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The efficiency of calcium phosphate (CaP) bone substitutes can be improved by tuning their resorption rate. The influence of both crystal orientation and ion doping on resorption is here investigated for beta-tricalcium phosphate (β-TCP). Non-doped and Mg-doped (1 and 6 mol%) sintered β-TCP samples were immersed in acidic solution (pH 4.4) to mimic the environmental conditions found underneath active osteoclasts. The surfaces of β-TCP samples were observed after acid-etching and compared to surfaces after osteoclastic resorption assays. β-TCP grains exhibited similar patterns with characteristic intra-crystalline pillars after acid-etching and after cell-mediated resorption. Electron BackScatter Diffraction analyses, coupled with Scanning Electron Microscopy, Inductively Coupled Plasma-Mass Spectrometry and X-Ray Diffraction, demonstrated the influence of both grain orientation and doping on the process and kinetics of resorption. Grains with c-axis nearly perpendicular to the surface were preferentially etched in non-doped β-TCP samples, whereas all grains with simple axis (a, b or c) nearly normal to the surface were etched in 6 mol% Mg-doped samples. In addition, both the dissolution rate and the percentage of etched surface were lower in Mg-doped specimens. Finally, the alignment direction of the intra-crystalline pillars was correlated with the preferential direction for dissolution. STATEMENT OF SIGNIFICANCE: The present work focuses on the resorption behavior of calcium phosphate bioceramics. A simple and cost-effective alternative to osteoclast culture was implemented to identify which material features drive resorption. For the first time, it was demonstrated that crystal orientation, measured by Electron Backscatter Diffraction, is the discriminating factor between grains, which resorbed first, and grains, which resorbed slower. It also elucidated how resorption kinetics can be tuned by doping β-tricalcium phosphate with ions of interest. Doping with magnesium impacted lattice parameters. Therefore, the crystal orientations, which preferentially resorbed, changed, explaining the solubility decrease. These important findings pave the way for the design of optimized bone graft substitutes with tailored resorption kinetics., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Magnesium has a very promising adhibition in biomedical field for its excellent mechanical and biodegradable properties, however, the intelligent applications of biomedical magnesium developed difficultly due to its characteristic degradation. A intelligent biomedical magnesium was constructed on magnesium (Mg) surface by incorporating polydopamine (PD) and mechanized hollow mesoporous silica nanoparticles (HMSs) as smart delivery platform nanocontainers. The supramolecular nanovalves of mechanized HMSs consisted of alginate/chitosan multilayers by self-assembly, which are capable of entrapping rhodamine 6G in the mesopores and can release the cargo under the chemical environment of alkali or Mg iron stimuli that correspond to the degradation of biomedical Mg. The alkali/Mg 2+ dual stimuli-responsive release property of the HMSs endows the biodegradable Mg with controlled release potential. The well-designed smart delivery nanocontainers were combined with polydopamine deposited on Mg for excellent adhesion properties and positively charged amino group of PD. Furthermore, when the biomedical Mg with these mechanized HMSs was degraded in the simulated body environment, the alkali/Mg 2+ -triggered release of cargos from this smart delivery platform could bring a more functional application., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A novel bioglass composition (BGMS10), containing strontium and magnesium and characterized by an ultra-high crystallization temperature, is here employed for the first time to produce different composites with the addition of specific amounts of hydroxyapatite. After an investigation of the samples' bioactivity in vitro in a simulated body fluid solution (SBF) - according to a widely used protocol -, the biocompatibility of the new materials was tested with respect to murine fibroblasts both by direct and indirect tests, in order to evaluate possible cytotoxic effects of the materials' eluates. Although none of the samples were cytotoxic and their bioactivity in SBF increased with the increasing amount of the glass in the composite, thus showing the best performance in the case of pure BGMS10 glass, the findings of the biological investigation did not confirm those arising from the SBF assay. Surprisingly, while the composites with the lowest glass amount showed an enhanced biocompatibility in direct tests, on the contrary their biological responsiveness is typically lower in the indirect ones, based on filtered materials' extracts. This fact could be ascribed to the high release of particulate from the composites, which are more porous than the glassy samples: in fact, such pronounced dissolution may affect both the cell viability and the absorbance readings used in the colorimetric assays. The pure BGMS10 glass showed the best biological response only in the cell proliferation test (which is an indirect contact test), being able to stimulate cell proliferation in particular after 24 h. For these reasons, when considering bioactive glasses and bioglass-based composites, the results of direct cell culture assays should be integrated with those obtained by indirect ones, while the findings regarding the in vitro bioactivity in SBF should be interpreted with great care., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Mg-based stent is a promising candidate of the next generation fully degradable vascular stents. The latest progress includes the CE approval of the Magmaris ® WE43 based drug eluting stent. However, so far, the long term (more than 1 year implantation) in vivo degradation and the physiological effects caused by the degradation products were still unclear. In this study, a 20 month observation was carried out after the bare Mg-Nd-Zn-Zr (abbr. JDBM) stent prototype was implanted into the common carotid artery of New Zealand white rabbit in order to evaluate its safety, efficacy and especially degradation behavior. The degradation of the main second phase Mg 12 Nd was also studied. Results showed that the bare JDBM stent had good safety and efficacy with a complete re-endothelialization within 28 days. The JDBM stent struts were mostly replaced in situ by degradation products in 4 month. The important finding was that the volume and Ca concentration of the degradation products decreased in the long term, eliminating the clinicians' concern of possible vessel calcification. In addition, the alloying elements Mg and Zn in the stent could be safely metabolized as continuous enrichment in any of the main organs were not detected although Nd and Zr showed an abrupt increase in spleen and liver after 1 month implantation. Collectively, the long term in vivo results showed the rapid re-endothelialization of JDBM stent and the long term safety of the degradation products, indicating its great potential as the backbone of the fully degradable vascular stent., Statement of Significance: Mg-based stent is a promising candidate of the next generation fully degradable stents, especially after the recent market launch of one of its kind (Magmaris). However the fundamental question about the long term degradation and metabolic mechanism of Mg-based stent and its degradation products remain unanswered. We implanted our patented Mg-Nd-Zn-Zr bare stent into the common carotid artery of rabbits and conducted a 20 months observation. We found that the Ca containing degradation products could be further degraded in vivo. All the alloying elements showed no continuous enrichment in the main organs of rabbits. These findings eliminate the clinicians' concern of possible vessel calcification and element enrichment after the implantation of Mg alloy based stents to some extent., (Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Hydrogels are appealing biomaterials for applications in regenerative medicine due to their tunable physical and bioactive properties. Meanwhile, therapeutic metal ions, such as magnesium ion (Mg 2+ ), not only regulate the cellular behaviors but also stimulate local bone formation and healing. However, the effective delivery and tailored release of Mg 2+ remains a challenge, with few reports on hydrogels being used for Mg 2+ delivery. Bisphosphonate exhibits a variety of specific bioactivities and excellent binding affinity to multivalent cations such as Mg 2+ . Herein, we describe a nanocomposite hydrogel based on hyaluronic acid and self-assembled bisphosphonate-magnesium (BP-Mg) nanoparticles. These nanoparticles bearing acrylate groups on the surface not only function as effective multivalent crosslinkers to strengthen the hydrogel network structure, but also promote the mineralization of hydrogels and mediate sustained release of Mg 2+ . The released Mg 2+ ions facilitate stem cell adhesion and spreading on the hydrogel substrates in the absence of cell adhesion ligands, and promote osteogenesis of the seeded hMSCs in vitro. Furthermore, the acellular porous hydrogels alone can support in situ bone regeneration without using exogenous cells and inductive agents, thereby greatly simplifying the approaches of bone regeneration therapy., Statement of Significance: In this study, we developed a novel bioactive nanocomposite hydrogel based on hyaluronic acid and self-assembled bisphosphonate-magnesium (BP-Mg) nanoparticles. Such hydrogels are stabilized by the multivalent crosslinking domains formed by the aggregation of Ac-BP-Mg NPs, and therefore show enhanced mechanical properties, improved capacity for mineralization, and controlled release kinetics of Mg 2+ . Moreover, the released Mg 2+ can enhance cell adhesion and spreading, and further promote the osteogenic differentiation of hMSCs. Owing to these unique properties, these acellular hydrogels alone can well facilitate the in vivo bone regeneration at the intended sites. We believe that the strategy reported in this work opens up a new route to develop biopolymer-based nanocomposite hydrogels with enhanced physical and biological functionalities for regenerative medicine., (Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Site-specific controlled release of exogenous angiogenic growth factors, such as recombinant human basic fibroblast growth factor (rhbFGF), has become a promising approach to improve peripheral vascular disease. Here, we have developed an implant composed of spiral magnesium (Mg) and a coating made using poly(lactic-co-glycolic acid) (PLGA) with encapsulated rhbFGF (Mg-PLGA-rhbFGF). The encapsulated protein could release continually for 4weeks with well preserved bioactivity. We compared the angiogenic effect produced by Mg-PLGA-rhbFGF with that of a PLGA implant loaded with rhbFGF (PLGA-rhbFGF). The incorporation of Mg in the implant raised the microclimate pH in the polymer, which preserved the stability of rhbFGF. Mg-PLGA-rhbFGF exhibited advantages over PLGA-rhbFGF implant in terms of a cytocompatibility evaluation. An in vivo angiogenesis test further confirmed the efficacy of released rhbFGF. HE, CD31 and α-SMA staining revealed that the controlled release of rhbFGF from the Mg-PLGA-rhbFGF implant was superior in promoting angiogenesis compared with that of the PLGA-rhbFGF implant. Four weeks post-implantation, the capillary density of the Mg-PLGA-rhbFGF group was significantly higher than that of the PLGA-rhbFGF, control and the normal group (p<0.05, p<0.01 and p<0.01, respectively). Furthermore, the limb blood perfusion ratios of the Mg-PLGA-rhbFGF and PLGA-rhbFGF groups were dramatically increased, at 99.1±2.9% and 80.7±3.2%, respectively, whereas the ischemic limb did not recover in the control group. The biocompatibility of the implants was also evaluated. In conclusion, Mg-PLGA-based, sustained local delivery of rhbFGF promotes post-ischemic angiogenesis and blood flow recovery. The results suggest potential therapeutic usefulness of Mg-PLGA-rhbFGF for tissue ischemia., Statement of Significance: Magnesium (Mg)-based implant has been already used in patients with critical limb ischemia. Site-specific controlled release of recombinant human basic fibroblast growth factor (rhbFGF), has become a promising approach to improve peripheral vascular disease. We report here on a novel combination implant composed of spiral magnesium and a coating made using poly(lactic-co-glycolic acid) (PLGA) with encapsulated rhbFGF (Mg-PLGA-rhbFGF). The preparation method does not involve any complex processes and results in a high encapsulation efficiency (approximately 100%). The degradation of metal Mg raise the microclimate pH in the PLGA polymer, which could well preserve the bioactivity of rhbFGF incorporated in the implant. Mg-PLGA-based, sustained local delivery of rhbFGF promotes post-ischemic angiogenesis and blood flow recovery in rat limb ischemic model. This work marks the first report for controlled release of rhbFGF in combination with metal Mg, and suggests potential therapeutic usefulness of Mg-PLGA-rhbFGF for tissue ischemia., (Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Biomedical Mg alloy is promising for its widespread use clinically. In vitro and in vivo studies showed that the degradation products of biomedical Mg alloy were composed of O, P, Ca, Mg and other alloying elements. However, little is known about the metabolism of the degradation products. In this study, the in vitro macrophage phagocytosis of the degradation products of a biomedical Mg-Nd-Zn-Zr alloy was directly observed. This result affirms the necessity to investigate the long-term fate of Mg alloy degradation products in physiological environments. Besides, an electrochemical method was proposed to prepare enough amount of degradation products in vitro efficiently., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The aim of this work was preparation, characterization, bioactivity and biocompatibility evaluation of Mg-substituted fluorapatite (Mg-FA) nanopowders. Mg-FA nanopowders with a chemical composition of Ca10-xMgx(PO4)6F2, with x=0, 0.5, 1, and 2 were prepared by mechanically activated method. The in vitro bioactivity was investigated by soaking the powders in simulated body fluid (SBF) for various time periods to analyze the nucleation and growth of bone-like apatite on the surface of the samples. Cell viability and cell attachment were studied by MTT assay. Results indicated that the bioactivity of all of samples with different Mg content was improved compared with the pure FA. However, the mechanism of bioactivity is different and depends on the amount of Mg substitution. Finally, cell culture suggested that the addition of Mg(2+) has no adverse effect and Mg-FA samples have good biocompatibility. The Mg-FA material shows potential in satisfying the requirements of biomedical applications., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Pure Mg and a Mg-6wt.% Zn alloy were investigated as potential candidates for biodegradable implants for the urinary system. The in vitro corrosion behavior was studied by potentiodynamic polarization and immersion tests in simulated body fluid (SBF) at 37°C. The in vivo degradation and histocompatibility were examined through implantation into the bladders of Wistar rats. The alloying element Zn elevated the passivation potential and increased the cathodic current density. Both in vitro and in vivo degradation tests showed a faster corrosion rate for the Mg-6Zn alloy. Tissues stained with hematoxylin and eosin (HE) suggested that both pure Mg and Mg-6Zn alloy exhibited good histocompatibility in the bladder indwelling implantation and no differences between pure Mg and Mg-6Zn groups were found in bladder, liver and kidney tissues during the 2weeks implantation. Overall, this work presented instructive information on the degradation properties and histocompatibility of pure Mg and the Mg-6Zn alloy in the urinary system., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Two major problems for magnesium alloy implant are the high degradation rate and easy infection associated with implantation. Herein, a surface drug delivery system (Mg/Epoxy resin-ZnO/PCL-Ibuprofen) which can realize bi-directional controlled release of ibuprofen and Mg(2+) was designed via a dip coating process followed by spraying. The in vitro test demonstrated that the ibuprofen in drug-eluting compound material showed sustained release profiles for 22days, which can effectively solve the local cellular rejection and inflammation during the early stage of implantation. Besides, the drug carrier also exhibited improved corrosion resistance duel to the high combining strength between Epoxy resin-ZnO coating and magnesium alloy, so Mg(2+) can release slowly at first and then speeded up later. This approach may be suitable for coating other implant materials such as stainless steel, titanium alloy etc., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The influence of the composition of calcium (Ca(2+)), magnesium (Mg(2+)), and iron (Fe(3+)) ions in two concentration levels (low-500 mg/L of CaCl2, 125 mg/L of MgCl2, and 10 mg/L of FeCl3 and high-2,500 mg/L of CaCl2, 625 mg/L of MgCl2, and 50 mg/L of FeCl3) contained in water on the pharmacokinetics (PK) of oxytetracycline (OTC) was determined. OTC hydrochloride was administered at a dose of 25 mg/kg of body weight to broiler chickens divided into four groups of nine birds each, including 3 oral groups (in deionized water -control, in water with low ion concentration, and in water with high ion concentration) and 1 intravenous group. OTC concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry, after which non-compartmental pharmacokinetic analysis was conducted.The absolute bioavailability of OTC in the group of birds exposed to higher ions concentration was reduced (8.68% ± 2.56) as compared to the control (13.71% ± 2.60). Additionally, in this group, decrease in PK parameters such as: area under the concentration-time curve from 0 to infinity (15.36 μg × h/mL ± 4.36), from 0 to t (14.78 μg × h/mL ± 4.37), area under the first moment of curve from 0 to t (107.54 μg × h/mL ± 36.48), and maximum plasma concentration (2.13 μg/mL ± 0.32) were also observed. It is noteworthy, all mentioned parameters demonstrated a downward trend with high correlation coefficient (P = 0.004, P = 0.002, P = 0.005, P = 0.004, P = 0.011, respectively), reflecting the influence of increasing concentrations of Ca(2+), Mg(2+), and Fe(3+) ions on the decreasing absorption rate of OTC.Based on the current research results, it can be assumed that high concentrations of several ions applied concomitantly are able to decrease the absorption of OTC from gastrointestinal tract in broiler chickens. This occurrence might impair the drug's clinical efficacy toward some pathogenic microorganisms. It implies that using OTC on a farm may require administration of higher doses than the routine one when infections are caused by less sensitive pathogens., (© 2016 Poultry Science Association Inc.)

Due to their biodegradability, magnesium and magnesium-based alloys could represent the third generation of biomaterials. However, their mechanical properties and time of degradation have to match the needs of applications. Several approaches, such as choice of alloying elements or tailored microstructure, are employed to tailor corrosion behaviour. Due to the high electrochemical activity of Mg, numerous environmental factors (e.g. temperature and surrounding ion composition) influence its corrosion behaviour, making it unpredictable. Nevertheless, the need of reliable in vitro model(s) to predict in vivo implant degradation is increasing. In an attempt to find a correlation between in vitro and vivo corrosion rates, this review presents a systematic literature survey, as well as an attempt to correlate the different results., (Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The assimilation efficiency of Pb was measured in the candidate sentinel Cantareus aspersus, to assess its capacity to consistently represent the bioavailability of Pb. Three populations were compared from habitats with different levels of toxic and essential metals. For each, 36 snails were fed a laboratory diet with known concentrations of Pb, Ca and Mg over 64 days. Lead bioavailability was measured as the percentage assimilation by the soft tissues (mass in tissues as a fraction of that consumed), and its variation was assessed between populations, exposure periods, dietary Mg and replicates. The indicated bioavailability was consistent over time and Pb consumed, but differed between populations and diets. Population differences were due, in part, to their different growth rates: soft tissue growth was positively correlated with Pb mass and, in the most rapidly growing populations, this accounted for more than 40% of the variation in soft tissue Pb. Populations did not differ in their consumption of Pb, but the highest Mg diet induced higher food consumption and a reduced assimilation of Pb. Tissue growth determines retention and contributes to the variation in the bioavailability indicated by these populations, as do essential metals in the diet. Such variability has important implications for monitoring programmes using resident populations of sentinels to map the bioavailability of toxic metals or integrate a pollution signal over time., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The effect of joint administration of imipramine (IMI) and magnesium (Mg) on antidepressant-like activity was studied in mice using forced swim test (FST). Mg doses ineffective per se (5 and 10 mg/kg) given jointly with IMI also at ineffective doses (10 and 15 mg/kg) resulted in a potent reduction in the immobility time. Since these combined treatments did not influence locomotor activity, the antidepressant-like activity was not due to non-specific behavioral activation. Moreover, we estimated the effect of joint administration of magnesium and IMI in FST on serum and brain magnesium, IMI and its active metabolite desipramine (DMI) concentrations in mice. Swim stress (mice subjected to FST) increased the magnesium concentration in serum and decreased it in the brain compared to naive animals. Moreover administration of IMI increased (normalized) magnesium brain concentration, without influence on the serum level. Joint administration of IMI and magnesium did not influence magnesium (compared with FST) or IMI and DMI (compared with IMI treatment alone) concentrations in both examined tissues. The present data demonstrated an enhancement of the antidepressant-like effect by joint administration of IMI and magnesium in the FST, and further indicate the particular role of magnesium in the antidepressant action. Since there was no increase in IMI, DMI or magnesium concentration after joint administration of magnesium and IMI, the data suggest that pharmacodynamic rather than pharmacokinetic interaction between magnesium and IMI is accountable for behavioral effect in the FST.

Macronutrient (N, P, K, Mg, S, Ca), heavy metal (Fe, Zn, Mn, Cu, Ni, Cd, Pb) and Al concentrations in understorey bryophytes, lichens and vascular plant species growing in Scots pine forests at four distances from the Harjavalta Cu-Ni smelter (0.5, 2, 4 and 8 km) were compared to those at two background sites in Finland. The aim was to study the relationship between element accumulation and the distribution of the species along a pollution gradient. Elevated sulfur, nitrogen and heavy metal concentrations were found in all species groups near the pollution source. Macronutrient concentrations tended to decrease in the order: vascular plants>bryophytes>lichens, when all the species groups grew on the same plot. Heavy metal concentrations (except Mn) were the highest in bryophytes, followed by lichens, and were the lowest in vascular plants. In general, vascular plants, being capable of restricting the uptake of toxic elements, grew closer to the smelter than lichens, while bryophytes began to increase in the understorey vegetation at further distances from the smelter. A pioneer moss (Pohlia nutans) was an exception, because it accumulated considerably higher amounts of Cu and Ni than the other species and still survived close to the smelter. The abundance of most of the species decreased with increasing Cu and Ni concentrations in their tissues. Cetraria islandica, instead, showed a positive relationship between the abundance and Cu, Ni and S concentrations of the thallus. It is probable that, in addition to heavy metals, sporadically high SO(2) emissions have also affected the distribution of the plant species.

Background: Phytic acid has been reported to impair the absorption of minerals and trace elements such as calcium, zinc, and iron in humans. However, limited information is available on the effect of phytic acid on magnesium absorption., Objective: The objective was to evaluate the effect of phytic acid on fractional apparent magnesium absorption in humans., Design: Two stable-isotope studies were performed with 8-9 healthy adults per study. Test meals were based on 200 g phytic acid-free wheat bread; test meals with and without added phytic acid were served on days 1 and 3 according to a crossover design. Phytic acid was added in amounts similar to those naturally present in whole-meal (1.49 mmol) and in brown bread (0.75 mmol). Each test meal was labeled with 0.7 mmol (25)Mg or 1.1 mmol (26)Mg. The total magnesium content was standardized to 3.6 mmol in all test meals. Apparent magnesium absorption was based on fecal monitoring., Results: The addition of phytic acid lowered fractional apparent magnesium absorption from 32.5 +/- 6.9% (no added phytic acid) to 13.0 +/- 6.9% (1.49 mmol added phytic acid; P < 0.0005) and from 32.2 +/- 12.0% (no added phytic acid) to 24.0 +/- 12.9% (0.75 mmol added phytic acid; P < 0.01). The inhibiting effect of phytic acid was dose dependent (P < 0.005)., Conclusion: The results show that fractional magnesium absorption from white-wheat bread is significantly impaired by the addition of phytic acid, in a dose-dependent manner, at amounts similar to those naturally present in whole-meal and brown bread.

Grains produced by low-phytate barley and corn isolines homozygous for each species' respective low phytic acid 1-1 allele were compared to grain produced by near-isogenic normal or wild-type barley and corn in broiler chick feeds. Cobb x Cobb (384) chicks were used in a 10-d study. A randomized complete block design with a factorial arrangement of 2 x 2 x 3 was used with 4 replicates (8 chicks / replicate) per treatment. Twelve isocaloric and isonitrogenous treatment diets were formulated to contain 2 types of grain (barley and corn), 2 levels of grain (40% and 60%), and 3 sources of available P (wild-type grain, wild-type P-supplemented grain, and low-phytate grain). Growth parameters, bone parameters, total bone mineral, and apparent digestibilities were measured. The mean growth and bone responses were 1) higher for barley diets compared to corn diets, 2) higher for 60% grain inclusion compared to 40%, 3) higher for low-phytate compared to wild-type grains, and 4) not different for low-phytate compared to P-supplemented wild-type grain diets. Chicks fed low-phytate-based diets excreted 33 and 43% less P than chicks fed wild-type and P-supplemented wild-type diets, respectively. Correlations between percentage bone ash, total bone ash, and bone strength indicated a strong relationship and appear to support the use of bone strength analysis as a simpler method than ash content determination as an indication of P status. Feeding low-phytate grains will reduce the need for supplemental P in chick diets.

Background: The double-labeling (DL) method for determining magnesium absorption is less cumbersome than is the fecal monitoring method, which has been used most often, but it has not been validated., Objective: The aim of this study was to compare methods and several sampling protocols for determining magnesium absorption to establish a simple and reliable alternative to the fecal monitoring approach. Fecal monitoring was used as the standard against which the DL methods based on urine data (DLU), plasma data (DLP), and plasma kinetics with the use of a deconvolution analysis (DP) were compared., Design: Six healthy adult men received 70 mg (26)Mg orally and 30 mg (25)Mg intravenously. Multiple blood samples and complete urine and fecal samples were collected over 12 d. Stable-isotope ratios were determined by inductively coupled plasma mass spectrometry., Results: Results from DLU were not significantly different from the fecal monitoring reference value (0.48 +/- 0.05; +/- SD) when based on 3-d urine pools from 72 to 144 h (0.54 +/- 0.04) and when based on the 24-h urine pools from 48 to 72 h (0.49 +/- 0.06), 72 to 96 h (0.51 +/- 0.11), and 96 to 120 h (0.50 +/- 0.06). Results with the DLP method 72 h after isotope administration also compared well with those with the fecal monitoring method (0.54 +/- 0.09). Magnesium absorption was 0.47 +/- 0.06 with the DP method, which also agreed with the fecal monitoring value., Conclusions: The DL methods are an alternative to fecal monitoring when applied within the appropriate time intervals. Therefore, DLU-the simplest and least invasive approach-is recommended for determining magnesium absorption.

Background: There is increasing evidence that acid-base status has a significant effect on high-intensity physical performance, urolithiasis, and calcium metabolism. Experimental studies in adults showed that renal net acid excretion (NAE) can be reliably estimated from the composition of diets., Objective: We investigated whether a reasonable estimation of NAE is also possible from the dietary records of free-living children and adolescents., Design: Healthy children (aged 8 y; n = 165) and adolescents (aged 16-18 y; n = 73) each collected a 24-h urine sample and completed a weighed diet record on the same day. Urinary NAE was analyzed (NAE(an)) and estimated (NAE(es)). Potential renal acid load (PRAL), the diet-based component of NAE(es), corrects for intestinal absorption of ingested minerals and sulfur-containing protein. A urinary excretion rate of organic acids (OAs) proportional to body surface area was assumed for the complete estimate (NAE(es) = PRAL + OA(es))., Results: Significant (P < 0.001) correlations between NAE(es) and NAE(an) were seen in the children (r = 0.43) and the adolescents (r = 0.51). A simplified estimate based on only 4 components of dietary PRAL (protein, phosphorus, potassium, and magnesium) yielded almost identical associations. Mean simplified NAE(es) (32.6 +/- 13.9 and 58.4 +/- 22.0 mEq/d in the children and the adolescents, respectively) agreed reasonably with NAE(an) (32.4 +/- 15.5 and 52.8 +/- 24.3 mEq/d, respectively)., Conclusions: Predicting NAE from dietary intakes, food tables, and anthropometric data is also applicable during growth and yields appropriate estimates even when self-selected diets are consumed. The PRAL estimate based on only 4 nutrients may allow relatively simple assessment of the acidity of foods and diets.

The effects of nondigestible oligosaccharides including polyols on intestinal mineral absorption have been studied extensively in animal experiments, but their impact on mineral absorption in humans remains to be established. We investigated the effects of feeding two fermentable, low digestible carbohydrates, on the apparent absorption and balance of calcium (Ca) and magnesium (Mg) in humans. Nine healthy young men were given a control diet with dextrose or polyols, low digestible, fermentable carbohydrates (LHBC, HPFL) for 32-d periods according to a 3 x 3 Latin-square design. During the 18-d period of adaptation, the products were administered gradually in liquid form, up to a maximum of 100 g/d, which was then consumed for 14 d. Ca and Mg levels were measured in diets and in fecal and urine collections to assess apparent mineral absorption and balance. The relative apparent absorptions of Ca and Mg from the control diet were (means +/- SEM) 33.3 +/- 4.6 and 39.8 +/- 2.7%, respectively. Ingestion of both low digestible carbohydrates significantly increased the relative apparent absorption of Mg by about 25%. LHBC, but not HPFL, ingestion increased urinary Mg excretion. Apparent absorption, urinary excretion and balance of Ca were not altered by the ingestion of either low digestible carbohydrate. Ingestion of the low digestible, fermentable carbohydrates, with balanced diets, improved apparent Mg absorption without significant effects on apparent absorption or retention of Ca in healthy young men. Further human studies are therefore still needed to confirm the effects of these products in other populations.

There is overwhelming evidence that dietary fibers are an important component of human and animal diets and play an important role in human health. Because dietary fibers and some associated substances, such as phytate, have in vitro mineral-binding capacities, they have been thought to impair absorption of minerals such as calcium, iron and zinc, although magnesium absorption seems to be less affected. Indeed, the effect of dietary fibers depends largely on their own nature and characteristics, and also on mineral homeostasis. In 1977 it was observed that resistant starch, a fermentable dietary fiber, could improve Mg absorption in rats. More recently, attention has been focused on other fermentable substrates such as inulin and oligo- or polysaccharides, for their potential prebiotic and health effects. Studies conducted on different types of fermentable carbohydrates have confirmed their beneficial effect on Mg absorption in different animal species. The majority of these studies have also sought to determine the effects of fibers on other minerals such as calcium, iron and zinc. In contrast to the studies with Mg, these studies did not show a consistent effect on the absorption of these minerals. This is due to the particularities of sites and mechanism of Mg absorption. To date, four human studies have been carried out that generally confirmed the enhancing effect of fermentable oligo- or polysaccharides on Mg absorption.

The precise mechanisms of intestinal Mg absorption are still unclear and the possibility of an adaptative rise in the fraction of Mg absorbed as Mg intake is lowered is controversial. Mg deficiency has been studied extensively in rats where it is readily produced by dietary depletion. In this study, we investigated the effect of Mg intake on fractional absorption of Mg acutely and after adaptation to graded Mg intake in rats. For this purpose, male Wistar rats (n = 30) were fed a basal semipurified diet containing 600 mg Mg/kg (MgO) for 7 d. Three groups of 10 rats were then formed and fed the basal semipurified diet with 600, 300 or 150 mg Mg/kg, for 28 d. Apparent and true intestinal absorptions and fecal endogenous excretion of Mg were determined at the beginning and end of the experiment. As expected, plasma Mg levels were lower in the deficient groups than in the control by d 4 and differences were more marked at the end of the experiment. Erythrocyte Mg levels were significantly lower at the end of the experiment in the group fed the diet containing 150 mg Mg/kg. The amounts of Mg absorbed were directly proportional to the dietary Mg intakes in all three experimental groups at both testing periods. This indicated that the apparent and true intestinal absorption percentages of Mg were not different in rats fed the three different levels of dietary Mg. These results also show that fecal endogenous excretion of Mg was nearly directly proportional to the dietary Mg intakes. These results argue in favor of a passive diffusional process for intestinal Mg absorption.

Objective: Intravenous magnesium sulfate is widely used in obstetrics for the treatment of both preterm labor and preeclampsia. Although therapeutic levels of total magnesium have been proposed, the levels remain controversial. Because the active form of magnesium is the free or ionized form, it is essential to determine whether ionized magnesium and total magnesium levels are highly correlated in vivo. We sought to examine the correlation between ionized magnesium and total magnesium under basal and therapeutic conditions and to define the initiation and elimination pharmacokinetics of both forms during intravenous magnesium sulfate infusion., Study Design: Twenty-four singleton pregnant patients who were candidates for magnesium sulfate were studied (preterm labor, 15; preeclampsia, 9). Serial blood samples were taken before the magnesium sulfate infusion, during the first 4 hours after the initiation of magnesium sulfate infusion and for 4 hours after the discontinuation of the infusion., Results: Baseline levels of total magnesium and ionized magnesium were not different between patients with preterm labor and with preeclampsia. Among patients with preeclampsia, although not patients with preterm labor, the initial apparent volume of distribution was significantly smaller for total magnesium than for ionized magnesium (16,397 +/- 1441 vs 23,856 +/- 2745 mL, respectively; P =.03), and the elimination half-life was greater for total magnesium as compared to ionized magnesium (707 +/- 160 vs 313 +/- 29 minutes;P <.05). Linear regression analysis demonstrated a lack of correlation between ionized magnesium and total magnesium during the pretreatment period and during the steady state infusion for both preterm labor and preeclampsia., Conclusion: The measurement of total magnesium may not be adequate for the titration of therapeutic magnesium infusions in patients with preeclampsia or preterm labor because of the lack of correlation between total magnesium and the physiologically active ionized magnesium. Further studies may determine whether the measurement of ionized magnesium is a superior method for following the adequacy and safety of the treatment of preeclampsia and preterm labor.

Bartter syndrome and Gitelman syndrome are primary hereditary diseases characterized by hypokaliemia, alkalosis, hypertrophy of the juxtaglomerular complex with secondary hyperaldoteronism and normal blood pressure. They result from molecular disorders leading to a defect of sodium reabsorption in respectively the Henle's loop and the distal convoluted tubule. Biological adaptations of downstream tubular segments, i.e. distal convoluted tubule and collecting duct, are responsible for hypokaliemia, alkalosis, renin-aldosterone activation, prostaglandins hypersecretion and dysregulation of the urinary excretion of calcium and magnesium, illustrating the close integration of the regulation of different solutes in the distal tubular structures.

Background: Magnesium intakes in many industrialized countries are below recommended daily allowances. Magnesium-rich mineral water may contribute to coverage of magnesium requirements by providing significant amounts of natural, energy-free, bioavailable magnesium., Objective: The objectives were to determine magnesium bioavailability from magnesium-rich (110 mg/L) mineral water in healthy subjects when consumed alone and to evaluate the effect of simultaneous meal consumption., Design: Magnesium bioavailability was measured in 10 healthy women with the use of a crossover design. Stable magnesium isotopes ((25)Mg and (26)Mg) were administered orally with mineral water, which was consumed with or without a meal. Apparent magnesium absorption was determined by fecal monitoring, and magnesium retention was determined from urinary excretion of magnesium isotopes., Results: The mean (+/-SD) magnesium absorption from mineral water consumed alone was 45.7 +/- 4.6% (range: 40.2-55.5%) and was significantly greater (P = 0.0001) when it was consumed with a meal (52.3 +/- 3.9%; 46.2-60.2%), a relative difference of 14.4%. Magnesium retention also was significantly greater (P = 0.0004) when mineral water was consumed with a meal (41.5 +/- 4.2%; 35.2-50.6%) than when consumed alone (37.4 +/- 4.0%; 33.1-47.0%), a relative difference of 11.0%., Conclusions: In healthy young women, approximately 50% of the magnesium from magnesium-rich mineral water was absorbed when consumed alone. Magnesium bioavailability from mineral water is enhanced when the water is consumed with a meal, perhaps because of a slower gastrointestinal transit time, the presence of digestion products from the meal, or both. Regular consumption of magnesium-rich mineral water could make a valuable contribution to magnesium requirements.

The effects of bulk precipitation pH and growth period (growing and dormant) on cation enrichment beneath foliage were examined in a beech (Fagus moesiaca) forest stand during a 48-month period. The bulk precipitation pH values ranged from 4.2 to 7.2. The lowest values were observed in winter due to fossil fuel combustion in a nearby big city. The ratio of monthly ion fluxes of throughfall plus stemflow over monthly ion fluxes of bulk precipitation was chosen as an index of cation enrichment and, therefore, as the dependent variable. Bulk precipitation pH and growth period were chosen as independent factors. Precipitation interception (%) by tree canopies was also taken into account. It was found that the pH factor was significant only for H+ ion enrichment suggesting neutralization of H+ ions in the beech canopy, whereas Mg2+ and K+ enrichment were greater in the growing period, probably as a result of leaching. Crown interception was negatively significant for NH4+-N enrichment.

Objective: The purpose of this study was to determine the population pharmacokinetics of magnesium from sparse observational data in patients with preeclampsia., Study Design: Serum magnesium concentrations (1-11 per patient) were obtained retrospectively from the records of 116 patients with preeclampsia who had a loading dose of magnesium sulfate (16 or 20 mmol), followed by a maintenance dose (1 mmol/h) over an average of 28 hours. Population clearance, volume of distribution, and the baseline magnesium concentration were estimated using the NONMEM program., Results: The following population typical values, together with the interpatient variability (expressed as coefficient of variation) were obtained with the use of a 1-compartment model: systemic clearance, 4.28 L/h (37.3%); volume of distribution, 32.3 L (32.1%); baseline concentration, 0.811 mmol/L (18.5%). The average half-life was 5.2 hours. Clonus was not obtunded in 4 patients whose serum magnesium concentrations were similar to the average concentration of 1.7 mmol/L. The variability remaining unexplained after the population model was fitted to the data was 6.5% to 10.8%., Conclusion: This study extended knowledge of the pharmacokinetic disposition of magnesium in preeclampsia. The results are potentially useful for the calculation of loading and maintenance doses, particularly when the relationship between serum concentration and effect in preeclampsia is clarified.

Male rats were fed a fiber-free, purified diet containing either gelatinized tapioca starch that was not modified chemically (TS, 50 g/kg diet) or gelatinized chemically modified tapioca starch (CMS, 50 g/kg) for 21 d. TS was used as the control. The six kinds of gelatinized hydroxypropyl distarch phosphate (HDP) from tapioca with two different degrees of substitution (DS) and three different degrees of cross-linking (DC) were used as CMS sources. The wet weight and moisture of fecal output of the rats fed HDP with higher DS were 100 and 20% greater than that in the control rats, respectively. The weights of cecal wall and cecal contents were also 30 and 50% higher in the rats fed HDP with higher DS than those in the control rats. The pH of the cecal contents was more acidic in the rats fed HDP with higher DS than that in the control rats. Fecal excretion of bile acids was 40% higher in the rats fed HDP with higher DS than in the control rats. These effects of HDP were only slightly affected by the DC. The plasma cholesterol concentration was 16% lower in the rats fed HDP with higher DS and highest DC than in the control rats. The concentrations of liver lipids and plasma triglycerides and the cecal pool of organic acids were not affected by diet. The apparent absorptions of Ca and Mg were not affected by diet, but those of Zn and Fe were 75 and 70% lower in the rats fed HDP with higher DS than in the control rats. These results suggest that the physiological effects of HDP depend on the DS but not on the DC.

Young pigs were fed a diet moderately high or low in manganese (Mn) (0.95 +/- 0.10 mmol Mn/kg, n = 8 or 0.040 +/- 0.003 mmol Mn/kg, n = 6) and deficient in magnesium (Mg) (4.1 mmol Mg/kg) for 5 wk. All eight pigs consuming the high Mn diet died following convulsive seizures, whereas only two of six died in the group fed low Mn. In an attempt to determine the cause of death, a subsequent study examined the interactive effect of deficient dietary Mg and Mn on the tissue distribution of Mg and Mn. Pigs were individually fed, for 5 wk, diets that contained: 4.1 mmol Mg/kg and 36.0 micromol Mn/kg, 4.1 mmol Mg/kg and 0.91 mmol Mn/kg, 4.1 mmol Mg/kg and 0.91 mmol Mn/kg with added ultratrace minerals, or 41.1 mmol Mg/kg and 0. 91 mmol Mn/kg, and ultratrace minerals. Liver and skeletal muscle Mn concentrations were significantly elevated by increased dietary Mn. Increased dietary Mn did not affect heart Mn, but heart Mg concentrations were significantly depressed by high, as compared to low, dietary Mn (38.7 +/- 3.3 vs. 32.7 +/- 2.6 mmol Mg/kg). These data suggest high dietary Mn may exacerbate Mg deficiency in heart muscle and thus may be a complicating factor in the deaths observed in Mg-deficient pigs.

Adequate mineral intake is a crucial part of a healthy diet for children-it supports appropriate growth and development and provides protection against childhood conditions like anemia and helps to prevent future adult diseases such as osteoporosis. Challenges in performing and interpreting studies in infants and children have hampered the accurate assessment of their mineral utilization. Many of the most powerful techniques used in adults, such as radioisotope testing, are not appropriate for use in children. In recent years, advanced mineral stable-isotope techniques have been developed to fill this gap. Pediatric applications include studies of calcium absorption and kinetics during puberty and evaluation of the calcium-iron interaction in infants and toddlers. The effects of genetics in determining calcium absorption and bone turnover may become an important research area. The goals and methods of ongoing mineral stable-isotope research in infants and children are examined in this report. In the past, the cost and difficulties in obtaining isotopes have limited such research. This situation has improved considerably, although relatively few nutrition research laboratories are prepared to perform sample analyses.

We addressed the question whether the type of anion in potassium salts affects magnesium absorption and the transmural potential difference by using wethers (n = 8) fed a control diet and diets supplemented with equimolar amounts of KHCO(3), KCl or K-citrate according to a Latin-square design. The control diet contained 10.9 g K/kg dry matter and the high K diets contained 41.3 g K/kg dry matter. Compared with the control diet, KHCO(3) and K-citrate significantly reduced apparent Mg absorption by 9.5 and 6.5%, respectively. Supplemental KCl tended to reduce (P = 0.070) group mean magnesium absorption by 5.5%. Consumption of supplemental KHCO(3) and K-citrate produced a significant increase in the transmural potential difference (serosal side = positive) by 17.1 and 20.7 mV, respectively, whereas the addition of KCl to the diet did not. The individual values for the four diets tended to show a negative correlation (r = -0.336, n = 32, P = 0.060) between the transmural potential difference and apparent magnesium absorption. We conclude that different potassium salts have different effects on magnesium absorption in ruminants as caused by different effects on the transmural potential difference.

Some patients with variant angina show both ST segment elevation at rest and exercise-induced ST segment elevation. Magnesium deficiency has also been observed in patients with variant angina. This study investigated the correlation between the degree of magnesium deficiency and the efficacy of intravenous administration of magnesium in patients with variant angina. Fifteen patients with angiographically confirmed variant angina were assessed for magnesium deficiency and whether intravenous administration of magnesium (19.2 mEq/l) suppressed exercise-induced ST segment elevation. All 15 patients were studied with a magnesium retention test (0.2 mEq/kg over 4 hr) to analyze magnesium deficiency. In our study, magnesium retention rate in patients with variant angina was not higher than that of controls (57 +/- 24% vs 45 +/- 10%, NS). All 15 patients had anginal attacks during accelerated exercise combined with hyperventilation after placebo infusion, whereas only 8 patients had anginal attacks after magnesium administration. ST segment elevation occurred in 14 patients after placebo infusion, but in only 4 patients after magnesium administration. There were no correlations between disease activity, degree of magnesium deficiency or failure of suppression of ST elevation by the intravenous administration of magnesium. Intravenous administration of magnesium can suppress exercise-induced coronary spasms in some patients with variant angina, but the degree of magnesium deficiency did not correlate with the suppressions of exercise-induced ST elevation after magnesium administration. Intravenous administration of magnesium had limited efficacy in patients with variant angina and exercise-induced ST segment elevation.

Hypomagnesemia is a well known side-effect in patients receiving cisplatin-containing chemotherapy. Cisplatin induces hypomagnesemia through its renal toxicity possibly by a direct injury to mechanisms of magnesium reabsorption in the ascending limb of the loop of Henle as well as the distal tubule. Since the magnesium reabsorption process still remains to be fully characterized, the effect by cisplatin on this process remains uncertain. Hypomagnesemia is a frequent complication to chemotherapy with cisplatin affecting up to 90% of patients if no corrective measures are initiated. The clinical importance of this hypomagnesemia remains uncertain. Possible symptoms of hypomagnesemia can be impossible to distinguish from symptoms related to the underlying disease or the treatment with chemotherapy. Existing studies on how to supplement magnesium during treatment with cisplatin have focused mainly on the effect on serum magnesium values and erythrocyte magnesium concentrations but both parameters are poor indicators of body magnesium stores. As long as the relationship between hypomagnesemia and possible complications thereof remains poorly elucidated, it seems reasonable to try to avoid hypomagnesemia. The best results seem to be provided by adding magnesium to the pre- and posthydration fluids.

The specific effects of phytic acid (PA) and resistant starch (RS) on mineral bioavailability, namely, Ca, Mg, Fe, Zn and Cu, were investigated in rats adapted to semipurified diets. The diets provided either 73 g/100 g digestible wheat starch (DS) alone, or 53 g/100 g DS plus 20 g/100 g crude potato starch (RS) and either 0 or 1.1 g/100 g PA. A period of 3 wk was first planned to adapt the rats to their respective diets. Compared with rats fed the DS diets, those fed the RS diets had significant cecal hypertrophy and an accumulation of short-chain fatty acids, together with greater cecal blood flow. RS enhanced the cecal absorption of Ca and Mg (from 0.15 to 0.55 micromol/min for Ca, and from 0.10 to 0.35 micromol/min for Mg). Mineral balance was enhanced significantly by RS (Ca, +46%; Mg +50%; Fe +20%; Zn, + 33% and Cu, +61%). PA had no significant effect on Ca or Mg solubility and absorption in the cecum, and it failed to alter significantly Ca or Mg balance. The apparent absorption of Fe, Zn and Cu was significantly lower in rats fed the DS + PA diet than in rats fed the DS diet (Fe, -35%; Zn, -28%; and Cu, -31%). In rats adapted to the RS diet, the inhibitory effects of PA were practically abolished and the mineral balance was restored to the control values. We conclude that the negative effects of PA on mineral balance are relatively minor compared with the stimulatory effect of RS.

Few data are available regarding calcium and magnesium absorption and endogenous fecal excretion in children. We used a multitracer stable isotope technique to assess calcium and magnesium balance in 12 boys and 13 girls aged 9-14 y (mean weight: 42 kg) maintained on relatively high calcium intakes (mean: 1310 +/- 82 mg/d). There were no significant differences in absorption of calcium or magnesium from milk between boys and girls. Calcium retention (balance) correlated positively with calcidiol (25-hydroxyvitamin D) concentration (r = 0.48, P = 0.02) and serum alkaline phosphatase activity (r = 0.44, P = 0.03). There was no significant relation between magnesium balance and concentration. When data from this study were combined with our previously reported data, an increase in total calcium absorption was seen for pubertal (Tanner stages 2-4) but not prepubertal (Tanner stage 1) white children over the range of intakes from approximately 750 to 1350 mg/d. Despite intakes similar to the 1989 recommended dietary allowance for magnesium (mean intake: 6.4 +/- 1.2 mg.kg-1.d-1), 11 of the 25 subjects (6 girls and 5 boys) were in negative magnesium balance. We conclude that benefits from higher calcium intakes, < or = 1350 mg/d, were most apparent in pubertal children. In addiction, higher magnesium intakes should be considered for children.

Hypophosphatemia caused by phosphate depletion is associated with renal magnesium wasting. The cellular mechanisms of phosphate depletion were investigated in an immortalized mouse distal convoluted tubule (MDCT) cell line. Intracellular free Mg2+ concentration. [Mg2+]i was determined by microfluorescence. Mg2+ transport was assessed as a function of change in [Mg2+]i with time following placement of Mg(2+)-depleted cells into a buffer containing 1.5 mM magnesium. The uptake rate of Mg2+ into Mg(2+)-depleted cells cultured in normal phosphate, 1.0 mM, was 175 +/- 21 nM/second. Depletion of phosphate in the culture media was associated with a significant decrease in Mg2+ uptake, which was dependent on the degree of phosphate depletion and on the time cultured in phosphate-deficient media. Cells cultured for 16 hours in 0.3 mM and 0 mM phosphate possessed Mg2+ uptake rates of 105 +/- 18 nM/second and 15 +/- 12 nM/second, respectively. Diminished Mg2+ uptake was rapidly induced following placement in low phosphate and was fully reversed following readdition of phosphate to the culture media. The effects of phosphate depletion on Mg2+ uptake was post-translational in nature as fully up-regulated MDCT cells with maximal Mg2+ uptake was associated with a rapid decrease (within 30 min) in Mg2+ transport when placed in phosphate-deficient media. Although Mg2+ uptake is altered by the transmembrane voltage, diminished Mg2+ uptake associated with phosphate depletion was not dependent on changes in membrane voltage. Further, it was not associated with a sustained increase in intracellular Ca2+ concentration. Chlorothiazide, probably through hyperpolarization of the plasma membrane, stimulates Mg2+ uptake in normal. 283 +/- 23 nM/second, and phosphate-depleted cells, 203 +/- 29 nM/second, but failed to entirely correct the defective transport. These studies demonstrate that magnesium wasting associated with hypophosphatemia and phosphate depletion is due, in part, to diminished Mg2+ transport in the distal convoluted tubule. The evidence is that the actions of phosphate deficiency are through alterations of Mg2+ transport across the luminal membrane of the distal convoluted tubule cell.

Fifteen patients with uncomplicated mild to moderate primary hypertension (7 males, 8 females, age range 36-65 years) were submitted to a double blind randomized crossover study, receiving MgO 3 times a day at a daily dose of 1.0 g (600 mg/day of magnesium) and placebo for a period of 6 weeks. This was to test the effects of oral magnesium supplementation on blood pressure and sodium, potassium, calcium and magnesium intraerythrocyte concentrations. Concomitantly, plasma renin activity and serum aldosterone was also measured. Oral magnesium reduced significantly the systolic (delta = -7.6 mmHg, P < 0.05); diastolic (delta = -3.8 mmHg, P < 0.01) and mean blood pressure (delta = -5.9 mmHg, P < 0.01). After magnesium supplementation intraerythrocyte sodium concentration was reduced (delta = -0.55 mEq/l per cell, P < 0.01) and intraerythrocyte magnesium concentration was increased (delta = 1.20 mg/dl per cell, P < 0.01). The diminution of the blood pressure correlated positively with the reduction in intraerythrocyte sodium (r = 0.66, P < 0.01) after magnesium. However, our results have shown that the blood pressure response to oral magnesium was not homogeneous. Forty percent of our patients had their blood pressure effectively controlled (more than 10 mmHg reduction in mean blood pressure), being the hypotensive effect more evident in patients with recent hypertension and in those where the reduction in intraerythrocyte sodium was significantly greater than in the non-responder individuals. Intraerythrocyte potassium and calcium, serum aldosterone, plasma renin activity and urinary sodium excretion were maintained unchanged after magnesium supplementation. These data showed that oral magnesium supplementation may reduce the blood pressure, which can be partially explained by the decrease in intracellular sodium and augment in intracellular magnesium.

Dietary raw (RS2) vs. retrograded resistant starch (RS3) raises apparent magnesium absorption in rats. The mechanism proposed is that RS2 enhances magnesium avaibility for absorption; it does this by increasing ileal solubility of magnesium due to a reduction in pH as a consequence of RS2 fermentation in the gut. The mechanism implies that dietary RS2 vs. RS3 would raise true magnesium absorption and stimulate reabsorption of endogenous magnesium, leading to a lower fecal excretion of endogenous magnesium. Dietary lactulose vs. glucose raises apparent magnesium absorption, and the mechanism proposed is similar to that for the stimulatory effect of RS2 vs. RS3. Thus, we measured in rats fed RS3, RS2, glucose or lactulose true magnesium absorption on the basis of the retention of the orally and intraperitoneally administered radiotracer 28Mg. Feeding rats RS2 instead of RS3 significantly enhanced apparent but not true magnesium absorption, because RS2 lowered fecal excretion of endogenous magnesium. When compared with dietary glucose, lactulose significantly raised both apparent and true magnesium absorption, but did not affect fecal excretion of endogenous magnesium. It is suggested that the proposed mechanism by which RS2 and lactulose would enhance magnesium absorption is disproved by the present data.

We investigated the effects of fructooligosaccharides on the absorption of calcium, magnesium and water from the colon and rectum of rats fed a control diet or the control diet containing 50 g fructooligosaccharides/kg. Chromium-mordanted cellulose was used as an unabsorbable marker to calculate apparent absorption of calcium and magnesium. There was a positive correlation (r = 0.982, P < 0.001 in rats fed the control diet and r = 0.975, P < 0.001 in rats fed the fructooligosaccharides-containing diet) between the amount of chromium and the dry weight of each fecal pellet in the colon and rectum. Ratios of calcium to chromium and magnesium to chromium in fecal pellets in the colon and rectum were calibrated from the Ca:Cr and Mg:Cr ratios of cecal contents. In rats fed the fructooligosaccharides-containing diet, but not in rats fed the control diet, these ratios were correlated with the fractional length of transit along the colon and rectum, indicating linear disappearance of calcium and magnesium during the colorectal passage. Total apparent absorption of calcium and magnesium, predicted from regression equations with the Ca:Cr and Mg:Cr ratios of cecal contents, agreed well with those calculated from the Ca:Cr and Mg:Cr ratios of feces. The consumption of fructooligosaccharides did not affect net water absorption from the colon and rectum. These results indicated that fructooligosaccharides significantly increased calcium and magnesium absorption and that indigestible and fermentable carbohydrate facilitates colorectal absorption of calcium and magnesium.

In this study the effect of the positional distribution of stearic acid (18:0) and oleic acid (18:1) in a triacylglycerol on absorption of fat, energy and nutrients was investigated in young rats. In addition the effect of dietary calcium on these variables was studied. Forty rats were fed purified diets containing either a fat blend high in 2-oleoyl-distearate or a fat blend high in 1-oleoyl-distearate. Both diets were given at low (0.3 g/100 g) and high (1.0 g/100 g) dietary calcium concentrations. Total fat absorption, expressed as the percentage of fat intake, was significantly lower in rats fed 2-oleoyl-distearate compared with 1-oleoyl-distearate at both dietary calcium concentrations. When expressed as absolute figures, the lower fat absorption in rats fed 2-oleoyl-distearate compared with 1-oleoyl-distearate only reached statistical significance at the high dietary calcium concentration. The reduced absorption of total fat was mainly caused by the lower absorption of stearic acid. The percentage of, but not absolute, absorption of oleic acid and energy were lower in rats fed 2-oleoyl-distearate. Absolute and percentage of calcium absorption were lower in rats fed 2-oleoyl-distearate compared with 1-oleoyl-distearate. Absolute and percentage of magnesium absorption were not significantly affected by the positional distribution of stearic acid and oleic acid in the triacylglycerol, but were decreased at a high dietary calcium concentration. We concluded that the lowered stearic acid absorption from 2-oleoyl-distearate compared with 1-oleoyl-distearate might have been due to the greater formation of insoluble calcium and magnesium soaps in the intestine.

Tannins reportedly alter absorption and utilization of protein and minerals. The present study investigated the effect of tannins extracted from 'Mississippi Silver' cowpeas and black tea when incorporated into nutritionally balanced diets. Condensed tannins were incorporated into the diet of weanling male Sprague-Dawley rats at 0.0, 0.0057, 0.0171 and 0.057 g/100 g diet for 28 d. Ingestion of tannin from cowpeas or tea did not change significantly growth rate, protein efficiency ratio, apparent protein digestibility, nitrogen excretion, relative liver weight, or nitrogen concentration of liver. During d 11-18, apparent calcium absorption was lower in rats fed the medium and high levels of cowpea tannin and in those fed all levels of tea tannin compared with the control group. By wk 4, no differences were observed in apparent calcium absorption among treatment groups. Apparent magnesium absorption was not affected by dietary treatment, nor was femur content of calcium or magnesium. We conclude that at the levels of condensed tannins fed, a short-term reduction of apparent calcium absorption occurred; however, by wk 4 calcium absorption was comparable to that of the control group. The acute change that occurred in apparent calcium absorption did not influence bone calcium content.

Little is known about the absorption of magnesium from infant diets. Magnesium bioavailability was evaluated from infant diets that varied by protein and carbohydrate source; magnesium, calcium, and phosphorus contents; and the form of magnesium fortification. Diets were separated into soluble, insoluble, and fat fractions to determine magnesium distribution. Most of the magnesium (> 62%) was found in the soluble fraction. Gel filtration of the soluble fraction from all diets studied showed that > 95% of magnesium is free or associated with low-molecular-weight compounds. Distribution of 28Mg and native magnesium in fractions of the diets was similar, thus validating the use of an extrinsic label. In vitro digestion decreased the percent insoluble magnesium from as high as 35% to 2-8%. Whole-body retention of 28Mg-labeled diets in suckling rat pups 4 h after oral intubation ranged from 51% to 92%. No significant differences were found between human milk, cow milk, and infant formula. In conclusion, magnesium from the infant diets studied has high bioavailability, and moderate differences in their composition do not affect bioavailability significantly.

Apparent magnesium absorption is depressed in rats fed diets containing soybean protein or enriched with sodium phytate or phosphate in comparison with casein, whereas it is raised in rats fed lactose. However, the possibility that changes in apparent absorption are caused by changes in fecal excretion of endogenous magnesium cannot be excluded. We studied the effects of casein, soybean protein, sodium phytate, lactose and phosphate on apparent and true absorption of magnesium. True magnesium absorption was measured with the use of oral and intraperitoneal administration of tracer doses of 28Mg. Fecal excretion of endogenous magnesium was calculated from apparent and true absorption. True magnesium absorption was not affected by either substitution of soybean protein for casein or by the addition of sodium phytate to a diet containing casein. Endogenous magnesium excretion in feces was significantly increased by soybean protein and sodium phytate. Thus the observed impairment of apparent magnesium absorption in rats fed soybean protein or sodium phytate is due to enhanced fecal excretion of endogenous magnesium. With the other dietary treatments, enhanced fecal excretion of endogenous magnesium was not associated with a discrepancy in the effects on apparent and true magnesium absorption. Dietary lactose vs. dextrose and supplemental phosphate both stimulated fecal excretion of endogenous magnesium, but lactose raised both true and apparent magnesium absorption, and phosphate depressed both true and apparent magnesium absorption.

The effects of casein and soybean protein on magnesium absorption and magnesium concentration in the femur were investigated in rats. Purified diets containing either casein or soybean protein and three concentrations of added magnesium (0.82, 1.64 or 2.46 mmol/100 g diet) were used. The isonitrogenous diets were carefully balanced for the different mineral concentrations in the protein preparations. Absolute and percent magnesium absorption and urinary magnesium excretion were significantly decreased in rats fed soybean protein when compared with casein, irrespective of the dietary concentration of added magnesium. The magnesium content of femur was significantly lower in rats fed soybean protein, but this effect was seen only when the diet contained 0.82 mmol magnesium/100 g diet. The addition of sodium phytate to the casein diets, to a concentration identical to that in the diets containing soybean protein as provided by the soybean protein preparation, produced similar effects on magnesium absorption as the diets containing soybean protein. These results indicate that soybean protein, when compared with casein, decreases magnesium absorption through its phytate component.

We hypothesized that urinary excretion of calcium would be affected by both urinary excretion of acid and of total fixed anions. Calcium, magnesium and phosphorus utilization was examined in rats fed semipurified diets supplemented with approximately 0.4 mol sodium/kg diet or approximately 0.4 mol potassium/kg diet as chloride, sulfate, bisulfate, carbonate or bicarbonate salts in two studies. The ingestion of supplemental fixed anions (chloride, sulfate or bisulfate) increased urinary excretion of calcium, magnesium and phosphorus. It made no difference whether the anions were ingested as sodium or potassium salts. In Study 1, 80% of the variation in urinary calcium excretion could be explained on the basis of urinary excretion of sulfate, ammonia and total anions. In Study 2, 77% of the variation in urinary calcium excretion could be predicted on the basis of urinary excretion of total anions and sulfate. Although bone and plasma calcium concentrations were not responsive to these dietary changes, less magnesium was retained in bones of rats fed any of the supplemental salts.

We examined the potential of increased Ca in the diet to modify the effects of Pb on tissue metal concentrations, blood pressure and the incidence of renal tumours. We randomly assigned 48, 5-wk-old male Wistar rats to one of six treatment groups. They were fed a low (0.2%) or high (4.0%) Ca diet for 31 wk and given 0, 1.0 or 100 micrograms Pb/mL in drinking water. In the low Ca groups, increasing concentrations of Pb produced graded increases in mean blood pressure. Rats receiving 4.0% Ca had higher mean blood pressures than the animals fed the 0.2% Ca diet. The 4.0% Ca diet also caused renal and urinary bladder stones to develop in some rats. The high Ca diet did not prevent dose-dependent increases in tissue Pb accumulation, but it caused significant decreases in kidney Cu, femur Mg and Fe in kidney, liver and testis. Femur Mg and Fe and liver Fe concentrations were lowest in rats receiving 4.0% Ca and 100 micrograms Pb/mL. Precancerous and cancerous renal lesions occurred to the greatest extent in the rats receiving 100 micrograms Pb/mL and the high Ca diet. These results suggest that high dietary Ca does not protect against Pb-induced increases in blood pressure or Pb accumulation in tissues and may often produce nephrocalcinosis. In addition, high dietary Ca in the presence of Pb may increase the incidence of renal tumors.

Magnesium absorption has been studied in both humans and animals under diverse experimental conditions. As a result, the data often appear confusing and conflicting. In this review we attempt to summarize information concerning Mg absorption and, where possible, to reconcile apparently conflicting observations. Most studies suggest that Mg is absorbed predominantly in the distal intestine. At usual Mg intakes, Mg absorption occurs primarily by intercellular diffusional and solvent drag mechanisms. There is evidence for a saturable component of Mg absorption in the small intestine and the descending colon that is important at low dietary Mg intakes. Pharmacological doses of vitamin D increase Mg absorption in both vitamin D-deficient and vitamin D-replete animals. A substantial amount of Mg absorption, however, occurs independent of vitamin D. In addition, vitamin D may reduce Mg retention through increases in urinary Mg excretion. Intestinal interactions between Mg and calcium or phosphate have been demonstrated in both humans and animals. The nature of these interactions cannot be readily explained by data currently available.

Protein kinase C (Ca2+ and phospholipid-dependent protein kinase) was detected in human placenta and was partially purified using DEAE cellulose chromatography and Ultrogel filtration. Diolein alone did not act on this enzyme but exerted a strong stimulatory action when associated with phosphatidylserine and Ca2+. Similar results were obtained with the phorbol myristate acetate. The kinetic constants for ATP, histone HI or Mg2+ and the apparent Ka for Ca2+ and phosphatidylserine were determined.

trans-Aconitic acid has been implicated in magnesium deficiency of ruminants since the 1960s, but recent experiments indicated that much of it can be converted by rumen bacteria to tricarballylic acid (TCBA). Rats were used as experimental models in the studies described here because analogous experiments in ruminants would have been very expensive. When TCBA was fed to young male Sprague-Dawley rats as 2% of an AIN-76A diet with marginal (200 mg/kg) or adequate (500 mg/kg) Mg, virtually all of the dietary acid was recovered in the urine. Mg and Ca absorptions were unaffected by TCBA but urinary losses of Mg, Ca and Zn were higher than in pair-fed controls. TCBA was highly correlated (r = 0.93) with titratable acid excretion, and Mg, Ca and Zn retentions were reduced by 90, 35 and 56%, respectively. Rats fed 2% citric acid, a structurally similar but metabolizable acid, excreted more Zn than controls but did not excrete excess Mg or Ca. Since TCBA led to a depletion of Mg and other cations, it could be a contributing factor in the etiology of the Mg deficiency known as grass tetany in ruminants. Additional work in ruminants now seems warranted.