Flow control among microvessels coordinated by intercellular conduction

Optimal distribution of blood flow requires coordination of vasodilation among resistance vessels. During hyperemia, blood vessels dilate upstream from the initiating stimulus. Spreading vasodilation independent of flow changes has not been previously demonstrated. In the present study, iontophoresis of acetylcholine adjacent to single hamster cheek pouch arterioles in situ (diameter, 20 to 37 micrometers) induced a rapid bidirectional dilation that was not attenuated when blood flow was eliminated with vascular occlusion. This finding indicates that a vasodilatory stimulus is conducted along the arteriole and demonstrates the existence of a mechanism of intercellular communication that is capable of coordinating diameter changes among resistance vessels.     

Tumor angiogenesis. Gene expression patterns identified

Researchers have obtained the most detailed sketch yet of how cancerous tumors secure the blood supplies that nourish their growth. On page 1197, a team reports the results of a large-scale comparison of the genes expressed in the blood vessels of human colon cancers and of normal colon tissue. They've found that the gene expression patterns of the two types of vasculature are distinctly different. The findings could help researchers develop new anticancer drugs that work by homing in on the protein products of genes that are overexpressed in tumor vessels, thus shutting off the growth of blood vessels the tumor needs to survive.     

Brain blood flow: alteration by prior exposure to a learned task

Chicks with the eyelids of one eye sutured were trained to discriminate between grains and pebbles. The learned experience was completely recognizable by the naive eye that had been occluded during training. When both eyes were opened after monocular training, the velocity of blood flow through paired left and right brain regions was identical. However, when chicks were reexposed to the discrimination situation, blood flow through the cerebral hemisphere associated with the naive eye was greater than that through the hemisphere associated with the trained eye.     

Does the release of potassium from astrocyte endfeet regulate cerebral blood flow?

Local increases in neuronal activity within the brain lead to dilation of blood vessels and to increased regional cerebral blood flow. Increases in extracellular potassium concentration are known to dilate cerebral arterioles. Recent studies have suggested that the potassium released by active neurons is transported through astrocytic glial cells and released from their endfeet onto blood vessels. The results of computer simulations of potassium dynamics in the brain indicate that the release of potassium from astrocyte endfeet raises perivascular potassium concentration much more rapidly and to higher levels than does diffusion of potassium through extracellular space, particularly when the site of a potassium increase is some distance from the vessel wall. On the basis of this finding, it is proposed that the release of potassium from astrocyte endfeet plays an important role in regulating regional cerebral blood flow in response to changes in neuronal activity.     

Regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk

Lymphatic vessels develop from specialized endothelial cells in preexisting blood vessels, but the molecular signals that regulate this separation are unknown. Here we identify a failure to separate emerging lymphatic vessels from blood vessels in mice lacking the hematopoietic signaling protein SLP-76 or Syk. Blood-lymphatic connections lead to embryonic hemorrhage and arteriovenous shunting. Expression of slp-76 could not be detected in endothelial cells, and blood-filled lymphatics also arose in wild-type mice reconstituted with SLP-76-deficient bone marrow. These studies reveal a hematopoietic signaling pathway required for separation of the two major vascular networks in mammals.     

Induction of pancreatic differentiation by signals from blood vessels

Blood vessels supply developing organs with metabolic sustenance. Here, we demonstrate a role for blood vessels as a source of developmental signals during pancreatic organogenesis. In vitro experiments with embryonic mouse tissues demonstrate that blood vessel endothelium induces insulin expression in isolated endoderm. Removal of the dorsal aorta in Xenopus laevis embryos results in the failure of insulin expression in vivo. Furthermore, using transgenic mice, we show that ectopic vascularization in the posterior foregut leads to ectopic insulin expression and islet hyperplasia. These results indicate that vessels not only provide metabolic sustenance, but also provide inductive signals for organ development.     

南极独角雪冰鱼(Chionodraco hamatus)miR-204对斑马鱼胚胎血管发育的作用机制研究

南极独角雪冰鱼（Chionodraco hamatus）是目前已知的唯一缺乏血红蛋白、且不具有功能性血红细胞的脊椎动物。与相同生境下的其他南极鱼相比,其血管明显变粗,毛细血管增多。前期对南极独角雪冰鱼与近缘种伯氏肩孔南极鱼（Trematomus bernacchii）的血管microRNAs表达进行对比,发现南极独角雪冰鱼的miR-204的表达与伯氏肩孔南极鱼间存在显著差异,推测miR-204极有可能参与了南极冰鱼血管发育的调控。为证明此假设,运用斑马鱼（Barchydanio rerio）这一模式生物,利用斑马鱼胚胎显微注射技术、靶基因预测、双荧光素酶报告系统等一系列分子生物学手段对miR-204在斑马鱼血管发育中的调控作用进行探究。结果显示,抑制miR-204表达能使斑马鱼胚胎躯干部毛细血管增生。荧光素酶活性分析表明,miR-204可以显著降低trib3的表达,同时在斑马鱼胚胎中共注射miR-204和trib3后的GFP萤光强度显著降低,GFP蛋白量减少,说明miR-204对trib3有抑制作用。trib3最初发现是抑制果蝇胚胎和生殖细胞有丝分裂的假激酶,后续研究发现其参与动脉粥样硬化的调控以及糖尿病血管纤维化。综上,推测miR-204可能通过抑制trib3的表达进而调控毛细血管的增生。     

Blood flow measured by Doppler frequency shift of back-scattered ultrasound

The Doppler shift of ultrasound, scattered from moving elements within a stream of blood, is related to the velocity of blood flow. A flowmeter based on this principle has been constructed and was used to record blood flow through intact vessels in dogs.     

粉拟青霉菌对鹌鹑安全性的研究

用粉拟青霉(Paecilomyces farinosus)纯孢子对鹌鹑做了急性、亚急性喂食实验、急性腹腔注射实验及对眼和皮肤的刺激性实验,结果来出现死亡。动物的外观、行为、体重的增加、产蛋量和血液生化指标基本正常。孢子被食入或注入腹腔内72～96小时即失去生命力,不能生长繁殖。肉眼观察鹌鹑内脏组织及病理切片检查均未发现异常。孢子对眼和皮肤亦无刺激性。本文认为该菌对鹌鹑基本上是安全的。     

Receptor-mediated transport of insulin across endothelial cells

Hormones such as insulin are transported from the interior to the exterior of blood vessels. Whether endothelial cells, which line the inner walls of blood vessels have a role in this transport of hormones is not clear, but it is known that endothelial cells can internalize and release insulin rapidly with little degradation. The transport of iodine-125-labeled insulin was measured directly through the use of dual chambers separated by a horizontal monolayer of cultured bovine aortic endothelial cells. In this setting, endothelial cells took up and released the labeled insulin, thereby transporting it across the cells. The transport of insulin across the endothelial cells was temperature sensitive and was inhibited by unlabeled insulin and by antibody to insulin receptor in proportion to the ability of these substances to inhibit insulin binding to its receptor. More than 80 percent of the transported insulin was intact. These data suggest that insulin is rapidly transported across endothelial cells by a receptor-mediated process.     

Tumor regression by targeted gene delivery to the neovasculature

Efforts to influence the biology of blood vessels by gene delivery have been hampered by a lack of targeting vectors specific for endothelial cells in diseased tissues. Here we show that a cationic nanoparticle (NP) coupled to an integrin alphavbeta3-targeting ligand can deliver genes selectively to angiogenic blood vessels in tumor-bearing mice. The therapeutic efficacy of this approach was tested by generating NPs conjugated to a mutant Raf gene, ATPmu-Raf, which blocks endothelial signaling and angiogenesis in response to multiple growth factors. Systemic injection of the NP into mice resulted in apoptosis of the tumor-associated endothelium, ultimately leading to tumor cell apoptosis and sustained regression of established primary and metastatic tumors.     

内皮祖细胞生物学特性及其对改善新血管形成的影响

内皮祖细胞(Endothelial progenitor ceils,EPCs)是可以直接分化为血管内皮细胞的一种前体细胞.当机体受到损伤、缺血或是在药物等外界因素刺激下都可动员骨髓内的内皮祖细胞参与到机体的内循环.内皮祖细胞可以通过旁分泌促血管生成因子来促进管腔直接进入发芽状态的新生血管来调节血管生成.该文综述了EPC的来源、分离培养、数量的影响因素及其对血管生成作用等几个方面.     

Blood cells preserved in a mummy 2000 years old

Structures resembling red blood cells have been seen in mummies, but have been considered by some to be artifacts or molds. The finding of these structures, admixed with white blood cells, in the blood vessels of a mummified American Indian, confirms the original interpretation of preserved red blood cells.     

Shear-activated nanotherapeutics for drug targeting to obstructed blood vessels

Obstruction of critical blood vessels due to thrombosis or embolism is a leading cause of death worldwide. Here, we describe a biomimetic strategy that uses high shear stress caused by vascular narrowing as a targeting mechanism--in the same way platelets do--to deliver drugs to obstructed blood vessels. Microscale aggregates of nanoparticles were fabricated to break up into nanoscale components when exposed to abnormally high fluid shear stress. When coated with tissue plasminogen activator and administered intravenously in mice, these shear-activated nanotherapeutics induce rapid clot dissolution in a mesenteric injury model, restore normal flow dynamics, and increase survival in an otherwise fatal mouse pulmonary embolism model. This biophysical strategy for drug targeting, which lowers required doses and minimizes side effects while maximizing drug efficacy, offers a potential new approach for treatment of life-threatening diseases that result from acute vascular occlusion.     

THE NATURAL OCCURRENCE OF RIBOFLAVIN DEFICIENCY IN THE EYES OF DOGS

In four dogs, the diarrhea, increased salivation and mucous membrane lesions characteristic of blacktongue were relieved within 24 hours following the administration of 150 mgs nicotinic amide, whereas the lacrimation, photophobia and extreme injection of the eye vessels did not diminish. These severe eye lesions regressed greatly 24 hours after the injection of 50 mgs of riboflavin, and in 72 hours had disappeared. The simultaneous occurrence of nicotinic acid and riboflavin deficiency in four dogs is evidence that such deficiencies occur as mixed diseases rather than as single entities. These findings are further evidence of the universality of nutritional deficiencies, since they suggest that deficiency diseases among the pets of families with deficiency diseases are not uncommon. In at least one instance the finding of nutritional deficiencies in a dog eating scraps from the family table led to a better understanding of the ill health of the family, none of whom had diagnostic lesions of deficiency disease at the time, although they all complained of weakness, nervousness, irritability and loss of appetite-the vague and ill-defined symptoms characteristic of deficiency diseases in the early stages.     

Liver organogenesis promoted by endothelial cells prior to vascular function

The embryonic role of endothelial cells and nascent vessels in promoting organogenesis, prior to vascular function, is unclear. We find that early endothelial cells in mouse embryos surround newly specified hepatic endoderm and delimit the mesenchymal domain into which the liver bud grows. In flk-1 mutant embryos, which lack endothelial cells, hepatic specification occurs, but liver morphogenesis fails prior to mesenchyme invasion. We developed an embryo tissue explant system that permits liver bud vasculogenesis and show that in the absence of endothelial cells, or when the latter are inhibited, there is a selective defect in hepatic outgrowth. We conclude that vasculogenic endothelial cells and nascent vessels are critical for the earliest stages of organogenesis, prior to blood vessel function.     

Reductions in arterial diameter produced by chronic decreases in blood flow are endothelium-dependent

A 70 percent reduction in the rate of blood flow through the common carotid artery in rabbits caused a 21 percent decrease in the diameter of this artery within 2 weeks. The smooth muscle relaxant papaverine did not attenuate the response; therefore, such reductions in diameter probably reflect a structural modification of the arterial wall rather than sustained contraction of smooth muscle. This arterial response to reduced blood flow was abolished when the endothelium was removed from the vessels. It appears that the endothelium is essential for the compensatory arterial response to long-term changes in luminal blood flow rates.     

非洲鸵鸟食管组织学观察

应用常规石蜡切片,H—E染色,对非洲鸵鸟食管组织结构进行观察并与家禽和哺乳动物的食管进行比较．结果表明：非洲鸵鸟食管黏膜上皮为复层扁平上皮,但角质化不明显,固有膜内食管腺丰富,由腺细胞围成的管泡状腺直接开口于黏膜上皮,分泌大量黏液．食管肌层非常发达,分为内环肌、中纵肌、外环肌3层,环肌很厚,与纵肌的比例约为3：1、外膜是一层薄的纤维膜,内含丰富的血管．淋巴组织和神经.     

Leakage-resistant blood vessels in mice transgenically overexpressing angiopoietin-1

Angiopoietin-1 (Ang1) and vascular endothelial growth factor (VEGF) are endothelial cell-specific growth factors. Direct comparison of transgenic mice overexpressing these factors in the skin revealed that the VEGF-induced blood vessels were leaky, whereas those induced by Ang1 were nonleaky. Moreover, vessels in Ang1-overexpressing mice were resistant to leaks caused by inflammatory agents. Coexpression of Ang1 and VEGF had an additive effect on angiogenesis but resulted in leakage-resistant vessels typical of Ang1. Ang1 therefore may be useful for reducing microvascular leakage in diseases in which the leakage results from chronic inflammation or elevated VEGF and, in combination with VEGF, for promoting growth of nonleaky vessels.     

Chronic effects of osmotic opening of the blood-brain barrier in the monkey

In the monkey, the blood-brain barrier and the blood-aqueous and blood-vitreous barriers of the eye can be opened by internal carotid perfusion of solutions of 2 molar urea in a way compatible with survival and, in some few cases, without detectable neurological deficits. Urea presumably acts by osmotically shrinking the endothelial cells of the cerebrovascular vessels and opening their tight junctions. The high incidence of brain necrosis with neurological sequelae after perfusion of urea by the present technique precludes the use of osmotic opening of the blood-brain barrier for pharmacotherapy at this time.