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1.
The challenges of diagnosis and management of Gitelman syndrome.
Urwin, S, Willows, J, Sayer, JA
Clinical endocrinology. 2020;(1):3-10
Abstract
Gitelman syndrome is an inherited tubulopathy characterized by renal salt wasting from the distal convoluted tubule. Defects in the sodium chloride cotransporter (encoded by SLC12A3) underlie this autosomal recessive condition. This article focuses on the specific challenges of diagnosing and treating Gitelman syndrome, with use of an illustrative case report. Symptoms relate to decreased serum potassium and magnesium levels, which include muscle weakness, tetany, fatigue and palpitations. Sudden cardiac deaths have been reported. Making a diagnosis may be difficult given its rarity but is important. A knowledge of the serum and urine biochemical picture is vital to distinguish it from a broad differential diagnosis, and application of genetic testing can resolve difficult cases. There is a group of Gitelman syndrome heterozygous carriers that experience symptoms and electrolyte disturbance and these patients should be managed in a similar way, though here genetic investigations become key in securing a difficult diagnosis. Potassium and magnesium replacement is the cornerstone of treatment, though practically this can be hard for patients to manage and often does not fully relieve symptoms even when serum levels are normalized. Challenges arise due to the lack of randomized controlled trials focussing on treatment of this rare disease; hence, clinicians endorse strategies in line with correction of the underlying pathophysiology such as sodium loading or pharmacological treatments, which seem to help some patients. Focussed dietary advice and knowing the best tolerated preparations of potassium and magnesium medications are useful tools for the physician, as well as an awareness of the specific burdens that this patient group face in order to signpost appropriate support.
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2.
Magnesium and Pain.
Shin, HJ, Na, HS, Do, SH
Nutrients. 2020;(8)
Abstract
In terms of antinociceptive action, the main mode of action of magnesium involves its antagonist action at the N-methyl-d-aspartate (NMDA) receptor, which prevents central sensitization and attenuates preexisting pain hypersensitivity. Given the pivotal function of NMDA receptors in pain transduction, magnesium has been investigated in a variety of pain conditions. The oral and parenteral administration of magnesium via the intravenous, intrathecal, or epidural route may alleviate pain and perioperative anesthetic and analgesic requirements. These beneficial effects of magnesium therapy have also been reported in patients with neuropathic pain, such as malignancy-related neurologic symptoms, diabetic neuropathy, postherpetic neuralgia, and chemotherapy-induced peripheral neuropathy. In addition, magnesium treatment is reportedly able to alleviate fibromyalgia, dysmenorrhea, headaches, and acute migraine attacks. Although magnesium plays an evolving role in pain management, better understanding of the mechanism underlying its antinociceptive action and additional clinical studies is required to clarify its role as an adjuvant analgesic.
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3.
The Association between Excess Body Mass and Disturbances in Somatic Mineral Levels.
Banach, W, Nitschke, K, Krajewska, N, Mongiałło, W, Matuszak, O, Muszyński, J, Skrypnik, D
International journal of molecular sciences. 2020;(19)
Abstract
BACKGROUND Obesity and excess body weight are significant epidemiological issues, not only because they are costly to treat, but also because they are among the leading causes of death worldwide. In 2016, an estimated 40% of the global population was overweight, reflecting the importance of the issue. Obesity is linked to metabolism malfunction and concomitantly with altered mineral levels in the body. In this paper, we review alterations in somatic levels of iron, calcium, magnesium, copper, iodine, chromium, selenium, and zinc in relation to excess body mass. METHODOLOGY An electronic literature search was performed using PubMed. Our search covered original English research articles published over the past five years, culminating in 63 papers included for study. RESULTS The reviewed papers presented correlation between obesity and hypomagnesemia and hypozincemia. They also indicated that patients with excess body mass present increased body copper levels. Studies have similarly indicated that obesity appears to be associated with lower selenium levels in both blood and urine, which may be correlated with the decline and weakening of defenses against oxidative stress. It has been found that decreased level of chromium is connected with metabolic syndrome. Chromium supplementation influences body mass, but the effect of the supplementation depends on the chemical form of the chromium. It is hypothesized that obesity poses a risk of iodine deficiency and iodine absorption may be disrupted by increased fat intake in obese women. A range of studies have suggested that obesity is correlated with iron deficiency. On the other hand, some reports have indicated that excess body mass may coexist with iron excess. The relation between obesity and body iron level requires further investigation. Calcium signaling seems to be disturbed in obesity, due to the increased production of reactive oxygen species and low level of fast troponin isoform responsible for mediating calcium sensitivity of muscle relaxation. Correlation between excess body mass and calcium levels needs further research. CONCLUSIONS Excess body mass is associated with alterations in mineral levels in the body, in particular hypomagnesemia and decreased selenium (Se) and zinc (Zn) levels. Chromium (Cr) deficiency is associated with metabolic syndrome. Obese patients are at risk of iodine deficiency. Excess body mass is associated with elevated levels of copper (Cu). Data on the association between obesity and iron (Fe) levels are contradictory. Obesity coexists with disturbed calcium (Ca) signaling pathways. The association between obesity and body Ca levels has not been investigated in detail.
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4.
Magnesium and calcium ions: roles in bacterial cell attachment and biofilm structure maturation.
Wang, T, Flint, S, Palmer, J
Biofouling. 2019;(9):959-974
Abstract
The ubiquitous divalent cations magnesium and calcium are important nutrients required by bacteria for growth and cell maintenance. Multi-faceted roles are shown both in bacterial initial attachment and biofilm maturation. The effects of calcium and magnesium can be highlighted in physio-chemical interactions, gene regulation and bio-macromolecular structural modification, which lead to either promotion or inhibition of biofilms. This review outlines recent research addressing phenotypic changes and mechanisms undertaken by calcium and magnesium in affecting bacterial biofilm formation.
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5.
The Problematic Use of Dietary Reference Intakes to Assess Magnesium Status and Clinical Importance.
Nielsen, FH
Biological trace element research. 2019;(1):52-59
Abstract
Determination of the public health concern about magnesium (Mg) in health and disease has been confounded by the lack of a practical measure of status. This has resulted in a lack of consistency in associating Mg deficiency with specific pathological conditions. Some attempts at associating Mg with a chronic disease have used the Dietary Reference Intakes (DRIs) as a status assessment measure. Use of current DRIs for Mg is problematic because recent evidence suggests that they should be updated and based on body weight. An evidence-based suggested Estimated Average Requirement (EAR) and Recommended Dietary Allowance (RDA) for a 70-kg individual is 175 and 250 mg/day, respectively. However, numerous dietary and physiological factors can affect the need for Mg and thus affect the use of the current or suggested new DRIs to assess Mg status. Calcium intakes above normal requirements can decrease Mg balance and exacerbate signs of Mg deficiency. Mg deficiency apparently occurs often in obesity because of increased need to counteract the inflammatory stress induced by adipose tissue dysfunction. Deficiency in anti-oxidant nutrients such as vitamin E and selenium can exacerbate a response to low dietary Mg indicated by increased oxidative stress which can lead to chronic disease. Dietary modifiers of Mg absorption and excretion affect balance and thus the need for Mg. Factors decreasing Mg balance include low dietary protein and non-fermentable fiber, while factors that can increase balance include fructose and fermentable fiber and fructose-containing oligosaccharides. Use of the DRIs to assess the Mg status of a population or group needs to consider their physiological characteristics and dietary habits and be aware that the DRIs may need updating. The DRIs only can be considered a component of a toolbox that presently includes serum Mg concentration and the daily urinary Mg excretion to assess the Mg status of an individual.
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6.
Current Structural Knowledge on the CNNM Family of Magnesium Transport Mediators.
Giménez-Mascarell, P, González-Recio, I, Fernández-Rodríguez, C, Oyenarte, I, Müller, D, Martínez-Chantar, ML, Martínez-Cruz, LA
International journal of molecular sciences. 2019;(5)
Abstract
The cyclin and cystathionine β-synthase (CBS) domain magnesium transport mediators, CNNMs, are key players in maintaining the homeostasis of magnesium in different organs. The human family includes four members, whose impaired activity causes diseases such as Jalili Syndrome or Familial Hypomagnesemia, but is also linked to neuropathologic disorders, altered blood pressure, and infertility. Recent findings demonstrated that CNNMs are associated with the highly oncogenic phosphatases of the regenerating liver to promote tumor growth and metastasis, which has attracted renewed focus on their potential exploitation as targets for cancer treatment. However, the exact function of CNNMs remains unclear and is subject to debate, proposed as either direct transporters, sensors, or homeostatic factors. This review gathers the current structural knowledge on the CNNM family, highlighting similarities and differences with the closely related structural partners such as the bacterial Mg2+/Co2+ efflux protein CorC and the Mg2+ channel MgtE.
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7.
Serum magnesium level and hematoma expansion in patients with intracerebral hemorrhage.
Jafari, M, Di Napoli, M, Lattanzi, S, Mayer, SA, Bachour, S, Bershad, EM, Damani, R, Datta, YH, Divani, AA
Journal of the neurological sciences. 2019;:39-44
Abstract
Spontaneous intracerebral hemorrhage (ICH) is a devastating subtype of stroke that results in significant rates of mortality and morbidities. The initial hematoma volume, hematoma expansion (HE), blood pressure (BP), and coagulopathy are considered strong predictors of clinical outcomes and mortality. Low serum magnesium (Mg++) levels have been shown to be associated with larger initial hematoma and greater HE. Coagulopathy, platelet dysfunction, high BP, and increased inflammatory response might form the mechanistic link between low serum Mg++ levels, larger hematoma size and greater HE. However, randomized clinical trials administering intravenous Mg++ have shown no benefit over placebo in ICH patients. The confounding effect of hypocalcemia and a delay in Mg++ trafficking across the blood-brain barrier might explain the futile results for intravenous Mg++ therapy. In the current review, we will discuss the evidence regarding the possible role of low serum Mg++ level on HE in acute ICH.
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8.
ATP, Mg2+, Nuclear Phase Separation, and Genome Accessibility.
Wright, RHG, Le Dily, F, Beato, M
Trends in biochemical sciences. 2019;(7):565-574
Abstract
Misregulation of the processes controlling eukaryotic gene expression can result in disease. Gene expression is influenced by the surrounding chromatin; hence the nuclear environment is also of vital importance. Recently, understanding of chromatin hierarchical folding has increased together with the discovery of membrane-less organelles which are distinct, dynamic liquid droplets that merge and expand within the nucleus. These 'sieve'-like regions may compartmentalize and separate functionally distinct regions of chromatin. This article aims to discuss recent studies on nuclear phase within the context of poly(ADP-ribose), ATP, and Mg2+ levels, and we propose a combinatorial complex role for these molecules in phase separation and genome regulation. We also discuss the implications of this process for gene regulation and discuss possible strategies to test this.
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9.
Magnesium matrix nanocomposites for orthopedic applications: A review from mechanical, corrosion, and biological perspectives.
Shahin, M, Munir, K, Wen, C, Li, Y
Acta biomaterialia. 2019;:1-19
Abstract
Magnesium (Mg) and some of its alloys have attracted extensive interests for biomedical applications as they exhibit biodegradability and low elastic modulus that is closer to natural bones than the currently used metallic implant materials such as titanium (Ti) and its alloys, stainless steels, and cobalt-chromium (Co-Cr) alloys. However, the rapid degradation of Mg alloys and loss of their mechanical integrity before sufficient bone healing impede their clinical application. Our literature review shows that magnesium matrix nanocomposites (MMNCs) reinforced with nanoparticles possess enhanced strength, high corrosion resistance, and good biocompatibility. This article provides a detailed analysis of the effects of nanoparticle reinforcements on the mechanical properties, corrosion behavior, and biocompatibility of MMNCs as promising biodegradable implant materials. The governing equations to quantitatively predict the mechanical properties and underlying synergistic strengthening mechanisms in MMNCs are elucidated. The potential, recent advances, challenges and future research directions in relation to nanoparticles reinforced MMNCs are highlighted. STATEMENT OF SIGNIFICANCE Critically reviewing magnesium metal matrix nanocomposites (MMNCs) for the biomedical application. Clear definitions of strengthening mechanisms using reinforcement particle in the magnesium matrix, as there were controversial in governing equations of strengthening parameters. Providing better understanding of the effect of particle size, volume fraction, interfacial bonding, and uniform dispersion of reinforcement particles on MMNCs.
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10.
Hypomagnesemia and hypermagnesemia.
Van Laecke, S
Acta clinica Belgica. 2019;(1):41-47
Abstract
Introduction:Magnesium is an essential element which also has pleiotropic effects in humans. Recent studies have altered our interpretation of a disturbed magnesium balance both leading to hypomagnesemia and hypermagnesemia. Methods: a narrative review of their clinical relevance is presented. Results: Although magnesium balance is strictly controlled by the kidneys, hypomagnesemia is fairly common, especially in people with comorbid conditions. Increased renal magnesium wasting, often aggravated by drugs, is commonly found in conditions associated with unfavorable outcomes such as diabetes mellitus and sepsis. Depending on its severity hypomagnesemia may reveal itself by potentially hazardous neurological and cardiovascular symptoms. Intravenous magnesium is an evidence-based treatment of torsades de pointes and preeclampsia irrespective of the presence of preexisting hypomagnesemia. Magnesium deficiency and/or hypomagnesemia has been linked to cardiovascular disease, vascular calcification and endothelial function both in vitro and in vivo. (Severe) hypermagnesemia can be life-threatening but is almost exclusively observed in patients with substantially decreased kidney function associated with high magnesium intake through supplements or magnesium containing cathartics or antacids. Conclusion:It remains unclear whether mild hypermagnesemia confers survival benefit especially in subjects with decreased kidney function. The role of oral magnesium supplementation of chronic mild asymptomatic hypomagnesemia also merits further exploration through interventional studies in various study populations.