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Magnesium suppresses in vivo oxidative stress and ex vivo DNA damage induced by protracted ACTH treatment in rats.

Oxidative stress, arising from disrupted balance between reactive oxygen/nitrogen species (ROS/RNS) and antioxidant defences, has been implicated in the pathogenesis of stress-related disorders. There is a growing body of evidence that supports the relationship between the activity of the hypothalamic-pituitary-adrenal (HPA) stress system, oxidative stress and magnesium (Mg) homeostasis. The present study aimed to explore the gap in our current understanding of antigenotoxic and protective effects of Mg supplementation against excessive ROS production in male rats during chronic treatment with adrenocorticotropic hormone (ACTH). Our findings show that exposure to exogenous ACTH (10μg/day, s.c., for 21 days), as one of the key mediators of the HPA axis and stress response, produced an increase in superoxide anion levels and a decrease in superoxide dismutase activity in plasma. We observed that Mg supplementation, starting seven days prior to ACTH treatment and lasting 28 days (300mg/L of drinking water, per os), abolished these effects in experimental animals. Moreover, our study reveals that ACTH increased the susceptibility of peripheral blood lymphocytes to ex vivo H2O2-induced total and high-level oxidative DNA damage, while Mg completely reversed these effects. Collectively, these results highlight the promising role of Mg in stress-related conditions accompanied by increased oxidative stress in animals and support further investigation using human dietary trials.

Evaluation of standard versus prolonged magnesium infusion rates in hospitalized patients: a retrospective cohort study.

Hypomagnesemia is a common electrolyte abnormality in hospitalized patients. Prolonging the infusion rate of magnesium has been hypothesized to increase retention of magnesium, however, there is limited evidence to support prolonging the rate of infusion. To compare the absolute change in serum magnesium levels from baseline to levels drawn within 24 hours after the end of infusion between two groups receiving standard or prolonged infusion. This was a retrospective, observational cohort study comparing patients receiving magnesium infusion at a standard rate of 0.5 gm/h to those receiving magnesium infusion at a prolonged rate of 0.17gm/h. Of a total of 276 patients, 138 were included in each group. No differences existed between the groups for any demographic variables (all p>0.05). The absolute change in serum magnesium level was 0.41mg/dL versus 0.31mg/dL in the standard and the prolonged infusion groups, respectively (p=0.001). The length of stay after the initial magnesium dose was slightly longer with the prolonged infusion compared to the standard infusion, with a median of 2.9 days versus 3.6 days, respectively (p=0.02). No differences existed between the groups for any secondary or safety outcomes (all p>0.05). Hospitalized general patients did not benefit from the prolonged infusion of magnesium compared to standard infusion.

Correlation between magnesium sulphate exposure in utero and serum calcium and alkaline phosphatase levels in preterm infants

Magnesium sulphate (MgSO4) is administered to pregnant women at risk of preterm labour and eclampsia. Since prolonged exposure to antenatal MgSO4 is considered to be a risk factor for infant skeletal demineralization, we evaluated infants exposed to antenatal MgSO4 for bone and mineral metabolism using their umbilical cord blood. The study population comprised 137 preterm infants. Forty-three infants were exposed (exposure group) and 94 infants were not exposed (control group) to antenatal MgSO4. Blood samples from the umbilical cords and infants were analysed with respect to mineral metabolism, intact parathyroid hormone (iPTH) level, and alkaline phosphatase (ALP) level. Correlation between the level of these parameters and the duration and dosage of MgSO4 was also examined. Preterm infants in the exposure group were antenatally exposed to MgSO4 for a median (IQR) period of 14 (5-34) days and a dosage of 447 (138-1118) g. Serum calcium levels were lower (8.8 vs 9.4 mg/dL, p<0.001) and ALP levels were higher (312 vs 196 U/L, p<0.001) in the exposure group. Serum calcium levels did not correlate with MgSO4 administration dosage and therapy duration, however, ALP levels correlated with the duration and total dosage of MgSO4 (Spearman's rank correlation r [95% confidence interval]: 0.55 [0.30-0.73], p <0.001 and 0.63 [0.40-0.78], p <0.001, respectively). Prolonged periods and higher doses of antenatal MgSO4 exposure can cause in utero abnormal bone metabolism in preterm infants.

The relationship between venous insufficiency and serum magnesium level

Magnesium is the second most common cation in the cell. In addition to its role as a cofactor in many enzymatic pathways in physiological processes, it is necessary for the regular functioning of vascular smooth muscle cells. Magnesium deficiency has been associated with exacerbation of inflammation, which plays a role in the aetiopathogenesis of many diseases. To investigate the potential relationship between serum magnesium level and the development of chronic venous insufficiency by comparison with healthy individuals. The study included 394 patients with venous insufficiency based on physical examination findings and colour Doppler ultrasonography, and 206 controls without venous insufficiency. Venous insufficiency was defined by colour Doppler as reflux lasting 0.5 seconds or more in superficial veins, and longer than one second in femoral and popliteal veins. Clinical, haematological and biochemical parameters, including serum magnesium level and indicators of inflammation, were compared between groups. A total of 600 participants were included. There was no significant difference between the groups in terms of age and gender. In total, 187 (47.46%) patients with chronic venous insufficiency and 105 (50.97%) of the control group were male (p=0.414). The median age of the patients with chronic venous insufficiency was 48 (min-max: 41-49), and the median age of the control group was 49.00 (min-max: 45.00-60.25) (p=0.064). Serum magnesium level was found to be significantly lower in the group with chronic venous insufficiency compared to the control group; 1.90 mg/dL (min-max: 1.82-2) versus 2.1 mg/dL (min-max: 2-2.2) (p<0.001), respectively. Low serum magnesium levels may pose a potential risk for the development of chronic venous insufficiency, which is common in the community.

Open Access
Magnesemia in COVID-19 ICU patients: the relationship between serum magnesium level and mortality

This study aimed to investigate the relationship between serum magnesium (Mg) levels at the time of admission and survival in COVID-19 patients followed in the intensive care unit (ICU). In total, 461 patients over the age of 18 diagnosed with the COVID-19, followed in the COVID-19 ICU of our hospital, were included. Patients whose files could not be accessed were excluded. Data on patients' demographics, clinical features, and laboratory data were compared according to the Mg levels measured during their admission to the ICU. The patients were divided into five groups according to their Mg level: Group 1 (<1.8 mg/dL), Group 2 (1.8-<2 mg/dL), Group 3 (2-<2.2 mg/dL), Group 4 (2.2-<2.4 mg/dL), and Group 5 (>2.4 mg/dL). For patients with Mg value of <2 mg/dL, the proportion of males to females was roughly equal, however, the proportion of males was higher in other groups (p = 0.004). Overall, hypertension was the most common comorbid disease in patients, followed by diabetes mellitus in 32.1%. The latter was observed more frequently in Group 1 (<1.8 mg/dL) compared to the other groups (51.3%, p = 0.008). No significant difference was determined between the groups regarding laboratory values and treatments administered. Requirement of mechanical ventilation was significantly higher in Groups 1 (<1.8 mg/dL) and 5 (>2.4 mg/dL) than in other groups (p = 0.008). However, although mortality was also high in these groups, the difference was not statistically significant (p = 0.067). A correlation between serum Mg levels and mortality was not observed, but mortality and the need for mechanical ventilation were higher in groups with Mg levels <1.8 mg/dL and >2.4 mg/dL compared to other groups. We believe that it is critical to measure serum Mg levels while supporting COVID-19 patients with Mg in the ICU.

Development of a bio-relevant pH gradient dissolution method for a high-dose, weakly acidic drug, its optimization and IVIVC in Wistar rats: a case study of magnesium orotate dihydrate

Magnesium orotate dihydrate (MOD) is a weakly acidic drug (pKa 2.83) which belongs to Biopharmaceutical Classification System (BCS) Class I at a dose of 500 mg and to BCS Class II at a dose of 1,000 mg. It is clinically prescribed at a dose of 3,000 mg (in two to three divided doses). The aim of the present study was to develop a bio-relevant pH gradient dissolution method for MOD in order to evaluate whether its clinically practiced therapeutic dose may be absorbed or not. The developed method revealed that MOD undergoes slow, but complete dissolution within 180 minutes, corresponding to the time to achieve maximum serum concentration (Tmax) in vivo. Optimization studies revealed that a rotational speed of 75 rpm provided reliable results (relative standard deviation of less than 20% up to a 10-minute time point, and less than 10% for the other time points), and MOD underwent complete dissolution within the testing timeframe at this rotational speed. Based on a pharmacokinetics study and the Wagner Nelson method, the relative extent of MOD absorption, when administered at a high dose equivalent to a human dose of 1,524 mg in Wistar rats in comparison to its oral suspension, was greater than 90%. In vitro – in vivo correlation, established through a deconvolution method, showed excellent correlation between percent of drug dissolved and percent of drug absorbed (R²= 0.9303). Therefore, even when MOD is administered at a single high dose, it can undergo slow but complete dissolution and absorption in vivo.

Is serum magnesium level associated with atrial fibrillation in the mixed medical/surgical intensive care unit setting?

Although low serum magnesium level is a a relatively common problem in mixed medical/surgical intensive care units (ICUs), its association with new-onset atrial fibrillation (NOAF) has been studied to a lesser extent. We aimed to investigate the effect of magnesium levels on the development of NOAF in critically ill patients admitted to the mixed medical/surgical ICU. A total of 110 eligible patients (45 female, 65 male) were included in this case-control study. The age and sex-matched control group (n = 110) included patients with no atrial fibrillation from admission to discharge or death. The incidence of NOAF was 2.4% (n = 110) between January 2013 and June 2020. At NOAF onset or the matched time point, median serum magnesium levels were lower in the NOAF group than in the control group (0.84 [0.73-0.93] vs. 0.86 [0.79-0.97] mmol/L; p = 0.025). At NOAF onset or the matched time point, 24.5% (n = 27) in the NOAF group and 12.7% (n = 14) in the control group had hypomagnesemia (p = 0.037). Based on Model 1, multivariable analysis demonstrated magnesium level at NOAF onset or the matched time point (OR: 0.07; 95%CI: 0.01-0.44; p = 0.004), acute kidney injury (OR: 1.88; 95%CI: 1.03-3.40; p = 0.039), and APACHE II (OR: 1.04; 95% CI: 1.01-1.09; p = 0.046) as factors independently associated with an increased risk of NOAF. Based on Model 2, multivariable analysis demonstrated hypomagnesemia at NOAF onset or the matched time point (OR: 2.52; 95% CI: 1.19-5.36; p = 0.016) and APACHE II (OR: 1.04; 95%CI: 1.01-1.09; p = 0.043) as factors independently associated with an increased risk of NOAF. In multivariate analysis for hospital mortality, NOAF was an independent risk factor for hospital mortality (OR: 3.22; 95% CI: 1.69-6.13, p<0.001). The development of NOAF in critically ill patients increases mortality. Critically ill patients with hypermagnesemia should be carefully evaluated for risk of NOAF.