Effects of magnesium supplements on blood pressure, endothelial function and metabolic parameters in healthy young men with a family history of metabolic syndrome.

BACKGROUND AND AIMS: Magnesium plays an important role in the modulation of vascular tone and endothelial function and can regulate glucose and lipid metabolism. Patients with hypertension, metabolic syndrome (MetS) and diabetes mellitus (T2DM) have low body magnesium content; indeed, magnesium supplementation has been shown to have a positive effect on blood pressure (BP) and gluco-metabolic parameters. The aim of our study was to evaluate the effect of magnesium supplements on hemodynamic and metabolic parameters in healthy men with a positive family history of MetS or T2DM. METHODS AND RESULTS: In a randomized, double-blind, placebo-controlled 8-week crossover trial with a 4 week wash-out period, oral supplements of 8.1 mmol of magnesium-pidolate or placebo were administered twice a day to 14 healthy normomagnesemic participants, aged 23-33 years. The primary endpoint was office BP, measured with a semiautomatic oscillometric device. Secondary endpoints included characteristics of the MetS, namely endothelial function, arterial stiffness and inflammation. Plasma and urinary magnesium were measured in all participants while free intracellular magnesium was measured only in a subsample. There was no significant difference in either systolic and diastolic BP in participants post-magnesium supplementation and post-placebo treatment when compared to baseline BP measurements. Further, the metabolic, inflammatory and hemodynamic parameters did not vary significantly during the study. CONCLUSIONS: Our study showed no beneficial effect of magnesium supplements on BP, vascular function and glycolipid profile in young men with a family history of MetS/T2DM (trial registration at clinicaltrial.gov ID: NCT01181830; 12th of Aug 2010).

Anti-angiogenic effects of two cystine-knot miniproteins from tomato fruit.

BACKGROUND AND PURPOSE: Cystine-knot miniproteins are characterized by a similar molecular structure. Some cystine-knot miniproteins display therapeutically useful biological activities, as antithrombotic agents or tumour growth inhibitors. A critical event in the progression of tumours is the formation of new blood vessels. The aim of this work was to test two tomato cystine-knot miniproteins for their effects on endothelial cell proliferation and angiogenesis in vitro. EXPERIMENTAL APPROACH: Two tomato cystine-knot miniproteins (TCMPs) were expressed and purified either as recombinant or as native proteins from tomato fruits. The Matrigel assay was used to investigate the effects of TCMPs on in vitro angiogenesis. Viability and proliferation of endothelial cells were tested. Extracellular signal-regulated kinase (ERK)1/2 phosphorylation was assayed in either HUVEC or A431 epidermal growth factor receptor (EGFR)-overexpressing cells treated with TCMPs. EGFR phosphorylation was tested in A431 cells. KEY RESULTS: Both recombinant and native TCMPs inhibited in vitro angiogenesis of HUVEC cells at concentrations of 15-100 nM. The anti-angiogenic effect of TCMPs was associated with the inhibition of ERK phosphorylation. The two miniproteins did not alter the viability and proliferation of the endothelial cells. CONCLUSIONS AND IMPLICATIONS: The anti-angiogenetic properties of TCMPs are of potential pharmacological interest because they are common and natural components of the human diet, they possess low toxicity, they are active at submicromolar concentrations, they share a common molecular structure that can be used as a molecular platform for the design of molecules with enhanced biological activity.

Insulin and glucose mediate opposite intracellular ionized magnesium variations in human lymphocytes.

Insulin is capable of increasing intracellular magnesium, although very little is known about the effect of insulin on the biologically active fraction of magnesium, i.e. the ionized quota (Mg(i)(2+)), its interactions with glucose, and the cellular mechanisms involved in these processes. We studied the interactions of the effects of insulin and glucose on intracellular ionized magnesium in human lymphocytes. Mg(i)(2+) was measured using a fluorimetric method and the Mg(2+)-sensitive dye, furaptra. We found that insulin significantly increases the Mg(i)(2+)(without insulin 227 +/- 14 microM, with 10 microU/ml, insulin 301 +/- 30 microM, P<0.0001, n = 12) in a dose-dependent manner in all three glucose concentrations tested (5, 7 and 15 mmol/l). The half-maximal effect of insulin was approximately 0.8 microU/ml. Glucose and insulin showed opposite effects in their ability to modify Mg(i)(2+) in lymphocytes. Inhibitors of the membrane Na(+)- Mg(2+) transport system and of phosphatidylinositol (PI) 3-kinase abolish the insulin-mediated increase of Mg(i)(2+), thus suggesting that insulin is capable of increasing Mg(i)(2+) by modulating the activity of this transport system, possibly through the mediation of PI 3-kinase activation. Taking into account the relationship between insulin and glucose plasma levels and their opposing effects on Mg(i)(2+), this mechanism may represent the two limbs of a biphasic regulatory system of Mg(i)(2+) in both physiological and pathological conditions.

Determination of CDT, a marker of chronic alcohol abuse, for driving license issuing: immunoassay versus capillary electrophoresis.

The present work is aimed at a validation of the carbohydrate-deficient transferrin (CDT) determination in real cases by comparison between the a commercial immunometric method and a method based on capillary electrophoresis. Overall, 650 serum samples from subjects applying to re-obtain their driving license, previously withdrawn for "drunk driving", were investigated. A highly significant correlation (P < 0.001) was found between the results from immunoassay and capillary electrophoresis. However, particularly in the samples with CDT values around the cut-off or moderately elevated, a wide dispersion of the correlation data was found. This finding stresses the need to confirm by alternative techniques all the results from CDT immunoassays. For this purpose, capillary electrophoresis, because of its inherent characteristics of high selectivity, easy operation, high productivity and low operative costs looks well-suited for becoming the method of choice.