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Reproductive Sciences (Thousand Oaks,... Aug 2020Magnesium 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...
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 (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.
Topics: Animals; Dose-Response Relationship, Drug; Female; Gonadal Steroid Hormones; Magnesium Sulfate; Mice; Myometrium; Organ Culture Techniques; Oxytocin; Pregnancy; Uterine Contraction
PubMed: 32430707
DOI: 10.1007/s43032-020-00185-8 -
European Journal of Pharmacology Oct 2021In the present study, first, the role of high-fat diet (HFD) in insulin resistance (IR) in offspring with diabetic and non-diabetic parents, and then the effect of...
In the present study, first, the role of high-fat diet (HFD) in insulin resistance (IR) in offspring with diabetic and non-diabetic parents, and then the effect of magnesium sulfate (Mg) administration on improved IR in HFD diabetic parents, and their offspring were investigated. Induction of diabetes was carried out by eating HFD and a low dose of streptozotocin (STZ). Diabetic rats were divided into three groups: diabetic control (DC), insulin, and Mg-treated (Mg). The non-diabetic control (NDC) group received a normal diet. Their offspring were fed on a regular diet for four months. Blood glucose and body weight of all animals were measured weekly, and IPGTT, urine volume, and water intake were measured monthly. In both parents and their offspring, the hyperinsulinemic euglycemic clamp was conducted, and blood samples were obtained. In all groups, the expression of IRS1, Akt and GLUT4 genes in muscle was measured. The HFD-fed rats exhibited a significant increase in blood glucose, body weight and IPGTT. In diabetic parents and their offspring, Mg or insulin therapy lowered blood glucose, IPGTT, and HbA1c relative to the DC group. They also increased GIR in parents and their offspring. Compared to the DC group, the expression of IRS1, Akt and GLUT4 genes was increased in both parents. Mg had positive effects on the expression of IRS1, Akt and GLUT4 genes in Mg treated offspring and reduced IR in them. As a result, magnesium may have beneficial effects on IR by increasing the expression of IRS1, Akt and GLUT4 genes.
Topics: Animals; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diet, High-Fat; Female; Glucose Clamp Technique; Humans; Insulin Resistance; Magnesium Sulfate; Male; Rats; Streptozocin
PubMed: 34411605
DOI: 10.1016/j.ejphar.2021.174418 -
BMC Pregnancy and Childbirth Jun 2024To establish the population pharmacokinetics (PPK) of magnesium sulfate (MgSO)in women with preeclampsia (PE), and to determine the key covariates having an effect in...
OBJECTIVE
To establish the population pharmacokinetics (PPK) of magnesium sulfate (MgSO)in women with preeclampsia (PE), and to determine the key covariates having an effect in magnesium pharmacokinetics in Chinese PE.
METHODS
Pregnant women with PE prescribed MgSO4 were enrolled in this prospective study from April 2021 to April 2023. On the initial day of administration, the patients were administered a loading dose of 5 g in conjunction with 10 g of magnesium sulfate as a maintenance dose. On the second day, only the maintenance dose was administration, and maternal blood samples were taken at 0, 4, 5, and 12 h after the second day's 10 g maintenance dose. The software Phoenix was used to estimate PPK parameters of MgSO4, such as clearance (CL) and volume of distribution (V), and to model PPK models with patient demographic, clinical, and laboratory covariates.
RESULTS
A total of 199 blood samples were collected from 51 women with PE and PPK profiles were analyzed. The PPK of MgSO is consistent with to a one-compartment model. The base model adequately described the maternal serum magnesium concentrations after magnesium administration. The population parameter estimates were as follows: CL was 2.98 L/h, V was 25.07 L. The model predictions changed significantly with covariates (BMI, creatinine clearance, and furosemide). Furosemide statistically influences V. The creatinine clearance, BMI and furosemide jointly affects CL. Monte Carlo simulation results showed that a loading dose combined with a maintenance dose would need to be administered daily to achieve the therapeutic blood magnesium concentrations. For the non-furosemide group, the optimal dosing regimen was a 5 g loading dose combined with a 10 g maintenance dose of MgSO4. For the furosemide group, the optimal dosing regimen was a 2.5 g loading dose combined with a 10 g maintenance dose of MgSO4.
CONCLUSIONS
The magnesium PPK model was successfully developed and evaluated in Chinese preeclampsia population, and the dose optimization of MgSO was completed through Monte Carlo simulation.
Topics: Humans; Female; Magnesium Sulfate; Pre-Eclampsia; Pregnancy; Adult; Prospective Studies; China; Young Adult; Dose-Response Relationship, Drug; East Asian People
PubMed: 38872116
DOI: 10.1186/s12884-024-06620-x -
European Annals of Otorhinolaryngology,... Nov 2022The main objective of this study was to compare the wound infiltration (peritonsillar fossa) of magnesium sulphate combined with bupivacaine, bupivacaine alone and... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
The main objective of this study was to compare the wound infiltration (peritonsillar fossa) of magnesium sulphate combined with bupivacaine, bupivacaine alone and saline solution on post-tonsillectomy pain in children. The accessory objectives were to evaluate the effect of magnesium sulphate infiltration on prevention of laryngospasm and occurrence of nausea/vomiting.
METHODS
This study is a prospective; double blinded and randomized clinical trial. Seventy-five children undergoing tonsillectomy were enrolled. Patients were randomized into three groups using closed envelop technique. Group 1 (N=24) received saline solution (NaCl), group 2 (N=25) received 0.25% bupivacaine (1mg/kg) and group 3 received magnesium sulphate (5mg/kg) and 0.25% bupivacaine (1mg/kg) after tonsillectomy using three-point technique. Pain was evaluated using mCHEOPS scale. The occurrence of laryngospasm, nausea and vomiting was monitored.
RESULTS
The mCHEOPS scores of the group 3 were significantly lower than those of the group 2 and 1 (P<0.001). Time to first analgesic administration was longer for the group 3 than for the groups 2 and 1 (P<0.001). The mean consumption of additional analgesic drugs was lower for the group 3 than the other groups (P<0.001). There were no episodes of laryngospasm in the group 3 in comparison with the other groups. The difference of the incidence of nausea and vomiting was not statistically significant (P=0.628).
CONCLUSION
The adjunction of magnesium sulphate to bupivacaine proved to provide more efficient pain control than bupivacaine alone. However, the small number of participants and the absence of sampling at the P level of 0.005 do not allow to conclude with absolute certainty.
Topics: Child; Humans; Analgesics; Anesthetics, Local; Bupivacaine; Double-Blind Method; Laryngismus; Magnesium Sulfate; Nausea; Pain Measurement; Pain, Postoperative; Prospective Studies; Saline Solution; Tonsillectomy
PubMed: 35688677
DOI: 10.1016/j.anorl.2022.04.007 -
Journal of Clinical Anesthesia Oct 2023The current study tested the hypothesis that magnesium sulfate after reversal with sugammadex causes recurarization. (Randomized Controlled Trial)
Randomized Controlled Trial
STUDY OBJECTIVE
The current study tested the hypothesis that magnesium sulfate after reversal with sugammadex causes recurarization.
DESIGN
A single-center, prospective, randomized, double-blind, controlled trial.
SETTING
Terciary care hospital in Rio de Janeiro, Brazil.
PATIENTS
Included 60 patients undergoing for elective otolaryngological surgery.
INTERVENTIONS
All patients received total intravenous anesthesia and a single dose of rocuronium (0.6 mg/kg). In 30 patients, the neuromuscular blockade was reversed with sugammadex (4 mg/kg) at the reappearance of one or two posttetanic counts (deep-blockade series). In 30 other patients, sugammadex (2 mg/kg) was administered at the reappearance of the second twitch of the train-of-four (moderate-blockade series). After the normalized train-of-four ratio recovered to ≥0.9, the patients in each series were randomized to receive intravenous magnesium sulfate (60 mg/kg) or placebo for 10 min. Neuromuscular function was measured by acceleromyography.
MEASUREMENTS
The primary outcome was the number of patients who exhibited recurarization (normalized train-of-four ratio < 0.9). The secondary outcome was rescue with an additional dose of sugammadex after 60 min.
MAIN RESULTS
In the deep-blockade series, a normalized train-of-four ratio < 0.9 occurred in 9/14 (64%) patients receiving magnesium sulfate and 1/14 (7%) receiving placebo, RR 9.0 (95% CI: 62-1.30), and (p = 0.002), with four rescues with sugammadex. In the moderate-blockade series, neuromuscular blockade recurred in 11/15 (73%) patients receiving magnesium sulfate and in 0/14 (0%) receiving placebo (p < 0.001), with two rescues. The absolute differences in recurarization were 57% and 73% in the deep-blockade and moderate-blockade, respectively.
CONCLUSIONS
Single-dose magnesium sulfate led to a normalized train-of-four ratio < 0.9, 2 min after recovery from rocuronium-induced deep and moderate neuromuscular blockade using sugammadex. Additional sugammadex reversed prolonged recurarization.
Topics: Humans; Sugammadex; Rocuronium; gamma-Cyclodextrins; Magnesium Sulfate; Neuromuscular Nondepolarizing Agents; Prospective Studies; Androstanols; Brazil; Neuromuscular Blockade
PubMed: 37393856
DOI: 10.1016/j.jclinane.2023.111186 -
Inflammopharmacology Oct 2023To evaluate the effect of oral magnesium sulfate (MgSO) on the gene expression and serum levels of inflammatory cytokines including TNF-α, IL-18, IL-1β, IL-6, and... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To evaluate the effect of oral magnesium sulfate (MgSO) on the gene expression and serum levels of inflammatory cytokines including TNF-α, IL-18, IL-1β, IL-6, and IFN-γ in patients with moderate coronary artery disease (CAD).
METHODS
60 CAD patients were selected based on angiography findings and were randomly divided into two groups that received 300 mg/day MgSO (n = 30) or placebo (n = 30) for 3 months. Gene expression and serum levels of inflammatory cytokines were assessed.
RESULTS
After 3 months of intervention, gene expression and serum levels of IL-18 and TNF-α in the MgSOgroup were significantly less than the placebo group (P < 0.05). However, no significant difference in gene expression and serum levels of IL-1β, IL-6, and IFN-γ was observed between the two groups (P > 0.05). In addition, within group analysis demonstrate that Mg-treatment significantly decrease serum level of TNF-α and IL-18 as compared to pretreatment.
CONCLUSION
The results of our study demonstrate that 3-month magnesium sulfate administration (300 mg/day) to CAD patients could significantly decrease serum concentration and gene expression levels of IL-18 and TNF-α. Our findings support the potential beneficial effect of magnesium supplementation on alleviating CAD complications through modulating inflammatory cytokines.
Topics: Humans; Cytokines; Interleukin-18; Tumor Necrosis Factor-alpha; Magnesium Sulfate; Coronary Artery Disease; Interleukin-6; Gene Expression
PubMed: 37665448
DOI: 10.1007/s10787-023-01328-4 -
Obstetrics and Gynecology Jun 2020To test the primary hypothesis that extremely preterm children antenatally exposed to both magnesium sulfate and antenatal corticosteroids have a lower rate of severe... (Observational Study)
Observational Study
OBJECTIVE
To test the primary hypothesis that extremely preterm children antenatally exposed to both magnesium sulfate and antenatal corticosteroids have a lower rate of severe neurodevelopmental impairment or death compared with those exposed to antenatal corticosteroids alone.
METHODS
This was a prospective observational study of children born at 22 0/7-26 6/7 weeks of gestation from 2011 to 2014 at Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network hospitals (N=3,093). The primary outcome was severe neurodevelopmental impairment or death at 18-26 months of corrected age follow-up based on exposure to antenatal corticosteroids and magnesium sulfate or antenatal corticosteroids alone. Secondary outcomes included components of severe neurodevelopmental impairment by exposure group and comparisons of severe neurodevelopmental impairment or death between children exposed to both antenatal corticosteroids and magnesium sulfate with those exposed to magnesium sulfate alone or to neither antenatal corticosteroids nor magnesium sulfate. Logistic regression models adjusted for background characteristics.
RESULTS
Children exposed to both antenatal corticosteroids and magnesium sulfate had a lower rate of severe neurodevelopmental impairment or death (813/2,239, 36.3%) compared with those exposed to antenatal corticosteroids alone (225/508, 44.3%; adjusted odds ratio [aOR] 0.73; 95% CI 0.58-0.91), magnesium sulfate alone (47/89, 53%; aOR 0.49; 95% CI 0.29-0.82), or neither therapy (121/251; 48.2%; aOR 0.66, 95% CI 0.49-0.89). Similarly, children exposed to both antenatal corticosteroids and magnesium sulfate had a lower rate of death compared with either or neither therapy, but the rate of severe neurodevelopmental impairment among survivors did not differ between exposure groups.
CONCLUSION
In children born between 22 0/7 and 26 6/7 weeks of gestation, exposure to both antenatal corticosteroids and magnesium sulfate was associated with lower rates of severe neurodevelopmental impairment or death and death compared with exposure to antenatal corticosteroids alone.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, NCT00063063.
Topics: Adrenal Cortex Hormones; Child, Preschool; Databases, Factual; Female; Gestational Age; Humans; Infant; Infant Mortality; Infant, Extremely Premature; Infant, Newborn; Logistic Models; Magnesium Sulfate; Male; Neurodevelopmental Disorders; Pregnancy; Pregnancy Outcome; Prenatal Care; Prenatal Exposure Delayed Effects; Prospective Studies; United States
PubMed: 32459430
DOI: 10.1097/AOG.0000000000003882 -
Nutrients May 2022Little information exists about the plasma target nutritional needs of the >15 million premature infants <37 weeks gestation. Investigating ascorbic acid’s (AscA) role... (Observational Study)
Observational Study
Little information exists about the plasma target nutritional needs of the >15 million premature infants <37 weeks gestation. Investigating ascorbic acid’s (AscA) role in infant health, our study details the relationship of infant characteristics and maternal health on infant plasma AscA level (pAscA) during postnatal development. Furthermore, we determined pAscA influence during the first week of life (EpAscA) with later infant morbidities. We hypothesize that pAscA is influenced by gestational organ immaturity, as well as maternal factors, with EpAscA associated with greater morbidity risk. We conducted a prospective longitudinal observational study of pAscA, demographics and hospital course detailed in infants ≤34 weeks. Sixty-three subjects were included, with >200 urine and plasma data points analyzed. Maternal smoking, exposure to magnesium sulfate (MgSO4) and advancing gestational and postnatal age were associated with lower pAscA. Non-white infants and those ≤30 weeks that developed bronchopulmonary dysplasia or retinopathy of prematurity had lower pAscA. Prenatal smoking, MgSO4, birth gestational age and race negatively influence pAscA. These results show prenatal and postnatal developmental factors influencing initial pAscA and metabolism, potentially setting the stage for organ health and risk for disease. Assessment of dietary targets may need adjustment in this population.
Topics: Ascorbic Acid; Female; Gestational Age; Humans; Infant; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Magnesium Sulfate; Pregnancy; Prospective Studies
PubMed: 35683989
DOI: 10.3390/nu14112189 -
International Journal of Molecular... Mar 2023Mast cell degranulation impacts the development of pain and inflammation during tissue injury. We investigated the antinociceptive effect of a combination of...
Mast cell degranulation impacts the development of pain and inflammation during tissue injury. We investigated the antinociceptive effect of a combination of cromoglycate and magnesium in the orofacial model of pain and the histological profile of the effect of magnesium in orofacial pain. In male Wistar rats, formalin (1.5%, 100 µL) was injected subcutaneously into the right upper lip of rats after cromoglycate and/or magnesium. Pain was measured as the total time spent on pain-related behavior. Toluidine blue staining was used to visualize mast cells under the light microscope. In the formalin test, in phase 1, magnesium antagonized the antinociceptive effect of cromoglycate, while in phase 2, it potentiated or inhibited its effect. Magnesium significantly reduced mast cell degranulation in the acute phase by about 23% and in the second phase by about 40%. Pearson's coefficient did not show a significant correlation between mast cell degranulation and pain under treatment with magnesium. The cromoglycate-magnesium sulfate combination may prevent the development of inflammatory orofacial pain. The effect of a combination of cromoglycate-magnesium sulfate depends on the nature of the pain and the individual effects of the drugs. Magnesium reduced orofacial inflammation in the periphery, and this effect did not significantly contribute to its analgesic effect.
Topics: Rats; Animals; Male; Magnesium Sulfate; Magnesium; Cromolyn Sodium; Rats, Wistar; Cell Degranulation; Neuroinflammatory Diseases; Mast Cells; Facial Pain; Inflammation; Analgesics
PubMed: 37047214
DOI: 10.3390/ijms24076241 -
Turkish Journal of Medical Sciences 2023This study investigated the possible degeneration in cochlear morphology induced by preeclampsia (PE) and the therapeutic/preventive effect of vitamin D (Vit D) and...
BACKGROUND/AIM
This study investigated the possible degeneration in cochlear morphology induced by preeclampsia (PE) and the therapeutic/preventive effect of vitamin D (Vit D) and magnesium sulfate (MgSO) used separately and together on feto-maternal outcomes.
MATERIALS AND METHODS
We created PE in rats using a reduced uterine perfusion pressure (RUPP) animal model and recorded blood pressure (BP), embryonic survival (ES), and embryonic weight (EW) and evaluated cochlear morphology by electron microscopy.
RESULTS
The PE group had elevated BP, a decreased number and weight of live pups, and significant degeneration in the cochlea compared to the sham group. In the PEV group, we observed significant beneficial effects of Vit D supplementation at 14.5 and 19.5 dpc in terms of BP (p < 0.05), EW (p < 0.001), and cochlear degeneration compared to the PE group. In the PEM group, BP (p < 0.05) and cochlear degeneration nearly reached the level found in the sham group. However, although the EW was statistically different in the PE group, it did not reach sham group levels. We also observed that BP returned to sham level (p < 0.01) and noticed significant increases in the EW (p < 0.0001) and ES (p = 0.017) in the PEMV group compared to the PE group. According to the scanning electron microscope results, combined administration of VitD and MgSO is more effective than separate administration in improving cochlear degeneration induced by PE.
CONCLUSION
The administration of Vit D and MgSO during pregnancy has beneficial effects on PE pathology and may play a significant role in preventing PE-related complications, including cochlear degeneration.
Topics: Animals; Magnesium Sulfate; Pre-Eclampsia; Female; Pregnancy; Cochlea; Vitamin D; Rats; Disease Models, Animal; Rats, Sprague-Dawley
PubMed: 38813514
DOI: 10.55730/1300-0144.5730