Effect of daily versus twice weekly long-term iron supplementation on iron absorption and status in iron-deficient women: a stable isotope study.

OBJECTIVES: This work aims at studying the effect of daily versus twice weekly long-term Fe supplementation on Fe absorption and status in Fe-deficient women. DESIGN AND METHODS: The study design is a randomized controlled open study carried out in the Internal Medicine Department, CHU de Clermont-Ferrand, France. Twenty-four young women participated in this study and were randomized into two groups: Group 1 received 50 mg Fe daily, and group 2 received 50 mg Fe twice weekly for 3 months. On day 10 (D10) and on day 90 (D90) of Fe supplementation, blood samples were obtained, and women received orally about 5 mg of 57Fe, and blood was sampled at different times over 24 h. The 57Fe absorption was evaluated by calculating the areas under the curves (AUC). Fe and oxidative stress status were also assessed. RESULTS: 57Fe absorption was similar in both groups on D10 but was greatly decreased in Group 1 and remained high in Group 2 on D90. Fe status was more improved in Group 1 than in Group 2. Oxidative stress status remained statistically unchanged. CONCLUSIONS: Our study shows that daily Fe supplementation is able to correct an Fe deficiency much more than twice weekly Fe supplementation in young women.

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

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.

Enhanced tumor necrosis factor-alpha production following endotoxin challenge in rats is an early event during magnesium deficiency.

Magnesium (Mg) plays an essential role in fundamental cellular reactions and the importance of the immuno-inflammatory processes in the pathology of Mg deficiency has been recently reconsidered. The purpose of the present study was to assess the effect of different stages of Mg deficiency on endotoxin response and tumor necrosis factor-alpha (TNF alpha) production. Weaning male Wistar rats were pair fed either a Mg-deficient or a control diet. At day 7, lipopolysaccharide (LPS) induced no lethal effects in control rats but resulted in 70% mortality in Mg-deficient rats within 3 h. The vulnerability of Mg-deficient rats to LPS was associated with higher TNF alpha plasma values. Mg-deficient animals that received magnesium supplementation before endotoxin challenge had significantly increased survival. At day 2, control and Mg-deficient rats were also subjected to endotoxin challenge with or without magnesium pre-treatment. A significant increase in TNF alpha plasma level was observed in Mg-deficient rats compared to rats fed the control diet. Mg-deficient rats that received magnesium replacement therapy before endotoxin challenge had significantly lower TNF alpha plasma values than those receiving saline before endotoxin. Thus, the results of this experiment suggest that the activated or primed state of immune cells is an early event occurring in Mg deficiency.

Magnesium deficiency modulates hepatic lipogenesis and apolipoprotein gene expression in the rat.

The present study was performed to determine the effects of magnesium (Mg) deficiency upon plasma lipoproteins and hepatic apolipoprotein gene expression in the rat. The most obvious effect of Mg-deficiency on plasma lipids is a marked increase in post-prandial triacylglycerol concentration. This increased triglyceridemia persists in fasted rats. Density gradient ultracentrifugation analysis revealed marked alterations in the distribution of plasma lipoproteins in Mg-deficient rats. An increase in triacylglycerol-rich lipoproteins (TGRLP) was associated with a significant increase in plasma apolipoprotein B (apo B) concentration and was accompanied by selective accumulation of apo B-48. A decrease in high-density lipoproteins (HDL) was accompanied by a corresponding decrease in plasma apo E concentration and a concordant decrease in hepatic apo E mRNA abundance and biosynthesis. Hepatic apo B-100 synthesis was reduced by over 75% in Mg-deficient animals despite an increase in hepatic apo B mRNA abundance. However, this change in hepatic apo B gene expression was not associated with alterations in posttranscriptional apo B mRNA editing. These changes in apolipoprotein gene expression were associated with increased hepatic lipogenesis, despite the observation that net triacylglycerol secretion rates were not different between Mg-deficient and control animals. Taken together, the data demonstrate a complex pattern of alterations in hepatic lipid metabolism and apolipoprotein gene expression in the Mg-deficient rat and suggest a defect in the catabolism rather than secretion of TGLRP as the major factor underlying the altered plasma lipoprotein profile.

Inflammatory response following acute magnesium deficiency in the rat.

The importance of inflammatory processes in the pathology of Mg deficiency has been recently reconsidered but the sequence of events leading to the inflammatory response remains unclear. Thus, the purpose of the present study was to characterize more precisely the acute phase response following Mg deficiency in the rat. Weaning male Wistar rats were pair-fed either a Mg-deficient or a control diet for either 4 or 8 days. The characteristic allergy-like crisis of Mg-deficient rats was accompanied by a blood leukocyte response and changes in leukocytes subpopulations. A significant increase in interleukin-6 (IL-6) plasma level was observed in Mg-deficient rats compared to rats fed a control diet. The inflammatory process was accompanied by an increase in plasma levels of acute phase proteins. The concentrations of alpha2-macroglobulin and alpha1-acid glycoprotein in the plasma of Mg-deficient rats were higher than in control rats. This was accompanied in the liver by an increase in the level of mRNA coding for these proteins. Moreover, Mg-deficient rats showed a significant increase in plasma fibrinogen and a significant decrease in albumin concentrations. Macrophages found in greater number in the peritoneal cavity of Mg-deficient rats were activated endogenously and appeared to be primed for superoxide production following phorbol myristate acetate stimulation. A high plasma level of IL-6 could be detected as early as day 4 for the Mg-deficient diet. Substance P does not appear to be the initiator of inflammation since IL-6 increase was observed without plasma elevation of this neuropeptide. The fact that the inflammatory response was an early consequence of Mg deficiency suggests that reduced extracellular Mg might be responsible for the activated state of immune cells.

Study of magnesium bioavailability from ten organic and inorganic Mg salts in Mg-depleted rats using a stable isotope approach.

Literature data on the bioavailability of various Mg forms provide scarce information on the best Mg salt to be used in animal and human supplementation. This study aimed to investigate the bioavailability of different forms of Mg in rats using Mg stable isotopes. Eighty male Wistar rats aged 6 weeks were fed a semi-purified Mg-depleted diet for three weeks. The rats were then randomised into ten groups and received, for two more weeks, the same diet repleted with Mg (550 mg Mg/kg) as: oxide, chloride, sulphate, carbonate, acetate, pidolate, citrate, gluconate, lactate or aspartate. After 10 days of Mg-repleted diet, the rats received orally 1.8 mg of an enriched 26Mg. Faeces and urine were then collected for 4 consecutive days. Isotope ratios in faeces and urine were determined. The Mg absorption values obtained varied from 50% to 67%. Organic Mg salts were slightly more available than inorganic Mg salts. Mg gluconate exhibited the highest Mg bioavailability of the ten Mg salts studied. Urinary 26Mg excretion varied from 0.20 mg to 0.33 mg, and feeding with the organic pidolate, citrate, gluconate and aspartate salts resulted in higher urinary 26Mg excretion than with inorganic salts. Ultimately, 26Mg retention was higher in the rats receiving the organic salts such as gluconate, lactate and aspartate than in those receiving the inorganic salts. Taken together, these results indicate that 26Mg is sufficiently bioavailable from the ten different Mg salts studied in the present experiment, although Mg gluconate exhibited the highest bioavailability under these experimental conditions.

Erythrocyte magnesium influx and efflux in solid tumor bearing mice.

Mg metabolism is modified in tumors and tumor-bearing organisms. In particular cancer patients often display elevated erythrocyte Mg levels. For a better understanding of the increased erythrocyte Mg content, we attempted to determine Mg fluxes in erythrocytes from tumor-bearing mice by Mg stable isotopes, using a method developed in our laboratory. To characterize the animal Mg status, blood and tissue Mg levels and hematological parameters were assayed. Results showed that in tumor-bearing mice total erythrocyte Mg was about 46% higher than in controls, whereas plasma and tissues Mg levels were not modified; red blood cells and hemoglobin as well as hematocrits were significantly decreased, while mean corpuscular volume and mean corpuscular hemoglobin were slightly but significantly increased in tumor-bearing mice compared to controls (by 3% and 4%, respectively), a picture corresponding to a normochromic, slightly macrocytic anemia. Erythrocyte Mg efflux was about 20% higher (404 + 59 versus 330 + 45 micromol/L, respectively, p < 0.05) in tumor-bearing mice compared to controls, whereas influx was not significantly modified (130 + 11 versus 122 + 19 micromol/L, respectively). Our data therefore exclude that the increased Mg content observed in erythrocytes of tumor-bearing mice is due to decrease of Mg efflux, or to an increase of Mg influx. On the other hand, the increased Mg content observed in erythrocytes of tumor-bearing mice could simply result from an increase of young Mg-enriched erythrocytes produced by the enhanced erythropoiesis which follows tumor-induced anemia.

Hepatic apolipoprotein B synthesis in copper-deficient rats.

The present study was designed to examine if induction of apolipoprotein B synthesis is associated with hypercholesterolemia in copper-deficient rats. This hypercholesterolemia mainly resides in an increase in the HDL-1 and LDL and is associated with a significant increase in plasma apoB concentration. Liver apoB mRNA levels were not significantly modified in deficient animals as compared to control rats. Studies on liver apolipoprotein synthesis indicated that apoB100 synthesis was increased in deficient animals whereas apoB48 synthesis was unchanged. Thus, it appears that the increase in apoB synthesis in the liver of copper-deficient rats occurs at the posttranscriptional level. The selective increase in apoB100 synthesis indicates the possible impact of this deficiency on the editing of apoB. An increase in apoB100 synthesis by the liver in copper-deficient rats may significantly contribute to the increase in plasma concentration of LDL.

Functional alterations in sarcoplasmic reticulum membranes of magnesium-deficient rat skeletal muscle as consequences of free radical-mediated process.

Free radical-induced physiopathologies are generally thought to be mediated by membrane injuries. Using a pro-oxidant model induced by dietary magnesium deficiency, we have recently shown that skeletal muscle lesions occurred with a rise in the calcium level and enhanced free radical production. In this study, we investigated the physicochemical and biochemical properties of sarcoplasmic reticulum membranes isolated from hind limb muscles of weanling male rats pair fed magnesium-deficient or control diets for 12 d. The calcium-induced calcium efflux from preloaded vesicles was increased in membranes isolated from Mg-deficient rat muscle. In agreement with this latter observation, we demonstrated increased ryanodine binding affinity of the calcium channel. The Ca2(+)-ATPase activity of the pump was shown to be reduced. The viscosity state of the membranes, assessed by 1,6-diphenyl-1,3,5-hexatriene fluorescence anisotropy, was significantly increased in Mg-deficient membranes. Moreover, these membranes demonstrated an increased content of protein carbonyls as compared with controls. These functional as well as structural changes are closed to those described in sarcoplasmic reticulum membranes oxidatively modified in vitro. Together, these data fitted well with the concept that free radical-induced membrane damages resulting in calcium overload may be at the origin of skeletal muscle lesion during Mg-deficiency.

Apolipoprotein B gene expression in rat intestine. The effect of dietary fiber.

The effect of the dietary fiber on apo B mRNA level was studied in the intestine of rats that were fed either fiber-free or high-fiber (30% sugar-beet fiber) low-fat diets for 3 weeks. The fiber diet studied does not affect jejunal apo B mRNA levels but decreases the level of ileal apo B mRNA. In the rat cecum, in both fiber-free and fiber groups, we failed to detect the apo B mRNA. The test fiber diet feeding markedly increased fecal bile salt and cholesterol excretions. We suggest that dietary fiber can modify apo B expression in the intestine. The increased fecal bile salt excretion might be involved in such a modification.

The effect of copper supplementation on red blood cell oxidizability and plasma antioxidants in middle-aged healthy volunteers.

A multicenter European study (FoodCue) was undertaken to provide data on the significance of increased dietary copper as a pro-oxidant or antioxidant in vivo. The present work describes the effect of Cu supplementation on (2,2'-azo-bis(2-amidinopropane) hydrochloride (AAPH)-induced red blood cell oxidation in middle-aged people. Double-blinded copper supplementation was achieved in 26 healthy volunteers (50-70 years) with pills containing 3 mg CuSO(4), 3 mg Cu glycine chelate (CuG) and 6 mg CuG. Each 6 week supplementation period was preceded and followed by 6 weeks of washout (WO) on placebo. The results show significant increases in time necessary to achieve 50% hemolysis (LT(50)) after 3CuSO(4) and 6CuG compared with values after WO periods. Cu supplementation did not increase the levels of (Cu,Zn)SOD activity in red blood cells. Resistance to hemolysis was significantly and positively correlated (r =.30, p <.01) with alpha- and beta-carotene content in the plasma. Together, these data suggest that intake of copper as high as 7 mg/d has no pro-oxidant activity and may rather result in protection of red blood cells against oxidation. The decreased oxidizability of red blood cells did not result from increased (Cu,Zn)SOD activity and may occur through other mechanisms such as changes in membrane antioxidant content.

Plasma levels of 8-epiPGF2alpha, an in vivo marker of oxidative stress, are not affected by aging or Alzheimer's disease.

Free radicals are likely involved in the aging process and there is a growing body of evidence that free radical damage to cellular function is associated with a number of age-related diseases such as atherosclerosis, cancer, and neurologic disorders. The present study was designed to evaluate in a healthy population the evolution with age of 8-epiPGF2alpha plasma levels, a recently proposed marker of in vivo lipid peroxidation. Moreover we investigated this marker of oxidative stress in patients with Alzheimer's disease (AD), an age-related neurodegenerative disorder in the development of which free radicals have been involved. Our results show that in the healthy population studied, despite decreased antioxidant defenses with increasing age as monitored by antioxidant capacity measurement, plasma 8-epiPGF2alpha levels were not correlated with age. Moreover, we have demonstrated that AD patients presented no modification of plasma 8-epiPGF2alpha level and no major alteration of the antioxidant status. In conclusion, the measurement of plasma 8-epiPGF2alpha did not allow us to detect alterations in oxidative stress with aging or in AD.

Copper supplementation in humans does not affect the susceptibility of low density lipoprotein to in vitro induced oxidation (FOODCUE project).

The oxidative modification of low-density lipoprotein cholesterol (LDL) has been implicated in the pathogenesis of atherosclerosis. Copper (Cu) is essential for antioxidant enzymes in vivo and animal studies show that Cu deficiency is accompanied by increased atherogenesis and LDL susceptibility to oxidation. Nevertheless, Cu has been proposed as a pro-oxidant in vivo and is routinely used to induce lipid peroxidation in vitro. Given the dual role of Cu as an in vivo antioxidant and an in vitro pro-oxidant, a multicenter European study (FOODCUE) was instigated to provide data on the biological effects of increased dietary Cu. Four centers, Northern Ireland (coordinator), England, Denmark, and France, using different experimental protocols, examined the effect of Cu supplementation (3 or 6 mg/d) on top of normal Cu dietary intakes or Cu-controlled diets (0.7/1.6/6.0 mg/d), on Cu-mediated and peroxynitrite-initiated LDL oxidation in apparently healthy volunteers. Each center coordinated its own supplementation regimen and all samples were subsequently transported to Northern Ireland where lipid peroxidation analysis was completed. The results from all centers showed that dietary Cu supplementation had no effect on Cu- or peroxynitrite-induced LDL susceptibility to oxidation. These data show that high intakes (up to 6 mg Cu) for extended periods do not promote LDL susceptibility to in vitro-induced oxidation.

Hepatic apolipoprotein and LDL receptor gene expression in the genetically hypercholesterolemic (RICO) rat.

The present study was designed to examine apolipoprotein and LDL receptor gene expression in genetically hypercholesterolemic RICO rats. In the plasma of RICO rats as compared to SW (control) rats, the hypercholesterolemia (+41%) was associated with a significant increase in plasma apo B (+23%) and apo E (+68%) concentrations. Study of apolipoprotein synthesis in the liver has shown that this increase in plasma apo B and apo E concentrations was not associated with modification in their synthesis and mRNA levels. Study of apo E mRNA level in various tissues has shown only the modification in adrenals in RICO as compared to SW rats (2.7-fold increase). Study of LDL binding, LDL receptor mass and LDL receptor mRNA level in the liver of RICO and SW rats has shown no significant differences between these two strains. EDTA-resistant binding of rat LDL was lower in RICO than in SW rats suggesting that binding sites others than the LDL receptor are present in lesser amount in this hypercholesterolemic strain.

Role of spinal NMDA receptors, protein kinase C and nitric oxide synthase in the hyperalgesia induced by magnesium deficiency in rats.

1. Magnesium (Mg)-deficient rats develop a mechanical hyperalgesia which is reversed by a N-Methyl-D-Aspartate (NMDA) receptor antagonist. Given that functioning of this receptor-channel is modulated by Mg, we wondered whether facilitated activation of NMDA receptors in Mg deficiency state may in turn trigger a cascade of specific intracellular events present in persistent pain. Hence, we tested several antagonists of NMDA and non-NMDA receptors as well as compounds interfering with the functioning of intracellular second messengers for effects on hyperalgesia in Mg-deficient rats. 2. Hyperalgesic Mg-deficient rats were administered intrathecally (10 microl) or intraperitoneally with different antagonists. After drug injection, pain sensitivity was evaluated by assessing the vocalization threshold in response to a mechanical stimulus (paw pressure test) over 2 h. 3. Intrathecal administration of MgSO4 (1.6, 3.2, 4.8, 6.6 micromol) as well as NMDA receptor antagonists such as MK-801 (0.6, 6.0, 60 nmol), AP-5 (10.2, 40.6, 162.3 nmol) and DCKA (0.97, 9.7, 97 nmol) dose-dependently reversed the hyperalgesia. Chelerythrine chloride, a protein kinase C (PKC) inhibitor (1, 10.4, 104.2 nmol) and 7-NI, a specific nitric oxide (NO) synthase inhibitor (37.5, 75, 150 micromol x kg(-1), i.p.) induced an anti-hyperalgesic effect in a dose-dependent manner. SR-140333 (0.15, 1.5, 15 nmol) and SR-48968 (0.17, 1.7, 17 nmol), antagonists of neurokinin receptors, produced a significant, but moderate, increase in vocalization threshold. 4. These results demonstrate that Mg-deficiency induces a sensitization of nociceptive pathways in the spinal cord which involves NMDA and non-NMDA receptors. Furthermore, the data is consistent with an active role of PKC, NO and, to a lesser extent substance P in the intracellular mechanisms leading to hyperalgesia.

Magnesium metabolism in mice selected for high and low erythrocyte magnesium levels.

A genetic control of blood magnesium (Mg) levels has been suggested. To investigate the mechanisms and the biologic significance of this genetic regulation, a mouse model, ie, mice selected for low magnesium level (MGL) and high magnesium level (MGH), was developed. The purpose of this study was to explore the Mg status and Mg metabolism in female MGL and MGH mice. We observed that MGL mice had reduced total and ionized plasma Mg, lower erythrocyte Mg, lower tibia, and kidney Mg levels. In contrast, total urinary Mg and (25)Mg levels were significantly higher in MGL mice. MGL mice had smaller total Mg exchangeable pool masses compared with MGH, and fractional transport rates of Mg (exchange constant) were different. In vitro (25)Mg enrichments in erythrocytes from MGL mice were significantly lower. Moreover, Mg efflux from erythrocytes was significantly higher in MGL. In conclusion, this work demonstrates that MGL mice present lower body stores of Mg than MGH mice and lower body Mg retention. This is confirmed at a cellular level by a lower enrichment of (25)Mg in erythrocytes. The lower retention of Mg by MGL erythrocyte in comparison to MGH appears to be partly due to a higher Mg efflux in MGL erythrocyte. It can be hypothesized that a genetic factor that modulates Na(+)/Mg(2+) exchanger activity may be important in the regulation of Mg metabolism. Further investigations on the mechanisms responsible for differences in Mg retention between MGL and MGH mice could contribute to a better understanding of the genetic regulation of cellular Mg.

Compartmental analysis of magnesium kinetics in Mg-sufficient and Mg-deficient rats.

In this study, we determined magnesium kinetic values in normal rats using stable-isotope techniques. Additionally, we calculated the mass of the exchangeable pools of Mg in Mg-deficient rats to determine whether it can be used as a marker of Mg status. Rats were fed either a control diet (1,000 mg Mg/kg) or a Mg-deficient diet (60 mg Mg/kg). After 2 weeks on the experimental diets, each rat received an intravenous injection of 26Mg. The plasma Mg disappearance curve over the next 7 days was used to measure the mass and fractional transport rate of 3 rapidly exchanging Mg metabolic pools. In control rats, the mass of pool 1 (1.37 mg) was half that of pool 2 (2.46 mg), and pool 3 (47.7 mg) accounted for greater than 90% of exchangeable Mg. In Mg-deficient rats, we observed a significant decrease in the size of the 3 exchangeable pools of Mg (0.36, 0.72, and 20.2 mg, respectively) relative to the control rats. Furthermore, the fractional transport rate of Mg from pool 1 to pool 3 in Mg-deficient rats was 3 times the rate in the control rats, and the rate of irreversible loss from pool 1 was lower in Mg-deficient rats. In summary, this study allows us to establish Mg kinetic data in Mg-sufficient and Mg-deficient rats. The present experiment supports the conclusion that the isotopic test identifies animals with severe Mg deficiency.

Magnesium deficiency induces an hyperalgesia reversed by the NMDA receptor antagonist MK801.

The aim of this study was to determine the changes of the nociceptive thresholds in response to an acute mechanical stimulus (paw pressure) in magnesium (Mg)-deficient rats, and the involvement of the NMDA receptor in these changes. Changes in vocalization thresholds was determined after 7 days of feeding with a Mg-depleted diet. Compared with the control group, Mg-deficient rats showed a significant decrease in the vocalization thresholds (-35.8 +/- 2.5%, p < 0.001) reflecting hyperalgesia. In Mg-deprived rats, three doses (0.06, 0.12 and 0.24 mg/kg s.c.) of dizocilpine (MK801), a non-competitive NMDA receptor antagonist, significantly reversed the hyperalgesia in a dose-dependent manner for at least 48 h. No effect of MK801 was observed in the control group. These data provide evidence that Mg deficiency could constitute a new model of hyperalgesia involving NMDA receptors.

Stability of brain content of magnesium in experimental hypomagnesemia.

Magnesium is important in cerebral function. If there is a deficiency and neurological symptoms accrue, we hypothesised that Mg2+ deficiency causes neurological symptoms by decreasing the level of Mg2+ in cerebral tissue. The content of magnesium was determined in 12 brain structures in magnesium-deficient rats. Experiments were carried out for 40 days in two groups of Wistar male rats made magnesium-deficient (MD) by a well-controlled diet (50 mg of Mg2+/kg of food), and a control group (CG) rats fed normal diet (1 g of Mg2+/kg of food). At the end of the 40 days, the clinical signs of hypomagnesemia were sought in the MD rats and Mg2+ concentration levels were measured in the blood and brain. The results showed variable distribution of Mg2+ in the different brain structures, both in CG and MD rats; in the MD rats there is an important stability of global Mg2+ content of the brain. Although the global values for Mg2+ in the brain did not decline in MD rats, there was a significant decrease in Mg2+ in the brainstem. We conclude that the brain is able to maintain a stable concentration of Mg2+ during chronic hypomagnesemia, but its topographic variations could account for some of neurological signs accompanying this condition.

Divergence in plasmatic and urinary isoprostane levels in type 2 diabetes.

BACKGROUND: Oxidative stress is currently suggested as a mechanism underlying diabetes. The present study was designed to evaluate isoprostane levels in plasma and in urine in type 2 diabetic patients, and to compare them to other currently used biomarkers of oxidative stress. METHODS: The work was performed in a control group (n = 10) and in a type 2 diabetic group (n = 10). Besides the traditional biochemical parameters, we evaluated the plasma and urine levels of isoprostanes and malondialdehyde (MDA) as markers of oxidative stress. RESULTS: We found increased plasma and urine MDA in the diabetic patients and almost significantly decreased plasma vitamin E. Urinary isoprostane levels in diabetic patients were increased but they presented a strong tendency to a decrease in plasma isoprostanes. It is therefore suggested that, in the studied diabetic patients, although the production of isoprostanes in the body was increased (as other plasma oxidative stress biomarkers were altered) it did not lead to an increase in plasma isoprostane levels. It could be hypothesised that this results from an increased elimination of this metabolite and therefore an increased excretion in urine. CONCLUSION: Our results showed that the measurement of same oxidative stress biomarker, isoprostane, in two different biologic fluids, plasma and urine, led to divergent results and emphasised the importance to measure a biomarker both in the circulation fluid (plasma) and in the elimination fluid (urine), to have a general idea of what is occurring in the organism.