磁场疗法对人体微循环的生物效应

前言微循环的概念除了血液微循环以外，还包括组织液和淋巴液的微循环。但通常所说的微循环是指研究比较深入的血液微循环。它是在动脉系统的末稍和静脉系统的起始端之间网状毛细血管内的血液循环。微循环这个名词是在１９５４年第一届美国微循环会议上才正式确定和使用。它的基本功能是进行物质（O２、养料·CO２废物）交换。它是血液循环的基本功能单位，同时又有能量、信息传递功能。磁场对人体微循环生物效应微循环的毛细血管组织形态结构特点：口径小，一般为５～２５微米，最小处仅２微米。因此微循环内的血流速度很慢，流动速度仅…     

17β—雌二醇下调血管平滑肌内皮素A型受体的表达

为进一步探讨雌激素对心血管的保护作用,实验在双侧卵巢去势大鼠模型和培养的血管平滑肌细胞（VSMCs)上,观察17β－雌二醇（E2）对血管反应性及VSMCs增殖的影响,以RT－PCR和Western blot检测内皮素受体（ETAR）的表达,结果显示：去势雌性大鼠血管对内皮素（ET－1）的反应性明显增高,ETAR特异性受体阻断剂BQ123能完全阻断ET－1对VSMCs增殖的影响,E2能明显抑制ET－1对VSMCs增殖的作用,RT－PCR结果显示E2能抑制ETAR mRNA的表达,Western blot进一步证实E2能抑制ETAR蛋白表达,E2受体阻断剂Tamoxifen能部分抑制ET－1对VSMCs的增殖及ETAR的mRNA和蛋白 的表达。以上结果提示;ET－1促VSMCs增殖的效应主要是由ETAR介导的,雌激素能通过下调ETAR来抑制ET－1对VSMCs 促增殖的作用和血管对ET－1的反应,且此作用与雌激素受体有关。     

低切应力作用下体外培养动脉内皮细胞内皮素的表达

研究了切应力对完整血管的生物学作用以及应力引起血管重建过程中内皮素(ET)的变化．采用血管体外应力培养系统,将一段完整的猪颈总动脉在体外进行培养,设切应力分别为2Pa(％组)和0．5Pa(S5组),设置2、4、6．8．10．12、14．16和18h共9个时相观察点,非平衡法放射免疫检测灌流液中的ET含量．通过Logistic曲线方程拟合,分析切应力作用下完整动脉ET表达变化规律。结果显示：S20组ET总体变化不明显;S5组分泌速率在前12．37h内明显上升,而后又逐渐下降趋于稳定,且始终高于S20组。说明低切应力作用下ET的表达及分泌增高．结果提示,在低切应力引起的血管重建中,ET可能起着重要作用。     

烷化溶血磷脂对U266 细胞作用的实验研究

为研究烷化溶血磷脂(ET—18-OCH3)对骨髓瘤细胞系U266的体外杀伤作用。通过台盼蓝拒染法和克隆形成率来反映ET—18-OCH3对U266细胞的抗增殖效应;通过荧光显微镜、电镜观察细胞形态学变化,琼脂糖凝胶电泳观察DNA降解片段,流式细胞仪作DNA倍体分析来观察ET—18-OCH3诱导U266细胞凋亡的作用;通过RT—PCR检测bcl-2、c—myc mRNA水平,流式细胞仪检测Bcl-2、C—myc蛋白的表达来初步探讨其相关的作用机制。结果显示．U266细胞经ET—18-OCH3处理后细胞生长明显受抑,呈时间和剂量依赖性;荧光显微镜,电镜下观察均可见凋亡形态学改变,7．5μg／ml ET—18-OCH3作用24小时后出现典型的DNA降解片段。流式细胞仪检测凋亡率为17．53％;RT—PCR显示bcl-2、c-myc mRNA表达均随ET—18-OCH3作用时间的增加而减弱,ET—18-OCH3作用24小时后,bcl-2、c—myc mRNA分别减少了86％、72％;流式细胞仪检测Bcl-2蛋白、C-myc蛋白分别减少了原来的17％、60％。研究结果表明,ET—18-OCH3对U266细胞的生长具有明显的抑制作用,并可诱导细胞的凋亡,具有明显的抗肿瘤效应。     

依托咪酯对成年大鼠脊髓胶状质局部突触传递的作用

应用盲插全细胞膜片钳技术,在成年大鼠脊髓薄片上观察依托咪酯(etomidate,ET)对脊髓胶状质局部突触传递的影响。实验结果显示,在钳制电压为-70mV时,500μmol/L的ET对微小兴奋性突触后电流(mEPSC)的持续时间、频率和幅度都无明显的作用。在钳制电压为0mV时,50μmol/L的ET使GABA能微小抑制性突触后电流(mIPSC)的持续时间延长45.57±12.46%(P<0.05),但对其频率和幅度无影响。同样在钳制电压为0mV的情况下,50μmol/L的ET对甘氨酸能mIPSC的持续时间、频率及幅度均无作用。以上结果表明,在成年大鼠的脊髓胶状质,ET主要通过延长GABA能mIPSC的持续时间,即延长受体通道的开放时间发挥作用,ET对于兴奋性的突触传递没有直接的作用。     

醛固酮对新生大鼠心肌成纤维细胞分泌ET、NO功能的影响

目的: 探讨醛固酮对新生大鼠心肌成纤维细胞(CFs)分泌内皮素(ET)、一氧化氮(NO)的影响.方法: 采用胰酶消化法和差速贴壁分离法获取CFs,应用放射免疫分析法、硝酸还原酶法分别测定不同条件下培养的CFs培养液中的ET、NO水平.结果: 一定浓度范围内的醛固酮可按剂量依赖方式促进CFs分泌ET,抑制CFs分泌NO,使ET/NO比值上升;螺内酯可阻断醛固酮的上述作用(P<0.01).结论: 醛固酮可能通过影响CFs分泌ET、NO,从而改变生物活性物质网络平衡关系,发挥其促心肌纤维化作用.     

盐酸戊乙奎醚对大白兔耳微循环的影响

目的 通过观察盐酸戊乙奎醚(长托宁)注射液对清醒状态大白兔耳微循环的影响,对盐酸戊乙奎醚改善微循环的作用作初步探讨和研究.方法 用微循环观测仪观测用药前大白兔耳廓微循环血管管径、血流速度、血流量等进行综合评估出正常微循环血流指标作为对照,观察盐酸戊乙奎醚用药后对家兔耳微循环血流量变化,并用山莨菪碱作药效对照.结果 两组...     

肾血管性高血压大鼠模型中ET1和CGRP的变化

目的探讨降钙素基因相关肽（CGRP）及血浆内皮素（ET1）在高血压病中的作用。方法选用正常血压大鼠42只,随机分对照组、手术组、假手术组,分别观察血压值、CGRP及ET1值。结果手术组与正常组比较血压明显高于正常对照组（P〈0．01）,假手术组与正常对照组比较,血压无明显变化（P〉0．05）;手术组与对照组比较CGRP显著升高（P〈0．01）;假手术组与正常对照组比较,CGRP未见升高（P〉0．05）。手术组与对照组比较ET1无明显变化（P〉0．05）。结论CGRP在肾血管性高血压的发生发展中具有保护作用。ET1与CGRP是心血管系统中的一对拮抗因子,与CGRP的作用相反,ET1有较强的缩血管作用,从而导致血压升高。     

发现内皮素A型受体拮抗剂

万有制药中央研究所与探索研究所共同从微生物中筛选出与血管内皮细胞产生的血管收缩肽、内皮素(ET)的A型受体(ET_A受体)特异结合、没有生理作用的物质(拮抗剂),并确定了其构造。这一成果为世界首创。通过分子设计开发使受体的亲和性提高140倍的物质,继体外实验之后,小鼠体内试验发现了ET受体拮抗剂的作用。ET受体拮抗剂将来有可能成为与ET有关的高血压和气喘病的治疗药。也可有助于阐明ET和疾患的关系。这项成果已在东京召开的第46届日本生物化学大会上发表。该小组使用大量表达ET_A受体的猪大动脉平滑肌培养细胞,从爱知县土壤中采收的微生物产物中找出     

同型半胱氨酸对血管内皮功能的影响及通心络超微粉的干预作用

目的：观察同型半胱氨酸对血管内皮功能的影响,并探讨通心络超微粉的干预作用。方法：健康雄性Wis-tar大鼠,随机分为对照组、模型组、通心络组。离体主动脉环技术检测血管内皮依赖性舒缩功能,微循环仪观察肠系膜微循环变化,放免方法检测血浆内皮素（ET）、血管紧张素Ⅱ（AngⅡ）、血栓素（TXA2）、前列环素（PGI2）的含量及血清超氧化物歧化酶（SOD）与谷胱苷肽过氧化物酶（GSH-Px）的活性、一氧化氮（NO）及丙二醛（MDA）的含量。结果：与对照组比较,模型组血管内皮依赖性舒张反应明显减弱（p〈0.01）,肠系膜毛细血管对乙酰胆碱的扩张幅度与扩张率显著下降（P〈0.05）。与模型组比较,通心络组血管舒张反应明显改善（P〈0.01）,肠系膜毛细血管对乙酰胆碱反应性升高;与对照组比较,模型组AngⅡ、ET、TXA2含量明显升高（P〈0.05,p〈0.01）,而PGI2含量明显降低（P〈0.05）,同时血清中SOD与GSH-Px活力、NO含量明显降低（P〈0.001,P〈0.05）。与模型组比较,通心络组血浆AngⅡ、ET、TXA2的含量显著降低（P〈0.01）,而PGI2的含量明显升高（P〈0.01）,同时血清中SOD活力与NO含量显著升高（P〈0.01,P〈0.05）。结论：①高同型半胱氨酸血症可使内皮依赖性血管舒缩功能减退,其机制可能与高同型半胱氨酸血症引发血管舒缩因子平衡紊乱及大量自由基的产生有关。②通心络超微粉可使同型半胱氨酸所致血管内皮依赖性舒张功能的异常明显改善,可能与其抑制自由基的过量生成及调节内皮舒缩因子的平衡有关。     

Clustering of dystonia in some pedigrees with autosomal dominant essential tremor suggests the existence of a distinct subtype of essential tremor

Background  

There is an ongoing debate whether essential tremor (ET) represents a monosymptomatic disorder or other neurologic symptoms are compatible with the diagnosis of ET. Many patients with clinically definite ET develop dystonia. It remains unknown whether tremor associated with dystonia represent a subtype of ET. We hypothesized that ET with dystonia represents a distinct subtype of ET.     

fMLP-stimulated release of reactive oxygen species from adherent leukocytes increases microvessel permeability

Our previous study (Am J Physiol Heart Circ Physiol 288: H1331-H1338, 2005) demonstrated that TNF-alpha induced significant leukocyte adhesion without causing increases in microvessel permeability, and that formyl-Met-Leu-Phe-OH (fMLP)-stimulated neutrophils in the absence of adhesion increased microvessel permeability via released reactive oxygen species (ROS). The objective of our present study is to investigate the mechanisms that regulate neutrophil respiratory burst and the roles of fMLP-stimulated ROS release from adherent leukocytes in microvessel permeability. A technique that combines single-microvessel perfusion with autologous blood perfusion was employed in venular microvessels of rat mesenteries. Leukocyte adhesion was induced by systemic application of TNF-alpha. Microvessel permeability was assessed by measuring hydraulic conductivity (L(p)). The 2-h autologous blood perfusion after TNF-alpha application increased leukocyte adhesion from 1.2 +/- 0.2 to 13.3 +/- 1.6 per 100 microm of vessel length without causing increases in L(p). When fMLP (10 microM) was applied to either perfusate (n = 5) or superfusate (n = 8) in the presence of adherent leukocytes, L(p) transiently increased to 4.9 +/- 0.9 and 4.4 +/- 0.3 times the control value, respectively. Application of superoxide dismutase or an iron chelator, deferoxamine mesylate, after fMLP application prevented or attenuated the L(p) increase. Chemiluminescence measurements in isolated neutrophils demonstrated that TNF-alpha alone did not induce ROS release but that preexposure of neutrophils to TNF-alpha in vivo or in vitro potentiated fMLP-stimulated ROS release. These results suggest a priming role of TNF-alpha in fMLP-stimulated neutrophil respiratory burst and indicate that the released ROS play a key role in leukocyte-mediated permeability increases during acute inflammation.     

Gait variability magnitude but not structure is altered in essential tremor

Essential tremor (ET) is a common tremor disorder affecting postural/action tremor of the upper extremities and midline. Recent research revealed a cerebellar-like deficit during tandem gait in persons with ET, though spatiotemporal variability during normal gait in ET has been relatively ignored. The first purpose of this study was to investigate gait variability magnitude and structure in ET as compared to healthy older adults (HOA). To address this issue, 11 ET and 11 age-matched HOAs walked on a treadmill for 5 min at preferred walking speeds. HOAs walked for an additional minute while speed-matched to an ET participant. The second purpose was to describe the clinical correlates of gait variability in this population. To address this aim, 31 persons with ET walked on a treadmill for 5 min and completed the Fahn–Tolosa–Marin Tremor Rating Scale. Gait variability magnitude was derived by calculating coefficients of variation in stride length, stride time, step length, step time, and step width. Gait variability structure was derived using a detrended fluctuation analysis technique. At preferred walking speeds, ET participants walked significantly slower with significantly increased variability magnitude in all five spatiotemporal gait parameters. At speed-matched walking, ET participants exhibited significantly higher step width variability. Gait variability structure was not different between groups. We also observed that gait variability magnitude was predicted by severity of upper extremity and midline tremors. This study revealed that self-selected gait in ET is characterized by high variability that is associated with tremor severity in the upper extremity and midline.     

Xenobiotic export pumps,endothelin signaling,and tubular nephrotoxicants--a case of molecular hijacking

This article is a review on recent studies in intact renal proximal tubules that link tubular nephrotoxicants with endothelin (ET) regulation of xenobiotic export pump function. The data show that transport on p-glycoprotein and Mrp2 decreases rapidly when ET signals through an ET(B) receptor, NO synthase (NOS), and protein kinase C (PKC). Surprisingly, nephrotoxicants, such as radiocontrast agents, aminoglycoside antibiotics, and heavy metal salts, "hijack" this signaling pathway, causing ET release from the tubules, hormone binding to its receptor, activation of NOS and PKC, and reduced xenobiotic transport. These findings suggest a new common mechanism by which nephrotoxicants may act to disrupt renal tubular function.     

Abnormal Regional Homogeneity in Patients with Essential Tremor Revealed by Resting-State Functional MRI

Essential tremor (ET) is one of the most common movement disorders in human adults. It can be characterized as a progressive neurological disorder of which the most recognizable feature is a tremor of the arms or hands that is apparent during voluntary movements such as eating and writing. The pathology of ET remains unclear. Resting-state fMRI (RS-fMRI), as a non-invasive imaging technique, was employed to investigate abnormalities of functional connectivity in ET in the brain. Regional homogeneity (ReHo) was used as a metric of RS-fMRI to assess the local functional connectivity abnormality in ET with 20 ET patients and 20 age- and gender-matched healthy controls (HC). The ET group showed decreased ReHo in the anterior and posterior bilateral cerebellar lobes, the bilateral thalamus and the insular lobe, and increased ReHo in the bilateral prefrontal and parietal cortices, the left primary motor cortex and left supplementary motor area. The abnormal ReHo value of ET patients in the bilateral anterior cerebellar lobes and the right posterior cerebellar lobe were negatively correlated with the tremor severity score, while positively correlated with that in the left primary motor cortex. These findings suggest that the abnormality in cerebello-thalamo-cortical motor pathway is involved in tremor generation and propagation, which may be related to motor-related symptoms in ET patients. Meanwhile, the abnormality in the prefrontal and parietal regions may be associated with non-motor symptoms in ET. These findings suggest that the ReHo could be utilized for investigations of functional-pathological mechanism of ET.     

Nitric oxide and endothelin secretion by brain microvessel endothelial cells: Regulation by cyclic nucleotides

Endothelin (ET)-1 was originally characterized as a potent vasoconstrictor peptide secreted by vascular endothelial cells. It possesses a wide range of biological activities within the cardiovascular system and in other organs, including the brain. Also secreted by endothelial cells, nitric oxide (NO), has recently been identified as a relaxing factor, as well as a pleiotropic mediator, second messenger, immune defence molecule, and neurotransmitter. Most of the data concerning the secretion of these two agents in vitro has been collected from studies on macrovascular endothelial cells. Given the remarkable heterogeneity of endothelia in terms of morphology and function, we have analyzed the ability of brain microvessel endothelial cells in vitro to release ET-1 and NO, which, at the level of the blood-brain barrier, have perivascular astrocytes as potential targets. The present study was performed with immortalized rat brain microvessel endothelial cells, which display in culture a non transformed phenotype. Our data demonstrate that: (1) these cells release NO when induced by IFNγ and TNFα, (2) they constitutively secrete ET-1, and (3) cAMP potentiates the cytokine-induced NO release and exerts a biphasic regulation on ET-1 secretion: micromolar concentrations of 8-Br-cAMP inhibit and higher doses stimulate ET-1 secretion. This stimulation is blocked by EGTA and the calmodulin antagonist W7, but not by protein kinase C inhibitors, suggesting the involvement of the calmodulin branch of the calcium messenger system. These results suggest that cerebral microvessel endothelial cells may participate in vivo to the regulation of glial activity in the brain through the release of NO and ET-1. © 1993 Wiley-Liss, Inc.     

LINGO1 variants in the French-Canadian population

Essential tremor (ET) is a complex genetic disorder for which no causative gene has been found. Recently, a genome-wide association study reported that two variants in the LINGO1 locus were associated to this disease. The aim of the present study was to test if this specific association could be replicated using a French-Canadian cohort of 259 ET patients and 479 ethnically matched controls. Our genotyping results lead us to conclude that no association exists between the key variant rs9652490 and ET (P_corr = 1.00).