Current Treatment Practices for Adult Patients with Constipation in Japan.

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.

Glycation Interferes with the Expression of Sialyltransferases and Leads to Increased Polysialylation in Glioblastoma Cells.

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.

Combinatorial efficacy of Manuka honey and antibiotics in the in vitro control of staphylococci and their small colony variants.

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.

American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation.

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.

American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation.

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.

Light-Activated Chemically Reactive Fibrous Patch Revolutionizes Wound Repair Through the Prevention of Postoperative Adhesion.

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 MnO2 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.

Milk-derived exosomes carrying siRNA-KEAP1 promote diabetic wound healing by improving oxidative stress.

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.

Assessing the efficacy of magnesium oxide and riboflavin as preventative treatment of migraines in pregnancy.

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.

Hydrogen peroxide self-sufficient and glutathione-depleted nanoplatform for boosting chemodynamic therapy synergetic phototherapy.

Chemodynamic therapy (CDT), which suppresses tumors via the conversion of endogenous hydrogen peroxide (H2O2) to highly toxic hydroxyl radicals (•OH), is deemed as a cutting-edge antitumor strategy. However, the insufficient endogenous H2O2 and up-regulated antioxidant glutathione (GSH) in the tumor microenvironment (TME) greatly impede the therapeutic effect of CDT. Herein, a versatile nanoplatform MgO2@SnFe2O4@PEG (MSnFeP) is elaborately fabricated for boosting CDT synergetic phototherapy. In the TME, the activation of MSnFeP contributes to in situ supply of H2O2, 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 H2O2 deficiency and GSH overexpression, but also further enhances the therapeutic effect with the combination of phototherapy.

Dental Composites with Magnesium Doped Zinc Oxide Nanoparticles Prevent Secondary Caries in the Alloxan-Induced Diabetic Model.

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.

Naproxen sodium nanoparticles are less toxic and gastroprotective agents than the conventional NSAID drug naproxen sodium in Balb/c mice.

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-1ß, 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-1ß, 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.

The effect of preoperative oral magnesium oxide on the severity of postoperative pain among women undergoing hysterectomy.

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.

Evaluation of magnesium oxide and zinc oxide nanoparticles against multi-drug-resistance Mycobacterium tuberculosis.

OBJECTIVE: The current study has evaluated the MICs and MBCs of ZnONPs, MgONPs, and MgONPs-ZnONPs against H37Rv 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 HepG2 cell lines. RESULTS: The MIC of MgONPs and ZnONPs were 0.195 and 0.468 µg mL-1 against 104 of H37Rv Mtb. As well, 0.166 µg mL-1 of MgONPs-ZnONPs was able to inhibit 10-4 H37Rv Mtb. The MIC of MgONPs against 104 concentrations of MDR-Mtb was 12.5 µg mL-1. The MIC of MgONPs/ZnONPs against 104 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 104 concentrations of MDR-Mtb. The IC50 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 HepG2 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.

Magnesium Oxide in Constipation.

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.

The efficacy of magnesium oxide and sodium valproate in prevention of migraine headache: a randomized, controlled, double-blind, crossover study.

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.

Senna Versus Magnesium Oxide for the Treatment of Chronic Constipation: A Randomized, Placebo-Controlled Trial.

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.

Effect of lubiprostone on vinca alkaloid-induced constipation in patients with hematological malignancies: a propensity score-matched analysis.

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.

Lactobacillus reuteri DSM 17938 and Magnesium Oxide in Children with Functional Chronic Constipation: A Double-Blind and Randomized Clinical Trial.

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.

Gitelman syndrome combined with growth hormone deficiency: Three cases report.

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.

Gitelman's syndrome with hyperphosphatemia, effectively responding to single oral magnesium oxide administration: A case report.

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_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.