• 【AML M1表现为复发性急性大动脉血管血栓栓塞。】 复制标题 收藏 收藏
    DOI:10.1016/j.leukres.2006.08.010 复制DOI
    作者列表:Reisch N,Roehnisch T,Sadeghi M,Greiner L,Regenbogen C,Rieger J,Emmerich B,Oduncu F
    BACKGROUND & AIMS: :Acute leukemia may be associated with coagulopathy, predominantly severe bleeding diathesis caused by disseminated intravascular coagulation (DIC) and/or hyperfibrinolysis. Disordered hemostasis is characteristic for acute promyelocytic leukemia (APL, FAB M3). However, thromboembolic events such as arterial occlusion localized to the large vessels at presentation is very rare and almost exclusively linked to APL. We report a case of severe recurrent acute arterial thromboembolism at presentation in AML FAB M1. Most likely, the ischemic events in our patient resulted from leukemia as the thrombus material included many leukemic blasts. The thrombotic complications resulted in leg amputation in this patient. Despite leg amputation just a couple of hours before and extremely high infectious risk of the patient, chemotherapy was administered. The clinical course of cessation of the ischemic events and a fast reduction of the blasts in the peripheral blood smear after chemotherapeutic treatment of the patient outlines the importance and life saving role of early chemotherapy even under adverse circumstances.
    背景与目标: : 急性白血病可能与凝血病有关,主要是由弥散性血管内凝血 (DIC) 和/或纤维蛋白溶解亢进引起的严重出血素质。异常止血是急性早幼粒细胞白血病 (APL,FAB M3) 的特征。然而,血栓栓塞事件 (例如动脉阻塞) 在出现时定位于大血管是非常罕见的,并且几乎完全与APL有关。我们在AML FAB m1中报告了一例严重的复发性急性动脉血栓栓塞。最有可能的是,我们患者的缺血事件是由白血病引起的,因为血栓物质包括许多白血病母细胞。血栓并发症导致该患者腿部截肢。尽管仅在几个小时前就截肢了,并且患者的感染风险极高,但仍进行了化学疗法。在患者进行化学治疗后,缺血性事件停止和外周血涂片中原始细胞快速减少的临床过程概述了即使在不良情况下,早期化学疗法的重要性和挽救生命的作用。
  • 【选择性动脉栓塞术对胎盘植入进行保守治疗可保留未来的生育能力,并在随后的妊娠中获得良好的结果。】 复制标题 收藏 收藏
    DOI:10.1016/j.fertnstert.2006.02.128 复制DOI
    作者列表:Alanis M,Hurst BS,Marshburn PB,Matthews ML
    BACKGROUND & AIMS: OBJECTIVE:To present a case of selective arterial embolization for the treatment of placenta increta in a patient with subsequent pregnancy. DESIGN:Case report and literature review. SETTING:Community-based hospital. PATIENT(S):A 31-year-old G2P1 woman with placenta increta presenting with delayed postpartum hemorrhage. INTERVENTION(S):Selective uterine artery embolization. MAIN OUTCOME MEASURE(S):Cessation of uterine hemorrhage, future pregnancy. RESULT(S):The patient's uterine bleeding immediately resolved. She subsequently delivered a healthy neonate at term without recurrence of abnormal placentation. CONCLUSION(S):Arterial embolization is effective for treating placenta increta in women who wish to preserve fertility. A review of the literature demonstrates a 76.9% success rate and an 11% complication rate.
    背景与目标:
  • 【血管紧张素II激活动脉平滑肌细胞中的中间电导Ca2激活的K通道。】 复制标题 收藏 收藏
    DOI:10.1016/j.yjmcc.2006.07.010 复制DOI
    作者列表:Hayabuchi Y,Nakaya Y,Yasui S,Mawatari K,Mori K,Suzuki M,Kagami S
    BACKGROUND & AIMS: :Angiostensin II (Ang II) regulates the migration and proliferation of vascular smooth muscle cells. Recent studies indicate that intermediate-conductance Ca2+ -activated K+ (IKca) channels have an important role in cell migration and proliferation. It is not known, however, whether the action of Ang II is linked to IKca channel regulation. Here, we investigated the modulation of IKca channels by Ang II in artery smooth muscle cells. Functional IKca channel expression in cultured embryonic rat aorta smooth muscle (A10) cells was studied using the patch-clamp technique. These cells predominantly express IKca channels. In contrast, large-conductance Ca2+ -activated K+ (BKca) currents were rarely observed in excised patches. Ang II increased the IKca current in a contration-dependent manner. Losartan (1.0 microM), an AT1 selective antagonist, abolished the activation of IKca channels by Ang II. Pretreatment with 100 microM myristoylated protein kinase C inhibitor peptide 20-28 or 10 microM GF109203X completely abolished the AngII-induced activation of IKca currents, whereas the action of Ang II was not prevented in the presence of 100 microM Rp-cyclic 3', 5'-hydrogen phosphotiate adenosine triethylammonium, a protein kinase A inhibitor, or 1.0 microM KT-5823, a protein kinase G inhibitor. A membrane permeant analogue of diacylglycerol 1, 2-dioctanoyl-sn-glycerol (10 microM) induced the activation of IKca currents. These data suggest that Ang II activates IKca channels through the activation of protein kinase C, and the AT1 receptor is involved in the regulation of these channels.
    背景与目标: : Angiostensin II (Ang II) 调节血管平滑肌细胞的迁移和增殖。最近的研究表明,中间电导Ca2激活的K (IKca) 通道在细胞迁移和增殖中起重要作用。但是,尚不清楚Ang II的作用是否与IKca通道调节有关。在这里,我们研究了Ang II对动脉平滑肌细胞中IKca通道的调节。使用膜片钳技术研究了培养的胚胎大鼠主动脉平滑肌 (A10) 细胞中功能性IKca通道的表达。这些细胞主要表达IKca通道。相反,在切除的贴片中很少观察到大电导Ca2激活的K (BKca) 电流。Ang II以依赖于收缩的方式增加了IKca电流。氯沙坦 (1.0 microM),一种AT1选择性拮抗剂,通过Ang II消除了IKca通道的激活。用100 microM肉豆蔻酰化蛋白激酶C抑制剂肽20-28或10 microM GF109203X进行预处理完全消除了AngII诱导的IKca电流的激活,而在存在100 microM Rp-环状3 ',5'-磷酸氢腺苷三乙基铵的情况下,Ang II的作用没有被阻止,蛋白激酶a抑制剂,或1.0 microM KT-5823,蛋白激酶G抑制剂。二酰基甘油1,2-二酰基-sn-甘油 (10 microM) 的膜渗透类似物诱导了IKca电流的激活。这些数据表明Ang II通过激活蛋白激酶C激活IKca通道,AT1受体参与了这些通道的调节。
  • 【舒张期颈动脉纵向壁运动对衰老和冠状动脉疾病状态均敏感,而与动脉僵硬无关。】 复制标题 收藏 收藏
    DOI:10.1016/j.ultrasmedbio.2017.04.026 复制DOI
    作者列表:Au JS,Valentino SE,McPhee PG,MacDonald MJ
    BACKGROUND & AIMS: :We investigated the ability of systolic and diastolic carotid artery longitudinal wall motion (CALM) to delineate expected differences in arterial health in individuals representing a range of both age and health status. We recruited 161 younger healthy adults (aged 24 ± 5 y), 51 older healthy adults (aged 70 ± 5 y) and 14 adults with coronary artery disease (aged 67 ± 8 y) for resting assessment of CALM and arterial stiffness. All CALM parameters were reduced in the old healthy adults and adults with coronary artery disease compared with the young healthy adults (p < 0.01), with diastolic velocity and maximum diastolic acceleration being further reduced in the adults with coronary artery disease than in the older healthy adults (p < 0.01). Diastolic CALM parameters were more strongly related to age (β range: -0.46 to -0.53) than systolic CALM parameters (β range: -0.24 to -0.44). In contrast to previous examinations of a variety of CALM parameters, diastolic CALM may provide superior promise in terms of characterizing arterial wall properties, with additional sensitivity to cardiovascular disease status.
    背景与目标: : 我们研究了收缩期和舒张期颈动脉纵向壁运动 (CALM) 描绘代表年龄和健康状况范围的个体的动脉健康预期差异的能力。我们招募了161名年轻的健康成年人 (24 ± 5岁),51名老年健康成年人 (70 ± 5岁) 和14名患有冠状动脉疾病的成年人 (67 ± 8岁) 进行静息评估平静和动脉僵硬度。与年轻健康成年人相比,老年健康成年人和患有冠状动脉疾病的成年人的所有CALM参数均降低 (p <0.01),与老年健康成年人相比,患有冠状动脉疾病的成年人的舒张速度和最大舒张加速度进一步降低 (p <0.01)。舒张期平静参数与年龄 (β 范围: -0.46至-0.53) 的相关性高于收缩期平静参数 (β 范围: -0.24至-0.44)。与以前对各种平静参数的检查相比,舒张期平静在表征动脉壁特性方面可能具有出色的前景,并且对心血管疾病状态具有额外的敏感性。
  • 【模拟航空旅行期间肺动脉高压患者的低氧血症。】 复制标题 收藏 收藏
    DOI:10.1016/j.rmed.2012.10.007 复制DOI
    作者列表:Burns RM,Peacock AJ,Johnson MK,Church AC
    BACKGROUND & AIMS: BACKGROUND:Recent air travel recommendations suggest patients with precapillary pulmonary hypertension (PCPH) in New York Heart Association (NYHA) functional class 3 and 4 should have in-flight oxygen without the need for pre-flight testing. However it remains unclear as to how best to determine patients fitness to fly. METHODS:This study (i) investigates the effect of hypoxic challenge testing (HCT) on the arterial oxygen levels in a cohort of 36 patients with PCPH and (ii) compares the relative frequency with which FC and HCT predict the requirement for in-flight oxygen. RESULTS:The degree of arterial hypoxaemia induced by HCT (fall in partial pressure of oxygen in arterial blood (PaO(2)) 2.36 kPa, 95% CI 2.06-2.66 kPa) was similar to the drop observed in other published studies of chronic respiratory diseases. Following current air travel recommendations based on FC, 25 patients of the cohort would require in-flight oxygen whilst 10 subjects failed the HCT. Fourteen subjects had flown post-diagnosis. Of these, nine subjects should have had in-flight oxygen based on FC but were asymptomatic without. Also one who passed the HCT had developed symptoms during the flight whilst three who failed the HCT were asymptomatic flying without in-flight oxygen. CONCLUSIONS:Hypoxaemia induced by simulated air travel in patients with PCPH is similar to that seen in published studies of patients with other chronic respiratory diseases. HCT failed to predict correctly who had developed symptoms during an aircraft flight in a significant minority of the study subjects. Similarly guidelines based on functional class result in a major increase in the proportion of patients being advised to use oxygen, many of whom had been asymptomatic on previous flights without it. More work is required to improve prediction of need for in-flight oxygen in patients with PCPH.
    背景与目标:
  • 【基于设备的动脉高血压治疗方法。】 复制标题 收藏 收藏
    DOI:10.1007/s11906-017-0755-9 复制DOI
    作者列表:Jordan J
    BACKGROUND & AIMS: :Device-based antihypertensive treatments have primarily been developed and clinically tested for patients with hypertension refractory to pharmacological treatment. Most but not all device-based treatments target the sympathetic nervous system and provided important new insight in the mechanisms of human hypertension. This review provides an overview on the scientific rational and clinical data on recent device-based antihypertensive treatment approaches. Device-based treatments targeting the sympathetic nervous system include catheter-based renal nerve ablation, electrical carotid sinus stimulation, modulation of baroreflex transduction through a dedicated carotid stent, carotid body denervation, and deep brain stimulation. Creation of a defined arteriovenous stent with a coupler device and removal of stimulatory antibodies against alpha adrenoreceptors have also been tested. The clinical evidence differs from therapy to therapy with the largest dataset for renal nerve ablation followed by electrical carotid sinus stimulation. Yet, none has been proven efficacious in sham-controlled clinical trials, and none has been shown to reduce cardiovascular morbidity or mortality. Before efficacy is proven, these treatments should not be part of routine medical care and only be applied in the setting of clinical studies.
    背景与目标: : 基于设备的抗高血压治疗主要是针对药物治疗难治的高血压患者开发和临床测试的。大多数但不是所有基于设备的治疗都针对交感神经系统,并为人类高血压的机制提供了重要的新见解。这篇综述概述了有关基于设备的降压治疗方法的科学合理和临床数据。针对交感神经系统的基于设备的治疗包括基于导管的肾神经消融,颈动脉窦电刺激,通过专用颈动脉支架调节压力反射传导,颈动脉体去神经支配和深部脑刺激。还测试了使用耦合器装置创建定义的动静脉支架并去除针对 α 肾上腺素受体的刺激抗体。临床证据因治疗而异,其最大数据集用于肾神经消融,然后进行颈动脉窦电刺激。然而,在假对照临床试验中,没有一项被证明是有效的,也没有一项被证明可以降低心血管疾病的发病率或死亡率。在证明疗效之前,这些治疗方法不应成为常规医疗保健的一部分,而仅适用于临床研究。
  • 【外周静脉疾病与动脉内皮功能障碍的关系: 概念验证研究。】 复制标题 收藏 收藏
    DOI:10.1258/phleb.2012.012048 复制DOI
    作者列表:Moro L,Pedone C,Serino FM,Incalzi RA
    BACKGROUND & AIMS: :The objective of the study was to evaluate the association between peripheral venous disease (PVD) and arterial endothelial dysfunction (ED). Arterial and venous diseases have been always considered as two completely different entities, but the recent discovery of a relationship between arterial and venous thrombosis have challenged this assumption. ED, considered to be an early process in the pathophysiology of atherosclerotic disease, could represent a common pathogenetic background. We studied 39 healthy volunteers (median age: 34 years; men: 25.6%). PVD was diagnosed using ultrasound examination, arterial ED using flow-mediated dilation (FMD) and FMD normalized for the peak shear rate (nFMD). Compared with controls, participants with PVD had a lower FMD (15.2 versus 23.4%, P < 0.001) and nFMD (12.7 × 10(-3) versus 19 × 10(-3)/second, P < 0.001). People with the most clinically evident disease had the worst endothelial function. In conclusion, our findings, if confirmed in larger population, might corroborate the idea that venous and arterial disease could have common causes.
    背景与目标: : 该研究的目的是评估外周静脉疾病 (PVD) 与动脉内皮功能障碍 (ED) 之间的关系。动脉和静脉疾病一直被认为是两个完全不同的实体,但是最近发现动脉和静脉血栓形成之间的关系对这一假设提出了挑战。ED被认为是动脉粥样硬化疾病病理生理的早期过程,可能代表了共同的发病背景。我们研究了39名健康志愿者 (中位年龄: 34岁; 男性: 25.6%)。使用超声检查诊断PVD,使用血流介导的扩张 (FMD) 进行动脉ED,并针对峰值剪切速率 (nFMD) 标准化FMD。与对照组相比,PVD参与者的FMD (15.2 vs 23.4%,P <0.001) 和nFMD (12.7 × 10(-3) vs 19 × 10(-3)/秒,P <0.001) 较低。临床上最明显的疾病患者的内皮功能最差。总之,如果在更多人群中得到证实,我们的发现可能证实了静脉和动脉疾病可能具有共同原因的观点。
  • 【血浆中瘦素和脂联素的单次或连续测量对肺动脉高压有预后价值吗?】 复制标题 收藏 收藏
    DOI:10.1177/2045893217717219 复制DOI
    作者列表:Tonelli AR,Fares WH,Dakkak W,Rao Y,Zhou X,Dweik RA
    BACKGROUND & AIMS: :Leptin (a neuroendocrine peptide that enhances metabolism and acts on the hypothalamus to suppress appetite) and adiponectin (a protein that has insulin-sensitizing, anti-inflammatory, and antiproliferative properties) are involved in the pathobiology of pulmonary arterial hypertension (PAH). We hypothesized that plasma leptin and adiponectin as well as the leptin/adiponectin ratio are abnormal in PAH patients and their levels track with disease severity and functional changes during follow-up. We tested this hypothesis in a cohort of patients included in the 16-week, international, multicenter, double-blind, placebo-controlled FREEDOM-C2 study. Blood was collected at baseline and week 16 in 178 out of 310 randomized patients with PAH. Baseline plasma leptin and adiponectin concentrations were 25 ± 31 ng/mL and 7.8 ± 6.1 ug/mL, respectively. Leptin, adiponectin, and leptin/adiponectin (mean ± SD) changes at 16 week were of small magnitude. Leptin at baseline was significantly associated with older age, higher BMI, higher Borg dyspnea index, and lower NT-pro BNP. Women had higher levels of leptin than men (30.5 ± 33.2 versus 7.2 ± 6.4 ng/mL), even when adjusting for background therapy and etiology (linear regression: β = 21.8, P < 0.001). Adiponectin was negatively associated with BMI and positively associated with NT-pro BNP. Changes in leptin, adiponectin, and leptin/adiponectin ratio adjusted for weight at 16 weeks did not predict functional class, distance walk in 6 min or survival at one, two, three, or four years. Plasma leptin and adiponectin at baseline and their change at 16-week do not appear to significantly impact prognosis in PAH.
    背景与目标: : 瘦素 (一种神经内分泌肽,可增强新陈代谢并作用于下丘脑以抑制食欲) 和脂联素 (一种具有胰岛素致敏,抗炎和抗增殖特性的蛋白质) 参与肺动脉高压 (PAH) 的病理生物学。我们假设PAH患者的血浆瘦素和脂联素以及瘦素/脂联素比率异常,并且它们的水平与随访期间的疾病严重程度和功能变化有关。我们在16周,国际,多中心,双盲,安慰剂对照FREEDOM-C2研究的患者队列中测试了这一假设。在310例PAH随机患者中,178例在基线和第16周采集血液。基线血浆瘦素和脂联素浓度分别为25   ±   31  ng/mL和7.8   ±   6.1 ug/mL。16周时瘦素、脂联素、瘦素/脂联素 (mean   ±  SD) 变化幅度较小。基线时瘦素与年龄较大、BMI较高、Borg呼吸困难指数和NT-pro BNP较低显著相关。即使在调整背景治疗和病因 (线性回归: β   =   21.8,p  <  0.001) 的情况下,女性的瘦素水平也高于男性 (30.5   ±   33.2对7.2   ±   6.4  ng/mL)。脂联素与BMI呈负相关,与NT-pro BNP呈正相关。瘦素,脂联素和瘦素/脂联素比在16周时根据体重调整后的变化不能预测功能等级,6  min的步行距离或1、2、3或4年的存活。基线时血浆瘦素和脂联素及其在16周时的变化似乎并未显着影响PAH的预后。
  • 【早期植入多个弹簧圈,以治疗持续性动脉导管不完全经导管闭塞后的严重溶血。】 复制标题 收藏 收藏
    DOI:10.1136/hrt.77.5.477 复制DOI
    作者列表:Cheung YF,Leung MP,Chau KT
    BACKGROUND & AIMS: An 18 month old girl with an angiographically measured ductus of 4.5 mm underwent transcatheter occlusion of the persistent arterial duct with a 17 mm Rashkind umbrella and an occluding spring coil. Severe intravascular haemolysis developed 20 hours later. Significant residual ductal leakage was noted and the residual duct measured 6 mm. Previous underestimation might have been related to ductal spasm as a catheter was placed across the duct before angiography. The haemolysis was abolished within 48 hours by a previously unreported approach of antegrade transcatheter closure of the residual duct by multiple spring coils.

    背景与目标: 一名18个月大的女孩,其血管造影测量的4.5毫米导管,用17毫米的Rashkind伞和阻塞的弹簧线圈经导管闭塞了持续性动脉导管。20小时后出现严重的血管内溶血。注意到明显的残余导管泄漏,并且6毫米测量了残余导管。先前的低估可能与导管痉挛有关,因为在血管造影之前将导管穿过导管放置。通过先前未报道的通过多个弹簧线圈顺行经导管闭合残余导管的方法,在48小时内消除了溶血。
  • 【胶原刚度调节细胞收缩和基质重塑基因表达。】 复制标题 收藏 收藏
    DOI:10.1002/jbm.a.31423 复制DOI
    作者列表:Karamichos D,Brown RA,Mudera V
    BACKGROUND & AIMS: :Cell-level mechanical and 3D spatial cues are essential to the organization and architecture of new tissues that form during growth, repair or in bioreactors. Fibroblast-seeded 3D collagen constructs have been used as bioartifical extracellular matrix (ECM) providing a 3D environment to embedded resident cells. As cells attach to scaffold fibrils, they generate quantifiable contractile forces which depend on cell type, cell attachment, cell density, growth factors, and matrix stiffness. The aim of this study was to quantify the cytomechanical and molecular responses of human dermal (HDF) and neonatal foreskin fibroblasts (HNFF) seeded in constructs of increased stiffness. We also tested the effect of blocking early attachment using serum starvation on these outputs. Constructs were placed under uniaxial strains of 0-10% to increase scaffold stiffness, prior to gel contraction, and force generation was monitored using a tensional culture force monitor (t-CFM). Increased matrix stiffness reduced generation of quantifiable cellular force (up to 70%) over 24 h in both cell types and delayed the onset of measurable contraction (upto sevenfold). The delay of measurable force generation was cell lineage dependent but not FCS dependent. Gene expression of MMP-2, TIMP-2, and collagen type III expression in HDFs were significantly upregulated in constructs of increased stiffness. HNFFs did not show any significant changes in these gene expressions indicating a lineage specific response.
    背景与目标: : 细胞水平的机械和3D空间线索对于在生长,修复或生物反应器中形成的新组织的组织和结构至关重要。成纤维细胞种子的3D胶原蛋白构建体已被用作生物人工细胞外基质 (ECM),为嵌入的常驻细胞提供3D环境。当细胞附着在支架原纤维上时,它们会产生可量化的收缩力,这取决于细胞类型,细胞附着,细胞密度,生长因子和基质刚度。这项研究的目的是量化接种在硬度增加的构建体中的人真皮 (HDF) 和新生儿包皮成纤维细胞 (HNFF) 的细胞机械和分子反应。我们还测试了使用血清饥饿阻断早期附着对这些输出的影响。在凝胶收缩之前,将构建体置于0-10% 的单轴应变下以增加支架刚度,并使用张力培养力监测器 (t-cfm) 监测力的产生。在两种细胞类型中,增加的基质刚度在24小时内减少了可量化的细胞力 (高达70%) 的产生,并延迟了可测量的收缩的开始 (高达7倍)。可测量的力产生的延迟与细胞谱系有关,但与FCS无关。在刚度增加的构建体中,HDFs中MMP-2,TIMP-2和III型胶原表达的基因表达显着上调。HNFFs在这些基因表达中未显示任何显着变化,表明谱系特异性反应。
  • 【磷酸盐粘合剂治疗对早期慢性肾脏病血管僵硬度的影响。】 复制标题 收藏 收藏
    DOI:10.1159/000353569 复制DOI
    作者列表:Seifert ME,de las Fuentes L,Rothstein M,Dietzen DJ,Bierhals AJ,Cheng SC,Ross W,Windus D,Dávila-Román VG,Hruska KA
    BACKGROUND & AIMS: BACKGROUND/AIMS:Cardiovascular disease (CVD) is increased in chronic kidney disease (CKD), and contributed to by the CKD-mineral bone disorder (CKD-MBD). CKD-MBD begins in early CKD and its vascular manifestations begin with vascular stiffness proceeding to increased carotid artery intima-media thickness (cIMT) and vascular calcification (VC). Phosphorus is associated with this progression and is considered a CVD risk factor in CKD. We hypothesized that modifying phosphorus balance with lanthanum carbonate (LaCO3) in early CKD would not produce hypophosphatemia and may affect vascular manifestations of CKD-MBD. METHODS:We randomized 38 subjects with normophosphatemic stage 3 CKD to a fixed dose of LaCO3 or matching placebo without adjusting dietary phosphorus in a 12-month randomized, double-blind, pilot and feasibility study. The primary outcome was the change in serum phosphorus. Secondary outcomes were changes in measures of phosphate homeostasis and vascular stiffness assessed by carotid-femoral pulse wave velocity (PWV), cIMT and VC over 12 months. RESULTS:There were no statistically significant differences between LaCO3 and placebo with respect to the change in serum phosphorus, urinary phosphorus, tubular reabsorption of phosphorus, PWV, cIMT, or VC. Biomarkers of the early CKD-MBD such as plasma fibroblast growth factor-23, Dickkopf-related protein 1 (DKK1), and sclerostin were increased 2- to 3-fold at baseline, but were not affected by LaCO3. CONCLUSION:Twelve months of LaCO3 had no effect on serum phosphorus and did not alter phosphate homeostasis, PWV, cIMT, VC, or biomarkers of CKD-MBD.
    背景与目标:
  • 【动脉内皮衍生的超极化: 在妊娠适应和并发症中的潜在作用。】 复制标题 收藏 收藏
    DOI:10.1097/FJC.0b013e31827b6367 复制DOI
    作者列表:Morton JS,Davidge ST
    BACKGROUND & AIMS: :Pregnancy encompasses substantial changes in vascular function to accommodate dramatic increases in blood volume and uteroplacental blood flow to the growing fetus. Despite increased hemodynamics, decreased peripheral resistance results in a reduction in mean arterial blood pressure. Vascular tone, and hence peripheral resistance, is determined by a delicate balance of constrictor and dilator capacities. In the normal physiological response to pregnancy, endothelial-derived hyperpolarization (EDH) has been shown to be a major contributor; both EDH and nitric oxide (NO) are predominantly involved in providing an increased vascular capacity for vasodilation. The ability of EDH and NO to adequately accommodate increased blood volume is tested in pathological states such as placental insufficiency or diabetes and both EDH and NO-dependent mechanisms seem to be impacted in these situations. Pregnancy complications also have an impact on the cardiovascular health of the offspring. In adult offspring born from complicated pregnancies, the data suggest that EDH mechanisms are largely maintained, whereas NO is commonly reduced. A diversity of EDH mechanisms may be useful in providing many targets for potential therapeutic avenues for compromised pregnancies; however, further research delineating the mechanisms of EDH and the interactions of NO and EDH, in normal and pathological pregnancies is required.
    背景与目标: : 怀孕包括血管功能的重大变化,以适应血容量和子宫胎盘血流量的急剧增加。尽管血流动力学增加,但外周阻力降低会导致平均动脉血压降低。血管张力以及外周阻力是由收缩器和扩张器能力的微妙平衡决定的。在对妊娠的正常生理反应中,内皮衍生的超极化 (EDH) 已被证明是主要的贡献者; EDH和一氧化氮 (NO) 都主要参与增加血管舒张能力。在病理状态 (例如胎盘功能不全或糖尿病) 中测试了EDH和NO充分适应增加的血容量的能力,在这些情况下,EDH和NO依赖性机制似乎都受到影响。妊娠并发症也会对后代的心血管健康产生影响。在复杂怀孕出生的成年后代中,数据表明EDH机制在很大程度上得以维持,而NO通常会减少。EDH机制的多样性可能有助于为受损妊娠的潜在治疗途径提供许多靶标; 但是,需要进一步研究描述正常和病理性妊娠中EDH的机制以及NO和EDH的相互作用。
  • 【结缔组织生长因子与肝脏硬度的相关性通过瞬时弹性成像在胆道闭锁中测量。】 复制标题 收藏 收藏
    DOI:10.1111/hepr.12015 复制DOI
    作者列表:Honsawek S,Udomsinprasert W,Chirathaworn C,Anomasiri W,Vejchapipat P,Poovorawan Y
    BACKGROUND & AIMS: AIM:Biliary atresia (BA) is a neonatal liver disease defined as chronic progressive fibrotic obliteration of extrahepatic bile ducts. The objective of this study was to determine the association of serum connective tissue growth factor (CTGF) with clinical outcome and liver stiffness measurement. METHODS:Eighty-two BA patients post-Kasai operation and 28 healthy controls were recruited. BA patients were categorized into two groups based on their portal hypertension (PH) status. Serum CTGF levels were determined by enzyme-linked immunosorbent assay. Liver stiffness scores were measured by transient elastography. RESULTS:BA patients had greater CTGF levels (905.9 ± 57.7 vs 238.3 ± 23.5 pg/mL, P < 0.001) and higher liver stiffness values than controls (28.2 ± 2.6 vs 5.0 ± 0.5 kPa, P < 0.001). Serum CTGF levels were remarkably elevated in BA patients with PH compared to those without PH (1092.4 ± 73.9 vs 582.6 ± 45.7 pg/mL, P < 0.001). Furthermore, BA patients with PH had significantly higher liver stiffness values compared to those without PH (37.3 ± 3.0 vs 10.6 ± 1.1 kPa, P < 0.001). Additionally, serum CTGF was positively correlated with liver stiffness (r = 0.875, P < 0.001) and total bilirubin (r = 0.462, P < 0.001). There was an inverse correlation between serum CTGF and serum albumin (r = -0.579, P < 0.001). CONCLUSION:High serum CTGF was associated with a poor outcome in BA patients. Accordingly, serum CTGF and transient elastography may serve as non-invasive biomarkers reflecting the disease severity in postoperative BA patients.
    背景与目标:
  • 【动脉壁低密度脂蛋白氧化动力学模型及其在动脉粥样硬化病变预测中的应用。】 复制标题 收藏 收藏
    DOI:10.1016/j.chemphyslip.2013.07.006 复制DOI
    作者列表:Karimi S,Dadvar M,Modarress H,Dabir B
    BACKGROUND & AIMS: :Oxidation of low-density lipoprotein (LDL) is one of the major factors in atherogenic process. Trapped oxidized LDL (Ox-LDL) in the subendothelial matrix is taken up by macrophage and leads to foam cell generation creating the first step in atherosclerosis development. Many researchers have studied LDL oxidation using in vitro cell-induced LDL oxidation model. The present study provides a kinetic model for LDL oxidation in intima layer that can be used in modeling of atherosclerotic lesions development. This is accomplished by considering lipid peroxidation kinetic in LDL through a system of elementary reactions. In comparison, characteristics of our proposed kinetic model are consistent with the results of previous experimental models from other researches. Furthermore, our proposed LDL oxidation model is added to the mass transfer equation in order to predict the LDL concentration distribution in intima layer which is usually difficult to measure experimentally. According to the results, LDL oxidation kinetic constant is an important parameter that affects LDL concentration in intima layer so that existence of antioxidants that is responsible for the reduction of initiating rates and prevention of radical formations, have increased the concentration of LDL in intima by reducing the LDL oxidation rate.
    背景与目标: : 低密度脂蛋白 (LDL) 的氧化是动脉粥样硬化过程的主要因素之一。内皮下基质中捕获的氧化LDL (Ox-LDL) 被巨噬细胞摄取,并导致泡沫细胞的产生,从而形成动脉粥样硬化发展的第一步。许多研究人员使用体外细胞诱导的LDL氧化模型研究了LDL氧化。本研究提供了内膜层LDL氧化的动力学模型,可用于模拟动脉粥样硬化病变的发展。这是通过通过基本反应系统考虑LDL中的脂质过氧化动力学来实现的。相比之下,我们提出的动力学模型的特征与其他研究的先前实验模型的结果一致。此外,我们提出的LDL氧化模型被添加到传质方程中,以预测内膜层中的LDL浓度分布,这通常很难通过实验进行测量。根据结果,LDL氧化动力学常数是影响内膜层中LDL浓度的重要参数,因此抗氧化剂的存在负责降低起始速率和防止自由基形成,通过降低LDL氧化速率来增加内膜中LDL的浓度。
  • 【缬沙坦可独立于降低血压而改善2型糖尿病的动脉僵硬度。】 复制标题 收藏 收藏
    DOI:10.1161/HYPERTENSIONAHA.108.111674 复制DOI
    作者列表:Karalliedde J,Smith A,DeAngelis L,Mirenda V,Kandra A,Botha J,Ferber P,Viberti G
    BACKGROUND & AIMS: :Increased arterial stiffness, as estimated from aortic pulse wave velocity (Ao-PWV), and albuminuria are independent predictors for cardiovascular disease in type 2 diabetes mellitus (T2DM). Whether angiotensin receptor blockers (ARBs), drugs with cardio-renal protective effects, improve Ao-PWV to a greater extent than other equipotent antihypertensive medications remains unclear. After a 4-week washout phase, we compared the effects of valsartan (n=66), an ARB, with that of amlodipine (n=65), a calcium channel blocker on Ao-PWV in 131 T2DM patients with pulse pressure (PP) >or=60 mm Hg and raised albumin excretion rate (AER) in a 24-week randomized, double-blind, parallel group study. Hydrochlorothiazide (HCTZ) 25 mg/d was added to valsartan 160 mg and amlodipine 5 mg/od uptitrated to 10 mg/od after 4 weeks to ensure equivalent BP control. After 24 weeks brachial and central aortic PP had fallen to a similar extent with attained mean (SD) brachial and central PP of 61.6 (13.6) and 47.3 (14.1) mm Hg in the valsartan/HCTZ group and 61.5 (12.2) and 47.3 (9.9) mm Hg in the amlodipine group, respectively. Ao-PWV showed a significantly greater reduction, mean (95% CI), -0.9 m/s (-1.4 to -0.3) for valsartan/HCTZ compared to amlodipine (P=0.002). AER fell significantly only with Val/HCTZ from 30.8(20.4, 46.5) to 18.2(12.5, 26.3) mcg/min, (P=0.01) with between treatment difference in favor of Val/HCTZ of -15.3mcg/min (P<0.001). Changes in AER and Ao-PWV were not correlated. Valsartan/HCTZ improves arterial stiffness and AER to a significantly greater extent than amlodipine despite similar central and brachial BP control. These 2 effects, which appear independent of each other, may explain the specific cardio-renal protective properties of ARBs.
    背景与目标: : 根据主动脉脉搏波速度 (Ao-PWV) 估计,动脉僵硬度增加和蛋白尿是2型糖尿病 (T2DM) 心血管疾病的独立预测因素。血管紧张素受体阻滞剂 (arb) 是具有心肺保护作用的药物,是否比其他同等降压药物在更大程度上改善Ao-PWV尚不清楚。经过4周的冲洗阶段,我们比较了缬沙坦 (n = 66) (ARB) 和氨氯地平 (n = 65) 的作用,在一项为期24周的随机,双盲,平行组研究中,131例脉压 (PP)> 或 = 60毫米Hg且白蛋白排泄率 (AER) 升高的T2DM患者的Ao-PWV钙通道阻滞剂。将氢氯噻嗪 (HCTZ) 25 mg/d添加至缬沙坦160 mg,并在4周后将氨氯地平5 mg/od上调至10 mg/od,以确保等效的BP控制。24周后,在缬沙坦/HCTZ组和61.5 (12.2) 和47.3 (9.9) mm Hg的平均 (SD) 肱动脉和中央PP下降到类似的程度,达到61.6 (13.6) 和47.3 (14.1) mm Hg在氨氯地平组,分别。与氨氯地平 (P = 0.002) 相比,缬沙坦/HCTZ的Ao-PWV降低幅度明显更大,平均 (95% CI),-0.9 m/s (-1.4至-0.3)。仅Val/HCTZ从30.8(20.4,46.5) 到18.2(12.5,26.3) mcg/min,AER显着下降 (P = 0.01),两种治疗之间的差异有利于Val/HCTZ为-15.3mcg/min (P<0.001)。AER和Ao-PWV的变化不相关。尽管中枢和肱动脉血压控制相似,但缬沙坦/HCTZ比氨氯地平在更大程度上改善了动脉僵硬度和AER。这两种作用似乎彼此独立,可以解释arb的特定心肺保护特性。

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