Mechanism of zinc stress on magnesium deficiency in rice plants (Oryza sativa L.): Insights from magnesium isotopes.

Magnesium (Mg) and zinc (Zn) are essential nutrients for plants. Mg deficiency often occurs in rice plants grown in Zn-polluted soil. However, the mechanism for this correlation is unclear. Here, we performed culture experiments on rice plants (Oryza sativa L.) and used Mg isotopes to investigate mechanisms of Zn stress on plant Mg deficiency. Our results show that excess Zn can significantly reduce the uptake of Mg in rice tissues. The root displays positive Δ26Mgplant-nutrient values (δ26Mgplant-δ26Mgnutrient; 1.90 ‰ to 2.06 ‰), which suggests that Mg enters the root cells mainly via Mg-specific transporters rather than non-selective diffusion. The decreased Δ26Mgplant-nutrient values with increasing Zn supply can be explained by the competition between Zn and Mg, both of which combine with same transporters in roots. In contrast, the shoots (stem and leaf) display much lower δ26Mg values than roots, which suggests that the transport of Mg from roots to aerial biomass is mainly via free Mg ions, during which Zn cannot competitively inhibit the movement of Mg. Our study suggests that the Mg deficiency in rice plants can be caused by high Zn-levels in soils and highlights the necessity of soil Zn-remediation in solving Mg deficiency problems in rice plants.

A Rare Case of Neonatal Hypomagnesemia with Secondary Hypocalcemia Caused by a Novel Homozygous TRPM6 Gene Variant.

BACKGROUND Familial hypomagnesemia with secondary hypocalcemia (HSH) is a rare autosomal recessive disorder (OMIM# 602014) caused by mutations in the gene encoding transient receptor potential melastatin 6 (TRPM6)) on chromosome 9q22, a channel involved in epithelial magnesium resorption. While a plethora of studies have delineated various clinical manifestations pertinent to this mutation, the literature is devoid of connections between TRPM6 mutations and bleeding diathesis, or sudden infant death syndrome (SIDS). This report presents a case of familial HSH associated with the novel homozygous TRPM6 gene variant c.5281C>G p. (Arg1761Gly) chr9: 77354845. CASE REPORT This report details a 26-day-old neonate, born full term with optimal Apgar scores, who experienced an abrupt emergence of apnea, cyanosis, bilateral nasal bleeding, and diminished alertness. Despite the neonate's initially unremarkable clinical birth indicators, a meticulous assessment unveiled a pronounced family history of SIDS, including a sibling previously diagnosed with hypomagnesemia. Laboratory examination of the infant demonstrated severe hypomagnesemia and hypocalcemia, conditions which were promptly ameliorated following intravenous administration of magnesium and calcium. Whole-exome sequencing identified a homozygous TRPM6 gene mutation c.5281C>G p. (Arg1761Gly) at chr9: 77354845. This gene is crucial for magnesium regulation. The mutation involves a cytosine-to-guanine shift, resulting in an arginine to glycine amino acid substitution at position 1761 of the TRPM6 protein. CONCLUSIONS This report has highlighted that infantile hypomagnesemia may be associated with symptoms and signs that can mimic infection, or it can present with seizures. Although familial HSH is a rare genetic disorder that can be identified by genetic testing, correction of hypomagnesemia is the most important and immediate clinical management strategy.

Leaf diffusional capacity largely contributes to the reduced photosynthesis in rice plants under magnesium deficiency.

Numerous studies have clarified the impacts of magnesium (Mg) on leaf photosynthesis from the perspectives of protein synthesis, enzymes activation and carbohydrate partitioning. However, it still remains largely unknown how stomatal and mesophyll conductances (gs and gm, respectively) are regulated by Mg. In the present study, leaf gas exchanges, leaf hydraulic parameters, leaf structural traits and cell wall composition were examined in rice plants grown under high and low Mg treatments to elucidate the impacts of Mg on gs and gm. Our results showed that reduction of leaf photosynthesis under Mg deficiency was mainly caused by the decreased gm, followed by reduced leaf biochemical capacity and gs, and leaf outside-xylem hydraulic conductance (Kox) was the major factor restricting gs under Mg deficiency. Moreover, increased leaf hemicellulose, lignin and pectin contents and decreased cell wall effective porosity were observed in low Mg plants relative to high Mg plants. These results suggest that Kox and cell wall composition play important roles in regulating gs and gm, respectively, in rice plants under Mg shortages.

Renal diseases that course with hypomagnesemia. Comments on a new hereditary hypomagnesemic tubulopathy.

Renal diseases associated with hypomagnesemia are a complex and diverse group of tubulopathies caused by mutations in genes encoding proteins that are expressed in the thick ascending limb of the loop of Henle and in the distal convoluted tubule. In this paper, we review the initial description, the clinical expressiveness and etiology of four of the first hypomagnesemic tubulopathies described: type 3 Bartter and Gitelman diseases, Autosomal recessive hypomagnesemia with secondary hypocalcemia and Familial hypomagnesemia with hypercalciuria and nephrocalcinosis. The basic biochemical patterns observed in renal tubular hypomagnesemias and the modalities of transport and interaction that occur between the transporters involved in the reabsorption of magnesium in the distal convoluted tubule are described below. Finally, the recent report of a new renal disease with hypomagnesemia, type 2 hypomagnesemia with secondary hypocalcemia caused by reduced TRPM7 channel activity is described.

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.

Enfermedades renales que cursan con hipomagnesemia. Comentarios acerca de una nueva tubulopatía hipomagnesémica de origen genético / Renal diseases that course with hypomagnesemia. Comments on a new hereditary hypomagnesemic tubulopathy

Las enfermedades renales que cursan con hipomagnesemia son un grupo complejo y variopinto de tubulopatías producidas por mutaciones en genes que codifican proteínas que se expresan en la rama gruesa ascendente del asa de Henle y en el túbulo contorneado distal. En el presente artículo revisamos la descripción inicial, la expresividad clínica y la etiología de cuatro de las primeras causas de tubulopatías hipomagnesémicas que se describieron: las enfermedades de Bartter tipo 3 y Gitelman, la hipomagnesemia con hipocalcemia secundaria autosómica recesiva y la hipomagnesemia familiar con hipercalciuria y nefrocalcinosis. A continuación, se describen los patrones bioquímicos básicos que se observan en las hipomagnesemias tubulares renales y las modalidades de transporte e interacción que concurren entre los transportadores implicados en la reabsorción de magnesio en el túbulo contorneado distal. Finalmente, se comunica la reciente descripción de una nueva tubulopatía hipomagnesémica, la hipomagnesemia con hipocalcemia secundaria tipo 2 causada por una reducción de la actividad del canal TRPM7 (AU)

Renal diseases associated with hypomagnesemia are a complex and diverse group of tubulopathies caused by mutations in genes encoding proteins that are expressed in the thick ascending limb of the loop of Henle and in the distal convoluted tubule. In this paper, we review the initial description, the clinical expressiveness and etiology of four of the first hypomagnesemic tubulopathies described: Type 3 Bartter and Gitelman diseases,Autosomal recessive hypomagnesemia with secondary hypocalcemia and Familial hypomagnesemia with hypercalciuria and nephrocalcinosis. The basic biochemical patterns observed in renal tubular hypomagnesemias and the modalities of transport and interaction that occur between the transporters involved in the reabsorption of magnesium in the distal convoluted tubule are described below. Finally, the recent report of a new renal disease with hypomagnesemia, Type 2 hypomagnesemia with secondary hypocalcemia caused by reduced TRPM7 channel activity is described (AU)

Rare cause of recurrent hypocalcaemia and functional hypoparathyroidism due to hypomagnesaemia caused by TRPM6 gene mutation.

Magnesium is essential for the functioning and release of parathyroid hormone. Therefore, its deficiency can present as functional hypoparathyroidism. This case report describes a rare inherited disorder called congenital hypomagnesaemia with secondary hypocalcaemia due to TRPM6 gene mutation. This disease clinically and biochemically mimics hypoparathyroidism. However, unlike hypoparathyroidism, it can be treated only by long-term oral magnesium supplements. The patient presented to us with recurrent hypocalcaemic convulsions. The laboratory picture in each admission was similar to that of hypoparathyroidism. However, the hypocalcaemia persisted, and it was noticed to be associated with persistent hypomagnesaemia. A defect in the tubular magnesium reabsorption was postulated and a genetic analysis of the patient was done, which revealed a TRPM6 mutation causing hypomagnesaemia by excessive renal excretion of magnesium. The child responded well to oral magnesium supplements and is currently developmentally appropriate for her age and thriving well.

Association of Magnesium Depletion Score with Congestive Heart Failure: Results from the NHANES 2007-2016.

The magnesium depletion score (MDS) is considered a new valuable and reliable predictor of body magnesium status. This study aimed to explore the association between MDS and congestive heart failure (CHF) among US adults. A total of 19,227 eligible participants from the 2007-2016 National Health and Nutrition Examination Survey were enrolled in this study and then divided into three groups according to the level of MDS (none to low: MDS=0-1, middle: MDS=2, high: MDS=3-5). Sample-weighted logistic regression models were applied to calculate odds ratios (ORs) and 95% confidence intervals (CIs) exploring the independent relationship between MDS and CHF. The estimated prevalence of CHF increased with the increasing level of MDS (none to low: 0.86%, middle: 4.06%, high: 13.52%; P < 0.001). Compared to those in the none-to-low group, participants in the middle and high groups were at significantly higher risk of CHF after adjusting for various covariates (model 3: OR=1.55, 95%CI: 1.05-2.30, P < 0.001; OR=3.20, 95%CI: 2.07-4.96, P < 0.001; respectively). Subgroup analyses indicated that adequate dietary magnesium intake could reduce the risk of CHF in participants who did not meet the recommended dietary allowance (RDA) for magnesium. Besides, there was an interaction between coronary artery disease and MDS on CHF (P for interaction < 0.001). These findings indicated that MDS, a novel indicator estimating magnesium deficiency, is associated with the risk of CHF in non-institutionalized US civilians. Participants whose dietary magnesium intake reaches the RDA might be at lower risk.

Improving diagnosis and treatment of hypomagnesemia.

Magnesium is one of the most abundant cations in the body and acts as a cofactor in more than 600 biochemical reactions. Hypomagnesemia is a highly prevalent condition, especially in subjects with comorbid conditions, but has received less attention than other electrolyte disturbances. This review will discuss magnesium physiology, absorption, storage, distribution across the body, and kidney excretion. After reviewing the regulation of magnesium homeostasis, we will focus on the etiology and clinical presentation of hypomagnesemia. The role of laboratory medicine in hypomagnesemia will be the main purpose of this review, and we will discuss the laboratory tests and different samples and methods for its measurement. Although free magnesium is physiologically active, total serum magnesium is the most commonly used measurement in laboratory medicine and is apt for clinical purposes; however, it is not appropriately used, and many patients with hypomagnesemia remain undiagnosed and not treated. Using information technologies, laboratory medicine can largely improve the diagnosis and treatment of hypomagnesemia through the design and establishment of automatic demand management and result management interventions by acting in the first and last steps of the laboratory cycle, test requests, and actions taken after test results, to unmask patients with hypomagnesemia and improve the number of patients undergoing treatment.

Hereditary hypomagnesemia with secondary hypocalcemia caused by a novel mutation in TRPM6 gene.

OBJECTIVES: Hereditary hypomagnesemia with secondary hypocalcemia (HSH), which results from variations in the transient receptor potential melastatin 6 (TRPM6) genes, is a rare hereditary cause of extremely low serum magnesium levels. We describe an infant with triggered seizures due to hypomagnesemia and a novel mutation in TRPM6 gene was identified. CASE PRESENTATION: A 10-month-old boy presented with multidrug resistant seizures, and axial hypotonia due to severe hypomagnesemia. Electroencephalography and neuroimaging of the patient was normal. He had a favorable outcome with magnesium supplement. In this study, the patient underwent clinical exome sequencing (CES) which detected a novel homozygous variant in the TRPM6 gene: NM_017662.5: c.5571-3C>G. After replacing his magnesium orally, he was free from seizures and had an encouraging outcome at the twelfth-month follow-up. CONCLUSIONS: HSH often presents with developmental issues, treatment-resistant seizures, and increased neuromuscular excitability. Untreated hypomagnesemia can potentially be fatal and severely impair cognitive function. Clinical suspicion is essential for early diagnosis and treatment.

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)

[Severe hypomagnesemia in a man with alcohol dependence: a forgotten electrolyte in a neglected population]. / Ernstig magnesiumtekort bij alcoholverslaving.

BACKGROUND: Symptoms of acute alcohol withdrawal like tremors, seizures and delirium are commonly treated with benzodiazepines and vitamins. When complaints are not reacting to this treatment, an alternative diagnosis must be considered. Although hypomagnesemia is present in at least 30 percent of the patients with alcohol dependence, it can provoke and maintain these complaints. CASE DESCRIPTION: We present a 43-year-old man with alcohol dependence, who shows neurological, muscular, and cardiac consequences of an undiagnosed hypomagnesemia. CONCLUSION: In daily clinical practice there is not enough attention for magnesium deficits, especially in patients with alcohol dependence. Serious complications can be prevented by recognizing and treating magnesium deficiency more adequately.

Magnesium-An Ion with Multiple Invaluable Actions, Often Insufficiently Supplied: From In Vitro to Clinical Research.

Magnesium (Mg) is a key ion for numerous metabolic processes, being a cofactor of over 600 enzymes involved in cell metabolism and multiple biological processes [...].

Role of magnesium-L-Threonate in alleviating skin/muscle incision and retraction induced mechanical allodynia and anxiodepressive-like behaviors in male rats.

Chronic postsurgical pain (CPSP) and its emotional comorbidities poses health burden to patients who have received the surgical treatment. However, its underlying mechanism remains unclear. Emerging studies indicate that magnesium deficiency is associated with neurological diseases, and magnesium supplement confers protection under these disease conditions. In this study, we examined the role and mechanism of magnesium deficiency in the pathology of surgery-induced allodynia and negative emotion using a rat model of skin/muscle incision and retraction (SMIR) and investigated the therapeutic effects of magnesium supplementation by oral magnesium-L-Threonate (L-TAMS) in SMIR-injured rats. In the SMIR model, rats developed mechanical allodynia and anxiodepressive-like behaviors. Further, SMIR caused microglia and astrocyte activation and enhanced expression of pro-inflammatory cytokine (TNF-α, IL-1ß and IL-6) in the anterior cingulate cortex (ACC). Importantly, magnesium ion (Mg2+) levels decreased in the serum and cerebrospinal fluid (CSF) of SMIR-injured rats, which exhibited high correlation with pain and emotion behavioral phenotypes in these rats. Repeated oral administration of L-TAMS increased serum and CSF levels of Mg2+ in SMIR-injured rats. Notably, L-TAMS administration reversed SMIR-induced mechanical allodynia and anxiodepressive-like behaviors but did not affect pain and emotional behaviors in sham rats. Moreover, L-TAMS administration suppressed SMIR-caused glial activation and proinflammatory cytokine expression in the ACC but had no such effect in sham rats. Together, our study demonstrates the contributing role of magnesium deficiency in the pathology of surgery-induced chronic pain and negative emotion. Moreover, we suggest that L-TAMS might be a novel approach to treat CPSP and its emotional comorbidities.

Hipomagnesemia secundaria a omeprazol / Hypomagnesaemia following omeprazole

La hipomagnesemia asociada al tratamiento crónico con inhibidores de la bomba de protones (IBP) es una entidad poco frecuente, aunque potencialmente grave. Su mecanismo continúa siendo desconocido. Cuando la magnesemia cae por debajo de 0,5 mEq/L, las manifestaciones clínicas neuromusculares y cardíacas pueden aparecer. En el momento agudo, la reposición precoz de magnesio y, en muchos casos, de otros iones como el calcio y el potasio, suele ser el tratamiento. Sin embargo, su normalización definitiva requiere, por lo general, la supresión del tratamiento con IBP.(AU)

Hypomagnesaemia associated with chronic treatment with Proton Pump Inhibitors (PPIs) is a rare entity, although potentially severe. Its mechanism remains unknown. When the magnesaemia falls below 0.5 mEq/L, neuromuscular and cardiac clinical manifestations may appear. At the acute stage, early replacement of magnesium and, in most cases, calcium and potassium, is usually the treatment. However, its definitive normalization requires the withdrawal of PPI treatment.(AU)

Magnesium Deficiency and Cardiometabolic Disease.

Magnesium (Mg2+) has many physiological functions within the body. These include important roles in maintaining cardiovascular functioning, where it contributes to the regulation of cardiac excitation-contraction coupling, endothelial functioning and haemostasis. The haemostatic roles of Mg2+ impact upon both the protein and cellular arms of coagulation. In this review, we examine how Mg2+ homeostasis is maintained within the body and highlight the various molecular roles attributed to Mg2+ in the cardiovascular system. In addition, we describe how nutritional and/or disease-associated magnesium deficiency, seen in some metabolic conditions, has the potential to influence cardiac and vascular outcomes. Finally, we also examine the potential for magnesium supplements to be employed in the prevention and treatment of cardiovascular disorders and in the management of cardiometabolic health.

Physiological and transcriptomic responses to magnesium deficiency in Neolamarckia Cadamba.

Magnesium (Mg2+) is a critical component of chlorophyll and enzymes involved in various physiological and biochemical processes essential for plant growth, biomass accumulation, and photosynthesis. Mg2+ deficiency (MgD) is common in hot and rainy subtropical areas due to its easy loss from soil. Neolamarckia cadamba, an important tropical tree in South Asia, faces severe effects of MgD, however, the responses of N. cadamba to MgD stress remain unclear. In here, effects of N. cadamba under MgD stress were investigated. The study revealed that MgD had lower plant biomass, fresh and dry weight, root length, root volume, and surface area compared to CK (normal Mg2+). As treatment time increased, the leaves began to yellow, and lesions appeared. Chlorophyll a, chlorophyll b, and total chlorophyll content, along with fluorescence-related parameters and leaf photosynthetic capacity, were significantly reduced in MgD stress compared to CK treatment. Transcriptome analysis showed that transporters as well as transcription factors (TFs) from MYC (v-myc avian myelocytomatosis viral oncogene homolog), MYB (v-myb avian myeloblastosis viral oncogene homolog), bHLH (basic helix-loop-helix) and WRKY families were upregulated in leaves at 10 d of MgD stress, indicating that magnesium signaling transduction might be activated to compensate MgD. In addition, genes including chlorophyll(ide) b reductase (NYC1/NOL) chlorophyll/bacteriochlorophyll synthase (G4) and 7-hydroxymethyl chlorophyll a reductase synthesizing (HCAR) chlorophyll a and chlorophyll b were down-regulated in leaves, while those scavenging reactive oxygen species (ROS) were mainly up-regulated at 10 d of MgD stress. These results shed light on underlying MgD in N. cadamba.

The Urinary Excretion of Magnesium as an Effective Magnesium Deficiency State Indicator: A Controlled Intervention Trial.

With the western influence in our diets, food consumption has changed, and our magnesium (Mg) intake is no longer optimal. Serum Mg (S-Mg) level is currently used as an indicator of Mg deficiency and is strictly regulated via compensatory mechanisms. It is believed that a 24-h urine collection can be used to evaluate potential Mg deficiency. This study aimed to assess whether Mg deficiency state as found in urine Mg (U-Mg) excretion and improving such deficiency with a diet that meets the Recommended Dietary Allowances (RDAs) of Mg for 15 d. Healthy Japanese women were recruited for Study 1 (n=22) and Study 2 (n=10). Study 1 was 1-d balance test, where fasting blood and 24-h urine samples were collected. Study 2 was 15-d diet load test, where fasting blood (days 1, 7, and 15) and 24-h urine (odd days) were collected. All test meals were made certain to have met the RDA for Mg for women in their 20s. In Studies 1 and 2, S-Mg was within the normal range. In Study 1, U-Mg excretion was 67.7±17.0 mg/d, with a large dispersion. In Study 2, U-Mg excretion on days 7 and 15 was significantly higher than on day 1, but have no significant differences in U-Mg excretion between days 7-15. U-Mg excretion can be a valuable indicator to evaluate Mg state. In young women, improvements in Mg deficient state were observed after 7-15 d of taking meals that met the RDAs of Mg.