Magnesium chloride or magnesium sulfate: a genuine question.

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.

Magnesium depletion with hypo- or hyper- function of the biological clock may be involved in chronopathological forms of asthma.

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.

Elemental maps in human allantochorial placental vessels cells. 4. Isoproterenol and sodium nitroprusside effects.

The ionic channels (particularly, K+ and Ca2+ channels) regulate, via the membrane potential, the ionic distribution into the vascular 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 NO donor (sodium nitroprusside, SNP) and of a beta-adrenergic stimulator (isoproterenol, ISO). The addition of SNP or ISO induced no modification of the Na, K, Cl, P, S, Mg and Ca concentrations in VSMCs. In VECs, a same effect was observed except an increase of the Mg concentration with ISO. Theses results indicated a retroactive control (active feedback) of the internal ionic distribution by endothelial factors, ionic channels and exchangers.

Importance of magnesium depletion with hypofunction of the biological clock in the pathophysiology of headhaches with photophobia, sudden infant death and some clinical forms of multiple sclerosis.

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.

Elemental maps in human allantochorial placental vessels cells. 3. 5-hydroxytryptamine effects.

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.

Importance of the ratio between ionized and total Mg in serum or plasma: new data on the regulation of Mg status and practical importance of total Mg concentration in the investigation of Mg imbalance.

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.

Chronopathological forms of magnesium depletion with hypofunction or with hyperfunction of the biological clock.

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.

Magnesium regulation of Ca2+ channels in smooth muscle and endothelial cells of human allantochorial placental vessels.

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 suggested 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.

Association effects of vitamin B6 and various magnesium salts on a pharmacological model: the human amniotic membrane.

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.

Physiopathology of symptomatic and latent forms of central nervous hyperexcitability due to magnesium deficiency: a current general scheme.

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.

Magnesium pidolate and magnesium aspartate effects on human amniotic membrane ionic permeability in vitro.

The effects of Mg pidolate and Mg aspartate were studied on the ionic transfer through a membraneous model: the human isolated amniotic membrane. The ionic transfer was evaluated by the measure of the total conductance in the maternal to fetal way (GtM) and in the fetal to maternal way (GtF) and of the ionic fluxes (F1 on the maternal side (MS), F2 on the fetal side (FS)) and of the ratio F1/F2. Whatever the Mg pidolate concentration, GtM and GtF remained constant. Mg aspartate had a concentration-dependent effect on GtM (decrease-increase) and a monophasic effect on GtF (decrease). F1 and F2 were decreased by the two Mg salts, and the ratio F1/F2 remained constant after addition of Mg pidolate and was increased by Mg aspartate. The results were explained in terms of screening and/or binding interactions with the polar surface moieties and were compared with results obtained in previous studies with other Mg salts. The results indicated the importance of the anion associated with Mg element in the ionic transfer.

Calcium channels, potassium channels and membrane potential of smooth muscle cells of human allantochorial placental vessels.

The membrane potential (Um), the main factor of the excitation-contraction coupling, of human allantochorial placental vascular smooth muscle cells (VSMCs) has been previously shown to depend on voltage-sensitive K+ channels. These channels were blocked by high external K+. To characterize other channels which regulated Um, various constrictor or/and vasodilators and channel blockers were used. Serotonin depolarized VSMCs, in normal medium, but induced a more marked depolarization in VSMCs predepolarized by high external K+. This depolarization was inhibited by nifedipine, a blocker of voltage-gated Ca2+ channels. Acetylcholine, sodium nitroprusside (without effect on Um in normal medium), hyperpolarized the predepolarized-high K+ medium VSMCs. This hyperpolarization was inhibited after addition of charybotoxin (a blocker of Ca2+-activated K+ channels) or/and glibenclamide (a blocker of ATP-sensitive K+ channels). A similar effect was obtained with isoproterenol. These results indicated that membrane potential of human placental allantochorial VSMCs was regulated by voltage-gated, Ca2+- and ATP-sensitive K+ channels and by voltage-dependent Ca2+ channels.

Cardiovasoprotective foods and nutrients: possible importance of magnesium intake.

Various highly efficient cardiovasoprotective diets associate reduced intake of total and saturated fats, reasonable supply of monounsaturated fat and omega-3 fatty acids, moderate consumption of alcohol, increased intake of cereals, fruits, vegetables, fish and low fat dairy products. Among several protective nutrients magnesium should be given particular consideration because of the very frequent occurrence of chronic primary magnesium deficiency which appears to act as a cardiovascular risk factor and also reversely, because of the noticeable high level of the magnesium content in cardiovasoprotective diets.

Magnesium status and ageing: an update.

Ageing constitutes a risk factor for magnesium deficit. Primary magnesium deficit originates from two etiological mechanisms: deficiency and depletion. Primary magnesium deficiency is due to insufficient magnesium intake. Dietary amounts of magnesium are marginal in the whole population whatever the age. Nutritional deficiencies are more pronounced in institutionalized than in free-living ageing groups. Primary magnesium depletion is due to dysregulation of factors controlling magnesium status: intestinal magnesium hypoabsorption, reduced magnesium bone uptake and mobilisation, sometimes urinary leakage, hyperadrenoglucocorticism by decreased adaptability to stress, insulin-resistance and adrenergic hyporeceptivity. Secondary magnesium deficit in ageing largely results from various pathologies and treatments common to elderly persons: i.e. non insulin dependent diabetes mellitus and use of hypermagnesuric diuretics. Magnesium deficit may participate in the clinical pattern of ageing: mainly neuromuscular, cardiovascular and renal symptomatologies. The consequences of hyperadrenoglucocorticism--whose non response to dexamethasone suppression test appears the simplest marker--may concern immunosuppression, muscle atrophy, centralization of fat mass, osteoporosis, hyperglycemia, hyperlipidemia, atherosclerosis, disturbances in mood and mental performances through accelerated hippocampal ageing particularly. Treatment of magnesium deficiency requires simple oral physiological magnesium supplementation. Treatment of the different types of magnesium depletion leads to a more or less specific control of pathophysiological disturbances of the required magnesium substrate. Open and double blind studies on the effects of the treatments of magnesium deficiency and of magnesium depletions in geriatic populations are too scarce. Further study is necessary to assess the accurate place of magnesium deficit in the physiopathology of ageing.

Comparative experimental study of Mg lactate, vitamin B6 and their association on the permeability of a human membrane. 2. Effects on cellular and paracellular ionic transfer through isolated amniotic membrane.

The comparative effects of Mg lactate, pyridoxine chlorhydrate and their association were observed on the various components of the human transamniotic conductance Gt. The use of both microelectrodes and metabolic inhibitors indicates 12 components of Gt: 8 cellular components Gc (Na-K, ATPase, Na-H and Cl-HCO3 antiports, Na-K-2Cl cotransport, Na-Mg exchanger and Na, K, Cl channels), one coupling component and three paracellular components Gp (Na, K, Cl). Mg lactate had a monophasic action on some components (decrease or increase conductance), according to its concentration, on maternal side (MS): GpNa, GpK, GpCl, K channels, conductance due to Na-K, ATPase. On fetal side (FS), there is a monophasic action on GpK, Na channels and a biphasic action (decrease then increase conductance) on GpNa and Na/Mg (as on MS). Pyridoxine chlorhydrate had a monophasic action on GpNa (MS, FS), GpK (MS), Na/Mg (MS, FS) and a biphasic action on GpK (FS), Na channels (MS, FS). The association of both Mg lactate and pyridoxine chlorhydrate implicated a biphasic action on all cationic components on both sides (GpNa, GpK, Na and K channels, Na/H, Na-K-2Cl, Na/Mg. The anionic components were not modified with regard to agents. The Mg lactate + vitamin B6 association interferes specifically with the cationic conductance components with regard to individual components.

Neurotic, neuromuscular and autonomic nervous form of magnesium imbalance.

The nervous form of magnesium imbalance represents the best documented experimental and clinical aspects of magnesium disorders. The nervous form of primary magnesium deficit (MD) in the adult appears as the best descriptive model for analysis of the symptomatology, aetiology, physiopathology, diagnosis and therapy of the most frequent form of MD. Nervous hyperexcitability due to chronic MD in the adult results in a non-specific clinical pattern with associated central and peripheral neuromuscular symptoms, analogous to the symptomatology previously described in medical literature as latent tetany, hyperventilation syndrome, spasmophilia, chronic fatigue syndrome, neurocirculatory asthenia and idiopathic Barlow's disease. On encountering this non-specific pattern, the signs of neuromuscular hyperexcitability are of much greater importance. Trousseau's sign is less sensitive than Chvostek's sign, but their sensitivities are increased by hyperventilation (Von Bondsdorff's test). Examination of the precordial area will be conducted in order to search clinical stigmata of mitral valve prolapse (MVP) which is a frequent dyskinesia due to chronic MD (about a quarter to one-third of cases). The electromyogram (EMG) shows one (or several) trains of autorhythmic activities beating for more than 2 min of one of the three tetanic activities (uniplets, multiplets or 'complex tonicoclonic tracings') during one of the three facilitation procedures: tourniquet-induced ischaemia lasting 10 min. post-ischaemia lasting 10 min after the removal of the tourniquet and hyperventilation over 5 min. A repetitive EMG constitutes the principal mark of nervous hyperexcitability (NHE) due to MD. The echocardiogram (ECC) is the best tool for detecting MVP, the 2-dimensional ECC with pulsed Doppler being more accurate than time-motion ECC. The routine ionic investigations comprise five static tests: plasma and erythrocyte magnesium, plasma calcium and daily magnesiuria and calciuria. An evaluation of magnesium intake is desirable. Normal concentrations of magnesium in blood do not rule out the diagnosis of the nervous form of primary chronic MD. The histograms of MD group reveal Gaussian type magnesaemias with significantly lower means and the constituent elements can be individually hypo- (one-third of cases), normo- (about two-thirds of cases) and even, exceptionally, hyper-magnesaemic. The diagnosis of MD requires an oral magnesium load test. At physiological dose (5 mg of Mg/kg/day), oral magnesium is totally devoid of the pharmacological effects of parenteral magnesium. Corrections of symptomatology by this oral physiological magnesium load is the best proof that it was due to magnesium deficiency. In particular clinical forms, more sophisticated studies may be useful: standard and quantitative electroencephalograms, electropolygraphic studies of afternoon sleep, electronystagmography, optokinetic test, skin conductance reflex, psychometric inventories, standard or monitoring electrocardiogram, treadmill test, other static and dynamic investigations: e.g. ionized free Mg2+, lymphocyte Mg, brain Mg, cerebrospinal Mg, Mg balance, Mg parenteral load test, glucose load, and even radio-isotope study, the only one able to reveal intestinal magnesium hypersecretion. Nervous primary chronic MD progresses by phases of decompensation against a background of latency. Marginal magnesium deficiency, that is to say an insufficient magnesium intake which merely requires simple oral physiological supplementation, is fundamental in the aetiology of primary magnesium deficit. However a constitutional homeostatic lability of the nervous system or of magnesium metabolism such as belonging to the B35 type of HLA group must be involved. Part of the aetiology of this magnesium deficit is a magnesium depletion, where the disorder which induces magnesium deficit is related to a dysregulation of the control mechanisms of magnesium status which requires a more or less difficult

Implication of external Mg2+ ions in the depolarization of smooth muscle cell membrane of the human chorionic placental vessels: an hypothesis.

The membrane potential (MP) of the smooth muscle cells of human allantochorial placental vessels is the major factor which explains the excitation-contraction coupling. Indeed, the smooth muscle cells of these vessels may be considered as tonic because they only respond to excitatory stimuli with graded depolarization. On the contrary, the phasic smooth muscles generate action potentials and some generate electrical slow waves as well. The depolarization of smooth muscle cell membranes may be a consequence of various factors, particularly the secretion of endothelium-derived depolarizing factors (EDDF). The modifications of the ionic composition of external medium interfere with the membrane potential values. The increase of [Mg2+]o (Cl- or SO4[2-]) depolarizes the membrane. This effect in vitro seems inconsistent with the known vasodilator action of external Mg2+. To explain this result, an hypothetical scheme is proposed on the probable targets of local and systemic Mg2+ effects: a direct action of external Mg2+ ions on the membrane potential by secretion of depolarizing endothelial factors which depolarize the membrane; an indirect action on the membrane potential by regulation of K+ and Ca2+ channels; an action on the concentration of internal Mg2+; an interaction with internal Ca2+ concentration and regulation of the Na+/Ca2+ exchanger. A data review of Mg2+ ions effects on smooth muscles is realized to corroborate this scheme.

Comparative experimental study of Mg lactate, vitamin B6 and their association on the permeability of a human membrane. 1. Effect on the total ionic transfer through isolated amniotic membrane.

The effects of Mg lactate, vitamin B6 and their association were studied on the ionic transfer through a membranous model: the human isolated amniotic membrane. The ionic transfer was evaluated by measuring of the total conductance in the maternal to fetal way (GtM) and in the fetal to maternal way (GtF) and of the ionic fluxes (F1 on the maternal side, F2 on the fetal side) and of the ratio F1/F2. Whatever the concentration, Mg lactate decreased GtM, F1, F2, F1/F2 but had a concentration-dependent effect on GtF. Vitamin B6 had no significant effect on GtF, F1, F2, F1/F2, but decreased GtM whatever its concentration. The association Mg lactate + vitamin B6 presented a biphasic action on GtM, GtF, F1, F2 and F1/F2: decrease at low ratio and increase from ratio equal to 8. This association induced interesting effect in the case of therapeutic use in comparison with the effects of separated compounds.

Are age-related neurodegenerative diseases linked with various types of magnesium depletion?

Age-related human neurodegenerative diseases are a major social and medical problem. It is therefore logical to take into consideration every theory with an overall approach to neurodegenerative diseases. This environmental proposal relies mainly on data concerning the Western Pacific amyotrophic lateral sclerosis-Parkinsonism-dementia complex (WP ALS-PD) considered as 'a prototypal human neurodegenerative disease' and on extrapolation from it to the bulk of neurodegenerative diseases (NDD). NDD would be due to an accelerated ageing process in certain populations of neurons due to the noxious synergy of (1) increased environmental slow deleterious factors (such as slow toxins) and of (2) decreased environmental protective factors (Mg deficient intake particularly). First, it was observed that three apparently dissimilar conditions occurred at extraordinary high rates in the Guam area: motoneuron disease (ALS), Parkinson's disease (P) and Alzheimer's-like dementia (D). Next, several other foci of endemic ALS-PD were found in Asia and Oceania in three Western Pacific population groups. These included the Chamorro people in Mariana Islands (Guam and Rota), the Auyu and Jakai people of West New Guinea and the Japanese residents of the Kii peninsula (Honshu island). The post-Second World War decline of the occurrence of WP ALS-PD in all three high incidence disease foci coupled with the absence of demonstrable heritable or transmissible factors had led to focus the search for the cause of this degenerative disease on nontransmissible environmental factors that are disappearing as the susceptible population groups acculturate to modern way. Epidemiologic study has shown that preference for traditional Chamorro food is the only one of 23 tested variables significantly associated with an increased risk for PD. An early suggestion incriminated the toxic seed of the false sago palm (Cycas circinalis L) which was used in traditional food and medicine. Laboratory investigation of cycad seed revealed the presence of various toxins and particularly of an 'unusual' non protein aminoacid: L-BMAA (beta-N-methylamino-L-alanine), an excitotoxic aminoacid. This slow toxin presents some structural similarity to another 'unusual' excitotoxic aminoacid: L-BOAA (beta-N-oxalyl-amino-L-alanine), an exogenous neurotoxin present in the grass pea (Lathyrus sativus) whose excessive consumption may cause lathyrism. The excitotoxicity of both L-BMAA and L-BOAA mainly concerns non-NMDA receptors. The neurotoxicity of these aminoacids varies with experimental models failing to induce an experimental model akin to WP ALS-PD or displaying many of the motor-system and behavioral changes of WP ALS-PD. It may be due to the presence of physiological levels of bicarbonate or of various toxic cofactors: bio-organic such as cycasin or inorganic such as pollutant metals e.g. aluminum or manganese, together with the lack of protective factors (e.g. calcium and magnesium deficiencies). Combined Al intoxication with Ca-Mg deficiencies is a reasonable model to investigate the pathogenesis of neurodegenerative diseases and eventually to screen their treatments. It may also be considered as a model of magnesium deficit, but it does not concern simple magnesium deficiency reversible with mere oral physiological magnesium supplementation. Magnesium deficiency cannot result in neurodegenerative disease. Combined Al intoxication with Ca-Mg deficiencies is not reversible through physiological oral magnesium supplementation. It therefore constitutes a type of experimental magnesium depletion model, instrumental in the investigation of the pathogenesis of magnesium depletion and in the screening of its still unknown possible treatments. (ABSTRACT TRUNCATED)