Phosphorylation of Myristoylated Alanine-Rich C Kinase Substrate (MARCKS) by Proline-Directed Protein Kinases and Its Dephosphorylation

Abstract: Excitatory amino acid (EAA) neurotransmitters may play a role in the pathophysiology of traumatic injury to the CNS. Although NMDA receptor antagonists have been reported to have therapeutic efficacy in animal models of brain injury, these compounds may have unacceptable toxicity for clinical use. One alternative approach is to inhibit the release of EAAs following traumatic injury. The present study examined the effects of administration of a novel sodium channel blocker and EAA release inhibitor, BW1003C87, or the NMDA receptor-associated ion channel blocker magnesium chloride on cerebral edema formation following experimental brain injury in the rat. Animals (n = 33) were subjected to fluid percussion brain injury of moderate severity (2.3 atm) over the left parietal cortex. Fifteen minutes after injury, the animals received a constant infusion of BW1003C87 (10 mg/kg, i.v.), magnesium chloride (300 µmol/kg, i.v.), or saline over 15 min (2.75 ml/kg/15 min). In all animals, regional tissue water content in brain was assessed at 48 h after injury, using the wet weight/dry weight technique. In saline-treated control animals, fluid percussion brain injury produced significant regional brain edema in injured left parietal cortex ( p < 0.001), the cortical area adjacent to the site of maximal injury ( p < 0.001), left hippocampus ( p < 0.001), and left thalamus ( p = 0.02) at 48 h after brain injury. Administration of BW1003C87 15 min postinjury significantly reduced focal brain edema in the cortical area adjacent to the site of maximal injury ( p < 0.02) and left hippocampus ( p < 0.01), whereas magnesium chloride attenuated edema in left hippocampus ( p = 0.02). These results suggest that excitatory neurotransmission may play an important role in the pathogenesis of posttraumatic brain edema and that pre- or post-synaptic blockade of glutamate receptor systems may attenuate part of the deleterious sequelae of traumatic brain injury.     

糖尿病白内障术后黄斑水肿与房水细胞因子的关系

为了探讨2型糖尿病白内障术后黄斑水肿与房水中细胞因子的关系,本研究选取2016年2月至2017年7月在我院治疗的2型糖尿病白内障患者117例117眼,均行超声乳化白内障摘除术,观察术后4周黄斑水肿发生情况以及房水中多种细胞因子水平。研究结果显示:术后4周,有37眼发生黄斑水肿(观察组),未发生黄斑水肿80眼(对照组);观察组术后4周黄斑区视网膜厚度为(247.28±18.37)μm,明显高于对照组(p<0.05),且明显高于术前水平(p<0.05);观察组术后4周干扰素诱导蛋白-10 (IP-10)、巨噬细胞趋化蛋白(MCP-1)、血管内皮生长因子(VEGF)和细胞因子转化生长因子-β2 (TGF-β2)水平分别为(6.01±0.89) pg/mL、(340.03±45.39) pg/mL、(812.28±40.06) pg/mL和(40.05±10.03) pg/mL,明显高于对照组(p<0.05),且高于术前水平(p<0.05);观察组和对照组手术前后粒细胞-巨噬细胞集落刺激因子(GM-CSF)和碱性成纤维细胞生长因子(b-FGF)比较差异无统计学意义(p>0.05);术后4周IP-10、MCP-1、VEGF和TGF-β2水平与黄斑区视网膜厚度呈正相关(r=0.452, 0.501, 0.466和0.470, p<0.05)。本研究的结果初步说明,房水中IP-10、MCP-1、VEGF和TGF-2水平与2型糖尿病白内障术后黄斑水肿有一定关系,有可能成为黄斑水肿的特异性评价指标,值得进一步研究。     

Effect of nutritional copper deficiency on carrageenin edema in the rat

The effects of nutritional copper deficiency on carrageenin edema in the rat were investigated with emphasis on studying the correlation between the degree of copper deficiency and the degree of edema. Carrageenin paw edema in both copper-sufficient and copper-deficient groups of rats was compared after either 20, 40, or 60 d on respective diets. The degree of copper deficiency was quantitated by analyzing total copper concentrations in a number of tissues. Other copper dependent parameters were also determined. Results indicated that: (1) although copper sufficient rats showed relatively little change in the degree of edema, copper-deficient rats showed a steady and significant increase in edema from d 20 to 40 to 60; (2) paw edema in copper-deficient animals was highly and negatively correlated to the concentrations of copper in the liver; the correlation with liver Cu,Zn-superoxide dismutase activity, however, was inconsistent; (3) paw edema was not correlated either to copper concentration in tissues other than liver or to plasma ceruloplasmin activity; and (4) aggravation of carrageenin edema in copper-deficient animals seemed to be mediated via an as yet unknown secondary effect of copper deficiency.     

Magnetic resonance analysis of the effects of acute ammonia intoxication on rat brain. Role of NMDA receptors

Acute ammonia intoxication leads to rapid death, which is prevented by blocking N -methyl- d -aspartate (NMDA) receptors. The subsequent mechanisms leading to death remain unclear. Brain edema seems an important step. The aim of this work was to study the effects of acute ammonia intoxication on different cerebral parameters in vivo using magnetic resonance and to assess which effects are mediated by NMDA receptors activation. To assess edema induction, we injected rats with ammonium acetate and measured apparent diffusion coefficient (ADC) in 16 brain areas. We also analyzed the effects on T1, T2, and T2* maps and whether these effects are prevented by blocking NMDA receptors. The effects of acute ammonia intoxication are different in different brain areas. T1 relaxation time is reduced in eight areas. T2 relaxation time is reduced only in ventral thalamus and globus pallidus. ADC values increased in hippocampus, caudate-putamen, substantia nigra and cerebellar cortex, reflecting vasogenic edema. ADC decreased in hypothalamus, reflecting cytotoxic edema. Myo-inositol increased in cerebellum and substantia nigra, reflecting vasogenic edema. N -acetyl-aspartate decreased in cerebellum, reflecting neuronal damage. Changes in N -acetyl-aspartate, T1 and T2 are prevented by blocking NMDA receptors with MK-801 while changes in ADC or myo-inositol (induction of edema) are not.     

Relevance of anti-reactive oxygen species activity to anti-inflammatory activity of components of Eviprostat, a phytotherapeutic agent for benign prostatic hyperplasia

Inflammation is a common finding in benign prostatic hyperplasia (BPH). The phytotherapeutic agent eviprostat is a popular treatment for BPH in Japan and Germany. This agent consists of five components; four are extracted from Chimaphila umbellata, Populus tremula, Pulsatilla pratensis and Equisetum arvense (coded as EVI-1, EVI-2, EVI-3 and EVI-4, respectively) and the fifth is germ oil from Triticum aestivum (coded as EVI-5). In this study, the effects of each component on the reactive oxygen species (ROS), superoxide anion (O2-) and hydroxyl radical (OH*) generated in cell-free systems and human neutrophils, and on carrageenin-induced paw edema in rats were investigated. EVI-1, EVI-2 and EVI-4 suppressed the O2- levels in the xanthine/xanthine oxidase system, and EVI-1, EVI-2, EVI-3 and EVI-4 abolished the OH* produced in a Fenton-type reaction system, so that EVI-1, EVI-2 and EVI-4 possessed inhibitory action with respect to both O2- and OH*. EVI-1, EVI-2 and EVI-4 also reduced ROS levels in phorbol myristate acetate-stimulated neutrophils. The paw swelling was inhibited by a mixture of EVI-1, EVI-2, EVI-3, EVI-4 and EVI-5 (a mixture which is equivalent to eviprostat) or by a mixture of EVI-1, EVI-2 and EVI-4, even though each component alone did not significantly inhibit the swelling. These findings suggest that the suppression of ROS by EVI-1, EVI-2 and EVI-4 may partly contribute to the anti-inflammatory action of eviprostat, and this action may be implicated in its therapeutic effect on BPH.     

压脚痛阈测定法的改进和应用

本文介绍一种改进的压脚测痛法。采用电机驱动替代用手挤压橡皮球完成升压过程;通过一个自动的电路切断结构判定抽脚反应,较目视更加客观;用读数保持电路记录压力变化,较直接读取刻度值更加准确,可靠。这些优点,业经电针和吗啡镇痛实验验证。     

Liposome-entrapped superoxide dismutase reduces ischemia/reperfusion ‘oxidative stress’ in gerbil brain

Bilateral common carotid artery occlusion (15 min.) followed by two hours of recirculation reduced mitochondrial superoxide dismutase (SOD) and glutathione reductase (GR) activities, and increased susceptibility of mitochondrial membranes to in vitro lipid peroxidation in brain regions (i.e., cortex, striatum and hippocampus) of Mongolian gerbil. Intraperitoneal bolus injection (2 mg/kg b.w.) of liposome-entrapped CuZn superoxide dismutase (l-SOD) increased the endogenous SOD activity in normal brain tissue and, when given at the end of ischemia, counteracted both the ischemic reduction of endogenous SOD and the increased peroxidation of mitochondrial membranes. 1-SOD treatment was ineffective in reducing brain swelling, suggesting that superoxide radicals are not a main participant in the process of (post)ischemic brain edema formation.