Effect of chronic magnesium supplementation on magnesium distribution in healthy volunteers evaluated by 31P-NMRS and ion selective electrodes.

AIMS: The role of magnesium (Mg) intake in the prevention and treatment of diseases is greatly debated. Mg biodistribution after chronic Mg supplementation was investigated, using state-of-the-art technology to detect changes in free ionized Mg, both at extra- and intracellular levels. METHODS: Thirty young healthy male volunteers participated in a randomised, placebo (P)-controlled, double-blind trial. The treated group (MgS) took 12 mmol magnesium lactate daily for 1 month. Subjects underwent in vivo 31P-NMR spectroscopy and complete clinical and biological examinations, on the first and last day of the trial. Total Mg was measured in plasma, red blood cells and 24 h urine ([Mg]U ). Plasma ionized Mg was measured by ion-selective electrodes. Intracellular free Mg concentrations of skeletal muscle and brain tissues were determined noninvasively by in vivo 31P-NMR at 3T. NMR data were automatically processed with the dedicated software MAGAN. RESULTS: Only [Mg]U changed significantly after treatment (in mmol/24 h, for P, from 4.2+/-1.4 before to 4.1+/-1.3 after and, for MgS, from 3.9+/-1.1 before to 5. 1+/-1.1 after, t=2.15, P=0.04). The two groups did not differ, either before or after the trial, in any other parameter, whether clinical, biological or in relation with the Mg status. CONCLUSIONS: Chronic oral administration of Mg tablets to young healthy male volunteers at usual pharmaceutical doses does not alter Mg biodistribution. This study shows that an adequate and very complete noninvasive methodology is now available and compatible with the organization of clinical protocols which aim at a thorough evaluation of Mg biodistribution.

Proton NMR observation of glycogen in vivo.

Our previous solution studies of the proton relaxation properties of glycogen H1 have shown significant dipolar cross-relaxation with intra-ring H2 and inter-ring H4' protons characterized by a correlation time tau c = 2.7 x 10(-9) s. This leads to a significant negative Nuclear Overhauser Enhancement (NOE) of glycogen H1 following either transient or steady state perturbations of the longitudinal magnetization of dipolar coupled protons, especially H2 and H4'. Here we use the NOE to edit selectively the H1 resonance of glycogen in the rat liver in vivo using a surface coil probe. The approach shows the possibility of measuring glycogen in vivo with high sensitivity using 1H NMR.

In vivo regulation of rat muscle glycogen resynthesis after intense exercise.

Time courses of the glycogen synthesis rate and of the glucose 6-phosphate (G-6-P) concentration after an electrically induced exercise were followed in the anesthetized rat gastrocnemius by in vivo 13C and 31P nuclear magnetic resonance (NMR) spectroscopy, respectively. The ratio of glycogen synthase I to glycogen synthase I and D (I/I+D) and allosteric activation by G-6-P were also studied in vitro on muscles sampled at rest and 10 min (early recovery) and 100 min (late recovery) after exercise. From early recovery to late recovery, the in vivo glycogen synthesis rate dropped from 0.46 +/- 0.06 to 0.11 +/- 0.04 mmol.kg wet tissue-1.min-1, the G-6-P concentration from 0.83 +/- 0.08 to 0.32 +/- 0.05 mmol/kg wet tissue, and I/I+D from 83 +/- 4 to 47 +/- 1%. The combination of the changes in G-6-P concentration and in I/I+D quantitatively describes the fourfold decrease in glycogen synthesis rate from early to late recovery. These results demonstrate that phosphorylation, determining glycogen synthase I/I+D, and allosteric control of glycogen synthase by G-6-P contribute approximately equally to the regulation of the postexercise in vivo glycogen synthesis rate.

Efficacy of lactobionate-enriched cardioplegic solution in preserving compliance of cold-stored heart transplants.

Cardioplegic solutions of the extracellular type are commonly used as storage media for heart transplants. Because this type of formulation was not originally designed for preventing hypothermically induced edema, we assessed the effects of supplementing a standard, extracellular-like cardioplegic solution with the high molecular weight impermeant lactobionate on water content and postischemic compliance of isolated rat hearts. In one series of experiments, hearts were immersed in either a standard cardioplegic solution of the extracellular type or in the same solution supplemented with lactobionate (80 mmol/L). Hearts were then processed for measurements of water content after 4 hours, 6 hours, and 8 hours of storage at 4 degrees C. In a second series of experiments, hearts were stored in the same solutions for 4 hours and 8 hours and subsequently reperfused for 1 hour on a Langendorff column, at which time left ventricular pressure-volume curves were constructed and compared with those obtained during the preischemic perfusion. Lactobionate-treated hearts gained significantly less water than controls after 4 hours and 6 hours of storage, but the difference was no longer significant at the 8-hour time point. In contrast, the treated group yielded a significantly better recovery of compliance after both 4 hours and 8 hours of storage, suggesting that lactobionate might exert protective effects in addition to those caused by its impermeant properties, possibly involving calcium chelation and subsequent limitation of calcium-dependent contracture. Extracellular-type cardioplegic solutions are attractive because a single solution can be used during all phases of the transplantation procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Proton and phosphorus NMR study of RNA self-complementary hexamers: influence of the 5-methylcytidine on the conformational transitions and the molecular motions.

We present proton and phosphorus NMR data, which contribute to explain why the 5-methylcytidine (m5C) differently affects the conformational transitions of CGUAm5CG (Bloch et al., FEBS Letters 219, 464 (1987)) and CGm5CGCG (Ceolin et al., J. Am. Chem. Soc. 109, 2539 (1987)). The atypical intermediate form observed in the random coil to A-like duplex transition of CGm5CGCG is determined: this original duplex structure exhibits a frame-shift pairing of the two strands, with a partial conservation of the A-type structure. In the case of CGUAm5CG such a pairing process would lead to a complete mismatch pairing. This feature probably explains that the NMR data of CGUACG and CGUAm5CG are similar and consistent with a random coil to A-type helix transition. Nevertheless a significant difference between the correlation times observed for the molecular motions of the two duplexes is detected. Another example of unusual conformational transition of methylated RNA oligomers is given by CAm5CGUG.

Antiandrogen implanted in brain stimulates male reproductive system.

Chronic intrahypothalanic implantation of cyproterone, an antiandrogen, in male rats resulted in specific stimulation of testes, seminal vesicles, and prostates. Implantation of cholesterol-filled or empty tubes in the median eminence in controls was ineffective. We conclude that decreases in the amount of testosterone reaching specific receptors in the median eminence or in nearby regions activate a mechanism that produces increased gonadotropin secretion.