Glibenclamide for the Treatment of Ischemic and Hemorrhagic Stroke

Ischemic and hemorrhagic strokes are associated with severe functional disability and high mortality. Except for recombinant tissue plasminogen activator, therapies targeting the underlying pathophysiology of central nervous system (CNS) ischemia and hemorrhage are strikingly lacking. Sur1-regulated channels play essential roles in necrotic cell death and cerebral edema following ischemic insults, and in neuroinflammation after hemorrhagic injuries. Inhibiting endothelial, neuronal, astrocytic and oligodendroglial sulfonylurea receptor 1–transient receptor potential melastatin 4 (Sur1–Trpm4) channels and, in some cases, microglial K_ATP (Sur1–Kir6.2) channels, with glibenclamide is protective in a variety of contexts. Robust preclinical studies have shown that glibenclamide and other sulfonylurea agents reduce infarct volumes, edema and hemorrhagic conversion, and improve outcomes in rodent models of ischemic stroke. Retrospective studies suggest that diabetic patients on sulfonylurea drugs at stroke presentation fare better if they continue on drug. Additional laboratory investigations have implicated Sur1 in the pathophysiology of hemorrhagic CNS insults. In clinically relevant models of subarachnoid hemorrhage, glibenclamide reduces adverse neuroinflammatory and behavioral outcomes. Here, we provide an overview of the preclinical studies of glibenclamide therapy for CNS ischemia and hemorrhage, discuss the available data from clinical investigations, and conclude with promising preclinical results that suggest glibenclamide may be an effective therapeutic option for ischemic and hemorrhagic stroke.     

黑龙江省节水增粮行动(2012—2015年)实施方案

文章通过对黑龙江省高效节水现状,存在问题的分析,结合黑龙江省高效节水发展的支撑能力,阐述黑龙江省节水增粮目标、任务及总体布局,为黑龙江省2012—2015年节水增粮实施提供依据。     

Dielectric,ferroelectric, and piezoelectric properties of lead-free Ba0.95Ca0.05Ti1-xZrxO3 ceramics

Abstract

Ba_0.95Ca_0.05Ti_1-xZr_xO₃ (BCTZO) ceramics were prepared by a solid state reaction method. The samples were characterized by X-ray diffraction (XRD), Scanning electron microscopy (SEM) and X-ray absorption near edge structure (XANES). The ceramics exhibit a pure perovskite structure. The average grain size gradually decreases with increasing Zr concentration. XANES results indicate that the intensities of pre-edge peaks dropped with increasing Zr concentration. The BCTZO ceramic of x?=?0.05 has the optimum electrical properties with the maximum dielectric constant (ε'_m), remanent polarization (2P_r), coercive electric field (2E_c) and piezoelectric charge constant (d₃₃) of 7,244, 12.54 (μC/cm²), 5.29 (kV/cm) and 288 (pC/N), respectively.     

Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study

There is currently an outbreak of respiratory disease caused by a novel coronavirus. The virus has been named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the disease it causes has been named coronavirus disease 2019 (COVID-19). More than 16% of patients developed acute respiratory distress syndrome, and the fatality ratio was 1%–2%. No specific treatment has been reported. Herein, we examined the effects of favipiravir (FPV) versus lopinavir (LPV)/ritonavir (RTV) for the treatment of COVID-19. Patients with laboratory-confirmed COVID-19 who received oral FPV (Day 1: 1600 mg twice daily; Days 2–14: 600 mg twice daily) plus interferon (IFN)-α by aerosol inhalation (5 million international unit (IU) twice daily) were included in the FPV arm of this study, whereas patients who were treated with LPV/RTV (Days 1–14: 400 mg/100 mg twice daily) plus IFN-α by aerosol inhalation (5 million IU twice daily) were included in the control arm. Changes in chest computed tomography (CT), viral clearance, and drug safety were compared between the two groups. For the 35 patients enrolled in the FPV arm and the 45 patients in the control arm, all baseline characteristics were comparable between the two arms. A shorter viral clearance median time was found for the FPV arm versus the control arm (4 d (interquartile range (IQR): 2.5–9) versus 11 d (IQR: 8–13), P < 0.001). The FPV arm also showed significant improvement in chest CT compared with the control arm, with an improvement rate of 91.43% versus 62.22% (P = 0.004). After adjustment for potential confounders, the FPV arm also showed a significantly higher improvement rate in chest CT. Multivariable Cox regression showed that FPV was independently associated with faster viral clearance. In addition, fewer adverse events were found in the FPV arm than in the control arm. In this open-label before-after controlled study, FPV showed better therapeutic responses on COVID-19 in terms of disease progression and viral clearance. These preliminary clinical results provide useful information of treatments for SARS-CoV-2 infection.     

Effects of Ketone Bodies on Brain Metabolism and Function in Neurodegenerative Diseases

Under normal physiological conditions the brain primarily utilizes glucose for ATP generation. However, in situations where glucose is sparse, e.g., during prolonged fasting, ketone bodies become an important energy source for the brain. The brain’s utilization of ketones seems to depend mainly on the concentration in the blood, thus many dietary approaches such as ketogenic diets, ingestion of ketogenic medium-chain fatty acids or exogenous ketones, facilitate significant changes in the brain’s metabolism. Therefore, these approaches may ameliorate the energy crisis in neurodegenerative diseases, which are characterized by a deterioration of the brain’s glucose metabolism, providing a therapeutic advantage in these diseases. Most clinical studies examining the neuroprotective role of ketone bodies have been conducted in patients with Alzheimer’s disease, where brain imaging studies support the notion of enhancing brain energy metabolism with ketones. Likewise, a few studies show modest functional improvements in patients with Parkinson’s disease and cognitive benefits in patients with—or at risk of—Alzheimer’s disease after ketogenic interventions. Here, we summarize current knowledge on how ketogenic interventions support brain metabolism and discuss the therapeutic role of ketones in neurodegenerative disease, emphasizing clinical data.     

高密度聚乙烯/丁苯橡胶热塑性硫化胶的形状记忆性能

采用动态硫化法制备了高密度聚乙烯(HDPE)/丁苯橡胶(SBR)热塑性硫化胶(TPV),研究了橡塑比、定型温度、回复温度及增容剂苯乙烯-丁二烯-苯乙烯嵌段共聚物(SBS)对HDPE/SBR TPV形状记忆性能的影响,观察了其微观结构,提出了形状记忆行为机制。结果表明,HDPE/SBR TPV具有典型的"海-岛"结构,拉伸后其表面存在明显的取向结构;SBS能显著提高HDPE/SBR TPV的形状记忆性能,当SBS用量为6份、定型温度和回复温度均为120℃时,HDPE/SBR TPV的形状记忆性能最佳。     

海绵负载纳米Al2O3复合吸附剂去除水中硒研究

研究制备了海绵负载纳米Al2O3微球的复合吸附剂(NAS),并用于对Se(Ⅳ)和Se(Ⅵ)的吸附。结果表明,合成的纳米Al2O3微球(NAO)的平均尺寸为200~400 nm,在海绵上负载NAO会使其分散性更好。当NAO负载量分别为80 mg/g和60 mg/g时,NAS对Se(Ⅳ)和Se(Ⅵ)的吸附性能为佳,分别需要60、120 min达到平衡,适应pH为2~5;两者均符合准2级动力学模型;NAS对Se(Ⅳ)、Se(Ⅵ)的最大吸附容量分别为137.2、143.9 mg/g,能很好地与Freundlich模型拟合,说明NAS表面不均匀,且属于多层吸附。经过2次的循环,对Se(Ⅳ)和Se(Ⅵ)的去除率有所降低,但均仍保持在一定的水平,说明NAS可再生循环利用。NAS作为一种新型吸附剂去除水中Se具有较好的应用前景。     

Lipase‐catalyzed synthesis of aliphatic poly(β‐thioether ester) with various methylene group contents: thermal properties,crystallization and degradation

A series of novel aliphatic poly(β‐thioether ester)s with various methylene group contents were prepared by direct lipase‐catalyzed polycondensation of the monomer with an acid‐labile β‐thiopropionate group. The polycondensation reaction using immobilized lipase B from Candida antarctica was carried out in diphenyl ether at 90 °C. Poly(β‐thioether ester)s with high molecular weights of 20 500–57 000 Da and narrow polydispersities in the range 1.40–1.48 were obtained. Thermogravimetric analysis, differential scanning calorimetry and wide‐angle X‐ray diffraction were used to investigate the thermal properties and crystal structures of these polyesters. All the poly(β‐thioether ester)s were semicrystalline polymers and thermally stable up to at least 200 °C. In vitro degradation studies showed that they can rapidly degrade under acidic conditions by the hydrolysis of the β‐thiopropionate groups, suggesting their potential as acid‐degradable polymeric materials. © 2019 Society of Chemical Industry