Absorción mineral y retención ósea en ratas normales en crecimiento por el consumo de un yogur experimental reducido en lactosa que contiene galactooligosacáridos (GOS) / Mineral absorption and bone retention in normal growing rats by consumption of an experimental lactose-reduced yogurt containing galactooligosaccharides (GOS)

Introducción: Los GOS son prebióticos naturales presentes en la leche materna que pue-den obtenerse enzimáticamente a partir de la lactosa de leche de vaca durante la fabricación de yogur. El producto lácteo resultante será reducido en lactosa y contendrá prebióticos y bacterias potencialmente probióticas. Sin embargo, mantendrá la baja relación Ca/Pi que aporta la leche de vaca, lo que podría alterar el remodelamiento óseo y la mineralización. Objetivo: comparar si un yogur reducido en lactosa que contiene GOS (YE) ofrece ventajas adicionales respecto de un yogur regular sin GOS (YR) sobre las absorciones (Abs) de Ca y Pi, retención y calidad ósea durante el crecimiento normal. Al destete, ratas machos fueron divididas en 3 grupos alimentados con AIN ́93-G (C), YE o YR durante 28 días. Resultados: YE mostró el mayor aumento de lactobacilos fecales; producción de ácidos grasos de cadena corta especialmente p, profundidad de las criptas colónicas y menor pH cecal. El %AbsCa y %AbsPi aumentó en el siguiente órden: YE> YR> C (p < 0,05). El contenido de Ca y Pi en fémur, la densidad y contenido mineral óseos y los parámetros biomecánicos fueron similares en YE y C, mientras que YR mostró valores significativa-mente menores (p < 0,05). Conclusiones: YE aumentó las Abs y biodisponibilidad de minerales, alcanzando la retención y calidad ósea de C. El aumento en las Abs observado en YR no logró obtener la retención y calidad ósea de C. Conclusión: YE habría contrarrestado el efecto negativo del mayor aporte de Pi de la leche de vaca y sería una buena estrategia para lograr el pico de masa ósea y calidad del hueso adecuados, especialmente en individuos intolerantes a la lactosa. (AU)

Breast milk contains an optimal calcium/phosphate (Ca/Pi) ratio and GOS. These natural prebiotics can be enzymatically produced via cow's milk lactose inyogurt manufacture. This milk product is low in lactose and contains prebiotics and potentially probiotic bacteria but maintains a low Ca/Pi ratio that could alter bone remodeling and mineralization. We evaluated if a lactose-reduced yogurt containing GOS (YE) offers additional advantages over regular yogurt without GOS (YR) on Ca and Pi absorption (Abs), bone retention and quality during normal growth. Weaning male rats were divided into 3 groups fed AIN'93-G (C), YE or YR for 28 days. Results: YE showed the highest increase in fecal lactobacilli; short-chain fatty acids production, especially propionate and butyrate; intestine crypt depth, and the lowest cecal pH. AbsCa% and AbsPi% increased in this order: YE> YR> C (p <0.05). Ca and Pi content in femur, bone density and mineral content, and biomechanical parameters were similar in YE and C, while YR showed the significantly lowest value (p < 0.05). Conclusions: YE increased mineral Abs reaching the retention and bone quality of C. Although YR increased Abs, bone retention and quality did not achieve C values. Seemingly, YE compensated for the negative effect of the higher Pi supply and would be a good strategy to achieve adequate peak bone mass and bone quality, especially in lactose intolerant individuals. (AU)

A Magnesium-Incorporated Nanoporous Titanium Coating for Rapid Osseointegration.

PURPOSE: Micro-arc oxidation (MAO) is a fast and effective method to prepare nanoporous coatings with high biological activity and bonding strength. Simple micro/nano-coatings cannot fully meet the requirements of osteogenesis. To further improve the biological activity of a titanium surface, we successfully added biological magnesium (Mg2+) to a coating by micro-arc oxidation and evaluated the optimal magnesium concentration in the electrolyte, biocompatibility, cell adhesion, proliferation, and osteogenesis in vitro. METHODS: Nanoporous titanium coatings with different concentrations of magnesium were prepared by micro-arc oxidation and characterized by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS). The Mg2+ release ability of the magnesium-incorporated nanoporous titanium coatings was determined by inductively coupled plasma emission spectrometry (ICP-OES). The cytotoxicity of the magnesium-incorporated nanoporous titanium coatings was detected with live/dead double-staining tests. A CCK-8 assay was employed to evaluate cell proliferation, and FITC-phalloidin was used to determine the structure of the cytoskeleton by staining ß-actin. Alkaline phosphatase (ALP) activity was evaluated by alizarin red S (ARS) staining to determine the effect of the coatings on osteogenic differentiation in vitro. The mRNA expression of osteogenic differentiation-related markers was measured using qRT-PCR. RESULTS: EDS analyses revealed the successful addition of magnesium to the microporous coatings. The best magnesium concentration of the electrolyte for preparing the new coating was determined. The results showed that the nano-coatings prepared using the electrolyte with 2 g/L magnesium acetate best promoted the adhesion, proliferation, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). CONCLUSION: These results suggest that the new titanium metal coating with a dual effect of promoting bone morphology and supplying the biological ion Mg2+ can be beneficial for rapid osseointegration.

Optimizing an Osteosarcoma-Fibroblast Coculture Model to Study Antitumoral Activity of Magnesium-Based Biomaterials.

Osteosarcoma is among the most common cancers in young patients and is responsible for one-tenth of all cancer-related deaths in children. Surgery often leads to bone defects in excised tissue, while residual cancer cells may remain. Degradable magnesium alloys get increasing attention as orthopedic implants, and some studies have reported potential antitumor activity. However, most of the studies do not take the complex interaction between malignant cells and their surrounding stroma into account. Here, we applied a coculture model consisting of green fluorescent osteosarcoma cells and red fluorescent fibroblasts on extruded Mg and Mg-6Ag with a tailored degradation rate. In contrast to non-degrading Ti-based material, both Mg-based materials reduced relative tumor cell numbers. Comparing the influence of the material on a sparse and dense coculture, relative cell numbers were found to be statistically different, thus relevant, while magnesium alloy degradations were observed as cell density-independent. We concluded that the sparse coculture model is a suitable mechanistic system to further study the antitumor effects of Mg-based material.

Magnesium oil enriched transdermal nanogel of methotrexate for improved arthritic joint mobility, repair, and reduced inflammation.

Aim: Methotrexate (Mtx) is prescribed to reduce pain and inflammation in arthritis patients; however, improved repair and mobility of joints still are the major concerns. Magnesium oil (MO) improves joint mobility and repair; therefore, MO-assisted transdermal delivery of Mtx was aimed.Methods: MO integrated Mtx nanoemulsion (Mtx-MONE) was prepared with uniform size (175 ± 35.4 nm), pH (6.15 ± 0.3) near to skin pH, and high entrapment efficiency (65 ± 8.6%). Mtx-MONE was transformed to nanogel (Mtx-MONEG) with semisolid consistency (43,408 ± 77.72 cP) and good spreadability (3.63 ± 0.033 mJ).Results: Mtx-MONEG showed significant reduction in oedema, arthritic scores, level of inflammatory cytokines, and improved walking as compared to diseased control. MO offered additional improvements in joints, mobility, and repair.Conclusion: Transdermal delivery of Mtx has been successfully achieved by Mtx-MONEG. Tremendous recovery from inflammation, improved joints mobility and repair, and reduced pain strongly support the use of MO as an adjutant of Mtx for improved transdermal application.

Potassium affects the phytoextraction potential of Tanzania guinea grass under cadmium stress.

The supply of potassium (K) is a strategy to increase the tolerance of plants exposed to Cd toxicity. The aim of this study was to verify the influence of K on the growth and potential of Tanzania guinea grass (Panicum maximum Jacq. cv. Tanzania (syn. Megathyrsus maximus (Jacq.) B.K. Simon & S.W.L. Jacobs)) for Cd phytoextraction as well as to evaluate nutritional attributes of this grass under conditions of Cd stress. The experiment was conducted in a randomized complete block design, using a 3 × 4 factorial arrangement, with three replications. Three rates of K (0.4, 6.0, and 11.6 mmol L-1) were combined with four rates of Cd (0.0, 0.5, 1.0, and 1.5 mmol L-1) in nutrient solution. Two plant growth periods were evaluated. The increase in K supply to plants exposed to Cd rates of up to 1.0 mmol L-1 caused increase in morphogenic and production attributes, as well as reduction in tiller mortality rate, in the second growth period. K concentrations (in both harvests) increased, while calcium and magnesium concentrations in the second harvest decreased with increasing Cd rates. The high availability of Cd (1.5 mmol L-1) in the nutrient solution caused decrease in relative chlorophyll index (RCI) in both harvests. The high supply of K to plants exposed to Cd resulted in high shoot dry mass production, reducing Cd concentration in the photosynthetic tissues (which means great tolerance of the plant) and increasing the accumulation of this metal in the shoots that can be harvested. Therefore, K increases the Cd phytoextraction capacity of Tanzania guinea grass.

Degradation behaviors and cytocompatibility of Mg/ß-tricalcium phosphate composites produced by spark plasma sintering.

Magnesium (Mg)-based materials have shown great potentials for bioresorbable implant applications. Previous studies showed that Mg with 10 and 20 vol % ß-tricalcium phosphate (ß-TCP) composites produced by spark plasma sintering, improved mechanical properties when compared with pure Mg. The objectives of this study were to evaluate the degradation behaviors of Mg/10% ß-TCP and Mg/20% ß-TCP composites in revised stimulated body fluid (rSBF), and to determine their cytocompatibility with bone marrow derived mesenchymal stem cells (BMSCs) using the direct culture method. During the 11 days of immersion in rSBF, Mg/ß-TCP composites showed different degradation behaviors at different immersion periods, that is, the initial stage (0-1 hr), the mid-term stage (1 hr to 2 days), and the long-term stage (2-11 days). The counter effects of mass loss due to microgalvanic corrosion and mass gain due to deposition of Ca-P containing layers resulted in slower Mg2+ ion release for Mg/20% ß-TCP than Mg/10% ß-TCP in the mid-term, but eventually 16% mass loss for Mg/20% ß-TCP and 10% mass loss for Mg/10% ß-TCP after 11 days of immersion. The in vitro studies with BMSCs showed the highest cell adhesion density (i.e., 68% of seeding density) on the plate surrounding the Mg/10% ß-TCP sample, that is, under the indirect contact condition of direct culture. The ß-TCP showed a positive effect on direct adhesion of BMSCs on the surface of Mg/ß-TCP composites. This study elucidated the degradation behaviors and the cytocompatibility of Mg/ß-TCP composites in vitro; and, further studies on Mg/ceramic composites are needed to determine their potential for clinical applications. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2238-2253, 2019.

Magnesium in Breast Cancer: What Is Its Influence on the Progression of This Disease?

Breast cancer is a disease of high mortality, characterized by the progressive accumulation of mutations that contribute to the uncontrolled development of breast tissue cells. Literature shows that disturbances in mineral homeostasis, such as magnesium, may interfere with tumor progression. The objective of this study is to provide updated information about magnesium's role in the pathogenesis of breast cancer. A review of literature was carried out from a search for articles in the PubMed and CAPES Periodicals databases published between 1995 and 2016 with the cross-references of the descriptors "magnesium," "breast neoplasms," and "oxidative stress" and the corresponding words in Portuguese. We included studies on the metabolism and bioavailability of magnesium and studies related to breast cancer and excluded articles in which only the abstract was available, dissertations, theses, articles involving adjuvant and/or neoadjuvant therapies, and supplementation of minerals in breast cancer patients. Magnesium is a mineral that participates in the metabolism of various nutrients and nucleic acids. In the presence of breast cancer, neoplastic cells increase the expression of magnesium transport channels, which raises the intracellular concentration of the mineral, contributing to tumor growth through its function of increasing energy demand. The data obtained in this review illustrates the influence of magnesium on the progression of breast cancer. However, the existing data are scarce and inconsistent, which demonstrates a need for further studies on the subject with a goal to have better control of the disease.

Pharmacokinetics of Magnesium Bolus Therapy in Cardiothoracic Surgery.

OBJECTIVE: To investigate the pharmacokinetics of a 20 mmol magnesium bolus in regards to serum and urinary magnesium concentration, volume of distribution, and half-life. DESIGN: Prospective, experimental study. SETTING: A university-affiliated teaching hospital. PARTICIPANTS: Twenty consecutive cardiac surgery patients treated with magnesium bolus therapy for prevention of arrhythmia. INTERVENTIONS: A 20-mmol bolus of magnesium sulfate was administered intravenously. MEASUREMENTS AND MAIN RESULTS: Median magnesium levels increased from 1.04 (interquartile range 0.94-1.23) mmol/L to 1.72 (1.57-2.14) mmol/L after 60 minutes of magnesium infusion (p < 0.001) but decreased to 1.27 (1.21-1.36) and 1.16 (1.11-1.21) mmol/L after 6 and 12 hours, respectively. Urinary magnesium concentration increased from 6.3 (4.2-14.5) mmol/L to 19.1 (7.4-34.5) mmol/L after 60 minutes (p < 0.001), followed by 22.7 (18.4-36.7) and 15 (8.4-19.7) mmol/L after 6 and 12 hours, respectively. Over the 12-hour observation period, the cumulative urinary magnesium excretion was 19.1 mmol (95.5% of the dose given). The median magnesium clearance was 10 (4.7-15.8) mL/min and increased to 14.9 (3.8-20.7; p = 0.934) mL/min at 60 minutes. The estimated volume of distribution was 0.31 (0.28-0.34) L/kg. CONCLUSION: Magnesium bolus therapy after cardiac surgery leads to a significant but short-lived increase of magnesium serum concentration due to renal excretion and distribution, and the magnesium balance is neutral after 12 hours.

In Vitro Bioavailability of Calcium, Magnesium, Iron, Zinc, and Copper from Gluten-Free Breads Supplemented with Natural Additives.

The aim of this study was to measure the content of calcium, magnesium, iron, zinc, and copper and determine the bioavailability of these ingredients in gluten-free breads fortified with milk and selected seeds. Due to the increasing prevalence of celiac disease and mineral deficiencies, it has become necessary to produce food with higher nutritional values which maintains the appropriate product characteristics. This study was designed for gluten-free breads fortified with milk and seeds such as flax, poppy, sunflower seeds, pumpkin seeds or nuts, and flour with amaranth. Subsequently, digestion was performed in vitro and the potential bioavailability of the minerals was measured. In the case of calcium, magnesium, iron, and copper, higher bioavailability was observed in rice bread, and, in the case of copper and zinc, in buckwheat bread. This demonstrated a clear increase in bioavailability of all the minerals when the bread were enriched. However, satisfactory results are obtained only for the individual micronutrients.

Nanocomposite hydrogels stabilized by self-assembled multivalent bisphosphonate-magnesium nanoparticles mediate sustained release of magnesium ion and promote in-situ bone regeneration.

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 (Mg2+), not only regulate the cellular behaviors but also stimulate local bone formation and healing. However, the effective delivery and tailored release of Mg2+ remains a challenge, with few reports on hydrogels being used for Mg2+ delivery. Bisphosphonate exhibits a variety of specific bioactivities and excellent binding affinity to multivalent cations such as Mg2+. 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 Mg2+. The released Mg2+ 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 Mg2+. Moreover, the released Mg2+ 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.

A pro-angiogenic degradable Mg-poly(lactic-co-glycolic acid) implant combined with rhbFGF in a rat limb ischemia model.

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.

Macrophage phagocytosis of biomedical Mg alloy degradation products prepared by electrochemical method.

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.

Magnesium silicide nanoparticles as a deoxygenation agent for cancer starvation therapy.

A material that rapidly absorbs molecular oxygen (known as an oxygen scavenger or deoxygenation agent (DOA)) has various industrial applications, such as in food preservation, anticorrosion of metal and coal deoxidation. Given that oxygen is vital to cancer growth, to starve tumours through the consumption of intratumoral oxygen is a potentially useful strategy in fighting cancer. Here we show that an injectable polymer-modified magnesium silicide (Mg2Si) nanoparticle can act as a DOA by scavenging oxygen in tumours and form by-products that block tumour capillaries from being reoxygenated. The nanoparticles are prepared by a self-propagating high-temperature synthesis strategy. In the acidic tumour microenvironment, the Mg2Si releases silane, which efficiently reacts with both tissue-dissolved and haemoglobin-bound oxygen to form silicon oxide (SiO2) aggregates. This in situ formation of SiO2 blocks the tumour blood capillaries and prevents tumours from receiving new supplies of oxygen and nutrients.

Differential magnesium implant corrosion coat formation and contribution to bone bonding.

Magnesium alloys are presently under investigation as promising biodegradable implant materials with osteoconductive properties. To study the molecular mechanisms involved, the potential contribution of soluble magnesium corrosion products to the stimulation of osteoblastic cell differentiation was examined. However, no evidence for the stimulation of osteoblast differentiation could be obtained when cultured mesenchymal precursor cells were differentiated in the presence of metallic magnesium or in cell culture medium containing elevated magnesium ion levels. Similarly, in soft tissue no bone induction by metallic magnesium or by the corrosion product magnesium hydroxide could be observed in a mouse model. Motivated by the comparatively rapid accumulation solid corrosion products physicochemical processes were examined as an alternative mechanism to explain the stimulation of bone growth by magnesium-based implants. During exposure to physiological solutions a structured corrosion coat formed on magnesium whereby the elements calcium and phosphate were enriched in the outermost layer which could play a role in the established biocompatible behavior of magnesium implants. When magnesium pins were inserted into avital bones, corrosion lead to increases in the pull out force, suggesting that the expanding corrosion layer was interlocking with the surrounding bone. Since mechanical stress is a well-established inducer of bone growth, volume increases caused by the rapid accumulation of corrosion products and the resulting force development could be a key mechanism and provide an explanation for the observed stimulatory effects of magnesium-based implants in hard tissue. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 697-709, 2017.

MRI contrast agents: Classification and application (Review).

Magnetic resonance imaging (MRI) contrast agents are categorised according to the following specific features: chemical composition including the presence or absence of metal atoms, route of administration, magnetic properties, effect on the magnetic resonance image, biodistribution and imaging applications. The majority of these agents are either paramagnetic ion complexes or superparamagnetic magnetite particles and contain lanthanide elements such as gadolinium (Gd3+) or transition metal manganese (Mn2+). These elements shorten the T1 or T2 relaxation time, thereby causing increased signal intensity on T1-weighted images or reduced signal intensity on T2-weighted images. Most paramagnetic contrast agents are positive agents. These agents shorten the T1, so the enhanced parts appear bright on T1-weighted images. Dysprosium, superparamagnetic agents and ferromagnetic agents are negative contrast agents. The enhanced parts appear darker on T2-weighted images. MRI contrast agents incorporating chelating agents reduces storage in the human body, enhances excretion and reduces toxicity. MRI contrast agents may be administered orally or intravenously. According to biodistribution and applications, MRI contrast agents may be categorised into three types: extracellular fluid, blood pool and target/organ-specific agents. A number of contrast agents have been developed to selectively distinguish liver pathologies. Some agents are also capable of targeting other organs, inflammation as well as specific tumors.

Effect of Mg content on the bioactivity and biocompatibility of Mg-substituted fluorapatite nanopowders fabricated via mechanical activation.

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.

The acute effect of high-dose intravenous vitamin C and other nutrients on blood pressure: a cohort study.

BACKGROUND: Regular intake of vitamin C/ascorbate reduces blood pressure (BP) in hypertensives. High-dose intravenous vitamin C (IVC) achieves higher plasma levels; however, there is a paucity of research on acute BP effects. Our study is the first to investigate the effect of high-dose IVC, with or without concomitant i.v. nutrients, on BP during i.v. METHODS: A cohort of adult patients scheduled to receive IVC treatment for infection, cancer or fatigue, as prescribed by their treating doctor, participated at a Melbourne clinic, Australia. Ambulatory BP was assessed every 10 min over 90 min during i.v. TREATMENT: Patients received 15-100 g of IVC alone or in addition to i.v. vitamin B, glutathione, magnesium or zinc. BP change over time adjusted for baseline BP, IVC dosage, i.v. treatment and BMI was analysed. RESULTS: A total of 77 mostly normotensive patients participated, with a third receiving IVC alone (42±20 g), and two-thirds also received other i.v. nutrients. IVC alone (>30 g) reduced the mean BP up to 8-9 mmHg in prehypertensive patients. In contrast, concomitant intravenous vitamin B12 (IVB12) significantly increased the mean BP by 11-13 mmHg. Comparison of BP change during IVC versus IVC+IVB12 indicated a highly significant difference [systolic blood pressure: mean difference (SD)=16.6 (17.8) mmHg, P<0.001; diastolic blood pressure: mean difference (SD)=12.5 (16.7) mmHg, P=0.003]. CONCLUSION: Our study suggests an acute BP-reducing effect of high-dose IVC, particularly with dosages above 30 g, and in patients with prehypertension and normal BMI. Furthermore, our study indicated a marked and clinically relevant hypertensive effect of IVB12, suggesting routine BP monitoring during i.v. therapy in clinical practice.

Accumulation of metals in cancerous and healthy tissues of patients with lung cancer in Southern Poland.

The aim of this study was to investigate whether the concentrations of metals differ among patients with and without lung cancer with different smoking status and living in industrialized environments. We also evaluated the relationships between metals and blood parameters including hematocrit level (Hct), hemoglobin concentration (Hb), red (RBC) and white (WBC) blood cells numbers. Concentrations of metals were measured with AAS (copper - Cu, iron - Fe, magnesium - Mg, zinc - Zn) and CV-AAS (mercury - Hg). Neither smoking status nor industrialization could be considered as a significant factor for metals accumulation in blood, lungs and tumor tissues, with the exception of mercury which differed in the aspect of industrialization. According to the type of the disease, Fe, Hg and Mg concentrations differed significantly in lungs. Correlations between metals and blood parameters were observed. Additionally, concentrations of Mg, Cu and Zn were correlated between lungs and tumor tissue of patients with cancer as well as they all were related to each other in lungs, tumor and blood tissues.

Nickel phytoremediation potential of the Mediterranean Alyssoides utriculata (L.) Medik.

This study investigated the accumulation and distribution of nickel in the leaves and roots of the Mediterranean shrub Alyssoides utriculata to assess its potential use in phytoremediation of Ni contaminated soils. Total (AAS and ICP-MS) Ni, Ca and Mg contents were analyzed in the plants and related to their bioavailability (in EDTA) in serpentine and non-serpentine soils. To find the relationships between the soil available Ni and the Ni content of this species, we also evaluated possible interactions with Ca and Mg. The bioaccumulation factor (BF) and the translocation factor (TF) were determined to assess the tolerance strategies developed by A. utriculata and to evaluate its potential for phytoextraction or phytostabilization. The leaf Ni is higher than 1000 µg g(-1) which categorizes the species as a Ni-hyperaccumulator and a great candidate for Ni-phytoextraction purposes. In addition to the accumulation of Ni, the leaf Mg is also correlated with soil bioavailable concentrations. The Ca uptake and translocation were significantly lower in serpentine plants (higher Ni), as such, the leaf Ca is probably greatly influenced either by the soil's Ni or the soil Ca/Mg ratio. The BFs and TFs are strongly higher than 1 and generally did not significantly differed between plants from serpentine (higher Ni) and non-serpentine soils (lower Ni). The present study highlights for the first time that A. utriculata could be suitable for cleaning Ni-contaminated areas and provides a contribution to the very small volume of data available on the potential use of native Mediterranean plant species from contaminated sites in phytoremediation technologies.

New TRPM6 missense mutations linked to hypomagnesemia with secondary hypocalcemia.

Despite recent progress in our understanding of renal magnesium (Mg(2+)) handling, the molecular mechanisms accounting for transepithelial Mg(2+) transport are still poorly understood. Mutations in the TRPM6 gene, encoding the epithelial Mg(2+) channel TRPM6 (transient receptor potential melastatin 6), have been proven to be the molecular cause of hypomagnesemia with secondary hypocalcemia (HSH; OMIM 602014). HSH manifests in the newborn period being characterized by very low serum Mg(2+) levels (<0.4 mmol/l) accompanied by low serum calcium (Ca(2+)) concentrations. A proportion of previously described TRPM6 mutations lead to a truncated TRPM6 protein resulting in a complete loss-of-function of the ion channel. In addition, five-point mutations have been previously described. The aim of this study was to complement the current clinical picture by adding the molecular data from five new missense mutations found in five patients with HSH. To this end, patch-clamp analysis and cell surface measurements were performed to assess the effect of the various mutations on TRPM6 channel function. All mutant channels, expressed in HEK293 cells, showed loss-of-function, whereas no severe trafficking impairment to the plasma membrane surface was observed. We conclude that the new TRPM6 missense mutations lead to dysregulated intestinal/renal Mg(2+) (re)absorption as a consequence of loss of TRPM6 channel function.