Magnesium (Mg2+) Deficiency, Not Well-Recognized Non-Infectious Pandemic: Origin and Consequence of Chronic Inflammatory and Oxidative Stress-Associated Diseases.

Magnesium (Mg2+) is an essential mineral nutrient, necessary for many biochemical reactions in the human body, including energy metabolism, protein and DNA synthesis, maintenance of the electrical potential of nervous and cardiac tissues, control of blood glucose, and regulation of blood pressure. However, currently, the world population suffers from a severe problem because the consumption of Mg2+ in the diet is deficient and generalized in the populations. Mg2+ deficiency causes oxidative stress (OS) due to the increase in reactive oxygen species (ROS) that originate from mitochondrial dysfunction, activation of the renin-angiotensin-aldosterone system (RAAS), and abnormal regulation of calcium homeostasis. In addition, Mg2+ deficiency also causes inflammation by increasing the production of proinflammatory molecules such as interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha (TNF-α), which in turn can exacerbate the production of ROS. The combination of inflammation and OS induced by Mg2+ deficiency increases the risk of developing chronic diseases. This review describes Mg2+ deficiency, its complications, and its relationship with OS and chronic inflammatory diseases. In addition, the importance of increasing the intake of Mg2+ throughout the world is highlighted.

Antioxidant/anti-inflammatory effect of Mg2+ in coronavirus disease 2019 (COVID-19).

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), characterised by high levels of inflammation and oxidative stress (OS). Oxidative stress induces oxidative damage to lipids, proteins, and DNA, causing tissue damage. Both inflammation and OS contribute to multi-organ failure in severe cases. Magnesium (Mg2+ ) regulates many processes, including antioxidant and anti-inflammatory responses, as well as the proper functioning of other micronutrients such as vitamin D. In addition, Mg2+ participates as a second signalling messenger in the activation of T cells. Therefore, Mg2+ deficiency can cause immunodeficiency, exaggerated acute inflammatory response, decreased antioxidant response, and OS. Supplementation with Mg2+ has an anti-inflammatory response by reducing the levels of nuclear factor kappa B (NF-κB), interleukin (IL) -6, and tumor necrosis factor alpha. Furthermore, Mg2+ supplementation improves mitochondrial function and increases the antioxidant glutathione (GSH) content, reducing OS. Therefore, Mg2+ supplementation is a potential way to reduce inflammation and OS, strengthening the immune system to manage COVID-19. This narrative review will address Mg2+ deficiency associated with a worse disease prognosis, Mg2+ supplementation as a potent antioxidant and anti-inflammatory therapy during and after COVID-19 disease, and suggest that randomised controlled trials are indicated.

Gitelman syndrome, a rare cause of refractory hypokalemia. A case report / Símdrome de Gitelman, causa rara de hipopotasemia refractaria. Reporte de caso

Abstract Introduction: Gitelman syndrome is a rare hereditary primary renal tubular disorder, with a prevalence of approximately 1 to 10 cases per 40 000 people. It does not have specific symptoms, so its diagnosis depends on high clinical suspicion by the treating physical and a sequential approach to hypokalemia, especially in young patients. Thus, a diagnostic algorithm is proposed at the end of this report. Case presentation: A 23-year-old woman with a history of hospitalization due to hypokalemia presented to the emergency service with intermittent cramping in her lower limbs, which was exacerbated by gastrointestinal symptoms. Laboratory tests reported the following findings: metabolic alkalosis, elevated levels of potassium, magnesium, chloride and sodium in urine, and reduced levels of calcium in urine. Thus, potassium supplementation and eplerenone administration were started, obtaining the complete resolution of symptoms. At her last follow-up appointment, the patient was asymptomatic, and her serum electrolyte levels were normal. In addition, during her hospital stay and due to the high suspicion of Gitelman syndrome, a genetic study was performed, which reported a mutation of the SCL12A3 gene, confirming the diagnosis. Conclusion: The sequential approach to a patient with recurrent hypokalemia is very important to reach an accurate diagnosis among a wide range of differential diagnoses.

Resumen Introducción. El síndrome de Gitelman es un trastorno tubular renal primario hereditario poco frecuente, con una prevalencia aproximada de 1 a 10 casos por cada 40 000 personas; su sintomatologia es inespecífica, por lo que su diagnóstico depende de la alta sospecha clínica por parte del médico tratante y de un abordaje secuencial de la hipopotasemia, sobre todo en pacientes jóvenes, para lo cual se propone un algoritmo diagnóstico al final de este reporte. Presentación de caso. Mujer de 23 años con antecedente de hospitalización por hipopotasemia, quien consultó por calambres musculares intermitentes en miembros inferiores, los cuales se agudizaron debido a síntomas gastrointestinales. En los exámenes de laboratorio se reportaron los siguientes hallazgos: alcalosis metabólica, niveles elevados de potasio, magnesio, cloro y sodio en orina, y niveles reducidos de calcio en orina, por lo que se inició suplementación de potasio y manejo con eplerenona, obteniéndose resolución completa de los síntomas. En su último control, la paciente se encontraba asintomática y sus niveles séricos de electrolitos eran normales. Además, durante la hospitalización, y debido a la alta sospecha de síndrome de Gitelman, se solicitó estudio genético que reportó mutación del gen SCL12A3, confirmándose el diagnóstico. Conclusión. El abordaje secuencial de un paciente con hipopotasemia recurrente es de gran importancia para realizar un diagnóstico certero ante una amplia gama de diagnósticos diferenciales.

Características clínicas de la hipomagnesemia en pacientes adultos / Clinical characteristics of hypomagnesemia in adult patients

Introducción: Las causas de hipomagnesemia son diversas: disminución de la ingesta, redistribución o translocación de Mg extracelular al intracelular, pérdida gastrointestinal y pérdida renal. El objetivo fue determinar las características clínicas de la hipomagnesemia en pacientes internados en el Departamento de Medicina Interna del Hospital Nacional (Itauguá, Paraguay) en el periodo 2018 - 2019. Materiales y métodos: Se aplicó un diseño observacional, descriptivo, retrospectivo. Se incluyeron pacientes adultos con Mg sérico ≤ 1,5 mg/dL. Se midieron variables demográficas, manifestaciones clínicas neuromusculares, metabólicas y electrocardiográficas. La investigación fue aprobada por el Comité de Ética de la Universidad Nacional de Itapúa (Paraguay). Resultados: Se detectó hipomagnesemia en 8,2% de los pacientes. La edad media de los mismos fue 55 años y 53% eran del sexo masculino. Las comorbilidades más frecuentes fueron hipertensión arterial (63%), diabetes mellitus (30%) y enfermedad renal crónica (16%). La hipomagnesemia se presentó con vómitos (34%), diarreas (13%), uso de omeprazol (97%), furosemida (31%) y corticoides (24%). Los síntomas predominantes fueron ansiedad (9%) y espasmos musculares (8%). Las alteraciones electrocardiográficas comunes fueron fibrilación auricular (11%), trastornos de la repolarización (18%) y prolongación del complejo QRS (9%). Conclusión: La hipomagnesemia se detectó en 8,2% de los pacientes y se presentó con vómitos (34%), diarreas (13%), uso de omeprazol (97%), furosemida (31%) y corticoides (24%).

Introduction: The causes of hypomagnesemia are diverse: decreased intake, redistribution or translocation of extracellular to intracellular magnesium, gastrointestinal loss and kidney loss. The objective was to determine the clinical characteristics of hypomagnesemia in patients admitted to the Internal Medicine Department of the National Hospital (Itauguá, Paraguay) in the period 2018 - 2019. Materials and methods: We conducted an observational, descriptive, retrospective design. We included adult patients with serum Mg ≤ 1.5 mg / dL. We measured demographic variables, neuromuscular, metabolic and electrocardiographic clinical manifestations. The research was approved by the Ethics Committee of the National University of Itapúa (Paraguay). Results: Hypomagnesemia was detected in 8.2% of the patients. Their mean age was 55 years and 53% were male. The most frequent comorbidities were hypertension (63%), diabetes mellitus (30%) and chronic kidney disease (16%). Hypomagnesemia was presented with vomiting (34%), diarrhea (13%), and use of omeprazole (97%), furosemide (31%) and corticosteroids (24%). The predominant symptoms were anxiety (9%) and muscle spasms (8%). Common electrocardiographic abnormalities were atrial fibrillation (11%), repolarization disorders (18%) and prolongation of the QRS complex (9%). Conclusion: We detected hypomagnesemia in 8.2% of patients and was presented with vomiting (34%), diarrhea (13%), use of omeprazole (97%), furosemide (31%) and corticosteroids (24%).

Association between reduced serum levels of magnesium and the presence of poor glycemic control and complications in type 1 diabetes mellitus: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the association between reduced serum magnesium levels and poor glycemic control and/or complications in patients with type 1 diabetes mellitus through a systematic review and meta-analysis. METHODS: The articles were selected using the Medline/PubMed, Web of Science, Scopus and Scielo databases. Eligibility criteria were cross-sectional, cohort or case-control observational studies that assessed the association between reduced magnesium levels and poor glycemic control and/or complications in patients with type 1 diabetes mellitus. RESULTS: Nine articles were included in the systematic review and two in the meta-analysis, all articles being cross-sectional. Among the seven studies that were designed to evaluate glycemic control, five showed an association between reduced levels of magnesium and poor glycemic control, and these findings were corroborated by the meta-analysis. Among the two studies in which dyslipidemia was evaluated, both showed higher levels of triglycerides, total cholesterol and LDL cholesterol, and lower levels of HDL cholesterol in patients with lower levels of magnesium as compared to those with higher magnesium levels. The three studies that evaluated diabetes kidney disease and the two studies that evaluated diabetic retinopathy found divergent results. CONCLUSION: There is an association between reduced levels of magnesium and poor glycemic control in patients with type 1 diabetes mellitus, however, this needs further studies.

Severe magnesium deficiency compromises systemic bone mineral density and aggravates inflammatory bone resorption.

We sought to evaluate the effects of magnesium (Mg) intake deficiency on bone metabolism in rats with induced periodontal disease (PD). Holtzman rats were randomly divided into two groups: Control - animals fed a standard diet and test - animals fed a diet with 90% Mg deficiency. After 60 days on the diets, all animals received ligature on the lower left first molars to induce PD. Animals were euthanized after 30 days following ligature placement. Blood and urine were collected for determination of serum concentrations of Mg, calcium, osteocalcin (OCN), alkaline phosphatase and parathyroid hormone (PTH) by enzyme-linked immunosorbent assay, and the urinary concentration of deoxypyridinoline (DPD). Systemic bone mineral density (BMD), bone volume and architectural bone parameters were evaluated by micro-CT in L4 lumbar vertebrae and mandible. Tartrate-resistant acid phosphatase staining and immunohistochemical (IHC) analysis of inducible nitric oxide synthase (iNOS), Runt-related transcription factor 2 (RUNX2), CD86, CD80, proliferating cell nuclear antigen, vascular endothelial growth factor, OCN and osteopontin were investigated. Reverse-transcription polymerase chain reaction was employed to assess mRNA expression of receptor-activator of nuclear factor-kB ligand, osteoprotegerin (OPG) and interleukin (IL)-6. Mg deficiency was associated with higher concentrations of PTH and DPD, and significant decrease on both systemic and mandibular BMD, as well as greater severity of alveolar and trabecular bone loss. Significant increase in osteoclasts was observed in the test group with PD. IHC analysis showed significant increase in the expression of iNOS and decreased expression of OCN and RUNX2. Increased IL-6 mRNA and decreased OPG mRNA expressions were evidenced in the test group with PD. Mg deficiency caused systemic effects indicative of altered bone metabolism in the vertebrae and affected both immune and stromal cells, aggravating inflammatory bone resorption in the ligature-induced model of periodontitis.

Restrição dietética de magnésio associada à dieta hiperlipídica: implicações sobre a homeostase do mineral e sensibilidade à insulina / Dietary magnesium restriction associated with a high-fat diet: implications on mineral homeostasis and insulin sensitivity

A resistência dos tecidos à ação da insulina é uma das principais complicações do excesso de peso. O aumento da gordura corporal, decorrente do consumo excessivo de nutrientes, é acompanhado por um quadro de inflamação crônica de baixa intensidade que está relacionado com a fisiopatologia da resistência à insulina. O magnésio (Mg) é um mineral envolvido com diversos processos fisiológicos e bioquímicos, especialmente aqueles relacionados ao metabolismo energético e ao controle glicêmico. Apesar de a deficiência deste mineral estar relacionada com condições pré-diabéticas, não está claro se a inadequação dietética promove alterações na sensibilidade à insulina e/ou se condições de resistência à insulina causam distúrbios na homeostase de Mg. O objetivo deste trabalho foi investigar os efeitos da restrição dietética de Mg e sua associação com o excesso de lipídios sobre a homeostase do mineral e a sensibilidade à insulina. Ratos Wistar, machos, com peso entre 97-123 g, permaneceram em gaiolas individuais por 24 semanas. Os animais receberam rações normolipídicas (CON, 7% de lipídios) ou hiperlipídicas (HL, 32% de lipídios), adequadas (CON e HL Mg; 500 mg de Mg/kg de ração; n = 6 para cada grupo) ou com restrição de Mg (Mg[50] e HL Mg[50]; 50 mg de Mg/kg de ração; n = 6 para cada grupo). O consumo da dieta HL promoveu maior acúmulo de tecido adiposo e maior ganho de peso corporal (p < 0,05). Os animais que consumiram rações com restrição de Mg apresentaram hipomagnesemia (p<0,01), menor excreção urinária (p < 0,01) e fecal (p < 0,001) de Mg e menor concentração óssea desse mineral (p < 0,001). No entanto, não foram observadas alterações no Mg muscular (p > 0,05). O grupo HL Mg[50] apresentou maior concentração de Mg no eritrócito quando comparado aos outros grupos. A restrição dietética de Mg, isoladamente, não promoveu alterações na sensibilidade à insulina (avaliada pelo teste de tolerância à insulina). Quando associada à dieta hiperlipídica, resultou em aumento da glicemia de jejum e em redução da sensibilidade à insulina, após 16 semanas (p < 0,01). Em nível molecular, a fosforilação da proteína quinase B (Akt) no músculo e no fígado foi significantemente menor no grupo HL Mg[50] (p < 0,05). A restrição dietética de Mg induziu ao aumento do conteúdo proteico dos canais TRPM6 e TRPM7 no rim, independentemente da sensibilidade à insulina. Os resultados deste estudo apontam que a deficiência de Mg tende a agravar as repercussões metabólicas do consumo de dietas hiperlipídicas na sensibilidade à insulina e que a resistência à insulina altera a compartimentalização do Mg

Insulin resistance is one of the main complications of overweight. Increase body fat, due to excessive consumption of nutrients is accompanied by a chronic low-grade inflammation related to insulin resistance pathophysiology. Magnesium (Mg) is a mineral involved in many physiological and biochemical processes, especially those related to energy metabolism and glycemic control. Although Mg deficiency is related to pre-diabetic conditions, it is unclear whether dietary inadequacy promotes changes in insulin sensitivity and/or if conditions of insulin resistance cause disturbances in Mg homeostasis. This work aimed to investigate the effects of dietary Mg restriction and its association with high-fat diet on mineral homeostasis and insulin sensitivity. Male Wistar rat (97-123 g) remained in individual cages for 24 weeks. Animals received normolipid diet (CON, 7% lipid) or high-fat diet (HF, 32% lipid), adequate (CON and HF, 500 mg Mg / kg diet, n = 6 for each group) or Mg restricted (Mg[50] and HF Mg[50], 50 mg of Mg / kg of diet, n = 6 for each group). High-fat diet promoted a greater adipose tissue excess and body weight gain (p<0.05). Animals with Mg restricted diet had hypomagnesemia (p<0.01), lower Mg urinary (p<0.01) and faecal loss (p<0.001) and lower bone Mg concentration (p<0.001). However, no changes were observed in muscle Mg (p>0.05). HF Mg[50] group presented higher concentration of erythrocyte Mg when compared to the other groups. Singly, dietary Mg restriction did not induce changes in insulin sensitivity (as assessed by the insulin tolerance test). When associated with high-fat diet, dietary Mg restriction resulted in higher fasting glycemia and lower insulin sensitivity after 16 weeks (p<0.01). At the molecular level, protein kinase B (Akt) phosphorylation in muscle and liver was significantly lower in HFMg [50] group (p<0.05). Dietary Mg restriction induced increased protein content of renal TRPM6 and TRPM7 channels, regardless of insulin sensitivity. The results of this study indicate that Mg deficiency worsens metabolic effects of high-fat diet on insulin sensitivity. In addition, insulin resistance changes Mg compartmentalization

Magnesium deficiency results in an increased formation of osteoclasts.

Magnesium (Mg(2+)) deficiency is a frequently occurring disorder that leads to loss of bone mass, abnormal bone growth and skeletal weakness. It is not clear whether Mg(2+) deficiency affects the formation and/or activity of osteoclasts. We evaluated the effect of Mg(2+) restriction on these parameters. Bone marrow cells from long bone and jaw of mice were seeded on plastic and on bone in medium containing different concentrations of Mg(2+) (0.8 mM which is 100% of the normal value, 0.4, 0.08 and 0 mM). The effect of Mg(2+) deficiency was evaluated on osteoclast precursors for their viability after 3 days and proliferation rate after 3 and 6 days, as was mRNA expression of osteoclastogenesis-related genes and Mg(2+)-related genes. After 6 days of incubation, the number of tartrate resistant acid phosphatase-positive (TRACP(+)) multinucleated cells was determined, and the TRACP activity of the medium was measured. Osteoclastic activity was assessed at 8 days by resorption pit analysis. Mg(2+) deficiency resulted in increased numbers of osteoclast-like cells, a phenomenon found for both types of marrow. Mg(2+) deficiency had no effect on cell viability and proliferation. Increased osteoclastogenesis due to Mg(2+) deficiency was reflected in higher expression of osteoclast-related genes. However, resorption per osteoclast and TRACP activity were lower in the absence of Mg(2+). In conclusion, Mg(2+) deficiency augmented osteoclastogenesis but appeared to inhibit the activity of these cells. Together, our in vitro data suggest that altered osteoclast numbers and activity may contribute to the skeletal phenotype as seen in Mg(2+) deficient patients.

Efeito da deficiência de magnésio sobre o metabolismo do tecido ósseo / The effect of magnesium deficiency on bone metabolism

O magnésio (Mg+2) é um mineral que possui um importante papel na homeostase mineral, podendo afetar diretamente a função das células ósseas e a formação da hidroxiapatita. Entretanto, até o presente momento existem poucos estudos avaliando os mecanismos relacionados à alteração do metabolismo ósseo frente à deficiência de Mg. O objetivo desse estudo foi avaliar, in vitro, o efeito da deficiência de magnésio sobre a osteoclastogênese e atividade de osteoclastos. Também foi objetivo avaliar, in vivo, o efeito da deficiência de magnésio na dieta sobre o metabolismo ósseo, doença periodontal e tecido ósseo ao redor de implantes com osseointegração estabelecida. Para o estudo in vitro, foram avaliadas células indiferenciadas da medula óssea de ossos longos e mandíbula de camundongos. As células foram cultivadas em plástico e sobre tecido ósseo, em meios de cultura com diferentes concentrações de Mg (0.8 Mm que é considerada a quantidade adequada de Mg; e meios com redução do Mg, 0.4 Mm; 0.08 Mm; e 0 Mm). Após 3 dias de cultura, foram avaliadas a viabilidade celular, a taxa de proliferação celular e a expressão gênica, por PCR, de genes relacionadas à osteoclastogênese (c-fms, RANK, DC STAMP, c-fos, TNFα e IL-1ß) e ao metabolismo do Mg (TRPM-7 e MRS2). Após 6 dias de cultura, foram avaliados os parâmetros: número de células osteoclásticas (coloração de TRACP), atividade (liberação de TRACP) e taxa de proliferação celular. Após 8 dias de cultura a atividade dos osteoclastos foi avaliada por análise de pit de reabsorção. Para o estudo in vivo, foram utilizados 30 ratos, divididos em 2 grupos: grupo controle (CTL), que recebeu dieta com conteúdo adequado de magnésio, e grupo Mg, que recebeu dieta com redução de 90% da necessidade diária do mineral. Após um período de adequação ao ambiente do biotério, todos os animais foram submetidos à cirurgia de instalação de um implante na tíbia direita (dia 0). Decorrido um período de 60 dias, necessário à osseointegração dos implantes, os animais de cada grupo foram aleatoriamente divididos conforme a dieta que receberam (grupo CTL e grupo Mg). Após um período de 60 dias, todos os animais receberam uma ligadura no primeiro molar inferior esquerdo. Os animais foram sacrificados, com aprofundamento da anestesia, após um período de 150 dias do início do experimento. No dia do sacrifício foram coletadas amostras de sangue e urina, para avaliação das concentrações urinária de creatinina e deoxipiridinolina (DPD) e sérica de cálcio (Ca), magnésio (Mg), osteocalcina (OCN) e paratormônio (PTH). Para avaliação sistêmica foram realizadas análises de densitometria óssea (DEXA) do fêmur e vértebras lombares além da análise histológica do fêmur. Para avaliação do tecido mandibular foram realizadas análise da densidade radiográfica, análise histológica, análise macroscópica e PCR (RANKL, OPG e IL-6). E finalmente, para avaliação do tecido ósseo ao redor dos implantes foram realizadas análises de densidade radiográfica, torque de remoção e análise histométrica. Como resultados foram observadas, no experimento in vitro, um aumento na quantidade e tamanho dos osteoclastos, provenientes de ossos longos e mandíbula, quando cultivados em meio com deficiência de Mg. A maior quantidade de osteoclastos pode ser devido ao aumento na expressão gênica de c-fos, DC-STAMP, TNF-α e IL-1ß. Não houve alteração na viabilidade e taxa de proliferação celular na deficiência de Mg. Entretanto houve uma diminuição na atividade osteoclástica na deficiência de Mg. Os estudos in vivo demonstraram a deficiência de Mg resultou em diminuição da concentração sérica de Mg. Foi evidenciado que a deficiência do mineral teve uma influência negativa sobre o tecido ósseo, comprovada pela diminuição da densidade do fêmur e vértebras lombares, aumento na concentração de DPD e de PTH. Em análises específicas da mandíbula foi observada a diminuição na densidade radiográfica e o aumento na perda óssea alveolar relacionada à indução de doença periodontal. Nas análises específicas dos sítios de instalação dos implantes, apesar de não ter sido observada alteração na quantidade de tecido ósseo ao redor dos implantes, foi constatada a redução na espessura das corticais e diminuição nos valores de torque de remoção. Assim, dentro das limitações do estudo, pode-se concluir que a deficiência de Mg apresentou uma influência negativa sobre o metabolismo ósseo, agindo diretamente sobre a osteoclastogênese. A restrição de Mg resultou em perda de massa óssea sistêmica, bem como redução da resistência biomecânica dos implantes e perda óssea associada à doença periodontal induzida. Os resultados sugerem que a deficiência de Mg acentua a severidade da doença periodontal e influencia negativamente a manutenção de implantes com osseointegração estabelecida.

Magnesium (Mg) deficiency is very common condition in the world population. This mineral has an important role on bone homeostasis. However, there has been little research regarding the mechanisms in which magnesium deficiency alters bone metabolism. Also, the understanding of the factors associated to bone metabolism is of interesting for the prognosis of oral therapies, such as on periodontal disease and on osseointegrated dental implants. The aim of this study was to evaluate, in vitro, whether Mg deficiency affects the formation and/or activity of osteoclasts. And also to evaluate, in vivo, the effect of Mg intake deficiency on bone metabolism, periodontal disease and the bone tissue around osseointegrated implants. For the in vitro study, bone marrow cells from long bone and jaw of mice were seeded on plastic and on bone in medium containing different concentrations of Mg (0.8 mM which is 100% of the normal value, 0.4, 0.08 and 0 mM). The effect of Mg deficiency was evaluated on cell viability after 3 days and proliferation rate after 3 and 6 days, as was mRNA expression of osteoclastogenesis-related genes (M-CSF, RANK, c-fos, DC STAMP, TNF-α and IL-1ß) and Mg-related genes (TRPM7 and MRS2). After 6 days of incubation, the number of tartrate resistant acid phosphatase-positive multinucleated cells (TRACP+ -MNCs) was determined, and the TRACP activity of the medium was measured. Osteoclastic activity was assessed at 8 days by resorption pit analysis. For the in vivo studies, 30 rats received an implant in the right tibial metaphysis. After 60 days for healing of the implants, the animals were divided into groups according to the diet received. Control group (CTL) received a standard diet with adequate Mg content while test group (Mg) received the same diet except for a 90% reduction of magnesium. After 60 days of magnesium deficiency all animals received a ligature in the left lower first molar. The animals were sacrificed after 90 days of the start of the diet. It was evaluated calcium (Ca), magnesium (Mg), osteocalcin (OCN) and parathyroid hormone (PTH) serum levels and the deoxypyridinoline level (DPD) in the urine. The effect of magnesium deficiency on bone mineral density (BMD) was evaluated by densitometry of the lumbar vertebrae and femur and the histological analysis of the femur. The mandible BMD was assessed using digital radiography; alveolar bone loss was evaluated by linear (CEJ-bone crest) and area measurements. We used RT-PCR to assess mRNA expression (RANKL, OPG and IL-6) in the gingival tissues, and histological analysis was carried for the evaluation of inflammation, alveolar bone loss and for the number of osteoclasts. While the effect of bone tissue around titanium implants was evaluated by radiographic measurement of cortical bone thickness and BMD. The effect on biomechanical characteristics was verified by implant removal torque testing and the histometric analysis was carried out to evaluate the bone tissue around the osseointegrated implants. In vitro results showed that Mg deficiency resulted in increased numbers of osteoclast-like cells; a phenomenon found for both types of marrow. Mg deficiency had no effect on cell viability and proliferation. Increased osteoclastogenesis due to Mg deficiency was reflected in higher expression of osteoclast-related genes. However, resorptions per osteoclast, as well as TRACP activity were lower in the absence of Mg. The in vivo results showed that Mg deficiency was associated with higher concentrations of PTH, DPD and significant decreases on both systemic and mandibular BMD, but not around osseointegrated implants. There was a greater severity of alveolar bone loss, although there were no significant differences on mRNA expression for the target genes. Mg deficiency also resulted in decreased cortical bone thickness and lower values of removal torque of the implants. In vitro data suggest that altered osteoclast numbers and activity may contribute to the skeletal phenotype on magnesium deficiency. The in vivo study concluded that magnesium deficient diet had a negative influence on bone metabolism as well as on the severity of periodontal disease and on bone tissue around the implants

Hypomagnesemia is a risk factor for nonrecovery of renal function and mortality in AIDS patients with acute kidney injury

The objective of the present study was to determine the prevalence of electrolyte disturbances in AIDS patients developing acute kidney injury in the hospital setting, as well as to determine whether such disturbances constitute a risk factor for nephrotoxic and ischemic injury. A prospective, observational cohort study was carried out. Hospitalized AIDS patients were evaluated for age; gender; coinfection with hepatitis; diabetes mellitus; hypertension; time since HIV seroconversion; CD4 count; HIV viral load; proteinuria; serum levels of creatinine, urea, sodium, potassium and magnesium; antiretroviral use; nephrotoxic drug use; sepsis; intensive care unit (ICU) admission, and the need for dialysis. Each of these characteristics was correlated with the development of acute kidney injury, with recovery of renal function and with survival. Fifty-four patients developed acute kidney injury: 72 percent were males, 59 percent had been HIV-infected for >5 years, 72 percent had CD4 counts <200 cells/mm³, 87 percent developed electrolyte disturbances, 33 percent recovered renal function, and 56 percent survived. ICU admission, dialysis, sepsis and hypomagnesemia were all significantly associated with nonrecovery of renal function and with mortality. Nonrecovery of renal function was significantly associated with hypomagnesemia, as was mortality in the multivariate analysis. The risks for nonrecovery of renal function and for death were 6.94 and 6.92 times greater, respectively, for patients with hypomagnesemia. In hospitalized AIDS patients, hypomagnesemia is a risk factor for nonrecovery of renal function and for in-hospital mortality. To determine whether hypomagnesemia is a determinant or simply a marker of critical illness, further studies involving magnesium supplementation in AIDS patients are warranted.

Aspectos atuais da relação entre exercício físico, estresse oxidativo e magnésio / Current aspects of the relationship between physical exercise, oxidative stress and magnesium

Este trabalho visa a contribuir com informações atualizadas sobre a relação entre exercício, estresse oxidativo e magnésio. São escassos os trabalhos que discutem a produção de radicais livres nesse contexto. A deficiência de magnésio altera a fluidez das membranas celulares e mitocondriais e promove perturbações na homeostase do cálcio e na atividade das defesas antioxidantes. No exercício, a falta de magnésio nos tecidos musculares os torna mais suscetíveis à infiltração de macrófagos e neutrófilos e ao rompimento do sarcolema, dificultando o processo de regeneração e podendo ocasionar queda no desempenho físico. Conclui-se que o papel metabólico da deficiência de magnésio no estresse oxidativo induzido pelo exercício deve ser mais pesquisado, focalizando os seus efeitos na musculatura esquelética em indivíduos que praticam exercício regular e na deficiência marginal de magnésio.

This article contributes to updated information about the relationship between exercise, oxidative stress and magnesium. There are few studies that discuss free radical production in this context. Magnesium deficiency alters cellular and mitochondrial membrane fluidity and promotes disturbances on calcium homeostasis and on the activity of antioxidant defenses. During exercise, lack of magnesium in muscle tissue turns them more susceptible to macrophage and neutrophil infiltration and to sarcolema damage, impairing the regeneration process and leading to decreased physical performance. In conclusion, the metabolic role of magnesium deficiency on exercise-induced oxidative stress should be further researched, focusing on its effects on skeletal muscle in individuals who practice regular physical exercise and in marginal magnesium deficiency.

Efeito da dieta com deficiência de magnésio sobre a manutenção da osseointegração de implantes de titânio: análise radiográfica, densitométrica e de torque reverso / Effect of magnesium deficiency on diet on the maintenance of the osseointegration on titanium implants: radiographic, densitometric and removal torque study

A deficiência de magnésio (Mg) na dieta pode ser considerada um fator de risco para o desenvolvimento de osteoporose. A diminuição de Mg na dieta está relacionada à perda de massa óssea em humanos; e em animais, estudos têm demonstrado osteopenia, crescimento ósseo anormal e fragilidade esqueletal. Este estudo avaliou a influência da deficiência de Mg na dieta em ratos jovens e adultos sobre o torque de remoção de implantes e sobre a densidade óssea e radiográfica ao redor de implantes osseointegrados instalados na tíbia dos ratos. Noventa ratos Holtzman foram separados em 2 grupos (n=45; 180 gr - animais jovens/ n=45; 360 gr - animais adultos); cada animal recebeu um implante em cada metáfise tibial. Após a osseointegração dos implantes (60 dias), os dois grupos de animais foram sub-divididos em três grupos: grupo Controle (CTRL, n=15), grupo de deficiência de Mg de 75% (Mg1; n=15) e grupo de deficiência de Mg de 90% (Mg2; n=15). Após 150 dias da instalação dos implantes, todos os animais foram sacrificados. Foram coletadas amostras de sangue e urina, realizada a densitometria óssea das vértebras lombares (L2, L3 e L4) e do fêmur, realizada a densidade óssea radiográfica e mensuração da espessura da cortical óssea, além do teste biomecânico de torque de remoção dos implantes. A análise densitométrica (vértebras lombares e fêmur) e os valores da concentração plasmática e urinária de Mg confirmaram o comprometimento sistêmico dos animais, mostrando valores menores de densidade óssea para os grupos Mg1 e Mg2. A análise da densidade radiográfica demonstrou alterações no osso cortical e medular dos grupos Mg1 e Mg2. A análise da espessura da cortical óssea demonstrou alterações na espessura do osso cortical, apresentando valores menores nos grupos Mg1 e Mg2. A análise do torque de remoção dos implantes nos animais jovens mostrou diminuição dos valores de torque com diferença significante para os grupos Mg1 e Mg2 (P <0.05) com relação ao grupo controle. Nos animais adultos, os valores de torque de remoção nos grupos Mg1 e Mg2 também foram menores, mas não foram significantes. De acordo com este estudo, observou-se que a deficiência de Mg na dieta causa influência negativa nas características biomecânicas do tecido ósseo ao redor de implantes osseointegrados

Low dietary magnesium (Mg) may be a risk factor for osteoporosis. Mg intake has been associated with bone mass loss in humans. Mg deficiency in animal models has showed osteopenia, impaired bone growth and skeletal fragility. This study evaluated the influence of magnesium deficiency on diet in young and adult rats on the removal torque of osseointegrated titanium implants. Ninety male Holtzman rats (n=45; 180 gr - young rats / n=45; 360 gr - adult rats) were divided in two groups and received a titanium implant in the tibia metaphysis. After the healing period of 60 days, the animals were randomly divided in three sub-groups: control group (CTRL, n=15 animals), 75% magnesium deficiency group (Mg1, n=15 animals) and 90% magnesium deficiency group (Mg2, n=15 animals). The dietary magnesium deficiency was induced in two groups (Mg1 and Mg2) for 90 days. After 150 days postimplant placement, all animals were sacrificed and collected samples of blood and urine. Densitometry of femur and lumbar vertebrae was performed by dual-energy x-ray absorptiometry (DXA), bone density was measured by digital radiographs at 6 points on sides of the implant and was performed the measurement of the thickness of the cortical bone. All implants were subjected to removal torque. Densitometric analysis (femur and lumbar vertebrae) and serum and urinary magnesium concentration confirmed a systemic impairment of the animals, showing lower bone mineral density for Mg1 and Mg2 in young and adult rats. The analysis of radiographic bone density revealed a negative impact of the Mg deficiency in the cancellous and cortical bone. Analysis of the thickness of cortical bone showed alterations on cortical bone in Mg1 and Mg2 groups. Analysis of the removal torque of the implants in young rats showed a decrease of the removal torque for the Mg1 and Mg2 groups (P <0.05) with a statistical difference in relation to the CTRL group. Analysis of the removal torque of the implants in adult rats showed a decrease of the removal torque for the Mg1 and Mg2 groups but without statistical difference in relation to the CTRL group. According to this study, magnesium deficiency on diet was observed to have a negative influence on the biomechanical characteristics of bone tissue around osseointegrated implants

Efeito da deficiência de magnésio na dieta sobre a densidade e o metabolismo ósseo ao redor de implantes com osseointegração estabelecida: estudo em ratos / Effect of magnesium deficiency in diet on bone density and bone metabolism around osseointegrated implants: study in rats

Introdução: O magnésio (Mg+2) é essencial para a vida, sendo importante em reações enzimáticas de vários tipos celulares, além de ter um papel importante no tecido ósseo e na homeostase mineral, podendo afetar diretamente a função das células ósseas e a formação da hidroxiapatita. O entendimento de fatores associados à modificação do metabolismo ósseo é de extremo interesse na reabilitação oral com implantes osseointegrados. O contato íntimo entre o metal do implante e o tecido ósseo é fundamental para o sucesso desta forma de tratamento. Diversas alterações sistêmicas, dentre elas a deficiência de Mg, podem representar um risco à osseointegração, podendo afetar a remodelação e diminuir o contato osso-implante. Objetivo: Avaliar, em animais com diferentes idades, o efeito da deficiência de magnésio na dieta sobre o metabolismo ósseo ao redor de implantes de Ticp (titânio comercialmente puro) com osseointegração estabelecida Material e Método: Foram utilizados 90 ratos machos, divididos em 2 grupos de acordo com a idade, sendo constituídos por animais jovens (60 dias) e adultos (150 dias). Após adaptação ao ambiente do biotério, todos os animais foram submetidos à cirurgia de instalação dos implantes nas tíbias direita e esquerda (dia 0). Decorrido um período de 60 dias, necessário à osseointegração dos implantes, os animais de cada grupo foram então subdivididos em 3 subgrupos conforme a dieta que iriam receber (dieta padrão, dieta com redução de 75% do magnésio necessário diariamente e dieta com redução de 90% do magnésio necessário diariamente), a qual foi administrada por mais 90 dias para instalação da deficiência mineral. No período de 24 horas antes do sacrifício foram coletadas amostras de urina. Após o sacrifício, foram coletadas amostras de soro para determinação da concentração de magnésio (Mg) e cálcio (Ca). O efeito da deficiência sobre a densidade óssea esqueletal foi avaliado por meio de densitometria óssea (DXA) da coluna lombar e fêmur, enquanto a densidade óssea ao redor dos implantes foi avaliada por meio de densidade óssea radiográfica. Para avaliação do efeito da deficiência de Mg sobre o metabolismo ósseo foi realizado PCR semi­quantitativo para os genes RANKL e OPG do periósteo adjacente ao implante. Resultado: A diminuição da concentração sérica e urinária de magnésio (p<0.05) foi constatada para os grupos de animais jovens e adultos. A análise densitométrica das vértebras lombares e do fêmur demonstrou a perda sistêmica de massa óssea tanto em animais jovens como adultos, sendo mais significante para os subgrupos com maior deficiência e nas avaliações globais. Foi demonstrada uma redução estatisticamente significante da densidade óssea radiográfica ao redor dos implantes, para todas as regiões (p<0.01) dos subgrupos com deficiência de Mg, em ambos os grupos. A análise por PCR, para os animais jovens, demonstrou uma tendência de aumento da expressão de RANKL e um aumento estatisticamente significante (p<0.05) da expressão de OPG entre os subgrupos CTL e Mg2. Nos animais adultos, houve uma tendência de diminuição da expressão de OPG e aumento da expressão de RANKL. Conclusão: A deficiência de magnésio resultou em perda de massa óssea sistêmica e perda de densidade óssea ao redor dos implantes com osseointegração estabelecida independente da idade, entretanto são necessários mais estudos sobre o mecanismo de sinalização da indução de perda óssea

Introduction: Magnesium (Mg+2) is essential for life, it is important for many enzymatic reactions of several kinds of cells. Magnesium is very important for bone and mineral homeostasis; it can directly affect bone cell functions and crystal formation (hydroxyapatite). The factors associated to the modification of bone metabolism are extremely important in oral rehabilitation of osseointegrated implants. The intimate bone to implant contact is fundamental for the success of this kind of treatment. Several systemic alterations, like magnesium deficiency, can represent a risk factor to implants osseointegration, it could affect bone remodeling and reduce the bone-implants contact. Objective: This study evaluated, in animals with different ages, the effect of magnesium deficiency in diet on bone metabolism around integrated implants. Methods: Ninety male Holtzman rats were divided in 2 groups by the age, young animals were 60 days years old and adult animals were 150 days years old. After acclimation to the vivarium, all the animals were submitted to a titanium implant at right and left tibias (day 0). After a healing period of 60 days the animals were ramdonly divided into 3 subgroups: rats were fed either normal control magnesium diet (CTL), a reduction of 75% of magnesium diet (Mg1) and a reduction of 90% of magnesium diet (Mg2). After 90 days on the experimental diet the animals were sacrificed. In order to confirm the systemic deficiency of magnesium the serum and urine were colleted for determination of magnesium and calcium concentration. In order to confirm the systemic osteopenia, a dual-energy X-ray absorptiometry (DEXA) was performed in lombar vertebra and femur. For evaluation of bone density around integrated implants, radiographs were taken. And for evaluation of magnesium deficiency in osseous metabolism, mRNA levels of RANKL and OPG were quantified. Results: The decrease of magnesium concentration in serum and urine confirmed magnesium deficiency in both groups (p<0.05). Densitometric measurments of the femur and lumbar vertebrae confirmed systemic bone mass loss in both groups. The measurements for radiographic bone density around integrated implants showed a decreased in bone density in all regions of all experimental groups (p>0.01). The mRNA levels for RANKL were slighted but not significantly increased in both groups. The mRNA levels for OPG were significantly increased in young animals (p>0.05) and not significantly decreased in adult animals. Conclusion: According to this study, magnesium deficiency on diet resulted in loss of systemic bone mass and bone density around integrated implant. However more studies are necessary for the signalization of bone loss mechanism