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【medical-news】【资讯翻译】AHA2012：CSL-112可增加人体胆固醇转运
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希望参与动态版其他活动的会员请查看版面右边栏的置顶部分。原文链接：http://www.theheart.org/article/1474767.doCSL-112 increases cholesterol efflux in humansLos Angeles, CA - Initial clinical trials with the novel apolipoprotein A1 (apoA1) formulation CSL-112 (CSL Laboratories, Victoria, Australia) have shown that it rapidly enhances key biomarkers of the early stages of reverse cholesterol transport. It is thus being positioned as a new therapeutic approach to quickly lower the atherosclerosis burden in an attempt to reduce cardiovascular events in the initial days after an ACS.CSL-112 is a reconstituted formulation of apoA1, the main component of HDL, derived from human plasma and reconstituted to form HDL particles suitable for infusion. As the natural function of HDL is to promote cholesterol efflux (the removal of cholesterol from tissue such as the arterial wall and subsequent transport to the liver for clearance from the body), the hope is that by rapidly raising HDL levels, CSL-112 will quickly reduce cholesterol-loaded plaques that contribute to cardiovascular events.Phase 2 trials of CSL-112 are currently under way in stable coronary artery disease patients, and a phase 2b study in ACS patients is now planned.&Speed is a big deal&Dr Samuel Wright (CSL Laboratories, King of Prussia, PA) commented to heartwire: &The idea is to give a series of two-hour IV infusions of CSL-112 soon after an ACS event. This is an acute therapy for an acute condition in a period of very high risk.& He added: &In the first 30 days after an ACS, there is a very high risk of a subsequent MI. Speed is a big deal. We need therapies that act quickly. A two-hour infusion of CSL-112 starts to work immediately, giving a 100% increase in apoA1 within two hours. In comparison, niacin raises apoA1 by only 3% after eight weeks.&At last week's American Heart Association (AHA) 2012 Scientific Sessions, researchers from CSL presented two phase 1 studies of CSL-112 demonstrating that the product induces cholesterol efflux from macrophages into the plasma, the initial step in reverse cholesterol transport.Although there are now doubts surrounding the HDL field following the failure of initial HDL-raising therapies to show any reduction in cardiovascular events, CSL suggests that that not all forms of HDL are equally effective in promoting reverse cholesterol transport and that the HDL formed by the cholesteryl ester transfer protein (CETP) inhibitors so far tested (torcetrapib and dalcetrapib) may not promote cholesterol efflux as effectively as CSL-112.Nissen: &A very reasonable hypothesis&Commenting on CSL-112 for heartwire, Dr Steve Nissen (Cleveland Clinic, OH) explained: &This is a very different approach from the other HDL-raising drugs we have seen before, in that it is the smaller prebeta-HDL that is being infused. Unlike the alpha HDL, which is raised with niacin and the CETP inhibitors, prebeta-HDL is not already heavily laden with cholesterol, so the theory is that it has more potential to load up with cholesterol from atherosclerotic plaques.&While Nissen believes this is &a very reasonable hypothesis,& he also cautions that &the road to hell is paved with biological plausibility.& He points out that the current phase 1 studies show substantial changes in measures of reverse cholesterol transport, which is encouraging, but that &these are still surrogate end points and do not predict the ultimate success of a drug.& However, he adds, &You need a lot of different shots at goal to get one in the back of the net, and this novel approach is certainly worth pursuing further in a large clinical trial.&HDL raised &higher and faster&Speaking at an AHA press conference, Dr Andreas Gille (CSL, Victoria, Australia) noted that increased cholesterol-efflux capacity has recently been shown to be associated with reduced MI risk. He added: &We have previously shown CSL-112 to be an efficient acceptor of cholesterol in in vitro studies. Now we have also shown that it is effective in humans, raising HDL to higher levels and faster than any other previous therapy.&In one trial presented at the AHA meeting, 57 healthy volunteers were given a single infusion of CSL-112 at dose levels of 5 to 135 mg/kg. Blood samples taken from the volunteers were then tested and showed dose-proportional increases in HDL cholesterol, prebeta1-HDL, and cholesterol-efflux capacity from macrophages. The top dose of CSL-112 increased prebeta1-HDL by 3600% and global cholesterol efflux by 270%. There were no changes in levels of apoB, non-HDL cholesterol, and non-HDL triglycerides.In a second placebo-controlled study in 36 healthy subjects, three dose regimens were studied: four once-weekly infusions of 3.4 g, four once-weekly infusions of 6.8 g, and eight twice-weekly infusions of 3.4 g. Results showed that infusions of CSL-112 caused immediate large increases in cholesterol-efflux capacity, prebeta1-HDL, and HDL in serum or plasma. Prebeta1-HDL were elevated up to 20-fold. For all three regimens, all biomarker responses were dose dependent and had a similar magnitude and time course after the first and last infusions. Increases in HDL peaked at 24 to 48 hours after infusion, but levels remained elevated after 72 hours. The results suggested that when compared with a single infusion of CSL112, multiple infusions may provide greater efflux of cholesterol, the researchers said.Safety dataSafety data with CSL-112 will be scrutinized closely, because a previous version of the product, CSL-111, was discontinued due to liver toxicity. The company says it has reformulated the product (to produce CSL-112) to be less likely to cause liver problems.In the 36-patient study, there where were no treatment-related serious adverse events reported. Overall, a similar proportion of subjects in the placebo group and CSL-112-treatment groups reported at least one adverse event, and none were reported as product-related. The most common adverse event was vessel puncture-site hematoma (seen in 18 of 36 subjects), which was reported by similar proportions of subjects administered CSL-112 or placebo. In the CSL-112-treatment group, no clinically significant abnormalities were observed in serum biochemistry, hematology, and urine parameters. In addition, there were no remarkable changes seen in platelet function, vital signs, or ECG and no evidence of immunogenicity to CSL-112.The researchers concluded: &This first clinical trial evaluating repeat dosing of CSL-112 demonstrated that once- or twice-weekly infusions in healthy subjects had acceptable safety and pharmacokinetic profiles that are sufficiently robust to warrant further testing in patients.&A third study presented at the AHA meeting was reported to show anti-inflammatory properties of CSL-112, which may also be beneficial in reducing cardiovascular events. In the in vitro study using human blood, CSL-112 caused a strong inhibition of the expression of intracellular adhesion molecule-1 (ICAM-1) (CD54) on both monocytes and neutrophils and inhibited the secretion of proinflammatory cytokines (TNF, IL-1, and IL-6) and chemokines (IL-8, RANTES, and macrophage inflammatory protein 1 [Mip-1])
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欢迎交流、指正……CSL-112 increases cholesterol efflux in humansCSL-112可增加人体胆固醇逆转运Los Angeles, CA - Initial clinical trials with the novel apolipoprotein A1 (apoA1) formulation CSL-112 (CSL Laboratories, Victoria, Australia) have shown that it rapidly enhances key biomarkers of the early stages of reverse cholesterol transport. It is thus being positioned as a new therapeutic approach to quickly lower the atherosclerosis burden in an attempt to reduce cardiovascular events in the initial days after an ACS.加利福尼亚州，洛杉矶——关于新型载脂蛋白A1（apoA1）配方CSL-112（澳大利亚维多利亚州CSL实验室）的原创性临床研究证实，CSL-112能够迅速提高胆固醇逆转运初始过程中的关键性标志物。因此，它被定为成一种新的治疗方法来迅速降低动脉粥样硬化负担，从而尝试减少ACS之后最初几天里的心血管事件。CSL-112 is a reconstituted formulation of apoA1, the main component of HDL, derived from human plasma and reconstituted to form HDL particles suitable for infusion. As the natural function of HDL is to promote cholesterol efflux (the removal of cholesterol from tissue such as the arterial wall and subsequent transport to the liver for clearance from the body), the hope is that by rapidly raising HDL levels, CSL-112 will quickly reduce cholesterol-loaded plaques that contribute to cardiovascular events. 载脂蛋白A1（apoA1）是HDL的主要成分，来源于人血浆，而CSL-112是apoA1重组形成的适合运输的HDL微粒。因为天然HDL的功能就是促进胆固醇的流出/逆转运（从组织中清楚胆固醇，比如心室壁，随后运输到肝脏以从体内清除），其带给我们的希望就是能够借助于它来迅速升高HDL含量水平，CSL-112将迅速减少负载胆固醇的斑块，从而有利于心血管事件（的降低）。Phase 2 trials of CSL-112 are currently under way in stable coronary artery disease patients, and a phase 2b study in ACS patients is now planned. CSL-112的2期试验目前正在稳定的冠状动脉疾病患者身上进行，同时对ACS病人的2b期研究也正在计划中。&Speed is a big deal&“速度是一个大问题”Dr Samuel Wright (CSL Laboratories, King of Prussia, PA) commented to heartwire: &The idea is to give a series of two-hour IV infusions of CSL-112 soon after an ACS event. This is an acute therapy for an acute condition in a period of very high risk.& He added: &In the first 30 days after an ACS, there is a very high risk of a subsequent MI. Speed is a big deal. We need therapies that act quickly. A two-hour infusion of CSL-112 starts to work immediately, giving a 100% increase in apoA1 within two hours. In comparison, niacin raises apoA1 by only 3% after eight weeks.& Samuel Wright博士（CSL实验室，King of Prussia, PA）接受heartwire采访时评论道：“这一想法是在ACS事件之后迅速给予CSL-112一系列2小时的静脉输注。在这一段非常高的风险时期内，这是一种紧急状态下的紧急治疗方法。”接着他又补充道：“在ACS之后的起初30天内，继发MI的风险非常高。速度是一个大问题。我们需要采取迅速的治疗方法。给予2小时的CSL-112输注可以立即起效，可以在2小时内实现载脂蛋白A1的一个100%的升高。而相比之下，烟酸在8周之后也仅仅使apoA1升高了3%。”At last week's American Heart Association (AHA) 2012 Scientific Sessions, researchers from CSL presented two phase 1 studies of CSL-112 demonstrating that the product induces cholesterol efflux from macrophages into the plasma, the initial step in reverse cholesterol transport. 在上周的美国心脏病协会（AHA）2012年度科学会议上，来自CSL的研究人员呈现了两项CSL-112的1期研究，结果显示这一产品（CSL-112）诱导胆固醇从巨噬细胞外流至血浆，这是胆固醇逆转运的第一步。Although there are now doubts surrounding the HDL field following the failure of initial HDL-raising therapies to show any reduction in cardiovascular events, CSL suggests that that not all forms of HDL are equally effective in promoting reverse cholesterol transport and that the HDL formed by the cholesteryl ester transfer protein (CETP) inhibitors so far tested (torcetrapib and dalcetrapib) may not promote cholesterol efflux as effectively as CSL-112.早期提高HDL治疗未显现出任何心血管事件的减少，尽管继此之后，现在围绕HDL领域有很多怀疑，但CSL提示并非所有形式的HDL都可以一样有效地促进胆固醇的逆转运，并且借助胆固醇酯转移蛋白（CETP）抑制剂（torcetrapib和dalcetrapib）所形成的HDL就目前测试来看，或许并不能像CSL-112那样能有效地促进胆固醇的流出。Nissen: &A very reasonable hypothesis& Nissen：“一个非常合理的假设”Commenting on CSL-112 for heartwire, Dr Steve Nissen (Cleveland Clinic, OH) explained: &This is a very different approach from the other HDL-raising drugs we have seen before, in that it is the smaller prebeta-HDL that is being infused. Unlike the alpha HDL, which is raised with niacin and the CETP inhibitors, prebeta-HDL is not already heavily laden with cholesterol, so the theory is that it has more potential to load up with cholesterol from atherosclerotic plaques.& 在对heartwire谈及CSL-112时，俄亥俄州Cleveland诊所的Steve Nissen博士解释道：“这是一种与我们之前所见到的其他升高HDL的药物不同的方法，在这种方法中，输注了体积较小的prebeta-HDL。与α-HDL会增加烟酸和CETP抑制剂不同，prebeta-HDL没有载满胆固醇，因此就有了这样的理论：它（prebeta-HDL）有更大的潜能可以从动脉粥样硬化斑块中装载胆固醇。”While Nissen believes this is &a very reasonable hypothesis,& he also cautions that &the road to hell is paved with biological plausibility.& He points out that the current phase 1 studies show substantial changes in measures of reverse cholesterol transport, which is encouraging, but that &these are still surrogate end points and do not predict the ultimate success of a drug.& However, he adds, &You need a lot of different shots at goal to get one in the back of the net, and this novel approach is certainly worth pursuing further in a large clinical trial.&尽管Nissen相信这是“一个非常合理的假设”，但他同时也警示说“通向地狱的道路上也铺满了生物合理性。”他指出目前的1期研究显示胆固醇逆向转运措施上发生了重大变化，这是非常令人鼓舞的，但“这些都仍旧是替代终点，并不能预示着一种药物的最终成功。”然而，他补充道“你需要在一张大网的后面对不同的目标出击，以得到其中一个，而这种新方法肯定值得在一项大型临床试验中得到进一步的验证。”HDL raised &higher and faster&HDL升的“更高、更快”Speaking at an AHA press conference, Dr Andreas Gille (CSL, Victoria, Australia) noted that increased cholesterol-efflux capacity has recently been shown to be associated with reduced MI risk. He added: &We have previously shown CSL-112 to be an efficient acceptor of cholesterol in in vitro studies. Now we have also shown that it is effective in humans, raising HDL to higher levels and faster than any other previous therapy.& 在AHA的新闻发布会上，澳大利亚维多利亚州CSL实验室的Andreas Gille博士指出增加胆固醇的外排能力最近已被证实可以降低MI风险。他补充道：“我们在之前的体外研究中已经证实CSL-112是胆固醇一种有效的受体。现在我们也证实在人类它也是有效的，CSL-112可以比之前其他任何治疗都恩能够更高更快地升高HDL的含量水平。”In one trial presented at the AHA meeting, 57 healthy volunteers were given a single infusion of CSL-112 at dose levels of 5 to 135 mg/kg. Blood samples taken from the volunteers were then tested and showed dose-proportional increases in HDL cholesterol, prebeta1-HDL, and cholesterol-efflux capacity from macrophages. The top dose of CSL-112 increased prebeta1-HDL by 3600% and global cholesterol efflux by 270%. There were no changes in levels of apoB, non-HDL cholesterol, and non-HDL triglycerides.在AHA会议上呈现的一项试验当中，57位健康的志愿者给予单次输注CSL-112，剂量水平在5-135mg/kg不等。而后化验志愿者的血样，结果显示HDL胆固醇、prebeta1-HDL，以及从巨噬细胞排出胆固醇的能力与剂量呈正比增加。最高剂量输注CSL-112者prebeta1-HDL增加了3600%，同时总胆固醇排出增加270%。apoB、非HDL胆固醇，以及非HDL甘油三酯的含量水平没有变化。In a second placebo-controlled study in 36 healthy subjects, three dose regimens were studied: four once-weekly infusions of 3.4 g, four once-weekly infusions of 6.8 g, and eight twice-weekly infusions of 3.4 g. Results showed that infusions of CSL-112 caused immediate large increases in cholesterol-efflux capacity, prebeta1-HDL, and HDL in serum or plasma. Prebeta1-HDL were elevated up to 20-fold. For all three regimens, all biomarker responses were dose dependent and had a similar magnitude and time course after the first and last infusions. Increases in HDL peaked at 24 to 48 hours after infusion, but levels remained elevated after 72 hours. The results suggested that when compared with a single infusion of CSL112, multiple infusions may provide greater efflux of cholesterol, the researchers said. 在第二项安慰剂对照研究当中，共有36例健康对象参与，研究设3个剂量方案：四每周一次输注3.4g，四每周一次输注6.8g，以及八每周两次输注3.4g。结果显示输注CSL-112可以立即引起胆固醇排出能力、血清中prebeta1-HDL和HDL的大幅增加。Prebeta1-HDL的量升高达到20倍。对于所有这三种方案，所有生物标志物的反应都呈剂量依赖性，且在第一次和最后一次输注后都有类似的改变幅度和时间进程。输注后24-48小时HDL增加达到峰值，但在72小时后依然维持这一抬高水平。结果显示，与单次输注CSL-112相比，多次输注可能更大程度地排出胆固醇，研究人员说。Safety data安全数据Safety data with CSL-112 will be scrutinized closely, because a previous version of the product, CSL-111, was discontinued due to liver toxicity. The company says it has reformulated the product (to produce CSL-112) to be less likely to cause liver problems.有关CSL-112的安全数据将被密切审查，因为之前所研究的一种产品——CSL-111，已经由于其肝毒性而停产。公司表示他们已经重新生产新产品——CSL-112，将不太可能再会引起肝脏问题。In the 36-patient study, there where were no treatment-related serious adverse events reported. Overall, a similar proportion of subjects in the placebo group and CSL-112-treatment groups reported at least one adverse event, and none were reported as product-related. The most common adverse event was vessel puncture-site hematoma (seen in 18 of 36 subjects), which was reported by similar proportions of subjects administered CSL-112 or placebo. In the CSL-112-treatment group, no clinically significant abnormalities were observed in serum biochemistry, hematology, and urine parameters. In addition, there were no remarkable changes seen in platelet function, vital signs, or ECG and no evidence of immunogenicity to CSL-112.在36例患者参与的研究中，未见报道有与治疗相关的严重不良事件。总体来看，安慰剂组和CSL-112治疗组各报道至少1例不良事件，在各组中所占的比例类似。最常见的不良事件就是血管穿刺部位血肿（36例对象中出现18例），给予CSL-112或安慰剂的对象中报道比例所占类似。在CSL-112治疗组，观察血清生化、血液，以及尿液参数未见有显著临床意义的异常。此外，血小板功能、生命征象或ECG也没有显著的改变，同时也没有CSL-112致免疫性的证据。The researchers concluded: &This first clinical trial evaluating repeat dosing of CSL-112 demonstrated that once- or twice-weekly infusions in healthy subjects had acceptable safety and pharmacokinetic profiles that are sufficiently robust to warrant further testing in patients.&研究人员总结道：“这是第一次临床研究来评估重复剂量的CSL-112，研究证实健康对象每周一次或两次的输注具有可接受的安全性，同时（研究所得的）药物代谢动力学资料也足以保证未来进一步在患者中的研究测试。”A third study presented at the AHA meeting was reported to show anti-inflammatory properties of CSL-112, which may also be beneficial in reducing cardiovascular events. In the in vitro study using human blood, CSL-112 caused a strong inhibition of the expression of intracellular adhesion molecule-1 (ICAM-1) (CD54) on both monocytes and neutrophils and inhibited the secretion of proinflammatory cytokines (TNFα, IL-1β, and IL-6) and chemokines (IL-8, RANTES, and macrophage inflammatory protein 1β [Mip-1β]). AHA会议上呈现的第三项研究报道显示CSL-112具有抗炎的性质，这一特性对于减少心血管事件也需是有益的。在使用人血液所做的体外研究当中，CSL-112引起单核细胞和中性粒细胞二者细胞间粘附分子（ICAM-1）（CD54）表达的强烈抑制，同时CSL-112也抑制促炎性细胞因子（TNFα，IL-1β和IL-6）、趋化因子（IL-8，T细胞激活分泌调节因子（RANTES）和巨噬细胞炎性蛋白1β [Mip-1β]）的分泌。
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2122字CSL-112可增加人体胆固醇逆转运加利福尼亚州，洛杉矶——关于新型载脂蛋白A1（apoA1）配方CSL-112（澳大利亚维多利亚州CSL实验室）的原创性临床研究证实，CSL-112能够迅速提高胆固醇逆转运初始过程中的关键性标志物。因此，它被定为成一种新的治疗方法来迅速降低动脉粥样硬化负担，从而尝试减少ACS之后最初几天里的心血管事件。载脂蛋白A1（apoA1）是HDL的主要成分，来源于人血浆，而CSL-112是apoA1重组形成的适合运输的HDL微粒。因为天然HDL的功能就是促进胆固醇的流出/逆转运（从组织中清楚胆固醇，比如心室壁，随后运输到肝脏以从体内清除），其带给我们的希望就是能够借助于它来迅速升高HDL含量水平，CSL-112将迅速减少负载胆固醇的斑块，从而有利于心血管事件（的降低）。CSL-112的2期试验目前正在稳定的冠状动脉疾病患者身上进行，同时对ACS病人的2b期研究也正在计划中。“速度是一个大问题”Samuel Wright博士（CSL实验室，King of Prussia, PA）接受heartwire采访时评论道：“这一想法是在ACS事件之后迅速给予CSL-112一系列2小时的静脉输注。在这一段非常高的风险时期内，这是一种紧急状态下的紧急治疗方法。”接着他又补充道：“在ACS之后的起初30天内，继发MI的风险非常高。速度是一个大问题。我们需要采取迅速的治疗方法。给予2小时的CSL-112输注可以立即起效，可以在2小时内实现载脂蛋白A1的一个100%的升高。而相比之下，烟酸在8周之后也仅仅使apoA1升高了3%。”在上周的美国心脏病协会（AHA）2012年度科学会议上，来自CSL的研究人员呈现了两项CSL-112的1期研究，结果显示这一产品（CSL-112）诱导胆固醇从巨噬细胞外流至血浆，这是胆固醇逆转运的第一步。早期提高HDL治疗未显现出任何心血管事件的减少，尽管继此之后，现在围绕HDL领域有很多怀疑，但CSL提示并非所有形式的HDL都可以一样有效地促进胆固醇的逆转运，并且借助胆固醇酯转移蛋白（CETP）抑制剂（torcetrapib和dalcetrapib）所形成的HDL就目前测试来看，或许并不能像CSL-112那样能有效地促进胆固醇的流出。Nissen：“一个非常合理的假设”在对heartwire谈及CSL-112时，俄亥俄州Cleveland诊所的Steve Nissen博士解释道：“这是一种与我们之前所见到的其他升高HDL的药物不同的方法，在这种方法中，输注了体积较小的prebeta-HDL。与α-HDL会增加烟酸和CETP抑制剂不同，prebeta-HDL没有载满胆固醇，因此就有了这样的理论：它（prebeta-HDL）有更大的潜能可以从动脉粥样硬化斑块中装载胆固醇。”尽管Nissen相信这是“一个非常合理的假设”，但他同时也警示说“通向地狱的道路上也铺满了生物合理性。”他指出目前的1期研究显示胆固醇逆向转运措施上发生了重大变化，这是非常令人鼓舞的，但“这些都仍旧是替代终点，并不能预示着一种药物的最终成功。”然而，他补充道“你需要在一张大网的后面对不同的目标出击，以得到其中一个，而这种新方法肯定值得在一项大型临床试验中得到进一步的验证。”HDL升的“更高、更快”在AHA的新闻发布会上，澳大利亚维多利亚州CSL实验室的Andreas Gille博士指出增加胆固醇的外排能力最近已被证实可以降低MI风险。他补充道：“我们在之前的体外研究中已经证实CSL-112是胆固醇一种有效的受体。现在我们也证实在人类它也是有效的，CSL-112可以比之前其他任何治疗都恩能够更高更快地升高HDL的含量水平。”在AHA会议上呈现的一项试验当中，57位健康的志愿者给予单次输注CSL-112，剂量水平在5-135mg/kg不等。而后化验志愿者的血样，结果显示HDL胆固醇、prebeta1-HDL，以及从巨噬细胞排出胆固醇的能力与剂量呈正比增加。最高剂量输注CSL-112者prebeta1-HDL增加了3600%，同时总胆固醇排出增加270%。apoB、非HDL胆固醇，以及非HDL甘油三酯的含量水平没有变化。在第二项安慰剂对照研究当中，共有36例健康对象参与，研究设3个剂量方案：四每周一次输注3.4g，四每周一次输注6.8g，以及八每周两次输注3.4g。结果显示输注CSL-112可以立即引起胆固醇排出能力、血清中prebeta1-HDL和HDL的大幅增加。Prebeta1-HDL的量升高达到20倍。对于所有这三种方案，所有生物标志物的反应都呈剂量依赖性，且在第一次和最后一次输注后都有类似的改变幅度和时间进程。输注后24-48小时HDL增加达到峰值，但在72小时后依然维持这一抬高水平。结果显示，与单次输注CSL-112相比，多次输注可能更大程度地排出胆固醇，研究人员说。安全数据有关CSL-112的安全数据将被密切审查，因为之前所研究的一种产品——CSL-111，已经由于其肝毒性而停产。公司表示他们已经重新生产新产品——CSL-112，将不太可能再会引起肝脏问题。在36例患者参与的研究中，未见报道有与治疗相关的严重不良事件。总体来看，安慰剂组和CSL-112治疗组各报道至少1例不良事件，在各组中所占的比例类似。最常见的不良事件就是血管穿刺部位血肿（36例对象中出现18例），给予CSL-112或安慰剂的对象中报道比例所占类似。在CSL-112治疗组，观察血清生化、血液，以及尿液参数未见有显著临床意义的异常。此外，血小板功能、生命征象或ECG也没有显著的改变，同时也没有CSL-112致免疫性的证据。研究人员总结道：“这是第一次临床研究来评估重复剂量的CSL-112，研究证实健康对象每周一次或两次的输注具有可接受的安全性，同时（研究所得的）药物代谢动力学资料也足以保证未来进一步在患者中的研究测试。”AHA会议上呈现的第三项研究报道显示CSL-112具有抗炎的性质，这一特性对于减少心血管事件也需是有益的。在使用人血液所做的体外研究当中，CSL-112引起单核细胞和中性粒细胞二者细胞间粘附分子（ICAM-1）（CD54）表达的强烈抑制，同时CSL-112也抑制促炎性细胞因子（TNFα，IL-1β和IL-6）、趋化因子（IL-8，T细胞激活分泌调节因子（RANTES）和巨噬细胞炎性蛋白1β [Mip-1β]）的分泌。
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Los Angeles, CA - Initial clinical trials withthe novel apolipoprotein A1 (apoA1) formulation CSL-112 (CSL Laboratories, Victoria,Australia) have shown that it rapidly enhances key biomarkers of the earlystages of reverse cholesterol transport.加利福尼亚州，洛杉矶——关于新型载脂蛋白A1（apoA1）配方CSL-112（澳大利亚维多利亚州CSL实验室）的原创性临床研究证实，CSL-112是早期阶段快速提高胆固醇逆转运的关键生物标志物。因此，它被定为成一种新的治疗方法来迅速降低动脉粥样硬化负担，从而尝试减少ACS之后最初几天里的心血管事件。 修改建议：CSL-112能够迅速提高胆固醇逆转运初始过程中的关键性标志物。理由：CSL-112并不是key biomarker.CSL-112 is a reconstituted formulation ofapoA1, the main component of HDL, derived from human plasma and reconstitutedto form HDL particles suitable for infusion. CSL-112是载脂蛋白A1（apoA1）的一种重组形式，HDL的主要成分，来源于人血浆，CSL重组形成HDL微颗粒以适于运输。 修改建议：载脂蛋白A1（apoA1）是HDL的主要成分，来源于人血浆，而CSL-112是apoA1重组形成的适合运输的HDL微粒。Although there are nowdoubts surrounding the HDL field following the failure of initial HDL-raisingtherapies to show any reduction in cardiovascular events,CSL suggests that not all forms of HDL are equallyeffective in promoting reverse cholesterol transport and that the HDL formed bythe cholesteryl ester transfer protein (CETP) inhibitors so far tested(torcetrapib and dalcetrapib) may not promote cholesterol efflux as effectivelyas CSL-112.早期提高HDL治疗未显现出任何心血管事件的减少，尽管继此之后，现在围绕HDL领域有很多怀疑，但CSL提示并非所有形式的HDL都可以一样有效地促进胆固醇的逆转运，并且借助胆固醇酯转移蛋白（CETP）抑制剂（torcetrapib和dalcetrapib）所形成的HDL就目前测试来看，或许并不能像CSL-112那样能有效地促进胆固醇的流出。修改建议：尽管在早期提高HDL疗法未减少心血管事件的失败之后，人们对HDL领域疑心重重，但CSL提示，不同形式的HDL促进胆固醇逆转运的效率不尽相同。如胆固醇酯转移蛋白（CETP）抑制剂（torcetrapib和dalcetrapib）形成的HDL，就目前研究而言，其促进胆固醇流出的效率可能不如CSL-112。This is a very different approach from theother HDL-raising drugs we have seen before, in that it is the smaller prebeta-HDL that is being infused. 这是一种与我们之前所见到的其他升高HDL的药物不同的方法，在这种方法中，输注了更少量的prebeta-HDL。 修改建议：“smaller prebeta-HDL”应译为“体积较小的prebeta-HDL”，因为prebeta-HDL比alpha-HDL体积小，带的胆固醇少
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coffeecoffee Los Angeles, CA - Initial clinical trials withthe novel apolipoprotein A1 (apoA1) formulation CSL-112 (CSL Laboratories, Victoria,Australia) have shown that it rapidly enhances key biomarkers of the earlystages of reverse cholesterol transport.加利福尼亚州，洛杉矶——关于新型载脂蛋白A1（apoA1）配方CSL-112（澳大利亚维多利亚州CSL实验室）的原创性临床研究证实，CSL-112是早期阶段快速提高胆固醇逆转运的关键生物标志物。因此，它被定为成一种新的治疗方法来迅速降低动脉粥样硬化负担，从而尝试减少ACS之后最初几天里的心血管事件。修改建议：CSL-112能够迅速提高胆固醇逆转运初始过程中的关键性标志物。理由：CSL-112并不是key biomarker.--赞同，已在原文中做修改；CSL-112 is a reconstituted formulation ofapoA1, the main component of HDL, derived from human plasma and reconstitutedto form HDL particles suitable for infusion. CSL-112是载脂蛋白A1（apoA1）的一种重组形式，HDL的主要成分，来源于人血浆，CSL重组形成HDL微颗粒以适于运输。修改建议：载脂蛋白A1（apoA1）是HDL的主要成分，来源于人血浆，而CSL-112是apoA1重组形成的适合运输的HDL微粒。--赞同，已在原文中做修改；Although there are nowdoubts surrounding the HDL field following the failure of initial HDL-raisingtherapies to show any reduction in cardiovascular events,CSL suggests that not all forms of HDL are equallyeffective in promoting reverse cholesterol transport and that the HDL formed bythe cholesteryl ester transfer protein (CETP) inhibitors so far tested(torcetrapib and dalcetrapib) may not promote cholesterol efflux as effectivelyas CSL-112.早期提高HDL治疗未显现出任何心血管事件的减少，尽管继此之后，现在围绕HDL领域有很多怀疑，但CSL提示并非所有形式的HDL都可以一样有效地促进胆固醇的逆转运，并且借助胆固醇酯转移蛋白（CETP）抑制剂（torcetrapib和dalcetrapib）所形成的HDL就目前测试来看，或许并不能像CSL-112那样能有效地促进胆固醇的流出。修改建议：尽管在早期提高HDL疗法未减少心血管事件的失败之后，人们对HDL领域疑心重重，但CSL提示，不同形式的HDL促进胆固醇逆转运的效率不尽相同。如胆固醇酯转移蛋白（CETP）抑制剂（torcetrapib和dalcetrapib）形成的HDL，就目前研究而言，其促进胆固醇流出的效率可能不如CSL-112。--这两句的翻译，我还是坚持我个人意见，原译文和修改译文的理解并无偏差，可能只是个人语言习惯的差异，所以我还是坚持我的译法；This is a very different approach from theother HDL-raising drugs we have seen before, in that it is the smaller prebeta-HDL that is being infused. 这是一种与我们之前所见到的其他升高HDL的药物不同的方法，在这种方法中，输注了更少量的prebeta-HDL。修改建议：“smaller prebeta-HDL”应译为“体积较小的prebeta-HDL”，因为prebeta-HDL比alpha-HDL体积小，带的胆固醇少--赞同，已在原文中做修改；多谢指正，欢迎对其他多修改、指正……投票支持……
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