gadolinium

  • 文章类型: Journal Article
    简介:与大脑中钆(Gd)沉积相关的部位(例如,苍白球)已知含有高浓度的三价铁。关于脑中Gd沉积的机制存在相当多的争论。铁运输机制在Gd沉积中的作用尚未确定。因此,我们试图确定Gd沉积是否可以通过改变铁暴露来控制。方法:雌性Sprague-Dawley大鼠接受2-6ppm控制铁水平的饮食,6ppt(20g/kg羰基铁)或48ppm持续3周以诱导缺铁,过载或正常。他们保持这些饮食,同时在2周内静脉注射累积10mmol/kg剂量的gadodiamide,然后在收获组织之前将gadodiamide冲洗3天或3周。通过ICP-MS分析组织中的Gd浓度。结果:日粮铁和总Gd浓度对各器官无显著影响,但是铁状态对大脑中Gd的分布有显着影响。对于为期3周的淘汰队列,大脑总沉积增加和膳食铁减少的趋势不显著,与其他组相比,低铁组嗅球的Gd高约4倍。相对于3天冲洗组,在3周冲洗组的低铁组总脑Gd中观察到显著的脑积累,并且在其他组织中未观察到积累。通过饮食铁进行分层时,股骨Gd浓度与其他器官中的浓度之间存在很强的负相关。讨论:基于Gd的线性造影剂(GBCA)的Gd脑沉积取决于铁状态,可能通过可变的转铁蛋白饱和度。这种铁依赖性似乎与外围沉积的Gd的重新分布有关(例如,在骨头中)进入大脑。
    Introduction: Sites associated with gadolinium (Gd) deposition in the brain (e.g., the globus pallidus) are known to contain high concentrations of ferric iron. There is considerable debate over the mechanism of Gd deposition in the brain. The role of iron transport mechanisms in Gd deposition has not been determined. Thus, we seek to identify if Gd deposition can be controlled by modifying iron exposure. Methods: Female Sprague-Dawley rats were given diets with controlled iron levels at 2-6 ppm, 6 ppt (20 g/kg Fe carbonyl) or 48 ppm for 3 weeks to induce iron deficiency, overload or normalcy. They were kept on those diets while receiving a cumulative 10 mmol/kg dose of gadodiamide intravenously over 2 weeks, then left to washout gadodiamide for 3 days or 3 weeks before tissues were harvested. Gd concentrations in tissues were analyzed by ICP-MS. Results: There were no significant effect of dietary iron and total Gd concentrations in the organs, but there was a significant effect of iron status on Gd distribution in the brain. For the 3-week washout cohort, there was a non-significant trend of increasing total brain deposition and decreasing dietary iron, and about 4-fold more Gd in the olfactory bulbs of the low iron group compared to the other groups. Significant brain accumulation was observed in the low iron group total brain Gd in the 3-week washout group relative to the 3-day washout group and no accumulation was observed in other tissues. There was a strong negative correlation between femur Gd concentrations and concentrations in other organs when stratifying by dietary iron. Discussion: Gd brain deposition from linear Gd-based contrast agents (GBCAs) are dependent upon iron status, likely through variable transferrin saturation. This iron dependence appears to be associated with redistribution of peripheral deposited Gd (e.g., in the bone) into the brain.
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  • 文章类型: Journal Article
    动脉粥样硬化是动脉的慢性炎症状态并且代表各种心血管疾病的主要原因。尽管不断取得进展,寻找动脉粥样硬化的有效抗炎治疗策略仍然是一个挑战.这里,我们评估了分子磁共振成像(MRI)可视化01BSUR的影响的潜力,抗白细胞介素-1β单克隆抗体,用于治疗小鼠模型中的动脉粥样硬化。将雄性载脂蛋白E缺陷小鼠分为治疗组(01BSUR,2×0.3mg/kg皮下,n=10)和对照组(不治疗,n=10),并接受高脂肪饮食八周。在3TMRI扫描仪上使用弹性蛋白靶向的基于钆的对比探针(静脉内0.2mmol/kg)评估斑块负荷。在施用弹性蛋白特异性MRI探针(p<0.05)后,与对照组(pre:3.70679168;post:13.2982156)相比,在01BSUR组(pre:3.93042664;post:8.4007067)中,T1加权成像显示显著较低的对比噪声(CNR)比。组织学检查表明,与对照动物相比,治疗组的斑块大小显著减小(p<0.05)和斑块弹性蛋白含量显著降低(p<0.05)。这项研究表明,01BSUR阻碍了小鼠模型中动脉粥样硬化的进展。使用弹性蛋白靶向MRI探针,我们可以在MRI中量化这些治疗效果。
    Atherosclerosis is a chronic inflammatory condition of the arteries and represents the primary cause of various cardiovascular diseases. Despite ongoing progress, finding effective anti-inflammatory therapeutic strategies for atherosclerosis remains a challenge. Here, we assessed the potential of molecular magnetic resonance imaging (MRI) to visualize the effects of 01BSUR, an anti-interleukin-1β monoclonal antibody, for treating atherosclerosis in a murine model. Male apolipoprotein E-deficient mice were divided into a therapy group (01BSUR, 2 × 0.3 mg/kg subcutaneously, n = 10) and control group (no treatment, n = 10) and received a high-fat diet for eight weeks. The plaque burden was assessed using an elastin-targeted gadolinium-based contrast probe (0.2 mmol/kg intravenously) on a 3 T MRI scanner. T1-weighted imaging showed a significantly lower contrast-to-noise (CNR) ratio in the 01BSUR group (pre: 3.93042664; post: 8.4007067) compared to the control group (pre: 3.70679168; post: 13.2982156) following administration of the elastin-specific MRI probe (p < 0.05). Histological examinations demonstrated a significant reduction in plaque size (p < 0.05) and a significant decrease in plaque elastin content (p < 0.05) in the treatment group compared to control animals. This study demonstrated that 01BSUR hinders the progression of atherosclerosis in a mouse model. Using an elastin-targeted MRI probe, we could quantify these therapeutic effects in MRI.
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  • 文章类型: Journal Article
    背景:肝纤维化的准确诊断对于预防肝硬化和肝肿瘤至关重要。肝纤维化由CD44表达升高的活化肝星状细胞(HSC)驱动。我们开发了透明质酸(HA)涂层的基于钆的纳米探针,以特异性靶向CD44用于使用T1加权磁共振成像(MRI)诊断肝纤维化。
    方法:通过热分解合成NaGdF4纳米颗粒(NPs),并用聚乙二醇(PEG)修饰以获得非靶向性NaGdF4@PEGNPs。这些随后用HA包被以靶向HSC,导致肝纤维化靶向NaGdF4@PEG@HA纳米探针。表征包括透射电子显微镜和X射线衍射。使用细胞计数试剂盒-8(CCK-8)评估细胞活力。使用流式细胞术和共聚焦激光扫描显微镜(CLSM)观察到小鼠HSCsJS1细胞通过配体-受体相互作用对NaGdF4@PEG@HA纳米探针的内化。使用甲硫氨酸-胆碱缺乏(MCD)饮食在C57BL/6小鼠中诱导肝纤维化。使用GEDiscovery3.0TMR750扫描仪分析了纤维化和正常肝脏中的MRI性能和纳米探针分布。
    结果:NaGdF4@PEG@HA纳米探针表现出均匀的形态,低毒性,和较高的T1弛豫率(7.645mM-s-s)。CLSM和流式细胞术证明与NaGdF4@PEG相比,JS1细胞对NaGdF4@PEG@HA纳米探针的有效吞噬作用。在注射NaGdF4@PEG@HA后,MRI扫描显示纤维化肝脏中的T1信号高于正常肝脏。NaGdF4@PEG@HA在纤维化小鼠中表现出更高的靶向能力。
    结论:NaGdF4@PEG@HA纳米探针有效靶向具有高T1弛豫率的HSCs,促进肝脏纤维化的有效MRI诊断。
    BACKGROUND: Accurate diagnosis of liver fibrosis is crucial for preventing cirrhosis and liver tumors. Liver fibrosis is driven by activated hepatic stellate cells (HSCs) with elevated CD44 expression. We developed hyaluronic acid (HA)-coated gadolinium-based nanoprobes to specifically target CD44 for diagnosing liver fibrosis using T1-weighted magnetic resonance imaging (MRI).
    METHODS: NaGdF4 nanoparticles (NPs) were synthesized via thermal decomposition and modified with polyethylene glycol (PEG) to obtain non-targeting NaGdF4@PEG NPs. These were subsequently coated with HA to target HSCs, resulting in liver fibrosis-targeting NaGdF4@PEG@HA nanoprobes. Characterization includedd transmission electron microscopy and X-ray diffraction. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8). Internalization of NaGdF4@PEG@HA nanoprobes by mouse HSCs JS1 cells via ligand-receptor interaction was observed using flow cytometry and confocal laser scanning microscopy (CLSM). Liver fibrosis was induced in C57BL/6 mice using a methionine-choline deficient (MCD) diet. MRI performance and nanoprobe distribution in fibrotic and normal livers were analyzed using a GE Discovery 3.0T MR 750 scanner.
    RESULTS: NaGdF4@PEG@HA nanoprobes exhibited homogeneous morphology, low toxicity, and a high T1 relaxation rate (7.645 mM⁻¹s⁻¹). CLSM and flow cytometry demonstrated effective phagocytosis of NaGdF4@PEG@HA nanoprobes by JS1 cells compared to NaGdF4@PEG. MRI scans revealed higher T1 signals in fibrotic livers compared to normal livers after injection of NaGdF4@PEG@HA. NaGdF4@PEG@HA demonstrated higher targeting ability in fibrotic mice.
    CONCLUSIONS: NaGdF4@PEG@HA nanoprobes effectively target HSCs with high T1 relaxation rate, facilitating efficient MRI diagnosis of liver fibrosis.
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  • 文章类型: Journal Article
    研究表明,钆离子的加入对结构有显著影响,形态学,通过溶胶-凝胶自动燃烧法合成的Ni-Co尖晶石铁氧体的吸附性能。研究还表明,Gd含量越高,晶格参数的增加越大,这表明Gd3离子均匀地取代了八面体Fe3离子。使用SEM和EDS研究了Gd掺杂的Ni-Co铁氧体的形态和化学组成。添加到NiCoFe基质中的Gd使BET表面积增加50%(从48到72m2/g),并促进平均半径为3.9到4.9nm的中孔的形成。Gd掺杂铁氧体的pHPZC值在7.22-7.39范围内,这意味着铁氧体表面在自然pH值下将获得正电荷,所以这将通过静电相互作用力促进刚果红阴离子染料的吸附。朗缪尔,Freundlich,和Dubinin-Radushkevich模型解释了CR在Ni0.5Co0.5GdxFe2-xO4吸附剂表面的吸附机理。已估计离子-共价参数来描述表面酸碱性质。总的来说,这项研究强调了Gd3掺杂作为增强镍钴铁氧体吸附性能的有前途的方法的潜力。
    The study shows that the addition of gadolinium ions has a significant impact on the structure, morphology, and adsorption properties of Ni-Co spinel ferrite that was synthesized by the sol-gel auto-combustion method. The research also indicates that the higher the Gd content, the greater the increase in the lattice parameter, which suggests that Gd3+ ions uniformly replaced the octahedral Fe3+ ions. The morphology and chemical composition of Gd-doped Ni-Co ferrites have been studied using SEM and EDS. Gd adding to the NiCoFe matrix increases the BET surface area by 50% (from 48 to 72 m2/g) and promotes the formation of mesopores with an average radius from 3.9 to 4.9 nm. The pHPZC values of Gd-doped ferrites are in the range of 7.22-7.39, which means that the ferrite surface will acquire a positive charge at natural pH, so this will promote the adsorption of Congo red anionic dye through electrostatic interaction forces. Langmuir, Freundlich, and Dubinin-Radushkevich models were used to explain the mechanism of CR adsorption on the Ni0.5Co0.5GdxFe2-xO4 adsorbent surface. The ionic-covalent parameter has been estimated to describe the surface acid-base properties. Overall, this study highlights the potential of Gd3+ doping as a promising approach for enhancing the adsorption properties of nickel-cobalt ferrites.
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  • 文章类型: Journal Article
    微结构,机械,具有不同Zn/Gd比的挤压镁合金的体外和体内行为,Mg-2Gd-2Zn-0.5Zr(Zn/Gd=1),Mg-2Gd-6Zn-0.5Zr(Zn/Gd=3),研究了Mg-10Gd-1Zn-0.5Zr(Zn/Gd=0.1)。结果表明,主要的次要相如W(Mg3Zn3Gd2),(Mg,Zn)3Gd,合金中的LPSO(长周期堆积顺序)和I(Mg3Zn6Gd)相取决于Zn/Gd比。这些第二相影响合金的机械和生物学特性。在研究的合金中,Mg-10Gd-1Zn-0.5Zr合金表现出最高的屈服强度和抗拉强度为270(±9.29)和330MPa(±15.8),分别,具有12%的相当好的伸长率(±2.36)。Mg-10Gd-1Zn-0.5Zr降解膜中Gd2O3的存在增强了膜的电阻,这导致了最低的生物降解,更好的生存能力,和体外条件下的细胞增殖。短期(大鼠皮下植入1个月)体内研究表明,Mg-10Gd-1Zn-0.5Zr合金以0.35mm/y(±0.02)的速率降解,对重要器官没有任何毒性。
    Microstructure, mechanical, in vitro and in vivo behavior of extruded Mg alloys with varying Zn/Gd ratios, Mg-2Gd-2Zn-0.5Zr (Zn/Gd = 1), Mg-2Gd-6Zn-0.5Zr (Zn/Gd = 3), and Mg-10Gd-1Zn-0.5Zr (Zn/Gd = 0.1) were investigated. The results revealed that the major secondary phases such as W (Mg3Zn3Gd2), (Mg,Zn)3Gd, LPSO (Long period stacking order) and I (Mg3Zn6Gd) phase in alloys depended on Zn/Gd ratio. These second phases influenced the mechanical as well as biological characteristics of the alloys. Among studied alloys, Mg-10Gd-1Zn-0.5Zr alloy showed the highest yield strength and tensile strength of 270 (±9.29) and 330 MPa (±15.8), respectively, with a reasonably good elongation of 12% (±2.36). The presence of Gd2O3 in the degradation film of Mg-10Gd-1Zn-0.5Zr enhanced the resistance offered by the film, which resulted in its lowest biodegradation, better viability, and cell proliferation under in vitro condition. The short term (subcutaneous implantation in rats for 1 month) in vivo studies showed that the alloy Mg-10Gd-1Zn-0.5Zr degraded at a rate of 0.35 mm/y (±0.02) and did not induce any toxicity to the vital organs.
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  • 文章类型: Journal Article
    目的:确定更换钆基造影剂(GBCAs)对减少GBCA相关急性药物不良反应(ADRs)复发的预防作用。
    方法:本回顾性研究,观察,2016年1月至2021年12月进行的单中心研究包括238743项连续GBCA增强MRI检查.我们专注于在任何这些检查中经历急性GBCA相关ADR的患者亚组,随后进行了随访GBCA增强MRI检查,直到2023年7月。与最初引起急性ADR的GBCA相比,随访检查涉及相同(无变化组)或不同(变化组)的GBCA。基线参与者特征,GBCA的通用配置文件,给药,碘化造影剂的既往不良反应史,并对GBCA相关急性ADRs的症状进行回顾性分析。使用具有广义估计方程和倾向得分匹配的多变量逻辑回归。
    结果:共报告了1042例急性不良反应(0.44%;95%置信区间[CI]:0.41%-0.46%)。在研究期间内经历GBCA相关的急性ADR后,共有三百七十三例患者接受了GBCA增强MRI检查;在任何随访检查中,31.9%(119/373)再次经历了急性ADR。根据多变量逻辑回归(调整后比值比[OR]:0.35;95%CI:0.13-0.90;P=0.03)和倾向评分匹配分析(14.3%[6/42]vs.36.9%[31/84],分别为;OR:0.32,95%CI:0.11-0.94;P=0.04)。碘化造影剂的ADR病史(OR:1.14,95%CI:0.68-1.90;P=0.62)和术前用药(校正OR:2.09,95%CI:0.93-4.68;P=0.07)与GBCA相关的急性ADR复发没有显着相关。对复发性变态反应样超敏反应的单独分析显示了相似的结果(校正OR:0.20,95%CI:0.06-0.65;P<0.01)。
    结论:改变GBCA可降低GBCA相关急性ADR复发的风险。
    OBJECTIVE: To determine the preventive effect of changing gadolinium-based contrast agents (GBCAs) to reduce the recurrence of GBCA-associated acute adverse drug reactions (ADRs).
    METHODS: This retrospective, observational, single-center study-conducted between January 2016 and December 2021-included 238743 consecutive GBCA-enhanced MRI examinations. We focused on a subgroup of patients who experienced acute GBCA-associated ADRs during any of these examinations and subsequently underwent follow-up GBCA-enhanced MRI examinations up until July 2023. The follow-up examinations involved either the same (non-change group) or different (change group) GBCAs compared to the ones that initially caused the acute ADR. Baseline participant characteristics, generic profile of the GBCAs, administration of premedication, history of prior ADR to iodinated contrast media, and symptoms of GBCA-associated acute ADRs were retrospectively analyzed. Multivariable logistic regression with generalized estimating equations and propensity score matching were used.
    RESULTS: A total of 1042 instances of acute ADRs (0.44%; 95% confidence interval [CI]: 0.41%-0.46%) were reported. Three-hundred and seventy-three patients underwent GBCA-enhanced MRI examinations after experiencing GBCA-associated acute ADRs within the study period; 31.9% (119/373) reexperienced acute ADRs at any of the follow-up examinations. The ADR recurrence was significantly lower in the GBCA change group than in the non-change group according to multivariable logistic regression (adjusted odds ratio [OR]: 0.35; 95% CI: 0.13-0.90; P = 0.03) and analysis with propensity score matching (14.3% [6/42] vs. 36.9% [31/84], respectively; OR: 0.32, 95% CI: 0.11-0.94; P = 0.04). A history of an ADR to iodinated contrast media (OR: 1.14, 95% CI: 0.68-1.90; P = 0.62) and premedication (adjusted OR: 2.09, 95% CI: 0.93-4.68; P = 0.07) were not significantly associated with GBCA-associated acute ADR recurrence. A separate analysis for recurrent allergic-like hypersensitivity reactions demonstrated similar results (adjusted OR: 0.20, 95% CI: 0.06-0.65; P < 0.01).
    CONCLUSIONS: Changing GBCAs may reduce the risk of GBCA-associated acute ADR recurrence.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    基于钆的造影剂越来越多地用于临床实践。虽然这些药物已被证实是肾源性系统性纤维化的病因,越来越多的文献支持它们在静脉内使用钆后暴露和鞘内给药后脑病相关症状中的作用.基于钆的造影剂是多齿有机配体,其强烈地结合金属离子以降低金属的毒性。阳离子钆从这些螯合物中解离并导致疾病的概念在患者和提供者中普遍存在。我们假设非配体结合的(可溶性)钆在患者体内会非常低。可溶性,离子钆不可能是介导任何疾病的第一步。新墨西哥州肾脏研究所是第一个从啮齿动物的磁共振成像造影剂中鉴定皮肤和肾脏组织中富含钆的纳米颗粒。2023年,他们在肾功能正常的人的肾细胞中发现了类似的纳米颗粒,可能来自造影剂。我们怀疑这些纳米颗粒是磁共振成像造影剂慢性毒性的介质。本文探讨了钆对比剂与临床报告和啮齿动物模型支持的不良健康结果之间的关联。
    Gadolinium-based contrast agents are increasingly used in clinical practice. While these pharmaceuticals are verified causal agents in nephrogenic systemic fibrosis, there is a growing body of literature supporting their role as causal agents in symptoms associated with gadolinium exposure after intravenous use and encephalopathy following intrathecal administration. Gadolinium-based contrast agents are multidentate organic ligands that strongly bind the metal ion to reduce the toxicity of the metal. The notion that cationic gadolinium dissociates from these chelates and causes the disease is prevalent among patients and providers. We hypothesize that non-ligand-bound (soluble) gadolinium will be exceedingly low in patients. Soluble, ionic gadolinium is not likely to be the initial step in mediating any disease. The Kidney Institute of New Mexico was the first to identify gadolinium-rich nanoparticles in skin and kidney tissues from magnetic resonance imaging contrast agents in rodents. In 2023, they found similar nanoparticles in the kidney cells of humans with normal renal function, likely from contrast agents. We suspect these nanoparticles are the mediators of chronic toxicity from magnetic resonance imaging contrast agents. This article explores associations between gadolinium contrast and adverse health outcomes supported by clinical reports and rodent models.
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  • 文章类型: English Abstract
    Reactions to contrast media are unpredictable. This article examines the use of iodinated and gadolinium-based contrast agents in medical imaging. It explores their clinical presentation, associated risk factors, precautions prior to their administration, and treatment options in the event of a reaction. By highlighting these essential aspects, the article aims to inform healthcare professionals on the safe and effective management of these agents during imaging procedures. The effectiveness of the different premedication protocols proposed in the literature has not yet been established. In particular, premedication does not prevent serious allergic reactions.
    Les réactions aux produits de contraste sont imprévisibles. Cet article examine l’utilisation des agents de contraste iodés et à base de gadolinium en imagerie médicale. Il explore la présentation clinique de leurs réactions, les facteurs de risque, les précautions préalables à leur administration et les options de traitement en cas de réaction. En mettant en lumière ces aspects essentiels, l’article vise à informer les professionnels de la santé sur la gestion sécuritaire et efficace de ces agents lors des procédures d’imagerie. L’efficacité des différents protocoles de prémédication proposés dans la littérature n’est pas établie. En particulier, la prémédication ne prévient pas les réactions allergiques graves.
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