Low intracellular magnesium in patients with acute pancreatitis and hypocalcemia.

To determine the role of magnesium deficiency in the pathogenesis of hypocalcemia in acute pancreatitis, we measured magnesium levels in serum and in peripheral blood mononuclear cells in 29 patients with acute pancreatitis, 14 of whom had hypocalcemia and 15 of whom had normal calcium levels. Only six patients had overt hypomagnesemia (serum magnesium less than 0.70 mmol per liter [1.7 mg per dl]). The mean serum magnesium concentration in hypocalcemic patients was not significantly lower than in normocalcemic patients, but the mononuclear cell magnesium content in hypocalcemic patients with pancreatitis was significantly lower than in normocalcemic patients with pancreatitis (P less than .01). The serum magnesium level did not correlate with that of serum calcium or the mononuclear cell magnesium content, but the latter did significantly correlate with the serum calcium concentration (r = .81, P less than .001). Most patients with hypocalcemia had a low intracellular magnesium content. Three normomagnesemic, hypocalcemic patients with alcoholic pancreatitis also underwent low-dose parenteral magnesium tolerance testing and showed increased retention of the magnesium load. We conclude that patients with acute pancreatitis and hypocalcemia commonly have magnesium deficiency despite normal serum magnesium concentrations. Magnesium deficiency may play a significant role in the pathogenesis of hypocalcemia in patients with acute pancreatitis.     

Deficiency of calcium and magnesium induces apoptosis via scavenger receptor BI

AimsCells undergo apoptosis in stressed status such as in intracellular calcium overload or extracellular calcium/magnesium deficiency. The mechanisms of how deficiency of the divalent metal ions induces apoptosis remain to be defined. Scavenger receptor BI (SR-BI) is a high density lipoprotein (HDL) receptor. Recent studies demonstrated that SR-BI is a stress response molecule which induces apoptosis upon serum deprivation. In this study, we assessed our hypothesis that the deficiency of calcium/magnesium induces apoptosis via SR-BI apoptotic pathway.Main methodsWe employed CHO cell lines expressing vector and SR-BI to test the effect of SR-BI on apoptosis induced by deficiency of calcium, magnesium and zinc in culture medium. The regain of different metal ions in deficient medium was also performed, respectively. Cell death was detected by morphological changes and quantified by LDH cytotoxicity assay. Apoptosis was also assessed by DNA ladder assay and DNA condensation assay. The SR-BIC323G mutant cells which lack the apoptotic activity of SR-BI were employed to verify the SR-BI-dependent effect on calcium/magnesium induced apoptosis.Key findingsThe deficiency of calcium/magnesium induced cell apoptosis in CHO-SR-BI cells, but not in CHO-vector cells. Moreover, no apoptotic cell death was observed in SR-BIC323G mutant cells, indicating that the deficiency of divalent metal ions induces apoptosis in a SR-BI-dependent manner. Furthermore, the restoration of calcium or magnesium, but not zinc, protected CHO-SR-BI cells from apoptotic cell death, in a dose-dependent fashion.SignificanceThese findings extend our understanding about how calcium and magnesium deficiency induces apoptosis.     

Marginal Zinc Deficiency Increases Magnesium Retention and Impairs Calcium Utilization in Rats

An experiment with rats was conducted to determine whether magnesium retention is increased and calcium utilization is altered by a marginal zinc deficiency and whether increased oxidative stress induced by a marginal copper deficiency exacerbated responses to a marginal zinc deficiency. Weanling rats were assigned to six groups of ten with dietary treatment variables of low zinc (5 mg/kg for 2 weeks and 8 mg/kg for 7 weeks), low copper (1.5 mg/kg), adequate zinc (15 mg/kg), and adequate copper (6 mg/kg). Two groups of rats were fed the adequate-zinc diet with low or adequate copper and pair-fed with corresponding rats fed the low-zinc diet. When compared to the pair-fed rats, marginal zinc deficiency significantly decreased the urinary excretion of magnesium and calcium, increased the concentrations of magnesium and calcium in the tibia, increased the concentration of magnesium in the kidney, and increased the urinary excretion of helical peptide (bone breakdown product). Marginal copper deficiency decreased extracellular superoxide dismutase and glutathione, which suggests increased oxidative stress. None of the variables responding to the marginal zinc deficiency were significantly altered by the marginal copper deficiency. The findings in the present experiment suggest that increased magnesium retention and impaired calcium utilization are indicators of marginal zinc deficiency. Mention of a trademark or proprietary product does not constitute a guarantee or warranty by the U.S. Department of Agriculture and does not imply its approval to the exclusion of other products that also might be suitable. The U.S. Department of Agriculture, Agricultural Research Service, Northern Plains Area is an equal opportunity/affirmative action employer, and all agency services are available without discrimination.     

A mild magnesium deprivation affects calcium excretion but not bone strength and shape, including changes induced by nickel deprivation, in the rat

An experiment was performed to determine the effect of a mild magnesium deprivation on calcium metabolism and bone composition, shape, and strength in rats, and whether nickel deprivation exacerbated or alleviated any changes caused by the magnesium deprivation. Weanling male rats were assigned to groups of 10 in a factorial arrangement, with variables being supplemental nickel at 0 and 1 mg/kg and magnesium at 250 and 500 mg/kg of diet. The basal diet contained about 30 ng Ni/g. Urine was collected for 24 h during wk 8 and 12, and rats were euthanized 13 wk after dietary treatments began. Mild magnesium deprivation decreased the urinary excretion of calcium and increased the tibia concentration of calcium but did not affect femur shape or strength (measured by a three-point bending test). Dietary nickel did not alter these effects of magnesium deficiency. Nickel deprivation increased the urinary excretion of phosphorus and the femur strength variables maximum force and moment of inertia. Strength differences might have been the result of changes in bone shape. Magnesium deprivation did not alter the effects of nickel deprivation on bone. The findings indicate that a mild magnesium deficiency affects calcium metabolism but that this does not markedly affect bone strength or shape, and these effects are not modified by dietary nickel. Also, nickel deprivation affects phosphorus metabolism and bone strength and shape; these effects apparently are not caused by changes in magnesium metabolism or utilization.     

Effects of β1 →4 Linked Galactooligosaccharides on Use of Magnesium and Calcification of the Kidney and Heart in Rats Fed Excess Dietary Phosphorus and Calcium

Magnesium deficiency was induced in male Wistar rats by adding an excess of phosphorus and calcium to the diet (1.195 g of phosphorus and 1.04g of calcium/100g of diet). Feeding of these animals with a diet containing β1→4 linked galactooligosaccharides (4′-GOS) (5g of 4′-GOS/100g of diet) increased the apparent magnesium absorption ratios and the concentrations of magnesium in the serum and femur, and reduced accumulation of calcium in the kidney and heart. We speculate that the use of magnesium increased by feeding 4′-GOS to a limited extent prevented the lower magnesium status and the severity of calcification of the kidney and heart caused by excess dietary phosphorus and calcium.     

Pathogenetic role of magnesium deficiency in ophthalmic diseases

Magnesium is one of the most important regulatory cation involved in several biological processes. It is important for maintaining the structural and functional integrity of several vital ocular tissues such as cornea, lens and retina. The magnesium content of lens, especially in its peripheral part, is higher than that in aqueous and vitreous humor. Magnesium has also been shown to play critically important role in retinal functions. Magnesium plays significant role as a cofactor for more than 350 enzymes in the body and regulates neuroexcitability and several ion channels. Membrane associated ATPase functions that are crucial in regulating the intracellular ionic environment, are magnesium-dependent. Moreover, the enzymes involved in ATP production and hydrolysis are also magnesium-dependent. Magnesium deficiency by interfering with ATPase functions causes increased intracellular calcium and sodium and decreases intracellular potassium concentration. Such ionic imbalances in turn alter the other cellular enzymatic reactions and form the basis of the association of magnesium deficiency with ophthalmic diseases such as cataract. In presence of magnesium deficiency, an imbalance between mediators of vasoconstriction and vasorelaxation may underlie the vasospasm, which is one of the pathogenic factors in primary open angle glaucoma. Furthermore, magnesium deficiency is also a contributing factor in increased oxidative stress and inducible NOS stimulation that can further contribute in the initiation and progression of ocular pathologies such as cataract, glaucoma and diabetic retinopathy. In this paper we review the association of disturbances of magnesium homeostasis with several ophthalmic diseases.     

Genetic variation in SLC7A2 interacts with calcium and magnesium intakes in modulating the risk of colorectal polyps

Solute carrier family 7, member 2 (SLC7A2) gene encodes a protein called cationic amino acid transporter 2, which mediates the transport of arginine, lysine and ornithine. l-Arginine is necessary for cancer development and progression, including an important role in colorectal cancer pathogenesis. Furthermore, previous studies found that both calcium and magnesium inhibit the transport of arginine. Thus, calcium, magnesium or calcium:magnesium intake ratio may interact with polymorphisms in the SLC7A2 gene in association with colorectal cancer. We conducted a two-phase case–control study within the Tennessee Colorectal Polyps Study. In the first phase, 23 tagging single-nucleotide polymorphisms in the SLC7A2 gene were included for 725 colorectal adenoma cases and 755 controls. In the second phase conducted in an independent set of 607 cases and 2113 controls, we replicated the significant findings in the first phase. We observed that rs2720574 significantly interacted with calcium:magnesium intake ratio in association with odds of adenoma, particularly multiple/advanced adenoma. In the combined analysis, among those with a calcium:magnesium intake ratio below 2.78, individuals who carried GC/CC genotypes demonstrated higher odds of adenoma [OR (95% CI):1.36 (1.11–1.68)] and multiple/advanced adenoma [OR (95% CI): 1.68 (1.28, 2.20)] than those who carried the GG genotype. The P values for interactions between calcium:magnesium intake ratio and rs2720574 were .002 for all adenomas and <.001 for multiple/advanced adenoma. Among those with the GG genotype, a high calcium:magnesium ratio was associated with increased odds of colorectal adenoma [OR (95% CI): 1.73 (1.27–2.36)] and advanced/multiple adenomas [1.62 (1.05–2.50)], whereas among those with the GC/CC genotypes, high calcium:magnesium ratio was related to reduced odds of colorectal adenoma [0.64 (0.42–0.99)] and advanced/multiple adenomas [0.55 (0.31–1.00)].     

High Calcium–Magnesium Ratio in Hair Is Associated with Coronary Artery Calcification in Middle-Aged and Elderly Individuals

The interaction between calcium and magnesium as a risk modifier for cardiovascular disease (CVD) has been largely overlooked in previous studies, for the strict regulatory system in blood has been thought to keep such homeostatic interactions under tight control. This study aimed to investigate the association between calcium–magnesium ratio in hair and subclinical coronary artery calcification. Using multiple linear regression analysis, we examined the associations between calcium–magnesium ratio in hair and the coronary calcium score (CCS) in 216 Koreans aged 40 years and above (122 men and 94 women). We found that the calcium-to-magnesium ratio in hair was independently and positively associated with CCS after adjusting for age and sex (regression coefficient 6.051 ± 2.329, P = 0.010). When we assessed the association between the calcium–magnesium ratio and CCS after adjusting for potential cardiovascular risk factors and vascular function modifying drugs, we found that the strength of association with CCS was comparable to before (regression coefficient 5.434 ± 2.523, P = 0.032). Our findings suggest that among middle-aged and elderly Koreans without clinical CVD, the association between coronary artery calcification and hair calcium–magnesium ratio is stronger in those with a higher calcium–magnesium ratio in hair than in those with a lower ratio.     

Dental Phenotype in Jalili Syndrome Due to a c.1312 dupC Homozygous Mutation in the CNNM4 Gene

Jalili syndrome denotes a recessively inherited combination of an eye disease (cone-rod dystrophy) and a dental disorder (amelogenesis imperfecta), which is caused by mutations in the CNNM4 gene. Whereas the ophthalmic consequences of these mutations have been studied comprehensively, the dental phenotype has obtained less attention. A defective transport of magnesium ions by the photoreceptors of the retina is assumed to account for the progressive visual impairment. Since magnesium is also incorporated in the mineral of dental hard tissues, we hypothesized that magnesium concentrations in defective enamel resulting from mutations in CNNM4 would be abnormal, if a similar deficiency of magnesium transport also accounted for the amelogenesis imperfecta. Thus, a detailed analysis of the dental hard tissues was performed in two boys of Kosovan origin affected by Jalili syndrome. Retinal dystrophy of the patients was diagnosed by a comprehensive eye examination and full-field electroretinography. A mutational analysis revealed a c.1312 dupC homozygous mutation in CNNM4, a genetic defect which had already been identified in other Kosovan families and putatively results in loss-of-function of the protein. The evaluation of six primary teeth using light and scanning electron microscopy as well as energy-dispersive X-ray spectroscopy showed that dental enamel was thin and deficient in mineral, suggesting a hypoplastic/hypomineralized type of amelogenesis imperfecta. The reduced mineral density of enamel was accompanied by decreased amounts of calcium, but significantly elevated levels of magnesium. In dentin, however, a similar mineral deficiency was associated with reduced magnesium and normal calcium levels. It is concluded that the c.1312 dupC mutation of CNNM4 results in mineralization defects of both enamel and dentin, which are associated with significantly abnormal magnesium concentrations. Thus, we could not disprove the hypothesis that a disrupted magnesium transport is involved in the development of the dental abnormalities observed in Jalili syndrome.     

Familial hypocalciuric hypercalcaemia and acute pancreatitis.

Four families with familial hypocalciuric hypercalcaemia were studied. The probands presented with abdominal pain, which in three was due to acute pancreatitis; in two the condition was life threatening. Serum concentrations of calcium, magnesium, phosphate, and immunoassayable parathyroid hormone, urinary calcium excretion, and the rate of renal tubular reabsorption of phosphate were measured; the findings were compared with results in 10 patients with primary hyperparathyroidism matched for serum calcium concentration to establish differences between the diseases. Familial hypocalciuric hypercalcaemia should be suspected in patients with hypercalcaemia in whom daily urinary calcium excretion is below 5 mmol (200 mg) provided renal insufficiency, vitamin D deficiency, and ingestion of drugs that reduce calcium excretion have been excluded. Most cases appear to run a benign course, but some may suffer considerable morbidity. Surgical treatment should be reserved for patients with severe complications, when all parathyroid tissue should be removed.     

Magnesium and the inflammatory response: potential physiopathological implications

The purpose of this review is to summarize experimental findings showing that magnesium modulates cellular events involved in inflammation. Experimental magnesium deficiency in the rat induces after a few days a clinical inflammatory syndrome characterized by leukocyte and macrophage activation, release of inflammatory cytokines and acute phase proteins, excessive production of free radicals. Increase in extracellular magnesium concentration, decreases inflammatory response while reduction in the extracellular magnesium results in cell activation. Because magnesium acts as a natural calcium antagonist, the molecular basis for inflammatory response is probably the result of modulation of intracellular calcium concentration. The priming of phagocytic cells, the opening calcium channel and activation of N-methyl-d-aspartate (NMDA) receptors, the activation of nuclear factor-kappa B (NFkappaB) have been considered as potential mechanisms. Moreover, magnesium deficiency induces a systemic stress response by activation of neuro endocrinological pathways. As nervous and immune systems interact bidirectionally, the roles of neuromediators have also been considered. Magnesium deficiency contributes to an exaggerated response to immune stress and oxidative stress is the consequence of the inflammatory response. Inflammation contributes to the pro-atherogenic changes in lipoprotein metabolism, endothelial dysfunction, thrombosis, hypertension and explains the aggravating effect of magnesium deficiency on the development of metabolic syndrome. Further studies are still needed to assess more accurately the role of magnesium in immune response in humans, but these experimental findings in animal models suggest that inflammation is the missing link to explain the role of magnesium in many pathological conditions.     

Magnesium deficiency in the Japanese quail

Morphological effects of magnesium deficiency on liver cells and general aspects of its influence on the metabolism were investigated in young quails. Magnesium deficiency was characterized by a depressed growth, a high mortality rate, a decrease in hematocrit and magnesium and calcium plasma concentrations. Magnesium deficiency reduced the magnesium concentration in heart by 44%, but did not affect the concentration in liver. Ultrastructural aspect of liver parenchymal cells revealed that the number of mitochondria per cell section was decreased and the average area of a mitochondrion was greater in deficient quails than in control animals. The significance of these morphological changes was discussed in relation to disturbances in energy metabolism of these organelles. From these results, japanese quail appeared as an interesting experimental model for studies on metabolic disturbances in magnesium deficiency.     

Low Blood Mononuclear Cell Magnesium Content and Hypocalcemia in Normomagnesemic Patients

Hypomagnesemia can cause hypocalcemia. Because less than 1% of the total body magnesium (Mg) is in extracellular fluids, however, patients may be Mg-deficient despite normal serum Mg concentrations. To determine if hypocalcemia can be seen in patients who have normal serum Mg concentrations but low intracellular Mg, we studied the serum and mononuclear cell Mg contents in 82 alcoholic subjects, 30 of whom had hypocalcemia that could not be explained by other known causes of hypocalcemia. The mononuclear cell Mg content in both hypomagnesemic and normomagnesemic patients with and without hypocalcemia was significantly lower than in normal controls. The serum Mg level did not correlate with the mononuclear cell Mg or serum calcium level, but hypocalcemic patients had a significantly lower mononuclear cell content than normocalcemic patients. Six patients underwent parenteral Mg tolerance testing as an additional measure of Mg deficiency and had increased Mg retention. The serum calcium concentration returned to normal in hypocalcemic patients who were given magnesium intravenously.     

The effect of pH on rate constants, ion selectivity and thermodynamic properties of fluorescent calcium and magnesium indicators

Fluorescent calcium indicators fluo-3, fura-2 and indo-1, and fluorescent magnesium indicators mag-fura-2 (FURAPTRA) and mag-indo-1 were evaluated for the effects of pH on their association and dissociation rates, ion selectivity and thermodynamic properties. Calcium indicator affinities for Ca and Mg were reduced and the discrimination between Ca and Mg decreased in fura-2 and indo-1 at acidic pH. Alterations in apparent dissociation constants were caused primarily by reduced association rates. Magnesium indicators did not show these changes. The enthalphies of the calcium indicators' Ca complex were 1-3 kcal/mole and magnesium indicators' Mg complex were 7-9 kcal/mole. The potential effects of a biexponential dissociation rate of fluo-3 and of Ca interactions with magnesium indicators were examined.     

Effects of dietary caffeine on renal handling of minerals in adult women

Thirty-seven women, aged 31-78 years, on two separate mornings consumed a decaffeinated beverage to which 6 mg caffeine/kg lean body mass or no caffeine were added. Total urine output of water, calcium, magnesium, sodium, chloride, potassium and creatinine increased in the two hours following caffeine ingestion when compared to the control beverage. Increased urinary mineral (mg)/urinary creatinine (g) ratios were seen for calcium (120 to 200), magnesium (70 to 110), sodium (3,800 to 6,200) and chloride (9,200 to 14,800), following the caffeinated beverage. Creatinine clearance did not change significantly. The percent reabsorption of calcium (98.6% to 97.5%, p less than .001) and magnesium (97.0% to 94.2%, p less than .0001) decreased significantly during the post-caffeine period. The calcium and magnesium filtered loads did not differ significantly between the caffeine and no caffeine beverages. Therefore, caffeine-induced urinary loss of calcium and magnesium is largely attributable to a reduction in calcium and magnesium renal reabsorption, although the physiological mechanism and tubular segment affected remain to be established.     

INFLUENCE OF SUPPLEMENTAL INORGANIC NUTRIENTS ON GROWTH,SURVIVORSHIP, AND MYCORRHIZAL RELATIONSHIPS OF SCHIZACHYRIUM SCOPARIUM (POACEAE) GROWN IN FUMIGATED AND UNFUMIGATED SOIL

Little bluestem grass Schizachyrium scoparium ([Michx.] Nash) plants were grown under field conditions for 2 years in soils fumigated with methyl bromide and chloropicrin, or in unfumigated soil, and treated with supplemental inorganic nutrients (bases calcium and magnesium) phosphorus, nitrogen, and potassium. Most differences in measured plant responses were due to interactions between fumigation and nutrient treatments. These included biomass production, root mass per unit length (μg/cm), root lengths, flowering culm production, percent colonization, colonized root length, and spore production in rhizosphere soil. Plants generally responded to mycorrhizal fungal colonization by reducing total root length and producing thicker roots. Treatment of plants with bases appeared to profoundly affect the mycorrhizal association by reducing sporulation of vesicular-arbuscular mycorrhizal fungi and increasing colonization. When fumigated or unfumigated soils were considered separately, base-treated plants produced more biomass than other treatments. Base-treated plants grown on unfumigated soil had more flowering culms and longer colonized root lengths than all other plants. Percent colonization by mycorrhizal fungi and colonized root length were positively correlated with phosphorus/nitrogen ratios, but the ratio was not correlated with plant biomass production. This suggests that phosphorus is not a limiting nutrient in our soil and investment in a mycorrhizal association may not result in enhanced plant growth. The base-nutrient effects may indicate a need to reevaluate earlier studies of macro nutrient effects that did not take into account the role played by calcium and magnesium in assessing fungus-host plant interactions.     

Improved methods for reducing calcium and magnesium concentrations in tissue culture medium: application to studies of lymphoblast proliferation in vitro.

We have compared several methods for reducing calcium and magnesium concentrations in tissue culture medium, with the objective of producing selective deficiency effects on the growth of mouse (L5178Y) and human (P1R) lymphoblasts. In experiments in which calcium- and magnesium- "free" McCoy's medium was supplemented with 15% horse or fetal calf serum, enough calcium and magnesium was provided by serum to support normal lymphoblast growth rate. Either dialysis or chelating-resin treatment of horse or fetal calf serum reduced calcium and magnesium contents approximately 100-fold. Use of dialyzed sera resulted in reduced growth rate, although in most cases the reduction in growth could be attributed to other effects of dialysis on serum, inasmuch as growth in those experiments was not restored to normal by the addition of calcium and magnesium to the medium. In contrast, the reduction of lymphoblast growth rate that occurred when resin-treated serum was used was always attributable to removal of calcium and magnesium, as normal growth always occurred in cultures to which calcium and magnesium were added. To demostrate a growth-inhibiting effect on either mouse or human lymphoblasts by severe reduction of either calcium or magnesium in the presence of normal amounts of the alternative cation, it was necessary to (a) expose McCoy's Ca-Mg-"free" medium to chelating-resin to reduce further the residual cation concentrations; (b) wash cells from stock cultures in a medium devoid of calcium and magnesium prior to inoculation into experimental cultures; (c) reduce the proportion of serum in the final medium from 15 to 5%; and (d) add 100 muM EGTA to cultures. Under these conditions, growth of both cell types was completely abolished in the presence of normal magnesium but in the absence of added calcium, and markedly reduced in the presence of normal calcium but in the absence of magnesium. These modifications did not compromise growth in cultures containing normal concentrations of both ions.     

A clinical approach to common electrolyte problems: 4. Hypomagnesemia.

Magnesium plays a critical role in many cell functions. Hypomagnesemia may occur because of decreased intake or absorption, internal redistribution or increased loss of this element through either renal or nonrenal routes. Manifestations of magnesium deficiency include alterations in calcium, phosphate and potassium homeostasis along with cardiac disorders such as malignant ventricular arrhythmias refractory to conventional therapy, enhanced sensitivity to digoxin and, possibly, coronary artery vasospasm and sudden death. Other features of magnesium deficiency include a host of neuromuscular and neuropsychiatric disorders. In this review we detail mechanisms that may lead to magnesium deficiency, summarize the clinical features of the deficiency and provide a clinical approach to the diagnosis and treatment of this electrolyte disorder.     

Stimulated and Unstimulated Saliva Levels of Calcium and Magnesium in Giardiasis

Giardia lamblia causes malabsorption. The aim of this study was to evaluate serum and saliva calcium and magnesium levels in patients with giardiasis. Thirty patients with giardiasis as a case and 30 person without giardiasis as a control group were enrolled. The stimulated and unstimulated whole saliva and serum calcium and magnesium levels were assayed by Arsenazo reaction and xylidyl blue complex methods, respectively. Mean calcium and magnesium level was low in serum and stimulated saliva of case group than that of controls. However, they were higher in the unstimulated saliva of the case group. It is suggested that patients suffering from giardiasis have low calcium and magnesium levels, and they lose the most of calcium and magnesium by saliva during unstimulated condition.     

钙对黄瓜子叶愈伤组织中硝酸还原酶(NR)活性的影响

本文采用黄瓜子叶愈伤组织,研究了不同钙培养下,对愈伤组织生长、硝酸盐吸收,NR活性以及组织中钙、镁含量的影响。结果表明,缺钙后,愈伤组织生长、硝酸盐吸收、NR活性等都比正常钙培养下的愈伤组织降低。这与用整株植物所得结果基本一致,对此结果进行了讨论。