Hepatotoxicity of cantharidin is associated with the altered bile acid metabolism

Cantharidin (CTD) is an effective antitumor agent. However, it exhibits significant hepatotoxicity, the mechanism of which remains unclear. In this study, biochemical and histopathological analyses complemented with ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS)-based targeted metabolomic analysis of bile acids (BAs) were employed to investigate CTD-induced hepatotoxicity in rats. Sixteen male and female Sprague–Dawley rats were randomly divided into two groups: control and CTD (1.0 mg/kg) groups. Serum and liver samples were collected after 28 days of intervention. Biochemical, histopathological, and BA metabolomic analyses were performed for all samples. Further, the key biomarkers of CTD-induced hepatotoxicity were identified via multivariate and metabolic pathway analyses. In addition, metabolite–gene–enzyme network and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to identify the signaling pathways related to CTD-induced hepatotoxicity. The results revealed significantly increased levels of biochemical indices (alanine aminotransferase, aspartate aminotransferase, and total bile acid). Histopathological analysis revealed that the hepatocytes were damaged. Further, 20 endogenous BAs were quantitated via UHPLC-MS/MS, and multivariate and metabolic pathway analyses of BAs revealed that hyocholic acid, cholic acid, and chenodeoxycholic acid were the key biomarkers of CTD-induced hepatotoxicity. Meanwhile, primary and secondary BA biosynthesis and taurine and hypotaurine metabolism were found to be associated with the mechanism by which CTD induced hepatotoxicity in rats. This study provides useful insights for research on the mechanism of CTD-induced hepatotoxicity.     

Efeitos do sulfato de magnésio e da milrinona sobre o vasoespasmo cerebral após hemorragia subaracnoidea por aneurisma: estudo randômico

Background

Aneurysmal subarachnoid hemorrhage is an important cause of premature death and disability worldwide. Magnesium sulphate is shown to have a neuroprotective effect and it reverses cerebral vasospasm. Milrinone is also used in the treatment of cerebral vasospasm. The aim of the present study was to compare the effect of prophylactic magnesium sulphate and milrinone on the incidence of cerebral vasospasm after subarachnoid hemorrhage.

Efeitos de tramadol,magnésio e cetamina por via intra‐articular sobre a dor pós‐operatória em meniscectomia artroscópica

Objective

Postoperative pain control is important in terms of early recovery and rehabilitation in arthroscopic meniscectomy. For this purpose, we aimed to compare the effects of intraarticular tramadol, magnesium, and ketamine with combinations of pericapsular bupivacaine on postoperative pain and recovery in arthroscopic meniscectomy.

Magnesium modification of a calcium phosphate cement alters bone marrow stromal cell behavior via an integrin-mediated mechanism

The chemical composition, structure and surface characteristics of biomaterials/scaffold can affect the adsorption of proteins, and this in turn influences the subsequent cellular response and tissue regeneration. With magnesium/calcium phosphate cements (MCPC) as model, the effects of magnesium (Mg) on the initial adhesion and osteogenic differentiation of bone marrow stromal cells (BMSCs) as well as the underlying mechanism were investigated. A series of MCPCs with different magnesium phosphate cement (MPC) content (0∼20%) in calcium phosphate cement (CPC) were synthesized. MCPCs with moderate proportion of MPC (5% and 10%, referred to as 5MCPC and 10MCPC) were found to effectively modulate the orientation of the adsorbed fibronectin (Fn) to exhibit enhanced receptor binding affinity, and to up-regulate integrin α5β1 expression of BMSCs, especially for 5MCPC. As a result, the attachment, morphology, focal adhesion formation, actin filaments assembly and osteogenic differentiation of BMSCs on 5MCPC were strongly enhanced. Further in vivo experiments confirmed that 5MCPC induced promoted osteogenesis in comparison to ot her CPC/MCPCs. Our results also suggested that the Mg on the underlying substrates but not the dissolved Mg ions was the main contributor to the above positive effects. Based on these results, it can be inferred that the specific interaction of Fn and integrin α5β1 had predominant effect on the MCPC-induced enhanced cellular response of BMSCs. These results provide a new strategy to regulate BMSCs adhesion and osteogenic differentiation by adjusting the Mg/Ca content and distribution in CPC, guiding the development of osteoinductive scaffolds for bone tissue regeneration.     

Magnesium lithospermate B acts against dextran sodiumsulfate-induced ulcerative colitis by inhibiting activation of the NRLP3/ASC/Caspase-1 pathway

This study aimed to observe the therapeutic effects of magnesium lithospermate B on acute and chronic colitis induced by dextran sodiumsulfate (DSS) and the role of inflammasome complex (NOD-like receptor protein, NLRP; apoptosis-associated speck-like protein containing, ASC; caspase-1). Establishment of acute and chronic colitis models were by using 5% DSS oral administration in BALB/C male mice. Magnesium lithospermate B (240 mg/kg body weight) was given by subcutaneous injection. Samples were collected for biomarker assay, histological examination, immunohistochemical evaluation and western blot. There was obvious increase in TNF-α level and NLPR3, ASC, and caspase-1 expressions in acute and chronic colitis groups compared with the normal control. Significant decrease of the tumor necrosis factor-α level and the expressions of NLPR3, ASC, and caspase-1 were observed after treatment with magnesium lithospermate B. This study showed that magnesium lithospermate B could be used to treat acute and chronic colitis by inhibiting the activation of the NLRP3/ASC/Caspase-1 pathway.     

School-age human figure drawings by very preterm infants: Validity of the Draw-a-Man test to detect behavioral and cognitive disorders

Detecting an abnormal developmental trajectory in very preterm infants remains challenging. The objective of this study was to determine the correlation between the Draw-a-Man test (DAMT) and behavioral and cognitive disabilities in very preterm infants. From the school-age follow-up of the Premag study, which evaluated the neuroprotective effect of prenatal magnesium sulfate before 33 weeks of gestation, 281 human figure drawings were assessed (mean age, 11 years). Behavioral and cognitive disabilities were associated with delayed DAMTs but test performance indicators were insufficient to use DAMT as a screening or a diagnostic test.     

“2019 SOGC临床实践指南：硫酸镁对胎儿的神经保护作用”解读

脑性瘫痪（cerebral palsy，CP）是早产儿常见且严重的并发症，严重威胁早产儿健康。越来越多的证据表明，产前应用硫酸镁进行神经保护可减少早产儿CP的发生。2019年加拿大妇产科医生协会（The Society of Obstetricians and Gynaecologists of Canada，SOGC）归纳和整理了硫酸镁胎儿神经保护作用的最新临床研究证据，针对使用硫酸镁的孕龄、时机、给药方案、是否需要二次用药及新生儿复苏等临床问题，给出了相应临床意见和推荐。现对其推荐要点进行解读，以期为我国医务工作者提供借鉴。     

The effect of magnesium sulfate on post off-pump coronary artery bypass grafting bleeding

BackgroundMagnesium level alteration may cause coagulation abnormality resulting in bleeding complication after off-pump coronary artery bypass grafting. In this study, we investigated the effect of magnesium on the postoperative coagulation profile and bleeding in OPCAB patients.MethodsIn a double blind clinical trial, six hundred patients were randomly allocated to two groups: group A (n = 150) and group B (n = 450). Group A received 50 mg/kg of magnesium sulfate (MS) in 100 ml 0.9% NaCl solution over 20 min before the anesthesia induction. Group B or control group received only 100 ml 0.9% NaCl solution at the same time points. OPCAB was performed with standard technique and device. Blood samples were collected 30 min before and 6 h after the surgery to analyze hemoglobin and blood coagulation tests. Postoperative exploration for bleeding, blood transfusion, and volume of transfusion was recorded. The two groups compared with t-test and χ² tests and p-valve <0.05 were considered as significant.ResultsHowever, postoperative hemoglobin was statistically lower in group A compared with group B, but platelet, PT, and aPTT tests were not statistically different between two groups. The serum MS level, exploration for bleeding, volume of packed cell transfusion, and volume of postoperative bleeding were statistically different between group A vs group B.ConclusionPreoperative MS use may be associated with the postoperative platelet dysfunction and increased tendency to bleeding. This is an important risk factor for postoperative bleeding in the OPCAB in absence of CPB use.     

硫酸镁和/或沙丁胺醇雾化吸入对哮喘患儿吸入乙酰胆碱激发后肺功能影响的随机对照研究

目的观察硫酸镁雾化能否改善哮喘患儿吸入乙酰胆碱激发后的肺功能,并与雾化吸入沙丁胺醇和硫酸镁＋沙丁胺醇进行比较。方法330例乙酰胆碱激发试验阳性的哮喘患儿随机分为3组,3组分别给予雾化吸入硫酸镁,沙丁胺醇,硫酸镁+沙丁胺醇,观察用药后2个时点（10 和20 min）第1秒用力呼气量（FEV1）、最大呼气流速(PEF）的肺功能指标。结果①3组患儿用药后2个时点的FEV1、PEF值均较激发值显著上升（P<0.05）,但3组2个时点的FEV1、PEF值两两比较差异无统计学意义（P>0.05）;②沙丁胺醇组及硫酸镁+沙丁胺醇组2个时点的FEV1、PEF值占预计值的百分比高于硫酸镁组（P<0.05）;③硫酸镁组和硫酸镁+沙丁胺醇组用药后20 min时点的FEV1及PEF值占预计值的百分比高于用药后10 min时点的百分比（P<0.05）。 结论硫酸镁雾化吸入能改善哮喘患儿吸入乙酰胆碱激发后的肺功能,但其效果不如单用沙丁胺醇;硫酸镁+沙丁胺醇联合应用不具有协同效应。