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Introduction: It is well known that the concentration of anaesthetic drugs that meet the requirements of clinical surgery will have an impact on the brain's ability to learn, remember, cognitive function and performance, but doctors and scientists still cannot explain how anaesthetic causes patients to temporarily lose consciousnessScientists in the United States have identified how anaesthetic affects human consciousness, according to a new study published May 28 in the Proceedings of the National Academy of Sciencessurgery would be unthinkable without general anaesthetic, so despite 175 years of medical history, doctors and scientists still can't explain how anaesthetic temporarily renders a patient unconsciousOn the evening of May 28, a new study by the Scripps Research Institute was published in the Proceedings of the National Academy of Sciences (PNAS) to solve the long-standing medical mysteryUsing modern nanoscale microscopy, combined with clever experiments in living cells and fruit flies, scientists showed how lipid clusters in cell membranes act as missing intermediates in two-part mechanismsShort anaesthetic can transfer lipid clusters from an orderly state to a disordered state, and then repeat back and forth, leading to a large number of follow-up effects, which eventually lead to a change in consciousnessthe discovery of DrRichard Lerner, a fellow at the National Academy of Sciences and a chemist at the Scripps Institution, and DrScott Hansen, a molecular biologist, solves a century-old scientific debate that is still brewing: is an anesthetic acting directly on a cell membrane door called an ion channel, or is it somehow acting on a cell membrane to signal cellular changes in a new, unexpected way? After nearly five years of experimentation, appeals, debate and challenges, they say, they have finally come to the conclusion that this is a two-step process that begins with the membraneAnesthetics disrupt an orderly lipid cluster in the cell membrane known as a "fat raft" and thus initiate a signal"We think there is no doubt that this new approach is being used for other brain functions beyond consciousness, allowing us to now further decipher other mysteries of the brain,"Lerner said"。1846, in a tumor patient at Massachusetts General Hospital in Boston, the ability of ethyl to cause consciousness was first demonstrated, when ether became so obvious in a surgical room later known as the "Ether Dome" that by 1899, the German pharmacologist Hans Horst Meyer and the 1901 British biologist Charles Ernest Overton wisely concluded that the efficacy of the anaesthetic was determinedHansen recalls that when he drafted an appropriations application to further investigate the historic issue, he turned to Google to think he couldn't be the only one convinced of the role of the fat raftTo Hansen's delight, Lerner's 1997 PNAS paper had assumptions about whole hemp endogenous analogues, and anesthesia had such an important practical meaning that I couldn't believe we didn't know how all of these aneses cause people to lose consciousness Hansen says that many other scientists, through a century of experiments, have found the same answer, but they lack several key elements: first, microscopes can see biological complexes smaller than the diffraction limits of light, and second, recent insights into the properties of cell membranes, and the complex tissues and functions that make up their various lipid complexes "They've been looking for a lot of lipids and they haven't seen lipid signals, in large part because of a lack of technology," said Hansen, "。 a postdoctoral researcher at Hansen's lab using Nobel Prize-winning microscope technology, especially a microscope called dSTORM, known as a "direct random optical reconstruction microscope," and Hansen explained that soaking cells in chloroform would greatly increase the diameter and area of the cell membrane lipid cluster GM1 Hansen says what he sees is a shift in the GM1 cluster organization from crowding to chaos When it becomes disordered, GM1 overflows its contents, including an enzyme called phosphase D2 (PLD2) inhaling anaesthetic can damage the appearance structure of the GM1 domain labeled PLD2 with fluorescent chemicals, Hansen was able to observe PLD2 like a billiard through a dSTORM microscope to move from GM1's home to another less popular lipid cluster PIP2 This activates key molecules in the PIP2 cluster, including the TREK1 potassium ion channel and its lipid activator phospholipidic acid (PA) The activation of TREK1 essentially freezes the ability of neurons to activate, leading to loss of consciousness, Hansen said The TREK1 potassium ion channel releases potassium ions, which cause the nerves to become hyperpolarized, more difficult to emit, and only shut down "。 inhaling anesthetic activates TREK-1 depends on PLD2 Lerner insists they have validated the findings in a living animal model Common black-bellied fruit flies provide this data Removing the expression of PLD in fruit flies makes them resistant to sedative action In fact, they need twice as much anaesthetic to show the same response "All flies eventually lose consciousness, suggesting that PLD helps set a threshold, but is not the only way to control anaesthetic sensitivity," they wrote "。 "People will start to look at everything you can imagine: sleep , consciousness, all those related disorders," says Lerner "Ether is a gift for helping us understand the problems of consciousness It illuminates a way that has not yet been recognized, and the brain has apparently evolved to control higher-order functions "
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Source: for The Conversion Medicine Platform