Asthma is a chronic, inflammatory disorder of the airways leading to airflow limitation. Its worldwide rise, mainly in developed countries, is a matter of concern. Nocturnal asthma (NA) frequently occurs and concerns two thirds of asthmatics. But, it remains controversial whether NA is a distinct entity or is a manifestation of more severe asthma. Generally, it is considered as an exacerbation of the underlying pathology. The pathological mechanisms most likely involve endogenous circadian rhythms with pathological consequences on both respiratory inflammation and hyperresponsiveness. A decrease in blood and tissue magnesium levels is frequently reported in asthma and often testifies to a true magnesium depletion. The link with magnesium status and chronobiology are well established. The quality of magnesium status directly influences the Biological Clock (BC) function, represented by the suprachiasmatic nuclei and the pineal gland. Conversely, BC dysrythmias influence the magnesium status. Two types of magnesium deficits must be clearly distinguished: deficiency corresponding to an insufficient intake which can be corrected through mere nutritional Mg supplementation and depletion due to a dysregulation of the magnesium status which cannot be corrected through nutritional supplementation only, but requires the more or less specific correction of the dysregulation mechanisms. Both in clinical and in animal experiments, the dysregulation mechanisms of magnesium depletion associate a reduced magnesium intake with various types of stress including biological clock dysrhythmias. The differenciation between Mg depletion forms with hyperfunction of BC (HBC) and forms with hypofunction of BC (hBC) is seminal and the main biological marker is melatonin (MT) production alteration. We hypothesize that magnesium depletion with HBC or hBC may be involved in chronopathological forms of asthma. Nocturnal asthma would be linked to HBC, represented by an increase in MT levels. The corresponding clinical forms associate diverse expressions of nervous hypoexcitability such as depression, cluster headaches, dyssomnia, mainly advanced sleep phase syndrome, some clinical forms of chronic fatigue syndrome and of fibromyalgia. The main comorbidities are depression and/or asthenia. They take place during the night or the "bad" seasons (autumn and winter) when sunshine is at a minimum. The corresponding chronopathological therapy relies on bright light phototherapy sometimes with additional psychoanaleptics. Conversely, asthma forms linked to hBC are less frequently studied as a whole and present a decrease in MT levels. They associate various signs of nervous hyperexcitability such as anxiety, diurnal cephalalgia (mainly migraine), dyssomnia, mainly delayed sleep phase syndrome, and some clinical forms of chronic fatigue syndrome and of fibromyalgia. The treatment relies on diverse forms of "darkness therapy", possibly with the help of some psycholeptics. Finally, the treatment of asthma involves the maintenance of a standard dosing schedule of anti-asthma drugs, a balanced magnesium intake and the appropriate treatment of the chronopathological disorders.

MgSO4 is routinely used in therapeutics despite its toxicity. The aim of the present review was to compare MgSO4 and MgCl2 effects in order to answer the question whether MgSO4 could be or not replaced by MgCl2. Considering that the two salts have both similar and proper effects, a clear-cut conclusion is not easy to draw. However, choosing MgCl2 seems advisable because of its more interesting clinical and pharmacological effects and its lower tissue toxicity as compared to MgSO4.

The beginnings of magnesium research, from the 18th century to the first quarter of the twentieth century, consists mainly of the development of chemical and pharmacological knowledge. The modern period began in 1926 when the essential character of magnesium was acknowledged.The early part of the modern period, up to the 1960s, saw the foundation of our knowledge of the basic physiological, epidemiological and clinical aspects.The present modern period began in 1971 with the First International Symposium on Magnesium and the subsequent creation of SDRM (the international Society for the Development of Research on Magnesium), an international coordinating structure, which promotes the publication of magnesium books (volumes of proceedings and monographs) and of journals: Magnesium Research the international official organ of SDRM and several national journals: the Journal of Japanese Society for Magnesium Research (Japan), the Buletin informativ al societatii romane de cercetare a magneziului (Romania), the Journal of Elementology (Poland) and which regularly organizes national and international meetings. The next great international meeting will be held on October 23-26, 2006 in Osaka (Japan). We will discuss the latest research findings on magnesium in health and disease. The subject shows that today magnesium research remains active in basic sciences and embraces all the facets of pathology.

Chronic primary Mg deficiency is frequent. About 20% of the population consumes less than two-thirds of the RDA for Mg. Women, particularly, have low intakes. For example, in France, 23% of women and 18% of men have inadequate intakes. Mg deficiency during pregnancy can induce maternal, fetal, and pediatric consequences that might last throughout life. Studies of gestational Mg deficiency in animals show that Mg deficiency may have marked effects on parturition and postuterine involution. It has interfered with fetal growth and development, and caused morbidity from hematological effects and disturbances in temperature regulation, to teratogenic effects. Emphasis, here, is on effects of chronic clinical gestational Mg deficiency as it affects the infant. Premature labor, contributed to by uterine hyperexcitability caused by chronic maternal Mg deficiency, that can be intensified by stress, gives rise to preterm birth. If the only cause of uterine overactivity is Mg deficiency, its supplementation constitutes nontoxic tocolytic treatment, as an adjuvant treatment, that is devoid of toxicity and enhances efficacy and safety of tocolytic drugs such as beta-2 mimetics. Evidence is considered that Mg deficiency or Mg depletion can contribute to the Sudden Infant Death Syndrome (SIDS). SIDS may be a fetal consequence of maternal Mg deficiency through impaired control of Brown Adipose Tissue (BAT) thermoregulation mechanisms leading to a modified temperature set point. SIDS can result from dysthermias: hypo- or hyperthermic forms. Possibly, simple nutritional Mg supplements might be preventive. Various stresses in an infant can transform simple Mg deficiency into Mg depletion. For example, lying prone can be stressful for the baby, as can parental smoking. The role of chronopathological stress appears to be often neglected, as it constitutes a clinical form of primary hypofunction of the biological clock [with its anatomical and clinical stigma such as reduced production of melatonin (MT) and of its urinary metabolite: 6 Sulfatoxy-Melatonin (6 SMT)]. SIDS might be linked to impaired maturation of both the photoneuroendocrine system and BAT. Prophylaxis of this form of SIDS should include atoxic nutritional Mg therapy for pregnant women with total light deprivation at night for the infant. Consequences of maternal primary Mg deficiency have been inadequately studied. To determine ultimate outcomes of gestational Mg deficiency in infants, a long-term multicenter placebo-controlled prospective study should undertaken on effects of maternal nutritional Mg supplementation on lethality/morbidity in fetus, neonates, infants, children and adults, not only during pregnancy and the baby's first year, but throughout life.

Mg depletion is a type of Mg deficit due to a dysregulation of the Mg status. It cannot be corrected through nutritional supplementation only, but requires the most specific correction of the dysregulating mechanism. Among those, Biological Clock (BC) dysrhythmias are to be considered. The aim of this study is to analyze the clinical forms of Mg depletion with hypofunction of the Biological Clock (hBC). hBC may be due to either Primary disorders of BC [Suprachiasmatic Nuclei (SCN) and pineal gland (PG)] or Secondary with homeostatic response [reactive Photophobia (Pphi] to light neurostimulating effects [Nervous Hyper Excitability (NHE)]. The symptomatology is mainly diurnal and observed during fair weather (Spring,Summer). The elective marker of hBC is represented by a decrease in melatonin and in its metabolites in various fluids. The clinical forms of NHE due to Mg depletion with hBC are central and peripheral. The central forms associate anxiety, headaches and dyssomnia. The peripheral manifestations are neuromuscular: photosensitive epilepsia mainly. Three chronopathological forms of Mg depletion with hBC have been highlighted: 1. Headaches with Pphi: mainly migraine; 2. Sudden Infant Death Syndrome (SIDS); 3. Multiple Sclerosis (MS).- Headaches with Pphi, migraine particularly. These cephalalgias are diurnal with Pphi and are aggravated during the fair seasons (particularly during midnight sun-summer). Migraine is their typical form with its dishabituation to visual stimuli and its occipital cortex hyperexcitability. Comorbidity with anxiety is frequent. In 2/3 of the cases, it appears first.- SIDS might be linked to an impaired maturation of both photoendocrine system and brown adipose tissue. MS may be associated with primary disorders of BC Clinical forms of Mg depletion with hBC in MS present diurnal exacerbations and relapses during fair seasons. They have been underestimated because they disagree with the dogma of the << latitude gradient >>, presently questioned. Comorbidities with anxiety and migraine are frequent.hBC may be treated by using darkness therapy with a balanced Mg status. Absolute light deprivation should only be used only in acute indications and is time-limited. Partial substitutive therapy and chromatotherapy have not been validated yet and are still uncertain.

Regulation of vascular tone in the fetal extracorporeal circulation most likely depends on circulating hormones, local paracrine mechanisms and changes in membrane potential of vascular smooth muscle cells (VSMCs) and of vascular endothelial cells (VECs). The membrane potential is a function of the physiological activities of ionic channels (particularly, K+ and Ca2+ channels in these cells). These channels regulate the ionic distribution into these cells. Micro-particle induced X-ray emission (PIXE) analysis was applied to determine the ionic composition of VSMC and of VEC in the placental human allantochorial vessels in a physiological survival medium (Hanks’ solution) modified by the addition of acetylcholine (ACh: which opens the calcium-sensitive K+ channels, KCa) and of high concentration of K+ (which blocks the voltage-sensitive K+ channels, Kdf). In VSMC (media layer), the addition of ACh induced no modification of the Na, K, Cl, P, S, Mg and Ca concentrations and high K+ medium increased significantly the Cl and K concentrations, the other ion concentrations remaining constant. In endothelium (VEC), ACh addition implicated a significant increase of Na and K concentration, and high K+ medium, a significant increase in Cl and K concentration. These results indicated the importance of Kdf, KCa and KATP channels in the regulation of K+ intracellular distribution in VSMC and VEC and the possible intervention of a Na–K–2Cl cotransport and corroborated the previous electrophysiological data.

The membrane potential, a regulator of vascular tone, is a function of the physiological activities of ionic channels (particularly, K+ and Ca2+ channels in these cells). These channels regulate the ionic distribution into these cells. Micro-particule induced X-ray emission (PIXE) analysis was applied to determine the ionic composition of vascular smooth muscle cells (VSMCs) and of vascular endothelial cells (VECs) in the placental human allantochorial vessels in a physiological medium (Hanks' solution) modified by the addition of a chemical stimulus: 5-hydroxytryptamine (5-HT), an activator of the voltage-sensitive Ca2+ channels. In VSMCs (media layer), the addition of 5-HT induced no modification of the Na, K, Cl, P, S and Ca. concentrations but increased Mg concentration. In endothelium (VECs) 5-HT addition implicated an increase of the K, S, Ca concentrations, the concentration of the other ions remained constant. In VECs, Ca and K increase is due to open of L-type voltage-dependent Ca2+ channels and of K-Ca channels. 5-HT induces also a secretion of endothelium hyperpolarizing factors which implicate decrease of [Ca2+](i) in VSMCs opposite to a direct increase by 5-HT. Increase in [Mg2+](i) may be due to activation of the Ca/Mg exchanger.

The elemental ionic distribution in the epithelial layer (EL) and in connective tissue (CT = compact layer + fibroblast layer) of the human amniotic membrane has been studied in reference samples, after conservation in a physiological fluid (Hanks' solution) and after addition of 2 mM MgCl2 in Hanks' solution. Particle induced X-ray emission and Rutherford backscattering spectrometry techniques were used to provide quantitative measurements. In physiological fluid, with regard to reference samples, the monovalent ions (Na+, K +, Cl-) concentrations were identical on both layers. This data indicates that the connective tissue, in particular the compact layer, acts as a buffer which fix minerals. Mg2+ and Ca2+ levels were higher in EL than in CT. The addition of MgCl2 in Hanks' solution induced a decrease of the monovalent ion concentrations in both layers except Na+ level in EL which remained constant, an increase of the Mg2+ level in both layers, while the Ca2+ remained constant. These data indicate the possible role of connective tissue in pregnancies complicated by poly or oligohydramnios.

Physiological beta stimulation may be involved in the regulation of magnesium status namely by homeostatic increase of magnesemia during magnesium deficiency. But conversely excessive beta stimulation namely by use of pharmacological high doses of beta mimetics may induce a decrease of magnesemia. Two different types of magnesium therapy ought to be distinguished. Nutritional magnesium therapy which may physiologically palliate a magnesium deficiency due to an insufficient magnesium intake. It is devoid of any toxicity. Pharmacological magnesium therapy, whatever the magnesium status, causes a iatrogenic magnesium load. It may induce magnesium toxicity. Tocolysis is the one common obstetrical indication for beta mimetics and magnesium. Beta-2 mimetics are the reference tocolytic drugs in most countries. But high doses of beta-2 mimetics for suppression of premature labor are associated to a high incidence of maternal, fetal and neonatal side effects. Tocolysis must then be discontinued or limited to shorter treatments with the lowest possible doses. Nutritional magnesium therapy which palliates gestational magnesium deficiency is efficient and atoxic. Conversely, high doses of intravenous MgSO4 for tocolysis are less efficient and unsafe. Because of its maternal and above all pediatric side effects, this maternal pharmacological magnesium therapy should be abandoned for tocolysis. Investigation of the therapeutic ratio of various magnesium salts before their clinical use could help to determine if other anions different from sulfate could decrease the toxicity. Beta-2 agonists are first line asthma therapy, but their safety is debated. Asthma and Chronic Obstructive Pulmonary Disease (COPD) per se may induce magnesium depletion related to a dysregulation of the control mechanisms of magnesium status. It requires a correction of its causal regulation, but nutritional magnesium supplementation is ineffective. When chronic primary magnesium deficiency coexists with obstructive bronchial disorders, it constitutes a decompensatory factor. Atoxic nutritional magnesium therapy may palliate this coexistent magnesium deficiency. Pharmacological magnesium treatment for obstructive pulmonary diseases is not very efficient with low safety. Combination of palliating nutritional magnesium therapy and of beta-2 mimetics for tocolysis or pulmonary obstructive indications may be beneficial and remain atoxic. Conversely combination of intravenous tocolytic high doses of magnesium and of beta-2 mimetics is contra-indicated because of its dubious efficiency and its possible toxicity. The possible role of SO4- as regards toxicity must be discussed. Contra-indications of lower intravenous or inhaled Mg doses for pulmonary bronchial obstruction are less imperative than for tocolysis. The selection of a particular magnesium salt among others should take into account reliable plasmacological and toxicological data. It seems necessary to determine the therapeutic ratio (LD50/ED50) of the various available magnesium salts before pharmacological use.

Extracellular magnesium salts are known to interfere with ionic channels in the cellular membranes. The membrane potential, a regulator of vascular tone, is a function of the physiological activities of ionic channels (particularly, K+ and Ca2+ channels in these cells). These channels regulate the ionic distribution into these cells. Micro-Particule Induced X-ray Emission (PIXE) analysis was applied to determine the ionic composition of vascular smooth muscle cells (VSMC) and of vascular endothelial cells (VEC) in the placental human allantochorial vessels in a physiological medium (Hanks' solution) modified by the addition of 2 mM MgCl2 or 2 mM MgSO4 which block the calcium-sensitive K+ channels (K(Ca)), the ATP-sensitive K+ channels (K(ATP)) and the voltage-sensitive K+ (K(df)) and Ca2+ channels. In VSMC (media layer), the addition of MgCl2 induced no modification of the K, Cl, P, S and Ca concentrations but increased the Na and Mg concentrations and the addition of MgSO4 only significantly increased the Mg concentration, the other ion concentrations remaining constant. In endothelium (VEC), MgCl2 or MgSO4 addition implicated the same observations as in VSMC. These results confirmed the blockage of K(df), K(Ca), K(ATP) and Ca channels in VSMC and VEC by magnesium salts, the relationship between Mg2+ ions and internal Na and demonstrated the possible intervention of a Na+/Mg2+ exchanger.

The main mechanisms of the chronopathological forms of magnesium depletion associate a low Mg intake with various dysregulating biorhythms. The differentiation between forms with hyperfunction and forms with hypofunction of the biological clock is seminal and the main marker is the production of melatonin (MT). The clinical forms of the various patterns of the chronopathological forms of Mg depletion may be central or peripheral. The clinical forms with hyperfunction of the biological clock (marker: increase in MT) may associate diverse expressions of nervous hypoexcitability: depression (i.e. Seasonal affective disease); cephalalgias nocturnal, without photophobia (i.e. cluster headaches); dyssomnia LASPS (advanced sleep phase syndrome) particularly]; asthenia and myalgias (i.e. fibromyalgia, chronic fatigue syndrome). The main comorbidity is found with depressive states. The therapy relies on classical bright light phototherapy, sometimes associated with psychoanaleptics. The clinical forms with hypofunction of biological clock (marker: decrease in MT) may associate various signs of nervous hyperexcitability (HEN): anxiety (from generalized anxiety to panic attacks); cephalalgias diurnal with photophobia (mainly migraine); dyssomnia [DSPS (delayed sleep phase syndrome) particularly, jet lag, night work disorders, age related insomnia, sometimes with inappropriate behaviour; photogenic epilepsia, generalized or focal; some clinical forms of chronic fatigue syndrome and fibromyalgia. The main comorbidity is between migraine and epilepsia. The treatment relies on the diverse forms of darkness therapy, possibly with the help of some psycholeptics: anxiolytics and anticonvulsants. The indications of chromatotherapy remain to be validated.

Protection from heavy metals is a problem that has not been solved in a satisfactory manner so far. Usage of complexing agents in therapy of exposed workers results in both favorable outcome and recognized adverse effects. In the field of environmental protection, they cannot be used in practice, meaning that the risk of escape of metal pollutant from factory premises and their attack on the environnement remains present. The age of chemistry ('Chemistry, key to better living') has led to potent development of industry producing, at the same time, major problems induced by diffusion of metal pollutants, the nightmare of our times, like Camus' 'Plague'. According to the available results, it remains to be answered whether magnesium may influence this important problem, i.e. is this approaches the issue justifiable?

Sudden Infant Death Syndrome (SIDS) might be due to the fetal consequences of a Mg maternal deficiency, which might be prevented by simple atoxic nutritional Mg intake by the mother. Various stresses in the pregnant women or in the infant may transform a simple Mg deficiency into Mg depletion which may not be cured by nutritional Mg supplement, but requires a correction of its causal dysregulation. Beside the well established risk factors in baby care and in the environment, it is important to stress the possible role of a primary hypofunction of the biological clock. This may be treated by darkness therapy: total light deprivation at night for the infant and atoxic nutritional Mg supplement for the pregnant women. The place in the prevention of SIDS of Mg therapy for the infant and of the use of melatonin, L-tryptophan and taurine is now uncertain yet.

Biological clock and magnesium status are linked. Central magnesium regulation may be hypothetized. Balanced magnesium status is requested to obtain efficiency of suprachiasmatic nuclei and of pineal gland. Conventional bright light therapy appears as a speedy and efficient antidepressant medication useful for the treatment of various types of depression, and of non migrainous headaches also. Although decrease in melatonin production seems accessory, increases of serotonergy and perhaps of Reactive Oxygen Species constitute the main mechanisms of action. Chromatotherapy emphazizes the effects of short exposure to specific colors. Although the increased production of melatonin constitutes the best marker of darkness, it is only an accessory mechanism of its action. The psycholeptic sedative effects of darkness, like those of magnesium, rely on direct membraneous and oxidant actions, neural mediated effects (i.e. stimulation of inhibitory neuromodulators such as GABA and taurine), and on antagonism of neuroactive gases (CO and NO). Darkness therapyper se, partial substitutive therapy with melatonin and with their mimicking agents (Mg, L-Tryptophan,Taurine) apply to all the chronopathological forms of magnesium depletion with decreased production of melatonin: sleep disorders, migraine, chronic fatigue syndrome, fibromyalgia, some forms of asthma and of sudden infant death syndrome. Further research should assess the importance of the chronopathological forms of magnesium depletion in the physiopathology of these disorders.

There is an inverse relationship between Mg balance and the ratio ionized Mg/total Mg in serum or plasma: in Mg excess, the ratio is decreased and in Mg deficiency the ratio is increased. It works as if a subtle homeostasic compensatory reaction modified the proportion of the most biologically active fraction of blood Mg in order to reduce the effects of Mg imbalance. Easy, available and unexpensive, the evaluation of total Mg in plasma or serum appears as a better marker than ionized Mg in Mg imbalance: it should be priviledged as the initial investigation in clinical practice.

In human allantochorial placental vessels, the vascular tone is regulated by membrane potential controlled by the ion flux through K+ and Ca2+ channels. The effects of MgCl2 and MgSO4 were studied on the membrane potential of vascular smooth muscle cells [VSMCs) and of endothelial cells (VECs). The membrane potential was the main factor of the excitation-contraction coupling of placental vessels. The VSMCs and VECs were predepolarized by high external K+, which blocked voltage-sensitive K+ channels, and depolarized by serotonin addition which activated Ca2+ influx through voltage-gated Ca2+ channels. Addition of MgCl2 or MgSO4 in the external medium induced a depolarization level lower than the previous level, as nifedipine a Ca2+ blocker, corresponding to a Ca2+ influx reduction in VSMCs and VECs and inducing relaxation of the cells. The effect of MgCl2 and MgSO4 was the same on VSMCs and VECs, but the depolarization level reduction was more important with MgCl2 than MgSO4 on VSMCs. These data suggest ed that Mg salts regulated the Ca2+ influx through voltage-gated Ca2+ channels in VSMCs and VECs and consequently the tonus of human allantochorial placental vessels and that there was a difference between Mg salts.

The effects of the association of vitamin B6 and Mg salts: aspartate, citrate, lactate, pidolate, sulfate, were studied on the ionic transfer through a membraneous pharmacological model: the isolated human amniotic membrane. The ionic transfer was evaluated by measure of the total conductance in the maternal to fetal way (GtM) and in the fetal to maternal way (GtF), of the ionic fluxes (F1 on the maternal side, F2 on the fetal side) and of the ratio F1/F2. The results were explained in terms of monophasic (decrease: screening or increase: binding interactions with the polar surface moities) or biphasic (decrease then increase) action. The results indicated: Mg aspartate decreased GtF, F1, F2 whatever concentration and had a concentration-dependent effect on GtM, F1/F2. The addition of vitamin B6 induced a new concentration-dependent effect (biphasic action: decrease then increase) on GtF, F1 and also modified F2, F1/F2. Mg citrate decreased GtM, GtF, F2 whatever the concentration and had a concentration-dependent effect on F1, F1/F2. The addition of vitamin B6 induced a new biphasic effect on GtM and GtF. Mg lactate decreased GtM, F1, F2, F1/F2 whatever the concentration but had a concentration-dependent effect on GtF. The addition of vitamin B6 induced a new biphasic effect on GtM, F1, F2, F1/F2. Mg pidolate had no effect on GtM, GtF, F2, F1/F2 and decreased F1. The addition of vitamin B6 did not induce variation. Mg sulfate had no effect on GtM, increased GtF and decreased F1, F2, F1/F2. The addition of vitamin B6 induced a new concentration-dependent effect on F2. The association between vitamin B6 and Mg salts implicated a new action on components of the amniotic ionic transfer characterized by a biphasic action (decrease then increase concentration-dependent effect). This effect was dependent on the anion associated with magnesium. The magnesium salts may be classified with regard to the beneficial effect due to the association with vitamin B6 in the following decreasing order: aspartate and lactate, citrate, pidolate, sulfate.

Symptomatic forms of central nervous hyperexcitability (NHE) due to magnesium deficiency results from the sum of direct cellular effects and of local and systemic mediated effects inducing depolarization and NHE. Direct effects associate decreased energy and cationic gradient with disturbances in Ca distribution, decreased second messenger nucleotidic ratio and increased susceptibility to peroxidation. Local mediated effects associate increased activity of excitatory neuromediators: acetylcholine, catecholamines and ionotropic - (NMDA and non-NMDA) - receptors of excitatory aminoacids (EAA), with decreased activity of inhibitory neuromediators: GABA, taurine, glutaurine, adenosine and K receptors of opioids. Systemic mediated effects associate increased production of inflammatory mediators: neuropeptides, prostanoids, cytokines Th 1, aldehydes with decreased activity of oxidant and antialdehyde defences. Compensatory factors instrumental in the latency of NHE due to magnesium deficiency may also be direct or mediated. Increased intracellular pH, modifications of Ca and Mg binding proteins, increase in 'magnesium-like' polyamines, stimulation of cellular antioxidant system; decreased activity of EAA metabotropic receptors and of opioid mu (and delta) receptors, increased activity of inhibitory neuromediators, increased production of anti-inflammatory mediator such as cytokines Th 2, stimulation of systemic antioxidant and antialdehyde defences. A lot of diverse compounds are able to palliate symptomatic NHE due to magnesium deficiency either by pharmacodynamic effects or through physiopathological intervention. The efficiency of these treatments can be evaluated on multiple disparate parameters. The pattern of NHE due to magnesium deficiency differs according to species, strains, gender, age and intensity of magnesium deficiency. For example: hot plate test showed a hypoalgesia 'morphine-like' pattern induced by magnesium deficiency cured by magnesium acetyltaurinate in mice whilst paw pressure test showed a hyperalgic pattern caused by magnesium deficiency cured by dizolcipine in rats. Now it seems difficult to rank hierarchically the various physiopathological mechanisms of NHE due to magnesium deficiency. But the proposed general scheme of the factors controlling this NHE provides a possible explanation of both diffuse symptomatic and latent forms and stresses the complexity of the physiopathological mechanisms of central NHE due to magnesium deficiency.

Micro-Particle Induced X-ray Emission (PIXE) analysis was applied to determine the ionic composition of different layers of human placental vessels. The laminae of arterial walls were clearly identified by means of their elemental maps. In the same manner, the endothelial cells bordering the lumen were identified, cell by cell, and analyzed separately. Using this model, we investigated the influence of incubations in various physiological fluids on the ionic composition of the walls and of endothelial cells.