Glomeruli and microvessels of the rabbit kidney contain both A1- and A2-adenosine receptors

Summary Rabbit renal cortices were fractionated by collagenase dispersion and glomeruli, microvessels and tubuli purified on a discontinuous sucrose gradient. Binding experiments with (–)[¹²⁵I]N⁶-(4-hydroxyphenylisopropyl)-adenosine ([¹²⁵I]HPIA) provided evidence for the presence of A₁-adenosine receptors in the glomerular and microvascular fraction. With glomeruli, saturation isotherms for specific [¹²⁵I]HPIA binding were mono-phasic with a K _D of 1.3 nmol/l and a B _maxof 7.7 fmol/mg protein. In kinetic experiments, an association rate constant of 4.9 × 105 (mol/ 1)^–1 s^–1 and a dissociation rate constant of 4.3 × 10^–4 s^–1 were obtained, yielding a K _D of 0.9 nmol/l. Adenosine analogs displaced [¹²⁵I]HPIA binding with a rank order of potency typical of A₁-adenosine receptors; furthermore, binding was inhibited by methylxanthines and modulated by GTP. Saturation experiments with the microvessels revealed a K _D of 1.9 nmol/l and a B _max of 13.4 fmol/mg protein. However, no inhibition of glomerular and microvascular adenylate cyclase activity could be demonstrated, but instead both 5-N-ethylcarboxamido-adenosine (NECA) and N⁶-(R-phenylisopropyl)-adenosine (R-PIA) stimulated enzyme activity, with EC₅₀ values of 0.14 mol/l and 1.5 mol/l, respectively. The concentration-response curve for NECA was shifted to the right (factor 9) by 10 mol/l 8-phenyltheophylline. On the other hand, computer simulation of biphasic curves (adenylate cyclase inhibition in the presence of activation via a stimulatory receptor) indicates that the failure to observe an A₁-adenosine receptor-mediated inhibition of adenylate cyclase activity in the presence of stimulatory adenosine receptors may be attributable to methodological constraints. The results demonstrate that both A₁- and A₂-adenosine receptors are present in rabbit glomeruli and microvessels. It is suggested that both receptors are involved in the control of renin secretion.Abbreviations R-PIA (–)N⁶(R-phenylisopropyl)-adenosine - NECA 5-(N-ethyl-carboxamido)-adenosine - S-PIA (+)N⁶-(S-phenylisopropyl)-adenosine - I-HPIA (–)N⁶-(3-iodo-4-hydroxy-phenylisopropyl)-adenosine - HPIA (–)N⁶-(4-hydroxyphenylisopropyl)-adenosine - [¹²⁵I]HPIA (–)N6-(3-[¹²⁵I]iodo-4-hydroxy-phenylisopropyl)-adenosine - ATP adenosine-5-triphosphate - cAMP cyclic 3,5-adenosine-monophosphate - GTP guanosine-5-triphosphate - HEPES 4-(2-hydroxyethyl)-1-piperazine-ethanesulfonic acid - EDTA (ethylenedinitrilo)-tetraacetic acid Send offprint requests to W. Schütz at the above addressThis study was supported by the Fonds zur Förderung der wissenachiftlichen Forschung in Österreich (Project 5712)     

原发性肝细胞癌微血管侵犯的术前预测模型构建及临床意义

目的构建原发性肝细胞癌(HCC)微血管侵犯(MVI)的术前预测模型并验证其准确性。方法回顾性分析2017年1月至2019年6月行肝切除术的160例HCC患者的临床病理资料,观察患者MVI情况。采用SPSS20.0软件对数据进行处理分析,计数资料采用χ^2检验;计量资料采用t检验;采用单因素和多因素Logistic回归分析影响MVI的独立危险因素,并构建HCC患者MVI的术前预测模型,通过描绘受试者工作特征曲线(ROC)并计算曲线下面积(AUC)从而来评估模型的预测能力,并以术后病理诊断结果为金标准对预测模型进行验证。结果在160例患者中,有MVI者86例,无MVI者74例。对单因素分析有统计学意义的资料进行Logistic多因素分析,结果显示:肿瘤直径、瘤周低回声晕环、甲胎蛋白(AFP)水平、血小板与淋巴细胞比值(PLR)水平、循环肿瘤DNA(ctDNA)浓度是HCC的MVI独立危险因素。根据Logistic回归分析各变量的回归系数构建预测模型,通过绘制ROC曲线,计算出AUC值为0.914(95%CI 0.820~0.962),当最佳临界值为0.069时对HCC患者MVI具有预测价值,灵敏度为86.5%,特异度为87.9%,约登指数为0.74。以术后病理诊断为金标准,验证预测模型,灵敏度为88.4%,特异度为93.2%,两者灵敏度和特异度无统计学差异(P>0.05)。结论基于Logistic多因素回归分析建立预测模型具有较高的灵敏度和特异性,对HCC微血管侵犯的患者具有较高的预测价值,可为HCC患者的术前治疗方案、手术规划提供参考。     

脑梗死后微血管渗透性改变及出血性转化的预测

目的探讨缺血性脑梗死后急性期和亚急性期微血管渗透性改变及脑梗死后出血性转化(hemorrhagic transformation,HT)的预测。材料与方法收集缺血性脑梗死病人43例,急性期10例,亚急性期33例,进行常规MRI及DCE-MRI扫描。利用药代动力学模型计算容积转运常数Ktrans,比较每一个病人梗死区和对侧正常脑组织的Ktrans值以及出血组和非出血组的Ktrans值有无差异,比较不同时期梗死区强化对预测HT的意义。结果所有病人梗死区Ktrans值较对侧正常脑组织明显增高(P0.05)。10例在急性期有脑实质强化的病人都有继发出血,在亚急性期和慢性期15例病人有继发出血,18例没有继发出血,Fisher's精确检验有统计学意义(P0.05)。与亚急性期HT或没有HT的病人相比,急性期有HT组病人的Ktrans值明显增高(P0.05),但是亚急性期HT和非HT的病人Ktrans值比较没有统计学差异(P0.05)。结论急性期脑实质强化对HT的预测有更高的特异性,且渗透性比亚急性期更高。早期脑实质强化及HT与毛细血管内皮的紧密连接和基底膜损伤有关。后期脑实质强化及HT与侧枝循环的建立有关,DCE-MRI可以定量评估血脑屏障的渗透性,对进一步研究HT的分型提供更科学的依据。     

血液稀释造成家兔低血压后电针的升压效应

本实验在麻醉的家兔上进行。结果发现，３０％急性失血组补给生理盐水仪血液等容稀释造成家兔低血压后再电针“足三里”穴，具有明显的升压作用（Ｐ＜０．０１）和心率稍减慢，眼结膜微血管血流有加速，血管口径稍有变大，这是血液稀释加电针的作用．５０％急性失血组补给生理盐水等容稀释使血压降低后再电针已不具有升压作用，但能维持血压在一定水平，心率加快，眼结膜微血管血流变慢（Ｐ＜０．０１），部分管径关闭。     

Cerebral microvessel perfusion and pathologic alteration of the brain during drowsiness and coma caused by brain tumor: a laboratory study on rats

BACKGROUND: In cerebral compression, deterioration of consciousness and coma are traditionally thought to be caused by compression, shift, hemorrhage, or herniation of the brain stem. The objective of this study was to evaluate vascular perfusion and pathologic alteration in the entire brain during drowsiness and coma. METHODS: Brain tumors were developed in 3 newborn rat litters by inoculation of KSV (a murine erythroblastosis virus) into their brain. Within several weeks, brain tumors developed. When the animals became drowsy or comatose, their brains were perfused with microbarium, India ink, or paraformaldehyde solution. In 2 animals, the brain vasculature was casted with plastic materials. The brains were either fixed for magnification radiography or prepared for histologic examination. RESULTS: The brains of control animals showed an abundance of microvessels and penetrating capillaries located perpendicular to the cortex and deep within the brain. The latter entities cannot be detected even in the best routine cerebral angiography in human beings. Microvessels were obstructed, in a patchy and dispersed fashion, during drowsiness, especially in the ipsilateral hemisphere. Obstruction of microvessels was present not only in the brain stem but also in the rest of the brain and in the cerebellum of comatose animals; larger vessels appeared to be markedly narrowed. The study also revealed evidence of diffuse infarcts, cellular ischemia, swelling, and periventricular damage throughout the brain. CONCLUSIONS: During drowsiness and coma caused by cerebral compression, cerebral capillaries progressively obstruct not only in the brain stem but also throughout the brain, considerably in a more severe pattern during coma than during drowsiness. These likely cause the diffuse neurologic disabilities and behavioral changes often seen after recovery from coma caused by cerebral compression.     

Inflammatory factors are elevated in brain microvessels in Alzheimer’s disease

In Alzheimer’s disease (AD) inflammatory processes occur in pathologically vulnerable brain regions. The objective of this study is to compare both the release and the presence of microvessel-associated cytokines in vessels isolated from the brains of AD patients to microvessels from control brains. Microvessels are isolated from the cortices of AD patients and age-matched controls, without evidence of neurodegenerative disease. Inflammatory factors in the media are quantitated by ELISA and microvessel-associated mediators assessed by Western blot. Our results demonstrate that unstimulated AD microvessels release significantly higher levels of interleukin-1β-(IL-1β), IL-6, and tumor necrosis factor (TNF-) compared to non-AD microvessels. Levels of microvessel-associated monocyte chemoattractant protein (MCP-1) and IL-1β are high in AD-derived microvessels, but not detectable in non-AD microvessels. These results suggest that the cerebral microcirculation contributes inflammatory mediators to the milieu of the AD brain and may be involved in the pathogenesis of neuronal injury and death in this disorder.     

椎间盘退变与终板内微血管形态改变的相关性研究

目的:通过观测大白兔椎间盘退变过程中椎间盘终板内的血管形态以及血流量的改变,探讨终板内微血管的改变与椎间盘退变之间的相关性。方法:选用40只新西兰大白兔随机分为2组,通过切除造模组20只免腰椎棘间、棘上韧带及棘突、关节突,造成力学失稳状态诱导形成椎间盘退变模型。分别在术后4、8个月通过扫描电镜、血流激光多普勒仪测定椎体终板内的血管形态以及血流量。结果:在椎间盘退变过程中,椎间盘终板内的血管芽形态逐渐被破坏,微血管数量相应减少,终板内的血流量也明显减少,同时终板内血流量中心部位(靠近髓核区域)血流量多于终板内周围区域的血流量。结论:椎体终板内微血管的改变可能是椎间盘退变的促进因素。     

Age-related microvascular degeneration in the human cerebral periventricular white matter

Clinical studies have identified white matter (WM) lesions as hyperintensive regions in the MRI images of elderly patients. Since a cerebrovascular origin was attributed to such lesions, the present analysis set out to define the microvascular histopathologic changes in the periventricular WM in the aged. Post-mortem samples of the frontal, parietal, and occipital periventricular WM of 40–90-year-old subjects were prepared for quantitative light and electron microscopy. Light microscopic examination revealed microvascular fibrohyalinosis as the most common type of microvascular damage in the elderly. Ultrastructural analysis identified the microvascular thickening as collagen deposits affecting the basement membrane. The vascular density did not correlate with the age. The basement membrane pathology significantly increased, while the number of intact microvessels gradually decreased, with advancing age in the frontal and occipital WM. Finally, peripheral atherosclerosis coincided with massive microvascular fibrosis, particularly in the frontal WM. Our results demonstrate an age-related microvascular degeneration in the periventricular WM, which may contribute to the development of WM lesions by hindering a sufficient supply of nutrients to the affected WM sites. Furthermore, the data accord with previous observations identifying the frontal lobe as the site at which WM vulnerability is most pronounced. Finally, atherosclerosis in large, peripheral vessels is considered to be a predictive marker of microvascular pathology in the WM.     

淋巴管与微血管密度在乳腺癌患者预后中的意义

目的 探讨淋巴管密度和微血管密度在乳腺癌预后中的意义.方法 选择69例乳腺浸润性导管癌标本,应用免疫组织化学SP染色法用D240、CD31分别标记淋巴管和微血管后进行密度计数,对淋巴管密度（lymphatic vessel density,LVD）、微血管密度（microvessel density,MVD）与临床病理特征及患者的预后关系进行统计学分析.结果 肿瘤周围淋巴管密度（peri-lymphatic vessel density,P-LVD）明显高于肿瘤内淋巴管密度（intra-lymphatic vessel density,I-LVD）及对照组淋巴管密度（P＜0.01）.I-LVD与患者年龄、肿块大小、组织学分级、淋巴管浸润、淋巴结转移、雌激素受体（estrogen receptor,ER）,孕激素受体（progesterone receptor,PR）及人类表皮生长因子受体2（human epidermal growth factor receptor-2,HER2）的表达等临床病理因素无关（P＞0.05）,而P-LVD与淋巴结转移,肿瘤的临床分期密切相关（P =0.003、0.026）,MVD仅与临床分期密切相关（P=0.038）.在生存分析中发现P-LVD、MVD与患者的总生存期、无病生存期密切相关（P =0.007、0.008、0.014、0.024,log-rank检验）,多因素分析提示P-LVD、MVD是患者总生存期的独立预后因素.结论 乳腺癌P-LVD、MVD与患者的预后密切相关,通过定量分析,P-LVD、MVD可预测乳腺癌患者的预后.     

三叉神经痛与三叉神经及血管关系的MRI表现相关研究

目的:探讨MRI显示血管神经关系对三叉神经痛的诊断价值。方法:对50例三叉神经痛患者行常规MRI扫描和三维时间飞跃-扰相梯度回波(3D-TOF-SPGR)序列薄层扫描,观察双侧三叉神经周围是否存在血管影,并测定双侧三叉神经长轴与邻近血管的距离。结果:常规MRI扫描发现有三叉神经痛症状的一侧血管压迫神经阳性率60%,非疼痛侧阳性率6%;3D-TOF-SPGR序列扫描发现疼痛侧神经血管神经接触或受压变形阳性率84%,非疼痛侧阳性率8%。结论:MRI诊断三叉神经痛具有较高的临床价值。对微小血管的显示方面,3D-TOF-SPGR序列扫描优于常规MRI扫描。