Sodium/Glucose Cotransporter 2 Inhibitors and Magnesium Homeostasis: A Review.

Magnesium (Mg2+), also known as "the forgotten ion," is the second most abundant intracellular cation and is essential in a broad range of intracellular physiological and biochemical reactions. Its deficiency, hypomagnesemia (Mg2+<1.8mg/dL), is a prevalent condition and routinely poses challenges in its management in clinical practice. Sodium/glucose cotransporter 2 (SGLT2) inhibitors have emerged as a new class of drugs with treating hypomagnesemia as their unique extraglycemic benefit. The beneficial effect of SGLT2 inhibitors on magnesium balance in patients with diabetes with or without hypomagnesemia has been noted as a class effect in recent meta-analysis data from randomized clinical trials. Some reports have demonstrated their role in treating refractory hypomagnesemia in patients with or without diabetes. Moreover, studies on animal models have attempted to illustrate the effect of SGLT2 inhibitors on Mg2+homeostasis. In this review, we discuss the current evidence and possible pathophysiological mechanisms, and we provide directions for further research. We conclude by suggesting the effect of SGLT2 inhibitors on Mg2+homeostasis is a class effect, with certain patients gaining significant benefits. Further studies are needed to examine whether SGLT2 inhibitors can become a desperately needed novel class of medicines in treating hypomagnesemia.

Impact of magnesium infusion rate on serum magnesium level after magnesium replacement in hospitalized surgical patients with hypomagnesemia: A 11-year retrospective cohort study

Background: Hypomagnesemia is common for surgical patients and often requires intravenous (IV) magnesium replacement. Due to the renal handling mechanism of magnesium, prolonging the duration of an IV magnesium infusion has been postulated to improve magnesium retention by reducing the renal excretion of magnesium. However, the evidence supporting this hypothesis is limited. Objective: To determine the change in serum magnesium level after IV magnesium replacement from baseline compared between prolonged (infusion rate < 0.5 g/h) and short infusions (infusion rate < 0.5 g/h) in hospitalized surgical patients. Methods: Medical records of surgical patients with hypomagnesemia who received IV magnesium replacement for three consecutive days and admitted to a university hospital between 2012 and 2022 were reviewed. Patients were separated by the replacement rate into two cohorts: prolonged infusion and short infusion. The primary outcome was a change in serum magnesium per gram administered from the baseline. The secondary outcome was the percentage of patients who achieved an optimal serum magnesium level after IV magnesium replacement. Results: 114 participants were enrolled in the study. The short infusion cohort showed a significantly greater increase in serum magnesium change per gram administered from baseline (0.07 mg/dL/g) compared to the prolonged infusion cohort (0.05 mg/dL/g) (p = 0.04). The difference of serum magnesium level between the two cohorts was 0.013 mg/dL/g of Mg. The percentage of patients who achieved the optimal serum magnesium level after IV magnesium replacement was not different between the two cohorts (prolonged infusion 66.7% vs. short infusion 70.2%; p = 0.84). The change in serum magnesium levels was influenced by renal function and the timing of serum magnesium level measurement after IV magnesium replacement (AU)

[Indications for magnesium supplementation an example of alcoholism]. / O pokazaniyakh k naznacheniyu preparatov magniya na primere alkogolizma.

Supplementation of various substances (metabolites, microelements, vitamins) is sometimes recommended without sufficient indications. To decide whether a supplementation is needed, the question should be answered whether there is a deficiency, and if there is, if it can be compensated by diet. Magnesium (Mg) deficiency has been associated with cardiovascular diseases, certain metabolic and neuropsychiatric disorders. Hypomagnesemia is above-average in alcoholism; however, alcoholics should not be a priori assumed to have Mg deficiency. Mild depletion does not necessarily require supplementation. The parenteral route is mandatory in severe Mg deficiency. Hypermagnesemia may result from excessive supplementation. Intravenous infusions of Mg-containing solutions have sometimes been used in alcoholics without sufficient indications. In conditions of suboptimal procedural quality assurance, endovascular and other invasive manipulations can lead to transmission of viral hepatitis. It has been suggested to include Mg in routine blood ionograms. The contents of Mg in different foodstuffs should be taken into account in patients at risk of Mg deficiency to better manage the diet.

Magnesium as an Important Factor in the Pathogenesis and Treatment of Migraine-From Theory to Practice.

So far, no coherent and convincing theory has been developed to fully explain the pathogenesis of migraine, although many researchers and experts emphasize its association with spreading cortical depression, oxidative stress, vascular changes, nervous excitement, neurotransmitter release, and electrolyte disturbances. The contribution of magnesium deficiency to the induction of cortical depression or abnormal glutamatergic neurotransmission is a likely mechanism of the magnesium-migraine relationship. Hence, there is interest in various methods of assessing magnesium ion deficiency and attempts to study the relationship of its intra- and extracellular levels with the induction of migraine attacks. At the same time, many clinicians believe that magnesium supplementation in the right dose and form can be a treatment to prevent migraine attacks, especially in those patients who have identified contraindications to standard medications or their different preferences. However, there are no reliable publications confirming the role of magnesium deficiency in the diet as a factor causing migraine attacks. It also seems interesting to deepen the research on the administration of high doses of magnesium intravenously during migraine attacks. The aim of the study was to discuss the probable mechanisms of correlation of magnesium deficiency with migraine, as well as to present the current clinical proposals for the use of various magnesium preparations in complementary or substitute pharmacotherapy of migraine. The summary of the results of research and clinical observations to date gives hope of finding a trigger for migraine attacks (especially migraine with aura), which may turn out to be easy to diagnose and eliminate with pharmacological and dietary supplementation.

The emerging role of magnesium in CKD.

Increasing evidence has suggested a clinical relevance of magnesium in the context of vascular calcification and mortality among patients with CKD. Hypomagnesemia is not rare among non-dialysis CKD patients despite their decreased glomerular filtration rates; the prevalence rate was about 15% even in CKD stages G4 and G5. Among several potential causes of hypomagnesemia, tubular dysfunction/interstitial fibrosis may play a pivotal role in the development of hypomagnesemia in CKD, which impairs tubular magnesium reabsorption. Magnesium deficiency may, in turn, be involved in the progression of CKD. An in vitro study has revealed that magnesium deficiency aggravates tubular cell death and inflammation induced by phosphate load. In a cohort study of patients with CKD, low-serum magnesium levels enhanced the risk of end-stage kidney disease related to high-serum phosphate levels, suggesting a close relationship between magnesium deficiency and phosphate toxicity. More importantly, magnesium has a potent capacity to inhibit the calcification of vascular smooth muscle cells induced by phosphate. A randomized trial has shown the efficacy of oral magnesium oxide in retarding the progression of coronary artery calcification among non-dialysis CKD patients. Thus, magnesium might provide better cardiovascular prognosis; indeed, hemodialysis patients with mild hypermagnesemia exhibited the lowest mortality rate. Further randomized trials are needed to assess the impact of magnesium in terms of hard clinical outcomes among CKD patients.

Lung squamous cell carcinoma with severe hypomagnesemia due to cisplatin plus gemcitabine in combination with necitumumab therapy: A case report.

A 72-year-old man, diagnosed with advanced lung squamous cell carcinoma, was administered of cisplatin plus gemcitabine with necitumumab, a human monoclonal antibody that binds to the epidermal growth factor receptor (EGFR), as a sixth-line treatment. Tumor shrinkage was observed, but asymptomatic grade 4 hypomagnesemia occurred on day 8 of the second cycle. He received magnesium replenishment and hypomagnesemia recovered on day 40, but tumor progression was observed during the period of magnesium correction. Hypomagnesemia is known as a major adverse event of treatment with anti-EGFR antibodies, but there have been no case reports of severe hypomagnesemia or its clinical course.

Long-term Clinical Follow-up of Patients with Familial Hypomagnesemia with Secondary Hypocalcemia

Objective: Familial hypomagnesemia with secondary hypocalcemia (HSH) is an autosomal recessive disease caused by a mutation in the transient receptor potential melastatin 6 (TRPM6) gene and is characterized by selective magnesium malabsorption. Affected cases are usually diagnosed during infancy and usually present with seizures due to hypocalcemia and hypomagnesemia. Irreversible neurological deficits and arrhythmias can be observed without appropriate treatment. The aim was to evaluate the long-term follow-up of patients with genetically confirmed HSH. Methods: A total of six patients with HSH, two of whom were siblings, were included. Age at diagnosis, clinical, laboratory and follow-up data on admission were recorded. All 39 exons of the TRPM6 gene and flanking exon-intron junctions from genomic DNA were amplified and sequenced in all cases. Results: The median (range) follow-up duration was 12.1 (7.6-21.7) years. All cases were diagnosed in infancy. Four different mutations, three of which had not been previously reported, were detected in the TRPM6 gene. Treatment compliance was good and there were no severe complications in the long-term follow-up of cases. However, mental retardation, specific learning difficulty and attention deficit/hyperactive disorder were observed as comorbidities. Conclusion: Of the four different TRPM6 mutations in this small cohort, three had not been previously reported. The long-term prognosis of HSH appears to be good, given early diagnosis and good treatment compliance. This long-term follow-up and prognostic data and the three novel mutations will contribute to the published evidence concerning this rare condition, HSH, and it is hoped will prevent negative outcomes.

Magnesium in Obesity, Metabolic Syndrome, and Type 2 Diabetes.

Magnesium (Mg2+) deficiency is probably the most underestimated electrolyte imbalance in Western countries. It is frequent in obese patients, subjects with type-2 diabetes and metabolic syndrome, both in adulthood and in childhood. This narrative review aims to offer insights into the pathophysiological mechanisms linking Mg2+ deficiency with obesity and the risk of developing metabolic syndrome and type 2 diabetes. Literature highlights critical issues about the treatment of Mg2+ deficiency, such as the lack of a clear definition of Mg2+ nutritional status, the use of different Mg2+ salts and dosage and the different duration of the Mg2+ supplementation. Despite the lack of agreement, an appropriate dietary pattern, including the right intake of Mg2+, improves metabolic syndrome by reducing blood pressure, hyperglycemia, and hypertriglyceridemia. This occurs through the modulation of gene expression and proteomic profile as well as through a positive influence on the composition of the intestinal microbiota and the metabolism of vitamins B1 and D.

Treatment Difficulties in Hypomagnesemia Secondary to the Transient Receptor Potential Melastatin 6 Gene: A Case Report with Novel Mutation

Hypomagnesemia is a rare cause of seizures in childhood but should be kept in mind in recurrent and intractable seizures and hypocalcemia in communities where consanguineous marriages are common. Familial hypomagnesemia with secondary hypocalcemia is a rare genetic cause of hypomagnesemia, due to variants in the transient receptor potential melastatin 6 (TRPM6) genes. Here, a three year-old boy with a novel variant in this gene and had difficulties with enteral hypomagnesemia treatment is presented. He had recurrent seizures since two years of age and was diagnosed with epilepsy and treated with multiple antiepileptic drugs. Subsequently, he was diagnosed with rickets due to severe hypocalcemia at another center. The patient was hypotonic and neurodevelopmentally poor. The most prominent laboratory finding was of hypomagnesemia with secondary hypocalcemia. The genetic analysis revealed a novel variant in the TRPM6 gene. After parental treatment of intravenous magnesium (Mg2+) sulfate and calcium, the treatment was switched to enteral Mg2+ medications, due to persistent hypomagnesemia and the gastrointestinal side-effects, different oral preparations were used. The patient was stable on an oral maintenance dose of Mg2+ oxide with borderline blood Mg2+ levels and resolution of hypocalcemia. Hypomagnesemia is one of the causes of hypocalcemia. Enteral replacement is the key treatment but the treatment should be individualized for each patient. Normalization of hypomagnesemia is not always easy and should not be the aim of the treatment.

SARS-CoV-2: influence of phosphate and magnesium, moderated by vitamin D, on energy (ATP) metabolism and on severity of COVID-19.

The use of vitamin D to reduce the severity of COVID-19 complications is receiving considerable attention, backed by encouraging data. Its purported mode of action is as an immune modulator. Vitamin D, however, also affects the metabolism of phosphate and Mg, which may well play a critical role in SARS-CoV-2 pathogenesis. SARS-CoV-2 may induce a cytokine storm that drains ATP whose regeneration requires phosphate and Mg. These minerals, however, are often deficient in conditions that predispose people to severe COVID-19, including older age (especially males), diabetes, obesity, and usage of diuretics. Symptoms observed in severe COVID-19 also fit well with those seen in classical hypophosphatemia and hypomagnesemia, such as thrombocytopenia, coagulopathy, dysfunction of liver and kidneys, neurologic disturbances, immunodeficiency, failure of heart and lungs, delayed weaning from a respirator, cardiac arrhythmia, seizures, and, finally, multiorgan failure. Deficiencies of phosphate and Mg can be amplified by kidney problems commonly observed in patients with COVID-19 resulting in their wastage into urine. Available data show that phosphate and Mg are deficient in COVID-19, with phosphate showing a remarkable correlation with its severity. In one experiment, patients with COVID-19 were supplemented with a cocktail of vitamin D3, Mg, and vitamin B12, with very encouraging results. We, thus, argue that patients with COVID-19 should be monitored and treated for phosphate and Mg deficiencies, ideally already in the early phases of infection. Supplementation of phosphate and Mg combined with vitamin D could also be implemented as a preventative strategy in populations at risk.

[Pathogenetic aspects of magnesium deficiency in connective tissue dysplasia syndrome].

The problem of connective tissue dysplasia is currently becoming particularly relevant because of significant increase of individuals with characteristic abnormalities in the structure of connective tissue. The lack of some micronutrients, arising during ontogenesis in the organism, can determine a high risk of worsening connective tissue homeostasis. Recently, the decisive role of magnesium deficiency in the progression of this disease has been demonstrated. The aim of the study was to substantiate the need for magnesium diet therapy in individuals with connective tissue dysplasia basing on the study of the pathogenetic significance of magnesium deficiency in this pathology. Material and methods. The electronic resources of the portals PubMed-NCBI, MEDLINE, the Scientific Electronic Library eLIBRARY.RU, CyberLeninka and the Google Academy were used. Results and discussion. The analysis of the obtained data made it possible to identify fundamentally new provisions on the main mechanisms of the magnesium influence on the metabolic state of all components of connective tissue. It was proved that magnesium deficiency is a predictor of worsening connective tissue homeostasis, increasing in the number of dysplastic symptoms and their severity. This pathogenetically justifies prescribing a balanced diet to patients with connective tissue dysplasia, including products rich in magnesium, taking into account its recommended daily intake, depending on age of patients. Conclusion. Adequate daily intake of magnesium will increase the mechanical properties and functionality of the connective tissue, and should be recommended for patients with connective tissue dysplasia to prevent the development of complications, maintain the quality of life and improve the prognosis for this disease.

[Magnesium: Relevance for general practitioners - a position paper of the Society for Magnesium Research e. V.] / Magnesium: Bedeutung für die hausärztliche Praxis ­ Positionspapier der Gesellschaft für Magnesium-Forschung e. V.

Magnesium deficiency is to be expected in the population and particularly among risk groups. Magnesium deficiency can cause numerous symptoms, is per se pathological and thus requires treatment. Diagnostics is based on clinical symptoms in conjunction with anamnestic criteria and laboratory parameters. Insufficient magnesium supply is associated with an increased risk for many diseases, e. g. metabolic syndrome, type 2 diabetes and cardiovascular diseases. Magnesium deficiency often appears as comorbidity and may exacerbate diseases. Physicians should pay more attention to magnesium in order to avoid deficits as a cause for multiple symptoms and risk factor for diseases. Optimisation of magnesium status may make an important contribution to the prevention of diseases. Oral magnesium therapy is safe and cost effective.

Headaches and Magnesium: Mechanisms, Bioavailability, Therapeutic Efficacy and Potential Advantage of Magnesium Pidolate.

Magnesium deficiency may occur for several reasons, such as inadequate intake or increased gastrointestinal or renal loss. A large body of literature suggests a relationship between magnesium deficiency and mild and moderate tension-type headaches and migraines. A number of double-blind randomized placebo-controlled trials have shown that magnesium is efficacious in relieving headaches and have led to the recommendation of oral magnesium for headache relief in several national and international guidelines. Among several magnesium salts available to treat magnesium deficiency, magnesium pidolate may have high bioavailability and good penetration at the intracellular level. Here, we discuss the cellular and molecular effects of magnesium deficiency in the brain and the clinical evidence supporting the use of magnesium for the treatment of headaches and migraines.

[Atrial fibrillation and QT prolongation due to proton pump inhibitor-induced hypomagnesemia]. / Fibrillation atriale et allongement du QT sur hypomagnésémie secondaire à un traitement par inhibiteur de la pompe à protons.

Proton pump inhibitors are widely prescribed but their long-term use can expose patients to adverse effects. Some of these are not very well known, including hypomagnesemia. Hypomagnesemia can be manifested by cardiac complications such as supraventricular arrhythmia or QT prolongation, increasing the risk of torsade de pointe. We present a case of atrial fibrillation triggered by severe hypomagnesemia secondary to proton pump inhibitor use and exacerbated by thiazide diuretic treatment. Conversion to sinus rhythm showed a prolonged corrected QT interval. We approach the pathophysiology and the electrophysiologic effects of hypomagnesemia.

[Hypomagnesemia in newborns with hypoxic ischemic encephalopathy and whole-body hypothermia]. / Hipomagnesemia en recién nacidos con encefalopatía hipóxico isquémica en hipotermia corporal total.

INTRODUCTION: In newborns with the diagnosis of hypoxic-ischemic encephalopathy (HIE) treated with hypother mia, metabolic alterations are observed, which are associated with neurological prognosis. Hypo magnesemia has been reported frequently in the literature in these patients, but it is not measured or corrected in all neonatal healthcare centers. OBJECTIVE: To evaluate the frequency of hypomag nesemia and hypocalcemia in newborns with HIE treated with whole-body hypothermia and to evaluate the response to the magnesium sulfate administration. PATIENTS AND METHOD: Prospective, observational and descriptive study in hospitalized newborns with the diagnosis of HIE and trea ted with whole-body hypothermia between the years 2016 and 2017. Serial blood measurement of magnesemia (Mg) and calcemia (Ca) was performed. When presenting an Mg level < 1.8 mg/dl, supplementation with magnesium sulfate was administered to maintain levels between 1.9 and 2.8 mg/dl. The frecuency of hypomagnesemia, hypocalcemia and clinical evolution was registered. A descriptive statistical analysis was performed, with central tendency measures. RESULTS: Sixteen ca ses were included, 13 of them presented hypomagnesemia (81.3%), with early-onset (6-36 hours of life), which was normalized with magnesium sulfate treatment, receiving a second dose 4 patients. Six of 16 patients presented hypocalcemia (37.5 %). CONCLUSIONS: Hypomagnesemia is frequent (80%), similar to that described in the literature, and should be controlled and corrected early, given its physiological role, in the same way that calcium is controlled.

The Coordination Chemistry of Bio-Relevant Ligands and Their Magnesium Complexes.

The coordination chemistry of magnesium (Mg2+) was extensively explored. More recently; magnesium; which plays a role in over 80% of metabolic functions and governs over 350 enzymatic processes; is becoming increasingly linked to chronic disease-predominantly due to magnesium deficiency (hypomagnesemia). Supplemental dietary magnesium utilizing biorelevant chelate ligands is a proven method for counteracting hypomagnesemia. However, the coordination chemistry of such bio-relevant magnesium complexes is yet to be extensively explored or elucidated. It is the aim of this review to comprehensively describe what is currently known about common bio-relevant magnesium complexes from the perspective of coordination chemistry.

Magnesium supplementation and preeclampsia in low-income pregnant women - a randomized double-blind clinical trial.

BACKGROUND: Preeclampsia is the major cause of maternal morbidity and mortality in developing countries. Magnesium sulfate is considered first-line therapy against eclampsia and magnesium deficiency in pregnancy has been associated with unfavourable perinatal outcomes. However there are doubts if magnesium supplementation during pregnancy can previne preeclampsia especially in population with high nutritional risk. This trial aims to verify the effect of oral magnesium supplmentation on preeclampsia incidence in low income pregnant women. METHODS: This randomized, double-blind, placebo-controlled trial investigated the effect of oral magnesium citrate supplementation for preeclampsia in low-income Brazilian pregnant women, i.e. annual per capita income of US$ 1025 or less. Participants were admitted to the study with gestational age between 12 and 20 weeks. Magnesium serum level was measured pre-randomization and participants with hypermagnesemia were excluded. After randomizationg participants received magnesium citrate capsule (300 mg magnesium citrate) or a daily placebo capsule, until delivery. Intent-to-treat analysis was performed. RESULTS: A total of 416 pregnant women were screened and 318 enrolled according to the inclusion criteria; 159 for each arm. Twenty-eight pregnant women were lost to follow-up. 55/290 (18.9%) of pregnant women developed preeclampsia; 26/143 (18.1%) in magnesium group and 29/147 (19.7%) in the control group; OR 0.90 (CI 95% 0.48-1.69), p = 0.747. No cases of eclampsia were registered. CONCLUSION: Oral magnesium supplementation did not reduce preeclampsia incidence in low-income and low-risk pregnant women. TRIAL REGISTRATION: Registered at ClinicalTrials.gov (Identifier NCT02032186), December 19, 2013.

Normalization of magnesium deficiency attenuated mechanical allodynia, depressive-like behaviors, and memory deficits associated with cyclophosphamide-induced cystitis by inhibiting TNF-α/NF-κB signaling in female rats.

BACKGROUND: Bladder-related pain symptoms in patients with bladder pain syndrome/interstitial cystitis (BPS/IC) are often accompanied by depression and memory deficits. Magnesium deficiency contributes to neuroinflammation and is associated with pain, depression, and memory deficits. Neuroinflammation is involved in the mechanical allodynia of cyclophosphamide (CYP)-induced cystitis. Magnesium-L-Threonate (L-TAMS) supplementation can attenuate neuroinflammation. This study aimed to determine whether and how L-TAMS influences mechanical allodynia and accompanying depressive symptoms and memory deficits in CYP-induced cystitis. METHODS: Injection of CYP (50 mg/kg, intraperitoneally, every 3 days for 3 doses) was used to establish a rat model of BPS/IC. L-TAMS was administered in drinking water (604 mg·kg-1·day-1). Mechanical allodynia in the lower abdomen was assessed with von Frey filaments using the up-down method. Forced swim test (FST) and sucrose preference test (SPT) were used to measure depressive-like behaviors. Novel object recognition test (NORT) was used to detect short-term memory function. Concentrations of Mg2+ in serum and cerebrospinal fluid (CSF) were measured by calmagite chronometry. Western blot and immunofluorescence staining measured the expression of tumor necrosis factor-α/nuclear factor-κB (TNF-α/NF-κB), interleukin-1ß (IL-1ß), and N-methyl-D-aspartate receptor type 2B subunit (NR2B) of the N-methyl-D-aspartate receptor in the L6-S1 spinal dorsal horn (SDH) and hippocampus. RESULTS: Free Mg2+ was reduced in the serum and CSF of the CYP-induced cystitis rats on days 8, 12, and 20 after the first CYP injection. Magnesium deficiency in the serum and CSF correlated with the mechanical withdrawal threshold, depressive-like behaviors, and short-term memory deficits (STMD). Oral application of L-TAMS prevented magnesium deficiency and attenuated mechanical allodynia (n = 14) and normalized depressive-like behaviors (n = 10) and STMD (n = 10). The upregulation of TNF-α/NF-κB signaling and IL-1ß in the L6-S1 SDH or hippocampus was reversed by L-TAMS. The change in NR2B expression in the SDH and hippocampus in the cystitis model was normalized by L-TAMS. CONCLUSIONS: Normalization of magnesium deficiency by L-TAMS attenuated mechanical allodynia, depressive-like behaviors, and STMD in the CYP-induced cystitis model via inhibition of TNF-α/NF-κВ signaling and normalization of NR2B expression. Our study provides evidence that L-TAMS may have therapeutic value for treating pain and comorbid depression or memory deficits in BPS/IC patients.

Hipomagnesemia en recién nacidos con encefalopatía hipóxico isquémica en hipotermia corporal total / Hypomagnesemia in newborns with hypoxic ischemic encephalopathy and whole-body hypothermia

Resumen: Introducción: En recién nacidos (RN) con encefalopatía hipóxico isquémica (EHI) en hipotermia se describen alte raciones metabólicas que se asocian a pronóstico neurológico. La hipomagnesemia ha sido reportada en la literatura, pero no es medida ni corregida en todos los centros de atención neonatal. Objeti vo: Evaluar la frecuencia de hipomagnesemia e hipocalcemia en RN con EHI en tratamiento con hipotermia corporal total y evaluar la respuesta al aporte de sulfato de magnesio. Pacientes y Méto do: Estudio prospectivo, observational y descriptivo en RN con EHI sometidos a hipotermia corporal total, hospitalizados entre los años 2016-2017. Se realizó medición seriada en sangre de magnesemia (Mg) y calcemia (Ca). Con Mg menor o igual de 1,8 mg/dl se administró suplemento como sulfato de Mg para mantener niveles entre 1,9 y 2,8 mg/dl. Se describió la frecuencia de hipomagnesemia e hipocalcemia y su presentación en el tiempo. Se realizó registro prospectivo de evolución clínica. Se hizo un análisis estadístico descriptivo, con medidas de tendencia central. Resultados: Se incluyeron 16 pacientes. Presentaron hipomagnesemia 13/16 (81,3%), la que fue precoz (6-36 h de vida), nor malizándose con aporte de sulfato de magnesio, requiriendo 2a dosis 4 de ellos. Presentaron hipo- calcemia 6/16 (37,5%). Conclusiones: La hipomagnesemia es frecuente (80%), similar a lo descrito en la literatura. Dado su importancia fisiológica debe controlarse y corregirse, de igual manera que el calcio.

Abstract: Introduction: In newborns with the diagnosis of hypoxic-ischemic encephalopathy (HIE) treated with hypother mia, metabolic alterations are observed, which are associated with neurological prognosis. Hypo magnesemia has been reported frequently in the literature in these patients, but it is not measured or corrected in all neonatal healthcare centers. Objective: To evaluate the frequency of hypomag nesemia and hypocalcemia in newborns with HIE treated with whole-body hypothermia and to evaluate the response to the magnesium sulfate administration. Patients and Method: Prospective, observational and descriptive study in hospitalized newborns with the diagnosis of HIE and trea ted with whole-body hypothermia between the years 2016 and 2017. Serial blood measurement of magnesemia (Mg) and calcemia (Ca) was performed. When presenting an Mg level < 1.8 mg/dl, supplementation with magnesium sulfate was administered to maintain levels between 1.9 and 2.8 mg/dl. The frecuency of hypomagnesemia, hypocalcemia and clinical evolution was registered. A descriptive statistical analysis was performed, with central tendency measures. Results: Sixteen ca ses were included, 13 of them presented hypomagnesemia (81.3%), with early-onset (6-36 hours of life), which was normalized with magnesium sulfate treatment, receiving a second dose 4 patients. Six of 16 patients presented hypocalcemia (37.5 %). Conclusions: Hypomagnesemia is frequent (80%), similar to that described in the literature, and should be controlled and corrected early, given its physiological role, in the same way that calcium is controlled.

Effect of oral administration of Magnesium N-Acetyltaurinate on synaptic plasticity in rodents.

While magnesium deficiency is common and its effects well known on the nervous system, very few studies has been dedicated to the efficiency of magnesium replacement treatments on the central nervous system. In this study, the effects of oral administration of magnesium salts of acetyl-taurinate on the central manifestations of magnesium deficiency is described in rats submitted to low-magnesium diet and in a murine model of Alzheimer's disease. We tested the effect of ATA Mg®, a salt combining magnesium and taurine, on the hippocampus, a critical component of cognition. 7-10-month-old rats were submitted to dietary magnesium deprivation for 64 days. The effect of magnesium deficiency was studied in ex vivo hippocampal slices. We showed that long-term potentiation of synaptic transmission in the hippocampus was significantly improved by the oral administration of ATA Mg® at a dose of 50 mg/kg bw/day, which is comparable to the recommended dose in humans. 7-10-months-old transgenic APP/PS1 mice, a model of Alzheimer's disease, received ATA Mg® during 24 days at a dose of 700 mg/kg bw/day which is the dose used in previous studies demonstrating the positive effect of magnesium supplementation. We showed that long-term potentiation was significantly improved in the treated mice. Moreover, the expression of NR2B subunit of NMDA receptors, known to be involved in synaptic plasticity, was significantly increased in the hippocampus. These results demonstrate the ability of ATA Mg® to improve the symptoms related to chronic magnesium deficiency at the level of the hippocampus suggesting its bioavailability and effectiveness in reaching the central nervous system.