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Background: Periodontal Disease (PD) associated with Type 2 Diabetes Mellitus (T2DM) is a chronic condition that affects the oral cavity of people living with T2DM. The mechanisms of the interaction between type 2 Diabetes Mellitus and Periodontal diseases are complex and involve multiple pathophysiological pathways related to the systemic inflammatory process and oxidative stress. Non-surgical periodontal treatment (NSTP) is considered the standard for the management of this disease; however, patients with systemic conditions such as type 2 Diabetes Mellitus do not seem to respond adequately. For this reason, the use of complementary treatments has been suggested to support non-surgical periodontal treatment to reduce the clinical consequences of the disease and improve the systemic conditions of the patient. The use of zinc gluconate and magnesium oxide as an adjunct to non-surgical periodontal treatment and its effects on periodontal clinical features and oxidative stress in patients with Periodontal diseases -type 2 Diabetes Mellitus is poorly understood., Methods: A quasi-experimental study was performed in patients with periodontal diseases associated with T2DM. Initially, 45 subjects who met the selection criteria were included. 19 were assigned to a control group [non-surgical periodontal treatment] and 20 to the experimental group (non-surgical periodontal treatment + 500 mg of magnesium oxide and 50 mg of zinc gluconate for oral supplementation for 30 days) and the data of 6 patients were eliminated. Sociodemographic characteristics, physiological factors, biochemical parameters, and clinical features of periodontal diseases were assessed., Results: In this research a change in periodontal clinical characteristics was observed, which has been associated with disease remission. Additionally, a shift in MDA levels was presented for both groups. Furthermore, the supplementation group showed an increase in antioxidant enzymes when compared to the group that only received NSPT., Conclusion: The use of Zinc gluconate and magnesium oxide can serve as a complementary treatment to non-surgical periodontal treatment, that supports the remission of PD as a result of regulation-reduction of oxidative biomarkers and increase in antioxidant enzymes activity., Trial Registration: https://www.isrctn.com ISRCTN 14,092,381. September 13º 2023. Retrospective Registration., (© 2024. The Author(s).)

Magnesium is one of the recommended treatments for calcium stone formers (CSFs) with hyperoxaluria. In this study, we compared the effect of magnesium oxide (MgO) or magnesium citrate (MgCit) with placebo on 24-hour urine (24-U) metabolites and the calcium oxalate supersaturation index (CaOx SS). In a randomized, double-blind, placebo-controlled clinical trial, 90 CSFs with idiopathic hyperoxaluria were recruited from a tertiary stone prevention clinic. Patients were randomly assigned into three groups: 120 mg MgO, 120 mg MgCit or placebo (supplements were taken three times per day, with meals). Finally, 76 patients were included in the final analysis. Analyses of 24-U were performed at baseline and after eight weeks. Study outcomes included changes in 24-U oxalate, magnesium, citrate, and CaOx SS. Dietary factors were controlled by 24-hour food recalls. Repeated measure ANOVA was used to compare the results. After the intervention, both MgO and MgCit supplements decreased 24-U oxalate excretion (-8.13±16.45 in the MgO group and -16.99±18.02 in the MgCit group) and CaOx SS compared to the placebo, with the effects of MgCit reaching statistical significance (p=0.011 and p=0.010, respectively). An increasing trend was observed for 24-U magnesium and citrate excretion without significant differences among groups. Interestingly, MgCit exhibited a significantly greater inhibitory effect on 24-U oxalate in patients with normal urine magnesium levels (p=0.021). Clinically, both MgO and MgCit reduced 24-U oxalate and CaOx SS compared to placebo. However, MgCit demonstrated a greater effect, especially in patients with normal urine magnesium levels.

Objectives: The initiation of peripherally acting μ-opioid receptor antagonists (PAMORAs) should be considered 2 weeks after conventional laxatives have failed to achieve an adequate response, and affected patients should be evaluated every 2 weeks thereafter. However, this guidance is difficult to implement in acute care hospitals. This study aimed to examine how naldemedine (PAMORA) should be introduced in combination with other laxatives in the acute care setting., Methods: This retrospective study evaluated 93 inpatients who received at least four doses of naldemedine. We investigated changes in the average daily defecation counts during the first 7 days after compared with before naldemedine administration and the incidence of diarrhoea., Results: Daily defecation counts during the first 7 days after compared with before naldemedine administration were greater in both the naldemedine, magnesium oxide (MgO) and another laxative group, and in the naldemedine and another laxative other than MgO group than in the naldemedine only group. The incidence rates of diarrhoea were significantly higher in the naldemedine, MgO, and another laxative group, and in the naldemedine and another laxative other than MgO group than in the naldemedine only group., Conclusions: The introduction of naldemedine alone or in combination with MgO should be considered., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The prevalence of constipation in Japan is estimated to be 2-5%. Constipation is a disease found in older adults. In particular, Japan is an aging society, with 65% of men and 80.5% of women aged 65 years or older accounting for the majority of its population. Chronic constipation may be associated with survival, cardiovascular events, decreased quality of life, and death. This study summarizes the recent findings regarding constipation treatment practice in Japan., Summary: Until recently, the diagnosis of constipation was mainly based on medical interviews; however, with the recent development of handheld ultrasound devices, both physicians and nurses can easily and objectively diagnose fecal retention. Magnesium oxide and stimulant laxatives have been the mainstay treatments; however, since 2012, more than five new drugs for treating constipation have become available in Japan., Key Messages: Magnesium oxide is less effective in patients who use acid-secretion inhibitors and patients who have undergone total gastrectomy and should be cared for hypermagnesemia. In addition, regular use of stimulant laxatives may lead to colonic inertia and decreased bowel movements; therefore, they should be used only occasionally. The following is an overview of the different uses of conventional and newer laxatives for treating constipation., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Glioblastoma (GBM) is a highly aggressive brain tumor that often utilizes aerobic glycolysis for energy production (Warburg effect), resulting in increased methylglyoxal (MGO) production. MGO, a reactive dicarbonyl compound, causes protein alterations and cellular dysfunction via glycation. In this study, we investigated the effect of glycation on sialylation, a common post-translational modification implicated in cancer. Our experiments using glioma cell lines, human astrocytes (hA), and primary glioma samples revealed different gene expressions of sialyltransferases among cells, highlighting the complexity of the system. Glycation has a differential effect on sialyltransferase expression, upregulating ST8SIA4 in the LN229 and U251 cell lines and decreasing the expression in normal hA. Subsequently, polysialylation increased in the LN229 and U251 cell lines and decreased in hA. This increase in polysialylation could lead to a more aggressive phenotype due to its involvement in cancer hallmark processes such as immune evasion, resistance to apoptosis, and enhancing invasion. Our findings provide insights into the mechanisms underlying GBM aggressiveness and suggest that targeting glycation and sialylation could be a potential therapeutic strategy.

Purpose: The purpose of this study is to assess the efficacy of magnesium oxide (MgO) alone and, secondarily, MgO plus riboflavin as preventive treatment of migraines in pregnancy. We hypothesize that MgO alone will be effective for the majority of patients and, when clinically indicated, the addition of riboflavin will result in further benefit., Methods: This was a retrospective cohort study of pregnant patients treated for migraines between 2015 and 2020. We evaluated pre-/post-differences in the following primary outcomes: migraine frequency, severity, and duration. Secondary outcomes included associated migraine symptoms., Results: Of 203 total patients, 117 received MgO alone and 86 received MgO plus riboflavin. There were no significant differences in baseline demographics between the two groups. There was a statistically significant decrease in migraine frequency, severity, and duration in the groups receiving MgO alone and MgO plus riboflavin (p < 0.01 for all). In total, 154 patients reported migraine-associated symptoms, of which 119 (77%) improved after treatment, 18 (12%) did not improve, and 17 (11%) patients' data were missing. The MgO plus riboflavin group had a lower gestational age at treatment initiation and was more likely to receive treatment prior to pregnancy (p < 0.01). Significant differences were observed for several baseline migraine symptoms, including photophobia, phonophobia, nausea, and vomiting, which were more common in the group receiving MgO plus riboflavin (p < 0.05 for all)., Conclusion: Migraine frequency, severity, and duration all decreased with MgO alone and MgO plus riboflavin in this pregnancy cohort. Associated symptoms also significantly decreased for both groups., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Staphylococci are among the list of problematic bacteria contributing to the global antibiotic resistance (ABR) crisis. Their ability to adopt the small colony variant (SCV) phenotype, induced by prolonged antibiotic chemotherapy, complicates staphylococcal infection control options. Novel and alternative approaches are needed to tackle staphylococcal infections and curb ABR. Manuka honey (MH), a non-antibiotic alternative is recognized for its unique antibacterial activity based on its methylglyoxal (MGO) component., Methods: In this study, MH (MGO 830+) was tested in combination with gentamicin (GEN), rifampicin (RIF), or vancomycin (VA) against staphylococcal wildtype (WT) and SCVs. To our knowledge, there are no current studies in the literature documenting the effects of MH on staphylococcal SCVs. While Staphylococcus aureus is well-studied for its international ABR burden, limited data exists demonstrating the effects of MH on S. epidermidis and S. lugdunensis whose pathogenic relevance and contribution to ABR is also rising., Results & Discussion: The three staphylococci were most susceptible to RIF (0.06-0.24 μg/ml), then GEN (0.12-0.49 μg/ml), and lastly VA (0.49-0.96 μg/ml). The MICs of MH were 7%, 7-8%, and 6-7% (w/v), respectively. Fractional inhibitory concentration (FIC) evaluations showed that the combined MH + antibiotic effect was either additive (FICI 1-2), or partially synergistic (FICI >0.5-1). While all three antibiotics induced SCVs in vitro , stable SCVs were observed in GEN treatments only. The addition of MH to these GEN-SCV-induction analyses resulted in complete suppression of SCVs (p<0.001) in all three staphylococci, suggesting that MH's antibacterial properties interfered with GEN's SCV induction mechanisms. Moreover, the addition of MH to growth cultures of recovered stable SCVs resulted in the inhibition of SCV growth by at least 99%, indicating MH's ability to prevent subsequent SCV growth. These in vitro analyses demonstrated MH's broad-spectrum capabilities not only in improving WT staphylococci susceptibility to the three antibiotics, but also mitigated the development and subsequent growth of their SCV phenotypes. MH in combination with antibiotics has the potential to not only resensitize staphylococci to antibiotics and consequently require less antibiotic usage, but in instances where prolonged chemotherapy is employed, the development and growth of SCVs would be hampered, providing a better clinical outcome, all of which mitigate ABR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liang, Adeleye and Onyango.)

Diabetic wounds are a serious complication of diabetes mellitus (DM) that can lead to persistent infection, amputation, and even death. Prolonged oxidative stress has been widely recognized as a major instigator in the development of diabetic wounds; therefore, oxidative stress is considered a promising therapeutic target. In the present study, Keap1/Nrf2 signaling was confirmed to be activated in streptozotocin (STZ)-induced diabetic mice and methylglyoxal (MGO)-treated human umbilical vein endothelial cells (HUVECs). Knockdown of Keap1 by siRNA reversed the increase in Keap1 levels, promoted the nuclear translocation of Nrf2, and increased the expression of HO-1, an antioxidant protein. To explore therapeutic delivery strategies, milk-derived exosomes (mEXOs) were developed as a novel, efficient, and non-toxic siRNA carrier. SiRNA-Keap1 (siKeap1) was loaded into mEXOs by sonication, and the obtained mEXOs-siKeap1 were found to promote HUVEC proliferation and migration while relieving oxidative stress in MGO-treated HUVECs. Meanwhile, in a mouse model of diabetic wounds, injection of mEXOs-siKeap1 significantly accelerated diabetic wound healing with enhanced collagen formation and neovascularization. Taken together, these data support the development of Keap1 knockdown as a potential therapeutic strategy for diabetic wounds and demonstrated the feasibility of mEXOs as a scalable, biocompatible, and cost-effective siRNA delivery system. The therapeutic effect of siKeap1-loaded mEXOs on diabetic wound healing was assessed. First, we found that the expression of Keap1 was upregulated in the wounds of diabetic mice and in human umbilical vein endothelial cells (HUVECs) pretreated with methylglyoxal (MGO). Next, we extracted exosomes from raw milk by differential centrifugation and loaded siKeap1 into milk-derived exosomes by sonication. The in vitro application of the synthetic complex (mEXOs-siKeap1) was found to increase the nuclear localization of Nrf2 and the expression of the antioxidant protein HO-1, thus reversing oxidative stress. Furthermore, in vivo mEXOs-siKeap1 administration significantly accelerated the healing rate of diabetic wounds (Scheme 1). Scheme 1 Schematic diagram. A Synthesis of mEXOs-siKeap1 complex. B Mechanism of mEXOs-siKeap1 in vitro. C The treatment effect of mEXOs-siKeap1 on an in vivo mouse model of diabetic wounds., (© 2023. Controlled Release Society.)

Introduction: Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological Association and the American College of Gastroenterology, aims to inform clinicians and patients by providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults., Methods: The American Gastroenterological Association and the American College of Gastroenterology formed a multidisciplinary guideline panel that conducted systematic reviews of the following agents: fiber, osmotic laxatives (polyethylene glycol, magnesium oxide, lactulose), stimulant laxatives (bisacodyl, sodium picosulfate, senna), secretagogues (lubiprostone, linaclotide, plecanatide), and serotonin type 4 agonist (prucalopride). The panel prioritized clinical questions and outcomes and used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence for each intervention. The Evidence to Decision framework was used to develop clinical recommendations based on the balance between the desirable and undesirable effects, patient values, costs, and health equity considerations., Results: The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based on available evidence, the panel made strong recommendations for the use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults. Conditional recommendations were made for the use of fiber, lactulose, senna, magnesium oxide, and lubiprostone., Discussion: This document provides a comprehensive outline of the various over-the-counter and prescription pharmacological agents available for the treatment of CIC. The guidelines are meant to provide a framework for approaching the management of CIC; clinical providers should engage in shared decision making based on patient preferences as well as medication cost and availability. Limitations and gaps in the evidence are highlighted to help guide future research opportunities and enhance the care of patients with chronic constipation., (Copyright © 2023 by The American College of Gastroenterology and the American Gastroenterological Association.)

Introduction: Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological Association and the American College of Gastroenterology, aims to inform clinicians and patients by providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults., Methods: The American Gastroenterological Association and the American College of Gastroenterology formed a multidisciplinary guideline panel that conducted systematic reviews of the following agents: fiber, osmotic laxatives (polyethylene glycol, magnesium oxide, lactulose), stimulant laxatives (bisacodyl, sodium picosulfate, senna), secretagogues (lubiprostone, linaclotide, plecanatide), and serotonin type 4 agonist (prucalopride). The panel prioritized clinical questions and outcomes and used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence for each intervention. The Evidence to Decision framework was used to develop clinical recommendations based on the balance between the desirable and undesirable effects, patient values, costs, and health equity considerations., Results: The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based on available evidence, the panel made strong recommendations for the use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults. Conditional recommendations were made for the use of fiber, lactulose, senna, magnesium oxide, and lubiprostone., Discussion: This document provides a comprehensive outline of the various over-the-counter and prescription pharmacological agents available for the treatment of CIC. The guidelines are meant to provide a framework for approaching the management of CIC; clinical providers should engage in shared decision making based on patient preferences as well as medication cost and availability. Limitations and gaps in the evidence are highlighted to help guide future research opportunities and enhance the care of patients with chronic constipation., (Copyright © 2023. Published by Elsevier Inc.)

A light-activated chemically reactive fibrous patch (ChemPatch) with tissue adhesion and wound healing activity was developed for preventing postoperative peritoneal adhesion. ChemPatch was constructed by an integrative electrospinning fabrication strategy, generating multifunctional PCL-NHS fibers encapsulating antioxidant curcumin and MnO 2 nanoparticles. ChemPatch exhibited excellent photothermal conversion, which not only reformed the physical state to match the tissue but also improved conjugation between ChemPatch and tissues, allowing for strong attachment. Importantly, ChemPatch possessed good antioxidant and radical scavenging activity, which protected cells in an oxidative microenvironment and improved tissue regeneration. Particularly, ChemPatch acted as a multifunctional barrier and could not only promote reepithelialization and revascularization in wound defect model but simultaneously ameliorate inflammation and prevent postoperative peritoneal adhesion in a mouse cecal defect model. Thus, ChemPatch represents a dual-active bioadhesive barrier for reducing the incidence and severity of peritoneal adhesions.

Chemodynamic therapy (CDT), which suppresses tumors via the conversion of endogenous hydrogen peroxide (H 2 O 2 ) to highly toxic hydroxyl radicals (•OH), is deemed as a cutting-edge antitumor strategy. However, the insufficient endogenous H 2 O 2 and up-regulated antioxidant glutathione (GSH) in the tumor microenvironment (TME) greatly impede the therapeutic effect of CDT. Herein, a versatile nanoplatform MgO 2 @SnFe 2 O 4 @PEG (MSnFeP) is elaborately fabricated for boosting CDT synergetic phototherapy. In the TME, the activation of MSnFeP contributes to in situ supply of H 2 O 2 , generation of •OH and consumption of GSH for boosted CDT. Furthermore, photothermal therapy (PTT) and photodynamic therapy (PDT) are simultaneously stimulated by near-infrared (NIR) light exposure on MSnFeP to increase the toxic free radical yield. This strategy not only amplifies the CDT efficacy hindered by H 2 O 2 deficiency and GSH overexpression, but also further enhances the therapeutic effect with the combination of phototherapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Antibacterial restorative materials against caries-causing bacteria are highly preferred among high-risk patients, such as the elderly, and patients with metabolic diseases such as diabetes. This study aimed to enhance the antibacterial potential of resin composite with Magnesium-doped Zinc oxide (Mg-doped ZnO) nanoparticles (NPs) and to look for their effectiveness in the alloxan-induced diabetic model. Hexagonal Mg-doped ZnO NPs (22.3 nm diameter) were synthesized by co-precipitation method and characterized through ultraviolet-visible (UV-Vis), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS) analysis. The Mg-doped ZnO NPs (1, 2.5 and 5% w/w) were then evaluated for antibacterial activity using a closed system in vitro biofilm model. Significant enhancement in the antibacterial properties was observed in composites with 1% Mg-doped ZnO compared to composites with bare ZnO reinforced NPs (Streptococcus mutans, p = 0.0005; Enterococcus faecalis, p = 0.0074, Saliva microcosm, p < 0.0001; Diabetic Saliva microcosm, p < 0.0001). At 1−2.5% Mg-doped ZnO NPs concentration, compressive strength and biocompatibility of composites were not affected. The pH buffering effect was also achieved at these concentrations, hence not allowing optimal conditions for the anaerobic bacteria to grow. Furthermore, composites with Mg-doped ZnO prevented secondary caries formation in the secondary caries model of alloxan-induced diabetes. Therefore, Mg-doped ZnO NPs are highly recommended as an antibacterial agent for resin composites to avoid biofilm and subsequent secondary caries formation in high-risk patients.

Background: Magnesium sulfate has been reported to be effective in perioperative pain treatment and in blunting somatic, autonomic, and endocrine reflexes provoked by noxious stimuli. The pre-emptive analgesic effects of magnesium in reducing postoperative pain could be beneficial in abdominal and gynecologic surgeries., Objective: The aim of study was to compare the pre-emptive analgesic effects of oral magnesium oxide and naproxen for hysterectomy surgery., Methods: This study evaluated all patients who were candidates for hysterectomy in 2 months. The 64 patients were randomly divided into two groups using a random allocation sequence. The patients in the intervention and control groups received either magnesium oxide tablet (500 mg) or naproxen tablet (500 mg) orally half an hour before surgery, respectively. The severity of postoperative pain is assumed as a primary outcome which is evaluated using the visual analogue scale (VAS)., Results: In this study, 64 patients were assessed. The results showed age, weight, systolic and diastolic blood pressure, and pulse rate of the patients in the two groups were not significantly different (p > 0.05). The mean score of pain intensity for these patients was significantly lower than the patients receiving naproxen (p-value: 0.03). Besides, more than one-quarter of patients in the magnesium oxide group (n = 9, 28.12%) received this analgesia with lower dose than the patients in the naproxen group (p-value: 0.03)., Conclusion: The results of this study showed that preoperative oral magnesium oxide had a significant effect on the severity of postoperative pain and consumption of postoperative analgesia., (© 2022. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Use of non-steroidal anti-inflammatory drugs (NSAIDs) is one of the leading causes of gastric ulcers. Excellent therapeutic properties have made the use of NSAIDs widespread. Nano-drug delivery to reduce systemic toxicity through modulating drug pharmacokinetics may be a better choice. Presently, we investigated if naproxen nanoformulation (PVA capped NPRS-MgO NPs) is less toxic to be used as an alternative drug. Groups of mice were assigned to control, NPRS-treated, CNF-treated, UNF-treated, and MgO NPs-treated groups. Analyses included gross examination of gastric mucosa, calculation of ulcer and inhibition indices, determination of tissue levels of reactive oxygen species (ROS), malondialdehyde (MDA), catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), and reduced glutathione (GSH), histological and immunohistochemical assessment of i-NOS, COX-2, and caspase-3 of stomach mucosa, q-PCR for the detection of mRNA expression of IL-1β, IL-6, and TNF-α. Results were compared statistically at P < 0.05. Compared to NPRS-treated mice which developed multiple ulcers, had elevated MDA and ROS levels, and deceased CAT, POD, SOD, and GSH levels, significantly increased expression of IL-1β, IL-6, and TNF-α mRNA, damaged surface epithelium with disrupted glandular architecture and leucocyte infiltration of lamina propria with a marked increase in mucosal COX-2, i-NOS, and caspase-3 expression, oral administration of coated and uncoated naproxen nanoformulations prevented the gross mucosal damage by a restoration of all biochemical, histological, and immunohistochemical alterations to near control levels. The present study demonstrates that naproxen sodium nanoformulation has a gastroprotective action and in the clinical setting can be a better alternative to conventional naproxen., Competing Interests: Declaration of Competing Interest No potential conflicts of interest relevant to this article are reported., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: The current study has evaluated the MICs and MBCs of ZnONPs, MgONPs, and MgONPs-ZnONPs against H 37 Rv Mtb and MDR-Mtb., Methods: Mixture, magnesium oxide nanoparticles (NPs) and zinc oxide (MgONPs-ZnONPs) were prepared. The microplate alamar blue (MABA) assay and the proportion method were used to evaluate of anti-tubercular activity against MDR-MTB. MTT test was done to MgONPs-ZnONPs against Vero and HepG 2 cell lines., Results: The MIC of MgONPs and ZnONPs were 0.195 and 0.468 μg mL -1 against 10 4 of H 37 Rv Mtb. As well, 0.166 μg mL -1 of MgONPs-ZnONPs was able to inhibit 10 -4 H 37 Rv Mtb. The MIC of MgONPs against 10 4 concentrations of MDR-Mtb was 12.5 μg mL -1 . The MIC of MgONPs/ZnONPs against 10 4 concentrations of MDR-Mtb reached to 0.664 μg mL -1 . The MBC value of ZnONPs increased to 1.875 μg mL -1 against 10 -4 concentrations of MDR-Mtb. Testing showed that the MBCs of MgONPs/ZnONPs reached to 1.328 μg mL -1 against 10 4 concentrations of MDR-Mtb. The IC 50 against MDR-TB was 0.779 μg mL -1 for ZnONPs and 0.883 μg mL -1 for MgONPs-ZnONPs. The MgONPs-ZnONPs was not toxic to Vero cell lines however ZnONPs could inhibit the Vero and HepG 2 cell lines., Conclusion: We found that ZnONPs and mixture MgONPs-ZnONPs not only have higher bactericide behavior but might have also synergistic effects against MDR-TB., (Copyright © 2020 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Migraine is a disabling disorder that affects the quality of life of patients. Different medications have been used in prevention of migraine headache. In this study, we evaluated the effectiveness of magnesium oxide in comparison with valproate sodium in preventing migraine headache attacks. This is a single-center, randomized, controlled, crossover trial which is double-blind, 24-week, 2-sequence, 2-period, 2-treatment. After patient randomization into two sequences, the intervention group received magnesium oxide 500 mg and the control group received valproate sodium 400 mg two tablets each day (every 12 h) for 8 weeks. The primary efficacy variable was reduction in the number of migraine attacks and number of days with moderate or severe headache and hours with headache (duration) per month in the final of 8 weeks in comparison with baseline. Seventy patients were randomized and seven dropped out, leaving 63 for analysis. In an intention-to-treat analysis, 31 patients were in group 1 (magnesium oxide-valproate) and 32 patients were in group 2 (valproate-magnesium oxide). The mean number of migraine attacks and days per month was 1.72 ± 1.18 and 2.09 ± 1.70, with a mean duration of 15.50 ± 21.80 h in magnesium group and 1.27 ± 1.27 and 2.22 ± 1.96, with a mean duration 13.38 ± 14.10 in valproate group. This study has shown that 500 mg magnesium oxide appears to be effective in migraine prophylaxis similar to valproate sodium without significant adverse effect.

Magnesium oxide has been widely used as a laxative for many years in East Asia, yet its prescription has largely been based on empirical knowledge. In recent years, several new laxatives have been developed, which has led to a resurgence in interest and increased scientific evidence surrounding the use of magnesium oxide, which is convenient to administer, of low cost, and safe. Despite these advantages, emerging clinical evidence indicates that the use of magnesium oxide should take account of the most appropriate dose, the serum concentration, drug-drug interactions, and the potential for side effects, especially in the elderly and in patients with renal impairment. The aim of this review is to evaluate the evidence base for the clinical use of magnesium oxide for treating constipation and provide a pragmatic guide to its advantages and disadvantages.

Introduction: This is the first prospective, double-blinded, randomized, placebo-controlled trial to evaluate the safety and efficacy of a stimulant laxative compared with an osmotic agent for the treatment of chronic idiopathic constipation., Methods: Patients were randomly administered stimulant laxative (senna, 1.0 g), osmotic agent (magnesium oxide [MgO], 1.5 g), or placebo for 28 consecutive days. The primary endpoint was overall symptom improvement. Secondary endpoints were spontaneous bowel movement (SBM), complete SBM, and patient assessment of constipation quality of life (QOL)., Results: Ninety patients (mean age, 42 years; 93% women; mean duration of symptoms, 9.9 years) were enrolled; all completed the study. The response rate for overall improvement was 11.7% in the placebo group, 69.2% in the senna group, and 68.3% in the MgO group (P < 0.0001). Change in SBM was significantly greater in the senna and MgO groups than that in the placebo group (P < 0.001). Similarly, change in complete SBM was significantly greater in the senna and MgO groups than that in the placebo group (P < 0.01). On the patient assessment of constipation QOL, significant improvements were seen in the senna and MgO groups compared with those in the placebo group (senna, P < 0.05; MgO, P < 0.001). The frequency of severe treatment-related adverse events was 0%., Discussion: Senna and MgO significantly improved the frequency of bowel movements and QOL score and seem to be effective in the treatment of constipation., (Copyright © 2020 by The American College of Gastroenterology.)

Patients receiving vinca alkaloids for hematological malignancies frequently experience constipation that is unresponsive to laxatives. Research on treatment of vinca alkaloid-induced constipation is limited. This study aimed to determine whether the chloride channel activator lubiprostone ameliorates vinca alkaloid-induced constipation in patients with hematological malignancies. In this retrospective cohort study, vinca alkaloid-induced constipation (grade ≥ 3 using the Common Terminology Criteria for Adverse Events) was investigated in patients treated for hematological malignancies between July 2014 and June 2019 who had already been prescribed osmotic laxatives and additionally received either a stimulant laxative or lubiprostone. Univariate and multivariate analyses were performed to identify the risk factors for persistent constipation after introduction of the second laxative. A propensity score model was used to match 67 patients taking a stimulant laxative and 67 treated with lubiprostone, and the occurrence of intractable constipation was compared between groups. Overall, 203 patients were included, among whom 50 (25%) had constipation. On multivariate analysis, body mass index, opioid use, and addition of lubiprostone were independently associated with constipation. Patients treated with lubiprostone were significantly less likely to experience intractable constipation than did those treated with stimulant laxatives (10% vs. 34%, P = 0.002). Moreover, post-constipation diarrhea was significantly less frequent among patients treated with lubiprostone (42% vs. 63%, P = 0.024). Lubiprostone was more effective than stimulant laxatives at treating vinca alkaloid-induced intractable constipation in patients with hematological malignancies, and its use could enable safe vinca alkaloid chemotherapy.

Objective: Chronic functional constipation is a frequent condition. The aim of the study was to evaluate the efficacy of the probiotic Lactobacillus (L.) reuteri DSM 17938 and magnesium oxide (MgO) for relieving chronic functional constipation in children., Study Design: A prospective, double-blind, placebo-controlled, randomized, and parallel-group trial was conducted in five pediatric outpatient clinics in Japan. Sixty patients who were more than six months old and under six years of age with a diagnosis of functional constipation according to Rome IV criteria were randomly divided into three groups: group A (n = 20) received L. reuteri DSM 17938 and lactose hydrate as a placebo of MgO; group B (n = 19) received L. reuteri DSM 17938 and MgO; and group C (n = 21) received a placebo of L. reuteri DSM 17938 and MgO., Results: All three groups exhibited significant improvement in defecation frequency in the fourth week compared with the baseline condition (group A: p < 0.05; group B: p < 0.05; group C: p < 0.05). The MgO group and combination group showed a significant decrease in stool consistency, but the L. reuteri DSM 17938 group did not (group A: p = 0.079; group B: p < 0.05; group C: p < 0.05). MgO significantly suppressed the presence of the genus Dialister. Defecation frequency negatively correlated with the frequency of Clostridiales-belonging bacteria among the gut microbiome., Conclusions: L. rueteri DSM 17938 and MgO were both effective in the management of functional constipation in young children. MgO caused an imbalance in the gastrointestinal microbiome, which was not the case in the probiotic group., Competing Interests: The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

A geochemical model was established to predict the chemical and hydraulic performances of MgO columns used to treat a nickel- and cobalt-contaminated groundwater. Using the PHREEQC software, an advection-reaction simulation was carried out to re-create the outlet concentrations observed during a previous axial column laboratory test. Reaction kinetics were introduced to calculate the rates of brucite dissolution as well as iron and manganese oxidation. Pore volume diminution during the test was also predicted using the volume of goethite precipitates generated. The floating-sphere model was applied to calculate the equivalent hydraulic conductivity (K eq ) of the column. The geometry of the model's cells was then adjusted to represent a radial centripetal filter containing the same amount of reactive MgO. The K eq predictions for the centripetal filter showed that the loss of permeability in the filter could be significantly delayed by changing the filter's flow configuration. While those results are promising, further testing is necessary to provide additional experimental results for radial filters., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Rationale: Gitelman syndrome (GS) is a rare autosomal recessive hereditary salt-losing tubulopathy caused by loss-of-function mutations in the SLC12A3 gene. It is usually characterized by hypokalemia, metabolic alkalosis, hypomagnesemia, and hypocalciuria. There are only a few reports on GS combined with growth hormone deficiency (GHD)., Patient Concerns: Three patients presented with weakness, spasm, and growth retardation, respectively., Diagnoses: GS was diagnosed based on the clinical symptoms, laboratory test results, and genetic analysis. GH stimulation tests were performed when the magnesium level returned to normal under magnesium oxide (MgO) therapy., Interventions: Initially, all patients received oral replacement of MgO and potassium chloride, and 2 of them received simultaneous spironolactone therapy. Recombinant human growth hormone (rhGH) therapy was initiated after they were diagnosed with GHD., Outcomes: All 3 patients exhibited satisfactory growth velocity and normal serum magnesium level, although the potassium level was still slightly lower than normal., Lessons: We suggest that all GS patients should undergo genetic evaluation, especially regarding SLC12A3 gene mutation. GHD should be considered if these patients have short stature. rhGH therapy is useful for stimulating the patients' growth, and it may increase the serum magnesium level.

Background: Hypomagnesemia (Hypo-Mg) predicts mortality and chronic kidney disease (CKD) progression. However, in CKD, its prevalence, kidney-intrinsic risk factors, and the effectiveness of oral magnesium (Mg) therapy on serum Mg levels is uncertain., Methods: In a cross-sectional study enrolling pre-dialysis outpatients with CKD, the prevalence of electrolyte abnormalities (Mg, sodium, potassium, calcium and phosphorus) was compared. In an open-label randomized controlled trial (RCT), we randomly assigned CKD patients to either the magnesium oxide (MgO) or control arm. The outcome was serum Mg levels at 1 year., Results: In 5126 patients, Hypo-Mg was the most common electrolyte abnormality (14.7%) with similar prevalence across stages of CKD. Positive proteinuria was a risk factor of Hypo-Mg (odds ratio 2.2; 95% confidence interval 1.2-4.0). However, stratifying the analyses by diabetes mellitus (DM), it was not significant in DM (Pinteraction = 0.04). We enrolled 114 patients in the RCT. Baseline analyses showed that higher proteinuria was associated with higher fractional excretion of Mg. This relationship between proteinuria and renal Mg wasting was mediated by urinary tubular markers in mediation analyses. In the MgO arm, higher proteinuria or tubular markers predicted a significantly lower 1-year increase in serum Mg. In patients with a urinary protein-to-creatinine ratio (uPCR) <0.3 g/gCre, serum Mg at 1 year was 2.4 and 2.0 mg/dL in the MgO and control arms, respectively (P < 0.001), with no significant between-group difference in patients whose uPCR was ≥0.3 g/gCre (Pinteraction=0.001)., Conclusions: Proteinuria leads to renal Mg wasting through tubular injuries, which explains the high prevalence of Hypo-Mg in CKD., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Rationale: The Gitelman's syndrome (GS) is characterized by metabolic alkalosis, hypokalemia, hypomagnesemia, and hypocalciuria. However, the involvement of this deranged electrolyte balance in patients with GS in parathyroid hormone action has not been known., Patient Concerns: We report a 34-year-old woman with muscle weakness and tetany/seizures caused by electrolyte imbalance. She had hyperphosphatemia and hypocalciuric hypocalcemia in addition to severe hypomagnesemia with low potassium in the absence of metabolic alkalosis. We identified 2 heterozygous mutations in the solute carrier family 12 member 3 gene in this case (c.1732G>A, p.Val578Met and c.2537&#95;38delTT, p.846fs) by targeted sequence for all causative genes of salt-losing tubulopathies., Diagnoses: A diagnosis of GS. Hypocalcemia and hyperphosphatemia were suggested to relate with the secondary obstruction of appropriate parathyroid hormone release following severe hypomagnesemia in GS., Interventions: She was treated with single oral magnesium oxide administration., Outcomes: The electrolyte imbalance including hypocalcemia and hyperphosphatemia were resolved with a remission of clinical manifestations., Lessons: These observations, in this case, suggest that even severe hypomagnesemia caused by GS was associated with resistance to appropriate parathyroid hormone secretion. Through this case, we recognize that secondary hypoparathyroidism would be triggered by severe hypomagnesemia in GS.

Purpose: SN-38, an active metabolite of irinotecan, is reabsorbed by the intestinal tract during excretion, causing diarrhoea and neutropenia. In addition, the association between blood levels of SN-38 and neutropenia has been reported previously, and the rapid excretion of SN-38 from the intestinal tract is considered to prevent neutropenia. Oral alkalization drugs are used as prophylactic agents for suppressing SN-38 reabsorption. The relationship between oral alkalization drugs and neutropenia, however, has not been well studied. The aim of this study was to investigate the relationship between oral alkalization drugs and neutropenia in irinotecan-treated patients., Methods and Results: Patients with cervical or ovarian cancer were administered irinotecan and investigated by medical chart reviews to determine whether oral alkalization drugs were effective at ameliorating irinotecan-induced neutropenia. The drug combination in the oral alkalization drugs-ursodeoxycholic acid, magnesium oxide, and sodium hydrogen carbonate-significantly improved neutrophil counts and reduced dose intensity compared with those of non-users. In the large-scale Japanese Adverse Drug Event Report database, the reporting odds ratio of irinotecan-induced neutropenia was significantly lower when irinotecan had been given in combination with oral alkalization drugs., Conclusions: These data indicate that oral alkalization drugs may reduce the frequency of neutropenia caused by irinotecan administration, making it possible to increase the dose safely.

Hypermagnesemia is generally considered an exceptional iatrogenic condition usually caused by magnesium-containing cathartics. In particular, this condition often develops when magnesium-containing cathartics are administered to elderly patients with renal insufficiency or bowel movement dysfunction. Although magnesium oxide (MgO) is widely prescribed as a laxative, serum magnesium concentration has not been examined in most cases. In this report, we present the cases of four elderly patients with constipation and symptomatic hypermagnesemia caused by MgO ingestion, one of which had a lethal course. All of the patients were older than 65 years and with renal dysfunction. In addition, they had difficulties in expressing their symptoms because of cerebrovascular events or dementia. These cases suggest that hypermagnesemia caused by magnesium-containing cathartics is more likely to develop than previously recognized and that physicians should be aware that patients with chronic kidney disease and the elderly are at risk of hypermagnesemia on magnesium administration. We recommend serum magnesium monitoring for high-risk patients after initial prescription or dose increase.

Background: Magnesium is an essential intracellular cation. Magnesium deficiency is common in the general population and its prevalence among patients with cirrhosis is even higher. Correlation between serum levels and total body content is poor because most magnesium is intracellular. Minimal hepatic encephalopathy is a subclinical phase of hepatic encephalopathy with no overt symptoms. Cognitive exams can reveal minor changes in coordination, attention, and visuomotor function, whereas language and verbal intelligence are usually relatively spared., Objectives: To assess the correlation between intracellular and serum magnesium levels and minimal hepatic encephalopathy., Methods: Outpatients with a diagnosis of compensated liver cirrhosis were enrolled in this randomized, double-blinded study. Patients were recruited for the study from November 2013 to January 2014, and were randomly assigned to a control (placebo) or an interventional (treated with magnesium oxide) group. Serum and intracellular magnesium levels were measured at enrollment and at the end of the study. Cognitive function was assessed by a specialized occupational therapist., Results: Forty-two patients met the inclusion criteria, 29 of whom were included in this study. Among these, 83% had abnormal cognitive exam results compatible with minimal hepatic encephalopathy. While only 10% had hypomagnesemia, 33.3% had low levels of intracellular magnesium. Initial intracellular and serum magnesium levels positively correlated with cognitive performance., Conclusions: Magnesium deficiency is common among patients with compensated liver cirrhosis. We found an association between magnesium deficiency and impairment in several cognitive function tests. This finding suggests involvement of magnesium in the pathophysiology of minimal hepatic encephalopathy.

The objective of this study was to innovate an effective oral sustained release hepatoprotective formula for - the water soluble drug - caffeine. Caffeine is rapidly absorbed and eliminated which dictates frequent administration to achieve adequate therapeutic effect. A w/o Pickering emulsion incorporating caffeine in the internal phase was primed. It contained wheat germ oil and was stabilized by synthesized magnesium oxide nanoparticles (MgO NPs). Components selection was based on their antioxidant, hepatoprotective and anticarcinogenic effects. The MgO NPs were prepared via sol-gel method, and then were characterized using X-ray diffractometry, transmission electron microscopy, contact angle and cytotoxicity. The Pickering emulsion formula stabilized by MgO NPs (F1) was compared to another stabilized by conventional MgO particles (F2). Both were evaluated regarding droplet size, stability and caffeine release. F1 was stable against phase separation for a 2 months period. Its droplets mean size was 665.9 ± 90 nm. F1 afforded sustained release for caffeine that reached 70% within 48 h that followed zero order kinetics. 100 ppm of F1 showed nearly 36% growth inhibition of hepatocellular carcinoma (HEPG2). In vivo and histopathalogical evaluations were conducted on CCl 4 intoxicated rats. Biochemical analysis for liver enzymes - (ALT and AST), oxidative stress biomarkers and the inflammation marker (protein kinase C) - revealed that the selected formula elicited significant hepatoprotection. This formula acted as an economical approach to multiple therapy and afforded safe effective sustained level for caffeine., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Traditional chemotherapy against breast cancer usually accompanied with metastasis. Thus, it is significant to enhance anti-tumor and anti-metastasis efficacy simultaneously. The extracellular environment of most tumors is acidic with pH 6.5-6.9, which play an important role in driving promotion of tumor metastasis. Herein, we developed an intratumoral injectable phospholipids-based phase separation gel (PPSG) co-loaded with 5-fluotouracil (5FU) and magnesium oxide (MgO), termed as 5FU + MgO-PPSG. It was prepared by simple mixing, and showed in the appearance of a clear and yellow solution with good fluidity. After intratumoral injection, PPSG system achieved phase transition and sustained released alkaline substance to neutralize acidic microenvironment in tumor site. Both in vitro and in vivo research showed a strong anti-tumor and anti-metastasis efficacy. 4T1-bearing mice after administration with 5FU + MgO-PPSG was achieved significantly prolonged survival time, compared with other groups. In conclusion, the novel 5FU + MgO-PPSG system might have a great potential to improve treatment method against breast metastasis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

We presented and discussed one interesting medical prescription by doctor Giuseppe Moscati (1880-1927), who prescribed magnesium oxide (magnesia usta) to a patient with the diagnosis of "neuralgia of the celiac plexus of rheumatic origin". Besides the traditional use of magnesium as antacid remedy at the time, we raised the hypothesis that magnesium could be administered by Moscati in order to treat the neuralgia itself. Considering the scientific background of Moscati at the school of Filippo Bottazzi (1867-1941), a father of Italian biochemistry, we suggested that the doctor tried to apply the preliminary concepts acquired from electrophysiological studies on magnesium to his clinical practice. Only after decades, magnesium was recognized a fundamental ion in the energy metabolism and in contributing to maintain the ionic intracellular homeostasis, including for neurons.

We sought to investigate whether magnesium oxide bound to soy protein (MGP) increases serum magnesium concentrations with less diarrhea compared to commonly prescribed magnesium salts. Subjects were switched to MGP at a near-equivalent daily elemental magnesium dose. Mean serum magnesium levels were compared. If magnesium levels remained <1.7 mg/dL after switching to MGP, subjects were enrolled into Part 2 and received a one-time MGP dose adjustment. The MGP daily dose was increased by 266 mg. For both parts 1 and 2, subjects recorded the number and quality of their stools to assess gastrointestinal (GI) tolerability of MGP. Twelve pediatric kidney transplant recipients completed Part 1. Mean serum magnesium levels increased from 1.61 (SD 0.1) on standard MG to 1.69 (SD 0.1); t(11) = 2.6, P = .02 on MGP. Five subjects completed Part 2, and all achieved serum magnesium ≥1.7 mg/dL (mean 1.75 mg/dL, SD 0.06; t(4) = 2.7, P = .06). Subjects reported the same number of, but looser bowel movements with MGP; however, individuals did not perceive intolerable GI symptoms with MGP therapy and all chose to remain on MGP at the end of the study. At an equivalent mg/kg/d dose of elemental magnesium, serum magnesium levels on MGP were significantly higher., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To describe the course of Meniere's disease with noninvasive treatment during the first few years after initial diagnosis., Methods: A retrospective review of consecutive patients with newly diagnosed definite Meniere's disease between 2013 and 2016 and a minimum follow-up of 1 year. Patients received a written plan for low sodium, water therapy, and treatment with a diuretic and/or betahistine. Subjects were screened and treated for vestibular migraine as needed. Vertigo control and hearing status at most recent follow-up were assessed., Results: Forty-four subjects had an average follow up of 24.3 months. Thirty-four percent had Meniere's disease and vestibular migraine, and 84% had unilateral Meniere's disease. Seventy-five percent had vertigo well controlled at most recent follow-up, with only noninvasive treatments. Age, gender, body mass index, presence of vestibular migraine, bilateral disease, and duration of follow-up did not predict noninvasive treatment failure. Worse hearing threshold at 250 Hz and lower pure tone average (PTA) at the time of diagnosis did predict failure. Fifty-two percent of ears had improved PTA at most recent visit, 20% had no change, and 28% were worse Conclusions: Encountering excellent vertigo control and stable hearing after a new diagnosis of Meniere's disease is possible with noninvasive treatments. Worse hearing status at diagnosis predicted treatment failure.

We report a case of fatal hypermagnesemia in a 53-year-old woman admitted for acute exacerbation of chronic obstructive pulmonary disease and with a history of chronic constipation treated regularly with magnesium-containing laxatives. On admission, her magnesium level was 2.0mg/dL, which rose to a peak of 10.8mg/dL despite hydration and diuresis in the presence of a normal kidney function. Continuous renal replacement therapy was promptly initiated, which reduced her serum magnesium levels, but her condition continued to deteriorate precipitously progressing to shock leading to oligoanuric renal failure, and she died 2 days later. A review of the literature shows that though rare and often unsuspected, severe hypermagnesemia frequently results in death even in individuals with normal renal function despite renal replacement therapy. In patients with constipation, retention of magnesium-based laxative in the gut apparently serves as a reservoir for continuous magnesium absorption and contributes to mortality., (Published by Elsevier Inc.)

Duloxetine is a serotonin/noradrenaline reuptake inhibitor that is used as an antidepressant. However, it is known to cause constipation as a side effect. Magnesium compounds, such as magnesium oxide and magnesium hydroxide aqueous solution, are often combined with duloxetine to ameliorate the constipation caused by duloxetine. However, there is concern that these magnesium compounds might alter the effects of duloxetine via physicochemical interactions. In this study, we attempted to clarify the interactions that take place between duloxetine and magnesium oxide using in vivo and in vitro experiments. We evaluated the influence of magnesium oxide on in vitro duloxetine concentrations using HPLC. In addition, we examined the in vivo antidepressant-like effects and serum concentrations of duloxetine in rats. In the in vitro experiment, the duloxetine concentration was significantly decreased by co-treatment with magnesium oxide. In the in vivo experiment, the antidepressant-like effects of duloxetine were not affected by the combined oral administration of magnesium oxide and a duloxetine formulation although the serum duloxetine level was significantly decreased. However, the antidepressant-like effects of a duloxetine reagent were significantly attenuated by the co-administration of magnesium oxide. These results suggest that duloxetine and magnesium oxide directly interact and that such interactions affect the absorption and antidepressant-like effects of duloxetine.

Importance: Magnesium supplements are widely marketed for prophylaxis of nocturnal leg cramps (NLC) despite no evidence of significant benefit., Objective: To determine whether magnesium oxide is better than placebo for NLC prophylaxis., Design, Setting, and Participants: A randomized, double-blind, placebo-controlled clinical trial of 2 weeks eligibility screening followed by 4 weeks of treatment was conducted in northern Israel, from February to October 2013. An intention-to-treat data analysis was performed from March 22, 2014, to April 17, 2016. We used a volunteer sample of community-dwelling individuals experiencing NLC, 21 years or older, with 4 or more documented episodes of NLC during 2 weeks of screening., Interventions: Capsules containing either magnesium oxide or a similar-looking placebo to be taken orally, once daily at bedtime for a period of 4 weeks., Main Outcomes and Measures: The primary outcome was the difference in the mean number of NLC per week between the screening and treatment phases. Secondary outcomes included severity and duration of NLC, quality of life, and quality of sleep., Results: Of the 166 volunteers, 72 (43%) were excluded, of whom 15 declined to participate and 57 did not meet the inclusion criteria. Of the 94 individuals (39% male; mean [SD] age, 64.9 [11.1] years) randomly assigned to magnesium oxide (48) or placebo (46), 6 did not complete the study protocol (3 in each group). Mean (SD) change of NLC was -3.41 (4.05) (from 7.84 [5.68] to 4.44 [5.66]) and -3.03 (4.53) (from 8.51 [5.20] to 5.48 [4.93]) per week in the magnesium oxide and placebo groups, respectively, a difference between groups of 0.38 (0.48) NLC per week (P = .67 in an intention-to-treat analysis). There were no between-group differences in the severity and duration of NLC, quality of life, or quality of sleep., Conclusions and Relevance: Oral magnesium oxide was not superior to placebo for older adults experiencing NLC. The decrease in the mean number of NLC per week, from the screening to the treatment phase in both groups, is probably a placebo effect that may explain the wide use of magnesium for NLC., Trial Registration: clinicaltrials.gov Identifier: NCT01709968.

Gastrointestinal complications are common after coronary artery bypass graft surgery. These complications are ranged from nausea and vomiting to mesenteric ischemia and liver failure. It seems that nausea, vomiting, and constipation are related to magnesium deficiency. This study was designed to examine the effect of oral magnesium supplementation on the incidence of gastrointestinal complications in patients undergoing cardiac surgery. In a single blinded randomized clinical trial, 102 patients who were undergoing coronary artery bypass graft surgery were randomly allocated into two groups, 52 patients in the intervention and 50 patients in control group. Patients in the experimental group received 800 milligram magnesium oxide (2 tablets each of them containing 240 mg elemental magnesium) daily from the admission to discharge from hospital. The incidence of post-operative nausea and vomiting, constipation, and atrial fibrillation was compared between the groups. Our results showed that postoperative hypomagnesemia is present in 41.20 and 70.80 percent of the patients in the intervention and control group patients, respectively. The overall incidence of constipation was 62%. Patients who received magnesium supplementation experienced less atrial fibrillation, nausea, vomiting, and constipation. Our data showed that oral magnesium supplementation could reduce the postoperative complications. Despite the better status in the intervention group, the hypomagnesemia was present in many of intervention group patients. It seems that supplementation with higher doses is needed.

Management of constipation in patients receiving cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) or CHOP-like chemotherapy regimens is important for prevention of paralytic ileus. We reported earlier that the laxative action of magnesium oxide is reversed by the concomitant use of antacids in cancer patients receiving opioid analgesics. Here, we assessed the prevalence of prophylactic laxative medication for the control of constipation in patients receiving CHOP or CHOP-like regimens for non-Hodgkin's lymphoma. Data obtained from 211 eligible patients were retrospectively analyzed. Almost all patients (99%) received anti-ulcer agents such as proton pump inhibitors and H 2 receptor antagonists for the prophylaxis of gastric disorders associated with prednisolone. Prophylactic laxatives were prescribed in 86 patients (40.8%), in which magnesium oxide was used most predominantly (88.4%). However, magnesium oxide at doses of ≦2000 mg/d was not effective for prevention of constipation, although the compound totally inhibited the incidence of constipation at doses higher than 2000 mg/d. Therefore, it is important to avoid negative drug interaction between magnesium oxide and antacids in patients receiving CHOP chemotherapy.

Aims: We investigated the relationship between renal function and serum magnesium concentration in elderly patients treated with magnesium oxide (MgO) in an outpatient setting of an urban hospital in Japan., Methods: In the present study, 44 elderly outpatients (23 patients with constipation treated with daily oral MgO and 21 untreated patients in the control group) who visited Kameyama municipal medical center were enrolled. Variables were age, sex, weight, height, serum magnesium concentration, serum blood urea nitrogen level, serum creatinine level, use of other magnesium-containing supplements and symptoms associated with hypermagnesemia. We calculated the estimated glomerular filtration rate (eGFR) and classified patients based on eGFR category., Results: Compared with the control group, the MgO group showed a significantly higher concentration of serum magnesium (median 2.2 mg/dL [interquartile range 2.1-2.3] vs 2.4 mg/dL [2.2-2.6], P < 0.001). Hypermagnesemia (>2.6 mg/dL) was noted only in the MgO group. However, symptoms associated with hypermagnesemia occurred in patients from both groups, with no significant difference between groups. In the MgO group, significant difference was seen in the median serum magnesium concentration between eGFR categories (P < 0.05). The category G4 (eGFR 15-29 mL/min/1.73 m(2) ) group had the highest serum magnesium concentration in the MgO group (3.0 mg/L [2.9-3.1])., Conclusions: Elderly patients treated with MgO have higher serum magnesium levels compared with the control group. MgO should be prescribed with caution in patients with low renal function as shown by a GFR category G3b or less (eGFR < 30 mL/min/1.73 m(2) ). Geriatr Gerontol Int 2016; 16: 600-605., (© 2015 Japan Geriatrics Society.)

Purpose: To determine the preventive effect of a periodontal dressing containing colophony, zinc oxide and magnesium oxide applied after scaling and root planing on clinical variables, subgingival bacteria and local immune response in patients with chronic periodontitis., Materials and Methods: In this randomised prospective clinical study, 28 volunteers with generalised moderate chronic periodontitis were treated with full-mouth scaling in a split-mouth design. In the test quadrants, the periodontal dressing was applied during the first three days. At baseline and after 6 and 12 weeks, probing pocket depth (PD), attachment level (AL) and bleeding on probing (BOP) were recorded, and subgingival plaque samples were taken for laboratory analysis., Results: In both groups, PD, AL and BOP were significantly reduced (p=0.001). BOP was significantly lower in the control than the test group after 6 weeks (p=0.046). Significantly reduced bacterial counts of Porphyromonas gingivalis were found in the control group after 12 weeks (p=0.013). No differences were found for the microbiological results between the groups. After 12 weeks, interleukin (IL)-8 and matrix metalloproteinase (MMP)-8 were significantly higher in the test group (p=0.023 and p=0.003, respectively)., Conclusion: The adjunctive application of a periodontal dressing had no additional preventive effect on clinical data 12 weeks after scaling and root planing.

Infected kidney stones refer to stones that form because of urinary tract infections with urease-producing bacteria, secondarily infected stones of any composition, or stones obstructing the urinary tract leading to pyelonephritis. The mainstay of treatment of infection stones is complete stone removal. Kidney stones that obstruct the urinary tract and cause obstructive pyelonephritis are also frequently referred to as infected stones. Obstructive pyelonephritis is a urologic emergency as it can result in sepsis and even death. Infection stones and obstructive stones causing pyelonephritis are different disease processes, and their workup and management are described separately., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Hot flashes are a common symptom in breast cancer survivors that can negatively impact quality of life. Preliminary data suggested that magnesium might be used as an effective low-cost treatment of hot flashes with minimal adverse effects., Methods: A four-arm, double-blind, placebo-controlled, randomized trial was conducted. Postmenopausal women with a history of breast cancer and bothersome hot flashes were randomized into treatment groups of magnesium oxide 800 or 1,200 mg daily or corresponding placebo groups at a 2:2:(1:1) ratio. Hot flash frequency and hot flash score (number × mean severity) were measured using a validated hot flash diary. A 1-week baseline period preceded initiation of study medication. The primary endpoint was intrapatient difference in mean hot flash score between baseline and treatment periods, comparing each magnesium group with the combined placebo groups using a gatekeeping procedure. Results were analyzed using repeated-measures and growth curve models on weekly hot flash scores based on a modified intent-to-treat principle., Results: Two hundred eighty-nine women enrolled between December 2011 and March 2013. Study groups were well balanced for baseline characteristics. Mean hot flash scores, mean hot flash frequencies, and associated changes during the treatment period were similar for each group. An increased incidence of diarrhea and a corresponding lower incidence of constipation were reported in magnesium arms compared with placebo. No statistically significant difference in other toxicities or quality-of-life measures was observed., Conclusions: The results of this trial do not support the use of magnesium oxide for hot flashes.

For afternoon colonoscopy, same-day administration of sodium picosulfate, magnesium oxide, and citric acid (PM/Ca) is recommended. However, few studies have evaluated the bowel-cleansing efficacy and safety of this regimen. The aim of this study was to compare the bowel-cleansing efficacy, side effects, and patient's tolerability of a same-day split administration of PM/Ca with polyethylene glycol (PEG) for afternoon colonoscopy. Patients were randomly assigned to a PM/Ca group or a PEG group. The PM/Ca group consumed 1 sachet of PM/Ca at 06:00 and 1 sachet of PM/Ca 4 hours before the colonoscopy. They also took 2 tablets of bisacodyl before sleep on the night before. The PEG group consumed 2 L of PEG at 06:00 and 2 L of PEG 4 hours before the colonoscopy. All subjects were instructed to finish the bowel cleanser or fluid at least 2 hours before colonoscopy. All colonoscopic examinations were performed in the afternoon on the same day. The bowel-cleansing efficacy was scored using 2 scales: the Ottawa Bowel Preparation Scale (OBPS) and the Aronchick scale. Ease of using the bowel cleanser was rated from 1 (very easy) to 5 (very difficult). Two hundred nine patients underwent colonoscopy. The bowel-cleansing scores by OBPS did not differ between groups (5.0 vs 4.9, P = 0.63). Ease of using the bowel cleanser was superior in the PM/Ca group (P < 0.01). The cleansing efficacy of PM/Ca administered on the day of colonoscopy is comparable to that of PEG. Patients prefer PM/Ca.

Background: Constipation is an uncomfortable and common condition that affects many, irrespective of age. Since 1500 BC and before, health care practitioners have provided treatments and prevention strategies to patients for chronic constipation despite the significant variation in both medical and personal perceptions of the condition., Objective: To review relevant research evidence from clinical studies investigating the efficacy and safety of commercially available pharmacological laxatives in Canada, with emphasis on studies adopting the Rome criteria for defining functional constipation., Search Methods: PubMed, Medline, Embase and Evidence-Based Medicine Reviews databases were searched for blinded or randomized clinical trials and meta-analyses assessing the efficacy of nonstimulant and stimulant laxatives for the treatment of functional constipation., Results: A total of 19 clinical studies and four meta-analyses were retrieved and abstracted regarding study design, participants, interventions and outcomes. The majority of studies focused on polyethylene glycol compared with placebo. Both nonstimulant and stimulant laxatives provided better relief of constipation symptoms than placebo according to both objective and subjective measures. Only one study compared the efficacy of a nonstimulant versus a stimulant laxative, while only two reported changes in quality of life. All studies reported minor side effects due to laxative use, regardless of treatment duration, which ranged from one week to one year. Laxatives were well tolerated by both adults and children.

Post-transplantation hypomagnesemia is common and predicts diabetes. Magnesium improves glycemic control in diabetics and insulin sensitivity in insulin resistant subjects. We aimed to assess the effectiveness of oral magnesium for improving glycemic control and insulin sensitivity at 3 months post-transplantation. We conducted a single-center, open-label, randomized parallel group study. We included adults with serum magnesium <1.7 mg/dl within 2 weeks after kidney transplantation. We randomized participants to 450 mg magnesium oxide up to three times daily or no treatment. The primary endpoint was the mean difference in fasting glycemia. Secondary endpoints were the mean difference in area under the curve (AUC) of glucose during an oral glucose tolerance test and insulin resistance measured by Homeostasis Model of Assessment-Insulin Resistance (HOMA-IR). Analyses were on intention-to-treat basis. In patients randomized to magnesium oxide (N = 27) versus no treatment (N = 27), fasting glycemia on average was 11.5 mg/dl lower (95% CI 1.7 to 21.3; P = 0.02). There was no difference between the two groups neither for 2 h AUC, where the mean value was 1164 mg/dl/min (95% CI -1884 to 4284; P = 0.45) lower in the treatment group nor for HOMA-IR. Magnesium supplements modestly improved fasting glycemia without effect on insulin resistance. Higher baseline glycemia among patients in the control group may have driven the positive outcome (ClinicalTrials.gov number: NCT01889576)., (© 2014 Steunstichting ESOT.)