Ion Channel Conformational Coupling in Ischemic Neuronal Death
Long-Jun Wu in Nonclassical Ion Channels in the Nervous System, 2021
This chapter introduces several typical ion channels involved in ischemic brain damage and compare the differences between their ion conduction-dependent and -independent functions. Activation of an ion channel leads to conformational changes. One obvious and direct consequence of conformational changes is to open the pore for ion flux. An increasing number of ion channel-binding proteins have been revealed by affinity purification–mass spectrometry and proximity labeling analysis. Voltage-gated potassium channels are transmembrane proteins regulating resting membrane potential and action potential firing patterns. The chapter focuses on ion channel conformational coupling in neurons under conditions of ischemic stroke and how this mechanism contributes to neuronal death. Intercellular communications are critical for almost all essential functions of an organism, such as breeding, metabolic activities, and learning/memory. Necroptosis is a major death pathway of ischemic neuronal demise. Ischemic attack causes multiple pathological alterations in an affected brain, including extracellular acidosis and oxidative stress.
Disorders in tHemostasis System and Changes in the Rheological Properties of the Blood in Ischemic Heart Disease and Diabetes Mellitus Patients
E.I. Sokolov in Obesity and Diabetes Mellitus, 2020
This chapter examines disorders in tHemostasis system and shows the changes in the rheological properties of the blood in Ischemic heart disease and diabetes mellitus patients. Hemostasis is an evolutionally developed and genetically determined adaptation system of an organism. It includes an integrated unity of the various physiological constants of an organism that ensure the functions of the organism under conditions of stress. The regulation of the hemostasis system is a closed dynamic organization of central and peripheral mechanisms. Antithrombin III is the most powerful inhibitor of blood coagulation, it is synthesized by the endothelium and hepatocytes, is on the surface of the endothelial cells and in the blood, and is responsible for 75–90% of the spontaneous anticoagulant activity of the blood. The anticoagulating effect of heparin is aimed at inactivating thrombin, which is manifest only in the presence of antithrombin III.
The Peak and Decline of the Coronary Heart Disease Pandemic in the United States, 1970-2010
William G. Rothstein in The Coronary Heart Disease Pandemic in the Twentieth Century, 2017
Coronary heart disease was the leading cause of death in the adult population of the United States at the peak of the pandemic in the 1950s and 1960s. The 1950s and 1960s were the peak years of the coronary heart disease pandemic in the United States, when all age, sex, and race groups had their highest mortality rates. Coronary heart disease mortality rates stabilized for age groups 35-44 and 45-54 about 1950 and remained at that level to 1970, with slight differences by race. Minor discontinuities in the ischemic heart disease category that occurred among revisions eight, nine, and ten of the International Classification of Diseases had only a small effect on mortality rates. Mortality rates from the disease began to decrease for all of these population groups in the 1970s and stopped decreasing about 1990 for younger age groups but continued to decrease after 2000 for older age groups.
MiRNAs: potential diagnostic and therapeutic targets for cerebral ischaemia
Published in Neurological Research, 2016
Ruixia Zhu, Xu Liu, Ying Zhu, Zhiyi He
MiRNAs are short single-stranded non-coding RNAs that cause degradation or repression of target mRNAs by base pairing with their 3′-untranslated regions. Recent studies have shown that miRNAs play an important role in the occurrence and development of cerebral ischaemia, as well as exerting regulatory effects. Additionally, circulating miRNAs in peripheral blood, which are dysregulated following cerebral ischaemia, have recently been identified as useful biomarkers in diagnosis and prognosis of cerebral ischaemia. Single-nucleotide polymorphisms (SNPs) located in miRNA genes or target sites are likely to cause complex functional consequences by affecting miRNA biogenesis or target selection. Research on miRNA-SNPs is rapidly growing, and recent studies have identified a significant relationship between miRNAs and ischemic disease. We also address the latest advances in miRNA-based therapeutic approaches for ischemic disease. In conclusion, our review summarizes current research regarding miRNAs and cerebral ischaemia, focusing on the regulatory role of miRNAs in cerebral ischaemia, as well as the potential of miRNAs as biomarkers and therapeutic targets in cerebral ischaemia.
Edaravone's free radical scavenging mechanisms of neuroprotection against cerebral ischemia: review of the literature
Published in International Journal of Neuroscience, 2015
Yanxin Ren, Bing Wei, Xirui Song, Nan An, Yiying Zhou, Xinxin Jin, Yuyang Zhang
Free radicals and oxidative stress play key roles in cerebral ischemic pathogenesis and represent pharmacological targets for treatment. Edaravone (Edv), one of antioxidant agents that have been used in acute ischemic stroke in both clinical settings and animal experiments, exerts neuroprotective effect on ischemic injured brains. This review is aimed to elaborate the latest molecular mechanisms of the neuroprotection of Edv on cerebral ischemia and provide reasonable evidence in its clinical application. It is found that Edv has neuroprotective influence on cerebral ischemia, which is closely related to the facets of scavenging reactive oxygen species (ROS), hydroxyl radical (ċOH) and reactive nitrogen species (RNS). And it is a good antioxidant agent that can be safely used in the treatment of cerebral ischemia and chronic neurodegenerative disorders as well as other ischemia/reperfusion (I/R)-related diseases. The combination of Edv with thrombolytic therapy also can be applied in clinical settings and will be greatly beneficial to patients with stroke.
Robot-assisted partial nephrectomy: How to minimise renal ischaemia
Published in Arab Journal of Urology, 2018
Chandran Tanabalan, Avi Raman, Faiz Mumtaz
Renal ischaemia research has shown an increase in renal damage proportional to ischaemic time. Therefore, we assessed the importance of renal ischaemic times for warm and cold ischaemia approaches, and explored the different surgical techniques that can help to minimise renal ischaemia in robot-assisted partial nephrectomy (RAPN). Minimising renal ischaemia during nephron-sparing surgery (NSS) is a key factor in preserving postoperative renal function. Current data support a safe warm ischaemia time (WIT) of ≤25 min and cold ischaemic time of ≤35 min, resulting in no significant deterioration in renal function. In general, patients undergoing NSS have increased comorbidities, including chronic kidney disease, and in these patients it is difficult to predict their postoperative renal function recovery. With RAPN, efforts should be made to keep the WIT to 25 min, but may not lead to superior functional outcome. Careful preoperative planning, tumour factors, and meticulous surgical technique are critical for optimum patient outcome.