deserves further investigation.

Inhibition of Bcl-2 Sensitizes Mitochondrial Permeability Transition Pore (MPTP) Opening in Ischemia-Damaged Mitochondria

PubMed Central

Chen, Qun; Xu, Haishan; Xu, Aijun; Ross, Thomas; Bowler, Elizabeth; Hu, Ying; Lesnefsky, Edward J.

2015-01-01

Background Mitochondria are critical to cardiac injury during reperfusion as a result of damage sustained during ischemia, including the loss of bcl-2. We asked if bcl-2 depletion not only leads to selective permeation of the outer mitochondrial membrane (MOMP) favoring cytochrome c release and programmed cell death, but also favors opening of the mitochondrial permeability transition pore (MPTP). An increase in MPTP susceptibility would support a role for bcl-2 depletion mediated cell death in the calcium overload setting of early reperfusion via MPTP as well as later in reperfusion via MOMP as myocardial calcium content normalizes. Methods Calcium retention capacity (CRC) was used to reflect the sensitivity of the MPTP opening in isolated cardiac mitochondria. To study the relationship between bcl-2 inhibition and MPTP opening, mitochondria were incubated with a bcl-2 inhibitor (HA14-1) and CRC measured. The contribution of preserved bcl-2 content to MPTP opening following ischemia-reperfusion was explored using transgenic bcl-2 overexpressed mice. Results CRC was decreased in mitochondria following reperfusion compared to ischemia alone, indicating that reperfusion further sensitizes to MPTP opening. Incubation of ischemia-damaged mitochondria with increasing HA14-1concentrations increased calcium-stimulated MPTP opening, supporting that functional inhibition of bcl-2 during simulated reperfusion favors MPTP opening. Moreover, HA14-1 sensitivity was increased by ischemia compared to non-ischemic controls. Overexpression of bcl-2 attenuated MPTP opening in following ischemia-reperfusion. HA14-1 inhibition also increased the permeability of the outer membrane in the absence of exogenous calcium, indicating that bcl-2 inhibition favors MOMP when calcium is low. Conclusions The depletion and functional inhibition of bcl-2 contributes to cardiac injury by increasing susceptibility to MPTP opening in high calcium environments and MOMP in the absence of calcium overload. Thus, ischemia-damaged mitochondria with decreased bcl-2 content are susceptible to MPTP opening in early reperfusion and MOMP later in reperfusion when cytosolic calcium has normalized. PMID:25756500

Nutritional rickets: vitamin D, calcium, and the genetic make-up.

PubMed

El Kholy, Mohamed; Elsedfy, Heba; Fernández-Cancio, Monica; Hamza, Rasha Tarif; Amr, Nermine Hussein; Ahmed, Alaa Youssef; Toaima, Nadin Nabil; Audí, Laura

2017-02-01

The prevalence of vitamin D (vitD) deficiency presenting as rickets is increasing worldwide. Insufficient sun exposure, vitD administration, and/or calcium intake are the main causes. However, vitD system-related genes may also have a role. Prospective study: 109 rachitic children completed a 6-mo study period or until rachitic manifestations disappeared. Thirty children were selected as controls. Clinical and biochemical data were evaluated at baseline in patients and controls and biochemistry re-evaluated at radiological healing. Therapy was stratified in three different protocols. Fifty-four single-nucleotide polymorphisms (SNPs) of five vitD system genes (VDR, CP2R1, CYP27B1, CYP24A1, and GC) were genotyped and their association with clinical and biochemcial data was analyzed. Therapy response was similar in terms of radiological healing although it was not so in terms of biochemical normalization. Only VDR gene (promoter, start-codon, and intronic genotypes) was rickets-associated in terms of serum 25-OH-D, calcium, radiological severity and time needed to heal. Eight patients with sufficient calcium intake and 25-OH-D levels carried a VDR genotype lacking minor allele homozygous genotypes at SNPs spread along the gene. Although patients presented epidemiologic factors strongly contributing to rickets, genetic modulation affecting predisposition, severity, and clinical course is exerted, at least in part, by VDR gene polymorphic variation.

The use of allodermis prepared from Euro skin bank to prepare autologous tissue engineered skin for clinical use.

PubMed

Deshpande, P; Ralston, D R; MacNeil, S

2013-09-01

Over the past two decades a range of 3D models for human skin have been described. Some include native collagen and intrinsic basement membrane proteins and fibroblasts, others are based on xenogeneic collagen or synthetic supports often without fibroblasts. The aim of this study was to look at the influence of media calcium, basement membrane and fibroblasts on the quality of 3D tissue engineered skin produced using human de-epidermized acellular dermis. In this study we deliberately used Euro skin as the source of the donor dermis to examine to what extent this could provide an effective dermal substrate for producing 3D skin for clinical use. Keratinocytes were cultured in the presence and absence of fibroblasts and both with and without basement membrane on decellularized dermis at calcium concentrations ranging from 250μM to 1.6mM over a period of 14 days. Results showed the formation of a well attached epithelium with many of the features of normal skin in the presence of a basement membrane. This was largely independent of the presence of fibroblasts and not greatly influenced by the concentration of calcium in the media. However there was a clear requirement for physiological levels of calcium in the formation of a stratified epithelium in the absence of a basement membrane. Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.

Activation of mTOR controls the loss of TCRζ in lupus T cells through HRES-1/Rab4-regulated lysosomal degradation

PubMed Central

Fernandez, David R.; Telarico, Tiffany; Bonilla, Eduardo; Li, Qing; Banerjee, Sanjay; Middleton, Frank A.; Phillips, Paul E.; Crow, Mary K.; Oess, Stefanie; Muller-Esterl, Werner; Perl, Andras

2008-01-01

Persistent mitochondrial hyperpolarization (MHP) and enhanced calcium fluxing underlie aberrant T-cell activation and death pathway selection in systemic lupus erythematosus. Treatment with rapamycin, which effectively controls disease activity, normalizes CD3/CD28-induced calcium fluxing but fails to influence MHP, suggesting that altered calcium fluxing is downstream or independent of mitochondrial dysfunction. Here, we show that activity of the mammalian target of rapamycin (mTOR), which is a sensor of the mitochondrial transmembrane potential, is increased in lupus T cells. Activation of mTOR causes the over-expression of the Rab5A and HRES-1/Rab4 small GTPases that regulate endocytic recycling of surface receptors. Pull-down studies revealed a direct interaction of HRES-1/Rab4 with the T-cell receptor/CD3ζ chain (TCRζ). Importantly, the deficiency of the TCRζ chain and Lck and compensatory upregulation of the Fcε receptor type I γ chain (FcεRIγ) and Syk, which mediate enhanced calcium fluxing in lupus T cells, was reversed in patients treated with rapamcyin in vivo. Knockdown of HRES-1/Rab4 by siRNA and inhibitors of lysosomal function augmented TCRζ protein levels. The results suggest that activation of mTOR causes the loss of TCRζ in lupus T cells through HRES-1/Rab4-dependent lysosomal degradation. PMID:19201859

Effect of incorporation of calcium lactate on physico-chemical, textural, and sensory properties of restructured buffalo meat loaves

PubMed Central

Irshad, A.; Sharma, B. D.; Ahmed, S. R.; Talukder, S.; Malav, O. P.; Kumar, Ashish

2016-01-01

Aim: The present study was conducted to develop a functional meat product by fortifying calcium (in the form of calcium lactate) with restructured buffalo meat loaf (RBML). Materials and Methods: Deboned buffalo meat obtained from the carcass of adult female buffalo within 5-6 h of slaughter and stored under frozen condition. Calcium fortified RBML were prepared by replacing the lean buffalo meat with calcium lactate powder at 0%, 1%, 1.25%, and 1.5% level through the pre-standardized procedure. The developed products were evaluated for physico-chemical properties, proximate composition, calcium concentration (mg/100 g), water activity (aw), Lovibond® tintometer color units, texture profile analysis (TPA), and sensory qualities as per-standard procedures. Results: Of the various product quality parameters evaluated, cooking yield (%), product pH, moisture (%), protein (%), fat (%), and water activity (aw) decreases significantly with increasing level of calcium lactate. Calcium content of fortified functional RBMLs was 135.02, 165.73, and 203.85 mg/100 g as compared to 6.48 mg/100 g in control. Most of the sensory scores at 1% and 1.25% levels of calcium lactate in treatment products remained comparable among themselves and control product, with a gradual decline. Conclusions: The present study concluded that 1.25% calcium lactate was the optimum level for the fortification of calcium in RBML without affecting the textural and sensory properties which could meet out 15% of recommended dietary allowance for calcium. PMID:27051201

Effect of incorporation of calcium lactate on physico-chemical, textural, and sensory properties of restructured buffalo meat loaves.

PubMed

Irshad, A; Sharma, B D; Ahmed, S R; Talukder, S; Malav, O P; Kumar, Ashish

2016-02-01

The present study was conducted to develop a functional meat product by fortifying calcium (in the form of calcium lactate) with restructured buffalo meat loaf (RBML). Deboned buffalo meat obtained from the carcass of adult female buffalo within 5-6 h of slaughter and stored under frozen condition. Calcium fortified RBML were prepared by replacing the lean buffalo meat with calcium lactate powder at 0%, 1%, 1.25%, and 1.5% level through the pre-standardized procedure. The developed products were evaluated for physico-chemical properties, proximate composition, calcium concentration (mg/100 g), water activity (aw), Lovibond(®) tintometer color units, texture profile analysis (TPA), and sensory qualities as per-standard procedures. Of the various product quality parameters evaluated, cooking yield (%), product pH, moisture (%), protein (%), fat (%), and water activity (aw) decreases significantly with increasing level of calcium lactate. Calcium content of fortified functional RBMLs was 135.02, 165.73, and 203.85 mg/100 g as compared to 6.48 mg/100 g in control. Most of the sensory scores at 1% and 1.25% levels of calcium lactate in treatment products remained comparable among themselves and control product, with a gradual decline. The present study concluded that 1.25% calcium lactate was the optimum level for the fortification of calcium in RBML without affecting the textural and sensory properties which could meet out 15% of recommended dietary allowance for calcium.

Safety and Efficacy of Stosstherapy in Nutritional Rickets.

PubMed

Chatterjee, Daipayan; Swamy, Mathad K S; Gupta, Vikas; Sharma, Vasu; Sharma, Akshat; Chatterjee, Krishti

2017-03-01

Stosstherapy has been used since early 19 th century for treating nutritional rickets. However, there are no clear cut guidelines for the biochemical monitoring of this treatment. Repeated blood tests at short intervals increase the cost of therapy and noncompliance. A prospective study was conducted on 191 cases of nutritional rickets below 10 years of age to evaluate the effectivity of stosstherapy. All cases were treated with a single intramuscular injection of vitamin D (600.000 IU) along with oral calcium (50 mg/kg) and vitamin D (400 IU per day) until radiological resolution. Dietary modifications and adequate sunlight exposure were also recommended. The mean age of presentation was 2 years 9 months. Mean sunlight exposure was 17 minutes/week with 90% having low sunlight exposure (<30 minutes/week). Prolonged breast feeding (>6 months) was found in 93.7% of the cases. With treatment, the clinical features started resolving by 1 month with complete resolution of most of the features over a period of 1 year. By 6 months, all the study subjects had complete radiological resolution. Serum levels of calcium and alkaline phosphatase (ALP) were restored by 6 months in most cases while phosphate and vitamin D levels normalized by 6 weeks. Stosstherapy is a safe, cheap and effective method of treating nutritional rickets. Biochemical tests at initial presentation followed by vitamin D assay at 6 weeks and calcium, phosphate and ALP assays at 6 months is recommended in the monitoring of these patients. For regular monitoring, only ALP assay is recommended, provided one abstains from repeat injection of vitamin D based on high ALP levels.

The Transient Role for Calcium and Vitamin D during the Developmental Hair Follicle Cycle.

PubMed

Mady, Leila J; Ajibade, Dare V; Hsaio, Connie; Teichert, Arnaud; Fong, Chak; Wang, Yongmei; Christakos, Sylvia; Bikle, Daniel D

2016-07-01

The role for 1,25-dihydroxyvitamin D3 and/or calcium in hair follicle cycling is not clear despite their impact on keratinocyte differentiation. We found that calbindin-D9k null (knockout) pups generated from calbindin-D9k knockout females fed a vitamin D-deficient, low-calcium (0.47%) diet develop transient alopecia. The pups appear phenotypically normal until 13 days of age, after which the hair progressively sheds in a caudocephalic direction, resulting in truncal alopecia totalis by 20-23 days, with spontaneous recovery by 28 days. Histological studies showed markedly dystrophic hair follicles, loss of hair shafts with increased apoptosis, and hyperplastic epidermis during this time. Ha1 expression is lost during catagen in all mice but recovers more slowly in the knockout pups on the vitamin D-deficient, low-calcium diet. Keratin 1 expression is reduced throughout days 19-28. The expressions of involucrin, loricrin, and cathepsin L is initially increased by day 19 but subsequently falls below those of controls by day 23, as does that of desmoglein 3. Feeding the mothers a high-vitamin D/high-calcium (2%)/lactose (20%) diet lessens the phenotype, and knockout pups fostered to mothers fed a normal diet do not develop alopecia. Our results show that in calbindin-D9k knockout pups, a maternal vitamin D-deficient/low-calcium diet leads to transient noncicatricial alopecia. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Chronic alcohol feeding potentiates hormone‐induced calcium signalling in hepatocytes

PubMed Central

Bartlett, Paula J.; Antony, Anil Noronha; Agarwal, Amit; Hilly, Mauricette; Prince, Victoria L.; Combettes, Laurent; Hoek, Jan B.

2017-01-01

Key points Chronic alcohol consumption causes a spectrum of liver diseases, but the pathogenic mechanisms driving the onset and progression of disease are not clearly defined.We show that chronic alcohol feeding sensitizes rat hepatocytes to Ca2+‐mobilizing hormones resulting in a leftward shift in the concentration–response relationship and the transition from oscillatory to more sustained and prolonged Ca2+ increases.Our data demonstrate that alcohol‐dependent adaptation in the Ca2+ signalling pathway occurs at the level of hormone‐induced inositol 1,4,5 trisphosphate (IP3) production and does not involve changes in the sensitivity of the IP3 receptor or size of internal Ca2+ stores.We suggest that prolonged and aberrant hormone‐evoked Ca2+ increases may stimulate the production of mitochondrial reactive oxygen species and contribute to alcohol‐induced hepatocyte injury. Abstract ‘Adaptive’ responses of the liver to chronic alcohol consumption may underlie the development of cell and tissue injury. Alcohol administration can perturb multiple signalling pathways including phosphoinositide‐dependent cytosolic calcium ([Ca2+]i) increases, which can adversely affect mitochondrial Ca2+ levels, reactive oxygen species production and energy metabolism. Our data indicate that chronic alcohol feeding induces a leftward shift in the dose–response for Ca2+‐mobilizing hormones resulting in more sustained and prolonged [Ca2+]i increases in both cultured hepatocytes and hepatocytes within the intact perfused liver. Ca2+ increases were initiated at lower hormone concentrations, and intercellular calcium wave propagation rates were faster in alcoholics compared to controls. Acute alcohol treatment (25 mm) completely inhibited hormone‐induced calcium increases in control livers, but not after chronic alcohol‐feeding, suggesting desensitization to the inhibitory actions of ethanol. Hormone‐induced inositol 1,4,5 trisphosphate (IP3) accumulation and phospholipase C (PLC) activity were significantly potentiated in hepatocytes from alcohol‐fed rats compared to controls. Removal of extracellular calcium, or chelation of intracellular calcium did not normalize the differences in hormone‐stimulated PLC activity, indicating calcium‐dependent PLCs are not upregulated by alcohol. We propose that the liver ‘adapts’ to chronic alcohol exposure by increasing hormone‐dependent IP3 formation, leading to aberrant calcium increases, which may contribute to hepatocyte injury. PMID:28220501

Gibberellin mediates daylength-controlled differentiation of vegetative meristems in strawberry (Fragaria × ananassa Duch)

PubMed Central

Hytönen, Timo; Elomaa, Paula; Moritz, Thomas; Junttila, Olavi

2009-01-01

Background Differentiation of long and short shoots is an important developmental trait in several species of the Rosaceae family. However, the physiological mechanisms controlling this differentiation are largely unknown. We have studied the role of gibberellin (GA) in regulation of shoot differentiation in strawberry (Fragaria × ananassa Duch.) cv. Korona. In strawberry, differentiation of axillary buds to runners (long shoot) or to crown branches (short shoot) is promoted by long-day and short-day conditions, respectively. Formation of crown branches is a prerequisite for satisfactory flowering because inflorescences are formed from the apical meristems of the crown. Results We found that both prohexadione-calcium and short photoperiod inhibited runner initiation and consequently led to induction of crown branching. In both cases, this correlated with a similar decline in GA1 level. Exogenous GA3 completely reversed the effect of prohexadione-calcium in a long photoperiod, but was only marginally effective in short-day grown plants. However, transfer of GA3-treated plants from short days to long days restored the normal runner formation. This did not occur in plants that were not treated with GA3. We also studied GA signalling homeostasis and found that the expression levels of several GA biosynthetic, signalling and target genes were similarly affected by prohexadione-calcium and short photoperiod in runner tips and axillary buds, respectively. Conclusion GA is needed for runner initiation in strawberry, and the inhibition of GA biosynthesis leads to the formation of crown branches. Our findings of similar changes in GA levels and in GA signalling homeostasis after prohexadione-calcium and short-day treatments, and photoperiod-dependent responsiveness of the axillary buds to GA indicate that GA plays a role also in the photoperiod-regulated differentiation of axillary buds. We propose that tightly regulated GA activity may control induction of cell division in subapical tissues of axillary buds, being one of the signals determining bud fate. PMID:19210764

Correlation of mammographic density and serum calcium levels in patients with primary breast cancer.

PubMed

Hack, Carolin C; Stoll, Martin J; Jud, Sebastian M; Heusinger, Katharina; Adler, Werner; Haeberle, Lothar; Ganslandt, Thomas; Heindl, Felix; Schulz-Wendtland, Rüdiger; Cavallaro, Alexander; Uder, Michael; Beckmann, Matthias W; Fasching, Peter A; Bayer, Christian M

2017-06-01

Percentage mammographic breast density (PMD) is one of the most important risk factors for breast cancer (BC). Calcium, vitamin D, bisphosphonates, and denosumab have been considered and partly confirmed as factors potentially influencing the risk of BC. This retrospective observational study investigated the association between serum calcium level and PMD. A total of 982 BC patients identified in the research database at the University Breast Center for Franconia with unilateral BC, calcium and albumin values, and mammogram at the time of first diagnosis were included. PMD was assessed, using a semiautomated method by two readers. Linear regression analyses were conducted to investigate the impact on PMD of the parameters of serum calcium level adjusted for albumin level, and well-known clinical predictors such as age, body mass index (BMI), menopausal status and confounder for serum calcium like season in which the BC was diagnosed. Increased calcium levels were associated with reduced PMD (P = 0.024). Furthermore, PMD was inversely associated with BMI (P < 0.001) and age (P < 0.001). There was also an association between PMD and menopausal status (P < 0.001). The goodness-of-fit of the regression model was moderate. This is the first study assessing the association between serum calcium level and PMD. An inverse association with adjusted serum calcium levels was observed. These findings add to previously published data relating to vitamin D, bisphosphonates, denosumab, and the RANK/RANKL signaling pathway in breast cancer risk and prevention. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Use of fly ash in diets of cage and floor broilers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pharr, C.L.; Andrews, L.D.

1980-09-01

Three experiments were conducted to compare limestone to fly ash from a coal-fired generator station as a calcium source for broilers. In experiment 1, 5 male and 5 female broiler chicks were placed in each of 32 cages. Sixteen cages of birds were fed a ration with limestone supplying 30% of the total calcium and 16 cages were fed a ration with 30% of the total calcium supplied by fly ash. The total calcium and phosphorus levels of the rations were 1.0% and .5%, respectively. In this experiment no significant difference was found for 8-week body weight between diets wheremore » the added calcium was from limestone or fly ash. In experiment 2 a group of 40 male and 40 female cage reared broilers and 40 male and 40 female floor reared broilers were fed a basal diet of limestone providing 33% of the total calcium. Three diets with increasing fly ash levels were fed to three cage groups of 40 male and 40 female broilers providing 33, 46, and 45% of the total calcium of .9, 1.1, and 1.8%, respectively. Broilers fed the highest fly ash level weighed significantly less at 8 weeks than the caged controls but did not differ from the other treatments. Bone breaking strength as measured by the Allo Kramer Shear Press was similar between the basal and low level fly ash group and increased with higher fly ash levels. In experiment 3 four groups of 40 male broilers in cages were fed limestone diets with graded levels of limestone for the calcium source. Another four groups of 40 caged male broilers were fed fly ash diets with equivalent graded levels of fly ash for the calcium source. Both limestone and fly ash diets provided .17, .34, .51, and .68% calcium of a total calcium content of .28, .45, .62, and .79%, respectively.« less

Regulation of Chloride Channels by Protein Kinase C in Normal and Cystic Fibrosis Airway Epithelia

NASA Astrophysics Data System (ADS)

Li, Ming; McCann, John D.; Anderson, Matthew P.; Clancy, John P.; Liedtke, Carole M.; Nairn, Angus C.; Greengard, Paul; Welsh, Michael J.

1989-06-01

Apical membrane chloride channels control chloride secretion by airway epithelial cells. Defective regulation of these channels is a prominent characteristic of cystic fibrosis. In normal intact cells, activation of protein kinase C (PKC) by phorbol ester either stimulated or inhibited chloride secretion, depending on the physiological status of the cell. In cell-free membrane patches, PKC also had a dual effect: at a high calcium concentration, PKC inactivated chloride channels; at a low calcium concentration, PKC activated chloride channels. In cystic fibrosis cells, PKC-dependent channel inactivation was normal, but activation was defective. Thus it appears that PKC phosphorylates and regulates two different sites on the channel or on an associated membrane protein, one of which is defective in cystic fibrosis.

Inhibition of 4NQO-Induced Oral Carcinogenesis by Dietary Oyster Shell Calcium

PubMed Central

Chen, Ying; Jiang, Yi; Liao, Liyan; Zhu, Xiaoxin; Tang, Shengan; Yang, Qing; Sun, Lihua; Li, Yujie; Gao, Shuangrong; Xie, Zhongjian

2015-01-01

Oyster has gained much attention recently for its anticancer activity but it is unclear whether calcium, the major antitumor ingredient in oyster shell, is responsible for the anticarcinogenic role of the oyster. To address this issue, C57BL/6 mice were fed with the carcinogen 4-nitroquinoline-1-oxide (4NQO, 50 µg/mL) and normal diet or a diet containing oyster powder, oyster calcium, or calcium depleted oyster powder. The tongue tissue specimens isolated from these mice were histologically evaluated for hyperplasia, dysplasia, and papillary lesions, and then analyzed for proliferation and differentiation markers by immunohistochemistry. The results showed that mice on the diet containing oyster calcium significantly reduced rates of tumors in the tongue and proliferation and enhanced differentiation in the oral epithelium compared with the diet containing calcium depleted oyster powder. These results suggest that calcium in oyster plays a critical role in suppressing formation of oral squamous cell carcinoma and proliferation and promoting differentiation of the oral epithelium. PMID:26293805

Salivary calcium concentration and periodontal health of young adults in relation to tobacco smoking.

PubMed

Sutej, Ivana; Peros, Kristina; Benutic, Anica; Capak, Krunoslav; Basic, Kresimir; Rosin-Grget, Kata

2012-01-01

To evaluate the effect of tobacco smoking and salivary calcium on the periodontal status of young adults. Plaque index, gingival bleeding on probing, supragingival calculus, DMFT index, salivary flow, pH and salivary calcium in unstimulated salivary samples were recorded in smokers and nonsmokers. There were no significant differences between smokers and nonsmokers with respect to salivary flow (P = 0.08) and calcium level (P = 0.09). Significant correlations (P < 0.05) were found between a higher calcium level and higher probing depth (r = 0.60), higher number of teeth with probing depth of more than 4 mm (r = 0.70), greater clinical attachment level (r = 0.49) and lower number of teeth bleeding on probing (r = -0.50). Moderate smoking of tobacco cigarettes in young healthy subjects may not have a significant impact on salivary flow or calcium concentrations in unstimulated saliva, but an association exists between an increased level of salivary calcium and development of periodontal disease.

[Risk of hypocalcemia after thyroid surgery].

PubMed

Shulutko, A M; Semikov, V I; Gryaznov, S E; Gorbacheva, A V; Patalova, A R; Mansurova, G T; Kazakova, V A

2015-01-01

To reveal calcium metabolism disorders that frequently occur after thyroid surgery. The study included 202 patients who underwent thyroid surgery for different diseases and had normal calcium level in peripheral blood at baseline. Based on laboratory data postoperative hypocalcemia was diagnosed in 57 (28.8%) patients. It was not always accompanied by clinical symptoms. Clinical picture depended on degree of hypocalcemia. Symptoms was diagnosed more frequently if calcium concentration was less than 2.1 mmol/l. Clinical manifestations were absent in 64.9% of cases on background of hypocalcemia. Incidence of hypocalcemia was higher after thyroidectomy compared to organ-preserving surgery. Symptoms of hypocalcemia occurred after thyroidectomy only. Casual parathyroidectomy does not always cause hypocalcemia. Only in 14% of patients with hypocalcemia excised parathyroid was identified in specimen. At the same time 7.6% of patients with postoperative normocalcaemia also had excised parathyroids in specimens. Symptoms of hypocalcemia does not always occur at 1 day after surgery. They can appear later, for example at 5 days postoperatively and depend on severity of hypocalcemia. Thyroidectomy has high risk of postoperative hypocalcemia with clinical symptoms (19.6%) that is transient in 15.5% of cases and permanent in 4.1% of patients.

Estimation of Mineral and Trace Element Profile in Bubaline Milk Affected with Subclinical Mastitis.

PubMed

Singh, Mahavir; Yadav, Poonam; Sharma, Anshu; Garg, V K; Mittal, Dinesh

2017-04-01

The milk samples from buffaloes of Murrah breed at mid lactation stage, reared at an organised dairy farm, were screened for subclinical mastitis based on bacteriological examination and somatic cell count following International Dairy Federation criteria. Milk samples from subclinical mastitis infected and healthy buffaloes were analysed to evaluate physicochemical alterations in terms of protein, fat, pH, electrical conductivity, chloride, minerals (sodium, potassium and calcium) and trace elements (iron, zinc, copper and selenium). In the present study, protein, fat, zinc, iron, calcium and selenium content was significantly lower (P < 0.001), while pH and electrical conductivity were significantly higher in mastitic milk as compared to normal milk. Concentration of electrolytes mainly sodium and chloride significantly increased with higher somatic cell count in mastitic milk and to maintain osmolality; potassium levels decreased proportionately. Correlation matrix revealed significantly positive interdependences of somatic cell count with pH, electrical conductivity, sodium and chloride. However, protein, fat, calcium and potassium were correlated negatively with elevated somatic cell count in mastitic milk. It is concluded that udder infections resulting in elevated somatic cells may alter the mineral and trace element profile of milk, and magnitude of changes may have diagnostic and prognostic value.

Localized intracellular calcium signaling in muscle: calcium sparks and calcium quarks.

PubMed

Niggli, E

1999-01-01

Subcellularly localized Ca2+ signals in cardiac and skeletal muscle have recently been identified as elementary Ca2+ signaling events. The signals, termed Ca2+ sparks and Ca2+ quarks, represent openings of Ca2+ release channels located in the membrane of the sarcoplasmic reticulum (SR). In cardiac muscle, the revolutionary discovery of Ca2+ sparks has allowed the development of a fundamentally different concept for the amplification of Ca2+ signals by Ca(2+)-induced Ca2+ release. In such a system, a graded amplification of the triggering Ca2+ signal entering the myocyte via L-type Ca2+ channels is accomplished by a recruitment process whereby individual SR Ca2+ release units are locally controlled by L-type Ca2+ channels. In skeletal muscle, the initial SR Ca2+ release is governed by voltage-sensors but subsequently activates additional Ca2+ sparks by Ca(2+)-induced Ca2+ release from the SR. Results from studies on elementary Ca2+ release events will improve our knowledge of muscle Ca2+ signaling at all levels of complexity, from the molecule to normal cellular function, and from the regulation of cardiac and skeletal muscle force to the pathophysiology of excitation-contraction coupling.

A case of sleep apnea syndrome manifesting severe hypertension with high plasma norepinephrine levels.

PubMed

Makino, Shinya; Iwata, Masanobu; Fujiwara, Masayoshi; Ike, Shinpei; Tateyama, Hitone

2006-06-01

A 55-year-old female was admitted to our hospital with severe hypertension (274/140 mmHg). Endocrinological examination revealed that her plasma levels of norepinephrine (NE) was elevated with high levels of urinary NE, normetanephrine and vanillylmandelic acid (VMA), suggesting the presence of pheochromocytoma. However, neither computed tomography nor MIBG scintigraphy detected any catecholamine-producing tumor in or outside the adrenal glands. She was screened with full polysomnography because of heavy snoring, and the diagnosis of severe obstructive sleep apnea syndrome (OSAS) was made. She was treated with calcium channel blocker for three weeks, but severe hypertension persisted. After treatment with nasal continuous positive airway pressure (CPAP) was added, her blood pressure gradually lowered week by week. Concomitantly, the levels of plasma and urinary NE, urinary normetanephrine and urinary VMA were normalized following nasal CPAP therapy for 2 weeks. Additional treatments with alpha-adrenergic blocker further decreased her home blood pressure. After a year, she continued nasal CPAP therapy and her blood pressure was nearly below 160/100 mmHg. Urinary NE level was slightly above normal range and other catecholamines stayed within the normal range. This case shows that patients with OSAS could develop severe hypertension through elevated sympathetic tone, mimicking pheochromocytoma. Nasal CPAP therapy is recommended not only to improve hypertension and catecholamine excess but also to distinguish the condition from pheochromocytoma.

Plating and stripping calcium in an organic electrolyte

NASA Astrophysics Data System (ADS)

Wang, Da; Gao, Xiangwen; Chen, Yuhui; Jin, Liyu; Kuss, Christian; Bruce, Peter G.

2018-01-01

There is considerable interest in multivalent cation batteries, such as those based on magnesium, calcium or aluminium. Most attention has focused on magnesium. In all cases the metal anode represents a significant challenge. Recent work has shown that calcium can be plated and stripped, but only at elevated temperatures, 75 to 100 °C, with small capacities, typically 0.165 mAh cm-2, and accompanied by significant side reactions. Here we demonstrate that calcium can be plated and stripped at room temperature with capacities of 1 mAh cm-2 at a rate of 1 mA cm-2, with low polarization (~100 mV) and in excess of 50 cycles. The dominant product is calcium, accompanied by a small amount of CaH2 that forms by reaction between the deposited calcium and the electrolyte, Ca(BH4)2 in tetrahydrofuran (THF). This occurs in preference to the reactions which take place in most electrolyte solutions forming CaCO3, Ca(OH)2 and calcium alkoxides, and normally terminate the electrochemistry. The CaH2 protects the calcium metal at open circuit. Although this work does not solve all the problems of calcium as an anode in calcium-ion batteries, it does demonstrate that significant quantities of calcium can be plated and stripped at room temperature with low polarization.

Toward the establishment of standardized in vitro tests for lipid-based formulations, part 6: effects of varying pancreatin and calcium levels.

PubMed

Sassene, Philip; Kleberg, Karen; Williams, Hywel D; Bakala-N'Goma, Jean-Claude; Carrière, Frédéric; Calderone, Marilyn; Jannin, Vincent; Igonin, Annabel; Partheil, Anette; Marchaud, Delphine; Jule, Eduardo; Vertommen, Jan; Maio, Mario; Blundell, Ross; Benameur, Hassan; Porter, Christopher J H; Pouton, Colin W; Müllertz, Anette

2014-11-01

The impact of pancreatin and calcium addition on a wide array of lipid-based formulations (LBFs) during in vitro lipolysis, with regard to digestion rates and distribution of the model drug danazol, was investigated. Pancreatin primarily affected the extent of digestion, leaving drug distribution somewhat unaffected. Calcium only affected the extent of digestion slightly but had a major influence on drug distribution, with more drug precipitating at higher calcium levels. This is likely to be caused by a combination of removal of lipolysis products from solution by the formation of calcium soaps and calcium precipitating with bile acids, events known to reduce the solubilizing capacity of LBFs dispersed in biorelevant media. Further, during the digestion of hydrophilic LBFs, like IIIA-LC, the un-ionized-ionized ratio of free fatty acids (FFA) remained unchanged at physiological calcium levels. This makes the titration curves at pH 6.5 representable for digestion. However, caution should be taken when interpreting lipolysis curves of lipophilic LBFs, like I-LC, at pH 6.5, at physiological levels of calcium (1.4 mM); un-ionized-ionized ratio of FFA might change during digestion, rendering the lipolysis curve at pH 6.5 non-representable for the total digestion. The ratio of un-ionized-ionized FFAs can be maintained during digestion by applying non-physiological levels of calcium, resulting in a modified drug distribution with increased drug precipitation. However, as the main objective of the in vitro digestion model is to evaluate drug distribution, which is believed to have an impact on bioavailability in vivo, a physiological level (1.4 mM) of calcium is preferred.

A randomized clinical trial of the effects of supplemental calcium and vitamin D3 on markers of their metabolism in normal mucosa of colorectal adenoma patients.

PubMed

Ahearn, Thomas U; McCullough, Marjorie L; Flanders, W Dana; Long, Qi; Sidelnikov, Eduard; Fedirko, Veronika; Daniel, Carrie R; Rutherford, Robin E; Shaukat, Aasma; Bostick, Roberd M

2011-01-15

In cancer cell lines and rodent models, calcium and vitamin D favorably modulate cell proliferation, differentiation, and apoptosis in colonic epithelia. These effects may be modulated by local expression of the calcium receptor (CaR), the vitamin D receptor (VDR), and the P450 cytochromes, CYP27B1 and CYP24A1; however, they have yet to be investigated in humans. To address this gap, we conducted a randomized, double-blinded, placebo-controlled 2×2 factorial clinical trial. Patients with at least one pathology-confirmed colorectal adenoma were treated with 2 g/d elemental calcium and/or 800 IU/d vitamin D3 versus placebo over 6 months (n=92; 23 per group). CaR, VDR, CYP27B1, and CYP24A1 expression and distribution in biopsies of normal appearing rectal mucosa were detected by standardized, automated immunohistochemistry and quantified by image analysis. In the calcium-supplemented group, CaR expression increased 27% (P=0.03) and CYP24A1 expression decreased 21% (P=0.79). In the vitamin D3-supplemented group, CaR expression increased 39% (P=0.01) and CYP27B1 expression increased 159% (P=0.06). In patients supplemented with both calcium and vitamin D3, VDR expression increased 19% (P=0.13) and CaR expression increased 24% (P=0.05). These results provide mechanistic support for further investigation of calcium and vitamin D3 as chemopreventive agents against colorectal neoplasms, and CaR, VDR, CYP27B1, and CYP24A1 as modifiable, preneoplastic risk biomarkers for colorectal neoplasms. © 2010 AACR.

Contributions of two types of calcium channels to synaptic transmission and plasticity.

PubMed

Edmonds, B; Klein, M; Dale, N; Kandel, E R

1990-11-23

In Aplysia sensory and motor neurons in culture, the contributions of the major classes of calcium current can be selectively examined while transmitter release and its modulation are examined. A slowly inactivating, dihydropyridine-sensitive calcium current does not contribute either to normal synaptic transmission or to any of three different forms of plasticity: presynaptic inhibition, homosynaptic depression, and presynaptic facilitation. This current does contribute, however, to a fourth form of plasticity--modulation of transmitter release by tonic depolarization of the sensory neuron. By contrast, a second calcium current, which is rapidly inactivating and dihydropyridine-insensitive, contributes to release elicited by the transient depolarization of an action potential and to the other three forms of plasticity.

Indirect evidence of calcitonin secretion in man.

PubMed

Caniggia, A; Gennari, C; Vattimo, A; Nardi, P; Nuti, R

1976-09-01

1. The effect of calcitonin, a large amount of calcium given orally, pentagastrin and glucagon on plasma 47Ca radioactivity curves in subjects pretreated with 47Ca was examined. 2. A sudden increase of plasma radioactivity after intravenous administration of calcitonin and pentagastrin and after the oral calcium load was observed in normal subjects; the intravenous infusion of glucagon was less effective. 3. Two thyroparathyroidectomized patients who responded to the calcitonin infusion did not respond to the oral calcium load. 4. These data may be considered to offer indirect evidence of endogenous calcitonin secretion in man.

Presynaptic strontium dynamics and synaptic transmission.

PubMed Central

Xu-Friedman, M A; Regehr, W G

1999-01-01

Strontium can replace calcium in triggering neurotransmitter release, although peak release is reduced and the duration of release is prolonged. Strontium has therefore become useful in probing release, but its mechanism of action is not well understood. Here we study the action of strontium at the granule cell to Purkinje cell synapse in mouse cerebellar slices. Presynaptic residual strontium levels were monitored with fluorescent indicators, which all responded to strontium (fura-2, calcium orange, fura-2FF, magnesium green, and mag-fura-5). When calcium was replaced by equimolar concentrations of strontium in the external bath, strontium and calcium both entered presynaptic terminals. Contaminating calcium was eliminated by including EGTA in the extracellular bath, or by loading parallel fibers with EGTA, enabling the actions of strontium to be studied in isolation. After a single stimulus, strontium reached higher peak free levels than did calcium (approximately 1.7 times greater), and decayed more slowly (half-decay time 189 ms for strontium and 32 ms for calcium). These differences in calcium and strontium dynamics are likely a consequence of greater strontium permeability through calcium channels, lower affinity of the endogenous buffer for strontium, and less efficient extrusion of strontium. Measurements of presynaptic divalent levels help to explain properties of release evoked by strontium. Parallel fiber synaptic currents triggered by strontium are smaller in amplitude and longer in duration than those triggered by calcium. In both calcium and strontium, release consists of two components, one more steeply dependent on divalent levels than the other. Strontium drives both components less effectively than does calcium, suggesting that the affinities of the sensors involved in both phases of release are lower for strontium than for calcium. Thus, the larger and slower strontium transients account for the prominent slow component of release triggered by strontium. PMID:10096899

Localized hepatic tuberculosis presenting as severe hypercalcemia.

PubMed

Arrais Morais, Matheus; Cardoso Teixeira, Lorena Lane; de Sousa Brandão Torres, Dennyse; da Rocha Klautau Neto, Prócion Barreto; Machado Kahwage, Amanda

2018-04-01

Hypercalcemia might present itself in association with granulomatous diseases such as tuberculosis. We report a rare case of a 62-year-old man with hypercalcemia due to hepatic tuberculosis. The diagnosis was based on laparoscopic and a histopathological examination. After treatment with anti-tuberculosis medication, the patient's serum calcium levels were within normal limits. Tuberculosis needs to be excluded as a diagnosis in any febrile patient with hypercalcemia, especially in countries where tuberculosis is endemic. Copyright © 2017 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

Primary hyperparathyroidism associated with a giant cell tumor: One case in the distal radius.

PubMed

Ouzaa, M R; Bennis, A; Iken, M; Abouzzahir, A; Boussouga, M; Jaafar, A

2015-10-01

Hyperparathyroidism can present itself as brown tumors (or osteolytic expansive lesions) that usually disappear after normalization of calcium and phosphate levels. It rarely occurs simultaneously with a giant cell tumor. The authors report one case of a localized form at the distal radius in a patient being followed for primary hyperparathyroidism. The diagnostic challenges related to the clinical and radiological similarities of these two pathological entities are discussed, as they can lead to delays in therapeutic management. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

[Calcium and magnesium concentrations in "Healthy" and lithiasic human kidney (author's transl)].

PubMed

Terhorst, B; Stoeppler, M

1976-07-01

Calcium and magnesium levels in the cortex, medulla, and papilla of human kidney from 32 so-called healthy patients and from eleven patients with calcium-oxalate lithiasis were determined by atom-absorption spectralphotometry. A positive calcium gradient with the highest calcium concentration in the papilla was found in all kidneys. Compared to the control group, that calcium concentration in the lithiasic kidneys was reduced by 50% in the papilla, but in the cortex and medulla, the levels were the same. A relative depletion of calcium in the papilla in hypercalciuria goes against the theory that the papilla is the main center of development of calcium-containing stones. The magnesium concentration was practically the same in cortex, medulla, and papilla, and no significant difference was found between lithiasic and healthy kidneys. These findings underline the central role of calcium in the genesis of calcium-containing stones.

Impaired calcium sensing distinguishes primary hyperparathyroidism (PHPT) patients with low bone mineral density.

PubMed

Weber, Thomas J; Koh, James; Thomas, Samantha M; Hogue, Joyce A; Scheri, Randall P; Roman, Sanziana A; Sosa, Julie A

2017-09-01

A subset of PHPT patients exhibit a more severe disease phenotype characterized by bone loss, fractures, recurrent nephrolithiasis, and other dysfunctions, but the underlying reasons for this disparity in clinical presentation remain unknown. We sought to identify new mechanistic indices that could inform more personalized management of PHPT. Pre-, peri-, and postoperative data and demographic, clinical, and pathological information from patients undergoing parathyroidectomy for PHPT were collected. Univariate and partial Spearman correlation was used to estimate the association of parathyroid tumor calcium sensing capacity with select variables. An unselected series of 237 patients aged >18years and undergoing parathyroidectomy for PHPT were enrolled. Calcium sensing capacity, expressed as the concentration required for half-maximal biochemical response (EC50), was evaluated in parathyroid tumors from an unselected series of 74 patients and assessed for association with clinical parameters. The hypothesis was that greater disease severity would be associated with attenuated calcium sensitivity and biochemically autonomous parathyroid tumor behavior. Parathyroid tumors segregated into two distinct groups of calcium responsiveness (EC50<3.0 and ≥3.0mM). The low EC50 group (n=27) demonstrated a mean calcium EC50 value of 2.49mM [95% confidence interval (CI): 2.43-2.54mM], consistent with reference normal activity. In contrast, the high EC50 group (n=47) displayed attenuated calcium sensitivity with a mean EC50 value of 3.48mM [95% CI: 3.41-3.55mM]. Retrospective analysis of the clinical registry data suggested that high calcium EC50 patients presented with a more significant preoperative bone mineral density (BMD) deficit with a t-score of -2.7, (95% CI: -3.4 to -1.9) versus 0.9, (95% CI: -2.1 to -0.4) in low EC50 patients (p<0.001). After adjusting for gender, age, BMI, 25 OH vitamin D level and preoperative iPTH, lowest t-score and calcium EC50 were inversely correlated, with a partial Spearman correlation coefficient of -0.35 (p=0.02). Impaired calcium sensing in parathyroid tumors is selectively observed in a subset of patients with more severe bone mineral density deficit. Assessment of parathyroid tumor biochemical behavior may be a useful predictor of disease severity as measured by bone mineral density in patients with PHPT. Copyright © 2017 Elsevier Inc. All rights reserved.

Action of bradykinin potentiating factor (BPF) and dimercaprol (BAL) on the responses to bradykinin of isolated preparations of rat intestines.

PubMed

Camargo, A; Ferreira, S H

1971-06-01

BPF and BAL inhibited kininase activity of homogenates of rat intestine. However, BFP potentiated and BAL inhibited the contractions induced by bradykinin on rat isolated duodenum (low calcium solution) and terminal ileum (normal calcium solution). Neither BPF nor BAL affects the relaxation induced by bradykinin of rat duodenum bathed in normal Tyrode. These results suggest that two different types of pharmacological receptor are involved in the action of bradykinin on rat intestine, and that other factors besides the inhibition of agonist destruction participate in the mechanism of potentiation of kinin action by BPF.

Action of bradykinin potentiating factor (BPF) and dimercaprol (BAL) on the responses to bradykinin of isolated preparations of rat intestines

PubMed Central

Camargo, A.; Ferreira, S. H.

1971-01-01

BPF and BAL inhibited kininase activity of homogenates of rat intestine. However, BFP potentiated and BAL inhibited the contractions induced by bradykinin on rat isolated duodenum (low calcium solution) and terminal ileum (normal calcium solution). Neither BPF nor BAL affects the relaxation induced by bradykinin of rat duodenum bathed in normal Tyrode. These results suggest that two different types of pharmacological receptor are involved in the action of bradykinin on rat intestine, and that other factors besides the inhibition of agonist destruction participate in the mechanism of potentiation of kinin action by BPF. PMID:5091164

Significance of serum levels of vitamin D and some related minerals in breast cancer patients

PubMed Central

Abdelgawad, Iman A; El-Mously, Rawya H; Saber, Magdy M; Mansour, Ossama A; Shouman, Samia A

2015-01-01

Vitamin D and calcium are involved in a wide range of proliferation, apoptosis and cell signaling activities in the body. Suboptimal concentrations may lead to cancer development. The role of phosphate in cancer metabolism is particularly relevant in breast cancer while, magnesium deficiency favors DNA mutations leading to carcinogenesis. Objectives: To determine serum levels of vitamin D, calcium, phosphorus, magnesium, and parathormone in female breast cancer patients and to assess their association with some prognostic factors in breast cancer. Design and methods: This study is done on 98 newly diagnosed female breast cancer patients and 49 age matched apparently healthy female volunteers as controls. Serum samples from all patients and controls were subjected to 25-OH Vit D, calcium, phosphorus, magnesium, and parathormone measurements. Results: In the breast cancer group, the median serum levels of 25-OH Vit D were 15 ng/ml, while it was 21 ng/ml in the control group. Levels of 25-OH Vit D and other tested minerals were significantly lower while calcium:magnesium (Ca:Mg) ratio, and calcium:phosphorus (Ca:P) ratio were significantly higher in the breast cancer group. Significant negative correlation was detected between phosphorus and calcium, ionized calcium , calcium magnesium ratio, and calcium phosphorus ratio. Conclusion: It is not only the deficient levels of Vit D and other related minerals, but the combination of the abnormal levels of all the studied parameters that might contribute to the development of cancer. Further studies with larger number of patient are needed. PMID:26097595

[Otosclerosis- or the loss of the natural variant of inertness ( of the labyrinth capsule)].

PubMed

Kiselev, A S

2012-01-01

The author suggests an original hypothesis of otosclerosis based on the analyses of the literature publications for many years and his personal clinical observations. The normal labyrinth capsule is considered to be bradytrophic, i.e. inert and showing an extremely low level of metabolic processes. The disturbance of bradytrophicity under the action of individual factors and/or especially their combination make it involved in the maintenance of calcium homeostasis in the body. The validity of this conjecture is confirmed by the results of histological investigations, viz. the appearance of diquide or xplasma-like, bone in the labyrinth of the patients suffering otosclerosis. Such bone resorption is known to occur in other parts of the bony skeletontoo and should be regarded as a normal physiological process contributing to the replenishment of blood calcium deficiency.The subsequent reorganization (remodeling) of any part of the bony skeleton is physiologically neutral. In the labyrinth capsule,with its small size and delicate structure, such reorganization induces the otosclerotic process responsible for dysfunction of the membranaceous labyrinth. The surgical treatment of the patients presenting with otosclerosis should be supplemented by conservative treatment intended to slow down the otosclerotic reorganization and to restore bradytrophicity of the labyrinth capsule.

On the role of calcium in adrenocorticotropin-induced changes in mitochondrial pregnenolone synthesis.

PubMed

Farese, R V; Prudente, W J

1978-10-01

The importance of calcium in the ACTH-induced increase in adrenal mitochondrial pregnenolone synthesis was evaluated. In mitochondria prepared in the absence of EDTA and albumin, calcium enhanced the binding of cholesterol to cytochrome P-450 and subsequent pregnenolone synthesis. Although these effects of calcium were slightly greater in control than in ACTH-treated mitochondria, a sizeable effect of ACTH remained even at high calcium levels (500 micron). In mitochondria prepared from adrenals homogenized in fluid containing EDTA and albumin, ACTH-induced effects on pregnenolone synthesis were relatively poor unless calcium was added to the incubation mixture. High concentrations of added calcium (500 micron or greater) obviated the need for the labile protein required for ACTH-induced effects in intact mitochondria, presumably by disrupting mitochondria and allowing an "unrestrained" interaction of cholesterol with cytochrome P-450. Thus, cholesterol-rich mitochondria from ACTH plus cycloheximide-treated rats produced large amounts of pregnenolone when high (probably unphysiological) calcium concentrations were present. The present findings suggest that calcium is required at the mitochondrial level for ACTH-induced effects on pregnenolone synthesis, and the reported ACTH-induced increase in intraadrenal calcium may thus amplify the effects of ACTH on steroidogenesis. However, it seems unlikely that calcium is the agent primarily responsible for mediating the ACTH-induced steroidogenic effect at the mitochondrial level.

Biological and medical significance of calcium phosphates.

PubMed

Dorozhkin, Sergey V; Epple, Matthias

2002-09-02

The inorganic part of hard tissues (bones and teeth) of mammals consists of calcium phosphate, mainly of apatitic structure. Similarly, most undesired calcifications (i.e. those appearing as a result of various diseases) of mammals also contain calcium phosphate. For example, atherosclerosis results in blood-vessel blockage caused by a solid composite of cholesterol with calcium phosphate. Dental caries result in a replacement of less soluble and hard apatite by more soluble and softer calcium hydrogenphosphates. Osteoporosis is a demineralization of bone. Therefore, from a chemical point of view, processes of normal (bone and teeth formation and growth) and pathological (atherosclerosis and dental calculus) calcifications are just an in vivo crystallization of calcium phosphate. Similarly, dental caries and osteoporosis can be considered to be in vivo dissolution of calcium phosphates. On the other hand, because of the chemical similarity with biological calcified tissues, all calcium phosphates are remarkably biocompatible. This property is widely used in medicine for biomaterials that are either entirely made of or coated with calcium phosphate. For example, self-setting bone cements made of calcium phosphates are helpful in bone repair and titanium substitutes covered with a surface layer of calcium phosphates are used for hip-joint endoprostheses and tooth substitutes, to facilitate the growth of bone and thereby raise the mechanical stability. Calcium phosphates have a great biological and medical significance and in this review we give an overview of the current knowledge in this subject.

Serum calcium changes and risk of type 2 diabetes mellitus in Asian population.

PubMed

Suh, Sunghwan; Bae, Ji Cheol; Jin, Sang-Man; Jee, Jae Hwan; Park, Mi Kyoung; Kim, Duk Kyu; Kim, Jae Hyeon

2017-11-01

We examined the association between changes in serum calcium levels with the incidence of type 2 diabetes mellitus (T2DM) in apparently healthy South Korean subjects. A retrospective longitudinal analysis was conducted with subjects who had participated in comprehensive health check-ups at least four times over a 7-year period (between 2006 and 2012). In total, 23,121 subjects were categorized into tertiles based on changes in their albumin-adjusted serum calcium levels. Multivariate Cox regression models were fitted to assess the association between changes in serum calcium levels during follow-up and the relative risk of diabetes incidence. After a median follow-up of 57.4months, 1,929 (8.3%) new cases of T2DM occurred. Simple linear regression analysis showed serum calcium level changes correlated positively with changes in HbA1c and fasting plasma glucose (FPG) levels (B=5.72, p<0.001 for FPG; B=0.13, p<0.001 for HbA1c). An increase in albumin-adjusted serum calcium levels during follow-up was related to an increased risk of T2DM. After adjustment for potential confounders, the risk of T2DM was 1.6 times greater for subjects whose albumin-adjusted serum calcium levels were in the highest change tertile during follow-up than for subjects whose levels were in the lowest tertile (HR 1.65, 95% CI 1.44-1.88, P<0.001). The elevation of albumin-adjusted serum calcium levels was associated with an increased risk of T2DM, independent of baseline glycemic status. Copyright © 2017 Elsevier B.V. All rights reserved.

Incidence of postoperative pain after use of calcium hydroxide mixed with normal saline or 0.2% chlorhexidine digluconate as intracanal medicament in the treatment of apical periodontitis.

PubMed

Menakaya, Ifeoma Nkiruka; Oderinu, Olabisi Hajarat; Adegbulugbe, Ilemobade Cyril; Shaba, Olufemi Peter

2015-10-01

To compare the incidence of postoperative pain after the use of calcium hydroxide powder mixed with normal saline or 0.2% chlorhexidine digluconate as intracanal medicament. Fifty-five subjects aged 17-60 years with teeth diagnosed to have apical periodontitis. Two-visit conventional root canal treatment of seventy teeth. The teeth were divided by randomization (balloting) into two groups: control group and experimental group, each with thirty-five teeth treated with calcium hydroxide mixed with normal saline or with 0.2% chlorhexidine digluconate as intracanal medicament respectively. Incidence of postoperative pain was assessed using the universal pain assessment tool and whether or not analgesic was taken. Incidence of post-operative pain. Postoperative pain occurred only at 1-day and 1-week reviews. In the control group, the overall incidence of pain was the same at both review periods (5.7%), while the experimental group showed a slight decrease in incidence between 1-day (17.2%) and 1-week (11.4%) reviews. Incidence of flare-ups was more in the experimental group (11.4%) than in the control group (5.7%). No significant statistical differences between the two groups were observed (p > 0.05). The incidence of postoperative pain was lower in the normal saline treatment group, but the difference was not statistically significant.

Effects of calcium hydroxide addition on the physical and chemical properties of a calcium silicate-based sealer.

PubMed

Kuga, Milton Carlos; Duarte, Marco Antonio Hungaro; Sant'anna-Júnior, Arnaldo; Keine, Kátia Cristina; Faria, Gisele; Dantas, Andrea Abi Rached; Guiotti, Flávia Angélica

2014-06-01

Recently, various calcium silicate-based sealers have been introduced for use in root canal filling. The MTA Fillapex is one of these sealers, but some of its physicochemical properties are not in accordance with the ISO requirements. The aim of this study was to evaluate the flowability, pH level and calcium release of pure MTA Fillapex (MTAF) or containing 5% (MTAF5) or 10% (MTAF10) calcium hydroxide (CH), in weight, in comparison with AH Plus sealer. The flowability test was performed according to the ISO 6876:2001 requirements. For the pH level and calcium ion release analyses, the sealers were placed individually (n=10) in plastic tubes and immersed in deionized water. After 24 hours, 7 and 14 days, the water in which each specimen had been immersed was evaluated to determine the pH level changes and calcium released. Flowability, pH level and calcium release data were analyzed statistically by the ANOVA test (α=5%). In relation to flowability: MTAF>AH Plus>MTAF5>MTAF10. In relation to the pH level, for 24 h: MTAF5=MTAF10=MTAF>AH Plus; for 7 and 14 days: MTAF5=MTAF10>MTAF>AH Plus. For the calcium release, for all periods: MTAF>MTAF5=MTAF10>AH Plus. The addition of 5% CH to the MTA Fillapex (in weight) is an alternative to reduce the high flowability presented by the sealer, without interfering in its alkalization potential.

Evaluation of Serum Calcium as a Predictor of Biochemical Recurrence following Salvage Radiation Therapy for Prostate Cancer

PubMed Central

Peterson, Jennifer L.; Buskirk, Steven J.; Heckman, Michael G.; Parker, Alexander S.; Diehl, Nancy N.; Tzou, Katherine S.; Paryani, Nitesh N.; Ko, Stephen J.; Daugherty, Larry C.; Vallow, Laura A.; Pisansky, Thomas M.

2013-01-01

Background. Previous reports have shown a positive association between serum calcium level and prostate cancer mortality. However, there is no data regarding whether higher serum calcium levels are associated with increased risk of biochemical recurrence (BCR) following salvage radiation therapy (SRT) for prostate cancer. Herein, we evaluate the association between pretreatment serum calcium levels and BCR in a cohort of men who underwent SRT. Methods. We evaluated 165 patients who underwent SRT at our institution. Median dose was 65.0 Gy (range: 54.0–72.4 Gy). We considered serum calcium as both a continuous variable and a 3-level categorical variable (low [≤9.0 mg/dL], moderate [>9.0 mg/dL and ≤9.35 mg/dL], and high [>9.35 mg/dL]) based on sample tertiles. Results. We observed no evidence of a linear association between serum calcium and BCR (relative risk (RR): 0.96, P = 0.76). Compared to men with low calcium, there was no significantly increased risk of BCR for men with moderate (RR: 0.94, P = 0.79) or high (RR: 1.08, P = 0.76) serum calcium levels. Adjustment for clinical, pathological, and SRT characteristics in multivariable analyses did not alter these findings. Conclusion. Our results provide evidence that pretreatment serum calcium is unlikely to be a useful tool in predicting BCR risk following SRT. PMID:23606986

Effect of Oestrogen on Altering the Serum and Urinary Levels of Calcium, Phosphate and Magnesium in Hysterectomised Women Compared to Natural Menopausal South Indian Women: A Case Control Study.

PubMed

Sonu, Yeldose; Avinash, S S; Sreekantha; Arun Kumar, K; Malathi, M; Shivashankara, A R

2016-07-01

Given the paucity of studies conducted to know the effect of suddenness and earlier onset of endocrinological changes associated with hysterectomy, on the serum and urinary levels of calcium, magnesium and phosphate the present study was conducted to compare the levels of calcium, magnesium and phosphate in serum and urine of hysterectomised and natural menopausal south Indian women. This is a cross-sectional observational study. The study included three groups of 30 healthy premenopausal, 30 early surgical menopausal and 30 natural post menopausal women. Women suffering from any endocrine disease were excluded. Analysis was performed in serum and urine sample. The levels of calcium, magnesium and phosphate in serum and calcium/creatinine, magnesium/creatinine and phosphate/creatinine ratio were estimated in urine by spectrophotometric method. Hysterectomised women (serum calcium: 8.7 ± 0.09 mg/dl; urine calcium/creatinine: 0.16 ± 0.02) have significantly low serum calcium (p < 0.001) and high urinary calcium/creatinine (p = 0.002) ratio and post menopausal women (serum magnesium: 2.1 ± 0.03; serum phosphate: 4.4 ± 0.16; urinary calcium/creatinine: 0.17 ± 0.02; urinary magnesium/creatinine: 0.09 ± 0.01) have significantly high serum magnesium (p = 0.016), serum phosphate (p = 0.043) and high urinary calcium/creatinine (p = 0.002), magnesium/creatinine ratio (p = 0.025) compared to healthy pre menopausal women. Post menopausal women (serum calcium: 9.1 ± 0.08) have significantly high serum calcium and phosphate compared to hysterectomised women (serum phosphate: 3.93 ± 0.11). Hysterectomised women have significantly low serum calcium, oestrogen and high urinary calcium/creatinine ratio compared to healthy premenopausal women and low serum calcium and low serum phosphate compared to natural postmenopausal women. Natural postmenopausal women had low serum oestrogen and high serum magnesium, serum phosphate, urinary calcium creatinine ratio and urinary magnesium creatinine ratio compared to healthy premenopausal women.

Association Between Serum Calcium Level and Extent of Bleeding in Patients With Intracerebral Hemorrhage.

PubMed

Morotti, Andrea; Charidimou, Andreas; Phuah, Chia-Ling; Jessel, Michael J; Schwab, Kristin; Ayres, Alison M; Romero, Javier M; Viswanathan, Anand; Gurol, M Edip; Greenberg, Steven M; Anderson, Christopher D; Rosand, Jonathan; Goldstein, Joshua N

2016-11-01

Calcium is a key cofactor of the coagulation cascade and may play a role in the pathophysiology of intracerebral hemorrhage (ICH). To investigate whether a low serum calcium level is associated with an increase in the extent of bleeding in patients with ICH as measured by baseline hematoma volume and risk of hematoma expansion. Prospective cohort study of 2103 consecutive patients with primary ICH ascertained during the period between 1994 and 2015 at an academic medical center. The statistical analysis was performed in January 2016. Total calcium level was measured on admission, and hypocalcemia was defined as a serum calcium level of less than 8.4 mg/dL. Baseline and follow-up hematoma volumes, detected by noncontrast computed tomography, were measured using a computer-assisted semiautomatic analysis. Hematoma expansion was defined as an increase of more than 30% or 6 mL from baseline ICH volume. Associations between serum calcium level and baseline hematoma volume and between serum calcium level and ICH expansion were investigated in multivariable linear and logistic regression models, respectively. A total of 2123 patients with primary ICH were screened, and 2103 patients met the inclusion criteria (mean [SD] age, 72.7 [12.5] years; 54.3% male patients), of whom 229 (10.9%) had hypocalcemia on admission. Hypocalcemic patients had a higher median baseline hematoma volume than did normocalcemic patients (37 mL [IQR, 15-72 mL] vs 16 mL [IQR, 6-44 mL]; P < .001). Low calcium levels were independently associated with higher baseline ICH volume (β = -0.13, SE = .03, P < .001). A total of 1393 patients underwent follow-up noncontrast computed tomography and were included in the ICH expansion analysis. In this subgroup, a higher serum calcium level was associated with reduced risk of ICH expansion (odds ratio, 0.55 [95% CI, 0.35-0.86]; P = .01), after adjusting for other confounders. Hypocalcemia correlates with the extent of bleeding in patients with ICH. A low calcium level may be associated with a subtle coagulopathy predisposing to increased bleeding and might therefore be a promising therapeutic target for acute ICH treatment trials.

Human colon tissue in organ culture: calcium and multi-mineral-induced mucosal differentiation

PubMed Central

Dame, Michael K.; Veerapaneni, Indiradevi; Bhagavathula, Narasimharao; Naik, Madhav; Varani, James

2011-01-01

We have recently shown that a multi-mineral extract from the marine red algae, Lithothamnion calcareum, suppresses colon polyp formation and inflammation in mice. In the present study, we used intact human colon tissue in organ culture to compare responses initiated by Ca2+ supplementation versus the multi-mineral extract. Normal human colon tissue was treated for 2 d in culture with various concentrations of calcium or the mineral-rich extract. The tissue was then prepared for histology/immunohistochemistry, and the culture supernatants were assayed for levels of type I procollagen and type I collagen. At higher Ca2+ concentrations or with the mineral-rich extract, proliferation of epithelial cells at the base and walls of the mucosal crypts was suppressed, as visualized by reduced Ki67 staining. E-cadherin, a marker of differentiation, was more strongly expressed at the upper third of the crypt and at the luminal surface. Treatment with Ca2+ or with the multi-mineral extract influenced collagen turnover, with decreased procollagen and increased type I collagen. These data suggest that calcium or mineral-rich extract has the capacity to (1) promote differentiation in human colon tissue in organ culture and (2) modulate stromal function as assessed by increased levels of type I collagen. Taken together, these data suggest that human colon tissue in organ culture (supporting in vivo finding in mice) will provide a valuable model for the preclinical assessment of agents that regulate growth and differentiation in the colonic mucosa. PMID:21104039

Effects of microgravity on bone and calcium homeostasis

NASA Astrophysics Data System (ADS)

Zérath, E.

Mechanical function is known to be of crucial importance for the maintenance of bone tissue. Gravity on one hand and muscular effort on the other hand are required for normal skeletal structure. It has been shown by numerous experimental studies that loss of total-body calcium, and marked skeletal changes occur in people who have flown in space. However, most of the pertinent investigations have been conducted on animal models, including rats and non-human primates, and a reasonably clear picture of bone response to spaceflight has emerged during the past few years. Osteopenia induced by microgravity was found to be associated with reduction in both cortical and trabecular bone formation, alteration in mineralization patterns, and disorganization of collagen, and non-collagenous protein metabolism. Recently, cell-culture techniques have offered a direct approach of altered gravity effects at the osteoblastic-cell level. But the fundamental mechanisms by which bone and calcium are lost during spaceflight are not yet fully known. Infrequenccy and high financial cost of flights have created the necessity to develop on-Earth models designed to mimic weightlessness effects. Antiorthostatic suspension devices are now commonly used to obtain hindlimb unloading in rats, with skeletal effects similar to those observed after spaceflight. Therefore, actual and ``simulated'' spaceflights, with investigations conducted at whole body and cellular levels, are needed to elucidate pathogeny of bone loss in space, to develop effective countermeasures, and to study recovery processes of bone changes after return to Earth.

Gentamicin treatment in exercised mdx mice: Identification of dystrophin-sensitive pathways and evaluation of efficacy in work-loaded dystrophic muscle.

PubMed

De Luca, Annamaria; Nico, Beatrice; Rolland, Jean-François; Cozzoli, Anna; Burdi, Rosa; Mangieri, Domenica; Giannuzzi, Viviana; Liantonio, Antonella; Cippone, Valentina; De Bellis, Michela; Nicchia, Grazia Paola; Camerino, Giulia Maria; Frigeri, Antonio; Svelto, Maria; Camerino, Diana Conte

2008-11-01

Aminoglycosides force read through of premature stop codon mutations and introduce new mutation-specific gene-corrective strategies in Duchenne muscular dystrophy. A chronic treatment with gentamicin (32 mg/kg/daily i.p., 8-12 weeks) was performed in exercised mdx mice with the dual aim to clarify the dependence on dystrophin of the functional, biochemical and histological alterations present in dystrophic muscle and to verify the long term efficiency of small molecule gene-corrective strategies in work-loaded dystrophic muscle. The treatment counteracted the exercise-induced impairment of in vivo forelimb strength after 6-8 weeks. We observed an increase in dystrophin expression level in all the fibers, although lower than that observed in normal fibers, and found a concomitant recovery of aquaporin-4 at sarcolemma. A significant reduction in centronucleated fibers, in the area of necrosis and in the percentage of nuclear factor-kB-positive nuclei was observed in gastrocnemious muscle of treated animals. Plasma creatine kinase was reduced by 70%. Ex vivo, gentamicin restored membrane ionic conductance in mdx diaphragm and limb muscle fibers. No effects were observed on the altered calcium homeostasis and sarcolemmal calcium permeability, detected by electrophysiological and microspectrofluorimetric approaches. Thus, the maintenance of a partial level of dystrophin is sufficient to reinforce sarcolemmal stability, reducing leakiness, inflammation and fiber damage, while correction of altered calcium homeostasis needs greater expression of dystrophin or direct interventions on the channels involved.

Effects of isoflurane anesthesia on ensemble patterns of Ca2+ activity in mouse v1: reduced direction selectivity independent of increased correlations in cellular activity.

PubMed

Goltstein, Pieter M; Montijn, Jorrit S; Pennartz, Cyriel M A

2015-01-01

Anesthesia affects brain activity at the molecular, neuronal and network level, but it is not well-understood how tuning properties of sensory neurons and network connectivity change under its influence. Using in vivo two-photon calcium imaging we matched neuron identity across episodes of wakefulness and anesthesia in the same mouse and recorded spontaneous and visually evoked activity patterns of neuronal ensembles in these two states. Correlations in spontaneous patterns of calcium activity between pairs of neurons were increased under anesthesia. While orientation selectivity remained unaffected by anesthesia, this treatment reduced direction selectivity, which was attributable to an increased response to the null-direction. As compared to anesthesia, populations of V1 neurons coded more mutual information on opposite stimulus directions during wakefulness, whereas information on stimulus orientation differences was lower. Increases in correlations of calcium activity during visual stimulation were correlated with poorer population coding, which raised the hypothesis that the anesthesia-induced increase in correlations may be causal to degrading directional coding. Visual stimulation under anesthesia, however, decorrelated ongoing activity patterns to a level comparable to wakefulness. Because visual stimulation thus appears to 'break' the strength of pairwise correlations normally found in spontaneous activity under anesthesia, the changes in correlational structure cannot explain the awake-anesthesia difference in direction coding. The population-wide decrease in coding for stimulus direction thus occurs independently of anesthesia-induced increments in correlations of spontaneous activity.

Effects of Isoflurane Anesthesia on Ensemble Patterns of Ca2+ Activity in Mouse V1: Reduced Direction Selectivity Independent of Increased Correlations in Cellular Activity

PubMed Central

Goltstein, Pieter M.; Montijn, Jorrit S.; Pennartz, Cyriel M. A.

2015-01-01

Anesthesia affects brain activity at the molecular, neuronal and network level, but it is not well-understood how tuning properties of sensory neurons and network connectivity change under its influence. Using in vivo two-photon calcium imaging we matched neuron identity across episodes of wakefulness and anesthesia in the same mouse and recorded spontaneous and visually evoked activity patterns of neuronal ensembles in these two states. Correlations in spontaneous patterns of calcium activity between pairs of neurons were increased under anesthesia. While orientation selectivity remained unaffected by anesthesia, this treatment reduced direction selectivity, which was attributable to an increased response to the null-direction. As compared to anesthesia, populations of V1 neurons coded more mutual information on opposite stimulus directions during wakefulness, whereas information on stimulus orientation differences was lower. Increases in correlations of calcium activity during visual stimulation were correlated with poorer population coding, which raised the hypothesis that the anesthesia-induced increase in correlations may be causal to degrading directional coding. Visual stimulation under anesthesia, however, decorrelated ongoing activity patterns to a level comparable to wakefulness. Because visual stimulation thus appears to ‘break’ the strength of pairwise correlations normally found in spontaneous activity under anesthesia, the changes in correlational structure cannot explain the awake-anesthesia difference in direction coding. The population-wide decrease in coding for stimulus direction thus occurs independently of anesthesia-induced increments in correlations of spontaneous activity. PMID:25706867

Prostaglandin D2 regulates human colonic ion transport via the DP1 receptor.

PubMed

Medani, M; Collins, D; Mohan, H M; Walsh, E; Winter, D C; Baird, A W

2015-02-01

Prostaglandin D2 is released by mast cells and is important in allergies. Its role in gastrointestinal function is not clearly defined. This study aimed to determine the effect of exogenous PGD2 on ion transport in ex vivo normal human colonic mucosa. Mucosal sheets were mounted in Ussing chambers and voltage clamped to zero electric potential. Ion transport was quantified as changes in short-circuit current. In separate experiments epithelial monolayers or colonic crypts, isolated by calcium chelation, were treated with PGD2 and cAMP levels determined by ELISA or calcium levels were determined by fluorimetry. PGD2 caused a sustained, concentration-dependent rise in short-circuit current by increasing chloride secretion (EC50=376nM). This effect of PGD2 is mediated by the DP1 receptor, as the selective DP1 receptor antagonist BW A686C inhibited PGD2-induced but not PGE2-induced rise in short-circuit current. PGD2 also increased intracellular cAMP in isolated colonic crypts with no measurable influence on cytosolic calcium. PGD2 induces chloride secretion in isolated human colonic mucosa in a concentration-dependent manner with concomitant elevation of cytoplasmic cAMP in epithelial cells. The involvement of DP2 receptor subtypes has not previously been considered in regulation of ion transport in human intestine. Since inflammatory stimuli may induce production of eicosanoids, selective regulation of these pathways may be pivotal in determining therapeutic strategies and in understanding disease. Copyright © 2014. Published by Elsevier Inc.

Randomized crossover study comparing the phosphate-binding efficacy of calcium ketoglutarate versus calcium carbonate in patients on chronic hemodialysis.

PubMed

Bro, S; Rasmussen, R A; Handberg, J; Olgaard, K; Feldt-Rasmussen, B

1998-02-01

The objective of the study was to evaluate the phosphate-binding efficacy, side effects, and cost of therapy of calcium ketoglutarate granulate as compared with calcium carbonate tablets in patients on chronic hemodialysis. The study design used was a randomized, crossover open trial, and the main outcome measurements were plasma ionized calcium levels, plasma phosphate levels, plasma intact parathyroid hormone (PTH) levels, requirements for supplemental aluminum-aminoacetate therapy, patient tolerance, and cost of therapy. Nineteen patients on chronic hemodialysis were treated with a dialysate calcium concentration of 1.25 mmol/L and a fixed alfacalcidol dose for at least 2 months. All had previously tolerated therapy with calcium carbonate. Of the 19 patients included, 10 completed both treatment arms. After 12 weeks of therapy, the mean (+/-SEM) plasma ionized calcium level was significantly lower in the ketoglutarate arm compared with the calcium carbonate arm (4.8+/-0.1 mg/dL v 5.2+/-0.1 mg/dL; P = 0.004), whereas the mean plasma phosphate (4.5+/-0.3 mg/dL v 5.1+/-0.1 mg/dL) and PTH levels (266+/-125 pg/mL v 301+/-148 pg/mL) did not differ significantly between the two treatment arms. Supplemental aluminum-aminoacetate was not required during calcium ketoglutarate treatment, while two patients needed this supplement when treated with calcium carbonate. Five of 17 (29%) patients were withdrawn from calcium ketoglutarate therapy within 1 to 2 weeks due to intolerance (anorexia, vomiting, diarrhea, general uneasiness), whereas the remaining 12 patients did not experience any side effects at all. The five patients with calcium ketoglutarate intolerance all had pre-existing gastrointestinal symptoms; four of them had received treatment with cimetidine or omeprazol before inclusion into the study. Calculations based on median doses after 12 weeks showed that the cost of the therapy in Denmark was 10 times higher for calcium ketoglutarate compared with calcium carbonate (US$6.00/d v US$0.65/d). Calcium ketoglutarate may be an effective and safe alternative to treatment with aluminum-containing phosphate binders in patients on hemodialysis who are intolerant of calcium carbonate or acetate because of hypercalcemia. However, care must be exercised when dealing with patients with pre-existing gastrointestinal discomfort. Due to the high cost of the therapy, calcium ketoglutarate should be used only for selected patients.

Combined system for high-time-resolution dual-excitation fluorescence photometry and fluorescence imaging of calcium transients in single normal and diseased skeletal muscle fibers

NASA Astrophysics Data System (ADS)

Uttenweiler, Dietmar; Wojciechowski, Reinhold; Makabe, Makoto; Veigel, Claudia; Fink, Rainer H.

1994-12-01

Fast photometric measurements and video-imaging of fluorescent indicators both are powerful tools in measuring the intracellular free calcium concentration of muscle and many other cells. as photometric systems yield a high temporal resolution, calcium imaging systems have high spatial but significantly reduced temporal resolution. Therefore we have developed an integrated system combining both methods and based mostly on standard components. As a common, sensitive Ca2+- indicator we used the fluorescent probe Fura-2, which is alternatingly excited for ratio measurements at 340/380 nm. We used a commercially available dual excitation photometric system (OSP-3; Olympus) for attaching a CCD-camera and a frame grabber board. To achieve the synchronization we had to design circuitries for external triggering, synchronization and accurate control of the filter changer, which we added to the system. Additionally, the software for a triggered image acquisition was developed. With this integrated setup one can easily switch between the fast photometric mode (ratio frequency 100 Hz) and the imaging mode (ratio frequency 4.17 Hz). The calcium images are correlated with the 25 times faster spot measurements and are analyzed by means of image processing. With this combined system we study release and uptake of calcium ions of normal and diseased skeletal muscle from mdx mice. Such a system will also be important for other cellular studies in which fluorescence indicators are used to monitor similar time dependent alterations as well as changes in cellular distributions of calcium.

Deliberate total parathyroidectomy: a potentially novel therapy for tumor-induced hypophosphatemic osteomalacia.

PubMed

Bhadada, Sanjay K; Palnitkar, Saroj; Qiu, Shijing; Parikh, Nayana; Talpos, Gary B; Rao, Sudhaker D

2013-11-01

Tumor-induced osteomalacia (TIO) is an acquired hypophosphatemic metabolic bone disorder that can be cured by removing or ablating the offending tumor. However, when the tumor cannot be localized, lifelong therapy with oral phosphate and calcitriol or cinacalcet with close monitoring is required. A 56-year-old man was diagnosed with TIO in 1990. Initial therapy consisted of oral phosphate and calcitriol with symptomatic and biochemical improvement and healing of osteomalacia. Eight years later, hypercalcemic hyperparathyroidism developed, requiring subtotal parathyroidectomy with a transient increase in serum phosphate and normalization of serum calcium and PTH. Recurrent hypercalcemic hyperparathyroidism developed after 10 years of medical therapy. A deliberate total parathyroidectomy produced a prompt rise in serum phosphate into the normal range > 3.0 mg/dL and remained normal during the next 4 years of follow-up, despite continued very high serum fibroblast growth factor-23 levels throughout the 23-year follow-up. We report an unusual case of a TIO patient with long-term follow-up who developed recurrent hypercalcemic hyperparathyroidism on long-term oral phosphate therapy. Deliberate total parathyroidectomy normalized serum phosphate despite persistently elevated fibroblast growth factor-23 levels. Total parathyroidectomy offers a potentially novel therapy in some patients with TIO in whom medical therapy is not feasible or the tumor is unresectable.

Calcium supplementation prevents endothelial cell activation: possible relevance to preeclampsia.

PubMed

Chen, Qi; Tong, Mancy; Wu, Man; Stone, Peter R; Snowise, Saul; Chamley, Lawrence W

2013-09-01

Preeclampsia is a leading cause of maternal and fetal mortality and morbidity. A hallmark of preeclampsia is endothelial cell dysfunction/activation in response to 'toxins' from the placenta. Necrotic trophoblastic debris (NTD) is one possible placental toxin and other activators of endothelial cells include inflammatory cytokines. Calcium supplementation appears to protect 'at-risk' women from developing preeclampsia but how is unclear. Placental explants were cultured with interleukin-6 (IL-6) in varied concentrations of calcium. The resultant trophoblastic debris was exposed to endothelial cells. Endothelial cells were exposed to activators including NTD, IL-6, and preeclamptic sera in the presence of varied concentrations of calcium and activation monitored by quantifying cell surface markers by ELISA. Raising the levels of calcium did not prevent the IL-6-induced shedding of NTD from placental explants but did prevent the activation of endothelial cells in response to IL-6, preeclamptic sera, or NTD. Reducing the level of calcium directly induced the activation of endothelial cells. Inhibiting nitric oxide synthetase ablated the ability of high calcium levels to protect endothelial cell activation. The activity of endothelial cell nitric oxide synthetase was blocked with L-N-nitroarginine methyl ester. Our results demonstrate calcium levels do not affect the shedding of trophoblastic debris but are important to endothelial cell activation and supplemental calcium may reverse the activation of the endothelium in preeclamptic women. These results may in part explain the benefits of calcium supplementation in the reduction of risk for developing preeclampsia and provide in-vitro mechanistic support for the use of calcium supplementation in at-risk women.

Effect of methanolic extract of Musa sapientum leaves on gastrointestinal transit time in normal and alloxan induced diabetic rats: possible mechanism of action.

PubMed

Adewoye, E O; Ige, A O; Latona, C T

2011-11-23

Disorders of gastrointestinal motility have been associated with diabetes mellitus. Hyperglycaemia particularly has been reported to inhibit gastrointestinal transit time while glibenclamide, a sulphonylurea and insulin, both increased transit time. Musa sapientum has also been reported as an antidiabetic agent but there is dearth of information on the effect of this plant on gastrointestinal motility. This study was therefore carried out to investigate the effect of methanolic extract of Musa sapientum leaves (MEMSL) on gastrointestinal transit time (GITT) in male albino rats with and without hyperglycaemia and to elucidate possible mechanism by which this extract functions. Fifty five albino rats were divided into 11 groups of five animals each. All animals were fasted for 24hrs before the begining of the experiment. Group 1 served as control; while the remaining groups (2 - 11) were treated with 250mg/kg; 500mg/kg MEMSL; diabetic control; diabetic treated with 250mg/kg; 500mg/kg MEMSL; diabetic treated with glibenclamide (5mg/kg); normal rats treated with nifedipine (50mg/kg); normal rats treated with calcium chloride (CaCl2) only (10mg/kg); groups 10 and 11 were both pretreated with CaCl2 and subsequently treated with 250mg/kg and 500mg/kg MEMSL respectively. All plant extracts used for treatments were dissolved in normal saline and administered orally using orogastric tube. Charcoal meal was used as marker in the estimation of GITT. The study showed significant decrease in GITT in the normal rats treated with 250mg/kg and 500mg/kg of extract. However, in the diabetic rats treated with 500mg/kg MEMSL, there was significant increase in GITT and this is comparable with the gut response to glibenclamide (5mg/kg). Musa sapientum extract produced significant decrease in transit time in the calcium chloride pre-treated normal rats and this is comparable to the effect observed in Nifedipine treated group. The significant reduction in GITT produced by MEMSL in the normal rats reflects a strong possibility of MEMSL acting as calcium channel antagonist through the voltage gated calcium channel which may be due to the presence of alkaloids, saponins, cardenolides. There is the possibility of the extract acting as an inhibitor of potassium channel at higher concentration as observed in glibenclamide treated groups.

Calcium sensor regulation of the CaV2.1 Ca2+ channel contributes to long-term potentiation and spatial learning.

PubMed

Nanou, Evanthia; Scheuer, Todd; Catterall, William A

2016-11-15

Many forms of short-term synaptic plasticity rely on regulation of presynaptic voltage-gated Ca 2+ type 2.1 (Ca V 2.1) channels. However, the contribution of regulation of Ca V 2.1 channels to other forms of neuroplasticity and to learning and memory are not known. Here we have studied mice with a mutation (IM-AA) that disrupts regulation of Ca V 2.1 channels by calmodulin and related calcium sensor proteins. Surprisingly, we find that long-term potentiation (LTP) of synaptic transmission at the Schaffer collateral-CA1 synapse in the hippocampus is substantially weakened, even though this form of synaptic plasticity is thought to be primarily generated postsynaptically. LTP in response to θ-burst stimulation and to 100-Hz tetanic stimulation is much reduced. However, a normal level of LTP can be generated by repetitive 100-Hz stimulation or by depolarization of the postsynaptic cell to prevent block of NMDA-specific glutamate receptors by Mg 2+ The ratio of postsynaptic responses of NMDA-specific glutamate receptors to those of AMPA-specific glutamate receptors is decreased, but the postsynaptic current from activation of NMDA-specific glutamate receptors is progressively increased during trains of stimuli and exceeds WT by the end of 1-s trains. Strikingly, these impairments in long-term synaptic plasticity and the previously documented impairments in short-term synaptic plasticity in IM-AA mice are associated with pronounced deficits in spatial learning and memory in context-dependent fear conditioning and in the Barnes circular maze. Thus, regulation of Ca V 2.1 channels by calcium sensor proteins is required for normal short-term synaptic plasticity, LTP, and spatial learning and memory in mice.

Vitamin D Is a Regulator of Endothelial Nitric Oxide Synthase and Arterial Stiffness in Mice

PubMed Central

Andrukhova, Olena; Slavic, Svetlana; Zeitz, Ute; Riesen, Sabine C.; Heppelmann, Monika S.; Ambrisko, Tamas D.; Markovic, Mato; Kuebler, Wolfgang M.

2014-01-01

The vitamin D hormone 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] is essential for the preservation of serum calcium and phosphate levels but may also be important for the regulation of cardiovascular function. Epidemiological data in humans have shown that vitamin D insufficiency is associated with hypertension, left ventricular hypertrophy, increased arterial stiffness, and endothelial dysfunction in normal subjects and in patients with chronic kidney disease and type 2 diabetes. However, the pathophysiological mechanisms underlying these associations remain largely unexplained. In this study, we aimed to decipher the mechanisms by which 1,25(OH)2D3 may regulate systemic vascular tone and cardiac function, using mice carrying a mutant, functionally inactive vitamin D receptor (VDR). To normalize calcium homeostasis in VDR mutant mice, we fed the mice lifelong with the so-called rescue diet enriched with calcium, phosphate, and lactose. Here, we report that VDR mutant mice are characterized by lower bioavailability of the vasodilator nitric oxide (NO) due to reduced expression of the key NO synthesizing enzyme, endothelial NO synthase, leading to endothelial dysfunction, increased arterial stiffness, increased aortic impedance, structural remodeling of the aorta, and impaired systolic and diastolic heart function at later ages, independent of changes in the renin-angiotensin system. We further demonstrate that 1,25(OH)2D3 is a direct transcriptional regulator of endothelial NO synthase. Our data demonstrate the importance of intact VDR signaling in the preservation of vascular function and may provide a mechanistic explanation for epidemiological data in humans showing that vitamin D insufficiency is associated with hypertension and endothelial dysfunction. PMID:24284821

A magnesium based phosphate binder reduces vascular calcification without affecting bone in chronic renal failure rats.

PubMed

Neven, Ellen; De Schutter, Tineke M; Dams, Geert; Gundlach, Kristina; Steppan, Sonja; Büchel, Janine; Passlick-Deetjen, Jutta; D'Haese, Patrick C; Behets, Geert J

2014-01-01

The alternative phosphate binder calcium acetate/magnesium carbonate (CaMg) effectively reduces hyperphosphatemia, the most important inducer of vascular calcification, in chronic renal failure (CRF). In this study, the effect of low dose CaMg on vascular calcification and possible effects of CaMg on bone turnover, a persistent clinical controversy, were evaluated in chronic renal failure rats. Adenine-induced CRF rats were treated daily with 185 mg/kg CaMg or vehicle for 5 weeks. The aortic calcium content and area% calcification were measured to evaluate the effect of CaMg. To study the effect of CaMg on bone remodeling, rats underwent 5/6th nephrectomy combined with either a normal phosphorus diet or a high phosphorus diet to differentiate between possible bone effects resulting from either CaMg-induced phosphate deficiency or a direct effect of Mg. Vehicle or CaMg was administered at doses of 185 and 375 mg/kg/day for 8 weeks. Bone histomorphometry was performed. Aortic calcium content was significantly reduced by 185 mg/kg/day CaMg. CaMg ameliorated features of hyperparathyroid bone disease. In CRF rats on a normal phosphorus diet, the highest CaMg dose caused an increase in osteoid area due to phosphate depletion. The high phosphorus diet combined with the highest CaMg dose prevented the phosphate depletion and thus the rise in osteoid area. CaMg had no effect on osteoblast/osteoclast or dynamic bone parameters, and did not alter bone Mg levels. CaMg at doses that reduce vascular calcification did not show any harmful effect on bone turnover.

Erosion protection by calcium lactate/sodium fluoride rinses under different salivary flows in vitro.

PubMed

Borges, Alessandra B; Scaramucci, Taís; Lippert, Frank; Zero, Domenick T; Hara, Anderson T

2014-01-01

This study investigated the effect of a calcium lactate prerinse on sodium fluoride protection in an in vitro erosion-remineralization model simulating two different salivary flow rates. Enamel and dentin specimens were randomly assigned to 6 groups (n = 8), according to the combination between rinse treatments - deionized water (DIW), 12 mM NaF (NaF) or 150 mM calcium lactate followed by NaF (CaL + NaF) - and unstimulated salivary flow rates - 0.5 or 0.05 ml/min - simulating normal and low salivary flow rates, respectively. The specimens were placed into custom-made devices, creating a sealed chamber on the specimen surface connected to a peristaltic pump. Citric acid was injected into the chamber for 2 min, followed by artificial saliva (0.5 or 0.05 ml/min) for 60 min. This cycle was repeated 4×/day for 3 days. Rinse treatments were performed daily 30 min after the 1st and 4th erosive challenges, for 1 min each time. Surface loss was determined by optical profilometry. KOH-soluble fluoride and structurally bound fluoride were determined in specimens at the end of the experiment. Data were analyzed by 2-way ANOVA and Tukey tests (α = 0.05). NaF and CaL + NaF exhibited significantly lower enamel and dentin loss than DIW, with no difference between them for normal flow conditions. The low salivary flow rate increased enamel and dentin loss, except for CaL + NaF, which presented overall higher KOH-soluble and structurally bound fluoride levels. The results suggest that the NaF rinse was able to reduce erosion progression. Although the CaL prerinse considerably increased F availability, it enhanced NaF protection against dentin erosion only under hyposalivatory conditions.

The l-α-Lysophosphatidylinositol/GPR55 System and Its Potential Role in Human Obesity

PubMed Central

Moreno-Navarrete, José María; Catalán, Victoria; Whyte, Lauren; Díaz-Arteaga, Adenis; Vázquez-Martínez, Rafael; Rotellar, Fernando; Guzmán, Rocío; Gómez-Ambrosi, Javier; Pulido, Marina R.; Russell, Wendy R.; Imbernón, Mónica; Ross, Ruth A.; Malagón, María M.; Dieguez, Carlos; Fernández-Real, José Manuel; Frühbeck, Gema; Nogueiras, Ruben

2012-01-01

GPR55 is a putative cannabinoid receptor, and l-α-lysophosphatidylinositol (LPI) is its only known endogenous ligand. We investigated 1) whether GPR55 is expressed in fat and liver; 2) the correlation of both GPR55 and LPI with several metabolic parameters; and 3) the actions of LPI on human adipocytes. We analyzed CB1, CB2, and GPR55 gene expression and circulating LPI levels in two independent cohorts of obese and lean subjects, with both normal or impaired glucose tolerance and type 2 diabetes. Ex vivo experiments were used to measure intracellular calcium and lipid accumulation. GPR55 levels were augmented in the adipose tissue of obese subjects and further so in obese patients with type 2 diabetes when compared with nonobese subjects. Visceral adipose tissue GPR55 correlated positively with weight, BMI, and percent fat mass, particularly in women. Hepatic GPR55 gene expression was similar in obese and type 2 diabetic subjects. Circulating LPI levels were increased in obese patients and correlated with fat percentage and BMI in women. LPI increased the expression of lipogenic genes in visceral adipose tissue explants and intracellular calcium in differentiated visceral adipocytes. These findings indicate that the LPI/GPR55 system is positively associated with obesity in humans. PMID:22179809

Levetiracetam Reverses Synaptic Deficits Produced by Overexpression of SV2A

PubMed Central

Yao, Jia; Bleckert, Adam; Hill, Jessica; Bajjalieh, Sandra M.

2011-01-01

Levetiracetam is an FDA-approved drug used to treat epilepsy and other disorders of the nervous system. Although it is known that levetiracetam binds the synaptic vesicle protein SV2A, how drug binding affects synaptic functioning remains unknown. Here we report that levetiracetam reverses the effects of excess SV2A in autaptic hippocampal neurons. Expression of an SV2A-EGFP fusion protein produced a ∼1.5-fold increase in synaptic levels of SV2, and resulted in reduced synaptic release probability. The overexpression phenotype parallels that seen in neurons from SV2 knockout mice, which experience severe seizures. Overexpression of SV2A also increased synaptic levels of the calcium-sensor protein synaptotagmin, an SV2-binding protein whose stability and trafficking are regulated by SV2. Treatment with levetiracetam rescued normal neurotransmission and restored normal levels of SV2 and synaptotagmin at the synapse. These results indicate that changes in SV2 expression in either direction impact neurotransmission, and suggest that levetiracetam may modulate SV2 protein interactions. PMID:22220214

Biochemical effects of lead exposure on battery manufacture workers with reference to blood pressure, calcium metabolism and bone mineral density.

PubMed

Dongre, Nilima N; Suryakar, Adinath N; Patil, Arun J; Hundekari, Indira A; Devarnavadagi, Basavaraj B

2013-01-01

Lead is one of the most widely scattered toxic metals in the environment and used by mankind for over 9,000 years. Lead in the environment may be derived from natural or anthropogenic sources. In humans, lead can cause a wide range of biological effects depending upon the level and duration of exposure. The purpose of this study was to find out the effect of lead exposure on systolic and diastolic blood pressure, serum calcium, ionized calcium, phosphorus, parathyroid hormone and vitamin D and examine the overall effect of all these parameters on the bone mineral density of battery manufacture workers. For this study ninety battery manufacture workers were selected and divided in three groups depending upon duration of lead exposure. Group I-workers with duration of lead exposure 1-5 years, Group II-workers with duration of lead exposure 6-10 years and Group III-workers with duration of lead exposure more than 10 years. Each group consisted of thirty workers. Thirty age matched healthy control subjects were taken for comparison. Demographic, occupational and clinical data were collected by using questionnaire and interview. The venous blood samples were collected from the study groups and normal healthy control group. At the time of blood collection random urine samples were collected in amber coloured bottles. The biochemical parameters were estimated by using standard assay procedures. Statistical analysis of the data was done using independent student't' test for parametric variables. Values were expressed as mean ± standard deviation (SD). P values of 0.05 or less were considered to be statistically significant. The blood lead levels and urinary lead levels of all workers were significantly increased (P < 0.001) in proportion to the duration of lead exposure as compared to controls. Systolic and diastolic blood pressure were significantly raised (P < 0.001) in all three study groups of battery manufacture workers as compared to controls. Serum Calcium, Ionized calcium, phosphorus were significantly decreased (P < 0.001) in all the three study groups. Serum vitamin D levels were lowered (P < 0.01) and serum PTH was increased (P < 0.01) in workers as compared to controls. The results of this study clearly indicate that the absorption of lead is more in these workers which adversely affects blood pressure, disturbs calcium and phosphorus metabolism which further impairs mineralization of bone resulting in decreased bone mineral density observed in these workers. Lead toxicity is still persistent in battery manufacture workers though they are using sophisticated techniques in these industries. There is a need to protect the workers from the health hazards of occupational lead exposure.

Effects of Different Levels of Calcium Intake on Brain Cell Apoptosis in Fluorosis Rat Offspring and Its Molecular Mechanism.

PubMed

Sun, Yan; Ke, Lulu; Zheng, Xiangren; Li, Tao; Ouyang, Wei; Zhang, Zigui

2017-04-01

The purpose of the investigation is to reveal the influence of dietary calcium on fluorosis-induced brain cell apoptosis in rat offspring, as well as the underlying molecular mechanism. Sprague-Dawley (SD) female rats were randomly divided into five groups: control group, fluoride group, low calcium, low calcium fluoride group, and high calcium fluoride group. SD male rats were used for breeding only. After 3 months, male and female rats were mated in a 1:1 ratio. Subsequently, 18-day-old gestation rats and 14- and 28-day-old rats were used as experimental subjects. We determined the blood/urine fluoride, the blood/urine calcium, the apoptosis in the hippocampus, and the expression levels of apoptosis-related genes, namely Bcl-2, caspase 12, and JNK. Blood or blood/urine fluoride levels and apoptotic cells were found significantly increased in fluorosis rat offspring as compared to controls. Furthermore, the Bcl-2 messenger RNA (mRNA) expression levels significantly decreased, and caspase 12 mRNA levels significantly increased in each age group as compared to controls. Compared with the fluoride group, the blood/urine fluoride content and apoptotic cells evidently decreased in the high calcium fluoride group, Bcl-2 mRNA expression significantly increased and caspase 12 mRNA expression significantly decreased in each age group. All results showed no gender difference. Based on these results, the molecular mechanisms of fluorosis-induced brain cell apoptosis in rat offspring may include the decrease in Bcl-2 mRNA expression level and increase in caspase 12 mRNA expression signaling pathways. High calcium intake could reverse these gene expression trends. By contrast, low calcium intake intensified the toxic effects of fluoride on brain cells.

The effects of gum arabic oral treatment on the metabolic profile of chronic renal failure patients under regular haemodialysis in Central Sudan.

PubMed

Ali, Adil Ahmed; Ali, Khalid Eltom; Fadlalla, Abd Eigani; Khalid, Khalid Eltahir

2008-01-10

This study aimed at assessing the effect of gum arabic (Acacia senegal) oral treatment on the metabolic profile of chronic renal failure (CRF) patients. A total of 36 CRF patients (under regular haemodialysis) and 10 normal subjects participated in this study. The patients were randomly allocated into three groups-group A: 12 CRF patients under low-protein diet (LPD) (<40 g day(-1)) and gum arabic (50 g day(-1)) treatment; group B: 14 CRF patients under LPD and gum arabic, iron (ferrous sulphate, 200 mg day(-1)) and folic acid (5 mg day(-1)) treatment; group C (control group): 10 CRF patients under LPD and iron and folic acid treatment and group D: 10 normal volunteers (on normal diet) under daily dose of 50 g gum arabic. Each of the above treatments was continued for three consecutive months. Blood samples were collected from each subject before treatment and twice per month "pre-dialysis" for 3 months. Biochemical parameters measured were: serum urea, serum creatinine, serum uric acid, serum calcium and serum phosphorus. By the end of the 3 months of treatment, serum urea levels significantly decreased by 31.2 and 44.18% for group A and B, respectively, compared with the baseline (0.01 < p < 0.001) and control group (p < 0.05). Serum creatinine levels significantly decreased in the groups of gum users (A, B and D) by 9.94, 12.65 and 11.7%, respectively, compared with the control group (p < 0.001). There was a significant decrease (p < 0.05) in serum uric acid levels by 14 and 19.9% for group A and B, respectively, compared with the baseline. Serum calcium levels increased by 12.64, 15.75 and 8.75% for group A, B and D, respectively, and these increases were significantly different (0.05 < p < 0.001) from baseline and control group for groups A and B. Serum phosphorus levels significantly decreased by 22.54% for group A, 17.69% for group B and 7.71% for group D, compared with the baseline (0.05 < p < 0.001). From this study, we conclude that oral administration of gum arabic could conceivably alleviate adverse effects of CRF.

Differences in otosclerotic and normal human stapedial osteoblast properties are normalized by alendronate in vitro.

PubMed

Gronowicz, Gloria; Richardson, Yvonne L; Flynn, John; Kveton, John; Eisen, Marc; Leonard, Gerald; Aronow, Michael; Rodner, Craig; Parham, Kourosh

2014-10-01

Identify and compare phenotypic properties of osteoblasts from patients with otosclerosis (OSO), normal bones (HOB), and normal stapes (NSO) to determine a possible cause for OSO hypermineralization and assess any effects of the bisphosphonate, alendronate. OSO (n = 11), NSO (n = 4), and HOB (n = 13) cultures were assayed for proliferation, adhesion, mineralization, and gene expression with and without 10(-10)M-10(-8)M alendronate. Academic hospital. Cultures were matched for age, sex, and passage number. Cell attachment and proliferation + alendronate were determined by Coulter counting cells and assaying tritiated thymidine uptake, respectively. At 7, 14, and 21 days of culture + alendronate, calcium content and gene expression by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were determined. OSO had significantly more cells adhere but less proliferation than NSO or HOB. Calcification was significantly increased in OSO compared to HOB and NSO. NSO and HOB had similar cell adhesion and proliferation rates. A dose-dependent effect of alendronate on OSO adhesion, proliferation, and mineralization was found, resulting in levels equal to NSO and HOB. All cultures expressed osteoblast-specific genes such as RUNX2, alkaline phosphatase, type I collagen, and osteocalcin. However, osteopontin was dramatically reduced, 9.4-fold at 14 days, in OSO compared to NSO. Receptor activator of nuclear factor κB ligand/osteoprotegerin (RANKL/OPG), important in bone resorption, was elevated in OSO with decreased levels of OPG levels. Alendronate had little effect on gene expression in HOB but in OSO increased osteopontin levels and decreased RANKL/OPG. OSO cultures displayed properties of hypermineralization due to decreased osteopontin (OPN) and also had increased RANKL/OPG, which were normalized by alendronate. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

A Study of Early Afterdepolarizations in a Model for Human Ventricular Tissue

PubMed Central

Vandersickel, Nele; Kazbanov, Ivan V.; Nuitermans, Anita; Weise, Louis D.; Pandit, Rahul; Panfilov, Alexander V.

2014-01-01

Sudden cardiac death is often caused by cardiac arrhythmias. Recently, special attention has been given to a certain arrhythmogenic condition, the long-QT syndrome, which occurs as a result of genetic mutations or drug toxicity. The underlying mechanisms of arrhythmias, caused by the long-QT syndrome, are not fully understood. However, arrhythmias are often connected to special excitations of cardiac cells, called early afterdepolarizations (EADs), which are depolarizations during the repolarizing phase of the action potential. So far, EADs have been studied mainly in isolated cardiac cells. However, the question on how EADs at the single-cell level can result in fibrillation at the tissue level, especially in human cell models, has not been widely studied yet. In this paper, we study wave patterns that result from single-cell EAD dynamics in a mathematical model for human ventricular cardiac tissue. We induce EADs by modeling experimental conditions which have been shown to evoke EADs at a single-cell level: by an increase of L-type Ca currents and a decrease of the delayed rectifier potassium currents. We show that, at the tissue level and depending on these parameters, three types of abnormal wave patterns emerge. We classify them into two types of spiral fibrillation and one type of oscillatory dynamics. Moreover, we find that the emergent wave patterns can be driven by calcium or sodium currents and we find phase waves in the oscillatory excitation regime. From our simulations we predict that arrhythmias caused by EADs can occur during normal wave propagation and do not require tissue heterogeneities. Experimental verification of our results is possible for experiments at the cell-culture level, where EADs can be induced by an increase of the L-type calcium conductance and by the application of I blockers, and the properties of the emergent patterns can be studied by optical mapping of the voltage and calcium. PMID:24427289

Iron promotes protein insolubility and aging in C. elegans

PubMed Central

Klang, Ida M.; Schilling, Birgit; Sorensen, Dylan J.; Sahu, Alexandria K.; Kapahi, Pankaj; Andersen, Julie K.; Swoboda, Peter; Killilea, David W.; Gibson, Bradford W.; Lithgow, Gordon J.

2014-01-01

Many late-onset proteotoxic diseases are accompanied by a disruption in homeostasis of metals (metallostasis) including iron, copper and zinc. Although aging is the most prominent risk factor for these disorders, the impact of aging on metallostasis and its role in proteotoxic disease remain poorly understood. Moreover, it is not clear whether a loss of metallostasis influences normal aging. We have investigated the role of metallostasis in longevity of Caenorhabditis elegans. We found that calcium, copper, iron, and manganese levels increase as a function of age, while potassium and phosphorus levels tend to decrease. Increased dietary iron significantly accelerated the age-related accumulation of insoluble protein, a molecular pathology of aging. Proteomic analysis revealed widespread effects of dietary iron in multiple organelles and tissues. Pharmacological interventions to block accumulation of specific metals attenuated many models of proteotoxicity and extended normal lifespan. Collectively, these results suggest that a loss of metallostasis with aging contributes to age-related protein aggregation. PMID:25554795

Radiofrequency Ablation Followed by Percutaneous Ethanol Ablation Leading to Long-Term Remission of Hyperparathyroidism

PubMed Central

Menon, Arun S.; Nazar, P. K.; Moorthy, Srikanth; Kumar, Harish; Nair, Vasantha; Pavithran, Praveen Valiyaparambil; Bhavani, Nisha; Menon, Vadayath Usha; Abraham, Nithya; Jayakumar, R. Vasukutty

2017-01-01

A 30-year-old male with cerebral palsy and motor impairment presented with right femur fracture. He had gradually worsening mobility and contractures of all extremities for the preceding 5 years. Evaluation showed multiple vertebral and femoral fractures, severe osteoporosis, a large parathyroid adenoma, and parathormone (PTH) exceeding 2500 pg/mL. Because of poor general health and high anesthetic risk, parathyroidectomy was deemed impractical. Ultrasound-guided radiofrequency ablation (RFA) helped achieve 50% size reduction and PTH levels with better control of hypercalcemia. Later, as calcium and PTH remained elevated, percutaneous ethanol ablation was performed with resultant normalization of PTH and substantial symptomatic improvement. Two years later, he still remains normocalcaemic with normal PTH levels. We propose that RFA and percutaneous ethanol ablation be considered as effective short-term options for surgically difficult cases, which could even help achieve long-term remission. Although not previously reported, our case illustrates that both RFA and percutaneous ethanol ablation could be safely performed successively achieving long-term remission. PMID:29264521

Liquefaction of calcium-containing subbituminous coals and coals of lower rank

DOEpatents

Brunson, Roy J.

1979-01-01

An improved process for the treatment of a calcium-containing subbituminous coal and coals of lower rank to form insoluble, thermally stable calcium salts which remain within the solids portions of the residue on liquefaction of the coal, thereby suppressing the formation of scale, made up largely of calcium carbonate which normally forms within the coal liquefaction reactor (i.e., coal liquefaction zone), e.g., on reactor surfaces, lines, auxiliary equipment and the like. An oxide of sulfur, in liquid phase, is contacted with a coal feed sufficient to impregnate the pores of the coal. The impregnated coal, in particulate form, can thereafter be liquefied in a coal liquefaction reactor (reaction zone) at coal liquefaction conditions without significant formation of scale.

Visualization of Calcium Dynamics in Kidney Proximal Tubules

PubMed Central

Szebényi, Kornélia; Füredi, András; Kolacsek, Orsolya; Csohány, Rózsa; Prókai, Ágnes; Kis-Petik, Katalin; Szabó, Attila; Bősze, Zsuzsanna; Bender, Balázs; Tóvári, József; Enyedi, Ágnes; Orbán, Tamás I.

2015-01-01

Intrarenal changes in cytoplasmic calcium levels have a key role in determining pathologic and pharmacologic responses in major kidney diseases. However, cell-specific delivery of calcium-sensitive probes in vivo remains problematic. We generated a transgenic rat stably expressing the green fluorescent protein-calmodulin–based genetically encoded calcium indicator (GCaMP2) predominantly in the kidney proximal tubules. The transposon-based method used allowed the generation of homozygous transgenic rats containing one copy of the transgene per allele with a defined insertion pattern, without genetic or phenotypic alterations. We applied in vitro confocal and in vivo two-photon microscopy to examine basal calcium levels and ligand- and drug-induced alterations in these levels in proximal tubular epithelial cells. Notably, renal ischemia induced a transient increase in cellular calcium, and reperfusion resulted in a secondary calcium load, which was significantly decreased by systemic administration of specific blockers of the angiotensin receptor and the Na-Ca exchanger. The parallel examination of in vivo cellular calcium dynamics and renal circulation by fluorescent probes opens new possibilities for physiologic and pharmacologic investigations. PMID:25788535

Serum fibroblastic growth factor 23 in acute Sarcoidosis and normal kidney function.

PubMed

Sexton, Donal J; O'Reilly, M W; Geoghegan, P; Kinsella, S M; Moran, P J; O'Regan, A W

2016-08-01

Serum fibroblastic growth factor (FGF) 23 has recently been established as a major physiological regulator of phosphate homeostasis and may have a causal role in adverse cardiovascular and bone outcomes. However its role in states of disordered phosphate homeostasis and normal kidney function is as yet under characterised. To investigate whether this biomarker of vascular calcification and adverse bone outcomes is detectable in patients with sarcoidosis. We conducted a cross sectional study on a convenience sample of patients presenting with acute sarcoidosis to a respiratory tertiary referral unit. We set out to systematically examine the characteristics and determinants of serum FGF-23 in patients presenting with acute sarcoidosis. We studied 39 patients, 26 were male. Mean (SD) age was 33 (9.6) years. 15.4% of patients had a serum level of FGF-23 ≥ 9.9 pg/mL. The remaining 84.6% of patients had a serum FGF-23 < 9.9 pg/mL. Those with a detectable serum FGF-23 had a significantly higher serum calcium (P = 0.007), and lower serum iPTH (P<0.001). Serum phosphate and 25-hydroxyvitamin D were not statistically significantly different between groups (P=0.25 and P=0.83). The proportion of patients with stage II disease on CXR was higher in those with a detectable FGF-23 (P<0.001). Serum FGF-23 was below the level of detection in the majority of this cohort of patients presenting with acute sarcoidosis. A detectable serum FGF-23 was associated with a higher serum calcium and lower serum iPTH.

Quantitative Mineralogical Composition of Calculi and Urine Abnormalities for Calcium Oxalate Stone Formers: A Single-Center Results.

PubMed

Kustov, Andrey V; Strelnikov, Alexander I

2018-05-03

The paper focuses on the relationship of risk factors and metabolic disorders with mineralogical composition of calculi, age and gender of calcium oxalate stone formers. Stone mineralogical composition, 24 hour biochemistry and pH-profile of urine were examined for sixty four stone formers using powder X-ray diffraction, spectrophotometric and potentiometric techniques. The analysis indicated that 44 % of calculi were composed of pure calcium oxalate monohydrate, whereas other 56 % contained both monohydrate and dihydrate or usually their mixtures with hydroxyl apatite. Hypocitraturia, hypercalciuria and hyperuricosuria were identified as the most frequent disorders. Patients with pure calcium oxalate stones and calcium oxalate mixed with apatite revealed different patterns including age, acid-base balance of urine, calcium, citrate excretion etc.Conclusions: Our results demonstrate that most patients simultaneously reveal several risk factors. The special attention should be paid to normalize the daily citrate, calcium and urate excretion. High risk patients, such as postmenopausal females or stone formers with a high apatite content require a specific metabolic evaluation towards in highlighting abnormalities associated with stone formation.

Space-flight simulations of calcium metabolism using a mathematical model of calcium regulation

NASA Technical Reports Server (NTRS)

Brand, S. N.

1985-01-01

The results of a series of simulation studies of calcium matabolic changes which have been recorded during human exposure to bed rest and space flight are presented. Space flight and bed rest data demonstrate losses of total body calcium during exposure to hypogravic environments. These losses are evidenced by higher than normal rates of urine calcium excretion and by negative calcium balances. In addition, intestinal absorption rates and bone mineral content are assumed to decrease. The bed rest and space flight simulations were executed on a mathematical model of the calcium metabolic system. The purpose of the simulations is to theoretically test hypotheses and predict system responses which are occurring during given experimental stresses. In this case, hypogravity occurs through the comparison of simulation and experimental data and through the analysis of model structure and system responses. The model reliably simulates the responses of selected bed rest and space flight parameters. When experimental data are available, the simulated skeletal responses and regulatory factors involved in the responses agree with space flight data collected on rodents. In addition, areas within the model that need improvement are identified.

Kinetics of copper ion absorption by cross-linked calcium polyacrylate membranes

NASA Technical Reports Server (NTRS)

Philipp, W. H.; May, C. E.

1983-01-01

The absorption of copper ions from aqueous copper acetate solutions by cross-linked calcium acrylate membranes was found to obey parabolic kinetics similar to that found for oxidation of metals that form protective oxide layers. For pure calcium polyacrylate membranes the rate constant was essentially independent of copper acetate concentration and film thickness. For a cross-linked copolymer film of polyvinyl alcohol and calcium polyacrylate, the rate constant was much greater and dependent on the concentration of copper acetate. The proposed mechanism in each case involves the formation of a copper polyacrylate phase on the surface of the membrane. The diffusion of the copper ion through this phase appears to be the rate controlling step for the copolymer film. The diffusion of the calcium ion is apparently the rate controlling step for the calcium polyacrylate. At low pH, the copper polyacrylate phase consists of the normal copper salt; at higher pH, the phase appears to be the basic copper salt.

Assessment of fluoride-induced changes on physicochemical and structural properties of bone and the impact of calcium on its control in rabbits.

PubMed

Gopalakrishnan, Subarayan Bothi; Viswanathan, Gopalan

2012-03-01

Bone deformities caused by the chronic intake of large quantities of fluoride and the beneficial effect of calcium on its control have been studied for many years, but only limited data are available on the quantitative effect of fluoride intake and the beneficial impact of calcium on fluoride-induced changes in bone at the molecular level. It is necessary to determine the degree of fluoride-induced changes in bone at different levels of fluoride intake to evaluate the optimum safe intake level of fluoride for maintaining bone health and quality. The ameliorative effect of calcium at different dose levels on minimizing fluoride-induced changes in bone is important to quantify the amount of calcium intake necessary for reducing fluoride toxicity. Thirty rabbits, 2 months old, were divided into five groups. Group I animals received 1 mg/l fluoride and 0.11% calcium diet; groups II and III received 10 mg/l fluoride and diet with 0.11% or 2.11% calcium, respectively; and groups IV and V received 150 mg/l fluoride and diet with 2.11% or 0.11% calcium, respectively. Analysis of bone density, ash content, fluoride, calcium, phosphorus, and Ca:P molar ratio levels after 6 months of treatment indicated that animals that received high fluoride with low-calcium diet showed significant detrimental changes in physicochemical properties of bone. Animals that received fluoride with high calcium intake showed notable amelioration of the impact of calcium on fluoride-induced changes in bone. The degree of fluoride-induced characteristic changes in structural properties such as crystalline size, crystallinity, and crystallographic "c"-axis length of bone apatite cells was also assessed by X-ray diffraction and Fourier transform infrared studies. X-ray images showed bone deformity changes such as transverse stress growth lines, soft tissue ossification, and calcification in different parts of bones as a result of high fluoride accumulation and the beneficial role of calcium intake on its control.

Metabolic responses to high protein diet in Korean elite bodybuilders with high-intensity resistance exercise

PubMed Central

2011-01-01

Background High protein diet has been known to cause metabolic acidosis, which is manifested by increased urinary excretion of nitrogen and calcium. Bodybuilders habitually consumed excessive dietary protein over the amounts recommended for them to promote muscle mass accretion. This study investigated the metabolic response to high protein consumption in the elite bodybuilders. Methods Eight elite Korean bodybuilders within the age from 18 to 25, mean age 21.5 ± 2.6. For data collection, anthropometry, blood and urinary analysis, and dietary assessment were conducted. Results They consumed large amounts of protein (4.3 ± 1.2 g/kg BW/day) and calories (5,621.7 ± 1,354.7 kcal/day), as well as more than the recommended amounts of vitamins and minerals, including potassium and calcium. Serum creatinine (1.3 ± 0.1 mg/dl) and potassium (5.9 ± 0.8 mmol/L), and urinary urea nitrogen (24.7 ± 9.5 mg/dl) and creatinine (2.3 ± 0.7 mg/dl) were observed to be higher than the normal reference ranges. Urinary calcium (0.3 ± 0.1 mg/dl), and phosphorus (1.3 ± 0.4 mg/dl) were on the border of upper limit of the reference range and the urine pH was in normal range. Conclusions Increased urinary excretion of urea nitrogen and creatinine might be due to the high rates of protein metabolism that follow high protein intake and muscle turnover. The obvious evidence of metabolic acidosis in response to high protein diet in the subjects with high potassium intake and intensive resistance exercise were not shown in this study results. However, this study implied that resistance exercise with adequate mineral supplementation, such as potassium and calcium, could reduce or offset the negative effects of protein-generated metabolic changes. This study provides preliminary information of metabolic response to high protein intake in bodybuilders who engaged in high-intensity resistance exercise. Further studies will be needed to determine the effects of the intensity of exercise and the level of mineral intakes, especially potassium and calcium, which have a role to maintain acid-base homeostasis, on protein metabolism in large population of bodybuilders. PMID:21722409

Bone mineralization is elevated and less heterogeneous in adults with type 2 diabetes and osteoarthritis compared to controls with osteoarthritis alone

PubMed Central

Pritchard, J.M.; Papaioannou, A.; Tomowich, C.; Giangregorio, L.M.; Atkinson, S.A.; Beattie, K.A.; Adachi, J.D.; DeBeer, J.; Winemaker, M.; Avram, V.; Schwarcz, H.P.

2016-01-01

Purpose The purpose of this study was to determine whether trabecular bone mineralization differed in adults with type 2 diabetes compared to adults without type 2 diabetes. Methods Proximal femur specimens were obtained following a total hip replacement procedure from men and women ≥65 years of age with and without type 2 diabetes. A scanning electron microscope was used for quantitative backscattered electron imaging (qBEI) analysis of trabecular bone samples from the femoral neck. Gray scale images (pixel size=5.6 μm2) were uploaded to ImageJ software and gray level (GL) values were converted to calcium concentrations (weight [wt] % calcium [Ca]) using data obtained with energy dispersive X-ray spectrometry. The following bone mineralization density distribution (BMDD) outcomes were collected: the weighted mean bone calcium concentration (CaMEAN), the most frequently occurring bone calcium concentration (CaPEAK) and mineralization heterogeneity (CaWIDTH). Differences between groups were assessed using the Student’s t-test for normally distributed data and Mann–Whitney U-test for non-normally distributed data. An alpha value of <0.05 was considered significant. Results Thirty-five Caucasian participants were recruited (mean [standard deviation, SD] age, 75.5 [6.5] years): 14 adults with type 2 diabetes (years since type 2 diabetes diagnosis, 13.5 [7.4] years) and 21 adults without type 2 diabetes. In the adults with type 2 diabetes, bone CaMEAN was 4.9% greater (20.36 [0.98] wt.% Ca versus 19.40 [1.07] wt.% Ca, p=0.015) and CaWIDTH was 9.4% lower (median [interquartile range] 3.55 [2.99–4.12] wt.% Ca versus 3.95 [0.71] wt.% Ca, p<0.001) compared to controls. There was no between-group difference in CaPEAK (21.12 [0.97] wt.% Ca for type 2 diabetes versus 20.44 [1.30] wt.% Ca for controls, p=0.121). Conclusion The combination of elevated mean calcium concentration in bone and lower mineralization heterogeneity in adults with type 2 diabetes may have deleterious effects on the biomechanical properties of bone. These microscopic alterations in bone mineralization, which may be mediated by suppressed bone remodeling, further elucidate higher fracture risk in adults with type 2 diabetes. PMID:23356988

Evaluation of vitamin D3 intakes up to 15,000 international units/day and serum 25-hydroxyvitamin D concentrations up to 300 nmol/L on calcium metabolism in a community setting.

PubMed

Kimball, S M; Mirhosseini, N; Holick, M F

2017-01-01

Supplementation by the general public with vitamin D at doses above the Tolerable Upper Level of Intake (UL) is becoming quite common. The objective of the current analysis was to characterize the effect of vitamin D supplementation at doses up to 15,000 IU/d in a community-based program on vitamin D status, calcium homeostasis as well as on kidney, liver and immune function. We evaluated data collected for 3,882 participants in a community program for whom there were blood measurements at program entry and at follow-up within 6-18 months between 2013 and 2015. Participants were supplemented with a wide range of vitamin D doses (1,000 - 15,000 IU/d) aimed at achieving serum 25-hydroxyvitamin D [25(OH)D] levels of at least 100 nmol/L. Serum 25(OH)D concentrations up to 300 nmol/L were achieved without perturbation of calcium homeostasis or incidence of toxicity. Hypercalcemia and hypercalciuria were not related to an increase in 25(OH)D concentrations nor vitamin D dose. To achieve serum 25(OH)D levels >100 nmol/L on average, required vitamin D intakes of 6,000 IU/d for normal Body Mass Index (BMI), 7,000 IU/d for overweight and 8,000 IU/d for obese. Doses of vitamin D in excess of 6,000 IU/d were required to achieve serum 25(OH)D concentrations above 100 nmol/L, especially in individuals who were overweight or obese without any evidence of toxicity. Serum 25(OH)D concentrations up to 300 nmol/L were found to be safe.

TMEM203 Is a Novel Regulator of Intracellular Calcium Homeostasis and Is Required for Spermatogenesis

PubMed Central

Shambharkar, Prashant B.; Bittinger, Mark; Latario, Brian; Xiong, ZhaoHui; Bandyopadhyay, Somnath; Davis, Vanessa; Lin, Victor; Yang, Yi; Valdez, Reginald; Labow, Mark A.

2015-01-01

Intracellular calcium signaling is critical for initiating and sustaining diverse cellular functions including transcription, synaptic signaling, muscle contraction, apoptosis and fertilization. Trans-membrane 203 (TMEM203) was identified here in cDNA overexpression screens for proteins capable of modulating intracellular calcium levels using activation of a calcium/calcineurin regulated transcription factor as an indicator. Overexpression of TMEM203 resulted in a reduction of Endoplasmic Reticulum (ER) calcium stores and elevation in basal cytoplasmic calcium levels. TMEM203 protein was localized to the ER and found associated with a number of ER proteins which regulate ER calcium entry and efflux. Mouse Embryonic Fibroblasts (MEFs) derived from Tmem203 deficient mice had reduced ER calcium stores and altered calcium homeostasis. Tmem203 deficient mice were viable though male knockout mice were infertile and exhibited a severe block in spermiogenesis and spermiation. Expression profiling studies showed significant alternations in expression of calcium channels and pumps in testes and concurrently Tmem203 deficient spermatocytes demonstrated significantly altered calcium handling. Thus Tmem203 is an evolutionarily conserved regulator of cellular calcium homeostasis, is required for spermatogenesis and provides a causal link between intracellular calcium regulation and spermiogenesis. PMID:25996873

Effects of calcium and vitamin D supplementation on blood pressure and serum lipids and carotenoids: a randomized, double-blind, placebo-controlled, clinical trial.

PubMed

Chai, Weiwen; Cooney, Robert V; Franke, Adrian A; Bostick, Roberd M

2013-09-01

To estimate the effects of calcium or vitamin D supplementation or a combination of both on blood pressure and serum lipid and carotenoid levels. Ninety-two colorectal adenoma patients were randomized in a pilot, double-blind, placebo-controlled clinical trial of supplemental vitamin D3 800 IU and elemental calcium 2.0 g (as calcium carbonate) alone or in combination in divided doses twice daily with meals over 6 months. Relative to placebo, mean serum triglycerides decreased 30% (P = .10) and 32% (P = .10) in the calcium and calcium plus vitamin D3 treatment groups, respectively. When the two calcium intervention groups were pooled and compared with the pooled noncalcium groups, the estimated supplemental calcium treatment effects were statistically significant for triglycerides (P = .04). Similar but nonstatistically significant decreases (5%-7%) were observed for serum total cholesterol levels. Mean systolic blood pressure increased 6% (P = .08) in the calcium group; otherwise, there were no appreciable changes in systolic or diastolic blood pressures in any active treatment group. Mean serum total carotenoid levels decreased 14% (P = .07) in the calcium and 9% (P = .10) in the calcium plus vitamin D3 groups. Our results suggest that supplemental calcium alone or combined with vitamin D3 but not vitamin D3 alone may reduce serum lipids and lipophilic micronutrients. Copyright © 2013 Elsevier Inc. All rights reserved.

Vasopressin regulates renal calcium excretion in humans

PubMed Central

Hanouna, Guillaume; Haymann, Jean-Philippe; Baud, Laurent; Letavernier, Emmanuel

2015-01-01

Antidiuretic hormone or arginine vasopressin (AVP) increases water reabsorption in the collecting ducts of the kidney. Three decades ago, experimental models have shown that AVP may increase calcium reabsorption in rat kidney. The objective of this study was to assess whether AVP modulates renal calcium excretion in humans. We analyzed calcium, potassium, and sodium fractional excretion in eight patients affected by insipidus diabetes (nephrogenic or central) under acute vasopressin receptor agonist action and in 10 patients undergoing oral water load test affected or not by inappropriate antidiuretic hormone secretion (SIADH). Synthetic V2 receptor agonist (dDAVP) reduced significantly calcium fractional excretion from 1.71% to 0.58% (P < 0.05) in patients with central diabetes insipidus. In patients with nephrogenic diabetes insipidus (resistant to AVP), calcium fractional excretion did not change significantly after injection (0.48–0.68%, P = NS). In normal subjects undergoing oral water load test, calcium fractional excretion increased significantly from 1.02% to 2.54% (P < 0.05). Patients affected by SIADH had a high calcium fractional excretion at baseline that remained stable during test from 3.30% to 3.33% (P = NS), possibly resulting from a reduced calcium absorption in renal proximal tubule. In both groups, there was a significant correlation between urine output and calcium renal excretion. In humans, dDAVP decreases calcium fractional excretion in the short term. Conversely, water intake, which lowers AVP concentration, increases calcium fractional excretion. The correlation between urine output and calcium excretion suggests that AVP-related antidiuresis increases calcium reabsorption in collecting ducts. PMID:26620256

Serum 25-hydroxyvitamin D is associated with reduced verbal episodic memory in healthy, middle-aged and older adults.

PubMed

Lam, Virginie; Albrecht, Matthew A; Takechi, Ryusuke; Prasopsang, Prachya; Lee, Ya Ping; Foster, Jonathan K; Mamo, John C L

2016-06-01

There is increasing evidence supporting an association of higher serum vitamin D concentration with better cognitive performance in older individuals. However, to date, consideration of the putative association between vitamin D and cognition has been based principally on studies investigating clinical participant samples manifesting vitamin D deficiency, particularly in older people. Moreover, relationships between vitamin D and cognition are typically not considered in the context of counter-regulatory calcium-modulating hormones or calcium homeostasis. Serum vitamin D/bioactive (ionised) calcium/parathyroid hormone homeostasis was considered in the context of cognitive performance in healthy, middle-aged and older individuals. A cross-sectional sample of 179 participants between the ages of 47-84 years was recruited for this study (114 females, 65 males). Participants provided fasting blood samples for analysis of serum 25-hydroxyvitamin D levels, ionised calcium (iCa) and parathyroid hormone (PTH) and completed cognitive measures of verbal episodic learning and memory. Serum 25-hydroxyvitamin D concentrations were negatively associated (with and without covariates of age, gender, depression and NART scores, iCa, and PTH) with measures of verbal episodic learning and memory, in particular with trial 5 of the Rey Auditory Verbal Learning Test (RAVLT) and long-delay free recall on the RAVLT. Overall, the findings from this study suggest an association between higher vitamin D status and poorer performance on verbal episodic memory in middle-aged and older individuals with normal vitamin D-calcium-PTH homeostasis. Despite requiring replication in other participant samples, this is a potentially important finding as it indicates that it may not be beneficial from a cognitive perspective to provide vitamin D supplements in individuals with already adequate vitamin D status.

Effects of calcium hydroxide addition on the physical and chemical properties of a calcium silicate-based sealer

PubMed Central

KUGA, Milton Carlos; DUARTE, Marco Antonio Hungaro; SANT'ANNA-JÚNIOR, Arnaldo; KEINE, Kátia Cristina; FARIA, Gisele; DANTAS, Andrea Abi Rached; GUIOTTI, Flávia Angélica

2014-01-01

Recently, various calcium silicate-based sealers have been introduced for use in root canal filling. The MTA Fillapex is one of these sealers, but some of its physicochemical properties are not in accordance with the ISO requirements. Objective The aim of this study was to evaluate the flowability, pH level and calcium release of pure MTA Fillapex (MTAF) or containing 5% (MTAF5) or 10% (MTAF10) calcium hydroxide (CH), in weight, in comparison with AH Plus sealer. Material and Methods The flowability test was performed according to the ISO 6876:2001 requirements. For the pH level and calcium ion release analyses, the sealers were placed individually (n=10) in plastic tubes and immersed in deionized water. After 24 hours, 7 and 14 days, the water in which each specimen had been immersed was evaluated to determine the pH level changes and calcium released. Flowability, pH level and calcium release data were analyzed statistically by the ANOVA test (α=5%). Results In relation to flowability: MTAF>AH Plus>MTAF5>MTAF10. In relation to the pH level, for 24 h: MTAF5=MTAF10=MTAF>AH Plus; for 7 and 14 days: MTAF5=MTAF10>MTAF>AH Plus. For the calcium release, for all periods: MTAF>MTAF5=MTAF10>AH Plus. Conclusions The addition of 5% CH to the MTA Fillapex (in weight) is an alternative to reduce the high flowability presented by the sealer, without interfering in its alkalization potential. PMID:25025558

Hypercalcaemia secondary to hypervitaminosis a in a patient with chronic renal failure.

PubMed

Hammoud, D; El Haddad, B; Abdallah, J

2014-01-01

Vitamin A toxicity is a well-described medical condition with a multitude of potential presenting signs and symptoms. It can be divided into acute and chronic toxicity. Serum vitamin A concentrations are raised in chronic renal failure even with ingestion of less than the usual toxic doses. Hypercalcaemia can occasionally be associated with high levels of vitamin A but it is rare. In this report, we describe a 67- year old female patient with chronic kidney disease who was taking vitamin A supplements for approximately 10 years. The patient had worsening of her chronic kidney disease over the last years and developed chronic hypercalcaemia. Her vitamin A level was elevated with a daily intake of 7000 IU. The vitamin A supplement was stopped. A few months later, vitamin A level diminished substantially and serum calcium levels returned to normal.

Dietary phosphate restriction normalizes biochemical and skeletal abnormalities in a murine model of tumoral calcinosis.

PubMed

Ichikawa, Shoji; Austin, Anthony M; Gray, Amie K; Allen, Matthew R; Econs, Michael J

2011-12-01

Mutations in the GALNT3 gene cause tumoral calcinosis characterized by ectopic calcifications due to persistent hyperphosphatemia. We recently developed Galnt3 knockout mice in a mixed background, which had hyperphosphatemia with increased bone mineral density (BMD) and infertility in males. To test the effect of dietary phosphate intake on their phenotype, Galnt3 knockout mice were generated in the C57BL/6J strain and fed various phosphate diets: 0.1% (low), 0.3% (low normal), 0.6% (normal), and 1.65% (high). Sera were analyzed for calcium, phosphorus, alkaline phosphatase, creatinine, blood urine nitrogen, 1,25-dihydroxyvitamin D, osteocalcin, tartrate-resistant acid phosphatase 5b, and fibroblast growth factor 23 (Fgf23). Femurs were evaluated by dual-energy x-ray absorptiometry, dynamic histomorphometry, and/or microcomputed tomography. Galnt3 knockout mice in C57BL/6J had the same biochemical phenotype observed in our previous study: hyperphosphatemia, inappropriately normal 1,25-dihydroxyvitamin D level, decreased alkaline phosphatase activity, and low intact Fgf23 concentration but high Fgf23 fragments. Skeletal analyses of their femurs revealed significantly high BMD with increased cortical bone area and trabecular bone volume. On all four phosphate diets, Galnt3 knockout mice had consistently higher phosphorus levels and lower alkaline phosphatase and intact Fgf23 concentrations than littermate controls. The low-phosphate diet normalized serum phosphorus, alkaline phosphatase, and areal BMD but failed to correct male infertility in Galnt3 knockout mice. The high-phosphate diet did not increase serum phosphorus concentration in either mutant or control mice due to a compensatory increase in circulating intact Fgf23 levels. In conclusion, dietary phosphate restriction normalizes biochemical and skeletal phenotypes of Galnt3 knockout mice and, thus, can be an effective therapy for tumoral calcinosis.

Dietary Phosphate Restriction Normalizes Biochemical and Skeletal Abnormalities in a Murine Model of Tumoral Calcinosis

PubMed Central

Austin, Anthony M.; Gray, Amie K.; Allen, Matthew R.; Econs, Michael J.

2011-01-01

Mutations in the GALNT3 gene cause tumoral calcinosis characterized by ectopic calcifications due to persistent hyperphosphatemia. We recently developed Galnt3 knockout mice in a mixed background, which had hyperphosphatemia with increased bone mineral density (BMD) and infertility in males. To test the effect of dietary phosphate intake on their phenotype, Galnt3 knockout mice were generated in the C57BL/6J strain and fed various phosphate diets: 0.1% (low), 0.3% (low normal), 0.6% (normal), and 1.65% (high). Sera were analyzed for calcium, phosphorus, alkaline phosphatase, creatinine, blood urine nitrogen, 1,25-dihydroxyvitamin D, osteocalcin, tartrate-resistant acid phosphatase 5b, and fibroblast growth factor 23 (Fgf23). Femurs were evaluated by dual-energy x-ray absorptiometry, dynamic histomorphometry, and/or microcomputed tomography. Galnt3 knockout mice in C57BL/6J had the same biochemical phenotype observed in our previous study: hyperphosphatemia, inappropriately normal 1,25-dihydroxyvitamin D level, decreased alkaline phosphatase activity, and low intact Fgf23 concentration but high Fgf23 fragments. Skeletal analyses of their femurs revealed significantly high BMD with increased cortical bone area and trabecular bone volume. On all four phosphate diets, Galnt3 knockout mice had consistently higher phosphorus levels and lower alkaline phosphatase and intact Fgf23 concentrations than littermate controls. The low-phosphate diet normalized serum phosphorus, alkaline phosphatase, and areal BMD but failed to correct male infertility in Galnt3 knockout mice. The high-phosphate diet did not increase serum phosphorus concentration in either mutant or control mice due to a compensatory increase in circulating intact Fgf23 levels. In conclusion, dietary phosphate restriction normalizes biochemical and skeletal phenotypes of Galnt3 knockout mice and, thus, can be an effective therapy for tumoral calcinosis. PMID:22009723

Elevated 1,25-dihydroxyvitamin D levels in patients with chronic obstructive pulmonary disease treated with prednisone

NASA Technical Reports Server (NTRS)

Bikle, D. D.; Halloran, B.; Fong, L.; Steinbach, L.; Shellito, J.

1993-01-01

Glucocorticoid administration is a well established cause of osteopenia. Mechanisms underlying the deleterious effect of glucocorticoids on bone may include direct inhibition of bone formation as well as indirect effects through changes in intestinal calcium absorption, renal calcium excretion, and/or levels of the calciotropic hormones. To further examine the potential role of the calciotropic hormones we measured serum levels of PTH and 1,25 dihydroxyvitamin D [1,25(OH)2D], as well as serum and urine levels of calcium and vertebral bone density in patients with chronic obstructive pulmonary disease being managed with or without prednisone. Patients treated with prednisone had lower spinal bone density (53 vs. 106 mg/cm3) and higher serum calcium (2.40 vs. 2.33 mmol/l), urine calcium (6.9 vs. 2.7 mmol/24h), and 1,25(OH)2D levels (147 vs. 95 pmol/L). Compared to the patients not treated with glucocorticoids. PTH levels also tended to be higher (33 vs. 26 microliters-eq/ml), but the difference was not significant. Serum and urine calcium levels correlated positively with 1,25(OH)2D levels, but none of these measurements correlated with PTH levels. Our results suggest that prednisone treatment alters the regulation of 1,25(OH)2D production, and this may contribute to the loss of bone mineral induced by prednisone.

Behavior of heavy metals in human urine and blood following calcium disodium ethylenediamine tetraacetate injection: observations in metal workers.

PubMed

Sata, F; Araki, S; Murata, K; Aono, H

1998-06-12

To evaluate the effects of calcium disodium ethylenediamine tetraacetate (CaEDTA) on the behavior of 8 heavy metals in human urine and blood, CaEDTA was administered for 1 h by intravenous injection to 18 male metal foundry workers, whose blood lead concentrations (PbB) were between 16 and 59 (mean 34) microg/dl. Significant increases were found in urinary excretion of manganese, chromium, lead, zinc, and copper after the start of CaEDTA injection. Urinary chromium excretion reached a maximal level within 1 h after the start of injection, while urinary manganese, lead, and zinc excretion reached their highest concentrations between 1 and 2 h. Urinary copper excretion reached the highest level between 2 and 4 h. The rapid increases in urinary excretion of five metals were different from the "circadian rhythms," which are the normal, daily variations in renal glomerular filtration, reabsorption, and excretory mechanisms. Plasma lead concentrations were highest 1.5 h after the start of the 1-h injection, while plasma zinc concentration became lowest 5 h after the start of CaEDTA injection. Data suggest that manganese and chromium absorbed in human tissues might be mobilized by CaEDTA.

Effect of root canal obturation with calcium silicate materials on pH change in simulated root resorption defects.

PubMed

Aggarwal, Vivek; Singla, Mamta; Miglani, Sanjay; Sharma, Ritu

2018-01-01

This study evaluated the effect of 3 commercially available calcium silicate materials (CSMs) on pH changes in simulated root resorption defects. Simulated root resorption defects were prepared on the facial root surface of 40 mandibular premolars. The depth of each defect was individually calculated to standardize the remaining dentin thickness to 1 mm. Prepared canals were obturated with the 3 CSMs. Ten specimens were kept as controls, filled with unbuffered normal saline. The pH measurements were taken at 1 hour, 6 hours, 1 day, 1 week, 2 weeks, 3 weeks, 1 month, and 2 months. All CSM groups exhibited an initial alkaline pH of 9.0-9.7. The pH decreased to 8.0-8.5 after 2 months of storage. There were no significant differences between pH measurements at other time intervals. The CSM groups exhibited higher pH levels than the control group. The results showed that intracanal placement of the CSMs maintained initial pH levels of 9.0-9.7 inside the simulated resorption defects; these measurements gradually decreased to 8.0-8.5 over the span of 2 months.

Familial microscopic hematuria caused by hypercalciuria and hyperuricosuria.

PubMed

Praga, M; Alegre, R; Hernández, E; Morales, E; Domínguez-Gil, B; Carreño, A; Andrés, A

2000-01-01

We report 12 patients belonging to five different families in whom persistent isolated microhematuria was associated with hypercalciuria and/or hyperuricosuria. Four patients had episodes of gross hematuria, three patients had passed renal stones, and a history of nephrolithiasis was obtained in four of the families (80%). Calcium oxalate and uric acid crystals were commonly observed in the urine sediments. Urinary erythrocytes had a normal appearance on phase-microscopic examination. Reduction of calciuria and uricosuria by thiazide diuretics, allopurinol, forced fluid intake, and dietetic measures led to a persistent normalization of urine sediment with complete disappearance of hematuria. Determination of calcium and uric acid urinary excretions should be included in the study of familial hematuria.

Molecular Dynamics Simulations of Membrane-Bound STIM1 to Investigate Conformational Changes during STIM1 Activation upon Calcium Release.

PubMed

Mukherjee, Sreya; Karolak, Aleksandra; Debant, Marjolaine; Buscaglia, Paul; Renaudineau, Yves; Mignen, Olivier; Guida, Wayne C; Brooks, Wesley H

2017-02-27

Calcium is involved in important intracellular processes, such as intracellular signaling from cell membrane receptors to the nucleus. Typically, calcium levels are kept at less than 100 nM in the nucleus and cytosol, but some calcium is stored in the endoplasmic reticulum (ER) lumen for rapid release to activate intracellular calcium-dependent functions. Stromal interacting molecule 1 (STIM1) plays a critical role in early sensing of changes in the ER's calcium level, especially when there is a sudden release of stored calcium from the ER. Inactive STIM1, which has a bound calcium ion, is activated upon ion release. Following activation of STIM1, there is STIM1-assisted initiation of extracellular calcium entry through channels in the cell membrane. This extracellular calcium entering the cell then amplifies intracellular calcium-dependent actions. At the end of the process, ER levels of stored calcium are reestablished. The main focus of this work was to study the conformational changes accompanying homo- or heterodimerization of STIM1. For this purpose, the ER luminal portion of STIM1 (residues 58-236), which includes the sterile alpha motif (SAM) domain plus the calcium-binding EF-hand domains 1 and 2 attached to the STIM1 transmembrane region (TM), was modeled and embedded in a virtual membrane. Next, molecular dynamics simulations were performed to study the conformational changes that take place during STIM1 activation and subsequent protein-protein interactions. Indeed, the simulations revealed exposure of residues in the EF-hand domains, which may be important for dimerization steps. Altogether, understanding conformational changes in STIM1 can help in drug discovery when targeting this key protein in intracellular calcium functions.

Mixed-mode oscillations in a three-store calcium dynamics model

NASA Astrophysics Data System (ADS)

Liu, Peng; Liu, Xijun; Yu, Pei

2017-11-01

Calcium ions are important in cell process, which control cell functions. Many models on calcium oscillation have been proposed. Most of existing literature analyzed calcium oscillations using numerical methods, and found rich dynamical behaviours. In this paper, we explore a further study on an established three-store model, which contains endoplasmic reticulum (ER), mitochondria and calcium binding proteins. We conduct bifurcation analysis to identify two Hopf bifurcations, and apply normal form theory to study their stability and show that one of them is supercritical while the other is subcritical. Further, we transform the model into a slow-fast system, and then apply the geometrical singular perturbation theory to investigate the mechanism of generating slow-fast motions. The study reveals that the mechanism of generating the slow-fast oscillating behaviour in the three-store calcium model for certain parameter values is due to the relative fast change in the free calcium in cytosol, and relative slow changes in the free calcium in mitochondria and in the bounded Ca2+ binding sites on the cytosolic proteins. A further parametric study may provide some useful information for controlling harmful effect, by adjusting the amount of calcium in a human body. Numerical simulations are present to demonstrate the correct analytical predictions.

The interactive roles of zinc and calcium in mitochondrial dysfunction and neurodegeneration.

PubMed

Pivovarova, Natalia B; Stanika, Ruslan I; Kazanina, Galina; Villanueva, Idalis; Andrews, S Brian

2014-02-01

Zinc has been implicated in neurodegeneration following ischemia. In analogy with calcium, zinc has been proposed to induce toxicity via mitochondrial dysfunction, but the relative role of each cation in mitochondrial damage remains unclear. Here, we report that under conditions mimicking ischemia in hippocampal neurons - normal (2 mM) calcium plus elevated (> 100 μM) exogenous zinc - mitochondrial dysfunction evoked by glutamate, kainate or direct depolarization is, despite significant zinc uptake, primarily governed by calcium. Thus, robust mitochondrial ion accumulation, swelling, depolarization, and reactive oxygen species generation were only observed after toxic stimulation in calcium-containing media. This contrasts with the lack of any mitochondrial response in zinc-containing but calcium-free medium, even though zinc uptake and toxicity were strong under these conditions. Indeed, abnormally high, ionophore-induced zinc uptake was necessary to elicit any mitochondrial depolarization. In calcium- and zinc-containing media, depolarization-induced zinc uptake facilitated cell death and enhanced accumulation of mitochondrial calcium, which localized to characteristic matrix precipitates. Some of these contained detectable amounts of zinc. Together these data indicate that zinc uptake is generally insufficient to trigger mitochondrial dysfunction, so that mechanism(s) of zinc toxicity must be different from that of calcium. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

Association between blood pressure and magnesium and uric acid levels in indigenous Argentinean children at high altitude.

PubMed

Hirschler, Valeria; González, Claudio; Maccallini, Gustavo; Molinari, Claudia; Castano, Luis

2017-07-08

To determine the association between nontraditional risk factors such as magnesium and uric acid with blood pressure (BP) in Indigenous children. A total of 263 school-aged indigenous children living at high altitude were enrolled in a cross-sectional study in November 2011. Prehypertension (preHTN) and hypertension (HTN) were defined by systolic and/or diastolic BP ≥ 90th to <95th percentile or ≥95th percentile respectively, according to age, sex, and height. The prevalence of preHTN and HTN was 13.7 and 8.3%, respectively. Low magnesium levels were identified in 21.7% (57/263): 28.1% (16/57) of the children with low magnesium levels had preHTN versus 9.7% (20/206) with normal magnesium values. Furthermore, 21.8% (12/57) of the children with low magnesium levels had HTN versus 4.5% (20/206) with normal magnesium values. There was a significant association between mean arterial pressure and magnesium (r = -026), uric acid (r = 0.20), phosphorus (r = -0.17), z-BMI (r = 0.22), potassium (r = -0.10), HOMA-IR (r = 0.17), calcium (r = -0.10), and sodium (r = -0.13). Multiple linear regression analysis showed that mean arterial pressure was associated significantly and directly with BMI, age, gender, and uric acid; and inversely with magnesium, adjusted for sodium, calcium, phosphorus, potassium, and HOMA-IR (R 2  = 0.43). Furthermore, multiple logistic regression analyses showed that magnesium (OR = 0.015) and uric acid (OR = 2.95) were significantly associated with preHTN. Similar results were obtained when preHTN was replaced by HTN. Our results indicate that HTN was associated inversely with magnesium and positively with uric acid in indigenous school children. © 2017 Wiley Periodicals, Inc.

Glucocorticoids possess calcitonin-like antihypercalcemic properties in rats.

PubMed

Hirsch, P F; Imai, Y; Hosoya, Y; Ode, H; Maeda, S

1998-02-01

The interaction among parathyroid hormone (PTH), calcitonin (CT), and glucocorticoids on blood calcium (Ca) was examined. Prior studies had shown that adrenalectomy (ADX) reduced the fall in blood calcium in rats after parathyroidectomy (PTX). Convincing evidence was provided showing that the ADX effect in PTX rats was due to the loss of corticosterone, the major glucocorticoid in rats; restoring physiological blood levels of corticosterone abolished the ADX effect in PTX rats. The initial attempt of the present study was to explain the failure of ADX or exogenous glucocorticoids to alter serum Ca levels in rats with intact thyroid and parathyroid glands or in thyroidectomized rats with functional parathyroid transplants (PTT). We found, as previously reported, that the 5-h level of serum Ca in rats with parathyroid glands was not affected by s.c. hydrocortisone (cortisol) or by ADX. It was also not affected by thyroparathyroidectomy (TPTX) or after both ADX and TPTX in rats with PTT. These results suggested to us that the glucocorticoid effect to lower serum was inhibited by endogenous parathyroid hormone (PTH) from the parathyroid gland and/or by normal levels of blood Ca. Both of these proposed mechanisms were examined and failed to explain the absence of the ADX effect as well as the glucocorticoid effect in normocalcemic parathyroid-intact rats, because an ADX effect was observed in TPTX rats given hypercalcemic doses of rat or bovine PTH 1-34 or calcitriol. Also, administered cortisol restricted the increased hypercalcemia induced by PTH in ADX-TPTX rats. Expanding on the results in TPTX rats with induced hypercalcemia, we found that neither the ADX effect nor the glucocorticoid effect occurred in thyroid-intact rats with or without functional PTT. These as well as previous results show that: 1. Glucocorticoids, like CT, restrict hypercalcemia in TPTX rats. 2. The ADX effect and its reversal by glucocorticoids in rats with induced hypercalcemia occur only in the absence of the thyroid gland (removal of CT). 3. Glucocorticoids, like CT, lower serum calcium during the hypocalcemia after PTX, an effect that occurs in the presence or absence of the thyroid gland. This study did not reveal why neither ADX nor exogenous glucocorticoids altered serum calcium levels in normocalcemic rats with either intact parathyroid glands or PTT. We conclude that under appropriate conditions, glucocorticoids act in a fashion similar to that of CT in restricting hypercalcemia and in lowering blood Ca.

The mechanosensory calcium-selective ion channel: key component of a plasmalemmal control centre?

NASA Technical Reports Server (NTRS)

Pickard, B. G.; Ding, J. P.

1993-01-01

Mechanosensory calcium-selective ion channels probably serve to detect not only mechanical stress but also electrical, thermal, and diverse chemical stimuli. Because all stimuli result in a common output, most notably a shift in second messenger calcium concentration, the channels are presumed to serve as signal integrators. Further, insofar as second messenger calcium in turn gives rise to mechanical, electrical, and diverse chemical changes, the channels are postulated to initiate regulatory feedbacks. It is proposed that the channels and the feedback loops play a wide range of roles in regulating normal plant function, as well as in mediating disturbance of normal function by environmental stressors and various pathogens. In developing evidence for the physiological performance of the channel, a model for a cluster of regulatory plasmalemmal proteins and cytoskeletal elements grouped around a set of wall-to-membrane and transmembrane linkers has proved useful. An illustration of how the model might operate is presented. It is founded on the demonstration that several xenobiotics interfere both with normal channel behaviour and with gravitropic reception. Accordingly, the first part of the illustration deals with how the channels and the control system within which they putatively operate might initiate gravitropism. Assuming that gravitropism is an asymmetric expression of growth, the activities of the channels and the plasmalemmal control system are extrapolated to account for regulation of both rate and allometry of cell expansion. Finally, it is discussed how light, hormones, redox agents and herbicides could in principle affect growth via the putative plasmalemmal control cluster or centre.

Effect of Hypergravity on Carbonanhydrase Reactivity in inner Ear Ioncytes of developing Cichlid Fish

NASA Astrophysics Data System (ADS)

Beier, M.; Anken, R.; Rahmann, H.

It has been shown earlier that hypergravity slows down inner ear otolith growth in developing fish. Otolith growth in terms of mineralisation mainly depends on the enzyme carboanhydrase (CAH), which is responsible for the provision of the pH- value necessary for calcium carbonate deposition and thus also is presumed to play a prominent role in Ménière's disease (a sensory - motor disorder inducing vertigo and kinetosis). Larval siblings of cichlid fish (Oreochromis mossambicus) were subjected to hypergravity (3g; 6 hours) during development and separated into normally and kinetotically swimming individuals following the transfer to 1g (i.e., stopping the centrifuge; kinetotically behaving fish performed spinning movements). Subsequently, CAH was histochemically demonstrated in inner ear ionocytes (cells involved in the endolymphatic ion exchange) and enzyme reactivity was determined densitometrically. The results showed that CAH-reactivity was significantly increased in normally behaving hyper-g specimens as compared to controls kept at 1g, whereas no difference in enzyme reactivity was evident between the controls and kinetotically behaving fish. On the background of earlier studies, according to which (1) hypergravity induces a decrease of otolith growth and (2) the otolithic calcium incorporation (visualized using the calcium -tracer alizarin complexone) of kinetotically swimming hyper - g fish was lower as compared to normally behaving hyper - g animals, the present study strongly supports the concept that an increase in CAH-reactivity may result in a decrease of otolithic calcium deposition. The mechanism regulating CAH-activity hitherto remains to be determined. Acknowledgement: This work was financially supported by the German Aerospace Center (DLR) (FKZ: 50 WB 9997).

Gitelman or Bartter type 3 syndrome? A case of distal convoluted tubulopathy caused by CLCNKB gene mutation

PubMed Central

Cruz, António José; Castro, Alexandra

2013-01-01

A 32-year-old woman with no significant medical history was sent to our consultation due to hypokalaemia (<3.0 mmol/l). Her main complaints were longstanding polyuria and nocturia. Physical examination was normal. Basic investigations showed normal renal function, low serum potassium (2.7 mmol/l) and magnesium (0.79 mmol/l), metabolic alkalosis (pH 7.54; bicarbonate 32.5 mmol/l), elevated urinary potassium (185 mmol/24 h) and normal urinary calcium (246 mg/24 h). Thiazide test revealed blunted response. Chronic vomiting and the abuse of diuretics were excluded. Genetic tests for SLC12A3 gene mutation described in Gitelman syndrome (GS) came negative. CLCNKB gene mutation analysis present in both GS and Bartter (BS) type 3 syndromes was positive. The patient is now being treated with potassium and magnesium oral supplements, ramipril and spironolactone with stable near-normal potassium and magnesium levels. This article presents the case of a patient with hypokalaemia caused by CLCNKB gene mutation hard to categorise as GS or BS type 3. PMID:23345488

Gitelman or Bartter type 3 syndrome? A case of distal convoluted tubulopathy caused by CLCNKB gene mutation.

PubMed

Cruz, António José; Castro, Alexandra

2013-01-22

A 32-year-old woman with no significant medical history was sent to our consultation due to hypokalaemia (<3.0 mmol/l). Her main complaints were longstanding polyuria and nocturia. Physical examination was normal. Basic investigations showed normal renal function, low serum potassium (2.7 mmol/l) and magnesium (0.79 mmol/l), metabolic alkalosis (pH 7.54; bicarbonate 32.5 mmol/l), elevated urinary potassium (185 mmol/24 h) and normal urinary calcium (246 mg/24 h). Thiazide test revealed blunted response. Chronic vomiting and the abuse of diuretics were excluded. Genetic tests for SLC12A3 gene mutation described in Gitelman syndrome (GS) came negative. CLCNKB gene mutation analysis present in both GS and Bartter (BS) type 3 syndromes was positive. The patient is now being treated with potassium and magnesium oral supplements, ramipril and spironolactone with stable near-normal potassium and magnesium levels. This article presents the case of a patient with hypokalaemia caused by CLCNKB gene mutation hard to categorise as GS or BS type 3.

Measurements of intracellular calcium signals in polarized primary cultures of normal and cystic fibrosis human airway epithelia.

PubMed

Ribeiro, Carla M P

2011-01-01

The airways are continuously challenged by a variety of stimuli including bacteria, viruses, allergens, and inflammatory factors that act as agonists for G protein-coupled receptors (GPCR). Intracellular calcium (Ca(2+) (i)) mobilization in airway epithelia in response to extracellular stimuli regulates key airway innate defense functions, e.g., Ca(2+)-activated Cl(-) secretion, ciliary beating, mucin secretion, and inflammatory responses. Because Ca(2+) (i) mobilization in response to luminal stimuli is larger in CF vs. normal human airway epithelia, alterations in Ca(2+) (i) signals have been associated with the pathogenesis of CF airway disease. Hence, assessment of Ca(2+) (i) signaling has become an important area of CF research. This chapter will focus on measurements of cytoplasmic and mitochondrial Ca(2+) signals resulting from GPCR activation in polarized primary cultures of normal and CF human bronchial epithelia (HBE).

Supplementation of α-Tocopherol Attenuates Minerals Disturbance, Oxidative Stress and Apoptosis Occurring in Favism.

PubMed

Koriem, Khaled M M; Arbid, Mahmoud S; Gomaa, Nawal E

2017-10-01

The favism is a metabolic disease that characterized with an acute hemolytic anemia where α-tocopherol is a type of tocopherol accumulated inside the human body. The objective of such a study was established to evaluate the effect of α-tocopherol in favism disorders. A total of 75 human cases were divided into 5 groups as follow; group 1 normal cases without any treatment and group 2 normal cases orally administrated α-tocopherol (200 mg/kg) once a day over 30 days period. Group 3 favism patients without any treatment. Groups 4 and 5 favism patients orally administrated 100 and 200 mg α-tocopherol/kg, respectively once a day over 30 days period. The results obtained revealed that oral administration of α-tocopherol into normal cases over 30 days period did not induce any biological change. In favism, hemoglobin, hematocrit, red and white blood cells, serum glucose, glucose-6-phosphate dehydrogenase, total protein, albumin, globulin, aspartate and alanine aminotransferases, blood glutathione, superoxide dismutase, glutathione peroxidase and serum calcium, phosphorous, sodium, potassium and chloride levels were significantly decreased. On the other hand, serum alkaline phosphatase, bilirubin, selenium, zinc, manganese, copper and iron, malondialdehyde levels showed significant increase in favism. Supplementation with α-tocopherol into favism restores all the above mentioned parameters to approach the normal levels. Also, α-tocopherol has anti-apoptotic effect in favism. In conclusion, α-tocopherol attenuates minerals disturbance, oxidative stress and apoptosis occurring in favism.

Intracellular sphingosine releases calcium from lysosomes.

PubMed

Höglinger, Doris; Haberkant, Per; Aguilera-Romero, Auxiliadora; Riezman, Howard; Porter, Forbes D; Platt, Frances M; Galione, Antony; Schultz, Carsten

2015-11-27

To elucidate new functions of sphingosine (Sph), we demonstrate that the spontaneous elevation of intracellular Sph levels via caged Sph leads to a significant and transient calcium release from acidic stores that is independent of sphingosine 1-phosphate, extracellular and ER calcium levels. This photo-induced Sph-driven calcium release requires the two-pore channel 1 (TPC1) residing on endosomes and lysosomes. Further, uncaging of Sph leads to the translocation of the autophagy-relevant transcription factor EB (TFEB) to the nucleus specifically after lysosomal calcium release. We confirm that Sph accumulates in late endosomes and lysosomes of cells derived from Niemann-Pick disease type C (NPC) patients and demonstrate a greatly reduced calcium release upon Sph uncaging. We conclude that sphingosine is a positive regulator of calcium release from acidic stores and that understanding the interplay between Sph homeostasis, calcium signaling and autophagy will be crucial in developing new therapies for lipid storage disorders such as NPC.

CalQuo: automated, simultaneous single-cell and population-level quantification of global intracellular Ca2+ responses.

PubMed

Fritzsche, Marco; Fernandes, Ricardo A; Colin-York, Huw; Santos, Ana M; Lee, Steven F; Lagerholm, B Christoffer; Davis, Simon J; Eggeling, Christian

2015-11-13

Detecting intracellular calcium signaling with fluorescent calcium indicator dyes is often coupled with microscopy techniques to follow the activation state of non-excitable cells, including lymphocytes. However, the analysis of global intracellular calcium responses both at the single-cell level and in large ensembles simultaneously has yet to be automated. Here, we present a new software package, CalQuo (Calcium Quantification), which allows the automated analysis and simultaneous monitoring of global fluorescent calcium reporter-based signaling responses in up to 1000 single cells per experiment, at temporal resolutions of sub-seconds to seconds. CalQuo quantifies the number and fraction of responding cells, the temporal dependence of calcium signaling and provides global and individual calcium-reporter fluorescence intensity profiles. We demonstrate the utility of the new method by comparing the calcium-based signaling responses of genetically manipulated human lymphocytic cell lines.

Hypomagnesemia associated with hypocalcemia after total thyroidectomy: an observational study.

PubMed

Mahmoud, Renata Regina da Graça Lorencetti; Neto, Vergilius José Furtado de Araujo; Alves, Wellington; Lin, Chin Shien; Leite, Ana Kober Nogueira; Matos, Leandro Luongo; Filho, Vergilius José Furtado de Araujo; Cernea, Claudio Roberto

2016-06-01

Serum magnesium is frequently low in patients with hypocalcemia after total thyroidectomy. The aim of the present study was to analyze the variations in serum magnesium and calcium concentrations after total thyroidectomy, and the relationship between both ions. We conducted an observational study of 142 patients who had undergone total thyroidectomy, measuring serum calcium and magnesium levels preoperatively and on the day following surgery. The incidence of postoperative hypocalcemia was compared with that of postoperative hypomagnesemia. A total of 142, total thyroidectomies were performed: 54 patients (38%) presented with hypocalcemia on the first postoperative day. A marked decrease in blood magnesium in the group of patients with hypocalcemia was observed when compared to those with normal calcemia on the first postoperative day (mean variation respectively, 0.125 ± 0.065 mmol/L versus 0.035 ± 0.020 mmol/L; P = 0.0002). Hypomagnesemia is significantly associated with early hypocalcemia following thyroidectomy.

Role of TRP ion channels in cancer and tumorigenesis.

PubMed

Shapovalov, George; Ritaine, Abigael; Skryma, Roman; Prevarskaya, Natalia

2016-05-01

Transient receptor potential (TRP) channels are recently identified proteins that form a versatile family of ion channels, the majority of which are calcium permeable and exhibit complex regulatory patterns with sensitivity to multiple environmental factors. While this sensitivity has captured early attention, leading to recognition of TRP channels as environmental and chemical sensors, many later studies concentrated on the regulation of intracellular calcium by TRP channels. Due to mutations, dysregulation of ion channel gating or expression levels, normal spatiotemporal patterns of local Ca(2+) distribution become distorted. This causes deregulation of downstream effectors sensitive to changes in Ca(2+) homeostasis that, in turn, promotes pathophysiological cancer hallmarks, such as enhanced survival, proliferation and invasion. These observations give rise to the appreciation of the important contributions that TRP channels make to many cellular processes controlling cell fate and positioning these channels as important players in cancer regulation. This review discusses the accumulated scientific knowledge focused on TRP channel involvement in regulation of cell fate in various transformed tissues.

Effect of oral mineral and energy supplementation on blood mineral concentrations, energetic and inflammatory profile, and milk yield in dairy cows affected with dystocia.

PubMed

Benzaquen, M; Galvão, K N; Coleman, A E; Santos, J E P; Goff, J P; Risco, C A

2015-05-01

The objectives of this study were to determine the effect of mineral/energy supplementation of dairy cows with dystocia on blood mineral concentrations, energetic and inflammatory profiles, and milk yield. Multiparous Holstein cows with dystocia were randomly assigned into two groups, (1) treated with a mineral/energy supplement (DME, n= 18) and (2) not treated (DNT, n= 22). A group of cows with normal parturition were randomly selected and were left untreated (NNT, n= 25). Cows in DME received an oral drench of 110 g of calcium and 400 g of propionate as calcium propionate plus 110 g potassium chloride and 150 g of magnesium sulfate administered within 6 h of calving and again 3 days post-partum. Compared to cows with a normal parturition, dystocic cows had decreased plasma calcium concentrations, increased plasma haptoglobin, decreased milk yield at 1 day post-partum, and tended to have increased rectal temperatures from 1 to 12 days post-partum. Compared with cows in DNT, those in DME had decreased plasma calcium concentrations and increased plasma magnesium concentrations 2 and 3 days post-partum, and a tendency for an increase in rectal temperature from 1 to 12 days post-partum. Dystocia is detrimental to calcium homeostasis post-partum, but mineral/energy supplementation as undertaken in this study is not recommended for use in cows with dystocia. Copyright © 2015 Elsevier Ltd. All rights reserved.

Presentation and management of osteoporosis presenting in association with pregnancy or lactation.

PubMed

Kovacs, C S; Ralston, S H

2015-09-01

In this review, we summarize our current understanding of the pathophysiology of fragility fractures that occur for the first time during pregnancy and lactation, and provide guidance on appropriate investigations and treatment strategies. Most affected women will have had no prior bone density reading, and so the extent of bone loss that may have occurred during pregnancy or lactation is uncertain. During pregnancy, intestinal calcium absorption doubles in order to meet the fetal demand for calcium, but if maternal intake of calcium is insufficient to meet the combined needs of the mother and baby, the maternal skeleton will undergo resorption during the third trimester. During lactation, several hormonal changes, independent of maternal calcium intake, program a 5-10 % loss of trabecular mineral content in order to provide calcium to milk. After weaning the baby, the maternal skeleton is normally restored to its prior mineral content and strength. This physiological bone resorption during reproduction does not normally cause fractures; instead, women who do fracture are more likely to have additional secondary causes of bone loss and fragility. Transient osteoporosis of the hip may affect one or both femoral heads during pregnancy but it involves localized edema and not skeletal resorption. Case reports have described the use of calcitonin, bisphosphonates, strontium ranelate, teriparatide, vertebroplasty, and kyphoplasty to treat post-partum vertebral fractures. However, the need for such treatments is uncertain given that a progressive increase in bone mass subsequently occurs in most women who present with a fracture during pregnancy or lactation.

Evidence for net renal tubule oxalate secretion in patients with calcium kidney stones

PubMed Central

Zisman, Anna L.; Asplin, John R.; Worcester, Elaine M.; Coe, Fredric L.

2011-01-01

Little is known about the renal handling of oxalate in patients with idiopathic hypercalciuria (IH). To explore the role of tubular oxalate handling in IH and to evaluate whether differences exist between IH and normal controls, we studied 19 IH subjects, 8 normal subjects, and 2 bariatric stone formers (BSF) during a 1-day General Clinical Research Center protocol utilizing a low-oxalate diet. Urine and blood samples were collected at 30- to 60-min intervals while subjects were fasting and after they ate three meals providing known amounts of calcium, phosphorus, sodium, protein, oxalate, and calories. Plasma oxalate concentrations and oxalate-filtered loads were similar between patients (includes IH and BSF) and controls in both the fasting and fed states. Urinary oxalate excretion was significantly higher in patients vs. controls regardless of feeding state. Fractional excretion of oxalate (FEOx) was >1, suggesting tubular secretion of oxalate, in 6 of 19 IH and both BSF, compared with none of the controls (P < 0.00001). Adjusted for water extraction along the nephron, urine oxalate rose more rapidly among patients than normal subjects with increases in plasma oxalate. Our findings identify tubular secretion of oxalate as a key mediator of hyperoxaluria in calcium stone formers, potentially as a means of maintaining plasma oxalate in a tight range. PMID:21123489

Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium

PubMed Central

Pavlov, Tengis S.; Ilatovskaya, Daria V.; Palygin, Oleg; Levchenko, Vladislav; Pochynyuk, Oleh; Staruschenko, Alexander

2015-01-01

Cyst initiation and expansion during polycystic kidney disease is a complex process characterized by abnormalities in tubular cell proliferation, luminal fluid accumulation and extracellular matrix formation. Activity of ion channels and intracellular calcium signaling are key physiologic parameters which determine functions of tubular epithelium. We developed a method suitable for real-time observation of ion channels activity with patch-clamp technique and registration of intracellular Ca2+ level in epithelial monolayers freshly isolated from renal cysts. PCK rats, a genetic model of autosomal recessive polycystic kidney disease (ARPKD), were used here for ex vivo analysis of ion channels and calcium flux. Described here is a detailed step-by-step procedure designed to isolate cystic monolayers and non-dilated tubules from PCK or normal Sprague Dawley (SD) rats, and monitor single channel activity and intracellular Ca2+ dynamics. This method does not require enzymatic processing and allows analysis in a native setting of freshly isolated epithelial monolayer. Moreover, this technique is very sensitive to intracellular calcium changes and generates high resolution images for precise measurements. Finally, isolated cystic epithelium can be further used for staining with antibodies or dyes, preparation of primary cultures and purification for various biochemical assays. PMID:26381526

Salivary flow rate, pH, and concentrations of calcium, phosphate, and sIgA in Brazilian pregnant and non-pregnant women

PubMed Central

Rockenbach, Maria I; Marinho, Sandra A; Veeck, Elaine B; Lindemann, Laura; Shinkai, Rosemary S

2006-01-01

Background Studies on salivary variables and pregnancy in Latin America are scarce. This study aimed to compare salivary flow rate, pH, and concentrations of calcium, phosphate, and sIgA of unstimulated whole saliva in pregnant and non-pregnant Brazilians. Methods Cross-sectional study. Sample was composed by 22 pregnant and 22 non-pregnant women attending the Obstetrics and Gynecology Clinics, São Lucas Hospital, in Porto Alegre city, South region of Brazil. Unstimulated whole saliva was collected to determine salivary flow rate, pH, and biochemical composition. Data were analyzed by Student t test and ANCOVA (two-tailed α = 0.05). Results No difference was found for salivary flow rates and concentrations of total calcium and phosphate between pregnant and non-pregnant women (p > 0.05). Pregnant women had lower pH (6.7) than non-pregnant women (7.5) (p < 0.001), but higher sIgA level (118.9 mg/L) than the latter (90.1 mg/L) (p = 0.026). Conclusion Some of the tested variables of unstimulated whole saliva were different between pregnant and non-pregnant Brazilians in this sample. Overall, the values of the tested salivary parameters were within the range of international references of normality. PMID:17132167

The Effects of Cosmos caudatus on Structural Bone Histomorphometry in Ovariectomized Rats

PubMed Central

Mohamed, Norazlina; Gwee Sian Khee, Sharon; Shuid, Ahmad Nazrun; Muhammad, Norliza; Suhaimi, Farihah; Othman, Faizah; Babji, Abdul Salam; Soelaiman, Ima-Nirwana

2012-01-01

Osteoporosis is considered a serious debilitating disease. Cosmos caudatus (ulam raja), a plant containing antioxidant compounds and minerals, may be used to treat and prevent osteoporosis. This study determines the effectiveness of C. caudatus as bone protective agent in postmenopausal osteoporosis rat model. Thirty-two female rats, aged 3 months old, were divided into 4 groups. Group one was sham operated (sham) while group two was ovariectomized. These two groups were given ionized water by forced feeding. Groups three and four were ovariectomized and given calcium 1% ad libitum and force-fed with C. caudatus at the dose of 500 mg/kg, respectively. Treatments were given six days per week for a period of eight weeks. Body weight was monitored every week and structural bone histomorphometry analyses of the femur bones were performed. Ovariectomy decreased trabecular bone volume (BV/TV), decreased trabecular number (Tb.N), and increased trabecular separation (Tb.Sp). Both calcium 1% and 500 mg/kg C. caudatus reversed the above structural bone histomorphometric parameters to normal level. C. caudatus shows better effect compared to calcium 1% on trabecular number (Tb.N) and trabecular separation (Tb.Sp). Therefore, Cosmos caudatus 500 mg/kg has the potential to act as the therapeutic agent to restore bone damage in postmenopausal women. PMID:22924056

The Effects of Cosmos caudatus on Structural Bone Histomorphometry in Ovariectomized Rats.

PubMed

Mohamed, Norazlina; Gwee Sian Khee, Sharon; Shuid, Ahmad Nazrun; Muhammad, Norliza; Suhaimi, Farihah; Othman, Faizah; Babji, Abdul Salam; Soelaiman, Ima-Nirwana

2012-01-01

Osteoporosis is considered a serious debilitating disease. Cosmos caudatus (ulam raja), a plant containing antioxidant compounds and minerals, may be used to treat and prevent osteoporosis. This study determines the effectiveness of C. caudatus as bone protective agent in postmenopausal osteoporosis rat model. Thirty-two female rats, aged 3 months old, were divided into 4 groups. Group one was sham operated (sham) while group two was ovariectomized. These two groups were given ionized water by forced feeding. Groups three and four were ovariectomized and given calcium 1% ad libitum and force-fed with C. caudatus at the dose of 500 mg/kg, respectively. Treatments were given six days per week for a period of eight weeks. Body weight was monitored every week and structural bone histomorphometry analyses of the femur bones were performed. Ovariectomy decreased trabecular bone volume (BV/TV), decreased trabecular number (Tb.N), and increased trabecular separation (Tb.Sp). Both calcium 1% and 500 mg/kg C. caudatus reversed the above structural bone histomorphometric parameters to normal level. C. caudatus shows better effect compared to calcium 1% on trabecular number (Tb.N) and trabecular separation (Tb.Sp). Therefore, Cosmos caudatus 500 mg/kg has the potential to act as the therapeutic agent to restore bone damage in postmenopausal women.

The complex nature of calcium cation interactions with phospholipid bilayers

PubMed Central

Melcrová, Adéla; Pokorna, Sarka; Pullanchery, Saranya; Kohagen, Miriam; Jurkiewicz, Piotr; Hof, Martin; Jungwirth, Pavel; Cremer, Paul S.; Cwiklik, Lukasz

2016-01-01

Understanding interactions of calcium with lipid membranes at the molecular level is of great importance in light of their involvement in calcium signaling, association of proteins with cellular membranes, and membrane fusion. We quantify these interactions in detail by employing a combination of spectroscopic methods with atomistic molecular dynamics simulations. Namely, time-resolved fluorescent spectroscopy of lipid vesicles and vibrational sum frequency spectroscopy of lipid monolayers are used to characterize local binding sites of calcium in zwitterionic and anionic model lipid assemblies, while dynamic light scattering and zeta potential measurements are employed for macroscopic characterization of lipid vesicles in calcium-containing environments. To gain additional atomic-level information, the experiments are complemented by molecular simulations that utilize an accurate force field for calcium ions with scaled charges effectively accounting for electronic polarization effects. We demonstrate that lipid membranes have substantial calcium-binding capacity, with several types of binding sites present. Significantly, the binding mode depends on calcium concentration with important implications for calcium buffering, synaptic plasticity, and protein-membrane association. PMID:27905555

The complex nature of calcium cation interactions with phospholipid bilayers

NASA Astrophysics Data System (ADS)

Melcrová, Adéla; Pokorna, Sarka; Pullanchery, Saranya; Kohagen, Miriam; Jurkiewicz, Piotr; Hof, Martin; Jungwirth, Pavel; Cremer, Paul S.; Cwiklik, Lukasz

2016-12-01

Understanding interactions of calcium with lipid membranes at the molecular level is of great importance in light of their involvement in calcium signaling, association of proteins with cellular membranes, and membrane fusion. We quantify these interactions in detail by employing a combination of spectroscopic methods with atomistic molecular dynamics simulations. Namely, time-resolved fluorescent spectroscopy of lipid vesicles and vibrational sum frequency spectroscopy of lipid monolayers are used to characterize local binding sites of calcium in zwitterionic and anionic model lipid assemblies, while dynamic light scattering and zeta potential measurements are employed for macroscopic characterization of lipid vesicles in calcium-containing environments. To gain additional atomic-level information, the experiments are complemented by molecular simulations that utilize an accurate force field for calcium ions with scaled charges effectively accounting for electronic polarization effects. We demonstrate that lipid membranes have substantial calcium-binding capacity, with several types of binding sites present. Significantly, the binding mode depends on calcium concentration with important implications for calcium buffering, synaptic plasticity, and protein-membrane association.

Vitamin D (25(OH)D) in patients with chronic kidney disease stages 2-5.

PubMed

Restrepo Valencia, César Augusto; Aguirre Arango, José Vicente

2016-09-30

To establish the impact the chronic kidney disease stage has in the native vitamin D levels in patients not undergoing dialysis treatment. A study performed in Manizales, Colombia, a city located 2,200 meters above sea level, without important stational variations. Patients with 18 years of age or more, with chronic kidney disease stages 2 to 5 and not undergoing dialysis treatment were recruited for this study. Demographic and anthropometric variations were evaluated as well as solar exposure, CKD etiology and laboratory variables related to bone and mineral diseases. For each CKD clinical stage, correlations were evaluated for vitamin D levels, laboratory results for bone and mineral diseases, solar exposure and ethnicity. Three hundred thirty-three patients were evaluated with a median age of 71 years, most of them mestizo (71%), 173 were women. The main CKD etiology was hypertensive nephropathy (32.2%). 21.1% of patients had normal vitamin D levels, 70.1% were within insufficient range and 8.8% were in deficit. A negative correlation was found between the levels of vitamin 25 (OH) D and the values for: creatinine, phosphorous, calcium x phosphorous product, PTH, 24 hours urine protein and BMI. A positive relationship was found for calcium and albumin. Positive significant statistical correlation was found for vitamin 25(OH) D levels and solar exposure for stages 3b and 4 of CKD. It is common to find low levels of vitamin 25(OH) D in patients with CKD; these can contribute to the appearance of secondary hyperparathyroidism.

Vitamin D (25(OH)D) in patients with chronic kidney disease stages 2-5

PubMed Central

Aguirre Arango, José Vicente

2016-01-01

Objective: To establish the impact the chronic kidney disease stage has in the native vitamin D levels in patients not undergoing dialysis treatment. Methods: A study performed in Manizales, Colombia, a city located 2,200 meters above sea level, without important stational variations. Patients with 18 years of age or more, with chronic kidney disease stages 2 to 5 and not undergoing dialysis treatment were recruited for this study. Demographic and anthropometric variations were evaluated as well as solar exposure, CKD etiology and laboratory variables related to bone and mineral diseases. For each CKD clinical stage, correlations were evaluated for vitamin D levels, laboratory results for bone and mineral diseases, solar exposure and ethnicity. Results: Three hundred thirty-three patients were evaluated with a median age of 71 years, most of them mestizo (71%), 173 were women. The main CKD etiology was hypertensive nephropathy (32.2%). 21.1% of patients had normal vitamin D levels, 70.1% were within insufficient range and 8.8% were in deficit. A negative correlation was found between the levels of vitamin 25 (OH) D and the values for: creatinine, phosphorous, calcium x phosphorous product, PTH, 24 hours urine protein and BMI. A positive relationship was found for calcium and albumin. Positive significant statistical correlation was found for vitamin 25(OH) D levels and solar exposure for stages 3b and 4 of CKD. Conclusions: It is common to find low levels of vitamin 25(OH) D in patients with CKD; these can contribute to the appearance of secondary hyperparathyroidism. PMID:27821896

Mechanisms of Intracellular Calcium Homeostasis in MC3T3-E1 Cells and Bone Tissues of Sprague-Dawley Rats Exposed to Fluoride.

PubMed

Duan, Xiao-qin; Li, Yan-hui; Zhang, Xiu-yun; Zhao, Zhi-tao; Wang, Ying; Wang, Huan; Li, Guang-sheng; Jing, Ling

2016-04-01

Calcium homeostasis of osteoblasts (OBs) has an important role in the physiology and pathology of bone tissue. In order to study the mechanisms of intracellular calcium homeostasis, MC3T3-E1 cells and Sprague-Dawley rats were treated with different concentrations of fluoride. Then, we examined intracellular-free calcium ion ([Ca(2+)]i) in MC3T3-E1 cells as well as mRNA and protein levels of Cav1.2, the main subunit of L-type voltage-dependent calcium channels (VDCCs), Na(+)/Ca(2+) exchange carriers (NCS), and plasma membrane Ca(2+)-ATPase (PMCA), inositol 1,4,5-trisphosphate receptor (IP3R) channels, sarco/endoplasmic reticulum calcium ATPase 2b (SERCA2b)/ATP2A2 in vitro, and rat bone tissues in vivo. Our results showed that [Ca(2+)]i of fluoride-treated OBs increased in a concentration-dependent manner with an increase in the concentration of fluoride. We also found that the low dose of fluoride led to high expression levels of Cav1.2, NCS-1, and PMCA and low expression levels of IP3R and SERCA2b/ATP2A2, while the high dose of fluoride induced an increase in SERCA2b/ATP2A2 levels and decrease in Cav1.2, PMCA, NCS-1, and IP3R levels. These results demonstrate that calcium channels and calcium pumps of plasma and endoplasmic reticulum (ER) membranes keep intracellular calcium homeostasis by regulating Cav1.2, NCS-1, PMCA, IP3R, and SERCA2b/ATP2A2 expression.

Calcium Bioavailability from Mineral Waters with Different Mineralization in Comparison to Milk and a Supplement.

PubMed

Greupner, Theresa; Schneider, Inga; Hahn, Andreas

2017-07-01

The aim of the present study was to compare the bioavailability of calcium from 3 mineral waters with different concentrations of minerals with that of milk and a calcium supplement. A single-center, randomized controlled trial with a crossover design with 21 healthy men and women was conducted at the Institute of Food Science and Human Nutrition, Leibniz University Hannover. The participants consumed the 5 test products providing 300 mg of calcium each on 5 examination days with 1-week wash-out phases in between. Primary outcome variables were the area under the curve of serum calcium levels for 10-hour (AUC 0-10h ) and 24-hour urinary calcium excretion. In all groups, no significant differences in the AUC 0-10h of serum calcium levels as well as in the 24-hour urinary calcium excretion were observed. Likewise, mean changes in serum phosphate and urinary phosphate, as well as serum parathormone, showed no differences between the groups. Given an equivalent bioavailability of calcium in all test products, neither a high concentration of SO 4 2- or of HCO 3 influenced the bioavailability of calcium. Accordingly, the use of mineral water with high concentrations of calcium constitutes a calorie-free calcium source that can improve calcium supply.

Interactions between calcium and phosphorus in the regulation of the production of fibroblast growth factor 23 in vivo

PubMed Central

Quinn, Stephen J.; Thomsen, Alex R. B.; Pang, Jian L.; Kantham, Lakshmi; Bräuner-Osborne, Hans; Pollak, Martin; Goltzman, David

2013-01-01

Calcium and phosphorus homeostasis are highly interrelated and share common regulatory hormones, including FGF23. However, little is known about calcium's role in the regulation of FGF23. We sought to investigate the regulatory roles of calcium and phosphorus in FGF23 production using genetic mouse models with targeted inactivation of PTH (PTH KO) or both PTH and the calcium-sensing receptor (CaSR; PTH-CaSR DKO). In wild-type, PTH KO, and PTH-CaSR DKO mice, elevation of either serum calcium or phosphorus by intraperitoneal injection increased serum FGF23 levels. In PTH KO and PTH-CaSR DKO mice, however, increases in serum phosphorus by dietary manipulation were accompanied by severe hypocalcemia, which appeared to blunt stimulation of FGF23 release. Increases in dietary phosphorus in PTH-CaSR DKO mice markedly decreased serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] despite no change in FGF23, suggesting direct regulation of 1,25(OH)2D3 synthesis by serum phosphorus. Calcium-mediated increases in serum FGF23 required a threshold level of serum phosphorus of about 5 mg/dl. Analogously, phosphorus-elicited increases in FGF23 were markedly blunted if serum calcium was less than 8 mg/dl. The best correlation between calcium and phosphorus and serum FGF23 was found between FGF23 and the calcium × phosphorus product. Since calcium stimulated FGF23 production in the PTH-CaSR DKO mice, this effect cannot be mediated by the full-length CaSR. Thus the regulation of FGF23 by both calcium and phosphorus appears to be fundamentally important in coordinating the serum levels of both mineral ions and ensuring that the calcium × phosphorus product remains within a physiological range. PMID:23233539

Gitelman syndrome manifesting in early childhood and leading to delayed puberty: a case report.

PubMed

Raza, Farhan; Sultan, Mubashar; Qamar, Khola; Jawad, Ali; Jawa, Ali

2012-10-02

Gitelman syndrome is an inherited autosomal recessive renal salt-wasting disorder. It presents with variable clinical symptoms including muscle weakness and fatigue, and the diagnosis is based on metabolic alkalosis, hypokalemia, hypomagnesemia and hypocalciuria. It is usually diagnosed incidentally in early adulthood. There are rare cases of Gitelman syndrome presenting in early childhood; however, to the best of our knowledge it has not previously been associated with delayed puberty. A 17-year-old South Asian man with recurrent episodes of generalized muscle weakness, fatigue and cramps from the age of two years was admitted for further workup. Before the age of 12 years, the episodes had been mild, but they then got progressively worse. Other symptoms include polyuria, polydipsia, nocturia, paresthesia and occasional watery diarrhea. He also had a history of short stature, poor weight gain and delayed developmental landmarks. His family history was unremarkable except for the consanguineous marriage of his parents. An examination revealed a thin and lean man with blood pressure of 95/60mmHg. His height and weight were below the third percentile and his sexual development was at Tanner Stage II. Laboratory work revealed serum sodium of 124mmol/L, potassium 2.4mmol/L, calcium 6.5mmol/L and magnesium of 1.2mg/dL. His testosterone level was low (0.85ng/mL, normal for his age 2.67 to 10.12ng/mL) with normal levels of luteinizing hormone and follicle-stimulating hormone. The sex hormone findings were attributed to delayed puberty. A 24-hour urinary analysis revealed decreased excretion of calcium (25.9mg/24 hours). Based on the findings of hypokalemic metabolic alkalosis without hypertension, severe hypomagnesemia and hypocalciuria, a diagnosis of Gitelman syndrome was made. Treatment was started with oral supplementation of potassium, magnesium and calcium along with spironolactone and liberal salt intake. Diagnosis of Gitelman syndrome is usually made incidentally during adolescence or early adulthood based on clinical and biochemical findings. We report that Gitelman syndrome can present during the early childhood years. If undiagnosed and untreated, it can lead to growth retardation and delayed puberty.

Hyperparathyroidism in black patients: an update.

PubMed Central

Yates, W. D.; Chatman, D. M.; Rogers, N.; Chung, E. B.; Nunez, A.; Leffall, L. D.

1992-01-01

Cervical exploration with removal of the pathologic gland or glands is effective treatment for parathyroid adenomas and hyperplasia. This article reports the results of a retrospective study of 41 patients who underwent elective cervical exploration for primary hyperparathyroidism at Howard University Hospital between 1974 and 1989. Preoperative localization studies for primary neck exploration consisted of an ultrasound of the neck. Removing the diseased gland/glands resulted in the resolution of the patients' symptoms and the return of calcium levels to normal. Complications included transient hypocalcemia, a wound hematoma, and a postoperative death. Images Figure 1 Figure 2 Figure 3 PMID:1507262

Monitoring Calcium in Trout Eggs Exposed to Hydrazine.

DTIC Science & Technology

1981-07-10

differentiation processes (Chapman, 1980). The high level of calcium in the notochord can be attributed to poor circulation which is characteristic of this...healthy muscle of the same individual. The notochord of the 8.0 mg/P group showed a higher calcium level than the control group. The chorion did not...calcium can alter the process . The above would suggest that even if some hydrazine is converted to N2 and thereby produce the gas bubble disease

Scrotal calcinosis: idiopathic or dystrophic?

PubMed

Dubey, Suparna; Sharma, Rajeev; Maheshwari, Veena

2010-02-15

Scrotal calcinosis is a rare benign local process characterized by multiple, painless, hard scrotal nodules in the absence of any systemic metabolic disorder. Histological examination reveals extensive deposition of calcium in the dermis, which may be surrounded by histiocytes and an inflammatory giant cell reaction. Numerous theories have been propounded to explain the pathogenesis of this condition, but the principal debate revolves around whether the calcium is deposited at the site of previous epithelial cysts or the calcified nodules are purely idiopathic. This is the largest study of scrotal calcinosis to date with 100 cases, on which clinical, biochemical, radiological, cytopathological, and histopathological examinations were conducted. The histological picture shows a continuous spectrum of changes ranging from intact epithelial cysts (41.0%) - both normal and inflamed; through inflamed cysts containing calcific material in the lumen but with intact cyst wall (53.0%); calcified inflamed cysts with partial epithelial lining (11.0%); to 'naked' calcium deposits lying in the dermis (100%), sometimes compressing surrounding collagen fibres to form a pseudocyst (56.0%). The presence of normal values of calcium and phosphorus along with this spectrum of changes in histology both support the theory that these form by dystrophic calcification of epithelial cysts in a progression that involves inflammation, rupture, calcification and obliteration of the cyst wall.

Pheochromocytoma, papillary thyroid carcinoma.

PubMed

Nasser, Tariq; Qari, Faiza

2009-08-01

A 53-year-old woman presented with labile and difficult to control hypertension on 3 different anti-hypertensive medications. Abdominal computed tomography and ultrasonography of the thyroid gland showed a 1.8 cm thyroid nodule. Fine needle aspiration biopsy of the thyroid nodule revealed papillary thyroid carcinoma. Serum thyroid stimulating hormone and free thyroxine, calcitonin, carcinoembryonic antigen, intact parathyroid hormone, and calcium levels were within normal limits. A 24-hour urine metanephrine showed significant elevation in urine metanephrine of approximately 3 times the upper limit of normal, and the result of 131I-metaiodobenzyleguanjdjne (131I-MIBG) scintigraphy confirmed that the adrenal mass was pheochromocytoma. Right adrenalectomy and total thyroidectomy were performed. The final pathology was pheochromocytoma and papillary thyroid carcinoma. An analysis of c-ret porto-oncogene mutation yielded a negative result. This unusual association of 2 tumors represents a new entity.

Calcium in drinking water: effect on iron stores in Danish blood donors-results from the Danish Blood Donor Study.

PubMed

Rigas, Andreas S; Ejsing, Benedikte H; Sørensen, Erik; Pedersen, Ole B; Hjalgrim, Henrik; Erikstrup, Christian; Ullum, Henrik

2018-06-01

Studies confirm that calcium inhibits iron absorption. Danish tap water comes from groundwater, which contains varying amounts of calcium depending on the subsoil. We investigated the association of calcium in drinking water with iron levels in Danish blood donors. We used data on Danish blood donors including dietary and lifestyle habits, blood donation history, and physiologic characteristics including measures of ferritin levels along with information on area of residence from The Danish Blood Donor Study. Data on calcium levels in groundwater ("water hardness") were obtained through the Geological Survey of Denmark and Greenland. We performed multiple linear and logistic regression analyses to evaluate the effect of water hardness on ferritin levels and risk of having iron deficiency (defined as ferritin levels <15 ng/mL), stratified by sex. There was a significant negative association between water hardness and ferritin levels in both men and women. Risk of iron deficiency was correspondingly increased in both men (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.14-2.12) and women (OR, 1.20; 95% CI, 1.03-1.40) with increasing water hardness. In analyses restricted to individuals who received supplemental iron tablets no significant association between groundwater hardness and ferritin levels was observed. As measured by ferritin levels, residential drinking water calcium content is associated with blood donors- iron levels and risk of iron deficiency. However, effect sizes are small. © 2018 AABB.

Effects of storage time on the motility, mortality and calcium levels of Atlantic salmon Salmo salar spermatozoa.

PubMed

Parodi, J; Guerra, G; Cuevas, M; Ramírez-Reveco, A; Romero, F

2017-04-01

This study estimates spermatozoa mortality, morphology, motility and intracellular calcium levels in Atlantic salmon Salmo salar milt after prolonged storage. Milt samples were preserved at 4° C for 25 days and then evaluated for mortality. Motility remained high for the first 3 days and the mortality was low during the first 5 days of storage. A decrease of >50% in calcium content was observed after 5 days of storage. When spermatozoa were activated, calcium levels increased >200% in relative fluorescence units (RFU); this rate of increase was lost when the samples were stored for extended periods of time and was only partially manifested in a zero calcium solution. The results suggest that in vitro storage of S. salar spermatozoa at 4° C for a period of 3 days preserves motility and limits mortality to levels similar to those of fresh spermatozoa. This method also maintains intracellular calcium storage critical for spermatozoa performance. © 2017 The Fisheries Society of the British Isles.

Calcium acetate or calcium carbonate for hyperphosphatemia of hemodialysis patients: a meta-analysis.

PubMed

Wang, Yong; Xie, Guoqiang; Huang, Yuanhang; Zhang, Han; Yang, Bo; Mao, Zhiguo

2015-01-01

High levels of serum phosphorus both at baseline and during follow-up are associated with increased mortality in dialysis patients, and administration of phosphate binders was independently associated with improved survival among hemodialysis population. Calcium-based phosphate binders are the most commonly used phosphate binders in developing countries for their relatively low costs. To compare the efficacy and safety between calcium carbonate and calcium acetate in the treatment of hyperphosphatemia in hemodialysis patients. PubMed, EMBASE, Cochrane Library, Google scholar and Chinese databases (Wanfang, Weipu, National Knowledge Infrastructure of China) were searched for relevant studies published before March 2014. Reference lists of nephrology textbooks and review articles were checked. A meta-analysis of randomized controlled trials (RCTs) and quasi-RCTs that assessed the effects and adverse events of calcium acetate and calcium carbonate in adult patients with MHD was performed using Review Manager 5.0. A total of ten studies (625 participants) were included in this meta-analysis. There was insufficient data in all-cause mortality and cardiovascular events for meta-analysis. Compared with calcium carbonate group, the serum phosphorus was significantly lower in calcium acetate group after4 weeks' administration (MD -0.15 mmol/L, 95% CI -0.28 to -0.01) and after 8 weeks' administration (MD -0.25 mmol/L, 95% CI -0.40 to -0.11). There was no difference in serum calcium levels or the incidence of hypercalcemia between two groups at 4 weeks and 8 weeks. No statistical difference was found in parathyroid hormone (PTH) levels or serum calcium by phosphorus (Ca x P) product. There was significantly higher risk of intolerance with calcium acetate treatment (RR 3.46, 95% CI 1.48 to 8.26). For hyperphosphatemia treatment, calcium acetate showed better efficacy and with a higher incidence of intolerance compared with calcium carbonate. There are insufficient data to establish the comparative superiority of the two calcium-based phosphate binders on all-cause mortality and cardiovascular end-points in hemodialysis patients.

Hypoparathyroidism: what is the best calcium carbonate supplementation intake form?

PubMed

Gollino, Loraine; Biagioni, Maria Fernanda Giovanetti; Sabatini, Nathalia Regina; Tagliarini, José Vicente; Corrente, José Eduardo; Paiva, Sérgio Alberto Rupp de; Mazeto, Gláucia Maria Ferreira da Silva

2017-11-15

In hypoparathyroidism, calcium supplementation using calcium carbonate is necessary for the hypocalcemia control. The best calcium carbonate intake form is unknown, be it associated with feeding, juice or in fasting. The objective was to evaluate the calcium, phosphorus and Calcium×Phosphorus product serum levels of hypoparathyroidism women after total thyroidectomy, following calcium carbonate intake in three different forms. A crossover study was carried out with patients presenting definitive hypoparathyroidism, assessed in different situations (fasting, with water, orange juice, breakfast with a one-week washout). Through the review of clinical data records of tertiary hospital patients from 1994 to 2010, 12 adult women (18 50 years old) were identified and diagnosed with definitive post-thyroidectomy hypoparathyroidism. The laboratory results of calcium and phosphorus serum levels dosed before and every 30min were assessed, for 5h, after calcium carbonate intake (elementary calcium 500mg). The maximum peak average values for calcium, phosphorus and Calcium×Phosphorus product were 8.63mg/dL (water), 8.77mg/dL (orange juice) and 8.95mg/dL (breakfast); 4.04mg/dL (water), 4.03mg/dL (orange juice) and 4.12mg/dL (breakfast); 34.3mg 2 /dL 2 (water), 35.8mg 2 /dL 2 (orange juice) and 34.5mg 2 /dL 2 (breakfast), respectively, and the area under the curve 2433mg/dLmin (water), 2577mg/dLmin (orange juice) and 2506mg/dLmin (breakfast), 1203mg/dLmin (water), 1052mg/dLmin (orange juice) and 1128mg/dLmin (breakfast), respectively. There was no significant difference among the three different tests (p>0.05). The calcium, phosphorus and Calcium×Phosphorus product serum levels evolved in a similar fashion in the three calcium carbonate intake forms. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Role of cellular oxalate in oxalate clearance of patients with calcium oxalate monohydrate stone formation and normal controls.

PubMed

Oehlschläger, Sven; Fuessel, Susanne; Meye, Axel; Herrmann, Jana; Froehner, Michael; Albrecht, Steffen; Wirth, Manfred P

2009-03-01

To examine the cellular, plasma, and urinary oxalate and erythrocyte oxalate flux in patients with calcium oxalate monohydrate (COM) stone formation vs normal controls. Pathologic oxalate clearance in humans is mostly integrated in calcium oxalate stone formation. An underlying cause of deficient oxalate clearance could be defective transmembrane oxalate transport, which, in many tissues, is regulated by an anion exchanger (SLC26). We studied 2 groups: 40 normal controls and 41 patients with COM stone formation. Red blood cells were divided for cellular oxalate measurement and for resuspension in a buffered solution (pH 7.40); 0.1 mmol/L oxalate was added. The supernatant was measured for oxalate immediately and 1 hour after incubation. The plasma and urinary oxalate were analyzed in parallel. The mean cellular oxalate concentrations were significantly greater in the normal controls (5.25 +/- 0.47 micromol/L) than in those with COM stone formation (2.36 +/- 0.28 micromol/L; P < .01). The mean urinary oxalate concentrations were significantly greater in those with COM stone formation (0.31 +/- 0.02 mmol/L) than in the controls (0.24 +/- 0.02 mmol/L; P < .01). The cellular oxalate concentrations correlated significantly with the plasma (r = 0.49-0.63; P < .01) and urinary oxalate (r = -0.29-0.41; P < .03) concentrations in both groups. The plasma oxalate concentrations correlated significantly with the urinary oxalate concentrations (r = -0.30; P < .03) in the controls and with the erythrocyte oxalate flux (r = 0.25; P < .05) in those with COM stone formation. Our data implicate the presence of a cellular oxalate buffer to stabilize plasma and urinary oxalate concentrations in normal controls.

Low-concentration hydrogen peroxide can upregulate keratinocyte intracellular calcium and PAR-2 expression in a human keratinocyte-melanocyte co-culture system.

PubMed

Li, Jian; Tang, Lu-Yan; Fu, Wen-Wen; Yuan, Jin; Sheng, You-Yu; Yang, Qin-Ping

2016-12-01

Hydrogen peroxide (H 2 O 2 ) may have a biphasic effect on melanin synthesis and melanosome transfer. High H 2 O 2 concentrations are involved in impaired melanosome transfer in vitiligo. However, low H 2 O 2 concentration promotes the beneficial proliferation and migration of melanocytes. The aim of this study was to explore low H 2 O 2 and its mechanism in melanosome transfer, protease-activated receptor-2 (PAR-2) expression and calcium balance. Melanosomes were fluorescein-labeled for clear visualization of their transfer. The expression of protease-activated receptor-2 (PAR-2) in keratinocytes was determined by western blot analysis. Flow cytometry was employed to evaluate the effects of H 2 O 2 on calcium levels in keratinocytes. Fluorescence microscopy showed the upregulation of melanosome transfer into keratinocytes following 0.3 mM H 2 O 2 treatment in the co-cultures rather than in the untreated control groups, which was associated with higher expression of PAR-2 protein and increased calcium concentration. The addition of a PAR-2 antagonist inhibited the positive activity of H 2 O 2 and calcium flow in keratinocytes. When calcium flow was blocked by a calcium chelator, the addition of H 2 O 2 did not increase the PAR-2 expression level in keratinocytes, therefore, inhibiting dendrite formation and melanosome transfer. Low H 2 O 2 concentration promotes melanosome transfer with increased PAR-2 expression level and calcium concentration in keratinocytes. In addition, the interaction between melanocytes and keratinocytes is more beneficial to enhance calcium levels in keratinocytes which mediate melanin transfer. Moreover, low H 2 O 2 concentration promotes dendrite formation, in which extracellular calcium and Par-2 were involved.

Monitoring Endoplasmic Reticulum Calcium Homeostasis Using a Gaussia Luciferase SERCaMP.

PubMed

Henderson, Mark J; Wires, Emily S; Trychta, Kathleen A; Yan, Xiaokang; Harvey, Brandon K

2015-09-06

The endoplasmic reticulum (ER) contains the highest level of intracellular calcium, with concentrations approximately 5,000-fold greater than cytoplasmic levels. Tight control over ER calcium is imperative for protein folding, modification and trafficking. Perturbations to ER calcium can result in the activation of the unfolded protein response, a three-prong ER stress response mechanism, and contribute to pathogenesis in a variety of diseases. The ability to monitor ER calcium alterations during disease onset and progression is important in principle, yet challenging in practice. Currently available methods for monitoring ER calcium, such as calcium-dependent fluorescent dyes and proteins, have provided insight into ER calcium dynamics in cells, however these tools are not well suited for in vivo studies. Our lab has demonstrated that a modification to the carboxy-terminus of Gaussia luciferase confers secretion of the reporter in response to ER calcium depletion. The methods for using a luciferase based, secreted ER calcium monitoring protein (SERCaMP) for in vitro and in vivo applications are described herein. This video highlights hepatic injections, pharmacological manipulation of GLuc-SERCaMP, blood collection and processing, and assay parameters for longitudinal monitoring of ER calcium.

Assessment the levels of tartrate-resistant acid phosphatase (TRAP) on mice fed with eggshell calcium citrate malate.

PubMed

Yu, Yiding; Zhang, Mingdi; Lin, Songyi; Wang, Liyan; Liu, Jingbo; Jones, Gregory; Huang, Hsiang-Chi

2013-07-01

Optimized conditions were obtained by one-factor-at-a-time test (OFAT) and ternary quadratic regression orthogonal composite design (TQROCD) respectively. By pulse electric fields (PEF) technology, the process of eggshell calcium citrate malate (ESCCM), eggshell calcium citrate (ESCC) and eggshells calcium malate (ESCM) were comprehensive compared. The levels of tartrate-resistant acid phosphatase (TRAP) and the bioavailability on mice fed with eggshell calcium citrate malate (ESCCM) treated by pulsed electric field (PEF) were evaluated. Results showed that the rates of calcium dissolution of the different acids studied can be arranged as ESCCM (7.90 mg/mL)>ESCC (7.12 mg/mL)>ESCM (7.08 mg/mL) from highest to lowest rate of dissolution. At the same dose 133.0 mg kg(-1) d(-1), the levels of TRAP in the ESCCM treatment groups were significantly lower than those in ESCM and ESCC (P<0.05). Bone calcium content in the mice fed with ESCCM was generally higher than fed with ESCM and ESCC. Copyright © 2013 Elsevier B.V. All rights reserved.

Effect of aluminum on bidirectional calcium flux in rat everted intestinal sacs.

PubMed

Adler, A J; Zara, C; Berlyne, G M

1989-09-01

The effect of aluminum on intestinal calcium absorption was determined in male Sprague-Dawley rats using an everted intestinal sac technique. Bidirectional calcium flux in the duodena and ilea of normal rats was assessed by means of dual calcium isotopes. Two micromolar aluminum significantly inhibited net calcium absorption (J net) in the duodenum through suppression of mucosato-serosa flux (J m----s). Jm----s was reduced from 2.21 +/- 0.50 mumol Ca.h-1.g wet wt-1 in controls to 0.93 +/- 0.35 mumol Ca.h-1.g-1 in aluminum exposed sacs, and Jnet was reduced from 1.88 +/- 0.14 mumol Ca.h-1.g-1 to 0.55 +/- 0.41 mumol Ca.h-1.g-1 (P less than 0.001). Serosa-to-mucosa calcium flux (Js----m) was not similarly influenced by aluminum. Inhibition of Jm----s occurred whether aluminum was initially present on the mucosal or serosal side of the duodenal sac and inhibition of Jnet calcium by 2 muM A1 occurred at all ambient concentrations of calcium studied. In the ileum, aluminum had no effect on any component of calcium flux. Aluminum did not induce any suppression of glucose transport in either the duodenum or ileum, suggesting that the effect on calcium transport is relatively specific. These results suggest that aluminum inhibits calcium absorption in the duodenum through an effect on active mucosa-to-serosa transport, but has no effect on ileal calcium absorption, which in the rat is not mediated by an active process.

Effect of hydro-alcoholic extract of Vernonia cinerea Less. against ethylene glycol-induced urolithiasis in rats.

PubMed

Hiremath, Ravindra D; Jalalpure, Sunil S

2016-01-01

Aim of this study is to evaluate antiurolithiatic potential of whole plant hydro-alcoholic (30:70) extract of Vernonia cinerea Less. in accordance to its claims made in ancient literature and also being one of the ingredients of cystone, a marketed formulation widely used in the management of urolithiasis. To induce urolithiasis, 0.75% v/v ethylene glycol was administered orally for 14 days. The curative dose of 400 mg/kg b.w. and preventive doses of 100, 200, and 400 mg/kg b.w. were administered from 15 th to 28 th and 1 st to 28 days, respectively. Cystone 750 mg/kg b.w. was selected as the reference standard for both curative and preventive doses. On 28 th day, urinate of 24 h was collected and subjected for estimation of calcium, oxalate, and phosphates. Serum biochemical and kidney homogenate analysis was done for determination of renal oxalate contents. The diseased Group II showed marked increase ( P < 0.001 vs. normal Group I) in levels of urine calcium, oxalate, and phosphate. Serum creatinine, urea, and uric acid levels were also increased. Histopathological studies of kidney sections revealed significant changes. Treatment with hydro-alcoholic extract of V. cinerea showed significant ( P < 0.01 vs. calculi-induced Group II) dose-dependent activity. A progressive increase in urine output, body weight, and decline in concentrations of stone-forming components such as calcium, oxalates, and phosphates was observed. It can be inferred that V. cinerea Less. is effective in ethylene glycol-induced urolithiasis and may have a potential in preventing and curing urolithiasis.

Genetic Ablation of Calcium-independent Phospholipase A2γ Induces Glomerular Injury in Mice*

PubMed Central

Elimam, Hanan; Papillon, Joan; Kaufman, Daniel R.; Guillemette, Julie; Aoudjit, Lamine; Gross, Richard W.; Takano, Tomoko; Cybulsky, Andrey V.

2016-01-01

Glomerular visceral epithelial cells (podocytes) play a critical role in the maintenance of glomerular permselectivity. Podocyte injury, manifesting as proteinuria, is the cause of many glomerular diseases. We reported previously that calcium-independent phospholipase A2γ (iPLA2γ) is cytoprotective against complement-mediated glomerular epithelial cell injury. Studies in iPLA2γ KO mice have demonstrated an important role for iPLA2γ in mitochondrial lipid turnover, membrane structure, and metabolism. The aim of the present study was to employ iPLA2γ KO mice to better understand the role of iPLA2γ in normal glomerular and podocyte function as well as in glomerular injury. We show that deletion of iPLA2γ did not cause detectable albuminuria; however, it resulted in mitochondrial structural abnormalities and enhanced autophagy in podocytes as well as loss of podocytes in aging KO mice. Moreover, after induction of anti-glomerular basement membrane nephritis in young mice, iPLA2γ KO mice exhibited significantly increased levels of albuminuria, podocyte injury, and loss of podocytes compared with wild type. Thus, iPLA2γ has a protective functional role in the normal glomerulus and in glomerulonephritis. Understanding the role of iPLA2γ in glomerular pathophysiology provides opportunities for the development of novel therapeutic approaches to glomerular injury and proteinuria. PMID:27226532

Determining appropriate nutritional interventions for South African children living in informal urban settlements.

PubMed

Coutsoudis, A; Jinabhai, C C; Coovadia, H M; Mametja, L D

1994-09-01

Rapid urbanisation in South Africa has led to the creation of informal shack settlements where the health status of children is in jeopardy; it needs to be monitored so that appropriate intervention strategies can be formulated. Accordingly, the nutritional status of 190 children (3-6 years of age) living in Besters, a typical urban shack settlement north of Durban, was assessed anthropometrically. In addition the following biochemical values were determined: vitamins A and E, calcium, magnesium, phosphorus, albumin, haemoglobin, serum iron and ferritin and percentage of transferrin saturation. Malnutrition was evident in 13% of the children who were underweight (below the National Center for Health Statistics (NCHS) third weight-for-age percentile) and 27% who were stunted (below the NCHS third height-for-age percentile). Concentrations of albumin, calcium, magnesium, phosphorus and vitamin E were close to normal, with no more than 10% of the sample having values outside the normal range. However, 44% of the children had low serum retinol levels (< 20 micrograms/dl) and 21% of the children had anaemia (haemoglobin < 11 micrograms/dl). Significant positive correlations were found between serum retinol and all biochemical indicators of iron status except serum ferritin. This study highlights the fact that nutrient deficiencies are interrelated, particularly protein energy malnutrition and poor vitamin A and iron status. A broad multifaceted comprehensive health intervention programme is therefore required.

Calcium Signaling Pathway Genes RUNX2 and CACNA1C Are Associated With Calcific Aortic Valve Disease

PubMed Central

Guauque-Olarte, Sandra; Messika-Zeitoun, David; Droit, Arnaud; Lamontagne, Maxime; Tremblay-Marchand, Joël; Lavoie-Charland, Emilie; Gaudreault, Nathalie; Arsenault, Benoit J.; Dubé, Marie-Pierre; Tardif, Jean-Claude; Body, Simon C.; Seidman, Jonathan G.; Boileau, Catherine; Mathieu, Patrick; Pibarot, Philippe; Bossé, Yohan

2016-01-01

Background Calcific aortic valve stenosis (AS) is a life-threatening disease with no medical therapy. The genetic architecture of AS remains elusive. This study combines genome-wide association studies, gene expression, and expression quantitative trait loci mapping in human valve tissues to identify susceptibility genes of AS. Methods and Results A meta-analysis was performed combining the results of 2 genome-wide association studies in 474 and 486 cases from Quebec City (Canada) and Paris (France), respectively. Corresponding controls consisted of 2988 and 1864 individuals with European ancestry from the database of genotypes and phenotypes. mRNA expression levels were evaluated in 9 calcified and 8 normal aortic valves by RNA sequencing. The results were integrated with valve expression quantitative trait loci data obtained from 22 AS patients. Twenty-five single-nucleotide polymorphisms had P<5×10−6 in the genome-wide association studies meta-analysis. The calcium signaling pathway was the top gene set enriched for genes mapped to moderately AS-associated single-nucleotide polymorphisms. Genes in this pathway were found differentially expressed in valves with and without AS. Two single-nucleotide polymorphisms located in RUNX2 (runt-related transcription factor 2), encoding an osteogenic transcription factor, demonstrated some association with AS (genome-wide association studies P=5.33×10−5). The mRNA expression levels of RUNX2 were upregulated in calcified valves and associated with eQTL-SNPs. CACNA1C encoding a subunit of a voltage-dependent calcium channel was upregulated in calcified valves. The eQTL-SNP with the most significant association with AS located in CACNA1C was associated with higher expression of the gene. Conclusions This integrative genomic study confirmed the role of RUNX2 as a potential driver of AS and identified a new AS susceptibility gene, CACNA1C, belonging to the calcium signaling pathway. PMID:26553695