Showing papers in "Magnesium Research in 2006"

Update on the relationship between magnesium and exercise

Abstract: Magnesium is involved in numerous processes that affect muscle function including oxygen uptake, energy production and electrolyte balance. Thus, the relationship between magnesium status and exercise has received significant research attention. This research has shown that exercise induces a redistribution of magnesium in the body to accommodate metabolic needs. There is evidence that marginal magnesium deficiency impairs exercise performance and amplifies the negative consequences of strenuous exercise (e.g., oxidative stress). Strenuous exercise apparently increases urinary and sweat losses that may increase magnesium requirements by 10-20%. Based on dietary surveys and recent human experiments, a magnesium intake less than 260 mg/day for male and 220 mg/day for female athletes may result in a magnesium-deficient status. Recent surveys also indicate that a significant number of individuals routinely have magnesium intakes that may result in a deficient status. Athletes participating in sports requiring weight control (e.g., wrestling, gymnastics) are apparently especially vulnerable to an inadequate magnesium status. Magnesium supplementation or increased dietary intake of magnesium will have beneficial effects on exercise performance in magnesium-deficient individuals. Magnesium supplementation of physically active individuals with adequate magnesium status has not been shown to enhance physical performance. An activity-linked RNI or RDA based on long-term balance data from well-controlled human experiments should be determined so that physically active individuals can ascertain whether they have a magnesium intake that may affect their performance or enhance their risk to adverse health consequences (e.g., immunosuppression, oxidative damage, arrhythmias).

High fructose consumption combined with low dietary magnesium intake may increase the incidence of the metabolic syndrome by inducing inflammation.

Abstract: The metabolic syndrome is a cluster of common pathologies: abdominal obesity linked to an excess of visceral fat, insulin resistance, dyslipidemia and hypertension. This syndrome is occurring at epidemic rates, with dramatic consequences for human health worldwide, and appears to have emerged largely from changes in our diet and reduced physical activity. An important but not well-appreciated dietary change has been the substantial increase in fructose intake, which appears to be an important causative factor in the metabolic syndrome. There is also experimental and clinical evidence that the amount of magnesium in the western diet is insufficient to meet individual needs and that magnesium deficiency may contribute to insulin resistance. In recent years, several studies have been published that implicate subclinical chronic inflammation as an important pathogenic factor in the development of metabolic syndrome. Pro-inflammatory molecules produced by adipose tissue have been implicated in the development of insulin resistance. The present review will discuss experimental evidence showing that the metabolic syndrome, high fructose intake and low magnesium diet may all be linked to the inflammatory response. In many ways, fructose-fed rats display the changes observed in the metabolic syndrome and recent studies indicate that high-fructose feeding is associated with NADPH oxidase and renin-angiotensin activation. The production of reactive oxygen species results in the initiation and development of insulin resistance, hyperlipemia and high blood pressure in this model. In this rat model, a few days of experimental magnesium deficiency produces a clinical inflammatory syndrome characterized by leukocyte and macrophage activation, release of inflammatory cytokines, appearance of the acute phase proteins and excessive production of free radicals. Because magnesium acts as a natural calcium antagonist, the molecular basis for the inflammatory response is probably the result of a modulation of the intracellular calcium concentration. Potential mechanisms include the priming of phagocytic cells, the opening of calcium channels, activation of N-methyl-D-aspartate (NMDA) receptors, the activation of nuclear factor-kappaB (NFkB) and activation of the renin-angiotensin system. Since magnesium deficiency has a pro-inflammatory effect, the expected consequence would be an increased risk of developing insulin resistance when magnesium deficiency is combined with a high-fructose diet. Accordingly, magnesium deficiency combined with a high-fructose diet induces insulin resistance, hypertension, dyslipidemia, endothelial activation and prothrombic changes in combination with the upregulation of markers of inflammation and oxidative stress.

Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6. I. Attention deficit hyperactivity disorders.

Abstract: Some previous studies have reported the involvement of magnesium (Mg) deficiency in children with ADHD syndrome. In this work, 40 children with clinical symptoms of ADHD were followed clinically and biologically during a magnesium-vitamin B6 (Mg-B6) regimen (6 mg/kg/d Mg, 0.6 mg/kg/d vit-B6) which was set up for at least 8 weeks. Symptoms of ADHD (hyperactivity, hyperemotivity/ aggressiveness, lack of attention at school) were scored (0-4) at different times; in parallel, intraerythrocyte Mg2+ (Erc-Mg) and blood ionized Ca2+ (i-Ca) were measured. Children from the ADHD group showed significantly lower Erc-Mg values than control children (n = 36). In almost all cases of ADHD, Mg-B6 regimen for at least two months significantly modified the clinical symptoms of the disease: namely, hyperactivity and hyperemotivity/aggressiveness were reduced, school attention was improved. In parallel, the Mg-B6 regimen led to a significant increase in Erc-Mg values. When the Mg-B6 treatment was stopped, clinical symptoms of the disease reappeared in few weeks together with a decrease in Erc-Mg values. This study brings additional information about the therapeutic role of a Mg-B6 regimen in children with ADHD symptoms.

Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6. II. Pervasive developmental disorder-autism.

Abstract: Previous studies reported positive results with the use of Mg-vitamin B6 in autism. Despite these reports, this intervention remains controversial. In order to study relationships between changes in clinical symtoms and biological parameters, 33 children (mean age: 4 [1-10] years old) with clinical symptoms of pervasive developmental disorder or autism (PDD, as defined in DSM-IV) were followed for at least 6 months; another group of 36 children (same age) devoided of any known pathology was used as control. All PDD children received a magnesium-vit B6 (Mg-B6) regimen (6 mg/kg/d Mg and 0.6 mg/kg/d vit B6). Intraerythrocyte Mg2+ (Erc-Mg), serum Mg2+ (s-Mg) and blood ionized Ca2+ (i-Ca) were measured before and after treatment. Clinical symptoms of PDD were scored (0 to 4). In contrast to s-Mg or i-Ca, PDD children exhibited significantly lower Erc-Mg values than controls (2.17 +/- 0.4 versus 2.73 +/- 0.23 mmol/L; 16/33). The Mg-B6 regimen led to an increase in Erc-Mg values (2.42 +/- 0.41 (after) versus 2.17 +/- 0.4 mmol/l (before), 11/17) and this supplementation improved PDD symptoms in 23/33 children (p < 0.0001) with no adverse effects: social interactions (23/33), communication (24/33), stereotyped restricted behavior (18/33), and abnormal/delayed functioning (17/33); 15/33 children were improved in the first three groups of symptoms. When the Mg-B6 treatment was stopped, PDD symtoms reappeared in few weeks. A statistically significant relationship was found in Erc-Mg values from children before treatment and their mothers. In conclusion, this study suggests that the behavioral improvement observed with the combination vitamin B6-magnesium in PDD/autism is associated with concomitant modifications of Erc-Mg values.

Concentration, compartmentation and metabolic function of intracellular free Mg2+.

Abstract: Intracellular total Mg2+ and free Mg2+ are compartmentalized between cell organelles and within the cytosol. Different values of [Mg2+]i in the cytosol of the same cell type were measured by various investigators. A main reason for the differences is the uncertainty of the dissociation constants used for the Mg furaptra complex in the fluorescence method and for MgATP when 31P NMR was employed. The more realistic KD values of Mg furaptra and MgATP measured under in situ conditions are higher than the KDs used by most investigators. The [Mg2+]is obtained and the KDs used by various authors were presented. The role of intracellular Mg2, in metabolic functions and the action of various effectors on [Mg2+]i and [Ca2+] was reviewed. Intracellular Mg2+ may have a permissive role supporting the effector-induced mechanisms that are mediated by Ca2+ as a second messenger.

Ageing, hippocampal synaptic activity and magnesium

Abstract: Ageing is associated with a general decline in physiological functions. Amongst the different aspects of body deterioration, cognitive impairments, and particularly defects in learning and memory, represent one of the most frequent features in the elderly. However, a great variability exists among aged subjects. Clinical reports and experimental data in animal models of ageing have shown that age-associated memory deficits are broadly identical to those induced by damage to the hippocampus. It is therefore not surprising that many functional properties of hippocampal neuronal networks are particularly altered with ageing. Whereas passive membrane properties of neurons are conserved with age, neuronal excitability is altered, in keeping with weaker performances of aged subjects in memory tasks. Synaptic transmission within hippocampal networks also decreases in brain ageing. Deficits concern both glutamatergic and cholinergic pathways, which represent the main excitatory neurotransmitter systems responsible for neuronal communication in the hippocampus. In addition, long-term changes in synaptic transmission, possible cellular substrates for learning and memory, are also impaired in ageing in correlation with cognitive impairments. Neuronal properties and synaptic plasticity closely depend on ion exchanges between intra- and extracellular compartments. Changes in ion regulation during ageing may therefore participate in altering functional properties of neuronal networks. Calcium dysregulation has been extensively investigated in brain ageing but the role of magnesium has received less attention though ageing constitutes a risk factor for magnesium deficit. One of general properties of magnesium at presynaptic fibre terminals is to reduce transmitter release. At the postsynaptic level, it closely controls the activation of the N-methyl-D-aspartate receptor, a subtype of glutamate receptor, which is critical for the expression of long-term changes in synaptic transmission. In addition, magnesium is a cofactor of many enzymes localized either in neurons or in glial cells that control neuronal properties and synaptic plasticity such as protein-kinase C, calcium/calmodulin-dependent protein kinase II and serine racemase. It is therefore likely that a change in magnesium concentration would significantly impair synaptic functions in the aged hippocampus. Experiments addressing this question remain too scarce but recent data indicate that magnesium is involved in age-related deficits in transmitter release, neuronal excitability and in some forms of synaptic plasticity such as long-term depression of synaptic transmission. Further studies are still necessary to better delineate to what extent magnesium contributes to the impaired cellular mechanisms of cognitive functions in the elderly which will help to develop new strategies to minimize age-related memory declines.

Is magnesium neuroprotective following global and focal cerebral ischaemia? A review of published studies

Abstract: Neuroprotective activity with magnesium associated with animal models of cerebral ischaemia, seizure, perinatal hypoxia/ischaemia, subarachnoid haemorrhage and traumatic brain injury has provided the justification for clinical stroke trials. However, the recent IMAGES stroke clinical trial found magnesium to be largely ineffective. Hence, due to the negative stroke trial outcome, current FAST-MAG trial and our own experience with magnesium in cerebral ischaemia animal models, we thought it prudent to review these preclinical and clinical studies. We reviewed nine studies describing the use of magnesium following global cerebral ischaemia and fourteen following focal cerebral ischaemia. Four global ischaemia and six focal ischaemia studies did not show a significant neuroprotective effect with magnesium. In the majority of positive magnesium studies animal body temperature was not monitored post-ischaemia. Thus the effects of post-ischaemic hypothermia cannot be ruled out as a confounding factor in positive magnesium cerebral ischaemia studies. Moreover, data from our own laboratory indicates that magnesium is only neuroprotective when combined with post-ischaemic hypothermia. These data provide a possible explanation of why the IMAGES trial was largely unsuccessful, as current stroke patient management does not involve hypothermia induction. Future preclinical and clinical cerebral ischaemia trials with magnesium should consider combining treatment with mild hypothermia.

Anxiety and stress among science students. Study of calcium and magnesium alterations.

Abstract: Stress and anxiety of university science students (Chemistry) was evaluated in basal conditions and during exams using validated stress and anxiety questionnaires. The relations between the data obtained and various biochemical markers were established. Results showed that the evaluated students did not experience stress increase as a consequence of exams but suffered a significant increase in anxiety. The psychological findings agree with the urinary biomarkers studied. It is known that anxiety is related to partial magnesium reduction associated with a urinary magnesium excretion increase, as observed in the present data. Nevertheless, stress also correlates with a urinary calcium increase which was not detected in the present study.

Possible relationship between low birth weight and magnesium status: from the standpoint of "fetal origin" hypothesis.

Abstract: Magnesium deficiency in pregnant women is frequently seen because of inadequate or low intake of magnesium. Magnesium deficiency during pregnancy can induce not only maternal and fetal nutritional problems, but also consequences that might last in offspring throughout life. Many epidemiological studies have shown that restricted fetal growth, i.e. intrauterine growth retardation (IUGR), is associated with an increased risk of insulin resistance in adult life. We previously postulated that the intracellular magnesium of cord blood platelets is lower in the small for gestational age group than in the appropriate for gestational age group, suggesting that intrauterine magnesium deficiency may result in IUGR. Taken together, intrauterine magnesium deficiency in the fetus may lead to or program the insulin resistance after birth. We hypothesize that intrauterine magnesium deficiency may induce a metabolic syndrome in later life. Prospective studies will further clarify whether infants with IUGR induced by magnesium deficiency are at higher risk for metabolic syndromes in childhood or adulthood.

Influence of graded magnesium deficiencies on white blood cell counts and lymphocyte subpopulations in rats.

Abstract: Increased white blood cell counts or leukocytosis have been observed primarily in young rats fed diets extremely low in Mg (< 60 ppm) and high in phosphorus (0.5 % P). We investigated the influence that acute and moderate Mg deficiencies have on blood leukocytes at high and low dietary phosphorus levels. For four weeks, male Sprague-Dawley rats (initially 7 weeks old) were fed diets containing 30, 60, 120, 208, or 850 ppm Mg and either 0.3 % or 0.5 % dietary phosphorus. Total leukocytes were increased in rats fed 30 ppm Mg (p < 0.0001), and the leukocyte subpopulation counts of lymphocytes, neutrophils, monocytes and eosinophils increased significantly only in the rats fed 30 ppm Mg (p < 0.0001). B-cells decreased significantly as a percentage of lymphocytes (p < 0.0093) as dietary Mg decreased. As total counts in blood, B-cells, CD4 and CD8 cells were significantly increased in the rats consuming the 30 ppm Mg diet. Dietary phosphorus only had an effect in combination with the lowest dietary Mg. These results demonstrate a threshold effect for increased leukocytes during a Mg deficiency of four weeks. A Mg deficiency of a longer duration may show different results.

Contents of bioelements and toxic metals in a Polish population determined by hair analysis. Part 2. Young persons aged 10-20 years.

Abstract: The aim of this study was to define referential values of 5 basic bioelements (Ca, Mg, Zn, Cu, Fe) in the hair of Polish young persons aged 10-20 years, based on the research conducted from 1991 to 2004 on a group of over 3420 healthy young persons Mean concentrations of two toxic metals (Pb and Cd) in over 2000 young men were also investigated The results of biochemical tests were analyzed with the program STATISTICA 70 (StatSoft PL) Significant differences between girls' and boys' hair Ca, Mg and Zn in the same age group were observed (p = 00000) It was determined that boys have smaller concentrations of hair Ca, Mg and Zn than girls No significant differences were observed between concentrations of Cu and Fe in the hair of girls and boys of the same age in the tested period Significantly greater amounts of Pb and Cd characterize boys Analyses of correlations confirm significance (p < 005000) of synergistic interactions between bioelements: Ca-Mg (r = +080), Ca-Zn (r = +052), Ca-Cu (r = +014), Mg-Zn (r = +050), Mg-Cu (r = +013), Zn-Cu (r = +011), Cu-Fe (r = +004) Significance (p < 005000) of antagonistic interactions of bioelements with toxic metals: Zn-Pb (r = -030), Mg-Pb (r = -020), Ca-Pb (r = -018) and Zn-Cd (r = -007) was confirmed Significance (p < 005000) of synergistic effects with toxic elements: Pb-Cd (r = +034), Fe-Pb (r = +022), Fe-Cd (r = +013) was determined Compatibility of the statistically mapped basic characteristics of young persons' developmental age with the functions of concentrations in tested hair bioelements was confirmed Young persons whose concentrations of selected hair bioelements showed values outside the reference ranges and who had higher concentrations of toxic metals should undergo further diagnostic tests since the results of previous tests could be a sign of disturbances leading to various diseases Analyses of the concentrations of bioelements and toxic metals in humans based on hair analysis can be useful as a convenient, non-invasive and painless method in the diagnosis of pathological states Combined with other analytical data, this method can be used by practising physicians as a complementary diagnostic procedure

Mechanisms, regulation and pathologic significance of Mg2+ efflux from erythrocytes.

Abstract: Mg2+ efflux from erythrocytes can be performed by the Na+/Mg2+ antiport and by Na+-independent Mg2+ efflux. Na+-independent Mg2+ efflux functions via the unspecific choline exchanger as choline/Mg2+ or K+/Mg2+ antiport and as Mg2+ efflux accompanied by intracellular Cl- for charge compensation, as found for example in sucrose medium. Na+/Mg2+ antiport in erythrocytes exchanges 2 extracellular Na+ for 1 intracellular Mg2+. Driving forces are the Na+ and Mg2+ gradients. By reversing these gradients, the Na+/Mg2+ antiporter can mediate Mg2+ influx. The Na+/Mg2+ antiporter can exchange 24Mg2+ for 28Mg2+ and other divalent cations for intracellular Mg2+. In the exchange mechanism, extra- and intracellular Na+ can compete with Mg2+. Na+/Mg2+ antiport is inhibited by amiloride, quinidine and imipramine. Na+/Mg2+ antiport is drastically activated by intracellular Mg2+ due to an allosteric transition. The affinity of intracellular Mg2+ to the Na+/Mg2+ antiporter is dependent on intracellular ATP due to phosphorylation. Besides this mechanism, in non Mg2+-loaded erythrocytes, the activity of Na+/Mg2+ antiport is regulated by phosphorylation-dephosphorylation and by intracellular Cl-. The drastically Mg2+-activated Na+/Mg2+ antiporter is not further stimulated by phosphorylation and intracellular Cl-. Na+-independent Mg2+ efflux via the choline exchanger is also inhibited by amiloride, quinidine and imipramine, and can also be regulated by phosphorylation-dephosphorylation. Na+/Mg2+ antiport of erythrocytes is altered in various pathologic conditions.

Dietary magnesium deficiency decreases plasma melatonin in rats.

Abstract: It has been postulated that Mg depletion is associated with decreased melatonin. Exogenous magnesium (Mg) has been found to increase the activity of serotonin N-acetyltransferase, an enzyme in the pathway for melatonin synthesis; but no data have been found on the effect of Mg deficiency on plasma melatonin. This pilot study examined the effect of a dietary Mg deficiency on plasma melatonin in male, Sprague-Dawley rats. Weanling rats were placed on a Mg-deficient (150 ppm) or a Mg-adequate (1000 ppm) diets for four weeks, after which they were sacrificed 4, 5 or 7 hours into the dark cycle. Plasma was assayed for melatonin concentrations. A significant decrease (p = 0.0101) occurred in mean (+/- SEM) plasma melatonin levels of the Mg-deficient animals (50 +/- 6.4 pg/mL) when compared to the Mg-adequate animals (75 +/- 6.6 pg/mL). There was no obvious phase shift in the melatonin profile of the Mg-deficient animals when compared to the Mg-adequate animals.

Magnesium therapy in acoustic trauma

Abstract: Acoustic trauma is one of the major causes of hearing loss and tinnitus, particularly in industrial environments. Noise-induced hearing loss (NIHL) results in direct mechanical damage as well as in indirect metabolic processes. Metabolic disorders have multiple origins: ionic, ischemic, excitotoxic and production of cochlear free radicals causing cell death, due to necrosis or apoptosis. The efficacy of magnesium, administered either to prevent or to treat NIHL has been demonstrated in several studies in animals and in humans. Magnesium, which easily crosses the hematocochlear barrier, presents neuroprotective and vasodilatory effects, and thus, is able to limit the cochlear damage. Magnesium therapy is well documented because it is usually prescribed in other pathologies. Its side effects and contraindications are few and it is cheap. This article presents also some arguments that emphasize the interest of magnesium therapy in acoustic trauma.

Serum magnesium profile in heroin addicts: according to psychiatric comorbidity.

Abstract: Psychiatric comorbidity in heroin addiction can modify both the biological pattern and clinical course of this disorder. Because of the role of magnesium in neurotransmission and its specific patterns in some psychiatric conditions, such as depression and schizophrenia, we studied a sample of heroin dependent subjects, with and without psychiatric comorbidity. A sample of 162 drug addicts (123 men and 39 women, mean age 32.3 +/- 6.7) was diagnosed for the presence of psychiatric comorbidity with DSM IV criteria. They were subsequently divided in 4 subgroups: No comorbidity, Anxiety Disorders, Mood Disorders, Personality Disorders. Differences in serum magnesium level between the groups were analysed with the Anova method, with age as covariate. Results show that serum Mg++ levels are significantly higher in patients with heroin dependence and personality disorders compared to patients with depression comorbidity and without comorbidity. Psychiatric codiagnosis significantly modifies Mg++ levels in this drug dependent sample. Gender modifies Mg levels in no comorbid subjects so that females show significantly lower Mg++ levels compared to males. The presence of psychiatric comorbidity abates this difference.

The effect of preoperative magnesium supplementation on blood catecholamine concentrations in patients undergoing CABG

Abstract: Background. It is well known that magnesium (Mg) plays an important role in many physiological processes such as regulation of blood catecholamine concentrations, particularly epinephrine (E) and norepinephrine (NE). The complex character of extracorporeal circulation (ECC) with intraoperative normovolemic haemodilution (NH) may alter blood Mg levels, which is likely to result in disorders of E and NE. The aim of this study was to analyze the influence of preoperative Mg supplementation on E and NE in patients undergoing CABG. Patients and methods. Forty male patients undergoing CABG under general anaesthesia were included. Patients were randomly divided into two groups: A – the patients receiving pre-operative magnesium supplementation and B – patients without pre-operative magnesium supplementation. The Mg, E and NE blood concentrations were measured in five stages: 1) before anesthesia after the radial artery cannulation, 2) during NH and ECC, 3) immediately after surgery, 4) in the morning of the 1 st postoperative day, 5) in the morning of the 2 nd postoperative day. The Mg levels were determined by spectrophotometric methods, E and NE were measured by radioimmunoassay methods. Results. The CABG caused a decrease of Mg and an increase of E and NE in both groups, but the changes were significantly higher in group B. Conclusions. 1) CABG causes a decrease of Mg and an increase of E and NE; 2) Preoperative, oral supplementation of Mg substantially reduces intra- and postoperative disorders.

Changes of blood magnesium concentration in patients undergoing surgical myocardial revascularisation.

Abstract: Background. Magnesium (Mg) is the second most relevant intracellular element, which plays an important role in many physiological processes. Magnesium disorders are particularly important in haemodynamically unstable patients, such as patients after extracorporeal circulation. The aim of this study was to analyze the changes in blood Mg levels in patients undergoing coronary artery bypass procedures with extracorporeal circulation. Patients and Methods. Twenty male patients, aged 50-69, undergoing CABG with ECC under general anaesthesia, were included in the study. All of them were operated on due to Io and IIo degree coronary disease (according to CCS). The blood concentrations of Mg were examined in five stages: 1) before the induction of anaesthesia; 2) during extracorporeal circulation; 3) after surgery; 4) in the morning of the first postoperative day; 5) in the morning of the second postoperative day. The blood Mg concentrations were determined by spectrophotometric methods. Results. The blood concentration of Mg decreased during extracorporeal circulation and immediately after surgery and increased in the morning of the first and second postoperative days. Conclusion. The CABG with extracorporeal circulation resulted in a significant decrease in blood Mg concentration.

Magnesium intake is inversely associated with the prevalence of tooth loss in Japanese pregnant women: the Osaka Maternal and Child Health Study

Abstract: There have only been a few studies on the role of mineral intake in tooth loss. We investigated the association between mineral intake and the prevalence of tooth loss in Japan. We used the baseline data on 1002 pregnant women who were enrolled in the Osaka Maternal and Child Health Study between November 2001 and March 2003. Tooth loss was defined as the previous extraction of one or more teeth. Nutrient intake was assessed by a validated diet history questionnaire. Prevalence odds ratios and confidence intervals were estimated by applying a multiple logistic regression model. The adjusted odds ratio upon comparison of the highest quartile with the lowest quartile of magnesium intake was 0.64 (95% confidence interval, 0.42-0.99), showing a tendency for an inverse dose-response relationship (p for linear trend = 0.05). There were no associations between the level of consumption of calcium, phosphate, iron, zinc, or copper and tooth loss. The present findings suggest that intake of magnesium is related to reduced prevalence of tooth loss among young Japanese women.

Protective effects of calcium-magnesium soft gels in morphine tolerant and dependent mice.

Abstract: The present study was aimed at evaluating the acute effects of Calcium-Magnesium soft gels (CalMag) in morphine tolerant and dependent mice. Mice were rendered tolerant and dependent on morphine by subcutaneous injection of morphine over a fixed time period. Withdrawal signs were precipitated by injecting naloxone 2 h after the final injection of morphine. The tail-pinch assay was used to investigate the effects of various compounds on the development and reversal of morphine tolerance. Acute injection of CalMag (containing 50 mg/kg calcium and 25 mg/kg magnesium) significantly reduced the number of jumps, stands and fast breathing in morphine dependent mice. Co-administration of calcium (50 mg/kg) and magnesium (25 mg/kg) was also effective in preventing the development of morphine tolerance and dependence. Administration of calcium (up to 50 mg/kg) alone did not significantly block the development of tolerance and dependence. The mean latency to pain was significantly increased in animals pretreated with CalMag (containing 50 mg/kg calcium and 25 mg/kg magnesium). The mixture of calcium and magnesium at specific concentrations seem to be critical for preventing the development of morphine tolerance and dependence.

Magnesium-deficient diet-induced reduction in protein utilization in rats is reversed by dietary magnesium supplementation

Abstract: We investigated the effect of dietary magnesium (Mg) level on protein utilization in rats. Male Wistar rats were fed a control diet (control group) and a Mg-deficient diet (Mg-deficient group) for 28 days. After 28 days, the diet of half of the Mg-deficient group (recovery group) was changed from the Mg-deficient diet to the control diet for either 7 or 14 days. After 28 days, final body weight, weight gain and food efficiency were significantly decreased due to the Mg-deficient diet. Apparent Mg absorption, Mg retention and serum Mg levels were also significantly decreased due to the Mg-deficient diet. Furthermore, the Mg-deficient group showed a significant increase in urinary nitrogen (N) excretion and significant decreases in N retention and serum albumin level. At day 7 and 14 after changing the Mg-deficient diet to the control diet, apparent Mg absorption, Mg retention and serum Mg levels were significantly increased in the recovery group as compared with those in the Mg-deficient group. However, with regard to final body weight, weight gain and food efficiency, no significant differences were observed between the Mg-deficient group and the recovery group. At day 14 after changing the diet, urinary N excretion was significantly decreased and N retention was significantly increased in the recovery group as compared with the Mg-deficient group. At day 7 and 14 after changing the diet, the serum albumin level was also significantly increased in the recovery group as compared with that in the Mg-deficient group. These results suggest that: 1) the Mg-deficient diet depresses protein utilization; 2) the Mg-deficient diet-induced impairment of protein utilization is reversed by dietary Mg supplementation; and 3) the Mg-deficient diet-induced growth retardation is not completely reversed after 14 days of Mg supplementation.

Moderate magnesium-restricted diet affects bone formation and bone resorption in rats

Abstract: This study investigated the effects of moderate magnesium (Mg)-restricted diet on bone formation and bone resorption in rats. Weanling Wistar strain rats were randomly divided into three dietary groups of 6 rats each and fed their respective diets; a control diet containing 0.05% Mg (C), a half Mg diet containing 0.025% Mg (1/2Mg), or a one-fifth Mg diet containing 0.01% Mg (1/5Mg), for 21 days. Serum osteocalcin level was significantly reduced with decreasing dietary Mg level. Urinary excretion of C-terminal telopeptide of type 1 collagen was significantly higher in the 1/5Mg group than in the C group. Serum insulin-like growth factor-1 (IGF-1) level was significantly lower in the 1/2Mg and 1/5Mg groups than in the C group. Serum soluble receptor activator of nuclear factor-kappaB ligand (sRANKL) level was significantly higher in the 1/2Mg and 1/5Mg groups than in the C group. These results showed that a moderate Mg-restricted diet induced a decrease in bone formation and an increase in bone resorption. Furthermore, these changes of bone formation and bone resorption might be caused by serum IGF-1 and sRANKL levels, respectively.

Blood magnesium concentration and dopamine or dobutamine infusion demand in patients during CABG (coronary artery bypass grafting) with normovolemic haemodilution.

Abstract: It is well known that magnesium (Mg) plays an essential role in cardiac protection. Mg has many beneficial effects on the myocardium and cardiac function, e.g. it improves contractility and reduces the number of cardiac arrhythmia episodes. The inotropically positive effects of Mg are interesting and worth stressing. High blood Mg concentration may result in an increase in cardiac contraction strength, which may be important for haemodynamic stabilization, and thus it is likely to decrease the demand for dopamine and dobutamine infusions. However, the exact determination of correlation between blood Mg concentrations and dopamine or dobutamine infusion demand is still unknown. The aim of the study was to assess the demand for dopamine or dobutamine infusion in relation to changes in blood magnesium concentrations in patients undergoing CABG (Coronary artery bypass graft) with extracorporeal circulation and normovolemic haemodilution. The study included 20 male patients, aged 53-70 (61.1 ± 6.9) who underwent general anaesthesia and coronary artery bypass grafting (CABG) with extracorporeal circulation (ECC) and normovolemic haemodilution (NH) due to stable angina pectoris. The patients were retrospectively divided into three groups: A – patients who did not receive dopamine or dobutamine infusion, B – those receiving only D infusion in the doses dependent on their clinical state and C – those receiving DB infusion in the doses dependent on their clinical state. Mg was measured in 7 stages: 1) just before anaesthesia after the radial artery cannulation, 2) during normovolemic haemodilution and ECC, 3) immediately after surgery, 4) in the evening of the surgery day, 5) in the morning of the 1 st postoperative day, 6) in the evening of 1 st postoperative day, 7) in the morning of the 2 nd postoperative day. The spectrophotometric methods were used to determine Mg. The CABG procedure resulted in a decrease in Mg. Its level returned to normal in the evening of surgery day. The NH caused a similar Mg decrease in groups A, B and C, but these significantly low values of Mg were observed only in stage 2. There was no correlation between blood Mg concentrations and dopamine or dobutamine infusion demand. In conclusion: 1) The CABG procedure resulted in decreased blood magnesium concentrations. 2) The Mg changes do not correlate with dopamine or dobutamine infusion demand.

Onset of nephrocalcinosis depends on dietary phosphorus concentration in male rats fed a magnesium-deficient diet.

Abstract: Although a magnesium (Mg)-deficient diet is generally known to induce nephrocalcinosis, our previous study observed that despite the administration of a Mg-deficient diet, the kidney calcium (Ca) and phosphorus (P) concentrations were not increased in male rats. We speculated that this result was due to the P concentration of the experimental diet based on the AIN-93G formula used in the previous study. In the present study, male rats were fed modified AIN-93G diets containing the two different Mg concentrations [0.5 g per kg diet (normal-Mg) or Mg-free (Mg-deficient)] and three different P concentrations [3 (3-P), 5 (5-P) or 7 (7-P) g per kg diet]. By histological examination of the kidney, nephrocalcinosis was not observed in rats fed on the Mg-deficient diet containing 3-P. While nephrocalcinosis appeared in rats fed on the Mg-deficient diet containing 5-P and 7-P. The degree of nephrocalcinosis was severe in rats fed on the Mg-deficient diet containing 7-P compared with rats fed on the Mg-deficient diet containing 5-P. These results demonstrated that the Mg-deficient diet based on AIN-93G formula dose not induce nephrocalcinosis and that the Mg-deficient diet based on AIN-93G formula with increased dietary P concentrations induces nephrocalcinosis in male rats. We suggest that the onset of nephrocalcinosis could depend on the dietary P concentration in male rats fed on a Mg-deficient diet.

Stimulation of choline/Mg2+ antiport in rat erythrocytes by mefloquine.

Abstract: In non Mg(2+)-loaded and non malaria-infected rat erythrocytes, mefloquine (100 micromol x l (-1)) stimulated choline/Mg2+ antiport without affecting the Na+/Mg2+ antiport. The stimulation of the choline/Mg2+ antiport by mefloquine, found in this study, and by trifluoperazine and fluvoxamine, reported previously [Ebel et al. Biochim Biophys Acta 2004; 1167: 132-40], was associated with CF3 groups attached to the quinoline or benzene ring. The effect of mefloquine on choline/Mg2+ antiport in vitro was not related to the antimalarial action of mefloquine in vivo. In rat erythrocytes, the choline/Mg2+ antiport can be differentiated from the Na+/Mg2+ antiport through the use of cinchonine that inhibited the choline/Mg2+ antiport [Ebel et al. Biochim Biophys Acta 2002; 1559: 135-44], and mefloquine that stimulated the choline/Mg2+ antiport, whereby the Na+/Mg2+ antiport was not affected by either drug at proper concentrations. The Na+/Mg2+ antiport and choline/Mg2+ antiports behave as different molecular entities.