PubMed Health⌕ Search

Biomedical subjects

J Durlach

Publications and source records attributed to J Durlach.

At least 73 records · Page 4Linked to original sources

A new method of in vitro prescreening evaluation of several Mg salts.

The human amniotic membrane may be considered a model for the prescreening evaluation of the membrane effects of several Mg salts because it is an asymmetrical membrane (polarity of the 2 sides: the ratio between the total ionic conductance Gt both ways and the ratio between the ionic flux from the mother to the fetus (F1) and the ionic flux from the fetus to the mother (F2) are different from 1), samples of which can be obtained without ethical problems, and which is easily usable. Whatever the tested salt, the ratio F1/F2 must be constant or increased without alterations of the ionic fluxes (+/-20%), because a toxic metal (As) has no effect on F1/F2, but strongly decreases the ionic fluxes. To apply this model to the study of the effects of Mg salts, two conditions should be considered: 1) Mg oral therapy: Mg deficit increases the membrane fluidity and the increase of Mg concentration rigidifies the membrane, i.e. decreases Gt; the plasma level of Mg being equal to 1 mM, Mg salts would be tested at 1 mM and Gt should be decreased; and 2) Mg parenteral therapy: the Mg effects should be opposite to those of pollutants and alcohol, which reduce Gt; a dose of 3 mM is chosen and Gt should be increased. The general scheme to study Mg salts is the following: observation of the variation of F1/F2 at 1 mM and of the evolution of Gt, and identical observations at 3 mM. This in vitro prescreening method, indirectly applicable to in vivo effects, gives a classification of Mg salts which may be completed by a study of the 10 components of Gt in the case of identical results for Mg salts.

Amnion↗

A new method of in vitro prescreening evaluation of the relationship between toxic and common metal ions.

The human amniotic membrane, an asymmetrical and nonexcitable epithelium with sites differently situated on the fetal and maternal sides, may be considered a model for investigating the relationship between toxic and common metal ions. The method is based on the observation of the ionic transfer across the amnion, estimated by measuring the total ionic conductance Gt from the mother to the fetus and from the fetus to the mother. It is important to note that opposite effects between two ions are not necessarily correlated with antagonism; indeed, pollutants decrease ionic conductance Gt and Mg increases it, but Mg is not an antagonist of all pollutants. To define antagonism between two ions, the Dixon curves theory should be applied. These curves represent the variation of Gt when the concentration of common metal increases (1 mM, 3 mM), while the concentration of toxic metal is maintained constant (3 concentrations of toxic metal are used). The straight lines obtained are either parallel to each other (noncompetitive inhibition), parallel to the x axis (no interaction between common and toxic metals), or the 3 lines intersect at a common point equal to the inhibition constant. At pharmacological doses, there is competitive inhibition (specific antagonism) between Mg and Cd, Zn and Cd, Ca and Cd, and Mg and Pb, and noncompetitive inhibition between Mg and Hg. This method may rapidly indicate a membrane interaction between common and toxic metals.

Amnion↗

Comparative study of effects of magnesium and taurine on electrical parameters of natural and artificial membranes. VIII. Effect on the ultrastructure of human amniotic epithelial cells.

The ultrastructure of human amniotic epithelial cells from normal pregnancies, at term, was studied using transmission electron microscopy. The results were analysed by a stereological method which indicates the ratio between the volume of the intercellular space (R1, the microvilli (R2), and the podocytes (R3) versus the cell volume. At low concentration (2 mM), MgCl2 decreased R1 and R3 and had no significant effect on R2. In contrast, taurine (2 mM) increased R1 and had no significant effect on R2 and R3. There is no vicarious action between Mg and taurine. These data are in contrast to the results obtained after electrophysiological studies, which indicates that the structural targets for Mg and taurine are different from the targets responsible for ionic transfer.

Amnion↗

Toxic metals and human amniotic ion permeability. II. Ultrastructural study and relationship with magnesium.

Measurement of the ratio between the volume of the intercellular space (R1), the microvilli (R2), the podocytes (R3), and the nucleus (R4) versus the cell volume indicates the effects of lead (Pb), cadmium (Cd), arsenic (As), and mercury (Hg) on the ultrastructure of the human epithelial cells. R1 is decreased by all toxic metals except Pb. R2 is increased by Cd and As, and decreased by Pb. R3 is not affected. R4 is increased only by As. The addition of MgCl2 to the bathing medium antagonizes the effect of Cd on the intercellular space, of Pb on the microvilli, and of As on nucleus. On the other hand, Mg enhances the effects of Pb on R1 and those of Cd and As on R2. Mg may be either a competitive inhibitor or an activator of the effects of the toxic substances examined in relation to their storage sites.

Amnion↗

Circadian variations in vigilance states in the alcohol-dependent rat.

Waking and sleep states were studied in the alcohol-dependent rat after administration of ethanol (416 mg/kg/hr) by indwelling intragastric catheter (IGC) for 13 days. Electropolygraphic recordings performed for a total of 24 hr from the start of withdrawal were compared with those of control rats receiving water by IGC and showed 1) that rapid eye movement sleep was the most sensitive of the four vigilance states studied. A decrease was noted both for the total duration of recording and for the light period; 2) that nonactive wakefulness was the only vigilance state to show an inversion of percentages between the light and dark period; 3) that the light period was the best time for studying changes in vigilance states. Changes included increased percentages of active and nonactive wakefulness and decreased percentages of slow-wave and rapid eye movement sleep. This was due to a change in the number of episodes rather to a change in their mean duration. No significant change occurred during the dark period.

Alcohol Withdrawal Delirium↗

Comparative study of effects of magnesium and taurine on electrical parameters of natural and artificial membranes. VII. Effects on cellular and paracellular ionic transfer through isolated human amnion.

The comparative effects of 2 mM magnesium and taurine on various components of the human transamniotic conductance, Gt, were observed. The use of both microelectrodes and metabolic inhibitors enables 10 components of Gt to be distinguished: six cellular components (Na-K ATPase, Na-H antiport, Na-K-2Cl cotransport and Na, K, Cl channels), one coupling component, and three paracellular components (Na, K, Cl). Mg increased all components of Gt while taurine only increased five of them (Na and K channels, coupling, Na and K paracellular conductance). A potentiometric effect of taurine on Mg2+ modified membrane, obtained on paracellular components, was not measured on cellular components. There was only a vicarious effect between Mg and taurine on the non-enzymatic cellular and paracellular transfer of Na and K.

Amnion↗

[New data on the membrane mechanisms of antagonism between magnesium and alcohol: physiologic and therapeutic implications].

The aim of this study is to analyze the mechanisms involved in membrane antagonism between magnesium and ethanol. The use of both microelectrodes and metabolic inhibitors leads to distinguish 10 components of trans-amniotic conductance: 6 cellular, 1 coupling and 3 paracellular. The 6 cellular components are made up of 3 enzymatic and 3 apparently non enzymatic components. Na+K+ATPase dependent pathway, Na+H+ antiport, Na+K+2Cl- cotransport represent the 3 enzymatic components and the Na+, Cl-, K+ channels: the 3 so-called free of enzymatic mediation components. Cellular components and coupling components expressed as micromohs per "inverse" cm2 are quantitatively less important in this leaky membrane than paracellular components expressed as millimohs per "inverse" cm2. The 3 paracellular components are the Na+, Cl-, K+ pathways. On the 2 sides of aminos, the studied doses 2 mM of a Mg salt (Cl2Mg),--a concentration corresponding to the plasma level observed after therapeutic parenteral Mg load--and 0.4 g of ethanol--a concentration frequently observed in plasma after alcohol ingestion--are added to aerated Hanks' solution at 37 +/- 1 degree C and pH 7.4. Adjunction of magnesium 5 minutes before and 3 minutes after addition of ethanol permits to study the preventive and curative antagonistic effects of magnesium on ethanol action. Under these experimental conditions, magnesium significantly (p less than 0.01) increases and ethanol significantly (p less than 0.01) decreases trans-amniotic conductance. Besides magnesium significantly (p less than 0.01) induces both preventive and curative antagonistic effects on the decrease of trans amniotic conductance induced by ethanol. Moreover analysis of the 10 trans amniotic conductance components shows that both these separate effects and antagonisms are respectively neither perfectly symmetrical nor perfectly antagonistic. Magnesium significantly increases the whole group of the 10 components of trans-amniotic conductance while ethanol only decreases 7 of them. It does not exert any action on cellular Na+ and K+ channels or on the paracellular Cl- pathway. Furthermore membranous antagonistic effects between magnesium and ethanol only involve 4 components among the 7 ways affected by ethanol. They do not concern the 3 cellular enzymatic components: monovalent cation pump, Na(+)-H+ antiport, Na+K+2Cl- cotransport. As a conclusion: firstly it is not possible to extrapolate from opposite effects on conductance to antagonistic effects. Secondly an apparently perfect antagonism described from macrostudies may reveal itself imperfect when using more sophisticated microstudies. Thirdly though magnesium is a real membranous antagonist of ethanol, it cannot be described as an ideal antagonist.(ABSTRACT TRUNCATED AT 400 WORDS)

Amnion↗

Magnesium depletion and pathogenesis of Alzheimer's disease.

Mg depletion, particularly in the hippocampus, appears to represent an important pathogenic factor in Alzheimer's disease. It is associated with high aluminium incorporation into brain neurones. This type of Mg deficit cannot respond to mere Mg supplementation, but requires correction of the dysregulation inducing this Mg depletion. Further research should seek to control the alterations of albumin, which may induce this brain Mg depletion.

Alzheimer Disease↗

Historical review of the effects of marginal intake of magnesium in chronic experimental magnesium deficiency.

After the discovery of magnesium as an essential nutrient in 1926, research focused upon the identification of effects of an acute deficiency state and determination of the requirement for the mineral for normal growth and reproduction. In this early work, marginal intakes of magnesium were reported to result in alterations of tissue composition. Since the 1970s, research has shown that the ability to adapt to a marginal intake of magnesium, which is commonplace in developed countries, is limited. In fact, a low intake of the mineral for an extended period of time may be associated with abnormalities in reproduction, growth, and development and may be a factor in the pathogenesis of disorders of neuromuscular, cardiovascular, renal, and immune function. Problems related to the use of pharmacological agents or to trace metals, such as aluminium, may be worsened in the presence of a low intake of magnesium. Evidence presented illustrates that, although physical signs of magnesium deficiency may be absent, that is to say in cases of latent clinical forms, a marginal dietary inadequacy of the mineral over a long period of time could result in significant problems.

Animals↗

New experimental and clinical data on the relationship between magnesium and sport.

Exercise under certain conditions appears to lead to Mg depletion and may worsen a state of deficiency when Mg intake is inadequate. Whereas hypermagnesaemia occurs following short term high intensity exercise as the consequence of a decrease in plasma volume and a shift of cellular magnesium resulting from acidosis, prolonged submaximal exercise is accompanied by hypomagnesaemia. Discordant findings on the effect of physical exercise on erythrocyte concentrations have been reported. A mechanism for the observed decrease in plasma magnesium concentration after long term physical exercise could be a shift of Mg into the erythrocyte. However, in several studies the decrease in plasma Mg was not accompanied by an increase in RBC Mg, but a decrease in cellular Mg was observed. Urinary Mg losses during an endurance event could play a role in this depletion but are often reduced, reflecting renal compensation. Loss of Mg by sweating takes place only when there is a failure in sweat homeostasis, a situation which arises when exercise is made in conditions of damp atmosphere and high temperature. Stress caused by physical exercise is capable of inducing Mg deficit by various mechanisms. A possible explanation for decreased plasma Mg concentration during long endurance events is the effect of lipolysis. Since fatty acids are mobilized for muscle energy, lipolysis would cause a decrease in plasma Mg. In developed countries Mg intake is often marginal and sport is a factor which is particularly likely to expose athletes to Mg deficit through metabolic depletion linked to exercise itself, which can only aggravate the consequences of a frequent marginal deficiency. Mg depletion and deficiency therefore play a role in the pathophysiology of physical exercise. Experiments on animals have shown that severe Mg deficiency reduces physical performance and in particular the efficiency of energy metabolism. These data, however, do not correspond to those of marginal deficiency most commonly observed in humans. Clinical symptomatology, both in athletes and in other patients, is dominated by the symptomatology of neuromuscular hyperexcitability. Medical authorities in sport have enforced obligatory tests for latent tetany in athletes, with ionic assessment. The effects of the correction of magnesium deficiency are judged from clinical signs, Chvosteck sign, electromyogram and echocardiogram findings and plasma Mg, erythrocyte and urine analysis. These may also be complemented by cardiac and respiratory investigations after exercise. The positive effects (analysis after a minimum period of one month) of a simple oral supplement administered in physiological doses (5 mg/kg body weight/day) provides evidence for the existence of a deficiency.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Modification of the human transamniotic ionic transfer after addition of anti-cancer metals.

The effects of anticancer metals (Ga, Cis-Pt, Se) on the ionic transfer through the isolated human amnion, expressed as the measure of the transamniotic conductance Gt, the ionic fluxes and the flux ratio (mother-fetus/fetus-mother: F1/F2) were studied. The 3 metals decrease Gt on the maternal side by a screening effect and have a little effect on the fetal side. The ionic fluxes are decreased on the maternal and on the fetal sides. The flux ratio is reduced by Cis-Pt but becomes constant with Ga and Se. The action of the anticancer metals is identical to the action of the carcinogenic metals on the transamniotic transfer and the membrane does not seem to be the target of the anticancerous action.

Amnion↗

Ultrastructural effects of magnesium on human amniotic epithelial cells.

The ultrastructure of the human amniotic epithelial cells from normal pregnancies, at term, was studied using scanning and transmission electron microscopy. The results were analysed by a stereological method which indicates the ratio between the volume of the intercellular space (R1), the microvilli (R2), and the podocytes (R3) versus the cell volume. An increase in this ratio indicates a higher structure and a facilitation of ion transport through the membrane. At low concentration (2 mM), MgSO4 increased R1 and R2 but decreased R3, whereas MgCl2 decreased R1 and R3 and had no significant effect on R2. At high concentration (10 mM), MgCl2 decreased R1 and increased R2 and R3, while MgSO4 had no significant effect on R1, increased R2, and decreased R3. The results are in part consistent with the results obtained after electrophysiological studies.

Amnion↗

Magnesium: a competitive inhibitor of lead and cadmium. Ultrastructural studies of the human amniotic epithelial cell.

The measure of the ratio between the volume of intercellular space (R1), the microvilli (R2), and the podocytes (R3) versus the cell volume indicates the effect of lead (Pb) and cadmium (Cd) on the ultrastructure of the human amniotic epithelial cell. Cd decreased R1 significantly, increased R2 and had no effect on R3. Pb had no effect on R1 or R3 but decreased R2 significantly. The addition of Mg chloride to the bathing medium antagonized the effect of Cd on the intercellular spaces and podocytes. The antagonistic effect of Mg on Pb was observed only on microvilli. These results are consistent with the data obtained with electrophysiological studies which show that Mg is a competitive inhibitor of Pb and Cd.

Amnion↗

A qualitative theory of the screening-binding effects of magnesium salts on epithelial cell membranes: a new hypothesis.

A theoretical explanation is given of the screening-binding effects of various magnesium salts on the ionic permeability of epithelial amniotic cell membranes. It is suggested that the 'screening process' induces an increase in the electrical membrane resistance and in membrane stability which is a unique action at low concentration. At high concentration, the binding process induces a reduction or an increase in these parameters as a function of the magnesium salt present. The different effects are due to changes in the distribution and in the repartition of the fixed charges on the cell membrane.

Amnion↗

Recommended dietary amounts of magnesium: Mg RDA.

In developed countries, the recommended dietary amounts of magnesium have been set at 6 mg/kg day. The magnesium requirements for optimal health in the adult population depend on mesological and constitutional conditioning factors. They may intervene at every stage of magnesium metabolism: absorption, circulation, storage and excretion. The influence of other nutrients is more significant on magnesium absorption than on urinary excretion. Among the multiple interactions it is important to emphasize the maintenance of a Ca/Mg ratio close to 2 in the intake. Magnesium deficit and stress reinforce each other in a pathogenic vicious circle. The Bw35 allele of HLA typing and behavioural type A discriminate two constitutional factors increasing magnesium requirements. The effective passive regulatory mechanism for magnesium overload, the lability of the active regulatory mechanisms for magnesium deficit and the considerable need for exchangeable magnesium are factors which attribute special importance to balance studies in determining the magnesium intake which prevents negative magnesium balance and magnesium deficiency. Marginal primary magnesium deficit affects a large proportion of the population (15 to 20%), in keeping with a daily mean magnesium intake slightly over 4 mg/kg day versus the Mg RDA of 6 mg/kg day. A physiological oral magnesium load test, evaluated through non-specific and specific clinical and paraclinical items, constitutes the best proof that the clinical pattern depends on an insufficient magnesium intake, confirmed after one month of supplementation. Further research appears necessary.(ABSTRACT TRUNCATED AT 250 WORDS)

Developing Countries↗