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The Beneficial Effects of Antenatal Magnesium clinical trial was conducted between 1997 and 2007, and demonstrated a significant reduction in cerebral palsy (CP) in preterm infants who were exposed to peripartum magnesium sulfate (MgSO4). However, the mechanism by which MgSO4 confers neuroprotection remains incompletely understood. Cord blood samples from this study were interrogated during an era when next-generation sequencing was not widely accessible and few gene expression differences or biomarkers were identified between treatment groups. Our goal was to use bulk RNA deep sequencing to identify differentially expressed genes comparing the following four groups: newborns who ultimately developed CP treated with MgSO4 or placebo, and controls (newborns who ultimately did not develop CP) treated with MgSO4 or placebo. Those who died after birth were excluded. We found that MgSO4 upregulated expression of SCN5A only in the control group, with no change in gene expression in cord blood of newborns who ultimately developed CP. Regardless of MgSO4 exposure, expression of NPBWR1 and FTO was upregulated in cord blood of newborns who ultimately developed CP compared with controls. These data support that MgSO4 may not exert its neuroprotective effect through changes in gene expression. Moreover, NPBWR1 and FTO may be useful as biomarkers and may suggest new mechanistic pathways to pursue in understanding the pathogenesis of CP. The small number of cases ultimately available for this secondary analysis, with male predominance and mild CP phenotype, is a limitation of the study. In addition, differentially expressed genes were not validated by qRT-PCR., (© 2022 S. Karger AG, Basel.)

Background: Recent studies have shown an increased risk of acute kidney injury (AKI) induced by vancomycin + piperacillin-tazobactam (VPT) combination. In this study, the efficacy of intravenous magnesium sulfate in prevention of VPT induced AKI in critically ill patients admitted to the ICU has been evaluated., Methods: In an open-label, placebo-controlled, randomized clinical trial, 72 adults (≥ 18 years old) who had indications to receive VPT as empiric therapy were assigned to the magnesium or control group in 1:1 ratio. Concomitant with VPT, intravenous infusion of magnesium sulfate was started for patients in the magnesium group. The target serum level of magnesium was defined 3 mg/dl. Patients in the control group received normal saline as placebo. The target serum level of magnesium was defined 1.9 mg/dl in this group. The study's primary outcome was incidence of AKI during and up to 48 h after the treatment course. Escalation and de-escalation of VPT regimen, duration of hospitalization, length of ICU stay and 28-day mortality were secondary outcomes., Results: Thirty patients in each group completed the examination. Five patients in the magnesium group and 11 patients in the control group experienced AKI (p = 0.072). De-escalation of VPT regimen was done approximately in 60% of patients. Duration of hospitalization and length of ICU stay were not statistically different between the groups. Finally, 28-day mortality was 23.33% in each group. Although the incidence of AKI was not statistically different between the groups in unadjusted logistic regression model, it became significant after adjusting for confounding factors [unadjusted model (OR = 0.34; 95% CI: 0.10-1.16, p = 0.084), adjusted model: (OR = 0.26; 95% CI: 0.07-0.96, p = 0.04)]., Conclusions: Administration of magnesium sulfate with the target serum levels around 3 mg/dL reduced the incidence of AKI in critically ill patients who were receiving VPT as empric therapy., (© 2021. Springer Nature Switzerland AG.)

The prevalence of metabolic syndrome (MetS) is increasing, and patients with MetS are at an increased risk of cardiovascular disease and diabetes. There is a close link between hypomagnesemia and MetS. Administration of sodium-glucose transporter 2 (SGLT2) inhibitors has been reported to increase serum magnesium levels in patients with diabetes. We investigated the alterations in renal magnesium handling in an animal model of MetS and analyzed the effects of SGLT2 inhibitors. Adult rats were fed a fructose-rich diet to induce MetS in the first 3 months and were then treated with either dapagliflozin or magnesium sulfate-containing drinking water for another 3 months. Fructose-fed animals had increased insulin resistance, hypomagnesemia, and decreased urinary magnesium excretion. Dapagliflozin treatment improved insulin resistance by decreasing glucose and insulin levels, increased serum magnesium levels, and reduced urinary magnesium excretion. Serum vitamin D and parathyroid hormone levels were decreased in fructose-fed animals, and the levels remained low despite dapagliflozin and magnesium supplementation. In the kidney, claudin-16, TRPM6/7, and FXDY expression was increased in fructose-fed animals. Dapagliflozin increased intracellular magnesium concentration, and this effect was inhibited by TRPM6 blockade and the EGFR antagonist. We concluded that high fructose intake combined with a low-magnesium diet induced MetS and hypomagnesemia. Both dapagliflozin and magnesium sulfate supplementation improved the features of MetS and increased serum magnesium levels. Expression levels of magnesium transporters such as claudin-16, TRPM6/7, and FXYD2 were increased in fructose-fed animals and in those administered dapagliflozin and magnesium sulfate. Dapagliflozin enhances TRPM6-mediated trans-epithelial magnesium transport in renal tubule cells.

The study aimed to investigate the role of magnesium sulfate prophylaxis in nephrotoxicity caused by colistin. Thirty Wistar Albino rats were divided into four groups: control, colistin, magnesium (Mg), and Mg+colistin. The drugs were administered to the groups for seven days. Urea-creatinine values were measured at the beginning (T0) and end (T1) of the study. Malondialdehyde (MDA) levels were measured in plasma and kidney tissue, glutathione (GSH) levels were analyzed in the erythrocyte and kidney tissues. At the end of the study, the semiquantitative score (SQS) was calculated by the histopathological examination of the kidneys. Urea values significantly decreased in Mg and Mg+colistin groups compared to the baseline (p=0.013 and p=0.001). At the time of T1, these groups had significantly lower urea values than the colistin and control groups. Creatinine value was significantly increased in the colistin group compared to baseline (p=0.005), the creatinine value in the colistin group was significantly higher than the Mg+colistin group (p=0.011). Plasma MDA levels were significantly higher in the colistin group compared to the other groups at the time of T1 (p<0.001). The Mg+colistin group had lower renal MDA levels than the colistin group. The colistin group had significantly higher renal tubular grade (p=0.035), renal affected area (p<0.001), and SQS (p=0.001) than the Mg+colistin group. The results of the study suggested that Mg sulfate may have a nephrotoxicity-reducing effect on colistin., (Copyright © 2021 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

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Objective: The study focused on the separation effects of ultrasound blood flow signal detection, based on empirical mode decomposition (EMD) algorithm, and the clinical efficacy of Compound Danshen injection and magnesium sulfate in the treatment of pregnancy-induced hypertension (PIH) syndrome., Methods: The empirical mode decomposition (EMD) algorithm was optimized first and compared with other algorithms for the accuracy and stability in separation of blood flow signals. 80 patients with PIH syndrome undergoing ultrasound examination were selected as the research subjects and randomly divided into control group and observation group according to the actual treatment methods. 40 cases in the observation group were treated with Compound Danshen injection + magnesium sulfate, and 40 cases in the control group were treated with magnesium sulfate. After the treatment, the clinical indicators of the two groups of patients were analyzed., Results: The accuracy and stability in separating blood flow signal of the optimized EMD algorithm were better than those of other algorithms. After treatment, the total effective rate and blood pressure control of the observation group were significantly better than those of the control group, and the incidence of adverse maternal and infant outcomes was significantly lower than that of the control group. After treatment, the endothelin-1 (ET-1), C-reactive protein (CRP), and homocysteine (Hcy) indexes of the two groups of patients decreased significantly, and the decrease level of the observation group was significantly greater than that of the control group ( P   <  0.05). The prothrombin time (PT), fibrinogen (FIB), activated partial thromboplastin time (APTT), and plasma thrombin time (TT) levels of the two groups after treatment were better than those before treatment, and the observation group was better than the control group ( P   <  0.05)., Conclusion: The optimized EMD algorithm is of great value for the separation of ultrasound blood flow signals. For patients with PIH syndrome, Compound Danshen injection combined with magnesium sulfate can be used as a treatment plan, which can improve maternal and infant outcomes; control blood pressure; reduce 24 h urine protein and serum ET-1, Hcy, and CRP levels; and improve coagulation function. It is worthy of promotion., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Xia Zhao et al.)

The interactions of ligands with nucleic acids are central to numerous reactions in the biological cell. How such reactions are affected by harsh environmental conditions such as low temperatures, high pressures, and high concentrations of destructive ions is still largely unknown. To elucidate the ions' role in shaping habitability in extraterrestrial environments and the deep subsurface of Earth with respect to fundamental biochemical processes, we investigated the effect of selected salts (MgCl 2 , MgSO 4 , and Mg(ClO 4 ) 2 ) and high hydrostatic pressure (relevant for the subsurface of that planet) on the complex formation between tRNA and the ligand ThT. The results show that Mg 2+ salts reduce the binding tendency of ThT to tRNA. This effect is largely due to the interaction of ThT with the salt anions, which leads to a strong decrease in the activity of the ligand. However, at mM concentrations, binding is still favored. The ions alter the thermodynamics of binding, rendering complex formation that is more entropy driven. Remarkably, the pressure favors ligand binding regardless of the type of salt. Although the binding constant is reduced, the harsh conditions in the subsurface of Earth, Mars, and icy moons do not necessarily preclude nucleic acid-ligand interactions of the type studied here.

Background: The aim of this study is to compare the efficacy of the microplegia solution and Del Nido cardioplegia solution in coronary artery bypass surgery with clinical, biochemical, and echocardiographic data., Methods: Three hundred patients, who underwent coronary artery bypass surgery between January 2017 and January 2020, by the same surgical team were included in the study. Preoperative, operative and postoperative data (cardiac biomarker levels, cross-clamp and CPB times, echocardiographic measurements, etc.) of the patients were compared., Results: In the study, cross-clamp time was significantly shorter in the DN cardioplegia group (55.60 ± 13.49 min/75.58 ± 12.43 min, P = 0.024). No significant difference was observed between the two groups in terms of intensive care stay, extubation time, hospital stay, and cardiopulmonary bypass time. In our study, it was shown that both the left and right ventricular ejection fraction was better protected in the Del Nido cardioplegia group (5.34±3.03 vs. 3.40±2.84, P = 0.017 and 3.82±1.19 vs. 2.28±1.87, P = 0.047, respectively), and the need for inotrope support was lower in this group (28% vs. 44%, P < 0.021). There was no significant difference between the groups, in terms of blood transfusion rates, IABP requirement., Conclusion: In light of short-term results, we can say that Del Nido cardioplegia provides better myocardial protection than microplegia. In addition, Del Nido cardioplegia can be given as a single dose for 90 minutes of cross-clamp time and therefore can be preferred to increase surgical comfort and reduce cross-clamp times.

Objective: To investigate the effect of using del Nido cardioplegia+terminal hot-shot blood cardioplegia on myocardial protection and rhythm in isolated coronary bypass patients., Material and Methods: A total of 122 patients were given cold (+4-8C') del Nido cardioplegia antegrade and evaluated. Del Nido+terminal warm blood cardioplegia (TWBCP) was applied to 63 patients out of 122 patients, while del Nido cardioplegia alone was applied to the other 59 patients. The preoperative and postoperative data of the patients were recorded and compared., Results: There was a significant statistical difference between the groups, in terms of volume with more cardioplegia in the del Nido+terminal warm blood cardioplegia group. Although there was no significant difference between cardiac arrest times in both groups, a statistically significant difference was found in the del Nido+terminal warm blood cardioplegia group in the starting to work time of the heart. No difference found between the groups regarding myocardial preservation., Conclusions: We can add a return to spontaneous sinus rhythm to the advantages of terminal warm blood cardioplegia and del Nido cardioplegia in literature. We think it would be a good strategy to extend the safe ischemic time limit of del Nido to 120 minutes with a terminal warm blood cardioplegia. It seems that cardioplegia techniques that will be developed by adding the successful and superior results of crystalloid cardioplegia applications, such as single dose del Nido in various open heart surgery operations and the superior myocardial return effects of terminal warm blood cardioplegia, will be used routinely in the future.

Background: Spinal anesthesia is commonly employed during inguinal hernial surgeries. Its short duration may, however, be considered a limitation, especially for bilateral hernial repair. The aim of this research is to investigate the analgesic and hemodynamic effects of intravenous infusion of both MgSO 4 and dexmedetomidine on patients undergoing bilateral inguinal hernia surgeries under spinal anesthesia., Methods: This study was a prospective, randomized, double-blinded controlled trail. It included 60 male patients who had been scheduled for bilateral elective inguinal hernia surgery under spinal anesthesia at Kasr Al-Aini hospital. Patients were randomly allocated to one of three groups (n = 20 each) to receive 50 mL of 0.9% saline intravenous infusion of either dexmedetomidine 0.5 μg.kg -1 . h -1 (Group D) or magnesium sulphate 15 mg.kg -1 . h -1 (Group M) or normal saline (Group S). The primary outcome of this study was set as the total duration of analgesia. Secondary outcomes were set as the onset and duration of sensory and motor blockade, perioperative hemodynamics, and the total 24-hour postoperative morphine consumption., Results: Durations of sensory and motor blockades as well as durations of analgesia were all significantly longer among patients in Group D (mean 2.2, 3.5, 5.8 hours respectively) and Group M (mean 2.2, 3.3, 5.2 hours respectively), in comparison to Group S (mean 1.5, 2.7, 3.9 hours respectively). No significant differences were found in systolic or diastolic arterial blood pressure, heart rate oxygen saturation, cardiac output, or stroke volume among the study groups. Seven patients in Group D and four patients in Groups M and S developed hypotension., Conclusion: Intravenous infusion of either dexmedetomidine or MgSO 4 with spinal anesthesia effectively improves the quality of spinal anesthesia and prolongs the duration of postoperative analgesia and decreases the 24-hour postoperative morphine consumption. Results also demonstrated that the use of dexmedetomidine resulted in a slightly longer duration of analgesia, whilst the use of MgSO 4 resulted in slightly better hemodynamic stability., (Copyright © 2021 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.)

Here, we demonstrate that the two distinct formulations of our anti-sepsis drug candidate Rejuveinix (RJX), have a very favorable safety profile in Wistar Albino rats at dose levels comparable to the projected clinical dose levels. 14-day treatment with RJX-P (RJX PPP.18.1051) or RJX-B (RJX-B200702-CLN) similarly elevated the day 15 tissue levels of the antioxidant enzyme superoxide dismutase (SOD) as well as ascorbic acid in both the lungs and liver in a dose-dependent fashion. The activity of SOD and ascorbic acid levels were significantly higher in tissues of RJX-P or RJX-B treated rats than vehicle-treated control rats (p < 0.0001). There was no statistically significant difference between tissue SOD activity or ascorbic acid levels of rats treated with RJX-P vs. rats treated with RJX-B (p > 0.05). The observed elevations of the SOD and ascorbic acid levels were transient and were no longer detectable on day 28 following a 14-day recovery period. These results demonstrate that RJX-P and RJX-B are bioequivalent relative to their pharmacodynamic effects on tissue SOD and ascorbic acid levels. Furthermore, both formulations showed profound protective activity in a mouse model of sepsis. In agreement with the PD evaluations in rats and their proposed mechanism of action, both RJX-P and RJX-B exhibited near-identical potent and dose-dependent anti-oxidant and anti-inflammatory activity in the LPS-GalN model of ARDS and multi-organ failure in mice., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background/aim: The effects of systemic magnesium sulfate (MgSO4) on retina in preterm hypoxic-ischemic (HI) rat model are not known. Our aim was to investigate the effects of MgSO4 on retinal ganglion cell (RGC) count, retinal ganglion cell (RGC) apoptotic index, retinal vascular endothelial growth factor receptor-2 (VEGFR-2), and glial fibrillary acidic protein (GFAP) expressions in preterm HI rat model., Materials and Methods: Fifteen, postnatal day (PND) 7 rat pups were divided into 3 groups: 1. Sham-operated group, 2. HI group, and 3. MgSO4-treated HI group. The second and third groups underwent ischemia followed by exposure to hypoxia for 2 h (Vannucci model). The first and second groups received intraperitoneal saline and the third group received intraperitoneal MgSO4. On PND 10, eyes of the pups were evaluated for RGC count, apoptotic index, VEGFR-2, and GFAP expressions., Results: In both HI and MgSO4-treated HI group, the mean total RGC counts were found to be significantly decreased. However, the mean total RGC count in the MgSO4-treated HI group was significantly higher than that of the HI group. The mean apoptotic index was found to be significantly increased in the HI group. Retinal VEGFR-2 and GFAP expressions were found to be significantly higher in the HI group., Conclusions: Magnesium sulfate preconditioning and treatment in preterm HI rat model might diminish apoptosis, relatively preserve RGCs, and reduce retinal VEGFR-2 and GFAP expressions., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Objective: Antenatal magnesium sulfate (MgSO 4 ) treatment is associated with reduced risk of cerebral palsy in preterm infants. We aimed to investigate whether this treatment leads to any alterations on cerebral hemodynamics which could be detected by near-infrared spectroscopy (NIRS) readings in early postnatal life., Study Design: Infants with gestational ages (GAs) ≤ 32 weeks were divided into two groups regarding their exposure to antenatal neuroprotective MgSO 4 treatment or not. NIRS monitoring was performed to all infants, and readings were recorded for 2 hours each day during the first 3 days of life. The primary aim was to compare regional cerebral oxygen saturation (rcSO 2 ) and cerebral fractional tissue oxygen extraction (cFTOE) between the groups., Results: Sixty-six infants were exposed to antenatal MgSO 4 , while 64 of them did not. GA and birth weight were significantly lower in the treatment group ( p  < 0.01). No difference was observed in rcSO 2 and cFTOE levels in the first, second, and the third days of life ( p  > 0.05). An insignificant reduction in severe intraventricular hemorrhage rates was observed (8 vs. 15%, p  = 0.24)., Conclusion: We could not demonstrate any effect on cerebral oxygenation of preterm infants in early postnatal life that could be attributed to antenatal neuroprotective MgSO 4 treatment. Future studies are warranted to clarify the exact underlying mechanisms of neuroprotection., Competing Interests: None declared., (Thieme. All rights reserved.)

Intravenous magnesium sulfate (MgSO4) is used in equine practice to treat hypomagnesemia, dysrhythmias, neurological disorders, and calcium dysregulation. MgSO4 is also used as a calming agent in equestrian events. Hypercalcemia affects calcium-regulating hormones, as well as plasma and urinary electrolytes; however, the effect of hypermagnesemia on these variables is unknown. The goal of this study was to investigate the effect of hypermagnesemia on blood parathyroid hormone (PTH), calcitonin (CT), ionized calcium (Ca2+), ionized magnesium (Mg2+), sodium (Na+), potassium (K+), chloride (Cl-) and their urinary fractional excretion (F) after intravenous administration of MgSO4 in healthy horses. Twelve healthy female horses of 4-18 years of age and 432-600 kg of body weight received a single intravenous dose of MgSO4 (60 mg/kg) over 5 minutes, and blood and urine samples were collected at different time points over 360 minutes. Plasma Mg2+ concentrations increased 3.7-fold over baseline values at 5 minutes and remained elevated for 120 minutes (P < 0.05), Ca2+ concentrations decreased from 30-60 minutes (P < 0.05), but Na+, K+ and Cl- concentrations did not change. Serum PTH concentrations dropped initially to rebound and remain elevated from 30 to 60 minutes, while CT concentrations increased at 5 minutes to return to baseline by 10 minutes (P < 0.05). The FMg, FCa, FNa, FK, and FCl increased, while urine osmolality decreased from 30-60 minutes compared baseline (P < 0.05). Short-term experimental hypermagnesemia alters calcium-regulating hormones (PTH, CT), reduces plasma Ca2+ concentrations, and increases the urinary excretion of Mg2+, Ca2+, K+, Na+ and Cl- in healthy horses. This information has clinical implications for the short-term effects of hypermagnesemia on calcium-regulation, electrolytes, and neuromuscular activity, in particular with increasing use of Mg salts to treat horses with various acute and chronic conditions as well as a calming agent in equestrian events., Competing Interests: Dr. Stephen Schumacher is employed by the sponsor of the project (USEF). However, this affiliation does not alter our adherence to all PLOS ONE policies on sharing data and materials.

MgSO 4 has been used for the past two decades as neuroprotective treatment in a variety of preterm conditions. Despite the putative advantages of MgSO 4 as a neuroprotective agent in the preterm brain, the short- and long-term molecular function of MgSO 4 as a neuroprotective agent has not been fully elucidated. Neuregulin (NRG1)-ErbB4 signaling plays a critical role in embryonic brain development, in the biology of dopaminergic, GABAergic, and glutamatergic systems. We hypothesize that this pathway may be associated with the neuroprotective role of MgSO 4 . The current study aims to investigate the ability of MgSO 4 to modulate the normal developing expression pattern of selected genes related to the NRG1-ErbB, dopaminergic, GABAergic, and glutamatergic systems. We demonstrate that overall short-term treatment of dam rats with MgSO 4 affects the expression of fetal brain NRG1, NRG3, ErbB4, GAD67, tyrosine hydroxylase (TH), dopamine D 2 and D 1 receptors, GluN1, and GluN2B. More specifically, the administration of MgSO 4 alters the expression of NRG-ErbB, GAD67, TH, and D2R at early gestation day 16 (GD16) regardless of the activation of the maternal immune system by lipopolysaccharide (LPS). Our data suggest that MgSO 4 treatment may affect the expression of major neuronal systems and pathways mostly at an early gestation day. These changes might be an initial clue (foundation stone) in the molecular mechanism that underlies the beneficial effect of MgSO 4 as a neuroprotective agent for the developmental brain.

The role of Renin-Angiotensin-System (RAS) in the pathogenesis of preeclampsia and eclampsia is still unclear. Our aim was to investigate plasma angiotensin II concentration [Ang II] in women with normotensive pregnancies (NP, n = 22) and severe preeclampsia in use of magnesium sulfate (SPE, n = 29). Despite no difference between the groups (SPE: 47.8 pg/ml vs NP: 39.7 pg/ml, p = 0.195), lower maternal age (p = 0.007) and primigravida (p = 0.028) were associated with lower [Ang II]. Plasma [Ang II] increased over the 24 h of magnesium sulfate administration (r = 0.48, p = 0.009). Our findings suggest that RAS may be involved with the mechanism of magnesium protection against eclamptic seizure., (Copyright © 2020 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Nicotinamide adenine dinucleotide (NAD)/NAD phosphate (NADPH) is essential for numerous redox reactions and serve as co-factors in multiple metabolic processes in all organisms. NAD kinase (NADK) is an enzyme involved in the synthesis of NADP + from NAD + and ATP. Arabidopsis NADK2 (AtNADK2) is a chloroplast-localizing enzyme that provides recipients of reducing power in photosynthetic electron transfer. When Arabidopsis plants were grown on MS medium supplemented with 5 mM MgSO 4 , an AtNADK2-overexpressing line exhibited higher glutathione and total sulfur accumulation than control plants. Metabolomic analysis of major amino acids and organic acids using capillary electrophoresis-mass spectrometry demonstrated that overexpression of AtNADK2 affected a range of metabolic processes in response to MgSO 4 supplementation.

Preeclampsia is a complex disorder that is characterized by new onset hypertension and proteinuria at or after 20 weeks of gestation. Preeclampsia is a leading cause of maternal and fetal morbidity and mortality. MgSO 4 is commonly used to treat severe preeclampsia, but its mechanism of action is poorly understood, and investigations into the effects of MgSO 4 during the postpartum period are lacking. In this study, timed-pregnant Sprague-Dawley rats received low-dose lipopolysaccharide (LPS) on gestational day 14 to induce preeclampsia. Maternal and fetal outcomes and the macrophage profile 1 week after delivery were explored. On postpartum day (PD) 7, the maternal systolic blood pressure and urinary protein level were significantly increased, the number of M1 macrophages was increased and the number of M2 macrophages was decreased in the maternal kidney and brain; the median duration of gestation, the number of live fetuses, and the fetal weight/placenta weight ratio were significantly decreased; and the percentage of growth-restricted pups and fetal mortality were significantly increased in preeclampsia rats compared to normal pregnant control rats. Prophylactic MgSO 4 decreased blood pressure at PD7, improved pregnancy outcomes, and promoted the polarization of M2 macrophages in the kidney and of M2 microglia in the brain of preeclampsia rats. These findings confirm that the pathophysiology of preeclampsia involves the dysregulation of the inflammatory response and the activation of M1 macrophages in several target organs during pregnancy. MgSO 4 prophylaxis attenuates the postpartum effects of preeclampsia by promoting M2 macrophage polarization in the maternal kidney and brain.

Mg 2+ is an important cation in our body. It is an essential cofactor for many enzymes. Despite many works, nothing is known about the protective effects of MgSO 4 against hypoxia-induced lethality and oxidative damage in brain mitochondria. In this study, antihypoxic and antioxidative activities of MgSO 4 were evaluated by three experimental models of induced hypoxia (asphyctic, haemic, and circulatory) in mice. Mitochondria protective effects of MgSO 4 were evaluated in mouse brain after induction of different models of hypoxia. Antihypoxic activity was especially pronounced in asphyctic hypoxia, where MgSO 4 at dose 600 mg/kg showed the same activity as phenytoin, which used as a positive control ( P < 0.001). In the haemic model, MgSO 4 at all used doses significantly prolonged latency of death. In circulatory hypoxia, MgSO 4 (600 mg/kg) doubles the survival time. MgSO 4 significantly decreased lipid peroxidation and protein carbonyl and improved mitochondrial function and glutathione content in brain mitochondria compared to the control groups. The results obtained in this study showed that MgSO 4 administration has protective effects against lethality induced by different models of hypoxia and improves brain mitochondria oxidative damage., Competing Interests: The authors declared no conflicts of interest., (Copyright © 2020 Hamidreza Mohammadi et al.)

Magnesium sulfide nanoparticles (MgS NPs) is a nanomaterial that has an important place in diagnosis, treatment, diagnosis, and drug delivery systems. Neuroblastoma, a type of brain cancer, is an extremely difficult cancer to treat with today's treatment options. This study was carried out to determine the cytotoxic, oxidant, and antioxidant effects on the neuroblastoma cancer line (SH-SY5Y cell line) along with the green synthesis and characterization of MgS NPs structures. MgS NPs were synthesized by green synthesis using Na 2 S and Punica granatum, a cleaner method for toxic effects, and characterized using Scanning Electron Microscopy, Fourier Transform Infrared spectroscopy, X-Ray diffraction methods. In cell culture, SH-SY5Y cells were grown in a suitable nutrient medium under favorable conditions. Five different doses of MgS NPs (10, 25, 50, 75, and 100 µg/mL) were applied to the cell line for 24 h. The analysis of the MgS NPs applications was performed with MTT cytotoxicity test and total oxidant and total antioxidant tests. According to the data obtained, 75 μg/mL MgS NPs application decreased cancer cell viability up to 48.54%. MgS NPs exhibited a dose-dependent effect on the SH-SY5Y cell line. Also, it was determined that MgS NPs increased oxidant activity in neuroblastoma cells, which was compatible with the cytotoxicity test. As a result, MgS NPs exhibited an effective activity on the neuroblastoma cell line. It was clearly seen that NPs obtained by green synthesis prevented the related cancer line from proliferating.

Background: Magnesium sulfate (MgSO4) is widely used in analgesia for different conditions. Recent randomized controlled trials (RCTs) have evaluated the effects of MgSO4 on renal colic; however, this new evidence has not been synthesized. Thus, we conducted a systematic review and meta-analysis to assess the efficacy and safety of MgSO4 in comparison with control for renal colic., Methods: PubMed, EMBASE, and Scopus databases were searched from inception to February 2020. We included RCTs that evaluated MgSO4 vs control for patients with renal colic. Data were independently extracted by 2 reviewers and synthesized using a random-effects model., Results: Four studies with a total of 373 patients were analyzed. Intravenous MgSO4 15 to 50 mg/kg did not significantly reduce renal colic pain severity at 15 minutes (mean difference [MD] = 0.35, 95% confidence interval [CI] -0.51 to 1.21; 2 RCTs), 30 minutes (MD = 0.19, 95% CI -0.74 to 1.13; 4 RCTs), and 60 minutes (MD = -0.28, 95% CI -0.72 to 0.16; 3 RCTs) in comparison with controls. In patients who failed to respond to initial analgesics, intravenous MgSO4 15 mg/kg or 2 ml of 50% solution provided similar pain relief to ketorolac or morphine at 30 minutes (P = .90) and 60 minutes (P = .57). No significant hemodynamic changes were observed with short-term use of MgSO4 in these studies., Conclusion: MgSO4 provides no superior therapeutic benefits in comparison with control treatments. MgSO4 may be used as a rescue medication in patients not responding to initial analgesics. The short-term use of MgSO4 did not affect hemodynamic values.

Objectives: To evaluate the safety and efficacy of ketamine-magnesium combination to reduce attacks in a series of patients with refractory chronic cluster headache (rCCH)., Background: Refractory chronic cluster headache (CCH) is a rare but highly debilitating condition that needs new treatment options. A previous publication reported that a single infusion of ketamine-magnesium combination was effective in 2 patients with rCCH., Methods: The treatment was proposed to consecutive patients with rCCH seen in 2 French hospitals between November 2015 and February 2020 and who were resistant to at least 3 preventive treatments. They received a single ketamine infusion (0.5 mg/kg over 2 hours) combined with magnesium sulfate (3000 mg). The main outcome was a comparison of the number of daily attacks 2 weeks prior to the ketamine-magnesium infusion and 1 week after (on days 7 and 8). The second outcome was the percentage of responders (patients with ≥50% reduction in the frequency of daily attacks). Safety was assessed by the recording of adverse events during infusion. Descriptive statistics are presented as mean ± standard deviation., Results: Seventeen patients (14 men), with an age of 35.2 ± 8.1 years, were included. They presented with CCH for 6.6 ± 4.3 years. The number of daily attacks decreased from 4.3 ± 2.4 before treatment to 1.3 ± 1.0 after treatment (difference: -3.1 (95% CI: -4.5 to -1.6), P < .001). Seventy six percent (13/17) were responders. Transient and mild sedation was reported by 7/17 patients (41.2%)., Conclusions: The ketamine-magnesium combination seems an effective and well-tolerated therapy for rCCH. Placebo-controlled studies should be conducted to further confirm these findings., (© 2020 American Headache Society.)

Background: Maternal administration of magnesium sulfate (Mg) is used in humans to protect the fetal brain during preterm delivery. We sought to determine the neuroprotective mechanism of Mg in a rat model of late gestation maternal inflammation. Methods: Pregnant rats at 20 d of gestation (20 total, four groups, N  = 5 in each group) received i.p. LPS or saline. Dams were randomized for s.c. saline or Mg supplementation 2 h prior and following the LPS/saline injections. Dams were sacrificed 4 h following the last treatment. Fetal brains were collected from the four treatment groups. Fetal brain caspase 3 active form, NF-kB p65, neuronal nitric oxide synthase (phospho-nNos), and proinflammatory cytokines levels were determined by western blot. Results: Maternal LPS at e20 significantly ( p  < .01) increased fetal brain caspase 3 active form (af) (0.27 ± 0.02 versus 0.15 ± 0.06u), NFkB (0.23 ± 0.01 versus 0.13 ± 0.01u), and phospho-nNOS (0.22 ± 0.01 versus 0.12 ± 0.01u) and fetal brain proinflammatory cytokines (IL-6 0.21 ± 0.01 versus 0.11 ± 0.01 u; TNFα 0.29 ± 0.01 versus 0.15 ± 0.01u), compared with control fetuses. Mg treatment significantly ( p  < .05) reduced fetal brain caspase 3 af (0.16 ± 0.01u), NFkB p65 (0.11 ± 0.01u), phospho-nNOS (0.1 ± 0.01u), as well as brain proinflammatory cytokines (IL-6 0.07 ± 0.01u; TNFα 0.15 ± 0.01u) to levels similar to controls. Conclusion: Maternal inflammation-induced fetal brain injury at late gestation may be mediated by the activation of inflammatory response, oxidative stress, and apoptosis. Maternal Mg may attenuate the injury by inhibition of these putative pathways.

Background: The use of magnesium sulphate (MgSO4) in combination with antihypertensive drugs such as Labetalol is common in preeclampsia., Objectives: We aimed to examine the effects of MgSO4 and Labetalol on placental blood vessel reactivity in response to angiotensin II (ATII)., Methods: A dual-perfused single cotyledon model was used. Placentas from normal pregnancies were obtained. Selected cotyledons were cannulated and dually perfused. The intervillous space was infused for 60 minutes with three perfusion protocols: MgSO4 [7 mg%], MgSO4 [7 mg%], with Labetalol [1×10-4 mmol/L] and controls. After 60 minutes, ATII was injected as a bolus into the chorionic artery causing contraction/relaxation response in the fetal compartment. Perfusion pressure was measured continuously during contraction and relaxation phases., Results: Twenty complete experiments were performed (9 controls, 7 with MgSO4 (7mg%) and 4 with MgSO4 [7mg%] and Labetalol [1×10-4 mmol/L]). Basal perfusion pressure did not differ between the treatment groups. Mean area under the pressure curve (AUC), the amplitude of the contraction response and the relaxation factor did not differ significantly between the groups in response to ATII administration., Conclusions: Magnesium sulphate and Labetalol did not have any effect on feto-placental vasculature reactivity.

Background: To compare the safety and effectiveness of del Nido cardioplegia with blood-based St Thomas Hospital (BSTH) cardioplegia in myocardial protection in congenital heart surgery., Methods: It is a prospective, open-labeled, randomized controlled study conducted at National Heart Institute, Kuala Lumpur from July 2018 to July 2019. All patients with simple and complex congenital heart diseases (CHD) with good left ventricular function (left ventricular ejection fraction [LVEF] >50%) were included while those with LVEF <50% were excluded. A total of 100 patients were randomized into two groups of 50 each receiving either del Nido or BSTH cardioplegia. Primary end points were the spontaneous return of activity following aortic cross-clamp release and ventricular function between two groups. Secondary end point was myocardial injury as assessed by troponin T levels., Results: Cardiopulmonary bypass and aortic cross-clamp time, return of spontaneous cardiac activity following the aortic cross-clamp release, the duration of mechanical ventilation, and intensive care unit stay were comparable between two groups. Statistically significant difference was seen in the amount and number of cardioplegia doses delivered ( P < .001). The hemodilution was significantly less in the del Nido complex CHD group compared to BSTH cardioplegia ( P = .001) but no difference in blood usage ( P = .36). The myocardial injury was lesser (lower troponin T release) with del Nido compared to BSTH cardioplegia ( P = .6)., Conclusion: Our study showed that both del Nido and BSTH cardioplegia are comparable in terms of myocardial protection. However, single, less frequent, and lesser volume of del Nido cardioplegia makes it more suitable for complex repair.

Prenatal treatment with magnesium sulfate (MgSO 4 ) has neuroprotective effects in very preterm infants but its use has been associated with an increased rate of patent ductus arteriosus (DA). MgSO 4 is a vasodilator and thus may exert a direct relaxant effect in the DA. We aimed to investigate the vasoactive effects of MgSO 4 in the DA using the chicken embryo as experimental model. DA rings from 15-d (E15), 17-d (E17) and 19-d (E19) chicken embryos (total incubation: 21-d) were mounted in a wire myograph for isometric tension recordings. Exposure of DA rings to 21% O 2 induced a tonic contraction which was relaxed by MgSO 4 (2.4 - 7.2 mmol L -1 ) in a concentration-dependent manner (mean maximal relaxation E19: 51.4%, SE 6.3; EC 50 : 3.5 mmol L -1 , SE 0.7). The relaxation evoked by MgSO 4 was not significantly different between E15, E17 and E19 DA and was not affected by removal of the endothelium or by the presence of the nitric oxide synthase inhibitor L-NAME, the soluble guanylate cyclase inhibitor ODQ, or the cyclooxygenase inhibitor indomethacin. In contrast, when the DA rings were incubated in Ca 2+ -free solution, or in the presence of inhibitors of L-type Ca 2+ channels (nifedipine), or large-conductance Ca 2+ -activated K + (BK Ca ) channels (iberiotoxin), MgSO 4 -induced relaxation was impaired. Preincubation of the DA rings with MgSO 4 concentrations ranging from 0 to 6.0 mmol L -1 did not significantly affect O 2 -induced contraction that was only impaired by a concentration of 7.2 mmol L -1 . In conclusion, MgSO 4 induced endothelium-independent relaxation of chicken DA and this relaxation appeared to be mediated through stimulation of BK Ca channels and blockade of transmembrane flux of extracellular Ca 2+ . However, O 2 -induced DA contraction was only impaired by suprapharmacological concentrations of MgSO 4 (> 6.0 mmol L -1 ). Therefore, our data suggest that the higher incidence of patent DA in preterm infants exposed to MgSO 4 is unlikely to be due to a direct pharmacological effect of the drug on the DA.

Background: St. Thomas (ST) and Del Nido (DN) cardioplegic solutions are widely used for myocardial protection during cardiac surgery. In 2016, our university hospital shifted from modified St. Thomas to Del Nido solution for both adult and pediatric cardiac surgery. This retrospective study was conducted to compare ST and DN solutions regarding surgical workflow and clinical outcome in pediatric and adult patients undergoing cardiac surgery., Methods: We reviewed 220 patients who underwent cardiac surgery requiring cardioplegic arrest. Patients were categorized in 2 groups: ST (n = 110) and DN (n = 110). Each group included 60 pediatric and 50 adult patients. Demographic, intraoperative, and postoperative variables were collected., Results: In pediatric patients, no significant difference was found between the 2 groups regarding clamping time, bypass time, need for defibrillation, inotropic score, postoperative ejection fraction (EF), period of mechanical ventilation, intensive care unit stay, or postoperative arrhythmias. One patient in the ST group required mechanical support by extracorporeal membrane oxygenation. We had 5 cases of pediatric mortality (3 in DN and 2 in ST, P = .64). In adult patients, significantly fewer patients in the DN group needed defibrillation than in the ST group. No significant difference was found regarding clamping time, inotropic score, or intraaortic balloon pump use. Mortality in adult patients was 6 cases (4 in ST group and 2 in DN group)., Conclusion: DN cardioplegia solution is as safe as ST solution in pediatric and adult cardiac surgery. It has comparable results of myocardial protection and clinical outcome, with superiority regarding uninterrupted surgery and lower rate of defibrillation.

Background: Magnesium sulphate given to women immediately prior to very preterm birth protects the perinatal brain, so fewer babies die or develop cerebral palsy. How magnesium sulphate exerts these beneficial effects remains uncertain. The aim of the MagNUM Study was to assess the effect of exposure to antenatal magnesium sulphate on MRI measures of brain white matter microstructure at term equivalent age., Methods: Nested cohort study within the randomised Magnesium sulphate at 30 to <34 weeks' Gestational age Neuroprotection Trial (MAGENTA). Mothers at risk of preterm birth at 30 to <34 weeks' gestation were randomised to receive either 4 g of magnesium sulphate heptahydrate [8 mmol magnesium ions], or saline placebo, infused over 30 min when preterm birth was planned or expected within 24 h. Participating babies underwent diffusion tensor MRI at term equivalent age. The main outcomes were fractional anisotropy across the white matter tract skeleton compared using Tract-based Spatial Statistics (TBSS), with adjustment for postmenstrual age at birth and at MRI, and MRI site. Researchers and families were blind to treatment group allocation during data collection and analyses., Findings: Of the 109 participating babies the demographics of the 60 babies exposed to magnesium sulphate were similar to the 49 babies exposed to placebo. In babies whose mothers were allocated to magnesium sulphate, fractional anisotropy was higher within the corticospinal tracts and corona radiata, the superior and inferior longitudinal fasciculi, and the inferior fronto-occipital fasciculi compared to babies whose mothers were allocated placebo (P < 0.05)., Interpretation: In babies born preterm, antenatal magnesium sulphate exposure promotes development of white matter microstructure in pathways affecting both motor and cognitive function. This may be one mechanism for the neuroprotective effect of magnesium sulphate treatment prior to preterm birth., Funding: Health Research Council of New Zealand., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Diaphragm dysfunction could be induced by sepsis with subsequent ventilatory pump failure that is associated with local infiltration of inflammatory factors in the diaphragm. It has been shown that the administration of anticonvulsant agent, magnesium sulfate (MgSO4) could decrease systematic inflammatory response. We recently reported that MgSO4 could inhibit macrophages high mobility group box 1 (HMGB1) secretion that confirms its anti-inflammatory properties. Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signal pathway appears to be involved in the pathology of septic experimental animal's inflammatory response and involve in the pathogenic mechanisms of sepsis-induced diaphragm dysfunction. Thus, in this study, we are aiming to explore whether MgSO4 could ameliorate sepsis-induced diaphragm dysfunction via TLR4/NF-κB pathway in a rodent model with controlled mechanical ventilation (CMV) and subsequent septic challenge., Methods: Rats were randomly assigned into (1) control group: having an identical laparotomy but without ligation or puncture in the cecum; (2) CLP group: cecal ligation and puncture (CLP) with continuous saline infusion; (3) CLP + MgSO4 group: CLP with continuous MgSO4 administration; and (4) MgSO4 group: a sham surgery with MgSO4 administration. After surgery, all rats were submitted to CMV for 18 h. After completion of the study protocol, blood inflammatory cytokine/chemokine was detected by ELISA, as well as diaphragm contractility, TLR4, NF-κB (p65), phospho-NF-κB (p65) and HMGB1 protein expression., Results: The level of inflammatory cytokine/chemokine includes interleukin-6, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-2 (MIP-2) and HMGB1 in blood were significantly increased at 18-h post-CLP compared with the control group. We found that rats in the CLP group had substantial diaphragm dysfunction with a distinct downshift of the force-frequency curve. Furthermore, expression of HMGB1, TLR4, NF-κB (p65) and phospho-NF-κB (p65) in diaphragm were significantly increased in the CLP group. In contrast, MgSO4 attenuated the septic inflammation reaction in diaphragm and serum and preserved diaphragm function., Conclusion: MgSO4 protects against sepsis-induced diaphragm dysfunction. This may be associated with its anti-inflammatory effect on HMGB1/TLR4/NF-κB signal pathway.

Providing yeast with the right amount of mineral salts before fermentation can contribute to improving the entire technological process, resulting in a better-quality final product. The aim of this study was to assess the impact of apple must supplementation with mineral salts ((NH 4 ) 2 SO 4 , MgSO 4 , (NH 4 ) 3 PO 4 )) on enological parameters, antioxidant activity, total polyphenol content, and the profile of volatile cider compounds fermented with various yeast strains. Rubin cultivar must was inoculated with wine, cider, and distillery or wild yeast strains. Various mineral salts and their mixtures were introduced into the must in doses from 0.167 g/L to 0.5 g/L. The control sample consisted of ciders with no added mineral salts. The basic enological parameters, antioxidant properties, total polyphenol content, and their profile, as well as the composition of volatile compounds, were assessed in ciders. Must supplementation with magnesium salts significantly influenced the use of the analyzed element by yeast cells and was dependent on the yeast strain. In supplemented samples, a decrease in alcohol concentration and total acidity, as well as an increase in the content of extract and total polyphenols, was observed compared to the controls. The addition of ammonium salts caused a decrease in the amount of higher alcohols and magnesium salts, as well as a decrease in the concentration of some esters in ciders.

Magnesium sulfate is used as a tocolytic, but clinical efficacy has been seriously questioned. Our objective was to use controlled ex vivo conditions and known pregnancy stages, to investigate how 2 key factors, hormones and gestation, affect magnesium's tocolytic ability. We hypothesized that these factors could underlie the varying clinical findings around magnesium's efficacy. Myometrial strips were obtained from nonpregnant (n = 10), mid-pregnant (n = 12), and term-pregnant (n = 11) mouse uterus. The strips were mounted in organ baths superfused with oxygenated physiological saline at pH 7.4 and 37 °C. The effect of different concentrations of MgSO 4 (2-20 mM) was examined on spontaneous and oxytocin-induced (0.5-1 nM) contractions. Contractile properties (amplitude, frequency, and area under the curve) were measured before and after application of magnesium. Magnesium sulfate had a dose-dependent inhibitory effect on both spontaneous and oxytocin-induced contractions but was less effective in the presence of oxytocin. In spontaneous contractions, magnesium was more potent as gestation progressed (P < .0001). In the presence of oxytocin, however, there were no significant gestational differences in its effects on contraction. The rapid onset and reversal of magnesium's effects suggest an extracellular action on calcium entry. Taken together, we conclude that magnesium's actions are influenced by both gestational state and hormones, such that, at least in mice, it is least effective in early gestation with oxytocin present and most effective at term in the absence of oxytocin. That magnesium is least effective preterm and oxytocin decreases its effectiveness throughout gestation, may explain its disappointing clinical effects as a tocolytic.

Vascular endothelial growth factor (VEGF) is the most important regulator of angiogenesis which serves to provide sufficient blood supply, and can trigger both physiological and pathological angiogenesis. Recent studies have shown that VEGF increases in gynecological diseases (such as endometriosis, ovarian, and endometrial cancers) and is a prognostic factor in these pathologies. Therefore, VEGF should be maintained at appropriate levels. Magnesium is used in many gynecological practices (such as eclampsia, preeclampsia, dysmenorrhea, and climacteric symptoms) and the mechanisms of action are still under investigation. Redox status, which can be regulated by magnesium, was shown to affect VEGF expression. The aim of this study was to evaluate the effects of chronic magnesium use on VEGF and oxidative status in the uterus. Magnesium sulfate was administered to rats at doses of 30 mg/kg (intramuscular) for 2 weeks. VEGF, Superoxide dismutase (SOD), Glutathione peroxidase (GPx), and Malondialdehyde (MDA) levels were measured using ELISA; vascular and cellular alterations were determined by histology in the uterine tissue at the metoestrus phase. In the uterine tissue of Mg-treated subjects, magnesium levels increased while VEGF, SOD, GPx, and MDA levels decreased without histological changes. There was a negative correlation between uterine tissue magnesium levels and VEGF, SOD, GPx, and MDA levels. Consequently, the results of this study demonstrated that regular magnesium use decreased VEGF levels in uterus. Decreased VEGF levels were associated with decreased uterine oxidative stress. Chronic magnesium usage may protect the uterine tissue from certain diseases in which angiogenesis is critical.

MgSO 4 is effective in preventing spontaneous in vitro platelet agglutination in anticoagulant-induced pseudothrombocytopenia (PTCP). In order to learn more about its potential as an in vitro anticoagulant, platelets from MgSO 4 -anticoagulated blood were stimulated by several differentially-acting agonists (ADP, ARA, TRAP, epinephrine, collagen and ristocetin). Platelet aggregation in blood samples from 11 and 17 volunteers was measured by light-transmission aggregometry (LTA) according to Born and impedance aggregometry (Multiplate TM ), respectively. Agonist-induced platelet aggregation was markedly lower in MgSO 4 -anticoagulated samples when compared with citrate-anticoagulated samples (decrease of 95.75% (ristocetin), 69.02% (collagen) and 75.73% (epinephrine)) or hirudin-anticoagulated samples (decrease of 85.99% (ADP), 80.98% (ARA), 77.24% (ristocetin), 54.37% (collagen) and 50.14% (TRAP)). The anti-aggregatory effect of MgSO 4 is dose-dependent and readily detectable at a concentration of 7.5 mmol/l. Analysis of the agonist signaling pathways suggest that MgSO 4 interferes with the final step of platelet aggregation, namely the intracellular mobilization of Ca 2+ .

Objective: The objective of this study was to evaluate the effect of magnesium sulfate in the prevention of fetal growth restriction due to the impaired uterine blood supply in the rat model. Methods: A total number of 24 female rats were used in this study. They were mated overnight and randomly divided into control and treatment groups. After anesthesia and incising abdominal midline in day 17 of gestation, the uterine artery was occluded by an atraumatic clamp for 60 min. The rats of the control group received normal saline after surgery and the rats of treatment group received magnesium sulfate subcutaneously. The laparotomy was repeated on day 21 of gestation, and the number of alive and dead fetuses was counted in each horn. The viability of fetuses was evaluated. The weight of the placenta and fetuses and the distance between the head and tail as well as back to the abdomen of the fetuses were also measured. Samples of the amniotic fluid (AF) were collected during both surgeries for biochemical analyses of the glucose, urea, lactate, and pyruvate levels by an AutoAnalyzer. Results: Among the total fetuses in ischemic horn, only 50% survived in the control group. Dead fetuses had less body consistency and had a dark color. In contrary, only 7.6% of the fetuses in the treatment group were absorbed and 92.4% were completely healthy and developed. Parameters related to placenta weight, fetus weight, fetus length, and fetus width had significant differences and those of the treatment group were higher. Glucose and lactate levels of the AF in the treatment group were significantly lower and urea level was significantly higher than the control group in day 21 of gestation. The changes in pyruvate levels were not significant. Conclusion: In conclusion, magnesium sulfate may counteract with the effects of temporary uterine ischemia in pregnant rats and prevent intrauterine growth restriction.

Aim: To investigate the effects of magnesium sulfate on fetal baroreflex in normoxemia or acute fetal hypoxemia., Methods: Fetal baroreflex response was elicited using phenylephrine (30 μg) in saline and magnesium sulfate in 8 chronically treated and instrumented fetal sheep. Hypoxemia was induced using nitrogen gas inflow for 30 min. Baroreflex, calculated as the ratio of the fetal heart rate change to the mean arterial pressure, was monitored after magnesium sulfate administration and in rapid and nonrapid eye movement (NREM) sleep states. Baroreflex was assessed in response to hypoxemia in control groups in both the rapid and NREM sleep states., Results: Baroreflex was not significantly affected by saline, magnesium sulfate and rapid or NREM sleep states in normoxemic sheep. Hypoxemia increased the baroreflex in the saline-treated group (hypoxemic vs normoxemic rapid eye movement sleep: 4.37 ± 2.48 vs 2.72 ± 0.83; P < 0.05; hypoxemic vs normoxemic NREM sleep: 4.30 ± 1.47 vs 3.15 ± 0.83; P < 0.001). Magnesium sulfate decreased the baroreflex in the hypoxemic fetuses (magnesium sulfate hypoxemic vs. control normoxemic fetuses: 1.42 ± 0.92 vs 3.15 ± 0.83, P < 0.05)., Conclusion: The hypoxemic fetal sheep, from the ewes that were receiving magnesium sulfate, showed a significantly reduced in the baroreflex response. In clinical practice, baroreflex-related decelerations in hypoxemic fetuses of mothers receiving magnesium sulfate should be carefully interpreted., (© 2020 Japan Society of Obstetrics and Gynecology.)

Objective: To explore the regulatory effect of magnesium sulfate combined with nifedipine and labetalol on disease-related molecules in serum and placenta in the treatment of preeclampsia., Patients and Methods: Altogether 100 patients with preeclampsia admitted to the Children & Women's Healthcare of Laiwu City were selected. They were divided into control group and experimental group according to different treatment methods. Among them, 51 patients in the control group were treated with magnesium sulfate combined with nifedipine, and 49 patients in the experimental group were treated with labetalol on the basis of the treatment in the control group. The therapeutic effects of the two methods were compared. The levels of the following factors in the two groups were compared: kallikrein expression, pregnancy-associated plasma protein A (PAPP-A), pregnancy-specific β1 glycoprotein (SPI), placental growth factor (PLGF), human placental prolactin (HPL), transforming growth factor β1(TGF-β1), vascular cell adhesion molecule 1 (VCAM-1) and E-selectin in serum and placenta tissues., Results: After treatment, the blood pressure in the experimental group was lower than that in the control group (p<0.05). The expression of kallikrein in serum and placental tissue of the patients in the experimental group was higher than that of the patients in the control group (p<0.05); PAPP-A level was lower than that in the control group (p<0.05); TGF-β1 level was higher than that in the control group (p<0.05); VCAM-1 and E-selectin were lower than those in the control group (p<0.05), and kallikrein and TGF-β1 in serum and placenta in the non-occurrence group were higher than those in the occurrence group (p<0.05). The serum and placenta PAPP-A, VCAM-1, and E-selectin in the non-occurrence group were lower than those in the occurrence group (p<0.05)., Conclusions: Magnesium sulfate combined with nifedipine and labetalol has good efficacy in the treatment of preeclampsia. They can promote the expression of endogenous kallikrein, reduce the level of pregnancy-related hypertension predictors, and weaken the infiltration ability of cytotrophoblasts.

Itaconic acid (IA), a building block platform chemical, is produced industrially by Aspergillus terreus utilizing glucose. Lignocellulosic biomass can serve as a low cost source of sugars for IA production. However, the fungus could not produce IA from dilute acid pretreated and enzymatically saccharified wheat straw hydrolyzate even at 100-fold dilution. Furfural, hydroxymethyl furfural and acetic acid were inhibitory, as is typical, but Mn 2+ was particularly problematic for IA production. It was present in the hydrolyzate at a level that was 230 times over the inhibitory limit (50 ppb). Recently, it was found that PO 4 3- limitation decreased the inhibitory effect of Mn 2+ on IA production. In the present study, a novel medium was developed for production of IA by varying PO 4 3- , Fe 3+ and Cu 2+ concentrations using response surface methodology, which alleviated the strong inhibitory effect of Mn 2+ . The new medium contained 0.08 g KH 2 PO 4 , 3 g NH 4 NO 3 , 1 g MgSO 4 ·7H 2 O, 5 g CaCl 2 ·2 H 2 O, 0.83 mg FeCl 3 ·6H 2 O, 8 mg ZnSO 4 ·7H 2 O, and 45 mg CuSO 4 ·5H 2 O per liter. The fungus was able to produce IA very well in the presence of Mn 2+ up to 100 ppm in the medium. This medium will be extremely useful for IA production in the presence of Mn 2+ . This is the first report on the development of Mn 2+ tolerant medium for IA production by A. terreus., (© 2019 American Institute of Chemical Engineers.)

This study aimed at investigating the effects of intraperitoneal (IP) administration of magnesium sulfate (MgSO4) on testicular ischemia-reperfusion (IR) injury in rats. In total, 50 adult Wistar rats were randomly divided into 5 groups. Group 1 received no injection (control); however, group 2 was subjected to 2 h of I and 24 h of R. Subsequently, group 3 was subjected to 2 h of 1, and after 1 h of I, 125 mg/kg MgSO4 was injected intraperitoneally followed by 24 h of R. Groups 4 and 5 were subjected to the same process as group 3, whereas the rats were injected with 250 and 500 mg/kg of MgSO4, respectively. After 24 h, the left testes of all rats were removed for histological analysis and antioxidant activities. According to the results, there was a significant increase in tissue malondialdehyde (MDA) among I/R rats (P&lt;0.05), whereas MgSO4 decreased I/R-induced MDA (P&lt;0.05). Furthermore, experimental I/R diminished glutathione peroxidase (GPx) and superoxide dismutase (SOD) levels significantly (P&lt;0.05). Moreover, MgSO4 (250 and 500 mg/kg) increased GPx and SOD activity significantly in I/R rats (P&lt;0.05). Furthermore, seminiferous tubules degenerated, and few spermatocytes were observed in the testis tubules of the I/R rats. Regarding pathological parameters, seminiferous tubules and spermatocyte were normal in the testes of MgSO4 (250 and 500 mg/kg)-treated experimental I/R-induced rats. In conclusion, this study demonstrated the beneficial effects of MgSO4 on testicular IR injury in rats., (Copyright © 2020, Archives of Razi Institute. Published by Kowsar.)

Objective: The aim of this study was to investigate the protective effect of magnesium sulfate (MgSO4) on the cranial nerves of preeclampsia (PE) rats through the nuclear factor-κB (NF-κB)/intercellular adhesion molecule-1 (ICAM-1) pathway., Materials and Methods: A total of 30 pregnant rats were randomly divided into three groups, including control group, model group, and treatment group, with 10 rats in each group. Systolic blood pressure was measured at 13 d, 15 d, and 19 d. The apoptosis level in brain tissues was detected via Western blotting and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Protein expression of genes was detected using immunohistochemical staining. Moreover, the messenger ribonucleic acid (mRNA) expressions of NF-κB and ICAM-1 in brain tissues were determined through Reverse Transcription-Polymerase Chain Reaction (RT-PCR)., Results: Systolic blood pressure exhibited significant differences among the three groups at 15 d and 19 d of gestational age (p<0.05). At 15 d of gestational age, systolic blood pressure was significantly higher in model group than that of control group (p<0.05). However, it was slightly lower in treatment group than model group (p<0.05). At 19 d of gestational age, systolic blood pressure was significantly higher in model group than control group (p<0.05). However, it decreased remarkably in treatment group when compared with model group (p<0.05). In treatment group, systolic blood pressure at 19 d was significantly lower than that at 15 d (p<0.05). Subsequent Western blotting revealed that the protein expression of B-cell lymphoma-2 (Bcl-2) in brain tissues decreased evidently, whereas the expression of Bcl-2 associated X protein (Bax) increased significantly in model group compared with control group, showing statistically significant differences (p<0.01). The protein expression of Bcl-2 in brain tissues increased significantly, while the expression of Bax declined remarkably in treatment group compared with model group (p<0.01). The number of apoptotic cells in model group and treatment group increased significantly compared with that in control group, with the largest in model group (p<0.05). However, it remarkably declined in treatment group compared with model group (p<0.05). These results suggested that MgSO4 treatment could significantly reduce neuronal apoptosis in PE rats. According to the results of immunohistochemistry, the protein expressions of NF-κB and ICAM-1 in brain tissues were significantly higher in model group and treatment group than those in control group (p<0.05). However, they were significantly lower in treatment group than model group (p<0.05). RT-PCR results manifested that the mRNA expressions of NF-κB and ICAM-1 in brain tissues exhibited evident differences among the three groups (p<0.05). Model group and treatment group showed significantly up-regulated mRNA expressions of NF-κB and ICAM-1 in brain tissues compared with control group (p<0.05). The highest mRNA expression was observed in model group. However, treatment group exhibited remarkably decreased mRNA expressions of NF-κB and ICAM-1 in brain tissues compared with model group (p<0.05)., Conclusions: MgSO4 exerts a protective effect on cranial nerves of PE rats by inhibiting the NF-κB/ICAM-1 signaling pathway.

In this study, FeSO 4 supplementation ranging from 0 to 4.5 mM, and MgSO 4 supplementation ranging from 0 to 5.1 mM were investigated to observe the effect on the population dynamics, biochemical composition and fatty acid content of mixed microalgae grown in Anaerobic Liquid Digestate (ALD). Overall, 3.1 mM FeSO 4 addition into ALD increased the total protein content 60% and led to highest biomass (1.56 g L -1 ) and chlorophyll-a amount (18.7 mg L -1 ) produced. Meanwhile, 0.4 mM MgSO 4 addition increased the total carotenoid amount 2.2 folds and slightly increased the biomass amount. According to the microbial community analysis, Diphylleia rotans, Synechocystis PCC-6803 and Chlorella sorokiniana were identified as mostly detected species after confirmation with 4 different markers. The abundance of Chlorella sorokiniana and Synechocystis PCC-6803 increased almost 2 folds both in iron and magnesium addition. On the other hand, the dominancy of Diphylleia rotans was not affected by iron addition while drastically decreased (95%) with magnesium addition. This study helps to understand how the dynamics of symbiotic life changes if macro elements are added to the ALD and reveal that microalgae can adapt to adverse environmental conditions by fostering the diversity with a positive effect on high value product.

Objectives: In this study, changes in lactate clearance following magnesium supplementation were evaluated in critically ill patients with severe sepsis., Methods: Fifty-eight patients with severe sepsis were randomly assigned to receive either magnesium (n = 30) or placebo (n = 28). Patients in the magnesium group received intravenous magnesium sulfate to maintain serum magnesium level around 3 mg/dL for 3 days. The placebo group received the same volume of normal saline. Change in lactate clearance was considered primary outcome of the study., Results: Mean increase in the lactate clearance in the magnesium group was significantly higher than the placebo group on day 2 (27.53% vs. 23.79% respectively, p < 0.001) and day 3 (49.83% vs. 37.02% respectively, p < 0.001). Time to lactate clearance was also significantly shorter in the magnesium group than the placebo group (47.28 ± 20.59 vs. 61.20 ± 24.31 h respectively, p = 0.03). Sepsis-related mortality was not significantly different but median length of ICU stay was significantly shorter in the magnesium group than the placebo group (8 vs. 15 days respectively, p < 0.01)., Conclusions: Magnesium supplementation increased lactate clearance in critically ill patients with severe sepsis. Optimizing serum magnesium level near the upper limit of the normal range may improve severe sepsis outcomes.

Cyclophosphamide (CYP) is one of the alkylating chemotherapeutic agents and its adverse effects on folliculogenesis in the ovary are well-known due to the previous scientific research on this topic. Magnesium has various effects in organisms, including catalytic functions on the activation and inhibition of many enzymes, and regulatory functions on cell proliferation, cell cycle, and differentiation. In this study, the effects of magnesium sulfate (MgSO 4 ) on CYP induced ovarian damage were investigated. Immature Wistar-Albino female rats of 28-days were treated with pregnant mare serum gonadotrophin (PMSG) to develop the first generation of preovulatory follicles. Rats of the experimental groups were then treated with either CYP (100 mg/kg, i.p) and MgSO 4 (270 mg/kg loading dose; 27 mg/kg maintenance doseX12, i.p) solely or in combination. Following in-vivo 5-bromo-2-deoxyuridine (BrdU) labeling, animals were sacrificed and ovaries were embedded in paraffin and Epon. In the ovaries, added to the evaluation of general morphology and follicle count; BrdU and TUNEL-labeling, cleaved caspase-3 and p27 (cyclin-dependent kinase inhibitor) staining was also performed immunohistochemically and an ultrastructural evaluation was performed by transmission electron microscopy (TEM). The number of primordial follicles were decreased and multilaminar primary and atretic follicles were increased in CYP group. After MgSO 4 treatment, while primordial follicle pool were elevated, the number of atretic follicles were decreased. Additionally, decreased BrdU-labeling, increased cleaved caspase 3 immunoreactivity and increased TUNEL labeling were observed in CYP group. In CYP treated animals, observations showed that while MgSO 4 administration caused no alterations in BrdU proliferation index and caspase-3 immunoreactivity, it significantly reduced the TUNEL labeling. It was also observed that, while p27 immunoreactivity significantly increased in the nuclei of granulosa and theca cells in the CYP group; MgSO 4 treatment significantly reduced these immunoreactivities. The ultrastructural observations showed frequent apoptotic profiles in granulosa and theca cells in both early and advanced stages of follicles in the CYP group and the MgSO 4 treatment before the CYP application led to ultrastructural alleviation of the apoptotic process. In conclusion, our data suggest that MgSO 4 may provide an option of pharmacologic treatment for fertility preservation owing to the beneficial effects of on chemotherapy-induced accelerated follicular apoptotic process, and the protection of the primordial follicle pool., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Background: Magnesium sulfate (MgSO 4 ) is utilized for fetal neuroprotection in preterm birth but its mechanism of action is still poorly understood. P2X7 receptor (P2X7R) is required for secretion of IL-1β, and can be blocked by divalent cations such as magnesium (Mg) and its own antagonist, Brilliant Blue G (BBG). We sought to determine whether during inflammation MgSO 4 can block endothelial IL-1β secretion, using an in-vitro model., Methods: Human umbilical vein endothelial cell (HUVEC) cultures were treated with varying doses of LPS, 2'(3)-Ο-(4-Benzoylbenzoyl) adenosine-5'-triphosphate (BzATP), BBG and MgSO 4 for 3- or 24 h. We determined cell cytotoxicity, apoptosis, IL-1β mRNA expression, IL-1β production and secretion and P2X7R expression on HUVECs., Results: We demonstrated that MgSO 4 is efficacious in blocking IL-1β-mediated-inflammation in HUVECs, at both the initiation and propagation phases of inflammation. MgSO 4 exerts these anti-inflammatory effects via downregulation of P2X7Rs on HUVECs., Conclusion: LPS-exposure increases IL-1β production and secretion in HUVECs, which is further intensified by P2X7R agonist, BzATP while MgSO 4 inhibits IL-1β in both presence and absence of BzATP. This effect is similar to the results of P2X7R antagonist, BBG, suggesting that the anti-inflammatory effects of MgSO 4 is through P2X7R.

Management of chemotherapy-induced adverse effects and the associated pharmaceutical interventions as well as supportive care evidence creation are the most important responsibilities of oncology pharmacists. We have evaluated the (1) efficacy of long-term and successive pharmaceutical care in outpatient chemotherapy and (2) nephroprotective effects of magnesium (Mg) against cisplatin-induced nephrotoxicity (CIN). The results revealed that the adoption rate of pharmaceutical proposals was 98%, and that approximately 70% of the proposals attenuated painful symptoms. Moreover, approximately 60% of pharmaceutical interventions were established after the third visit; in particular, approximately 20% were suggested after the tenth visit. These results have shown that long-term and successive pharmaceutical care by oncology pharmacists in outpatient chemotherapy contributes to a safe and less onerous chemotherapy implementation. CIN frequency and serum creatinine elevation were significantly attenuated by Mg premedication during the cisplatin, docetaxel, and fluorouracil regimen, without changes in adverse effects and response rate. Mg premedication has been suggested to exert a protective effect against CIN without influencing on adverse effects and anti-tumor efficacy. The nephroprotective effect of Mg against CIN was evaluated using Wistar rats. Cisplatin (2.5 mg/kg) was administered once or three times weekly with or without 40 mg/kg MgSO 4 . The results revealed that Mg regulates the expression of organic cation transporter 2, multidrug and toxin extrusion protein 1, and copper transporter 1, leading to reduced renal platinum accumulation, which results in CIN attenuation. In conclusion, evaluation of pharmaceutical care and supportive care by oncology pharmacists is necessary for advanced care of cancer patients.

Background: Ketamine and magnesium sulphate showed synergic interaction in the tail-immersion test and additive interaction in the rat formalin test. Aim of study was to evaluate the influence of serotonergic and opioidergic system of this combination in the formalin test in rats., Methods: Antinociceptive activity was assessed by the formalin test in male Wistar rats (200-250 g). Antagonists (naloxone and methysergide) were administrated 5 min before and magnesium sulphate 5 min after ketamine injection. Formalin (2.5%, 100 μL) was injected into the right hind paw surface (intraplantar) of rats 5 min after ketamine/magnesium combination. Data were recorded as the total time spent in pain related behavior after the injection of formalin or vehicle (0.9% NaCl)., Results: In the intermediate phase of the formalin test, methysergide at a dose of 0.2 mg/kg did not have any effect, but at doses of 0.5 and 1 mg/kg it had a pronociceptive effect. Methysergide (0.2, 0.5 and 1 mg/kg) inhibited the antinociceptive effect of ketamine-magnesium sulphate combination. In the intermediate phase, naloxone at a dose of 0.2 mg/kg did not have any effect, but at a dose of 3 mg/kg it produced a pronociceptive effect. Naloxone (0.2 and 3 mg/kg) antagonized the antinociceptive effect of the ketamine (5 mg/kg)-magnesium sulphate (5 mg/kg) combination., Conclusion: The results of the present study suggest that serotonergic and opioidergic systems are involved, at least in part, in the antinociceptive effect of the ketamine-magnesium sulphate combination in the model of inflammatory pain in rats., (Copyright © 2019 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.)

Objective: The objective of this systematic review is to determine the efficacy of intravenous magnesium sulfate when used to attenuate hemodynamic fluctuations associated with the creation of pneumoperitoneum in adults undergoing laparoscopic surgery., Introduction: Laparoscopic surgery has gained popularity as a result of improved patient outcomes postoperatively, but pneumoperitoneum alters the patient's physiology and hemodynamic profile during the intraoperative period. Magnesium sulfate is a non-opioid agent known for its ability to blunt the physiologic sympathetic response associated with exposure to noxious stimuli. Magnesium sulfate may be efficacious in combating undesirable hemodynamic changes associated with pneumoperitoneum., Inclusion Criteria: Studies that included participants 18 years or older undergoing any laparoscopic surgery using pneumoperitoneum with CO2 insufflation will be considered. Studies will be excluded if patients were being treated for pheochromocytoma. Studies can employ any intravenous dosing strategy of magnesium sulfate, administered at any point in the perioperative period for the purpose of blunting the sympathetic response to creation of a pneumoperitoneum., Methods: A systematic search of MEDLINE, CINAHL, Cochrane Library, Google Scholar, Trip Database, MedNar, Grey Literature Report and ProQuest Dissertations and Theses will be conducted to identify both published and unpublished studies on the topic of interest. The search will be limited to studies written in English and performed on humans. Studies will be selected for review based on inclusion criteria and will be appraised by two reviewers using a standardized appraisal tool., Systematic Review Registration Number: PROSPERO CRD42019139991.

The effects of long-term oral administration of magnesium sulfate and insulin on hyperglycemia were investigated using Akt2 and IRS1 gene expression methods in streptozotocin-induced diabetic rats. Fifty rats were randomly divided into five experimental groups: 1, non-diabetic control (NDC); 2, Mg 2+ -treated non-diabetic control (Mg-NDC); 3, chronic diabetic (CD); 4, Mg 2+ -treated chronic diabetic (Mg-CD); and 5, insulin-treated chronic diabetic (Ins-CD). Streptozotocin was used to induce diabetes. The Mg-CD and Mg-NDC groups received 10 g/l of MgSO 4 added to drinking water. The Ins-CD group received 2.5 U/kg of insulin twice a day. Blood glucose level and body weight were measured every week. The intraperitoneal glucose tolerance test (IPGTT) was performed after 16 weeks. MgSO 4 administration improved the blood glucose level and IPGTT. It also increased Akt2 and IRS1 genes as well as protein expression. Insulin lowered the blood glucose level and increased IRS1 gene and protein expression, but did not affect Akt2 gene and protein expression. Glucose reduction after Mg therapy may be mediated, at least partially, via IRS1 and Akt2 genes and protein stimulation. In insulin-treated rats, insulin resistance was not significant due to the absence of Akt2 gene expression.

Brain edema is a fatal complication of acute ischemic stroke and associated with worse outcomes in patients. This study was designed to evaluate the effects of magnesium sulfate on vasogenic brain edema formation and blood-brain barrier (BBB) disruption caused by ischemia-reperfusion (IR) in a rat model of ischemic stroke. A total of 72 male Sprague-Dawley rats were categorized into the following three primary groups: sham, control ischemic, magnesium-sulfate-treated (300 mg/kg loading dose, followed by an additional 100 mg/kg) ischemic (n = 24 in each group). Transient focal cerebral ischemia was induced by 60-min-long occlusion of the left middle cerebral artery, followed by 24-h-long reperfusion. Sensorimotor deficits, infarct volume, and brain edema were evaluated at the end of the reperfusion period. The BBB permeability was assessed by Evans Blue extravasation technique. Lipid peroxidation levels were assessed by measuring the malondialdehyde content in the brain tissue homogenate, and the activities of the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase were detected according to the technical manual of the assay kits. Induction of cerebral ischemia in the control group produced considerable BBB damage in conjunction with severe brain edema formation. Treatment with magnesium sulfate significantly attenuated brain edema and protected BBB integrity in the ischemic lesioned hemisphere. In addition, magnesium sulfate reduced lipid peroxidation and increased antioxidant protection of brain tissue by upregulating the activities of antioxidant enzymes. Treatment with magnesium sulfate protected BBB integrity against IR-induced damage and reduced vasogenic edema formation partly via antioxidant mechanisms in a rat model of acute ischemic stroke.

Aims: To investigate presence or absence of clinically relevant drug interactions (pharmacokinetic and safety/tolerability) of OBE022 with standard-of-care medicines for preterm labour, enabling coadministration and further clinical development., Methods: Part A: open-label, randomized, 3-period crossover assessing coadministration of single doses of OBE022 (1100 mg) and MgSO 4 . Part B: open-label, single-sequence crossover assessing the interactions following administration of OBE022 (1000 mg/day) at steady state coadministered with single doses of atosiban, nifedipine and betamethasone. Twenty-five healthy nonpregnant women of reproductive age were enrolled (Part A: n = 12; Part B: n = 13)., Results: OBE022, alone or in combination with standard-of-care medications, was well tolerated. Headache and dizziness were the most frequently reported adverse events; dizziness occurred more often with the nifedipine/OBE022 combination. There were no clinically significant pharmacokinetic interactions when coadministered with MgSO 4 . Co-administration had no notable effect on atosiban exposure. Atosiban reduced exposure to OBE002 (peak concentration [C max ] 22%, area under the concentration-time curve [AUC] 19%). Coadministration with betamethasone slightly increased betamethasone exposure (C max  + 18%, AUC +27%) and OBE002 exposure (C max  + 35%, AUC +15%). These changes were not considered clinically significant. Coadministration with nifedipine slightly increased OBE002 exposure (C max  + 29%, AUC +24%) and markedly increased nifedipine exposure (C max by 2-fold and AUC by 2-fold), which may be clinically significant., Conclusions: The use of OBE022, a PGF2α antagonist prodrug, in combination with standard-of-care medicines may provide new treatment alternatives for preterm labour. All tested combinations were well tolerated. Nifedipine doses could potentially be reduced or staggered when coadministered with OBE022., (© 2019 The British Pharmacological Society.)

Objective: The objective of this study was to assess the cardioprotective effect of magnesium sulfate in patients with left ventricular concentric hypertrophy undergoing cardiac surgery., Design: The study was a double-blinded randomized study., Setting: This study was conducted at a cardiac center., Patients: The study included 250 patients., Intervention: The study included two groups (each = 125): Group M - the patients who received magnesium sulfate infusion (15 mg/kg/h). The infusion was started 20 min before induction, during surgery, and the first postoperative 24 h. Group C - the patients who received an equal amount of normal saline., Measurements: The variables included troponin I level, creatinine kinase-MB (CK-MB) level, electrocardiograph (ECG) with automatic ST-segment analysis (leads II and V), E/A peak ratio, end-diastolic volume, cardiac index (CI), heart rate, mean arterial blood pressure (MAP), mean arterial pulmonary pressure (mPAP), pulmonary and systemic vascular resistances, and pharmacological and mechanical support., Main Results: The troponin I level, CK-MB, and ECG changes were lower in Group M than Group C (P < 0.05). The E/A peak ratio and end-diastolic volume increased in Group M than Group C (P < 0.05). There was a significant increase in the CI and a decrease in the heart rate, mPAP, pulmonary vascular resistances, and pharmacological and mechanical support in Group M compared to Group C (P < 0.05). There were minimal changes in the MAP and systemic vascular resistance in Group M compared to Group C (P < 0.05)., Conclusion: The magnesium sulfate provides a cardioprotective effect in patients with concentric ventricular hypertrophy undergoing cardiac surgery. It decreases the incidence of perioperative myocardial infarction and arrhythmia. Furthermore, it decreases the requirement of pharmacological and mechanical support.