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Sabrina P Koh Philip Leadbitter Fiona Smithers 《Expert review of clinical pharmacology》2020,13(8):899-915
ABSTRACT
Introduction
Fifteen percent of proliferating infantile hemangioma (IH) require intervention because of the threat to function or life, ulceration, or tissue distortion. Propranolol is the mainstay treatment for problematic proliferating IH. Other β-blockers and angiotensin-converting enzyme (ACE) inhibitors have been explored as alternative treatments. 相似文献3.
Cathryn M. Kolka 《Clinical and experimental pharmacology & physiology》2020,47(1):168-175
The endocrine system relies on the vasculature for delivery of hormones throughout the body, and the capillary microvasculature is the site where the hormones cross from the blood into the target tissue. Once considered an inert wall, various studies have now highlighted the functions of the capillary endothelium to regulate transport and therefore affect or maintain the interstitial environment. The role of the capillary may be clear in areas where there is a continuous endothelium, yet there also appears to be a role of endothelial cells in tissues with a sinusoidal structure. Here we focused on the most common endocrine disorder, diabetes, and several of the target organs associated with the disease, including skeletal muscle, liver and pancreas. However, it is important to note that the ability of hormones to cross the endothelium to reach their target tissue is a component of all endocrine functions. It is also a consideration in organs throughout the body and may have greater impact for larger hormones with target tissues containing a continuous endothelium. We noted that the blood levels do not always equal interstitial levels, which is what the cells are exposed to, and discussed how this may change in diseases such as obesity and insulin resistance. The capillary endothelium is, therefore, an essential and understudied aspect of endocrinology and metabolism that can be altered in disease, which may be an appropriate target for treatment. 相似文献
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Hale Z Toklu Judy Muller-Delp Zhihui Yang ?ehkar Oktay Yasemin Sakarya Kevin Strang Payal Ghosh Michael D Delp Philip J Scarpace Kevin KW Wang Nihal Tümer 《Journal of cerebral blood flow and metabolism》2015,35(12):1950-1956
Overpressure blast-wave induced brain injury (OBI) leads to progressive pathophysiologic changes resulting in a reduction in brain blood flow, blood brain barrier breakdown, edema, and cerebral ischemia. The aim of this study was to evaluate cerebral vascular function after single and repeated OBI. Male Sprague-Dawley rats were divided into three groups: Control (Naive), single OBI (30 psi peak pressure, 1 to 2 msec duration), and repeated (days 1, 4, and 7) OBI (r-OBI). Rats were killed 24 hours after injury and the basilar artery was isolated, cannulated, and pressurized (90 cm H2O). Vascular responses to potassium chloride (KCl) (30 to 100 mmol/L), endothelin-1 (10−12 to 10−7 mol/L), acetylcholine (ACh) (10−10 to 10−4 mol/L) and diethylamine-NONO-ate (DEA-NONO-ate) (10−10 to 10−4 mol/L) were evaluated. The OBI resulted in an increase in the contractile responses to endothelin and a decrease in the relaxant responses to ACh in both single and r-OBI groups. However, impaired DEA-NONO-ate-induced vasodilation and increased wall thickness to lumen ratio were observed only in the r-OBI group. The endothelin-1 type A (ETA) receptor and endothelial nitric oxide synthase (eNOS) immunoreactivity were significantly enhanced by OBI. These findings indicate that both single and r-OBI impairs cerebral vascular endothelium-dependent dilation, potentially a consequence of endothelial dysfunction and/or vascular remodelling in basilar arteries after OBI. 相似文献
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Nektarios Barabutis 《Clinical and experimental pharmacology & physiology》2020,47(9):1632-1634
Growth hormone–releasing hormone is a hypothalamic neuropeptide, which regulates the secretion of growth hormone by the anterior pituitary gland. Recent evidence suggest that it exerts growth factor activities in a diverse variety of in vivo and in vitro experimental malignancies, which are counteracted by growth hormone–releasing hormone antagonists. Those peptides support lung endothelial barrier integrity by suppressing major inflammatory pathways and by inducing the endothelial defender P53. The present effort provides information regarding the effects of growth hormone–releasing hormone in the regulation of P53 and the unfolded protein response. Furthermore, it suggests the possible application of growth hormone–releasing hormone antagonists towards the management of acute lung injury, including the lethal acute respiratory distress syndrome. 相似文献
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Sowjanya Kallakuri Jianxin A. Yu Jade Li Yuanyuan Li Brant M. Weinstein Stefania Nicoli Zhaoxia Sun 《Journal of the American Society of Nephrology : JASN》2015,26(4):864-875
The cilium is a signaling platform of the vertebrate cell. It has a critical role in polycystic kidney disease and nephronophthisis. Cilia have been detected on endothelial cells, but the function of these organelles in the vasculature remains incompletely defined. In this study, using genetic and chemical genetic tools in the model organism zebrafish, we reveal an essential role of cilia in developmental vascular integrity. Embryos expressing mutant intraflagellar transport genes, which are essential and specific for cilia biogenesis, displayed increased risk of developmental intracranial hemorrhage, whereas the morphology of the vasculature remained normal. Moreover, cilia were present on endothelial cells in the developing zebrafish vasculature. We further show that the involvement of cilia in vascular integrity is endothelial autonomous, because endothelial-specific re-expression of intraflagellar transport genes in respective mutants rescued the intracranial hemorrhage phenotype. Finally, whereas inhibition of Hedgehog signaling increased the risk of intracranial hemorrhage in ciliary mutants, activation of the pathway rescued this phenotype. In contrast, embryos expressing an inactivating mutation in pkd2, one of two autosomal dominant cystic kidney disease genes, did not show increased risk of developmental intracranial hemorrhage. These results suggest that Hedgehog signaling is a major mechanism for this novel role of endothelial cilia in establishing vascular integrity. 相似文献
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目的:研究腺病毒介导的血管内皮因子受体(KDR)启动子-胸苷激酶系统对血管内皮细胞的旁观者效应。方法:采用新型腺病毒载体AdEasy系统,构建由KDR启动子调控的、腺病毒介导的、单纯疱疹病毒胸苷酸激酶基因系统(AdK—DR—HSv-tk),在人胚胎肾细胞系293细胞中包装、扩增后,体外感染表达KDR的人脐静脉血管内皮细胞(HUVEC),建立HUVEC/tk转化细胞株。观察丙氧鸟苷(GCV)对HUVEC、HUVEC/tk细胞的存活率及旁观者效应。结果:从病毒滴度及PCR检查,证实tk基因随病毒的感染已成功地导入293细胞及HUVEC细胞。HUVEC/tk细胞对丙氧鸟苷的敏感性显著高于亲代HUVEC细胞。HUVEC/tk及HUVEC+HUVEC/tk混合细胞还随丙氧乌苷浓度的增加受到明显的抑制。HUVEC+HUVEC/tk混合细胞的存活率,随HUVEC/tk细胞比例的增加而降低,说明腺病毒介导的KDR启动子-单纯疱疹病毒胸苷激酶/丙氧鸟苷系统不但能杀伤tk^+细胞,也能杀伤未导入tk的细胞,存在明显的旁观者效应。结论:腺病毒介导的KDR启动子单纯疱疹病毒胸苷激酶/丙氧乌苷系统对血管内皮细胞具有明显的杀伤及旁观者效应。 相似文献