Sample records for vascular permeability index

  1. Monitoring pulmonary vascular permeability using radiolabeled transferrin

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Basran, G.S.; Hardy, J.G.

    1988-07-01

    A simple, noninvasive technique for monitoring pulmonary vascular permeability in patients in critical care units is discussed. High vascular permeability is observed in patients with clinically defined adult respiratory distress syndrome (ARDS) but not in patients with hydrostatic pulmonary edema or in patients with minor pulmonary insults who are considered to be at risk of developing ARDS. The technique has been used in the field of therapeutics and pharmacology to test the effects of the putative antipermeability agents methylprednisolone and terbutaline sulfate. There appears to be a good correlation between the acute inhibitory effect of either drug on transferrin exudationmore » and patient prognosis. Thus, a byproduct of such drug studies may be an index of survival in patients with established ARDS.« less

  2. Extravascular lung water and the pulmonary vascular permeability index may improve the definition of ARDS.

    PubMed

    Perel, Azriel

    2013-01-24

    The recent Berlin definition has made some improvements in the older definition of acute respiratory distress syndrome (ARDS), although the concepts and components of the definition remained largely unchanged. In an effort to improve both predictive and face validity, the Berlin panel has examined a number of additional measures that may reflect increased pulmonary vascular permeability, including extravascular lung water. The panel concluded that although extravascular lung water has improved face validity and higher values are associated with mortality, it is infeasible to mandate on the basis of availability and the fact that it does not distinguish between hydrostatic and inflammatory pulmonary edema. However, the results of a multi-institutional study that appeared in the previous issue of Critical Care show that this latter reservation may not necessarily be true. By using extravascular lung water and the pulmonary vascular permeability index, both of which are derived from transpulmonary thermodilution, the authors could successfully differentiate between patients with ARDS and other patients in respiratory failure due to either cardiogenic edema or pleural effusion with atelectasis. This commentary discusses the merits and limitations of this study in view of the potential improvement that transpulmonary thermodilution may bring to the definition of ARDS.

  3. Pathophysiological consequences of VEGF-induced vascular permeability

    NASA Astrophysics Data System (ADS)

    Weis, Sara M.; Cheresh, David A.

    2005-09-01

    Although vascular endothelial growth factor (VEGF) induces angiogenesis, it also disrupts vascular barrier function in diseased tissues. Accordingly, VEGF expression in cancer and ischaemic disease has unexpected pathophysiological consequences. By uncoupling endothelial cell-cell junctions VEGF causes vascular permeability and oedema, resulting in extensive injury to ischaemic tissues after stroke or myocardial infarction. In cancer, VEGF-mediated disruption of the vascular barrier may potentiate tumour cell extravasation, leading to widespread metastatic disease. Therefore, by blocking the vascular permeability promoting effects of VEGF it may be feasible to reduce tissue injury after ischaemic disease and minimize the invasive properties of circulating tumour cells.

  4. [Prognostic value of extra-vascular lung water index and pulmonary vascular permeability index in patients with ARDS].

    PubMed

    Liu, Danqin; Zeng, Weixian; Zhou, Wangfeng; Dai, Yuanrong

    2015-11-24

    To investigate the correlation of the extra-vascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI) with disease severity and their prognostic value in patients with acute respiratory distress syndrome (ARDS). A total of 44 patients with ARDS from October 2012 to June 2014 admitted in the Second Affiliated Hospital of Wenzhou Medical University were recruited in this study. According to the severity, patients were divided into three groups (Mild group, Moderate group and Severe group); the acute physiology and chronic health evaluation system II score (APACHE II), the lung injury score (LIS), the pulse contour curve continuous cardiac output (PiCCO) and other clinical indicators were respectively monitored in the period of 24, 48, 72 hrs after admission; then the correlation of EVLWI, PVPI and oxygenation index (OI) among groups were analyzed; According to the prognosis, patients were divided into the survival group and the death group, both given the univariate and multivariate Logistic regression analysis; EVLWI, PVPI, APACHE II score, LIS and lactic acid were admitted into the receiver operating characteristic (ROC) curve analysis, and the prognosis was evaluated respectively. With the increase of disease severity, LIS and lactic acid gradually increased, the difference was significant among the three groups of Mild, Moderate and Severe (P<0.05). And the APACHE II score also increased gradually with the severity, but the difference was statistically significant only between the Mild group and the Severe group (P<0.01). And likewise, mild, moderate, severe ARDS patients had 1, 6, 9 cases of death, respectively. The 28-day mortality rate increased gradually after admission, with a significant difference between the Mild group and the Severe group (P<0.05). When all the 44 patients of three severities (during the 24 hrs period and during the 72 hrs period) were compared, the OI gradually decreased with the increase of severity of ARDS

  5. Strategies for improving chemotherapeutic delivery to solid tumors mediated by vascular permeability modulation

    NASA Astrophysics Data System (ADS)

    Roy Chaudhuri, Tista

    An essential mode of distribution of blood-borne chemotherapeutic agents within a solid tumor is via the micro-circulation. Poor tumor perfusion, because of a lack of functional vasculature or a lack of microvessels, as well as low tumor vascular permeability, can prevent adequate deposition of even low molecular-weight agents into the tumor. The modulation of tumor vascular function and density can provides numerous strategies for improving intratumor deposition of chemotherapeutic agents. Here we investigated strategies to improve drug delivery to two tumor types that share in common poor drug delivery, but differ in the underlying cause. First, in an angiogenesis-driven brain tumor model of Glioblastoma, the vascular permeability barrier, along with poorly-functional vasculature, hinders drug delivery. A strategy of nanoparticle-based tumor 'priming' to attack the vascular permeability barrier, employing sterically stabilized liposomal doxorubicin (SSL-DXR), was investigated. Functional and histological evaluation of tumor vasculature revealed that after an initial period of depressed vascular permeability and vascular pruning 3--4 days after SSL-DXR administration, vascular permeability and perfusion were restored and then elevated after 5--7 days. As a result of tumor priming, deposition of subsequently-administered nanoparticles was enhanced, and the efficacy of temozolomide (TMZ), if administered during the window of elevated permeability, was increased. The sequenced regimen resulted in a persistent reduction of the tumor proliferative index and a 40% suppression of tumor volume, compared to animals that received both agents simultaneously. Second, in a hypovascular, pancreatic ductal adenocarcinoma model, disruption of tumor-stromal communication via sonic hedgehog (sHH) signaling pathway inhibition mediated an indirect vascular proliferation and a more than 2-fold increase in intratumor nanoparticle deposition. Enhanced delivery of SSL-DXR in tumors pre

  6. Sensing of Vascular Permeability in Inflamed Vessel of Live Animal.

    PubMed

    Park, Sang A; Jeong, Soi; Choe, Young Ho; Hyun, Young-Min

    2018-01-01

    Increase in vascular permeability is a conclusive response in the progress of inflammation. Under controlled conditions, leukocytes are known to migrate across the vascular barriers to the sites of inflammation without severe vascular rupture. However, when inflammatory state becomes excessive, the leakage of blood components may occur and can be lethal. Basically, vascular permeability can be analyzed based on the intensity of blood outflow. To evaluate the amount and rate of leakage in live mice, we performed cremaster muscle exteriorization to visualize blood flow and neutrophil migration. Using two-photon intravital microscopy of the exteriorized cremaster muscle venules, we found that vascular barrier function is transiently and locally disrupted in the early stage of inflammatory condition induced by N-formylmethionyl-leucyl-phenylalanine (fMLP). Measurement of the concentration of intravenously (i.v.) injected Texas Red dextran inside and outside the vessels resulted in clear visualization of real-time increases in transient and local vascular permeability increase in real-time manner. We successfully demonstrated repeated leakage from a target site on a blood vessel in association with increasing severity of inflammation. Therefore, compared to other methods, two-photon intravital microscopy more accurately visualizes and quantifies vascular permeability even in a small part of blood vessels in live animals in real time.

  7. Effect of electromagnetic pulse exposure on brain micro vascular permeability in rats.

    PubMed

    Ding, Gui-Rong; Li, Kang-Chu; Wang, Xiao-Wu; Zhou, Yong-Chun; Qiu, Lian-Bo; Tan, Juan; Xu, Sheng-Long; Guo, Guo-Zhen

    2009-06-01

    To observe the effect of electromagnetic pulse (EMP) exposure on cerebral micro vascular permeability in rats. The whole-body of male Sprague-Dawley rats were exposed or sham exposed to 200 pulses or 400 pulses (1 Hz) of EMP at 200 kV/m. At 0.5, 1, 3, 6, and 12 h after EMP exposure, the permeability of cerebral micro vascular was detected by transmission electron microscopy and immunohistochemistry using lanthanum nitrate and endogenous albumin as vascular tracers, respectively. The lanthanum nitrate tracer was limited to the micro vascular lumen with no lanthanum nitrate or albumin tracer extravasation in control rat brain. After EMP exposure, the lanthanum nitrate ions reached the tight junction, basal lamina and pericapillary tissue. Similarly, the albumin immunopositive staining was identified in pericapillary tissue. The changes in brain micro vascular permeability were transient, the leakage of micro vascular vessels appeared at 1 h, and reached its peak at 3 h, and nearly recovered at 12 h, after EMP exposure. In addition, the leakage of micro vascular was more obvious after exposure of EMP at 400 pulses than after exposure of EMP at 200 pulses. Exposure to 200 and 400 pulses (1 Hz) of EMP at 200 kV/m can increase cerebral micro vascular permeability in rats, which is recoverable.

  8. Characterization of vascular permeability using a biomimetic microfluidic blood vessel model

    PubMed Central

    Thomas, Antony; Wang, Shunqiang; Sohrabi, Salman; Orr, Colin; He, Ran; Shi, Wentao; Liu, Yaling

    2017-01-01

    The inflammatory response in endothelial cells (ECs) leads to an increase in vascular permeability through the formation of gaps. However, the dynamic nature of vascular permeability and external factors involved is still elusive. In this work, we use a biomimetic blood vessel (BBV) microfluidic model to measure in real-time the change in permeability of the EC layer under culture in physiologically relevant flow conditions. This platform studies the dynamics and characterizes vascular permeability when the EC layer is triggered with an inflammatory agent using tracer molecules of three different sizes, and the results are compared to a transwell insert study. We also apply an analytical model to compare the permeability data from the different tracer molecules to understand the physiological and bio-transport significance of endothelial permeability based on the molecule of interest. A computational model of the BBV model is also built to understand the factors influencing transport of molecules of different sizes under flow. The endothelial monolayer cultured under flow in the BBV model was treated with thrombin, a serine protease that induces a rapid and reversible increase in endothelium permeability. On analysis of permeability data, it is found that the transport characteristics for fluorescein isothiocyanate (FITC) dye and FITC Dextran 4k Da molecules are similar in both BBV and transwell models, but FITC Dextran 70k Da molecules show increased permeability in the BBV model as convection flow (Peclet number > 1) influences the molecule transport in the BBV model. We also calculated from permeability data the relative increase in intercellular gap area during thrombin treatment for ECs in the BBV and transwell insert models to be between 12% and 15%. This relative increase was found to be within range of what we quantified from F-actin stained EC layer images. The work highlights the importance of incorporating flow in in vitro vascular models, especially

  9. Endotoxin increases pulmonary vascular protein permeability in the dog

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Welsh, C.H.; Dauber, I.M.; Weil, J.V.

    Endotoxin increases pulmonary vascular permeability consistently in some species but fails to reliably cause injury in the dog. We wondered whether this phenomenon depended on the method of injury assessment, as others have relied on edema measurement; we quantified injury by monitoring the rate of extravascular protein accumulation. /sup 113m/In-labeled protein and /sup 99m/Tc-labeled erythrocytes were injected into anesthetized dogs and monitored by an externally placed lung probe. A protein leak index, the rate of extravascular protein accumulation, was derived from the rate of increase in lung protein counts corrected for changes in intravascular protein activity. After administration of Salmonellamore » enteriditis endotoxin (4 micrograms/kg), the protein leak index was elevated 2.5-fold (41.1 +/- 4.6 X 10(-4) min-1) compared with control (16.0 +/- 2.8 X 10(-4) min-1). In contrast, wet-to-dry weight ratios failed to increase after endotoxin (4.6 +/- 0.8 vs. control values of 4.2 +/- 0.5 g/g dry bloodless lung). However, we observed that endotoxin increased lung dry weight (per unit body weight), which may have attenuated the change in wet-to-dry weight ratios. To determine whether low microvascular pressures following endotoxin attenuated edema formation, we increased pulmonary arterial wedge pressures in five dogs by saline infusion, which caused an increase in wet-to-dry weight ratios following endotoxin but no change in the five controls. We conclude that low dose endotoxin causes pulmonary vascular protein leak in the dog while edema formation is minimal or absent.« less

  10. New insight in quantitative analysis of vascular permeability during immune reaction (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Kalchenko, Vyacheslav; Molodij, Guillaume; Kuznetsov, Yuri; Smolyakov, Yuri; Israeli, David; Meglinski, Igor; Harmelin, Alon

    2016-03-01

    The use of fluorescence imaging of vascular permeability becomes a golden standard for assessing the inflammation process during experimental immune response in vivo. The use of the optical fluorescence imaging provides a very useful and simple tool to reach this purpose. The motivation comes from the necessity of a robust and simple quantification and data presentation of inflammation based on a vascular permeability. Changes of the fluorescent intensity, as a function of time is a widely accepted method to assess the vascular permeability during inflammation related to the immune response. In the present study we propose to bring a new dimension by applying a more sophisticated approach to the analysis of vascular reaction by using a quantitative analysis based on methods derived from astronomical observations, in particular by using a space-time Fourier filtering analysis followed by a polynomial orthogonal modes decomposition. We demonstrate that temporal evolution of the fluorescent intensity observed at certain pixels correlates quantitatively to the blood flow circulation at normal conditions. The approach allows to determine the regions of permeability and monitor both the fast kinetics related to the contrast material distribution in the circulatory system and slow kinetics associated with extravasation of the contrast material. Thus, we introduce a simple and convenient method for fast quantitative visualization of the leakage related to the inflammatory (immune) reaction in vivo.

  11. Isoflurane post-treatment improves pulmonary vascular permeability via upregulation of heme oxygenase-1.

    PubMed

    Dong, Xiang; Hu, Rong; Sun, Yu; Li, Qifang; Jiang, Hong

    2013-09-01

    Isoflurane (ISO) has been shown to attenuate acute lung injury (ALI). Induction of heme oxygenase-1 (HO-1) and suppression of inducible nitric oxide synthase (iNOS) expression provide cytoprotection in lung and vascular injury. The aim of this study was to investigate the effect of post-treatment with isoflurane on lung vascular permeability and the role of HO-1 in an ALI rat model induced by cecal ligation and puncture (CLP). Male Sprague-Dawley rats were randomly assigned to one of four groups: sham group, sham rats post-treated with vehicle (Sham); CLP group, CLP rats post-treated with vehicle (CLP); ISO group, CLP rats post-treated with isoflurane (ISO); and ZnPP group, CLP rats injected with zinc protoporphyrin IX (ZnPP), a competitive inhibitor of HO-1, 1 hour before the operation, and post-treated with isoflurane (ZnPP). Isoflurane (1.4%) was administered 2 hour after CLP. At 24 hour after CLP, the extent of ALI was evaluated by lung wet/dry ratio, Evans blue dye (EBD) extravasation, lung permeability index (LPI), as well as histological and immunohistochemical examinations. We also determined pulmonary iNOS and HO-1 expression. Compared with the CLP group, the isoflurane post-treatment group showed improved pulmonary microvascular permeability as detected by EBD extravasation, LPI, as well as histological and immunohistochemical examinations. Furthermore, isoflurane decreased iNOS and increased HO-1 expression in lung tissue. Pretreatment with ZnPP prevented the protective effects of isoflurane in rats. These findings indicate that the protective role of isoflurane post-conditioning against CLP-induced lung injury may be associated with its role in upregulating HO-1 in ALI.

  12. Vascular bursts enhance permeability of tumour blood vessels and improve nanoparticle delivery

    NASA Astrophysics Data System (ADS)

    Matsumoto, Yu; Nichols, Joseph W.; Toh, Kazuko; Nomoto, Takahiro; Cabral, Horacio; Miura, Yutaka; Christie, R. James; Yamada, Naoki; Ogura, Tadayoshi; Kano, Mitsunobu R.; Matsumura, Yasuhiro; Nishiyama, Nobuhiro; Yamasoba, Tatsuya; Bae, You Han; Kataoka, Kazunori

    2016-06-01

    Enhanced permeability in tumours is thought to result from malformed vascular walls with leaky cell-to-cell junctions. This assertion is backed by studies using electron microscopy and polymer casts that show incomplete pericyte coverage of tumour vessels and the presence of intercellular gaps. However, this gives the impression that tumour permeability is static amid a chaotic tumour environment. Using intravital confocal laser scanning microscopy we show that the permeability of tumour blood vessels includes a dynamic phenomenon characterized by vascular bursts followed by brief vigorous outward flow of fluid (named ‘eruptions’) into the tumour interstitial space. We propose that ‘dynamic vents’ form transient openings and closings at these leaky blood vessels. These stochastic eruptions may explain the enhanced extravasation of nanoparticles from the tumour blood vessels, and offer insights into the underlying distribution patterns of an administered drug.

  13. The regulation of vascular endothelial growth factor-induced microvascular permeability requires Rac and reactive oxygen species.

    PubMed

    Monaghan-Benson, Elizabeth; Burridge, Keith

    2009-09-18

    Vascular permeability is a complex process involving the coordinated regulation of multiple signaling pathways in the endothelial cell. It has long been documented that vascular endothelial growth factor (VEGF) greatly enhances microvascular permeability; however, the molecular mechanisms controlling VEGF-induced permeability remain unknown. Treatment of microvascular endothelial cells with VEGF led to an increase in reactive oxygen species (ROS) production. ROS are required for VEGF-induced permeability as treatment with the free radical scavenger, N-acetylcysteine, inhibited this effect. Additionally, treatment with VEGF caused ROS-dependent tyrosine phosphorylation of both vascular-endothelial (VE)-cadherin and beta-catenin. Rac1 was required for the VEGF-induced increase in permeability and adherens junction protein phosphorylation. Knockdown of Rac1 inhibited VEGF-induced ROS production consistent with Rac lying upstream of ROS in this pathway. Collectively, these data suggest that VEGF leads to a Rac-mediated generation of ROS, which, in turn, elevates the tyrosine phosphorylation of VE-cadherin and beta-catenin, ultimately regulating adherens junction integrity.

  14. Resistance of essential fatty acid-deficient rats to endotoxin-induced increases in vascular permeability

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, E.J.; Cook, J.A.; Spicer, K.M.

    Resistance to endotoxin in essential fatty acid-deficient (EFAD) rats is associated with reduced synthesis of certain arachidonic acid metabolites. It was hypothesized that EFAD rats would manifest decreased vascular permeability changes during endotoxemia as a consequence of reduced arachidonic acid metabolism. To test this hypothesis, changes in hematocrit (HCT) and mesenteric localization rate of technetium-labeled human serum albumin (99mTc-HSA) and red blood cells (99mTc-RBC) were assessed in EFAD and normal rats using gamma-camera imaging. Thirty minutes after Salmonella enteritidis endotoxin, EFAD rats exhibited less hemoconcentration as determined by % HCT than normal rats. Endotoxin caused a less severe change inmore » permeability index in the splanchnic region in EFAD rats than in normal rats (1.2 +/- 0.6 x 10(-3)min-1 vs. 4.9 +/- 1.7 x 10(-3)min-1 respectively, P less than 0.05). In contrast to 99mTc-HSA, mesenteric localization of 99mTc-RBC was not changed by endotoxin in control or EFAD rats. Supplementation with ethyl-arachidonic acid did not enhance susceptibility of EFAD rats to endotoxin-induced splanchnic permeability to 99mTc-HSA. Leukotrienes have been implicated as mediators of increased vascular permeability in endotoxin shock. Since LTC3 formation has been reported to be increased in EFA deficiency, we hypothesized that LTC3 may be less potent than LTC4. Thus the effect of LTC3 on mean arterial pressure and permeability was compared to LTC4 in normal rats. LTC3-induced increases in peak mean arterial pressure were less than LTC4 at 10 micrograms/kg (39 +/- 5 mm Hg vs. 58 +/- 4 mm Hg respectively, P less than 0.05) and at 20 micrograms/kg (56 +/- 4 mm Hg vs. 75 +/- 2 mm Hg respectively, P less than 0.05). LY171883 (30 mg/kg), an LTD4/E4 receptor antagonist, attenuated the pressor effect of LTC4, LTD4, and LTC3.« less

  15. Non-invasive optical modulation of local vascular permeability

    NASA Astrophysics Data System (ADS)

    Choi, Myunghwan; Choi, Chulhee

    2011-03-01

    For a systemically administered drug to act, it first needs to cross the vascular wall. This step represents a bottleneck for drug development, especially in the brain or retina, where tight junctions between endothelial cells form physiological barriers. Here, we demonstrate that femtosecond pulsed laser irradiation focused on the blood vessel wall induces transient permeabilization of plasma. Nonlinear absorption of the pulsed laser enabled the noninvasive modulation of vascular permeability with high spatial selectivity in three dimensions. By combining this method with systemic injection, we could locally deliver molecular probes in various tissues, such as brain cortex, meninges, ear, striated muscle, and bone. We suggest this method as a novel delivery tool for molecular probes or drugs.

  16. The clinical usefulness of extravascular lung water and pulmonary vascular permeability index to diagnose and characterize pulmonary edema: a prospective multicenter study on the quantitative differential diagnostic definition for acute lung injury/acute respiratory distress syndrome

    PubMed Central

    2012-01-01

    Introduction Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by features other than increased pulmonary vascular permeability. Pulmonary vascular permeability combined with increased extravascular lung water content has been considered a quantitative diagnostic criterion of ALI/ARDS. This prospective, multi-institutional, observational study aimed to clarify the clinical pathophysiological features of ALI/ARDS and establish its quantitative diagnostic criteria. Methods The extravascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI) were measured using the transpulmonary thermodilution method in 266 patients with PaO2/FiO2 ratio ≤ 300 mmHg and bilateral infiltration on chest radiography, in 23 ICUs of academic tertiary referral hospitals. Pulmonary edema was defined as EVLWI ≥ 10 ml/kg. Three experts retrospectively determined the pathophysiological features of respiratory insufficiency by considering the patients' history, clinical presentation, chest computed tomography and radiography, echocardiography, EVLWI and brain natriuretic peptide level, and the time course of all preceding findings under systemic and respiratory therapy. Results Patients were divided into the following three categories on the basis of the pathophysiological diagnostic differentiation of respiratory insufficiency: ALI/ARDS, cardiogenic edema, and pleural effusion with atelectasis, which were noted in 207 patients, 26 patients, and 33 patients, respectively. EVLWI was greater in ALI/ARDS and cardiogenic edema patients than in patients with pleural effusion with atelectasis (18.5 ± 6.8, 14.4 ± 4.0, and 8.3 ± 2.1, respectively; P < 0.01). PVPI was higher in ALI/ARDS patients than in cardiogenic edema or pleural effusion with atelectasis patients (3.2 ± 1.4, 2.0 ± 0.8, and 1.6 ± 0.5; P < 0.01). In ALI/ARDS patients, EVLWI increased with increasing pulmonary vascular permeability (r = 0.729, P < 0.01) and was weakly

  17. Modulation of VEGF-induced retinal vascular permeability by peroxisome proliferator-activated receptor-β/δ.

    PubMed

    Suarez, Sandra; McCollum, Gary W; Bretz, Colin A; Yang, Rong; Capozzi, Megan E; Penn, John S

    2014-11-18

    Vascular endothelial growth factor (VEGF)-induced retinal vascular permeability contributes to diabetic macular edema (DME), a serious vision-threatening condition. Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) antagonist/reverse agonist, GSK0660, inhibits VEGF-induced human retinal microvascular endothelial cell (HRMEC) proliferation, tubulogenesis, and oxygen-induced retinal vasculopathy in newborn rats. These VEGF-induced HRMEC behaviors and VEGF-induced disruption of endothelial cell junctional complexes may well share molecular signaling events. Thus, we sought to examine the role of PPARβ/δ in VEGF-induced retinal hyperpermeability. Transendothelial electrical resistance (TEER) measurements were performed on HRMEC monolayers to assess permeability. Claudin-1/Claudin-5 localization in HRMEC monolayers was determined by immunocytochemistry. Extracellular signal-regulated protein kinases 1 and 2 (Erk 1/2) phosphorylation, VEGF receptor 1 (VEGFR1) and R2 were assayed by Western blot analysis. Expression of VEGFR1 and R2 was measured by quantitative RT-PCR. Last, retinal vascular permeability was assayed in vivo by Evans blue extravasation. Human retinal microvascular endothelial cell monolayers treated with VEGF for 24 hours showed decreased TEER values that were completely reversed by the highest concentration of GSK0660 (10 μM) and PPARβ/δ-directed siRNA (20 μM). In HRMEC treated with VEGF, GSK0660 stabilized tight-junctions as evidenced by Claudin-1 staining, reduced phosphorylation of Erk1/2, and reduced VEGFR1/2 expression. Peroxisome proliferator-activated receptor β/δ siRNA had a similar effect on VEGFR expression and Claudin-1, supporting the specificity of GSK0660 in our experiments. Last, GSK0660 significantly inhibited VEGF-induced retinal vascular permeability and reduced retinal VEGFR1and R2 levels in C57BL/6 mice. These data suggest a protective effect for PPARβ/δ antagonism against VEGF-induced vascular permeability

  18. Modulation of VEGF-Induced Retinal Vascular Permeability by Peroxisome Proliferator-Activated Receptor-β/δ

    PubMed Central

    Suarez, Sandra; McCollum, Gary W.; Bretz, Colin A.; Yang, Rong; Capozzi, Megan E.; Penn, John S.

    2014-01-01

    Purpose. Vascular endothelial growth factor (VEGF)-induced retinal vascular permeability contributes to diabetic macular edema (DME), a serious vision-threatening condition. Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) antagonist/reverse agonist, GSK0660, inhibits VEGF-induced human retinal microvascular endothelial cell (HRMEC) proliferation, tubulogenesis, and oxygen-induced retinal vasculopathy in newborn rats. These VEGF-induced HRMEC behaviors and VEGF-induced disruption of endothelial cell junctional complexes may well share molecular signaling events. Thus, we sought to examine the role of PPARβ/δ in VEGF-induced retinal hyperpermeability. Methods. Transendothelial electrical resistance (TEER) measurements were performed on HRMEC monolayers to assess permeability. Claudin-1/Claudin-5 localization in HRMEC monolayers was determined by immunocytochemistry. Extracellular signal-regulated protein kinases 1 and 2 (Erk 1/2) phosphorylation, VEGF receptor 1 (VEGFR1) and R2 were assayed by Western blot analysis. Expression of VEGFR1 and R2 was measured by quantitative RT-PCR. Last, retinal vascular permeability was assayed in vivo by Evans blue extravasation. Results. Human retinal microvascular endothelial cell monolayers treated with VEGF for 24 hours showed decreased TEER values that were completely reversed by the highest concentration of GSK0660 (10 μM) and PPARβ/δ-directed siRNA (20 μM). In HRMEC treated with VEGF, GSK0660 stabilized tight-junctions as evidenced by Claudin-1 staining, reduced phosphorylation of Erk1/2, and reduced VEGFR1/2 expression. Peroxisome proliferator-activated receptor β/δ siRNA had a similar effect on VEGFR expression and Claudin-1, supporting the specificity of GSK0660 in our experiments. Last, GSK0660 significantly inhibited VEGF-induced retinal vascular permeability and reduced retinal VEGFR1and R2 levels in C57BL/6 mice. Conclusions. These data suggest a protective effect for PPARβ/δ antagonism against

  19. Over-vibration induced blood perfusion and vascular permeability changes may lead to vocal edema.

    PubMed

    Wang, Jiajia; Devine, Erin; Fang, Rui; Jiang, Jack J

    2017-01-01

    To observe blood perfusion and vascular permeability changes under varying vibration frequency exposures. Animal model. Blood perfusion was measured using laser Doppler flowmetry in eight rabbit auricular vessels (four rabbits) under nonvibration, and 62.5-Hz/1-mm, 125-Hz/1-mm, and 250-Hz/0.5-mm vibration frequency/amplitude exposures. Another 12 rabbits were randomly divided into vibration only and vibration with histamine groups. After 3 hours of continuous 125-Hz, 1-mm amplitude vibration of the auricle, vascular permeability was analyzed by absorbance of Evans blue-albumin complex. Significantly lower blood perfusion was observed in the vibration group, compared with no vibration exposure controls. Blood perfusion decreased 29 ± 16% as the vibration frequency was increased from 62.5 Hz to 125 Hz with the vibration amplitude constant at 1 mm. When the frequency was increased from 125 Hz to 250 Hz, while the amplitude was decreased from 1 mm to 0.5 mm, blood flow perfusion further decreased 29 ± 29%, and the decline tendency in blood perfusion showed no significant difference (P = .992). Meanwhile, in the vibration with histamine group, vascular permeability of the vibrated ears increased significantly compared to the nonvibrated ears (P = .005). Overvibration of the vocal folds due to voice overuse or abuse may significantly reduce blood perfusion, and increase vascular permeability in the vocal fold in inflammatory situations, which may lead to the formation of vocal edema. NA Laryngoscope, 127:148-152, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  20. Measurements of pulmonary vascular permeability with PET and gallium-68 transferrin

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mintun, M.A.; Dennis, D.R.; Welch, M.J.

    1987-11-01

    We quantified pulmonary vascular permeability with positron emission tomography (PET) and gallium-68-(/sup 68/Ga) labeled transferrin. Six dogs with oleic acid-induced lung injury confined to the left lower lobe, two normal human volunteers, and two patients with the adult respiratory distress syndrome (ARDS) were evaluated. Lung tissue-activity measurements were obtained from sequential 1-5 min PET scans collected over 60 min, after in vivo labeling of transferrin through intravenous administration of (/sup 68/Ga)citrate. Blood-activity measurements were measured from simultaneously obtained peripheral blood samples. A forward rate constant describing the movement of transferrin from pulmonary vascular to extravascular compartments, the pulmonary transcapillary escapemore » rate (PTCER), was then calculated from these data using a two-compartment model. In dogs, PTCER was 49 +/- 18 in normal lung tissue and 485 +/- 114 10(-4) min-1 in injured lung. A repeat study in these dogs 4 hr later showed no significant change. Values in the human subjects showed similarly marked differences between normal and abnormal lung tissue. We conclude that PET will be a useful method of evaluating vascular permeability changes after acute lung injury.« less

  1. Quantification of Tumor Vascular Permeability and Blood Volume by Positron Emission Tomography

    PubMed Central

    Chen, Haojun; Tong, Xiao; Lang, Lixin; Jacobson, Orit; Yung, Bryant C.; Yang, Xiangyu; Bai, Ruiliang; Kiesewetter, Dale O.; Ma, Ying; Wu, Hua; Niu, Gang; Chen, Xiaoyuan

    2017-01-01

    Purpose: Evans Blue (EB) is an azo dye that binds quantitatively with serum albumin. With an albumin binding, NOTA conjugated truncated Evan's blue (NEB) dye derived PET tracer, we aimed to establish a strategy for evaluating vascular permeability in malignant tumors via non-invasive PET. Experimental design: Sixty-minute dynamic PET using [18F]FAl-NEB was performed in three xenograft tumor models including INS-1 rat insulinoma, UM-SCC-22B human head and neck carcinoma and U-87 MG human glioblastoma. Tumor vascular permeability was quantified by the difference of the slopes between tumor and blood time-activity curve (TACs, expressed as Ps). The method was further substantiated by EB extraction and colorimetric assay and correlates with that calculated from dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). The changes in tumor vasculature at different time points were assessed with NEB PET in U-87 MG and UM-SCC-22B tumor models after treatment with bevacizumab or doxorubicin. Result: The Ps values calculated from tumor and blood TACs from multiple time-point static images are consistent with those from dynamic images. Moreover, the Ps showed a positive and significant correlation with extracted EB concentration and KPS-MRI generated from DCE-MRI, which further confirmed the soundness of this methodology. The antiangiogenic effect of bevacizumab could be revealed by NEB PET in U-87 MG tumors as early as 8 hrs after therapy, demonstrated by a substantial decrease of Ps. On the contrary, there was no significant change of Ps in bevacizumab treated UM-SCC-22B tumors, compared with control group. However, the significant changes of Pswere overestimated in doxorubicin treated UM-SCC-22B tumors. Conclusions: We successfully developed a relatively convenient and novel strategy to evaluate vascular permeability and blood volume using NEB PET. This method will be advantageous in evaluating vascular permeability, promoting drug delivery, and monitoring tumor

  2. [Significance of extravascular lung water index, pulmonary vascular permeability index, and in- trathoracic blood volume index in the differential diagnosis of burn-induced pulmonary edema].

    PubMed

    Lei, Li; Jiajun, Sheng; Guangyi, Wang; Kaiyang, Lyu; Jing, Qin; Gongcheng, Liu; Bing, Ma; Shichu, Xiao; Shihui, Zhu

    2015-06-01

    To appraise the significance of extravascular lung water index (EVLWI), pulmonary vascular permeability index (PVPI), and intrathoracic blood volume index (ITBVI) in the differential diagnosis of the type of burn-induced pulmonary edema. The clinical data of 38 patients, with severe burn hospitalized in our burn ICU from December 2011 to September 2014 suffering from the complication of pulmonary edema within one week post burn and treated with mechanical ventilation accompanied by pulse contour cardiac output monitoring, were retrospectively analyzed. The patients were divided into lung injury group ( L, n = 17) and hydrostatic group (H, n = 21) according to the diagnosis of pulmonary edema. EVLWI, PVPI, ITBVI, oxygenation index, and lung injury score ( LIS) were compared between two groups, and the correlations among the former four indexes and the correlations between each of the former three indexes and types of pulmonary edema were analyzed. Data were processed with t test, chi-square test, Mann-Whitney U test, Pearson correlation test, and accuracy test [receiver operating characteristic (ROC) curve]. There was no statistically significant difference in EVLWI between group L and group H, respectively (12.9 ± 3.1) and (12.1 ± 2.1) mL/kg, U = 159.5, P > 0.05. The PVPI and LIS of patients in group L were respectively 2.6 ± 0.5 and (2.1 ± 0.6) points, and they were significantly higher than those in group H [1.4 ± 0.3 and (1.0 ± 0.6) points, with U values respectively 4.5 and 36.5, P values below 0.01]. The ITBVI and oxygenation index of patients in group L were respectively (911 197) mL/m2 and (136 ± 69) mmHg (1 mmHg = 0.133 kPa), which were significantly lower than those in group H [(1,305 ± 168) mL/m2 and (212 ± 60) mmHg, with U values respectively 21.5 and 70.5, P values below 0.01]. In group L, there was obviously positive correlation between EVLWI and PVPI, or EVLWI and ITBVI (with r values respectively 0.553 and 0.807, P < 0.05 or P < 0.01), and

  3. Tumour-derived SPARC drives vascular permeability and extravasation through endothelial VCAM1 signalling to promote metastasis.

    PubMed

    Tichet, Mélanie; Prod'Homme, Virginie; Fenouille, Nina; Ambrosetti, Damien; Mallavialle, Aude; Cerezo, Michael; Ohanna, Mickaël; Audebert, Stéphane; Rocchi, Stéphane; Giacchero, Damien; Boukari, Fériel; Allegra, Maryline; Chambard, Jean-Claude; Lacour, Jean-Philippe; Michiels, Jean-François; Borg, Jean-Paul; Deckert, Marcel; Tartare-Deckert, Sophie

    2015-04-30

    Disruption of the endothelial barrier by tumour-derived secreted factors is a critical step in cancer cell extravasation and metastasis. Here, by comparative proteomic analysis of melanoma secretomes, we identify the matricellular protein SPARC as a novel tumour-derived vascular permeability factor. SPARC deficiency abrogates tumour-initiated permeability of lung capillaries and prevents extravasation, whereas SPARC overexpression enhances vascular leakiness, extravasation and lung metastasis. SPARC-induced paracellular permeability is dependent on the endothelial VCAM1 receptor and p38 MAPK signalling. Blocking VCAM1 impedes melanoma-induced endothelial permeability and extravasation. The clinical relevance of our findings is highlighted by high levels of SPARC detected in tumour from human pulmonary melanoma lesions. Our study establishes tumour-produced SPARC and VCAM1 as regulators of cancer extravasation, revealing a novel targetable interaction for prevention of metastasis.

  4. Application of a Novel Murine Ear Vein Model to Evaluate the Effects of a Vascular Radioprotectant on Radiation-Induced Vascular Permeability and Leukocyte Adhesion.

    PubMed

    Ashcraft, Kathleen A; Choudhury, Kingshuk Roy; Birer, Sam R; Hendargo, Hansford C; Patel, Pranalee; Eichenbaum, Gary; Dewhirst, Mark W

    2018-04-19

    Vascular injury after radiation exposure contributes to multiple types of tissue injury through a cascade of events. Some of the earliest consequences of radiation damage include increased vascular permeability and promotion of inflammation, which is partially manifested by increased leukocyte-endothelial (L/E) interactions. We describe herein a novel intravital imaging method to evaluate L/E interactions, as a function of shear stress, and vascular permeability at multiple time points after local irradiation to the ear. This model permitted analysis of quiescent vasculature that was not perturbed by any surgical manipulation prior to imaging. To evaluate the effects of radiation on vascular integrity, fluorescent dextran was injected intravenously and its extravasation in the extravascular space surrounding the ear vasculature was measured at days 3 and 7 after 6 Gy irradiation. The vascular permeability rate increased approximately twofold at both days 3 and 7 postirradiation ( P < 0.05). Leukocyte rolling, which is indicative of L/E interactions, was significantly increased in mice at 24 h postirradiation compared to that of nonirradiated mice. To assess our model, as a means for assessing vascular radioprotectants, we treated additional cohorts of mice with a thrombopoietin mimetic, TPOm (RWJ-800088). In addition to stimulating platelet formation, thrombopoietin can protect vasculature after several forms of injury. Thus, we hypothesized that TPOm would reduce vascular permeability and L/E adhesion after localized irradiation to the ear vasculature of mice. If TPOm reduced these consequences of radiation, it would validate the utility of our intravital imaging method. TPOm reduced radiation-induced vascular leakage to control levels at day 7. Furthermore, L/E cell interactions were also reduced in irradiated mice treated with TPOm, compared with mice receiving irradiation alone, particularly at high shear stress ( P = 0.03, Kruskal-Wallis). We conclude that the

  5. Arsenite induces endothelial cell permeability increase through a reactive oxygen species-vascular endothelial growth factor pathway.

    PubMed

    Bao, Lingzhi; Shi, Honglian

    2010-11-15

    As a potent environmental oxidative stressor, arsenic exposure has been reported to exacerbate cardiovascular diseases and increase vascular endothelial cell monolayer permeability. However, the underlying mechanism of this effect is not well understood. In this paper, we test our hypothesis that reactive oxygen species (ROS)-induced vascular endothelial growth factor (VEGF) expression may play an important role in an arsenic-caused increase of endothelial cell monolayer permeability. The mouse brain vascular endothelial cell bEnd3 monolayer was exposed to arsenite for 1, 3, and 6 days. The monolayer permeability, VEGF protein release, and ROS generation were determined. In addition, VE-cadherin and zonula occludens-1 (ZO-1), two membrane structure proteins, were immunostained to elucidate the effects of arsenite on the cell-cell junction. The roles of ROS and VEGF in arsenite-induced permeability was determined by inhibiting ROS with antioxidants and immuno-depleting VEGF with a VEGF antibody. We observed that arsenite increased bEnd3 monolayer permeability, elevated the production of cellular ROS, and increased VEGF release. VE-cadherin and ZO-1 disruptions were also found in cells treated with arsenite. Furthermore, both antioxidant (N-acetyl cysteine and tempol) and the VEGF antibody treatments significantly lowered the arsenite-induced permeability of the bEnd3 monolayer as well as VEGF expression. VE-cadherin and ZO-1 disruptions were also diminished by N-acetyl cysteine and the VEGF antibody. Our data suggest that the increase in VEGF expression caused by ROS may play an important role in the arsenite-induced increase in endothelial cell permeability.

  6. Effects of Extremely Low Frequency Electromagnetic Fields on Vascular Permeability of Circumventricular Organs in the Adult Rat

    NASA Astrophysics Data System (ADS)

    Gutiérrez-Mercado, Y. K.; Cañedo-Dorantes, L.; Bañuelos-Pineda, J.; Serrano-Luna, G.; Feria-Velasco, A.

    2008-08-01

    The present work deals with the effects of extremely low frequency electromagnetic fields (ELF-EMF) on blood vessels permeability to non liposoluble substances of the circumventricular organs (CVO) of adult rats. Male Wistar adult rats were exposed to ELF-EMF and vascular permeability to colloidal carbon was investigated with the use of histological techniques. Results were compared to corresponding data from sham-exposed and control groups of animals. Exposure to ELF-EMF increased the CVO vascular permeability to colloidal carbon intravascularly injected, particularly in the subfornical organ, the median eminence, the pineal gland and the area postrema.

  7. Limitations of the permeability-limited compartment model in estimating vascular permeability and interstitial volume fraction in DCE-MRI.

    PubMed

    Carreira, Guido Correia; Gemeinhardt, Ole; Gorenflo, Rudolf; Beyersdorff, Dirk; Franiel, Tobias; Plendl, Johanna; Lüdemann, Lutz

    2011-06-01

    Dynamic contrast-enhanced magnetic resonance imaging commonly uses compartment models to estimate tissue parameters in general and perfusion parameters in particular. Compartment models assume a homogeneous distribution of the injected tracer throughout the compartment volume. Since tracer distribution within a compartment cannot be assessed, the parameters obtained by means of a compartment model might differ from the actual physical values. This work systematically examines the widely used permeability-surface-limited one-compartment model to determine the reliability of the parameters obtained by comparing them with their actual values. A computer simulation was used to model spatial tracer distribution within the interstitial volume using diffusion of contrast agent in tissue. Vascular parameters were varied as well as tissue parameters. The vascular parameters used were capillary radius (4 and 12 μm), capillary permeability (from 0.03 to 3.3 μm/s) and intercapillary distances from 30 to 300 μm. The tissue parameters used were tortuosity (λ), porosity (α) and interstitial volume fraction (v(e)). Our results suggest that the permeability-surface-limited compartment model generally underestimates capillary permeability for capillaries with a radius of 4 μm by factors from ≈0.03 for α=0.04, to ≈ 0.1 for α=0.2, to ≈ 0.5 for α=1.0. An overestimation of actual capillary permeability for capillaries with a radius of 12 μm by a factor of ≥1.3 was found for α=1.0, while α=0.2 yielded an underestimation by a factor of ≈0.3 and α=0.04 by a factor of ≈ 0.03. The interstitial volume fraction, v(e), obtained by the compartment model differed with increasing intercapillary distances and for low vessel permeability, whereas v(e) was found to be estimated approximately accurately for P=0.3 μm/s and P=3.3 μm/s for vessel distances <100 μm. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Relative vascular permeability and vascularity across different regions of the rat nasal mucosa: implications for nasal physiology and drug delivery

    PubMed Central

    Kumar, Niyanta N.; Gautam, Mohan; Lochhead, Jeffrey J.; Wolak, Daniel J.; Ithapu, Vamsi; Singh, Vikas; Thorne, Robert G.

    2016-01-01

    Intranasal administration provides a non-invasive drug delivery route that has been proposed to target macromolecules either to the brain via direct extracellular cranial nerve-associated pathways or to the periphery via absorption into the systemic circulation. Delivering drugs to nasal regions that have lower vascular density and/or permeability may allow more drug to access the extracellular cranial nerve-associated pathways and therefore favor delivery to the brain. However, relative vascular permeabilities of the different nasal mucosal sites have not yet been reported. Here, we determined that the relative capillary permeability to hydrophilic macromolecule tracers is significantly greater in nasal respiratory regions than in olfactory regions. Mean capillary density in the nasal mucosa was also approximately 5-fold higher in nasal respiratory regions than in olfactory regions. Applying capillary pore theory and normalization to our permeability data yielded mean pore diameter estimates ranging from 13–17 nm for the nasal respiratory vasculature compared to <10 nm for the vasculature in olfactory regions. The results suggest lymphatic drainage for CNS immune responses may be favored in olfactory regions due to relatively lower clearance to the bloodstream. Lower blood clearance may also provide a reason to target the olfactory area for drug delivery to the brain. PMID:27558973

  9. Vascular Permeability and Remodelling Coincide with Inflammatory and Reparative Processes after Joint Bleeding in Factor VIII-Deficient Mice.

    PubMed

    Cooke, Esther J; Zhou, Jenny Y; Wyseure, Tine; Joshi, Shweta; Bhat, Vikas; Durden, Donald L; Mosnier, Laurent O; Drygalski, Annette von

    2018-06-01

    Vascular remodelling is a prominent feature of haemophilic arthropathy (HA) that may underlie re-bleeding, yet the nature of vascular changes and underlying mechanisms remain largely unknown. Here, we aimed to characterize synovial vascular remodelling and vessel integrity after haemarthrosis, as well as temporal changes in inflammatory and tissue-reparative pathways. Thirty acutely painful joints in patients with haemophilia (PWH) were imaged by musculoskeletal ultrasound with Power Doppler (MSKUS/PD) to detect vascular abnormalities and bloody effusions. Nineteen out of 30 painful joint episodes in PWH were associated with haemarthrosis, and abnormal vascular perfusion was unique to bleeding joints. A model of induced haemarthrosis in factor VIII (FVIII)-deficient mice was used for histological assessment of vascular remodelling (α-smooth muscle actin [αSMA] expression), and monitoring of in vivo vascular perfusion and permeability by MSKUS/PD and albumin extravasation, respectively. Inflammatory (M1) and reparative (M2) macrophage markers were quantified in murine synovium over a 10-week time course by real-time polymerase chain reaction. The abnormal vascular perfusion observed in PWH was recapitulated in FVIII-deficient mice after induced haemarthrosis. Neovascularization and increased vessel permeability were apparent 2 weeks post-bleed in FVIII-deficient mice, after a transient elevation of inflammatory macrophage M1 markers. These vascular changes subsided by week 4, while vascular remodelling, evidenced by architectural changes and pronounced αSMA expression, persisted alongside a reparative macrophage M2 response. In conclusion, haemarthrosis leads to transient inflammation coupled with neovascularization and associated vascular permeability, while subsequent tissue repair mechanisms coincide with vascular remodelling. Together, these vascular changes may promote re-bleeding and HA progression. Schattauer GmbH Stuttgart.

  10. VE-cadherin Y685F knock-in mouse is sensitive to vascular permeability in recurrent angiogenic organs.

    PubMed

    Sidibé, Adama; Polena, Helena; Pernet-Gallay, Karin; Razanajatovo, Jeremy; Mannic, Tiphaine; Chaumontel, Nicolas; Bama, Soumalamaya; Maréchal, Irène; Huber, Philippe; Gulino-Debrac, Danielle; Bouillet, Laurence; Vilgrain, Isabelle

    2014-08-01

    Covalent modifications such as tyrosine phosphorylation are associated with the breakdown of endothelial cell junctions and increased vascular permeability. We previously showed that vascular endothelial (VE)-cadherin was tyrosine phosphorylated in vivo in the mouse reproductive tract and that Y685 was a target site for Src in response to vascular endothelial growth factor in vitro. In the present study, we aimed to understand the implication of VE-cadherin phosphorylation at site Y685 in cyclic angiogenic organs. To achieve this aim, we generated a knock-in mouse carrying a tyrosine-to-phenylalanine point mutation of VE-cadherin Y685 (VE-Y685F). Although homozygous VE-Y685F mice were viable and fertile, the nulliparous knock-in female mice exhibited enlarged uteri with edema. This phenotype was observed in 30% of females between 4 to 14 mo old. Histological examination of longitudinal sections of the VE-Y685F uterus showed an extensive disorganization of myometrium and endometrium with highly edematous uterine glands, numerous areas with sparse cells, and increased accumulation of collagen fibers around blood vessels, indicating a fibrotic state. Analysis of cross section of ovaries showed the appearance of spontaneous cysts, which suggested increased vascular hyperpermeability. Electron microscopy analysis of capillaries in the ovary showed a slight but significant increase in the gap size between two adjacent endothelial cell membranes in the junctions of VE-Y685F mice (wild-type, 11.5 ± 0.3, n = 78; and VE-Y685F, 12.48 ± 0.3, n = 65; P = 0.045), as well as collagen fiber accumulation around capillaries. Miles assay revealed that either basal or vascular endothelial growth factor-stimulated permeability in the skin was increased in VE-Y685F mice. Since edema and fibrotic appearance have been identified as hallmarks of initial increased vascular permeability, we conclude that the site Y685 in VE-cadherin is involved in the physiological regulation of capillary

  11. Prediction of distribution volume of vancomycin in critically ill patients using extravascular lung water and pulmonary vascular permeability indices.

    PubMed

    Imaura, Masaharu; Yokoyama, Haruko; Kohyama, Tomoki; Nagafuchi, Hiroyuki; Kohata, Yuji; Takahashi, Hiroyuki; Yamada, Yasuhiko

    2012-11-01

    Alterations in distribution volume affect the concentrations of hydrophilic drugs in plasma and tissues at the time of initial therapy. When the distribution volume of hydrophilic antimicrobials is increased in critically ill patients with a serious infection, antimicrobial concentrations are reduced, which may adversely affect the efficacy of antimicrobial therapy. A transpulmonary thermodilution technique system (PiCCO) enables measurements of pulmonary vascular permeability index (PVPI) and extravascular lung water index (EVLWI), which are related to pulmonary edema and pulmonary vascular permeability, respectively. In addition, those indices may also be related to the distribution volume of hydrophilic antimicrobials. The aim of this study was to investigate the relationships of PVPI and EVLWI with the distribution volume of vancomycin (Vss), as well as to establish a method for estimating Vss for planning an appropriate initial dose for individual patients. Seven patients were administered vancomycin intravenously and underwent extended hemodynamic monitoring with the PiCCO system in the intensive care unit (ICU) from April 2009 to March 2011. Vss was calculated using the Bayesian method, and the relationships of PVPI and EVLWI with Vss were investigated. The relationship between Vss/actual body weight (ABW) and median EVLWI on days when blood levels were measured was significant (r = 0.900, p = 0.0057), whereas the relationship between Vss/ABW and PVPI was not significant (r = 0.649, p = 0.1112). EVLWI determined by the PiCCO system is useful to predict Vss and should lead to more effective vancomycin therapy for critically ill patients at the initial stage.

  12. The Robo4 cytoplasmic domain is dispensable for vascular permeability and neovascularization.

    PubMed

    Zhang, Feng; Prahst, Claudia; Mathivet, Thomas; Pibouin-Fragner, Laurence; Zhang, Jiasheng; Genet, Gael; Tong, Raymond; Dubrac, Alexandre; Eichmann, Anne

    2016-11-24

    Vascular permeability and neovascularization are implicated in many diseases including retinopathies and diabetic wound healing. Robo4 is an endothelial-specific transmembrane receptor that stabilizes the vasculature, as shown in Robo4 -/- mice that develop hyperpermeability, but how Robo4 signals remained unclear. Here we show that Robo4 deletion enhances permeability and revascularization in oxygen-induced retinopathy (OIR) and accelerates cutaneous wound healing. To determine Robo4 signalling pathways, we generated transgenic mice expressing a truncated Robo4 lacking the cytoplasmic domain (Robo4ΔCD). Robo4ΔCD expression is sufficient to prevent permeability, and inhibits OIR revascularization and wound healing in Robo4 -/- mice. Mechanistically, Robo4 does not affect Slit2 signalling, but Robo4 and Robo4ΔCD counteract Vegfr2-Y949 (Y951 in human VEGFR2) phosphorylation by signalling through the endothelial UNC5B receptor. We conclude that Robo4 inhibits angiogenesis and vessel permeability independently of its cytoplasmic domain, while activating VEGFR2-Y951 via ROBO4 inhibition might accelerate tissue revascularization in retinopathy of prematurity and in diabetic patients.

  13. Endothelin ETA Receptor Blockade, by Activating ETB Receptors, Increases Vascular Permeability and Induces Exaggerated Fluid Retention.

    PubMed

    Vercauteren, Magali; Trensz, Frederic; Pasquali, Anne; Cattaneo, Christophe; Strasser, Daniel S; Hess, Patrick; Iglarz, Marc; Clozel, Martine

    2017-05-01

    Endothelin (ET) receptor antagonists have been associated with fluid retention. It has been suggested that, of the two endothelin receptor subtypes, ET B receptors should not be blocked, because of their involvement in natriuresis and diuresis. Surprisingly, clinical data suggest that ET A -selective antagonists pose a greater risk of fluid overload than dual antagonists. The purpose of this study was to evaluate the contribution of each endothelin receptor to fluid retention and vascular permeability in rats. Sitaxentan and ambrisentan as ET A -selective antagonists and bosentan and macitentan as dual antagonists were used as representatives of each class, respectively. ET A -selective antagonism caused a dose-dependent hematocrit/hemoglobin decrease that was prevented by ET B -selective receptor antagonism. ET A -selective antagonism led to a significant blood pressure reduction, plasma volume expansion, and a greater increase in vascular permeability than dual antagonism. Isolated vessel experiments showed that ET A -selective antagonism increased vascular permeability via ET B receptor overstimulation. Acutely, ET A -selective but not dual antagonism activated sympathetic activity and increased plasma arginine vasopressin and aldosterone concentrations. The hematocrit/hemoglobin decrease induced by ET A -selective antagonism was reduced in Brattleboro rats and in Wistar rats treated with an arginine vasopressin receptor antagonist. Finally, the decrease in hematocrit/hemoglobin was larger in the venous than in the arterial side, suggesting fluid redistribution. In conclusion, by activating ET B receptors, endothelin receptor antagonists (particularly ET A -selective antagonists) favor edema formation by causing: 1) fluid retention resulting from arginine vasopressin and aldosterone activation secondary to vasodilation, and 2) increased vascular permeability. Plasma volume redistribution may explain the clinical observation of a hematocrit/hemoglobin decrease

  14. Estimating retinal vascular permeability using the adiabatic approximation to the tissue homogeneity model with fluorescein videoangiography

    NASA Astrophysics Data System (ADS)

    Tichauer, Kenneth M.; Osswald, Christian R.; Dosmar, Emily; Guthrie, Micah J.; Hones, Logan; Sinha, Lagnojita; Xu, Xiaochun; Mieler, William F.; St. Lawrence, Keith; Kang-Mieler, Jennifer J.

    2015-06-01

    Clinical symptoms of diabetic retinopathy are not detectable until damage to the retina reaches an irreversible stage, at least by today's treatment standards. As a result, there is a push to develop new, "sub-clinical" methods of predicting the onset of diabetic retinopathy before the onset of irreversible damage. With diabetic retinopathy being associated with the accumulation of long-term mild damage to the retinal vasculature, retinal blood vessel permeability has been proposed as a key parameter for detecting preclinical stages of retinopathy. In this study, a kinetic modeling approach used to quantify vascular permeability in dynamic contrast-enhanced medical imaging was evaluated in noise simulations and then applied to retinal videoangiography data in a diabetic rat for the first time to determine the potential for this approach to be employed clinically as an early indicator of diabetic retinopathy. Experimental levels of noise were found to introduce errors of less than 15% in estimates of blood flow and extraction fraction (a marker of vascular permeability), and fitting of rat retinal fluorescein angiography data provided stable maps of both parameters.

  15. Intravital lectin perfusion analysis of vascular permeability in human micro- and macro- blood vessels.

    PubMed

    Debbage, P L; Sölder, E; Seidl, S; Hutzler, P; Hugl, B; Ofner, D; Kreczy, A

    2001-10-01

    We previously applied intravital lectin perfusion in mouse models to elucidate mechanisms underlying vascular permeability. The present work transfers this technique to human models, analysing vascular permeability in macro- and microvessels. Human vascular endothelial surface carbohydrate biochemistry differs significantly from its murine counterpart, lacking alpha-galactosyl epitopes and expressing the L-fucose moiety in the glycocalyx; the poly-N-lactosamine glycan backbone is common to all mammals. We examined extensively lectin binding specificities in sections and in vivo, and then applied the poly-N-lactosamine-specific lectin LEA and the L-fucose-specific lectin UEA-I in human intravital perfusions. Transendothelial transport differed in macrovessels and microvessels. In microvessels of adult human fat tissue, rectal wall and rectal carcinomas, slow transendothelial transport by vesicles was followed by significant retention at the subendothelial basement membrane; paracellular passage was not observed. Passage time exceeded 1 h. Thus we found barrier mechanisms resembling those we described previously in murine tissues. In both adult and fetal macrovessels, the vena saphena magna and the umbilical vein, respectively, rapid passage across the endothelial lining was observed, the tracer localising completely in the subendothelial tissues within 15 min; vesicular transport was more rapid than in microvessels, and retention at the subendothelial basement membrane briefer.

  16. Lyophilized plasma attenuates vascular permeability, inflammation and lung injury in hemorrhagic shock.

    PubMed

    Pati, Shibani; Peng, Zhanglong; Wataha, Katherine; Miyazawa, Byron; Potter, Daniel R; Kozar, Rosemary A

    2018-01-01

    In severe trauma and hemorrhage the early and empiric use of fresh frozen plasma (FFP) is associated with decreased morbidity and mortality. However, utilization of FFP comes with the significant burden of shipping and storage of frozen blood products. Dried or lyophilized plasma (LP) can be stored at room temperature, transported easily, reconstituted rapidly with ready availability in remote and austere environments. We have previously demonstrated that FFP mitigates the endothelial injury that ensues after hemorrhagic shock (HS). In the current study, we sought to determine whether LP has similar properties to FFP in its ability to modulate endothelial dysfunction in vitro and in vivo. Single donor LP was compared to single donor FFP using the following measures of endothelial cell (EC) function in vitro: permeability and transendothelial monolayer resistance; adherens junction preservation; and leukocyte-EC adhesion. In vivo, using a model of murine HS, LP and FFP were compared in measures of HS- induced pulmonary vascular inflammation and edema. Both in vitro and in vivo in all measures of EC function, LP demonstrated similar effects to FFP. Both FFP and LP similarly reduced EC permeability, increased transendothelial resistance, decreased leukocyte-EC binding and persevered adherens junctions. In vivo, LP and FFP both comparably reduced pulmonary injury, inflammation and vascular leak. Both FFP and LP have similar potent protective effects on the vascular endothelium in vitro and in lung function in vivo following hemorrhagic shock. These data support the further development of LP as an effective plasma product for human use after trauma and hemorrhagic shock.

  17. Dynamic Measurement of Tumor Vascular Permeability and Perfusion using a Hybrid System for Simultaneous Magnetic Resonance and Fluorescence Imaging.

    PubMed

    Ren, Wuwei; Elmer, Andreas; Buehlmann, David; Augath, Mark-Aurel; Vats, Divya; Ripoll, Jorge; Rudin, Markus

    2016-04-01

    Assessing tumor vascular features including permeability and perfusion is essential for diagnostic and therapeutic purposes. The aim of this study was to compare fluorescence and magnetic resonance imaging (MRI)-based vascular readouts in subcutaneously implanted tumors in mice by simultaneous dynamic measurement of tracer uptake using a hybrid fluorescence molecular tomography (FMT)/MRI system. Vascular permeability was measured using a mixture of extravascular imaging agents, GdDOTA and the dye Cy5.5, and perfusion using a mixture of intravascular agents, Endorem and a fluorescent probe (Angiosense). Dynamic fluorescence reflectance imaging (dFRI) was integrated into the hybrid system for high temporal resolution. Excellent correspondence between uptake curves of Cy5.5/GdDOTA and Endorem/Angiosense has been found with correlation coefficients R > 0.98. The two modalities revealed good agreement regarding permeability coefficients and centers-of-gravity of the imaging agent distribution. The FMT/dFRI protocol presented is able to accurately map physiological processes and poses an attractive alternative to MRI for characterizing tumor neoangiogenesis.

  18. Vascular endothelial growth factor increases fenestral permeability in hepatic sinusoidal endothelial cells.

    PubMed

    Yokomori, Hiroaki; Oda, Masaya; Yoshimura, Kazunori; Nagai, Toshihiro; Ogi, Mariko; Nomura, Masahiko; Ishii, Hiromasa

    2003-12-01

    Vascular endothelial growth factor (VEGF) is an important regulator of vasculogenesis and vascular permeability. Hepatic sinusoidal endothelial cells (SECs) possess sieve-like pores that form an anastomosing labyrinth structure by the deeply invaginated plasma membrane. Caveolin is the principal structural protein in caveolae. In this study, we examined the role of VEGF on the fenestration and permeability of SECs and the relation with caveolin-1. SECs isolated from rat livers by collagenase infusion method were cultured for 24 h with (10 or 100 ng/ml) or without VEGF. The cells were then examined by transmission and scanning electron microscopy (EM). The expression of caveolin was investigated by confocal immunofluorescence, immunogold EM, and Western blot. Endocytosis and intracellular traffic was studied using horseradish peroxidase (HRP) reaction as a marker of fluid phase transport in SECs. Both transmission and scanning EM showed an increased number of sinusoidal endothelial fenestrae (SEF) in SECs cultured with VEGF. By confocal immunofluorescence, SECs cultured with VEGF displayed prominent caveolin-l-positive aggregates in the cytoplasm, especially surrounding the nucleus region. Immunogold EM depicted increased caveolin-1 reactivity on vesicles and vacuoles of VEGF-treated SECs compared with VEGF-nontreated cells. However, there was no change in the level of caveolin-1 protein expression on Western blot. After HRP injection, an increase of electron-dense tracer filled the SEF in cells treated with VEGF. Our results suggested that VEGF induced fenestration in SECs, accompanied by an increased number of caveolae-like vesicles. Increased caveolin-1 might be associated with vesicle formation but not with fenestration. Increased fenestration may augment hepatic sinusoidal permeability and transendothelial transport.

  19. Cortactin deficiency is associated with reduced neutrophil recruitment but increased vascular permeability in vivo.

    PubMed

    Schnoor, Michael; Lai, Frank P L; Zarbock, Alexander; Kläver, Ruth; Polaschegg, Christian; Schulte, Dörte; Weich, Herbert A; Oelkers, J Margit; Rottner, Klemens; Vestweber, Dietmar

    2011-08-01

    Neutrophil extravasation and the regulation of vascular permeability require dynamic actin rearrangements in the endothelium. In this study, we analyzed in vivo whether these processes require the function of the actin nucleation-promoting factor cortactin. Basal vascular permeability for high molecular weight substances was enhanced in cortactin-deficient mice. Despite this leakiness, neutrophil extravasation in the tumor necrosis factor-stimulated cremaster was inhibited by the loss of cortactin. The permeability defect was caused by reduced levels of activated Rap1 (Ras-related protein 1) in endothelial cells and could be rescued by activating Rap1 via the guanosine triphosphatase (GTPase) exchange factor EPAC (exchange protein directly activated by cAMP). The defect in neutrophil extravasation was caused by enhanced rolling velocity and reduced adhesion in postcapillary venules. Impaired rolling interactions were linked to contributions of β(2)-integrin ligands, and firm adhesion was compromised by reduced ICAM-1 (intercellular adhesion molecule 1) clustering around neutrophils. A signaling process known to be critical for the formation of ICAM-1-enriched contact areas and for transendothelial migration, the ICAM-1-mediated activation of the GTPase RhoG was blocked in cortactin-deficient endothelial cells. Our results represent the first physiological evidence that cortactin is crucial for orchestrating the molecular events leading to proper endothelial barrier function and leukocyte recruitment in vivo.

  20. Hydrogen-Rich Medium Attenuated Lipopolysaccharide-Induced Monocyte-Endothelial Cell Adhesion and Vascular Endothelial Permeability via Rho-Associated Coiled-Coil Protein Kinase.

    PubMed

    Xie, Keliang; Wang, Weina; Chen, Hongguang; Han, Huanzhi; Liu, Daquan; Wang, Guolin; Yu, Yonghao

    2015-07-01

    Sepsis is the leading cause of death in critically ill patients. In recent years, molecular hydrogen, as an effective free radical scavenger, has been shown a selective antioxidant and anti-inflammatory effect, and it is beneficial in the treatment of sepsis. Rho-associated coiled-coil protein kinase (ROCK) participates in junction between normal cells, and regulates vascular endothelial permeability. In this study, we used lipopolysaccharide to stimulate vascular endothelial cells and explored the effects of hydrogen-rich medium on the regulation of adhesion of monocytes to endothelial cells and vascular endothelial permeability. We found that hydrogen-rich medium could inhibit adhesion of monocytes to endothelial cells and decrease levels of adhesion molecules, whereas the levels of transepithelial/endothelial electrical resistance values and the expression of vascular endothelial cadherin were increased after hydrogen-rich medium treatment. Moreover, hydrogen-rich medium could lessen the expression of ROCK, as a similar effect of its inhibitor Y-27632. In addition, hydrogen-rich medium could also inhibit adhesion of polymorphonuclear neutrophils to endothelial cells. In conclusion, hydrogen-rich medium could regulate adhesion of monocytes/polymorphonuclear neutrophils to endothelial cells and vascular endothelial permeability, and this effect might be related to the decreased expression of ROCK protein.

  1. Clostridium sordellii lethal toxin kills mice by inducing a major increase in lung vascular permeability.

    PubMed

    Geny, Blandine; Khun, Huot; Fitting, Catherine; Zarantonelli, Leticia; Mazuet, Christelle; Cayet, Nadège; Szatanik, Marek; Prevost, Marie-Christine; Cavaillon, Jean-Marc; Huerre, Michel; Popoff, Michel R

    2007-03-01

    When intraperitoneally injected into Swiss mice, Clostridium sordellii lethal toxin reproduces the fatal toxic shock syndrome observed in humans and animals after natural infection. This animal model was used to study the mechanism of lethal toxin-induced death. Histopathological and biochemical analyses identified lung and heart as preferential organs targeted by lethal toxin. Massive extravasation of blood fluid in the thoracic cage, resulting from an increase in lung vascular permeability, generated profound modifications such as animal dehydration, increase in hematocrit, hypoxia, and finally, cardiorespiratory failure. Vascular permeability increase induced by lethal toxin resulted from modifications of lung endothelial cells as evidenced by electron microscopy. Immunohistochemical analysis demonstrated that VE-cadherin, a protein participating in intercellular adherens junctions, was redistributed from membrane to cytosol in lung endothelial cells. No major sign of lethal toxin-induced inflammation was observed that could participate in the toxic shock syndrome. The main effect of the lethal toxin is the glucosylation-dependent inactivation of small GTPases, in particular Rac, which is involved in actin polymerization occurring in vivo in lungs leading to E-cadherin junction destabilization. We conclude that the cells most susceptible to lethal toxin are lung vascular endothelial cells, the adherens junctions of which were altered after intoxication.

  2. Clostridium sordellii Lethal Toxin Kills Mice by Inducing a Major Increase in Lung Vascular Permeability

    PubMed Central

    Geny, Blandine; Khun, Huot; Fitting, Catherine; Zarantonelli, Leticia; Mazuet, Christelle; Cayet, Nadège; Szatanik, Marek; Prevost, Marie-Christine; Cavaillon, Jean-Marc; Huerre, Michel; Popoff, Michel R.

    2007-01-01

    When intraperitoneally injected into Swiss mice, Clostridium sordellii lethal toxin reproduces the fatal toxic shock syndrome observed in humans and animals after natural infection. This animal model was used to study the mechanism of lethal toxin-induced death. Histopathological and biochemical analyses identified lung and heart as preferential organs targeted by lethal toxin. Massive extravasation of blood fluid in the thoracic cage, resulting from an increase in lung vascular permeability, generated profound modifications such as animal dehydration, increase in hematocrit, hypoxia, and finally, cardiorespiratory failure. Vascular permeability increase induced by lethal toxin resulted from modifications of lung endothelial cells as evidenced by electron microscopy. Immunohistochemical analysis demonstrated that VE-cadherin, a protein participating in intercellular adherens junctions, was redistributed from membrane to cytosol in lung endothelial cells. No major sign of lethal toxin-induced inflammation was observed that could participate in the toxic shock syndrome. The main effect of the lethal toxin is the glucosylation-dependent inactivation of small GTPases, in particular Rac, which is involved in actin polymerization occurring in vivo in lungs leading to E-cadherin junction destabilization. We conclude that the cells most susceptible to lethal toxin are lung vascular endothelial cells, the adherens junctions of which were altered after intoxication. PMID:17322384

  3. Dissociation of VE-PTP from VE-cadherin is required for leukocyte extravasation and for VEGF-induced vascular permeability in vivo

    PubMed Central

    Broermann, Andre; Winderlich, Mark; Block, Helena; Frye, Maike; Rossaint, Jan; Zarbock, Alexander; Cagna, Giuseppe; Linnepe, Ruth; Schulte, Dörte; Nottebaum, Astrid Fee

    2011-01-01

    We have recently shown that vascular endothelial protein tyrosine phosphatase (VE-PTP), an endothelial membrane protein, associates with VE-cadherin and is required for optimal VE-cadherin function and endothelial cell contact integrity. The dissociation of VE-PTP from VE-cadherin is triggered by vascular endothelial growth factor (VEGF) and by the binding of leukocytes to endothelial cells in vitro, suggesting that this dissociation is a prerequisite for the destabilization of endothelial cell contacts. Here, we show that VE-cadherin/VE-PTP dissociation also occurs in vivo in response to LPS stimulation of the lung or systemic VEGF stimulation. To show that this dissociation is indeed necessary in vivo for leukocyte extravasation and VEGF-induced vascular permeability, we generated knock-in mice expressing the fusion proteins VE-cadherin-FK 506 binding protein and VE-PTP-FRB* under the control of the endogenous VE-cadherin promoter, thus replacing endogenous VE-cadherin. The additional domains in both fusion proteins allow the heterodimeric complex to be stabilized by a chemical compound (rapalog). We found that intravenous application of the rapalog strongly inhibited VEGF-induced (skin) and LPS-induced (lung) vascular permeability and inhibited neutrophil extravasation in the IL-1β inflamed cremaster and the LPS-inflamed lung. We conclude that the dissociation of VE-PTP from VE-cadherin is indeed required in vivo for the opening of endothelial cell contacts during induction of vascular permeability and leukocyte extravasation. PMID:22025303

  4. Rhubarb Antagonizes Matrix Metalloproteinase-9-induced Vascular Endothelial Permeability

    PubMed Central

    Cui, Yun-Liang; Zhang, Sheng; Tian, Zhao-Tao; Lin, Zhao-Fen; Chen, De-Chang

    2016-01-01

    Background: Intact endothelial structure and function are critical for maintaining microcirculatory homeostasis. Dysfunction of the latter is an underlying cause of various organ pathologies. In a previous study, we showed that rhubarb, a traditional Chinese medicine, protected intestinal mucosal microvascular endothelial cells in rats with metastasizing septicemia. In this study, we investigated the effects and mechanisms of rhubarb on matrix metalloproteinase-9 (MMP9)-induced vascular endothelial (VE) permeability. Methods: Rhubarb monomers were extracted and purified by a series of chromatography approaches. The identity of these monomers was analyzed by hydrogen-1 nuclear magnetic resonance (NMR), carbon-13 NMR, and distortionless enhancement by polarization transfer magnetic resonance spectroscopy. We established a human umbilical vein endothelial cell (HUVEC) monolayer on a Transwell insert. We measured the HUVEC permeability, proliferation, and the secretion of VE-cadherin into culture medium using fluorescein isothiocyanate-dextran assay, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, and enzyme-linked immunosorbent assay, respectively, in response to treatment with MMP9 and/or rhubarb monomers. Results: A total of 21 rhubarb monomers were extracted and identified. MMP9 significantly increased the permeability of the HUVEC monolayer, which was significantly reduced by five individual rhubarb monomer (emodin, 3,8-dihydroxy-1-methyl-anthraquinone-2-carboxylic acid, 1-O-caffeoyl-2-(4-hydroxyl-O-cinnamoyl)-β-D-glucose, daucosterol linoleate, and rhein) or a combination of all five monomers (1 μmol/L for each monomer). Mechanistically, the five-monomer mixture at 1 μmol/L promoted HUVEC proliferation. In addition, MMP9 stimulated the secretion of VE-cadherin into the culture medium, which was significantly inhibited by the five-monomer mixture. Conclusions: The rhubarb mixture of emodin, 3,8-dihydroxy-1-methyl-anthraquinone-2

  5. Antioxidant-related gene polymorphisms associated with the cardio-ankle vascular index in young Russians.

    PubMed

    Sorokin, Alexander V; Kotani, Kazuhiko; Bushueva, Olga Y; Polonikov, Alexey V

    2016-04-01

    The cardio-ankle vascular index is a measure of arterial stiffness, whereas oxidative stress underlies arterial pathology. This study aimed to investigate the association between the cardio-ankle vascular index and antioxidant-related gene polymorphisms in young Russians. A total of 89 patients (mean age, 21.6 years) were examined by the cardio-ankle vascular index and for 15 gene polymorphisms related to antioxidant enzymes including FMO3 (flavin-containing monooxygenase 3), GPX1 (glutathione peroxidase 1), and GPX4 (glutathione peroxidase 4). A higher cardio-ankle vascular index level was detected in carriers with the KK-genotype of FMO3 polymorphism rs2266782 than in those without (mean levels: 6.2 versus 5.6, respectively, p<0.05). Similarly, a higher cardio-ankle vascular index level was seen in carriers with the CC-genotype of GPX4 polymorphism rs713041 than in those without (6.0 versus 5.5, respectively, p<0.05). We did not observe significant associations between the cardio-ankle vascular index levels and the other gene polymorphisms. Although carriers with the LL-genotype of GPX1 polymorphism rs1050450 showed a higher diastolic blood pressure level than those without, the polymorphism did not affect the cardio-ankle vascular index level. This study showed a significant association between rs2266782 and rs713041 polymorphisms and arterial stiffness, as measured by the cardio-ankle vascular index, in young Russians. The pathways utilised by antioxidant enzymes may be responsible for early arterial stiffening in the Russian population.

  6. Effect of Melilotus suaveolens extract on pulmonary microvascular permeability by downregulating vascular endothelial growth factor expression in rats with sepsis

    PubMed Central

    LIU, MING-WEI; SU, MEI-XIAN; ZHANG, WEI; WANG, YUN HUI; QIN, LAN-FANG; LIU, XU; TIAN, MAO-LI; QIAN, CHUAN-YUN

    2015-01-01

    A typical indicator of sepsis is the development of progressive subcutaneous and body-cavity edema, which is caused by the breakdown of endothelial barrier function, leading to a marked increase in vascular permeability. Microvascular leakage predisposes to microvascular thrombosis, breakdown of microcirculatory flow and organ failure, which are common events preceding mortality in patients with severe sepsis. Melilotus suaveolens (M. suaveolens) is a Traditional Tibetan Medicine. Previous pharmacological studies have demonstrated that an ethanolic extract of M. suaveolens has powerful anti-inflammatory activity and leads to an improvement in capillary permeability. However, the mechanisms underlying its pharmacological activity remain elusive. The present study aimed to assess the impact of M. suaveolens extract tablets on pulmonary vascular permeability, and their effect on regulating lung inflammation and the expression of vascular endothelial growth factor (VEGF) in the lung tissue of rats with sepsis. A cecal ligation and puncture (CLP) sepsis model was established for both the control and treatment groups. ~2 h prior to surgery, 25 mg/kg of M. suaveolens extract tablet was administered to the treatment group. Polymerase chain reaction and western blot analyses were used to assess the expression of nuclear factor (NF)-κB and VEGF in the lung tissue, and ELISA was applied to detect changes in serum tumor necrosis factor-α as well as interleukins (IL) -1, -4, -6, and -10. The lung permeability, wet/dry weight ratio and lung pathology were determined. The results demonstrated that in the lung tissue of CLP-rats with sepsis, M. suaveolens extract inhibited the expression of NF-κB, reduced the inflammatory response and blocked the expression of VEGF, and thus significantly decreased lung microvascular permeability. The effects of M. Suaveolens extract may be of potential use in the treatment of CLP-mediated lung microvascular permeability. PMID:25571852

  7. Protective effects of hydrogen-rich medium on lipopolysaccharide-induced monocytic adhesion and vascular endothelial permeability through regulation of vascular endothelial cadherin.

    PubMed

    Yu, Y; Wang, W N; Han, H Z; Xie, K L; Wang, G L; Yu, Y H

    2015-06-11

    We observed the effect of hydrogen-rich medium on lipopolysaccharide (LPS)-induced human umbilical vein endothelial cells (HUVECs), hyaline leukocyte conglutination, and permeability of the endothelium. Endotheliocytes were inoculated on 6-well plates and randomly divided into 4 groups: control, H2, LPS, LPS+H2, H2, and LPS+H2 in saturated hydrogen-rich medium. We applied Wright's stain-ing to observe conglutination of hyaline leukocytes and HUVECs, flow cytometry to determine the content of vascular cell adhesion protein 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1), enzyme-linked immunosorbent assay to measure the E-selectin concentration in the cell liquor, the transendothelial electrical resistance (TEER) to test the permeability of endothelial cells, and Western blot and immunofluorescence to test the expression and distribution of vascular endothelial (VE)-cadherin. Compared with control cells, there was an increase in endothelium-hyaline leukocyte conglutination, a reduction in VCAM-1, ICAM-1, and E-selectin, and the TEER value increased obviously. Compared with LPS, there was an obvious reduction in the conglutination of LPS+H2 cells, a reduction in VCAM-1, ICAM-1, and E-selectin levels, and a reduction in the TEER-resistance value, while the expression of VE-cadherin increased. Fluorescence results showed that, compared with control cells, the VE-cadherin in LPS cells was in-complete at the cell joints. Compared with LPS cells, the VE-cadherin in LPS+H2 cells was even and complete at the cell joints. Liquid rich in hydrogen could reduce LPS-induced production of adhesion molecules and endothelium-hyaline leukocyte conglutination, and influence the expression and distribution of VE-cadherin to regulate the permeability of the endothelium.

  8. Hydrogels with precisely controlled integrin activation dictate vascular patterning and permeability

    NASA Astrophysics Data System (ADS)

    Li, Shuoran; Nih, Lina R.; Bachman, Haylee; Fei, Peng; Li, Yilei; Nam, Eunwoo; Dimatteo, Robert; Carmichael, S. Thomas; Barker, Thomas H.; Segura, Tatiana

    2017-09-01

    Integrin binding to bioengineered hydrogel scaffolds is essential for tissue regrowth and regeneration, yet not all integrin binding can lead to tissue repair. Here, we show that through engineering hydrogel materials to promote α3/α5β1 integrin binding, we can promote the formation of a space-filling and mature vasculature compared with hydrogel materials that promote αvβ3 integrin binding. In vitro, α3/α5β1 scaffolds promoted endothelial cells to sprout and branch, forming organized extensive networks that eventually reached and anastomosed with neighbouring branches. In vivo, α3/α5β1 scaffolds delivering vascular endothelial growth factor (VEGF) promoted non-tortuous blood vessel formation and non-leaky blood vessels by 10 days post-stroke. In contrast, materials that promote αvβ3 integrin binding promoted endothelial sprout clumping in vitro and leaky vessels in vivo. This work shows that precisely controlled integrin activation from a biomaterial can be harnessed to direct therapeutic vessel regeneration and reduce VEGF-induced vascular permeability in vivo.

  9. Hydrogels with precisely controlled integrin activation dictate vascular patterning and permeability

    PubMed Central

    Li, Shuoran; Nih, Lina R.; Bachman, Haylee; Fei, Peng; Li, Yilei; Nam, Eunwoo; Dimatteo, Robert; Carmichael, S. Thomas; Barker, Thomas H.; Segura, Tatiana

    2017-01-01

    Integrin binding to bioengineered hydrogel scaffolds is essential for tissue regrowth and regeneration, yet not all integrin binding can lead to tissue repair. Here, we show that through engineering hydrogel materials to promote α3/α5β1 integrin binding, we can promote the formation of a space filling and mature vasculature compared to hydrogel materials that promote a αvβ3 integrin binding. In vitro, α3/α5β1 scaffolds promoted endothelial cells to sprout and branch, forming organized extensive networks that eventually reached and anastomosed with neighboring branches. In vivo, α3/α5β1 scaffolds delivering vascular endothelial growth factor (VEGF) promoted non-tortuous blood vessel formation and non-leaky blood vessels by 10-days post stroke. In contrast, materials that promote αvβ3 integrin binding promoted endothelial sprout clumping in vitro and leaky vessels in vivo. This work shows that precisely controlled integrin activation from a biomaterial can be harnessed to direct therapeutic vessel regeneration and reduce VEGF induced vascular permeability in vivo. PMID:28783156

  10. Agmatine induces gastric protection against ischemic injury by reducing vascular permeability in rats

    PubMed Central

    Masri, Abeer A Al; Eter, Eman El

    2012-01-01

    AIM: To investigate the effect of administration of agmatine (AGM) on gastric protection against ischemia reperfusion (I/R) injury. METHODS: Three groups of rats (6/group); sham, gastric I/R injury, and gastric I/R + AGM (100 mg/kg, i.p. given 15 min prior to gastric ischemia) were recruited. Gastric injury was conducted by ligating celiac artery for 30 min and reperfusion for another 30 min. Gastric tissues were histologically studied and immunostained with angiopoietin 1 (Ang-1) and Ang-2. Vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein-1 (MCP-1) were measured in gastric tissue homogenate. To assess whether AKt/phosphatidyl inositol-3-kinase (PI3K) mediated the effect of AGM, an additional group was pretreated with Wortmannin (WM) (inhibitor of Akt/PI3K, 15 μg/kg, i.p.), prior to ischemic injury and AGM treatment, and examined histologically and immunostained. Another set of experiments was run to study vascular permeability of the stomach using Evan’s blue dye. RESULTS: AGM markedly reduced Evan’s blue dye extravasation (3.58 ± 0.975 μg/stomach vs 1.175 ± 0.374 μg/stomach, P < 0.05), VEGF (36.87 ± 2.71 pg/100 mg protein vs 48.4 ± 6.53 pg/100 mg protein, P < 0.05) and MCP-1 tissue level (29.5 ± 7 pg/100 mg protein vs 41.17 ± 10.4 pg/100 mg protein, P < 0.01). It preserved gastric histology and reduced congestion. Ang-1 and Ang-2 immunostaining were reduced in stomach sections of AGM-treated animals. The administration of WM abolished the protective effects of AGM and extensive hemorrhage and ulcerations were seen. CONCLUSION: AGM protects the stomach against I/R injury by reducing vascular permeability and inflammation. This protection is possibly mediated by Akt/PI3K. PMID:22611311

  11. TLR4 activation of TRPC6-dependent calcium signaling mediates endotoxin-induced lung vascular permeability and inflammation

    PubMed Central

    Tauseef, Mohammad; Knezevic, Nebojsa; Chava, Koteswara R.; Smith, Monica; Sukriti, Sukriti; Gianaris, Nicholas; Obukhov, Alexander G.; Vogel, Stephen M.; Schraufnagel, Dean E.; Dietrich, Alexander; Birnbaumer, Lutz; Malik, Asrar B.

    2012-01-01

    Lung vascular endothelial barrier disruption and the accompanying inflammation are primary pathogenic features of acute lung injury (ALI); however, the basis for the development of both remains unclear. Studies have shown that activation of transient receptor potential canonical (TRPC) channels induces Ca2+ entry, which is essential for increased endothelial permeability. Here, we addressed the role of Toll-like receptor 4 (TLR4) intersection with TRPC6-dependent Ca2+ signaling in endothelial cells (ECs) in mediating lung vascular leakage and inflammation. We find that the endotoxin (lipopolysaccharide; LPS) induces Ca2+ entry in ECs in a TLR4-dependent manner. Moreover, deletion of TRPC6 renders mice resistant to endotoxin-induced barrier dysfunction and inflammation, and protects against sepsis-induced lethality. TRPC6 induces Ca2+ entry in ECs, which is secondary to the generation of diacylglycerol (DAG) induced by LPS. Ca2+ entry mediated by TRPC6, in turn, activates the nonmuscle myosin light chain kinase (MYLK), which not only increases lung vascular permeability but also serves as a scaffold to promote the interaction of myeloid differentiation factor 88 and IL-1R–associated kinase 4, which are required for NF-κB activation and lung inflammation. Our findings suggest that TRPC6-dependent Ca2+ entry into ECs, secondary to TLR4-induced DAG generation, participates in mediating both lung vascular barrier disruption and inflammation induced by endotoxin. PMID:23045603

  12. Mice with targeted inactivation of ppap2b in endothelial and hematopoietic cells display enhanced vascular inflammation and permeability.

    PubMed

    Panchatcharam, Manikandan; Salous, Abdel K; Brandon, Jason; Miriyala, Sumitra; Wheeler, Jessica; Patil, Pooja; Sunkara, Manjula; Morris, Andrew J; Escalante-Alcalde, Diana; Smyth, Susan S

    2014-04-01

    Lipid phosphate phosphatase 3 (LPP3), encoded by the PPAP2B gene, is an integral membrane enzyme that dephosphorylates, and thereby terminates, the G-protein-coupled receptor-mediated signaling actions of lysophosphatidic acid (LPA) and sphingosine-1-phosphate. LPP3 is essential for normal vascular development in mice, and a common PPAP2B polymorphism is associated with increased risk of coronary artery disease in humans. Herein, we investigate the function of endothelial LPP3 to understand its role in the development and human disease. We developed mouse models with selective LPP3 deficiency in endothelial and hematopoietic cells. Tyrosine kinase Tek promoter-mediated inactivation of Ppap2b resulted in embryonic lethality because of vascular defects. LPP3 deficiency in adult mice, achieved using a tamoxifen-inducible Cre transgene under the control of the Tyrosine kinase Tek promoter, enhanced local and systemic inflammatory responses. Endothelial, but not hematopoietic, cell LPP3 deficiency led to significant increases in vascular permeability at baseline and enhanced sensitivity to inflammation-induced vascular leak. Endothelial barrier function was restored by pharmacological or genetic inhibition of either LPA production by the circulating lysophospholipase D autotaxin or of G-protein-coupled receptor-dependent LPA signaling. Our results identify a role for the autotaxin/LPA-signaling nexus as a mediator of endothelial permeability in inflammation and demonstrate that LPP3 limits these effects. These findings have implications for therapeutic targets to maintain vascular barrier function in inflammatory states.

  13. Exploiting passive nanomedicine accumulation at sites of enhanced vascular permeability for non-cancerous applications.

    PubMed

    Durymanov, Mikhail; Kamaletdinova, Tatiana; Lehmann, Sarah E; Reineke, Joshua

    2017-09-10

    Over the past few decades, enhanced permeability of tumor vasculature was actively exploited for targeted delivery of anticancer nanomedicines resulting in numerous pharmaceutical products. Formation of new immature and leaky vessels along with inflammatory remodeling of existing vessels accompany development of numerous diseases beyond cancer and present an opportunity for passive accumulation of intravenously administered nanomedicines in many pathological tissues. To date, applications of non-cancerous enhanced permeation have been relatively unexploited as target tissues and may create new therapy and prevention technologies for many disorders. Herein, we summarize the current knowledge on the nature of enhanced vascular permeability in multiple non-cancerous pathological tissues. We also discuss the clinical status of nanotherapeutics with selectivity based on passive accumulation in non-cancerous target tissues, their challenges, and prospects. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Protein-bounded uremic toxin p-cresylsulfate induces vascular permeability alternations.

    PubMed

    Tang, Wei-Hua; Wang, Chao-Ping; Yu, Teng-Hung; Tai, Pei-Yang; Liang, Shih-Shin; Hung, Wei-Chin; Wu, Cheng-Ching; Huang, Sung-Hao; Lee, Yau-Jiunn; Chen, Shih-Chieh

    2018-06-01

    The goal of the present studies is to investigate that the impact of p-cresylsulfate (PCS) on the endothelial barrier integrity via in situ exposure and systemic exposure. Vascular permeability changes induced by local injection of PCS were evaluated by the techniques of both Evans blue (EB) and India ink tracer. Rats were intravenously injected with EB or India ink followed by intradermal injections of various doses of PCS (0, 0.4, 2, 10 and 50 µmol/site) on rat back skins. At different time points, skin EB was extracted and quantified. The administration of India ink was used to demonstrate leaky microvessels. Skin PCS levels were also determined by liquid chromatography-mass spectrometry. We also investigated whether the increased endothelial leakage occurred in the aortic endothelium in rats treated with 5/6 nephrectomy and intraperitoneal injection of PCS 50 mg/kg/day for 4 weeks. The aortic endothelial integrity was evaluated by increased immunoglobulin G (IgG) leakage. High doses of PCS, but not lower doses, significantly induced vascular leakage as compared to saline injection and EB leakage exhibited in time-dependent manner. A time-correlated increase in leaky microvessels was detected in the tissues examined. The injected PCS declined with time and displayed an inverse relationship with vascular leakage. Chronic kidney disease (CKD) rats administered with PCS, compared to control rats, had significantly higher serum levels of PCS and apparent IgG deposition in the aortic intima. Increased endothelial leakage induced by PCS in skin microvessels and the aorta of CKD rats suggests that the PCS-induced endothelial barrier dysfunction.

  15. Short-Term Exposure to Urban Air Pollution and Influences on Placental Vascularization Indexes.

    PubMed

    Hettfleisch, Karen; Bernardes, Lisandra Stein; Carvalho, Mariana Azevedo; Pastro, Luciana Duzolina Manfré; Vieira, Sandra Elisabete; Saldiva, Silvia R D M; Saldiva, Paulo; Francisco, Rossana Pulcineli Vieira

    2017-04-01

    It has been widely demonstrated that air pollution can affect human health and that certain pollutant gases lead to adverse obstetric outcomes, such as preeclampsia and fetal growth restriction. We evaluated the influence of individual maternal exposure to air pollution on placental volume and vascularization evaluated in the first trimester of pregnancy. This was a cross-sectional study on low-risk pregnant women living in São Paulo, Brazil. The women carried passive personal NO 2 and O 3 monitors in the week preceding evaluation. We employed the virtual organ computer-aided analysis (VOCAL) technique using three-dimensional power Doppler ultrasound to evaluate placental volume and placental vascular indexes [vascularization index (VI), flow index (FI), and vascularization flow index (VFI)]. We analyzed the influence of pollutant levels on log-transformed placental vascularization and volume using multiple regression models. We evaluated 229 patients. Increased NO 2 levels had a significant negative association with log of VI ( p = 0.020 and beta = -0.153) and VFI ( p = 0.024 and beta = -0.151). NO 2 and O 3 had no influence on the log of placental volume or FI. NO 2 , an estimator of primary air pollutants, was significantly associated with diminished VI and VFI in the first trimester of pregnancy.

  16. Isoproterenol attenuates high vascular pressure-induced permeability increases in isolated rat lungs.

    PubMed

    Parker, J C; Ivey, C L

    1997-12-01

    To separate the contributions of cellular and basement membrane components of the alveolar capillary barrier to the increased microvascular permeability induced by high pulmonary venous pressures (Ppv), we subjected isolated rat lungs to increases in Ppv, which increased capillary filtration coefficient (Kfc) without significant hemorrhage (31 cmH2O) and with obvious extravasation of red blood cells (43 cmH2O). Isoproterenol (20 microM) was infused in one group (Iso) to identify a reversible cellular component of injury, and residual blood volumes were measured to assess extravasation of red blood cells through ruptured basement membranes. In untreated lungs (High Ppv group), Kfc increased 6.2 +/- 1.3 and 38.3 +/- 15.2 times baseline during the 31 and 43 cmH2O Ppv states. In Iso lungs, Kfc was 36.2% (P < 0.05) and 64.3% of that in the High Ppv group at these Ppv states. Residual blood volumes calculated from tissue hemoglobin contents were significantly increased by 53-66% in the high Ppv groups, compared with low vascular pressure controls, but there was no significant difference between High Ppv and Iso groups. Thus isoproterenol significantly attenuated vascular pressure-induced Kfc increases at moderate Ppv, possibly because of an endothelial effect, but it did not affect red cell extravasation at higher vascular pressures.

  17. [Regulative effects of hydrogen-rich medium on monocytic adhesion and vascular endothelial permeability].

    PubMed

    Wang, Wei-na; Xie, Ke-liang; Chen, Hong-guang; Han, Huan-zhi; Wang, Guo-lin; Yu, Yong-hao

    2013-11-19

    To explore the regulative effects of hydrogen-rich medium on lipopolysaccharide (LPS)-induced monocytes adhesion to human umbilical vein endothelial cells (HUVEC) and vascular endothelial permeability in vitro. Endothelial cells were seeded in 6-well plates and randomly divided into 4 groups (n = 42 each):control (A), hydrogen-rich medium (B), LPS (C) and LPS+hydrogen-rich medium (D). Cells were cultured in plain culture medium in groups A and C or in hydrogen-saturated culture medium in groups B and D.LPS 1 µg/ml was added into groups C and D.When forming a monolayer, monocytes were added into each group after 6, 12 and 24 h respectively. After a 90-minute co-culturing, adhesion status was detected by Wright-Giemsa stain.Supernatants were collected to detect the concentrations of vascular cell adhesion molecule-1 (VCAM-1) and E-selectin by enzyme-linked immunosorbent assay (ELISA). The expression of VE-cadherin was measured by Western blot. Cells were stained with immunofluorescence to show the distribution of VE-cadherin after a 24-hour incubation. Compared with group A, the adhesion of monocytes to endothelial cells increased (P < 0.05) in group C, the levels of E-selectin and VCAM-1 became elevated (P < 0.05) while the expression of VE-cadherin decreased significantly (P < 0.05). Compared with group C, adhesion decreased in group D (P < 0.05), the levels of E-selectin and VCAM-1 decreased (P < 0.05) while there was an increased expression of VE-cadherin (P < 0.05). Three timepoints showed the same tendency. The results of 24 h fluorescence indicated that, compared with group A, VE-cadherin was incomplete in cell-cell connections in group C.However it was complete and well-distributed in group D versus group C. Hydrogen-rich medium may reduce the LPS-induced release of adhesion molecules, lessen monocytic adhesion to HUVEC and regulate the expression of VE-cadherin to protect vascular permeability.

  18. Descriptive study of relationship between cardio-ankle vascular index and biomarkers in vascular-related diseases.

    PubMed

    Liu, Jinbo; Liu, Huan; Zhao, Hongwei; Shang, Guangyun; Zhou, Yingyan; Li, Lihong; Wang, Hongyu

    2017-01-01

    Cardio-ankle vascular index (CAVI) was supposed to be an independent predictor for vascular-related events. Biomarkers such as homocysteine (Hcy), N-terminal pro-brain natriuretic peptide (NT-proBNP), and urine albumin(microalbumin) (UAE) have involved the pathophysiological development of arteriosclerosis. The present study was to investigate relationship between CAVI and biomarkers in vascular-related diseases. A total of 656 subjects (M/F 272/384) from department of Vascular Medicine were enrolled into our study. They were divided into four groups according to the numbers of suffered diseases, healthy group (group 0: subjects without diseases of hypertension, diabetes mellitus (DM), coronary heart disease (CHD); n = 186), group 1 (with one of diseases of hypertension, CHD, DM; n = 237), group 2 (with two of diseases of hypertension, CHD, DM; n = 174), and group 3 (with all diseases of hypertension, CHD, DM; n = 59). CAVI was measured by VS-1000 apparatus. CAVI was increasing with increasing numbers of suffered vascular-related diseases. Similar results were found in the parameters of biomarkers such as Hcy, log NT-ProBNP, and log UAE. There were positive correlation between log NT-proBNP, Hcy, log UAE, and CAVI in the entire study group and nonhealthy group. Positive correlation between log UAE and CAVI were found in the entire study group after adjusting for age, body mass index (BMI), blood pressure, uric acid, and lipids. Multivariate analysis showed that log UAE was an independent associating factor of CAVI in all subjects. CAVI was significantly higher in subjects with hypertension, CHD, and DM. There was correlation between arterial stiffness and biomarkers such as NT-proBNP, Hcy, and UAE.

  19. Protective Effects of N-Acetyl Cysteine against Diesel Exhaust Particles-Induced Intracellular ROS Generates Pro-Inflammatory Cytokines to Mediate the Vascular Permeability of Capillary-Like Endothelial Tubes

    PubMed Central

    Tseng, Chia-Yi; Chang, Jing-Fen; Wang, Jhih-Syuan; Chang, Yu-Jung; Gordon, Marion K.; Chao, Ming-Wei

    2015-01-01

    Exposure to diesel exhaust particles (DEP) is associated with pulmonary and cardiovascular diseases. Previous studies using in vitro endothelial tubes as a simplified model of capillaries have found that DEP-induced ROS increase vascular permeability with rearrangement or internalization of adherens junctional VE-cadherin away from the plasma membrane. This allows DEPs to penetrate into the cell and capillary lumen. In addition, pro-inflammatory cytokines are up-regulated and mediate vascular permeability in response to DEP. However, the mechanisms through which these DEP-induced pro-inflammatory cytokines increase vascular permeability remain unknown. Hence, we examined the ability of DEP to induce permeability of human umbilical vein endothelial cell tube cells to investigate these mechanisms. Furthermore, supplementation with NAC reduces ROS production following exposure to DEP. HUVEC tube cells contributed to a pro-inflammatory response to DEP-induced intracellular ROS generation. Endothelial oxidative stress induced the release of TNF-α and IL-6 from tube cells, subsequently stimulating the secretion of VEGF-A independent of HO-1. Our data suggests that DEP-induced intracellular ROS and release of the pro-inflammatory cytokines TNF- α and IL-6, which would contribute to VEGF-A secretion and disrupt cell-cell borders and increase vasculature permeability. Addition of NAC suppresses DEP-induced ROS efficiently and reduces subsequent damages by increasing endogenous glutathione. PMID:26148005

  20. Isthmin is a novel vascular permeability inducer that functions through cell-surface GRP78-mediated Src activation.

    PubMed

    Venugopal, Shruthi; Chen, Mo; Liao, Wupeng; Er, Shi Yin; Wong, Wai-Shiu Fred; Ge, Ruowen

    2015-07-01

    Isthmin (ISM) is a recently identified 60 kDa secreted angiogenesis inhibitor. Two cell-surface receptors for ISM have been defined, the high-affinity glucose-regulated protein 78 kDa (GRP78) and the low-affinity αvβ5 integrin. As αvβ5 integrin plays an important role in pulmonary vascular permeability (VP) and ISM is highly expressed in mouse lung, we sought to clarify the role of ISM in VP. Recombinant ISM (rISM) dose-dependently enhances endothelial monolayer permeability in vitro and local dermal VP when administered intradermally in mice. Systemic rISM administration through intravenous injection leads to profound lung vascular hyperpermeability but not in other organs. Mechanistic investigations using molecular, biochemical approaches and specific chemical inhibitors revealed that ISM-GRP78 interaction triggers a direct interaction between GRP78 and Src, leading to Src activation and subsequent phosphorylation of adherens junction proteins and loss of junctional proteins from inter-endothelial junctions, resulting in enhanced VP. Dynamic studies of Src activation, VP and apoptosis revealed that ISM induces VP directly via Src activation while apoptosis contributes indirectly only after prolonged treatment. Furthermore, ISM is significantly up-regulated in lipopolysaccharide (LPS)-treated mouse lung. Blocking cell-surface GRP78 by systemic infusion of anti-GRP78 antibody significantly attenuates pulmonary vascular hyperpermeability in LPS-induced acute lung injury (ALI) in mice. ISM is a novel VP inducer that functions through cell-surface GRP78-mediated Src activation as well as induction of apoptosis. It induces a direct GRP78-Src interaction, leading to cytoplasmic Src activation. ISM contributes to pulmonary vascular hyperpermeability of LPS-induced ALI in mice. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  1. Tonic regulation of vascular permeability

    PubMed Central

    Curry, Fitz-Roy E.; Adamson, Roger H.

    2014-01-01

    Our major theme is that the layered structure of the endothelial barrier requires continuous activation of signaling pathways regulated by S1P and intracellular cAMP. These pathways modulate the adherens junction, continuity of tight junction strands, and the balance of synthesis and degradation of glycocalyx components. We evaluate recent evidence that baseline permeability is maintained by constant activity of mechanisms involving the small GTPases Rap1 and Rac1. In the basal state, the barrier is compromised when activities of the small GTPases are reduced by low S1P supply or delivery. With inflammatory stimulus, increased permeability can be understood in part as the action of signaling to reduce Rap1 and Rac1 activation. With the hypothesis that microvessel permeability and selectivity under both normal and inflammatory conditions are regulated by mechanisms that are continuously active it follows that when S1P or intracellular cAMP are elevated at the time of inflammatory stimulus, they can buffer changes induced by inflammatory agents and maintain normal barrier stability. When endothelium is exposed to inflammatory conditions and subsequently exposed to elevated S1P or intracellular cAMP, the same processes restore the functional barrier by first reestablishing the adherens junction, then modulating tight junctions and glycocalyx. In more extreme inflammatory conditions, loss of the inhibitory actions of Rac1 dependent mechanisms may promote expression of more inflammatory endothelial phenotypes by contributing to the up-regulation of RhoA dependent contractile mechanisms and the sustained loss of surface glycocalyx allowing access of inflammatory cells to the endothelium. PMID:23374222

  2. New continuous-flow total artificial heart and vascular permeability.

    PubMed

    Feng, Jun; Cohn, William E; Parnis, Steven M; Sodha, Neel R; Clements, Richard T; Sellke, Nicholas; Frazier, O Howard; Sellke, Frank W

    2015-12-01

    We tested the short-term effects of completely nonpulsatile versus pulsatile circulation after ventricular excision and replacement with total implantable pumps in an animal model on peripheral vascular permeability. Ten calves underwent cardiac replacement with two HeartMate III continuous-flow rotary pumps. In five calves, the pump speed was rapidly modulated to impart a low-frequency pulse pressure in the physiologic range (10-25 mm Hg) at a rate of 40 pulses per minute (PP). The remaining five calves were supported with a pulseless systemic circulation and no modulation of pump speed (NP). Skeletal muscle biopsies were obtained before cardiac replacement (baseline) and on postoperative days (PODs) 1, 7, and 14. Skeletal muscle-tissue water content was measured, and morphologic alterations of skeletal muscle were assessed. VE-cadherin, phospho-VE-cadherin, and CD31 were analyzed by immunohistochemistry. There were no significant changes in tissue water content and skeletal muscle morphology within group or between groups at baseline, PODs 1, 7, and 14, respectively. There were no significant alterations in the expression and/or distribution of VE-cadherin, phospho-VE-cadherin, and CD31 in skeletal muscle vasculature at baseline, PODs 1, 7, and 14 within each group or between the two groups, respectively. Although continuous-flow total artificial heart (CFTAH) with or without a pulse pressure caused slight increase in tissue water content and histologic damage scores at PODs 7 and 14, it failed to reach statistical significance. There was no significant adherens-junction protein degradation and phosphorylation in calf skeletal muscle microvasculature after CFTAH implantation, suggesting that short term of CFTAH with or without pulse pressure did not cause peripheral endothelial injury and did not increase the peripheral microvascular permeability. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Escherichia coli K1 invasion increases human brain microvascular endothelial cell monolayer permeability by disassembling vascular-endothelial cadherins at tight junctions.

    PubMed

    Sukumaran, Sunil K; Prasadarao, Nemani V

    2003-11-01

    We investigated the permeability changes that occur in the human brain microvascular endothelial cell (HBMEC) monolayer, an in vitro model of the blood-brain barrier, during Escherichia coli K1 infection. An increase in permeability of HBMECs and a decrease in transendothelial electrical resistance were observed. These permeability changes occurred only when HBMECs were infected with E. coli expressing outer membrane protein A (OmpA) and preceded the traversal of bacteria across the monolayer. Activated protein kinase C (PKC)-alpha interacts with vascular-endothelial cadherins (VECs) at the tight junctions of HBMECs, resulting in the dissociation of beta-catenins from VECs and leading to the increased permeability of the HBMEC monolayer. Overexpression of a dominant negative form of PKC-alpha in HBMECs blocked the E. coli-induced increase in permeability of HBMECs. Anti-OmpA and anti-OmpA receptor antibodies exerted inhibition of E. coli-induced permeability of HBMEC monolayers. This inhibition was the result of the absence of PKC-alpha activation in HBMECs treated with the antibodies.

  4. Atrial natriuretic factor increases vascular permeability

    NASA Technical Reports Server (NTRS)

    Lockette, Warren; Brennaman, Bruce

    1990-01-01

    An increase in central blood volume in microgravity may result in increased plasma levels of atrial natriuretic factor (ANF). In this study, it was determined whether ANF increases capillary permeability to plasma protein. Conscious, bilaterally nephrectomized male rats were infused with either saline, ANF + saline, or hexamethonium + saline over 2 h following bolus injections of (I-125)-albumin and (C-14)-dextran of similar molecular size. Blood pressure was monitored, and serial determinations of hematocrits were made. Animals infused with 1.0 microg/kg per min ANF had significantly higher hematocrits than animals infused with saline vehicle. Infusion of ANF increased the extravasation of (I-125)-albumin, but not (C-14)-dextran from the intravascular compartment. ANF also induced a depressor response in rats, but the change in blood pressure did not account for changes in capillary permeability to albumin; similar depressor responses induced by hexamethonium were not accompanied by increased extravasation of albumin from the intravascular compartment. ANF may decrease plasma volume by increasing permeability to albumin, and this effect of ANF may account for some of the signs and symptoms of space motion sickness.

  5. Atrial natriuretic factor increases vascular permeability

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lockette, W.; Brennaman, B.

    An increase in central blood volume in microgravity may result in increased plasma levels of atrial natriuretic factor (ANF). Since elevations in plasma ANF are found in clinical syndromes associated with edema, and since space motion sickness induced by microgravity is associated with an increase in central blood volume and facial edema, we determined whether ANF increases capillary permeability to plasma protein. Conscious, bilaterally nephrectomized male rats were infused with either saline, ANF + saline, or hexamethonium + saline over 2 h following bolus injections of 125I-albumin and 14C-dextran of similar molecular size. Blood pressure was monitored and serial determinationsmore » of hematocrits were made. Animals infused with 1.0 micrograms.kg-1.min-1 ANF had significantly higher hematocrits than animals infused with saline vehicle. Infusion of ANF increased the extravasation of 125I-albumin, but not 14C-dextran from the intravascular compartment. ANF also induced a depressor response in rats, but the change in blood pressure did not account for changes in capillary permeability to albumin; similar depressor responses induced by hexamethonium were not accompanied by increased extravasation of albumin from the intravascular compartment. ANF may decrease plasma volume by increasing permeability to albumin, and this effect of ANF may account for some of the signs and symptoms of space motion sickness.« less

  6. Studies on the vascular permeability induced by intrathecal substance P and bradykinin in the rat.

    PubMed

    Jacques, L; Couture, R

    1990-08-02

    The effects of substance P (SP), SP fragments, neurokinin A (NKA), neurokinin B (NKB) and selective agonists for neurokinin receptors were assessed on cutaneous vascular permeability after intrathecal (i.t.) administration in rats. Dose-dependent increases in plasma extravasation were observed with the following rank orders of potency ([p-Glu6]SP-(6-11) greater than SP greater than or equal to SP-(4-11) greater than [p-Glu5,MePhe8,Sar9]SP-(5-11) = [p-Glu5]SP-(5-11) greater than SP-(7-11) and SP greater than NKA greater than NKB). The N-terminal fragments SP-(1-4), SP-(1-7) and SP-(1-9) were inactive up to 65 nmol. The NK-1 receptor selective agonists [( beta-Ala4,Sar9,Met(O2)11]SP-(4-11) and [Pro9,Met(O2)11]SP) were more potent than the NK-2 ([Nle10]NKA-(4-10] and NK-3 ([beta-Asp4,MePhe7]NKB-(4-10) and [MePhe7]NKB) receptor-selective agonists. Plasma extravasation was also increased by i.t. bradykinin (BK, 8.1 nmol) while the fragment BK-(1-8), a potent B1-receptor-selective agonist, produced only a slight effect at 81 nmol. When BK was given after prior i.t. administration of 6.1 nmol of [Thi5.8,D-Phe7]BK, an antagonist of BK at the B2-receptor, the increase in vascular permeability was significantly attenuated. The analogue [Leu8]BK-(1-8) (10.3 nmol), an antagonist of BK at the B1-receptor, failed to modify the BK-induced plasma extravasation. Plasma extravasation induced by SP (6.5 nmol) and BK (8.1 nmol) was abolished in cervically vagotomized rats, and significantly reduced in both spinal rats and in capsaicin-treated animals. Conversely, bilateral adrenalectomy (48 h earlier) and intercollicular decerebration (30 min earlier) had no major effect on the response elicited either by SP or BK. The response to SP remained unaffected by methysergide and hexamethonium but was significantly reduced by methylnitrate atropine and diphenhydramine. Indomethacin significantly enhanced the plasma extravasation induced by SP. These results suggest that SP and BK may play a

  7. A sustained release formulation of novel quininib-hyaluronan microneedles inhibits angiogenesis and retinal vascular permeability in vivo.

    PubMed

    Galvin, Orla; Srivastava, Akshay; Carroll, Oliver; Kulkarni, Rajiv; Dykes, Steve; Vickers, Steven; Dickinson, Keith; Reynolds, Alison L; Kilty, Claire; Redmond, Gareth; Jones, Rob; Cheetham, Sharon; Pandit, Abhay; Kennedy, Breandán N

    2016-07-10

    Pathologic neovascularisation and ocular permeability are hallmarks of proliferative diabetic retinopathy and age-related macular degeneration. Current pharmacologic interventions targeting VEGF are effective in only 30-60% of patients and require multiple intraocular injections associated with iatrogenic infection. Thus, our goal is to develop novel small molecule drugs that are VEGF-independent are amenable to sustained ocular-release, and which reduce retinal angiogenesis and retinal vascular permeability. Here, the anti-angiogenic drug quininib was formulated into hyaluronan (HA) microneedles whose safety and efficacy was evaluated in vivo. Quininib-HA microneedles were formulated via desolvation from quininib-HA solution and subsequent cross-linking with 4-arm-PEG-amine prior to freeze-drying. Scanning electron microscopy revealed hollow needle-shaped particle ultrastructure, with a zeta potential of -35.5mV determined by electrophoretic light scattering. The incorporation efficiency and pharmacokinetic profile of quininib released in vitro from the microneedles was quantified by HPLC. Quininib incorporation into these microneedles was 90%. In vitro, 20% quininib was released over 4months; or in the presence of increasing concentrations of hyaluronidase, 60% incorporated quininib was released over 4months. Zebrafish hyaloid vasculature assays demonstrated quininib released from these microneedles significantly (p<0.0001) inhibited ocular developmental angiogenesis compared to control. Sustained amelioration of retinal vascular permeability (RVP) was demonstrated using a bespoke cysteinyl leukotriene induced rodent model. Quininib-HA microparticles significantly inhibited RVP in Brown Norway rats one month after administration compared to neat quininib control (p=0.0071). In summary, quininib-HA microneedles allow for sustained release of quininib; are safe in vivo and quininib released from these microneedles effectively inhibits angiogenesis and RVP in vivo

  8. Lignans from the stems and leaves of Brandisia hancei and their effects on VEGF-induced vascular permeability and migration of HRECs and DLAV formation in zebrafish.

    PubMed

    Lee, Ik-Soo; Kim, Young Sook; Jung, Seung-Hyun; Yu, Song Yi; Kim, Joo-Hwan; Sun, Hang; Kim, Jin Sook

    2015-01-01

    In our continuing search for novel antiangiogenic agents, a new lignan glycoside, (7R,8R)-1-(4-O-β-d-glucopyranosyl-3-methoxyphenyl)-2-{2-methoxy-4-[1-(E)-propene-3-ol]-phenoxyl}-propane-1,3-diol (1), along with three known lignans (2-4), were isolated from the 80% EtOH extract of Brandisia hancei stems and leaves. These isolates (1-4) were subjected to an in vitro bioassay to evaluate their effects on vascular endothelial growth factor (VEGF)-induced vascular permeability and migration of human retinal endothelial cells (HRECs). Of the compounds tested, compound 1 resulted in the greatest reduction in VEGF-induced vascular permeability by about 31.5% at 10 μM compared to the VEGF-treated control. In the migration assay, compounds 1 and 2 significantly decreased VEGF-induced HREC migration. Furthermore, zebrafish embryos treated with compounds 1 and 2 showed mild reductions of dorsal longitudinal anastomotic vessel (DLAV) formation.

  9. Development of a Digital Aquifer Permeability Map for the ...

    EPA Pesticide Factsheets

    Researchers at the U.S. Environmental Protection Agency’s Western Ecology Division have been developing hydrologic landscape maps for selected U.S. states in an effort to create a method to identify the intrinsic watershed attributes of landscapes in regions with little data. Each hydrologic landscape unit is assigned a categorical value from five key indices of macro-scale hydrologic behavior, including annual climate, climate seasonality, aquifer permeability, terrain, and soil permeability. The aquifer permeability index requires creation of a from-scratch dataset for each state. The permeability index for the Pacific Southwest (California, Nevada, and Arizona) expands and modifies the permeability index for the Pacific Northwest (Oregon, Washington, and Idaho), which preceded it. The permeability index was created by assigning geologic map units to one of 18 categories with presumed similar values of permeability to create a hydrolithologic map. The hydrolithologies were then further categorized into permeability index classifications of high, low, unknown and surface water. Unconsolidated, carbonate, volcanic, and undifferentiated units are classified more conservatively to better address uncertainty in source data. High vs. low permeability classifications are assigned qualitatively but follow a threshold guideline of 8.5x10-2 m/day hydraulic conductivity. Estimates of permeability from surface lithology is the current best practice for broad-sca

  10. Specificity and sensitivity of noninvasive measurement of pulmonary vascular protein leak.

    PubMed

    Dauber, I M; Pluss, W T; VanGrondelle, A; Trow, R S; Weil, J V

    1985-08-01

    Noninvasive techniques employing external counting of radiolabeled protein have the potential for measuring pulmonary vascular protein permeability, but their specificity and sensitivity remain unclear. We tested the specificity and sensitivity of a double-radioisotope method by injecting radiolabeled albumin (131I) and erythrocytes (99mTc) into anesthetized dogs and measuring the counts of each isotope for 150 min after injection with an external gamma probe fixed over the lung. We calculated the rate of increase of albumin counts measured by the probe (which reflects the rate at which protein leaks into the extravascular space). To assess permeability we normalized the rate of increase in albumin counts for changes in labeled erythrocyte signal to minimize influence of changes in vascular surface area and thus derived an albumin leak index. We measured the albumin leak index and gravimetric lung water during hydrostatic edema (acutely elevating left atrial pressure by left atrial balloon inflation: mean pulmonary arterial wedge pressure = 22.6 Torr) and in lung injury edema induced by high- (1.0 g/kg) and low-dose (0.25 g/kg) intravenous thiourea. To test specificity we compared hydrostatic and high-dose thiourea edema. The albumin leak index increased nearly fourfold from control after thiourea injury (27.2 +/- 2.3 X 10-4 vs. 7.6 +/- 0.9 X 10-4 min-1) but did not change from control levels after elevating left atrial pressure (8.9 +/- 1.2 X 10-4 min-1) despite comparable increases in gravimetric lung water. To test sensitivity we compared low-dose thiourea with controls. Following low-dose thiourea, the albumin leak index nearly doubled despite the absence of a measurable increase in lung water. We conclude that a noninvasive double radioisotope measurement of pulmonary vascular protein leak, employing external counting techniques and a simplified method of calculation, is specific for lung injury and is also sensitive enough to detect lung injury insufficient

  11. A substance P antagonist inhibits vagally induced increase in vascular permeability and bronchial smooth muscle contraction in the guinea pig

    PubMed Central

    Lundberg, J. M.; Saria, A.; Brodin, E.; Rosell, S.; Folkers, K.

    1983-01-01

    Electrical stimulation of the cervical vagus nerve in anesthetized guinea pigs induced a rapid increase in respiratory insufflation pressure, suggesting increased airway resistance. After intravenous administration of a substance P (SP) antagonist, [D-Arg1,D-Pro2,D-Trp7,9,Leu11]SP, the insufflation pressure response to vagal stimulation was reduced by 78% while the cardiovascular effects were unchanged. Histamine receptor-blocking agents were used to inhibit the effects of histamine release induced by the SP-antagonist. [D-Arg1,D-Pro2,D-Trp7,9,Leu11]SP also reduced the increase in insufflation pressure caused by intravenous SP or capsaicin. The long-lasting noncholinergic contraction of the main and hilus bronchi induced by field stimulation in vitro, as well as the contractile effects of SP and capsaicin, were also blocked by the SP antagonist. The cholinergic contractions and the noncholinergic tracheal relaxation on field stimulation in vitro were, however, not blocked by the antagonist. Vagal stimulation in vivo also increased vascular permeability in the respiratory tract and esophagus, causing a subepithelial edema as indicated by Evans blue extravasation. Previous treatment with [D-Arg1,D-Pro2,D-Trp7,9,Leu11]SP inhibited the permeability increase induced by both vagus nerve stimulation and exogenous SP. SP release from vagal sensory nerves was indirectly shown by reduction in the bronchial levels of SP after nerve stimulation in vivo. The data suggest that a major portion of the vagally or capsaicin-induced increase in smooth muscle tone is caused by SP release from sensory neurons. In addition, activation of vagal SP-containing sensory nerves induces local edema. Tracheobronchial afferent SP-containing C fibers may thus exert local control of smooth muscle tone and vascular permeability in normal and pathophysiological conditions. Images PMID:6189120

  12. Revealing the role of phospholipase Cβ3 in the regulation of VEGF-induced vascular permeability

    PubMed Central

    Hoeppner, Luke H.; Phoenix, Kathryn N.; Clark, Karl J.; Bhattacharya, Resham; Gong, Xun; Sciuto, Tracey E.; Vohra, Pawan; Suresh, Sandip; Bhattacharya, Santanu; Dvorak, Ann M.; Ekker, Stephen C.; Dvorak, Harold F.; Claffey, Kevin P.

    2012-01-01

    VEGF induces vascular permeability (VP) in ischemic diseases and cancer, leading to many pathophysiological consequences. The molecular mechanisms by which VEGF acts to induce hyperpermeability are poorly understood and in vivo models that easily facilitate real-time, genetic studies of VP do not exist. In the present study, we report a heat-inducible VEGF transgenic zebrafish (Danio rerio) model through which VP can be monitored in real time. Using this approach with morpholino-mediated gene knock-down and knockout mice, we describe a novel role of phospholipase Cβ3 as a negative regulator of VEGF-mediated VP by regulating intracellular Ca2+ release. Our results suggest an important effect of PLCβ3 on VP and provide a new model with which to identify genetic regulators of VP crucial to several disease processes. PMID:22674805

  13. Src inhibitor reduces permeability without disturbing vascularization and prevents bone destruction in steroid-associated osteonecrotic lesions in rabbits.

    PubMed

    He, Yi-Xin; Liu, Jin; Guo, Baosheng; Wang, Yi-Xiang; Pan, Xiaohua; Li, Defang; Tang, Tao; Chen, Yang; Peng, Songlin; Bian, Zhaoxiang; Liang, Zicai; Zhang, Bao-Ting; Lu, Aiping; Zhang, Ge

    2015-03-09

    To examine the therapeutic effect of Src inhibitor on the VEGF mediating vascular hyperpermeability and bone destruction within steroid-associated osteonecrotic lesions in rabbits. Rabbits with high risk for progress to destructive repair in steroid-associated osteonecrosis were selected according to our published protocol. The selected rabbits were systemically administrated with either Anti-VEGF antibody (Anti-VEGF Group) or Src inhibitor (Src-Inhibition Group) or VEGF (VEGF-Supplement Group) or a combination of VEGF and Src inhibitor (Supplement &Inhibition Group) or control vehicle (Control Group) for 4 weeks. At 0, 2 and 4 weeks after administration, in vivo dynamic MRI, micro-CT based-angiography, histomorphometry and immunoblotting were employed to evaluate the vascular and skeletal events in different groups. The incidence of the destructive repair in the Anti-VEGF Group, Src-Inhibition Group and Supplement &Inhibition Group was all significantly lower than that in the Control Group. The angiogenesis was promoted in VEGF-Supplement Group, Src-Inhibition Group and Supplement &Inhibition Group, while the hyperpermeability was inhibited in Anti-VEGF Group, Src-Inhibition Group and Supplement &Inhibition Group. The trabecular structure was improved in Src-Inhibition Group and Supplement &Inhibition Group. Src inhibitor could reduce permeability without disturbing vascularization and prevent destructive repair in steroid-associated osteonecrosis.

  14. Cardio-ankle vascular index (CAVI) differentiates pharmacological properties of vasodilators nicardipine and nitroglycerin in anesthetized rabbits.

    PubMed

    Chiba, Tatsuo; Yamanaka, Mari; Takagi, Sachie; Shimizu, Kazuhiro; Takahashi, Mao; Shirai, Kohji; Takahara, Akira

    2015-08-01

    Cardio-ankle vascular index (CAVI) has been developed for measurement of vascular stiffness from the aorta to tibial artery, which is clinically utilized for assessing the progress of arteriosclerosis. In this study, we established measuring system of the CAVI in rabbits, and assessed whether the index could reflect different pharmacological actions of nitroglycerin and nicardipine on the systemic vasculature. Rabbits were anesthetized with halothane, and the CAVI was calculated from the well-established basic equations with variables obtained from brachial and tibial blood pressure and phonocardiogram. Nicardipine (1, 3 and 10 μg/kg, i.v.) decreased the blood pressure, femoral vascular resistance, and heart-ankle pulse wave velocity (haPWV). Meanwhile, no significant change was detected in the CAVI at the low or middle dose, which reflects the defining feature of the CAVI that is independent of blood pressure. The index increased at the high dose. Nitroglycerin (2, 4 and 8 μg/kg, i.v.) decreased the blood pressure, femoral vascular resistance, and haPWV. Meanwhile, the CAVI was decreased during the nitroglycerin infusion, which may reflect its well-known pharmacological action dilating conduit arteries. These results suggest that the CAVI differentiates the properties of these vasodilators in vivo. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  15. Snake spectacle vessel permeability to sodium fluorescein.

    PubMed

    Bellhorn, Roy W; Strom, Ann R; Motta, Monica J; Doval, John; Hawkins, Michelle G; Paul-Murphy, Joanne

    2018-03-01

    Assess vascular permeability of the snake spectacle to sodium fluorescein during resting and shedding phases of the ecdysis cycle. Ball python (Python regius). The snake was anesthetized, and spectral domain optic coherence tomography was performed prior to angiographic procedures. An electronically controlled digital single-lens reflex camera with a dual-head flash equipped with filters suitable for fluorescein angiography was used to make images. Sodium fluorescein (10%) solution was administered by intracardiac injection. Angiographic images were made as fluorescein traversed the vasculature of the iris and spectacle. Individually acquired photographic frames were assessed and sequenced into pseudovideo image streams for further evaluation CONCLUSIONS: Fluorescein angiograms of the snake spectacle were readily obtained. Vascular permeability varied with the phase of ecdysis. Copious leakage of fluorescein occurred during the shedding phase. This angiographic method may provide diverse opportunities to investigate vascular aspects of snake spectacle ecdysis, dysecdysis, and the integument in general. © 2017 American College of Veterinary Ophthalmologists.

  16. Role of Staphylococcus aureus Virulence Factors in Inducing Inflammation and Vascular Permeability in a Mouse Model of Bacterial Endophthalmitis

    PubMed Central

    Kumar, Ajay; Kumar, Ashok

    2015-01-01

    Staphylococcus (S.) aureus is a common causative agent of bacterial endophthalmitis, a vision threatening complication of eye surgeries. The relative contribution of S. aureus virulence factors in the pathogenesis of endophthalmitis remains unclear. Here, we comprehensively analyzed the development of intraocular inflammation, vascular permeability, and the loss of retinal function in C57BL/6 mouse eyes, challenged with live S. aureus, heat-killed S. aureus (HKSA), peptidoglycan (PGN), lipoteichoic acid (LTA), staphylococcal protein A (SPA), α-toxin, and Toxic-shock syndrome toxin 1 (TSST1). Our data showed a dose-dependent (range 0.01 μg/eye to 1.0 μg/eye) increase in the levels of inflammatory mediators by all virulence factors. The cell wall components, particularly PGN and LTA, seem to induce higher levels of TNF-α, IL-6, KC, and MIP2, whereas the toxins induced IL-1β. Similarly, among the virulence factors, PGN induced higher PMN infiltration. The vascular permeability assay revealed significant leakage in eyes challenged with live SA (12-fold) and HKSA (7.3-fold), in comparison to other virulence factors (~2-fold) and controls. These changes coincided with retinal tissue damage, as evidenced by histological analysis. The electroretinogram (ERG) analysis revealed a significant decline in retinal function in eyes inoculated with live SA, followed by HKSA, SPA, and α-toxin. Together, these findings demonstrate the differential innate responses of the retina to S. aureus virulence factors, which contribute to intraocular inflammation and retinal function loss in endophthalmitis. PMID:26053426

  17. Hemodynamic comparison of mild and severe preeclampsia: concept of stroke systemic vascular resistance index.

    PubMed

    Scardo, J; Kiser, R; Dillon, A; Brost, B; Newman, R

    1996-01-01

    Our purpose was to compare baseline hemodynamic parameters of mild and severe preeclampsia. Patients admitted to the Medical University Labor and Delivery Unit with the diagnosis of preeclampsia who had not received prior antihypertensive or magnesium sulfate therapy were recruited for noninvasive hemodynamic monitoring with thoracic electrical bioimpedance. After stabilization in the lateral recumbent position, hemodynamic monitoring was begun. Baseline hemodynamic parameters, mean arterial pressure (MAP), heart rate (HR), systemic vascular resistance index (SVRI), cardiac index (CI), and stroke index (SI) were recorded. Stroke systemic vascular resistance index (SSVRI), the resistance imposed by vasculature on each beat of the heart, was calculated for each patient by multiplying SVRI by HR. For statistical analysis, unpaired Student's t-tests (two-tailed) were utilized (P < 0.01). Forty-one preeclamptic patients (20 mild, 21 severe) were enrolled. Mean gestational age of severe patients was 32.2 +/- 4.0 and of mild patients was 37.0 +/- 3.5. MAP, SBP, diastolic blood pressure, HR, and SSVRI were higher in the severe group. SVRI, CI, cardiac output, and SI did not differ significantly between groups. Severe preclampsia appears to be a more intensely vasoconstricted state than mild preeclampsia. Although CI is inversely proportional to SVRI, increased HR in severe preeclampsia prevents this expected decrease in cardiac output.

  18. Developmental regulation of vascular endothelial growth/permeability factor messenger ribonucleic acid levels in and vascularization of the villous placenta during baboon pregnancy.

    PubMed

    Hildebrandt, V A; Babischkin, J S; Koos, R D; Pepe, G J; Albrecht, E D

    2001-05-01

    Vascular endothelial growth/permeability factor (VEG/PF) has an important role in angiogenesis; however, very little is known about the developmental regulation of VEG/PF and the vascular system within the placenta during human pregnancy. In the present study, therefore, a developmental approach was used in the baboon to determine the placental source of VEG/PF and its fms-like tyrosine kinase (flt-1) and kinase-insert domain containing (KDR/flk-1) receptors, and whether the rise in estrogen with advancing pregnancy was associated with a corresponding increase in placental VEG/PF expression and vascularization. VEG/PF messenger RNA (mRNA) levels were determined by competitive RT-PCR in villous cell fractions isolated by Percoll gradient centrifugation from placentas obtained on days 45 and 54 (very early), 60 (early), 100 (mid), and 165-170 (late) of baboon pregnancy (term = 184 days). Maternal peripheral serum estradiol increased from very low concentrations early in gestation (0.15-0.20 ng/ml) to an early surge of over 2.5 ng/ml on days 60-85, and peak levels of 4-6 ng/ml late in baboon pregnancy. VEG/PF mRNA was expressed in low level in the syncytiotrophoblast (<2,000 attomol/microgram total RNA), and values in this fraction did not change significantly with advancing gestation. VEG/PF mRNA expression was slightly greater in the inner villous core cell fraction; however, levels decreased (P < 0.05) between early and late gestation. Cytotrophoblasts were a major source of VEG/PF mRNA and levels increased (P < 0.01) from 3,631 +/- 844 attomol/microgram total RNA on day 45 to 25,807 +/- 5,873 attomol/microgram total RNA on day 170. VEG/PF protein expression determined by immunocytochemistry was abundant in cytotrophoblasts and lower in the syncytiotrophoblast and inner villous core cells. The flt-1 and KDR/flk-1 receptors were expressed in the vascular endothelial cells of the baboon villous placenta. The percentage of villous placenta occupied by blood vessels

  19. The clinical applicability of an automated plethysmographic determination of the ankle-brachial index after vascular surgery.

    PubMed

    van der Slegt, Jasper; Verbogt, Nathalie Pa; Mulder, Paul Gh; Steunenberg, Stijn L; Steunenberg, Bastiaan E; van der Laan, Lijckle

    2016-10-01

    An automated ankle-brachial index device could lead to potential time savings and more accuracy in ankle-brachial index-determination after vascular surgery. This prospective cross-sectional study compared postprocedural ankle-brachial indices measured by a manual method with ankle-brachial indices of an automated plethysmographic method. Forty-two patients were included. No significant difference in time performing a measurement was observed (1.1 min, 95% CI: -0.2 to +2.4; P = 0.095). Mean ankle-brachial index with the automated method was 0.105 higher (95% CI: 0.017 to 0.193; P = 0.020) than with the manual method, with limits of agreement of -0.376 and +0.587. Total variance amounted to 0.0759 and the correlation between both methods was 0.60. Reliability expressed as maximum absolute difference (95% level) between duplicate ankle-brachial index-measurements under identical conditions was 0.350 (manual) and 0.152 (automated), although not significant (p = 0.053). Finally, the automated method had 34% points higher failure rate than the manual method. In conclusion based on this study, the automated ankle-brachial index-method seems not to be clinically applicable for measuring ankle-brachial index postoperatively in patients with vascular disease. © The Author(s) 2016.

  20. Pressure sensitivity of low permeability sandstones

    USGS Publications Warehouse

    Kilmer, N.H.; Morrow, N.R.; Pitman, Janet K.

    1987-01-01

    Detailed core analysis has been carried out on 32 tight sandstones with permeabilities ranging over four orders of magnitude (0.0002 to 4.8 mD at 5000 psi confining pressure). Relationships between gas permeability and net confining pressure were measured for cycles of loading and unloading. For some samples, permeabilities were measured both along and across bedding planes. Large variations in stress sensitivity of permeability were observed from one sample to another. The ratio of permeability at a nominal confining pressure of 500 psi to that at 5000 psi was used to define a stress sensitivity ratio. For a given sample, confining pressure vs permeability followed a linear log-log relationship, the slope of which provided an index of pressure sensitivity. This index, as obtained for first unloading data, was used in testing relationships between stress sensitivity and other measured rock properties. Pressure sensitivity tended to increase with increase in carbonate content and depth, and with decrease in porosity, permeability and sodium feldspar. However, scatter in these relationships increased as permeability decreased. Tests for correlations between pressure sensitivity and various linear combinations of variables are reported. Details of pore structure related to diagenetic changes appears to be of much greater significance to pressure sensitivity than mineral composition. ?? 1987.

  1. Perfluorohexadecanoic acid increases paracellular permeability in endothelial cells through the activation of plasma kallikrein-kinin system.

    PubMed

    Liu, Qian S; Hao, Fang; Sun, Zhendong; Long, Yanmin; Zhou, Qunfang; Jiang, Guibin

    2018-01-01

    Per- and polyfluoroalkyl substances (PFASs) are ubiquitous and high persistent in human blood, thus potentially inducing a myriad of deleterious consequences. Plasma kallikrein-kinin system (KKS), which physiologically regulates vascular permeability, is vulnerable to exogenous stimulators, like PFASs with long-chain alkyl backbone substituted by electronegative fluorine. The study on the interactions of PFASs with the KKS and the subsequent effects on vascular permeability would be helpful to illustrate how the chemicals penetrate the biological vascular barriers to reach different tissues. In present study, three representative PFASs, including perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and perfluorohexadecanoic acid (PFHxDA), were investigated for their effects on the activation of the KKS, paracellular permeability in human retina endothelial cells (HRECs) and integrity of the adherens junctions. In contrast to either PFOS or PFOA, PFHxDA efficiently triggered KKS activation in a concentration-dependent manner based on protease activity assays. The plasma activated by PFHxDA significantly increased paracellular permeability of HRECs through the degradation of adherens junctions. As evidenced by the antagonistic effect of aprotinin, PFHxDA-involved effects on vascular permeability were mediated by KKS activation. The results herein firstly revealed the mechanistic pathway for PFHxDA induced effects on vascular endothelial cells. Regarding the possible structure-related activities of the chemicals, this finding would be of great help in the risk assessment of PFASs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Quantitative MRI study of the permeability of peritumoral brain edema in lung cancer patients with brain metastases.

    PubMed

    Wang, Dan; Wang, Ming-Liang; Li, Yue-Hua

    2017-08-15

    To use Ktrans to evaluate the aggressiveness and vascular permeability of peritumoral edema in cases of lung cancer brain metastases. A total of 68 lung cancer patients with 92 metastatic brain lesions were enrolled (20 metastatic lesions only in the gray matter - group 1; and 72 metastatic lesions located in the gray and white matter junction - group 2). All patients underwent MRI examination, which involved a dual angle (2° and 15°) enhanced T1W-VIBE (volume interpolated breath-hold examination) sequence to calculate the T1 parameter map. We used the enhanced T1-3D sequence to measure the tumor volume. The vascular permeability coefficient (Ktrans) was calculated using the single-compartment Tofts model, motion registration, and quick input mode. We examined the correlations of Ktrans with the edema index (EI), Ktrans with the tumor volume, and Ktrans with the histological expression of MMP-9 or VEGF in the original lung tumor using Pearson's' correlation analysis. Ktrans and EI were highly correlated in group 2 (r=0.66687; P<0.001) and not correlated in group 1 (r=0.33096; P=0.15405). Ktrans was also moderately related to the positive expression of MMP-9 (r=0.50912; P<0.001) and VEGF (r=0.36995; P=0.00138) There is statistical correlation between Ktrans and EI for group 2, and no statistical correlation between Ktrans and EI for group 1. The Ktrans of the peritumoral brain edema may be used to indicate the aggressiveness and vascular permeability of brain metastases in patients with lung cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Cytotoxicity, permeability, and inflammation of metal oxide nanoparticles in human cardiac microvascular endothelial cells: cytotoxicity, permeability, and inflammation of metal oxide nanoparticles.

    PubMed

    Sun, Jing; Wang, Shaochuang; Zhao, Dong; Hun, Fei Han; Weng, Lei; Liu, Hui

    2011-10-01

    Wide applications and extreme potential of metal oxide nanoparticles (NPs) increase occupational and public exposure and may yield extraordinary hazards for human health. Exposure to NPs has a risk for dysfunction of the vascular endothelial cells. The objective of this study was to assess the cytotoxicity of six metal oxide NPs to human cardiac microvascular endothelial cells (HCMECs) in vitro. Metal oxide NPs used in this study included zinc oxide (ZnO), iron(III) oxide (Fe(2)O(3)), iron(II,III) oxide (Fe(3)O(4)), magnesium oxide (MgO), aluminum oxide (Al(2)O(3)), and copper(II) oxide (CuO). The cell viability, membrane leakage of lactate dehydrogenase, intracellular reactive oxygen species, permeability of plasma membrane, and expression of inflammatory markers vascular cell adhesion molecule-1, intercellular adhesion molecule-1, macrophage cationic peptide-1, and interleukin-8 in HCMECs were assessed under controlled and exposed conditions (12-24 h and 0.001-100 μg/ml of exposure). The results indicated that Fe(2)O(3), Fe(3)O(4), and Al(2)O(3) NPs did not have significant effects on cytotoxicity, permeability, and inflammation response in HCMECs at any of the concentrations tested. ZnO, CuO, and MgO NPs produced the cytotoxicity at the concentration-dependent and time-dependent manner, and elicited the permeability and inflammation response in HCMECs. These results demonstrated that cytotoxicity, permeability, and inflammation in vascular endothelial cells following exposure to metal oxide nanoparticles depended on particle composition, concentration, and exposure time. © Springer Science+Business Media B.V. 2011

  4. Neuroprotective effect of selective DPP-4 inhibitor in experimental vascular dementia.

    PubMed

    Jain, Swati; Sharma, Bhupesh

    2015-12-01

    Vascular risk factors are associated with a higher incidence of dementia. Diabetes mellitus is considered as a main risk factor for Alzheimer's disease and vascular dementia. Both forms of dementia are posing greater risk to the world population and are increasing at a faster rate. In the past we have reported the induction of vascular dementia by experimental diabetes. This study investigates the role of vildagliptin, a dipeptidyl peptidase-4 inhibitor in the pharmacological interdiction of pancreatectomy diabetes induced vascular endothelial dysfunction and subsequent vascular dementia in rats. Attentional set shifting and Morris water-maze test were used for assessment of learning and memory. Vascular endothelial function, blood brain barrier permeability, serum glucose, serum nitrite/nitrate, oxidative stress (viz. aortic superoxide anion, brain thiobarbituric acid reactive species and brain glutathione), brain calcium and inflammation (myeloperoxidase) were also estimated. Pancreatectomy diabetes rats have shown impairment of endothelial function, blood brain barrier permeability, learning and memory along with increase in brain inflammation, oxidative stress and calcium. Administration of vildagliptin has significantly attenuated pancreatectomy induced impairment of learning, memory, endothelial function, blood brain barrier permeability and biochemical parameters. It may be concluded that vildagliptin, a dipeptidyl peptidase-4 inhibitor may be considered as potential pharmacological agents for the management of pancreatectomy induced endothelial dysfunction and subsequent vascular dementia. The selective modulators of dipeptidyl peptidase-4 may further be explored for their possible benefits in vascular dementia. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Phenotypic heterogeneity in lung capillary and extra-alveolar endothelial cells. Increased extra-alveolar endothelial permeability is sufficient to decrease compliance.

    PubMed

    Lowe, Kevin; Alvarez, Diego; King, Judy; Stevens, Troy

    2007-11-01

    In acute respiratory distress syndrome, pulmonary vascular permeability increases, causing intravascular fluid and protein to move into the lung's interstitium. The classic model describing the formation of pulmonary edema suggests that fluid crossing the capillary endothelium is drawn by negative interstitial pressure into the potential space surrounding extra-alveolar vessels and, as interstitial pressure builds, is forced into the alveolar air space. However, the validity of this model is challenged by animal models of acute lung injury in which extra-alveolar vessels are more permeable than capillaries under a variety of conditions. In the current study, we sought to determine whether extravascular fluid accumulation can be produced because of increased permeability of either the capillary or extra-alveolar endothelium, and whether different pathophysiology results from such site-specific increases in permeability. We perfused isolated lungs with either the plant alkaloid thapsigargin, which increases extra-alveolar endothelial permeability, or with 4alpha-phorbol 12, 13-didecanoate, which increases capillary endothelial permeability. Both treatments produced equal increases in whole lung vascular permeability, but caused fluid accumulations in separate anatomical compartments. Light microscopy of isolated lungs showed that thapsigargin caused fluid cuffing of large vessels, while 4alpha-phorbol 12, 13-didecanoate caused alveolar flooding. Dynamic compliance was reduced in lungs with cuffing of large vessels, but not in lungs with alveolar flooding. Phenotypic differences between vascular segments resulted in site-specific increases in permeability, which have different pathophysiological outcomes. Our findings suggest that insults leading to acute respiratory distress syndrome may increase permeability in extra-alveolar or capillary vascular segments, resulting in different pathophysiological sequela.

  6. Changes in mast cells and in permeability of mesenteric microvessels under the effect of immobilization and electrostimulation

    NASA Technical Reports Server (NTRS)

    Gorizontova, M. P.

    1980-01-01

    It was shown that a reduction in the amount of mast cells in the mesentery and an increase in their degranulation was accompanied by an increase in vascular permeability of rat mesentery. It is supposed that immobilization and electrostimulation causing degranulation of mast cells prompted histamine and serotonin release from them, thus increasing the permeability of the venular portion of the microvascular bed. Prophylactic use of esculamin preparation with P-vitaminic activity decreased mast cell degranulation, which apparently prolonged the release of histamine and serotonin from them and normalized vascular permeability.

  7. Longitudinal investigation of permeability and distribution of macromolecules in mouse malignant transformation using PET.

    PubMed

    Rygh, Cecilie B; Qin, Shengping; Seo, Jai W; Mahakian, Lisa M; Zhang, Hua; Adamson, Roger; Chen, Jane Q; Borowsky, Alexander D; Cardiff, Robert D; Reed, Rolf K; Curry, Fitz-Roy E; Ferrara, Katherine W

    2011-02-01

    We apply positron emission tomography (PET) to elucidate changes in nanocarrier extravasation during the transition from premalignant to malignant cancer, providing insight into the use of imaging to characterize early cancerous lesions and the utility of nanoparticles in early disease. Albumin and liposomes were labeled with (64)Cu (half-life 12.7 hours), and longitudinal PET and CT imaging studies were conducted in a mouse model of ductal carcinoma in situ. A pharmacokinetic model was applied to estimate the tumor vascular volume and permeability. From early time points characterized by disseminated hyperproliferation, the enhanced vascular permeability facilitated lesion detection. During disease progression, the vascular volume fraction increased 1.6-fold and the apparent vascular permeability to albumin and liposomes increased ∼2.5-fold to 6.6 × 10(-8) and 1.3 × 10(-8) cm/s, respectively, with the accumulation of albumin increasing earlier in the disease process. In the malignant tumor, both tracers reached similar mean intratumoral concentrations of ∼6% ID/cc but the distribution of liposomes was more heterogeneous, ranging from 1% to 18% ID/cc compared with 1% to 9% ID/cc for albumin. The tumor-to-muscle ratio was 17.9 ± 8.1 and 7.1 ± 0.5 for liposomes and albumin, respectively, indicating a more specific delivery of liposomes than with albumin. PET imaging of radiolabeled particles, validated by confocal imaging and histology, detected the transition from premalignant to malignant lesions and effectively quantified the associated changes in vascular permeability. ©2010 AACR.

  8. Cardio-ankle vascular index is associated with cardiovascular target organ damage and vascular structure and function in patients with diabetes or metabolic syndrome, LOD-DIABETES study: a case series report.

    PubMed

    Gómez-Marcos, Manuel Ángel; Recio-Rodríguez, José Ignacio; Patino-Alonso, María Carmen; Agudo-Conde, Cristina; Gómez-Sánchez, Leticia; Gomez-Sanchez, Marta; Rodríguez-Sanchez, Emiliano; Maderuelo-Fernandez, Jose Angel; García-Ortiz, Luís

    2015-01-16

    The cardio ankle vascular index (CAVI) is a new index of the overall stiffness of the artery from the origin of the aorta to the ankle. This index can estimate the risk of atherosclerosis. We aimed to find the relationship between CAVI and target organ damage (TOD), vascular structure and function, and cardiovascular risk factors in Caucasian patients with type 2 diabetes mellitus or metabolic syndrome. We included 110 subjects from the LOD-Diabetes study, whose mean age was 61 ± 11 years, and 37.3% were women. Measurements of CAVI, brachial ankle pulse wave velocity (ba-PWV), and ankle brachial index (ABI) were taken using the VaSera device. Cardiovascular risk factors, renal function by creatinine, glomerular filtration rate, and albumin creatinine index were also obtained, as well as cardiac TOD with ECG and vascular TOD and carotid intima media thickness (IMT), carotid femoral PWV (cf-PWV), and the central and peripheral augmentation index (CAIx and PAIx). The Framingham-D'Agostino scale was used to measure cardiovascular risk. Mean CAVI was 8.7 ± 1.3. More than half (54%) of the participants showed one or more TOD (10% cardiac, 13% renal; 48% vascular), and 13% had ba-PWV ≥ 17.5 m/s. Patients with any TOD had the highest CAVI values: 1.15 (CI 95% 0.70 to 1.61, p < 0.001) and 1.14 (CI 95% 0.68 to 1.60, p < 0.001) when vascular TOD was presented, and 1.30 (CI 95% 0.51 to 2.10, p = 0.002) for the cardiac TOD. The CAVI values had a positive correlation with HbA1c and systolic and diastolic blood pressure, and a negative correlation with waist circumference and body mass index. The positive correlations of CAVI with IMT (β = 0.29; p < 0.01), cf-PWV (β = 0.83; p < 0.01), ba-PWV (β = 2.12; p < 0.01), CAIx (β = 3.42; p < 0.01), and PAIx (β = 5.05; p = 0.04) remained after adjustment for cardiovascular risk, body mass index, and antihypertensive, lipid-lowering, and antidiabetic drugs. The

  9. Loss of the Endothelial Glycocalyx Links Albuminuria and Vascular Dysfunction

    PubMed Central

    Ferguson, Joanne K.; Burford, James L.; Gevorgyan, Haykanush; Nakano, Daisuke; Harper, Steven J.; Bates, David O.; Peti-Peterdi, Janos

    2012-01-01

    Patients with albuminuria and CKD frequently have vascular dysfunction but the underlying mechanisms remain unclear. Because the endothelial surface layer, a meshwork of surface-bound and loosely adherent glycosaminoglycans and proteoglycans, modulates vascular function, its loss could contribute to both renal and systemic vascular dysfunction in proteinuric CKD. Using Munich-Wistar-Fromter (MWF) rats as a model of spontaneous albuminuric CKD, multiphoton fluorescence imaging and single-vessel physiology measurements revealed that old MWF rats exhibited widespread loss of the endothelial surface layer in parallel with defects in microvascular permeability to both water and albumin, in both continuous mesenteric microvessels and fenestrated glomerular microvessels. In contrast to young MWF rats, enzymatic disruption of the endothelial surface layer in old MWF rats resulted in neither additional loss of the layer nor additional changes in permeability. Intravenous injection of wheat germ agglutinin lectin and its adsorption onto the endothelial surface layer significantly improved glomerular albumin permeability. Taken together, these results suggest that widespread loss of the endothelial surface layer links albuminuric kidney disease with systemic vascular dysfunction, providing a potential therapeutic target for proteinuric kidney disease. PMID:22797190

  10. Vagus nerve stimulation blocks vascular permeability following burn injury in both local and distal sites

    PubMed Central

    Ortiz-Pomales, Yan T; Krzyzaniak, Michael; Coimbra, Raul; Baird, Andrew; Eliceiri, Brian P.

    2012-01-01

    Recent studies have shown that vagus nerve stimulation (VNS) can block the burn injury-induced systemic inflammatory response (SIRS). In this study we examined the potential for VNS to modulate vascular permeability (VP) in local sites (i.e. skin) and in secondary sites (i.e. lung) following burn injury. In a 30% total body surface area burn injury model, VP was measured using intravascular fluorescent dextran for quantification of the VP response in skin and lung. A peak in VP of the skin was observed 24 hours post-burn injury, that was blocked by VNS. Moreover, in the lung, VNS led to a reduction in burn-induced VP compared to sham-treated animals subjected to burn injury alone. The protective effects of VNS in this model were independent of the spleen, suggesting that the spleen was not a direct mediator of VNS. These studies identify a role for VNS in the regulation of VP in burns, with the translational potential of attenuating lung complications following burn injury. PMID:22694873

  11. Effect of platelet activating factor on endothelial permeability to plasma macromolecules

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Handley, D.A.; Arbeeny, C.M.; Lee, M.L.

    The effect of intrajugular administration of platelet activating factor (PAF-C16) on vascular permeability was examined in the guinea pig. To examine the loss of selective endothelial permeability, the extravasative effect of PAF was assessed by monitoring hemoconcentration and the plasma loss of /sup 125/I-albumin (6.7 nm), /sup 125/I-low density lipoproteins (22.0 nm) or /sup 125/I-very low density lipoproteins (62.1 nm). Extravasation was dose-dependent and began 1 min after PAF administration, continuing for 5-7 min. During extravasation, there was no evidence for selective plasma retention of any of the labeled plasma tracers, as measured by plasma radioactivity. These results suggest thatmore » PAF-induced extravasation is dose-dependent, with increases in vascular permeability sufficient to permit similar plasma efflux rates of albumin, low density lipoproteins and very low density lipoproteins.« less

  12. Towards cavitation-enhanced permeability in blood vessel on a chip

    NASA Astrophysics Data System (ADS)

    De Luca, R.; Silvani, G.; Scognamiglio, C.; Sinibaldi, G.; Peruzzi, G.; Chinappi, M.; Kiani, M. F.; Casciola, C. M.

    2017-08-01

    The development of targeted delivery systems releasing pharmaceutical agents directly at the desired site of action may improve their therapeutic efficiency while minimizing damage to healthy tissues, toxicity to the patient and drug waste. In this context, we have developed a bio-inspired microdevice mimicking the tumour microvasculature which represents a valuable tool for assessing the enhancement of blood vessel permeability due to cavitation. This novel system allows us to investigate the effects of ultrasound-driven microbubbles that temporarily open the endothelial intercellular junctions allowing drug to extravasate blood vessels into tumour tissues. The blood vessel on a chip consists of a tissue chamber and two independent vascular channels (width 200 µm, height 100 µm, length 2762 µm) cultured with endothelial cells placed side-by-side and separated by a series of 3 µm pores. Its geometry and dimensions mimic the three-dimensional morphology, size and flow characteristics of microvessels in vivo. The early stage of this project had a twofold objective: 1. To define the protocol for culturing of Human Umbilical Vein Endothelial Cells (HUVECs) within the vascular channel; 2. To develop a fluorescence based microscopy technique for measuring permeability. We have developed a reliable and reproducible protocol to culture endothelial cells within the artificial vessels in a realistic manner: HUVECs show the typical elongated shape in the direction of flow, exhibit tight junction formation and form a continuous layer with a central lumen that completely covers the channels wall. As expected, the permeability of cell-free device is higher than the one cultured with HUVECs in the vascular channels. The proposed blood vessel on a chip and the permeability measurement protocol have a significant potential to allow for the study of cavitation-enhanced permeability of the endothelium and improve efficiency in screening drug delivery systems.

  13. Results of the freeze resistance test, swelling index and coefficient of permeability of finegrained mining waste reinforced with cements

    NASA Astrophysics Data System (ADS)

    Morman, Justyna

    2018-04-01

    The article presents the result of laboratory tests for mining waste with grain size of 0 to 2 mm stabilized with cement. Used for stabilization of cement CEM I 42.5 R and blast furnace cement CEM III / A 42.5N - LH / HSR / NA and a plasticizer sealant. Cement was added to the mining waste test in the proportions of 5 - 8% in relation to the skeleton's weight. For the cemented samples, the freeze resistance test, swelling index, coefficient of permeability and pH of water leachate were tested. The addition of a cement binder resulted in diminishing the water permeability of mining waste and limiting the leaching of fine particles from the material.

  14. Regulation and function of endothelial glycocalyx layer in vascular diseases.

    PubMed

    Sieve, Irina; Münster-Kühnel, Anja K; Hilfiker-Kleiner, Denise

    2018-01-01

    In the vascular system, the endothelial surface layer (ESL) as the inner surface of blood vessels affects mechanotransduction, vascular permeability, rheology, thrombogenesis, and leukocyte adhesion. It creates barriers between endothelial cells and blood and neighbouring cells. The glycocalyx, composed of glycoconjugates and proteoglycans, is an integral component of the ESL and a key element in inter- and intracellular communication and tissue homeostasis. In pathophysiological conditions (atherosclerosis, infection, ischemia/reperfusion injury, diabetes, trauma and acute lung injury) glycocalyx-degrading factors, i.e. reactive oxygen and nitrogen species, matrix metalloproteinases, heparanase and sialidases, damage the ESL, thereby impairing endothelial functions. This leads to increased capillary permeability, leucocyte-endothelium interactions, thrombosis and vascular inflammation, the latter further driving glycocalyx destruction. The present review highlights current knowledge on the vasculoprotective role of the ESL, with specific emphasis on its remodelling in inflammatory vascular diseases and discusses its potential as a novel therapeutic target to treat vascular pathologies. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. VEGF isoforms have differential effects on permeability of human pulmonary microvascular endothelial cells.

    PubMed

    Ourradi, Khadija; Blythe, Thomas; Jarrett, Caroline; Barratt, Shaney L; Welsh, Gavin I; Millar, Ann B

    2017-06-02

    Alternative splicing of Vascular endothelial growth factor-A mRNA transcripts (commonly referred as VEGF) leads to the generation of functionally differing isoforms, the relative amounts of which have potentially significant physiological outcomes in conditions such as acute respiratory distress syndrome (ARDS). The effect of such isoforms on pulmonary vascular permeability is unknown. We hypothesised that VEGF 165 a and VEGF 165 b isoforms would have differing effects on pulmonary vascular permeability caused by differential activation of intercellular signal transduction pathways. To test this hypothesis we investigated the physiological effect of VEGF 165 a and VEGF 165 b on Human Pulmonary Microvascular Endothelial Cell (HPMEC) permeability using three different methods: trans-endothelial electrical resistance (TEER), Electric cell-substrate impedance sensing (ECIS) and FITC-BSA passage. In addition, potential downstream signalling pathways of the VEGF isoforms were investigated by Western blotting and the use of specific signalling inhibitors. VEGF 165 a increased HPMEC permeability using all three methods (paracellular and transcellular) and led to associated VE-cadherin and actin stress fibre changes. In contrast, VEGF 165 b decreased paracellular permeability and did not induce changes in VE-cadherin cell distribution. Furthermore, VEGF 165 a and VEGF 165 b had differing effects on both the phosphorylation of VEGF receptors and downstream signalling proteins pMEK, p42/44MAPK, p38 MAPK, pAKT and peNOS. Interestingly specific inhibition of the pMEK, p38 MAPK, PI3 kinase and eNOS pathways blocked the effects of both VEGF 165 a and VEGF 165 b on paracellular permeability and the effect of VEGF 165 a on proliferation/migration, suggesting that this difference in cellular response is mediated by an as yet unidentified signalling pathway(s). This study demonstrates that the novel isoform VEGF 165 a and VEGF 165 b induce differing effects on permeability in

  16. TNF-α Signals Through PKCζ/NF-κB to Alter the Tight Junction Complex and Increase Retinal Endothelial Cell Permeability

    PubMed Central

    Aveleira, Célia A.; Lin, Cheng-Mao; Abcouwer, Steven F.; Ambrósio, António F.; Antonetti, David A.

    2010-01-01

    OBJECTIVE Tumor necrosis factor-α (TNF-α) and interleukin-1 beta (IL-1β) are elevated in the vitreous of diabetic patients and in retinas of diabetic rats associated with increased retinal vascular permeability. However, the molecular mechanisms underlying retinal vascular permeability induced by these cytokines are poorly understood. In this study, the effects of IL-1β and TNF-α on retinal endothelial cell permeability were compared and the molecular mechanisms by which TNF-α increases cell permeability were elucidated. RESEARCH DESIGN AND METHODS Cytokine-induced retinal vascular permeability was measured in bovine retinal endothelial cells (BRECs) and rat retinas. Western blotting, quantitative real-time PCR, and immunocytochemistry were performed to determine tight junction protein expression and localization. RESULTS IL-1β and TNF-α increased BREC permeability, and TNF-α was more potent. TNF-α decreased the protein and mRNA content of the tight junction proteins ZO-1 and claudin-5 and altered the cellular localization of these tight junction proteins. Dexamethasone prevented TNF-α–induced cell permeability through glucocorticoid receptor transactivation and nuclear factor-kappaB (NF-κB) transrepression. Preventing NF-κB activation with an inhibitor κB kinase (IKK) chemical inhibitor or adenoviral overexpression of inhibitor κB alpha (IκBα) reduced TNF-α–stimulated permeability. Finally, inhibiting protein kinase C zeta (PKCζ) using both a peptide and a novel chemical inhibitor reduced NF-κB activation and completely prevented the alterations in the tight junction complex and cell permeability induced by TNF-α in cell culture and rat retinas. CONCLUSIONS These results suggest that PKCζ may provide a specific therapeutic target for the prevention of vascular permeability in retinal diseases characterized by elevated TNF-α, including diabetic retinopathy. PMID:20693346

  17. No causal impact of serum vascular endothelial growth factor level on temporal changes in body mass index in Japanese male workers: a five-year longitudinal study.

    PubMed

    Imatoh, Takuya; Kamimura, Seiichiro; Miyazaki, Motonobu

    2017-03-01

    It has been reported that adipocytes secrete vascular endothelial growth factor. Therefore, we conducted a 5-year longitudinal epidemiological study to further elucidate the association between vascular endothelial growth factor levels and temporal changes in body mass index. Our study subjects were Japanese male workers, who had regular health check-ups. Vascular endothelial growth factor levels were measured at baseline. To examine the association between vascular endothelial growth factor levels and overweight, we calculated the odds ratio using a multivariate logistic regression model. Moreover, linear mixed effect models were used to assess the association between vascular endothelial growth factor level and temporal changes in body mass index during the 5-year follow-up period. Vascular endothelial growth factor levels were marginally higher in subjects with a body mass index greater than 25 kg/m 2 compared with in those with a body mass index less than 25 kg/m 2 (505.4 vs. 465.5 pg/mL, P = 0.1) and were weakly correlated with leptin levels (β: 0.05, P = 0.07). In multivariate logistic regression, subjects in the highest vascular endothelial growth factor quantile were significantly associated with an increased risk for overweight compared with those in the lowest quantile (odds ratio 1.65, 95 % confidential interval: 1.10-2.50). Moreover P for trend was significant (P for trend = 0.003). However, the linear mixed effect model revealed that vascular endothelial growth factor levels were not associated with changes in body mass index over a 5-year period (quantile 2, β: 0.06, P = 0.46; quantile 3, β: -0.06, P = 0.45; quantile 4, β: -0.10, P = 0.22; quantile 1 as reference). Our results suggested that high vascular endothelial growth factor levels were significantly associated with overweight in Japanese males but high vascular endothelial growth factor levels did not necessarily cause obesity.

  18. Generalized nonlinear Schrödinger equation for dispersive susceptibility and permeability: application to negative index materials.

    PubMed

    Scalora, Michael; Syrchin, Maxim S; Akozbek, Neset; Poliakov, Evgeni Y; D'Aguanno, Giuseppe; Mattiucci, Nadia; Bloemer, Mark J; Zheltikov, Aleksei M

    2005-07-01

    A new generalized nonlinear Schrödinger equation describing the propagation of ultrashort pulses in bulk media exhibiting frequency dependent dielectric susceptibility and magnetic permeability is derived and used to characterize wave propagation in a negative index material. The equation has new features that are distinct from ordinary materials (mu=1): the linear and nonlinear coefficients can be tailored through the linear properties of the medium to attain any combination of signs unachievable in ordinary matter, with significant potential to realize a wide class of solitary waves.

  19. Hypertonic Saline Reduces Vascular Leakage in a Mouse Model of Severe Dengue

    PubMed Central

    Tan, Kar Wai; Angeli, Veronique; Moochhala, Shabbir; Ooi, Eng Eong; Alonso, Sylvie

    2013-01-01

    Dengue (DEN) is a mosquito-borne viral disease and represents a serious public health threat and an economical burden throughout the tropics. Dengue clinical manifestations range from mild acute febrile illness to severe DEN hemorrhagic fever/DEN shock syndrome (DHF/DSS). Currently, resuscitation with large volumes of isotonic fluid remains the gold standard of care for DEN patients who develop vascular leakage and shock. Here, we investigated the ability of small volume of hypertonic saline (HTS) suspensions to control vascular permeability in a mouse model of severe DEN associated with vascular leakage. Several HTS treatment regimens were considered and our results indicated that a single bolus of 7.5% NaCl at 4 mL per kg of body weight administered at the onset of detectable vascular leakage rapidly and significantly reduced vascular leak for several days after injection. This transient reduction of vascular leakage correlated with reduced intestine and liver damage with restoration of the hepatic functions, and resulted in delayed death of the infected animals. Mechanistically, we showed that HTS did not directly impact on the viral titers but resulted in lower immune cells counts and decreased systemic levels of soluble mediators involved in vascular permeability. In addition, we demonstrated that neutrophils do not play a critical role in DEN-associated vascular leakage and that the therapeutic effect of HTS is not mediated by its impact on the neutrophil counts. Together our data indicate that HTS treatment can transiently but rapidly reduce dengue-associated vascular leakage, and support the findings of a recent clinical trial which evaluated the efficacy of a hypertonic suspension to impact on vascular permeability in DSS children. PMID:23637867

  20. Vascular Physiology according to Clinical Scenario in Patients with Acute Heart Failure: Evaluation using the Cardio-Ankle Vascular Index.

    PubMed

    Goto, Toshihiko; Wakami, Kazuaki; Mori, Kento; Kikuchi, Shohei; Fukuta, Hidekatsu; Ohte, Nobuyuki

    2016-09-01

    Increased aortic stiffness may be an important cause of acute heart failure (AHF). Clinical scenario (CS), which classifies the pathophysiology of AHF based on the initial systolic blood pressure (sBP), was proposed to provide the most appropriate therapy for AHF patients. In CS, elevated aortic stiffness, vascular failure, has been considered as a feature of patients categorized as CS1 (sBP > 140 mmHg at initial presentation). However, whether elevated aortic stiffness, vascular failure, is present in such patients has not been fully elucidated. Therefore, we assessed aortic stiffness in AHF patients using the cardio-ankle vascular index (CAVI), which is considered to be independent of instantaneous blood pressure. Sixty-four consecutive AHF patients (mean age, 70.6 ± 12.8 years; 39 men) were classified with CS, based on their initial sBP: CS1: sBP > 140 mmHg (n = 29); CS2: sBP 100-140 mmHg (n = 22); and CS3: sBP < 100 mmHg (n = 13). There were significant group differences in CAVI (CS1 vs. CS2 vs. CS3: 9.7 ± 1.4 vs. 8.4 ± 1.7 vs. 8.3 ± 1.7, p = 0.006, analysis of variance). CAVI was significantly higher in CS1 than in CS2 (p = 0.02) and CS3 (p = 0.04). CAVI did not significantly correlate with sBP at the time of measurement of CAVI (r = 0.24 and p = 0.06). Aortic stiffness assessed using blood pressure-independent methodology apparently increased in CS1 AHF patients. We conclude that vascular failure is a feature of CS1 AHF initiation.

  1. Chronic uremia induces permeability changes, increased nitric oxide synthase expression, and structural modifications in the peritoneum.

    PubMed

    Combet, S; Ferrier, M L; Van Landschoot, M; Stoenoiu, M; Moulin, P; Miyata, T; Lameire, N; Devuyst, O

    2001-10-01

    Advanced glycation end products (AGE), growth factors, and nitric oxide contribute to alterations of the peritoneum during peritoneal dialysis (PD). These mediators are also involved in chronic uremia, a condition associated with increased permeability of serosal membranes. It is unknown whether chronic uremia per se modifies the peritoneum before PD initiation. A rat model of subtotal nephrectomy was used to measure peritoneal permeability after 3, 6, and 9 wk, in parallel with peritoneal nitric oxide synthase (NOS) isoform expression and activity and structural changes. Uremic rats were characterized by a higher peritoneal permeability for small solutes and an increased NOS activity due to the up-regulation of endothelial and neuronal NOS. The permeability changes and increased NOS activities correlated with the degree of renal failure. Focal areas of vascular proliferation and fibrosis were detected in uremic rats, in relation with a transient up-regulation of vascular endothelial growth factor and basic fibroblast growth factor, as well as vascular deposits of the AGE carboxymethyllysine and pentosidine. Correction of anemia with erythropoietin did not prevent the permeability or structural changes in uremic rats. Thus, in this rat model, uremia induces permeability and structural changes in the peritoneum, in parallel with AGE deposits and up-regulation of specific NOS isoforms and growth factors. These data suggest an independent contribution of uremia in the peritoneal changes during PD and offer a paradigm to better understand the modifications of serosal membranes in uremia.

  2. Inhibition of SUR1 Decreases the Vascular Permeability of Cerebral Metastases1

    PubMed Central

    Thompson, Eric M; Pishko, Gregory L; Muldoon, Leslie L; Neuwelt, Edward A

    2013-01-01

    Inhibition of sulfonylurea receptor 1 (SUR1) by glyburide has been shown to decrease edema after subarachnoid hemorrhage. We investigated if inhibiting SUR1 reduces cerebral edema due to metastases, the most common brain tumor, and explored the putative association of SUR1 and the endothelial tight junction protein, zona occludens-1 (ZO-1). Nude rats were intracerebrally implanted with small cell lung carcinoma (SCLC) LX1 or A2058 melanoma cells (n = 36). Rats were administered vehicle, glyburide (4.8 µg twice, orally), or dexamethasone (0.35 mg, intravenous). Blood-tumor barrier (BTB) permeability (Ktrans) was evaluated before and after treatment using dynamic contrast-enhanced magnetic resonance imaging. SUR1 and ZO-1 expression was evaluated using immunofluorescence and Western blots. In both models, SUR1 expression was significantly increased (P < .05) in tumors. In animals with SCLC, control mean Ktrans (percent change ± standard error) was 101.8 ± 36.6%, and both glyburide (-21.4 ± 14.2%, P < .01) and dexamethasone (-14.2 ± 13.1%, P < .01) decreased BTB permeability. In animals with melanoma, compared to controls (117.1 ± 43.4%), glyburide lowered BTB permeability increase (3.2 ± 15.4%, P < .05), while dexamethasone modestly lowered BTB permeability increase (63.1 ± 22.1%, P > .05). Both glyburide (P < .001) and dexamethasone (P < .01) decreased ZO-1 gap formation. By decreasing ZO-1 gaps, glyburide was at least as effective as dexamethasone at halting increased BTB permeability caused by SCLC and melanoma. Glyburide is a safe, inexpensive, and efficacious alternative to dexamethasone for the treatment of cerebral metastasis-related vasogenic edema. PMID:23633925

  3. Vasopeptidase inhibition with omapatrilat increases fluid and protein microvascular permeability in cat skeletal muscle.

    PubMed

    Persson, Johan; Morsing, Peter; Grände, Per-Olof

    2004-03-01

    Vasopeptidase inhibition is a new antihypertensive approach combining inhibition of angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP), but severe oedema, mainly angio-oedema, has been reported. As ACE and NEP catalyse degradation of the permeability-increasing peptide bradykinin, and NEP also catalyses degradation of permeability-increasing peptides such as atrial natriuretic peptide, substance P, endothelin-1 and angiotensin II, vasopeptidase inhibition may increase microvascular permeability. To analyse the effects of vasopeptidase inhibition on permeability. The study was performed on the autoperfused cat calf skeletal muscle, evaluating the effects on fluid and protein permeability of a clinically relevant dose of the vasopeptidase inhibitor, omapatrilat. The effects were compared with those of the vehicle, of selective ACE and NEP inhibition, and of omapatrilat during bradykinin receptor blockade. Effects on fluid permeability were determined with a capillary filtration coefficient (CFC) technique, and effects on protein permeability were assessed from changes in the osmotic reflection coefficient for albumin. After 1.5 h of intravenous infusion of omapatrilat (0.35 mg/kg per hour), mean arterial pressure was reduced from 114 mmHg to 86 mmHg (P < 0.01) and skeletal muscle vascular resistance was reduced from 14.5 peripheral resistance units (PRU) to 11.5 PRU (P < 0.05). CFC was increased by 22% (P < 0.01) and the reflection coefficient was decreased by 17% (P < 0.01). Infusion of vehicle had no effects. Inhibition of NEP increased permeability without affecting blood pressure, whereas ACE inhibition decreased blood pressure without affecting permeability. The increase in permeability associated with omapatrilat was reduced by bradykinin blockade. A clinically relevant antihypertensive dose of omapatrilat reduces vascular resistance and increases fluid and protein permeability, the permeability effect more by inhibition of NEP than by

  4. Heterogeneous blood-tumor barrier permeability determines drug efficacy in experimental brain metastases of breast cancer.

    PubMed

    Lockman, Paul R; Mittapalli, Rajendar K; Taskar, Kunal S; Rudraraju, Vinay; Gril, Brunilde; Bohn, Kaci A; Adkins, Chris E; Roberts, Amanda; Thorsheim, Helen R; Gaasch, Julie A; Huang, Suyun; Palmieri, Diane; Steeg, Patricia S; Smith, Quentin R

    2010-12-01

    Brain metastases of breast cancer appear to be increasing in incidence, confer significant morbidity, and threaten to compromise gains made in systemic chemotherapy. The blood-tumor barrier (BTB) is compromised in many brain metastases; however, the extent to which this influences chemotherapeutic delivery and efficacy is unknown. Herein, we answer this question by measuring BTB passive integrity, chemotherapeutic drug uptake, and anticancer efficacy in vivo in two breast cancer models that metastasize preferentially to brain. Experimental brain metastasis drug uptake and BTB permeability were simultaneously measured using novel fluorescent and phosphorescent imaging techniques in immune-compromised mice. Drug-induced apoptosis and vascular characteristics were assessed using immunofluorescent microscopy. Analysis of over 2,000 brain metastases from two models (human 231-BR-Her2 and murine 4T1-BR5) showed partial BTB permeability compromise in greater than 89% of lesions, varying in magnitude within and between metastases. Brain metastasis uptake of ¹⁴C-paclitaxel and ¹⁴C-doxorubicin was generally greater than normal brain but less than 15% of that of other tissues or peripheral metastases, and only reached cytotoxic concentrations in a small subset (∼10%) of the most permeable metastases. Neither drug significantly decreased the experimental brain metastatic ability of 231-BR-Her2 tumor cells. BTB permeability was associated with vascular remodeling and correlated with overexpression of the pericyte protein desmin. This work shows that the BTB remains a significant impediment to standard chemotherapeutic delivery and efficacy in experimental brain metastases of breast cancer. New brain permeable drugs will be needed. Evidence is presented for vascular remodeling in BTB permeability alterations. ©2010 AACR.

  5. Heterogeneous Blood-Tumor Barrier Permeability Determines Drug Efficacy in Experimental Brain Metastases of Breast Cancer

    PubMed Central

    Lockman, Paul R.; Mittapalli, Rajendar K.; Taskar, Kunal S.; Rudraraju, Vinay; Gril, Brunilde; Bohn, Kaci A.; Adkins, Chris E.; Roberts, Amanda; Thorsheim, Helen R.; Gaasch, Julie A.; Huang, Suyun; Palmieri, Diane; Steeg, Patricia S.; Smith, Quentin R.

    2010-01-01

    Purpose Brain metastases of breast cancer appear to be increasing in incidence, confer significant morbidity, and threaten to compromise gains made in systemic chemotherapy. The blood-tumor barrier (BTB) is compromised in many brain metastases, however, the extent to which this influences chemotherapeutic delivery and efficacy is unknown. Herein, we answer this question by measuring BTB passive integrity, chemotherapeutic drug uptake, and anticancer efficacy in vivo in two breast cancer models that metastasize preferentially to brain. Experimental Design Experimental brain metastasis drug uptake and BTB permeability were simultaneously measured using novel fluorescent and phosphorescent imaging techniques in immune compromised mice. Drug-induced apoptosis and vascular characteristics were assessed using immunofluorescent microscopy. Results Analysis of >2000 brain metastases from two models (human 231-BR-Her2 and murine 4T1-BR5) demonstrated partial BTB permeability compromise in >89% lesions, varying in magnitude within and between metastases. Brain metastasis uptake of 14C- paclitaxel and 14C- doxorubicin was generally greater than normal brain but <15% of that of other tissues or peripheral metastases, and only reached cytotoxic concentrations in a small subset (~10%) of the most permeable metastases. Neither drug significantly decreased the experimental brain metastatic ability of 231-BR-Her2 tumor cells. BTB permeability was associated with vascular remodeling and correlated with over expression of the pericyte protein, desmin. Conclusions This work demonstrates that the BTB remains a significant impediment to standard chemotherapeutic delivery and efficacy in experimental brain metastases of breast cancer. New brain permeable drugs will be needed. Evidence is presented for vascular remodeling in BTB permeability alterations. PMID:20829328

  6. Age-related changes in mouse bone permeability.

    PubMed

    Rodriguez-Florez, Naiara; Oyen, Michelle L; Shefelbine, Sandra J

    2014-03-21

    The determination of lacunar-canalicular permeability is essential for understanding local fluid flow in bone, which may indicate how bone senses changes in the mechanical environment to regulate mechano-adaptation. The estimates of lacunar-canalicular permeability found in the literature vary by up to eight orders of magnitude, and age-related permeability changes have not been measured in non-osteonal mouse bone. The objective of this study is to use a poroelastic approach based on nanoindentation data to characterize lacunar-canalicular permeability in murine bone as a function of age. Nine wild type C57BL/6 mice of different ages (2, 7 and 12 months) were used. Three tibiae from each age group were embedded in epoxy resin, cut in half and indented in the longitudinal direction in the mid-cortex using two spherical fluid indenter tips (R=238 μm and 500 μm). Results suggest that the lacunar-canalicular intrinsic permeability of mouse bone decreases from 2 to 7 months, with no significant changes from 7 to 12 months. The large indenter tip imposed larger contact sizes and sampled larger ranges of permeabilities, particularly for the old bone. This age-related difference in the distribution was not seen for indents with the smaller radius tip. We conclude that the small tip effectively measured lacunar-canalicular permeability, while larger tip indents were influenced by vascular permeability. Exploring the age-related changes in permeability of bone measured by nanoindentation will lead to a better understanding of the role of fluid flow in mechano-transduction. This understanding may help indicate alterations in bone adaptation and remodeling. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Palomid 529, a Novel Small-Molecule Drug, Is a TORC1/TORC2 Inhibitor That Reduces Tumor Growth, Tumor Angiogenesis, and Vascular Permeability

    PubMed Central

    Xue, Qi; Hopkins, Benjamin; Perruzzi, Carole; Udayakumar, Durga; Sherris, David; Benjamin, Laura E.

    2009-01-01

    It has become clear that the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is central for promoting both tumor and tumor stroma and is therefore a major target for anticancer drug development. First- and second-generation rapalogs (prototypical mTOR inhibitors) have shown promise but, due to the complex nature of mTOR signaling, can result in counterproductive feedback signaling to potentiate upstream Akt signaling. We present a novel PI3K/Akt/mTOR inhibitor, Palomid 529 (P529), which inhibits the TORC1 and TORC2 complexes and shows both inhibition of Akt signaling and mTOR signaling similarly in tumor and vasculature. We show that P529 inhibits tumor growth, angiogenesis, and vascular permeability. It retains the beneficial aspects of tumor vascular normalization that rapamycin boasts. However, P529 has the additional benefit of blocking pAktS473 signaling consistent with blocking TORC2 in all cells and thus bypassing feedback loops that lead to increased Akt signaling in some tumor cells. [Cancer Res 2008;68(22):9551–7] PMID:19010932

  8. Application of the Red List Index for conservation assessment of Spanish vascular plants.

    PubMed

    Saiz, Juan Carlos Moreno; Lozano, Felipe Domínguez; Gómez, Manuel Marrero; Baudet, Ángel Bañares

    2015-06-01

    The International Union for Conservation of Nature (IUCN) Red List Index (RLI) is used to measure trends in extinction risk of species over time. The development of 2 red lists for Spanish vascular flora during the past decade allowed us to apply the IUCN RLI to vascular plants in an area belonging to a global biodiversity hotspot. We used the Spanish Red Lists from 2000 and 2010 to assess changes in level of threat at a national scale and at the subnational scales of Canary Islands, Balearic Islands, and peninsular Spain. We assigned retrospective IUCN categories of threat to 98 species included in the Spanish Red List of 2010 but absent in the Spanish Red List of 2000. In addition, we tested the effect of different random and taxonomic and spatial Spanish samples on the overall RLI value. From 2000 to 2010, the IUCN categories of 768 species changed (10% of Spanish flora), mainly due to improved knowledge (63%), modifications in IUCN criteria (14%), and changes in threat status (12%). All measured national and subnational RLI values decreased during this period, indicating a general decline in the conservation status of the Spanish vascular flora. The Canarian RLI value (0.84) was the lowest, although the fastest deterioration in conservation status occurred on peninsular Spain (from 0.93 in 2000 to 0.92 in 2010). The RLI values based on subsamples of the Spanish Red List were not representative of RLI values for the entire country, which would discourage the use of small areas or small taxonomic samples to assess general trends in the endangerment of national biotas. The role of the RLI in monitoring of changes in biodiversity at the global and regional scales needs further reassessment because additional areas and taxa are necessary to determine whether the index is sufficiently sensitive for use in assessing temporal changes in species' risk of extinction. © 2015 Society for Conservation Biology.

  9. Dynamic magnetic resonance imaging assessment of vascular targeting agent effects in rat intracerebral tumor models

    PubMed Central

    Muldoon, Leslie L.; Gahramanov, Seymur; Li, Xin; Marshall, Deborah J.; Kraemer, Dale F.; Neuwelt, Edward A.

    2011-01-01

    We used dynamic MRI to evaluate the effects of monoclonal antibodies targeting brain tumor vasculature. Female athymic rats with intracerebral human tumor xenografts were untreated or treated with intetumumab, targeting αV-integrins, or bevacizumab, targeting vascular endothelial growth factor (n = 4–6 per group). Prior to treatment and at 1, 3, and 7 days after treatment, we performed standard MRI to assess tumor volume, dynamic susceptibility-contrast MRI with the blood-pool iron oxide nanoparticle ferumoxytol to evaluate relative cerebral blood volume (rCBV), and dynamic contrast-enhanced MRI to assess tumor vascular permeability. Tumor rCBV increased by 27 ± 13% over 7 days in untreated rats; intetumumab increased tumor rCBV by 65 ± 10%, whereas bevacizumab reduced tumor rCBV by 31 ± 10% at 7 days (P < .001 for group and day). Similarly, intetumumab increased brain tumor vascular permeability compared with controls at 3 and 7 days after treatment, whereas bevacizumab decreased tumor permeability within 24 hours (P = .0004 for group, P = .0081 for day). All tumors grew over the 7-day assessment period, but bevacizumab slowed the increase in tumor volume on MRI. We conclude that the vascular targeting agents intetumumab and bevacizumab had diametrically opposite effects on dynamic MRI of tumor vasculature in rat brain tumor models. Targeting αV-integrins increased tumor vascular permeability and blood volume, whereas bevacizumab decreased both measures. These findings have implications for chemotherapy delivery and antitumor efficacy. PMID:21123368

  10. Changes in permeability of the alveolar-capillary barrier in firefighters.

    PubMed Central

    Minty, B D; Royston, D; Jones, J G; Smith, D J; Searing, C S; Beeley, M

    1985-01-01

    The effect on alveolar-capillary barrier permeability of chronic exposure to a smoke produced by the partial combusion of diesel oil, paraffin, and wood was examined. An index of permeability was determined from the rate of transfer from the lung into the blood of the hydrophilic, labelled chelate 99mTc diethylene triamine penta-acetate (MW 492 dalton). The results of this test were expressed as the half time clearance of the tracer from the lung into the blood (T1/2 LB). The study was carried out at the Royal Naval Firefighting School, HMS Excellent. Permeability index was measured on seven non-smoking naval firefighting instructors who had worked at the school for periods of longer than two and a half months. Tests of airway function and carbon monoxide transfer factor were performed on four of these seven instructors. The results of the permeability index showed a T1/2 LB of 26 min +/- 5 (SEM) which differed significantly from that of normal non-smokers. By contrast all other lung function tests had values within the predicted normal range. PMID:3899161

  11. Changes in permeability of the alveolar-capillary barrier in firefighters.

    PubMed

    Minty, B D; Royston, D; Jones, J G; Smith, D J; Searing, C S; Beeley, M

    1985-09-01

    The effect on alveolar-capillary barrier permeability of chronic exposure to a smoke produced by the partial combusion of diesel oil, paraffin, and wood was examined. An index of permeability was determined from the rate of transfer from the lung into the blood of the hydrophilic, labelled chelate 99mTc diethylene triamine penta-acetate (MW 492 dalton). The results of this test were expressed as the half time clearance of the tracer from the lung into the blood (T1/2 LB). The study was carried out at the Royal Naval Firefighting School, HMS Excellent. Permeability index was measured on seven non-smoking naval firefighting instructors who had worked at the school for periods of longer than two and a half months. Tests of airway function and carbon monoxide transfer factor were performed on four of these seven instructors. The results of the permeability index showed a T1/2 LB of 26 min +/- 5 (SEM) which differed significantly from that of normal non-smokers. By contrast all other lung function tests had values within the predicted normal range.

  12. Role of vascular endothelial cell growth factor in Ovarian Hyperstimulation Syndrome.

    PubMed Central

    Levin, E R; Rosen, G F; Cassidenti, D L; Yee, B; Meldrum, D; Wisot, A; Pedram, A

    1998-01-01

    Controlled ovarian hyperstimulation with gonadotropins is followed by Ovarian Hyperstimulation Syndrome (OHSS) in some women. An unidentified capillary permeability factor from the ovary has been implicated, and vascular endothelial cell growth/permeability factor (VEGF) is a candidate protein. Follicular fluids (FF) from 80 women who received hormonal induction for infertility were studied. FFs were grouped according to oocyte production, from group I (0-7 oocytes) through group IV (23-31 oocytes). Group IV was comprised of four women with the most severe symptoms of OHSS. Endothelial cell (EC) permeability induced by the individual FF was highly correlated to oocytes produced (r2 = 0.73, P < 0.001). Group IV FF stimulated a 63+/-4% greater permeability than FF from group I patients (P < 0. 01), reversed 98% by anti-VEGF antibody. Group IV fluids contained the VEGF165 isoform and significantly greater concentrations of VEGF as compared with group I (1,105+/-87 pg/ml vs. 353+/-28 pg/ml, P < 0. 05). Significant cytoskeletal rearrangement of F-actin into stress fibers and a destruction of ZO-1 tight junction protein alignment was caused by group IV FF, mediated in part by nitric oxide. These mechanisms, which lead to increased EC permeability, were reversed by the VEGF antibody. Our results indicate that VEGF is the FF factor responsible for increased vascular permeability, thereby contributing to the pathogenesis of OHSS. PMID:9835623

  13. Arterial stiffness evaluation by cardio-ankle vascular index in hypertension and diabetes mellitus subjects.

    PubMed

    Wang, Hongyu; Liu, Jinbo; Zhao, Hongwei; Fu, Xiaobao; Shang, Guangyun; Zhou, Yingyan; Yu, Xiaolan; Zhao, Xujing; Wang, Guang; Shi, Hongyan

    2013-01-01

    Arterial stiffness is an independent predictor for vascular diseases. Cardio-ankle vascular index (CAVI) is a new index of arterial stiffness. In the present study, we investigated the possible risk factors involving CAVI in hypertension and diabetes mellitus (DM) subjects. One thousand sixty-three subjects (M/F 533/530) from Shougang Corporation Examination Center were divided into four groups: healthy group (n = 639); hypertension group (n = 312); DM group (n = 58); and hypertension with DM group (n = 54). CAVI was measured by VS-1000 apparatus. Our results showed that CAVI was significantly higher in hypertension subjects with DM than in healthy and hypertension group, respectively (8.59 ± 1.08 vs 7.23 ± 1.10; 8.59 ± 1.08 vs 7.94 ± 1.33; both P < .05). CAVI was positively correlated with age, systolic blood pressure, diastolic blood pressure, pulse pressure, fasting plasma glucose, HbA1c, uric acid, total cholesterol, triglycerides in the entire group (r = 0.633, 0.280, 0.172, 0.269, 0.209, 0.254, 0.176, 0.129, 0.175; all P < .05, respectively). There was negatively correlation between CAVI and high-density lipoprotein cholesterol in the entire group (r = -0.167; P < .05). Multivariate analysis showed that age, body mass index, HbA1c, and high-density lipoprotein cholesterol were independent associating factors of CAVI in all subjects (β = 0.699; P < .001, β = -0.189; P = .001, β = 0.144; P = .015, β = -0.136; P = .019, respectively). Our present study suggested that CAVI was significantly higher in hypertension subjects with DM compared with healthy and hypertension groups. Copyright © 2013 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

  14. Increased capillary permeability mediated by a dengue virus-induced lymphokine.

    PubMed Central

    Khanna, M; Chaturvedi, U C; Sharma, M C; Pandey, V C; Mathur, A

    1990-01-01

    The mechanism of increased capillary permeability, seen in cases of dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS), is not known. Dengue type 2 virus (DV) is known to induce production of a lymphokine, the cytotoxic factor (CF), by the T lymphocytes of mouse spleen. The data presented here show that intraperitoneal inoculation of CF in mice results in increased capillary permeability in a dose-dependent manner, as shown by leakage of intravenously injected radiolabelled iodine (125I) or Evans blue dye. Peak leakage occurred 30 min after inoculation of CF and the vascular integrity was restored by 2 hr. The increase in capillary permeability was abrogated by pretreatment of mice with anti-CF antibodies, avil (H1 receptor blocker) or ranitidine (H2 receptor blocker). The findings thus show that a DV-induced lymphokine, the CF, increases the capillary permeability via release of histamine. PMID:2312168

  15. Biomimetic carriers mimicking leukocyte plasma membrane to increase tumor vasculature permeability

    NASA Astrophysics Data System (ADS)

    Palomba, R.; Parodi, A.; Evangelopoulos, M.; Acciardo, S.; Corbo, C.; De Rosa, E.; Yazdi, I. K.; Scaria, S.; Molinaro, R.; Furman, N. E. Toledano; You, J.; Ferrari, M.; Salvatore, F.; Tasciotti, E.

    2016-10-01

    Recent advances in the field of nanomedicine have demonstrated that biomimicry can further improve targeting properties of current nanotechnologies while simultaneously enable carriers with a biological identity to better interact with the biological environment. Immune cells for example employ membrane proteins to target inflamed vasculature, locally increase vascular permeability, and extravasate across inflamed endothelium. Inspired by the physiology of immune cells, we recently developed a procedure to transfer leukocyte membranes onto nanoporous silicon particles (NPS), yielding Leukolike Vectors (LLV). LLV are composed of a surface coating containing multiple receptors that are critical in the cross-talk with the endothelium, mediating cellular accumulation in the tumor microenvironment while decreasing vascular barrier function. We previously demonstrated that lymphocyte function-associated antigen (LFA-1) transferred onto LLV was able to trigger the clustering of intercellular adhesion molecule 1 (ICAM-1) on endothelial cells. Herein, we provide a more comprehensive analysis of the working mechanism of LLV in vitro in activating this pathway and in vivo in enhancing vascular permeability. Our results suggest the biological activity of the leukocyte membrane can be retained upon transplant onto NPS and is critical in providing the particles with complex biological functions towards tumor vasculature.

  16. The effect of blood transfusion on pulmonary permeability in cardiac surgery patients: a prospective multicenter cohort study.

    PubMed

    Vlaar, Alexander P J; Cornet, Alexander D; Hofstra, Jorrit J; Porcelijn, Leendert; Beishuizen, Albertus; Kulik, Willem; Vroom, Margreeth B; Schultz, Marcus J; Groeneveld, A B Johan; Juffermans, Nicole P

    2012-01-01

    There is an association between blood transfusion and pulmonary complications in cardiac surgery. Mediators of increased pulmonary vascular leakage after transfusion are unknown. We hypothesized that factors may include antibodies or bioactive lipids, which have been implicated in transfusion-related acute lung injury. We performed a prospective cohort study in two university hospital intensive care units in the Netherlands. Pulmonary vascular permeability was measured in cardiac surgery patients after receiving no, restrictive (one or two transfusions), or multiple (five or more transfusions) transfusions (n=20 per group). The pulmonary leak index (PLI), using (67) Ga-labeled transferrin, was determined within 3 hours postoperatively. Blood products were screened for bioactive lipid accumulation and the presence of antibodies. The PLI was elevated in all groups after cardiac surgery. Transfused patients had a higher PLI compared to nontransfused patients (33×10(-3) ± 20×10(-3) vs. 23×10(-3) ± 11×10(-3)/min, p<0.01). The amount of red blood cell (RBC) products, but not of fresh-frozen plasma or platelets, was associated with an increase in PLI (β, 1.6 [0.2-3.0]). Concerning causative factors in the blood product, neither the level of bioactive lipids nor the presence of antibodies was associated with an increase in PLI. Patient factors such as surgery risk and time on cardiopulmonary bypass did not influence the risk of pulmonary leakage after blood transfusion. Transfusion in cardiothoracic surgery patients is associated with an increase in pulmonary capillary permeability, an effect that was dose dependent for RBC products. The level of bioactive lipids or the presence of HLA or HNA antibodies in the transfused products were not associated with increased pulmonary capillary permeability. © 2011 American Association of Blood Banks.

  17. Nitric Oxide Increases Arterial Endotheial Permeability through Mediating VE-Cadherin Expression during Arteriogenesis.

    PubMed

    Yang, Baolin; Cai, Baizhen; Deng, Panyue; Wu, Xiaoqiong; Guan, Yinglu; Zhang, Bin; Cai, Weijun; Schaper, Jutta; Schaper, Wolfgang

    2015-01-01

    Macrophage invasion is an important event during arteriogenesis, but the underlying mechanism is still only partially understood. The present study tested the hypothesis that nitric oxide (NO) and VE-cadherin, two key mediators for vascular permeability, contribute to this event in a rat ischemic hindlimb model. In addition, the effect of NO on expression of VE-caherin and endothelial permeability was also studied in cultured HUVECs. We found that: 1) in normal arteriolar vessels (NAV), eNOS was moderately expressed in endothelial cells (EC) and iNOS was rarely detected. In contrast, in collateral vessels (CVs) induced by simple femoral artery ligation, both eNOS and iNOS were significantly upregulated (P<0.05). Induced iNOS was found mainly in smooth muscle cells, but also in other vascular cells and macrophages; 2) in NAV VE-cadherin was strongly expressed in EC. In CVs, VE-cadherin was significantly downregulated, with a discontinuous and punctate pattern. Administration of nitric oxide donor DETA NONOate (NONOate) further reduced the amounts of Ve-cadherin in CVs, whereas NO synthase inhibitor L-NAME inhibited downregulation of VE-cadherin in CVs; 3) in normal rats Evans blue extravasation (EBE) was low in the musculus gracilis, FITC-dextron leakage was not detected in the vascular wall and few macrophages were observed in perivascular space. In contrast, EBE was significantly increased in femoral artery ligation rats, FITC-dextron leakage and increased amounts of macrophages were detected in CVs, which were further enhanced by administration of NONOate, but inhibited by L-NAME supplement; 4) in vitro experiments confirmed that an increase in NO production reduced VE-cadherin expression, correlated with increases in the permeability of HUVECs. In conclusion, our data for the first time reveal the expression profile of VE-cadherin and alterations of vascular permeability in CVs, suggesting that NO-mediated VE-cadherin pathway may be one important mechanism

  18. Nitric Oxide Increases Arterial Endotheial Permeability through Mediating VE-Cadherin Expression during Arteriogenesis

    PubMed Central

    Wu, Xiaoqiong; Guan, Yinglu; Zhang, Bin; Cai, Weijun; Schaper, Jutta; Schaper, Wolfgang

    2015-01-01

    Macrophage invasion is an important event during arteriogenesis, but the underlying mechanism is still only partially understood. The present study tested the hypothesis that nitric oxide (NO) and VE-cadherin, two key mediators for vascular permeability, contribute to this event in a rat ischemic hindlimb model. In addition, the effect of NO on expression of VE-caherin and endothelial permeability was also studied in cultured HUVECs. We found that: 1) in normal arteriolar vessels (NAV), eNOS was moderately expressed in endothelial cells (EC) and iNOS was rarely detected. In contrast, in collateral vessels (CVs) induced by simple femoral artery ligation, both eNOS and iNOS were significantly upregulated (P<0.05). Induced iNOS was found mainly in smooth muscle cells, but also in other vascular cells and macrophages; 2) in NAV VE-cadherin was strongly expressed in EC. In CVs, VE-cadherin was significantly downregulated, with a discontinuous and punctate pattern. Administration of nitric oxide donor DETA NONOate (NONOate) further reduced the amounts of Ve-cadherin in CVs, whereas NO synthase inhibitor L-NAME inhibited downregulation of VE-cadherin in CVs; 3) in normal rats Evans blue extravasation (EBE) was low in the musculus gracilis, FITC-dextron leakage was not detected in the vascular wall and few macrophages were observed in perivascular space. In contrast, EBE was significantly increased in femoral artery ligation rats, FITC-dextron leakage and increased amounts of macrophages were detected in CVs, which were further enhanced by administration of NONOate, but inhibited by L-NAME supplement; 4) in vitro experiments confirmed that an increase in NO production reduced VE-cadherin expression, correlated with increases in the permeability of HUVECs. In conclusion, our data for the first time reveal the expression profile of VE-cadherin and alterations of vascular permeability in CVs, suggesting that NO-mediated VE-cadherin pathway may be one important mechanism

  19. Endothelial glycocalyx dysfunction in disease: albuminuria and increased microvascular permeability.

    PubMed

    Salmon, Andrew H J; Satchell, Simon C

    2012-03-01

    Appreciation of the glomerular microcirculation as a specialized microcirculatory bed, rather than as an entirely separate entity, affords important insights into both glomerular and systemic microvascular pathophysiology. In this review we compare regulation of permeability in systemic and glomerular microcirculations, focusing particularly on the role of the endothelial glycocalyx, and consider the implications for disease processes. The luminal surface of vascular endothelium throughout the body is covered with endothelial glycocalyx, comprising surface-anchored proteoglycans, supplemented with adsorbed soluble proteoglycans, glycosaminoglycans and plasma constituents. In both continuous and fenestrated microvessels, this endothelial glycocalyx provides resistance to the transcapillary escape of water and macromolecules, acting as an integral component of the multilayered barrier provided by the walls of these microvessels (ie acting in concert with clefts or fenestrae across endothelial cell layers, basement membranes and pericytes). Dysfunction of any of these capillary wall components, including the endothelial glycocalyx, can disrupt normal microvascular permeability. Because of its ubiquitous nature, damage to the endothelial glycocalyx alters the permeability of multiple capillary beds: in the glomerulus this is clinically apparent as albuminuria. Generalized damage to the endothelial glycocalyx can therefore manifest as both albuminuria and increased systemic microvascular permeability. This triad of altered endothelial glycocalyx, albuminuria and increased systemic microvascular permeability occurs in a number of important diseases, such as diabetes, with accumulating evidence for a similar phenomenon in ischaemia-reperfusion injury and infectious disease. The detection of albuminuria therefore has implications for the function of the microcirculation as a whole. The importance of the endothelial glycocalyx for other aspects of vascular function

  20. Effect of perfusate hematocrit on urea permeability-surface area in isolated dog lung

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Parker, R.E.; Roselli, R.J.; Haselton, F.R.

    1986-10-01

    Seven dog lower left lung lobes were statically inflated and perfused at a constant rate for each lobe with a perfusate in which the hematocrit was altered over a wide range. The permeability-surface area of urea was calculated from multiple indicator dilution curves using two separate injectates for each hematocrit level. One injectate contained only /sup 125/I-albumin as the vascular reference tracer and the other contained both /sup 51/Cr-erythrocytes and /sup 125/I-albumin as the vascular reference tracers; both contained (/sup 14/C)urea as the permeating tracer. The results strongly indicate that the phenomenon of erythrocyte trapping of urea does not affectmore » the calculation of urea permeability-surface area product provided the appropriate albumin-erythrocyte composite reference tracer is utilized in its calculation.« less

  1. Angiopoietin-4 increases permeability of blood vessels and promotes lymphatic dilation.

    PubMed

    Kesler, Cristina T; Pereira, Ethel R; Cui, Cheryl H; Nelson, Gregory M; Masuck, David J; Baish, James W; Padera, Timothy P

    2015-09-01

    The angiopoietin (Ang) ligands are potential therapeutic targets for lymphatic related diseases, which include lymphedema and cancer. Ang-1 and Ang-2 functions are established, but those of Ang-4 are poorly understood. We used intravital fluorescence microscopy to characterize Ang-4 actions on T241 murine fibrosarcoma-associated vessels in mice. The diameters of lymphatic vessels draining Ang-4- or VEGF-C (positive control)-expressing tumors increased to 123 and 135 μm, respectively, and parental, mock-transduced (negative controls) and tumors expressing Ang-1 or Ang-2 remained at baseline (∼60 μm). Ang-4 decreased human dermal lymphatic endothelial cell (LEC) monolayer permeability by 27% while increasing human dermal blood endothelial cell (BEC) monolayer permeability by 200%. In vivo, Ang-4 stimulated a 4.5-fold increase in tumor-associated blood vessel permeability compared with control when measured using intravital quantitative multiphoton microscopy. Ang-4 activated receptor signaling in both LECs and BECs, evidenced by tyrosine kinase with Ig and endothelial growth factor homology domains-2 (TIE2) receptor, protein kinase B, and Erk1,2 phosphorylation detectable by immunoblotting. These data suggest that Ang-4 actions are mediated through cell-type-specific networks and that lymphatic vessel dilation occurs secondarily to increased vascular leakage. Ang-4 also promoted survival of LECs. Thus, blocking Ang-4 may prune the draining lymphatic vasculature and decrease interstitial fluid pressure (IFP) by reducing vascular permeability. © FASEB.

  2. Characterization of tumor microvascular structure and permeability: comparison between magnetic resonance imaging and intravital confocal imaging

    NASA Astrophysics Data System (ADS)

    Reitan, Nina Kristine; Thuen, Marte; Goa, Pa˚L. Erik; de Lange Davies, Catharina

    2010-05-01

    Solid tumors are characterized by abnormal blood vessel organization, structure, and function. These abnormalities give rise to enhanced vascular permeability and may predict therapeutic responses. The permeability and architecture of the microvasculature in human osteosarcoma tumors growing in dorsal window chambers in athymic mice were measured by confocal laser scanning microscopy (CLSM) and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Dextran (40 kDa) and Gadomer were used as molecular tracers for CLSM and DCE-MRI, respectively. A significant correlation was found between permeability indicators. The extravasation rate Ki as measured by CLSM correlated positively with DCE-MRI parameters, such as the volume transfer constant Ktrans and the initial slope of the contrast agent concentration-time curve. This demonstrates that these two techniques give complementary information. Extravasation was further related to microvascular structure and was found to correlate with the fractal dimension and vascular density. The structural parameter values that were obtained from CLSM images were higher for abnormal tumor vasculature than for normal vessels.

  3. Vascular Endothelial Growth Factor-A165b Restores Normal Glomerular Water Permeability in a Diphtheria-Toxin Mouse Model of Glomerular Injury.

    PubMed

    Stevens, Megan; Neal, Christopher R; Salmon, Andrew H J; Bates, David O; Harper, Steven J; Oltean, Sebastian

    2018-01-01

    Genetic cell ablation using the human diphtheria toxin receptor (hDTR) is a new strategy used for analysing cellular function. Diphtheria toxin (DT) is a cytotoxic protein that leaves mouse cells relatively unaffected, but upon binding to hDTR it ultimately leads to cell death. We used a podocyte-specific hDTR expressing (Pod-DTR) mouse to assess the anti-permeability and cyto-protective effects of the splice isoform vascular endothelial growth factor (VEGF-A165b). The Pod-DTR mouse was crossed with a mouse that over-expressed VEGF-A165b specifically in the podocytes (Neph-VEGF-A165b). Wild type (WT), Pod-DTR, Neph-VEGF-A165b and Pod-DTR X Neph-VEGF-A165b mice were treated with several doses of DT (1, 5, 100, and 1,000 ng/g bodyweight). Urine was collected and the glomerular water permeability (LpA/Vi) was measured ex vivo after 14 days. Structural analysis and podocyte marker expression were also assessed. Pod-DTR mice developed an increased glomerular LpA/Vi 14 days after administration of DT (all doses), which was prevented when the mice over-expressed VEGF-A165b. No major structural abnormalities, podocyte ablation or albuminuria was observed in Pod-DTR mice, indicating this to be a mild model of podocyte disease. However, a change in expression and localisation of nephrin within the podocytes was observed, indicating disruption of the slit diaphragm in the Pod-DTR mice. This was prevented in the Pod-DTR X Neph-VEGF-A165b mice. Although only a mild model of podocyte injury, over-expression of the anti-permeability VEGF-A165b isoform in the podocytes of Pod-DTR mice had a protective effect. Therefore, this study further highlights the therapeutic potential of VEGF-A165b in glomerular disease. © 2018 The Author(s) Published by S. Karger AG, Basel.

  4. Injuries to the vascular endothelium: vascular wall and endothelial dysfunction.

    PubMed

    Fisher, Mark

    2008-01-01

    Vascular endothelial injury has multiple elements, and this article focuses on ischemia-related processes that have particular relevance to ischemic stroke. Distinctions between necrotic and apoptotic cell death provide a basic science context in which to better understand the significance of classical core and penumbra concepts of acute stroke, with apoptotic processes particularly prominent in the penumbra. The mitochondria are understood to serve as a reservoir of proteins that mediate apoptosis. Oxidative stress pathways generating reactive oxygen species (ROS) are prominent in endothelial injury, both ischemic and nonischemic, with prominent roles of enzyme- and nonenzymemediated pathways; mitochondria once again have a critical role, particularly in the nonenzymatic pathways generating ROS. Inflammation also contributes to vascular endothelial injury, and endothelial cells have the capacity to rapidly increase expression of inflammatory mediators following ischemic challenge; this leads to enhanced leukocyte-endothelial interactions mediated by selectins and adhesion molecules. Preconditioning consists of a minor version of an injurious event, which in turn may protect vascular endothelium from injury following a more substantial event. Presence of the blood-brain barrier creates unique responses to endothelial injury, with permeability changes due to impairment of endothelial-matrix interactions compounding altered vasomotor tone and tissue perfusion mediated by nitric oxide. Pharmacological protection against vascular endothelial injury can be provided by several of the phosphodiesterases (cilostazol and dipyridamole), along with statins. Optimal clinical responses for protection of brain vascular endothelium may use preconditioning as a model, and will likely require combined protection against apoptosis, ROS, and inflammation.

  5. Direct visualization of the arterial wall water permeability barrier using CARS microscopy

    PubMed Central

    Lucotte, Bertrand M.; Powell, Chloe; Knutson, Jay R.; Combs, Christian A.; Malide, Daniela; Yu, Zu-Xi; Knepper, Mark; Patel, Keval D.; Pielach, Anna; Johnson, Errin; Borysova, Lyudmyla; Balaban, Robert S.

    2017-01-01

    The artery wall is equipped with a water permeation barrier that allows blood to flow at high pressure without significant water leak. The precise location of this barrier is unknown despite its importance in vascular function and its contribution to many vascular complications when it is compromised. Herein we map the water permeability in intact arteries, using coherent anti-Stokes Raman scattering (CARS) microscopy and isotopic perfusion experiments. Generation of the CARS signal is optimized for water imaging with broadband excitation. We identify the water permeation barrier as the endothelial basolateral membrane and show that the apical membrane is highly permeable. This is confirmed by the distribution of the AQP1 water channel within endothelial membranes. These results indicate that arterial pressure equilibrates within the endothelium and is transmitted to the supporting basement membrane and internal elastic lamina macromolecules with minimal deformation of the sensitive endothelial cell. Disruption of this pressure transmission could contribute to endothelial cell dysfunction in various pathologies. PMID:28373558

  6. Experimental Determination of the Permeability in the Lacunar-Canalicular Porosity of Bone

    PubMed Central

    Gailani, Gaffar; Benalla, Mohammed; Mahamud, Rashal; Cowin, Stephen C.; Cardoso, Luis

    2010-01-01

    Permeability of the mineralized bone tissue is a critical element in understanding fluid flow occurring in the lacunar-canalicular porosity (PLC) compartment of bone and its role in bone nutrition and mechanotransduction. However, the estimation of bone permeability at the tissue level is affected by the influence of the vascular porosity (PV) in macroscopic samples containing several osteons. In this communication, both analytical and experimental approaches are proposed to estimate the lacunar-canalicular permeability in a single osteon. Data from an experimental stress-relaxation test in a single osteon is used to derive the PLC permeability by curve fitting to theoretical results from a compressible transverse isotropic poroelastic model of a porous annular disk under a ramp loading history (Cowin and Mehrabadi 2007; Gailani and Cowin 2008). The PLC tissue intrinsic permeability in the radial direction of the osteon was found to be dependent on the strain rate used and within the range of O(10−24)−O(10−25). The reported values of PLC permeability are in reasonable agreement with previously reported values derived using FEA and nanoindentation approaches. PMID:19831477

  7. The effect of interstitial pressure on therapeutic agent transport: coupling with the tumor blood and lymphatic vascular systems

    PubMed Central

    Wu, Min; Frieboes, Hermann B.; Chaplain, Mark A.J.; McDougall, Steven R.; Cristini, Vittorio; Lowengrub, John

    2014-01-01

    Vascularized tumor growth is characterized by both abnormal interstitial fluid flow and the associated interstitial fluid pressure (IFP). Here, we study the effect that these conditions have on the transport of therapeutic agents during chemotherapy. We apply our recently developed vascular tumor growth model which couples a continuous growth component with a discrete angiogenesis model to show that hypertensive IFP is a physical barrier that may hinder vascular extravasation of agents through transvascular fluid flux convection, which drives the agents away from the tumor. This result is consistent with previous work using simpler models without blood flow or lymphatic drainage. We consider the vascular/interstitial/lymphatic fluid dynamics to show that tumors with larger lymphatic resistance increase the agent concentration more rapidly while also experiencing faster washout. In contrast, tumors with smaller lymphatic resistance accumulate less agents but are able to retain them for a longer time. The agent availability (area-under-the curve, or AUC) increases for less permeable agents as lymphatic resistance increases, and correspondingly decreases for more permeable agents. We also investigate the effect of vascular pathologies on agent transport. We show that elevated vascular hydraulic conductivity contributes to the highest AUC when the agent is less permeable, but leads to lower AUC when the agent is more permeable. We find that elevated interstitial hydraulic conductivity contributes to low AUC in general regardless of the transvascular agent transport capability. We also couple the agent transport with the tumor dynamics to simulate chemotherapy with the same vascularized tumor under different vascular pathologies. We show that tumors with an elevated interstitial hydraulic conductivity alone require the strongest dosage to shrink. We further show that tumors with elevated vascular hydraulic conductivity are more hypoxic during therapy and that the

  8. Design and development of multilayer vascular graft

    NASA Astrophysics Data System (ADS)

    Madhavan, Krishna

    2011-07-01

    Vascular graft is a widely-used medical device for the treatment of vascular diseases such as atherosclerosis and aneurysm as well as for the use of vascular access and pediatric shunt, which are major causes of mortality and morbidity in this world. Dysfunction of vascular grafts often occurs, particularly for grafts with diameter less than 6mm, and is associated with the design of graft materials. Mechanical strength, compliance, permeability, endothelialization and availability are issues of most concern for vascular graft materials. To address these issues, we have designed a biodegradable, compliant graft made of hybrid multilayer by combining an intimal equivalent, electrospun heparin-impregnated poly-epsilon-caprolactone nanofibers, with a medial equivalent, a crosslinked collagen-chitosan-based gel scaffold. The intimal equivalent is designed to build mechanical strength and stability suitable for in vivo grafting and to prevent thrombosis. The medial equivalent is designed to serve as a scaffold for the activity of the smooth muscle cells important for vascular healing and regeneration. Our results have shown that genipin is a biocompatible crosslinker to enhance the mechanical properties of collagen-chitosan based scaffolds, and the degradation time and the activity of smooth muscle cells in the scaffold can be modulated by the crosslinking degree. For vascular grafting and regeneration in vivo, an important design parameter of the hybrid multilayer is the interface adhesion between the intimal and medial equivalents. With diametrically opposite affinities to water, delamination of the two layers occurs. Physical or chemical modification techniques were thus used to enhance the adhesion. Microscopic examination and graft-relevant functional characterizations have been performed to evaluate these techniques. Results from characterization of microstructure and functional properties, including burst strength, compliance, water permeability and suture

  9. Eotaxin increases monolayer permeability of human coronary artery endothelial cells.

    PubMed

    Jamaluddin, Md Saha; Wang, Xinwen; Wang, Hao; Rafael, Cubas; Yao, Qizhi; Chen, Changyi

    2009-12-01

    The objective of this study was to determine the effects and molecular mechanisms of eotaxin, a newly discovered chemokine (CCL11), on endothelial permeability in the human coronary artery endothelial cells (HCAECs). Cells were treated with eotaxin, and the monolayer permeability was studied by using a costar transwell system with a Texas Red-labeled dextran tracer. Eotaxin significantly increased monolayer permeability in a concentration-dependent manner. In addition, eotaxin treatment significantly decreased the mRNA and protein levels of endothelial junction molecules including zonula occludens-1 (ZO-1), occludin, and claudin-1 in a concentration-dependent manner as determined by real-time RT-PCR and Western blot analysis, respectively. Increased oxidative stress was observed in eotaxin-treated HCAECs by analysis of cellular glutathione levels. Furthermore, eotaxin treatment substantially activated the phosphorylation of MAPK p38. HCAECs expressed CCR3. Consequently, antioxidants (ginkgolide B and MnTBAP), specific p38 inhibitor SB203580, and anti-CCR3 antibody effectively blocked the eotaxin-induced permeability increase in HCAECs. Eotaxin also increased the phosphorylation of Stat3 and nuclear translocation of NF-kappaB in HCAECs. Eotaxin increases vascular permeability through CCR3, the downregulation of tight junction proteins, increase of oxidative stress, and activation of MAPK p38, Stat3, and NF-kB pathways in HCAECs.

  10. VEGF increases paracellular permeability in brain endothelial cells via upregulation of EphA2.

    PubMed

    Miao, Ziwei; Dong, Yanbin; Fang, Wengang; Shang, Deshu; Liu, Dongxin; Zhang, Ke; Li, Bo; Chen, Yu-Hua

    2014-05-01

    Neurological disorders are associated with an increase in the permeability of human brain microvascular endothelial cells (HBMEC). Our previous findings have indicated that EphA2 could increase the permeability of HBMEC. Recent evidence has linked EphA2 and vascular endothelial growth factor (VEGF) to abnormalities in the vascular response. However, it is unclear whether EphA2 is involved in the VEGF-induced changes in the permeability of HBMEC. Here, changes in permeability were determined by measuring transendothelial electrical resistance (TEER) and the flux of FITC-dextran. We found that knockdown of EphA2 in HBMEC abolished the VEGF-induced reduction in TEER and increase in flux of fluorescent dextran. Moreover, VEGF-induced redistribution of ZO-1 and the recruitment of detergent-soluble occludin and claudin-5 were also prevented. Further results showed that VEGF increased EphA2 expression in a time- and dose-dependent manner, which was inhibited by a neutralizing antibody against VEGFR2 or SU1498. VEGF-induced EphA2 expression was suppressed in the brain endothelium following treatments with the PI3K inhibitor LY294002, Akt inhibitor or transfection with the dominant-negative PI3K mutants (Δp110). Similar results were obtained when ERK1/2 activation was inhibited by PD98059 or ERK1/2 siRNA transfection. Our data suggest that VEGF upregulates the expression of EphA2 in HBMEC through binding to VEGFR2 and subsequently activating the intracellular PI3K/Akt and ERK1/2 signaling pathways, which contribute to an increase in paracellular permeability. These data reveal a novel role for VEGF as a regulator of EphA2 expression in the brain endothelial cells and provide insights into the molecular mechanisms of VEGF-mediated changes in paracellular permeability. Copyright © 2014 Wiley Periodicals, Inc.

  11. Nerve cables formed in silicone chambers reconstitute a perineurial but not a vascular endoneurial permeability barrier.

    PubMed

    Azzam, N A; Zalewski, A A; Williams, L R; Azzam, R N

    1991-12-22

    The passage of molecules into the endoneurial environment of the axons of normal peripheral nerve is regulated by two permeability barriers, the perineurial-nerve barrier and the endoneurial blood-nerve barrier. These barriers exist because of the presence of tight junctions between adjacent perineurial cells and adjacent endothelial cells. In the present study we investigated whether permeability barriers form in nerve cables, which develop inside silicone chambers. The sciatic nerves of adult rats were cut, and the proximal and distal ends sutured into opposite ends of silicone chambers that were filled with dialyzed plasma. The presence of barriers was determined with the tracer horseradish peroxidase (HRP), which was injected intravenously and detected histochemically in tissues by light and electron microscopy. At four weeks, a regenerated nerve cable extended across the 10 mm length of each chamber. However, no permeability barriers were present since the reaction product for HRP was visible throughout the cable. At twenty-six weeks, all the axons in cables were gathered into minifascicles. Each minifascicle of axons was surrounded by perineurial cells. Blood vessels were excluded from the minifascicles by the perineurial cells and the vessels were permeable to HRP, thus indicating that their endothelial cells had not formed tight junctions. Despite the leakage of HRP from the excluded vessels, the tracer did not reach the axons because the perineurial cells encircling the minifascicles developed tight junctions. In some animals, the chambers were removed at four weeks to determine whether the chamber influenced barrier development. This manipulation had no effect since cables, with or without chambers, exhibited similar findings at twenty-six weeks. Our results indicate that nerve cables regenerate a perineurial but not an endoneurial permeability barrier. We conclude that axons in long-term cables are protected by only a perineurial permeability barrier.

  12. Endothelial Cell Permeability during Hantavirus Infection Involves Factor XII-Dependent Increased Activation of the Kallikrein-Kinin System

    PubMed Central

    Taylor, Shannon L.; Wahl-Jensen, Victoria; Copeland, Anna Maria; Jahrling, Peter B.; Schmaljohn, Connie S.

    2013-01-01

    Hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) are diseases caused by hantavirus infections and are characterized by vascular leakage due to alterations of the endothelial barrier. Hantavirus-infected endothelial cells (EC) display no overt cytopathology; consequently, pathogenesis models have focused either on the influx of immune cells and release of cytokines or on increased degradation of the adherens junction protein, vascular endothelial (VE)-cadherin, due to hantavirus-mediated hypersensitization of EC to vascular endothelial growth factor (VEGF). To examine endothelial leakage in a relevant in vitro system, we co-cultured endothelial and vascular smooth muscle cells (vSMC) to generate capillary blood vessel-like structures. In contrast to results obtained in monolayers of cultured EC, we found that despite viral replication in both cell types as well as the presence of VEGF, infected in vitro vessels neither lost integrity nor displayed evidence of VE-cadherin degradation. Here, we present evidence for a novel mechanism of hantavirus-induced vascular leakage involving activation of the plasma kallikrein-kinin system (KKS). We show that incubation of factor XII (FXII), prekallikrein (PK), and high molecular weight kininogen (HK) plasma proteins with hantavirus-infected EC results in increased cleavage of HK, higher enzymatic activities of FXIIa/kallikrein (KAL) and increased liberation of bradykinin (BK). Measuring cell permeability in real-time using electric cell-substrate impedance sensing (ECIS), we identified dramatic increases in endothelial cell permeability after KKS activation and liberation of BK. Furthermore, the alterations in permeability could be prevented using inhibitors that directly block BK binding, the activity of FXIIa, or the activity of KAL. Lastly, FXII binding and autoactivation is increased on the surface of hantavirus-infected EC. These data are the first to demonstrate KKS activation during

  13. Role of Nitric Oxide Isoforms in Vascular and Alveolar Development and Lung Injury in Vascular Endothelial Growth Factor Overexpressing Neonatal Mice Lungs.

    PubMed

    Syed, Mansoor A; Choo-Wing, Rayman; Homer, Robert J; Bhandari, Vineet

    2016-01-01

    The role of vascular endothelial growth factor (VEGF)-induced 3 different nitric oxide synthase (NOS) isoforms in lung development and injury in the newborn (NB) lung are not known. We hypothesized that VEGF-induced specific NOS pathways are critical regulators of lung development and injury. We studied NB wild type (WT), lung epithelial cell-targeted VEGF165 doxycycline-inducible overexpressing transgenic (VEGFTG), VEGFTG treated with a NOS1 inhibitor (L-NIO), VEGFTG x NOS2-/- and VEGFTG x NOS3+/- mice in room air (RA) for 7 postnatal (PN) days. Lung morphometry (chord length), vascular markers (Ang1, Ang2, Notch2, vWF, CD31 and VE-cadherin), cell proliferation (Ki67), vascular permeability, injury and oxidative stress markers (hemosiderin, nitrotyrosine and 8-OHdG) were evaluated. VEGF overexpression in RA led to increased chord length and vascular markers at PN7, which were significantly decreased to control values in VEGFTG x NOS2-/- and VEGFTG x NOS3+/- lungs. However, we found no noticeable effect on chord length and vascular markers in the VEGFTG / NOS1 inhibited group. In the NB VEGFTG mouse model, we found VEGF-induced vascular permeability in the NB murine lung was partially dependent on NOS2 and NOS3-signaling pathways. In addition, the inhibition of NOS2 and NOS3 resulted in a significant decrease in VEGF-induced hemosiderin, nitrotyrosine- and 8-OHdG positive cells at PN7. NOS1 inhibition had no significant effect. Our data showed that the complete absence of NOS2 and partial deficiency of NOS3 confers protection against VEGF-induced pathologic lung vascular and alveolar developmental changes, as well as injury markers. Inhibition of NOS1 does not have any modulating role on VEGF-induced changes in the NB lung. Overall, our data suggests that there is a significant differential regulation in the NOS-mediated effects of VEGF overexpression in the developing mouse lung.

  14. New noninvasive index for evaluation of the vascular age of healthy and sick people

    NASA Astrophysics Data System (ADS)

    Fine, Ilya; Kuznik, Boris I.; Kaminsky, Alexander V.; Shenkman, Louis; Kustovsjya, Evgeniya M.; Maximova, Olga G.

    2012-08-01

    We conducted a study on 861 healthy and sick subjects and demonstrated that some calculated parameters based on measurement of the dynamic light scattering (DLS) signal from the finger correlate highly with chronological age ranging from 1.5 to 85 years old. Measurements of DLS signals were obtained during both occlusion and nonocclusion of blood flow in the finger. For the nonocclusion case we found that the low-frequency component of the DLS signal significantly correlates with the biological age while the high-frequency component of the DLS signal resembles the arterial pulse-wave and does correlate with age. However, the most prominent correlation between the DLS characteristics and age was noted with the stasis stage measurements. We propose that the observed age-related phenomena are caused by alterations in local blood viscosity and interactions of the endothelial cells with erythrocytes. Further, a new noninvasive index based on the age-related optical characteristics was introduced. This noninvasive index may be used as a research and diagnostic tool to examine the endothelial and thrombolytic properties of the vascular system.

  15. New noninvasive index for evaluation of the vascular age of healthy and sick people.

    PubMed

    Fine, Ilya; Kuznik, Boris I; Kaminsky, Alexander V; Shenkman, Louis; Kustovsjya, Evgeniya M; Elena, Evgeniya M; Maximova, Olga G

    2012-08-01

    We conducted a study on 861 healthy and sick subjects and demonstrated that some calculated parameters based on measurement of the dynamic light scattering (DLS) signal from the finger correlate highly with chronological age ranging from 1.5 to 85 years old. Measurements of DLS signals were obtained during both occlusion and nonocclusion of blood flow in the finger. For the nonocclusion case we found that the low-frequency component of the DLS signal significantly correlates with the biological age while the high-frequency component of the DLS signal resembles the arterial pulse-wave and does correlate with age. However, the most prominent correlation between the DLS characteristics and age was noted with the stasis stage measurements. We propose that the observed age-related phenomena are caused by alterations in local blood viscosity and interactions of the endothelial cells with erythrocytes. Further, a new noninvasive index based on the age-related optical characteristics was introduced. This noninvasive index may be used as a research and diagnostic tool to examine the endothelial and thrombolytic properties of the vascular system.

  16. Cardioankle vascular index evaluations revealed that cotreatment of ARB Antihypertension medication with traditional Chinese medicine improved arterial functionality.

    PubMed

    Xu, Yan; Yan, Hua; Yao, Min J; Ma, Jie; Jia, Jun M; Ruan, Fen X; Yao, Zeng C; Huang, Hua M; Zheng, Jing; Chen, Ting; Lv, Hua; Endler, Alexander M

    2013-05-01

    Qian Yang He Ji (QYHJ) is a traditional Chinese medicine composed of Digitalis purpurea, Uncaria gambir, Fructus tribuli terrestris, and Ligustrum lucidum. Here, we explored whether combining an antihypertensive angiotensin II receptor blocker (ARB) therapy with QYHJ can improve the arterial functionality of hypertensive patients. One hundred and eight hypertensive patients were randomized into 2 groups; 1 group (n = 53) was treated with ARB and the other group (n = 55) was treated with ARB combined with QYHJ. Each of the 2 groups included 3 subgroups (pure hypertension, hypertension with diabetes, and hypertension with coronary heart disease) and was further divided into patients with and without complications. The cardioankle vascular index and intima-media thickness and pulse pressure were the outcome evaluation parameter. Combined QYHJ and ARB treatment reduced the values of cardioankle vascular index, systolic blood pressure, diastolic blood pressure, and pulse pressure to significantly lower levels than ARB treatment alone did in hypertension patients after 6 months of treatment. ARB improves hypertension, but a combined QYHJ treatment can additionally ameliorate the arterial functionality not only in solely hypertensive patients but also in hypertensive patients with diabetes and coronary heart disease complications. QYHJ coapplication might be a choice to further improve the arterial functionality during an ARB hypertension treatment.

  17. Vascular-targeted nanocarriers: design considerations and strategies for successful treatment of atherosclerosis and other vascular diseases.

    PubMed

    Kelley, William J; Safari, Hanieh; Lopez-Cazares, Genesis; Eniola-Adefeso, Omolola

    2016-11-01

    Vascular-targeted nanocarriers are an attractive option for the treatment of a number of cardiovascular diseases, as they allow for more specific delivery and increased efficacy of many small molecule drugs. However, immune clearance, limited cellular uptake, and particle-cell dynamics in blood flow can hinder nanocarrier efficacy in many applications. This review aims to investigate successful strategies for the use of vascular-targeted nanocarriers in the treatment of cardiovascular diseases such as atherosclerosis. In particular, the review will highlight strategies employed for actively targeting the components of the atherosclerotic plaque, including endothelial cells, macrophages, and platelets and passive targeting via endothelial permeability, as well as design specifications (such as size, shape, and density) aimed at enhancing the ability of nanocarriers to reach the vascular wall. WIREs Nanomed Nanobiotechnol 2016, 8:909-926. doi: 10.1002/wnan.1414 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

  18. Gadolinium prevents high airway pressure-induced permeability increases in isolated rat lungs.

    PubMed

    Parker, J C; Ivey, C L; Tucker, J A

    1998-04-01

    To determine the initial signaling event in the vascular permeability increase after high airway pressure injury, we compared groups of lungs ventilated at different peak inflation pressures (PIPs) with (gadolinium group) and without (control group) infusion of 20 microM gadolinium chloride, an inhibitor of endothelial stretch-activated cation channels. Microvascular permeability was assessed by using the capillary filtration coefficient (Kfc), a measure of capillary hydraulic conductivity. Kfc was measured after ventilation for 30-min periods with 7, 20, and 30 cmH2O PIP with 3 cmH2O positive end-expiratory pressure and with 35 cmH2O PIP with 8 cmH2O positive end-expiratory pressure. In control lungs, Kfc increased significantly to 1.8 and 3.7 times baseline after 30 and 35 cmH2O PIP, respectively. In the gadolinium group, Kfc was unchanged from baseline (0.060 +/- 0.010 ml . min-1 . cmH2O-1 . 100 g-1) after any PIP ventilation period. Pulmonary vascular resistance increased significantly from baseline in both groups before the last Kfc measurement but was not different between groups. These results suggest that microvascular permeability is actively modulated by a cellular response to mechanical injury and that stretch-activated cation channels may initiate this response through increases in intracellular calcium concentration.

  19. Surface-subsurface turbulent interaction at the interface of a permeable bed: influence of the wall permeability

    NASA Astrophysics Data System (ADS)

    Kim, T.; Blois, G.; Best, J.; Christensen, K. T.

    2017-12-01

    Coarse-gravel river beds possess a high degree of permeability. Flow interactions between surface and subsurface flow across the bed interface is key to a number of natural processes occurring in the hyporheic zone. In fact, it is increasingly recognized that these interactions drive mass, momentum and energy transport across the interface, and consequently control biochemical processes as well as stability of sediments. The current study explores the role of the wall permeability in surface and subsurface flow interaction under controlled experimental conditions on a physical model of a gravel bed. The present wall model was constructed by five layers of cubically arranged spheres (d=25.4mm, where d is a diameter) providing 48% of porosity. Surface topography was removed by cutting half of a diameter on the top layer of spheres to render the flow surface smooth and highlight the impact of the permeability on the overlying flow. An impermeable smooth wall was also considered as a baseline of comparison for the permeable wall flow. To obtain basic flow statistics, low-frame-rate high-resolution PIV measurements were performed first in the streamwise-wall-normal (x-y) plane and refractive-index matching was employed to optically access the flow within the permeable wall. Time-resolved PIV experiments in the same facility were followed to investigate the flow interaction across the wall interface in sptaio-temporal domain. In this paper, a detailed analysis of the first and second order velocity statistics as well as the amplitude modulation for the flow overlying the permeable smooth wall will be presented.

  20. The Semaphorin 4D- Plexin-B1- RhoA signaling axis recruits pericytes and regulates vascular permeability through endothelial production of PDGF-B and ANGPTL4

    PubMed Central

    Zhou, Hua; Yang, Ying-Hua; Basile, John R.

    2013-01-01

    Semaphorin 4D (SEMA4D) is a member of a family of transmembrane and secreted proteins that have been shown to act through its receptor Plexin-B1 to regulate axon growth cone guidance, lymphocyte activation, and bone density. SEMA4D is also overexpressed by some malignancies and plays a role in tumor-induced angiogenesis similar to vascular endothelial growth factor (VEGF), a protein that has been targeted as part of some cancer therapies. In an attempt to examine the different effects on tumor growth and vascularity for these two pro-angiogenic factors, we previously noted that while inhibition of both VEGF and SEMA4D restricted tumor vascularity and size, vessels forming under conditions of VEGF blockade retained their association with pericytes while those arising in a background of SEMA4D/ Plexin-B1 deficiency did not, an intriguing finding considering that alteration in pericyte association with endothelial cells is an emerging aspect of anti-angiogenic intervention in the treatment of cancer. Here we show through array analysis, immunoblots, migration and co-culture assays and VE-cadherin immunohistochemistry that SEMA4D production by head and neck carcinoma tumor cells induces expression of platelet-derived growth factor-B (PDGF-B) and angiopoietin-like protein 4 (ANGPTL4) from endothelial cells in a Plexin-B1/ Rho-dependent manner, thereby influencing proliferation and differentiation of pericytes and vascular permeability, whereas VEGF lacks these effects. These results partly explain the differences observed between SEMA4D and VEGF in pathological angiogenesis and suggest that targeting SEMA4D function along with VEGF could represent a novel anti-angiogenic therapeutic strategy for the treatment of solid tumors. PMID:24114199

  1. Carbohydrates and Endothelial Function: Is a Low-Carbohydrate Diet or a Low-Glycemic Index Diet Favourable for Vascular Health?

    PubMed Central

    Jovanovski, Elena; Zurbau, Andreea

    2015-01-01

    Low-carbohydrate diets have become increasingly popular in both media and clinical research settings. Although they may improve some metabolic markers, their effects on arterial function remain unclear. Endothelial dysfunction is the well-established response to cardiovascular risk factors and a pivotal feature that precedes atherosclerotic diseases. It has been demonstrated that a high carbohydrate-induced hyperglycemia and subsequent oxidative stress acutely worsen the efficacy of the endothelial vasodilatory system. Thus, in theory, a carbohydrate restricted diet may preserve the integrity of the arterial system. This review attempts to provide insight on whether low-carbohydrate diets have a favorable or detrimental impact on vascular function, or it is perhaps the quality of carbohydrate that should direct dietary recommendations. Research to date suggests that diets low in carbohydrate amount may negatively impact vascular endothelial function. Conversely, it appears that maintaining recommended carbohydrate intake with utilization of low glycemic index foods generates a more favorable vascular profile. Understanding these relationships will aid in deciphering the diverging role of modulating quantity and quality of carbohydrates on cardiovascular risk. PMID:25954727

  2. Carbohydrates and endothelial function: is a low-carbohydrate diet or a low-glycemic index diet favourable for vascular health?

    PubMed

    Jovanovski, Elena; Zurbau, Andreea; Vuksan, Vladimir

    2015-04-01

    Low-carbohydrate diets have become increasingly popular in both media and clinical research settings. Although they may improve some metabolic markers, their effects on arterial function remain unclear. Endothelial dysfunction is the well-established response to cardiovascular risk factors and a pivotal feature that precedes atherosclerotic diseases. It has been demonstrated that a high carbohydrate-induced hyperglycemia and subsequent oxidative stress acutely worsen the efficacy of the endothelial vasodilatory system. Thus, in theory, a carbohydrate restricted diet may preserve the integrity of the arterial system. This review attempts to provide insight on whether low-carbohydrate diets have a favorable or detrimental impact on vascular function, or it is perhaps the quality of carbohydrate that should direct dietary recommendations. Research to date suggests that diets low in carbohydrate amount may negatively impact vascular endothelial function. Conversely, it appears that maintaining recommended carbohydrate intake with utilization of low glycemic index foods generates a more favorable vascular profile. Understanding these relationships will aid in deciphering the diverging role of modulating quantity and quality of carbohydrates on cardiovascular risk.

  3. Transformable ferroelectric control of dynamic magnetic permeability

    NASA Astrophysics Data System (ADS)

    Jiang, Changjun; Jia, Chenglong; Wang, Fenglong; Zhou, Cai; Xue, Desheng

    2018-02-01

    Magnetic permeability, which measures the response of a material to an applied magnetic field, is crucial to the performance of magnetic devices and related technologies. Its dynamic value is usually a complex number with real and imaginary parts that describe, respectively, how much magnetic power can be stored and lost in the material. Control of permeability is therefore closely related to energy redistribution within a magnetic system or energy exchange between magnetic and other degrees of freedom via certain spin-dependent interactions. To avoid a high power consumption, direct manipulation of the permeability with an electric field through magnetoelectric coupling leads to high efficiency and simple operation, but remains a big challenge in both the fundamental physics and material science. Here we report unambiguous evidence of ferroelectric control of dynamic magnetic permeability in a Co /Pb (Mg1/3Nb2/3) 0.7Ti0.3O3 (Co/PMN-PT) heterostructure, in which the ferroelectric PMN-PT acts as an energy source for the ferromagnetic Co film via an interfacial linear magnetoelectric interaction. The electric field tuning of the magnitude and line shape of the permeability offers a highly localized means of controlling magnetization with ultralow power consumption. Additionally, the emergence of negative permeability promises a new way of realizing functional nanoscale metamaterials with adjustable refraction index.

  4. The effect of interstitial pressure on therapeutic agent transport: coupling with the tumor blood and lymphatic vascular systems.

    PubMed

    Wu, Min; Frieboes, Hermann B; Chaplain, Mark A J; McDougall, Steven R; Cristini, Vittorio; Lowengrub, John S

    2014-08-21

    Vascularized tumor growth is characterized by both abnormal interstitial fluid flow and the associated interstitial fluid pressure (IFP). Here, we study the effect that these conditions have on the transport of therapeutic agents during chemotherapy. We apply our recently developed vascular tumor growth model which couples a continuous growth component with a discrete angiogenesis model to show that hypertensive IFP is a physical barrier that may hinder vascular extravasation of agents through transvascular fluid flux convection, which drives the agents away from the tumor. This result is consistent with previous work using simpler models without blood flow or lymphatic drainage. We consider the vascular/interstitial/lymphatic fluid dynamics to show that tumors with larger lymphatic resistance increase the agent concentration more rapidly while also experiencing faster washout. In contrast, tumors with smaller lymphatic resistance accumulate less agents but are able to retain them for a longer time. The agent availability (area-under-the curve, or AUC) increases for less permeable agents as lymphatic resistance increases, and correspondingly decreases for more permeable agents. We also investigate the effect of vascular pathologies on agent transport. We show that elevated vascular hydraulic conductivity contributes to the highest AUC when the agent is less permeable, but to lower AUC when the agent is more permeable. We find that elevated interstitial hydraulic conductivity contributes to low AUC in general regardless of the transvascular agent transport capability. We also couple the agent transport with the tumor dynamics to simulate chemotherapy with the same vascularized tumor under different vascular pathologies. We show that tumors with an elevated interstitial hydraulic conductivity alone require the strongest dosage to shrink. We further show that tumors with elevated vascular hydraulic conductivity are more hypoxic during therapy and that the response

  5. Dynamic permeability of the lacunar–canalicular system in human cortical bone

    PubMed Central

    Benalla, M.; Palacio-Mancheno, P. E.; Fritton, S. P.; Cardoso, L.

    2013-01-01

    A new method for the experimental determination of the permeability of a small sample of a fluid-saturated hierarchically structured porous material is described and applied to the determination of the lacunar–canalicular permeability (KLC) in bone. The interest in the permeability of the lacunar–canalicular pore system (LCS) is due to the fact that the LCS is considered to be the site of bone mechanotransduction due to the loading-driven fluid flow over cellular structures. The permeability of this space has been estimated to be anywhere from 10−17 to 10−25 m2. However, the vascular pore system and LCS are intertwined, rendering the permeability of the much smaller-dimensioned LCS challenging to measure. In this study, we report a combined experimental and analytical approach that allowed the accurate determination of the KLC to be on the order of 10−22 m2 for human osteonal bone. It was found that the KLC has a linear dependence on loading frequency, decreasing at a rate of 2 × 10−24 m2/Hz from 1 to 100 Hz, and using the proposed model, the porosity alone was able to explain 86 % of the KLC variability. PMID:24146291

  6. Real-time estimation of paracellular permeability of cerebral endothelial cells by capacitance sensor array

    NASA Astrophysics Data System (ADS)

    Hyun Jo, Dong; Lee, Rimi; Hyoung Kim, Jin; Oh Jun, Hyoung; Geol Lee, Tae; Hun Kim, Jeong

    2015-06-01

    Vascular integrity is important in maintaining homeostasis of brain microenvironments. In various brain diseases including Alzheimer’s disease, stroke, and multiple sclerosis, increased paracellular permeability due to breakdown of blood-brain barrier is linked with initiation and progression of pathological conditions. We developed a capacitance sensor array to monitor dielectric responses of cerebral endothelial cell monolayer, which could be utilized to evaluate the integrity of brain microvasculature. Our system measured real-time capacitance values which demonstrated frequency- and time-dependent variations. With the measurement of capacitance at the frequency of 100 Hz, we could differentiate the effects of vascular endothelial growth factor (VEGF), a representative permeability-inducing factor, on endothelial cells and quantitatively analyse the normalized values. Interestingly, we showed differential capacitance values according to the status of endothelial cell monolayer, confluent or sparse, evidencing that the integrity of monolayer was associated with capacitance values. Another notable feature was that we could evaluate the expression of molecules in samples in our system with the reference of real-time capacitance values. We suggest that this dielectric spectroscopy system could be successfully implanted as a novel in vitro assay in the investigation of the roles of paracellular permeability in various brain diseases.

  7. Eotaxin Increases Monolayer Permeability of Human Coronary Artery Endothelial Cells

    PubMed Central

    Jamaluddin, Md Saha; Wang, Xinwen; Wang, Hao; Rafael, Cubas; Yao, Qizhi; Chen, Changyi

    2009-01-01

    Objective The objective of this study was to determine the effects and molecular mechanisms of eotaxin, a newly discovered chemokine (CCL11), on endothelial permeability in the human coronary artery endothelial cells (HCAECs). Methods and Results Cells were treated with eotaxin, and the monolayer permeability was studied by using a costar transwell system with a Texas-Red-labeled dextran tracer. Eotaxin significantly increased monolayer permeability in a concentration-dependent manner. In addition, eotaxin treatment significantly decreased the mRNA and protein levels of endothelial junction molecules including zonula occludens-1 (ZO-1), occludin and claudin-1 in a concentration-dependent manner as determined by real time RT-PCR and Western blot analysis, respectively. Increased oxidative stress was observed in eotaxin-treated HCAECs by analysis of cellular glutathione levels. Furthermore, eotaxin treatment substantially activated the phosphorylation of MAPK p38. HCAECs expressed CCR3. Consequently, antioxidants (ginkgolide B and MnTBAP), specific p38 inhibitor SB203580 and anti-CCR3 antibody effectively blocked the eotaxin-induced permeability increase in HCAECs. Eotaxin also increased phosphorylation of Stat3 and nuclear translocation of NF-κB in HCAECs. Conclusions Eotaxin increases vascular permeability through CCR3, the down regulation of tight junction proteins, increase of oxidative stress and activation of MAPK p38, Stat3 and NF-kB pathways in HCAECs. PMID:19778943

  8. Heavy Cigarette Smokers in a Chinese Population Display a Compromised Permeability Barrier

    PubMed Central

    Xin, Shujun; Ye, Li; Lv, Chengzhi; Elias, Peter M.

    2016-01-01

    Cigarette smoking is associated with various cutaneous disorders with defective permeability. Yet, whether cigarette smoking influences epidermal permeability barrier function is largely unknown. Here, we measured skin biophysical properties, including permeability barrier homeostasis, stratum corneum (SC) integrity, SC hydration, skin surface pH, and skin melanin/erythema index, in cigarette smokers. A total of 99 male volunteers were enrolled in this study. Smokers were categorized as light-to-moderate (<20 cigarettes/day) or heavy smokers (≥20 cigarettes/day). An MPA5 was used to measure SC hydration and skin melanin/erythema index on the dorsal hand, forehead, and cheek. Basal transepidermal water loss (TEWL) and barrier recovery rates were assessed on the forearm. A Skin-pH-Meter pH900 was used to measure skin surface pH. Our results showed that heavy cigarette smokers exhibited delayed barrier recovery after acute abrogation (1.02% ± 13.06 versus 16.48% ± 6.07), and barrier recovery rates correlated negatively with the number of daily cigarettes consumption (p = 0.0087). Changes in biophysical parameters in cigarette smokers varied with body sites. In conclusion, heavy cigarette smokers display compromised permeability barrier homeostasis, which could contribute, in part, to the increased prevalence of certain cutaneous disorders characterized by defective permeability. Thus, improving epidermal permeability barrier should be considered for heavy cigarette smokers. PMID:27437403

  9. Suppressive effects of lysozyme on polyphosphate-mediated vascular inflammatory responses

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chung, Jiwoo; Ku, Sae-Kwang; Lee, Suyeon

    Lysozyme, found in relatively high concentration in blood, saliva, tears, and milk, protects us from the ever-present danger of bacterial infection. Previous studies have reported proinflammatory responses of endothelial cells to the release of polyphosphate(PolyP). In this study, we examined the anti-inflammatory responses and mechanisms of lysozyme and its effects on PolyP-induced septic activities in human umbilical vein endothelial cells (HUVECs) and mice. The survival rates, septic biomarker levels, behavior of human neutrophils, and vascular permeability were determined in PolyP-activated HUVECs and mice. Lysozyme suppressed the PolyP-mediated vascular barrier permeability, upregulation of inflammatory biomarkers, adhesion/migration of leukocytes, and activation and/ormore » production of nuclear factor-κB, tumor necrosis factor-α, and interleukin-6. Furthermore, lysozyme demonstrated protective effects on PolyP-mediated lethal death and the levels of the related septic biomarkers. Therefore, these results indicated the therapeutic potential of lysozyme on various systemic inflammatory diseases, such as sepsis or septic shock. -- Highlights: •PolyP is shown to be an important mediator of vascular inflammation. •Lysozyme inhibited PolyP-mediated hyperpermeability. •Lysozyme inhibited PolyP-mediated septic response. •Lysozyme reduced PolyP-induced septic mortality.« less

  10. Study of the therapeutic benefit of cationic copolymer administration to vascular endothelium under mechanical stress

    PubMed Central

    Giantsos-Adams, Kristina; Lopez-Quintero, Veronica; Kopeckova, Pavla; Kopecek, Jindrich; Tarbell, John M.; Dull, Randal

    2015-01-01

    Pulmonary edema and the associated increases in vascular permeability continue to represent a significant clinical problem in the intensive care setting, with no current treatment modality other than supportive care and mechanical ventilation. Therapeutic compound(s) capable of attenuating changes in vascular barrier function would represent a significant advance in critical care medicine. We have previously reported the development of HPMA-based copolymers, targeted to endothelial glycocalyx that are able to enhance barrier function. In this work, we report the refinement of copolymer design and extend our physiological studies todemonstrate that the polymers: 1) reduce both shear stress and pressure-mediated increase in hydraulic conductivity, 2) reduce nitric oxide production in response to elevated hydrostatic pressure and, 3) reduce the capillary filtration coefficient (Kfc) in an isolated perfused mouse lung model. These copolymers represent an important tool for use in mechanotransduction research and a novel strategy for developing clinically useful copolymers for the treatment of vascular permeability. PMID:20932573

  11. Interstitial Fluid Flow and Drug Delivery in Vascularized Tumors: A Computational Model

    PubMed Central

    Welter, Michael; Rieger, Heiko

    2013-01-01

    Interstitial fluid is a solution that bathes and surrounds the human cells and provides them with nutrients and a way of waste removal. It is generally believed that elevated tumor interstitial fluid pressure (IFP) is partly responsible for the poor penetration and distribution of therapeutic agents in solid tumors, but the complex interplay of extravasation, permeabilities, vascular heterogeneities and diffusive and convective drug transport remains poorly understood. Here we consider–with the help of a theoretical model–the tumor IFP, interstitial fluid flow (IFF) and its impact upon drug delivery within tumor depending on biophysical determinants such as vessel network morphology, permeabilities and diffusive vs. convective transport. We developed a vascular tumor growth model, including vessel co-option, regression, and angiogenesis, that we extend here by the interstitium (represented by a porous medium obeying Darcy's law) and sources (vessels) and sinks (lymphatics) for IFF. With it we compute the spatial variation of the IFP and IFF and determine its correlation with the vascular network morphology and physiological parameters like vessel wall permeability, tissue conductivity, distribution of lymphatics etc. We find that an increased vascular wall conductivity together with a reduction of lymph function leads to increased tumor IFP, but also that the latter does not necessarily imply a decreased extravasation rate: Generally the IF flow rate is positively correlated with the various conductivities in the system. The IFF field is then used to determine the drug distribution after an injection via a convection diffusion reaction equation for intra- and extracellular concentrations with parameters guided by experimental data for the drug Doxorubicin. We observe that the interplay of convective and diffusive drug transport can lead to quite unexpected effects in the presence of a heterogeneous, compartmentalized vasculature. Finally we discuss various

  12. Interstitial fluid flow and drug delivery in vascularized tumors: a computational model.

    PubMed

    Welter, Michael; Rieger, Heiko

    2013-01-01

    Interstitial fluid is a solution that bathes and surrounds the human cells and provides them with nutrients and a way of waste removal. It is generally believed that elevated tumor interstitial fluid pressure (IFP) is partly responsible for the poor penetration and distribution of therapeutic agents in solid tumors, but the complex interplay of extravasation, permeabilities, vascular heterogeneities and diffusive and convective drug transport remains poorly understood. Here we consider-with the help of a theoretical model-the tumor IFP, interstitial fluid flow (IFF) and its impact upon drug delivery within tumor depending on biophysical determinants such as vessel network morphology, permeabilities and diffusive vs. convective transport. We developed a vascular tumor growth model, including vessel co-option, regression, and angiogenesis, that we extend here by the interstitium (represented by a porous medium obeying Darcy's law) and sources (vessels) and sinks (lymphatics) for IFF. With it we compute the spatial variation of the IFP and IFF and determine its correlation with the vascular network morphology and physiological parameters like vessel wall permeability, tissue conductivity, distribution of lymphatics etc. We find that an increased vascular wall conductivity together with a reduction of lymph function leads to increased tumor IFP, but also that the latter does not necessarily imply a decreased extravasation rate: Generally the IF flow rate is positively correlated with the various conductivities in the system. The IFF field is then used to determine the drug distribution after an injection via a convection diffusion reaction equation for intra- and extracellular concentrations with parameters guided by experimental data for the drug Doxorubicin. We observe that the interplay of convective and diffusive drug transport can lead to quite unexpected effects in the presence of a heterogeneous, compartmentalized vasculature. Finally we discuss various

  13. Assessment of Blood-brain Barrier Permeability by Intravenous Infusion of FITC-labeled Albumin in a Mouse Model of Neurodegenerative Disease.

    PubMed

    Di Pardo, Alba; Castaldo, Salvatore; Capocci, Luca; Amico, Enrico; Vittorio, Maglione

    2017-11-08

    Disruption of blood-brain barrier (BBB) integrity is a common feature for different neurological and neurodegenerative diseases. Although the interplay between perturbed BBB homeostasis and the pathogenesis of brain disorders needs further investigation, the development and validation of a reliable procedure to accurately detect BBB alterations may be crucial and represent a useful tool for potentially predicting disease progression and developing targeted therapeutic strategies. Here, we present an easy and efficient procedure for evaluating BBB leakage in a neurodegenerative condition like that occurring in a preclinical mouse model of Huntington disease, in which defects in the permeability of BBB are clearly detectable precociously in the disease. Specifically, the high molecular weight fluorescein isothiocyanate labelled (FITC)-albumin, which is able to cross the BBB only when the latter is impaired, is acutely infused into a mouse jugular vein and its distribution in the vascular or parenchymal districts is then determined by fluorescence microscopy. Accumulation of green fluorescent-albumin in the brain parenchyma functions as an index of aberrant BBB permeability and, when quantitated by using Image J processing software, is reported as Green Fluorescence Intensity.

  14. 3D Printed Vascular Networks Enhance Viability in High-Volume Perfusion Bioreactor.

    PubMed

    Ball, Owen; Nguyen, Bao-Ngoc B; Placone, Jesse K; Fisher, John P

    2016-12-01

    There is a significant clinical need for engineered bone graft substitutes that can quickly, effectively, and safely repair large segmental bone defects. One emerging field of interest involves the growth of engineered bone tissue in vitro within bioreactors, the most promising of which are perfusion bioreactors. Using bioreactor systems, tissue engineered bone constructs can be fabricated in vitro. However, these engineered constructs lack inherent vasculature and once implanted, quickly develop a necrotic core, where no nutrient exchange occurs. Here, we utilized COMSOL modeling to predict oxygen diffusion gradients throughout aggregated alginate constructs, which allowed for the computer-aided design of printable vascular networks, compatible with any large tissue engineered construct cultured in a perfusion bioreactor. We investigated the effect of 3D printed macroscale vascular networks with various porosities on the viability of human mesenchymal stem cells in vitro, using both gas-permeable, and non-gas permeable bioreactor growth chamber walls. Through the use of 3D printed vascular structures in conjunction with a tubular perfusion system bioreactor, cell viability was found to increase by as much as 50% in the core of these constructs, with in silico modeling predicting construct viability at steady state.

  15. 3D Printed Vascular Networks Enhance Viability in High-Volume Perfusion Bioreactor

    PubMed Central

    Ball, Owen; Nguyen, Bao-Ngoc B.; Placone, Jesse K.; Fisher, John P.

    2016-01-01

    There is a significant clinical need for engineered bone graft substitutes that can quickly, effectively, and safely repair large segmental bone defects. One emerging field of interest involves the growth of engineered bone tissue in vitro within bioreactors, the most promising of which are perfusion bioreactors. Using bioreactor systems, tissue engineered bone constructs can be fabricated in vitro. However, these engineered constructs lack inherent vasculature and once implanted, quickly develop a necrotic core, where no nutrient exchange occurs. Here, we utilized COMSOL modeling to predict oxygen diffusion gradients throughout aggregated alginate constructs, which allowed for the computer-aided design of printable vascular networks, compatible with any large tissue engineered construct cultured in a perfusion bioreactor. We investigated the effect of 3D printed macroscale vascular networks with various porosities on the viability of human mesenchymal stem cells in vitro, using both gas-permeable, and non-gas permeable bioreactor growth chamber walls. Through the use of 3D printed vascular structures in conjunction with a tubular perfusion system bioreactor, cell viability was found to increase by as much as 50% in the core of these constructs, with in silico modeling predicting construct viability at steady state. PMID:27272210

  16. Dual-Energy Micro-Computed Tomography Imaging of Radiation-Induced Vascular Changes in Primary Mouse Sarcomas

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Moding, Everett J.; Clark, Darin P.; Qi, Yi

    2013-04-01

    Purpose: To evaluate the effects of radiation therapy on primary tumor vasculature using dual-energy (DE) micro-computed tomography (micro-CT). Methods and Materials: Primary sarcomas were generated with mutant Kras and p53. Unirradiated tumors were compared with tumors irradiated with 20 Gy. A liposomal-iodinated contrast agent was administered 1 day after treatment, and mice were imaged immediately after injection (day 1) and 3 days later (day 4) with DE micro-CT. CT-derived tumor sizes were used to assess tumor growth. After DE decomposition, iodine maps were used to assess tumor fractional blood volume (FBV) at day 1 and tumor vascular permeability at daymore » 4. For comparison, tumor vascularity and vascular permeability were also evaluated histologically by use of CD31 immunofluorescence and fluorescently-labeled dextrans. Results: Radiation treatment significantly decreased tumor growth from day 1 to day 4 (P<.05). There was a positive correlation between CT measurement of tumor FBV on day 1 and extravasated iodine on day 4 with microvascular density (MVD) on day 4 (R{sup 2}=0.53) and dextran accumulation (R{sup 2}=0.63) on day 4, respectively. Despite no change in MVD measured by histology, tumor FBV significantly increased after irradiation as measured by DE micro-CT (0.070 vs 0.091, P<.05). Both dextran and liposomal-iodine accumulation in tumors increased significantly after irradiation, with dextran fractional area increasing 5.2-fold and liposomal-iodine concentration increasing 4.0-fold. Conclusions: DE micro-CT is an effective tool for noninvasive assessment of vascular changes in primary tumors. Tumor blood volume and vascular permeability increased after a single therapeutic dose of radiation treatment.« less

  17. Carboxyhaemoglobin and pulmonary epithelial permeability in man.

    PubMed Central

    Jones, J G; Minty, B D; Royston, D; Royston, J P

    1983-01-01

    The effect of cigarette smoke exposure on pulmonary epithelial permeability was studied in 45 smokers and 22 non-smokers. An index of cigarette smoke exposure was obtained from the carboxyhaemoglobin concentration (HbCO%). Pulmonary epithelial permeability was proportional to the half-time clearance rate of technetium-99m-labelled diethylene triamine pentacetate (99mTc DTPA) from lung to blood (T1/2LB). The relationship between T1/2LB and HbCO% was hyperbolic in form and the data could be fitted to the quadratic formula (formula; see text) where the parameters a0, a1, and a2 represent respectively the asymptotic T1/2LB value at large carboxyhaemoglobin values and the slope and shape of the curve. The values of these parameters were a0 4.4 (2.6), a1 = 77.8 (15.5), and a2 -25.5 (9.7) (SE). This is the first demonstration of a dose-response relationship between carboxyhaemoglobin and an increased permeability of the lungs in man and provides a technique for identifying the roles of carbon monoxide and other cigarette smoke constituents in causing increased pulmonary epithelial permeability. PMID:6344310

  18. Endothelial permeability is controlled by spatially defined cytoskeletal mechanics: atomic force microscopy force mapping of pulmonary endothelial monolayer.

    PubMed

    Birukova, Anna A; Arce, Fernando T; Moldobaeva, Nurgul; Dudek, Steven M; Garcia, Joe G N; Lal, Ratnesh; Birukov, Konstantin G

    2009-03-01

    Actomyosin contraction directly regulates endothelial cell (EC) permeability, but intracellular redistribution of cytoskeletal tension associated with EC permeability is poorly understood. We used atomic force microscopy (AFM), EC permeability assays, and fluorescence microscopy to link barrier regulation, cell remodeling, and cytoskeletal mechanical properties in EC treated with barrier-protective as well as barrier-disruptive agonists. Thrombin, vascular endothelial growth factor, and hydrogen peroxide increased EC permeability, disrupted cell junctions, and induced stress fiber formation. Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine, hepatocyte growth factor, and iloprost tightened EC barriers, enhanced peripheral actin cytoskeleton and adherens junctions, and abolished thrombin-induced permeability and EC remodeling. AFM force mapping and imaging showed differential distribution of cell stiffness: barrier-disruptive agonists increased stiffness in the central region, and barrier-protective agents decreased stiffness in the center and increased it at the periphery. Attenuation of thrombin-induced permeability correlates well with stiffness changes from the cell center to periphery. These results directly link for the first time the patterns of cell stiffness with specific EC permeability responses.

  19. Neutrophil Depletion Suppresses Pulmonary Vascular Hyperpermeability and Occurrence of Pulmonary Edema Caused by Hantavirus Infection in C.B-17 SCID Mice

    PubMed Central

    Koma, Takaaki; Yoshimatsu, Kumiko; Nagata, Noriyo; Sato, Yuko; Shimizu, Kenta; Yasuda, Shumpei P.; Amada, Takako; Nishio, Sanae; Hasegawa, Hideki

    2014-01-01

    ABSTRACT Hantavirus infections are characterized by vascular hyperpermeability and neutrophilia. However, the pathogenesis of this disease is poorly understood. Here, we demonstrate for the first time that pulmonary vascular permeability is increased by Hantaan virus infection and results in the development of pulmonary edema in C.B-17 severe combined immunodeficiency (SCID) mice lacking functional T cells and B cells. Increases in neutrophils in the lung and blood were observed when pulmonary edema began to be observed in the infected SCID mice. The occurrence of pulmonary edema was inhibited by neutrophil depletion. Moreover, the pulmonary vascular permeability was also significantly suppressed by neutrophil depletion in the infected mice. Taken together, the results suggest that neutrophils play an important role in pulmonary vascular hyperpermeability and the occurrence of pulmonary edema after hantavirus infection in SCID mice. IMPORTANCE Although hantavirus infections are characterized by the occurrence of pulmonary edema, the pathogenic mechanism remains largely unknown. In this study, we demonstrated for the first time in vivo that hantavirus infection increases pulmonary vascular permeability and results in the development of pulmonary edema in SCID mice. This novel mouse model for human hantavirus infection will be a valuable tool and will contribute to elucidation of the pathogenetic mechanisms. Although the involvement of neutrophils in the pathogenesis of hantavirus infection has largely been ignored, the results of this study using the mouse model suggest that neutrophils are involved in the vascular hyperpermeability and development of pulmonary edema in hantavirus infection. Further study of the mechanisms could lead to the development of specific treatment for hantavirus infection. PMID:24719427

  20. Reimbursement in hospital-based vascular surgery: Physician and practice perspective.

    PubMed

    Perri, Jennifer L; Zwolak, Robert M; Goodney, Philip P; Rutherford, Gretchen A; Powell, Richard J

    2017-07-01

    The purpose of this study was to determine change in value of a vascular surgery division to the health care system during 6 years at a hospital-based academic practice and to compare physician vs hospital revenue earned during this period. Total revenue generated by the vascular surgery service line at an academic medical center from 2010 through 2015 was evaluated. Total revenue was measured as the sum of physician (professional) and hospital (technical) net revenue for all vascular-related patient care. Adjustments were made for work performed, case complexity, and inflation. To reflect the effect of these variables, net revenue was indexed to work relative value units (wRVUs), case mix index, and consumer price index, which adjusted for work, case complexity, and inflation, respectively. Differences in physician and hospital net revenue were compared over time. Physician work, measured in RVUs per year, increased by 4%; case complexity, assessed with case mix index, increased by 10% for the 6-year measurement period. Despite stability in payer mix at 64% to 69% Medicare, both physician and hospital vascular-related revenue/wRVU decreased during this period. Unadjusted professional revenue/wRVU declined by 14.1% (P = .09); when considering case complexity, physician revenue/wRVU declined by 20.6% (P = .09). Taking into account both case complexity and inflation, physician revenue declined by 27.0% (P = .04). Comparatively, hospital revenue for vascular surgery services decreased by 13.8% (P = .07) when adjusting for unit work, complexity, and inflation. At medical centers where vascular surgeons are hospital based, vascular care reimbursement decreased substantially from 2010 to 2015 when case complexity and inflation were considered. Physician reimbursement (professional fees) decreased at a significantly greater rate than hospital reimbursement for vascular care. This trend has significant implications for salaried vascular surgeons in hospital

  1. Substrate stiffness-dependent exacerbation of endothelial permeability and inflammation: mechanisms and potential implications in ALI and PH (2017 Grover Conference Series)

    PubMed Central

    Karki, Pratap; Birukova, Anna A.

    2018-01-01

    The maintenance of endothelial barrier integrity is absolutely essential to prevent the vascular leak associated with pneumonia, pulmonary edema resulting from inhalation of toxins, acute elevation to high altitude, traumatic and septic lung injury, acute lung injury (ALI), and its life-threatening complication, acute respiratory distress syndrome (ARDS). In addition to the long-known edemagenic and inflammatory agonists, emerging evidences suggest that factors of endothelial cell (EC) mechanical microenvironment such as blood flow, mechanical strain of the vessel, or extracellular matrix stiffness also play an essential role in the control of endothelial permeability and inflammation. Recent studies from our group and others have demonstrated that substrate stiffening causes endothelial barrier disruption and renders EC more susceptible to agonist-induced cytoskeletal rearrangement and inflammation. Further in vivo studies have provided direct evidence that proinflammatory stimuli increase lung microvascular stiffness which in turn exacerbates endothelial permeability and inflammation and perpetuates a vicious circle of lung inflammation. Accumulating evidence suggests a key role for RhoA GTPases signaling in stiffness-dependent mechanotransduction mechanisms defining EC permeability and inflammatory responses. Vascular stiffening is also known to be a key contributor to other cardiovascular diseases such as arterial pulmonary hypertension (PH), although the precise role of stiffness in the development and progression of PH remains to be elucidated. This review summarizes the current understanding of stiffness-dependent regulation of pulmonary EC permeability and inflammation, and discusses potential implication of pulmonary vascular stiffness alterations at macro- and microscale in development and modulation of ALI and PH. PMID:29714090

  2. Endothelial glycocalyx: permeability barrier and mechanosensor.

    PubMed

    Curry, F E; Adamson, R H

    2012-04-01

    Endothelial cells are covered with a polysaccharide rich layer more than 400 nm thick, mechanical properties of which limit access of circulating plasma components to endothelial cell membranes. The barrier properties of this endothelial surface layer are deduced from the rate of tracer penetration into the layer and the mechanics of red and white cell movement through capillary microvessels. This review compares the mechanosensor and permeability properties of an inner layer (100-150 nm, close to the endothelial membrane) characterized as a quasi-periodic structure which accounts for key aspects of transvascular exchange and vascular permeability with those of the whole endothelial surface layers. We conclude that many of the barrier properties of the whole surface layer are not representative of the primary fiber matrix forming the molecular filter determining transvascular exchange. The differences between the properties of the whole layer and the inner glycocalyx structures likely reflect dynamic aspects of the endothelial surface layer including tracer binding to specific components, synthesis and degradation of key components, activation of signaling pathways in the endothelial cells when components of the surface layer are lost or degraded, and the spatial distribution of adhesion proteins in microdomains of the endothelial cell membrane.

  3. A review of recent advances in the assessment of bone porosity, permeability, and interstitial fluid flow

    PubMed Central

    Cardoso, Luis; Fritton, Susannah P.; Gailani, Gaffar; Benalla, Mohammed; Cowin, Stephen C.

    2012-01-01

    This contribution reviews recent research performed to assess the porosity and permeability of bone tissue with the objective of understanding interstitial fluid movement. Bone tissue mechanotransduction is considered to occur due to the passage of interstitial pore fluid adjacent to dendritic cell structures in the lacunar-canalicular porosity. The movement of interstitial fluid is also necessary for the nutrition of osteocytes. This review will focus on four topics related to improved assessment of bone interstitial fluid flow. First, the advantages and limitations of imaging technologies to visualize bone porosities and architecture at several length scales are summarized. Second, recent efforts to measure the vascular porosity and lacunar-canalicular microarchitecture are discussed. Third, studies associated with the measurement and estimation of the fluid pressure and permeability in the vascular and lacunar-canalicular domains are summarized. Fourth, the development of recent models to represent the interchange of fluids between the bone porosities is described. PMID:23174418

  4. Triglyceride-glucose index (TyG index) in comparison with fasting plasma glucose improved diabetes prediction in patients with normal fasting glucose: The Vascular-Metabolic CUN cohort.

    PubMed

    Navarro-González, David; Sánchez-Íñigo, Laura; Pastrana-Delgado, Juan; Fernández-Montero, Alejandro; Martinez, J Alfredo

    2016-05-01

    We evaluated the potential role of the triglyceride-glucose index (TyG index) as a predictor of diabetes in a White European cohort, and compared it to fasting plasma glucose (FPG) and triglycerides. 4820 patients of the Vascular-Metabolic CUN cohort (VMCUN cohort) were examined and followed up for 8.84years (±4.39). We performed a Cox proportional hazard ratio with repeated-measures analyses to assess the risk of developing type 2 diabetes across quartiles of FPG, triglycerides and the TyG index (ln[fasting triglycerides (mg/dl)×fasting plasma glucose (mg/dl)/2]), and plotted a receiver operating characteristics (ROC) curve for discrimination. There were 332 incident cases of type 2 diabetes involving 43,197.32person-years of follow-up. We observed a progressively increased risk of diabetes in subjects with TyG index levels of 8.31 or more. Among those with normal fasting glucose at baseline, <100mg/dl, subjects with the TyG index in the fourth quartile were 6.87 times more likely to develop diabetes (95% CI, 2.76-16.85; P for trend<0.001), as compared with the bottom quartile. The areas under the ROC curves (95% CI) were 0.75 (0.70-0.81) for TyG index, 0.66 (0.60-0.72) for FPG and 0.71 (0.65-0.77) for TG, in subjects with normal fasting glucose (p=0.017). Our data suggest that the TyG index is useful for the early identification of individuals at risk of type 2 diabetes. The TyG index seems to be a better predictor than FPG or triglycerides of the potential development of type 2 diabetes in normoglycemic patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Force control of endothelium permeability in mechanically stressed pulmonary micro-vascular endothelial cells.

    PubMed

    Wang, Bin; Caluch, Adam; Fodil, Redouane; Féréol, Sophie; Zadigue, Patricia; Pelle, Gabriel; Louis, Bruno; Isabey, Daniel

    2012-01-01

    Mechanical factors play a key role in the pathogenesis of Acute Respiratory Distress Syndrome (ARDS) and Ventilator-Induced Lung Injury (VILI) as contributing to alveolo-capillary barrier dysfunction. This study aims at elucidating the role of the cytoskeleton (CSK) and cell-matrix adhesion system in the stressed endothelium and more precisely in the loss of integrity of the endothelial barrier. We purposely develop a cellular model made of a monolayer of confluent Human Pulmonary Microvascular Endothelial Cells (HPMVECs) whose cytoskeleton (CSK) is directly exposed to sustained cyclic mechanical stress for 1 and 2 h. We used RGD-coated ferromagnetic beads and measured permeability before and after stress application. We find that endothelial permeability increases in the stressed endothelium, hence reflecting a loss of integrity. Structural and mechanical results suggest that this endothelial barrier alteration would be due to physically-founded discrepancies in latero-basal reinforcement of adhesion sites in response to the global increase in CSK stiffness or centripetal intracellular forces. Basal reinforcement of adhesion is presently evidenced by the marked redistribution of αvβ3 integrin with cluster formation in the stressed endothelium.

  6. Pulmonary vascular input impedance is a combined measure of pulmonary vascular resistance and stiffness and predicts clinical outcomes better than pulmonary vascular resistance alone in pediatric patients with pulmonary hypertension.

    PubMed

    Hunter, Kendall S; Lee, Po-Feng; Lanning, Craig J; Ivy, D Dunbar; Kirby, K Scott; Claussen, Lori R; Chan, K Chen; Shandas, Robin

    2008-01-01

    Pulmonary vascular resistance (PVR) is the current standard for evaluating reactivity in children with pulmonary arterial hypertension (PAH). However, PVR measures only the mean component of right ventricular afterload and neglects pulsatile effects. We recently developed and validated a method to measure pulmonary vascular input impedance, which revealed excellent correlation between the zero harmonic impedance value and PVR and suggested a correlation between higher-harmonic impedance values and pulmonary vascular stiffness. Here we show that input impedance can be measured routinely and easily in the catheterization laboratory, that impedance provides PVR and pulmonary vascular stiffness from a single measurement, and that impedance is a better predictor of disease outcomes compared with PVR. Pressure and velocity waveforms within the main pulmonary artery were measured during right heart catheterization of patients with normal pulmonary artery hemodynamics (n = 14) and those with PAH undergoing reactivity evaluation (49 subjects, 95 conditions). A correction factor needed to transform velocity into flow was obtained by calibrating against cardiac output. Input impedance was obtained off-line by dividing Fourier-transformed pressure and flow waveforms. Exceptional correlation was found between the indexed zero harmonic of impedance and indexed PVR (y = 1.095x + 1.381, R2 = 0.9620). In addition, the modulus sum of the first 2 harmonics of impedance was found to best correlate with indexed pulse pressure over stroke volume (y = 13.39x - 0.8058, R2 = 0.7962). Among a subset of patients with PAH (n = 25), cumulative logistic regression between outcomes to total indexed impedance was better (R(L)2 = 0.4012) than between outcomes and indexed PVR (R(L)2 = 0.3131). Input impedance can be consistently and easily obtained from pulse-wave Doppler and a single catheter pressure measurement, provides comprehensive characterization of the main components of RV afterload, and

  7. Investigation of temporal vascular effects induced by focused ultrasound treatment with speckle-variance optical coherence tomography

    PubMed Central

    Tsai, Meng-Tsan; Chang, Feng-Yu; Lee, Cheng-Kuang; Gong, Cihun-Siyong Alex; Lin, Yu-Xiang; Lee, Jiann-Der; Yang, Chih-Hsun; Liu, Hao-Li

    2014-01-01

    Focused ultrasound (FUS) can be used to locally and temporally enhance vascular permeability, improving the efficiency of drug delivery from the blood vessels into the surrounding tissue. However, it is difficult to evaluate in real time the effect induced by FUS and to noninvasively observe the permeability enhancement. In this study, speckle-variance optical coherence tomography (SVOCT) was implemented for the investigation of temporal effects on vessels induced by FUS treatment. With OCT scanning, the dynamic change in vessels during FUS exposure can be observed and studied. Moreover, the vascular effects induced by FUS treatment with and without the presence of microbubbles were investigated and quantitatively compared. Additionally, 2D and 3D speckle-variance images were used for quantitative observation of blood leakage from vessels due to the permeability enhancement caused by FUS, which could be an indicator that can be used to determine the influence of FUS power exposure. In conclusion, SVOCT can be a useful tool for monitoring FUS treatment in real time, facilitating the dynamic observation of temporal effects and helping to determine the optimal FUS power. PMID:25071945

  8. Sialic acids regulate microvessel permeability, revealed by novel in vivo studies of endothelial glycocalyx structure and function

    PubMed Central

    Betteridge, Kai B.; Arkill, Kenton P.; Neal, Christopher R.; Harper, Steven J.; Foster, Rebecca R.; Satchell, Simon C.; Bates, David O.

    2017-01-01

    Key points We have developed novel techniques for paired, direct, real‐time in vivo quantification of endothelial glycocalyx structure and associated microvessel permeability.Commonly used imaging and analysis techniques yield measurements of endothelial glycocalyx depth that vary by over an order of magnitude within the same vessel.The anatomical distance between maximal glycocalyx label and maximal endothelial cell plasma membrane label provides the most sensitive and reliable measure of endothelial glycocalyx depth.Sialic acid residues of the endothelial glycocalyx regulate glycocalyx structure and microvessel permeability to both water and albumin. Abstract The endothelial glycocalyx forms a continuous coat over the luminal surface of all vessels, and regulates multiple vascular functions. The contribution of individual components of the endothelial glycocalyx to one critical vascular function, microvascular permeability, remains unclear. We developed novel, real‐time, paired methodologies to study the contribution of sialic acids within the endothelial glycocalyx to the structural and functional permeability properties of the same microvessel in vivo. Single perfused rat mesenteric microvessels were perfused with fluorescent endothelial cell membrane and glycocalyx labels, and imaged with confocal microscopy. A broad range of glycocalyx depth measurements (0.17–3.02 μm) were obtained with different labels, imaging techniques and analysis methods. The distance between peak cell membrane and peak glycocalyx label provided the most reliable measure of endothelial glycocalyx anatomy, correlating with paired, numerically smaller values of endothelial glycocalyx depth (0.078 ± 0.016 μm) from electron micrographs of the same portion of the same vessel. Disruption of sialic acid residues within the endothelial glycocalyx using neuraminidase perfusion decreased endothelial glycocalyx depth and increased apparent solute permeability to albumin in the same

  9. Sphingosine kinase inhibition alleviates endothelial permeability induced by thrombin and activated neutrophils.

    PubMed

    Itagaki, Kiyoshi; Zhang, Qin; Hauser, Carl J

    2010-04-01

    Inflammation and microvascular thrombosis are interrelated causes of acute lung injury in the systemic inflammatory response syndrome. Neutrophils (polymorphonuclear neutrophil [PMN]) and endothelial cells (EC) activated by systemic inflammatory response syndrome interact to increase pulmonary vascular permeability, but the interactions between PMN and EC are difficult to study. Recently, we reported that sphingosine 1-phosphate is a second messenger eliciting store-operated calcium entry (SOCE) in response to inflammatory agonists in both PMN and EC. Store-operated calcium entry is therefore a target mechanism for the therapeutic modulation of inflammatory PMN-EC interactions. Here, we isolated, modeled, and studied the effects of pharmacologic SOCE inhibition using real-time systems to monitor EC permeability after exposure to activated PMN. We created systems to continuously assess permeability of human pulmonary artery endothelial cells and human microvascular endothelial cells from lung. Endothelial cells show increased permeability after challenge by activated PMN. Such permeability increases can be attenuated by exposure of the cocultures to sphingosine kinase (SK) inhibitors (SKI-2, N,N-dimethylsphingosine [DMS]) or Ca2+ entry inhibitors (Gd3+, MRS-1845). Human microvascular endothelial cells from lung pretreated with SKI-2 or DMS showed decreased permeability when later exposed to activated PMN. Likewise, when PMNs were activated with thapsigargin (TG) in the presence of SKI-2, DMS, Gd, or MRS-1845, their ability to cause EC permeability subsequently was reduced. SKI-2 also inhibited the activation of human pulmonary artery ECs by thrombin. These studies will provide a firm mechanistic foundation for understanding how systemic SOCE inhibition may be used to prevent acute lung injury in vivo.

  10. Crustal permeability

    USGS Publications Warehouse

    Gleeson, Tom; Ingebritsen, Steven E.

    2016-01-01

    Permeability is the primary control on fluid flow in the Earth’s crust and is key to a surprisingly wide range of geological processes, because it controls the advection of heat and solutes and the generation of anomalous pore pressures.  The practical importance of permeability – and the potential for large, dynamic changes in permeability – is highlighted by ongoing issues associated with hydraulic fracturing for hydrocarbon production (“fracking”), enhanced geothermal systems, and geologic carbon sequestration.  Although there are thousands of research papers on crustal permeability, this is the first book-length treatment.  This book bridges the historical dichotomy between the hydrogeologic perspective of permeability as a static material property and the perspective of other Earth scientists who have long recognized permeability as a dynamic parameter that changes in response to tectonism, fluid production, and geochemical reactions. 

  11. Vascular endothelial growth factor is upregulated by l-dopa in the parkinsonian brain: implications for the development of dyskinesia

    PubMed Central

    Francardo, Veronica; Lindgren, Hanna S.; Sillivan, Stephanie E.; O’Sullivan, Sean S.; Luksik, Andrew S.; Vassoler, Fair M.; Lees, Andrew J.; Konradi, Christine

    2011-01-01

    Angiogenesis and increased permeability of the blood–brain barrier have been reported to occur in animal models of Parkinson’s disease and l-dopa-induced dyskinesia, but the significance of these phenomena has remained unclear. Using a validated rat model of l-dopa-induced dyskinesia, this study demonstrates that chronic treatment with l-dopa dose dependently induces the expression of vascular endothelial growth factor in the basal ganglia nuclei. Vascular endothelial growth factor was abundantly expressed in astrocytes and astrocytic processes in the proximity of blood vessels. When co-administered with l-dopa, a small molecule inhibitor of vascular endothelial growth factor signalling significantly attenuated the development of dyskinesia and completely blocked the angiogenic response and associated increase in blood–brain barrier permeability induced by the treatment. The occurrence of angiogenesis and vascular endothelial growth factor upregulation was verified in post-mortem basal ganglia tissue from patients with Parkinson’s disease with a history of dyskinesia, who exhibited increased microvascular density, microvascular nestin expression and an upregulation of vascular endothelial growth factor messenger ribonucleic acid. These congruent findings in the rat model and human patients indicate that vascular endothelial growth factor is implicated in the pathophysiology of l-dopa-induced dyskinesia and emphasize an involvement of the microvascular compartment in the adverse effects of l-dopa pharmacotherapy in Parkinson’s disease. PMID:21771855

  12. The Phosphatase PTP-PEST/PTPN12 Regulates Endothelial Cell Migration and Adhesion, but Not Permeability, and Controls Vascular Development and Embryonic Viability*

    PubMed Central

    Souza, Cleiton Martins; Davidson, Dominique; Rhee, Inmoo; Gratton, Jean-Philippe; Davis, Elaine C.; Veillette, André

    2012-01-01

    Protein-tyrosine phosphatase (PTP)-PEST (PTPN12) is ubiquitously expressed. It is essential for normal embryonic development and embryonic viability in mice. Herein we addressed the involvement of PTP-PEST in endothelial cell functions using a combination of genetic and biochemical approaches. By generating primary endothelial cells from an inducible PTP-PEST-deficient mouse, we found that PTP-PEST is not needed for endothelial cell differentiation and proliferation or for the control of endothelial cell permeability. Nevertheless, it is required for integrin-mediated adhesion and migration of endothelial cells. PTP-PEST-deficient endothelial cells displayed increased tyrosine phosphorylation of Cas, paxillin, and Pyk2, which were previously also implicated in integrin functions. By eliminating PTP-PEST in endothelial cells in vivo, we obtained evidence that expression of PTP-PEST in endothelial cells is required for normal vascular development and embryonic viability. Therefore, PTP-PEST is a key regulator of integrin-mediated functions in endothelial cells seemingly through its capacity to control Cas, paxillin, and Pyk2. This function explains at least in part the essential role of PTP-PEST in embryonic development and viability. PMID:23105101

  13. Ascorbic Acid Prevents VEGF-induced Increases in Endothelial Barrier Permeability

    PubMed Central

    Ulker, Esad; Parker, William H.; Raj, Amita; Qu, Zhi-chao; May, James M.

    2015-01-01

    Vascular endothelial growth factor (VEGF) increases endothelial barrier permeability, an effect that may contribute to macular edema in diabetic retinopathy. Since vitamin C, or ascorbic acid, can tighten the endothelial permeability barrier, we examined whether it could prevent the increase in permeability due to VEGF in human umbilical vein endothelial cells (HUVECs). As previously observed, VEGF increased HUVEC permeability to radiolabeled inulin within 60 min in a concentration-dependent manner. Loading the cells with increasing concentrations of ascorbate progressively prevented the leakage caused by 100 ng/ml VEGF, with a significant inhibition at 13 μM and complete inhibition at 50 μM. Loading cells with 100 μM ascorbate also decreased basal generation of reactive oxygen species and prevented the increase caused by both 100 ng/ml VEGF. VEGF treatment decreased intracellular ascorbate by 25%, thus linking ascorbate oxidation to its prevention of VEGF-induced barrier leakage. The latter was blocked by treating the cells with 60 μM L-NAME (but not D-NAME) as well as by 30 μM sepiapterin, a precursor of tetrahydrobiopterin that is required for proper function of endothelial nitric oxide synthase (eNOS). These findings suggest that VEGF-induced barrier leakage uncouples eNOS. Ascorbate inhibition of the VEGF effect could thus be due either to scavenging superoxide or to peroxynitrite generated by the uncoupled eNOS, or more likely to its ability to recycle tetrahydrobiopterin, thus avoiding enzyme uncoupling in the first place. Ascorbate prevention of VEGF-induced increases in endothelial permeability opens the possibility that its repletion could benefit diabetic macular edema. PMID:26590088

  14. Regulation of Endothelial Permeability by Glutathione S-Transferase Pi Against Actin Polymerization.

    PubMed

    Yang, Yang; Yin, Fangyuan; Hang, Qiyun; Dong, Xiaoliang; Chen, Jiao; Li, Ling; Cao, Peng; Yin, Zhimin; Luo, Lan

    2018-01-01

    Inflammation-induced injury of the endothelial barrier occurs in several pathological conditions, including atherosclerosis, ischemia, and sepsis. Endothelial cytoskeleton rearrangement is an important pathological mechanism by which inflammatory stimulation triggers an increase of vascular endothelial permeability. However, the mechanism maintaining endothelial cell barrier function against inflammatory stress is not fully understood. Glutathione S-transferase pi (GSTpi) exists in various types of cells and protects them against different stresses. In our previous study, GSTpi was found to act as a negative regulator of inflammatory responses. We used a Transwell permeability assay to test the influence of GSTpi and its transferase activity on the increase of endothelial permeability induced by tumor necrosis factor alpha (TNF-α). TNF-α-induced actin remodeling and the influence of GSTpi were observed by using laser confocal microscopy. Western blotting was used to test the influence of GSTpi on TNF-α-activated p38 mitogen-activated protein kinase (MAPK)/MK2/heat shock protein 27 (HSP27). GSTpi reduced TNF-α-induced stress fiber formation and endothelial permeability increase by restraining actin cytoskeleton rearrangement, and this reduction was unrelated to its transferase activity. We found that GSTpi inhibited p38MAPK phosphorylation by directly binding p38 and influenced downstream substrate HSP27-induced actin remodeling. GSTpi inhibited TNF-α-induced actin remodeling, stress fiber formation and endothelial permeability increase by inhibiting the p38MAPK/HSP27 signaling pathway. © 2018 The Author(s). Published by S. Karger AG, Basel.

  15. Novel Fluorescein Angiography-Based Computer-Aided Algorithm for Assessment of Retinal Vessel Permeability

    PubMed Central

    Chassidim, Yoash; Parmet, Yisrael; Tomkins, Oren; Knyazer, Boris; Friedman, Alon; Levy, Jaime

    2013-01-01

    Purpose To present a novel method for quantitative assessment of retinal vessel permeability using a fluorescein angiography-based computer algorithm. Methods Twenty-one subjects (13 with diabetic retinopathy, 8 healthy volunteers) underwent fluorescein angiography (FA). Image pre-processing included removal of non-retinal and noisy images and registration to achieve spatial and temporal pixel-based analysis. Permeability was assessed for each pixel by computing intensity kinetics normalized to arterial values. A linear curve was fitted and the slope value was assigned, color-coded and displayed. The initial FA studies and the computed permeability maps were interpreted in a masked and randomized manner by three experienced ophthalmologists for statistical validation of diagnosis accuracy and efficacy. Results Permeability maps were successfully generated for all subjects. For healthy volunteers permeability values showed a normal distribution with a comparable range between subjects. Based on the mean cumulative histogram for the healthy population a threshold (99.5%) for pathological permeability was determined. Clear differences were found between patients and healthy subjects in the number and spatial distribution of pixels with pathological vascular leakage. The computed maps improved the discrimination between patients and healthy subjects, achieved sensitivity and specificity of 0.974 and 0.833 respectively, and significantly improved the consensus among raters for the localization of pathological regions. Conclusion The new algorithm allows quantification of retinal vessel permeability and provides objective, more sensitive and accurate evaluation than the present subjective clinical diagnosis. Future studies with a larger patients’ cohort and different retinal pathologies are awaited to further validate this new approach and its role in diagnosis and treatment follow-up. Successful evaluation of vasculature permeability may be used for the early

  16. Moss and vascular plant indices in Ohio wetlands have similar environmental predictors

    USGS Publications Warehouse

    Stapanian, Martin A.; Schumacher, William; Gara, Brian; Adams, Jean V.; Viau, Nick

    2016-01-01

    Mosses and vascular plants have been shown to be reliable indicators of wetland habitat delineation and environmental quality. Knowledge of the best ecological predictors of the quality of wetland moss and vascular plant communities may determine if similar management practices would simultaneously enhance both populations. We used Akaike's Information Criterion to identify models predicting a moss quality assessment index (MQAI) and a vascular plant index of biological integrity based on floristic quality (VIBI-FQ) from 27 emergent and 13 forested wetlands in Ohio, USA. The set of predictors included the six metrics from a wetlands disturbance index (ORAM) and two landscape development intensity indices (LDIs). The best single predictor of MQAI and one of the predictors of VIBI-FQ was an ORAM metric that assesses habitat alteration and disturbance within the wetland, such as mowing, grazing, and agricultural practices. However, the best single predictor of VIBI-FQ was an ORAM metric that assessed wetland vascular plant communities, interspersion, and microtopography. LDIs better predicted MQAI than VIBI-FQ, suggesting that mosses may either respond more rapidly to, or recover more slowly from, anthropogenic disturbance in the surrounding landscape than vascular plants. These results supported previous predictive studies on amphibian indices and metrics and a separate vegetation index, indicating that similar wetland management practices may result in qualitatively the same ecological response for three vastly different wetland biological communities (amphibians, vascular plants, and mosses).

  17. THE VASCULAR PATHOPHYSIOLOGY OF AN IRRADIATED GRAFT

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rubin, P.; Casarett, G.; Grise, J.W.

    1960-06-01

    The difference in the vascularization of grafted and normal skin forms a reasonable basis for explaining the differences in the radiation reactions of these structures. The radioisotope half time of disappearance following subcutaneous injection is an index of vascular integrity of the graft and serves as a parameter to predict its radioresponsiveness. In developing a concept of the spectrum of reactions of grafted skin to ionizing irradiation, knowledge of the radiopathologic changes in capillaries must be utilized with knowledge of the histophysiology of the vascularity of an autograft. (auth)

  18. Novel vascular endothelial growth factor blocker improves cellular viability and reduces hypobaric hypoxia-induced vascular leakage and oedema in rat brain.

    PubMed

    Saraswat, Deepika; Nehra, Sarita; Chaudhary, Kamal; CVS, Siva Prasad

    2015-05-01

    Vascular endothelial growth factor (VEGF) is an important cerebral angiogenic and permeability factor under hypoxia. There is a need to find effective molecules that may ameliorate hypoxia-induced cerebral oedema. In silico identification of novel candidate molecules that block VEGF-A site were identified and validated with a Ramachandran plot. The active site residues of VEGF-A were detected by Pocketfinder, CASTp, and DogSiteScorer. Based on in silico data, three VEGF-A blocker (VAB) candidate molecules (VAB1, VAB2, and VAB3) were checked for improvement in cellular viability and regulation of VEGF levels in N2a cells under hypoxia (0.5% O2 ). Additionally, the best candidate molecule's efficacy was assessed in male Sprague-Dawley rats for its ameliorative effect on cerebral oedema and vascular leakage under hypobaric hypoxia 7260 m. All experimental results were compared with the commercially available VEGF blocker sunitinib. Vascular endothelial growth factor-A blocker 1 was found most effective in increasing cellular viability and maintaining normal VEGF levels under hypoxia (0.5% oxygen) in N2a cells. Vascular endothelial growth factor-A blocker 1 effectively restored VEGF levels, decreased cerebral oedema, and reduced vascular leakage under hypobaric hypoxia when compared to sunitinib-treated rats. Vascular endothelial growth factor-A blocker 1 may be a promising candidate molecule for ameliorating hypobaric hypoxia-induced vasogenic oedema by regulating VEGF levels. © 2015 Wiley Publishing Asia Pty Ltd.

  19. Causation by Diesel Exhaust Particles of Endothelial Dysfunctions in Cytotoxicity, Pro-inflammation, Permeability, and Apoptosis Induced by ROS Generation.

    PubMed

    Tseng, Chia-Yi; Wang, Jhih-Syuan; Chao, Ming-Wei

    2017-10-01

    Epidemiological studies suggest that an increase of diesel exhaust particles (DEP) in ambient air corresponds to an increase in hospital-recorded myocardial infarctions within 48 h after exposure. Among the many theories to explain this data are endothelial dysfunction and translocation of DEP into vasculature. The mechanisms for such DEP-induced vascular permeability remain unknown. One of the major mechanisms underlying the effects of DEP is suggested to be oxidative stress. Experiments have shown that DEP induce the generation of reactive oxygen species (ROS), such as superoxide anion and H 2 O 2 in the HUVEC tube cells. Transcription factor Nrf2 is translocated to the cell nucleus, where it activates transcription of the antioxidative enzyme HO-1 and sequentially induces the release of vascular permeability factor VEGF-A. Furthermore, a recent study shows that DEP-induced intracellular ROS may cause the release of pro-inflammatory TNF-α and IL-6, which may induce endothelial permeability as well by promoting VEGF-A secretion independently of HO-1 activation. These results demonstrated that the adherens junction molecule, VE-cadherin, becomes redistributed from the membrane at cell-cell borders to the cytoplasm in response to DEP, separating the plasma membranes of adjacent cells. DEP were occasionally found in endothelial cell cytoplasm and in tube lumen. In addition, the induced ROS is cytotoxic to the endothelial tube-like HUVEC. Acute DEP exposure stimulates ATP depletion, followed by depolarization of their actin cytoskeleton, which sequentially inhibits PI3K/Akt activity and induces endothelial apoptosis. Nevertheless, high-dose DEP augments tube cell apoptosis up to 70 % but disrupts the p53 negative regulator Mdm2. In summary, exposure to DEP affects parameters influencing vasculature permeability and viability, i.e., oxidative stress and its upregulated antioxidative and pro-inflammatory responses, which sequentially induce vascular permeability

  20. Effect of permeability enhancers on paracellular permeability of acyclovir.

    PubMed

    Ates, Muge; Kaynak, Mustafa Sinan; Sahin, Selma

    2016-06-01

    According to Biopharmaceutics Classification System (BCS), acyclovir is a class III (high solubility, low permeability) compound, and it is transported through paracellular route by passive diffusion. The aim of this study was to investigate the effect of various pharmaceutical excipients on the intestinal permeability of acyclovir. The single-pass in-situ intestinal perfusion (SPIP) method was used to estimate the permeability values of acyclovir and metoprolol across different intestinal segments (jejunum, ileum and colon). Permeability coefficient (Peff ) of acyclovir was determined in the absence and presence of a permeation enhancer such as dimethyl β-cyclodextrin (DM-β-CD), sodium lauryl sulfate (SLS), sodium caprate (Cap-Na) and chitosan chloride. All enhancers increased the permeability of paracellularly transported acyclovir. Although Cap-Na has the highest permeability-enhancing effect in all segments, permeation-enhancing effect of chitosan and SLS was only significant in ileum. On the other hand, DM-β-CD slightly decreased the permeability in all intestinal segments. These findings have potential implication concerning the enhancement of absorption of paracellularly transported compounds with limited oral bioavailability. In the case of acyclovir, Cap-Na either alone or in combination with SLS or chitosan has the potential to improve its absorption and bioavailability and has yet to be explored. © 2016 Royal Pharmaceutical Society.

  1. Non-monotonic permeability variation during colloidal transport: Governing equations and analytical model

    NASA Astrophysics Data System (ADS)

    Chequer, L.; Russell, T.; Behr, A.; Genolet, L.; Kowollik, P.; Badalyan, A.; Zeinijahromi, A.; Bedrikovetsky, P.

    2018-02-01

    Permeability decline associated with the migration of natural reservoir fines impairs the well index of injection and production wells in aquifers and oilfields. In this study, we perform laboratory corefloods using aqueous solutions with different salinities in engineered rocks with different kaolinite content, yielding fines migration and permeability alteration. Unusual permeability growth has been observed at high salinities in rocks with low kaolinite concentrations. This has been attributed to permeability increase during particle detachment and re-attachment of already mobilised fines by electrostatic attraction to the rock in stagnant zones of the porous space. We refine the traditional model for fines migration by adding mathematical expressions for the particle re-attachment rate, particle detachment with delay relative to salinity decrease, and the attached-concentration-dependency of permeability. A one-dimensional flow problem that accounts for those three effects allows for an exact analytical solution. The modified model captures the observed effect of permeability increase at high water salinities in rocks with low kaolinite concentrations. The developed model matches the coreflooding data with high accuracy, and the obtained model coefficients vary within their usual intervals.

  2. Vascular dysfunction in women with a history of preeclampsia and intrauterine growth restriction: insights into future vascular risk.

    PubMed

    Yinon, Yoav; Kingdom, John C P; Odutayo, Ayodele; Moineddin, Rahim; Drewlo, Sascha; Lai, Vesta; Cherney, David Z I; Hladunewich, Michelle A

    2010-11-02

    Women with a history of placental disease are at increased risk for the future development of vascular disease. It is unknown whether preexisting endothelial dysfunction underlies both the predisposition to placental disease and the later development of vascular disease. The aim of this study was to assess vascular function in postpartum women and to determine whether differences emerged depending on the presentation of placental disease. Women with a history of early-onset preeclampsia (n=15), late-onset preeclampsia (n=9), intrauterine growth restriction without preeclampsia (n=9), and prior normal pregnancy (n=16) were studied 6 to 24 months postpartum. Flow-mediated vasodilatation and flow-independent (glyceryl trinitrate-induced) vasodilatation were studied through the use of high-resolution vascular ultrasound examination of the brachial artery. Arterial stiffness was assessed by pulse-wave analysis (augmentation index). Laboratory assessment included circulating angiogenic factors (vascular endothelial growth factor, soluble fms-like tyrosine kinase 1, placental growth factor, and soluble endoglin). Flow-mediated vasodilatation was significantly reduced in women with previous early-onset preeclampsia and intrauterine growth restriction compared with women with previous late-onset preeclampsia and control subjects (3.2±2.7% and 2.1±1.2% versus 7.9±3.8% and 9.1±3.5%, respectively; P<0.0001). Flow-independent vasodilatation was similar among all groups. Similarly, the radial augmentation index was significantly increased among women with previous early-onset preeclampsia and intrauterine growth restriction, but not among late preeclamptic women and control subjects (P=0.0105). Circulating angiogenic factors were similar in all groups. Only women with a history of early-onset preeclampsia or intrauterine growth restriction without preeclampsia exhibit impaired vascular function, which might explain their predisposition to placental disease and their higher

  3. Frictional stability-permeability relationships for fractures in shales: Friction-Permeability Relationships

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fang, Yi; Elsworth, Derek; Wang, Chaoyi

    There is wide concern that fluid injection in the subsurface, such as for the stimulation of shale reservoirs or for geological CO 2 sequestration (GCS), has the potential to induce seismicity that may change reservoir permeability due to fault slip. However, the impact of induced seismicity on fracture permeability evolution remains unclear due to the spectrum of modes of fault reactivation (e.g., stable versus unstable). As seismicity is controlled by the frictional response of fractures, we explore friction-stability-permeability relationships through the concurrent measurement of frictional and hydraulic properties of artificial fractures in Green River shale (GRS) and Opalinus shale (OPS).more » We observe that carbonate-rich GRS shows higher frictional strength but weak neutral frictional stability. The GRS fracture permeability declines during shearing while an increased sliding velocity reduces the rate of permeability decline. By comparison, the phyllosilicate-rich OPS has lower friction and strong stability while the fracture permeability is reduced due to the swelling behavior that dominates over the shearing induced permeability reduction. Hence, we conclude that the friction-stability-permeability relationship of a fracture is largely controlled by mineral composition and that shale mineral compositions with strong frictional stability may be particularly subject to permanent permeability reduction during fluid infiltration.« less

  4. Anti-inflammatory effects of polyamines in serotonin and carrageenan paw edemata - possible mechanism to increase vascular permeability inhibitory protein level which is regulated by glucocorticoids and superoxide radical.

    PubMed

    Oyanagui, Y

    1984-02-01

    Serotonin paw edema of mice and carrageenan paw edema of rats were inhibited by subcutaneously or orally administered certain polyamines. They must be given at least 2 h before serotonin challenge to get inhibitions which were blocked by the concomitant injections of cycloheximide. Thirty percent inhibitory dose (ID30) of polyamines (s.c.) 3 h before serotonin (s.c.) were: spermidine (8 mg/kg), spermine 28 mg/kg) and putrescine (55 mg/kg). Agmatine, cadaverine, ornithine, citrulline, lysine and arginine were not inhibitory even at 200 mg/kg. Three inhibitory polyamines were effective by oral administration but were not inhibitory by local administration into the paws. Intravenous injections of spermidine also required 2 h of lag period for inhibitions. Serotonin edema was inhibited by dexamethasone (1 mg/kg), prednisolone (1 mg/kg) or by superoxide dismutase (SOD, 5 mg/kg) in lag period requiring manner (s.c. and i.v.). High dose of cyclo-oxygenase inhibitors indomethacin and diclofenac sodium, lipo-oxygenase inhibitor BW755C (30 mg/kg s.c., respectively) and phospholipase A2 inhibitor quinacrine (100 mg/kg s.c.) failed to inhibit serotonin edema, suggesting that arachidonate metabolites are not participating in this model. ID30 of polyamines which were administered (s.c. and oral) to rats 3 h before carrageenan and determined at 3 h by paw weight were: spermidine (28 and 100 mg/kg), spermine (18 and 90 mg/kg) and putrescine (both greater than 200 mg/kg). Adrenalectomized rats responded to polyamines just as normal rats. Local vascular permeability, irritancy and acute toxicity were also tested in mice. Polyamines were proved to be glucocorticoid-type anti-inflammatory drugs. Polyamines may be mediators of glucocorticoids for the synthesis of the postulated vascular permeability inhibitory protein (called as 'vasoregulin' for convenience). Anti-inflammatory effect of glucocorticoid is recently explained by its capacity to induce phospholipase A2 inhibitory protein

  5. Platelet Activating Factor Contributes to Vascular Leak in Acute Dengue Infection

    PubMed Central

    Jeewandara, Chandima; Gomes, Laksiri; Wickramasinghe, N.; Gutowska-Owsiak, Danuta; Waithe, Dominic; Paranavitane, S. A.; Shyamali, N. L. A.; Ogg, Graham S.; Malavige, Gathsaurie Neelika

    2015-01-01

    Background Although plasma leakage is the hallmark of severe dengue infections, the factors that cause increased vascular permeability have not been identified. As platelet activating factor (PAF) is associated with an increase in vascular permeability in other diseases, we set out to investigate its role in acute dengue infection. Materials and Methods PAF levels were initially assessed in 25 patients with acute dengue infection to determine if they were increased in acute dengue. For investigation of the kinetics of PAF, serial PAF values were assessed in 36 patients. The effect of dengue serum on tight junction protein ZO-1 was determined by using human endothelial cell lines (HUVECs). The effect of dengue serum on and trans-endothelial resistance (TEER) was also measured on HUVECs. Results PAF levels were significantly higher in patients with acute dengue (n = 25; p = 0.001) when compared to healthy individuals (n = 12). In further investigation of the kinetics of PAF in serial blood samples of patients (n = 36), PAF levels rose just before the onset of the critical phase. PAF levels were significantly higher in patients with evidence of vascular leak throughout the course of the illness when compared to those with milder disease. Serum from patients with dengue significantly down-regulated expression of tight junction protein, ZO-1 (p = 0.004), HUVECs. This was significantly inhibited (p = 0.004) by use of a PAF receptor (PAFR) blocker. Serum from dengue patients also significantly reduced TEER and this reduction was also significantly (p = 0.02) inhibited by prior incubation with the PAFR blocker. Conclusion Our results suggest the PAF is likely to be playing a significant role in inducing vascular leak in acute dengue infection which offers a potential target for therapeutic intervention. PMID:25646838

  6. Critical role of sphingosine-1-phosphate receptor 2 (S1PR2) in acute vascular inflammation.

    PubMed

    Zhang, Guoqi; Yang, Li; Kim, Gab Seok; Ryan, Kieran; Lu, Shulin; O'Donnell, Rebekah K; Spokes, Katherine; Shapiro, Nathan; Aird, William C; Kluk, Michael J; Yano, Kiichiro; Sanchez, Teresa

    2013-07-18

    The endothelium, as the interface between blood and all tissues, plays a critical role in inflammation. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid, highly abundant in plasma, that potently regulates endothelial responses through interaction with its receptors (S1PRs). Here, we studied the role of S1PR2 in the regulation of the proadhesion and proinflammatory phenotype of the endothelium. By using genetic approaches and a S1PR2-specific antagonist (JTE013), we found that S1PR2 plays a key role in the permeability and inflammatory responses of the vascular endothelium during endotoxemia. Experiments with bone marrow chimeras (S1pr2(+/+) → S1pr2(+/+), S1pr2(+/+) → S1pr2(-/-), and S1pr2(-/-) → S1pr2(+/+)) indicate the critical role of S1PR2 in the stromal compartment, in the regulation of vascular permeability and vascular inflammation. In vitro, JTE013 potently inhibited tumor necrosis factor α-induced endothelial inflammation. Finally, we provide detailed mechanisms on the downstream signaling of S1PR2 in vascular inflammation that include the activation of the stress-activated protein kinase pathway that, together with the Rho-kinase nuclear factor kappa B pathway (NF-kB), are required for S1PR2-mediated endothelial inflammatory responses. Taken together, our data indicate that S1PR2 is a key regulator of the proinflammatory phenotype of the endothelium and identify S1PR2 as a novel therapeutic target for vascular disorders.

  7. Factors Associated with Placental Vascularization Measured by 3D Power Doppler Ultrasonographic Sphere Biopsy between 11 and 14 Weeks of Gestation.

    PubMed

    Demers, Suzanne; Boutin, Amelie; Dembickaja, Regina; Campanero, Mercedes; Nicolaides, Kypros

    2018-02-19

     Preeclampsia is associated with placental vascularization disorders. Ultrasonographic sphere biopsy (USSB) of the placenta can estimate the vascularization of the placenta and potentially the risk of preeclampsia. We aimed to explore the factors related to placental vascularization measured with USSB in the first trimester.  A prospective cohort was conducted in women recruited at 11 to 14 weeks. Three-dimensional acquisition of the placenta with power Doppler was undertaken along with crown-rump length (CRL). Using USSB of the full placental thickness at its center, vascularization index, flow index, and vascular flow index were measured. Pearson's correlation coefficients and multivariate linear regression were used to correlate the vascularization indices with CRL and maternal characteristics.  A total of 5,612 women were recruited at a mean gestational age of 12.8 ± 0.6 weeks. We observed that vascularization indices increase with CRL. After adjustment, we observed that maternal age, ethnicity other than Caucasian, and body mass index were associated with lower vascularization indices, while diabetes, smoking, and assisted reproduction technology were not. We observed that parous women without history of preeclampsia had greater vascularization indices compared with nulliparous women.  Placental vascularization indices assessed by USSB fluctuate with gestational age, ethnicity, maternal age, body mass index, and previous pregnancy history. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  8. Neutrophil proteinase 3 (PR3) acts on protease-activated receptor-2 (PAR-2) to enhance vascular endothelial cell barrier function

    PubMed Central

    Kuckleburg, Christopher J.; Newman, Peter J.

    2013-01-01

    The principle role of the vascular endothelium is to present a semi-impermeable barrier to soluble factors and circulating cells, while still permitting the passage of leukocytes from the bloodstream into the tissue. The process of diapedesis involves the selective disruption of endothelial cell junctions, an event that could in theory compromise vascular integrity. It is therefore somewhat surprising that neutrophil transmigration does not significantly impair endothelial barrier function. We examined whether neutrophils might secrete factors that promote vascular integrity during the latter stages of neutrophil transmigration, and found that neutrophil proteinase 3 (PR3) – a serine protease harbored in azurophilic granules – markedly enhanced barrier function in endothelial cells. PR3 functioned in this capacity both in its soluble form and in a complex with cell-surface NB1. PR3-mediated enhancement of endothelial cell junctional integrity required its proteolytic activity, as well as endothelial cell expression of the protease-activated receptor, PAR-2. Importantly, PR3 suppressed the vascular permeability changes and disruption of junctional proteins induced by the action of PAR-1 agonists. These findings establish the potential for neutrophil-derived PR3 to play a role in reestablishing vascular integrity following leukocyte transmigration, and in protecting endothelial cells from PAR-1-induced permeability changes that occur during thrombotic and inflammatory events. PMID:23202369

  9. Analysis of Basis Weight Uniformity of Microfiber Nonwovens and Its Impact on Permeability and Filtration Properties

    NASA Astrophysics Data System (ADS)

    Amirnasr, Elham

    It is widely recognized that nonwoven basis weight non-uniformity affects various properties of nonwovens. However, few studies can be found in this topic. The development of uniformity definition and measurement methods and the study of their impact on various web properties such as filtration properties and air permeability would be beneficial both in industrial applications and in academia. They can be utilized as a quality control tool and would provide insights about nonwoven behaviors that cannot be solely explained by average values. Therefore, for quantifying nonwoven web basis weight uniformity we purse to develop an optical analytical tool. The quadrant method and clustering analysis was utilized in an image analysis scheme to help define "uniformity" and its spatial variation. Implementing the quadrant method in an image analysis system allows the establishment of a uniformity index that can be used to quantify the degree of uniformity. Clustering analysis has also been modified and verified using uniform and random simulated images with known parameters. Number of clusters and cluster properties such as cluster size, member and density was determined. We also utilized this new measurement method to evaluate uniformity of nonwovens produced with different processes and investigated impacts of uniformity on filtration and permeability. The results of quadrant method shows that uniformity index computed from quadrant method demonstrate a good range for non-uniformity of nonwoven webs. Clustering analysis is also been applied on reference nonwoven with known visual uniformity. From clustering analysis results, cluster size is promising to be used as uniformity parameter. It is been shown that non-uniform nonwovens has provide lager cluster size than uniform nonwovens. It was been tried to find a relationship between web properties and uniformity index (as a web characteristic). To achieve this, filtration properties, air permeability, solidity and

  10. Fluorescein isothiocyanate (FITC)-Dextran Extravasation as a Measure of Blood-Brain Barrier Permeability

    PubMed Central

    Natarajan, Reka; Northrop, Nicole

    2017-01-01

    The blood-brain barrier (BBB) is formed in part by vascular endothelial cells that constitute the capillaries and microvessels of the brain. The function of this barrier is to maintain homeostasis within the brain microenvironment and buffer the brain from changes in the periphery. A dysfunction of the BBB would permit circulating molecules and pathogens typically restricted to the periphery to enter the brain and interfere with normal brain function. As increased permeability of the BBB is associated with several neuropathologies, it is important to have a reliable and sensitive method that determines BBB permeability and the degree of BBB disruption. A detailed protocol is presented for assessing the integrity of the BBB by transcardial perfusion of a 10,000 Da FITC labeled dextran molecule and its visualization to determine the degree of extravasation from brain microvessels. PMID:28398646

  11. Is trabecular bone permeability governed by molecular ordering-induced fluid viscosity gain? Arguments from re-evaluation of experimental data in the framework of homogenization theory.

    PubMed

    Abdalrahman, T; Scheiner, S; Hellmich, C

    2015-01-21

    It is generally agreed on that trabecular bone permeability, a physiologically important quantity, is governed by the material׳s (vascular or intertrabecular) porosity as well as by the viscosity of the pore-filling fluids. Still, there is less agreement on how these two key factors govern bone permeability. In order to shed more light onto this somewhat open issue, we here develop a random homogenization scheme for upscaling Poiseuille flow in the vascular porosity, up to Darcy-type permeability of the overall porous medium "trabecular bone". The underlying representative volume element of the macroscopic bone material contains two types of phases: a spherical, impermeable extracellular bone matrix phase interacts with interpenetrating cylindrical pore channel phases that are oriented in all different space directions. This type of interaction is modeled by means of a self-consistent homogenization scheme. While the permeability of the bone matrix equals to zero, the permeability of the pore phase is found through expressing the classical Hagen-Poiseuille law for laminar flow in the format of a "micro-Darcy law". The upscaling scheme contains pore size and porosity as geometrical input variables; however, they can be related to each other, based on well-known relations between porosity and specific bone surface. As two key results, validated through comprehensive experimental data, it appears (i) that the famous Kozeny-Carman constant (which relates bone permeability to the cube of the porosity, the square of the specific surface, as well as to the bone fluid viscosity) needs to be replaced by an again porosity-dependent rational function, and (ii) that the overall bone permeability is strongly affected by the pore fluid viscosity, which, in case of polarized fluids, is strongly increased due to the presence of electrically charged pore walls. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. The Andes Virus Nucleocapsid Protein Directs Basal Endothelial Cell Permeability by Activating RhoA

    PubMed Central

    Gorbunova, Elena E.; Simons, Matthew J.; Gavrilovskaya, Irina N.

    2016-01-01

    ABSTRACT Andes virus (ANDV) predominantly infects microvascular endothelial cells (MECs) and nonlytically causes an acute pulmonary edema termed hantavirus pulmonary syndrome (HPS). In HPS patients, virtually every pulmonary MEC is infected, MECs are enlarged, and infection results in vascular leakage and highly lethal pulmonary edema. We observed that MECs infected with the ANDV hantavirus or expressing the ANDV nucleocapsid (N) protein showed increased size and permeability by activating the Rheb and RhoA GTPases. Expression of ANDV N in MECs increased cell size by preventing tuberous sclerosis complex (TSC) repression of Rheb-mTOR-pS6K. N selectively bound the TSC2 N terminus (1 to 1403) within a complex containing TSC2/TSC1/TBC1D7, and endogenous TSC2 reciprocally coprecipitated N protein from ANDV-infected MECs. TSCs normally restrict RhoA-induced MEC permeability, and we found that ANDV infection or N protein expression constitutively activated RhoA. This suggests that the ANDV N protein alone is sufficient to activate signaling pathways that control MEC size and permeability. Further, RhoA small interfering RNA, dominant-negative RhoA(N19), and the RhoA/Rho kinase inhibitors fasudil and Y27632 dramatically reduced the permeability of ANDV-infected MECs by 80 to 90%. Fasudil also reduced the bradykinin-directed permeability of ANDV and Hantaan virus-infected MECs to control levels. These findings demonstrate that ANDV activation of RhoA causes MEC permeability and reveal a potential edemagenic mechanism for ANDV to constitutively inhibit the basal barrier integrity of infected MECs. The central importance of RhoA activation in MEC permeability further suggests therapeutically targeting RhoA, TSCs, and Rac1 as potential means of resolving capillary leakage during hantavirus infections. PMID:27795403

  13. Macrophage Blockade Using CSF1R Inhibitors Reverses the Vascular Leakage Underlying Malignant Ascites in Late-Stage Epithelial Ovarian Cancer

    PubMed Central

    Moughon, Diana L.; He, Huanhuan; Schokrpur, Shiruyeh; Jiang, Ziyue Karen; Yaqoob, Madeeha; David, John; Lin, Crystal; Iruela-Arispe, M. Luisa; Dorigo, Oliver; Wu, Lily

    2015-01-01

    Malignant ascites is a common complication in the late stages of epithelial ovarian cancer (EOC) that greatly diminishes the quality of life of patients. Malignant ascites is a known consequence of vascular dysfunction, but current approved treatments are not effective in preventing fluid accumulation. In this study, we investigated an alternative strategy of targeting macrophage functions to reverse the vascular pathology of malignant ascites using fluid from human patients and an immunocompetent murine model (ID8) of EOC that mirrors human disease by developing progressive vascular disorganization and leakiness culminating in massive ascites. We demonstrate that the macrophage content in ascites fluid from human patients and the ID8 model directly correlates with vascular permeability. To further substantiate macrophages’ role in the pathogenesis of malignant ascites, we blocked macrophage function in ID8 mice using a colony-stimulating factor 1 receptor kinase inhibitor (GW2580). Administration of GW2580 in the late stages of disease resulted in reduced infiltration of protumorigenic (M2) macrophages and dramatically decreased ascites volume. Moreover, the disorganized peritoneal vasculature became normalized and sera from GW2580-treated ascites protected against endothelial permeability. Therefore, our findings suggest that macrophage-targeted treatment may be a promising strategy toward a safe and effective means to control malignant ascites of EOC. PMID:26471360

  14. Therapeutic effect of apatinib-loaded nanoparticles on diabetes-induced retinal vascular leakage.

    PubMed

    Jeong, Ji Hoon; Nguyen, Hong Khanh; Lee, Jung Eun; Suh, Wonhee

    2016-01-01

    Apatinib, a novel and selective inhibitor of vascular endothelial growth factor (VEGF) receptor 2, has been demonstrated recently to exhibit anticancer efficacy by inhibiting the VEGF signaling pathway. Given the importance of VEGF in retinal vascular leakage, the present study was designed to investigate whether apatinib-loaded polymeric nanoparticles inhibit VEGF-mediated retinal vascular hyperpermeability and block diabetes-induced retinal vascular leakage. For the delivery of water-insoluble apatinib, the drug was encapsulated in nanoparticles composed of human serum albumin (HSA)-conjugated polyethylene glycol (PEG). In vitro paracellular permeability and transendothelial electric resistance assays showed that apatinib-loaded HSA-PEG (Apa-HSA-PEG) nanoparticles significantly inhibited VEGF-induced endothelial hyperpermeability in human retinal microvascular endothelial cells. In addition, they substantially reduced the VEGF-induced junctional loss and internalization of vascular endothelial-cadherin, a major component of endothelial junction complexes. In vivo intravitreal injection of Apa-HSA-PEG nanoparticles in mice blocked VEGF-induced retinal vascular leakage. These in vitro and in vivo data indicated that Apa-HSA-PEG nanoparticles efficiently blocked VEGF-induced breakdown of the blood-retinal barrier. In vivo experiments with streptozotocin-induced diabetic mice showed that an intravitreal injection of Apa-HSA-PEG nanoparticles substantially inhibited diabetes-induced retinal vascular leakage. These results demonstrated, for the first time, that apatinib-loaded nanoparticles may be a promising therapeutic agent for the prevention and treatment of diabetes-induced retinal vascular disorders.

  15. Therapeutic effect of apatinib-loaded nanoparticles on diabetes-induced retinal vascular leakage

    PubMed Central

    Jeong, Ji Hoon; Nguyen, Hong Khanh; Lee, Jung Eun; Suh, Wonhee

    2016-01-01

    Apatinib, a novel and selective inhibitor of vascular endothelial growth factor (VEGF) receptor 2, has been demonstrated recently to exhibit anticancer efficacy by inhibiting the VEGF signaling pathway. Given the importance of VEGF in retinal vascular leakage, the present study was designed to investigate whether apatinib-loaded polymeric nanoparticles inhibit VEGF-mediated retinal vascular hyperpermeability and block diabetes-induced retinal vascular leakage. For the delivery of water-insoluble apatinib, the drug was encapsulated in nanoparticles composed of human serum albumin (HSA)-conjugated polyethylene glycol (PEG). In vitro paracellular permeability and transendothelial electric resistance assays showed that apatinib-loaded HSA-PEG (Apa-HSA-PEG) nanoparticles significantly inhibited VEGF-induced endothelial hyperpermeability in human retinal microvascular endothelial cells. In addition, they substantially reduced the VEGF-induced junctional loss and internalization of vascular endothelial-cadherin, a major component of endothelial junction complexes. In vivo intravitreal injection of Apa-HSA-PEG nanoparticles in mice blocked VEGF-induced retinal vascular leakage. These in vitro and in vivo data indicated that Apa-HSA-PEG nanoparticles efficiently blocked VEGF-induced breakdown of the blood–retinal barrier. In vivo experiments with streptozotocin-induced diabetic mice showed that an intravitreal injection of Apa-HSA-PEG nanoparticles substantially inhibited diabetes-induced retinal vascular leakage. These results demonstrated, for the first time, that apatinib-loaded nanoparticles may be a promising therapeutic agent for the prevention and treatment of diabetes-induced retinal vascular disorders. PMID:27462154

  16. ALDOSTERONE DYSREGULATION WITH AGING PREDICTS RENAL-VASCULAR FUNCTION AND CARDIO-VASCULAR RISK

    PubMed Central

    Brown, Jenifer M.; Underwood, Patricia C.; Ferri, Claudio; Hopkins, Paul N.; Williams, Gordon H.; Adler, Gail K.; Vaidya, Anand

    2014-01-01

    Aging and abnormal aldosterone regulation are both associated with vascular disease. We hypothesized that aldosterone dysregulation influences the age-related risk of renal- and cardio-vascular disease. We conducted an analysis of 562 subjects who underwent detailed investigations under conditions of liberal and restricted dietary sodium intake (1,124 visits) in a Clinical Research Center. Aldosterone regulation was characterized by the ratio of maximal suppression-to-stimulation (supine serum aldosterone on a liberal sodium diet divided by the same measure on a restricted sodium diet). We previously demonstrated that higher levels of this Sodium-modulated Aldosterone Suppression-Stimulation Index (SASSI) indicate greater aldosterone dysregulation. Renal plasma flow (RPF) was determined via p-aminohippurate clearance to assess basal renal hemodynamics, and the renal-vascular responses to dietary sodium manipulation and angiotensin II (AngII) infusion. Cardiovascular risk was calculated using the Framingham Risk Score. In univariate linear regression, older age (β= -4.60, p<0.0001) and higher SASSI (β= -58.63, p=0.001) predicted lower RPF and a blunted RPF response to sodium loading and AngII infusion. We observed a continuous, independent, multivariate-adjusted interaction between age and SASSI, where the inverse relationship between SASSI and RPF was most apparent with older age (p<0.05). Higher SASSI and lower RPF independently predicted higher Framingham Risk Score (p<0.0001) and together displayed an additive effect. Aldosterone regulation and age may interact to mediate renal-vascular disease. Our findings suggest that the combination of aldosterone dysregulation and renal-vascular dysfunction could additively increase the risk of future cardiovascular outcomes; therefore, aldosterone dysregulation may represent a modifiable mechanism of age-related vascular disease. PMID:24664291

  17. Association of Metabolic Syndrome with the Cardioankle Vascular Index in Asymptomatic Korean Population

    PubMed Central

    Nam, Su-Hyun; Lee, Yun-Ah; Rho, Jun-Seung

    2015-01-01

    Aim. Metabolic syndrome is characterized by a cluster of atherosclerotic cardiovascular risk factors. The cardioankle vascular index (CAVI) reflects arterial stiffness and may be used as an indicator of atherosclerotic cardiovascular disease. In this study, we investigated the association of CAVI with metabolic syndrome. Methods. A total of 1,144 adults were included in this study. We measured CAVIs and examined blood samples to identify metabolic syndrome according to WHO Asia Pacific criteria and NCEP-ATPIII criteria. AST, ALT, r-GTP, BUN, creatinine, high sensitivity C-reactive protein, and uric acid were also measured. Results. CAVI values were significantly higher in subjects with metabolic syndrome than those without metabolic syndrome and increased according to the number of metabolic syndrome components present. Subjects with high fasting blood sugar levels or high blood pressure showed high CAVI values. Multiple regression analysis showed that age, sex, diastolic blood pressure, and uric acid were independent predictors of CAVI. Conclusion. Subjects with metabolic syndrome had high CAVIs, which indicated arterial stiffness, and were closely associated with an increase in the number of metabolic risk factors. The individual risk factors for metabolic syndrome have the synergistic effect of elevating arterial stiffness in asymptomatic Korean population. PMID:26273666

  18. Dissolution-Driven Permeability Reduction of a Fractured Carbonate Caprock

    PubMed Central

    Ellis, Brian R.; Fitts, Jeffrey P.; Bromhal, Grant S.; McIntyre, Dustin L.; Tappero, Ryan; Peters, Catherine A.

    2013-01-01

    Abstract Geochemical reactions may alter the permeability of leakage pathways in caprocks, which serve a critical role in confining CO2 in geologic carbon sequestration. A caprock specimen from a carbonate formation in the Michigan sedimentary Basin was fractured and studied in a high-pressure core flow experiment. Inflowing brine was saturated with CO2 at 40°C and 10 MPa, resulting in an initial pH of 4.6, and had a calcite saturation index of −0.8. Fracture permeability decreased during the experiment, but subsequent analyses did not reveal calcite precipitation. Instead, experimental observations indicate that calcite dissolution along the fracture pathway led to mobilization of less soluble mineral particles that clogged the flow path. Analyses of core sections via electron microscopy, synchrotron-based X-ray diffraction imaging, and the first application of microbeam Ca K-edge X-ray absorption near edge structure, provided evidence that these occlusions were fragments from the host rock rather than secondary precipitates. X-ray computed tomography showed a significant loss of rock mass within preferential flow paths, suggesting that dissolution also removed critical asperities and caused mechanical closure of the fracture. The decrease in fracture permeability despite a net removal of material along the fracture pathway demonstrates a nonintuitive, inverse relationship between dissolution and permeability evolution in a fractured carbonate caprock. PMID:23633894

  19. Crustal permeability

    USGS Publications Warehouse

    Ingebritsen, Steven E.; Gleeson, Tom

    2017-01-01

    Permeability is the dominant parameter in most hydrogeologic studies. There is abundant evidence for dynamic variations in permeability in time as well as space, and throughout the crust. Whether this dynamic behavior should be included in quantitative models depends on the problem at hand.

  20. A critical role for phosphatidylinositol (3,4,5)-trisphosphate-dependent Rac exchanger 1 in endothelial junction disruption and vascular hyperpermeability

    PubMed Central

    Naikawadi, Ram P.; Cheng, Ni; Vogel, Stephen M.; Qian, Feng; Wu, Dianqing; Malik, Asrar B.; Ye, Richard D.

    2013-01-01

    Rationale The small GTPase Rac is critical to vascular endothelial functions, yet its regulation in endothelial cells remains unclear. Understanding the upstream pathway may delineate Rac activation mechanisms and its role in maintaining vascular endothelial barrier integrity. Objective By investigating P-Rex1, one of the Rac-specific guanine nucleotide exchange factors (GEFs) previously known for G protein-coupled receptor (GPCR) signaling, we sought to determine whether Rac-GEF is a nodal for signal integration and potential target for drug intervention. Methods and Results Using gene deletion and siRNA silencing approach, we investigated the role of P-Rex1 in lung microvascular endothelial cells (HLMVECs). TNF-α exposure led to disruption of endothelial junctions, and silencing P-Rex1 protected junction integrity. TNF-α stimulated Rac activation and ROS production in a P-Rex1-dependent manner. Removal of P-Rex1 significantly reduced ICAM-1 expression, PMN transendothelial migration and leukocyte sequestration in TNF-α challenged mouse lungs. The P-Rex1 knockout mice were also refractory to lung vascular hyper-permeability and edema in a LPS-induced sepsis model. Conclusions These results demonstrate for the first time that P-Rex1 expressed in endothelial cells is activated downstream of TNF-α, which is not a GPCR agonist. Our data identify P-Rex1 as a critical mediator of vascular barrier disruption. Targeting P-Rex1 may effectively protect against TNF-α and LPS-induced endothelial junction disruption and vascular hyper-permeability. PMID:22965143

  1. Synergism between endotoxin priming and exotoxin challenge in provoking severe vascular leakage in rabbit lungs.

    PubMed

    Schütte, H; Rosseau, S; Czymek, R; Ermert, L; Walmrath, D; Krämer, H J; Seeger, W; Grimminger, F

    1997-09-01

    Lipopolysaccharides (LPS) of gram-negative bacteria prime rabbit lungs for enhanced thromboxane-mediated vasoconstriction upon subsequent challenge with the exotoxin Escherichia coli hemolysin (HlyA) (Walmrath et al. J. Exp. Med. 1994;180:1437-1443). We investigated the impact of endotoxin priming and subsequent HlyA challenge on lung vascular permeability while maintaining constancy of capillary pressure. Rabbit lungs were perfused in a pressure-controlled mode in the presence of the thromboxane receptor antagonist BM 13.505, with continuous monitoring of flow. Perfusion for 180 min with 10 ng/ml LPS did not provoke vasoconstriction or alteration of capillary filtration coefficient (Kfc) values. HlyA (0.021 hemolytic units/ml) induced thromboxane release and a transient decrease in perfusion flow in the absence of significant changes in Kfc. Similar results were obtained when LPS and HlyA were coapplied simultaneously. However, when the HlyA challenge was undertaken after 180 min of LPS priming, a manifold increase in Kfc values was noted, with concomitant severe lung edema formation, although capillary pressure remained unchanged. Thus, endotoxin primes the lung vasculature to respond with a severe increase in vascular permeability to a subsequent low-dose application of HlyA. Such synergism between endotoxin priming and exotoxin challenge in provoking lung vascular leakage may contribute to the pathogenesis of respiratory failure in sepsis and severe lung infection.

  2. Permeability of stylolite-bearing chalk

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lind, I.; Nykjaer, O.; Priisholm, S.

    1994-11-01

    Permeabilities were measured on core plugs from stylolite-bearing chalk of the Gorm field in the Danish North Sea. Air and liquid permeabilities were measured in directions parallel to and perpendicular to the stylolite surface. Permeability was measured with sleeve pressure equal to in-situ reservoir stress. Permeabilities of plugs with stylolites but without stylolite-associated fractures were equal in the two directions. The permeability is equal to the matrix permeability of non-stylolite-bearing chalk. In contrast, when fractures were associated with the stylolites, permeability was enhanced. The enhancement was most significant in the horizontal direction parallel to the stylolites.

  3. Mechanical and biocompatible characterizations of a readily available multilayer vascular graft

    PubMed Central

    Madhavan, Krishna; Elliott, Winston H; Bonani, Walter; Monnet, Eric; Tan, Wei

    2013-01-01

    There is always a considerable clinical need for vascular grafts. Considering the availability, physical and mechanical properties, and regenerative potential, we have developed and characterized readily available, strong, and compliant multilayer grafts that support cell culture and ingrowth. The grafts were made from heterogeneous materials and structures, including a thin, dense, nanofibrous core composed of poly-ε-caprolactone (PCL), and a thick, porous, hydrogel sleeve composed of genipin-crosslinked collagen–chitosan (GCC). Because the difference in physicochemical properties between PCL and GCC caused layer separation, the layer adhesion was identified as a determinant to graft property and integrity under physiological conditions. Thus, strategies to modify the layer interface, including increasing porosity of the PCL surface, decreasing hydrophobicity, and increasing interlayer crosslinking, were developed. Results from microscopic images showed that increasing PCL porosity was characterized by improved layer adhesion. The resultant graft was characterized by high compliance (4.5%), and desired permeability (528 mL/cm2/min), burst strength (695 mmHg), and suture strength (2.38 N) for readily grafting. Results also showed that PCL mainly contributed to the graft mechanical properties, whereas GCC reduced the water permeability. In addition to their complementary contributions to physical and mechanical properties, the distinct graft layers also provided layer-specific structures for seeding and culture of vascular endothelial and smooth muscle cells in vitro. Acellular graft constructs were readily used to replace abdominal aorta of rabbits, resulting in rapid cell ingrowth and flow reperfusion. The multilayer constructs capable of sustaining physiological conditions and promoting cellular activities could serve as a platform for future development of regenerative vascular grafts. PMID:23165922

  4. Curcumin modulates endothelial permeability and monocyte transendothelial migration by affecting endothelial cell dynamics.

    PubMed

    Monfoulet, Laurent-Emmanuel; Mercier, Sylvie; Bayle, Dominique; Tamaian, Radu; Barber-Chamoux, Nicolas; Morand, Christine; Milenkovic, Dragan

    2017-11-01

    Curcumin is a phenolic compound that exhibits beneficial properties for cardiometabolic health. We previously showed that curcumin reduced the infiltration of immune cells into the vascular wall and prevented atherosclerosis development in mice. This study aimed to investigate the effect of curcumin on monocyte adhesion and transendothelial migration (TEM) and to decipher the underlying mechanisms of these actions. Human umbilical vein endothelial cells (HUVECs) were exposed to curcumin (0.5-1μM) for 3h prior to their activation by Tumor Necrosis Factor alpha (TNF-α). Endothelial permeability, monocyte adhesion and transendothelial migration assays were conducted under static condition and shear stress that mimics blood flow. We further investigated the impact of curcumin on signaling pathways and on the expression of genes using macroarrays. Pre-exposure of endothelial cells to curcumin reduced monocyte adhesion and their transendothelial migration in both static and shear stress conditions. Curcumin also prevented changes in both endothelial permeability and the area of HUVECs when induced by TNF-α. We showed that curcumin modulated the expression of 15 genes involved in the control of cytoskeleton and endothelial junction dynamic. Finally, we showed that curcumin inhibited NF-κB signaling likely through an antagonist interplay with several kinases as suggested by molecular docking analysis. Our findings demonstrate the ability of curcumin to reduce monocyte TEM through a multimodal regulation of the endothelial cell dynamics with a potential benefit on the vascular endothelial function barrier. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Total ginsenosides synergize with ulinastatin against septic acute lung injury and acute respir atory distress syndrome

    PubMed Central

    Sun, Rongju; Li, Yana; Chen, Wei; Zhang, Fei; Li, Tanshi

    2015-01-01

    Total ginsenosides synergize with ulinastatin (UTI) against septic acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). We randomly divided 80 cases of severe sepsis-induced ALI and ARDS into a UTI group and a ginsenosides (GS)+UTI group. Continuous electrocardiac monitoring of pulse, respiratory rate, blood pressure, and heart rate; invasive hemodynamic monitoring; ventilator-assisted breathing and circulation support; and anti-infection as well as UTI treatment were given in the UTI group with GS treatment added for 7 consecutive days in the GS+UTI group. The indicators of pulmonary vascular permeability, pulmonary circulation, blood gases, and hemodynamics as well as APACHE II and ALI scores were detected on days 1, 3, and 7. The ALI score in the GS+UTI group was significantly decreased (P < 0.05) compared with that of the UTI group, and the indicators of pulmonary capillary permeability such as pulmonary vascular permeability index, extravascular lung water index, and oxygenation index, in the GS+UTI group improved significantly more than that of the UTI group. The indicators of hemodynamics and pulmonary circulation such as cardiac index, intrathoracic blood volume index, and central venous pressure improved significantly (P < 0.05), and the APACHE II score in the GS+UTI group was lower than that of the UTI group. GS can effectively collaborate with UTI against ALI and/or ARDS. PMID:26261640

  6. Time-dependent effect of clonidine on microvascular permeability during endotoxemia.

    PubMed

    Schmidt, Karsten; Hernekamp, Jochen Frederick; Philipsenburg, Christoph; Zivkovic, Aleksandar R; Brenner, Thorsten; Hofer, Stefan

    2015-09-01

    Endothelial leakage with accompanying tissue edema and increased leukocyte adhesion are characteristics of the vascular inflammatory response. Tissue edema formation is a key mechanism in sepsis pathophysiology contributing to impaired tissue oxygenation and the development of shock. Sepsis mortality is directly associated with the severity of these microcirculatory alterations. Dysfunction of the sympathetic nervous system can have deleterious effects in generalized inflammation. This study evaluated the effect of the adrenergic alpha 2 agonist clonidine on microvascular permeability and leukocyte adhesion during endotoxemia. Macromolecular leakage, leukocyte adhesion, and venular wall shear rate were examined in mesenteric postcapillary venules of rats by using intravital microscopy (IVM). Lipopolysaccharide (LPS) (4mg/kg/h) or equivalent volumes of saline were continuously infused following baseline IVM at 0min. IVM was repeated after 60 and 120min in endotoxemic and nonendotoxemic animals. Clonidine (10μg/kg) was applied as an i.v. bolus. Animals received either (i) saline alone, (ii) clonidine alone, (iii) clonidine 45min prior to LPS, (iv) clonidine 10min prior to LPS, (v) clonidine 30min after LPS, or (vi) LPS alone. Due to nonparametric data distribution, Wilcoxon test and Dunn's multiple comparisons test were used for data analysis. Data were considered statistically significant at p<0.05. LPS significantly increased microvascular permeability and leukocyte adhesion and decreased venular wall shear rate. Clonidine significantly reduced microvascular permeability when applied 45min before or 30min after LPS administration. Leukocyte adhesion and venular wall shear rate were not affected by clonidine during endotoxemia. Clonidine reduces microvascular permeability in endotoxemic animals in a time-dependent manner. Adrenergic alpha 2 agonists might prove beneficial in stabilizing capillary leakage during inflammation. Copyright © 2015 Elsevier Inc. All

  7. Quantifying Glomerular Permeability of Fluorescent Macromolecules Using 2-Photon Microscopy in Munich Wistar Rats

    PubMed Central

    Sandoval, Ruben M.; Molitoris, Bruce A.

    2013-01-01

    Kidney diseases involving urinary loss of large essential macromolecules, such as serum albumin, have long been thought to be caused by alterations in the permeability barrier comprised of podocytes, vascular endothelial cells, and a basement membrane working in unison. Data from our laboratory using intravital 2-photon microscopy revealed a more permeable glomerular filtration barrier (GFB) than previously thought under physiologic conditions, with retrieval of filtered albumin occurring in an early subset of cells called proximal tubule cells (PTC)1,2,3. Previous techniques used to study renal filtration and establishing the characteristic of the filtration barrier involved micropuncture of the lumen of these early tubular segments with sampling of the fluid content and analysis4. These studies determined albumin concentration in the luminal fluid to be virtually non-existent; corresponding closely to what is normally detected in the urine. However, characterization of dextran polymers with defined sizes by this technique revealed those of a size similar to serum albumin had higher levels in the tubular lumen and urine; suggesting increased permeability5. Herein is a detailed outline of the technique used to directly visualize and quantify glomerular fluorescent albumin permeability in vivo. This method allows for detection of filtered albumin across the filtration barrier into Bowman's space (the initial chamber of urinary filtration); and also allows quantification of albumin reabsorption by proximal tubules and visualization of subsequent albumin transcytosis6. The absence of fluorescent albumin along later tubular segments en route to the bladder highlights the efficiency of the retrieval pathway in the earlier proximal tubule segments. Moreover, when this technique was applied to determine permeability of dextrans having a similar size to albumin virtually identical permeability values were reported2. These observations directly support the need to expand

  8. Gender-specific association of serum uric acid levels and cardio-ankle vascular index in Chinese adults.

    PubMed

    Zheng, Xiaoya; Wei, Qiang; Long, Jian; Gong, Lilin; Chen, Hua; Luo, Rong; Ren, Wei; Wang, Yonghong

    2018-04-11

    Little is known about the relationship between serum uric acid (SUA) and cardio-ankle vascular index (CAVI) in Chinese population. Therefore, we aimed to investigate the gender difference in the association of SUA and CAVI in a southwestern Chinese population. Data were obtained from subjects via routine physical examinations in the Public Health Center of our hospital between 2011 and 2014 in Chongqing. The data included completed anthropometry and blood biochemical indicators. The CAVI were recorded using an automatically VaseraVS-1000 vascular screening system. We found females with hyperuricemia (HUA) had significantly higher CAVI than women with normal SUA (8.45 ± 1.40 vs 7.67 ± 1.15, P<0.05). Then we defined high CAVI as CAVI≥9 m/s, and compared the percentage of high CAVI, we found women with HUA had higher percentage of high CAVI than women with normal SUA (26.83% vs 9.38%, P<0.05). Those differences were not significant in males. Also, the logistic regression analysis found age and hypertension were major independent risk factors associated with high CAVI in both genders. HUA and hyperglycemia were independently associated with high CAVI in females with an OR of 3.65, 95%CI (1.37-9.73) and 3.02, 95%CI (1.38-6.63) respectively. However, these significant associations were not be found in males. Our data showed positive associations between elevated SUA levels and higher CAVI risk in the inland Chinese females, but not in males. The reason for the gender differences were still unclear, sex hormones may play a role. Further prospective studies including detailed personal information and multicenter were required.

  9. Extra permeability is required to model dynamic oxygen measurements: evidence for functional recruitment?

    PubMed Central

    Barrett, Matthew JP; Suresh, Vinod

    2013-01-01

    Neural activation triggers a rapid, focal increase in blood flow and thus oxygen delivery. Local oxygen consumption also increases, although not to the same extent as oxygen delivery. This ‘uncoupling' enables a number of widely-used functional neuroimaging techniques; however, the physiologic mechanisms that govern oxygen transport under these conditions remain unclear. Here, we explore this dynamic process using a new mathematical model. Motivated by experimental observations and previous modeling, we hypothesized that functional recruitment of capillaries has an important role during neural activation. Using conventional mechanisms alone, the model predictions were inconsistent with in vivo measurements of oxygen partial pressure. However, dynamically increasing net capillary permeability, a simple description of functional recruitment, led to predictions consistent with the data. Increasing permeability in all vessel types had the same effect, but two alternative mechanisms were unable to produce predictions consistent with the data. These results are further evidence that conventional models of oxygen transport are not sufficient to predict dynamic experimental data. The data and modeling suggest that it is necessary to include a mechanism that dynamically increases net vascular permeability. While the model cannot distinguish between the different possibilities, we speculate that functional recruitment could have this effect in vivo. PMID:23673433

  10. Assessment of tumor vascularization with functional computed tomography perfusion imaging in patients with cirrhotic liver disease.

    PubMed

    Li, Jin-Ping; Zhao, De-Li; Jiang, Hui-Jie; Huang, Ya-Hua; Li, Da-Qing; Wan, Yong; Liu, Xin-Ding; Wang, Jin-E

    2011-02-01

    Hepatocellular carcinoma (HCC) is a common malignant tumor in China, and early diagnosis is critical for patient outcome. In patients with HCC, it is mostly based on liver cirrhosis, developing from benign regenerative nodules and dysplastic nodules to HCC lesions, and a better understanding of its vascular supply and the hemodynamic changes may lead to early tumor detection. Angiogenesis is essential for the growth of primary and metastatic tumors due to changes in vascular perfusion, blood volume and permeability. These hemodynamic and physiological properties can be measured serially using functional computed tomography perfusion (CTP) imaging and can be used to assess the growth of HCC. This study aimed to clarify the physiological characteristics of tumor angiogenesis in cirrhotic liver disease by this fast imaging method. CTP was performed in 30 volunteers without liver disease (control subjects) and 49 patients with liver disease (experimental subjects: 27 with HCC and 22 with cirrhosis). All subjects were also evaluated by physical examination, laboratory screening and Doppler ultrasonography of the liver. The diagnosis of HCC was made according to the EASL criteria. All patients underwent contrast-enhanced ultrasonography, pre- and post-contrast triple-phase CT and CTP study. A mathematical deconvolution model was applied to provide hepatic blood flow (HBF), hepatic blood volume (HBV), mean transit time (MTT), permeability of capillary vessel surface (PS), hepatic arterial index (HAI), hepatic arterial perfusion (HAP) and hepatic portal perfusion (HPP) data. The Mann-Whitney U test was used to determine differences in perfusion parameters between the background cirrhotic liver parenchyma and HCC and between the cirrhotic liver parenchyma with HCC and that without HCC. In normal liver, the HAP/HVP ratio was about 1/4. HCC had significantly higher HAP and HAI and lower HPP than background liver parenchyma adjacent to the HCC. The value of HBF at the tumor

  11. Mast Cell Activation Protects Cornea by Promoting Neutrophil Infiltration via Stimulating ICAM-1 and Vascular Dilation in Fungal Keratitis.

    PubMed

    Xie, Yanting; Zhang, Hongmin; Liu, Susu; Chen, Guoming; He, Siyu; Li, Zhijie; Wang, Liya

    2018-05-30

    The role of mast cells (MCs) in fungal infection is largely unknown. This study was to explore a protective role and mechanism of MCs in fungal keratitis. Experimental fungal keratitis (FK) mouse model was developed. Mice untreated (UT) or receiving corneal wound without fungal infection (Mock) were used as controls. Large number of connective tissue MCs was found in normal mice. MC activation with degranulation was largely observed, and the percentage of degranulated/total cells was high in FK. Dilated limbal vasculature with increased permeability, as well as largely infiltrated neutrophils with stimulated ICAM-1 protein levels were observed in corneas of FK mice, when compared with Mock and UT mice. Interestingly, pretreatment with cromolyn sodium (Block) significantly blocked MC degranulation, dramatically suppressed vascular dilation and permeability, and markedly reduced neutrophil infiltration with lower ICAM-1 levels in FK mice at 6-24 hours. Furthermore, the Block mice manifested prolonged disease course, increased pathological damage, and vigorous fungus growth, with much higher corneal perforation rate than FK mice at 72 h. These findings reveal a novel phenomenon that MCs play a vital role in protecting cornea against fungal infection through degranulation that promotes neutrophil infiltration via stimulating ICAM-1 production and limbal vascular dilation and permeability.

  12. Investigating the effect of tumor vascularization on magnetic targeting in vivo using retrospective design of experiment.

    PubMed

    Mei, Kuo-Ching; Bai, Jie; Lorrio, Silvia; Wang, Julie Tzu-Wen; Al-Jamal, Khuloud T

    2016-11-01

    Nanocarriers take advantages of the enhanced permeability and retention (EPR) to accumulate passively in solid tumors. Magnetic targeting has shown to further enhance tumor accumulation in response to a magnetic field gradient. It is widely known that passive accumulation of nanocarriers varies hugely in tumor tissues of different tumor vascularization. It is hypothesized that magnetic targeting is likely to be influenced by such factors. In this work, magnetic targeting is assessed in a range of subcutaneously implanted murine tumors, namely, colon (CT26), breast (4T1), lung (Lewis lung carcinoma) cancer and melanoma (B16F10). Passively- and magnetically-driven tumor accumulation of the radiolabeled polymeric magnetic nanocapsules are assessed with gamma counting. The influence of tumor vasculature, namely, the tumor microvessel density, permeability and diameter on passive and magnetic tumor targeting is assessed with the aid of the retrospective design of experiment (DoE) approach. It is clear that the three tumor vascular parameters contribute greatly to both passive and magnetically targeted tumor accumulation but play different roles when nanocarriers are targeted to the tumor with different strategies. It is concluded that tumor permeability is a rate-limiting factor in both targeting modes. Diameter and microvessel density influence passive and magnetic tumor targeting, respectively. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  13. Targeting vascular (endothelial) dysfunction

    PubMed Central

    Steven, Sebastian; Weber, Alina; Shuvaev, Vladimir V.; Muzykantov, Vladimir R.; Laher, Ismail; Li, Huige; Lamas, Santiago

    2016-01-01

    Abstract Cardiovascular diseases are major contributors to global deaths and disability‐adjusted life years, with hypertension a significant risk factor for all causes of death. The endothelium that lines the inner wall of the vasculature regulates essential haemostatic functions, such as vascular tone, circulation of blood cells, inflammation and platelet activity. Endothelial dysfunction is an early predictor of atherosclerosis and future cardiovascular events. We review the prognostic value of obtaining measurements of endothelial function, the clinical techniques for its determination, the mechanisms leading to endothelial dysfunction and the therapeutic treatment of endothelial dysfunction. Since vascular oxidative stress and inflammation are major determinants of endothelial function, we have also addressed current antioxidant and anti‐inflammatory therapies. In the light of recent data that dispute the prognostic value of endothelial function in healthy human cohorts, we also discuss alternative diagnostic parameters such as vascular stiffness index and intima/media thickness ratio. We also suggest that assessing vascular function, including that of smooth muscle and even perivascular adipose tissue, may be an appropriate parameter for clinical investigations. Linked Articles This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc PMID:27187006

  14. Effect of nitroglycerin administration on cardio-ankle vascular index.

    PubMed

    Shimizu, Kazuhiro; Yamamoto, Tomoyuki; Takahashi, Mao; Sato, Shuji; Noike, Hirofumi; Shirai, Kohji

    2016-01-01

    The purpose of this study was to clarify the difference between effects of nitroglycerin (NTG) on the functional stiffness in patients with and without coronary artery disease (CAD) using a newly developed stiffness index, cardio-ankle vascular index (CAVI). The two subject groups in this study were normal controls (n=31) and CAD patients (n=25). The normal controls had no medical history and were not on regular medications. On the other hand, the CAD patients had received various treatments like antihypertensive drugs, hypoglycemic agents, and statins. This study was conducted in CAD patients under medications. After a single sublingual administration of NTG 0.3 mg, CAVI, blood pressure (BP), and heart rate (HR) were measured every 5 minutes for 20 minutes. Comparisons of each parameter before and after taking NTG were evaluated for statistical significance using analysis of variance and post hoc tests. Tukey-Kramer test was used for post hoc comparisons. In the normal controls, CAVI significantly decreased from baseline after 5, 10, and 15 minutes (from 6.5±0.9 to 5.2±0.9, 5.5±0.9, and 5.7±0.9, respectively). Systolic BP and HR were not significantly changed. Diastolic BP significantly decreased from baseline after 5 and 10 minutes (from 72±8 to 64±9 and 63±9 mmHg, respectively). On the other hand, CAVI, HR, and diastolic BP were not changed significantly in CAD patients. Systolic BP was significantly decreased from baseline after 5, 10, and 15 minutes (from 147±16 to 131±14, 129±12, and 129±13 mmHg, respectively). In the comparison of the two groups, ΔCAVI was not significantly different between the normal controls and CAD patients (-1.4±0.7 vs -1.4±0.9, -1.1±0.7 vs -1.4±1.0, -0.8±0.7 vs -1.2±1.0, and -0.5±0.7 vs -1.1±1.0 at 5, 10, 15, and 20 minutes, respectively). ΔHR was not significantly different between the two groups. ΔSystolic BP in the CAD patients was significantly higher than in the normal controls at 5, 10, 15, and 20 minutes

  15. Effect of nitroglycerin administration on cardio-ankle vascular index

    PubMed Central

    Shimizu, Kazuhiro; Yamamoto, Tomoyuki; Takahashi, Mao; Sato, Shuji; Noike, Hirofumi; Shirai, Kohji

    2016-01-01

    Purpose The purpose of this study was to clarify the difference between effects of nitroglycerin (NTG) on the functional stiffness in patients with and without coronary artery disease (CAD) using a newly developed stiffness index, cardio-ankle vascular index (CAVI). Subjects and methods The two subject groups in this study were normal controls (n=31) and CAD patients (n=25). The normal controls had no medical history and were not on regular medications. On the other hand, the CAD patients had received various treatments like antihypertensive drugs, hypoglycemic agents, and statins. This study was conducted in CAD patients under medications. After a single sublingual administration of NTG 0.3 mg, CAVI, blood pressure (BP), and heart rate (HR) were measured every 5 minutes for 20 minutes. Comparisons of each parameter before and after taking NTG were evaluated for statistical significance using analysis of variance and post hoc tests. Tukey–Kramer test was used for post hoc comparisons. Results In the normal controls, CAVI significantly decreased from baseline after 5, 10, and 15 minutes (from 6.5±0.9 to 5.2±0.9, 5.5±0.9, and 5.7±0.9, respectively). Systolic BP and HR were not significantly changed. Diastolic BP significantly decreased from baseline after 5 and 10 minutes (from 72±8 to 64±9 and 63±9 mmHg, respectively). On the other hand, CAVI, HR, and diastolic BP were not changed significantly in CAD patients. Systolic BP was significantly decreased from baseline after 5, 10, and 15 minutes (from 147±16 to 131±14, 129±12, and 129±13 mmHg, respectively). In the comparison of the two groups, ΔCAVI was not significantly different between the normal controls and CAD patients (−1.4±0.7 vs −1.4±0.9, −1.1±0.7 vs −1.4±1.0, −0.8±0.7 vs −1.2±1.0, and −0.5±0.7 vs −1.1±1.0 at 5, 10, 15, and 20 minutes, respectively). ΔHR was not significantly different between the two groups. ΔSystolic BP in the CAD patients was significantly higher than

  16. Relationship between Serum Uric Acid and Vascular Function and Structure Markers and Gender Difference in a Real-World Population of China-From Beijing Vascular Disease Patients Evaluation Study (BEST) Study.

    PubMed

    Liu, Huan; Liu, Jinbo; Zhao, Hongwei; Zhou, Yingyan; Li, Lihong; Wang, Hongyu

    2018-03-01

    The study was done to establish the relationship between serum uric acid (UA) and vascular function and structure parameters including carotid femoral pulse wave velocity (CF-PWV), carotid radial pulse wave velocity (CR-PWV), cardio ankle vascular index (CAVI), ankle brachial index (ABI), and carotid intima-media thickness (CIMT), and the gender difference in a real-world population from China. A total of 979 subjects were enrolled (aged 60.86±11.03 years, male 416 and female 563). Value of UA was divided by 100 (UA/100) for analysis. Body mass index (BMI), diastolic blood pressure (DBP), fasting plasma glucose (FPG), UA, and UA/100 were significantly higher in males compared with females (all p<0.05); pulse pressure (PP), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were lower in males than females (all p<0.05). All vascular parameters including CF-PWV, CR-PWV, CAVI, ABI, and CIMT were higher in males than females (all p<0.05). Multiple linear regression analysis showed that UA/100 was independently positively linearly correlated with CAVI (B=0.143, p=0.001) and negatively correlated with ABI in the male population (B=-0.012, p=0.020). In people with higher UA, the risk of higher CF-PWV was 1.593 (p<0.05). 1. All vascular parameters were higher in males than females. There was no gender difference in the relationship between UA and vascular markers except in ABI. 2. UA was independently linearly correlated with CAVI. 3. In people with higher UA level, the risk of higher CF-PWV increased. Therefore, higher UA may influence the vascular function mainly instead of vascular structure.

  17. Relationship between flow and incidence of thrombosis in polytetrafluoroethylene vascular grafts in free microvascular flaps in lambs.

    PubMed

    Paloma, V; Lasso, J M; Bazán, A; Serra, J M

    1999-09-01

    We have done an experimental study in lambs in which we investigated the influence of flow rate on free microvascular flaps using polytetrafluoroethylene (PTFE) vascular grafts. We set up five surgical groups in which blood flow was progressively increased through the PTFE vascular graft. In group I (venous autograft) we observed just one vascular thrombosis which was located at the site of the anastomosis. In group II (PTFE 3 x 10 mm) all the microvascular flaps became necrosed after the third postoperative day. In group III (PTFE 3 x 10 mm) necrosis also developed in all cases, but the anastomoses remained permeable no longer than eight days. In group IV (3 x 15 mm) the permeability in the microvascular free flaps was about 40% after 21 days, and in group V (3 x 10 mm) it reached 70%. To match graft flow rates with flap survival we did a regression analysis of flow rates for groups II, III, and V and the corresponding survival periods for the flaps. There was a clear and highly significant relationship (r = 0.717, p = 0.0001). In conclusion, it is necessary to maintain blood flow through the prosthesis at a rate higher than the thrombogenic threshold. When the flow rate in the vessels through the PTFE grafts was higher, the viability of the flaps was better. The ideal surgical technique should always be based on an arteriovenous fistula distal to the PTFE vascular graft. It is necessary to maintain blood flow through a prosthesis at a rate higher than the thrombogenic threshold.

  18. Mediterranean Diet, Alzheimer Disease, and Vascular Mediation

    PubMed Central

    Scarmeas, Nikolaos; Stern, Yaakov; Mayeux, Richard; Luchsinger, Jose A.

    2011-01-01

    Objectives To examine the association between the Mediterranean diet (MeDi) and Alzheimer disease (AD) in a different AD population and to investigate possible mediation by vascular pathways. Design, Setting, Patients, and Main Outcome Measures A case-control study nested within a community-based cohort in New York, NY. Adherence to the MeDi (0- to 9-point scale with higher scores indicating higher adherence) was the main predictor of AD status (194 patients with AD vs 1790 nondemented subjects) in logistic regression models that were adjusted for cohort, age, sex, ethnicity, education, apolipoprotein E genotype, caloric intake, smoking, medical comorbidity index, and body mass index (calculated as weight in kilograms divided by height in meters squared). We investigated whether there was attenuation of the association between MeDi and AD when vascular variables (stroke, diabetes mellitus, hypertension, heart disease, lipid levels) were simultaneously introduced in the models (which would constitute evidence of mediation). Results Higher adherence to the MeDi was associated with lower risk for AD (odds ratio, 0.76; 95% confidence interval, 0.67–0.87; P<.001). Compared with subjects in the lowest MeDi tertile, subjects in the middle MeDi tertile had an odds ratio of 0.47 (95% confidence interval, 0.29–0.76) and those at the highest tertile an odds ratio of 0.32 (95% confidence interval, 0.17–0.59) for AD (P for trend <.001). Introduction of the vascular variables in the model did not change the magnitude of the association. Conclusions We note once more that higher adherence to the MeDi is associated with a reduced risk for AD. The association does not seem to be mediated by vascular comorbidity. This could be the result of either other biological mechanisms (oxidative or inflammatory) being implicated or measurement error of the vascular variables. PMID:17030648

  19. Vascular nutritional correlates of late-life depression.

    PubMed

    Payne, Martha E; Hybels, Celia F; Bales, Connie W; Steffens, David C

    2006-09-01

    The authors sought to examine the association of vascular nutritional factors and depression in an elderly cohort of depression (currently and recently depressed) and comparison (never depressed) subjects. Nutrient intake over the past year was assessed in 196 elderly depression and comparison individuals with a Block 1998 food-frequency questionnaire. Nutrient intake, body mass index, and Keys score (a measure of the serum cholesterol-raising capacity of the diet) were determined. Subjects were age 60 and over and were participants in a longitudinal study of major depression. All subjects received psychiatric and medical comorbidity assessments; depression subjects also received psychiatric treatment. Vascular nutritional factors differed between depression and comparison subjects. The depression group had higher intake of saturated fat and cholesterol, higher body mass indices, lower alcohol intake, and higher Keys score than the comparison group. After controlling for age, sex, education, race, and medical comorbidity, associations remained for cholesterol, alcohol, and Keys score. Depression was found to be associated with overall dietary pattern as defined by total kilocalories, saturated fat, cholesterol, body mass index, polyunsaturated fat, sodium, and alcohol. This study provides evidence that dietary vascular risk factors differ in individuals with current or prior depression when compared with individuals with no history of depression.

  20. Review of gestational diabetes mellitus effects on vascular structure and function.

    PubMed

    Jensen, Louise A; Chik, Constance L; Ryan, Edmond A

    2016-05-01

    Vascular dysfunction has been described in women with a history of gestational diabetes mellitus. Furthermore, previous gestational diabetes mellitus increases the risk of developing Type 2 diabetes mellitus, a risk factor for cardiovascular disease. Factors contributing to vascular changes remain uncertain. The aim of this review was to summarize vascular structure and function changes found to occur in women with previous gestational diabetes mellitus and to identify factors that contribute to vascular dysfunction. A systematic search of electronic databases yielded 15 publications from 1998 to March 2014 that met the inclusion criteria. Our review confirmed that previous gestational diabetes mellitus contributes to vascular dysfunction, and the most consistent risk factor associated with previous gestational diabetes mellitus and vascular dysfunction was elevated body mass index. Heterogeneity existed across studies in determining the relationship of glycaemic levels and insulin resistance to vascular dysfunction. © The Author(s) 2016.

  1. Contributions of mast cells and vasoactive products, leukotrienes and chymase, to dengue virus-induced vascular leakage

    PubMed Central

    St John, Ashley L; Rathore, Abhay PS; Raghavan, Bhuvanakantham; Ng, Mah-Lee; Abraham, Soman N

    2013-01-01

    Dengue Virus (DENV), a flavivirus spread by mosquito vectors, can cause vascular leakage and hemorrhaging. However, the processes that underlie increased vascular permeability and pathological plasma leakage during viral hemorrhagic fevers are largely unknown. Mast cells (MCs) are activated in vivo during DENV infection, and we show that this elevates systemic levels of their vasoactive products, including chymase, and promotes vascular leakage. Treatment of infected animals with MC-stabilizing drugs or a leukotriene receptor antagonist restores vascular integrity during experimental DENV infection. Validation of these findings using human clinical samples revealed a direct correlation between MC activation and DENV disease severity. In humans, the MC-specific product, chymase, is a predictive biomarker distinguishing dengue fever (DF) and dengue hemorrhagic fever (DHF). Additionally, our findings reveal MCs as potential therapeutic targets to prevent DENV-induced vasculopathy, suggesting MC-stabilizing drugs should be evaluated for their effectiveness in improving disease outcomes during viral hemorrhagic fevers. DOI: http://dx.doi.org/10.7554/eLife.00481.001 PMID:23638300

  2. Role of Vitamin C in the Function of the Vascular Endothelium

    PubMed Central

    Harrison, Fiona E.

    2013-01-01

    Abstract Significance: Vitamin C, or ascorbic acid, has long been known to participate in several important functions in the vascular bed in support of endothelial cells. These functions include increasing the synthesis and deposition of type IV collagen in the basement membrane, stimulating endothelial proliferation, inhibiting apoptosis, scavenging radical species, and sparing endothelial cell-derived nitric oxide to help modulate blood flow. Although ascorbate may not be able to reverse inflammatory vascular diseases such as atherosclerosis, it may well play a role in preventing the endothelial dysfunction that is the earliest sign of many such diseases. Recent Advances: Beyond simply preventing scurvy, evidence is mounting that ascorbate is required for optimal function of many dioxygenase enzymes in addition to those involved in collagen synthesis. Several of these enzymes regulate the transcription of proteins involved in endothelial function, proliferation, and survival, including hypoxia-inducible factor-1α and histone and DNA demethylases. More recently, ascorbate has been found to acutely tighten the endothelial permeability barrier and, thus, may modulate access of ascorbate and other molecules into tissues and organs. Critical Issues: The issue of the optimal cellular content of ascorbate remains unresolved, but it appears that low millimolar ascorbate concentrations are normal in most animal tissues, in human leukocytes, and probably in the endothelium. Although there may be little benefit of increasing near maximal cellular ascorbate concentrations in normal people, many diseases and conditions have either systemic or localized cellular ascorbate deficiency as a cause for endothelial dysfunction, including early atherosclerosis, sepsis, smoking, and diabetes. Future Directions: A key focus for future studies of ascorbate and the vascular endothelium will likely be to determine the mechanisms and clinical relevance of ascorbate effects on endothelial

  3. Reflection coefficient and permeability of urea and ethylene glycol in the human red cell membrane

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Levitt, D.G.; Mlekoday, H.J.

    1983-02-01

    The reflection coefficient (sigma) and permeability (P) of urea and ethylene glycol were determined by fitting the equations of Kedem and Katchalsky (1958) to the change in light scattering produced by adding a permeable solute to a red cell suspension. The measurements incorporated three important modifications: (a) the injection artifact was eliminated by using echinocyte cells; (b) the use of an additional adjustable parameter (Km), the effective dissociation constant at the inner side of the membrane; (c) the light scattering is not directly proportional to cell volume (as is usually assumed) because refractive index and scattering properties of the cellmore » depend on the intracellular permeable solute concentration. This necessitates calibrating for known changes in refractive index (by the addition of dextran) and cell volume (by varying the NaCl concentration). The best fit was for sigma . 0.95, Po . 8.3 X 10(-4) cm/s, and Km . 100 mM for urea and sigma . 1.0, Po . 3.9 X 10(-4) cm/s, and Km . 30 mM for ethylene glycol. The effects of the inhibitors copper, phloretin, p-chloromercuriphenylsulfonate, and 5,5'-dithiobis (2-nitro) benzoic acid on the urea, ethylene glycol, and water permeability were determined. The results suggest that there are three separate, independent transport systems: one for water, one for urea and related compounds, and one for ethylene glycol and glycerol.« less

  4. Bioinspired Tuning of Hydrogel Permeability-Rigidity Dependency for 3D Cell Culture

    NASA Astrophysics Data System (ADS)

    Lee, Min Kyung; Rich, Max H.; Baek, Kwanghyun; Lee, Jonghwi; Kong, Hyunjoon

    2015-03-01

    Hydrogels are being extensively used for three-dimensional immobilization and culture of cells in fundamental biological studies, biochemical processes, and clinical treatments. However, it is still a challenge to support viability and regulate phenotypic activities of cells in a structurally stable gel, because the gel becomes less permeable with increasing rigidity. To resolve this challenge, this study demonstrates a unique method to enhance the permeability of a cell-laden hydrogel while avoiding a significant change in rigidity of the gel. Inspired by the grooved skin textures of marine organisms, a hydrogel is assembled to present computationally optimized micro-sized grooves on the surface. Separately, a gel is engineered to preset aligned microchannels similar to a plant's vascular bundles through a uniaxial freeze-drying process. The resulting gel displays significantly increased water diffusivity with reduced changes of gel stiffness, exclusively when the microgrooves and microchannels are aligned together. No significant enhancement of rehydration is achieved when the microgrooves and microchannels are not aligned. Such material design greatly enhances viability and neural differentiation of stem cells and 3D neural network formation within the gel.

  5. Association between plantar fascia vascularity and morphology and foot dysfunction in individuals with chronic plantar fasciitis.

    PubMed

    Chen, Hongying; Ho, Hok-Ming; Ying, Michael; Fu, Siu Ngor

    2013-10-01

    Single-cohort laboratory-based study. To identify whether plantar fascia vascularity and thickness are associated with foot pain and dysfunction in individuals with chronic plantar fasciitis. Background Altered plantar fascia vascularity and thickening of the fascia have been identified in individuals with chronic plantar fasciitis. Thirty-eight patients with chronic unilateral plantar fasciitis and 21 controls participated in this study. Proximal plantar fascia vascularization and thickness were assessed using ultrasound imaging, and pain and foot dysfunction were quantified with a visual analog scale and the Chinese version of the Foot Function Index, respectively. Paired t tests were used to assess the side-to-side differences in fascia thickness and vascularity index (VI) in the control and patient groups, and an unpaired t test was used to make comparisons with the patient group. Multiple regression analysis was performed to identify whether the VI and fascia thickness were associated with pain and foot dysfunction. There were significantly higher VI (mean ± SD, 2.4% ± 1.4%) and fascia thickness (5.0 ± 1.3 mm) values in the affected feet when compared with the unaffected feet in the patient group (VI, 1.4% ± 0.5%; fascia thickness, 3.3 ± 0.7 mm) and with the dominant side of the controls (VI, 1.6% ± 0.4%; fascia thickness, 2.9 ± 0.6 mm). After accounting for age, gender, body mass index, and duration of symptoms, the VI explained 13% and 33% of the variance in pain scores measured with a visual analog scale and the pain subscale of the Foot Function Index, respectively; the VI and fascia thickness explained 42% of the variance in the Foot Function Index. Individuals with unilateral chronic plantar fasciitis demonstrated significantly greater vascularity and thickened fascia on the affected side compared to the unaffected side and also to healthy controls. Fascia vascularity was associated independently with self-perceived pain, and both fascia

  6. Increased pulsatility index supports diagnosis of vascular parkinsonism versus idiopathic Parkinson's disease.

    PubMed

    Caba, L M; Ferrairó, J I T; Torres, I M; Costa, J F V; Muñoz, R B; Martin, A L

    2017-12-29

    The diagnosis of vascular parkinsonism (VP) is based on a series of clinical criteria and neuroimaging findings. An increase in transcranial Doppler ultrasonography pulsatility index (PI) has been described as a frequent finding in patients with VP. We aimed to confirm this association and to determine the PI value with the highest sensitivity and specificity for diagnosis of VP. PI was determined in all patients admitted to Hospital Universitari i Politècnic La Fe due to parkinsonism between January 2012 and June 2016. We assessed the probability of having VP based on PI values in patients with a definite diagnosis of either VP or idiopathic Parkinson's disease (IPD). A ROC curve was created to determine the PI value with the highest sensitivity and specificity. We assessed a total of 146 patients with suspected parkinsonism; 54 (37%) were diagnosed with IPD and 15 (10%) with VP. Patients with VP were significantly older than those with IPD (mean age of 79 vs 68.5, P=.00144) and had a higher PI (median of 1.29 [IQR: 1.09-1.38] vs 0.96 [IQR: 0.89-1.16], P=.01328). In our sample, a PI of 1.09 conferred 84% sensitivity and 70% specificity. In our series, the PI was significantly higher in patients with VP than in those with IPD. We therefore support the use of transcranial Doppler ultrasonography for the initial assessment of elderly patients with akinetic-rigid syndrome. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. Value of doppler ultrasonography in the study of hemodialysis peripheral vascular access dysfunction.

    PubMed

    Moreno Sánchez, T; Martín Hervás, C; Sola Martínez, E; Moreno Rodríguez, F

    2014-01-01

    The main objectives of this study were to evaluate the sensitivity and specificity of duplex Doppler ultrasonography in the study of hemodialysis peripheral vascular access dysfunction and to analyze the resistance index and flow in the afferent artery. We prospectively studied 178 patients with 178 peripheral vascular accesses that were dysfunctional in at least three consecutive hemodialysis sessions. Patients underwent duplex Doppler ultrasonography and clinical and laboratory follow-up for three months (provided angiography findings were negative). We calculated the sensitivity, specificity, predictive values, and coefficients of probability. We studied the morphology of the afferent artery, the arteriovenous anastomosis, and the efferent vein, and we measured the resistance index and the flow of the afferent artery, the diameter of the anastomosis, and the flow and peak systolic velocity in the efferent vein. The final sample consisted of 159 patients. The sensitivity, specificity, positive and negative predictive values, and positive and negative coefficients of probability were 0,98 (95% CI: 0,88-1.00), 0,74 (95% CI: 0,66-0,81), 0,96, 0,82, 3.7, and 0,03, respectively. The resistance index was less than 0,5 in 78.5% of the peripheral vascular accesses with normal function and greater than 0,5 in 86.1% of the dysfunctional peripheral vascular accesses. We found aneurysms in 19 of the native peripheral vascular accesses and pseudoaneurysms in 7 of the prosthetic grafts. Inverted flow was seen in 57 peripheral vascular accesses. Duplex Doppler ultrasonography is an efficacious method for detecting and characterizing stenosis and thrombosis in peripheral vascular accesses, and it provides information about the morphology and hemodynamics. Copyright © 2012 SERAM. Published by Elsevier Espana. All rights reserved.

  8. GSK-3Beta-Dependent Activation of GEF-H1/ROCK Signaling Promotes LPS-Induced Lung Vascular Endothelial Barrier Dysfunction and Acute Lung Injury.

    PubMed

    Yi, Lei; Huang, Xiaoqin; Guo, Feng; Zhou, Zengding; Chang, Mengling; Huan, Jingning

    2017-01-01

    The bacterial endotoxin or lipopolysaccharide (LPS) leads to the extensive vascular endothelial cells (EC) injury under septic conditions. Guanine nucleotide exchange factor-H1 (GEF-H1)/ROCK signaling not only involved in LPS-induced overexpression of pro-inflammatory mediator in ECs but also implicated in LPS-induced endothelial hyper-permeability. However, the mechanisms behind LPS-induced GEF-H1/ROCK signaling activation in the progress of EC injury remain incompletely understood. GEF-H1 localized on microtubules (MT) and is suppressed in its MT-bound state. MT disassembly promotes GEF-H1 release from MT and stimulates downstream ROCK-specific GEF activity. Since glycogen synthase kinase (GSK-3beta) participates in regulating MT dynamics under pathologic conditions, we examined the pivotal roles for GSK-3beta in modulating LPS-induced activation of GEF-H1/ROCK, increase of vascular endothelial permeability and severity of acute lung injury (ALI). In this study, we found that LPS induced human pulmonary endothelial cell (HPMEC) monolayers disruption accompanied by increase in GSK-3beta activity, activation of GEF-H1/ROCK signaling and decrease in beta-catenin and ZO-1 expression. Inhibition of GSK-3beta reduced HPMEC monolayers hyper-permeability and GEF-H1/ROCK activity in response to LPS. GSK-3beta/GEF-H1/ROCK signaling is implicated in regulating the expression of beta-catenin and ZO-1. In vivo , GSK-3beta inhibition attenuated LPS-induced activation of GEF-H1/ROCK pathway, lung edema and subsequent ALI. These findings present a new mechanism of GSK-3beta-dependent exacerbation of lung micro-vascular hyper-permeability and escalation of ALI via activation of GEF-H1/ROCK signaling and disruption of intracellular junctional proteins under septic condition.

  9. Targeted modulation of reactive oxygen species in the vascular endothelium.

    PubMed

    Shuvaev, Vladimir V; Muzykantov, Vladimir R

    2011-07-15

    'Endothelial cells lining vascular luminal surface represent an important site of signaling and injurious effects of reactive oxygen species (ROS) produced by other cells and endothelium itself in ischemia, inflammation and other pathological conditions. Targeted delivery of ROS modulating enzymes conjugated with antibodies to endothelial surface molecules (vascular immunotargeting) provides site-specific interventions in the endothelial ROS, unattainable by other formulations including PEG-modified enzymes. Targeting of ROS generating enzymes (e.g., glucose oxidase) provides ROS- and site-specific models of endothelial oxidative stress, whereas targeting of antioxidant enzymes SOD and catalase offers site-specific quenching of superoxide anion and H(2)O(2). These targeted antioxidant interventions help to clarify specific role of endothelial ROS in vascular and pulmonary pathologies and provide basis for design of targeted therapeutics for treatment of these pathologies. In particular, antibody/catalase conjugates alleviate acute lung ischemia/reperfusion injury, whereas antibody/SOD conjugates inhibit ROS-mediated vasoconstriction and inflammatory endothelial signaling. Encapsulation in protease-resistant, ROS-permeable carriers targeted to endothelium prolongs protective effects of antioxidant enzymes, further diversifying the means for targeted modulation of endothelial ROS. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Optical investigation of effective permeability of dilute magnetic dielectrics with magnetic field

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Banerjee, Ananya, E-mail: banerjee.ananya2008@gmail.com; Sarkar, A.

    The prime objective of this paper is to investigate the magnetic nature of dilute magnetic dielectrics (DMD) under variation of external magnetic field. The said variation is studied over developed nano-sized Gadolinium Oxide as a DMD system. The observed experimental field variation of the effective magnetic permeability is analyzed results of optical experiment. The experiment records the variation of Brewster angle of incident polarized LASER beam from the surface of developed DMD specimen with applied out of plane external magnetic field. The effective refractive index and hence relative magnetic permeability were estimated following electro-magnetic theory. The overall results obtained andmore » agreement between theory and experiment are good.« less

  11. A catalog of porosity and permeability from core plugs in siliciclastic rocks

    USGS Publications Warehouse

    Nelson, Philip H.; Kibler, Joyce E.

    2003-01-01

    Porosity and permeability measurements on cored samples from siliciclastic formations are presented for 70 data sets, taken from published data and descriptions. Data sets generally represent specific formations, usually from a limited number of wells. Each data set is represented by a written summary, a plot of permeability versus porosity, and a digital file of the data. The summaries include a publication reference, the geologic age of the formation, location, well names, depth range, various geologic descriptions, and core measurement conditions. Attributes such as grain size or depositional environment are identified by symbols on the plots. An index lists the authors and date, geologic age, formation name, sandstone classification, location, basin or structural province, and field name.

  12. Axial and Radial Permeability Evolutions of Compressed Sandstones: End Effects and Shear-band Induced Permeability Anisotropy

    NASA Astrophysics Data System (ADS)

    Dautriat, Jeremie; Gland, Nicolas; Guelard, Jean; Dimanov, Alexandre; Raphanel, Jean L.

    2009-07-01

    The influence of hydrostatic and uniaxial stress states on the porosity and permeability of sandstones has been investigated. The experimental procedure uses a special triaxial cell which allows permeability measurements in the axial and radial directions. The core sleeve is equipped with two pressure samplers placed distant from the ends. They provide mid-length axial permeability measure as opposed to the overall permeability measure, which is based on the flow imposed through the pistons of the triaxial cell. The core sleeve is also equipped to perform flows in two directions transverse to the axis of the sample. Two independent measures of axial and complementary radial permeability are thus obtained. Both Fontainebleau sandstone specimens with a porosity of about 5.8% to 8% and low permeability ranging from 2.5 mD to 30 mD and Bentheimer sandstone with a porosity of 24% and a high permeability of 3 D have been tested. The initial axial permeability values obtained by each method are in good agreement for the Fontainebleau sandstone. The Bentheimer sandstone samples present an axial mid-length permeability 1.6 times higher than the overall permeability. A similar discrepancy is also observed in the radial direction, also it relates essentially to the shape of flow lines induced by the radial flow. All the tested samples have shown a higher stress dependency of overall and radial permeability than mid-length permeability. The effect of compaction damage at the pistons/sample and radial ports/sample interfaces is discussed. The relevance of directional permeability measurements during continuous uniaxial compression loadings has been shown on the Bentheimer sandstone until the failure of the sample. We can efficiently measure the influence of brittle failure associated to dilatant regime on the permeability: It tends to increase in the failure propagation direction and to decrease strongly in the transverse direction.

  13. c-Met–mediated endothelial plasticity drives aberrant vascularization and chemoresistance in glioblastoma

    PubMed Central

    Huang, Menggui; Liu, Tianrun; Ma, Peihong; Mitteer, R. Alan; Zhang, Zhenting; Kim, Hyun Jun; Yeo, Eujin; Zhang, Duo; Cai, Peiqiang; Li, Chunsheng; Zhang, Lin; Zhao, Botao; Roccograndi, Laura; O’Rourke, Donald M.; Dahmane, Nadia; Gong, Yanqing; Koumenis, Constantinos

    2016-01-01

    Aberrant vascularization is a hallmark of cancer progression and treatment resistance. Here, we have shown that endothelial cell (EC) plasticity drives aberrant vascularization and chemoresistance in glioblastoma multiforme (GBM). By utilizing human patient specimens, as well as allograft and genetic murine GBM models, we revealed that a robust endothelial plasticity in GBM allows acquisition of fibroblast transformation (also known as endothelial mesenchymal transition [Endo-MT]), which is characterized by EC expression of fibroblast markers, and determined that a prominent population of GBM-associated fibroblast-like cells have EC origin. Tumor ECs acquired the mesenchymal gene signature without the loss of EC functions, leading to enhanced cell proliferation and migration, as well as vessel permeability. Furthermore, we identified a c-Met/ETS-1/matrix metalloproteinase–14 (MMP-14) axis that controls VE-cadherin degradation, Endo-MT, and vascular abnormality. Pharmacological c-Met inhibition induced vessel normalization in patient tumor–derived ECs. Finally, EC-specific KO of Met inhibited vascular transformation, normalized blood vessels, and reduced intratumoral hypoxia, culminating in suppressed tumor growth and prolonged survival in GBM-bearing mice after temozolomide treatment. Together, these findings illustrate a mechanism that controls aberrant tumor vascularization and suggest that targeting Endo-MT may offer selective and efficient strategies for antivascular and vessel normalization therapies in GBM, and possibly other malignant tumors. PMID:27043280

  14. Protein kinase C activation modulates reversible increase in cortical blood-brain barrier permeability and tight junction protein expression during hypoxia and posthypoxic reoxygenation.

    PubMed

    Willis, Colin L; Meske, Diana S; Davis, Thomas P

    2010-11-01

    Hypoxia (Hx) is a component of many disease states including stroke. Ischemic stroke occurs when there is a restriction of cerebral blood flow and oxygen to part of the brain. During the ischemic, and subsequent reperfusion phase of stroke, blood-brain barrier (BBB) integrity is lost with tight junction (TJ) protein disruption. However, the mechanisms of Hx and reoxygenation (HR)-induced loss of BBB integrity are not fully understood. We examined the role of protein kinase C (PKC) isozymes in modifying TJ protein expression in a rat model of global Hx. The Hx (6% O(2)) induced increased hippocampal and cortical vascular permeability to 4 and 10 kDa dextran fluorescein isothiocyanate (FITC) and endogenous rat-IgG. Cortical microvessels revealed morphologic changes in nPKC-θ distribution, increased nPKC-θ and aPKC-ζ protein expression, and activation by phosphorylation of nPKC-θ (Thr538) and aPKC-ζ (Thr410) residues after Hx treatment. Claudin-5, occludin, and ZO-1 showed disrupted organization at endothelial cell margins, whereas Western blot analysis showed increased TJ protein expression after Hx. The PKC inhibition with chelerythrine chloride (5 mg/kg intraperitoneally) attenuated Hx-induced hippocampal vascular permeability and claudin-5, PKC (θ and ζ) expression, and phosphorylation. This study supports the hypothesis that nPKC-θ and aPKC-ζ signaling mediates TJ protein disruption resulting in increased BBB permeability.

  15. Direct means of obtaining CAVI0-a corrected cardio-ankle vascular stiffness index (CAVI)-from conventional CAVI measurements or their underlying variables.

    PubMed

    Spronck, Bart; Mestanik, Michal; Tonhajzerova, Ingrid; Jurko, Alexander; Jurko, Tomas; Avolio, Alberto P; Butlin, Mark

    2017-09-21

    Cardio-ankle vascular index (CAVI) as measured using the VaSera device (CAVI VS , Fukuda Denshi), has been proposed as a stiffness index that does not depend on blood pressure. We have recently shown theoretically that CAVI VS still exhibits blood pressure dependence, and proposed the corrected index CAVI 0 . The present study aims to establish a method of calculating [Formula: see text] either (i) from VaSera-reported values of cardiac-brachial and brachial-ankle pulse transit times (tb and tba, respectively) and blood pressure, or (ii) directly from CAVI VS . To derive this method, the relationship among CAVI VS and its scale constants a and b, tb, tba, and blood pressure has to be established. From data of 497 subjects, eight candidate CAVI parameters were defined and calculated, containing all combinations of left or right tb/tba/blood pressure. Candidates were evaluated through correlation with measured left and right CAVI VS . Correlations were compared statistically. Once the correct candidates were determined, two constants (a and b) required for converting CAVI VS to CAVI 0 were estimated through linear regression. Left and right CAVI VS are calculated using left and right tba; however, both left and right CAVI VS are calculated using right brachial blood pressures and right tb. Constants a and b for conversion of CAVI VS to CAVI 0 were estimated to be 0.842 [0.836 0.848] and 0.753 [0.721 0.786] (mean [95%CI]), respectively. Equations to estimate CAVI 0 from CAVI VS , and to directly calculate CAVI 0 from the VaSera output are provided in this paper, as well as in a directly usable spreadsheet supplement. Our results permit straightforward calculation of [Formula: see text] during a study, as well as retrospective estimation of [Formula: see text] from CAVI VS in already published studies or where the original transit time values are not available, paving the way for thorough comparison of CAVI 0 to CAVI VS in clinical and research settings. Novelty and

  16. Pulmonary venous flow index as a predictor of pulmonary vascular resistance variability in congenital heart disease with increased pulmonary flow: a comparative study before and after oxygen inhalation.

    PubMed

    Rivera, Ivan Romero; Mendonça, Maria Alayde; Andrade, José Lázaro; Moises, Valdir; Campos, Orlando; Silva, Célia Camelo; Carvalho, Antonio Carlos

    2013-09-01

    There is no definitive and reliable echocardiographic method for estimating the pulmonary vascular resistance (PVR) to differentiate persistent vascular disease from dynamic pulmonary hypertension. The aim of this study was to analyze the relationship between the pulmonary venous blood flow velocity-time integral (VTIpv) and PVR. Eighteen patients (10 females; 4 months to 22 years of age) with congenital heart disease and left to right shunt were studied. They underwent complete cardiac catheterization, including measurements of the PVR and Qp:Qs ratio, before and after 100% oxygen inhalation. Simultaneous left inferior pulmonary venous flow VTIpv was obtained by Doppler echocardiography. The PVR decreased significantly from 5.0 ± 2.6 W to 2.8 ± 2.2 W (P = 0.0001) with a significant increase in the Qp:Qs ratio, from 3.2 ± 1.4 to 4.9 ± 2.4 (P = 0.0008), and the VTIpv increased significantly from 22.6 ± 4.7 cm to 28.1 ± 6.2 cm (P = 0.0002) after 100% oxygen inhalation. VTIpv correlated well with the PVR and Qp:Qs ratio (r = -0.74 and 0.72, respectively). Diagnostic indexes indicated a sensitivity of 86%, specificity of 75%, accuracy of 83%, a positive predictive value of 92% and a negative predictive value of 60%. The VTIpv correlated well with the PVR. The measurement of this index before and after oxygen inhalation may become a useful noninvasive test for differentiating persistent vascular disease from dynamic and flow-related pulmonary hypertension. © 2013, Wiley Periodicals, Inc.

  17. Experimental visualization of solutes transport in two-dimensional saturated permeable media

    NASA Astrophysics Data System (ADS)

    Muñoz, Edinsson; Herrera, Paulo

    2017-04-01

    intensity to concentrations in every pixel. We compared the concentrations calculated with image analysis to theoretical and numerical solutions. We also compared the estimated concentration distributions for a homogeneous and a heterogeneous experiments using as quantitative index the flow-related dilution index (Rolle et al., 2009). We conclude that in the heterogeneous case the dilution index was 1.5 times greater than in the homogeneous case, which confirms that heterogeneity due to inclusions of permeable materials can increase the transverse mixing or dilution of a conservative tracer.

  18. Gradual changes in permeability of inner mitochondrial membrane precede the mitochondrial permeability transition.

    PubMed

    Balakirev, M Y; Zimmer, G

    1998-08-01

    Some compounds are known to induce solute-nonselective permeability of the inner mitochondrial membrane (IMM) in Ca2+-loaded mitochondria. Existing data suggest that this process, following the opening of a mitochondrial permeability transition pore, is preceded by different solute-selective permeable states of IMM. At pH 7, for instance, the K0.5 for Ca2+-induced pore opening is 16 microM, a value 80-fold above a therapeutically relevant shift of intracellular Ca2+ during ischemia in vivo. The present work shows that in the absence of Ca2+, phenylarsine oxide and tetraalkyl thiuram disulfides (TDs) are able to induce a complex sequence of IMM permeability changes. At first, these agents activated an electrogenic K+ influx into the mitochondria. This K+-specific pathway had K0.5 = 35 mM for K+ and was inhibited by bromsulfalein with Ki = 2.5 microM. The inhibitors of mitochondrial KATP channel, ATP and glibenclamide, did not inhibit K+ transport via this pathway. Moreover, 50 microM glibenclamide induced by itself K+ influx into the mitochondria. After the increase in K+ permeability of IMM, mitochondria become increasingly permeable to protons. Mechanisms of H+ leak and nonselective permeability increase could also be different depending on the type of mitochondrial permeability transition (MPT) inducer. Thus, permeabilization of mitochondria induced by phenylarsine oxide was fully prevented by ADP and/or cyclosporin A, whereas TD-induced membrane alterations were insensitive toward these inhibitors. It is suggested that MPT in vivo leading to irreversible apoptosis is irrelevant in reversible ischemia/reperfusion injury. Copyright 1998 Academic Press.

  19. Placental vascular dysfunction, fetal and childhood growth, and cardiovascular development: the generation R study.

    PubMed

    Gaillard, Romy; Steegers, Eric A P; Tiemeier, Henning; Hofman, Albert; Jaddoe, Vincent W V

    2013-11-12

    Suboptimal fetal nutrition may influence early growth and cardiovascular development. We examined whether umbilical and uterine artery resistance indices, as measures of feto-placental and utero-placental vascular function, respectively, are associated with fetal and childhood growth and cardiovascular development. This study was embedded in a population-based prospective cohort study among 6716 mothers and their children. Umbilical artery pulsatility index and uterine artery resistance index and fetal growth were measured in third trimester. Childhood growth was repeatedly assessed from birth to the age of 6 years. We measured body fat distribution, left ventricular mass, and blood pressure at the age of 6 years. Higher third trimester umbilical and uterine artery vascular resistance were associated with lower fetal length and weight growth in third trimester resulting in a smaller size at birth among boys and girls (P values < 0.05). These differences in length and weight growth became smaller from the age of 6 months onwards, but were still present at the age of 6 years. Higher third trimester umbilical artery vascular resistance, but not uterine artery vascular resistance, was associated with higher childhood body mass index, total fat mass, android/gynoid fat mass ratio, and systolic blood pressure, and with a lower left ventricular mass (P values<0.05). These associations were not explained by birth weight. Stronger associations tended to be present among girls as compared with boys. Higher third trimester feto-placental vascular resistance, but not utero-placental vascular resistance, was associated with slower fetal growth rates and cardiovascular adaptations in childhood.

  20. Intestinal permeability study of minoxidil: assessment of minoxidil as a high permeability reference drug for biopharmaceutics classification.

    PubMed

    Ozawa, Makoto; Tsume, Yasuhiro; Zur, Moran; Dahan, Arik; Amidon, Gordon L

    2015-01-05

    The purpose of this study was to evaluate minoxidil as a high permeability reference drug for Biopharmaceutics Classification System (BCS). The permeability of minoxidil was determined in in situ intestinal perfusion studies in rodents and permeability studies across Caco-2 cell monolayers. The permeability of minoxidil was compared with that of metoprolol, an FDA reference drug for BCS classification. In rat perfusion studies, the permeability of minoxidil was somewhat higher than that of metoprolol in the jejunum, while minoxidil showed lower permeability than metoprolol in the ileum. The permeability of minoxidil was independent of intestinal segment, while the permeability of metoprolol was region-dependent. Similarly, in mouse perfusion study, the jejunal permeability of minoxidil was 2.5-fold higher than that of metoprolol. Minoxidil and metoprolol showed similar permeability in Caco-2 study at apical pH of 6.5 and basolateral pH of 7.4. The permeability of minoxidil was independent of pH, while metoprolol showed pH-dependent transport in Caco-2 study. Minoxidil exhibited similar permeability in the absorptive direction (AP-BL) in comparison with secretory direction (BL-AP), while metoprolol had higher efflux ratio (ER > 2) at apical pH of 6.5 and basolateral pH of 7.4. No concentration-dependent transport was observed for either minoxidil or metoprolol transport in Caco-2 study. Verapamil did not alter the transport of either compounds across Caco-2 cell monolayers. The permeability of minoxidil was independent of both pH and intestinal segment in intestinal perfusion studies and Caco-2 studies. Caco-2 studies also showed no involvement of carrier mediated transport in the absorption process of minoxidil. These results suggest that minoxidil may be an acceptable reference drug for BCS high permeability classification. However, minoxidil exhibited higher jejunal permeability than metoprolol and thus to use minoxidil as a reference drug would raise the

  1. Reproducibility and reliability of the ankle-brachial index as assessed by vascular experts, family physicians and nurses.

    PubMed

    Holland-Letz, Tim; Endres, Heinz G; Biedermann, Stefanie; Mahn, Matthias; Kunert, Joachim; Groh, Sabine; Pittrow, David; von Bilderling, Peter; Sternitzky, Reinhardt; Diehm, Curt

    2007-05-01

    The reliability of ankle-brachial index (ABI) measurements performed by different observer groups in primary care has not yet been determined. The aims of the study were to provide precise estimates for all effects influencing the variability of the ABI (patients' individual variability, intra- and inter-observer variability), with particular focus on the performance of different observer groups. Using a partially balanced incomplete block design, 144 unselected individuals aged > or = 65 years underwent double ABI measurements by one vascular surgeon or vascular physician, one family physician and one nurse with training in Doppler sonography. Three groups comprising a total of 108 individuals were analyzed (only two with ABI < 0.90). Errors for two repeated measurements for all three observer groups did not differ (experts 8.5%, family physicians 7.7%, and nurses 7.5%, p = 0.39). There was no relevant bias among observer groups. Intra-observer variability expressed as standard deviation divided by the mean was 8%, and inter-observer variability was 9%. In conclusion, reproducibility of the ABI measurement was good in this cohort of elderly patients who almost all had values in the normal range. The mean error of 8-9% within or between observers is smaller than with established screening measures. Since there were no differences among observers with different training backgrounds, our study confirms the appropriateness of ABI assessment for screening peripheral arterial disease (PAD) and generalized atherosclerosis in the primary case setting. Given the importance of the early detection and management of PAD, this diagnostic tool should be used routinely as a standard for PAD screening. Additional studies will be required to confirm our observations in patients with PAD of various severities.

  2. Measurements on stress dependent permeability

    NASA Astrophysics Data System (ADS)

    Risnes, R.; Faldaas, I.; Korsnes, R. I.; Norland, T.

    2003-04-01

    Hydrostatic loading is the conventional test procedure to determine the stress dependence of permeability. However, hydrostatic tests do not truly reflect the deviatoric stress state that exists in most reservoirs. The main objective of the present project was to study permeability changes under deviatoric stresses, like encountered in standard triaxial tests. However in measuring permeability in a triaxial cell, end effects may be important. The friction between the axial steel pistons and the sample may cause stress concentrations and thereby a non-homogeneous strain pattern towards the sample ends. To overcome this problem, the cell was modified to have pressure outlets from the mid-section of the sample, with the pressure tubes connected to the outside of the cell for pressure recording. The cell was designed for 1.5 in plugs with plug lengths of about 80 mm. Tests have been performed on two types of high porosity outcrop chalk: Liège chalk with porosity around 40 percent and permeability 1-2 millidarcy, and Aalborg chalk with porosity around 45 percent and permeability in the range 3-5 millidarcy. Methanol was used as saturating fluid for the chalks. In addition some sandstone samples from core material were included. The porosity values were rather high, around 30 percent, and the permeability ranged from around 50 millidarcy to over one Darcy. Synthetic oil was used as saturating fluid for the sandstone samples, to avoid any reactions with clay minerals. The results so far can be summarized as follows:(1) In almost all the tests, the permeability calculated by the overall pressure drop is smaller than the mid-section permeability. The reduction could typically be around 20 percent. This means that end-effects play an important role.(2) The permeability generally decrease with increasing hydrostatic stresses. This is in agreement with observations from other sources.(3) During deviatoric phases the average stress level is increasing, but the changes in

  3. Potential benefits of exercise on blood pressure and vascular function.

    PubMed

    Pal, Sebely; Radavelli-Bagatini, Simone; Ho, Suleen

    2013-01-01

    Physical activity seems to enhance cardiovascular fitness during the course of the lifecycle, improve blood pressure, and is associated with decreased prevalence of hypertension and coronary heart disease. It may also delay or prevent age-related increases in arterial stiffness. It is unclear if specific exercise types (aerobic, resistance, or combination) have a better effect on blood pressure and vascular function. This review was written based on previous original articles, systematic reviews, and meta-analyses indexed on PubMed from years 1975 to 2012 to identify studies on different types of exercise and the associations or effects on blood pressure and vascular function. In summary, aerobic exercise (30 to 40 minutes of training at 60% to 85% of predicted maximal heart rate, most days of the week) appears to significantly improve blood pressure and reduce augmentation index. Resistance training (three to four sets of eight to 12 repetitions at 10 repetition maximum, 3 days a week) appears to significantly improve blood pressure, whereas combination exercise training (15 minutes of aerobic and 15 minutes of resistance, 5 days a week) is beneficial to vascular function, but at a lower scale. Aerobic exercise seems to better benefit blood pressure and vascular function. Copyright © 2013 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

  4. Two barriers for sodium in vascular endothelium?

    PubMed Central

    Oberleithner, Hans

    2012-01-01

    Vascular endothelium plays a key role in blood pressure regulation. Recently, it has been shown that a 5% increase of plasma sodium concentration (sodium excess) stiffens endothelial cells by about 25%, leading to cellular dysfunction. Surface measurements demonstrated that the endothelial glycocalyx (eGC), an anionic biopolymer, deteriorates when sodium is elevated. In view of these results, a two-barrier model for sodium exiting the circulation across the endothelium is suggested. The first sodium barrier is the eGC which selectively buffers sodium ions with its negatively charged prote-oglycans.The second sodium barrier is the endothelial plasma membrane which contains sodium channels. Sodium excess, in the presence of aldosterone, leads to eGC break-down and, in parallel, to an up-regulation of plasma membrane sodium channels. The following hypothesis is postulated: Sodium excess increases vascular sodium permeability. Under such con-ditions (e.g. high-sodium diet), day-by-day ingested sodium, instead of being readily buffered by the eGC and then rapidly excreted by the kidneys, is distributed in the whole body before being finally excreted. Gradually, the sodium overload damages the organism. PMID:22471931

  5. Identifying tumor vascular permeability heterogeneity using reduced encoding techniques

    NASA Astrophysics Data System (ADS)

    Aref, Michael

    We test the hypothesis that the loss of spatial resolution to gain temporal resolution in clinical dynamic contrast enhanced (DCE) magnetic resonance mammography (MRM) causes partial volume effects that yield inaccurate permeability-surface area products (PS = Kp↔t) which results in erroneous diagnostic information and we offer a potential solution using reduced encoding techniques to solve this problem. We compared the PS obtained from DCE MRI at clinical MRI resolutions (2500 x 2500 mum resolution), to that obtained from resolutions analogous to histopathological in plane resolutions (938 x 938 mum and 469 x 469 mum resolution). Secondly, we determined the accuracy of PS obtained from Keyhole, Ṟeduced-encoding I&barbelow;maging by G&barbelow;eneralized-series Ṟeconstruction (RIGR), and Ṯwo-reference RIGR (TRIGR) using high-resolution baseline data (469 x 469 mum resolution) and clinical resolution dynamic data (2500 x 2500 mum resolution). Lastly, we statistically correlated two-compartment model fitting parameters (tumor EES volume fraction, ve, tumor plasma volume fraction, vp, and PS) obtained from DCE MRI at all three resolutions to histopathologically determined tumor diagnosis. In our model, female Sprague Dawley rats with N-ethyl-N-nitrosourea (ENU) induced mammary tumors imaged with fast T1-weighted gradient echo DCE MRI following a Gd-DTPA injection, there is a window of resolutions that detects similar PS "hot spots" compared to those obtained from the clinical imager resolution. The top five PS "hot spots" obtained from 469 mum resolution FFT are statistically different from those at 938 mum resolution FFT, p = 0.0014, and 2500 mum resolution FFT, p < 0.0001. Keyhole when compared with a FFT of similar resolution does not detect PS "hot spots" of similar value, p = 0.0002. PS "hot spots" obtained from RIGR compared to those from FFT are statistically the same value, p = 0.2734, but do not statistically agree on the location of mapped values

  6. Caveolin-1 siRNA increases the pulmonary microvascular and alveolar epithelial permeability in rats.

    PubMed

    Gao, Chengjin; Li, Rongrong; Huan, Jingning; Li, Wei

    2011-01-01

    Increased pulmonary microvascular and epithelial permeability are important contributors to pulmonary edema in acute lung injury. In this study, we used small interfering RNA (siRNA) to knock down caveolin-1 expression in rat lungs and to confirm the important role of caveolin-1 in regulating pulmonary edema. After pulmonary injection of siRNA against caveolin-1 messenger RNA incorporated in liposomes with three concentrations of 0.4, 0.8, and 1.2 mg/kg, the gene silencing rate and the effects of caveolin-1 siRNA on aquaporin (AQP)-1, AQP-5, and epithelial sodium channel (ENaC) were detected. For pulmonary permeability analysis, Evans blue fluorimetry, ratios of albumin concentrations between blood and bronchoalveolar lavage, and wet/dry weight ratios were measured. The impacts of caveolin-1 suppression on interendothelial junctions were evaluated by the performance of electron microscopy and the analysis of vascular endothelial (VE)-cadherin Western blot. Alveolar wall thickness analysis and chest fluoroscopy were performed to determine the pulmonary edema degree. After 72 hours of injection, the gene silencing rate of caveolin-1 siRNA is about 87%. AQP-1, AQP-5, ENaC-α, ENaC-β, ENaC-γ, and VE-cadherin protein levels were decreased by 63%, 66%, 80%, 90%, 89%, and 50%, respectively. Caveolin-1 siRNA also resulted in increasing microvascular and epithelial permeability and pulmonary edema. These data suggest that caveolin-1 plays an important part in regulating the pulmonary permeability by modifying AQP-1, AQP-5, ENaC, and VE-cadherin.

  7. Sub-core permeability and relative permeability characterization with Positron Emission Tomography

    NASA Astrophysics Data System (ADS)

    Zahasky, C.; Benson, S. M.

    2017-12-01

    This study utilizes preclinical micro-Positron Emission Tomography (PET) to image and quantify the transport behavior of pulses of a conservative aqueous radiotracer injected during single and multiphase flow experiments in a Berea sandstone core with axial parallel bedding heterogeneity. The core is discretized into streamtubes, and using the micro-PET data, expressions are derived from spatial moment analysis for calculating sub-core scale tracer flux and pore water velocity. Using the flux and velocity data, it is then possible to calculate porosity and saturation from volumetric flux balance, and calculate permeability and water relative permeability from Darcy's law. Full 3D simulations are then constructed based on this core characterization. Simulation results are compared with experimental results in order to test the assumptions of the simple streamtube model. Errors and limitations of this analysis will be discussed. These new methods of imaging and sub-core permeability and relative permeability measurements enable experimental quantification of transport behavior across scales.

  8. Epidermal Permeability Barrier Recovery Is Delayed in Vitiligo-Involved Sites

    PubMed Central

    Liu, J.; Man, W.Y.; Lv, C.Z.; Song, S.P.; Shi, Y.J.; Elias, P.M.; Man, M.Q.

    2010-01-01

    Background/Objectives Prior studies have demonstrated that both the skin surface pH and epidermal permeability barrier function vary with skin pigmentation types. Although melanin deficiency is the main feature of vitiligo, alterations in cutaneous biophysical properties in vitiligo have not yet been well defined. In the present study, stratum corneum (SC) hydration, the skin surface pH and epidermal permeability barrier function in vitiligo were evaluated. Methods A total of 30 volunteers with vitiligo comprising 19 males and 11 females aged 13–51 years (mean age: 27.91 ± 2.06 years) were enrolled in this study. The skin surface pH, SC hydration, melanin/erythema index and transepidermal water loss (TEWL) were measured by respective probes connected to a Courage-Khazaka MPA5. SC integrity was determined by measuring the TEWL following each D-Squame application. The barrier recovery rate was assessed at 5 h following barrier disruption by repeated tape stripping. Results In addition to SC hydration, both melanin and erythema index were significantly lower in vitiligo lesions than in contralateral, nonlesional sites, while no difference in skin surface pH between vitiligo-involved and uninvolved areas was observed. In addition, neither the basal TEWL nor SC integrity in the involved areas differed significantly from that in the uninvolved areas. However, barrier recovery in vitiligo-involved sites was significantly delayed in comparison with uninvolved sites (40.83 ± 5.39% vs. 58.30 ± 4.71%; t = 2.441; p < 0.02). Conclusion Barrier recovery following tape stripping of the SC is delayed in vitiligo. Therefore, improvement in epidermal permeability barrier function may be an important unrecognized factor to be considered in treating patients with vitiligo. PMID:20185976

  9. Parameterisation of multi-scale continuum perfusion models from discrete vascular networks.

    PubMed

    Hyde, Eoin R; Michler, Christian; Lee, Jack; Cookson, Andrew N; Chabiniok, Radek; Nordsletten, David A; Smith, Nicolas P

    2013-05-01

    Experimental data and advanced imaging techniques are increasingly enabling the extraction of detailed vascular anatomy from biological tissues. Incorporation of anatomical data within perfusion models is non-trivial, due to heterogeneous vessel density and disparate radii scales. Furthermore, previous idealised networks have assumed a spatially repeating motif or periodic canonical cell, thereby allowing for a flow solution via homogenisation. However, such periodicity is not observed throughout anatomical networks. In this study, we apply various spatial averaging methods to discrete vascular geometries in order to parameterise a continuum model of perfusion. Specifically, a multi-compartment Darcy model was used to provide vascular scale separation for the fluid flow. Permeability tensor fields were derived from both synthetic and anatomically realistic networks using (1) porosity-scaled isotropic, (2) Huyghe and Van Campen, and (3) projected-PCA methods. The Darcy pressure fields were compared via a root-mean-square error metric to an averaged Poiseuille pressure solution over the same domain. The method of Huyghe and Van Campen performed better than the other two methods in all simulations, even for relatively coarse networks. Furthermore, inter-compartment volumetric flux fields, determined using the spatially averaged discrete flux per unit pressure difference, were shown to be accurate across a range of pressure boundary conditions. This work justifies the application of continuum flow models to characterise perfusion resulting from flow in an underlying vascular network.

  10. Evaluation of a static stretching intervention on vascular endothelial function and arterial stiffness.

    PubMed

    Shinno, Hiromi; Kurose, Satoshi; Yamanaka, Yutaka; Higurashi, Kyoko; Fukushima, Yaeko; Tsutsumi, Hiromi; Kimura, Yutaka

    2017-06-01

    Maintenance and enhancement of vascular endothelial function contribute to the prevention of cardiovascular disease and prolong a healthy life expectancy. Given the reversible nature of vascular endothelial function, interventions to improve this function might prevent arteriosclerosis. Accordingly, we studied the effects of a 6-month static stretching intervention on vascular endothelial function (reactive hyperaemia peripheral arterial tonometry index: RH-PAT index) and arterial stiffness (brachial-ankle pulse wave velocity: baPWV) and investigated the reversibility of these effects after a 6-month detraining period following intervention completion. The study evaluated 22 healthy, non-smoking, premenopausal women aged ≥40 years. Subjects were randomly assigned to the full-intervention (n = 11; mean age: 48.6 ± 2.8 years) or a half-intervention that included a control period (n = 11; mean age: 46.9 ± 3.6 years). Body flexibility and vascular endothelial function improved significantly after 3 months of static stretching. In addition to these improvements, arterial stiffness improved significantly after a 6-month intervention. However, after a 6-month detraining period, vascular endothelial function, flexibility, and arterial stiffness all returned to preintervention conditions, demonstrating the reversibility of the obtained effects. A 3-month static stretching intervention was found to improve vascular endothelial function, and an additional 3-month intervention also improved arterial stiffness. However, these effects were reversed by detraining.

  11. HIV-1 Tat reduces nephrin in human podocytes: a potential mechanism for enhanced glomerular permeability in HIV-associated nephropathy.

    PubMed

    Doublier, Sophie; Zennaro, Cristina; Spatola, Tiziana; Lupia, Enrico; Bottelli, Antonella; Deregibus, Maria Chiara; Carraro, Michele; Conaldi, Pier Giulio; Camussi, Giovanni

    2007-02-19

    To determine whether HIV-1 Tat may directly alter glomerular permeability in HIV-associated nephropathy (HIVAN). Heavy proteinuria is a hallmark of HIVAN. The slit diaphragm is the ultimate glomerular filtration barrier critical for maintaining the efficiency of the ultrafiltration unit of the kidney. In this study, we evaluated the direct effect of Tat protein on the permeability of isolated glomeruli and on the expression of nephrin, the main slit diaphragm component, by human cultured podocytes. Permeability was studied by measuring the permeability to albumin in isolated rat glomeruli. We also evaluated the expression of nephrin in human cultured podocytes by using immunofluorescence and Western blot. We found that Tat increased albumin permeability in isolated glomeruli, and rapidly induced the redistribution and loss of nephrin in cultured podocytes. Pretreatment of glomeruli and podocytes with blocking antibodies showed that Tat reduced nephrin expression by engaging vascular endothelial growth factor receptors types 2 and 3 and the integrin alphavbeta3. Pre-incubation of podocytes with two platelet-activating factor (PAF) receptor antagonists prevented the loss and redistribution of nephrin induced by Tat, suggesting that PAF is an intracellular mediator of Tat action. Tat induced a rapid PAF synthesis by podocytes. When podocytes transfected to overexpress PAF-acetylhydrolase, the main catabolic enzyme of PAF, were stimulated with Tat, the redistribution and loss of nephrin was abrogated. The present results define a mechanism by which Tat may reduce nephrin expression in podocytes, thus increasing glomerular permeability. This provides new insights in the understanding of HIVAN pathogenesis.

  12. The 50 most influential original articles in vascular surgery during the last 25 years.

    PubMed

    Stegall, Frank; Corey, Michael; Dattilo, Jeffery

    2014-09-01

    We have compiled a list of the 50 most-cited original articles in the field of vascular surgery during the last 25 years to highlight the important changes in practice that have occurred during this interval and provide surgical trainees in vascular surgery ready access to such influential articles. A Web of Knowledge Citation Index Search was performed in December 2013 for the most-cited journal articles in the discipline of vascular surgery. We searched the term "vascular" in the cited reference search area and then further narrowed our results to exclude all categories except "surgery," "general internal medicine," and "cardiac/cardiovascular systems." We included only documents labeled as "articles" and those published in English. Articles dealing with cardiac surgery, interventional cardiology, and cardiovascular biology were excluded. Our search period was from January 1, 1988, through December 3, 2013. The 50 most frequently cited works were chosen, and a citation density was calculated for each, reflecting the average number of citations each received per year since publication. The articles were then sorted into a defined category, based on the clinical subject to which they pertained. The Citation Index Search resulted 80,379 articles, of which the top 50 were indexed and organized according to their citation density and area within the scope of clinical vascular surgery. The number of citations ranged from 218 to 3593. The median citation density was 50.2 (range, 11.3-201.3). This report is a representation of the most-cited original publications in the field of clinical vascular surgery during the last 25 years. This is an effort to highlight the seminal works that have shaped the discipline of vascular surgery as well as to provide a concise reference list for the surgical trainee in the process of his or her education. Copyright © 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

  13. Comparative field permeability measurement of permeable pavements using ASTM C1701 and NCAT permeameter methods.

    PubMed

    Li, Hui; Kayhanian, Masoud; Harvey, John T

    2013-03-30

    Fully permeable pavement is gradually gaining support as an alternative best management practice (BMP) for stormwater runoff management. As the use of these pavements increases, a definitive test method is needed to measure hydraulic performance and to evaluate clogging, both for performance studies and for assessment of permeability for construction quality assurance and maintenance needs assessment. Two of the most commonly used permeability measurement tests for porous asphalt and pervious concrete are the National Center for Asphalt Technology (NCAT) permeameter and ASTM C1701, respectively. This study was undertaken to compare measured values for both methods in the field on a variety of permeable pavements used in current practice. The field measurements were performed using six experimental section designs with different permeable pavement surface types including pervious concrete, porous asphalt and permeable interlocking concrete pavers. Multiple measurements were performed at five locations on each pavement test section. The results showed that: (i) silicone gel is a superior sealing material to prevent water leakage compared with conventional plumbing putty; (ii) both methods (NCAT and ASTM) can effectively be used to measure the permeability of all pavement types and the surface material type will not impact the measurement precision; (iii) the permeability values measured with the ASTM method were 50-90% (75% on average) lower than those measured with the NCAT method; (iv) the larger permeameter cylinder diameter used in the ASTM method improved the reliability and reduced the variability of the measured permeability. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. [Sonographic ovarian vascularization and volume in women with polycystic ovary syndrome treated with clomiphene citrate and metformin].

    PubMed

    de la Fuente-Valero, Jesús; Zapardiel-Gutiérrez, Ignacio; Orensanz-Fernández, Inmaculada; Alvarez-Alvarez, Pilar; Engels-Calvo, Virginia; Bajo-Arenas, José Manuel

    2010-01-01

    To measure the vascularization and ovarian volume with three-dimensional sonography in patients diagnosed of polycystic ovary syndrome with stimulated ovulation treatment, and to analyse the differences between the patients treated with clomiphen citrate versus clomiphen citrate and metformin. Therty patients were studied. Twenty ovulation cycles were obtained with clomiphen citrate and 17 with clomiphen citrate plus merformin (added in case of obesity or hyperglucemy/hyperinsulinemia). Ovarian volumes and vascular indexes were studied with 3D-sonography and results were analysed by treatment. There were no statistical differences of ovarian volume by treatment along the cycles, although bigger volume were found in ovulatory cycles compared to non-ovulatory ones (20,36 versus 13,89 ml, p = 0,026). No statistical differences were also found concerning vascular indexes, neither by treatment nor by the obtention of ovulation in the cycle. Ovarian volume and vascular indexes measured with three-dimensional sonography in patients diagnosed of polycystic ovary syndrome do not show differents values in patients treated with clomiphen citrate alone versus clomiphen citrate plus metformin.

  15. Predicting A Drug'S Membrane Permeability: Evolution of a Computational Model Validated with in Vitro Permeability Assay Data

    DOE PAGES

    Carpenter, Timothy S.; McNerney, M. Windy; Be, Nicholas A.; ...

    2016-02-16

    Membrane permeability is a key property to consider in drug design, especially when the drugs in question need to cross the blood-brain barrier (BBB). A comprehensive in vivo assessment of the BBB permeability of a drug takes considerable time and financial resources. A current, simplified in vitro model to investigate drug permeability is a Parallel Artificial Membrane Permeability Assay (PAMPA) that generally provides higher throughput and initial quantification of a drug's passive permeability. Computational methods can also be used to predict drug permeability. Our methods are highly advantageous as they do not require the synthesis of the desired drug, andmore » can be implemented rapidly using high-performance computing. In this study, we have used umbrella sampling Molecular Dynamics (MD) methods to assess the passive permeability of a range of compounds through a lipid bilayer. Furthermore, the permeability of these compounds was comprehensively quantified using the PAMPA assay to calibrate and validate the MD methodology. And after demonstrating a firm correlation between the two approaches, we then implemented our MD method to quantitatively predict the most permeable potential drug from a series of potential scaffolds. This permeability was then confirmed by the in vitro PAMPA methodology. Therefore, in this work we have illustrated the potential that these computational methods hold as useful tools to help predict a drug's permeability in a faster and more cost-effective manner. Release number: LLNL-ABS-677757.« less

  16. Predicting A Drug'S Membrane Permeability: Evolution of a Computational Model Validated with in Vitro Permeability Assay Data

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Carpenter, Timothy S.; McNerney, M. Windy; Be, Nicholas A.

    Membrane permeability is a key property to consider in drug design, especially when the drugs in question need to cross the blood-brain barrier (BBB). A comprehensive in vivo assessment of the BBB permeability of a drug takes considerable time and financial resources. A current, simplified in vitro model to investigate drug permeability is a Parallel Artificial Membrane Permeability Assay (PAMPA) that generally provides higher throughput and initial quantification of a drug's passive permeability. Computational methods can also be used to predict drug permeability. Our methods are highly advantageous as they do not require the synthesis of the desired drug, andmore » can be implemented rapidly using high-performance computing. In this study, we have used umbrella sampling Molecular Dynamics (MD) methods to assess the passive permeability of a range of compounds through a lipid bilayer. Furthermore, the permeability of these compounds was comprehensively quantified using the PAMPA assay to calibrate and validate the MD methodology. And after demonstrating a firm correlation between the two approaches, we then implemented our MD method to quantitatively predict the most permeable potential drug from a series of potential scaffolds. This permeability was then confirmed by the in vitro PAMPA methodology. Therefore, in this work we have illustrated the potential that these computational methods hold as useful tools to help predict a drug's permeability in a faster and more cost-effective manner. Release number: LLNL-ABS-677757.« less

  17. Rs964184 (APOA5-A4-C3-A1) is related to elevated plasma triglyceride levels, but not to an increased risk for vascular events in patients with clinically manifest vascular disease.

    PubMed

    van de Woestijne, Anton P; van der Graaf, Yolanda; de Bakker, Paul I W; Asselbergs, Folkert W; Spiering, Wilko; Visseren, Frank L J

    2014-01-01

    Single nucleotide polymorphisms in the APOA5-A4-C3-A1 gene complex are associated with elevated plasma triglycerides and elevated vascular risk in healthy populations. In patients with clinically manifest vascular disease, hypertriglyceridemia and metabolic syndrome are frequently present, but the contribution of these single nucleotide polymorphisms to plasma triglycerides, effect modification by obesity and risk of recurrent vascular events is unknown in these patients. Prospective cohort study of 5547 patients with vascular disease. Rs964184 (APOA5-A4-C3-A1 gene complex) was genotyped, and we evaluated the relation with plasma lipid levels, presence of metabolic syndrome and the risk for new vascular events. The minor allele of rs964184 was strongly associated with log plasma triglycerides (β 0.12; 95%CI 0.10-0.15, p = 1.1*10(-19)), and was also associated with 0.03 mmol/L lower high-density lipoprotein-cholesterol (95%CI 0.01-0.04), and 0.14 mmol/L higher non-high-density lipoprotein-cholesterol (95%CI 0.09-0.20). The minor allele frequency increased from 10.9% in patients with plasma triglycerides <1 mmol/L to 24.6% in patients with plasma triglycerides between 4 and 10 mmol/L. The relation between rs964184 and plasma triglycerides was modified by body mass index in patients with one minor allele (β 0.02; (95%CI -0.04-0.09) if body mass index <24 kg/m2, β 0.17 (95%CI 0.12-0.22) if body mass index >27 kg/m2, p for interaction = 0.02). The prevalence of the metabolic syndrome increased from 52% for patients with two copies of the major allele to 62% for patients with two copies of the minor allele (p = 0.01). Rs964184 was not related with recurrent vascular events (HR 0.99; 95%CI 0.86-1.13). The single nucleotide polymorphism rs964184 (APOA5-A4-C3-A1) is associated with elevated plasma triglycerides concentrations in patients with clinically manifest vascular disease. In carriers of one minor allele, the effect on plasma triglycerides was modified

  18. Vascular Hyperpermeability Response in Animals Systemically Exposed to Arsenic.

    PubMed

    Chen, Shih-Chieh; Chang, Chao-Yuah; Lin, Ming-Lu

    2018-01-01

    The mechanisms underlying cardiovascular diseases induced by chronic exposure to arsenic remain unclarified. The objectives of this study were to investigate whether increased vascular leakage is induced by inflammatory mustard oil in mice systemically exposed to various doses of arsenic and whether an increased vascular leakage response is still present in arsenic-fed mice after arsenic discontinuation for 2 or 6 months. ICR mice were fed water or various doses of sodium arsenite (10, 15, or 20 mg/kg/day; 5 days/week) for 8 weeks. In separate experiments, the mice were treated with sodium arsenite (20 mg/kg) for 2 or 8 weeks, followed by arsenic discontinuation for 2 or 6 months. Vascular permeability to inflammatory mustard oil was quantified using Evans blue (EB) techniques. Both arsenic-exposed and water-fed (control) mice displayed similar basal levels of EB leakage in the ears brushed with mineral oil, a vehicle of mustard oil. The levels of EB leakage induced by mustard oil in the arsenic groups fed with sodium arsenite (10 or 15 mg/kg) were similar to those of water-fed mice. However, increased levels of EB leakage in response to mustard oil stimulation were significantly higher in mice treated with sodium arsenite (20 mg/kg; high dose) than in arsenic-fed (10 or 15 mg/kg; low and middle doses) or control mice. After arsenic discontinuation for 2 or 6 months, mustard oil-induced vascular EB leakage in arsenic-fed (20 mg/kg) mice was similar to that in control mice. Dramatic increases in mustard oil-induced vascular leakage were only present in mice systemically exposed to the high arsenic dose, indicating the synergistic effects of the high arsenic dose and mustard oil.

  19. Adiponectin in Fresh Frozen Plasma Contributes to Restoration of Vascular Barrier Function after Hemorrhagic Shock

    PubMed Central

    Huby, Maria P.; Duan, Chaojun; Baer, Lisa; Peng, Zhanglong; Kozar, Rosemary A.; Doursout, Marie-Francoise; Holcomb, John B.; Wade, Charles E.; Ko, Tien C.

    2015-01-01

    Hemorrhagic shock is the leading cause of preventable deaths in civilian and military trauma. Use of fresh frozen plasma (FFP) in patients requiring massive transfusion is associated with improved outcomes. FFP contains significant amounts of adiponectin, which is known to have vascular protective function. We hypothesize that FFP improves vascular barrier function largely via adiponectin. Plasma adiponectin levels were measured in 19 severely injured patients in hemorrhagic shock (HS). Compared to normal individuals, plasma adiponectin levels decreased to 49% in HS patients prior to resuscitation (p<0.05) and increased to 64% post resuscitation (but not significant). In a HS mouse model, we demonstrated a similar decrease in plasma adiponectin to 54% but a significant increase to 79% by FFP resuscitation compared to baseline (p<0.05). HS disrupted lung vascular barrier function, leading to an increase in permeability. FFP resuscitation reversed these HS-induced effects. Immunodepletion of adiponectin from FFP abolished FFP's effects on blocking endothelial hyperpermeability in vitro, and on improving lung vascular barrier function in HS mice. Replenishment with adiponectin rescued FFP's effects. These findings suggest that adiponectin is an important component in FFP resuscitation contributing to the beneficial effects on vascular barrier function after HS. PMID:26263440

  20. Simultaneous acquisition of perfusion and permeability from corrected relaxation rates with dynamic susceptibility contrast dual gradient echo.

    PubMed

    Kim, Eun-Ju; Kim, Dae-Hong; Lee, Sang Hoon; Huh, Yong-Min; Song, Ho-Taek; Suh, Jin-Suck

    2004-04-01

    This study compared two methods, corrected (separation of T(1) and T(2)* effects) and uncorrected, in order to determine the suitability of the perfusion and permeability measures through Delta R(2)* and Delta R(1) analyses. A dynamic susceptibility contrast dual gradient echo (DSC-DGE) was used to image the fixed phantoms and flow phantoms (Sephadex perfusion phantoms and dialyzer phantom for the permeability measurements). The results confirmed that the corrected relaxation rate was linearly proportional to gadolinium-diethyltriamine pentaacetic acid (Gd-DTPA) concentration, whereas the uncorrected relaxation rate did not in the fixed phantom and simulation experiments. For the perfusion measurements, it was found that the correction process was necessary not only for the Delta R(1) time curve but also for the Delta R(2)* time curve analyses. Perfusion could not be measured without correcting the Delta R(2)* time curve. The water volume, which was expressed as the perfusion amount, was found to be closer to the theoretical value when using the corrected Delta R(1) curve in the calculations. However, this may occur in the low concentration of Gd-DTPA in tissue used in this study. For the permeability measurements based on the two-compartment model, the permeability factor (k(ev); e = extravascular, v = vascular) from the outside to the inside of the hollow fibers was greater in the corrected Delta R(1) method than in the uncorrected Delta R(1) method. The differences between the corrected and the uncorrected Delta R(1) values were confirmed by the simulation experiments. In conclusion, this study proposes that the correction for the relaxation rates, Delta R(2)* and Delta R(1), is indispensable in making accurate perfusion and permeability measurements, and that DSC-DGE is a useful method for obtaining information on perfusion and permeability, simultaneously.

  1. Short-Term Deposition of PM2.5 Particles on Contact Lens Surfaces: Effect on Oxygen Permeability and Refractive Index.

    PubMed

    Dong, Zhizhang; Ding, Xiaoyan; Li, Yong; Gan, Yifeng; Wang, Yanhui; Xu, Libin; Wang, Yahong; Zhou, Ying; Li, Juan

    2018-05-22

    To identify the deposition of fine (≤2.5 μm diameter) particulate matter (PM) particles (PM 2.5 ) on contact lens surfaces and to investigate the effects of such deposition on the oxygen permeability (OP) and refractive index (RI) of contact lenses. A total of 36 contact lenses, including rigid gas permeable (RGP) lens and soft contact lens (SCL), were investigated. RGP lens (n=12) and SCL (n=12) (experimental group) were incubated in a PM 2.5 solution for 24 h, after which PM 2.5 -treated RGP lens (n=6) and SCL (n=6) were further washed for 1 h in phosphate-buffered saline (PBS). All lenses were examined by field emission scanning electron microscopy. OP and RI of all lenses were measured. Average-sized PM 2.5 particles deposited on RGP contact lens and SCL surfaces after immersion in the PM 2.5 solution were 3.192 ± 1.637 and 2.158 ± 1.187/100 μm 2 , respectively. On RGP lens surfaces, we observed both large (≥2.5 µm diameter) and small (PM 2.5 ) particles. PM 2.5 particles were deposited in diffuse patterns, primarily along the honeycomb structural border of SCL, while no PM 2.5 particles were found in the honeycomb hole of SCL surfaces. Washing in PBS removed the larger PM particles from RGP lens surfaces, but left copious amounts of PM 2.5 particles. In contrast, nearly all PM particles were removed from SCL surfaces after PBS washing. OP values of RGP lens and SCL appeared to be unchanged by PM 2.5 deposition. RI values increased in both RGP lens and SCL groups after PM 2.5 deposition. However, these increases were not statistically significant, suggesting that PM 2.5 deposition itself does not cause fluctuations in contact lens RI. Deposition of PM 2.5 particles on contact lens surfaces varies according to lens material. PM 2.5 particles deposited on SCL, but only large particles on RGP surfaces were able to be removed by washing in PBS and did not appear to alter OP and RI of either lens type.

  2. Differences in cardio-ankle vascular index in a general Mediterranean population depending on the presence or absence of metabolic cardiovascular risk factors.

    PubMed

    Martí-Lluch, Ruth; Garcia-Gil, Maria Del Mar; Camós, Lourdes; Comas-Cufí, Marc; Elosua-Bayés, Marc; Blanch, Jordi; Ponjoan, Anna; Alves-Cabratosa, Lia; Elosua, Roberto; Grau, María; Marrugat, Jaume; Ramos, Rafel

    2017-09-01

    The main aim of this study is to describe the differences in the cardio-ankle vascular index (CAVI) in individuals with metabolic cardiovascular risk factors or a previous history of vascular diseases (WCVRF) compared to healthy individuals (free of risk factors and previous history of vascular diseases; FCVRF) in a general Mediterranean population. The secondary aim is to describe the proportion of CAVI≥9 depending on the cardiovascular risk category in both CVRF groups by sex. The study is a descriptive analysis of 2613 participants randomly selected in the Girona province (Catalonia, Spain). CAVI mean differences between sexes and age categories in both CVRF groups followed the same pattern, the FCVRF group (men 25.2%; women 14.4%) in turn had a lower prevalence of CAVI≥9 than the WCVRF group (men 57.9%; women 51.8%). The percentage of men and women with CAVI≥9 with low risk was 13.9% and 11.3% in the FCVRF group, and 31.8% and 42.0% in the WCVRF group; with moderate risk, it was 55.8% and 10.0% in the FCVRF group and 60.3% and 49.0% in the WCVRF group. In both sexes, FCVRF groups had a lower prevalence of CAVI≥9 as well as lower mean CAVI scores, across all 10 year-age categories from 40 to 69 years, than WCVRF groups. Moreover, CAVI≥9 was frequent in individuals with low and moderate coronary risk in the WCVRF group but also in the FCVRF group. These results suggest that CAVI assessment to detect asymptomatic arteriosclerosis could be a useful tool to improve cardiovascular risk stratification. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Inhibitory effect of the Ruscus extract and of the flavonoid hesperidine methylchalcone on increased microvascular permeability induced by various agents in the hamster cheek pouch.

    PubMed

    Bouskela, E; Cyrino, F Z; Marcelon, G

    1993-08-01

    The Ruscus extract and the flavonoid hesperidine methylchalcone (HMC) are used in treatment of venous insufficiency. In the present study, we used the hamster cheek pouch preparation and investigated the effects of these substances on increased microvascular permeability induced by bradykinin, histamine, and leukotriene B4 (LTB4) applied topically. Experiments were performed on male hamsters; 30 min after completion of the cheek pouch preparation, fluorescein-labeled dextran [molecular weight (mol wt) 150,000] was given intravenously (i.v.). Bradykinin, histamine, and LTB4 increased the number of fluorescent vascular leakage sites from postcapillary venules, evidence for an increase in macromolecular permeability, which was quantified in ultraviolet (UV)-light microscope as the number of leaky sites in the prepared area. Ruscus extract and HMC, given i.v., significantly inhibited the macromolecular permeability-increasing effect of bradykinin, LTB4, and histamine. Ruscus extract, applied topically, dose dependently inhibited the macromolecular permeability-increasing effect of histamine. Our results show that Ruscus extract and HMC have a protective effect against leakage of FITC-dextran in the cheek pouch after administration of various permeability-increasing substances, which further supports data previously reported on patients with venous insufficiency.

  4. Permeability-porosity relationships of subduction zone sediments

    USGS Publications Warehouse

    Gamage, Kusali; Screaton, Elizabeth; Bekins, B.; Aiello, I.

    2011-01-01

    Permeability-porosity relationships for sediments from the northern Barbados, Costa Rica, Nankai, and Peru subduction zones were examined based on sediment type, grain size distribution, and general mechanical and chemical compaction history. Greater correlation was observed between permeability and porosity in siliciclastic sediments, diatom oozes, and nannofossil chalks than in nannofossil oozes. For siliciclastic sediments, grouping of sediments by percentage of clay-sized material yields relationships that are generally consistent with results from other marine settings and suggests decreasing permeability as percentage of clay-sized material increases. Correction of measured porosities for smectite content improved the correlation of permeability-porosity relationships for siliciclastic sediments and diatom oozes. The relationship between permeability and porosity for diatom oozes is very similar to the relationship in siliciclastic sediments, and permeabilities of both sediment types are related to the amount of clay-size particles. In contrast, nannofossil oozes have higher permeability values by 1.5 orders of magnitude than siliciclastic sediments of the same porosity and show poor correlation between permeability and porosity. More indurated calcareous sediments, nannofossil chalks, overlap siliciclastic permeabilities at the lower end of their measured permeability range, suggesting similar consolidation patterns at depth. Thus, the lack of correlation between permeability and porosity for nannofossil oozes is likely related to variations in mechanical and chemical compaction at shallow depths. This study provides the foundation for a much-needed global database with fundamental properties that relate to permeability in marine settings. Further progress in delineating controls on permeability requires additional carefully documented permeability measurements on well-characterized samples. ?? 2010 Elsevier B.V.

  5. Permeability evolution of shale during spontaneous imbibition

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chakraborty, N.; Karpyn, Z. T.; Liu, S.

    Shales have small pore and throat sizes ranging from nano to micron scales, low porosity and limited permeability. The poor permeability and complex pore connectivity of shales pose technical challenges to (a) understanding flow and transport mechanisms in such systems and, (b) in predicting permeability changes under dynamic saturation conditions. This paper presents quantitative experimental evidence of the migration of water through a generic shale core plug using micro CT imaging. In addition, in-situ measurements of gas permeability were performed during counter-current spontaneous imbibition of water in nano-darcy permeability Marcellus and Haynesville core plugs. It was seen that water blocksmore » severely reduced the effective permeability of the core plugs, leading to losses of up to 99.5% of the initial permeability in experiments lasting 30 days. There was also evidence of clay swelling which further hindered gas flow. When results from this study were compared with similar counter-current gas permeability experiments reported in the literature, the initial (base) permeability of the rock was found to be a key factor in determining the time evolution of effective gas permeability during spontaneous imbibition. With time, a recovery of effective permeability was seen in the higher permeability rocks, while becoming progressively detrimental and irreversible in tighter rocks. Finally, these results suggest that matrix permeability of ultra-tight rocks is susceptible to water damage following hydraulic fracturing stimulation and, while shut-in/soaking time helps clearing-up fractures from resident fluid, its effect on the adjacent matrix permeability could be detrimental.« less

  6. Permeability evolution of shale during spontaneous imbibition

    DOE PAGES

    Chakraborty, N.; Karpyn, Z. T.; Liu, S.; ...

    2017-01-05

    Shales have small pore and throat sizes ranging from nano to micron scales, low porosity and limited permeability. The poor permeability and complex pore connectivity of shales pose technical challenges to (a) understanding flow and transport mechanisms in such systems and, (b) in predicting permeability changes under dynamic saturation conditions. This paper presents quantitative experimental evidence of the migration of water through a generic shale core plug using micro CT imaging. In addition, in-situ measurements of gas permeability were performed during counter-current spontaneous imbibition of water in nano-darcy permeability Marcellus and Haynesville core plugs. It was seen that water blocksmore » severely reduced the effective permeability of the core plugs, leading to losses of up to 99.5% of the initial permeability in experiments lasting 30 days. There was also evidence of clay swelling which further hindered gas flow. When results from this study were compared with similar counter-current gas permeability experiments reported in the literature, the initial (base) permeability of the rock was found to be a key factor in determining the time evolution of effective gas permeability during spontaneous imbibition. With time, a recovery of effective permeability was seen in the higher permeability rocks, while becoming progressively detrimental and irreversible in tighter rocks. Finally, these results suggest that matrix permeability of ultra-tight rocks is susceptible to water damage following hydraulic fracturing stimulation and, while shut-in/soaking time helps clearing-up fractures from resident fluid, its effect on the adjacent matrix permeability could be detrimental.« less

  7. Retinal pathology is associated with increased blood-retina barrier permeability in a diabetic and hypercholesterolaemic pig model: Beneficial effects of the LpPLA2 inhibitor Darapladib.

    PubMed

    Acharya, Nimish K; Qi, Xin; Goldwaser, Eric L; Godsey, George A; Wu, Hao; Kosciuk, Mary C; Freeman, Theresa A; Macphee, Colin H; Wilensky, Robert L; Venkataraman, Venkat; Nagele, Robert G

    2017-05-01

    Using a porcine model of diabetes mellitus and hypercholesterolaemia, we previously showed that diabetes mellitus and hypercholesterolaemia is associated with a chronic increase in blood-brain barrier permeability in the cerebral cortex, leading to selective binding of immunoglobulin G and deposition of amyloid-beta 1-42 peptide in pyramidal neurons. Treatment with Darapladib (GlaxoSmithKline, SB480848), an inhibitor of lipoprotein-associated phospholipase-A2, alleviated these effects. Here, investigation of the effects of chronic diabetes mellitus and hypercholesterolaemia on the pig retina revealed a corresponding increased permeability of the blood-retina barrier coupled with a leak of plasma components into the retina, alterations in retinal architecture, selective IgG binding to neurons in the ganglion cell layer, thinning of retinal layers due to cell loss and increased glial fibrillary acidic protein expression in Müller cells, all of which were curtailed by treatment with Darapladib. These findings suggest that chronic diabetes mellitus and hypercholesterolaemia induces increased blood-retina barrier permeability that may be linked to altered expression of blood-retina barrier-associated tight junction proteins, claudin and occludin, leading to structural changes in the retina consistent with diabetic retinopathy. Additionally, results suggest that drugs with vascular anti-inflammatory properties, such as Darapladib, may have beneficial effects on eye diseases strongly linked to vascular abnormalities such as diabetic retinopathy and age-related macular degeneration.

  8. Permeability of soils in Mississippi

    USGS Publications Warehouse

    O'Hara, Charles G.

    1994-01-01

    The permeability of soils in Mississippi was determined and mapped using a geographic information system (GIS). Soil permeabilities in Mississippi were determined to range in value from nearly 0.0 to values exceeding 5.0 inches per hour. The U.S. Soil Conservation Service's State Soil Geographic Data Base (STATSGO) was used as the primary source of data for the determination of area-weighted soil permeability. STATSGO provides soil layer properties that are spatially referenced to mapped areas. These mapped areas are referred to as polygons in the GIS. The polygons arc boundaries of soils mapped as a group and are given unique Map Unit Identifiers (MUIDs). The data describing the physical characteristics of the soils within each polygon are stored in a tabular data base format and are referred to as attributes. The U.S. Soil Conservation Service developed STATSGO to be primarily used as a guide for regional resource planning, management, and monitoring. STATSGO was designed so that soil information could be extracted from properties tables at the layer level, combined by component, and statistically expanded to cover the entire map unit. The results of this study provide a mapped value for permeability which is representative of the vertical permeability of soils in that area. The resultant permeability map provides a representative vertical soil permeability for a given area sufficient for county, multi- county, and area planning, and will be used as the soil permeability data component in the evaluation of the susceptibility of major aquifers to contami- nation in Mississippi.

  9. Seismic waves increase permeability.

    PubMed

    Elkhoury, Jean E; Brodsky, Emily E; Agnew, Duncan C

    2006-06-29

    Earthquakes have been observed to affect hydrological systems in a variety of ways--water well levels can change dramatically, streams can become fuller and spring discharges can increase at the time of earthquakes. Distant earthquakes may even increase the permeability in faults. Most of these hydrological observations can be explained by some form of permeability increase. Here we use the response of water well levels to solid Earth tides to measure permeability over a 20-year period. At the time of each of seven earthquakes in Southern California, we observe transient changes of up to 24 degrees in the phase of the water level response to the dilatational volumetric strain of the semidiurnal tidal components of wells at the Piñon Flat Observatory in Southern California. After the earthquakes, the phase gradually returns to the background value at a rate of less than 0.1 degrees per day. We use a model of axisymmetric flow driven by an imposed head oscillation through a single, laterally extensive, confined, homogeneous and isotropic aquifer to relate the phase response to aquifer properties. We interpret the changes in phase response as due to changes in permeability. At the time of the earthquakes, the permeability at the site increases by a factor as high as three. The permeability increase depends roughly linearly on the amplitude of seismic-wave peak ground velocity in the range of 0.21-2.1 cm s(-1). Such permeability increases are of interest to hydrologists and oil reservoir engineers as they affect fluid flow and might determine long-term evolution of hydrological and oil-bearing systems. They may also be interesting to seismologists, as the resulting pore pressure changes can affect earthquakes by changing normal stresses on faults.

  10. EPA Permeable Surface Research

    EPA Science Inventory

    EPA recognizes permeable surfaces as an effective post-construction infiltration-based Best Management Practice to mitigate the adverse effects of stormwater runoff. The professional user community conceptually embraces permeable surfaces as a tool for making runoff more closely...

  11. [Molecular mechanisms in vascular osteocartilaginous metaplasia: systematic review].

    PubMed

    Rosero Salazar, Doris Haydee

    2016-01-01

    The cartilage and bone metaplasia occurring in both the heart and blood vessels, are the result of risk factors or chronic diseases that gradually adversely affect the performance of a person in society; however, clinical signs are reversible in early and intermediate stages of alterations. To establish how the molecular mechanisms underlying the increased vascular metaplastic changes and possible aspects of treatment and prevention. A systematic review was performed by searching for articles indexed in PubMed, Scopus and Science Direct data from 1995 to 2015. The MeSH descriptors used were metaplasia and vascular calcification, which terms associated were molecular mechanisms, condrogenic and osteogenic. Multiple factors influence the metaplastic change, especially the pro-inflammatory associated with vascular oxidation and the presence of free radicals; this development is reversible by treatment with antioxidants and changes in lifestyle and secondary prevention as there is a diagnosis of chronic degenerative disease. The literature evidences that factors that reduce the tissue oxidative stress and promote the maintenance of vascular phenotype are protective and / or reducing the osteochondral metaplastic formations.

  12. Water and solute permeability of rat lung caveolae: high permeabilities explained by acyl chain unsaturation.

    PubMed

    Hill, Warren G; Almasri, Eyad; Ruiz, W Giovanni; Apodaca, Gerard; Zeidel, Mark L

    2005-07-01

    Caveolae are invaginated membrane structures with high levels of cholesterol, sphingomyelin, and caveolin protein that are predicted to exist as liquid-ordered domains with low water permeability. We isolated a caveolae-enriched membrane fraction without detergents from rat lung and characterized its permeability properties to nonelectrolytes and protons. Membrane permeability to water was 2.85 +/- 0.41 x 10(-3) cm/s, a value 5-10 times higher than expected based on comparisons with other cholesterol and sphingolipid-enriched membranes. Permeabilities to urea, ammonia, and protons were measured and found to be moderately high for urea and ammonia at 8.85 +/- 2.40 x 10(-7)and 6.84 +/- 1.03 x 10(-2) respectively and high for protons at 8.84 +/- 3.06 x 10(-2) cm/s. To examine whether caveolin or other integral membrane proteins were responsible for high permeabilities, liposomes designed to mimic the lipids of the inner and outer leaflets of the caveolar membrane were made. Osmotic water permeability to both liposome compositions were determined and a combined inner/outer leaflet water permeability was calculated and found to be close to that of native caveolae at 1.58 +/- 1.1 x 10(-3) cm/s. In caveolae, activation energy for water flux was high (19.4 kcal/mol) and water permeability was not inhibited by HgCl2; however, aquaporin 1 was detectable by immunoblotting. Immunostaining of rat lung with AQP1 and caveolin antisera revealed very low levels of colocalization. We conclude that aquaporin water channels do not contribute significantly to the observed water flux and that caveolae have relatively high water and solute permeabilities due to the high degree of unsaturation in their fatty acyl chains.

  13. Telemetric ambulatory arterial stiffness index, a predictor of cardio-cerebro-vascular mortality, is associated with aortic stiffness-determining factors.

    PubMed

    Li, Zhi-Yong; Xu, Tian-Ying; Zhang, Sai-Long; Zhou, Xiao-Ming; Xu, Xue-Wen; Guan, Yun-Feng; Lo, Ming; Miao, Chao-Yu

    2013-09-01

    Ambulatory arterial stiffness index (AASI) has been proposed as a new measure of arterial stiffness for predicting cardio-cerebro-vascular morbidity and mortality. However, there has been no research on the direct relationships between AASI and arterial stiffness-determining factors. We utilized beat-to-beat intra-aortic blood pressure (BP) telemetry to characterize AASI in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). By determination of aortic structural components and analysis of their correlations with AASI, we provided the first direct evidence for the associations between AASI and arterial stiffness-determining factors including the collagen content and collagen/elastin. Ambulatory arterial stiffness index was positively correlated with pulse pressure in both WKY and SHR, less dependent on BP and BP variability than pulse pressure, and relatively stable, especially the number of BP readings not less than ~36. The correlations between AASI and aortic components were comparable for various AASI values derived from BP readings not less than ~36. Not only AASI but also BP variability and pulse pressure demonstrated a direct relationship with arterial stiffness. These findings indicate AASI may become a routine measure in human arterial stiffness assessment. It is recommended to use a cluster of parameters such as AASI, BP variability, and pulse pressure for evaluating arterial stiffness. © 2013 John Wiley & Sons Ltd.

  14. High pulmonary vascular resistance in addition to low right ventricular stroke work index effectively predicts biventricular assist device requirement.

    PubMed

    Imamura, Teruhiko; Kinugawa, Koichiro; Kinoshita, Osamu; Nawata, Kan; Ono, Minoru

    2016-03-01

    Although the right ventricular stroke work index (RVSWI) is a good index for RV function, a low RVSWI is not necessarily an indicator for the need for a right ventricular assist device at the time of left VAD implantation. We here aimed to determine a more precise indicator for the need for a biventricular assist device (BiVAD). In total, 116 patients (mean age, 38 ± 14 years), who underwent hemodynamic assessments preoperatively including 12 BiVAD patients, and had been followed at our institute from 2003 to 2015, were included. Multivariate logistic regression analysis indicated that RVSWI and pulmonary vascular resistance (PVR) were independent predictors of BiVAD requirement (P < 0.05 for both). In addition, all patients were classified into 4 groups: (1) normal (RVSWI > 5 g/m, PVR < 3.7 WU), (2) pulmonary hypertension (RVSWI > 5, PVR > 3.7), (3) RV failure (RVSWI < 5, PVR < 3.7), and (4) both pulmonary hypertension and RV failure (RVSWI < 5, PVR > 3.7), and examined. Most of the patients in Group 4 (75 %), with acutely depressed hemodynamics and inflammatory responses in the myocardium, required BiVAD. Overall, patients with BiVAD had a worse survival rate as compared with those with LVAD alone. In conclusion, high PVR in addition to low RVSWI effectively predicts BiVAD requirement.

  15. Visualizing the Acute Effects of Vascular-Targeted Therapy In Vivo Using Intravital Microscopy and Magnetic Resonance Imaging: Correlation with Endothelial Apoptosis, Cytokine Induction, and Treatment Outcome1

    PubMed Central

    Seshadri, Mukund; Spernyak, Joseph A; Maiery, Patricia G; Cheney, Richard T; Mazurchuk, Richard; Bellnier, David A

    2007-01-01

    Abstract The acute effects of the vascular-disrupting agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) were investigated in vivo using intravital microscopy (IVM) and magnetic resonance imaging (MRI). Changes in vascular permeability and blood flow of syngeneic CT-26 murine colon adenocarcinomas were assessed at 4 and 24 hours after DMXAA treatment (30 mg/kg, i.p.) and correlated with induction of tumor necrosis factor-α (TNF-α), endothelial damage [CD31/terminal deoxynucleotidyl transferase (TdT)], and treatment outcome. Intravital imaging revealed a marked increase in vascular permeability 4 hours after treatment, consistent with increases in intratumoral mRNA and protein levels of TNF-α. Parallel contrast-enhanced MRI studies showed a ∼ 4-fold increase in longitudinal relaxation rates (ΔR1), indicative of increased contrast agent accumulation within the tumor. Dual immunostained tumor sections (CD31/TdT) revealed evidence of endothelial apoptosis at this time point. Twenty-four hours after treatment, extensive hemorrhage and complete disruption of vascular architecture were observed with IVM, along with a significant reduction in ΔR1; and virtual absence of CD31 immunostaining. DMXAA-induced tumor vascular damage resulted in significant long-term (60-day) cures compared to untreated controls. Multimodality imaging approaches are useful in visualizing the effects of antivascular therapy in vivo. Such approaches allow cross validation and correlation of findings with underlying molecular changes contributing to treatment outcome. PMID:17356709

  16. Vascular and Inflammatory Factors in the Pathophysiology of Blast-Induced Brain Injury

    PubMed Central

    Elder, Gregory A.; Gama Sosa, Miguel A.; De Gasperi, Rita; Stone, James Radford; Dickstein, Dara L.; Haghighi, Fatemeh; Hof, Patrick R.; Ahlers, Stephen T.

    2015-01-01

    Blast-related traumatic brain injury (TBI) has received much recent attention because of its frequency in the conflicts in Iraq and Afghanistan. This renewed interest has led to a rapid expansion of clinical and animal studies related to blast. In humans, high-level blast exposure is associated with a prominent hemorrhagic component. In animal models, blast exerts a variety of effects on the nervous system including vascular and inflammatory effects that can be seen with even low-level blast exposures which produce minimal or no neuronal pathology. Acutely, blast exposure in animals causes prominent vasospasm and decreased cerebral blood flow along with blood-brain barrier breakdown and increased vascular permeability. Besides direct effects on the central nervous system, evidence supports a role for a thoracically mediated effect of blast; whereby, pressure waves transmitted through the systemic circulation damage the brain. Chronically, a vascular pathology has been observed that is associated with alterations of the vascular extracellular matrix. Sustained microglial and astroglial reactions occur after blast exposure. Markers of a central and peripheral inflammatory response are found for sustained periods after blast injury and include elevation of inflammatory cytokines and other inflammatory mediators. At low levels of blast exposure, a microvascular pathology has been observed in the presence of an otherwise normal brain parenchyma, suggesting that the vasculature may be selectively vulnerable to blast injury. Chronic immune activation in brain following vascular injury may lead to neurobehavioral changes in the absence of direct neuronal pathology. Strategies aimed at preventing or reversing vascular damage or modulating the immune response may improve the chronic neuropsychiatric symptoms associated with blast-related TBI. PMID:25852632

  17. The mechanism of vascular leakage induced by leukotriene E4. Endothelial contraction.

    PubMed Central

    Joris, I.; Majno, G.; Corey, E. J.; Lewis, R. A.

    1987-01-01

    This study identifies the microvascular target of leukotriene E4 (LTE4) by vascular labeling with carbon black and establishes the mechanism of its action at the cellular level by electron microscopy. LTE4 and its tripeptide precursor, leukotriene C4 (LTC4) were injected subcutaneously in guinea pigs. With LTE4, venular labeling was intense at 1000 and 100 ng and slight at 10 ng, with extinction at 1 ng. LTC4 induced a ring of labeled venules around a blank central area, suggestive of vasospasm. The nonpeptidyl leukotriene LTB4 induced no labeling. Histamine (1000 ng) induced an area of vascular labeling about equal to that by 1000 ng LTE4, but the labeling of individual venules was more intense. By electron microscopy, LTE4 was found to induce gaps in the endothelium of the venules; the endothelial cells adjacent to the gaps bulged into the lumen and showed wrinkled nuclei, consistent with cellular contraction. This ultrastructural evidence suggests that LTE4 increases vascular permeability by contraction of endothelial cells selectively, in the postcapillary venules, as was previously demonstrated for other inflammatory mediators, including histamine, serotonin, and bradykinin. Images Figure 2 Figure 3 Figure 4 PMID:3028143

  18. Permeability During Magma Expansion and Compaction

    NASA Astrophysics Data System (ADS)

    Gonnermann, Helge. M.; Giachetti, Thomas; Fliedner, Céline; Nguyen, Chinh T.; Houghton, Bruce F.; Crozier, Joshua A.; Carey, Rebecca J.

    2017-12-01

    Plinian lapilli from the 1060 Common Era Glass Mountain rhyolitic eruption of Medicine Lake Volcano, California, were collected and analyzed for vesicularity and permeability. A subset of the samples were deformed at a temperature of 975°, under shear and normal stress, and postdeformation porosities and permeabilities were measured. Almost all undeformed samples fall within a narrow range of vesicularity (0.7-0.9), encompassing permeabilities between approximately 10-15 m2 and 10-10 m2. A percolation threshold of approximately 0.7 is required to fit the data by a power law, whereas a percolation threshold of approximately 0.5 is estimated by fitting connected and total vesicularity using percolation modeling. The Glass Mountain samples completely overlap with a range of explosively erupted silicic samples, and it remains unclear whether the erupting magmas became permeable at porosities of approximately 0.7 or at lower values. Sample deformation resulted in compaction and vesicle connectivity either increased or decreased. At small strains permeability of some samples increased, but at higher strains permeability decreased. Samples remain permeable down to vesicularities of less than 0.2, consistent with a potential hysteresis in permeability-porosity between expansion (vesiculation) and compaction (outgassing). We attribute this to retention of vesicle interconnectivity, albeit at reduced vesicle size, as well as bubble coalescence during shear deformation. We provide an equation that approximates the change in permeability during compaction. Based on a comparison with data from effusively erupted silicic samples, we propose that this equation can be used to model the change in permeability during compaction of effusively erupting magmas.

  19. Bioprinting for vascular and vascularized tissue biofabrication.

    PubMed

    Datta, Pallab; Ayan, Bugra; Ozbolat, Ibrahim T

    2017-03-15

    Bioprinting is a promising technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision. Bioprinting enables the deposition of various biologics including growth factors, cells, genes, neo-tissues and extra-cellular matrix-like hydrogels. Benefits of bioprinting have started to make a mark in the fields of tissue engineering, regenerative medicine and pharmaceutics. Specifically, in the field of tissue engineering, the creation of vascularized tissue constructs has remained a principal challenge till date. However, given the myriad advantages over other biofabrication methods, it becomes organic to expect that bioprinting can provide a viable solution for the vascularization problem, and facilitate the clinical translation of tissue engineered constructs. This article provides a comprehensive account of bioprinting of vascular and vascularized tissue constructs. The review is structured as introducing the scope of bioprinting in tissue engineering applications, key vascular anatomical features and then a thorough coverage of 3D bioprinting using extrusion-, droplet- and laser-based bioprinting for fabrication of vascular tissue constructs. The review then provides the reader with the use of bioprinting for obtaining thick vascularized tissues using sacrificial bioink materials. Current challenges are discussed, a comparative evaluation of different bioprinting modalities is presented and future prospects are provided to the reader. Biofabrication of living tissues and organs at the clinically-relevant volumes vitally depends on the integration of vascular network. Despite the great progress in traditional biofabrication approaches, building perfusable hierarchical vascular network is a major challenge. Bioprinting is an emerging technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision

  20. Assessment of placental volume and vascularization at 11-14 weeks of gestation in a Taiwanese population using three-dimensional power Doppler ultrasound.

    PubMed

    Wang, Hsing-I; Yang, Ming-Jie; Wang, Peng-Hui; Wu, Yi-Cheng; Chen, Chih-Yao

    2014-12-01

    The placental volume and vascular indices are crucial in helping doctors to evaluate early fetal growth and development. Inadequate placental volume or vascularity might indicate poor fetal growth or gestational complications. This study aimed to evaluate the placental volume and vascular indices during the period of 11-14 weeks of gestation in a Taiwanese population. From June 2006 to September 2009, three-dimensional power Doppler ultrasound was performed in 222 normal pregnancies from 11-14 weeks of gestation. Power Doppler ultrasound was applied to the placenta and the placental volume was obtained by a rotational technique (VOCAL). The three-dimensional power histogram was used to assess the placental vascular indices, including the mean gray value, the vascularization index, the flow index, and the vascularization flow index. The placental vascular indices were then plotted against gestational age (GA) and placental volume. Our results showed that the linear regression equation for placental volume using gestational week as the independent variable was placental volume = 18.852 × GA - 180.89 (r = 0.481, p < 0.05). All the placental vascular indices showed a constant distribution throughout the period 11-14 weeks of gestation. A tendency for a reduction in the placental mean gray value with gestational week was observed, but without statistical significance. All the placental vascular indices estimated by three-dimensional power Doppler ultrasonography showed a constant distribution throughout gestation. Copyright © 2014. Published by Elsevier Taiwan.

  1. Contrast-enhanced power Doppler endosonography and pathological assessment of vascularization in advanced gastric carcinomas--a feasibility study.

    PubMed

    Iordache, Sevastiţa; Filip, Maria-Monalisa; Georgescu, Claudia-Valentina; Angelescu, Cristina; Ciurea, Tudorel; Săftoiu, Adrian

    2012-06-01

    Besides representing angiogenesis markers, microvascular density (MVD) and vascular endothelial growth factor (VEGF) are two important tools for the assessment of prognosis in patients with gastric cancer. The aim of our study was to assess the Doppler parameters (resistivity and pulsatility indexes) and vascularity index (VI) calculated by contrast-enhanced power Doppler endoscopic ultrasound (CEPD-EUS) in correlation with the expression of intra-tumoral MVD and VEGF in patients with gastric cancer. The study included 20 consecutive patients with advanced gastric carcinoma, but without distant metastasis at initial assessment. All the patients were assessed by contrast-enhanced power Doppler endoscopic ultrasound (EUS) combined with pulsed Doppler examinations in the late venous phase. The vascularity index (VI) was calculated before and after injection of second generation microbubble contrast specific agent (SonoVue 2.4 mL), used as a Doppler signal enhancer. Moreover, pulsed Doppler parameters (resistivity and pulsatility indexes) were further calculated. The correlation between power Doppler parameters and pathological/molecular parameters (MVD assessed through immunohistochemistry with CD31 and CD34, as well as VEGF assessed through real-time PCR) was assessed. Kaplan-Meier survival analysis was used for the assessment of prognosis. Significantly statistical correlations were found between post-contrast VI and CD34 (p=0.0226), VEGF (p=0.0231), VEGF-A (p=0.0464) and VEGF-B (p=0.0022) while pre-contrast VI was correlated only with CD34 expression. Pulsatility index and resistivity index were not correlated with MVD or VEGF expression. Survival analysis demonstrated that VEGF-A is an accurate parameter for survival rate (p=0.045), as compared to VEGF (p=0.085) and VEGF-B (p=0.230). We did not find any correlation between the survival rate and ultrasound parameters (RI, PI, pre-contrast VI or post-contrast VI). Assessment of tumor vascularity using contrast

  2. Predicting the extent of metabolism using in vitro permeability rate measurements and in silico permeability rate predictions

    PubMed Central

    Hosey, Chelsea M; Benet, Leslie Z

    2015-01-01

    The Biopharmaceutics Drug Disposition Classification System (BDDCS) can be utilized to predict drug disposition, including interactions with other drugs and transporter or metabolizing enzyme effects based on the extent of metabolism and solubility of a drug. However, defining the extent of metabolism relies upon clinical data. Drugs exhibiting high passive intestinal permeability rates are extensively metabolized. Therefore, we aimed to determine if in vitro measures of permeability rate or in silico permeability rate predictions could predict the extent of metabolism, to determine a reference compound representing the permeability rate above which compounds would be expected to be extensively metabolized, and to predict the major route of elimination of compounds in a two-tier approach utilizing permeability rate and a previously published model predicting the major route of elimination of parent drug. Twenty-two in vitro permeability rate measurement data sets in Caco-2 and MDCK cell lines and PAMPA were collected from the literature, while in silico permeability rate predictions were calculated using ADMET Predictor™ or VolSurf+. The potential for permeability rate to differentiate between extensively and poorly metabolized compounds was analyzed with receiver operating characteristic curves. Compounds that yielded the highest sensitivity-specificity average were selected as permeability rate reference standards. The major route of elimination of poorly permeable drugs was predicted by our previously published model and the accuracies and predictive values were calculated. The areas under the receiver operating curves were >0.90 for in vitro measures of permeability rate and >0.80 for the VolSurf+ model of permeability rate, indicating they were able to predict the extent of metabolism of compounds. Labetalol and zidovudine predicted greater than 80% of extensively metabolized drugs correctly and greater than 80% of poorly metabolized drugs correctly in Caco

  3. Stroke injury, cognitive impairment and vascular dementia☆

    PubMed Central

    Kalaria, Raj N.; Akinyemi, Rufus; Ihara, Masafumi

    2016-01-01

    The global burden of ischaemic strokes is almost 4-fold greater than haemorrhagic strokes. Current evidence suggests that 25–30% of ischaemic stroke survivors develop immediate or delayed vascular cognitive impairment (VCI) or vascular dementia (VaD). Dementia after stroke injury may encompass all types of cognitive disorders. States of cognitive dysfunction before the index stroke are described under the umbrella of pre-stroke dementia, which may entail vascular changes as well as insidious neurodegenerative processes. Risk factors for cognitive impairment and dementia after stroke are multifactorial including older age, family history, genetic variants, low educational status, vascular comorbidities, prior transient ischaemic attack or recurrent stroke and depressive illness. Neuroimaging determinants of dementia after stroke comprise silent brain infarcts, white matter changes, lacunar infarcts and medial temporal lobe atrophy. Until recently, the neuropathology of dementia after stroke was poorly defined. Most of post-stroke dementia is consistent with VaD involving multiple substrates. Microinfarction, microvascular changes related to blood–brain barrier damage, focal neuronal atrophy and low burden of co-existing neurodegenerative pathology appear key substrates of dementia after stroke injury. The elucidation of mechanisms of dementia after stroke injury will enable establishment of effective strategy for symptomatic relief and prevention. Controlling vascular disease risk factors is essential to reduce the burden of cognitive dysfunction after stroke. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26806700

  4. Experimental Study on Permeability of Concrete

    NASA Astrophysics Data System (ADS)

    Yang, Honglu; Liu, Rentai; Zheng, Zhuo; Liu, Haojie; Gao, Yan; Liu, Yankai

    2018-01-01

    To study the influencing factors on permeability of pervious concrete, by adding inorganic organic composite materials obtained experimental results show that different aggregate size, aggregate cement ratio of different, different water cement ratio on the permeability performance. The permeability of the concrete was tested by using the self - made permeable device. The experimental results showed that the permeation coefficient of the experiment was obtained and the factors influencing the permeability of the concrete were compared and analyzed. At the same time, the porosity of pervious concrete was measured, the influence of various variables on porosity was studied, and the influence of various factors on the permeability of voids was found. Finally, through comprehensive analysis of a variety of factors, the optimal water cement ratio is 0.28. At this time, the pervious performance of concrete is optimal.

  5. Vortex rings impinging on permeable boundaries

    NASA Astrophysics Data System (ADS)

    Mujal-Colilles, Anna; Dalziel, Stuart B.; Bateman, Allen

    2015-01-01

    Experiments with vortex rings impinging permeable and solid boundaries are presented in order to investigate the influence of permeability. Utilizing Particle Image Velocimetry, we compared the behaviour of a vortex ring impinging four different reticulated foams (with permeability k ˜ 26 - 85 × 10-8 m2) and a solid boundary. Results show how permeability affects the stretching phenomena of the vortex ring and the formation and evolution of the secondary vortex ring with opposite sign. Moreover, permeability also affects the macroscopic no-slip boundary condition found on the solid boundary, turning it into an apparent slip boundary condition for the most permeable boundary. The apparent slip-boundary condition and the flux exchange between the ambient fluid and the foam are jointly responsible for both the modified formation of the secondary vortex and changes on the vortex ring diameter increase.

  6. Arterial ageing: from endothelial dysfunction to vascular calcification.

    PubMed

    Tesauro, M; Mauriello, A; Rovella, V; Annicchiarico-Petruzzelli, M; Cardillo, C; Melino, G; Di Daniele, N

    2017-05-01

    Complex structural and functional changes occur in the arterial system with advancing age. The aged artery is characterized by changes in microRNA expression patterns, autophagy, smooth muscle cell migration and proliferation, and arterial calcification with progressively increased mechanical vessel rigidity and stiffness. With age the vascular smooth muscle cells modify their phenotype from contractile to 'synthetic' determining the development of intimal thickening as early as the second decade of life as an adaptive response to forces acting on the arterial wall. The increased permeability observed in intimal thickening could represent the substrate on which low-level atherosclerotic stimuli can promote the development of advanced atherosclerotic lesions. In elderly patients the atherosclerotic plaques tend to be larger with increased vascular stenosis. In these plaques there is a progressive accumulation of both lipids and collagen and a decrease of inflammation. Similarly the plaques from elderly patients show more calcification as compared with those from younger patients. The coronary artery calcium score is a well-established marker of adverse cardiovascular outcomes. The presence of diffuse calcification in a severely stenotic segment probably induces changes in mechanical properties and shear stress of the arterial wall favouring the rupture of a vulnerable lesion in a less stenotic adjacent segment. Oxidative stress and inflammation appear to be the two primary pathological mechanisms of ageing-related endothelial dysfunction even in the absence of clinical disease. Arterial ageing is no longer considered an inexorable process. Only a better understanding of the link between ageing and vascular dysfunction can lead to significant advances in both preventative and therapeutic treatments with the aim that in the future vascular ageing may be halted or even reversed. © 2017 The Association for the Publication of the Journal of Internal Medicine.

  7. Film Permeability Determination Using Static Permeability Cells

    EPA Pesticide Factsheets

    The permeability of tarps to soil fumigant pesticides varies depending on the active ingredient chemical: dimethyl disulfide (DMDS), methyl bromide, chloropicrin, or other. The diffusion rate can be represented by the mass transfer coefficient (MTC).

  8. In vitro and in vivo assessment of cellular permeability and pharmacodynamics of S-nitrosylated Captopril, a nitric oxide donor

    PubMed Central

    Jia, Lee; Wong, Hong

    2001-01-01

    The present studies were aimed at testing the hypothesis that S-nitrosylated captopril (CapNO), a novel crystalline nitric oxide (NO) donor, readily permeates both in vitro and in vivo endothelial monolayers, resulting in its pharmacodynamic effects. CapNO and Captopril (Cap) were added to apical side of endothelial monolayers formed on microporous membranes, and the permeated drugs were collected from basolateral side and detected by a HPLC method. The permeability coefficient (Papp; cm sec−1) of CapNO across the endothelial monolayers was 6.0×10−5, higher than that of Cap (3.13×10−5), indicating the enhancement effect of the attached NO group in CapNO on cellular permeability. The Papp of CapNO and Cap across Caco-2 cells were 3.15×10−5 and 1.53×10−5, respectively. The low Papp of CapNO to Caco-2 cells may be attributed to the high membrane resistance of Caco-2 cells. A bolus injection of CapNO to epicardial coronary artery of chronically-instrumented awake dogs caused significant increases in coronary blood flow and coronary diameters dose-dependently without significant changes in aortic pressure. In contrast, the equimolar doses of Cap did not produce haemodynamic responses. Intravenous CapNO caused an instant increase in the regional cerebral blood flow determined by H2-clearance, whereas the equimolar doses of Cap did not enhance the cerebral blood flow. These results conclude that the NO group, an active component of CapNO, enhances both in vitro and in vivo endothelial permeability to the entire compound, resulting in instant increases in blood flow and vascular diameters. In contrast, the equimolar Cap does not have the instant vascular effects. PMID:11739246

  9. In vitro and in vivo assessment of cellular permeability and pharmacodynamics of S-nitrosylated captopril, a nitric oxide donor.

    PubMed

    Jia, L; Wong, H

    2001-12-01

    1. The present studies were aimed at testing the hypothesis that S-nitrosylated captopril (CapNO), a novel crystalline nitric oxide (NO) donor, readily permeates both in vitro and in vivo endothelial monolayers, resulting in its pharmacodynamic effects. 2. CapNO and Captopril (Cap) were added to apical side of endothelial monolayers formed on microporous membranes, and the permeated drugs were collected from basolateral side and detected by a HPLC method. The permeability coefficient (P(app); cm sec(-1)) of CapNO across the endothelial monolayers was 6.0 x 10(-5), higher than that of Cap (3.13 x 10(-5)), indicating the enhancement effect of the attached NO group in CapNO on cellular permeability. The P(app) of CapNO and Cap across Caco-2 cells were 3.15 x 10(-5) and 1.53 x 10(-5), respectively. The low P(app) of CapNO to Caco-2 cells may be attributed to the high membrane resistance of Caco-2 cells. 3. A bolus injection of CapNO to epicardial coronary artery of chronically-instrumented awake dogs caused significant increases in coronary blood flow and coronary diameters dose-dependently without significant changes in aortic pressure. In contrast, the equimolar doses of Cap did not produce haemodynamic responses. 4. Intravenous CapNO caused an instant increase in the regional cerebral blood flow determined by H(2)-clearance, whereas the equimolar doses of Cap did not enhance the cerebral blood flow. 5. These results conclude that the NO group, an active component of CapNO, enhances both in vitro and in vivo endothelial permeability to the entire compound, resulting in instant increases in blood flow and vascular diameters. In contrast, the equimolar Cap does not have the instant vascular effects.

  10. Circular Noncoding RNA HIPK3 Mediates Retinal Vascular Dysfunction in Diabetes Mellitus.

    PubMed

    Shan, Kun; Liu, Chang; Liu, Bai-Hui; Chen, Xue; Dong, Rui; Liu, Xin; Zhang, Yang-Yang; Liu, Ban; Zhang, Shu-Jie; Wang, Jia-Jian; Zhang, Sheng-Hai; Wu, Ji-Hong; Zhao, Chen; Yan, Biao

    2017-10-24

    The vascular complications of diabetes mellitus are the major causes of morbidity and mortality among people with diabetes. Circular RNAs are a class of endogenous noncoding RNAs that regulate gene expression in eukaryotes. In this study, we investigated the role of circular RNA in retinal vascular dysfunction induced by diabetes mellitus. Quantitative polymerase chain reactions, Sanger sequencing, and Northern blots were conducted to detect circular HIPK3 (circHIPK3) expression pattern on diabetes mellitus-related stresses. MTT (3-[4,5-dimethythiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assays, EdU (5-ethynyl-2'-deoxyuridine) incorporation assays, Transwell migration assays, and Matrigel assays were conducted to detect the role of circHIPK3 in retinal endothelial cell function in vitro. Retinal trypsin digestion, vascular permeability assays, and ELISA assays were conducted to detect the role of circHIPK3 in retinal vascular dysfunction in vivo. Bioinformatics analysis, luciferase activity assays, RNA pull-down assays, and in vitro studies were conducted to reveal the mechanism of circHIPK3-mediated retinal vascular dysfunction. circHIPK3 expression was significantly upregulated in diabetic retinas and retinal endothelial cells following stressors related to diabetes mellitus. circHIPK3 silencing or overexpressing circHIPK3 changed retinal endothelial cell viability, proliferation, migration, and tube formation in vitro. circHIPK3 silencing in vivo alleviated retinal vascular dysfunction, as shown by decreased retinal acellular capillaries, vascular leakage, and inflammation. circHIPK3 acted as an endogenous miR-30a-3p sponge to sequester and inhibit miR-30a-3p activity, which led to increased vascular endothelial growth factor-C, FZD4, and WNT2 expression. Ectopic expression of miR-30a-3p mimicked the effect of circHIPK3 silencing on vascular endothelial phenotypes in vivo and in vitro. The circular RNA circHIPK3 plays a role in diabetic retinopathy by

  11. Development of an ion-pair to improve the colon permeability of a low permeability drug: Atenolol.

    PubMed

    Lozoya-Agullo, Isabel; González-Álvarez, Isabel; González-Álvarez, Marta; Merino-Sanjuán, Matilde; Bermejo, Marival

    2016-10-10

    To ensure the optimal performance of oral controlled release formulations, drug colon permeability is one of the critical parameters. Consequently developing this kind of formulations for low permeability molecules requires strategies to increase their ability to cross the colonic membrane. The objective of this work is to show if an ion-pair formation can improve the colon permeability of atenolol as a low permeability drug model. Two counter ions have been tested: brilliant blue and bromophenol blue. The Distribution coefficients at pH7.00 (DpH7) of atenolol, atenolol + brilliant blue and atenolol + bromophenol blue were experimentally determined in n-octanol. Moreover, the colonic permeability was determined in rat colon using in situ closed loop perfusion method based in Doluisio's Technique. To check the potential effects of the counter ions on the membrane integrity, a histological assessment of colonic tissue was done. The results of the partitioning studies were inconclusive about ion-pair formation; nevertheless colon permeability was significantly increased by both counter ions (from 0.232±0.021cm/s to 0.508±0.038cm/s in the presence of brilliant blue and to 0.405±0.044cm/s in the presence of bromophenol blue). Neither damage on the membrane was observed on the histological studies, nor any change on paracellular permeability suggesting that the permeability enhancement could be attributed to the ion-pair formation. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Permeability-Porosity Relationships of Subduction Zone Sediments

    NASA Astrophysics Data System (ADS)

    Gamage, K.; Screaton, E.; Bekins, B.; Aiello, I.

    2008-12-01

    Permeability-porosity relationships for sediments from Northern Barbados, Costa Rica, Nankai, and Peru subduction zones were examined based on their sediment type and grain size distribution. Greater correlation was observed between permeability and porosity for siliciclastic sediments, diatom oozes, and nannofossil chalk than for nannofossil oozes. For siliciclastic sediments, grouping of sediments by clay content yields relationships that are generally consistent with results from other marine settings and suggest decreasing permeability for a given porosity as clay content increases. Correction of measured porosities for smectite content generally improves the quality of permeability-porosity relationships. The relationship between permeability and porosity for diatom oozes may be controlled by the amount of clay present in the ooze, causing diatom oozes to behave similarly to siliciclastic sediments. For a given porosity the nannofossil oozes have higher permeability values by 1.5 orders of magnitude than the siliciclastic sediments. However, the use of a permeability-porosity relation may not be appropriate for unconsolidated carbonates such as nannofossil oozes. This study provided insight to the effects of porosity correction for smectite, variations in lithology and grain size in permeability-porosity relationships. However, further progress in delineating controls on permeability will require more careful and better documented permeability tests on characterized samples.

  13. Biopharmaceutics permeability classification of lorcaserin, a selective 5-hydroxytryptamine 2C agonist: method suitability and permeability class membership.

    PubMed

    Chen, Chuan; Ma, Michael G; Fullenwider, Cody L; Chen, Weichao G; Sadeque, Abu J M

    2013-12-02

    The objectives of the study were (1) to demonstrate that a Caco-2 cell-based permeability assay, developed in our laboratory, is suitable to identify the permeability classification according to the US Food and Drug Administration Biopharmaceutics Classification System guidance, and (2) to use the validated Caco-2 method to determine permeability class membership of lorcaserin. Lorcaserin, marketed in United States as Belviq, is a selective human 5-hydroxytryptamine 2C agonist used for weight management. First, the permeability of twenty commercially available drugs was determined in the apical-to-basolateral direction at a final concentration of 10 μM, with the pH of transporter buffer in the apical and basolateral compartments being 6.8 and 7.4, respectively. A rank-order relationship between in vitro permeability results and the extent of human intestinal absorption for the drugs tested was observed. Second, the apparent permeability coefficient values of lorcaserin at 2, 20, and 200 μM and apical pH values of 6.8 and 7.4 in the apical-to-basolateral direction were determined using the validated method and found to be comparable to those of the high-permeability internal standard metoprolol. Lorcaserin permeability across Caco-2 cell monolayers was not dependent on the variation of apical pH. Furthermore, lorcaserin was not a substrate for efflux transporters such as P-glycoprotein. In conclusion, using the validated Caco-2 permeability assay, it was shown that lorcaserin is a highly permeable compound.

  14. Association of Classic Cardiovascular Risk Factors and Lifestyles With the Cardio-ankle Vascular Index in a General Mediterranean Population.

    PubMed

    Elosua-Bayés, Marc; Martí-Lluch, Ruth; García-Gil, María Del Mar; Camós, Lourdes; Comas-Cufí, Marc; Blanch, Jordi; Ponjoan, Anna; Alves-Cabratosa, Lia; Elosua, Roberto; Grau, María; Marrugat, Jaume; Ramos, Rafel

    2018-06-01

    The cardio-ankle vascular index (CAVI) assesses arterial stiffness. We aimed to describe the distribution of CAVI in a Mediterranean population, to determine the proportion of CAVI ≥ 9 by sex and coronary risk level, and to assess the association of CAVI with classic cardiovascular risk factors and lifestyle patterns. This cross-sectional study was based on the population of Girona province. The CAVI was measured using the VaSera VS-1500. Of 2613 individuals included in this study, the prevalence of CAVI ≥ 9 was 46.8% in men and 36.0% in women and significantly increased with coronary risk: from 21.1% and 24.8%, respectively to 76.7%, in the low-risk group, and 61.9% in the high-risk group. The CAVI increased with age in both sexes, being higher in men across all age groups. In men, CAVI ≥ 9 was associated with hypertension (OR, 2.70; 95%CI, 1.90-3.87) and diabetes (OR, 2.38; 95%CI, 1.52-3.78), body mass index (BMI) ≤ 25 to < 30 (OR, 0.44; 95%CI, 0.27-0.72) and BMI ≥ 30 (OR, 0.28; 95%CI, 0.14-0.58), and physical activity (OR, 0.66; 95%CI, 0.47-0.92). In women, CAVI ≥ 9 was associated with hypertension (OR, 2.22; 95%CI, 1.59-3.09), hypercholesterolemia (OR, 1.40; 95%CI, 1.01-1.94), and BMI ≥ 30 (OR, 0.38; 95%CI, 0.20-0.71). The CAVI increases with age and is higher in men than in women. This index is associated with classic risk factors and coronary risk. It could be a good predictive biomarker, but further follow-up studies are required to assess its added value to cardiovascular risk stratification. Copyright © 2017. Published by Elsevier España, S.L.U.

  15. End effects on stress dependent permeability measurements

    NASA Astrophysics Data System (ADS)

    Korsnes, R. I.; Risnes, R.; Faldaas, I.; Norland, T.

    2006-10-01

    Permeability changes have been studied under deviatoric stresses for chalk cores and under both hydrostatic- and deviatoric stresses for sandstone cores at room temperature. To avoid end effects in the triaxial cell, caused by friction between the axial steel pistons and the sample, the cell was modified to have pressure outlets from the mid-section of the sample with pressure tubes connected to the outside of the cell for pressure recording. Both permeabilities over the mid-section and over the total core were determined during the action of stresses. The chalk cores with permeability in the range of 1-3 × 10 - 15 m 2 and porosity of about 40-45% were flooded with methanol, while the sandstone cores with permeability values varying from 8 to 100 × 10 - 15 m 2 and porosity of about 30% were flooded with a mineral oil. Major observations were: For the chalk cores, 4 out of 8 samples showed a mid-section permeability with a factor of 1.2 to 1.4 higher than the overall permeability, the remaining 4 samples did not show differences in permeability values taking into account the error on measurements. For the sandstone samples, the mid-section permeability was a factor of 1.2 to 2.4 higher than the overall permeability. In all cases during the deviatoric phase, the change in permeability was rather small, even if the tests were run beyond the yield point. The permeability generally decreased with increasing hydrostatic stresses.

  16. Permeability of cork to gases.

    PubMed

    Faria, David P; Fonseca, Ana L; Pereira, Helen; Teodoro, Orlando M N D

    2011-04-27

    The permeability of gases through uncompressed cork was investigated. More than 100 samples were assessed from different plank qualities to provide a picture of the permeability distribution. A novel technique based on a mass spectrometer leak detector was used to directly measure the helium flow through the central area of small disks 10 mm in diameter and 2 mm thick. The permeability for nitrogen, oxygen, and other gases was measured by the pressure rise technique. Boiled and nonboiled cork samples from different sections were evaluated. An asymmetric frequency distribution ranging 3 orders of magnitude (roughly from 1 to 1000 μmol/(cm·atm·day)) for selected samples without macroscopic defects was found, having a peak below 100 μmol/(cm·atm·day). Correlation was found between density and permeability: higher density samples tend to show lower permeability. However, boiled cork showed a mean lower permeability despite having a lower density. The transport mechanism of gases through cork was also examined. Calculations suggest that gases permeate uncompressed cork mainly through small channels between cells under a molecular flow regime. The diameter of such channels was estimated to be in the range of 100 nm, in agreement with the plasmodesmata size in the cork cell walls.

  17. Fracture-permeability behavior of shale

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Carey, J. William; Lei, Zhou; Rougier, Esteban

    The fracture-permeability behavior of Utica shale, an important play for shale gas and oil, was investigated using a triaxial coreflood device and X-ray tomography in combination with finite-discrete element modeling (FDEM). Fractures generated in both compression and in a direct-shear configuration allowed permeability to be measured across the faces of cylindrical core. Shale with bedding planes perpendicular to direct-shear loading developed complex fracture networks and peak permeability of 30 mD that fell to 5 mD under hydrostatic conditions. Shale with bedding planes parallel to shear loading developed simple fractures with peak permeability as high as 900 mD. In addition tomore » the large anisotropy in fracture permeability, the amount of deformation required to initiate fractures was greater for perpendicular layering (about 1% versus 0.4%), and in both cases activation of existing fractures are more likely sources of permeability in shale gas plays or damaged caprock in CO₂ sequestration because of the significant deformation required to form new fracture networks. FDEM numerical simulations were able to replicate the main features of the fracturing processes while showing the importance of fluid penetration into fractures as well as layering in determining fracture patterns.« less

  18. Fracture-permeability behavior of shale

    DOE PAGES

    Carey, J. William; Lei, Zhou; Rougier, Esteban; ...

    2015-05-08

    The fracture-permeability behavior of Utica shale, an important play for shale gas and oil, was investigated using a triaxial coreflood device and X-ray tomography in combination with finite-discrete element modeling (FDEM). Fractures generated in both compression and in a direct-shear configuration allowed permeability to be measured across the faces of cylindrical core. Shale with bedding planes perpendicular to direct-shear loading developed complex fracture networks and peak permeability of 30 mD that fell to 5 mD under hydrostatic conditions. Shale with bedding planes parallel to shear loading developed simple fractures with peak permeability as high as 900 mD. In addition tomore » the large anisotropy in fracture permeability, the amount of deformation required to initiate fractures was greater for perpendicular layering (about 1% versus 0.4%), and in both cases activation of existing fractures are more likely sources of permeability in shale gas plays or damaged caprock in CO₂ sequestration because of the significant deformation required to form new fracture networks. FDEM numerical simulations were able to replicate the main features of the fracturing processes while showing the importance of fluid penetration into fractures as well as layering in determining fracture patterns.« less

  19. Lung heparan sulfates modulate Kfc during increased vascular pressure: evidence for glycocalyx-mediated mechanotransduction

    PubMed Central

    Cluff, Mark; Kingston, Joseph; Hill, Denzil; Chen, Haiyan; Hoehne, Soeren; Malleske, Daniel T.; Kaur, Rajwinederjit

    2012-01-01

    Lung endothelial cells respond to changes in vascular pressure through mechanotransduction pathways that alter barrier function via non-Starling mechanism(s). Components of the endothelial glycocalyx have been shown to participate in mechanotransduction in vitro and in systemic vessels, but the glycocalyx's role in mechanosensing and pulmonary barrier function has not been characterized. Mechanotransduction pathways may represent novel targets for therapeutic intervention during states of elevated pulmonary pressure such as acute heart failure, fluid overload, and mechanical ventilation. Our objective was to assess the effects of increasing vascular pressure on whole lung filtration coefficient (Kfc) and characterize the role of endothelial heparan sulfates in mediating mechanotransduction and associated increases in Kfc. Isolated perfused rat lung preparation was used to measure Kfc in response to changes in vascular pressure in combination with superimposed changes in airway pressure. The roles of heparan sulfates, nitric oxide, and reactive oxygen species were investigated. Increases in capillary pressure altered Kfc in a nonlinear relationship, suggesting non-Starling mechanism(s). nitro-l-arginine methyl ester and heparanase III attenuated the effects of increased capillary pressure on Kfc, demonstrating active mechanotransduction leading to barrier dysfunction. The nitric oxide (NO) donor S-nitrosoglutathione exacerbated pressure-mediated increase in Kfc. Ventilation strategies altered lung NO concentration and the Kfc response to increases in vascular pressure. This is the first study to demonstrate a role for the glycocalyx in whole lung mechanotransduction and has important implications in understanding the regulation of vascular permeability in the context of vascular pressure, fluid status, and ventilation strategies. PMID:22160307

  20. Pulmonary Vascular Input Impedance is a Combined Measure of Pulmonary Vascular Resistance and Stiffness and Predicts Clinical Outcomes Better than PVR Alone in Pediatric Patients with Pulmonary Hypertension

    PubMed Central

    Hunter, Kendall S.; Lee, Po-Feng; Lanning, Craig J.; Ivy, D. Dunbar; Kirby, K. Scott; Claussen, Lori R.; Chan, K. Chen; Shandas, Robin

    2011-01-01

    Background Pulmonary vascular resistance (PVR) is the current standard for evaluating reactivity in children with pulmonary arterial hypertension (PAH). However, PVR measures only the mean component of right ventricular afterload and neglects pulsatile effects. We recently developed and validated an method to measure pulmonary vascular input impedance, which revealed excellent correlation between the zero-harmonic impedance value and PVR, and suggested a correlation between higher harmonic impedance values and pulmonary vascular stiffness (PVS). Here we show that input impedance can be measured routinely and easily in the catheterization laboratory, that impedance provides PVR and PVS from a single measurement, and that impedance is a better predictor of disease outcomes compared to PVR. Methods Pressure and velocity waveforms within the main PA were measured during right-heart catheterization of patients with normal PA hemodynamics (n=14) and those with PAH undergoing reactivity evaluation (49 subjects; 95 conditions). A correction factor needed to transform velocity into flow was obtained by calibrating against cardiac output. Input impedance was obtained off-line by dividing Fourier-transformed pressure and flow waveforms. Results Exceptional correlation was found between the indexed zero harmonic of impedance and indexed PVR (y=1.095·x+1.381, R2=0.9620). Additionally, the modulus sum of the first two harmonics of impedance was found to best correlate with indexed pulse pressure over stroke volume (PP/SV) (y=13.39·x-0.8058, R2=0.7962). Amongst a subset of PAH patients (n=25), cumulative logistic regression between outcomes to total indexed impedance was better (RL2=0.4012) than between outcomes and indexed PVR (RL2=0.3131). Conclusions Input impedance can be consistently and easily obtained from PW Doppler and a single catheter pressure measurement, provides comprehensive characterization of the main components of RV afterload, and better predicts patient

  1. Oxidative Stress and Modification of Renal Vascular Permeability Are Associated with Acute Kidney Injury during P. berghei ANKA Infection

    PubMed Central

    Elias, Rosa Maria; Correa-Costa, Matheus; Barreto, Claudiene Rodrigues; Silva, Reinaldo Correia; Hayashida, Caroline Y.; Castoldi, Ângela; Gonçalves, Giselle Martins; Braga, Tarcio Teodoro; Barboza, Renato; Rios, Francisco José; Keller, Alexandre Castro; Cenedeze, Marcos Antonio; Hyane, Meire Ioshie; D'Império-Lima, Maria Regina; Figueiredo-Neto, Antônio Martins; Reis, Marlene Antônia; Marinho, Cláudio Romero Farias; Pacheco-Silva, Alvaro; Câmara, Niels Olsen Saraiva

    2012-01-01

    Malaria associated-acute kidney injury (AKI) is associated with 45% of mortality in adult patients hospitalized with severe form of the disease. However, the causes that lead to a framework of malaria-associated AKI are still poorly characterized. Some clinical studies speculate that oxidative stress products, a characteristic of Plasmodium infection, as well as proinflammatory response induced by the parasite are involved in its pathophysiology. Therefore, we aimed to investigate the development of malaria-associated AKI during infection by P. berghei ANKA, with special attention to the role played by the inflammatory response and the involvement of oxidative stress. For that, we took advantage of an experimental model of severe malaria that showed significant changes in the renal pathophysiology to investigate the role of malaria infection in the renal microvascular permeability and tissue injury. Therefore, BALB/c mice were infected with P. berghei ANKA. To assess renal function, creatinine, blood urea nitrogen, and ratio of proteinuria and creatininuria were evaluated. The products of oxidative stress, as well as cytokine profile were quantified in plasma and renal tissue. The change of renal microvascular permeability, tissue hypoxia and cellular apoptosis were also evaluated. Parasite infection resulted in renal dysfunction. Furthermore, we observed increased expression of adhesion molecule, proinflammatory cytokines and products of oxidative stress, associated with a decrease mRNA expression of HO-1 in kidney tissue of infected mice. The measurement of lipoprotein oxidizability also showed a significant increase in plasma of infected animals. Together, our findings support the idea that products of oxidative stress, as well as the immune response against the parasite are crucial to changes in kidney architecture and microvascular endothelial permeability of BALB/c mice infected with P. berghei ANKA. PMID:22952850

  2. Benchmarking of relative permeability

    NASA Astrophysics Data System (ADS)

    DiCarlo, D. A.

    2017-12-01

    Relative permeability is the key relation in terms of multi-phase flow through porous media. There are hundreds of published relative permeability curves for various media, some classic (Oak 90 and 91), some contradictory. This can lead to a confusing situation if one is trying to benchmark simulation results to "experimental data". Coming from the experimental side, I have found that modelers have too much trust in relative permeability data sets. In this talk, I will discuss reasons for discrepancies within and between data sets, and give guidance on which portions of the data sets are most solid in terms of matching through models.

  3. Clogging in permeable concrete: A review.

    PubMed

    Kia, Alalea; Wong, Hong S; Cheeseman, Christopher R

    2017-05-15

    Permeable concrete (or "pervious concrete" in North America) is used to reduce local flooding in urban areas and is an important sustainable urban drainage system. However, permeable concrete exhibits reduction in permeability due to clogging by particulates, which severely limits service life. This paper reviews the clogging mechanism and current mitigating strategies in order to inform future research needs. The pore structure of permeable concrete and characteristics of flowing particulates influence clogging, which occurs when particles build-up and block connected porosity. Permeable concrete requires regular maintenance by vacuum sweeping and pressure washing, but the effectiveness and viability of these methods is questionable. The potential for clogging is related to the tortuosity of the connected porosity, with greater tortuosity resulting in increased potential for clogging. Research is required to develop permeable concrete that can be poured on-site, which produces a pore structure with significantly reduced tortuosity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Permeable pavement study (Edison)

    EPA Pesticide Factsheets

    While permeable pavement is increasingly being used to control stormwater runoff, field-based, side-by-side investigations on the effects different pavement types have on nutrient concentrations present in stormwater runoff are limited. In 2009, the U.S. EPA constructed a 0.4-ha parking lot in Edison, New Jersey, that incorporated permeable interlocking concrete pavement (PICP), pervious concrete (PC), and porous asphalt (PA). Each permeable pavement type has four, 54.9-m2, lined sections that direct all infiltrate into 5.7-m3 tanks enabling complete volume collection and sampling. This paper highlights the results from a 12-month period when samples were collected from 13 rainfall/runoff events and analyzed for nitrogen species, orthophosphate, and organic carbon. Differences in infiltrate concentrations among the three permeable pavement types were assessed and compared with concentrations in rainwater samples and impervious asphalt runoff samples, which were collected as controls. Contrary to expectations based on the literature, the PA infiltrate had significantly larger total nitrogen (TN) concentrations than runoff and infiltrate from the other two permeable pavement types, indicating that nitrogen leached from materials in the PA strata. There was no significant difference in TN concentration between runoff and infiltrate from either PICP or PC, but TN in runoff was significantly larger than in the rainwater, suggesting meaningful inter-event dry de

  5. PTK787/ZK222584, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor, reduces uptake of the contrast agent GdDOTA by murine orthotopic B16/BL6 melanoma tumours and inhibits their growth in vivo.

    PubMed

    Rudin, Markus; McSheehy, Paul M J; Allegrini, Peter R; Rausch, Martin; Baumann, Diana; Becquet, Mike; Brecht, Karin; Brueggen, Josef; Ferretti, Stephane; Schaeffer, Fabienne; Schnell, Christian; Wood, Jeanette

    2005-08-01

    Assessment of tumour vascularity may characterize malignancy as well as predict responsiveness to anti-angiogenic therapy. Non-invasive measurement of tumour perfusion and blood vessel permeability assessed as the transfer constant, K(trans), can be provided by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Using the orthotopic murine tumour model B16/BL6 melanoma, the small contrast agent GdDOTA (DOTAREM(R); Guerbet, Paris) was applied to assess the vascular transfer constant, K(trans), and interstitial leakage space, whereas intravascular iron oxide nanoparticles (Endorem(R); Guerbet, Paris) were used to detect relative tumour blood volume (rTBV), and in one experiment blood flow index (BFI). No correlations were observed between these four parameters (r(2) always <0.05). The B16/BL6 primary tumour and lymph-node cervical (neck) metastases produced high levels of the permeability/growth factor, VEGF. To probe the model, the novel VEGF receptor (VEGF-R) tyrosine kinase inhibitor, PTK787/ZK222584 (PTK/ZK) was tested for anti-tumour efficacy and its effects on DCE-MRI measured parameters of tumour vascularity. Data from the non-invasive measure of tumour vascularity were compared with a histological measurement of vasculature using the DNA-staining dye H33342. PTK/ZK inhibited growth of the primary and, particularly, cervical tumour metastases following chronic treatment for 2 weeks (50 or 100 mg/kg daily) of 1-week-old tumours, or with 1 week of treatment against more established (2-week-old) tumours. After chronic treatment with PTK/ZK, DCE-MRI detected significant decreases in K(trans) and interstitial leakage space, but not rTBV of both primary tumours and cervical metastases. Histological data at this time-point showed a significant decrease in blood vessel density of the cervical metastases but not the primary tumours. However, in the cervical metastases, the mean blood vessel width was increased by 38%, suggesting overall no marked change in

  6. Negative index of refraction in metallic metamaterial comprising split-ring resonators.

    PubMed

    Dong, Zheng-Gao; Lei, Shuang-Ying; Xu, Ming-Xiang; Liu, Hui; Li, Tao; Wang, Fu-Ming; Zhu, Shi-Ning

    2008-05-01

    We numerically investigate the negative index of refraction in a metamaterial composed of metallic split-ring resonators, which exhibits simultaneously negative permittivity and permeability without resorting to additional metallic wires. It is confirmed that, in the left-handed band, negative permittivity is generated in analogy to the cut-wire metamaterial and negative permeability comes from the antisymmetric resonant mode, which occurs at a frequency band about 3 times higher than the fundamental magnetic resonance proposed by Pendry [IEEE Trans. Microwave Theory Tech. 47, 2075 (1999)].

  7. Endothelial Targeting of Semi-permeable Polymer Nanocarriers for Enzyme Therapies

    PubMed Central

    Dziubla, Thomas D; Shuvaev, Vladimir V.; Hong, Nan Kang; Hawkins, Brian; Muniswamy, Madesh; Takano, Hajime; Simone, Eric; Nakada, Marian T.; Fisher, Aron; Albelda, Steven M.; Muzykantov, Vladimir R.

    2007-01-01

    The medical utility of proteins, e.g. therapeutic enzymes, is greatly restricted by their liable nature and inadequate delivery. Most therapeutic enzymes do not accumulate in their targets and are inactivated by proteases. Targeting of enzymes encapsulated into substrate-permeable Polymeric Nano-Carriers (PNC) impermeable for proteases might overcome these limitations. To test this hypothesis, we designed endothelial targeted PNC loaded with catalase, the H2O2-detoxifying enzyme, and tested if this approach protects against vascular oxidative stress, a pathological process implicated in ischemia-reperfusion and other disease conditions. Encapsulation of catalase (MW 240KD), peroxidase (MW 42kD) and xanthine oxidase (XO, MW 300 kD) into ~300nm diameter PNC composed of co-polymers of PEG-PLGA (polyethylene glycol and poly-lactic/poly-glycolic acid) was in the range ~10% for all enzymes. PNC/catalase and PNC/peroxidase were protected from external proteolysis and exerted the enzymatic activity on their PNC diffusible substrates, H2O2 and ortho-phenylendiamine, whereas activity of encapsulated XO was negligible due to polymer impermeability to the substrate. PNC targeted to platelet-endothelial cell adhesion molecule-1 delivered active encapsulated catalase to endothelial cells and protected the endothelium against oxidative stress in cell culture and animal studies. Vascular targeting of PNC-loaded detoxifying enzymes may find wide medical applications including management of oxidative stress and other toxicities. PMID:17950837

  8. Dexamethasone reverses the effects of high glucose on human retinal endothelial cell permeability and proliferation in vitro.

    PubMed

    Stewart, E A; Saker, S; Amoaku, W M

    2016-10-01

    Diabetic macular oedema (DMO), a leading cause of preventable visual loss in the working population, is caused by an increase in microvascular endothelial cell permeability, and its prevalence is on the increase in parallel with the rising worldwide prevalence of diabetes. It is known that retinal vascular leakage in DMO is contributed to by VEGF upregulation as well as non-VEGF dependent inflammatory pathways, and the potential use of anti-inflammatory agents such as the glucocorticoids, including dexamethasone are being extensively studied. However, the mechanisms of action of dexamethasone in DMO reduction are not fully understood. Using human primary retinal endothelial cells (REC) the in vitro effect of dexamethasone in modulating the proliferation, permeability and gene expression of key tight and adheren junction components, and the expression of angiopoietins (Ang) 1 and 2 in high (25 mM) glucose conditions were investigated. High glucose decreased REC proliferation, an effect that was reversed by dexamethasone. High glucose conditions significantly increased REC permeability and decreased claudin-5, occludin and JAM-A gene expression; dexamethasone was effective in partially reversing these changes, restoring EC permeability to the normal or near normal state. High glucose levels resulted in reduction of Ang1 secretion, although Ang2 levels were consistently high. DEX increased Ang1 and decreased Ang2, indicating that the balance of Ang1/Ang2 may be important in determining functional changes in REC under high glucose conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Crustal permeability: Introduction to the special issue

    USGS Publications Warehouse

    Ingebritsen, Steven E.; Gleeson, Tom

    2015-01-01

    The topic of crustal permeability is of broad interest in light of the controlling effect of permeability on diverse geologic processes and also timely in light of the practical challenges associated with emerging technologies such as hydraulic fracturing for oil and gas production (‘fracking’), enhanced geothermal systems, and geologic carbon sequestration. This special issue of Geofluids is also motivated by the historical dichotomy between the hydrogeologic concept of permeability as a static material property that exerts control on fluid flow and the perspective of economic geologists, geophysicists, and crustal petrologists who have long recognized permeability as a dynamic parameter that changes in response to tectonism, fluid production, and geochemical reactions. Issues associated with fracking, enhanced geothermal systems, and geologic carbon sequestration have already begun to promote a constructive dialog between the static and dynamic views of permeability, and here we have made a conscious effort to include both viewpoints. This special issue also focuses on the quantification of permeability, encompassing both direct measurement of permeability in the uppermost crust and inferential permeability estimates, mainly for the deeper crust.

  10. Radiation-induced changes in the profile of spinal cord serotonin, prostaglandin synthesis, and vascular permeability

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Siegal, T.; Pfeffer, M.R.

    To investigate the profile of biochemical and physiological changes induced in the rat spinal cord by radiation, over a period of 8 months. The thoraco-lumbar spinal cords of Fisher rats were irradiated to a dose of 15 Gy. The rats were then followed and killed at various times afterward. Serotonin (5-HT) and its major metabolite 5-hydroxyindole-3-acetic acid (5-HIAA) were assayed as well as prostaglandin synthesis. Microvessel permeability was assessed by quantitative evaluation of Evans blue dye extravasation. None of the rats developed neurologic dysfunction, and histologic examination revealed only occasional gliosis in the ventral white matter at 240 days aftermore » irradiation. Serotonin levels were unchanged at 2, 14, and 56 days after radiation but increased at 120 and 240 days in the irradiated cord segments when compared to both the nonirradiated thoracic and cervical segments (p < 0.01) and age-matched controls (p < 0.03). The calculated utilization ratio of serotonin (5-HIAA/5-HT) remained unchanged. Immediately after radiation (at 3 and 24 h) an abrupt but brief increase in the synthesis of prostaglandin-E{sub 2} (PGE{sub 2}), thromboxane (TXB{sub 2}), and prostacyclin [6 keto-PGF1{alpha} (6KPGF)] was noted, which returned to normal at 3 days. This was followed after 7 and 14 days by a significant fall off in synthesis of all three prostaglandins. Thereafter, at 28, 56, 120, and 240 days, escalated production of thromboxane followed, white prostacyclin synthesis remained markedly reduced (-88% of control level at 240 days). Up to 7 days after radiation the calculated TXB{sub 2}/6KPGF ratio remained balanced, regardless of the observed abrupt early fluctuations in their rate of synthesis. Later, between 7 and 240 days after radiation, a significant imbalance was present which became more pronounced over time. In the first 24 h after radiation, a 104% increase in microvessel permeability was observed which returned to normal by 3 days. 57 refs., 3

  11. Interleukin-17A and vascular remodelling in severe asthma; lack of evidence for a direct role.

    PubMed

    Panariti, A; Baglole, C J; Sanchez, V; Eidelman, D H; Hussain, S; Olivenstein, R; Martin, J G; Hamid, Q

    2018-04-01

    Bronchial vascular remodelling may contribute to the severity of airway narrowing through mucosal congestion. Interleukin (IL)-17A is associated with the most severe asthmatic phenotype but whether it might contribute to vascular remodelling is uncertain. To assess vascular remodelling in severe asthma and whether IL-17A directly or indirectly may cause endothelial cell activation and angiogenesis. Bronchial vascularization was quantified in asthmatic subjects, COPD and healthy subjects together with the number of IL-17A + cells as well as the concentration of angiogenic factors in the sputum. The effect of IL-17A on in vitro angiogenesis, cell migration and endothelial permeability was assessed directly on primary human lung microvascular endothelial cells (HMVEC-L) or indirectly with conditioned medium derived from normal bronchial epithelial cells (NHBEC), fibroblasts (NHBF) and airway smooth muscle cells (ASMC) after IL-17A stimulation. Severe asthmatics have increased vascularity compared to the other groups, which correlates positively with the concentrations of angiogenic factors in sputum. Interestingly, we demonstrated that increased bronchial vascularity correlates positively with the number of subepithelial IL-17A + cells. However IL-17A had no direct effect on HMVEC-L function but it enhanced endothelial tube formation and cell migration through the production of angiogenic factors by NHBE and ASMC. Our results shed light on the role of IL-17A in vascular remodelling, most likely through stimulating the synthesis of other angiogenic factors. Knowledge of these pathways may aid in the identification of new therapeutic targets. © 2018 John Wiley & Sons Ltd.

  12. Quality of vascular surgery Web sites on the Internet.

    PubMed

    Grewal, Perbinder; Williams, Bryn; Alagaratnam, Swethan; Neffendorf, James; Soobrah, Ritish

    2012-11-01

    This study evaluated the readability, accessibility, usability, and reliability of vascular surgery information on the Internet in the English language. The Google, Yahoo, and MSN/Bing search engines were searched for "carotid endarterectomy," "EVAR or endovascular aneurysm repair," and "varicose veins or varicose veins surgery." The first 50 Web sites from each search engine for each topic were analyzed. The Flesch Reading Ease Score and Gunning Fog Index were calculated to assess readability. The LIDA tool (Minervation Ltd, Oxford, UK) was used to assess accessibility, usability, and reliability. The Web sites were difficult to read and comprehend. The mean Flesch Reading Ease scores were 53.53 for carotid endarterectomy, 50.53 for endovascular aneurysm repair, and 58.59 for varicose veins. The mean Gunning Fog Index scores were 12.3 for carotid endarterectomy, 12.12 for endovascular aneurysm repair, and 10.69 for varicose veins. The LIDA values for accessibility were good, but the results for usability and reliability were poor. Internet information on vascular surgical conditions and procedures is poorly written and unreliable. We suggest that health professionals should recommend Web sites that are easy to read and contain high-quality surgical information. Medical information on the Internet must be readable, accessible, usable, and reliable. Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

  13. Retinal microvascular changes and subsequent vascular events after ischemic stroke.

    PubMed

    De Silva, D A; Manzano, J J F; Liu, E Y; Woon, F-P; Wong, W-X; Chang, H-M; Chen, C; Lindley, R I; Wang, J J; Mitchell, P; Wong, T-Y; Wong, M-C

    2011-08-30

    Retinal microvasculature changes are associated with vascular events including stroke in healthy populations. It is not known whether retinal microvascular changes predict recurrent vascular events after ischemic stroke. We examined the relationship between retinal microvascular signs and subsequent vascular events in a prospective cohort of 652 acute ischemic stroke patients admitted to a tertiary hospital in Singapore from 2005 to 2007. Retinal photographs taken within 1 week of stroke onset were assessed in a masked manner for quantitative and qualitative measures. Follow-up data over 2-4 years were obtained by standardized telephone interview and then were verified from medical records. Predictors of recurrent vascular events (cerebrovascular, coronary, vascular death, and composite vascular events) were determined using Cox regression models. Follow-up data over a median of 29 months were obtained for 89% (652 patients) of the cohort. After adjustment for covariates including traditional risk factors and index stroke etiology, patients with severe arteriovenous nicking (AVN) were more likely to have a recurrent cerebrovascular event (hazard ratio [HR] 2.28, 95% confidence interval [CI] 1.20-4.33) compared with those without AVN. Patients with severe focal arteriolar narrowing (FAN) were more likely to have a recurrent cerebrovascular event (HR 2.75, 95% CI 1.14-6.63) or subsequent composite vascular event (HR 2.77, 95% CI 1.31-5.86) compared to those without FAN. Retinal microvascular changes predicted subsequent vascular events after ischemic stroke, independent of traditional risk factors and stroke subtype. Thus, retinal imaging has a potential role in predicting the risk of recurrent vascular events after ischemic stroke and in understanding novel vascular risk factors.

  14. Production of Experimental Malignant Pleural Effusions Is Dependent on Invasion of the Pleura and Expression of Vascular Endothelial Growth Factor/Vascular Permeability Factor by Human Lung Cancer Cells

    PubMed Central

    Yano, Seiji; Shinohara, Hisashi; Herbst, Roy S.; Kuniyasu, Hiroki; Bucana, Corazon D.; Ellis, Lee M.; Fidler, Isaiah J.

    2000-01-01

    We determined the molecular mechanisms that regulate the pathogenesis of malignant pleural effusion (PE) associated with advanced stage of human, non-small-cell lung cancer. Intravenous injection of human PC14 and PC14PE6 (adenocarcinoma) or H226 (squamous cell carcinoma) cells into nude mice yielded numerous lung lesions. PC14 and PC14PE6 lung lesions invaded the pleura and produced PE containing a high level of vascular endothelial growth factor (VEGF)-localized vascular hyperpermeability. Lung lesions produced by H226 cells were confined to the lung parenchyma with no PE. The level of expression of VEGF mRNA and protein by the cell lines directly correlated with extent of PE formation. Transfection of PC14PE6 cells with antisense VEGF165 gene did not inhibit invasion into the pleural space but reduced PE formation. H226 cells transfected with either sense VEGF 165 or sense VEGF 121 genes induced localized vascular hyperpermeability and produced PE only after direct implantation into the thoracic cavity. The production of PE was thus associated with the ability of tumor cells to invade the pleura, a property associated with expression of high levels of urokinase-type plasminogen activator and low levels of TIMP-2. Collectively, the data demonstrate that the production of malignant PE requires tumor cells to invade the pleura and express high levels of VEGF/VPF. PMID:11106562

  15. Relationship between the Kramers-Kronig relations and negative index of refraction

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Akyurtlu, Alkim; Kussow, Adil-Gerai

    2010-11-15

    The condition for a negative index of refraction with respect to the vacuum index is established in terms of permittivity and permeability susceptibilities. It is found that the imposition of analyticity to satisfy the Kramers-Kronig relations is a sufficiently general criterion for a physical negative index. The satisfaction of the Kramers-Kronig relations is a manifestation of the principle of causality and the predicted frequency region of negative index agrees with the Depine-Lakhtakia condition for the phase velocity being antidirected to the Poynting vector, although the conditions presented here do not assume a priori a negative solution branch for n.

  16. Studies on increased vascular permeability in the pathogenesis of lesions of connective tissue diseases: I. Experimental hyperlipidaemia and immune arthropathy.

    PubMed

    Valente, A J; Walton, K W

    1980-10-01

    In order to investigate the known associations between hyperlipidaemia and various rheumatic complaints, immune arthritis and hyperlipidaemia have been induced concurrently in rabbits. The results obtained show that: (1) Rabbit apolipoprotein B-containing lipoproteins (LpB), which are normally virtually excluded from joint fluid, gain access to the inflamed joint in the serous effusion and serve as intrinsic indicators of altered local permeability to macromolecules. (2) Much of the LpB entering the joint space is taken up by the phagocytic cells and, following intracellular hydrolysis, leaves a lipid residue. In some chronically affected joints these residues are modified so as to give rise to crystalline cholesterol and its esters. Such crystals may serve as a chronic irritant in the joint. (3) In addition intact LpB is found sequestered in the superficial layers of intra-articular collagenous structures of the challenged joint in a distribution identical with that of similarly sequestered immune complexes and complement, suggesting altered permeability of these intra-articular structures also.

  17. Platelet Vascular Endothelial Growth Factor is a Potential Mediator of Transfusion-Related Acute Lung Injury.

    PubMed

    Maloney, James P; Ambruso, Daniel R; Voelkel, Norbert F; Silliman, Christopher C

    The occurrence of non-hemolytic transfusion reactions is highest with platelet and plasma administration. Some of these reactions are characterized by endothelial leak, especially transfusion related acute lung injury (TRALI). Elevated concentrations of inflammatory mediators secreted by contaminating leukocytes during blood product storage may contribute to such reactions, but platelet-secreted mediators may also contribute. We hypothesized that platelet storage leads to accumulation of the endothelial permeability mediator vascular endothelial growth factor (VEGF), and that intravascular administration of exogenous VEGF leads to extensive binding to its lung receptors. Single donor, leukocyte-reduced apheresis platelet units were sampled over 5 days of storage. VEGF protein content of the centrifuged supernatant was determined by ELISA, and the potential contribution of VEGF from contaminating leukocytes was quantified. Isolated-perfused rat lungs were used to study the uptake of radiolabeled VEGF administered intravascularly, and the effect of unlabeled VEGF on lung leak. There was a time-dependent release of VEGF into the plasma fraction of the platelet concentrates (62 ± 9 pg/ml on day one, 149 ± 23 pg/ml on day 5; mean ± SEM, p<0.01, n=8) and a contribution by contaminating leukocytes was excluded. Exogenous 125I-VEGF bound avidly and specifically to the lung vasculature, and unlabeled VEGF in the lung perfusate caused vascular leak. Rising concentrations of VEGF occur during storage of single donor platelet concentrates due to platelet secretion or disintegration, but not due to leukocyte contamination. Exogenous VEGF at these concentrations rapidly binds to its receptors in the lung vessels. At higher VEGF concentrations, VEGF causes vascular leak in uninjured lungs. These data provide further evidence that VEGF may contribute to the increased lung permeability seen in TRALI associated with platelet products.

  18. Permeability Asymmetry in Composite Porous Ceramic Membranes

    NASA Astrophysics Data System (ADS)

    Kurcharov, I. M.; Laguntsov, N. I.; Uvarov, V. I.; Kurchatova, O. V.

    The results from the investigation of transport characteristics and gas transport asymmetry in bilayer composite membranes are submitted. These membranes are produced by SHS method. Asymmetric effect and hysteresis of permeability in nanoporous membranes are detected. It's shown, that permeability ratio (asymmetry value of permeability) increases up to several times. The asymmetry of permeability usually decreases monotonically with the pressure decrease.

  19. Strain-dependent permeability of volcanic rocks.

    NASA Astrophysics Data System (ADS)

    Farquharson, Jamie; Heap, Michael; Baud, Patrick

    2016-04-01

    We explore permeability evolution during deformation of volcanic materials using a suite of rocks with varying compositions and physical properties (such as porosity ϕ). 40 mm × 20 mm cylindrical samples were made from a range of extrusive rocks, including andesites from Colima, Mexico (ϕ˜0.08; 0.18; 0.21), Kumamoto, Japan (ϕ˜0.13), and Ruapehu, New Zealand (ϕ˜0.15), and basalt from Mt Etna, Italy (ϕ˜0.04). Gas permeability of each sample was measured before and after triaxial deformation using a steady-state benchtop permeameter. To study the strain-dependence of permeability in volcanic rocks, we deformed samples to 2, 3, 4, 6, and 12 % axial strain at a constant strain rate of 10-5 s-1. Further, the influence of failure mode - dilatant or compactant - on permeability was assessed by repeating experiments at different confining pressures. During triaxial deformation, porosity change of the samples was monitored by a servo-controlled pore fluid pump. Below an initial porosity of ˜0.18, and at low confining pressures (≤ 20 MPa), we observe a dilatant failure mode (shear fracture formation). With increasing axial strain, stress is accommodated by fault sliding and the generation of ash-sized gouge between the fracture planes. In higher-porosity samples, or at relatively higher confining pressures (≥ 60 MPa), we observe compactant deformation characterised by a monotonous decrease in porosity with increasing axial strain. The relative permeability k' is given by the change in permeability divided by the initial reference state. When behaviour is dilatant, k' tends to be positive: permeability increases with progressive deformation. However, results suggest that after a threshold amount of strain, k' can decrease. k' always is negative (permeability decreases during deformation) when compaction is the dominant behaviour. Our results show that - in the absence of a sealing or healing process - the efficiency of a fault to transmit fluids is correlated to

  20. Running multiple marathons is not a risk factor for premature subclinical vascular impairment.

    PubMed

    Pressler, Axel; Suchy, Christiane; Friedrichs, Tasja; Dallinger, Sophia; Grabs, Viola; Haller, Bernhard; Halle, Martin; Scherr, Johannes

    2017-08-01

    Background In contrast to the well-accepted benefits of moderate exercise, recent research has suggested potential deleterious effects of repeated marathon running on the cardiovascular system. We thus performed a comprehensive analysis of markers of subclinical vascular damage in a cohort of runners having finished multiple marathon races successfully. Design This was a prospective, observational study. Methods A total of 97 healthy male Munich marathon participants (mean age 44 ± 10 years) underwent detailed training history, cardiopulmonary exercise testing for assessment of peak oxygen uptake, ultrasound for assessment of intima-media-thickness as well as non-invasive assessments of ankle-brachial index, augmentation index, pulse wave velocity and reactive hyperaemia index. Results Runners had previously completed a median of eight (range 1-500) half marathons, six (1-100) full marathons and three (1-40) ultramarathons; mean weekly and annual training volumes were 59 ± 23 and 1639 ± 979 km. Mean peak oxygen uptake was 50 ± 8 ml/min/kg, and the Munich marathon was finished in 3:45 ± 0:32 h. Runners showed normal mean values for intima-media-thickness (0.60 ± 0.14 mm), ankle-brachial index (1.2 ± 0.1), augmentation index (17 ± 13%), pulse wave velocity (8.7 ± 1.4 cm/s) and reactive hyperaemia index (1.96 ± 0.50). Age was significantly and independently associated with intima-media-thickness ( r = 0.531; p < 0.001), augmentation index ( r = 0.593; p < 0.001) and pulse wave velocity ( r = 0.357; p < 0.001). However, no independent associations of peak oxygen uptake, marathon finishing time, number of completed races or weekly and annual training km with any of the vascular parameters were observed. Conclusions In this cohort of healthy male runners, running multiple marathon races did not pose an additional risk factor for premature subclinical vascular impairment beyond age.

  1. Resveratrol Ameliorates Arterial Stiffness Assessed by Cardio-Ankle Vascular Index in Patients With Type 2 Diabetes Mellitus.

    PubMed

    Imamura, Haruki; Yamaguchi, Takashi; Nagayama, Daiji; Saiki, Atsuhito; Shirai, Kohji; Tatsuno, Ichiro

    2017-08-03

    Resveratrol has been reported to have potent anti-atherosclerotic effects in animal studies. However, there are few interventional studies in human patients with atherosclerogenic diseases. The cardio-ankle vascular index (CAVI) reflects arterial stiffness and is a clinical surrogate marker of atherosclerosis. The aim of the present study was to investigate the effect of resveratrol on arterial stiffness assessed by CAVI in patients with type 2 diabetes mellitus (T2DM).In this double-blind, randomized, placebo-controlled study, 50 patients with T2DM received supplement of a 100mg resveratrol tablet (total resveratrol: oligo-stilbene 27.97 mg/100 mg/day) or placebo daily for 12 weeks. CAVI was assessed at baseline and the end of study. Body weight (BW), blood pressure (BP), glucose and lipid metabolic parameters, and diacron-reactive oxygen metabolites (d-ROMs; an oxidative stress marker) were also measured.Resveratrol supplementation decreased systolic BP (-5.5 ± 13.0 mmHg), d-ROMs (-25.6 ± 41.8 U.CARR), and CAVI (-0.4 ± 0.7) significantly (P < 0.05) and decreased BW (-0.8 ± 2.1 kg, P = 0.083) and body mass index (-0.5 ± 0.8 kg/m 2 , P = 0.092) slightly compared to baseline, while there were no significant changes in the placebo group. Decreases in CAVI and d-ROMs were significantly greater in the resveratrol group than in the placebo group. Multivariate logistic regression analysis identified resveratrol supplementation as an independent predictor for a CAVI decrease of more than 0.5.In conclusion, 12-week resveratrol supplementation may improve arterial stiffness and reduce oxidative stress in patients with T2DM. Resveratrol may be beneficial in preventing the development of atherosclerosis induced by diabetes. However, a large-scale cohort study is required to validate the present findings.

  2. Permeability and permeability anisotropy in Crab Orchard sandstone: Experimental insights into spatio-temporal effects

    NASA Astrophysics Data System (ADS)

    Gehne, Stephan; Benson, Philip M.

    2017-08-01

    Permeability in tight crustal rocks is primarily controlled by the connected porosity, shape and orientation of microcracks, the preferred orientation of cross-bedding, and sedimentary features such as layering. This leads to a significant permeability anisotropy. Less well studied, however, are the effects of time and stress recovery on the evolution of the permeability hysteresis which is becoming increasingly important in areas ranging from fluid migration in ore-forming processes to enhanced resource extraction. Here, we report new data simulating spatio-temporal permeability changes induced using effective pressure, simulating burial depth, on a tight sandstone (Crab Orchard). We find an initially (measured at 5 MPa) anisotropy of 2.5% in P-wave velocity and 180% in permeability anisotropy is significantly affected by the direction of the effective pressure change and cyclicity; anisotropy values decrease to 1% and 10% respectively after 3 cycles to 90 MPa and back. Furthermore, we measure a steadily increasing recovery time (10-20 min) for flow parallel to cross-bedding, and a far slower recovery time (20-50 min) for flow normal to cross-bedding. These data are interpreted via strain anisotropy and accommodation models, similar to the "seasoning" process often used in dynamic reservoir extraction.

  3. Vascular Anomalies (Part I): Classification and Diagnostics of Vascular Anomalies.

    PubMed

    Sadick, Maliha; Müller-Wille, René; Wildgruber, Moritz; Wohlgemuth, Walter A

    2018-06-06

    Vascular anomalies are a diagnostic and therapeutic challenge. They require dedicated interdisciplinary management. Optimal patient care relies on integral medical evaluation and a classification system established by experts in the field, to provide a better understanding of these complex vascular entities.  A dedicated classification system according to the International Society for the Study of Vascular Anomalies (ISSVA) and the German Interdisciplinary Society of Vascular Anomalies (DiGGefA) is presented. The vast spectrum of diagnostic modalities, ranging from ultrasound with color Doppler, conventional X-ray, CT with 4 D imaging and MRI as well as catheter angiography for appropriate assessment is discussed.  Congenital vascular anomalies are comprised of vascular tumors, based on endothelial cell proliferation and vascular malformations with underlying mesenchymal and angiogenetic disorder. Vascular tumors tend to regress with patient's age, vascular malformations increase in size and are subdivided into capillary, venous, lymphatic, arterio-venous and combined malformations, depending on their dominant vasculature. According to their appearance, venous malformations are the most common representative of vascular anomalies (70 %), followed by lymphatic malformations (12 %), arterio-venous malformations (8 %), combined malformation syndromes (6 %) and capillary malformations (4 %).  The aim is to provide an overview of the current classification system and diagnostic characterization of vascular anomalies in order to facilitate interdisciplinary management of vascular anomalies.   · Vascular anomalies are comprised of vascular tumors and vascular malformations, both considered to be rare diseases.. · Appropriate treatment depends on correct classification and diagnosis of vascular anomalies, which is based on established national and international classification systems, recommendations and guidelines.. · In the classification

  4. Discontinuities in effective permeability due to fracture percolation

    DOE PAGES

    Hyman, Jeffrey De'Haven; Karra, Satish; Carey, James William; ...

    2018-01-31

    Motivated by a triaxial coreflood experiment with a sample of Utica shale where an abrupt jump in permeability was observed, possibly due to the creation of a percolating fracture network through the sample, we perform numerical simulations based on the experiment to characterize how the effective permeability of otherwise low-permeability porous media depends on fracture formation, connectivity, and the contrast between the fracture and matrix permeabilities. While a change in effective permeability due to fracture formation is expected, the dependence of its magnitude upon the contrast between the matrix permeability and fracture permeability and the fracture network structure is poorlymore » characterized. We use two different high-fidelity fracture network models to characterize how effective permeability changes as percolation occurs. The first is a dynamic two-dimensional fracture propagation model designed to mimic the laboratory settings of the experiment. The second is a static three-dimensional discrete fracture network (DFN) model, whose fracture and network statistics are based on the fractured sample of Utica shale. Once the network connects the inflow and outflow boundaries, the effective permeability increases non-linearly with network density. In most networks considered, a jump in the effective permeability was observed when the embedded fracture network percolated. We characterize how the magnitude of the jump, should it occur, depends on the contrast between the fracture and matrix permeabilities. For small contrasts between the matrix and fracture permeabilities the change is insignificant. However, for larger contrasts, there is a substantial jump whose magnitude depends non-linearly on the difference between matrix and fracture permeabilities. A power-law relationship between the size of the jump and the difference between the matrix and fracture permeabilities is observed. In conclusion, the presented results underscore the importance of

  5. Discontinuities in effective permeability due to fracture percolation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hyman, Jeffrey De'Haven; Karra, Satish; Carey, James William

    Motivated by a triaxial coreflood experiment with a sample of Utica shale where an abrupt jump in permeability was observed, possibly due to the creation of a percolating fracture network through the sample, we perform numerical simulations based on the experiment to characterize how the effective permeability of otherwise low-permeability porous media depends on fracture formation, connectivity, and the contrast between the fracture and matrix permeabilities. While a change in effective permeability due to fracture formation is expected, the dependence of its magnitude upon the contrast between the matrix permeability and fracture permeability and the fracture network structure is poorlymore » characterized. We use two different high-fidelity fracture network models to characterize how effective permeability changes as percolation occurs. The first is a dynamic two-dimensional fracture propagation model designed to mimic the laboratory settings of the experiment. The second is a static three-dimensional discrete fracture network (DFN) model, whose fracture and network statistics are based on the fractured sample of Utica shale. Once the network connects the inflow and outflow boundaries, the effective permeability increases non-linearly with network density. In most networks considered, a jump in the effective permeability was observed when the embedded fracture network percolated. We characterize how the magnitude of the jump, should it occur, depends on the contrast between the fracture and matrix permeabilities. For small contrasts between the matrix and fracture permeabilities the change is insignificant. However, for larger contrasts, there is a substantial jump whose magnitude depends non-linearly on the difference between matrix and fracture permeabilities. A power-law relationship between the size of the jump and the difference between the matrix and fracture permeabilities is observed. In conclusion, the presented results underscore the importance of

  6. EPA Permeable Surface Research - Poster

    EPA Science Inventory

    EPA recognizes permeable surfaces as an effective post-construction infiltration-based Best Management Practice to mitigate the adverse effects of stormwater runoff. The professional user community conceptually embraces permeable surfaces as a tool for making runoff more closely...

  7. Membrane stress increases cation permeability in red cells.

    PubMed

    Johnson, R M

    1994-11-01

    The human red cell is known to increase its cation permeability when deformed by mechanical forces. Light-scattering measurements were used to quantitate the cell deformation, as ellipticity under shear. Permeability to sodium and potassium was not proportional to the cell deformation. An ellipticity of 0.75 was required to increase the permeability of the membrane to cations, and flux thereafter increased rapidly as the limits of cell extension were reached. Induction of membrane curvature by chemical agents also did not increase cation permeability. These results indicate that membrane deformation per se does not increase permeability, and that membrane tension is the effector for increased cation permeability. This may be relevant to some cation permeabilities observed by patch clamping.

  8. Exendin-4 alleviates retinal vascular leakage by protecting the blood-retinal barrier and reducing retinal vascular permeability in diabetic Goto-Kakizaki rats.

    PubMed

    Fan, Yichao; Liu, Kun; Wang, Qingping; Ruan, Yuanyuan; Ye, Wen; Zhang, Yu

    2014-10-01

    The breakdown of the inner endothelial blood-retinal barrier (BRB) and subsequent retinal vascular leakage are the main causes of vision loss due to diabetic retinopathy (DR). Exendin-4 (E4) is a long-acting agonist of the glucagon-like peptide 1 hormone receptor (GLP-1R) that is widely used in clinics and has shown a neuroprotective effect. Our previous studies demonstrated the protective effect of E4 in early experimental DR; however, the molecular and cellular mechanisms that mediate this protective effect are not fully known. The BRB plays a key role in DR. We speculated that E4 may exert its protective effects on the BRB. To test this hypothesis, E4 (0.1 μg/2 μL/eye) or vehicle were intravitreally injected into diabetic Goto-Kakizaki(GK) rats and control animals. The results revealed that E4 significantly inhibited the reductions in electroretinogram (ERG) amplitudes in the GK rats, particularly in the b-wave and oscillatory potentials (OPs). E4 upregulated retinal GLP-1R expression and downregulated the expressions of placental growth factor (PLGF) and vascular endothelial growth factor (VEGF) via the ERK and AKT/PKB pathways. Decreases in tight junction protein (i.e., claudin-5 and occludin) expression and increases in Evans blue permeation (EBP) were inhibited by E4. Similar results were also found in primary rat Müller cells in high glucose concentration cultures in vitro. We conclude that E4 may protect the BRB from diabetic insults by decreasing PLGF and ICAM-1 expression and maintaining the integrity of the BRB. Thus, E4 treatment may be an effective therapeutic approach for DR. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Vapor-liquid phase separator permeability results

    NASA Technical Reports Server (NTRS)

    Yuan, S. W. K.; Frederking, T. H. K.

    1981-01-01

    Continued studies are described in the area of vapor-liquid phase separator work with emphasis on permeabilities of porous sintered plugs (stainless steel, nominal pore size 2 micrometer). The temperature dependence of the permeability has been evaluated in classical fluid using He-4 gas at atmospheric pressure and in He-2 on the basis of a modified, thermosmotic permeability of the normal fluid.

  10. Expression of vascular endothelial growth factor mRNA in non-small-cell lung carcinomas

    PubMed Central

    Fontanini, G; Boldrini, L; Chinè, S; Pisaturo, F; Basolo, F; Calcinai, A; Lucchi, M; Mussi, A; Angeletti, C A; Bevilacqua, G

    1999-01-01

    The vascular endothelial growth factor (VEGF) has been shown to be strictly related to vascular permeability and endothelial cell growth under physiological and pathological conditions. In tumour development and progression, VEGF plays a pivotal role in the development of the tumoral vascular network, and useful information in the progression of human cancer can be obtained by analysing the vascular endothelial growth factor expression of the tumours. In this study, we investigated the vascular endothelial growth factor transcript expression in non-small-cell lung carcinomas to evaluate the significance of this factor in a group of cancers in which the vascular pattern has been shown to significantly affect progression. Surgical samples of 42 patients with NSCLC were studied using reverse transcription polymerase chain reaction (PCR) analysis and in situ hybridization. Thirty-three out of 42 cases (78.6%) showed VEGF transcript expression predominantly as transcripts for the secretory forms of VEGF (isoforms 121 and 165). In situ hybridization, performed on 24 out of 42 samples, showed that the VEGF transcript expression was in several cases present in the cytoplasm both of neoplastic and normal cells, even if the VEGF mRNA was less expressed in the corresponding non-tumoral part. The VEGF 121 expression was associated with hilar and/or mediastinal nodal involvement (P = 0.02), and, taken together, the VEGF isoforms were shown to significantly influence overall (P = 0.02) and disease-free survival (P = 0.03). As a regulator of tumour angiogenesis, VEGF may represent a useful indicator of progression and poor prognosis in non-small-cell lung carcinomas. © 1999 Cancer Research Campaign PMID:9888482

  11. Deriving a blood-mimicking fluid for particle image velocimetry in Sylgard-184 vascular models.

    PubMed

    Yousif, Majid Y; Holdsworth, David W; Poepping, Tamie L

    2009-01-01

    A new blood-mimicking fluid (BMF) has been developed for particle image velocimetry (PIV), which enables flow studies in vascular models (phantoms). A major difficulty in PIV that affects measurement accuracy is the refraction and distortion of light passing through the interface between the model and the fluid, due to the difference in refractive index (n) between the two materials. The problem can be eliminated by using a fluid with a refractive index matching that of the model. Such fluids are not commonly available, especially for vascular research where the fluid should also have a viscosity similar to human blood. In this work, a blood-mimicking fluid, composed of water (47.38% by weight), glycerol (36.94% by weight) and sodium iodide salt (15.68% by weight), was developed for compatibility with our silicone (Sylgard 184; n = 1.414) phantoms. The fluid exhibits a dynamic viscosity of 4.31+/-0.03 cP which lies within the range of human blood viscosity (4.4+/-0.6 cP). Both refractive index and viscosity were attained at 22.2+/-0.2 degrees C, which is a feasible room temperature, thus eliminating the need for a temperature-control system. The fluid will be used to study hemodynamics in vascular flow models fabricated from Sylgard 184.

  12. Predicting chemically-induced skin reactions. Part II: QSAR models of skin permeability and the relationships between skin permeability and skin sensitization

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Alves, Vinicius M.; Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599; Muratov, Eugene

    Skin permeability is widely considered to be mechanistically implicated in chemically-induced skin sensitization. Although many chemicals have been identified as skin sensitizers, there have been very few reports analyzing the relationships between molecular structure and skin permeability of sensitizers and non-sensitizers. The goals of this study were to: (i) compile, curate, and integrate the largest publicly available dataset of chemicals studied for their skin permeability; (ii) develop and rigorously validate QSAR models to predict skin permeability; and (iii) explore the complex relationships between skin sensitization and skin permeability. Based on the largest publicly available dataset compiled in this study, wemore » found no overall correlation between skin permeability and skin sensitization. In addition, cross-species correlation coefficient between human and rodent permeability data was found to be as low as R{sup 2} = 0.44. Human skin permeability models based on the random forest method have been developed and validated using OECD-compliant QSAR modeling workflow. Their external accuracy was high (Q{sup 2}{sub ext} = 0.73 for 63% of external compounds inside the applicability domain). The extended analysis using both experimentally-measured and QSAR-imputed data still confirmed the absence of any overall concordance between skin permeability and skin sensitization. This observation suggests that chemical modifications that affect skin permeability should not be presumed a priori to modulate the sensitization potential of chemicals. The models reported herein as well as those developed in the companion paper on skin sensitization suggest that it may be possible to rationally design compounds with the desired high skin permeability but low sensitization potential. - Highlights: • It was compiled the largest publicly-available skin permeability dataset. • Predictive QSAR models were developed for skin permeability. • No concordance between

  13. An ex vivo investigation into the transurothelial permeability and bladder wall distribution of the nonsteroidal anti-inflammatory ketorolac.

    PubMed

    Williams, Nicholas A; Bowen, Jenna L; Al-Jayyoussi, Ghaith; Gumbleton, Mark; Allender, Chris J; Li, Jamie; Harrah, Tim; Raja, Aditya; Joshi, Hrishi B

    2014-03-03

    Transurothelial drug delivery continues to be an attractive treatment option for a range of urological conditions; however, dosing regimens remain largely empirical. Recently, intravesical delivery of the nonsteroidal anti-inflammatory ketorolac has been shown to significantly reduce ureteral stent-related pain. While this latest development provides an opportunity for advancing the management of stent-related pain, clinical translation will undoubtedly require an understanding of the rate and extent of delivery of ketorolac into the bladder wall. Using an ex vivo porcine model, we evaluate the urothelial permeability and bladder wall distribution of ketorolac. The subsequent application of a pharmacokinetic (PK) model enables prediction of concentrations achieved in vivo. Ketorolac was applied to the urothelium and a transurothelial permeability coefficient (Kp) calculated. Relative drug distribution into the bladder wall after 90 min was determined. Ketorolac was able to permeate the urothelium (Kp = 2.63 × 10(-6) cm s(-1)), and after 90 min average concentrations of 400, 141 and 21 μg g(-1) were achieved in the urothelium, lamina propria and detrusor respectively. An average concentration of 87 μg g(-1) was achieved across the whole bladder wall. PK simulations (STELLA) were then carried out, using ex vivo values for Kp and muscle/saline partition coefficient (providing an estimation of vascular clearance), to predict 90 min in vivo ketorolac tissue concentrations. When dilution of the drug solution with urine and vascular clearance were taken into account, a reduced ketorolac concentration of 37 μg g(-1) across the whole bladder wall was predicted. These studies reveal crucial information about the urothelium's permeability to agents such as ketorolac and the concentrations achievable in the bladder wall. It would appear that levels of ketorolac delivered to the bladder wall intravesically would be sufficient to provide an anti-inflammatory effect. The

  14. Aryl Hydrocarbon Receptor Nuclear Translocator in Vascular Smooth Muscle Cells Is Required for Optimal Peripheral Perfusion Recovery.

    PubMed

    Borton, Anna Henry; Benson, Bryan L; Neilson, Lee E; Saunders, Ashley; Alaiti, M Amer; Huang, Alex Y; Jain, Mukesh K; Proweller, Aaron; Ramirez-Bergeron, Diana L

    2018-06-01

    Limb ischemia resulting from peripheral vascular disease is a common cause of morbidity. Vessel occlusion limits blood flow, creating a hypoxic environment that damages distal tissue, requiring therapeutic revascularization. Hypoxia-inducible factors (HIFs) are key transcriptional regulators of hypoxic vascular responses, including angiogenesis and arteriogenesis. Despite vascular smooth muscle cells' (VSMCs') importance in vessel integrity, little is known about their functional responses to hypoxia in peripheral vascular disease. This study investigated the role of VSMC HIF in mediating peripheral ischemic responses. We used Arnt SMKO mice with smooth muscle-specific deletion of aryl hydrocarbon receptor nuclear translocator (ARNT, HIF-1β), required for HIF transcriptional activity, in a femoral artery ligation model of peripheral vascular disease. Arnt SMKO mice exhibit impaired perfusion recovery despite normal collateral vessel dilation and angiogenic capillary responses. Decreased blood flow manifests in extensive tissue damage and hypoxia in ligated limbs of Arnt SMKO mice. Furthermore, loss of aryl hydrocarbon receptor nuclear translocator changes the proliferation, migration, and transcriptional profile of cultured VSMCs. Arnt SMKO mice display disrupted VSMC morphologic features and wrapping around arterioles and increased vascular permeability linked to decreased local blood flow. Our data demonstrate that traditional vascular remodeling responses are insufficient to provide robust peripheral tissue reperfusion in Arnt SMKO mice. In all, this study highlights HIF responses to hypoxia in arteriole VSMCs critical for the phenotypic and functional stability of vessels that aid in the recovery of blood flow in ischemic peripheral tissues. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  15. Defining clogging potential for permeable concrete.

    PubMed

    Kia, Alalea; Wong, Hong S; Cheeseman, Christopher R

    2018-08-15

    Permeable concrete is used to reduce urban flooding as it allows water to flow through normally impermeable infrastructure. It is prone to clogging by particulate matter and predicting the long-term performance of permeable concrete is challenging as there is currently no reliable means of characterising clogging potential. This paper reports on the performance of a range of laboratory-prepared and commercial permeable concretes, close packed glass spheres and aggregate particles of varying size, exposed to different clogging methods to understand this phenomena. New methods were developed to study clogging and define clogging potential. The tests involved applying flowing water containing sand and/or clay in cycles, and measuring the change in permeability. Substantial permeability reductions were observed in all samples, particularly when exposed to sand and clay simultaneously. Three methods were used to define clogging potential based on measuring the initial permeability decay, half-life cycle and number of cycles to full clogging. We show for the first time strong linear correlations between these parameters for a wide range of samples, indicating their use for service-life prediction. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. ACF7 regulates colonic permeability.

    PubMed

    Liang, Yong; Shi, Chenzhang; Yang, Jun; Chen, Hongqi; Xia, Yang; Zhang, Peng; Wang, Feng; Han, Huazhong; Qin, Huanlong

    2013-04-01

    Colonic paracellular permeability is regulated by various factors, including dynamics of the cytoskeleton. Recently, ACF7 has been found to play a critical role in cytoskeletal dynamics as an essential integrator. To elucidate the physiological importance of ACF7 and paracellular permeability, we conditionally knocked out ACF7 in the intestinal mucosa of mice. Histopathological findings indicated that ACF7 deficiency resulted in significant interstitial proliferation and columnar epithelial cell rearrangement. Decreased colonic paracellular permeability was detected using a Ussing chamber and the FITC-inulin method. In order to clarify the underlying mechanism, we further analyzed the expression levels of three important tight junction proteins. Downregulation of ZO-1, occludin and claudin-1 was identified. Immunofluorescence provided strong evidence that ZO-1, occludin and claudin-1 were weakly stained. We hypothesized that ACF7 regulates cytoskeleton dynamics to alter mucosal epithelial arrangement and colonic paracellular permeability.

  17. Ex vivo method to visualize and quantify vascular networks in native and tissue engineered skin.

    PubMed

    Egaña, José Tomás; Condurache, Alexandru; Lohmeyer, Jörn Andreas; Kremer, Mathias; Stöckelhuber, Beate M; Lavandero, Sergio; Machens, Hans-Günther

    2009-03-01

    Neovascularization plays a pivotal role in tissue engineering and tissue regeneration. However, reliable technologies to visualize and quantify blood vessel networks in target tissue areas are still pending. In this work, we introduce a new method which allows comparing vascularization levels in normal and tissue-engineered skin. Normal skin was isolated, and vascular dermal regeneration was analyzed based on tissue transillumination and computerized digital segmentation. For tissue-engineered skin, a bilateral full skin defect was created in a nude mouse model and then covered with a commercially available scaffold for dermal regeneration. After 3 weeks, the whole skin (including scaffold for dermal regeneration) was harvested, and vascularization levels were analyzed. The blood vessel network in the skin was better visualized by transillumination than by radio-angiographic studies, the gold standard for angiographies. After visualization, the whole vascular network was digitally segmented showing an excellent overlapping with the original pictures. Quantification over the digitally segmented picture was performed, and an index of vascularization area (VAI) and length (VLI) of the vessel network was obtained in target tissues. VAI/VLI ratio was calculated to obtain the vessel size index. We present a new technique which has several advantages compared to others, as animals do not require intravascular perfusions, total areas of interest can be quantitatively analyzed at once, and the same target tissue can be processed for further experimental analysis.

  18. Permeability of canine vocal fold lamina propria.

    PubMed

    Meyer, Jacob P; Kvit, Anton A; Devine, Erin E; Jiang, Jack

    2015-04-01

    Determine the permeability of excised canine vocal fold lamina propria. Basic science. Vocal folds were excised from canine larynges and mounted within a device to measure the flow of 0.9% saline through the tissue over time. The resultant fluid volume displaced over time was then used in a variation of Darcy's law to calculate the permeability of the tissue. Permeability was found through each anatomical plane of the vocal fold, with five samples per plane. Permeability was also found for lamina propria stretched to 10%, 20%, and 30% of its initial length to determine the effects of tensile strain on permeability, with five samples per level of strain. Permeability was found to be 1.40 × 10(-13) m(3) s/kg through the sagittal plane, 1.00 × 10(-13) m(3) s/kg through the coronal plane, and 4.02 × 10(-13) m(3) s/kg through the axial plane. It was significantly greater through the axial plane than both the sagittal (P = .025) and coronal (P = .009) planes. Permeability under strain through the sagittal plane was found to be 1.94 × 10(-13) m(3) s/kg under 10% strain, 3.35 × 10(-13) m(3) s/kg under 20% strain, and 4.80 × 10(-13) m(3) s/kg under 30% strain. The permeability significantly increased after 20% strain (P < .05). Permeability in canine vocal fold lamina propria was found to be increased along the anterior-posterior axis, following the length of the vocal folds. This may influence fluid distribution within the lamina propria during and after vibration. Similarly, permeability increased after 20% strain was imposed on the lamina propria, and may influence vocal fold dynamics during certain phonation tasks. NA Laryngoscope, 125:941-945, 2015. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

  19. The Clinical Impact of Cardiology Consultation Prior to Major Vascular Surgery.

    PubMed

    Davis, Frank M; Park, Yeo June; Grey, Scott F; Boniakowski, Anna E; Mansour, M Ashraf; Jain, Krishna M; Nypaver, Timothy; Grossman, Michael; Gurm, Hitinder; Henke, Peter K

    2018-01-01

    To understand statewide variation in preoperative cardiology consultation prior to major vascular surgery and to determine whether consultation was associated with differences in perioperative myocardial infarction (poMI). Medical consultation prior to major vascular surgery is obtained to reduce perioperative risk. Despite perceived benefit of preoperative consultation, evidence is lacking specifically for major vascular surgery on the effect of preoperative cardiac consultation. Patient and clinical data were obtained from a statewide vascular surgery registry between January 2012 and December 2014. Patients were risk stratified by revised cardiac risk index category and compared poMI between patients who did or did not receive a preoperative cardiology consultation. We then used logistic regression analysis to compare the rate of poMI across hospitals grouped into quartiles by rate of preoperative cardiology consultation. Our study population comprised 5191 patients undergoing open peripheral arterial bypass (n = 3037), open abdominal aortic aneurysm repair (n = 332), or endovascular aneurysm repair (n = 1822) at 29 hospitals. At the patient level, after risk-stratification by revised cardiac risk index category, there was no association between cardiac consultation and poMI. At the hospital level, preoperative cardiac consultation varied substantially between hospitals (6.9%-87.5%, P <0.001). High preoperative consulting hospitals (rate >66%) had a reduction in poMI (OR, 0.52; confidence interval: 0.28-0.98; P <0.05) compared with all other hospitals. These hospitals also had a statistically greater consultation rate with a variety of medical specialties. Preoperative cardiology consultation for vascular surgery varies greatly between institutions, and does not appear to impact poMI at the patient level. However, reduction of poMI was noted at the hospitals with the highest rate of preoperative cardiology consultation as well as a variety of medical services

  20. Microorganism Removal in Permeable Pavement Parking Lots ...

    EPA Pesticide Factsheets

    Three types of permeable pavements (pervious concrete, permeable interlocking concrete pavers, and porous asphalt) were monitored at the Edison Environmental Center in Edison, New Jersey for indicator organisms such as fecal coliform, enterococci, and E. coli. Results showed that porous asphalt had much lower concentration in monitored infiltrate compared to pervious concrete and permeable interlocking concrete pavers. Concentrations of monitored organisms in infiltrate from porous asphalt were consistently below the bathing water quality standard. Fecal coliform and enterococci exceeded bathing water quality standards more than 72% and 34% of the time for permeable interlocking concrete pavers and pervious concrete, respectively. Purpose is to evaluate the performance of permeable pavement in removing indicator organisms from infiltrating stormwater runoff.

  1. Influence of fiber packing structure on permeability

    NASA Technical Reports Server (NTRS)

    Cai, Zhong; Berdichevsky, Alexander L.

    1993-01-01

    The study on the permeability of an aligned fiber bundle is the key building block in modeling the permeability of advanced woven and braided preforms. Available results on the permeability of fiber bundles in the literature show that a substantial difference exists between numerical and analytical calculations on idealized fiber packing structures, such as square and hexagonal packing, and experimental measurements on practical fiber bundles. The present study focuses on the variation of the permeability of a fiber bundle under practical process conditions. Fiber bundles are considered as containing openings and fiber clusters within the bundle. Numerical simulations on the influence of various openings on the permeability were conducted. Idealized packing structures are used, but with introduced openings distributed in different patterns. Both longitudinal and transverse flow are considered. The results show that openings within the fiber bundle have substantial effect on the permeability. In the longitudinal flow case, the openings become the dominant flow path. In the transverse flow case, the fiber clusters reduce the gap sizes among fibers. Therefore the permeability is greatly influenced by these openings and clusters, respectively. In addition to the porosity or fiber volume fraction, which is commonly used in the permeability expression, another fiber bundle status parameter, the ultimate fiber volume fraction, is introduced to capture the disturbance within a fiber bundle.

  2. [Aspects of vascular physiology in clinical and vascular surgical practice: basic principles of vascular mechanics].

    PubMed

    Nocke, H; Meyer, F; Lessmann, V

    2014-10-01

    To be able to evaluate properly a vascular problem, basic concepts of vascular physiology need to be considered, as they have been taught in physiology for a long time. This article deals with selected definitions and laws of passive vascular mechanics, subdivided into parameters of vascular filling and parameters of vascular flow. PARAMETERS OF VASCULAR FILLING: During vascular filling the transmural pressure distends the vascular wall until it is balanced by the wall tension. The extent of this distension up to the point of balance depends on the elasticity of the wall. Transmural pressure, wall tension and elasticity are defined, and their respective importance is described by clinical examples, e.g. aneurysm and varix. PARAMETERS OF VASCULAR FLOW: The vascular flow can be divided into stationary and pulsating components. Both components are relevant for the bloodstream. Since the blood flow is directed in the circuit, it can be understood in first approximation as stationary ("direct current").The direct current model uses only the average values of the pulsating variables. The great advantage of the direct current model is that it can be described with simple laws, which are not valid without reservation, but often allow a first theoretical approach to a vascular problem: Ohm's law, driving pressure, flow resistance, Hagen-Poiseuille law, wall shear stress, law of continuity, Bernoulli's equation and Reynold's number are described and associated with clinical examples.The heart is a pressure-suction pump and produces a pulsating flow, the pulse. The pulse runs with pulse wave velocity, which is much larger than the blood flow velocity, through the arterial vascular system. During propagation, the pulse has to overcome the wave resistance (impedance). Wherever the wave resistance changes, e.g., at vascular bifurcations and in the periphery, it comes to reflections. The incident (forward) and reflected (backward) waves are superimposed to yield the resulting

  3. Anti-VEGF aptamer (pegaptanib) therapy for ocular vascular diseases.

    PubMed

    Ng, Eugene W M; Adamis, Anthony P

    2006-10-01

    Vascular endothelial growth factor (VEGF) is a central regulator of both physiological and pathological angiogenesis. Pegaptanib, a 28-nucleotide RNA aptamer specific for the VEGF(165) isoform, binds to it in the extracellular space, leaving other isoforms unaffected, and inhibits such key VEGF actions as promotion of endothelial cell proliferation and survival, and vascular permeability. Pegaptanib already has been examined as a treatment for two diseases associated with ocular neovascularization, age-related macular degeneration (AMD) and diabetic macular edema (DME). Preclinical studies have shown that VEGF(165) alone mediates pathological ocular neovascularization and that its inactivation by pegaptanib inhibits the choroidal neovascularization observed in patients with neovascular AMD. In contrast, physiological vascularization, which is supported by the VEGF(121) isoform, is unaffected by this inactivation of VEGF(165). In addition, animal model studies have shown that intravitreous injection of pegaptanib can inhibit the breakdown of the blood-retinal barrier characteristic of diabetes and even can reverse this damage to some degree. These preclinical findings formed the basis for randomized controlled trials examining the efficacy of pegaptanib as a therapy for AMD and DME. The VEGF Inhibition Study in Ocular Neovascularization (VISION) trial comprising two replicate, pivotal phase 3 studies, demonstrated that intravitreous injection of pegaptanib resulted in significant clinical benefit, compared with sham injection, for all prespecified clinical end points, irrespective of patient demographics or angiographic subtype, and led to pegaptanib's approval as a treatment for AMD. A phase 2 trial has provided support for the efficacy of intravitreous pegaptanib in the treatment of DME.

  4. Atrial Natriuretic Peptide Reduces Vascular Leakage and Choroidal Neovascularization

    PubMed Central

    Lara-Castillo, Nuria; Zandi, Souska; Nakao, Shintaro; Ito, Yasuhiro; Noda, Kousuke; She, Haicheng; Ahmed, Muna; Frimmel, Sonja; Ablonczy, Zsolt; Hafezi-Moghadam, Ali

    2009-01-01

    Atrial natriuretic peptide (ANP) is a hormone with diuretic, natriuretic, and vasodilatory properties. ANP blocks vascular endothelial growth factor (VEGF) production and signaling in vitro; however, its role in vascular leakage and angiogenesis is unknown. In vitro, retinal barrier permeability (transepithelial electrical resistance (TEER)) was measured in cultured retinal endothelial (HuREC) and retinal epithelial (ARPE-19) cells with VEGF (10 ng/ml), ANP (1 pM to 1 μmol/L), and/or isatin, an ANP receptor antagonist. In vivo, blood-retinal barrier (BRB) leakage was studied using the Evans Blue dye technique in rats treated with intravitreal injections of ANP, VEGF, or vehicle. Choroidal neovascularization was generated by laser injury, and 7 days later, lesion size and leakage was quantitated. ANP significantly reversed VEGF-induced BRB TEER reduction in both HuREC and ARPE-19 cells, modeling the inner and the outer BRB, respectively. Isatin, a specific ANP receptor antagonist, reversed ANP’s effect. ANP reduced the response of ARPE-19 cells to VEGF apically but not basolaterally, suggesting polarized expression of the ANP receptors in these cells. ANP’s TEER response was concentration but not time dependent. In vivo, ANP significantly reduced VEGF-induced BRB leakage and the size of laser-induced choroidal neovascularization lesions. In sum, ANP is an effective inhibitor of VEGF-induced vascular leakage and angiogenesis in vivo. These results may lead to new treatments for ocular diseases where VEGF plays a central role, such as age-related macular degeneration or diabetic retinopathy. PMID:19910509

  5. Efficient Permeability Measurement and Numerical Simulation of the Resin Flow in Low Permeability Preform Fabricated by Automated Dry Fiber Placement

    NASA Astrophysics Data System (ADS)

    Agogue, Romain; Chebil, Naziha; Deleglise-Lagardere, Mylène; Beauchene, Pierre; Park, Chung Hae

    2017-10-01

    We propose a new experimental method using a Hassler cell and air injection to measure the permeability of fiber preform while avoiding a race tracking effect. This method was proven to be particularly efficient to measure very low through-thickness permeability of preform fabricated by automated dry fiber placement. To validate the reliability of the permeability measurement, the experiments of viscous liquid infusion into the preform with or without a distribution medium were performed. The experimental data of flow front advancement was compared with the numerical simulation result using the permeability values obtained by the Hassler cell permeability measurement set-up as well as by the liquid infusion experiments. To address the computational cost issue, the model for the equivalent permeability of distribution medium was employed in the numerical simulation of liquid flow. The new concept using air injection and Hassler cell for the fiber preform permeability measurement was shown to be reliable and efficient.

  6. Use of plasma proteins as solubilizing agents in in vitro permeability experiments: correction for unbound drug concentration using the reciprocal permeability approach.

    PubMed

    Katneni, Kasiram; Charman, Susan A; Porter, Christopher J H

    2008-01-01

    The purpose of the present study was to explore the applicability of the reciprocal permeability approach to correct for changes in thermodynamic activity when in vitro permeability data are generated in the presence of plasma proteins. Diazepam (DIA), digoxin (DIG), and propranolol (PRO) permeability was assessed in the presence of bovine serum albumin (BSA) and bovine alpha-1-acid glycoprotein (AAG). The reciprocal permeability approach was subsequently employed to calculate the true permeability coefficient (Papp(corr)) and the operational protein association constant (nK(a)). For BSA binding, good agreement was observed between the Papp(corr) values and Papp values obtained in the absence of protein. For PRO and AAG, where binding affinity was high, deviation in the reciprocal permeability plots was evident suggesting ligand depletion at low drug/high protein concentrations. Bidirectional DIG permeability data in the presence of either BSA or AAG indicated that neither protein had an effect on the efflux transporters involved in DIG permeability. The data suggest that plasma proteins can be utilized in permeability experiments with no adverse effects on transporter function and that the reciprocal permeability approach can be used to correct permeability data for changes in unbound drug concentration. c) 2007 Wiley-Liss, Inc.

  7. Asynchronous arterial systolic expansion as a marker of vascular aging: assessment of the carotid artery with velocity vector imaging.

    PubMed

    Yang, Woo-In; Shim, Chi Y; Bang, Woo D; Oh, Chang M; Chang, Hyuk J; Chung, Namsik; Ha, Jong-Won

    2011-12-01

    Arterial elastic properties change with aging. Measurements of pulse wave velocity and augmentation index are useful for the evaluation of arterial stiffness. However, they likely represent only global characteristics of the arterial tree rather than local vascular alterations. The aim of this study was to evaluate whether local vascular properties assessed by velocity vector imaging differed with aging. Vascular properties of carotid arteries with ages were assessed in 100 healthy volunteers (52 men) ranging from 20 to 68 years using velocity vector imaging. The peak circumferential strain and strain rate of the six segments in left common carotid arteries were analyzed and the standard deviation of the time to peak circumferential strain and strain rate of the six segments, representing the synchronicity of the arterial expansion, were calculated. Central blood pressure, augmentation index and pulse wave velocity were assessed by commercially available radial artery tonometry, the SphygmoCor system (AtCor Medical, West Ryde, Australia). A validated generalized transfer function was used to acquire the central aortic pressures and pressure waveforms. Pulse wave velocity, augmentation index and velocity vector imaging parameters showed significant changes with age. However, the age-related changes in pulse wave velocity, augmentation index and velocity vector imaging parameters were different. The increase in pulse wave velocity was more prominent in older individuals, whereas the changes in augmentation index and carotid strain and strain rate were evident earlier, at the age of 30 years. Unlike augmentation index, which showed little change in older individuals, the standard deviation of time to peak strain and strain rate showed a steady increase from younger to older individuals. Asynchronous arterial expansion could be a useful discriminative marker of vascular aging independent of individual's age.

  8. Charge Inversion in semi-permeable membranes

    NASA Astrophysics Data System (ADS)

    Das, Siddhartha; Sinha, Shayandev; Jing, Haoyuan

    Role of semi-permeable membranes like lipid bilayer is ubiquitous in a myriad of physiological and pathological phenomena. Typically, lipid membranes are impermeable to ions and solutes; however, protein channels embedded in the membrane allow the passage of selective, small ions across the membrane enabling the membrane to adopt a semi-permeable nature. This semi-permeability, in turn, leads to electrostatic potential jump across the membrane, leading to effects such as regulation of intracellular calcium, extracellular-vesicle-membrane interactions, etc. In this study, we theoretically demonstrate that this semi-permeable nature may trigger the most remarkable charge inversion (CI) phenomenon in the cytosol-side of the negatively-charged lipid bilayer membrane that are selectively permeable to only positive ions of a given salt. This CI is manifested as the changing of the sign of the electrostatic potential from negative to positive from the membrane-cytosol interface to deep within the cytosol. We study the impact of the parameters such as the concentration of this salt with selectively permeable ions as well as the concentration of an external salt in the development of this CI phenomenon. We anticipate such CI will profoundly influence the interaction of membrane and intra-cellular moieties (e.g., exosome or multi-cellular vesicles) having implications for a host of biophysical processes.

  9. Additive Manufacturing of Vascular Grafts and Vascularized Tissue Constructs.

    PubMed

    Elomaa, Laura; Yang, Yunzhi Peter

    2017-10-01

    There is a great need for engineered vascular grafts among patients with cardiovascular diseases who are in need of bypass therapy and lack autologous healthy blood vessels. In addition, because of the severe worldwide shortage of organ donors, there is an increasing need for engineered vascularized tissue constructs as an alternative to organ transplants. Additive manufacturing (AM) offers great advantages and flexibility of fabrication of cell-laden, multimaterial, and anatomically shaped vascular grafts and vascularized tissue constructs. Various inkjet-, extrusion-, and photocrosslinking-based AM techniques have been applied to the fabrication of both self-standing vascular grafts and porous, vascularized tissue constructs. This review discusses the state-of-the-art research on the use of AM for vascular applications and the key criteria for biomaterials in the AM of both acellular and cellular constructs. We envision that new smart printing materials that can adapt to their environment and encourage rapid endothelialization and remodeling will be the key factor in the future for the successful AM of personalized and dynamic vascular tissue applications.

  10. Mechanisms of Microgravity Effect on Vascular Function

    NASA Technical Reports Server (NTRS)

    Purdy, Ralph E.

    1995-01-01

    The overall goal of the project is to characterize the effects of simulated microgravity on vascular function. Microgravity is simulated using the hindlimb unweighted (HU) rat, and the following vessels are removed from HU and paired control rats for in vitro analysis: abdominal aorta, carotid and femoral arteries, jugular and femoral veins. These vessels are cut into 3 mm long rings and mounted in tissue baths for the measurement of either isometric contraction, or relaxation of pre- contracted vessels. The isolated mesenteric vascular bed is perfused for the measurement of changes in perfusion pressure as an index of arteriolar constriction or dilation. This report presents, in addition to the statement of the overall goal of the project, a summary list of the specific hypotheses to be tested. These are followed by sections on results, conclusions, significance and plans for the next year.

  11. Vascular surgery research in the Gulf Cooperation Council countries.

    PubMed

    Jawas, Ali; Hefny, Ashraf F; Abbas, Alaa K; Abu-Zidan, Fikri M

    2014-04-01

    To evaluate the quantity and quality of published vascular surgery research articles from the Gulf Cooperation Council (GCC) countries so as to identify areas for improvement. Descriptive study. Published MEDLINE articles on vascular surgery from the GCC countries (1960-2010). Critical analysis of the articles. A total of 146 articles were studied, majority of which were case series/case reports (55.5%); 33% of the articles were prospective. The first author was from a university in 67.1% of the articles. Only one randomized controlled trial was found. The median (range) impact factor of the journals was 1.16 (0.16-12.64). Kuwait had the highest number of publications/country, standardized/100,000 inhabitants. There were 11 experimental studies, which were all from Kuwait. More statistically significant, experimental vascular surgery papers were published prior to 1993 (11/30 compared with 0/111 afterward, p < 0.0001; Fisher exact test). The GCC countries had the lowest vascular surgery research output compared with Turkey, Hong Kong, Singapore, and Japan when standardized by the population. The h index of the GCC countries' vascular research publications was the lowest (19) compared with the other four countries (29-97). Furthermore, the average citation of the GCC countries (5.81) was similar to Turkey (5.66), but less than Hong Kong (17.38), Singapore (12.79), and Japan (11.75). The quality and quantity of vascular surgery research in the GCC countries should be improved to answer important local questions related to vascular diseases. This needs better strategic planning and more collaboration between various institutions. Copyright © 2013. Published by Elsevier B.V.

  12. Angiopoietin-like 4 prevents metastasis through inhibition of vascular permeability and tumor cell motility and invasiveness.

    PubMed

    Galaup, Ariane; Cazes, Aurelie; Le Jan, Sebastien; Philippe, Josette; Connault, Elisabeth; Le Coz, Emmanuelle; Mekid, Halima; Mir, Lluis M; Opolon, Paule; Corvol, Pierre; Monnot, Catherine; Germain, Stephane

    2006-12-05

    Angiopoietin-like 4 (ANGPTL4), a secreted protein of the angiopoietin-like family, is induced by hypoxia in both tumor and endothelial cells as well as in hypoxic perinecrotic areas of numerous cancers. Here, we investigated whether ANGPTL4 might affect tumor growth as well as metastasis. Metastatic 3LL cells were therefore xenografted into control mice and mice in which ANGPTL4 was expressed by using in vivo DNA electrotransfer. Whereas primary tumors grew at a similar rate in both groups, 3LL cells metastasized less efficiently to the lungs of mice that expressed ANGPTL4. Fewer 3LL emboli were observed in primary tumors, suggesting that intravasation of 3LL cells was inhibited by ANGPTL4. Furthermore, melanoma B16F0 cells injected into the retro-orbital sinus also metastasized less efficiently in mice expressing ANGPTL4. Although B16F0 cells were observed in lung vessels, they rarely invaded the parenchyma, suggesting that ANGPTL4 affects extravasation. In addition, recombinant B16F0 cells that overexpress ANGPTL4 were generated, showing a lower capacity for in vitro migration, invasion, and adhesion than control cells. Expression of ANGPTL4 induced reorganization of the actin cytoskeleton through inhibition of actin stress fiber formation and vinculin localization at focal contacts. Together, these results show that ANGPTL4, through its action on both vascular and tumor compartments, prevents the metastatic process by inhibiting vascular activity as well as tumor cell motility and invasiveness.

  13. Angiopoietin-like 4 prevents metastasis through inhibition of vascular permeability and tumor cell motility and invasiveness

    PubMed Central

    Galaup, Ariane; Cazes, Aurelie; Le Jan, Sebastien; Philippe, Josette; Connault, Elisabeth; Le Coz, Emmanuelle; Mekid, Halima; Mir, Lluis M.; Opolon, Paule; Corvol, Pierre; Monnot, Catherine; Germain, Stephane

    2006-01-01

    Angiopoietin-like 4 (ANGPTL4), a secreted protein of the angiopoietin-like family, is induced by hypoxia in both tumor and endothelial cells as well as in hypoxic perinecrotic areas of numerous cancers. Here, we investigated whether ANGPTL4 might affect tumor growth as well as metastasis. Metastatic 3LL cells were therefore xenografted into control mice and mice in which ANGPTL4 was expressed by using in vivo DNA electrotransfer. Whereas primary tumors grew at a similar rate in both groups, 3LL cells metastasized less efficiently to the lungs of mice that expressed ANGPTL4. Fewer 3LL emboli were observed in primary tumors, suggesting that intravasation of 3LL cells was inhibited by ANGPTL4. Furthermore, melanoma B16F0 cells injected into the retro-orbital sinus also metastasized less efficiently in mice expressing ANGPTL4. Although B16F0 cells were observed in lung vessels, they rarely invaded the parenchyma, suggesting that ANGPTL4 affects extravasation. In addition, recombinant B16F0 cells that overexpress ANGPTL4 were generated, showing a lower capacity for in vitro migration, invasion, and adhesion than control cells. Expression of ANGPTL4 induced reorganization of the actin cytoskeleton through inhibition of actin stress fiber formation and vinculin localization at focal contacts. Together, these results show that ANGPTL4, through its action on both vascular and tumor compartments, prevents the metastatic process by inhibiting vascular activity as well as tumor cell motility and invasiveness. PMID:17130448

  14. A Radiation-Induced Hippocampal Vascular Injury Surrogate Marker Predicts Late Neurocognitive Dysfunction

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Farjam, Reza; Pramanik, Priyanka; Aryal, Madhava P.

    Purpose: We aimed to develop a hippocampal vascular injury surrogate marker for early prediction of late neurocognitive dysfunction in patients receiving brain radiation therapy (RT). Methods and Materials: Twenty-seven patients (17 males and 10 females, 31-80 years of age) were enrolled in an institutional review board-approved prospective longitudinal study. Patients received diagnoses of low-grade glioma or benign tumor and were treated by (3D) conformal or intensity-modulated RT with a median dose of 54 Gy (50.4-59.4 Gy in 1.8-Gy fractions). Six dynamic-contrast enhanced MRI scans were performed from pre-RT to 18-month post-RT, and quantified for vascular parameters related to blood-brain barrier permeability, K{sup trans},more » and the fraction of blood plasma volume, V{sub p}. The temporal changes in the means of hippocampal transfer constant K{sup trans} and V{sub p} after starting RT were modeled by integrating the dose effects with age, sex, hippocampal laterality, and presence of tumor or edema near a hippocampus. Finally, the early vascular dose response in hippocampi was correlated with neurocognitive dysfunction at 6 and 18 months post-RT. Results: The mean K{sup trans} Increased significantly from pre-RT to 1-month post-RT (P<.0004), which significantly depended on sex (P<.0007) and age (P<.00004), with the dose response more pronounced in older females. Also, the vascular dose response in the left hippocampus of females correlated significantly with changes in memory function at 6 (r=−0.95, P<.0006) and 18-months (r=−0.88, P<.02) post-RT. Conclusions: The early hippocampal vascular dose response could be a predictor of late neurocognitive dysfunction. A personalized hippocampus sparing strategy may be considered in the future.« less

  15. Permeability measurement and control for epoxy composites

    NASA Astrophysics Data System (ADS)

    Chang, Tsun-Hsu; Tsai, Cheng-Hung; Wong, Wei-Syuan; Chen, Yen-Ren; Chao, Hsien-Wen

    2017-08-01

    The coupling of the electric and magnetic fields leads to a strong interplay in materials' permittivity and permeability. Here, we proposed a specially designed cavity, called the mu cavity. The mu cavity, consisting of a mushroom structure inside a cylindrical resonator, is exclusively sensitive to permeability, but not to permittivity. It decouples materials' electromagnetic properties and allows an accurate measurement of the permeability. With the help of an epsilon cavity, these two cavities jointly determine the complex permeability and permittivity of the materials at microwave frequencies. Homemade epoxy-based composite materials were prepared and tested. Measurement and manipulation of the permeability and permittivity of the epoxy composites will be shown. The results will be compared with the effective medium theories.

  16. Effects of hypothyroidism on vascular /sup 125/I-albumin permeation and blood flow in rats

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tilton, R.G.; Pugliese, G.; Chang, K.

    1989-05-01

    Effects of hypothyroidism on vascular 125I-albumin permeation and on blood flow were assessed in multiple tissues of male Sprague-Dawley rats rendered hypothyroid by dietary supplementation with 0.5% (wt/wt) 2-thiouracil or by thyroidectomy. In both thiouracil-treated and thyroidectomized rats, body weights, kidney weight, arterial blood pressure, and pulse rate were decreased significantly v age-matched controls. After 10 to 12 weeks of thiouracil treatment, 125I-albumin permeation was increased significantly in the kidney, aorta, eye (anterior uvea, choroid, retina), skin, and new granulation tissue, remained unchanged in brain, sciatic nerve, and heart, and was decreased in forelimb skeletal muscle. A similar pattern wasmore » observed in thyroidectomized rats, except that increases in 125I-albumin permeation for all tissues were smaller than those observed in thiouracil-treated rats, and 125I-albumin permeation in retina did not differ from controls. In both thiouracil-treated and thyroidectomized rats, changes in blood flow (assessed with 15-microns, 85Sr-labeled microspheres) relative to the decrease in arterial blood pressure were indicative of a decrease in regional vascular resistance except in the choroid and in the kidney, in which vascular resistance was increased significantly. Glomerular filtration rate was decreased, but filtration fraction and urinary excretion of albumin remained unchanged by thiouracil treatment and thyroidectomy. These results indicate that vascular hemodynamics and endothelial cell barrier functional integrity are modulated in many different tissues by the thyroid. In view of the correspondence of hypothyroid- and diabetes-induced vascular permeability changes, these results raise the possibility that altered thyroid function in diabetes may play a role in the pathogenesis of diabetic vascular disease.« less

  17. De Novo Lipogenesis Maintains Vascular Homeostasis through Endothelial Nitric-oxide Synthase (eNOS) Palmitoylation*♦

    PubMed Central

    Wei, Xiaochao; Schneider, Jochen G.; Shenouda, Sherene M.; Lee, Ada; Towler, Dwight A.; Chakravarthy, Manu V.; Vita, Joseph A.; Semenkovich, Clay F.

    2011-01-01

    Endothelial dysfunction leads to lethal vascular complications in diabetes and related metabolic disorders. Here, we demonstrate that de novo lipogenesis, an insulin-dependent process driven by the multifunctional enzyme fatty-acid synthase (FAS), maintains endothelial function by targeting endothelial nitric-oxide synthase (eNOS) to the plasma membrane. In mice with endothelial inactivation of FAS (FASTie mice), eNOS membrane content and activity were decreased. eNOS and FAS were physically associated; eNOS palmitoylation was decreased in FAS-deficient cells, and incorporation of labeled carbon into eNOS-associated palmitate was FAS-dependent. FASTie mice manifested a proinflammatory state reflected as increases in vascular permeability, endothelial inflammatory markers, leukocyte migration, and susceptibility to LPS-induced death that was reversed with an NO donor. FAS-deficient endothelial cells showed deficient migratory capacity, and angiogenesis was decreased in FASTie mice subjected to hindlimb ischemia. Insulin induced FAS in endothelial cells freshly isolated from humans, and eNOS palmitoylation was decreased in mice with insulin-deficient or insulin-resistant diabetes. Thus, disrupting eNOS bioavailability through impaired lipogenesis identifies a novel mechanism coordinating nutritional status and tissue repair that may contribute to diabetic vascular disease. PMID:21098489

  18. Frictional stability-permeability relationships for fractures in shales

    NASA Astrophysics Data System (ADS)

    Fang, Yi; Elsworth, Derek; Wang, Chaoyi; Ishibashi, Takuya; Fitts, Jeffrey P.

    2017-03-01

    There is wide concern that fluid injection in the subsurface, such as for the stimulation of shale reservoirs or for geological CO2 sequestration (GCS), has the potential to induce seismicity that may change reservoir permeability due to fault slip. However, the impact of induced seismicity on fracture permeability evolution remains unclear due to the spectrum of modes of fault reactivation (e.g., stable versus unstable). As seismicity is controlled by the frictional response of fractures, we explore friction-stability-permeability relationships through the concurrent measurement of frictional and hydraulic properties of artificial fractures in Green River shale (GRS) and Opalinus shale (OPS). We observe that carbonate-rich GRS shows higher frictional strength but weak neutral frictional stability. The GRS fracture permeability declines during shearing while an increased sliding velocity reduces the rate of permeability decline. By comparison, the phyllosilicate-rich OPS has lower friction and strong stability while the fracture permeability is reduced due to the swelling behavior that dominates over the shearing induced permeability reduction. Hence, we conclude that the friction-stability-permeability relationship of a fracture is largely controlled by mineral composition and that shale mineral compositions with strong frictional stability may be particularly subject to permanent permeability reduction during fluid infiltration.

  19. Predicting chemically-induced skin reactions. Part II: QSAR models of skin permeability and the relationships between skin permeability and skin sensitization

    PubMed Central

    Alves, Vinicius M.; Muratov, Eugene; Fourches, Denis; Strickland, Judy; Kleinstreuer, Nicole; Andrade, Carolina H.; Tropsha, Alexander

    2015-01-01

    Skin permeability is widely considered to be mechanistically implicated in chemically-induced skin sensitization. Although many chemicals have been identified as skin sensitizers, there have been very few reports analyzing the relationships between molecular structure and skin permeability of sensitizers and non-sensitizers. The goals of this study were to: (i) compile, curate, and integrate the largest publicly available dataset of chemicals studied for their skin permeability; (ii) develop and rigorously validate QSAR models to predict skin permeability; and (iii) explore the complex relationships between skin sensitization and skin permeability. Based on the largest publicly available dataset compiled in this study, we found no overall correlation between skin permeability and skin sensitization. In addition, cross-species correlation coefficient between human and rodent permeability data was found to be as low as R2=0.44. Human skin permeability models based on the random forest method have been developed and validated using OECD-compliant QSAR modeling workflow. Their external accuracy was high (Q2ext = 0.73 for 63% of external compounds inside the applicability domain). The extended analysis using both experimentally-measured and QSAR-imputed data still confirmed the absence of any overall concordance between skin permeability and skin sensitization. This observation suggests that chemical modifications that affect skin permeability should not be presumed a priori to modulate the sensitization potential of chemicals. The models reported herein as well as those developed in the companion paper on skin sensitization suggest that it may be possible to rationally design compounds with the desired high skin permeability but low sensitization potential. PMID:25560673

  20. Markers of Vascular Perturbation Correlate with Airway Structural Change in Asthma

    PubMed Central

    Kruger, Stanley J.; Schiebler, Mark L.; Evans, Michael D.; Sorkness, Ronald L.; Denlinger, Loren C.; Busse, William W.; Jarjour, Nizar N.; Montgomery, Robert R.; Mosher, Deane F.; Fain, Sean B.

    2013-01-01

    Rationale: Air trapping and ventilation defects on imaging are characteristics of asthma. Airway wall thickening occurs in asthma and is associated with increased bronchial vascularity and vascular permeability. Vascular endothelial cell products have not been explored as a surrogate to mark structural airway changes in asthma. Objectives: Determine whether reporters of vascular endothelial cell perturbation correlate with airway imaging metrics in patients with asthma of varying severity. Methods: Plasma from Severe Asthma Research Program subjects was analyzed by ELISAs for soluble von Willebrand factor mature protein (VWF:Ag) and propeptide (VWFpp), P-selectin, and platelet factor 4. Additional subjects were analyzed over 48 hours after whole-lung antigen challenge. We calculated ventilation defect volume by hyperpolarized helium-3 magnetic resonance imaging and areas of low signal density by multidetector computed tomography (less than −856 Hounsfield units [HU] at functional residual capacity and −950 HU at total lung capacity [TLC]). Measurements and Main Results: VWFpp and VWFpp/Ag ratio correlated with and predicted greater percentage defect volume on hyperpolarized helium-3 magnetic resonance imaging. P-selectin correlated with and predicted greater area of low density on chest multidetector computed tomography less than −950 HU at TLC. Platelet factor 4 did not correlate. Following whole-lung antigen challenge, variation in VWFpp, VWFpp/Ag, and P-selectin among time-points was less than that among subjects, indicating stability and repeatability of the measurements. Conclusions: Plasma VWFpp and P-selectin may be useful as surrogates of functional and structural defects that are evident on imaging. The results raise important questions about why VWFpp and P-selectin are associated specifically with different imaging abnormalities. PMID:23855693

  1. Vascular tight junction disruption and angiogenesis in spontaneously hypertensive rat with neuroinflammatory white matter injury.

    PubMed

    Yang, Yi; Kimura-Ohba, Shihoko; Thompson, Jeffrey F; Salayandia, Victor M; Cossé, Melissa; Raz, Limor; Jalal, Fakhreya Y; Rosenberg, Gary A

    2018-06-01

    Vascular cognitive impairment is a major cause of dementia caused by chronic hypoxia, producing progressive damage to white matter (WM) secondary to blood-brain barrier (BBB) opening and vascular dysfunction. Tight junction proteins (TJPs), which maintain BBB integrity, are lost in acute ischemia. Although angiogenesis is critical for neurovascular remodeling, less is known about its role in chronic hypoxia. To study the impact of TJP degradation and angiogenesis during pathological progression of WM damage, we used the spontaneously hypertensive/stroke prone rats with unilateral carotid artery occlusion and Japanese permissive diet to model WM damage. MRI and IgG immunostaining showed regions with BBB damage, which corresponded with decreased endothelial TJPs, claudin-5, occludin, and ZO-1. Affected WM had increased expression of angiogenic factors, Ki67, NG2, VEGF-A, and MMP-3 in vascular endothelial cells and pericytes. To facilitate the study of angiogenesis, we treated rats with minocycline to block BBB disruption, reduce WM lesion size, and extend survival. Minocycline-treated rats showed increased VEGF-A protein, TJP formation, and oligodendrocyte proliferation. We propose that chronic hypoxia disrupts TJPs, increasing vascular permeability, and initiating angiogenesis in WM. Minocycline facilitated WM repair by reducing BBB damage and enhancing expression of TJPs and angiogenesis, ultimately preserving oligodendrocytes. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Reticuloendothelial clearance of blood-borne particulates: relevance to experimental lung microembolization and vascular injury.

    PubMed

    Niehaus, G D; Schumacker, P R; Saba, T M

    1980-04-01

    The rapid increase in sheep lung vascular permeability observed during Pseudomonas aeruginosa bacteremia may be due to embolization of the pulmonary microvasculature by bloodborne particulates. Since alterations in lung microvascular permeability during mild septicemia in sheep may reflect inefficient RES phagocytic clearance of bacteria as well as products of bacterial induced intravascular coagulation, the opsonic and phagocytic aspects of RES function in sheep (30-50 kg) were compared to other species. RES function was evaluated by both the clearance and relative organ uptake of gelatinized I(131) RE test lipid emulsion and gelatinized colloidal carbon. Immunoreactive opsonic a(2)SB glycoprotein levels were determined by electroimmunoassay. The phagocytic index for RES clearance of the gelatinized (500 mg/kg) test lipid in sheep was 0.019 +/- 0.002 corresponding to a half-time of 16.65 +/- 1.74 minutes. With colloidal carbon (64 mg/kg), the phagocytic index in sheep was 0.080 +/- 0.026, corresponding to a half-time of 6.16 +/- 1.99 minutes. The per cent of injected lipid emulsion (%ID) in major RE organs, on a total organ basis (TO), was: liver = 15.69 +/- 1.65%; spleen = 2.09 +/- 0.78%. Localization in the lung = 31.39 +/- 6.2%. The per cent of carbon localized in major RE organs (%ID/TO) was: liver = 21.37 +/- 1.9%; spleen = 1.95 +/- 0.55%. Localization in the lung = 32.70 +/- 4.55%. In contrast, clearance and organ distribution of the blood-borne test microparticles in rats and dogs at the same relative challenging dose revealed a much more intense and rapid liver and spleen RES uptake with minimal lung localization (1-2%). Immunoreactive opsonic protein concentrations varied greatly with species and directly correlated with efficiency of RES function. Levels observed were: dog = 1285 +/- 135 microg/ml; mouse = 1077 +/- 67 microg/ml; rat = 400 +/- 31 microg/ml; human = 297 +/- 10 microg/ml; and sheep = 184 +/- 13 microg/ml. After intravenous particulate

  3. Transverse Chemotactic Migration of Bacteria from High to Low Permeability Regions in a Dual Permeability Porous Microfluidic Device

    NASA Astrophysics Data System (ADS)

    Singh, R.; Olson, M. S.

    2011-12-01

    Low permeability regions sandwiched between high permeability regions such as clay lenses are difficult to treat using conventional treatment methods. Trace concentrations of contaminants such as non-aqueous phase liquids (NAPLs) remain trapped in these regions and over the time diffuse out into surrounding water thereby acting as a long term source of groundwater contamination. Bacterial chemotaxis (directed migration toward a contaminant source), may be helpful in enhancing bioremediation of such contaminated sites. This study is focused on simulating a two-dimensional dual-permeability groundwater contamination scenario using microfluidic devices and evaluating transverse chemotactic migration of bacteria from high to low permeability regions. A novel bi-layer polydimethylsiloxane (PDMS) microfluidic device was fabricated using photolithography and soft lithography techniques to simulate contamination of a dual- permeability region due to leakage from an underground storage tank into a low permeability region. This device consists of a porous channel through which a bacterial suspension (Escherchia Coli HCB33) is flown and another channel for injecting contaminant/chemo-attractant (DL-aspertic acid) into the porous channel. The pore arrangement in the porous channel contains a 2-D low permeability region surrounded by high permeability regions on both sides. Experiments were performed under chemotactic and non-chemotactic (replacing attractant with buffer solution in the non porous channel) conditions. Images were captured in transverse pore throats at cross-sections 4.9, 9.8, and 19.6 mm downstream from the attractant injection point and bacteria were enumerated in the middle of each pore throat. Bacterial chemotaxis was quantified in terms of the change in relative bacterial counts in each pore throat at cross-sections 9.8 and 19.6 mm with respect to counts at the cross-section at 4.9 mm. Under non-chemotactic conditions, relative bacterial count was observed

  4. Gas and Liquid Permeability Measurements in Wolfcamp Samples

    NASA Astrophysics Data System (ADS)

    Bhandari, A. R.; Flemings, P. B.; Ramiro-Ramirez, S.; Polito, P. J.

    2017-12-01

    Argon gas and liquid (dodecane) permeability measurements in three mixed quality Wolfcamp samples demonstrate it is possible to close multiple bedding parallel open artificial micro-fractures and obtain representative matrix permeability by applying two confining stress cycles at a constant pore pressure under effective stresses ranging from 6.9 MPa to 59.7 MPa. The fractured sample (with no bridging-cement in fractures) exhibited a three order decrease in permeability from 4.4×10-17 m2 to 2.1×10-20 m2. In contrast, the most intact sample exhibited initial liquid permeability of 1.61×10-19 m2 that declined gradually to 2.0×10-20 m2 over the same effective stress range. A third sample, that contained a bridging-cement (gypsum) fracture, exhibited much higher initial liquid permeability of 2.8×10-15 m2 and declined gradually to 1.3×10-17 m2 with stress; this suggested that it is difficult to close partially cemented fractures and that the permeability we measured was impacted by the presence of a propped-fracture and not the matrix. We developed a new permeability testing protocol and analytical approaches to interpret the evolution of fractures and resolve the matrix permeability using matrix permeability estimates based on initial pulse decay gas permeability measurements at effective stress of 6.9 MPa. The tested samples are an argillaceous siliceous siltstone facies within the Wolfcamp Formation. A better understanding of permeability will lead to new approaches to determine the best completion and production strategies and, more importantly, to reduce the high water cut problem in Wolfcamp reservoirs.

  5. Effect of extracorporeal cytokine removal on vascular barrier function in a septic shock patient.

    PubMed

    David, Sascha; Thamm, Kristina; Schmidt, Bernhard M W; Falk, Christine S; Kielstein, Jan T

    2017-01-01

    Sepsis and septic shock are major healthcare problems, affecting millions of individuals around the world each year. Pathophysiologically, septic multiple organ dysfunction (MOD) is a life-threatening condition caused by an overwhelming systemic inflammatory response of the host's organism to an infection. We experimentally tested if high circulating cytokine levels might increase vascular permeability-a critical hallmark of the disease-and if this phenomenon can be reversed by therapeutic cytokine removal (CytoSorb®) in an exemplary patient. A 32-year-old Caucasian female presented with septic shock and accompanying acute kidney injury (Sequential Organ Failure Assessment (SOFA) = 18) to our ICU. In spite of a broad anti-infective regimen, adequate fluid resuscitation, and high doses of inotropics and catecholamines, she remained refractory hypotensive. The extraordinary severity of septic shock suggested an immense overwhelming host response assumingly accompanied by a notable cytokine storm such as known from patients with toxic shock syndrome. Thus, a CytoSorb® filter was added to the dialysis circuit to remove excess shock-perpetuating cytokines. To analyze the endothelial phenotype in vitro before and after extracorporeal cytokine removal, we tested the septic shock patient's serum on human umbilical vein endothelial cells (HUVECs). The effect on endothelial integrity was assessed both on the morphological (fluorescent immunocytochemistry for VE-cadherin and F-actin) and functional (transendothelial electrical resistance (TER)) level that was recorded in real time with an "electric cell-substrate impedance sensing" (ECIS) system (ibidi). We found (1) severe alterations of cell-cell contacts and the cytoskeletal architecture and (2) profound functional permeability changes, the putative cellular correlate of the clinical vascular leakage syndrome. However, the endothelial barrier was protected from these profound adverse effects when HUVECs were challenged

  6. Paranodal permeability in `myelin mutants'

    PubMed Central

    Shroff, S.; Mierzwa, A.; Scherer, S.S.; Peles, E.; Arevalo, J.C.; Chao, M.V.; Rosenbluth, J.

    2011-01-01

    Fluorescent dextran tracers of varying sizes have been used to assess paranodal permeability in myelinated sciatic nerve fibers from control and three `myelin mutant' mice, Caspr-null, cst-null and shaking. We demonstrate that in all of these the paranode is permeable to small tracers (3kDa, 10kDa), which penetrate most fibers, and to larger tracers (40kDa, 70kDa), which penetrate far fewer fibers and move shorter distances over longer periods of time. Despite gross diminution in transverse bands in the Caspr-null and cst-null mice, the permeability of their paranodal junctions is equivalent to that in controls. Thus, deficiency of transverse bands in these mutants does not increase the permeability of their paranodal junctions to the dextrans we used, moving from the perinodal space through the paranode to the internodal periaxonal space. In addition, we show that the shaking mice, which have thinner myelin and shorter paranodes, show increased permeability to the same tracers despite the presence of transverse bands. We conclude that the extent of penetration of these tracers does not depend on the presence or absence of transverse bands but does depend on the length of the paranode and, in turn, on the length of `pathway 3', the helical extracellular pathway that passes through the paranode parallel to the lateral edge of the myelin sheath. PMID:21618613

  7. Dextran/Albumin hydrogel sealant for Dacron(R) vascular prosthesis.

    PubMed

    Lisman, Anna; Butruk, Beata; Wasiak, Iga; Ciach, Tomasz

    2014-05-01

    In this paper, the authors describe a novel type of hydrogel coating prepared from the copolymer of human serum albumin and oxidized dextran. The material was designed as a hydrogel sealant for polyester (Dacron®)-based vascular grafts. Dextran was chosen as a coating material due to its anti-thrombogenic properties. Prepared hydrogels were compared with similar, already known biomaterial made from gelatine with the same cross-linking agent. Obtained hydrogels, prepared from various ratios of oxidized dextran/albumin or oxidized dextran/gelatine, showed different cross-linking densities, which caused differences in swelling, degradation rate and mechanical properties. Permeability tests confirmed the complete tightness of the hydrogel-modified prosthesis. Results showed that application of the hydrogel coating provided leakage-free prosthesis and eliminated the need of pre-clotting.

  8. Phenol-soluble modulin α4 mediates Staphylococcus aureus-associated vascular leakage by stimulating heparin-binding protein release from neutrophils

    PubMed Central

    li, Lin; Pian, Yaya; Chen, Shaolong; Hao, Huaijie; Zheng, Yuling; Zhu, Li; Xu, Bin; Liu, Keke; Li, Min; Jiang, Hua; Jiang, Yongqiang

    2016-01-01

    Vascular leakage frequently occurs in patients with severe Staphylococcus aureus infection. However, the mechanism underlying S. aureus infection-induced vascular leakage remains unclear. Here, we identified the S. aureus virulence factor phenol-soluble modulin (PSM)α4 from the culture supernatant of strain USA300 as a stimulator of heparin-binding protein (HBP) release from polymorphonuclear neutrophils (PMNs) and demonstrated that PSMα4-induced HBP release from PMNs leads to vascular leakage. PSMα4 appeared less cytolytic than PSMα1–3 and was insensitive to lipoproteins; it significantly increased myeloperoxidase and elastase release from PMNs and cell surface CD63 expression in PMNs. PSMα4-induced HBP release required formyl peptide receptor 2 (FPR2) and phosphoinositide 3-kinase (PI3K) and depended on Ca2+ influx and cytoskeleton rearrangement. Thus, PSMα4 may stimulate HBP release by activating FPR2 and PI3K to initiate PMN degranulation. PSMα4-induced HBP release from PMNs increased endothelial cell monolayer permeability in vitro and induced vascular leakage in mice. This novel function of PSMα4 may contribute to the pathogenesis of S. aureus and may be a potential therapeutic target. PMID:27383625

  9. CO2 breakthrough pressure and permeability for unsaturated low-permeability sandstone of the Ordos Basin

    NASA Astrophysics Data System (ADS)

    Zhao, Yan; Yu, Qingchun

    2017-07-01

    With rising threats from greenhouse gases, capture and injection of CO2 into suitable underground formations is being considered as a method to reduce anthropogenic emissions of CO2 to the atmosphere. As the injected CO2 will remain in storage for hundreds of years, the safety of CO2 geologic sequestration is a major concern. The low-permeability sandstone of the Ordos Basin in China is regarded as both caprock and reservoir rock, so understanding the breakthrough pressure and permeability of the rock is necessary. Because part of the pore volume experiences a non-wetting phase during the CO2 injection and migration process, the rock may be in an unsaturated condition. And if accidental leakage occurs, CO2 will migrate up into the unsaturated zone. In this study, breakthrough experiments were performed at various degrees of water saturation with five core samples of low-permeability sandstone obtained from the Ordos Basin. The experiments were conducted at 40 °C and pressures of >8 MPa to simulate the geological conditions for CO2 sequestration. The results indicate that the degree of water saturation and the pore structure are the main factors affecting the rock breakthrough pressure and permeability, since the influence of calcite dissolution and clay mineral swelling during the saturation process is excluded. Increasing the average pore radius or most probable pore radius leads to a reduction in the breakthrough pressure and an increase by several orders of magnitude in scCO2 effective permeability. In addition, the breakthrough pressure rises and the scCO2 effective permeability decreases when the water saturation increases. However, when the average pore radius is greater than 0.151 μm, the degree of water saturation will has a little effect on the breakthrough pressure. On this foundation, if the most probable pore radius of the core sample reaches 1.760 μm, the breakthrough pressure will not be impacted by the increasing water saturation. We establish

  10. Evaluation of Clinical Outcomes and Renal Vascular Pathology among Patients with Lupus

    PubMed Central

    Barber, Claire; Herzenberg, Andrew; Aghdassi, Ellie; Su, Jiandong; Lou, Wendy; Qian, Gan; Yip, Jonathan; Nasr, Samih H.; Thomas, David; Scholey, James W.; Wither, Joan; Urowitz, Murray; Gladman, Dafna; Reich, Heather

    2012-01-01

    Summary Background and objectives The objective of this study was to determine the clinical significance of renal vascular lesions in lupus nephritis. Design, setting, participants, & measurements Renal vascular lesions defined as thrombotic microangiopathy, lupus vasculopathy, uncomplicated vascular immune deposits, and arterial sclerosis were evaluated in relation to renal and vascular morbidity and overall mortality. Results Biopsies from 161 patients revealed thrombotic microangiopathy (13), lupus vasculopathy (5), and arterial sclerosis (93). No renal vascular lesions were found in 24.8% of patients. At the time of biopsy, arterial sclerosis or lupus vasculopathy patients were older (arterial sclerosis=37.9±13.0 and lupus vasculopathy=44.4±8.9 versus controls=33.1±8.9 years, P<0.05), and the mean arterial pressure was higher in all groups compared with controls. Nephritis subtype, activity indices, and proteinuria were similar between groups, estimated GFR was lower in arterial sclerosis (70.5±33.3 versus 84.5±26.6 ml/min per 1.73 m2, P=0.03), and chronicity index (thrombotic microangiopathy=3.5, lupus vasculopathy=4.5, and arterial sclerosis=2.5) was higher in all renal vascular lesions subgroups versus controls (1.0, P<0.05). In 133 patients with similar follow-up, the association between renal vascular lesions and vascular events was significant (Fisher exact test, P=0.002) and remained so after multivariate analysis (exact conditional scores test, P=0.04), where the difference between arterial sclerosis and uncomplicated vascular immune deposits was most noticeable (odds ratio [95% confidence interval]=8.35[0.98, 83.12], P=0.05). The associations between renal vascular lesions, renal outcomes, and death were not significant, likely because of insufficient power. Conclusions Renal vascular lesions are common in SLE patients with nephritis and may be associated with arterial vascular events. PMID:22442181

  11. 46 CFR 172.240 - Permeability of spaces.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Permeability of spaces. 172.240 Section 172.240 Shipping... Permeability of spaces. When doing the calculations required in § 172.225, (a) The permeability of a floodable space, other than a machinery or cargo space, must be assumed as listed in Table 172.240; (b...

  12. 46 CFR 172.240 - Permeability of spaces.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Permeability of spaces. 172.240 Section 172.240 Shipping... Permeability of spaces. When doing the calculations required in § 172.225, (a) The permeability of a floodable space, other than a machinery or cargo space, must be assumed as listed in Table 172.240; (b...

  13. 46 CFR 172.240 - Permeability of spaces.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Permeability of spaces. 172.240 Section 172.240 Shipping... Permeability of spaces. When doing the calculations required in § 172.225, (a) The permeability of a floodable space, other than a machinery or cargo space, must be assumed as listed in Table 172.240; (b...

  14. 46 CFR 172.240 - Permeability of spaces.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Permeability of spaces. 172.240 Section 172.240 Shipping... Permeability of spaces. When doing the calculations required in § 172.225, (a) The permeability of a floodable space, other than a machinery or cargo space, must be assumed as listed in Table 172.240; (b...

  15. 46 CFR 172.240 - Permeability of spaces.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Permeability of spaces. 172.240 Section 172.240 Shipping... Permeability of spaces. When doing the calculations required in § 172.225, (a) The permeability of a floodable space, other than a machinery or cargo space, must be assumed as listed in Table 172.240; (b...

  16. Serum vascular endothelial growth factor and adiponectin levels in patients with benign and malignant gynecological diseases.

    PubMed

    Lasalandra, Carla; Coviello, Maria; Falco, Gaetano; Divella, Rosa; Trojano, Giuseppe; Laterza, Anna Maria; Quero, Carmela; Pepe, Vito; Zito, Francesco Alfredo; Quaranta, Michele

    2010-05-01

    One of the most specific and critical regulators of angiogenesis is vascular endothelial growth factor (VEGF), which regulates endothelial proliferation, permeability, and survival. Vascular endothelial growth factor is an angiogenic mediator in tumors and has been implicated in the pathogenesis and progression of cancer. Adipose tissue is a major endocrine and it secretes hormones termed adipokines. These factors are derived from adipocytes and include proteins and metabolites such as adiponectin. Recently, adiponectin was also shown to modulate angiogenesis. This study was designed to determine the serum VEGF and adiponectin levels in patients with benign and malignant gynecological diseases and if there was a correlation between serum VEGF and adiponectin. Serum samples, collected fasting before surgery or intervention, were available for total of 114 female patients recorded between October 2006 and December 2008. Diagnosis of benign and malignant gynaecological diseases was established by biopsy. Serum levels VEGF and adiponectin were using commercially available enzyme linked immunosorbent assay (R&D Systems Inc, Minneapolis, MN), respectively. Statistical analysis was performed by using the SPSS 9.0 software package (SPSS, Inc, Chicago, IL). The correlation between serum VEGF and serum Adiponectin was calculated using the Pearson correlation coefficient. P values of < 0.05 were considered statistically significant. Our results were analyzed on the basis of 2 different parameters: age and benign and malignant gynecological diseases of the patient. Only for serum VEGF levels was a significant difference observed (P = 0.004) between patients with benign and malignant gynecological diseases. A significantly inverse correlation between serum VEGF and adiponectin levels among patients with benign and malignant gynecological diseases was found. Adiponectin level is not correlated with body mass index. This is one of the first report on adiponectin in benign and

  17. Mapping permeability over the surface of the Earth

    USGS Publications Warehouse

    Gleeson, T.; Smith, L.; Moosdorf, N.; Hartmann, J.; Durr, H.H.; Manning, A.H.; Van Beek, L. P. H.; Jellinek, A. Mark

    2011-01-01

    Permeability, the ease of fluid flow through porous rocks and soils, is a fundamental but often poorly quantified component in the analysis of regional-scale water fluxes. Permeability is difficult to quantify because it varies over more than 13 orders of magnitude and is heterogeneous and dependent on flow direction. Indeed, at the regional scale, maps of permeability only exist for soil to depths of 1-2 m. Here we use an extensive compilation of results from hydrogeologic models to show that regional-scale (>5 km) permeability of consolidated and unconsolidated geologic units below soil horizons (hydrolithologies) can be characterized in a statistically meaningful way. The representative permeabilities of these hydrolithologies are used to map the distribution of near-surface (on the order of 100 m depth) permeability globally and over North America. The distribution of each hydrolithology is generally scale independent. The near-surface mean permeability is of the order of ???5 ?? 10-14 m2. The results provide the first global picture of near-surface permeability and will be of particular value for evaluating global water resources and modeling the influence of climate-surface-subsurface interactions on global climate change. Copyright ?? 2011 by the American Geophysical Union.

  18. Mapping permeability over the surface of the Earth

    USGS Publications Warehouse

    Gleeson, Tom; Smith, Leslie; Moosdorf, Nils; Hartmann, Jens; Durr, Hans H.; Manning, Andrew H.; van Beek, Ludovicus P. H.; Jellinek, A. Mark

    2011-01-01

    Permeability, the ease of fluid flow through porous rocks and soils, is a fundamental but often poorly quantified component in the analysis of regional-scale water fluxes. Permeability is difficult to quantify because it varies over more than 13 orders of magnitude and is heterogeneous and dependent on flow direction. Indeed, at the regional scale, maps of permeability only exist for soil to depths of 1-2 m. Here we use an extensive compilation of results from hydrogeologic models to show that regional-scale (>5 km) permeability of consolidated and unconsolidated geologic units below soil horizons (hydrolithologies) can be characterized in a statistically meaningful way. The representative permeabilities of these hydrolithologies are used to map the distribution of near-surface (on the order of 100 m depth) permeability globally and over North America. The distribution of each hydrolithology is generally scale independent. The near-surface mean permeability is of the order of -5 x 10-14 m2. The results provide the first global picture of near-surface permeability and will be of particular value for evaluating global water resources and modeling the influence of climate-surface-subsurface interactions on global climate change.

  19. Occipital blood-brain barrier permeability is an independent predictor of visual outcome in type 2 diabetes, irrespective of the retinal barrier: A longitudinal study.

    PubMed

    Abuhaiba, S I; Cordeiro, M; Amorim, A; Cruz, Â; Quendera, B; Ferreira, C; Ribeiro, L; Bernardes, R; Castelo-Branco, M

    2018-01-01

    Blood-brain barrier (BBB) permeability in type 2 diabetic patients has been previously shown to be altered in certain brain regions such as the basal ganglia and the hippocampus. Because of the histological and functional similarities between the BBB) and the blood-retinal barrier (BRB), we aimed to investigate how the permeability of both barriers predicts visual outcome. We included 2 control groups (acute unilateral stroke patients, n = 9; type 2 diabetics without BRB leakage n = 10) and a case study group of type 2 diabetics with established BRB leakage (n = 17). We evaluated sex, age, disease duration, metabolic impairment, retinopathy grade and BBB permeability as predictors of visual acuity at baseline, 12  and 24 months in the type 2 diabetics without BRB leakage group and the case study group. We have also explored differences in BBB permeability in the occipital lobe and frontal lobe in the 3 different groups. K trans (volume transfer coefficient) and V p (fractional plasma volume) were estimated. The BBB permeability parameter V p was higher in the case study group compared to the unaffected hemisphere of the stroke patient control group, suggesting vascular dynamics were changed in the occipital lobe of type 2 diabetics with established BRB leakage. These patients showed a significant correlation between glycated hemoglobin (HbA1C) levels and occipital and frontal K trans . We report for the first time that occipital BBB permeability is an independent predictor of visual acuity at baseline, as well as at 12 and 24 months, in type 2 diabetics with established BRB leakage. Our results suggest that occipital BBB permeability might be an independent biomarker for visual impairment in patients with established BRB leakage. © 2017 British Society for Neuroendocrinology.

  20. Permeability enhancement by shock cooling

    NASA Astrophysics Data System (ADS)

    Griffiths, Luke; Heap, Michael; Reuschlé, Thierry; Baud, Patrick; Schmittbuhl, Jean

    2015-04-01

    The permeability of an efficient reservoir, e.g. a geothermal reservoir, should be sufficient to permit the circulation of fluids. Generally speaking, permeability decreases over the life cycle of the geothermal system. As a result, is usually necessary to artificially maintain and enhance the natural permeability of these systems. One of the methods of enhancement -- studied here -- is thermal stimulation (injecting cold water at low pressure). This goal of this method is to encourage new thermal cracks within the reservoir host rocks, thereby increasing reservoir permeability. To investigate the development of thermal microcracking in the laboratory we selected two granites: a fine-grained (Garibaldi Grey granite, grain size = 0.5 mm) and a course-grained granite (Lanhelin granite, grain size = 2 mm). Both granites have an initial porosity of about 1%. Our samples were heated to a range of temperatures (100-1000 °C) and were either cooled slowly (1 °C/min) or shock cooled (100 °C/s). A systematic microstructural (2D crack area density, using standard stereological techniques, and 3D BET specific surface area measurements) and rock physical property (porosity, P-wave velocity, uniaxial compressive strength, and permeability) analysis was undertaken to understand the influence of slow and shock cooling on our reservoir granites. Microstructurally, we observe that the 2D crack surface area per unit volume and the specific surface area increase as a result of thermal stressing, and, for the same maximum temperature, crack surface area is higher in the shock cooled samples. This observation is echoed by our rock physical property measurements: we see greater changes for the shock cooled samples. We can conclude that shock cooling is an extremely efficient method of generating thermal microcracks and modifying rock physical properties. Our study highlights that thermal treatments are likely to be an efficient method for the "matrix" permeability enhancement of

  1. Modelling of Longwall Mining-Induced Strata Permeability Change

    NASA Astrophysics Data System (ADS)

    Adhikary, D. P.; Guo, H.

    2015-01-01

    The field measurement of permeability within the strata affected by mining is a challenging and expensive task, thus such tests may not be carried out in large numbers to cover all the overburden strata and coal seams being affected by mining. However, numerical modelling in conjunction with a limited number of targeted field measurements can be used efficiently in assessing the impact of mining on a regional scale. This paper presents the results of underground packer testing undertaken at a mine site in New South Wales in Australia and numerical simulations conducted to assess the mining-induced strata permeability change. The underground packer test results indicated that the drivage of main headings (roadways) had induced a significant change in permeability into the solid coal barrier. Permeability increased by more than 50 times at a distance of 11.2-11.5 m from the roadway rib into the solid coal barrier. The tests conducted in the roof strata above the longwall goaf indicated more than 1,000-fold increase in permeability. The measured permeability values varied widely and strangely on a number of occasions; for example the test conducted from the main headings at the 8.2-8.5 m test section in the solid coal barrier showed a decline in permeability value as compared to that at the 11.2-11.5 m section contrary to the expectations. It is envisaged that a number of factors during the tests might have had affected the measured values of permeability: (a) swelling and smearing of the borehole, possibly lowering the permeability values; (b) packer bypass by larger fractures; (c) test section lying in small but intact (without fractures) rock segment, possibly resulting in lower permeability values; and (d) test section lying right at the extensive fractures, possibly measuring higher permeability values. Once the anomalous measurement data were discarded, the numerical model results could be seen to match the remaining field permeability measurement data

  2. 46 CFR 174.090 - Permeability of spaces.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Permeability of spaces. 174.090 Section 174.090 Shipping... Permeability of spaces. When doing the calculations required in § 174.065— (a) The permeability of a floodable space, other than a machinery space, must be as listed in Table 174.090; and (b) Calculations in which a...

  3. 46 CFR 174.090 - Permeability of spaces.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Permeability of spaces. 174.090 Section 174.090 Shipping... Permeability of spaces. When doing the calculations required in § 174.065— (a) The permeability of a floodable space, other than a machinery space, must be as listed in Table 174.090; and (b) Calculations in which a...

  4. 46 CFR 174.090 - Permeability of spaces.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Permeability of spaces. 174.090 Section 174.090 Shipping... Permeability of spaces. When doing the calculations required in § 174.065— (a) The permeability of a floodable space, other than a machinery space, must be as listed in Table 174.090; and (b) Calculations in which a...

  5. 46 CFR 174.090 - Permeability of spaces.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Permeability of spaces. 174.090 Section 174.090 Shipping... Permeability of spaces. When doing the calculations required in § 174.065— (a) The permeability of a floodable space, other than a machinery space, must be as listed in Table 174.090; and (b) Calculations in which a...

  6. 46 CFR 172.140 - Permeability of spaces.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Permeability of spaces. 172.140 Section 172.140 Shipping... Subchapter O of This Chapter § 172.140 Permeability of spaces. (a) When doing the calculations required in § 172.130, the permeability of a floodable space other than a machinery space must be as listed in Table...

  7. 46 CFR 172.185 - Permeability of spaces.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Permeability of spaces. 172.185 Section 172.185 Shipping... Under Subchapter O of This Chapter § 172.185 Permeability of spaces. (a) When doing the calculations required in § 172.170, the permeability of a floodable space other than a machinery space must be as listed...

  8. 46 CFR 172.185 - Permeability of spaces.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Permeability of spaces. 172.185 Section 172.185 Shipping... Under Subchapter O of This Chapter § 172.185 Permeability of spaces. (a) When doing the calculations required in § 172.170, the permeability of a floodable space other than a machinery space must be as listed...

  9. 46 CFR 172.185 - Permeability of spaces.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Permeability of spaces. 172.185 Section 172.185 Shipping... Under Subchapter O of This Chapter § 172.185 Permeability of spaces. (a) When doing the calculations required in § 172.170, the permeability of a floodable space other than a machinery space must be as listed...

  10. 46 CFR 172.140 - Permeability of spaces.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Permeability of spaces. 172.140 Section 172.140 Shipping... Subchapter O of This Chapter § 172.140 Permeability of spaces. (a) When doing the calculations required in § 172.130, the permeability of a floodable space other than a machinery space must be as listed in Table...

  11. 46 CFR 172.140 - Permeability of spaces.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Permeability of spaces. 172.140 Section 172.140 Shipping... Subchapter O of This Chapter § 172.140 Permeability of spaces. (a) When doing the calculations required in § 172.130, the permeability of a floodable space other than a machinery space must be as listed in Table...

  12. 46 CFR 172.140 - Permeability of spaces.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Permeability of spaces. 172.140 Section 172.140 Shipping... Subchapter O of This Chapter § 172.140 Permeability of spaces. (a) When doing the calculations required in § 172.130, the permeability of a floodable space other than a machinery space must be as listed in Table...

  13. 46 CFR 172.140 - Permeability of spaces.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Permeability of spaces. 172.140 Section 172.140 Shipping... Subchapter O of This Chapter § 172.140 Permeability of spaces. (a) When doing the calculations required in § 172.130, the permeability of a floodable space other than a machinery space must be as listed in Table...

  14. 46 CFR 174.090 - Permeability of spaces.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Permeability of spaces. 174.090 Section 174.090 Shipping... Permeability of spaces. When doing the calculations required in § 174.065— (a) The permeability of a floodable space, other than a machinery space, must be as listed in Table 174.090; and (b) Calculations in which a...

  15. 46 CFR 172.185 - Permeability of spaces.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Permeability of spaces. 172.185 Section 172.185 Shipping... Under Subchapter O of This Chapter § 172.185 Permeability of spaces. (a) When doing the calculations required in § 172.170, the permeability of a floodable space other than a machinery space must be as listed...

  16. 46 CFR 172.185 - Permeability of spaces.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Permeability of spaces. 172.185 Section 172.185 Shipping... Under Subchapter O of This Chapter § 172.185 Permeability of spaces. (a) When doing the calculations required in § 172.170, the permeability of a floodable space other than a machinery space must be as listed...

  17. Polymer as Permeability Modifier in Porous Media

    NASA Astrophysics Data System (ADS)

    Parsa, S.; Weitz, D.

    2017-12-01

    Polymer flow through porous media is of particular interest in applications such as enhanced oil recovery and ground water remediation. We measure the effects of polymer flow on the permeability and local velocity distribution of a single phase flow in 3D micromodel of porous media using confocal microscopy and bulk permeability measurement. Our measurements show considerable reduction in permeability and increased velocity fluctuations with fluid velocities being diverted in some pores after polymer flow. We also find that the average velocity in the medium at constant imposed flow rate scales with the inverse square root of permeability.

  18. Evaluation of vascular space involvement in endometrial adenocarcinomas: laparoscopic vs abdominal hysterectomies.

    PubMed

    Folkins, Ann K; Nevadunsky, Nicole S; Saleemuddin, A; Jarboe, Elke A; Muto, Michael G; Feltmate, Colleen M; Crum, Chris P; Hirsch, Michelle S

    2010-08-01

    Recent reports have described 'vascular pseudoinvasion' in total laparoscopic hysterectomies with endometrial carcinoma. To better understand this phenomenon, we compared pathologic findings in these laparoscopic and total abdominal hysterectomies performed for uterine endometrioid adenocarcinoma. Reports from 58 robotically assisted laparoscopic and 39 abdominal hysterectomies with grade 1 or 2 endometrioid endometrial adenocarcinomas were reviewed for stage, depth of invasion, vascular space involvement, uterine weight, and lymph node metastases. In addition, attention was given to possible procedural artifacts, including vertical endomyometrial clefts, and inflammatory debris, benign endometrial glands, and disaggregated tumor cells in vascular spaces. All foci with vascular involvement were reviewed by three gynecologic pathologists. Nine of the 58 (16%) laparoscopic and 3 of the 39 (7%) abdominal hysterectomies contained vascular space involvement based on the original pathology reports (P-value=0.0833). No one histologic feature consistently distinguished laparoscopic from abdominal cases on blind review of the available cases. Disaggregated intravascular tumor cells were significantly associated with reported vascular involvement in both procedures (P-values<0.001 and 0.016), most of which were corroborated on review. Laparoscopic procedures tend to have a higher index of vascular involvement, which is associated with lower stage, fewer lymph node metastases, and less myometrial invasion; however, pathologists cannot consistently determine the procedure on histologic findings alone. Moreover, there is significant inter-observer variability in distinguishing true from artifactual vascular space involvement, even among pathologists at the same institution. The clinical significance of apparent true vascular space involvement seen adjacent to artifacts is unclear, as is the impact of laparoscopic hysterectomy on recurrence risk.

  19. Correlation between three-dimensional power Doppler and morphometric measurement of endometrial vascularity at the time of embryo implantation in women with unexplained recurrent miscarriage.

    PubMed

    Chen, Xiaoyan; Saravelos, Sotirios H; Liu, Yingyu; Huang, Jin; Wang, Chi Chiu; Li, Tin Chiu

    2017-06-01

    Power Doppler in combination with three-dimensional (3D-PD) ultrasonography has been used as a noninvasive tool to evaluate the vascularity. However, it is unclear whether 3D-PD can accurately reflect endometrial vascularization and replace the invasive endometrial biopsy. This study aims to investigate the correlation between 3D-PD and micro vessel morphometric measurement of endometrial vascularity. Twenty-five women with unexplained recurrent miscarriage were recruited for 3D-PD and endometrial biopsy on precisely day LH + 7. Immunohistochemistry using vWF was employed to identify micro vessels in endometrial biopsy specimens followed by the use of morphometric technique to measure the mean vessel diameter and volume fractions. The vascularization index (VI), flow index (FI) and vascularization flow index (VFI) assessed by 3D-PD were calculated for both the endometrial and sub-endometrial regions. There were no significant correlations between any of the ultrasonographic measurements (endometrial thickness, endometrial volume, endometrial VI/FI/VFI, sub-endometrial volume, sub-endometrial VI/FI/VFI) and morphometric features (number of micro vessel, mean diameter of micro vessel and volume fraction measurement of vessel). This study indicates that endometrial vascularity assessed by 3D-PD could not be used to reflect changes in micro vessels of the endometrium at the time of embryo implantation in women with unexplained recurrent miscarriage.

  20. In Vivo Imaging Reveals Significant Tumor Vascular Dysfunction and Increased Tumor Hypoxia-Inducible Factor-1α Expression Induced by High Single-Dose Irradiation in a Pancreatic Tumor Model

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Maeda, Azusa; Department of Medical Biophysics, University of Toronto, Toronto, Ontario; Chen, Yonghong

    Purpose: To investigate the effect of high-dose irradiation on pancreatic tumor vasculature and microenvironment using in vivo imaging techniques. Methods and Materials: A BxPC3 pancreatic tumor xenograft was established in a dorsal skinfold window chamber model and a subcutaneous hind leg model. Tumors were irradiated with a single dose of 4, 12, or 24 Gy. The dorsal skinfold window chamber model was used to assess tumor response, vascular function and permeability, platelet and leukocyte adhesion to the vascular endothelium, and tumor hypoxia for up to 14 days after 24-Gy irradiation. The hind leg model was used to monitor tumor size, hypoxia, and vascularitymore » for up to 65 days after 24-Gy irradiation. Tumors were assessed histologically to validate in vivo observations. Results: In vivo fluorescence imaging revealed temporary vascular dysfunction in tumors irradiated with a single dose of 4 to 24 Gy, but most significantly with a single dose of 24 Gy. Vascular functional recovery was observed by 14 days after irradiation in a dose-dependent manner. Furthermore, irradiation with 24 Gy caused platelet and leukocyte adhesion to the vascular endothelium within hours to days after irradiation. Vascular permeability was significantly higher in irradiated tumors compared with nonirradiated controls 14 days after irradiation. This observation corresponded with increased expression of hypoxia-inducible factor-1α in irradiated tumors. In the hind leg model, irradiation with a single dose of 24 Gy led to tumor growth delay, followed by tumor regrowth. Conclusions: Irradiation of the BxPC3 tumors with a single dose of 24 Gy caused transient vascular dysfunction and increased expression of hypoxia-inducible factor-1α. Such biological changes may impact tumor response to high single-dose and hypofractionated irradiation, and further investigations are needed to better understand the clinical outcomes of stereotactic body radiation therapy.« less

  1. [Primary Study on Noninvasive Detection of Vascular Function Based on Finger Temperature Change].

    PubMed

    Dong, Qing; Li, Xia; Wan, Yungao; Lu, Gaoquan; Wang, Xinxin; Zhang, Kuan

    2016-02-01

    By studying the relationship between fingertip temperature changes and arterial function during vascular reactivity test, we established a new non-invasive method for detecting vascular function, in order to provide an assistance for early diagnosis and prevention of cardiovascular diseases. We customized three modules respectively for blood occlusion, measurement of finger temperature and blood oxygen acquisition, and then we established the hardware of data acquisition system. And the software was programmed with Labview. Healthy subjects [group A, n = 24, (44.6 ± 9.0) years] and subjects with cardiovascular diseases [group B, n = 33, (57.2 ± 9.9) years)] were chosen for the study. Subject's finger temperature, blood oxygen and occlusion pressure of block side during and after unilateral arm brachial artery occlusion were recorded, as well as some other regular physiological indexes. By time-domain analysis, we extracted 12 parameters from fingertip temperature signal, including the initial temperature (Ti), temperature rebound (TR), the time of the temperature recovering to initial status (RIt) and other parameters from the finger temperature signal. We in the experiment also measured other regular physiological body mass index (BMI), systolic blood pressure (SBP), diastiolic blood pressure (DBP) and so on. Results showed that 8 parameters difference between the two group of data were significant. based on the statistical results. A discriminant function of vascular function status was established afterwards. We found in the study that the changes of finger temperature during unilateral arms brachial artery occlusion and open were closely related to vascular function. We hope that the method presented in this article could lay a foundation of early detection of vascular function.

  2. Permeability-porosity relationship for compaction of a low-permeability creeping material : Experimental evaluation using a single transient test

    NASA Astrophysics Data System (ADS)

    Ghabezloo, S.; Sulem, J.; Saint-Marc, J.

    2009-04-01

    It is well-known that there is no unique permeability-porosity relationship that can be applied to all porous materials. For a given evolution process that changes both permeability and porosity of a porous material, for example elastic or plastic compaction, microcracking or chemical alteration, it is usually assumed that there is an empirical relationship in the form of a power-law or exponential relationship between these parameters. The coefficients of these empirical relationships depend strongly on the properties of the material and of the evolution process. For the case of the power-law permeability-porosity relationship, a review of the literature shows that the exponent of this relation may be integer or non-integer, constant or variable, and the reported values of exponent vary between 1.1 and 25.4 for different materials and evolution processes, but no clear correlation between the exponenet and the petrophysical properties could be found. This wide variability of the permeability-porosity relationship highlights the necessity of experimental evaluation of this relationship for each material and evolution process. An experimental method is presented for the evaluation of a permeability-porosity relationship in a low-permeability porous material using the results of a single transient test. This method accounts for both elastic and non-elastic deformations of the sample during the test and is applied to a hardened class G oil well cement paste. An initial hydrostatic undrained loading is applied to the sample which generates an excess pore pressure, related to the applied hydrostatic stress by the Skempton coefficient of the material. The generated excess pore pressure is then released at one end of the sample while monitoring the pore pressure at the other end and the radial strain in the middle of the sample during the dissipation of the pore pressure. These measurements are back analysed using a finite-difference numerical scheme to evaluate the

  3. Active intestinal drug absorption and the solubility-permeability interplay.

    PubMed

    Porat, Daniel; Dahan, Arik

    2018-02-15

    The solubility-permeability interplay deals with the question: what is the concomitant effect on the drug's apparent permeability when increasing the apparent solubility with a solubility-enabling formulation? The solubility and the permeability are closely related, exhibit certain interplay between them, and ongoing research throughout the past decade shows that treating the one irrespectively of the other may be insufficient. The aim of this article is to provide an overview of the current knowledge on the solubility-permeability interplay when using solubility-enabling formulations for oral lipophilic drugs, highlighting active permeability aspects. A solubility-enabling formulation may affect the permeability in opposite directions; the passive permeability may decrease as a result of the apparent solubility increase, according to the solubility-permeability tradeoff, but at the same time, certain components of the formulation may inhibit/saturate efflux transporters (when relevant), resulting in significant apparent permeability increase. In these cases, excipients with both solubilizing and e.g. P-gp inhibitory properties may lead to concomitant increase of both the solubility and the permeability. Intelligent development of such formulation will account for the simultaneous effects of the excipients' nature/concentrations on the two arms composing the overall permeability: the passive and the active arms. Overall, thorough mechanistic understanding of the various factors involved in the solubility-permeability interplay may allow developing better solubility-enabling formulations, thereby exploiting the advantages analyzed in this article, offering oral delivery solution even for BCS class IV drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Role of reactive oxygen and nitrogen species in the vascular responses to inflammation

    PubMed Central

    Kvietys, Peter R.; Granger, D. Neil

    2012-01-01

    Inflammation is a complex and potentially life-threatening condition that involves the participation of a variety of chemical mediators, signaling pathways, and cell types. The microcirculation, which is critical for the initiation and perpetuation of an inflammatory response, exhibits several characteristic functional and structural changes in response to inflammation. These include vasomotor dysfunction (impaired vessel dilation and constriction), the adhesion and transendothelial migration of leukocytes, endothelial barrier dysfunction (increased vascular permeability), blood vessel proliferation (angiogenesis), and enhanced thrombus formation. These diverse responses of the microvasculature largely reflect the endothelial cell dysfunction that accompanies inflammation and the central role of these cells in modulating processes as varied as blood flow regulation, angiogenesis, and thrombogenesis. The importance of endothelial cells in inflammation-induced vascular dysfunction is also predicated on the ability of these cells to produce and respond to reactive oxygen and nitrogen species. Inflammation seems to upset the balance between nitric oxide and superoxide within (and surrounding) endothelial cells, which is necessary for normal vessel function. This review is focused on defining the molecular targets in the vessel wall that interact with reactive oxygen species and nitric oxide to produce the characteristic functional and structural changes that occur in response to inflammation. This analysis of the literature is consistent with the view that reactive oxygen and nitrogen species contribute significantly to the diverse vascular responses in inflammation and supports efforts that are directed at targeting these highly reactive species to maintain normal vascular health in pathological conditions that are associated with acute or chronic inflammation. PMID:22154653

  5. [Vascular Lesions of Vocal Folds - Part 2: Perpendicular Vascular Lesions].

    PubMed

    Arens, C; Glanz, H; Voigt-Zimmermann, S

    2015-11-01

    The present work aims at a systematic pathogenetic description of perpendicular vascular changes in the vocal folds. Unlike longitudinal vascular changes, like ectasia and meander, perpendicular vascular changes can be observed in bening lesions. They predominantly occur as typical vascular loops in exophytic lesions, especially in recurrent respiratory papillomatosis (RRP), pre-cancerous and cancerous diseases of the larynx and vocal folds. Neoangiogenesis is caused by an epithelial growth stimulus in the early phase of cancerous genesis. In RRP the VVC impress by a single, long vessel loop with a narrow angle turning point in the each single papilla of the papilloma. In pre- and cancerous lesions the vascular loop is located directly underneath the epithelium. During progressive tumor growth, vascular loops develop an increasingly irregular, convoluted, spirally shape. The arrangement of the vascular loops is primarily still symmetrical. In the preliminary stage of tumor development occurs by neoangiogenesis to a microvascular compression. In advanced vocal fold carcinoma the regular vascular vocal fold structure is destroyed. The various stages of tumor growth are also characterized by typical primary epithelial and secondary connective tissue changes. The characteristic triad of vascular, epithelial and connective tissue changes therefore plays an important role in differential diagnosis. © Georg Thieme Verlag KG Stuttgart · New York.

  6. Leukocyte Subtype Counts and Its Association with Vascular Structure and Function in Adults with Intermediate Cardiovascular Risk. MARK Study

    PubMed Central

    Gomez-Sanchez, Leticia; García-Ortiz, Luis; Recio-Rodríguez, José I.; Patino-Alonso, Maria C.; Agudo-Conde, Cristina; Rigo, Fernando; Ramos, Rafel; Martí, Ruth; Gomez-Marcos, Manuel A.

    2015-01-01

    Objectives We investigated the relationship between leukocyte subtype counts and vascular structure and function based on carotid intima-media thickness, pulse wave velocity, central augmentation index and cardio-ankle vascular index by gender in intermediate cardiovascular risk patients. Methods This study analyzed 500 subjects who were included in the MARK study, aged 35 to 74 years (mean: 60.3±8.4), 45.6% women. Measurement: Brachial ankle Pulse Wave Velocity (ba-PWV) estimate by equation, Cardio-AnkleVascular Index (CAVI) using the VaSera device and Carotid ultrasound was used to measure carotid Intima Media Thickness (IMT). The Mobil-O-Graph was used to measure the Central Augmentation Index (CAIx). Results Total leukocyte, neutrophil and monocyte counts were positively correlated with IMT (p < 0.01) in men. Monocyte count was positively correlated with CAIx in women (p < 0.01). In a multiple linear regression analysis, the IMT mean maintained a positive association with the neutrophil count (β = 1.500, p = 0.007) in men. CAIx maintained a positive association with the monocyte count (β = 2.445, p = 0.022) in women. Conclusion The results of this study suggest that the relationship between subtype circulating leukocyte counts and vascular structure and function, although small, may be different by gender. In men, the neutrophil count was positively correlated with IMT and in women, the monocyte count with CAIx, in a large sample of intermediate-risk patients. These association were maintained after adjusting for age and other confounders. Trial Registration ClinicalTrials.gov NCT01428934 PMID:25885665

  7. Long-term Metal Performance of Three Permeable Pavements

    EPA Science Inventory

    EPA constructed a 4,000-m2 parking lot surfaced with three permeable pavements (permeable interlocking concrete pavers, pervious concrete, and porous asphalt) on the Edison Environmental Center in Edison, NJ in 2009. Samples from each permeable pavement infiltrate were collected...

  8. [Quantification and monitoring of vascular resistance in the lower limbs by the Doppler method (animal model)

    NASA Technical Reports Server (NTRS)

    Arbeille, P.; Berson, M.; Blondeau, B.; Durand, A.; Bodard, S.; Locatelli, A.; Fox, G. E. (Principal Investigator)

    1995-01-01

    The object of this study was to define and validate a non-invasive method of evaluation and monitoring of vascular resistances in the leg. Blood flow velocity was measured by Doppler ultrasound in an animal model (ewe) with similar blood flow characteristics in the lower limb as man and allowing access to the required invasive measurements for validation of the method (pressure and flow). Vascular resistances distal to the measuring point (femoral, for example) were assessed using the resistance index R = D/S, S being the peak systolic deflection and D that of diastolic reflux of the Doppler spectral analysis of flow in the femoral artery. The values and variations of this resistance index were compared with the vascular resistances calculated from measurements of pressure and flow at the point of Doppler sampling and expressed in mmHg/ml/min. Femoral flow was measured by Doppler ultrasound (Doppler-echo), and mean pressure by an arterial catheter introduced into the abdominal aorta. Compression of the lower limb veins induced a venous return resulting in a reduction of cardiac output and femoral flow. During compression, femoral flow decreased by an average of 29% (p < 0.001) although mean pressure and heart rate did not change significantly. The femoral resistance index (Rf) increased by an average of 37.5% (p < 0.01) and vascular resistances increased by 45.9% (p < 0.01). Injection of 1 mg adrenaline induced peripheral vasoconstriction with an increase in blood pressure and a decrease in heart rate and femoral flow.(ABSTRACT TRUNCATED AT 250 WORDS).

  9. Permeable Pavement Research - Edison, New Jersey

    EPA Science Inventory

    This presentation provides the background and summary of results collected at the permeable pavement parking lot monitored at the EPA facility in Edison, NJ. This parking lot is surfaced with permeable interlocking concrete pavers (PICP), pervious concrete, and porous asphalt. ...

  10. Coexistence of pheochromocytoma with uncommon vascular lesions

    PubMed Central

    Kota, Sunil Kumar; Kota, Siva Krishna; Meher, Lalit Kumar; Jammula, Sruti; Panda, Sandip; Modi, Kirtikumar D.

    2012-01-01

    Background: Pheochromocytoma/paragangliomas have been described to be associated with rare vascular abnormalities like renal artery stenosis. Coexistence of physiologically significant renal artery lesions is a compounding factor that alters management and prognosis of pheochromocytoma patients. Apart from individual case reports, data on such association in Indian population is not available. The aim of this study is to find the nature and prevalence of associated vascular abnormalities. Materials and Methods: From 1990 to 2010, a total of 50 patients were diagnosed with pheochromocytoma/paragangliomas. Hospital charts of these patients were reviewed retrospectively to identify those with unusual vascular abnormalities. Available literature was also reviewed. Results: Of the 50 patients with pheochromocytoma, 7 (14%) had coexisting vascular lesions including renal artery stenosis in 4, aortoarteritis in 1, aortic aneurysm in 1 and inferior vena cava thrombosis in 1. Pheochromocytoma was adrenal in 42 and extra adrenal in 8. Laparoscopic adrenalectomy was done in the patients. One patient with renal artery stenosis due to intimal fibrosis was subjected to percutaneous balloon angioplasty; the other three improved after adrenalectomy and lysis of fibrous adhesive bands. The patient with aortoarteritos was treated with oral steroids. Inferior vena cava thrombosis was reversed with anticoagulants. The patient with abdominal aortic aneurysm was advised for annual follow-up on account of its size of 4.5 cm and asymptomatic presentation. Conclusion: There are multiple mechanisms that can lead to renal artery stenosis and other vascular abnormalities in a case of pheochromocytoma. A high index of suspicion is necessary to enable both entities to be diagnosed preoperatively and allow proper planning of surgical therapy. Incomplete diagnosis may lead to persistent hypertension postoperatively in a case of associated renal artery stenosis. PMID:23226643

  11. Retinal vascular changes are a marker for cerebral vascular diseases

    PubMed Central

    Moss, Heather E.

    2016-01-01

    The retinal circulation is a potential marker of cerebral vascular disease because it shares origin and drainage with the intracranial circulation and because it can be directly visualized using ophthalmoscopy. Cross sectional and cohort studies have demonstrated associations between chronic retinal and cerebral vascular disease, acute retinal and cerebral vascular disease and chronic retinal vascular disease and acute cerebral vascular disease. In particular, certain qualitative features of retinopathy, retinal artery occlusion and increased retinal vein caliber are associated with concurrent and future cerebrovascular events. These associations persist after accounting for confounding variables known to be disease-causing in both circulations, which supports the potential use of retinal vasculature findings to stratify individuals with regards to cerebral vascular disease risk. PMID:26008809

  12. Structural and conformational determinants of macrocycle cell permeability.

    PubMed

    Over, Björn; Matsson, Pär; Tyrchan, Christian; Artursson, Per; Doak, Bradley C; Foley, Michael A; Hilgendorf, Constanze; Johnston, Stephen E; Lee, Maurice D; Lewis, Richard J; McCarren, Patrick; Muncipinto, Giovanni; Norinder, Ulf; Perry, Matthew W D; Duvall, Jeremy R; Kihlberg, Jan

    2016-12-01

    Macrocycles are of increasing interest as chemical probes and drugs for intractable targets like protein-protein interactions, but the determinants of their cell permeability and oral absorption are poorly understood. To enable rational design of cell-permeable macrocycles, we generated an extensive data set under consistent experimental conditions for more than 200 non-peptidic, de novo-designed macrocycles from the Broad Institute's diversity-oriented screening collection. This revealed how specific functional groups, substituents and molecular properties impact cell permeability. Analysis of energy-minimized structures for stereo- and regioisomeric sets provided fundamental insight into how dynamic, intramolecular interactions in the 3D conformations of macrocycles may be linked to physicochemical properties and permeability. Combined use of quantitative structure-permeability modeling and the procedure for conformational analysis now, for the first time, provides chemists with a rational approach to design cell-permeable non-peptidic macrocycles with potential for oral absorption.

  13. Update to permeable pavement research at the Edison ...

    EPA Pesticide Factsheets

    Abstract: The EPA’s Urban Watershed Management Branch (UWMB) has been monitoring the permeable pavement demonstration site at the Edison Environmental Center, NJ since 2010. This site has three different types of permeable pavement including: interlocking concrete permeable pavers; porous concrete; and permeable asphalt. The parking lot is instrumented with water content reflectometers and thermistors for continuous monitoring and has four lined sections for each surface to capture permeable pavement infiltrate for water quality analyses.Previous technical releases concerning the demonstration site focused on monitoring techniques, observed chloride and nutrient concentrations, and infiltration and evaporation rates. Thispresentation summarizes past findings and addresses current water quality efforts. This presentation summarizes past findings and addresses current water quality efforts.

  14. Pulmonary vascular dysfunction in ARDS

    PubMed Central

    2014-01-01

    potential mechanisms for such a link, the existing evidence does not allow firm conclusions to be drawn. Nonetheless, abnormally elevated PVR/TPG may provide a useful index of disease severity and progression. Further studies are required to understand the role and importance of pulmonary vascular dysfunction in ARDS in the era of lung-protective ventilation. PMID:25593744

  15. Lunar electrical conductivity and magnetic permeability

    NASA Technical Reports Server (NTRS)

    Dyal, P.; Parkin, C. W.; Daily, W. D.

    1975-01-01

    Improved analytical techniques are applied to a large Apollo magnetometer data set to yield values of electroconductivity, temperature, magnetic permeability, and iron abundance. Average bulk electroconductivity of the moon is calculated to be .0007 mho/m; a rapid increase with depth to about .003 mho/m within 250 km is indicated. The temperature profile, obtained from the electroconductivity profile for olivine, indicates high lunar temperatures at relatively shallow depths. Magnetic permeability of the moon relative to its environment is calculated to be 1.008 plus or minus .005; a permeability relative to free space of 1.012 plus 0.011, minus 0.008 is obtained. Lunar iron abundances corresponding to this permeability value are 2.5 plus 2.3, minus 1.7 wt% free iron and 5.0-13.5 wt% total iron for a moon composed of a combination of free iron, olivine, and orthopyroxene.

  16. Measuring Permeability of Composite Cryotank Laminants

    NASA Technical Reports Server (NTRS)

    Oliver, Stanley T.; Selvidge, Shawn; Watwood, Michael C.

    2004-01-01

    This paper describes a test method developed to identify whether certain materials and material systems are suitable candidates for large pressurized reusable cryogenic tanks intended for use in current and future manned launch systems. It provides a quick way to screen numerous candidate materials for permeability under anticipated loading environments consistent with flight conditions, as well as addressing reusability issues. cryogenic tank, where the major design issue was hydrogen permeability. It was successfully used to evaluate samples subjected to biaxial loading while maintaining test temperatures near liquid hydrogen. After each sample was thermally preconditioned, a cyclic pressure load was applied to simulate the in-plane strain. First permeability was measured while a sample was under load. Then the sample was unloaded and allowed to return to ambient temperature. The test was repeated to simulate reusability, in order to evaluate its effects on material permeability.

  17. Update to Permeable Pavement Research at the Edison ...

    EPA Pesticide Factsheets

    The EPA’s Urban Watershed Management Branch (UWMB) has been monitoring the permeable pavement demonstration site at the Edison Environmental Center, NJ since 2010. This site has three different types of permeable pavements including interlocking concrete permeable pavers, pervious concrete, and porous asphalt. The permeable pavements are limited to parking spaces while adjacent driving lanes are impermeable and drain to the permeable surfaces. The parking lot is instrumented for continuous monitoring with thermistors and water content reflectometers that measure moisture as infiltrate passes through the storage gallery beneath the permeable pavements into the underlying native soil. Each permeable surface of the parking lot has four lined sections that capture infiltrate in tanks for water quality analyses; these tanks are capable of holding volumes up to 4.1 m3, which represents up to 38 mm (1.5 in.) for direct rainfall on the porous pavement and runoff from adjacent driving lanes that drain into the permeable surface.Previous technical releases concerning the demonstration site focused on monitoring techniques, observed chloride and nutrient concentrations, surface hydrology, and infiltration and evaporation rates. This presentation summarizes these past findings and addresses current water quality efforts including pH, solids analysis, total organic carbon, and chemical oxygen demand. Stormwater runoff continues to be a major cause of water pollution in

  18. Permeability of compacting porous lavas

    NASA Astrophysics Data System (ADS)

    Ashwell, P. A.; Kendrick, J. E.; Lavallée, Y.; Kennedy, B. M.; Hess, K.-U.; von Aulock, F. W.; Wadsworth, F. B.; Vasseur, J.; Dingwell, D. B.

    2015-03-01

    The highly transient nature of outgassing commonly observed at volcanoes is in part controlled by the permeability of lava domes and shallow conduits. Lava domes generally consist of a porous outer carapace surrounding a denser lava core with internal shear zones of variable porosity. Here we examine densification using uniaxial compression experiments on variably crystalline and porous rhyolitic dome lavas from the Taupo Volcanic Zone. Experiments were conducted at 900°C and an applied stress of 3 MPa to 60% strain, while monitoring acoustic emissions to track cracking. The evolution of the porous network was assessed via X-ray computed tomography, He-pycnometry, and relative gas permeability. High starting connected porosities led to low apparent viscosities and high strain rates, initially accompanied by abundant acoustic emissions. As compaction ensued, the lavas evolved; apparent viscosity increased and strain rate decreased due to strain hardening of the suspensions. Permeability fluctuations resulted from the interplay between viscous flow and brittle failure. Where phenocrysts were abundant, cracks had limited spatial extent, and pore closure decreased axial and radial permeability proportionally, maintaining the initial anisotropy. In crystal-poor lavas, axial cracks had a more profound effect, and permeability anisotropy switched to favor axial flow. Irrespective of porosity, both crystalline samples compacted to a threshold minimum porosity of 17-19%, whereas the crystal-poor sample did not achieve its compaction limit. This indicates that unconfined loading of porous dome lavas does not necessarily form an impermeable plug and may be hindered, in part by the presence of crystals.

  19. Alterations in Intestinal Permeability After Thermal Injury,

    DTIC Science & Technology

    1992-01-01

    intestinal permeability has been documented in the infected group. Our finding of increased intestinal many clinical states, including celiac disease ...Crohn’s permeability before the episode of infection suggests, but disease , and other intestinal mucosal disorders.6,7 It was does not prove, a causal...permeability to sugars in patients with Crohn’s disease ofresult in endotoxemia only in those patients who develop the terminal ileus and colon. Digestion

  20. [Association between neuropathy and peripheral vascular insufficiency in patients with diabetes mellitus type 2].

    PubMed

    Millán-Guerrero, Rebeca O; Vásquez, Clemente; Isaís-Millán, Sara; Trujillo-Hernández, Benjamín; Caballero-Hoyos, Ramiro

    2011-01-01

    Diabetes mellitus (DM) can present complications of neuropathy and peripheral arterial disease with high risk for developing foot ulcers and consequent amputations. To identify the association between peripheral vascular disease, and neuropathy in type 2 Diabetes mellitus patients from the Hospital General de Zona No. 1 IMSS in Colima, Mexico. Cross-sectional study of 80 patients with diabetes mellitus evaluated by means of the Edinburgh Claudication Questionnaire, Michigan Neuropathy Screening Instrument, ankle-arm index, Motor Nerve Conduction Velocity and H-reflex. 51 women and 29 men were studied. Mean age was 53.9 +/- 9.6 years, mean diabetes mellitus progression was 8 +/- 6.6 years and mean glucose level was 283 +/- 110 mg/mL. Neuropathy presented in 65 patients (81.2%). Ankle/arm index revealed 19% of patients presented with moderate peripheral vascular insufficiency. Motor Nerve Conduction Velocity was abnormal in 40% of patients and H-reflex was absent in 70%. Grade 2 motor-sensitive polyneuropathy was found in 70-80% of patients and moderate peripheral vascular insufficiency in 19%. It can thus be inferred that the complication of diabetic neuropathy appears before that of peripheral vessel damage.

  1. Nanoemulsions as self-emulsified drug delivery carriers for enhanced permeability of the poorly water-soluble selective β₁-adrenoreceptor blocker Talinolol.

    PubMed

    Ghai, Damanjeet; Sinha, Vivek Ranjan

    2012-07-01

    To enhance the bioavailability of the poorly water-soluble drug talinolol, a self-nanoemulsifying drug delivery system (SNEDDS) comprising 5% (w/v) Brij-721 ethanolic solution (Smix), triacetin, and water, in the ratio of 40:20:40 (% w/w) was developed by constructing pseudo-ternary phase diagrams and evaluated for droplet size, polydispersity index, and surface morphology of nanoemulsions. The effect of nanodrug carriers on drug release and permeability was assessed using stripped porcine jejunum and everted rat gut sac method and compared with hydroalcoholic drug solution, oily solution, and conventional emulsion and suspension. The SNEDDS showed a significant (P < 0.001) increase in drug release, permeability, and in vivo bioavailability as compared to drug suspension. This may be attributed to increased solubility and enhanced permeability of the drug from nanosized emulsion. In this study, a self-nanoemulsifying drug delivery system was utilized to enhance the bioavailability of the poorly water-soluble beta-blocker talinolol. Significant increase in drug release, permeability, and in vivo bioavailability were demonstrated as compared to standard drug suspension. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Comparison of NIRS, laser Doppler flowmetry, photoplethysmography, and pulse oximetry during vascular occlusion challenges.

    PubMed

    Abay, T Y; Kyriacou, P A

    2016-04-01

    Monitoring changes in blood volume, blood flow, and oxygenation in tissues is of vital importance in fields such as reconstructive surgery and trauma medicine. Near infrared spectroscopy (NIRS), laser Doppler (LDF) flowmetry, photoplethysmography (PPG), and pulse oximetry (PO) contribute to such fields due to their safe and noninvasive nature. However, the techniques have been rarely investigated simultaneously or altogether. The aim of this study was to investigate all the techniques simultaneously on healthy subjects during vascular occlusion challenges. Sensors were attached on the forearm (NIRS and LDF) and fingers (PPG and PO) of 19 healthy volunteers. Different degrees of vascular occlusion were induced by inflating a pressure cuff on the upper arm. The responses of tissue oxygenation index (NIRS), tissue haemoglobin index (NIRS), flux (LDF), perfusion index (PPG), and arterial oxygen saturation (PO) have been recorded and analyzed. Moreover, the optical densities were calculated from slow varying dc PPG, in order to distinguish changes in venous blood volumes. The indexes showed significant changes (p  <  0.05) in almost all occlusions, either venous or over-systolic occlusions. However, differentiation between venous and arterial occlusion by LDF may be challenging and the perfusion index (PI) may not be adequate to indicate venous occlusions. Optical densities may be an additional tool to detect venous occlusions by PPG.

  3. Honeycomb Core Permeability Under Mechanical Loads

    NASA Technical Reports Server (NTRS)

    Glass, David E.; Raman, V. V.; Venkat, Venki S.; Sankaran, Sankara N.

    1997-01-01

    A method for characterizing the air permeability of sandwich core materials as a function of applied shear stress was developed. The core material for the test specimens was either Hexcel HRP-3/16-8.0 and or DuPont Korex-1/8-4.5 and was nominally one-half inch thick and six inches square. The facesheets where made of Hercules' AS4/8552 graphite/epoxy (Gr/Ep) composites and were nominally 0.059-in. thick. Cytec's Metalbond 1515-3M epoxy film adhesive was used for co-curing the facesheets to the core. The permeability of the specimens during both static (tension) and dynamic (reversed and non-reversed) shear loads were measured. The permeability was measured as the rate of air flow through the core from a circular 1-in2 area of the core exposed to an air pressure of 10.0 psig. In both the static and dynamic testing, the Korex core experienced sudden increases in core permeability corresponding to a core catastrophic failure, while the URP core experienced a gradual increase in the permeability prior to core failure. The Korex core failed at lower loads than the HRP core both in the transverse and ribbon directions.

  4. Treating vascular lesions.

    PubMed

    Astner, Susanne; Anderson, R Rox

    2005-01-01

    The treatment of acquired vascular lesions is one of the most commonly requested and performed cutaneous laser procedures. Furthermore, every year, 40,000 children are born in the United States each with congenital vascular lesions and malformations. Laser treatment of vascular lesion is based on the principle of selective photothermolysis, conceived in the 1980s. A variety of different lasers and light sources have since been used in the treatment of vascular lesions: lasers with wavelengths between green and yellow, near infrared lasers, and broadband light sources. Despite limitations, this remains the treatment of choice today. This publication addresses acquired and congenital vascular lesions as different entities and proposes a separation of vascular lesions into those that can easily be treated from those where clearance is difficult. Different treatment modalities and the various endpoints of individual vascular lesions will be discussed.

  5. A Comparative Study on Quantitative Assessment of Blood Flow and Vascularization in Polycystic Ovary Syndrome Patients and Normal Women Using Three-Dimensional Power Doppler Ultrasonography.

    PubMed

    Garg, Nitasha; Khaira, Harkiran Kaur; Kaur, Manjot; Sinha, Smita

    2018-04-01

    To compare the quantitative assessment of blood flow and vascularization of ovaries in polycystic ovary syndrome patients and normal women using three-dimensional power Doppler ultrasonography. This cross-sectional quantitative study was conducted on women of reproductive age group (15-45 years) attending Gynaecology OPD AIMSR, Bathinda, Punjab. Thirty women were enrolled in polycystic ovarian syndrome (PCOS) group and 30 healthy women in control group. Women were categorized as polycystic ovary syndrome according to Rotterdam's criteria. The women with PCOS underwent transvaginal USG Doppler on day 6 of the cycle using 3D power Doppler USG equipment (GE Voluson E8), and vascularization index (VI), flow index (FI) and vascularization flow index (VFI) were measured. The mean values of VI, FI and VFI measured by power Doppler ultrasonography were significantly increased ( P value = 0.000) in women with PCOS when compared with healthy women. This study suggests that blood flow and vascularization measured by 3D power Doppler ultrasonography in ovaries of polycystic ovary syndrome patients were significantly more than the ovaries of normal women.

  6. Liquid-permeable electrode

    DOEpatents

    Folser, George R.

    1980-01-01

    Electrodes for use in an electrolytic cell, which are liquid-permeable and have low electrical resistance and high internal surface area are provided of a rigid, porous, carbonaceous matrix having activated carbon uniformly embedded throughout. The activated carbon may be catalyzed with platinum for improved electron transfer between electrode and electrolyte. Activated carbon is mixed with a powdered thermosetting phenolic resin and compacted to the desired shape in a heated mold to melt the resin and form the green electrode. The compact is then heated to a pyrolyzing temperature to carbonize and volatilize the resin, forming a rigid, porous structure. The permeable structure and high internal surface area are useful in electrolytic cells where it is necessary to continuously remove the products of the electrochemical reaction.

  7. The transition from brittle faulting to cataclastic flow: Permeability evolution

    NASA Astrophysics Data System (ADS)

    Zhu, Wenlu; Wong, Teng-Fong

    1997-02-01

    Triaxial compression experiments were conducted to investigate influences of stress and failure mode on axial permeability of five sandstones with porosities ranging from 15% to 35%. In the cataclastic flow regime, permeability and porosity changes closely track one another. A drastic decrease in permeability was triggered by the onset of shear-enhanced compaction caused by grain crushing and pore collapse. The compactive yield stress C* maps out a boundary in stress space separating two different types of permeability evolution. Before C* is attained, permeability and porosity both decrease with increasing effective mean stress, but they are independent of deviatoric stresses. However, with loading beyond C*, both permeability and porosity changes are strongly dependent on the deviatoric and effective mean stresses. In the brittle faulting regime, permeability and porosity changes are more complex. Before the onset of shear-induced dilation C', both permeability and porosity decrease with increasing effective mean stress. Beyond C', permeability may actually decrease in a dilating rock prior to brittle failure. After the peak stress has been attained, the development of a relatively impermeable shear band causes an accelerated decrease of permeability. Permeability evolution in porous sandstones is compared with that in low-porosity crystalline rocks. A conceptual model for the coupling of deformation and fluid transport is proposed in the form of a deformation-permeability map.

  8. [Vascular lesions of vocal folds--part 1: horizontal vascular lesions].

    PubMed

    Voigt-Zimmermann, S; Arens, C

    2014-12-01

    In recent decades, the endoscopic methods and technologies for laryngeal examination have improved so much that not only epithelial changes, but also vascular changes are recognizable at earlier stages. When comparing newer and older literature, the associated increasingly differentiated descriptions of such visible vascular changes of the vocal folds lead to terminological blurring and shifts of meaning. This complicates the technical-scientific discourse. The aim of the present work is a theoretical and conceptual clarification of early vascular changes of vocal folds. Horizontal changes of benigne vascular diseases, e. g. vessel ectasia, meander, increasing number and branching of vessels, change of direction may develop in to manifest vascular lesions, like varicosis, polyps and in case of ruptures to haemorrhages of vocal folds. These beginning and reversible vascular changes, when early detected and discussed basing on etiological knowledge, may lead to more differentiated prognostic statements and adequate therapeutic decisions, e. g. phonosurgery, functional voice therapy, voice hygiene and voice rest. Vertical vascular changes, like vessel loops, occur primarily in laryngeal papilloma, pre-cancerous and cancerous changes of the vocal folds. Already in small cancerous lesions of the vocal folds the vascular architecture is completely destroyed. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Hyaluronic Acid in Vascular and Immune Homeostasis during Normal Pregnancy and Preeclampsia

    PubMed Central

    Ziganshina, M. M.; Pavlovich, S. V.; Bovin, N. V.; Sukhikh, G. T.

    2016-01-01

    Preeclampsia (PE) is a multisystem pathologic state that clinically manifests itself after the 20th week of pregnancy. It is characterized by high maternal and perinatal morbidity and mortality. According to modern concepts, the impairment of trophoblast invasion into maternal spiral arteries, leading to the development of ischemia in placenta, is considered to be the major pathogenetic factor of PE development. Ischemic lesions initiate the development of a systemic inflammatory response (SIR) and endothelial dysfunction, which is the main cause of the multiple organ failure in PE. Some data has appear indicating the importance of a glycans-forming endothelial glycocalyx and extracellular matrix (ECM) for placenta morphogenesis, as well as their role in the regulation of vascular permeability and vascular tone in hypertension disorders and, in particular, PE. Since intact glycocalyx and ECM are considered to be the major factors that maintain the physiological vascular tone and adequate intercellular interactions, their value in PE pathogenesis is underestimated. This review is focused on hyaluronic acid (HA) as the key glycan providing the organization and stabilization of the ECM and glycocalyx, its distribution in tissues in the case of presence or absence of placental pathology, as well as on the regulatory function of hyaluronic acids of various molecular weights in different physiological and pathophysiological processes. The summarized data will provide a better understanding of the PE pathogenesis, with the main focus on glycopathology. PMID:27795844

  10. Diabetes enhances vulnerability to particulate air pollution-associated impairment in vascular reactivity and endothelial function.

    PubMed

    O'Neill, Marie S; Veves, Aristidis; Zanobetti, Antonella; Sarnat, Jeremy A; Gold, Diane R; Economides, Panayiotis A; Horton, Edward S; Schwartz, Joel

    2005-06-07

    Epidemiological studies suggest that people with diabetes are vulnerable to cardiovascular health effects associated with exposure to particle air pollution. Endothelial and vascular function is impaired in diabetes and may be related to increased cardiovascular risk. We examined whether endothelium-dependent and -independent vascular reactivity was associated with particle exposure in individuals with and without diabetes. Study subjects were 270 greater-Boston residents. We measured 24-hour average ambient levels of air pollution (fine particles [PM2.5], particle number, black carbon, and sulfates [SO4(2-)]) approximately 500 m from the patient examination site. Pollutant concentrations were evaluated for associations with vascular reactivity. Linear regressions were fit to the percent change in brachial artery diameter (flow mediated and nitroglycerin mediated), with the particulate pollutant index, apparent temperature, season, age, race, sex, smoking history, and body mass index as predictors. Models were fit to all subjects and then stratified by diagnosed diabetes versus at risk for diabetes. Six-day moving averages of all 4 particle metrics were associated with decreased vascular reactivity among patients with diabetes but not those at risk. Interquartile range increases in SO4(2-) were associated with decreased flow-mediated (-10.7%; 95% CI, -17.3 to -3.5) and nitroglycerin-mediated (-5.4%; 95% CI, -10.5 to -0.1) vascular reactivity among those with diabetes. Black carbon increases were associated with decreased flow-mediated vascular reactivity (-12.6%; 95% CI, -21.7 to -2.4), and PM2.5 was associated with nitroglycerin-mediated reactivity (-7.6%; 95% CI, -12.8 to -2.1). Effects were stronger in type II than type I diabetes. Diabetes confers vulnerability to particles associated with coal-burning power plants and traffic.

  11. EphrinA1 Inhibits Vascular Endothelial Growth Factor-Induced Intracellular Signaling and Suppresses Retinal Neovascularization and Blood-Retinal Barrier Breakdown

    PubMed Central

    Ojima, Tomonari; Takagi, Hitoshi; Suzuma, Kiyoshi; Oh, Hideyasu; Suzuma, Izumi; Ohashi, Hirokazu; Watanabe, Daisuke; Suganami, Eri; Murakami, Tomoaki; Kurimoto, Masafumi; Honda, Yoshihito; Yoshimura, Nagahisa

    2006-01-01

    The Eph receptor/ephrin system is a recently discovered regulator of vascular development during embryogenesis. Activation of EphA2, one of the Eph receptors, reportedly suppresses cell proliferation and adhesion in a wide range of cell types, including vascular endothelial cells. Vascular endothelial growth factor (VEGF) plays a primary role in both pathological angiogenesis and abnormal vascular leakage in diabetic retinopathy. In the study described herein, we demonstrated that EphA2 stimulation by ephrinA1 in cultured bovine retinal endothelial cells inhibits VEGF-induced VEGFR2 receptor phosphorylation and its downstream signaling cascades, including PKC (protein kinase C)-ERK (extracellular signal-regulated kinase) 1/2 and Akt. This inhibition resulted in the reduction of VEGF-induced angiogenic cell activity, including migration, tube formation, and cellular proliferation. These inhibitory effects were further confirmed in animal models. Intraocular injection of ephrinA1 suppressed ischemic retinal neovascularization in a dose-dependent manner in a mouse model. At a dose of 125 ng/eye, the inhibition was 36.0 ± 14.9% (P < 0.001). EphrinA1 also inhibited VEGF-induced retinal vascular permeability in a rat model by 46.0 ± 10.0% (P < 0.05). These findings suggest a novel therapeutic potential for EphA2/ephrinA1 in the treatment of neovascularization and vasopermeability abnormalities in diabetic retinopathy. PMID:16400034

  12. 64Cu-ATSM internal radiotherapy to treat tumors with bevacizumab-induced vascular decrease and hypoxia in human colon carcinoma xenografts.

    PubMed

    Yoshii, Yukie; Yoshimoto, Mitsuyoshi; Matsumoto, Hiroki; Furukawa, Takako; Zhang, Ming-Rong; Inubushi, Masayuki; Tsuji, Atsushi B; Fujibayashi, Yasuhisa; Higashi, Tatsuya; Saga, Tsuneo

    2017-10-24

    Bevacizumab, an anti-vascular endothelial growth factor (VEGF) antibody, is an antiangiogenic agent clinically used for various cancers. However, repeated use of this agent leads to tumor-decreased vascularity and hypoxia with activation of an HIF-1 signaling pathway, which results in drug delivery deficiency and induction of malignant behaviors in tumors. Here, we developed a novel strategy to treat tumors with bevacizumab-induced vascular decrease and hypoxia using 64 Cu-diacetyl-bis ( N 4 -methylthiosemicarbazone) ( 64 Cu-ATSM), a potential theranostic agent, which possesses high tissue permeability and can target over-reduced conditions under hypoxia in tumors, with a human colon carcinoma HT-29 tumor-bearing mouse model. The long-term treatment with bevacizumab caused decreased blood vessel density and activation of an HIF-1 signaling pathway; increased uptake of 64 Cu-ATSM was also observed despite limited blood vessel density in HT-29 tumors. In vivo high-resolution SPECT/PET/CT imaging confirmed reduced vascularity and increased proportion of 64 Cu-ATSM uptake areas within the bevacizumab-treated tumors. 64 Cu-ATSM therapy was effective to inhibit tumor growth and prolong survival of the bevacizumab-treated tumor-bearing mice without major adverse effects. In conclusion, 64 Cu-ATSM therapy effectively enhanced anti-tumor effects in tumors with bevacizumab-induced vascular decrease and hypoxia. 64 Cu-ATSM therapy could represent a novel approach as an add-on to antiangiogenic therapy.

  13. Textile inspired flexible metamaterial with negative refractive index

    NASA Astrophysics Data System (ADS)

    Burgnies, L.; Lheurette, É.; Lippens, D.

    2015-04-01

    This work introduces metallo-dielectric woven fabric as a metamaterial for phase-front manipulation. Dispersion diagram as well as effective medium parameters retrieved from reflection and transmission coefficients point out negative values of refractive index. By numerical simulations, it is evidenced that a pair of meandered metallic wires, arranged in a top to bottom configuration, can yield to a textile metamaterial with simultaneously negative permittivity and permeability. While the effective negative permittivity stems from the metallic grid arrangement, resonating current loop resulting from the top to bottom configuration of two meandered metallic wires in near proximity produces magnetic activity with negative permeability. By adjusting the distance between pairs of metallic wires, the electric plasma frequency can be shifted to overlap the magnetic resonance. Finally, it is shown that the woven metamaterial is insensitive to the incident angle up to around 60°.

  14. Detection of semi-volatile organic compounds in permeable pavement infiltrate

    EPA Science Inventory

    Abstract The Edison Environmental Center (EEC) has a research and demonstration permeable parking lot comprised of three different permeable systems: permeable asphalt, porous concrete and interlocking concrete permeable pavers. Water quality and quantity analysis has been ongoin...

  15. Differential permeability of the blood-testis barrier during reinitiation of spermatogenesis in adult male rats.

    PubMed

    Haverfield, Jenna T; Meachem, Sarah J; Nicholls, Peter K; Rainczuk, Katarzyna E; Simpson, Evan R; Stanton, Peter G

    2014-03-01

    The blood-testis barrier (BTB) sequesters meiotic spermatocytes and differentiating spermatids away from the vascular environment. We aimed to assess whether meiosis and postmeiotic differentiation could occur when the BTB is permeable. Using a model of meiotic suppression and reinitiation, BTB function was assessed using permeability tracers of small, medium, and large (0.6-, 70-, and 150-kDa) sizes to emulate blood- and lymphatic-borne factors that could cross the BTB. Adult rats (n = 9/group) received the GnRH antagonist acyline (10 wk) to suppress gonadotropins, followed by testosterone (24cm Silastic implant), for 2, 4, 7, 10, 15, and 35 days. In acyline-suppressed testes, all tracers permeated the seminiferous epithelium. As spermatocytes up to diplotene stage XIII reappeared, both the 0.6- and 70-kDa tracers, but not 150 kDa, permeated around these cells. Intriguingly, the 0.6- and 70-kDa tracers were excluded from pachytene spermatocytes at stages VII and VIII but not in subsequent stages. The BTB became progressively impermeable to the 0.6- and 70-kDa tracers as stages IV-VII round spermatids reappeared in the epithelium. This coincided with the appearance of the tight junction protein, claudin-12, in Sertoli cells and at the BTB. We conclude that meiosis can occur when the BTB is permeable to factors up to 70 kDa during the reinitiation of spermatogenesis. Moreover, BTB closure corresponds with the presence of particular pachytene spermatocytes and round spermatids. This research has implications for understanding the effects of BTB dynamics in normal spermatogenesis and also potentially in states where spermatogenesis is suppressed, such as male hormonal contraception or infertility.

  16. Permeability and contractile responses of collecting lymphatic vessels elicited by atrial and brain natriuretic peptides

    PubMed Central

    Scallan, Joshua P; Davis, Michael J; Huxley, Virginia H

    2013-01-01

    Atrial and brain natriuretic peptides (ANP and BNP, respectively) are cardiac hormones released into the bloodstream in response to hypervolaemia or fluid shifts to the central circulation. The actions of both peptides include natriuresis and diuresis, a decrease in systemic blood pressure, and inhibition of the renin–angiotensin–aldosterone system. Further, ANP and BNP elicit increases in blood microvessel permeability sufficient to cause protein and fluid extravasation into the interstitium to reduce the vascular volume. Given the importance of the lymphatic vasculature in maintaining fluid balance, we tested the hypothesis that ANP or BNP (100 nm) would likewise elevate lymphatic permeability (Ps) to serum albumin. Using a microfluorometric technique adapted to in vivo lymphatic vessels, we determined that rat mesenteric collecting lymphatic Ps to rat serum albumin increased by 2.0 ± 0.4-fold (P= 0.01, n= 7) and 2.7 ± 0.8-fold (P= 0.07, n= 7) with ANP and BNP, respectively. In addition to measuring Ps responses, we observed changes in spontaneous contraction amplitude and frequency from the albumin flux tracings in vivo. Notably, ANP abolished spontaneous contraction amplitude (P= 0.005) and frequency (P= 0.006), while BNP augmented both parameters by ∼2-fold (P < 0.01 each). These effects of ANP and BNP on contractile function were examined further by using an in vitro assay. In aggregate, these data support the theory that an increase in collecting lymphatic permeability opposes the absorptive function of the lymphatic capillaries, and aids in the retention of protein and fluid in the interstitial space to counteract volume expansion. PMID:23897233

  17. Permeability and contractile responses of collecting lymphatic vessels elicited by atrial and brain natriuretic peptides.

    PubMed

    Scallan, Joshua P; Davis, Michael J; Huxley, Virginia H

    2013-10-15

    Atrial and brain natriuretic peptides (ANP and BNP, respectively) are cardiac hormones released into the bloodstream in response to hypervolaemia or fluid shifts to the central circulation. The actions of both peptides include natriuresis and diuresis, a decrease in systemic blood pressure, and inhibition of the renin-angiotensin-aldosterone system. Further, ANP and BNP elicit increases in blood microvessel permeability sufficient to cause protein and fluid extravasation into the interstitium to reduce the vascular volume. Given the importance of the lymphatic vasculature in maintaining fluid balance, we tested the hypothesis that ANP or BNP (100 nM) would likewise elevate lymphatic permeability (Ps) to serum albumin. Using a microfluorometric technique adapted to in vivo lymphatic vessels, we determined that rat mesenteric collecting lymphatic Ps to rat serum albumin increased by 2.0 ± 0.4-fold (P = 0.01, n = 7) and 2.7 ± 0.8-fold (P = 0.07, n = 7) with ANP and BNP, respectively. In addition to measuring Ps responses, we observed changes in spontaneous contraction amplitude and frequency from the albumin flux tracings in vivo. Notably, ANP abolished spontaneous contraction amplitude (P = 0.005) and frequency (P = 0.006), while BNP augmented both parameters by ∼2-fold (P < 0.01 each). These effects of ANP and BNP on contractile function were examined further by using an in vitro assay. In aggregate, these data support the theory that an increase in collecting lymphatic permeability opposes the absorptive function of the lymphatic capillaries, and aids in the retention of protein and fluid in the interstitial space to counteract volume expansion.

  18. Long-term Metal Performance of Three Permeable Pavements ...

    EPA Pesticide Factsheets

    EPA constructed a 4,000-m2 parking lot surfaced with three permeable pavements (permeable interlocking concrete pavers, pervious concrete, and porous asphalt) on the Edison Environmental Center in Edison, NJ in 2009. Samples from each permeable pavement infiltrate were collected for six years beginning in January 2010 and analyzed for twenty-two metals. Although the infiltrate metals concentrations varied by surface, metal concentrations in more than 99% of the permeable pavement infiltrate samples met both the groundwater effluent limitations and maximum contaminant levels in national primary drinking water regulations for barium, chromium, copper, manganese, nickel and zinc. Arsenic, cadmium, lead and antimony met those standards in 60% to 98% of the samples with no measurable difference found among pavements. Aluminum and iron in pervious concrete and porous asphalt infiltrates met standards at more than 90%, however permeable interlocking concrete paver infiltrates have 50% and 93% samples exceeds standards, respectively. Concentrations of arsenic, iron, potassium, lithium, magnesium, antimony, tin, manganese, and zinc in all permeable pavement infiltrates decreased with time, whereas, aluminum, barium, calcium, chromium and strontium in porous asphalt infiltrates increased. Most metal concentrations in permeable pavement infiltrates either exhibited no significant difference between snow/no-snow seasons or showed statistically larger concentrations

  19. Stainless Steel Permeability

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Buchenauer, Dean A.; Karnesky, Richard A.

    An understanding of the behavior of hydrogen isotopes in materials is critical to predicting tritium transport in structural metals (at high pressure), estimating tritium losses during production (fission environment), and predicting in-vessel inventory for future fusion devices (plasma driven permeation). Current models often assume equilibrium diffusivity and solubility for a class of materials (e.g. stainless steels or aluminum alloys), neglecting trapping effects or, at best, considering a single population of trapping sites. Permeation and trapping studies of the particular castings and forgings enable greater confidence and reduced margins in the models. For FY15, we have continued our investigation of themore » role of ferrite in permeation for steels of interest to GTS, through measurements of the duplex steel 2507. We also initiated an investigation of the permeability in work hardened materials, to follow up on earlier observations of unusual permeability in a particular region of 304L forgings. Samples were prepared and characterized for ferrite content and coated with palladium to prevent oxidation. Issues with the poor reproducibility of measurements at low permeability were overcome, although the techniques in use are tedious. Funding through TPBAR and GTS were secured for a research grade quadrupole mass spectrometer (QMS) and replacement turbo pumps, which should improve the fidelity and throughput of measurements in FY16.« less

  20. Permeability, storage and hydraulic diffusivity controlled by earthquakes

    NASA Astrophysics Data System (ADS)

    Brodsky, E. E.; Fulton, P. M.; Xue, L.

    2016-12-01

    Earthquakes can increase permeability in fractured rocks. In the farfield, such permeability increases are attributed to seismic waves and can last for months after the initial earthquake. Laboratory studies suggest that unclogging of fractures by the transient flow driven by seismic waves is a viable mechanism. These dynamic permeability increases may contribute to permeability enhancement in the seismic clouds accompanying hydraulic fracking. Permeability enhancement by seismic waves could potentially be engineered and the experiments suggest the process will be most effective at a preferred frequency. We have recently observed similar processes inside active fault zones after major earthquakes. A borehole observatory in the fault that generated the M9.0 2011 Tohoku earthquake reveals a sequence of temperature pulses during the secondary aftershock sequence of an M7.3 aftershock. The pulses are attributed to fluid advection by a flow through a zone of transiently increased permeability. Directly after the M7.3 earthquake, the newly damaged fault zone is highly susceptible to further permeability enhancement, but ultimately heals within a month and becomes no longer as sensitive. The observation suggests that the newly damaged fault zone is more prone to fluid pulsing than would be expected based on the long-term permeability structure. Even longer term healing is seen inside the fault zone of the 2008 M7.9 Wenchuan earthquake. The competition between damage and healing (or clogging and unclogging) results in dynamically controlled permeability, storage and hydraulic diffusivity. Recent measurements of in situ fault zone architecture at the 1-10 meter scale suggest that active fault zones often have hydraulic diffusivities near 10-2 m2/s. This uniformity is true even within the damage zone of the San Andreas fault where permeability and storage increases balance each other to achieve this value of diffusivity over a 400 m wide region. We speculate that fault zones

  1. Permeability hysterisis of limestone during isotropic compression.

    PubMed

    Selvadurai, A P S; Głowacki, A

    2008-01-01

    The evolution of permeability hysterisis in Indiana Limestone during application of isotropic confining pressures up to 60 MPa was measured by conducting one-dimensional constant flow rate tests. These tests were carried out either during monotonic application of the confining pressure or during loading-partial unloading cycles. Irreversible permeability changes occurred during both monotonic and repeated incremental compression of the limestone. Mathematical relationships are developed for describing the evolution of path-dependent permeability during isotropic compression.

  2. Role of mitochondrial permeability transition pores in mitochondrial autophagy.

    PubMed

    Rodriguez-Enriquez, Sara; He, Lihua; Lemasters, John J

    2004-12-01

    During autophagy, cells rid themselves of damaged and superfluous mitochondria, as well as other organelles. This activation of mitochondrial turnover could be the result of changes in the physiological state of mitochondria. Confocal microscopy and fluorescence techniques indicate that onset of mitochondrial permeability transition is one such change. The mitochondrial permeability transition is a reversible phenomenon whereby the mitochondrial inner membrane becomes freely permeable to solutes of less than 1500 Da. At onset of the mitochondrial permeability transition, mitochondria depolarize, uncouple, and undergo large amplitude swelling due to opening of permeability transition pores, which may form by aggregation of damaged, misfolded membrane proteins. When injurious cellular stresses occur, cells may protect themselves using autophagy to remove damaged mitochondria and mutated mitochondrial DNA. Ca(2+) overloading, reactive oxygen and nitrogen species, decreased mitochondrial membrane potential, and oxidation of pyridine nucleotides and glutathione all promote mitochondrial damage and onset of the mitochondrial permeability transition. The mitochondrial permeability transition is also associated with necrosis and apoptosis after a variety of stimuli. This review emphasizes the role of the mitochondrial permeability transition as a key event in mitochondrial autophagy.

  3. RS3PE syndrome presenting as vascular endothelial growth factor associated disorder

    PubMed Central

    Arima, K; Origuchi, T; Tamai, M; Iwanaga, N; Izumi, Y; Huang, M; Tanaka, F; Kamachi, M; Aratake, K; Nakamura, H; Ida, H; Uetani, M; Kawakami, A; Eguchi, K

    2005-01-01

    Methods: Vascular endothelial growth factor165 (VEGF165), tumour necrosis factor α (TNFα), and interleukin 1ß (IL1ß) were measured by enzyme linked immunosorbent assay (ELISA) in serum samples from three patients with RS3PE syndrome. As controls, serum samples from 26 healthy volunteers, 12 patients with rheumatoid arthritis, 10 patients with systemic lupus erythematosus, 13 patients with polymyositis/dermatomyositis, 13 patients with vasculitis syndrome, and 6 patients with mixed connective tissue disease were also analysed. Synovial hypervascularity of patients with RS3PE syndrome was estimated by rate of enhancement (E-rate) in a dynamic MRI study. Results: Serum concentrations of VEGF165 (mean (SD) 2223.3 (156.3) pg/ml) were significantly higher in patients with active RS3PE syndrome than in controls before corticosteroid treatment. TNFα and IL1ß levels were similar in patients and controls. Synovial hypervascularity in affected joints and subcutaneous oedema decreased during corticosteroid treatment, in parallel with the fall in serum VEGF165. Conclusions: VEGF promotes synovial inflammation and vascular permeability in patients with RS3PE syndrome, suggesting that RS3PE can be classified as a VEGF associated disorder. PMID:16227418

  4. Cardiorespiratory Fitness is a Strong Predictor of the Cardio-ankle Vascular Index in Hypertensive Middle-aged and Elderly Japanese Men.

    PubMed

    Tanisawa, Kumpei; Ito, Tomoko; Sun, Xiaomin; Kawakami, Ryoko; Oshima, Satomi; Gando, Yuko; Cao, Zhen-Bo; Sakamoto, Shizuo; Higuchi, Mitsuru

    2015-01-01

    This study aimed to examine whether cardiorespiratory fitness (CRF) is associated with arterial stiffening, evaluated using the cardio-ankle vascular index (CAVI), independent of visceral fat (VF) in middle-aged and elderly Japanese men. We also examined whether the relationship between CRF and the CAVI is modified by age and/or hypertension. The CAVI was determined in 157 Japanese men (age range, 30-79 years), including 96 hypertensive subjects (61.1%). CRF was assessed by measuring the peak oxygen uptake (VO2peak). The subjects were divided into low- and high-CRF groups, and the VF area was assessed using magnetic resonance imaging. The VO2peak correlated with the CAVI following adjustment for age and body mass index in the middle-aged and elderly groups (all the subjects: r=-0.285, p<0.001; middle-aged: r=-0.240, p=0.040; elderly: r=-0.225, p=0.049). VF also correlated with the CAVI (r=0.230, p=0.004). A multiple linear regression analysis revealed that age (β=0.406, p<0.001) and the VO2peak (β=-0.186, p=0.015) were associated with the CAVI independently of VF and the mean blood pressure. Two way ANCOVA adjusted for age demonstrated that the hypertensive individuals had higher CAVI values than the normotensive individuals in the low-CRF group, whereas no significant differences in the CAVI were observed in the high-CRF group (p for interaction <0.05). In the present study, CRF was found to be associated with the CAVI, independent of age and VF, in hypertensive middle-aged and elderly Japanese men.

  5. Tc-99m Radiolabeled Alendronate Sodium Microemulsion: Characterization and Permeability Studies Across Caco-2 Cells.

    PubMed

    Elitez, Yetkin; Ekinci, Meliha; Ilem-Ozdemir, Derya; Gundogdu, Evren; Asikoglu, Makbule

    2018-01-01

    Alendronate sodium (ALD) is used orally but it is poorly absorbed from the gastrointestinal (GI) tract. For this reason, microemulsion system was chosen to evaluate ALD from the GI tract after oral delivery. This study was aimed to prepare water-in-oil (w/o) microemulsion formulation of ALD and evaluate the permeability of ALD microemulsion from Caco-2 cell lines with radioactive and nonradioactive studies. The ALD microemulsion was developed by using pseudo-ternary phase diagram and composed of Soybean oil, Colliphor EL, Tween 80, Transcutol and distilled water. The prepared ALD microemulsion was characterized by physical appearance, droplet size, viscosity, pH, electrical conductivity and refractive index. The stability of the formulation was investigated for 6 months at 25±2°C/60±5% of relative humidity (RH) as well as at 40±2°C/75±5% RH. After that 1 mg of ALD was radiolabeled with 99mTc and added to microemulsion. The permeability studies were performed with both 99mTc-ALD microemulsion and ALD microemulsion. The experimental results suggested that ALD microemulsion presented adequate stability with droplet size varying from 37.8±0.9 to 39.9±1.2 nm during incubation time. In addition, ALD microemulsion was radiolabeled with high labeling efficiency (>95%). In a non-radioactive study, ALD permeability was found to be 45 µg.mL-1 and microemulsion has high permeability percentage when compared to another study. The novel w/o microemulsion formulation has been developed for oral delivery of ALD. Based on the results, permeability of ALD could be significantly improved by the microemulsion formulation. In addition, 99mTc-ALD microemulsion in capsule can be used for bone disease treatment and diagnosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Caprock integrity susceptibility to permeable fracture creation

    DOE PAGES

    Frash, Luke; Carey, James William; Ickes, Timothy Lee; ...

    2017-07-14

    Caprock leakage is of crucial concern for environmentally and economically sustainable development of carbon dioxide sequestration and utilization operations. One potential leakage pathway is through fractures or faults that penetrate the caprock. In this study, we investigate the permeability induced by fracturing initially intact Marcellus shale outcrop specimens at stressed conditions using a triaxial direct-shear method. Measurements of induced permeability, fracture geometry, displacement, and applied stresses were all obtained at stressed conditions to investigate the coupled processes of fracturing and fluid flow as may occur in the subsurface. Fracture geometry was directly observed at stressed conditions using X-ray radiography video.more » Numerical simulation was performed to evaluate the stress distribution developed in the experiments. Our experiments show that permeability induced by fracturing is strongly dependent on the stresses at which the fractures are created, the magnitude of shearing displacement, and the duration of flow. The strongest permeability contrast was observed when comparing specimens fractured at low stress to others fractured at higher stress. Measureable fracture permeability decreased by up to 7 orders of magnitude over a corresponding triaxial confining stress range of 3.5 MPa to 30 MPa. These results show that increasing stress, depth, and time are all significant permeability inhibitors that may limit potential leakage through fractured caprock.« less

  7. Caprock integrity susceptibility to permeable fracture creation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Frash, Luke; Carey, James William; Ickes, Timothy Lee

    Caprock leakage is of crucial concern for environmentally and economically sustainable development of carbon dioxide sequestration and utilization operations. One potential leakage pathway is through fractures or faults that penetrate the caprock. In this study, we investigate the permeability induced by fracturing initially intact Marcellus shale outcrop specimens at stressed conditions using a triaxial direct-shear method. Measurements of induced permeability, fracture geometry, displacement, and applied stresses were all obtained at stressed conditions to investigate the coupled processes of fracturing and fluid flow as may occur in the subsurface. Fracture geometry was directly observed at stressed conditions using X-ray radiography video.more » Numerical simulation was performed to evaluate the stress distribution developed in the experiments. Our experiments show that permeability induced by fracturing is strongly dependent on the stresses at which the fractures are created, the magnitude of shearing displacement, and the duration of flow. The strongest permeability contrast was observed when comparing specimens fractured at low stress to others fractured at higher stress. Measureable fracture permeability decreased by up to 7 orders of magnitude over a corresponding triaxial confining stress range of 3.5 MPa to 30 MPa. These results show that increasing stress, depth, and time are all significant permeability inhibitors that may limit potential leakage through fractured caprock.« less

  8. Cell permeability beyond the rule of 5.

    PubMed

    Matsson, Pär; Doak, Bradley C; Over, Björn; Kihlberg, Jan

    2016-06-01

    Drug discovery for difficult targets that have large and flat binding sites is often better suited to compounds beyond the "rule of 5" (bRo5). However, such compounds carry higher pharmacokinetic risks, such as low solubility and permeability, and increased efflux and metabolism. Interestingly, recent drug approvals and studies suggest that cell permeable and orally bioavailable drugs can be discovered far into bRo5 space. Tactics such as reduction or shielding of polarity by N-methylation, bulky side chains and intramolecular hydrogen bonds may be used to increase cell permeability in this space, but often results in decreased solubility. Conformationally flexible compounds can, however, combine high permeability and solubility, properties that are keys for cell permeability and intestinal absorption. Recent developments in computational conformational analysis will aid design of such compounds and hence prediction of cell permeability. Transporter mediated efflux occurs for most investigated drugs in bRo5 space, however it is commonly overcome by high local intestinal concentrations on oral administration. In contrast, there is little data to support significant impact of transporter-mediated intestinal absorption in bRo5 space. Current knowledge of compound properties that govern transporter effects of bRo5 drugs is limited and requires further fundamental and comprehensive studies. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Vascular Cognitive Impairment.

    PubMed

    Dichgans, Martin; Leys, Didier

    2017-02-03

    Cerebrovascular disease typically manifests with stroke, cognitive impairment, or both. Vascular cognitive impairment refers to all forms of cognitive disorder associated with cerebrovascular disease, regardless of the specific mechanisms involved. It encompasses the full range of cognitive deficits from mild cognitive impairment to dementia. In principle, any of the multiple causes of clinical stroke can cause vascular cognitive impairment. Recent work further highlights a role of microinfarcts, microhemorrhages, strategic white matter tracts, loss of microstructural tissue integrity, and secondary neurodegeneration. Vascular brain injury results in loss of structural and functional connectivity and, hence, compromise of functional networks within the brain. Vascular cognitive impairment is common both after stroke and in stroke-free individuals presenting to dementia clinics, and vascular pathology frequently coexists with neurodegenerative pathology, resulting in mixed forms of mild cognitive impairment or dementia. Vascular dementia is now recognized as the second most common form of dementia after Alzheimer's disease, and there is increasing awareness that targeting vascular risk may help to prevent dementia, even of the Alzheimer type. Recent advances in neuroimaging, neuropathology, epidemiology, and genetics have led to a deeper understanding of how vascular disease affects cognition. These new findings provide an opportunity for the present reappraisal of vascular cognitive impairment. We further briefly address current therapeutic concepts. © 2017 American Heart Association, Inc.

  10. Harnessing Electrostatic Forces to Grow Bio-inspired Hierarchical Vascular Networks

    NASA Astrophysics Data System (ADS)

    Behler, Kristopher; Melrose, Zachary; Schott, Andrew; Wetzel, Eric

    2012-02-01

    Vascular networks provide a system for fluid distribution. Artificial vascular materials with enhanced properties are currently being developed that could ultimately be integrated into systems reliant upon fluid transport while retaining their structural properties. An uninterrupted and controllable supply of liquid is optimal for many applications such as continual self-healing materials, in-situ delivery of index matched fluids, thermal management and drug delivery systems could benefit from a bio-inspired vascular approach that combines complex network geometries with minimal processing parameters. Two such approaches to induce vascular networks are electrohydrodynamic viscous fingering (EHVF) and electrical treeing (ET). EHVF is a phenomenon that occurs when a low viscosity liquid is forced through a high viscosity fluid or matrix, resulting in branches due to capillary and viscous forces in the high viscosity material. By applying voltages of 0 -- 60 kV, finger diameter is reduced. ET is the result of partial discharges in a dielectric material. In the vicinity of a small diameter electrode, the local electric field is greater than the global dielectric strength, causing a localized, step-wise, breakdown to occur forming a highly branched interconnected structure. ET is a viable method to produce networks on a smaller, micron, scale than the products of the EHVF method.

  11. Involvement of Vascular Endothelial Growth Factor in Kaposi's Sarcoma Associated with Acquired Immunodeficiency Syndrome

    PubMed Central

    Sakurada, Shinsaku; Kato, Tetsuji; Mashiba, Kohichi; Mori, Shigeo

    1996-01-01

    To examine the role of vascular endothelial growth factor (VEGF) in the development of edema associated with Kaposi's sarcoma (KS) in acquired immunodeficiency syndrome (AIDS), we exploited animal model systems to detect the activity that induces vascular hyper‐permeability (VHP) using cultured AIDS‐KS spindle cells. Cultured AIDS‐KS spindle cells and conditioned medium (AIDS‐KS‐CM) that had been semi‐purified through a heparin affinity column were tested for the ability to induce VHP in animals. The AIDS‐KS spindle cells and AIDS‐KS‐CM induced VHP that was histamine‐independent. The VHP‐inducing activity was detected in the 0.5 M NaCl fraction from the heparin affinity column and was blocked by anti‐VEGF neutralizing antibody. In addition, the production of VEGF was demonstrated in fresh AIDS‐KS tissue as well as in cultured AIDS‐KS cells, while control cells were negative for VEGF production. From these observations, we concluded that AIDS‐KS cells produce a factor(s) that promotes VHP, and this factor could be VEGF. PMID:9045943

  12. The Presence of Vascular Mimicry Predicts High Risk of Clear Cell Renal Cell Carcinoma after Radical Nephrectomy.

    PubMed

    Zhou, Lin; Chang, Yuan; Xu, Le; Liu, Zheng; Fu, Qiang; Yang, Yuanfeng; Lin, Zongming; Xu, Jiejie

    2016-08-01

    Vascular mimicry is a type of tumor cell plasticity. The aim of this study was to determine the prognostic value of vascular mimicry in patients with clear cell renal cell carcinoma. We performed a retrospective cohort study in 387 patients with clear cell renal cell carcinoma who underwent radical nephrectomy at Zhongshan Hospital, Fudan University between 2008 and 2009. Pathological features, baseline patient characteristics and followup data were recorded. Vascular mimicry in clear cell renal cell carcinoma tissue was identified by CD31-periodic acid-Schiff double staining. Univariate and multivariate Cox regression models were used to analyze the impact of prognostic factors on recurrence-free survival. The concordance index and the Akaike information criterion were used to assess the predictive accuracy and sufficiency of different models. Positive vascular mimicry staining occurred in 25 of 387 clear cell renal cell carcinoma cases (6.5%) and it was associated with an increased risk of recurrence (log-rank p <0.001). Incorporating vascular mimicry into pT stage, Fuhrman grade and Leibovich score helped refine individual risk stratification. Moreover, vascular mimicry was identified as an independent prognostic factor (p = 0.001). It was entered into a nomogram together with pT stage, Fuhrman grade, tumor size and necrosis. In the primary cohort the Harrell concordance index for the established nomogram to predict recurrence-free survival was slightly higher than that of the Leibovich model (0.850 vs. 0.823), which failed to reach statistical significance (p = 0.158). Vascular mimicry could be a potential prognosticator for recurrence-free survival in patients with clear cell renal cell carcinoma after radical nephrectomy. Further external validation and functional analysis should be pursued to assess its potential prognostic and therapeutic values for clear cell renal cell carcinoma. Copyright © 2016 American Urological Association Education and Research

  13. Branding of vascular surgery.

    PubMed

    Perler, Bruce A

    2008-03-01

    The Society for Vascular Surgery surveyed primary care physicians (PCPs) to understand how PCPs make referral decisions for their patients with peripheral vascular disease. Responses were received from 250 PCPs in 44 states. More than 80% of the respondents characterized their experiences with vascular surgeons as positive or very positive. PCPs perceive that vascular surgeons perform "invasive" procedures and refer patients with the most severe vascular disease to vascular surgeons but were more than twice as likely to refer patients to cardiologists, believing they are better able to perform minimally invasive procedures. Nevertheless, PCPs are receptive to the notion of increasing referrals to vascular surgeons. A successful branding campaign will require considerable education of referring physicians about the totality of traditional vascular and endovascular care increasingly provided by the contemporary vascular surgical practice and will be most effective at the local grassroots level.

  14. Low-loss single-layer metamaterial with negative index of refraction at visible wavelengths.

    PubMed

    García-Meca, C; Ortuño, R; Salvador, R; Martínez, A; Martí, J

    2007-07-23

    We present a structure exhibiting a negative index of refraction at visible or near infrared frequencies using a single metal layer. This contrasts with recently developed structures based on metal-dielectric-metal composites. The proposed metamaterial consists of periodically arranged thick stripes interacting with each other to give rise to a negative permeability. Improved designs that allow for a negative index for both polarizations are also presented. The structures are numerically analyzed and it is shown that the dimensions can be engineered to shift the negative index band within a region ranging from telecommunication wavelengths down to blue light.

  15. Drug Delivery to the Brain by Focused Ultrasound Induced Blood-Brain Barrier Disruption: Quantitative Evaluation of Enhanced Permeability of Cerebral Vasculature Using Two-Photon Microscopy

    PubMed Central

    Nhan, Tam; Burgess, Alison; Cho, Eunice E.; Stefanovic, Bojana; Lilge, Lothar; Hynynen, Kullervo

    2013-01-01

    Reversible and localized blood-brain barrier disruption (BBBD) using focused ultrasound (FUS) in combination with intravascularly administered microbubbles (MBs) has been established as a non-invasive method for drug delivery to the brain. Using two-photon fluorescence microscopy (2PFM), we imaged the cerebral vasculature during BBBD and observed the extravasation of fluorescent dye in real-time in vivo. We measured the enhanced permeability upon BBBD for both 10kDa and 70kDa dextran conjugated Texas Red (TR) at the acoustic pressure range of 0.2-0.8 MPa and found permeability constants of TR10kDa and TR70kDa vary from 0.0006 to 0.0359 min−1 and 0.0003 to 0.0231 min−1, respectively. For both substances, a linear regression was applied on the permeability constant against the acoustic pressure and the slope from best-fit was found to be 0.039±0.005 min−1/MPa and 0.018±0.005 min−1/MPa, respectively. In addition, the pressure threshold for successfully induced BBBD was confirmed to be 0.4-0.6 MPa. Finally, we identified two types of leakage kinetics (fast and slow) that exhibit distinct permeability constants and temporal disruption onsets, as well as demonstrated their correlations with the applied acoustic pressure and vessel diameter. Direct assessment of vascular permeability and insights on its dependency on acoustic pressure, vessel size and leakage kinetics are important for treatment strategies of BBBD-based drug delivery. PMID:24008151

  16. Cardio-vascular reserve index (CVRI) during exercise complies with the pattern assumed by the cardiovascular reserve hypothesis.

    PubMed

    Segel, Michael J; Bobrovsky, Ben-Zion; Gabbay, Itay E; Ben-Dov, Issahar; Reuveny, Ronen; Gabbay, Uri

    2017-05-01

    The Cardio-vascular reserve index (CVRI) had been empirically validated in diverse morbidities as a quantitative estimate of the reserve assumed by the cardiovascular reserve hypothesis. This work evaluates whether CVRI during exercise complies with the cardiovascular reserve hypothesis. Retrospective study based on a database of patients who underwent cardio-pulmonary exercise testing (CPX) for diverse indications. Patient's physiological measurements were retrieved at four predefined CPX stages (rest, anaerobic threshold, peak exercise and after 2min of recovery). CVRI was individually calculated retrospectively at each stage. Mean CVRI at rest was 0.81, significantly higher (p<0.001) than at all other stages. CVRI decreased with exercise, reaching an average at peak exercise of 0.35, significant lower than at other stages (p<0.001) and very similar regardless of exercise capacity (mean CVRI 0.33-0.37 in 4 groups classified by exercise capacity, p>0.05). CVRI after 2min of recovery rose considerably, most in the group with the best exercise capacity and least in those with the lowest exercise capacity. CVRI during exercise fits the pattern predicted by the cardiovascular reserve hypothesis. CVRI decreased with exercise reaching a minimum at peak exercise and rising with recovery. The CVRI nadir at peak exercise, similar across groups classified by exercise capacity, complies with the assumed exhaustion threshold. The clinical utility of CVRI should be further evaluated. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Studying the Variation in Gas Permeability of Porous Building Substrates

    NASA Astrophysics Data System (ADS)

    Townsend, L.; Savidge, C. R.; Hu, L.; Rizzo, D. M.; Hayden, N. J.; Dewoolkar, M.

    2009-12-01

    Understanding permeability of building materials is important for problems involving studies of contaminant transport. Examples include contamination from fire, acid rain, and chemical and biological weapons. Our research investigates the gas permeability of porous building substrates such as concretes, limestones, sandstones, and bricks. Each sample was cored to produce 70 mm (2.75”) diameter cores approximately 75-130 mm (3-5”) tall. The surface gas permeability was measured on the top surface of these specimens using the AutoScan II device manufactured by New England Research, Inc. The measurements were taken along a 3 mm grid producing a map of surface gas permeability. An example map is shown in Figure 1. The macroscopic measurements were performed along the entire cored specimen. A second set of measurements were made on a 5 mm thick slice cut from the top of each specimen to examine whether these measurements compare better with the surface measurements. The macroscopic gas permeability was measured for all specimens using ASTM D 4525. The results are summarized in Table 1. In general, the surface and macroscopic gas permeability measurements (Table 1) compare reasonably well (within one order of magnitude). The permeability of the 5 mm slices is not significantly different from the entire core for the specimens tested. Figure 1. Results of surface permeability mappingof Ohio Sandstone using the AutoScan II device. a) Map of gas permeability b) Range of gas permeability c) Density function of permeability. Table 1. Gas permeability values (mD)

  18. Estimation of the superhigh-frequency magnetic permeability of alsifer from the measured permeability of composites

    NASA Astrophysics Data System (ADS)

    Starostenko, S. N.; Rozanov, K. N.; Shiryaev, A. O.; Lagar'kov, A. N.; Shalygin, A. N.

    2017-11-01

    The magnetic permeability of alsifer was restored from the frequency dependences of the dielectric and magnetic permeabilities of powder alsifer (AlSiFe alloy)-wax matrix composites. The permeabilities were measured using the coaxial line technique within a frequency range of 0.05-20 GHz. The effect of the concentration, shape, and size of powder particles on the microwave magnetic properties of composites was considered. A good agreement between the measurement results and the Maxwell-Garnett formula generalized with consideration for the particle shape, the percolation threshold, and the skin-effect was obtained. The found sizes of particles agreed with electron microscopy and granulometry data. Both the frequency and the ferromagnetic resonance line figure of merit (FOM) for lamellar particles proved to be higher than for spherical ones. Alsifer powders were shown to be promising fillers for radioabsorbing materials.

  19. Difference between ejection times measured at two different peripheral locations as a novel marker of vascular stiffness

    PubMed Central

    Obata, Yurie; Ruzankin, Pavel; Berkowitz, Dan E.; Steppan, Jochen

    2017-01-01

    Pulse wave velocity (PWV) has been recommended as an arterial damage assessment tool and a surrogate of arterial stiffness. However, the current technology does not allow to measure PWV both continuously and in real-time. We reported previously that peripherally measured ejection time (ET) overestimates ET measured centrally. This difference in ET is associated with the inherent vascular properties of the vessel. In the current study we examined ETs derived from plethysmography simultaneously at different peripheral locations and examined the influence of the underlying arterial properties on ET prolongation by changing the subject’s position. We calculated the ET difference between two peripheral locations (ΔET) and its corresponding PWV for the same heartbeat. The ΔET increased with a corresponding decrease in PWV. The difference between ΔET in the supine and standing (which we call ET index) was higher in young subjects with low mean arterial pressure and low PWV. These results suggest that the difference in ET between two peripheral locations in the supine vs standing positions represents the underlying vascular properties. We propose ΔET in the supine position as a potential novel real-time continuous and non-invasive parameter of vascular properties, and the ET index as a potential non-invasive parameter of vascular reactivity. PMID:29186151

  20. Comparison of the effects of letrozole and cabergoline on vascular permeability, ovarian diameter, ovarian tissue VEGF levels, and blood PEDF levels, in a rat model of ovarian hyperstimulation syndrome.

    PubMed

    Şahin, Nur; Apaydın, Nesin; Töz, Emrah; Sivrikoz, Oya Nermin; Genç, Mine; Turan, Gülüzar Arzu; Cengiz, Hakan; Eskicioğlu, Fatma

    2016-05-01

    To evaluate the effects of letrozole and cabergoline in a rat model of ovarian hyperstimulation syndrome (OHSS). In this prospective, controlled experimental study, the 28 female Wistar rats were divided into four subgroups (one non-stimulated control and three OHSS-positive groups: placebo, letrozole, and cabergoline). To induce OHSS, rats were injected with 10 IU of pregnant mare serum gonadotropin from day 29 to day 32 of life, followed by subcutaneous injection of 30 IU hCG on day 33. Letrozole rats received with a single dose of 0.1 mg/kg letrozole via oral gavage, on the hCG day. Cabergoline rats received with a single dose of 100 µg/kg cabergoline via oral gavage, on the hCG day. All animals were compared in terms of body weight, vascular permeability (VP), ovarian diameter, ovarian tissue VEGF expression (assessed via immunohistochemical staining), and blood pigment epithelium-derived growth factor (PEDF) levels. The OHSS-positive placebo group (group 2) exhibited the highest VP, ovarian diameter, extent of VEGF staining, and lowest PEDF level, as expected. No significant difference was evident between the letrozole and cabergoline groups in terms of any of body weight; VP; PEDF level; ovarian diameter; or the staining intensity of, or percentage staining for, VEGF in ovarian tissues. Letrozole and cabergoline were equally effective to prevent OHSS, reducing the ovarian diameter, VP, and PEDF and VEGF levels to similar extents.

  1. Scanning electron microscopy observation of vascularization around hydroxyapatite using vascular corrosion casts.

    PubMed

    Chang, C S; Su, C Y; Lin, T C

    1999-01-01

    An intimate relationship exists between the regenerative response of the vascular and osseous elements following hydroxyapatite (HA) implantation. In order to fully comprehend the 3-dimensional vascular architecture around HA, dense HA particles were implanted into the tibiae of dogs. Following healing periods of 2 weeks, 1 month, and 3 months, the tibiae were prepared by the corrosion cast technique. Under scanning electron microscopy (SEM) observation, the characteristic vascular morphology of the HA-implanted cavity was successfully demonstrated. The initial vascularization began in the form of loose sinusoidal capillaries. Many sinusoids formed a complex network by anastomosing with each other. The newly formed vessels extended centripetally from the peripheral cavity wall and from the periosteal surface. Under greater magnification, the tapered vascular sprouting was shown to project into the space that was previously occupied by an HA particle. The presence of vascular sprouting is clearly an important indicator of angiogenesis. Increasing vascularization was demonstrated with time. The presence of vessels in the Haversian's canal indicated the more established vascularization. Almost full vascularization of the HA-implanted cavity was seen 3 months after implantation. The vascular organizational layout of the cavity was also clearly shown in the fractured transverse-sectioned sample. In the control without HA implantation, the central region of the cavity showed a hollow pattern in the initial stage. The vascularization looked like it was collapsing and not fully filling the cavity. However, remarkable differences of the final vascular pattern could not be found between the study and control group after 3-month implantation. The study provides the time-lapsed 3-dimensional vascular changes of the HA-implanted cavity, as well as the value of the corrosion cast technique in examining the bony circulation. Copyright 1999 John Wiley & Sons, Inc.

  2. Preliminary study of soil permeability properties using principal component analysis

    NASA Astrophysics Data System (ADS)

    Yulianti, M.; Sudriani, Y.; Rustini, H. A.

    2018-02-01

    Soil permeability measurement is undoubtedly important in carrying out soil-water research such as rainfall-runoff modelling, irrigation water distribution systems, etc. It is also known that acquiring reliable soil permeability data is rather laborious, time-consuming, and costly. Therefore, it is desirable to develop the prediction model. Several studies of empirical equations for predicting permeability have been undertaken by many researchers. These studies derived the models from areas which soil characteristics are different from Indonesian soil, which suggest a possibility that these permeability models are site-specific. The purpose of this study is to identify which soil parameters correspond strongly to soil permeability and propose a preliminary model for permeability prediction. Principal component analysis (PCA) was applied to 16 parameters analysed from 37 sites consist of 91 samples obtained from Batanghari Watershed. Findings indicated five variables that have strong correlation with soil permeability, and we recommend a preliminary permeability model, which is potential for further development.

  3. Petrophysics of low-permeability medina sandstone, northwestern Pennsylvania, Appalachian Basin

    USGS Publications Warehouse

    Castle, J.W.; Byrnes, A.P.

    1998-01-01

    Petrophysical core testing combined with geophysical log analysis of low-permeability, Lower Silurian sandstones of the Appalachian basin provides guidelines and equations for predicting gas producibility. Permeability values are predictable from the borehole logs by applying empirically derived equations based on correlation between in-situ porosity and in-situ effective gas permeability. An Archie-form equation provides reasonable accuracy of log-derived water saturations because of saturated brine salinities and low clay content in the sands. Although measured porosity and permeability average less than 6% and 0.1 mD, infrequent values as high as 18% and 1,048 mD occur. Values of effective gas permeability at irreducible water saturation (Swi) range from 60% to 99% of routine values for the highest permeability rocks to several orders of magnitude less for the lowest permeability rocks. Sandstones having porosity greater than 6% and effective gas permeability greater than 0.01 mD exhibit Swi less than 20%. With decreasing porosity, Swi sharply increases to values near 40% at 3 porosity%. Analysis of cumulative storage and flow capacity indicates zones with porosity greater than 6% generally contain over 90% of flow capacity and hold a major portion of storage capacity. For rocks with Swi < 20%, gas relative permeabilities exceed 45%. Gas relative permeability and hydrocarbon volume decrease rapidly with increasing Swi as porosity drops below 6%. At Swi above 40%, gas relative permeabilities are less than approximately 10%.

  4. Effect of Aggressive lipid-lowering treatment with Rosuvastatin on vascular endoTHelium function: evaluation of vascular endothelium function (EARTH study).

    PubMed

    Takayama, Tadateru; Hiro, Takafumi; Yoda, Shunichi; Fukamachi, Daisuke; Haruta, Hironori; Kogo, Takaaki; Mineki, Takashi; Murata, Hironobu; Oshima, Toru; Hirayama, Atsushi

    2018-06-01

    Vascular endothelial dysfunction plays an important role in the process of atherosclerosis up to the final stage of plaque rupture. Vascular endothelial dysfunction is reversible, and can be recovered by medications and life-style changes. Improvement in endothelial function may reduce cardiovascular events and improve long-term prognosis. A total of 50 patients with stable angina and dyslipidemia were enrolled, including patients who had not received prior treatment with statins and had serum LDL-C levels ≥ 100 mg/dL, and patients who had previously received statin treatment. All agreed to register regardless of their LDL-C level. Rosuvastatin was initially administered at a dose of 2.5 mg and appropriately titrated up to the maximum dose of 20 mg or until LDL-C levels lower than 80 mg/dL were achieved, for 24 weeks. Endothelial function was assessed by the reactive hyperemia peripheral arterial tonometry (RH-PAT) index in the radial artery by Endo-PAT ® 2000 (Endo-PAT ® 2000, software version 3.0.4, Itamar Medical Ltd., Caesarea, Israel). RH-PAT data were digitally analyzed online by Endo-PAT ® 2000 at baseline and at 24 weeks. LDL-C and MDA-LDL-C decreased from 112.6 ± 23.3 to 85.5 ± 20.2 mg/dL and from 135.1 ± 36.4 to 113.9 ± 23.5 mg/dL respectively (p < 0.0001). However, HDL-C, hs-CRP and TG did not change significantly after treatment. RH-PAT index levels significantly improved, from 1.60 ± 0.31 to 1.77 ± 0.57 (p = 0.04) after treatment, and the percent change of the RH-PAT index was 12.8 ± 36.9%. Results of multivariate analysis show that serum LDL-C levels over 24 weeks did not act as a predictor of improvement of the RH-PAT index. However, HbA1c at baseline was an independent predictor which influenced the 24-week RH-PAT index level. The RH-PAT index of patients with high HbA1c at baseline did not improve after administration of rosuvastatin but it did improve in patients with low HbA1c at baseline. Aggressive

  5. Prefabrication of axial vascularized tissue engineering coral bone by an arteriovenous loop: a better model.

    PubMed

    Dong, Qing-shan; Shang, Hong-tao; Wu, Wei; Chen, Fu-lin; Zhang, Jun-rui; Guo, Jia-ping; Mao, Tian-qiu

    2012-08-01

    The most important problem for the survival of thick 3-dimensional tissues is the lack of vascularization in the context of bone tissue engineering. In this study, a modified arteriovenous loop (AVL) was developed to prefabricate an axial vascularized tissue engineering coral bone in rabbit, with comparison of the arteriovenous bundle (AVB) model. An arteriovenous fistula between rabbit femoral artery and vein was anastomosed to form an AVL. It was placed in a circular side groove of the coral block. The complex was wrapped with an expanded-polytetrafluoroethylene membrane and implanted beneath inguinal skin. After 2, 4, 6 and 8 weeks, the degree of vascularization was evaluated by India ink perfusion, histological examination, vascular casts, and scanning electron microscopy images of vascular endangium. Newly formed fibrous tissues and vasculature extended over the surfaces and invaded the interspaces of entire coral block. The new blood vessels robustly sprouted from the AVL. Those invaginated cavities in the vascular endangium from scanning electron microscopy indicated vessel's sprouted pores. Above indexes in AVL model are all superior to that in AVB model, indicating that the modified AVL model could more effectively develop vascularization in larger tissue engineering bone. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Non-invasive determination by cardiovascular magnetic resonance of right ventricular-vascular coupling in children and adolescents with pulmonary hypertension.

    PubMed

    Truong, Uyen; Patel, Sonali; Kheyfets, Vitaly; Dunning, Jamie; Fonseca, Brian; Barker, Alex J; Ivy, Dunbar; Shandas, Robin; Hunter, Kendall

    2015-09-16

    Pediatric pulmonary hypertension (PH) remains a disease with high morbidity and mortality in children. Understanding ventricular-vascular coupling, a measure of how well matched the ventricular and vascular function are, may elucidate pathway leading to right heart failure. Ventricular vascular coupling ratio (VVCR), comprised of effective elastance (Ea, index of arterial load) and right ventricular maximal end-systolic elastance (Ees, index of contractility), is conventionally determined by catheterization. Here, we apply a non-invasive approach to determining VVCR in pediatric subjects with PH. This retrospective study included PH subjects who had a cardiovascular magnetic resonance (CMR) study within 14 days of cardiac catheterization. PH was defined as mean pulmonary artery pressure (mPAP) ≥ 25 mmHg on prior or current catheterization. A non-invasive measure of VVCR was derived from CMR-only (VVCRm) and compared to VVCR estimated by catheterization-derived single beat estimation (VVCRs). Indexed pulmonary vascular resistance (PVRi) and pulmonary vascular reactivity were determined during the catheterization procedure. Pearson correlation coefficients were calculated between PVRi and VVCRm. Receiver operating characteristic (ROC) curve analysis determined the diagnostic value of VVCRm in predicting vascular reactivity. Seventeen subjects (3 months-23 years; mean 11.3 ± 7.4 years) were identified between January 2009-August 2013 for inclusion with equal gender distributions. Mean mPAP was 35 mmHg ± 15 and PVRi was 8.5 Woods unit x m2 ± 7.8. VVCRm (range 0.43-2.82) increased with increasing severity as defined by PVRi (p < 0.001), and was highly correlated with PVRi (r = 0.92, 95 % CI 0.79-0.97, p < 0.0001). Regression of VVCRm and PVRi demonstrated differing lines when separated by reactivity. VVCRm was significantly correlated with VVCRs (r = 0.79, CI 0.48-0.99, p <0.0001). ROC curve analysis showed high accuracy of

  7. Regulation of lung endothelial permeability and inflammatory responses by prostaglandin A2: role of EP4 receptor

    PubMed Central

    Ohmura, Tomomi; Tian, Yufeng; Sarich, Nicolene; Ke, Yunbo; Meliton, Angelo; Shah, Alok S.; Andreasson, Katrin; Birukov, Konstantin G.; Birukova, Anna A.

    2017-01-01

    The role of prostaglandin A2 (PGA2) in modulation of vascular endothelial function is unknown. We investigated effects of PGA2 on pulmonary endothelial cell (EC) permeability and inflammatory activation and identified a receptor mediating these effects. PGA2 enhanced the EC barrier and protected against barrier dysfunction caused by vasoactive peptide thrombin and proinflammatory bacterial wall lipopolysaccharide (LPS). Receptor screening using pharmacological and molecular inhibitory approaches identified EP4 as a novel PGA2 receptor. EP4 mediated barrier-protective effects of PGA2 by activating Rap1/Rac1 GTPase and protein kinase A targets at cell adhesions and cytoskeleton: VE-cadherin, p120-catenin, ZO-1, cortactin, and VASP. PGA2 also suppressed LPS-induced inflammatory signaling by inhibiting the NFκB pathway and expression of EC adhesion molecules ICAM1 and VCAM1. These effects were abolished by pharmacological or molecular inhibition of EP4. In vivo, PGA2 was protective in two distinct models of acute lung injury (ALI): LPS-induced inflammatory injury and two-hit ALI caused by suboptimal mechanical ventilation and injection of thrombin receptor–activating peptide. These protective effects were abolished in mice with endothelial-specific EP4 knockout. The results suggest a novel role for the PGA2–EP4 axis in vascular EC protection that is critical for improvement of pathological states associated with increased vascular leakage and inflammation. PMID:28428256

  8. Microvascular Permeability of Skeletal Muscle After Eccentric Contraction-Induced Muscle Injury: In Vivo Imaging Using Two-Photon Laser Scanning Microscopy.

    PubMed

    Hotta, Kazuki; Behnke, Bradley Jon; Masamoto, Kazuto; Shimotsu, Rie; Onodera, Naoya; Yamaguchi, Akihiko; Poole, David C; Kano, Yutaka

    2018-05-03

    Via modulation of endothelial integrity and vascular permeability in response to damage skeletal muscle microvessels play a crucial permissive role in tissue leukocyte invasion. However, direct visual evidence of altered microvascular permeability of skeletal muscle has not been technically feasible impairing mechanistic understanding of these responses. Two-photon laser scanning microscopy (TPLSM) allows three-dimensional in vivo imaging of skeletal muscle microcirculation. We hypothesized that the regulation of microvessels permeability in vivo is temporally related to acute inflammatory and regenerative processes following muscle injury. To test our hypothesis, tibialis anterior muscle of anesthetized male Wistar rats were subjected to eccentric contractions (ECC) via electrical stimulation. The skeletal muscle microcirculation was imaged by an intravenously infused fluorescent dye (rhodamine b isothiocyanate dextran) to assess microvascular permeability via TPLSM 1, 3 and 7 days after ECC. Immunohistochemistry on muscle sections was performed to determine the proportion of VEGF-A positive fibers in the damaged muscle. Compared with control rats, the volumetrically-determined interstitial leakage of fluorescent dye (5.1 {plus minus} 1.4, 5.3 {plus minus} 1.2 vs. 0.51 {plus minus} 0.14 μm 3 x 10 6 , P < 0.05 respectively days 1 and 3 vs. control) and percentage of VEGF-A positive fibers in the damaged muscle (10 {plus minus} 0.4, 22 {plus minus} 1.1 vs. 0%; days 1 and 3 vs. control) were significantly higher on days 1 and 3 after ECC. The interstitial leakage volume returned to control by day 7. These results suggest that microvascular hyperpermeability assessed by in vivo TPLSM imaging is associated with ECC-induced muscle damage and increased VEGF expression.

  9. Increased intestinal macromolecular permeability and urine nitrite excretion associated with liver cirrhosis with ascites.

    PubMed

    Lee, Soong; Son, Seung-Cheol; Han, Moon-Jong; Kim, Woo-Jin; Kim, Soo-Hyun; Kim, Hye-Ran; Jeon, Woo-Kyu; Park, Ki-Hong; Shin, Myung-Geun

    2008-06-28

    To determine intestinal permeability, the serum tumor necrosis factor (TNF)-alpha level and urine nitric oxide (NO) metabolites are altered in liver cirrhosis (LC) with or without ascites. Fifty-three patients with LC and 26 healthy control subjects were enrolled in the study. The intestinal permeability value is expressed as the percentage of polyethylene glycol (PEG) 400 and 3350 retrieval in 8-h urine samples as determined by high performance liquid chromatography. Serum TNF-alpha concentrations and urine NO metabolites were determined using an enzyme-linked immunosorbent assay (ELISA) and Greiss reaction method, respectively. The intestinal permeability index was significantly higher in patients with LC with ascites than in healthy control subjects or patients with LC without ascites (0.88 +/- 0.12 vs 0.52 +/- 0.05 or 0.53 +/- 0.03, P < 0.05) and correlated with urine nitrite excretion (r = 0.98). Interestingly, the serum TNF-alpha concentration was significantly higher in LC without ascites than in control subjects or in LC with ascites (198.9 +/- 55.8 pg/mL vs 40.9 +/- 12.3 pg/mL or 32.1 +/- 13.3 pg/mL, P < 0.05). Urine nitrite excretion was significantly higher in LC with ascites than in the control subjects or in LC without ascites (1170.9 +/- 28.7 micromol/L vs 903.1 +/- 55.1 micromol/L or 956.7 +/- 47.7 micromol/L, P < 0.05). Increased intestinal macromolecular permeability and NO is probably of importance in the pathophysiology and progression of LC with ascites, but the serum TNF-alpha concentration was not related to LC with ascites.

  10. Using artificial intelligence to predict permeability from petrographic data

    NASA Astrophysics Data System (ADS)

    Ali, Maqsood; Chawathé, Adwait

    2000-10-01

    Petrographic data collected during thin section analysis can be invaluable for understanding the factors that control permeability distribution. Reliable prediction of permeability is important for reservoir characterization. The petrographic elements (mineralogy, porosity types, cements and clays, and pore morphology) interact with each other uniquely to generate a specific permeability distribution. It is difficult to quantify accurately this interaction and its consequent effect on permeability, emphasizing the non-linear nature of the process. To capture these non-linear interactions, neural networks were used to predict permeability from petrographic data. The neural net was used as a multivariate correlative tool because of its ability to learn the non-linear relationships between multiple input and output variables. The study was conducted on the upper Queen formation called the Shattuck Member (Permian age). The Shattuck Member is composed of very fine-grained arkosic sandstone. The core samples were available from the Sulimar Queen and South Lucky Lake fields located in Chaves County, New Mexico. Nineteen petrographic elements were collected for each permeability value using a combined minipermeameter-petrographic technique. In order to reduce noise and overfitting the permeability model, these petrographic elements were screened, and their control (ranking) with respect to permeability was determined using fuzzy logic. Since the fuzzy logic algorithm provides unbiased ranking, it was used to reduce the dimensionality of the input variables. Based on the fuzzy logic ranking, only the most influential petrographic elements were selected as inputs for permeability prediction. The neural net was trained and tested using data from Well 1-16 in the Sulimar Queen field. Relying on the ranking obtained from the fuzzy logic analysis, the net was trained using the most influential three, five, and ten petrographic elements. A fast algorithm (the scaled conjugate

  11. KML001 displays vascular disrupting properties and irinotecan combined antitumor activities in a murine tumor model.

    PubMed

    Moon, Chang Hoon; Lee, Seung Ju; Lee, Ho Yong; Lee, Jong Cheol; Cha, Heejeong; Cho, Wha Ja; Park, Jeong Woo; Park, Hyun Jin; Seo, Jin; Lee, Young Han; Song, Ho-Taek; Min, Young Joo

    2013-01-01

    KML001 is sodium metaarsenite, and has shown cytotoxic activity in human tumor cell lines. The anti-cancer mechanism of KML001 involves cancer cell destruction due to DNA damage at the telomeres of cancer cell chromosomes. In this study, we assessed the vascular disrupting properties of KML001 and investigated whether KML001 as VDA is able to increase anti-tumor activity in irinotecan combined treatment. We used a murine model of the CT26 colon carcinoma cell line. CT26 isograft mice treated intraperitoneally with 10 mg/kg KML001 displayed extensive central necrosis of tumor by 24 h. The vascular disrupting effects of KML001 were assessed by dynamic contrast enhanced magnetic resonance imaging. Gadopentetic acid-diethylene triaminepentaacetic acid contrast enhancement was markedly decreased in KML001-treated mice one day after treatment, whereas persistently high signal enhancement was observed in mice injected with saline. Rate constant K(ep) value representing capillary permeability was significantly decreased (p<0.05) in mice treated with KML001. Cytoskeletal changes of human umbilical vein endothelial cells (HUVECs) treated with 10 uM KML001 were assessed by immune blotting and confocal imaging. KML001 degraded tubulin protein in HUVECs, which may be related to vascular disrupting properties of KML001. Finally, in the mouse CT26 isograft model, KML001 combined with irinotecan significantly delayed tumor growth as compared to control and irinotecan alone. These results suggest that KML001 is a novel vascular disrupting agent, which exhibits significant vascular shut-down activity and enhances anti-tumor activity in combination with chemotherapy. These data further suggest an avenue for effective combination therapy in treating solid tumors.

  12. KML001 Displays Vascular Disrupting Properties and Irinotecan Combined Antitumor Activities in a Murine Tumor Model

    PubMed Central

    Moon, Chang Hoon; Lee, Seung Ju; Lee, Ho Yong; Lee, Jong Cheol; Cha, HeeJeong; Cho, Wha Ja; Park, Jeong Woo; Park, Hyun Jin; Seo, Jin; Lee, Young Han; Song, Ho-Taek; Min, Young Joo

    2013-01-01

    KML001 is sodium metaarsenite, and has shown cytotoxic activity in human tumor cell lines. The anti-cancer mechanism of KML001 involves cancer cell destruction due to DNA damage at the telomeres of cancer cell chromosomes. In this study, we assessed the vascular disrupting properties of KML001 and investigated whether KML001 as VDA is able to increase anti-tumor activity in irinotecan combined treatment. We used a murine model of the CT26 colon carcinoma cell line. CT26 isograft mice treated intraperitoneally with 10 mg/kg KML001 displayed extensive central necrosis of tumor by 24 h. The vascular disrupting effects of KML001 were assessed by dynamic contrast enhanced magnetic resonance imaging. Gadopentetic acid-diethylene triaminepentaacetic acid contrast enhancement was markedly decreased in KML001-treated mice one day after treatment, whereas persistently high signal enhancement was observed in mice injected with saline. Rate constant Kep value representing capillary permeability was significantly decreased (p<0.05) in mice treated with KML001. Cytoskeletal changes of human umbilical vein endothelial cells (HUVECs) treated with 10 uM KML001 were assessed by immune blotting and confocal imaging. KML001 degraded tubulin protein in HUVECs, which may be related to vascular disrupting properties of KML001. Finally, in the mouse CT26 isograft model, KML001 combined with irinotecan significantly delayed tumor growth as compared to control and irinotecan alone. These results suggest that KML001 is a novel vascular disrupting agent, which exhibits significant vascular shut-down activity and enhances anti-tumor activity in combination with chemotherapy. These data further suggest an avenue for effective combination therapy in treating solid tumors. PMID:23326531

  13. Assessing tumor vascularization as a potential biomarker of imatinib resistance in gastrointestinal stromal tumors by dynamic contrast-enhanced magnetic resonance imaging.

    PubMed

    Consolino, Lorena; Longo, Dario Livio; Sciortino, Marianna; Dastrù, Walter; Cabodi, Sara; Giovenzana, Giovanni Battista; Aime, Silvio

    2017-07-01

    Most metastatic gastrointestinal stromal tumors (GISTs) develop resistance to the first-line imatinib treatment. Recently, increased vessel density and angiogenic markers were reported in GISTs with a poor prognosis, suggesting that angiogenesis is implicated in GIST tumor progression and resistance. The purpose of this study was to investigate the relationship between tumor vasculature and imatinib resistance in different GIST mouse models using a noninvasive magnetic resonance imaging (MRI) functional approach. Immunodeficient mice (n = 8 for each cell line) were grafted with imatinib-sensitive (GIST882 and GIST-T1) and imatinib-resistant (GIST430) human cell lines. Dynamic contrast-enhanced MRI (DCE-MRI) was performed on GIST xenografts to quantify tumor vessel permeability (K trans ) and vascular volume fraction (v p ). Microvessel density (MVD), permeability (mean dextran density, MDD), and angiogenic markers were evaluated by immunofluorescence and western blot assays. Dynamic contrast-enhanced magnetic resonance imaging showed significantly increased vessel density (P < 0.0001) and permeability (P = 0.0002) in imatinib-resistant tumors compared to imatinib-sensitive ones. Strong positive correlations were observed between MRI estimates, K trans and v p , and their related ex vivo values, MVD (r = 0.78 for K trans and r = 0.82 for v p ) and MDD (r = 0.77 for K trans and r = 0.94 for v p ). In addition, higher expression of vascular endothelial growth factor receptors (VEGFR2 and VEFGR3) was seen in GIST430. Dynamic contrast-enhanced magnetic resonance imaging highlighted marked differences in tumor vasculature and microenvironment properties between imatinib-resistant and imatinib-sensitive GISTs, as also confirmed by ex vivo assays. These results provide new insights into the role that DCE-MRI could play in GIST characterization and response to GIST treatment. Validation studies are needed to confirm these findings.

  14. Air permeability and trapped-air content in two soils

    USGS Publications Warehouse

    Stonestrom, David A.; Rubin, Jacob

    1989-01-01

    To improve understanding of hysteretic air permeability relations, a need exists for data on the water content dependence of air permeability, matric pressure, and air trapping (especially for wetting-drying cycles). To obtain these data, a special instrument was designed. The instrument is a combination of a gas permeameter (for air permeability determination), a suction plate apparatus (for retentivity curve determination), and an air pycnometer (for trapped-air-volume determination). This design allowed values of air permeability, matric pressure, and air trapping to be codetermined, i.e., determined at the same values of water content using the same sample and the same inflow-outflow boundaries. Such data were obtained for two nonswelling soils. The validity of the air permeability determinations was repeatedly confirmed by rigorous tests of Darcy's law. During initial drying from complete water saturation, supplementary measurements were made to assess the magnitude of gas slip. The extended Darcy equation accurately described the measured flux gradient relations for each condition of absolute gas pressure tested. Air permeability functions exhibited zero-permeability regions at high water contents as well as an abruptly appearing hysteresis at low water contents. Measurements in the zero-permeability regions revealed that the total amount of air in general exceeded the amount of trapped air. This indicates that the medium' s air space is partitioned into three measurable domains: through-flowing air, locally accessible air (i.e., air accessible from only one flow boundary), and trapped air. During repeated wetting and drying, the disappearance and reappearance of air permeability coincided closely with the reappearance and disappearance, respectively, of trapped air. The observed relation between critical features of the air permeability functions and those of the air-trapping functions suggest that water-based blockages play a significant role in the

  15. Options for Dealing with Pressure Dependence of Pulse Wave Velocity as a Measure of Arterial Stiffness: An Update of Cardio-Ankle Vascular Index (CAVI) and CAVI0.

    PubMed

    Spronck, Bart; Delhaas, Tammo; Butlin, Mark; Reesink, Koen D; Avolio, Alberto P

    2018-03-01

    Pulse wave velocity (PWV), a marker of arterial stiffness, is known to change instantaneously with changes in blood pressure. In this mini-review, we discuss two main approaches for handling the blood pressure dependence of PWV: (1) converting PWV into a pressure-independent index, and (2) correcting PWV per se for the pressure dependence. Under option 1, we focus on cardio-ankle vascular index (CAVI). CAVI is essentially a form of stiffness index β - CAVI is estimated for a (heart-to-ankle) trajectory, whereas β is estimated for a single artery from pressure and diameter measurements. Stiffness index β, and therefore also CAVI, have been shown to theoretically exhibit a slight residual blood pressure dependence due to the use of diastolic blood pressure instead of a fixed reference blood pressure. Additionally, CAVI exhibits pressure dependence due to the use of an estimated derivative of the pressure-diameter relationship. In this mini-review, we will address CAVI's blood pressure dependence theoretically, but also statistically. Furthermore, we review corrected indices (CAVI 0 and β 0 ) that theoretically do not show a residual blood pressure dependence. Under option 2, three ways of correcting PWV are reviewed: (1) using an exponential relationship between pressure and cross-sectional area, (2) by statistical model adjustment, and (3) through reference values or rule of thumb. Method 2 requires a population to be studied to characterise the statistical model, and method 3 requires a representative reference study. Given these limitations, method 1 seems preferable for correcting PWV per se for its blood pressure dependence. In summary, several options are available to handle the blood pressure dependence of PWV. If a blood pressure-independent index is sought, CAVI 0 is theoretically preferable over CAVI. If correcting PWV per se is required, using an exponential pressure-area relationship provides the user with a method to correct PWV on an individual

  16. Quantitative analysis of vascular parameters for micro-CT imaging of vascular networks with multi-resolution.

    PubMed

    Zhao, Fengjun; Liang, Jimin; Chen, Xueli; Liu, Junting; Chen, Dongmei; Yang, Xiang; Tian, Jie

    2016-03-01

    Previous studies showed that all the vascular parameters from both the morphological and topological parameters were affected with the altering of imaging resolutions. However, neither the sensitivity analysis of the vascular parameters at multiple resolutions nor the distinguishability estimation of vascular parameters from different data groups has been discussed. In this paper, we proposed a quantitative analysis method of vascular parameters for vascular networks of multi-resolution, by analyzing the sensitivity of vascular parameters at multiple resolutions and estimating the distinguishability of vascular parameters from different data groups. Combining the sensitivity and distinguishability, we designed a hybrid formulation to estimate the integrated performance of vascular parameters in a multi-resolution framework. Among the vascular parameters, degree of anisotropy and junction degree were two insensitive parameters that were nearly irrelevant with resolution degradation; vascular area, connectivity density, vascular length, vascular junction and segment number were five parameters that could better distinguish the vascular networks from different groups and abide by the ground truth. Vascular area, connectivity density, vascular length and segment number not only were insensitive to multi-resolution but could also better distinguish vascular networks from different groups, which provided guidance for the quantification of the vascular networks in multi-resolution frameworks.

  17. Quantifying Evaporation in a Permeable Pavement System

    EPA Science Inventory

    Studies quantifying evaporation from permeable pavement systems are limited to a few laboratory studies and one field application. This research quantifies evaporation for a larger-scale field application by measuring the water balance from lined permeable pavement sections. Th...

  18. A blood-mimicking fluid for particle image velocimetry with silicone vascular models

    NASA Astrophysics Data System (ADS)

    Yousif, Majid Y.; Holdsworth, David W.; Poepping, Tamie L.

    2011-03-01

    For accurate particle image velocimetry measurements in hemodynamics studies, it is important to use a fluid with a refractive index ( n) matching that of the vascular models (phantoms) and ideally a dynamic viscosity matching human blood. In this work, a blood-mimicking fluid (BMF) composed of water, glycerol, and sodium iodide was formulated for a range of refractive indices to match most common silicone elastomers ( n = 1.40-1.43) and with corresponding dynamic viscosity within the average cited range of healthy human blood (4.4 ± 0.5 cP). Both refractive index and viscosity were attained at room temperature (22.2 ± 0.2°C), which eliminates the need for a temperature-control system. An optimally matched BMF, suitable for use in a vascular phantom ( n = 1.4140 ± 0.0008, Sylgard 184), was demonstrated with composition (by weight) of 47.38% water, 36.94% glycerol (44:56 glycerol-water ratio), and 15.68% sodium iodide salt, resulting in a dynamic viscosity of 4 .31 ± 0 .03 cP.

  19. Diabetic hyperglycemia reduces Ca2+ permeability of extrasynaptic AMPA receptors in AII amacrine cells

    PubMed Central

    Castilho, Áurea; Madsen, Eirik; Ambrósio, António F.; Veruki, Margaret L.

    2015-01-01

    There is increasing evidence that diabetic retinopathy is a primary neuropathological disorder that precedes the microvascular pathology associated with later stages of the disease. Recently, we found evidence for altered functional properties of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in A17, but not AII, amacrine cells in the mammalian retina, and the observed changes were consistent with an upregulation of the GluA2 subunit, a key determinant of functional properties of AMPA receptors, including Ca2+ permeability and current-voltage (I-V) rectification properties. Here, we have investigated functional changes of extrasynaptic AMPA receptors in AII amacrine cells evoked by diabetes. With patch-clamp recording of nucleated patches from retinal slices, we measured Ca2+ permeability and I–V rectification in rats with ∼3 wk of streptozotocin-induced diabetes and age-matched, noninjected controls. Under bi-ionic conditions (extracellular Ca2+ concentration = 30 mM, intracellular Cs+ concentration = 171 mM), the reversal potential (Erev) of AMPA-evoked currents indicated a significant reduction of Ca2+ permeability in diabetic animals [Erev = −17.7 mV, relative permeability of Ca2+ compared with Cs+ (PCa/PCs) = 1.39] compared with normal animals (Erev = −7.7 mV, PCa/PCs = 2.35). Insulin treatment prevented the reduction of Ca2+ permeability. I–V rectification was examined by calculating a rectification index (RI) as the ratio of the AMPA-evoked conductance at +40 and −60 mV. The degree of inward rectification in patches from diabetic animals (RI = 0.48) was significantly reduced compared with that in normal animals (RI = 0.30). These results suggest that diabetes evokes a change in the functional properties of extrasynaptic AMPA receptors of AII amacrine cells. These changes could be representative for extrasynaptic AMPA receptors elsewhere in AII amacrine cells and suggest that synaptic and extrasynaptic AMPA

  20. Relationships of methacholine and adenosine monophosphate responsiveness with serum vascular endothelial growth factor in children with asthma.

    PubMed

    Yoo, Young; Choi, Ic Sun; Byeon, Jung Hye; Lee, Seung Min; La, Kyong Suk; Choi, Byung Min; Park, Sang Hee; Choung, Ji Tae

    2010-01-01

    Airway hyperresponsiveness, which is a characteristic feature of asthma, is usually measured by means of bronchial challenge with direct or indirect stimuli. Vascular endothelial growth factor (VEGF) increases vascular permeability and angiogenesis, leads to mucosal edema, narrows the airway diameter, and reduces airway flow. To examine the relationships between serum VEGF level and airway responsiveness to methacholine and adenosine monophosphate (AMP) in children with asthma. Peripheral blood eosinophil counts, serum eosinophil cationic protein (ECP) concentrations, and serum VEGF concentrations were measured in 31 asthmatic children and 26 control subjects. Methacholine and AMP bronchial challenges were performed on children with asthma. Children with asthma had a significantly higher mean (SD) level of VEGF than controls (361.2 [212.0] vs 102.7 [50.0] pg/mL; P < .001). Blood eosinophil counts and serum ECP levels significantly correlated inversely with AMP provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20% (PC20) (r = -0.474, P =.01; r = -0.442, P =.03, respectively), but not with methacholine PC20 (r = -0.228, P = .26; r = -0.338, P =.10, respectively). Serum VEGF levels significantly correlated with airway responsiveness to AMP (r = -0.462; P = .009) but not to methacholine (r = -0.243; P = .19). Serum VEGF levels were increased in children with asthma and were related to airway responsiveness to AMP but not to methacholine. Increased VEGF levels in asthmatic children may result in increased airway responsiveness by mechanisms related to airway inflammation or increased permeability of airway vasculature.

  1. A novel decision tree approach based on transcranial Doppler sonography to screen for blunt cervical vascular injuries.

    PubMed

    Purvis, Dianna; Aldaghlas, Tayseer; Trickey, Amber W; Rizzo, Anne; Sikdar, Siddhartha

    2013-06-01

    Early detection and treatment of blunt cervical vascular injuries prevent adverse neurologic sequelae. Current screening criteria can miss up to 22% of these injuries. The study objective was to investigate bedside transcranial Doppler sonography for detecting blunt cervical vascular injuries in trauma patients using a novel decision tree approach. This prospective pilot study was conducted at a level I trauma center. Patients undergoing computed tomographic angiography for suspected blunt cervical vascular injuries were studied with transcranial Doppler sonography. Extracranial and intracranial vasculatures were examined with a portable power M-mode transcranial Doppler unit. The middle cerebral artery mean flow velocity, pulsatility index, and their asymmetries were used to quantify flow patterns and develop an injury decision tree screening protocol. Student t tests validated associations between injuries and transcranial Doppler predictive measures. We evaluated 27 trauma patients with 13 injuries. Single vertebral artery injuries were most common (38.5%), followed by single internal carotid artery injuries (30%). Compared to patients without injuries, mean flow velocity asymmetry was higher for single internal carotid artery (P = .003) and single vertebral artery (P = .004) injuries. Similarly, pulsatility index asymmetry was higher in single internal carotid artery (P = .015) and single vertebral artery (P = .042) injuries, whereas the lowest pulsatility index was elevated for bilateral vertebral artery injuries (P = .006). The decision tree yielded 92% specificity, 93% sensitivity, and 93% correct classifications. In this pilot feasibility study, transcranial Doppler measures were significantly associated with the blunt cervical vascular injury status, suggesting that transcranial Doppler sonography might be a viable bedside screening tool for trauma. Patient-specific hemodynamic information from transcranial Doppler assessment has the potential to alter

  2. Permeability-porosity data sets for sandstones

    USGS Publications Warehouse

    Nelson, P.H.

    2004-01-01

    Due to the variable nature of permeability-porosity relations, core should be obtained and permeability (k) and porosity (??) should be determined on core plugs in the laboratory for the formation of interest. A catalog of k versus (??) data sets is now available on the Web. Examples from the catalog are considered to illustrate some aspects of k versus ?? dependencies in siliciclastic reservoirs.

  3. Peroxisomal membrane permeability and solute transfer.

    PubMed

    Antonenkov, Vasily D; Hiltunen, J Kalervo

    2006-12-01

    The review is dedicated to recent progress in the study of peroxisomal membrane permeability to solutes which has been a matter of debate for more than 40 years. Apparently, the mammalian peroxisomal membrane is freely permeable to small solute molecules owing to the presence of pore-forming channels. However, the membrane forms a permeability barrier for 'bulky' solutes including cofactors (NAD/H, NADP/H, CoA, and acetyl/acyl-CoA esters) and ATP. Therefore, peroxisomes need specific protein transporters to transfer these compounds across the membrane. Recent electrophysiological studies have revealed channel-forming activities in the mammalian peroxisomal membrane. The possible involvement of the channels in the transfer of small metabolites and in the formation of peroxisomal shuttle systems is described.

  4. Vascular Endothelial Growth Factor in Eye Disease

    PubMed Central

    Penn, J.S.; Madan, A.; Caldwell, R.B.; Bartoli, M.; Caldwell, R.W.; Hartnett, M.E.

    2012-01-01

    Collectively, angiogenic ocular conditions represent the leading cause of irreversible vision loss in developed countries. In the U.S., for example, retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration are the principal causes of blindness in the infant, working age and elderly populations, respectively. Evidence suggests that vascular endothelial growth factor (VEGF), a 40 kDa dimeric glycoprotein, promotes angiogenesis in each of these conditions, making it a highly significant therapeutic target. However, VEGF is pleiotropic, affecting a broad spectrum of endothelial, neuronal and glial behaviors, and confounding the validity of anti-VEGF strategies, particularly under chronic disease conditions. In fact, among other functions VEGF can influence cell proliferation, cell migration, proteolysis, cell survival and vessel permeability in a wide variety of biological contexts. This article will describe the roles played by VEGF in the pathogenesis of retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. The potential disadvantages of inhibiting VEGF will be discussed, as will the rationales for targeting other VEGF-related modulators of angiogenesis. PMID:18653375

  5. Highly tunable refractive index visible-light metasurface from block copolymer self-assembly.

    PubMed

    Kim, Ju Young; Kim, Hyowook; Kim, Bong Hoon; Chang, Taeyong; Lim, Joonwon; Jin, Hyeong Min; Mun, Jeong Ho; Choi, Young Joo; Chung, Kyungjae; Shin, Jonghwa; Fan, Shanhui; Kim, Sang Ouk

    2016-09-29

    The refractive index of natural transparent materials is limited to 2-3 throughout the visible wavelength range. Wider controllability of the refractive index is desired for novel optical applications such as nanoimaging and integrated photonics. We report that metamaterials consisting of period and symmetry-tunable self-assembled nanopatterns can provide a controllable refractive index medium for a broad wavelength range, including the visible region. Our approach exploits the independent control of permeability and permittivity with nanoscale objects smaller than the skin depth. The precise manipulation of the interobject distance in block copolymer nanopatterns via pattern shrinkage increased the effective refractive index up to 5.10. The effective refractive index remains above 3.0 over more than 1,000 nm wavelength bandwidth. Spatially graded and anisotropic refractive indices are also obtained with the design of transitional and rotational symmetry modification.

  6. Highly tunable refractive index visible-light metasurface from block copolymer self-assembly

    PubMed Central

    Kim, Ju Young; Kim, Hyowook; Kim, Bong Hoon; Chang, Taeyong; Lim, Joonwon; Jin, Hyeong Min; Mun, Jeong Ho; Choi, Young Joo; Chung, Kyungjae; Shin, Jonghwa; Fan, Shanhui; Kim, Sang Ouk

    2016-01-01

    The refractive index of natural transparent materials is limited to 2–3 throughout the visible wavelength range. Wider controllability of the refractive index is desired for novel optical applications such as nanoimaging and integrated photonics. We report that metamaterials consisting of period and symmetry-tunable self-assembled nanopatterns can provide a controllable refractive index medium for a broad wavelength range, including the visible region. Our approach exploits the independent control of permeability and permittivity with nanoscale objects smaller than the skin depth. The precise manipulation of the interobject distance in block copolymer nanopatterns via pattern shrinkage increased the effective refractive index up to 5.10. The effective refractive index remains above 3.0 over more than 1,000 nm wavelength bandwidth. Spatially graded and anisotropic refractive indices are also obtained with the design of transitional and rotational symmetry modification. PMID:27683077

  7. Permeability Evolution of Slowly Slipping Faults in Shale Reservoirs

    NASA Astrophysics Data System (ADS)

    Wu, Wei; Reece, Julia S.; Gensterblum, Yves; Zoback, Mark D.

    2017-11-01

    Slow slip on preexisting faults during hydraulic fracturing is a process that significantly influences shale gas production in extremely low permeability "shale" (unconventional) reservoirs. We experimentally examined the impacts of mineralogy, surface roughness, and effective stress on permeability evolution of slowly slipping faults in Eagle Ford shale samples. Our results show that fault permeability decreases with slip at higher effective stress but increases with slip at lower effective stress. The permeabilities of saw cut faults fully recover after cycling effective stress from 2.5 to 17.5 to 2.5 MPa and increase with slip at constant effective stress due to asperity damage and dilation associated with slip. However, the permeabilities of natural faults only partially recover after cycling effective stress returns to 2.5 MPa and decrease with slip due to produced gouge blocking fluid flow pathways. Our results suggest that slowly slipping faults have the potential to enhance reservoir stimulation in extremely low permeability reservoirs.

  8. Influence of vascular network design on gas transfer in lung assist device technology.

    PubMed

    Bassett, Erik K; Hoganson, David M; Lo, Justin H; Penson, Elliot J N; Vacanti, Joseph P

    2011-01-01

    Blood oxygenators are vital for the critically ill, but their use is limited to the hospital setting. A portable blood oxygenator or a lung assist device for ambulatory or long-term use would greatly benefit patients with chronic lung disease. In this work, a biomimetic blood oxygenator system was developed which consisted of a microfluidic vascular network covered by a gas permeable silicone membrane. This system was used to determine the influence of key microfluidic parameters-channel size, oxygen exposure length, and blood shear rate-on blood oxygenation and carbon dioxide removal. Total gas transfer increased linearly with flow rate, independent of channel size and oxygen exposure length. On average, CO(2) transfer was 4.3 times higher than oxygen transfer. Blood oxygen saturation was also found to depend on the flow rate per channel but in an inverse manner; oxygenation decreased and approached an asymptote as the flow rate per channel increased. These relationships can be used to optimize future biomimetic vascular networks for specific lung applications: gas transfer for carbon dioxide removal in patients with chronic obstructive pulmonary disease or oxygenation for premature infants requiring complete lung replacement therapy.

  9. Vascular ring

    MedlinePlus

    ... with aberrant subclavian and left ligamentum ateriosus; Congenital heart defect - vascular ring; Birth defect heart - vascular ring ... accounts for less than 1% of all congenital heart problems. The condition occurs as often in males ...

  10. Novel CCR3 Antagonists Are Effective Mono- and Combination Inhibitors of Choroidal Neovascular Growth and Vascular Permeability.

    PubMed

    Nagai, Nori; Ju, Meihua; Izumi-Nagai, Kanako; Robbie, Scott J; Bainbridge, James W; Gale, David C; Pierre, Esaie; Krauss, Achim H P; Adamson, Peter; Shima, David T; Ng, Yin-Shan

    2015-09-01

    Choroidal neovascularization (CNV) is a defining feature of wet age-related macular degeneration. We examined the functional role of CCR3 in the development of CNV in mice and primates. CCR3 was associated with spontaneous CNV lesions in the newly described JR5558 mice, whereas CCR3 ligands localized to CNV-associated macrophages and the retinal pigment epithelium/choroid complex. Intravitreal injection of neutralizing antibodies against vascular endothelial growth factor receptor 2, CCR3, CC chemokine ligand 11/eotaxin-1, and CC chemokine ligand 24/eotaxin-2 all reduced CNV area and lesion number in these mice. Systemic administration of the CCR3 antagonists GW766994X and GW782415X reduced spontaneous CNV in JR5558 mice and laser-induced CNV in mouse and primate models in a dose-dependent fashion. Combination treatment with antivascular endothelial growth factor receptor 2 antibody and GW766994X yielded additive reductions in CNV area and hyperpermeability in mice. Interestingly, topical GW766994X and intravitreal anti-CCR3 antibody yielded strong systemic effects, reducing CNV in the untreated, contralateral eye. Contrarily, ocular administration of GW782415X in primates failed to substantially elevate plasma drug levels or to reduce the development of grade IV CNV lesions. These findings suggest that CCR3 signaling may be an attractive therapeutic target for CNV, utilizing a pathway that is at least partly distinct from that of vascular endothelial growth factor receptor. The findings also demonstrate that systemic exposure to CCR3 antagonists may be crucial for CNV-targeted activity. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  11. Fast Laplace solver approach to pore-scale permeability

    NASA Astrophysics Data System (ADS)

    Arns, C. H.; Adler, P. M.

    2018-02-01

    We introduce a powerful and easily implemented method to calculate the permeability of porous media at the pore scale using an approximation based on the Poiseulle equation to calculate permeability to fluid flow with a Laplace solver. The method consists of calculating the Euclidean distance map of the fluid phase to assign local conductivities and lends itself naturally to the treatment of multiscale problems. We compare with analytical solutions as well as experimental measurements and lattice Boltzmann calculations of permeability for Fontainebleau sandstone. The solver is significantly more stable than the lattice Boltzmann approach, uses less memory, and is significantly faster. Permeabilities are in excellent agreement over a wide range of porosities.

  12. A somatostatin analog improves tilt table tolerance by decreasing splanchnic vascular conductance

    PubMed Central

    Florian, J. P.; Curren, M. J.; Pawelczyk, J. A.

    2012-01-01

    Splanchnic hemodynamics and tilt table tolerance were assessed after an infusion of placebo or octreotide acetate, a somatostatin analog whose vascular effects are largely confined to the splanchnic circulation. We hypothesized that reductions in splanchnic blood flow (SpBF) and splanchnic vascular conductance (SpVC) would be related to improvements in tilt table tolerance. In randomized, double-blind, crossover trials, hemodynamic variables were collected in 14 women and 16 men during baseline, 70° head-up tilt (HUT), and recovery. A repeated-measures analysis of variance was used to compare changes from baseline with respect to sex and condition. HUT elicited an increase in heart rate and decreases in mean arterial pressure, cardiac index, stroke index, and systemic vascular conductance. Additionally, SpVC and non-SpVC were lower during HUT. Octreotide reduced SpBF and SpVC and increased systemic vascular conductance and non-SpVC. Changes in SpBF and SpVC between supine and HUT were smaller in women (P < 0.05). Tilt table tolerance was increased after administration of octreotide [median tilt time: 15.7 vs. 37.0 min (P < 0.05) and 21.8 vs. 45.0 min (P < 0.05) for women and men, respectively]. A significant relationship existed between change (Δ) in SpBF (placebo-octreotide) and Δtilt time in women (Δtilt time = 2.5–0.0083 ΔSpBF, P < 0.01), but not men (Δtilt time = 3.41–0.0008 ΔSpBF, P = 0.59). In conclusion, administration of octreotide acetate improved tilt table tolerance, which was associated with a decrease in SpVC. In women, but not men, the magnitude of reduction in SpBF was positively associated with improvements in tilt tolerance. PMID:22345429

  13. Evaluation of the permeability of agricultural films to various fumigants.

    PubMed

    Qian, Yaorong; Kamel, Alaa; Stafford, Charles; Nguyen, Thuy; Chism, William J; Dawson, Jeffrey; Smith, Charles W

    2011-11-15

    A variety of agricultural films are commercially available for managing emissions and enhancing pest control during soil fumigation. These films are manufactured using different materials and processes which can ultimately result in different permeability to fumigants. A systematic laboratory study of the permeability of the agricultural films to nine fumigants was conducted to evaluate the performance of commonly used film products, including polyethylene, metalized, and high-barrier films. The permeability, as expressed by mass transfer coefficient (cm/h), of 27 different films from 13 manufacturers ranged from below 1 × 10(-4) cm/h to above 10 cm/h at 25 °C under ambient relative humidity test conditions. The wide range in permeability of commercially available films demonstrates the need to use films which are appropriate for the fumigation application. The effects of environmental factors, such as temperature and humidity, on the film permeability were also investigated. It was found that high relative humidity could drastically increase the permeability of the high-barrier films. The permeability of some high-barrier films was increased by 2-3 orders of magnitude when the films were tested at high relative humidity. Increasing the temperature from 25 to 40 °C increased the permeability for some high-barrier films up to 10 times more than the permeability at 25 °C, although the effect was minimal for several of these films. Analysis of the distribution of the permeability of the films under ambient humidity conditions to nine fumigants indicated that the 27 films largely followed the material type, although the permeability varied considerably among the films of similar material.

  14. Improved pulmonary vascular reactivity and decreased hypertrophic remodeling during nonhypercapnic acidosis in experimental pulmonary hypertension

    PubMed Central

    Christou, Helen; Reslan, Ossama M.; Mam, Virak; Tanbe, Alain F.; Vitali, Sally H.; Touma, Marlin; Arons, Elena; Mitsialis, S. Alex; Kourembanas, Stella

    2012-01-01

    Pulmonary hypertension (PH) is characterized by pulmonary arteriolar remodeling with excessive pulmonary vascular smooth muscle cell (VSMC) proliferation. This results in decreased responsiveness of pulmonary circulation to vasodilator therapies. We have shown that extracellular acidosis inhibits VSMC proliferation and migration in vitro. Here we tested whether induction of nonhypercapnic acidosis in vivo ameliorates PH and the underlying pulmonary vascular remodeling and dysfunction. Adult male Sprague-Dawley rats were exposed to hypoxia (8.5% O2) for 2 wk, or injected subcutaneously with monocrotaline (MCT, 60 mg/kg) to develop PH. Acidosis was induced with NH4Cl (1.5%) in the drinking water 5 days prior to and during the 2 wk of hypoxic exposure (prevention protocol), or after MCT injection from day 21 to 28 (reversal protocol). Right ventricular systolic pressure (RVSP) and Fulton's index were measured, and pulmonary arteriolar remodeling was analyzed. Pulmonary and mesenteric artery contraction to phenylephrine (Phe) and high KCl, and relaxation to acetylcholine (ACh) and sodium nitroprusside (SNP) were examined ex vivo. Hypoxic and MCT-treated rats demonstrated increased RVSP, Fulton's index, and pulmonary arteriolar thickening. In pulmonary arteries of hypoxic and MCT rats there was reduced contraction to Phe and KCl and reduced vasodilation to ACh and SNP. Acidosis prevented hypoxia-induced PH, reversed MCT-induced PH, and resulted in reduction in all indexes of PH including RVSP, Fulton's index, and pulmonary arteriolar remodeling. Pulmonary artery contraction to Phe and KCl was preserved or improved, and relaxation to ACh and SNP was enhanced in NH4Cl-treated PH animals. Acidosis alone did not affect the hemodynamics or pulmonary vascular function. Phe and KCl contraction and ACh and SNP relaxation were not different in mesenteric arteries of all groups. Thus nonhypercapnic acidosis ameliorates experimental PH, attenuates pulmonary arteriolar thickening

  15. 64Cu-ATSM internal radiotherapy to treat tumors with bevacizumab-induced vascular decrease and hypoxia in human colon carcinoma xenografts

    PubMed Central

    Yoshii, Yukie; Yoshimoto, Mitsuyoshi; Matsumoto, Hiroki; Furukawa, Takako; Zhang, Ming-Rong; Inubushi, Masayuki; Tsuji, Atsushi B.; Fujibayashi, Yasuhisa; Higashi, Tatsuya; Saga, Tsuneo

    2017-01-01

    Bevacizumab, an anti-vascular endothelial growth factor (VEGF) antibody, is an antiangiogenic agent clinically used for various cancers. However, repeated use of this agent leads to tumor-decreased vascularity and hypoxia with activation of an HIF-1 signaling pathway, which results in drug delivery deficiency and induction of malignant behaviors in tumors. Here, we developed a novel strategy to treat tumors with bevacizumab-induced vascular decrease and hypoxia using 64Cu-diacetyl-bis (N4-methylthiosemicarbazone) (64Cu-ATSM), a potential theranostic agent, which possesses high tissue permeability and can target over-reduced conditions under hypoxia in tumors, with a human colon carcinoma HT-29 tumor-bearing mouse model. The long-term treatment with bevacizumab caused decreased blood vessel density and activation of an HIF-1 signaling pathway; increased uptake of 64Cu-ATSM was also observed despite limited blood vessel density in HT-29 tumors. In vivo high-resolution SPECT/PET/CT imaging confirmed reduced vascularity and increased proportion of 64Cu-ATSM uptake areas within the bevacizumab-treated tumors. 64Cu-ATSM therapy was effective to inhibit tumor growth and prolong survival of the bevacizumab-treated tumor-bearing mice without major adverse effects. In conclusion, 64Cu-ATSM therapy effectively enhanced anti-tumor effects in tumors with bevacizumab-induced vascular decrease and hypoxia. 64Cu-ATSM therapy could represent a novel approach as an add-on to antiangiogenic therapy. PMID:29179478

  16. The vascular permeabilizing factors histamine and serotonin induce angiogenesis through TR3/Nur77 and subsequently truncate it through thrombospondin-1

    PubMed Central

    Qin, Liuliang; Zhao, Dezheng; Xu, Jianfeng; Ren, Xianghui; Terwilliger, Ernest F.; Parangi, Sareh; Lawler, Jack; Dvorak, Harold F.

    2013-01-01

    Angiogenesis plays an important role in cancer and in many other human diseases. Vascular endothelial growth factor-A (VEGF-A), the best known angiogenic factor, was originally discovered as a potent vascular permeability factor (VPF), suggesting that other vascular permeabilizing agents, such as histamine and serotonin, might also have angiogenic activity. We recently demonstrated that, like VEGF-A, histamine and serotonin up-regulate the orphan nuclear receptor and transcription factor TR3 (mouse homolog Nur77) and that TR3/Nur77 is essential for their vascular permeabilizing activities. We now report that histamine and serotonin are also angiogenic factors that, at low micromolar concentrations, induce endothelial cell proliferation, migration and tube formation in vitro, and angiogenesis in vivo. All of these responses are mediated through specific histamine and serotonin receptors, are independent of VEGF-A, and are directly dependent on TR3/Nur77. Initially, the angiogenic response closely resembled that induced by VEGF-A, with generation of “mother” vessels. However, after ∼10 days, mother vessels began to regress as histamine and serotonin, unlike VEGF-A, up-regulated the potent angiogenesis inhibitor thrombospondin-1, thereby triggering a negative feedback loop. Thus, histamine and serotonin induce an angiogenic response that fits the time scale of acute inflammation. PMID:23315169

  17. Association between smoking status and the parameters of vascular structure and function in adults: results from the EVIDENT study.

    PubMed

    Recio-Rodriguez, Jose I; Gomez-Marcos, Manuel A; Patino Alonso, Maria C; Martin-Cantera, Carlos; Ibañez-Jalon, Elisa; Melguizo-Bejar, Amor; Garcia-Ortiz, Luis

    2013-12-01

    The present study analyses the relation between smoking status and the parameters used to assess vascular structure and function. This cross-sectional, multi-centre study involved a random sample of 1553 participants from the EVIDENT study. The smoking status, peripheral augmentation index and ankle-brachial index were measured in all participants. In a small subset of the main population (265 participants), the carotid intima-media thickness and pulse wave velocity were also measured. After controlling for the effect of age, sex and other risk factors, present smokers have higher values of carotid intima-media thickness (p = 0.011). Along the same lines, current smokers have higher values of pulse wave velocity and lower mean values of ankle-brachial index but without statistical significance in both cases. Among the parameters of vascular structure and function analysed, only the IMT shows association with the smoking status, after adjusting for confounders.

  18. Gas Permeable Chemochromic Compositions for Hydrogen Sensing

    NASA Technical Reports Server (NTRS)

    Mohajeri, Nahid (Inventor); Muradov, Nazim (Inventor); Tabatabaie-Raissi, Ali (Inventor); Bokerman, Gary (Inventor)

    2013-01-01

    A (H2) sensor composition includes a gas permeable matrix material intermixed and encapsulating at least one chemochromic pigment. The chemochromic pigment produces a detectable change in color of the overall sensor composition in the presence of H2 gas. The matrix material provides high H2 permeability, which permits fast permeation of H2 gas. In one embodiment, the chemochromic pigment comprises PdO/TiO2. The sensor can be embodied as a two layer structure with the gas permeable matrix material intermixed with the chemochromic pigment in one layer and a second layer which provides a support or overcoat layer.

  19. The effects of a multiflavonoid supplement on vascular and hemodynamic parameters following acute exercise.

    PubMed

    Kappus, Rebecca M; Curry, Chelsea D; McAnulty, Steve; Welsh, Janice; Morris, David; Nieman, David C; Soukup, Jeffrey; Collier, Scott R

    2011-01-01

    Antioxidants can decrease oxidative stress and combined with acute exercise they may lead to further decreases in blood pressure. The purpose of this study was to investigate the effects of 2 weeks of antioxidant supplementation on vascular distensibility and cardiovascular hemodynamics during postexercise hypotension. Twenty young subjects were randomized to placebo (n = 10) or antioxidant supplementation (n = 10) for two weeks. Antioxidant status, vascular distensibility, and hemodynamics were obtained before, immediately, and 30 minutes after an acute bout of aerobic exercise both before and after supplementation. Two weeks of antioxidant supplementation resulted in a greater systolic blood pressure (SBP) decrease during postexercise hypotension (PEH) and significant decreases in augmentation index versus placebo (12.5% versus 3.5%, resp.). Also ferric-reducing ability of plasma (FRAP) increased significantly (interaction P = 0.024) after supplementation. Supplementation showed an additive effect on PEH associated with increased FRAP values and decreases in systolic blood pressure and augmentation index.

  20. The Effects of a Multiflavonoid Supplement on Vascular and Hemodynamic Parameters following Acute Exercise

    PubMed Central

    Kappus, Rebecca M.; Curry, Chelsea D.; McAnulty, Steve; Welsh, Janice; Morris, David; Nieman, David C.; Soukup, Jeffrey; Collier, Scott R.

    2011-01-01

    Antioxidants can decrease oxidative stress and combined with acute exercise they may lead to further decreases in blood pressure. The purpose of this study was to investigate the effects of 2 weeks of antioxidant supplementation on vascular distensibility and cardiovascular hemodynamics during postexercise hypotension. Methods. Twenty young subjects were randomized to placebo (n = 10) or antioxidant supplementation (n = 10) for two weeks. Antioxidant status, vascular distensibility, and hemodynamics were obtained before, immediately, and 30 minutes after an acute bout of aerobic exercise both before and after supplementation. Results. Two weeks of antioxidant supplementation resulted in a greater systolic blood pressure (SBP) decrease during postexercise hypotension (PEH) and significant decreases in augmentation index versus placebo (12.5% versus 3.5%, resp.). Also ferric-reducing ability of plasma (FRAP) increased significantly (interaction P = 0.024) after supplementation. Conclusion. Supplementation showed an additive effect on PEH associated with increased FRAP values and decreases in systolic blood pressure and augmentation index. PMID:22191012