• 【镉通过一系列引起细胞毒性的三波活性氧来影响烟草细胞。】 复制标题 收藏 收藏
    DOI:10.1111/j.1365-3040.2006.01571.x 复制DOI
    作者列表:Garnier L,Simon-Plas F,Thuleau P,Agnel JP,Blein JP,Ranjeva R,Montillet JL
    BACKGROUND & AIMS: :Cadmium is suspected to exert its toxic action on cells through oxidative damage. However, the transition metal is unable to directly generate reactive oxygen species (ROS) via redox reactions with molecular oxygen in a biological environment. Here, we show that bright yellow-2 (BY-2) tobacco cells exposed to millimolar concentrations of CdCl(2) developed cell death within 2-3 h. The death process was preceded by two successive waves of ROS differing in their nature and subcellular localization. Firstly, these consisted in the transient NADPH oxidase-dependent accumulation of H(2)O(2) followed by the accumulation of O(2) (-*) in mitochondria. A third wave of ROS consisting in fatty acid hydroperoxide accumulation was concomitant with cell death. Accumulation of H(2)O(2) was preceded by an increase in cytosolic free calcium concentration originating from internal pools that was essential to activate the NADPH oxidase. The cell line gp3, impaired in NADPH oxidase activity, and that was unable to accumulate H(2)O(2) in response to Cd(2+), was nevertheless poisoned by the metal. Therefore, this first wave of ROS was not sufficient to trigger all the cadmium-dependent deleterious effects. However, we show that the accumulation of O(2) (-*) of mitochondrial origin and membrane peroxidation are key players in Cd(2+)-induced cell death.
    背景与目标: :镉被怀疑通过氧化损伤对细胞产生毒性作用。然而,在生物环境中,过渡金属不能通过与分子氧的氧化还原反应直接产生活性氧(ROS)。在这里,我们表明,暴露于毫摩尔浓度的CdCl(2)的亮黄色2(BY-2)烟草细胞在2-3小时内发展出细胞死亡。死亡过程之前是连续两次的ROS,其性质和亚细胞定位各不相同。首先,这些包括线粒体中H(2)O(2)的瞬时NADPH氧化酶依赖性积累,然后是线粒体中O(2)(-*)的积累。 ROS的第三波涉及脂肪酸氢过氧化物的积累,并伴随着细胞死亡。 H(2)O(2)的积累之前是来自内部池的胞浆游离钙浓度的增加,这对于激活NADPH氧化酶至关重要。然而,细胞系gp3在NADPH氧化酶活性中受损,并且无法响应Cd(2)积聚H(2)O(2),但仍被金属中毒。因此,ROS的第一波不足以触发所有依赖镉的有害作用。但是,我们显示线粒体起源的O(2)(-*)和膜过氧化的积累是Cd(2)诱导的细胞死亡的关键因素。
  • 【等轴测肌力的历史依赖性:先前拉伸或缩短幅度的影响。】 复制标题 收藏 收藏
    DOI:10.1016/j.jbiomech.2006.06.014 复制DOI
    作者列表:Bullimore SR,Leonard TR,Rassier DE,Herzog W
    BACKGROUND & AIMS: :It is well-recognised that steady-state isometric muscle force is decreased following active shortening (force depression, FD) and increased following active stretch (force enhancement, FE). It has also been demonstrated that passive muscle force is increased following active stretch (passive FE). Several studies have reported that FD increases with shortening amplitude and that FE and passive FE increase with stretch amplitude. Here, we investigate whether these trends continue with further increases in shortening or stretch amplitude. Experiments were performed using in situ cat soleus muscles (n=8 for FD; n=7 for FE and passive FE). FD, FE and passive FE were measured after shortening or stretch contractions that covered as wide a range of amplitudes as practically possible without damaging the muscles. FD increased approximately linearly with shortening amplitude, over the full range of amplitudes investigated. This is consistent with the hypothesis that FD arises from a stress-induced inhibition of crossbridges. FE increased with stretch amplitude only up to a point, and then levelled off. Passive FE, and the transient increase in force at the end of stretch, showed relationships to stretch amplitude that were qualitatively very similar to the relationship for FE, increasing only until the same critical stretch amplitude had been reached. We conclude that FE and passive FE do not increase with stretch amplitude under all circumstances. This finding has important consequences for determining the mechanisms underlying FE and passive FE because any mechanism that is proposed to explain them must be able to predict it.
    背景与目标: :众所周知,稳态等距肌肉力量在主动缩短(力量压迫,FD)后降低,而在主动伸展(力量增强,FE)后增加。还已经证明,主动拉伸(被动FE)后,被动肌肉的力量会增加。几项研究报告说,FD随着幅度的减小而增加,而FE和被动FE随拉伸幅度而增加。在这里,我们调查这些趋势是否继续缩短或拉伸幅度的进一步增加。使用原位猫的比目鱼肌进行实验(FD为n = 8; FE和被动FE为n = 7)。 FD,FE和被动FE是在收缩或拉伸收缩后测量的,收缩或拉伸收缩实际上覆盖了尽可能宽的幅度范围,而不会损坏肌肉。在所研究的整个振幅范围内,FD随振幅的减小而近似线性地增加。这与FD是由应力引起的跨桥抑制作用引起的假设相一致的。 FE随拉伸幅度仅增加到一个点,然后趋于平稳。被动有限元,以及拉伸结束时力的瞬时增加,表明与拉伸幅度的关系在质量上与有限元的关系非常相似,仅在达到相同的临界拉伸幅度之前才增加。我们得出结论,在所有情况下,有限元和无源有限元都不会随拉伸幅度的增加而增加。这一发现对确定有限元和被动有限元的机制具有重要意义,因为提议用来解释它们的任何机制都必须能够对其进行预测。
  • 【血管紧张素II激活动脉平滑肌细胞中介导的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: :血管紧张素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,中导Ca2激活的K(IKca)通道在细胞迁移和增殖中具有重要作用。但是,尚不清楚Ang II的作用是否与IKca通道调节有关。在这里,我们研究了血管平滑肌细胞中Ang II对IKca通道的调节作用。使用膜片钳技术研究了在培养的大鼠大鼠主动脉平滑肌(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,在切除的斑块中很少观察到大电导的Ca2激活的K(BKca)电流。 Ang II以依赖冲突的方式增加了IKca电流。 Losartan(1.0 microM),一种AT1选择性拮抗剂,取消了Ang II对IKca通道的激活。用100 microM肉豆蔻酰化的蛋白激酶C抑制剂肽20-28或10 microM GF109203X进行的预处理完全消除了AngII诱导的IKca电流激活,而在存在100 microM Rp-环3',5的情况下并未阻止Ang II的作用。 -磷酸磷酸氢腺苷三乙铵,一种蛋白激酶A抑制剂,或1.0 microM KT-5823,一种蛋白激酶G抑制剂。二酰基甘油1、2-二辛酰基-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通过蛋白激酶C的激活来激活IKca通道,而AT1受体参与了这些通道的调节。
  • 【肌腱单元的机械和形态特性对运行经济性的影响。】 复制标题 收藏 收藏
    DOI:10.1242/jeb.02340 复制DOI
    作者列表:Arampatzis A,De Monte G,Karamanidis K,Morey-Klapsing G,Stafilidis S,Brüggemann GP
    BACKGROUND & AIMS: :The purpose of this study was to test the hypothesis that runners having different running economies show differences in the mechanical and morphological properties of their muscle-tendon units (MTU) in the lower extremities. Twenty eight long-distance runners (body mass: 76.8+/-6.7 kg, height: 182+/-6 cm, age: 28.1+/-4.5 years) participated in the study. The subjects ran on a treadmill at three velocities (3.0, 3.5 and 4.0 m s(-1)) for 15 min each. The V(O(2)) consumption was measured by spirometry. At all three examined velocities the kinematics of the left leg were captured whilst running on the treadmill using a high-speed digital video camera operating at 250 Hz. Furthermore the runners performed isometric maximal voluntary plantarflexion and knee extension contractions at eleven different MTU lengths with their left leg on a dynamometer. The distal aponeuroses of the gastrocnemius medialis (GM) and vastus lateralis (VL) were visualised by ultrasound during plantarflexion and knee extension, respectively. The morphological properties of the GM and VL (fascicle length, angle of pennation, and thickness) were determined at three different lengths for each MTU. A cluster analysis was used to classify the subjects into three groups according to their V(O(2)) consumption at all three velocities (high running economy, N=10; moderate running economy, N=12; low running economy, N=6). Neither the kinematic parameters nor the morphological properties of the GM and VL showed significant differences between groups. The most economical runners showed a higher contractile strength and a higher normalised tendon stiffness (relationship between tendon force and tendon strain) in the triceps surae MTU and a higher compliance of the quadriceps tendon and aponeurosis at low level tendon forces. It is suggested that at low level forces the more compliant quadriceps tendon and aponeurosis will increase the force potential of the muscle while running and therefore the volume of active muscle at a given force generation will decrease.
    背景与目标: :这项研究的目的是检验以下假设:具有不同运行经济状况的跑步者在下肢的肌腱单元(MTU)的机械和形态特性上存在差异。参加研究的有28名长跑运动员(体重:76.8 /-6.7公斤,身高:182 / -6厘米,年龄:28.1 /-4.5岁)。受试者分别以三种速度(3.0、3.5和4.0 m s(-1))在跑步机上跑步15分钟。 V(O(2))消耗量通过肺活量测定法进行测量。在所有三个检查的速度下,使用在250 Hz下运行的高速数码摄像机在跑步机上跑步时,捕获左腿的运动学信息。此外,跑步者在其左腿放在测力计上以11种不同的MTU长度进行等距最大自愿足底屈伸和膝盖伸展收缩。分别在足底屈曲和膝关节屈伸期间通过超声观察腓肠肌的远端腱膜(GM)和股外侧肌(VL)。对于每个MTU,在三种不同的长度下确定了GM和VL的形态学特性(纤维束长度,垂垂角度和厚度)。根据所有三个速度(高运行经济性,N = 10;中等运行经济性,N = 12;低运行经济性,N = 6)。 GM和VL的运动学参数和形态学特性均未显示组之间的显着差异。最经济的跑步者在肱三头肌MTU中表现出更高的收缩强度和更高的标准化肌腱刚度(肌腱力与肌腱应变之间的关系),在低水平的肌腱力下,股四头肌和腱膜的顺应性更高。建议在低水平的力量下,股四头肌和腱膜的顺应性会增加跑步时肌肉的力量,因此在给定的力量产生下,活跃肌肉的体积会减少。
  • 【环氧二十碳三烯酸通过鸟嘌呤核苷酸结合蛋白激活冠状动脉平滑肌中的K通道。】 复制标题 收藏 收藏
    DOI:10.1161/01.res.80.6.877 复制DOI
    作者列表:Li PL,Campbell WB
    BACKGROUND & AIMS: Epoxyeicosatrienoic acids (EETs) are endothelium-derived arachidonic acid metabolites of cytochrome P450. They dilate coronary arteries, open K+ channels, and hyperpolarize vascular smooth muscles. However, the mechanisms of these smooth muscle actions remain unknown. This study examined the effects of EETs on the large-conductance Ca(2+)-activated K+ channel (KCa) in smooth muscle cells of small bovine coronary arteries. In cell-attached patch-clamp experiments, 11,12-EET produced a 0.5- to 10-fold increase in the activity of the KCa channels when added in concentrations of 1, 10, and 100 nmol/L. In the inside-out excised membrane patch mode, 11,12-EET was without effect on the activity of the KCa channel unless GTP (0.5 mmol/L) or GTP and ATP (1 mmol/L) were added to the bath solution. In the presence of GTP and ATP, the increase in the KCa channel activity with 11,12-EET in inside-out patches was comparable to that in cell-attached patches. This effect of 11,12-EET in inside-out patches was blocked by the addition of GDP-beta-S (100 mumol/L). In outside-out patches, 11,12-EET also increased the KCa channel activity when GTP and ATP were added to the pipette solution. The addition of a specific anti-Gs alpha antibody (100 nmol/L) in the pipette solution completely blocked the activation of the KCa channels induced by 11,12-EET. An anti-G beta gamma or anti-Gi alpha antibody was without effect. We conclude that 11,12-EET activates the KCa channels by a Gs alpha-mediated mechanism. This mechanism contributes to the effects of EETs as endothelium-derived hyperpolarizing factors to hyperpolarize and relax arterial smooth muscle.

    背景与目标: 环氧二十碳三烯酸(EET)是内皮细胞色素P450的花生四烯酸代谢产物。它们扩张冠状动脉,打开K通道,并使血管平滑肌超极化。但是,这些平滑肌动作的机制仍然未知。这项研究检查了EETs对小牛冠状动脉平滑肌细胞中大电导Ca(2)激活的K通道(KCa)的影响。在贴有细胞的膜片钳实验中,当以1,10和100 nmol / L的浓度添加时,11,12-EET使KCa通道的活性增加0.5至10倍。在由内而外的切膜模式下,除非将GTP(0.5 mmol / L)或GTP和ATP(1 mmol / L)添加到浴液中,否则11,12-EET对KCa通道的活性没有影响。在存在GTP和ATP的情况下,由内而外的贴片中11,12-EET的KCa通道活性的增加与细胞附着的贴片中的KCa通道活性的增加相当。通过添加GDP-β-S(100 mumol / L),阻止了由内而外的11,12-EET的这种作用。在外向斑块中,将GTP和ATP添加到移液器中时,11,12-EET也增加了KCa通道活性。在移液器中添加特异性抗Gsα抗体(100 nmol / L)完全阻断了11,12-EET诱导的KCa通道的激活。抗Gβγ或抗Giα抗体无效。我们得出的结论是11,12-EET通过Gs alpha介导的机制激活了KCa通道。这种机制有助于将EETs作为内皮源的超极化因子来使动脉平滑肌超极化和松弛。

  • 【异位错构瘤性胸腺生长在伪装成肉瘤的胸锁乳突肌中。】 复制标题 收藏 收藏
    DOI:10.1080/0284431051003592 复制DOI
    作者列表:Iida E,Okazaki M,Sarukawa S,Motoi T,Kikuchi Y
    BACKGROUND & AIMS: :The distinction between ectopic hamartomatous thymoma and sarcoma is difficult, and preoperative biopsy and intraoperative histopathological examination fail to give a definitive diagnosis. It is important to recognise ectopic hamartomatous thymoma as one of the differential diagnoses of a cervical tumour.
    背景与目标: :异位错构瘤性胸腺瘤和肉瘤很难区分,术前活检和术中组织病理学检查不能明确诊断。重要的是要认识到异位错构瘤性胸腺瘤是宫颈肿瘤的鉴别诊断之一。
  • 【体内VEGF亚型与VEGFR-1,VEGFR-2和神经纤毛蛋白的相互作用:人骨骼肌的计算模型。】 复制标题 收藏 收藏
    DOI:10.1152/ajpheart.00637.2006 复制DOI
    作者列表:Mac Gabhann F,Popel AS
    BACKGROUND & AIMS: :The vascular endothelial growth factor (VEGF) family of cytokines is involved in the maintenance of existing adult blood vessels as well as in angiogenesis, the sprouting of new vessels. To study the proangiogenic activation of VEGF receptors (VEGFRs) by VEGF family members in skeletal muscle, we develop a computational model of VEGF isoforms (VEGF(121), VEGF(165)), their cell surface receptors, and the extracellular matrix in in vivo tissue. We build upon our validated model of the biochemical interactions between VEGF isoforms and receptor tyrosine kinases (VEGFR-1 and VEGFR-2) and nonsignaling neuropilin-1 coreceptors in vitro. The model is general and could be applied to any tissue; here we apply the model to simulate the transport of VEGF isoforms in human vastus lateralis muscle, which is extensively studied in physiological experiments. The simulations predict the distribution of VEGF isoforms in resting (nonexercising) muscle and the activation of VEGFR signaling. Little of the VEGF protein in muscle is present as free, unbound extracellular cytokine; the majority is bound to the cell surface receptors or to the extracellular matrix. However, interstitial sequestration of VEGF(165) does not affect steady-state receptor binding. In the absence of neuropilin, VEGF(121) and VEGF(165) behave similarly, but neuropilin enhances the binding of VEGF(165) to VEGFR-2. This model is the first to study VEGF tissue distribution and receptor activation in human muscle, and it provides a platform for the design and evaluation of therapeutic approaches.
    背景与目标: :细胞因子的血管内皮生长因子(VEGF)家族与现有成人血管的维护以及血管生成,新血管的萌发有关。为了研究骨骼肌中VEGF家族成员对VEGF受体(VEGFRs)的促血管生成激活作用,我们建立了VEGF同种型(VEGF(121),VEGF(165)),它们的细胞表面受体和细胞外基质的计算模型。体内组织。我们建立了我们的体外VEGF同工型和受体酪氨酸激酶(VEGFR-1和VEGFR-2)和无信号Neuropilin-1共受体之间的生化相互作用的验证模型。该模型是通用模型,可以应用于任何组织。在这里,我们应用该模型来模拟VEGF同工型在人股外侧肌中的运输,这在生理实验中已得到广泛研究。模拟预测了静息(非运动)肌肉中VEGF亚型的分布和VEGFR信号的激活。肌肉中很少有VEGF蛋白以游离的,未结合的细胞外细胞因子的形式存在。大多数与细胞表面受体或细胞外基质结合。但是,间质隔离VEGF(165)不会影响稳态受体结合。在没有神经纤毛蛋白的情况下,VEGF(121)和VEGF(165)的行为相似,但是神经纤毛蛋白会增强VEGF(165)与VEGFR-2的结合。该模型是第一个研究人肌肉中VEGF组织分布和受体激活的模型,它为设计和评估治疗方法提供了平台。
  • 【比目鱼肌的代谢特征与高血压父母的后代中胰岛素作用有关。】 复制标题 收藏 收藏
    DOI:10.1016/j.metabol.2006.06.010 复制DOI
    作者列表:Kratochvílová S,Vyhnanovská P,Vlasáková Z,Hájek M,Skibová J,Pelikánová T
    BACKGROUND & AIMS: :Insulin resistance affecting skeletal muscle metabolism is present in the prehypertensive state. The aim of our study was to test the hypothesis that blood pressure value is related to skeletal muscle composition, measured by (31)P magnetic resonance (MR) spectroscopy, and to insulin sensitivity in the offspring of hypertensive parents (OH) and healthy controls. Study groups consisted of 10 healthy young lean OH with normal glucose tolerance, confirmed with oral glucose tolerance test, and 13 controls matched for age, sex, and body mass index. Insulin action was estimated as glucose disposal (M), glucose metabolic clearance rate (MCR), and insulin sensitivity index (M/I) during a 10-hour hyperinsulinemic euglycemic clamp. The sum of immunoreactive insulin values from the oral glucose tolerance test was calculated. (31)P MR spectroscopy was performed on a whole-body MR scanner (Siemens Vision, Erlangen, Germany) operating at 1.5 T and equipped with actively shielded gradient coils. There were no differences in common metabolic and anthropometric parameters between OH and controls except for the blood pressure, which was in the range of normal to high-normal level in OH. Mean blood pressure was significantly higher in OH (95.73 +/- 4.39 vs 83.76 +/- 3.95 mm Hg; P < .001). Trend toward insulin resistance was registered in OH with significantly lower M/I (0.74 +/- 0.47 vs 1.42 +/- 0.65 mg x kg(-1) x min(-1) x mIU(-1) x L(-1); P < .05). There were no significant differences in total serum magnesium (sMg) levels between OH and controls, although a positive correlation exists between sMg and insulin sensitivity expressed as M (r = 0.63, P < .01), MCR (r = 0.54, P < .01), and M/I (r = 0.51, P < .05). No differences in signal intensities of phosphocreatine (PCr), phosphomonoesters, phosphodiesters, inorganic phosphates (Pi), adenosine triphosphates (Patp and betaATP), and calculated concentrations of intracellular ionized magnesium (Mgi) and H(+) ions between the groups were detected. Systolic blood pressure correlates positively with PCr/Patp (r = 0.43, P < .05), Pi/Patp (r = 0.413, P < .05), and Pi/betaATP (r = 0.48, P < .05). Diastolic blood pressure correlates positively only with the ratio Pi/betaATP (r = 0.42, P < .05). The sum of immunoreactive insulin values correlates with PCr/betaATP (r = 0.53, P < .01) and with Pi/betaATP (r = 0.6, P < .01). In conclusion, increase in blood pressure and insulin resistance were confirmed in offspring of OH. Insulin sensitivity is related to sMg and the elevation of blood pressure is associated with the activation of energy metabolism in skeletal muscle. The relationship between muscle energetic characteristics and markers of insulin resistance suggests that the alteration of energy metabolism may be present in early stages of metabolic syndrome.
    背景与目标: :在高血压前状态下,会影响骨骼肌新陈代谢的胰岛素抵抗。我们研究的目的是检验以下假设:血压值与通过(31)P磁共振(MR)光谱法测量的骨骼肌成分以及高血压父母(OH)和健康对照的后代的胰岛素敏感性有关。研究组包括10名健康正常的年轻瘦肉OH,其葡萄糖耐量正常,经口服葡萄糖耐量试验确认,另有13个对照的年龄,性别和体重指数匹配。在10小时高胰岛素正常血糖钳制期间,胰岛素作用估计为葡萄糖处置(M),葡萄糖代谢清除率(MCR)和胰岛素敏感性指数(M / I)。计算来自口服葡萄糖耐量试验的免疫反应性胰岛素值的总和。 (31)P MR光谱是在全身MR扫描仪(Siemens Vision,Erlangen,德国)上以1.5 T操作并配备有源屏蔽梯度线圈进行的。 OH和对照组之间的共同代谢和人体测量学参数没有差异,除了血压处于OH正常水平到高正常水平的范围之内。 OH的平均血压显着升高(95.73 /-4.39与83.76 /-3.95 mm Hg; P <.001)。在OH中出现胰岛素抵抗的趋势,M / I显着降低(0.74 /-0.47对1.42 /-0.65 mg x kg(-1)x min(-1)x mIU(-1)x L(-1); P <.05)。尽管sMg与胰岛素敏感性之间呈正相关,分别以M(r = 0.63,P <.01),MCR(r = 0.54,P < .01)和M / I(r = 0.51,P <.05)。两组之间没有发现磷酸肌酸(PCr),磷酸单酯,磷酸二酯,无机磷酸盐(Pi),三磷酸腺苷(Patp和betaATP)的信号强度差异以及计算出的细胞内离子化镁(Mgi)和H()离子浓度。收缩压与PCr / Patp(r = 0.43,P <.05),Pi / Patp(r = 0.413,P <.05)和Pi / betaATP(r = 0.48,P <.05)正相关。舒张压仅与Pi / betaATP比率呈正相关(r = 0.42,P <.05)。免疫反应性胰岛素值的总和与PCr / betaATP(r = 0.53,P <.01)和Pi / betaATP(r = 0.6,P <.01)相关。总之,在OH的后代中证实了血压升高和胰岛素抵抗。胰岛素敏感性与sMg有关,血压升高与骨骼肌能量代谢的激活有关。肌肉能量特性与胰岛素抵抗标志物之间的关系表明,能量代谢的改变可能在代谢综合征的早期出现。
  • 【肌肉干/祖细胞中的甲状腺激素信号传导和脱碘酶作用。】 复制标题 收藏 收藏
    DOI:10.1016/j.mce.2017.06.014 复制DOI
    作者列表:Ambrosio R,De Stefano MA,Di Girolamo D,Salvatore D
    BACKGROUND & AIMS: :Thyroid hormone (TH) regulates such crucial biological functions as normal growth, development and metabolism of nearly all vertebrate tissues. In skeletal muscle, TH plays a critical role in regulating the function of satellite cells, the bona fide skeletal muscle stem cells. Deiodinases (D2 and D3) have been found to modulate the expression of various TH target genes in satellite cells. Regulation of the expression and activity of the deiodinases constitutes a cell-autonomous, pre-receptor mechanism that controls crucial steps during the various phases of myogenesis. Here, we review the roles of deiodinases in skeletal muscle stem cells, particularly in muscle homeostasis and upon regeneration. We focus on the role of T3 in stem cell functions and in commitment towards lineage progression. We also discuss how deiodinases might be therapeutically exploited to improve satellite-cell-mediated muscle repair in skeletal muscle disorders or injury.
    背景与目标: 甲状腺激素(TH)调节至关重要的生物学功能,例如几乎所有脊椎动物组织的正常生长,发育和代谢。在骨骼肌中,TH在调节卫星细胞(真正的骨骼肌干细胞)的功能中起着至关重要的作用。已发现脱碘酶(D2和D3)可调节卫星细胞中各种TH靶基因的表达。脱碘酶的表达和活性的调节构成了细胞自主的前受体机制,该机制在肌生成的各个阶段中控制关键步骤。在这里,我们回顾了脱碘酶在骨骼肌干细胞中的作用,特别是在肌肉稳态和再生中。我们专注于T3在干细胞功能中的作用以及对谱系进展的承诺。我们还将讨论如何在骨骼肌疾病或损伤中治疗性利用脱碘酶来改善卫星细胞介导的肌肉修复。
  • 【线和表面网格模型之间的比较,以表示肌肉骨骼模型中的肩袖肌肉几何形状。】 复制标题 收藏 收藏
    DOI:10.1080/10255842.2017.1340463 复制DOI
    作者列表:Hoffmann M,Haering D,Begon M
    BACKGROUND & AIMS: :Accurate muscle geometry (muscle length and moment arm) is required to estimate muscle function when using musculoskeletal modelling. In shoulder, muscles are often modelled as a collection of independent line segments, leading to non-physiological muscles trajectory, especially for the rotator cuff muscles. To prevent this, a surface mesh model was developed and validated against 7 MRI positions in one participant. Mean moment arm errors was 11.4% for the line vs. 8.8% for the mesh model. While the model with independent lines led to some non-physiological trajectories, the mesh model gave lower misestimations of muscle lengths and moment arms.
    背景与目标: :使用肌肉骨骼模型时,需要准确的肌肉几何形状(肌肉长度和力矩臂)来估计肌肉功能。在肩部,肌肉通常被建模为独立线段的集合,从而导致非生理性的肌肉运动轨迹,特别是对于肩袖肌。为了防止这种情况,开发了一个表面网格模型,并针对一位参与者的7个MRI位置进行了验证。直线的平均弯矩臂误差为11.4%,而网格模型为8.8%。尽管具有独立线的模型导致了一些非生理轨迹,但网格模型给出了较低的肌肉长度和弯矩臂错误估计。
  • 【数字(2D:4D)比率与老年人的肌肉质量(MM)和力量(MS)相关:子宫内雄激素暴露的可能影响。】 复制标题 收藏 收藏
    DOI:10.1016/j.archger.2012.11.003 复制DOI
    作者列表:Halil M,Gurel EI,Kuyumcu ME,Karaismailoglu S,Yesil Y,Ozturk ZA,Yavuz BB,Cankurtaran M,Ariogul S
    BACKGROUND & AIMS: :Decline in MM and MS with aging, defined as sarcopenia, is related with physical disability, poor quality of life and death. Its mechanisms are not fully understood. Testosterone increases muscle protein synthesis. However, the effects of in utero androgen exposure to MM and MS in older adults have not been studied. In utero androgen exposure is inversely related with 2D:4D ratio. The aim of this study was to investigate the relationship between 2D:4D ratio as an indicator of in utero androgen exposure and MM and MS in elderly patients. A total of 151 older adults were included. Calf-circumference (CC) and skeletal muscle mass index (SMI) were used for the assessment of MM and hand grip strength for the assessment of MS. Mean age ± SD of the patients was 73.72 ± 6.23. Fifty-two (34.4%) of patients were male, 99 (65.6%) were female. Right and left 2D:4D were significantly and negatively correlated with hand grip strength (r=-0.365, p=0.018 and r=-0.434, p=0.005, respectively), CC (r=-0.422, p=0.002 and r=-0.459, p=0.001, respectively) and SMI (r=-0.354, p=0.018 and r=-0.348, p=0.022, respectively) in men. In women, right and left 2D:4D were significantly and negatively correlated with hand grip strength (r=-0.252, p=0.022 and r=-0.234, p=0.033, respectively), CC (r=-0.229, p=0.024 and r=-0.302, p=0.003, respectively) and SMI (r=-0.382, p<0.001 and r=-0.431, p<0.001, respectively). In this study, we found that 2D:4D ratio was significantly and negatively correlated with parameters depicting MM and MS which may suggest the possible role of in utero androgen exposure in the development of MM and MS loss in the elderly.
    背景与目标: :衰老的MM和MS的下降(定义为肌肉减少症)与身体残疾,不良的生活和死亡质量有关。其机制尚不完全清楚。睾丸激素可增加肌肉蛋白质的合成。但是,尚未研究子宫内雄激素暴露于老年人的MM和MS的影响。在子宫内,雄激素暴露与2D:4D比率成反比。这项研究的目的是调查老年患者子宫内雄激素暴露的指标2D:4D比值与MM和MS之间的关系。总共包括151位老年人。小腿围(CC)和骨骼肌质量指数(SMI)用于MM评估,手握力用于MS评估。患者的平均年龄±SD为73.72±6.23。男性(52)(34.4%),女性(99)(65.6%)。左右2D:4D与握力强度显着负相关(分别为r = -0.365,p = 0.018和r = -0.434,p = 0.005),CC(r = -0.422,p = 0.002和r = -0.459,p = 0.001)和SMI(r = -0.354,p = 0.018和r = -0.348,p = 0.022)。在女性中,左右2D:4D与握力强度显着负相关(分别为r = -0.252,p = 0.022和r = -0.234,p = 0.033),CC(r = -0.229,p = 0.024)和r = -0.302,p = 0.003)和SMI(r = -0.382,p <0.001和r = -0.431,p <0.001)。在这项研究中,我们发现2D:4D比率与描述MM和MS的参数显着负相关,这可能表明子宫内雄激素暴露在老年人MM和MS丢失发展中的可能作用。
  • 【在缺氧和常氧的吸气肌肉负荷期间,静息肢体肌肉灌注。】 复制标题 收藏 收藏
    DOI:10.1016/j.resp.2017.06.003 复制DOI
    作者列表:Klenze H,Köhler TC,Farquharson F,Walterspacher S,Duerschmied D,Roecker K,Kabitz HJ,Walker DJ
    BACKGROUND & AIMS: INTRODUCTION:Fatiguing of respiratory muscles reduces peripheral muscle perfusion. Further, acute hypoxia enhances respiratory muscle fatigue. This study investigated the effects of inspiratory muscle loading (IML) on resting locomotor muscle perfusion in hypoxia compared to normoxia. METHODS:Ten subjects completed two study days of fatiguing IML (blinded, randomized) in normobaric hypoxia (targeted oxygen saturation 80%) and normoxia, respectively. Contrast-enhanced ultrasound (CEUS) of the gastrocnemius muscle and popliteal doppler ultrasonography were used to monitor muscle perfusion. Based on CEUS and monitored cardiac output, perfusion surrogate parameters (CLPaer and CLPap) were established. RESULTS:Muscle perfusion declines early during IML in normoxia (CLPaer: -54±25%, p<0.01; CLPap: -58±32%, p<0.01) and hypoxia (CLPaer: -43±23%, p<0.01; CLPap: -41±20%, p<0.01). Hypoxia compared to normoxia increased cardiac output before (+23±19%, p<0.01 ANOVA) and during (+22±20%, p<0.01 ANOVA) IML, while local muscle perfusion during IML remained unchanged (CLPaer: p=0.41 ANOVA; CLPap: p=0.29 ANOVA). CONCLUSION:Acute hypoxia compared to normoxia does not affect locomotor muscle perfusion during fatiguing IML.
    背景与目标: 引言:呼吸肌疲劳会减少周围肌肉的灌注。此外,急性缺氧会增强呼吸肌疲劳。这项研究调查了吸氧量(IML)与低氧相比低氧对静息运动肌灌注的影响。
    方法:十名受试者分别在常压低氧(目标血氧饱和度为80%)和常氧下完成了对IML(盲,随机)疲劳训练的两个研究日。腓肠肌的造影增强超声(CEUS)和pop肌多普勒超声检查可监测肌肉灌注情况。基于CEUS和监测的心输出量,建立灌注替代参数(CLPaer和CLPap)。
    结果:常氧(CLPaer:-54±25%,p <0.01; CLPap:-58±32%,p <0.01)和缺氧(CLPaer:-43±23%,p <0.01)在IML早期肌肉灌注下降。 CLPap:-41±20%,p <0.01)。与常氧相比,低氧增加了IML之前(23±19%,p <0.01 ANOVA)和期间(22±20%,p <0.01 ANOVA)的心输出量,而IML期间的局部肌肉灌注保持不变(CLPaer:p = 0.41 ANOVA; CLPap:p = 0.29 ANOVA)。
    结论:与常氧相比,急性缺氧并不影响IML疲劳期间运动肌的灌注。
  • 【小儿心脏手术后局部静脉血氧饱和度与混合静脉血饱和度的关系。】 复制标题 收藏 收藏
    DOI:10.1111/aas.12016 复制DOI
    作者列表:Moreno GE,Pilán ML,Manara C,Magliola R,Vassallo JC,Balestrini M,Lenz AM,Krynski M,Althabe M,Landry L
    BACKGROUND & AIMS: BACKGROUND:Central venous oxygen saturation (ScvO2) remains the gold standard surrogate for tissue oxygen extraction in paediatric cardiac surgery. Near-infrared spectroscopy (NIRS) has been developed as a non-invasive diagnostic tool for regional oxygen saturation. The aim was to compare regional oxygen saturation measured by NIRS with ScvO2 in postoperative paediatric cardiac patients. METHODS:In this prospective study, we included newborns and infants younger than 45 days undergoing heart surgery. We recorded continuous ScvO2 and NIRS regional saturation placed on the forehead (B) and right flank (S) for 48 h postoperatively. A Bland-Altman's analysis was used to assess the agreement between these measurements. RESULTS:A total of 23 patients were included with a median age of 12 days (2-46) and median weight of 3.1 kg (2.3-4.47). The mean difference (MD) ScvO2- B NIRS was 10.45% with limits of agreement (LOA) -17.23 to 38.13% and ScvO2- S NIRS MD 7.16% with LOA: -25.51 to 39.84%. The single ventricle ScvO2- S NIRS subgroup had MD within ± 5%; however, wide LOA was observed. The remaining subgroups showed MD nearly above ± 5%, with wide LOA. CONCLUSIONS:The regional oxygen saturation of brain and kidney did not match ScvO2 as estimation of global tissue perfusion. Nevertheless, NIRS may still provide information regarding regional circulation that may help in the management of neonatal cardiac surgery patients.
    背景与目标: 背景:中央静脉血氧饱和度(ScvO2)仍然是小儿心脏外科手术中组织氧提取的金标准。近红外光谱法(NIRS)已被开发为一种用于区域血氧饱和度的非侵入性诊断工具。目的是比较由NIRS和ScvO2测得的小儿心脏术后患者的局部血氧饱和度。
    方法:在这项前瞻性研究中,我们纳入了接受心脏手术的45天以下的新生儿和婴儿。我们记录了连续的ScvO2和NIRS区域饱和度放置在术后48 h的前额(B)和右胁(S)上。用布兰德-奥特曼(Bland-Altman)分析来评估这些测量之间的一致性。
    结果:总共纳入23名患者,中位年龄为12天(2-46),中位体重为3.1 kg(2.3-4.47)。 ScvO2-B NIRS的平均差异(MD)为10.45%,协议限制(LOA)为-17.23至38.13%,Slovo2- S NIRS MD的7.16%LOA为-25.51至39.84%。单心室ScvO2-S NIRS亚组的MD≤±5%。但是,观察到广泛的LOA。其余亚组的MD值接近±5%,LOA较宽。
    结论:脑和肾脏的局部血氧饱和度与ScvO2不符,无法估计整体组织灌注。尽管如此,NIRS仍可能提供有关区域循环的信息,这可能有助于新生儿心脏外科手术患者的管理。
  • 【天然非结构化α-突触核蛋白向其α-螺旋构象的转化显着减弱了活性氧的产生。】 复制标题 收藏 收藏
    DOI:10.1016/j.jinorgbio.2012.09.001 复制DOI
    作者列表:Zhou B,Hao Y,Wang C,Li D,Liu YN,Zhou F
    BACKGROUND & AIMS: :The intracellular α-synuclein (α-syn) protein, whose conformational change and aggregation have been closely linked to the pathology of Parkingson's disease (PD), is highly populated at the presynaptic termini and remains there in the α-helical conformation. In this study, circular dichroism confirmed that natively unstructured α-syn in aqueous solution was transformed to its α-helical conformation upon addition of trifluoroethanol (TFE). Electrochemical and UV-visible spectroscopic experiments reveal that both Cu (I) and Cu (II) are stabilized, with the former being stabilized by about two orders of magnitude. Compared to unstructured α-syn (Binolfi et al., J. Am. Chem. Soc. 133 (2011) 194-196), α-helical α-syn stabilizes Cu (I) by more than three orders of magnitude. Through the measurements of H(2)O(2) and hydroxyl radicals (OH) in solutions containing different forms of Cu (II) (free and complexed by unstructured or α-helical α-syn), we demonstrate that the significantly enhanced Cu (I) binding affinity helps inhibit the production of highly toxic reactive oxygen species, especially the hydroxyl radicals. Our study provides strong evidence that, as a possible means to prevent neuronal cell damage, conversion of the natively unstructured α-syn to its α-helical conformation in vivo could significantly attenuate the copper-modulated ROS production.
    背景与目标: :胞内α-突触核蛋白(α-syn)蛋白的构象变化和聚集与Parkingson氏病(PD)的病理密切相关,在突触前末端高密度分布,并一直保持在α-螺旋构象中。在这项研究中,圆二色性证实,加入三氟乙醇(TFE)后,水溶液中的天然非结构化α-syn转变为其α-螺旋构象。电化学和紫外可见光谱实验表明,Cu(I)和Cu(II)都稳定了,前者稳定了大约两个数量级。与非结构化α-syn相比(Binolfi等人,J.Am.Chem.Soc.133(2011)194-196),α-螺旋α-syn使Cu(I)稳定三个以上数量级。通过测量H(2)O(2)和羟基自由基(OH)在包含不同形式的Cu(II)(游离且由非结构化或α-螺旋α-syn络合)的溶液中,我们证明了显着增强的Cu (I)结合亲和力有助于抑制剧毒活性氧的产生,特别是羟基自由基的产生。我们的研究提供了有力的证据,作为一种可能的预防神经元细胞损伤的方法,体内天然非结构化的α-syn转化为其α-螺旋构象可以显着减弱铜调节的ROS产生。
  • 【霍奇金淋巴瘤幸存者中与癌症相关的疲劳和肌肉质量。】 复制标题 收藏 收藏
    DOI:10.1177/1534735417712009 复制DOI
    作者列表:de Lima FD,Bottaro M,de Oliveira Valeriano R,Cruz L,Battaglini CL,Vieira CA,de Oliveira RJ
    BACKGROUND & AIMS: :The purpose of this study was to compare fatigue, strength, body composition, muscle thickness, and muscle quality between Hodgkin's lymphoma survivors (HLS) and apparently healthy subjects matched by age, gender, and physical activity levels (CON). Twelve HLS (32.16 ± 8.06) and 36 CON (32.42 ± 7.64) were enrolled in the study. Fatigue was assessed using the 20-item Multidimensional Fatigue Inventory, muscle strength using an isokinetic dynamometer, body composition using dual-energy X-ray absorptiometry, and thickness and muscle quality using B-mode ultrasound. Differences between HLS and CON were analyzed using independent samples t tests. No significant differences were observed between groups for any demographic characteristics: age ( P = .922), weight ( P = .943), height ( P = .511), body mass index ( P = .796), fat mass ( P = .688), fat-free mass ( P = .520), and percent body fat ( P = .446). No significant differences were observed for strength (peak torque; P = .552), relative peak torque ( P = .200), muscle thickness ( P > .05) and muscle quality ( P > .05). However, self-perceived fatigue was significantly higher in HLS than in CON ( P = .009). It appears that when HLS are matched by age and physical activity levels to CON, no significant difference in body composition, muscle thickness, muscle quality, or strength is observed. Self-perceived fatigue, as predicted, is higher in HLS, which may have implications and should be considered when prescribing exercise training to this cancer population.
    背景与目标: :本研究的目的是比较霍奇金淋巴瘤幸存者(HLS)与显然健康的受试者之间的疲劳,强度,身体成分,肌肉厚度和肌肉质量,并根据年龄,性别和身体活动水平(CON)进行比较。十二项HLS(32.16±8.06)和36 CON(32.42±7.64)被纳入研究。使用20个项目的多维疲劳清单评估疲劳,使用等速测功机评估肌肉强度,使用双能X射线吸收仪评估身体成分,并使用B型超声评估厚度和肌肉质量。使用独立样本t检验分析了HLS和CON之间的差异。两组之间在任何人口统计学特征上均未观察到显着差异:年龄(P = .922),体重(P = .943),身高(P = .511),体重指数(P = .796),脂肪质量(P = .688),不含脂肪的质量(P = .520)和体内脂肪百分比(P = .446)。在强度(峰值扭矩; P = .552),相对峰值扭矩(P = .200),肌肉厚度(P> .05)和肌肉质量(P> .05)方面,均未观察到显着差异。但是,HLS的自我感觉疲劳明显高于CON(P = .009)。看起来,当HLS通过年龄和身体活动水平与CON相匹配时,在身体组成,肌肉厚度,肌肉质量或强度上均未观察到显着差异。正如预期的那样,HLS中的自我感觉疲劳较高,这可能会产生影响,在为该癌症人群开具运动训练处方时应考虑在内。

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