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1.
Coline Grisotto Janice Taïl Cynthia Planesse Nicolas Diotel Marie-Paule Gonthier Olivier Meilhac David Couret 《International journal of molecular sciences》2021,22(9)
Background: Stroke in context of type 2 diabetes (T2D) is associated with a poorer outcome than in non-diabetic conditions. We aimed at creating a new reproducible mouse model of stroke in impaired glucose tolerance conditions induced by high-fat diet. Methods: Adult C57BL6 mice were fed for 2 months with either normal diet (ND) or high-fat diet (HFD). We used a model of Middle Cerebral Artery Occlusion (MCAO) for 90 min. Oral Glucose Tolerance Test (OGTT) and Insulin Tolerance Test (ITT) were used to assess pre-diabetic status. Brain infarct volume, hemorrhagic transformation (HT) as well as systemic and cerebral inflammatory markers were evaluated. Results: HFD was associated with an increased body weight and glycemia following OGTT. The HFD group presented a significant increase in brain infarct volume (38.7 (IQR 30–46.7%) vs. 28.45 (IQR 21–30%); p = 0.016) and HT (HFD: 2 (IQR 1–5) vs. ND: 0 (IQR 0–1); p = 0.012) and higher levels of IL-6 and MCP-1 in infarcted hemisphere compared to the ND group. Conclusion: Two months of HFD in adult mice were sufficient to alter the lipid profile and the control of hyperglycemia. These metabolic perturbations were significantly associated with increased infarct volume and hemorrhagic complications. 相似文献
2.
Nicholas Caffes David B. Kurland Volodymyr Gerzanich J. Marc Simard 《International journal of molecular sciences》2015,16(3):4973-4984
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 KATP (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. 相似文献
3.
Dovile Stravinskiene Aiste Sliziene Lina Baranauskiene Vilma Petrikaite Aurelija Zvirbliene 《International journal of molecular sciences》2020,21(24)
Monoclonal and recombinant antibodies are widely used for the diagnostics and therapy of cancer. They are generated to interact with cell surface proteins which are usually involved in the development and progression of cancer. Carbonic anhydrase XII (CA XII) contributes to the survival of tumors under hypoxic conditions thus is considered a candidate target for antibody-based therapy. In this study, we have generated a novel collection of monoclonal antibodies (MAbs) against the recombinant extracellular domain of CA XII produced in HEK-293 cells. Eighteen out of 24 MAbs were reactive with cellular CA XII on the surface of live kidney and lung cancer cells as determined by flow cytometry. One MAb 14D6 also inhibited the enzymatic activity of recombinant CA XII as measured by the stopped-flow assay. MAb 14D6 showed the migrastatic effect on human lung carcinoma A549 and renal carcinoma A498 cell lines in a ‘wound healing’ assay. It did not reduce the growth of multicellular lung and renal cancer spheroids but reduced the cell viability by the ATP Bioluminescence assay. Epitope mapping revealed the surface-exposed amino acid sequence (35-FGPDGENS-42) close to the catalytic center of CA XII recognized by the MAb 14D6. The variable regions of the heavy and light chains of MAb 14D6 were sequenced and their complementarity-determining regions were defined. The obtained variable sequences were used to generate recombinant antibodies in two formats: single-chain fragment variable (scFv) expressed in E. coli and scFv fused to human IgG1 Fc fragment (scFv-Fc) expressed in Chinese Hamster Ovary (CHO) cells. Both recombinant antibodies maintained the same specificity for CA XII as the parental MAb 14D6. The novel antibodies may represent promising tools for CA XII-related cancer research and immunotherapy. 相似文献
4.
《Planning》2019,(2)
2017年,美国心脏病学会和美国心脏协会提出将高血压诊断标准降为130/80 mm Hg (1 mm Hg=0. 133 kPa),这与其他指南有所不同。降压治疗的核心目标在于靶器官的保护,近年来降压治疗与脑小血管病预防的相关问题日益受到临床重视。目前研究结果表明,降压治疗对腔隙性卒中患者的二级预防以及白质病变进展的预防可能有一定积极意义,但确切的降压目标值并未确定。血压与临床结局可能呈现J型关系,血压过低或过高可能均有害,而取得最大获益的降压目标有待进一步探索。 相似文献
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6.
分析了设备对PCB电镀过程中孔中镀液更新之影响,为有效地利用设备条件改善孔中镀液的更新提供了一些方法及理论数据。 相似文献
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8.
钨合金圆筒爆破试验破片分布的统计分析 总被引:1,自引:1,他引:0
采用圆筒爆破试验方法研究了易碎型钨合金的破片分布特征,并与93W合金的结果进行了对比.对破片的数量和质量分布特征进行了统计分析,发现易碎型钨合金的破片率明显高于93W合金,而且破片的均匀性也明显好于93W合金,但易碎钨合金的破片回收率低于93W合金,而且受装药量的影响较大. 相似文献
9.
Berrin-Wasserman Stacy; Winnick Wilma A.; Borod Joan C. 《Canadian Metallurgical Quarterly》2003,17(3):429
Does sentence generation and/or stimulus emotionality enhance verbal memory in patients with neurological impairment? This question was addressed by testing 40 patients with unilateral stroke (20 with left-brain and 20 with right-brain damage) and 20 healthy control participants for recall and recognition of 48 target words. During encoding, emotional and nonemotional words were either presented in sentences (read condition) or used to form sentences (generate condition). Both word emotionality and generative processing improved memory performance in all groups. The authors suggest that a similar influence (i.e., cognitive activation) underlies both of these memory-enhancing effects, although the putative origins of the 2 effects are quite different. Neuropsychological underpinnings and clinical implications of these phenomena are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
10.
Christos Bouras Agisilaos Konidaris 《International Journal of Communication Systems》2005,18(2):119-142
Redundant data transfers over the Web, can be mainly attributed to the repeated transfers of unchanged data. Web caches and Web proxies are some of the solutions that have been proposed, to deal with the issue of redundant data transfers. In this paper we focus on the efficient estimation and reduction of redundant data transfers over the Web. We first prove that a vast amount of redundant data is transferred in Web pages that are considered to carry fresh data. We show this by following an approach based on Web page fragmentation and manipulation. Web pages are broken down to fragments, based on specific criteria. We then deal with these fragments as independent constructors of the Web page and study their change patterns independently and in the context of the whole Web page. After the fragmentation process, we propose solutions for dealing with redundant data transfers. This paper has been based on our previous work on ‘Web Components’ but also on related work by other researchers. It utilises a proxy based, client/server architecture, and imposes changes to the algorithms executed on the Proxy server and on clients. We show that our proposed solution can considerably reduce the amount of redundant data transferred on the Web. Copyright © 2004 John Wiley & Sons, Ltd. 相似文献