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A Vascular Permeability Defect in Experimental Cholera.  

National Technical Information Service (NTIS)

A method for demonstrating vascular leakage, utilizing colloidal iron-dextran, was applied in the study of experimental cholera in infant rabbits. An increase of vascular permeability, delayed in onset and prolonged in duration, consistent with the clinic...

G. T. Keusch P. Atthasampunna R. A. Finkelstein



Animal Models of Increased Lung Vascular Permeability  

Microsoft Academic Search

\\u000a The pulmonary microvascular endothelium regulates vascular water and solute flux into tissues. Vascular barrier function is\\u000a physically established by tight junctions and adherens junctions between neighboring endothelial cells. Endothelial permeability\\u000a together with vascular oncotic and hydrostatic pressures control fluid and solute movement into the pulmonary interstitium\\u000a via paracellular and transcellular pathways. Transvascular fluid flux into the interstitium is constantly counteracted

Sara Hanif Mirza; M. Kamran Mirza; Asrar B. Malik



PubMed Central

A steeply mounting gradient of permeability is demonstrable along the meshwork of capillaries which connects the arterioles and venules of the skin of the frog. The venules incorporated in the meshwork are even more permeable than the capillary meshes giving into them. The presence of the gradient under such differing conditions as exist along frog and mammalian capillaries enables one to rule out certain factors which might be invoked to explain it; and it is not explainable in terms of those influences generally recognized as conditioning exchange between the blood and tissues. Not improbably it results from a structural differentiation along the capillary.

Rous, Peyton; Smith, Frederick



Tonic regulation of vascular permeability.  


Our major theme is that the layered structure of the endothelial barrier requires continuous activation of signalling pathways regulated by sphingosine-1-phosphate (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 signalling 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 re-establishing 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

Curry, F-R E; Adamson, R H



Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in breast cancer  

Microsoft Academic Search

Solid tumors must induce a vascular stroma to grow beyond a minimal size, and the intensity of the angiogenic response has been correlated with prognosis in breast cancer patients. Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), is a secreted protein that has been implicated in tumor-associated angiogenesis. Vascular permeability factor directly stimulates endothelial cell growth

Lawrence F Brown; Brygida Berse; Robert W Jackman; Kathi Tognazzi; Anthony J Guidi; Harold F Dvorak; Donald R Senger; James L Connolly; Stuart J Schnitt



Pathophysiological consequences of VEGF-induced vascular permeability  

NASA Astrophysics Data System (ADS)

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.

Weis, Sara M.; Cheresh, David A.



Overexpression of Vascular Permeability Factor\\/Vascular Endothelial Growth Factor and its Receptors in Psoriasis  

Microsoft Academic Search

Summary Psoriatic skin is characterized by microvascular hyperpermeability and angioproliferation, but the mechanisms responsible are unknown. We report here that the hyperplastic epidermis of psoriatic skin expresses strikingly increased amounts of vascular permeability factor (VPF; vascular endothelial growth factor), a selective endothelial cell mitogen that enhances microvascular permeability. Moreover, two VPF receptors, kdr and fit-l, are overexpressed by papillary dermal

Michael Detmar; Lawrence F. Brown; Kevin P. Claffey; Kiang-Teck Yeo; Olivier Kocher; Robert W. Jackman; Brygida Berse; Harold F. Dvorak



PEDF Regulates Vascular Permeability by a ?-Secretase-Mediated Pathway  

PubMed Central

Increased vascular permeability is an inciting event in many vascular complications including diabetic retinopathy. We have previously reported that pigment epithelium-derived factor (PEDF) is able to inhibit vascular endothelial growth factor (VEGF)-induced angiogenesis through a novel ?-secretase-dependent pathway. In this study, we asked whether inhibition of VEGF-induced permeability by PEDF is also ?-secretase-mediated and to dissect the potential mechanisms involved. Vascular permeability was assessed in vitro by measuring transendothelial resistance and paracellular permeability to dextran and in vivo by following leakage of intravenous FITC-labelled albumin into the retina in the presence or absence of VEGF and PEDF in varying combinations. Experiments were undertaken in the presence or absence of a ?-secretase inhibitor. To assess junctional integrity immunohistochemistry for the adherens junction (AJ) proteins, VE-cadherin and ?-catenin, and the tight junction (TJ) protein, claudin-5 was undertaken using cultured cells and flat mount retinas. Protein expression and the association between AJ proteins, VEGF receptors (VEGFRs) and ?-secretase constituents were determined by immunoprecipitation and Western Blot analysis. In selected experiments the effect of hypoxia on junctional integrity was also assessed. PEDF inhibition of VEGF-induced permeability, both in cultured microvascular endothelial cell monolayers and in vivo in the mouse retinal vasculature, is mediated by ?-secretase. PEDF acted by a) preventing dissociation of AJ and TJ proteins and b) regulating both the association of VEGF receptors with AJ proteins and the subsequent phosphorylation of the AJ proteins, VE-cadherin and ?-catenin. Association of ?-secretase with AJ proteins appears to be critical in the regulation of vascular permeability. Although hypoxia increased VEGFR expression there was a significant dissociation of VEGFR from AJ proteins. In conclusion, PEDF regulates VEGF-induced vascular permeability via a novel ?-secretase dependent pathway and targeting downstream effectors of PEDF action may represent a promising therapeutic strategy for preventing or ameliorating increased vascular permeability.

Qi, Xiaoping; Li Calzi, Sergio; Caballero, Sergio; Shaw, Lynn; Ruan, Qing; Grant, Maria B.; Boulton, Michael E.



Vascular permeability and late radiation fibrosis in mouse lung  

Microsoft Academic Search

It has been suggested that fibrosis which developed after irradiation is caused by increases in vascular permeability. Plasma proteins leak into irradiated tissue where fibrinogen may be converted into fibrin which is gradually replaced by fibrous tissue. Vascular and fibrotic changes in mouse lung were investigated after X irradiation of the right hemithorax. Blood volume and accumulation of extravascular proteins



Characterization of Human Platelet Vascular Permeability-Enhancing Activity  

PubMed Central

Human platelet acid extract obtained from both whole platelets and from isolated subcellular granules was partially purified by DEAE-cellulose chromatography and Sephadex gel filtration. The heat-stable, nondialyzable cationic protein fraction with a mol wt of approximately 30,000 produced a biphasic increase in vascular permeability in rabbit skin and also had antiheparin activity. The acute (15 min) increase in vascular permeability was blocked by prior treatment of the animal with antihistamine and was characterized histologically by edema of perivascular tissues and dilation of capillaries and veinules. The delayed (3 hr) permeability effect was not blocked by antihistamine and was characterized histologically by leukocytic infiltration into the skin. The experiments described suggest that human platelet lysosomal release of cationic proteins may increase vascular permeability by several mechanisms including endogenous histamine release as well as delayed chemotaxis. Images

Nachman, Ralph L.; Weksler, Babette; Ferris, Barbara



Endotoxin increases pulmonary vascular protein permeability in the dog  

SciTech Connect

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 Salmonella 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.

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



Nitric oxide modulates vascular permeability in the rat coronary circulation.  

PubMed Central

1. The objective of the present study was to assess whether inhibition of nitric oxide (NO) production could modulate vascular permeability in the coronary circulation in conscious rats. 2. Intravenous injection of NG-nitro-L-arginine methyl ester (L-NAME, 2 mg kg-1) resulted in a slowly developing hypertension and evoked twofold increases in vascular permeability in the left ventricle and right atrium as measured by the extravasation of Evans blue dye. Maintenance of mean arterial blood pressure at the level observed following L-NAME injection by infusion of noradrenaline (620-820 ng kg-1 min-1) did not induce significant protein extravasation in the coronary circulation. 3. L-NAME treatment markedly enhanced (up to 490%) protein extravasation both in the left ventricle and right atrium in response to platelet-activating factor (PAF, 1.9 nmol kg-1, i.v.) and endothelin-1 (1 nmol kg-1, i.v.). Noradrenaline infusion potentiated (up to 69%) endothelin-1-induced protein extravasation. The permeability effect of PAF was only slightly enhanced by noradrenaline. 4. The present findings indicate that inhibition of endogenous NO synthesis leads to an increase in protein extravasation and to potentiation of the permeability effects of PAF and endothelin-1 in the coronary circulation. These results also suggest that NO may be an important regulator of vascular permeability under physiological and pathological conditions.

Filep, J. G.; Foldes-Filep, E.; Sirois, P.



Time-Dependent Vascular Regression and Permeability Changes in Established Human Tumor Xenografts Induced by an Anti-Vascular Endothelial Growth Factor\\/Vascular Permeability Factor Antibody  

Microsoft Academic Search

The hyperpermeability of tumor vessels to macromolecules, compared with normal vessels, is presumably due to vascular endothelial growth factor\\/vascular permeability factor (VEGF\\/VPF) released by neoplastic and\\/or host cells. In addition, VEGF\\/VPF is a potent angiogenic factor. Removal of this growth factor may reduce the permeability and inhibit tumor angiogenesis. To test these hypotheses, we transplanted a human glioblastoma (U87), a

Fan Yuan; Yi Chen; Marc Dellian; Nina Safabakhsh; Napoleone Ferrara; Rakesh K. Jain



Time-dependent vascular regression and permeability changes in established human tumor xenografts induced by an anti-vascular endothelial growth factor/vascular permeability factor antibody  

PubMed Central

The hyperpermeability of tumor vessels to macromolecules, compared with normal vessels, is presumably due to vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) released by neoplastic and/or host cells. In addition, VEGF/VPF is a potent angiogenic factor. Removal of this growth factor may reduce the permeability and inhibit tumor angiogenesis. To test these hypotheses, we transplanted a human glioblastoma (U87), a human colon adenocarcinoma (LS174T), and a human melanoma (P-MEL) into two locations in immunodeficient mice: the cranial window and the dorsal skinfold chamber. The mice bearing vascularized tumors were treated with a bolus (0.2 ml) of either a neutralizing antibody (A4.6.1) (492 ?g/ml) against VEGF/VPF or PBS (control). We found that tumor vascular permeability to albumin in antibody-treated groups was lower than in the matched controls and that the effect of the antibody was time-dependent and influenced by the mode of injection. Tumor vascular permeability did not respond to i.p. injection of the antibody until 4 days posttreatment. However, the permeability was reduced within 6 h after i.v. injection of the same amount of antibody. In addition to the reduction in vascular permeability, the tumor vessels became smaller in diameter and less tortuous after antibody injections and eventually disappeared from the surface after four consecutive treatments in U87 tumors. These results demonstrate that tumor vascular permeability can be reduced by neutralization of endogenous VEGF/VPF and suggest that angiogenesis and the maintenance of integrity of tumor vessels require the presence of VEGF/VPF in the tissue microenvironment. The latter finding reveals a new mechanism of tumor vessel regression—i.e., blocking the interactions between VEGF/VPF and endothelial cells or inhibiting VEGF/VPF synthesis in solid tumors causes dramatic reduction in vessel diameter, which may block the passage of blood elements and thus lead to vascular regression.

Yuan, Fan; Chen, Yi; Dellian, Marc; Safabakhsh, Nina; Ferrara, Napoleone; Jain, Rakesh K.



Human Mesenchymal Stem Cells Inhibit Vascular Permeability by Modulating Vascular Endothelial Cadherin/?-Catenin Signaling  

PubMed Central

The barrier formed by endothelial cells (ECs) plays an important role in tissue homeostasis by restricting passage of circulating molecules and inflammatory cells. Disruption of the endothelial barrier in pathologic conditions often leads to uncontrolled inflammation and tissue damage. An important component of this barrier is adherens junctions, which restrict paracellular permeability. The transmembrane protein vascular endothelial (VE)-cadherin and its cytoplasmic binding partner ?-catenin are major components of functional adherens junctions. We show that mesenchymal stem cells (MSCs) significantly reduce endothelial permeability in cocultured human umbilical vascular endothelial cells (HUVECs) and following exposure to vascular endothelial growth factor, a potent barrier permeability-enhancing agent. When grown in cocultures with HUVECs, MSCs increased VE-cadherin levels and enhanced recruitment of both VE-cadherin and ?-catenin to the plasma membrane. Enhanced membrane localization of ?-catenin was associated with a decrease in ?-catenin-driven gene transcription. Disruption of the VE-cadherin/?-catenin interaction by overexpressing a truncated VE-cadherin lacking the ?-catenin interacting domain blocked the permeability-stabilizing effect of MSCs. Interestingly, a conditioned medium from HUVEC-MSC cocultures, but not from HUVEC or MSC cells cultured alone, significantly reduced endothelial permeability. In addition, intravenous administration of MSCs to brain-injured rodents reduced injury-induced enhanced blood–brain barrier permeability. Similar to the effect on in vitro cultures, this stabilizing effect on blood–brain barrier function was associated with increased expression of VE-cadherin. Taken together, these results identify a putative mechanism by which MSCs can modulate vascular EC permeability. Further, our results suggest that the mediator(s) of these vascular protective effects is a secreted factor(s) released as a result of direct MSC–EC interaction.

Khakoo, Aarif Y.; Zhao, Jing; Jimenez, Fernando; Gerber, Michael H.; Harting, Matthew; Redell, John B.; Grill, Raymond; Matsuo, Yoichi; Guha, Sushovan; Cox, Charles S.; Reitz, Marvin S.; Holcomb, John B.; Dash, Pramod K.



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

NASA Astrophysics Data System (ADS)

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-treated with sHH-inhibitor led to a 90% lifespan extension in animals that received a single cycle of the combined regimen, and a 200% extension in animals receiving 3-cycles of treatment, compared to control animals or those receiving either of the agents alone. We surmise that direct or indirect modulation of tumor vasculature can provide new opportunities for combination therapies that could improve delivery and efficacy of both small- and large- molecular weight agents in treatment-resistant solid tumors.

Roy Chaudhuri, Tista


Hydrogen Peroxide Induces Vascular Permeability via Regulation of Vascular Endothelial Growth Factor  

Microsoft Academic Search

Oxidative stress plays critical roles in initiation and\\/or worsening of respiratory disease process. Although reactive oxygen species (ROS) are shown to cause vascular leakage, the mechanisms by which ROS induce an increase in vascular permeability are not clearly understood. In this study, we have used a murine model to evaluate the effect of hydrogen peroxide (H2O2) to examine roles of

Kyung Sun Lee; So Ri Kim; Seoung Ju Park; Hee Sun Park; Kyung Hoon Min; Min Hee Lee; Sun Mi Jin; Gong Yong Jin; Wan Hee Yoo; Yong Chul Lee


Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis.  

PubMed Central

Vascular permeability factor (VPF) is an Mr 40-kD protein that has been purified from the conditioned medium of guinea pig line 10 tumor cells grown in vitro, and increases fluid permeability from blood vessels when injected intradermally. Addition of VPF to cultures of vascular endothelial cells in vitro unexpectedly stimulated cellular proliferation. VPF promoted the growth of new blood vessels when administered into healing rabbit bone grafts or rat corneas. The identity of the growth factor activity with VPF was established in four ways: (a) the molecular weight of the activity in preparative SDS-PAGE was the same as VPF (Mr approximately 40 kD); (b) multiple isoforms (pI greater than or equal to 8) for both VPF and the growth-promoting activity were observed; (c) a single, unique NH2-terminal amino acid sequence was obtained; (d) both growth factor and permeability-enhancing activities were immunoadsorbed using antipeptide IgG that recognized the amino terminus of VPF. Furthermore, 125I-VPF was shown to bind specifically and with high affinity to endothelial cells in vitro and could be chemically cross-linked to a high-molecular weight cell surface receptor, thus demonstrating a mechanism whereby VPF can interact directly with endothelial cells. Unlike other endothelial cell growth factors, VPF did not stimulate [3H]thymidine incorporation or promote growth of other cell types including mouse 3T3 fibroblasts or bovine smooth muscle cells. VPF, therefore, appears to be unique in its ability to specifically promote increased vascular permeability, endothelial cell growth, and angio-genesis. Images

Connolly, D T; Heuvelman, D M; Nelson, R; Olander, J V; Eppley, B L; Delfino, J J; Siegel, N R; Leimgruber, R M; Feder, J



Mechanism of dexamethasone suppression of brain tumor-associated vascular permeability in rats. Involvement of the glucocorticoid receptor and vascular permeability factor.  

PubMed Central

Brain tumor-associated cerebral edema arises because tumor capillaries lack normal blood-brain barrier function; vascular permeability factor (VPF, also known as vascular endothelial growth factor, VEGF) is a likely mediator of this phenomenon. Clinically, dexamethasone reduces brain tumor-associated vascular permeability through poorly understood mechanisms. Our goals were to determine if suppression of permeability by dexamethasone might involve inhibition of VPF action or expression, and if dexamethasone effects in this setting are mediated by the glucocorticoid receptor (GR). In two rat models of permeability (peripheral vascular permeability induced by intradermal injection of 9L glioma cell-conditioned medium or purified VPF, and intracerebral vascular permeability induced by implanted 9L glioma), dexamethasone suppressed permeability in a dose-dependent manner. Since 80% of the permeability-inducing activity in 9L-conditioned medium was removed by anti-VPF antibodies, we examined dexamethasone effects of VPF expression in 9L cells. Dexamethasone inhibited FCS- and PDGF-dependent induction of VPF expression. At all levels (intradermal, intracranial, and cell culture), dexamethasone effects were reversed by the GR antagonist mifepristone (RU486). Dexamethasone may decrease brain tumor-associated vascular permeability by two GR-dependent mechanisms: reduction of the response of the vasculature to tumor-derived permeability factors (including VPF), and reduction of VPF expression by tumor cells.

Heiss, J D; Papavassiliou, E; Merrill, M J; Nieman, L; Knightly, J J; Walbridge, S; Edwards, N A; Oldfield, E H



Regulation of Vascular Permeability by Sphingosine 1-Phosphate  

PubMed Central

A significant and sustained increase in vascular permeability is a hallmark of acute inflammatory diseases such as acute lung injury (ALI) and sepsis and is an essential component of tumor metastasis, angiogenesis, and atherosclerosis. Sphingosine 1-phosphate (S1P), an endogenous bioactive lipid produced in many cell types, regulates endothelial barrier function by activation of its G-protein coupled receptor SIP1. S1P enhances vascular barrier function through a series of profound events initiated by SIP1 ligation with subsequent downstream activation of the Rho family of small GTPases, cytoskeletal reorganization, adherens junction and tight junction assembly, and focal adhesion formation. Furthermore, recent studies have identified transactivation of SIP1 signaling by other barrier enhancing agents as a common mechanism for promoting endothelial barrier function. This review summarizes the state of our current knowledge about the mechanisms through which the S1P/SIP1 axis reduces vascular permeability, which remains an area of active investigation that will hopefully produce novel therapeutic agents in the near future.

Wang, Lichun; Dudek, Steven M.



Gap Junction Channel Modulates Pulmonary Vascular Permeability through Calcium in Acute Lung Injury: An Experimental Study  

Microsoft Academic Search

Background: Increased pulmonary vascular permeability is a hallmark of acute lung injury (ALI). Gap junction channels (GJCs) connect adjacent cells and facilitate ion exchange. It remained unclear whether GJCs modulate pulmonary permeability in ALI through intracellular calcium. Objectives: This study aimed to verify if GJCs in pulmonary microvessel endothelial cells (PMVECs) modulate pulmonary vascular permeability in ALI via intracellular calcium.

Jinzhou Zhang; Wen Wang; Jing Sun; Qiang Li; Jincheng Liu; Hailong Zhu; Tao Chen; Hongbing Wang; Shiqiang Yu; Guocheng Sun; Wensheng Chen; Dinghua Yi



Intermittent claudication incites systemic neutrophil activation and increased vascular permeability.  


Reperfusion following severe ischaemia incites a systemic response involving neutrophil activation and vascular injury. Recent work suggests that intermittent claudication may also be capable of inducing similar changes, reversible by revascularization. This observation may have implications for the treatment of claudication and explain the high associated cardiovascular mortality. This hypothesis was investigated using an in vivo model. Rats underwent repeated hindlimb stimulation after common iliac artery ligation. Intravital fluorescence microscopy was used to observe postcapillary venules of the tibialis anterior muscle in the hindlimb. This revealed a bilateral increase in leucocyte-endothelial adhesion and vascular permeability to albumin after unilateral subtotal ischaemia and muscle stimulation, associated with increased urinary albumin excretion. These results provide further evidence supporting the association of intermittent claudication with potentially deleterious systemic manifestations. PMID:8443644

Hickey, N C; Hudlicka, O; Gosling, P; Shearman, C P; Simms, M H



Increased lung vascular permeability after pancreatitis and trypsin infusion.  

PubMed Central

We examined the role of proteases in mediating lung vascular injury after acute hemorrhagic pancreatitis. Studies were made in sheep in which pulmonary lymph was collected for assessment of the changes in transvascular fluid and protein exchange. The induction of pancreatitis by injection of trypsin and sodium taurocholate into the pancreas resulted in increases in pulmonary lymph flow and transvascular protein clearance (lymph flow x lymph-to-plasma protein concentration ratio). The pulmonary vascular pressures did not change significantly after pancreatitis, indicating that the increases in pulmonary lymph flow and protein clearance were due to increased pulmonary endothelial permeability. The response to pancreatitis was also characterized by decreases in concentrations of fibrinogen, platelets, and granulocytes. Pulmonary leukostasis was a common morphologic feature in this group. In another group, an intravenous infusion of trypsin, which produced decreases in antiprotease activity comparable to those observed after pancreatitis, also resulted in increases in pulmonary lymph flow and transvascular protein clearance. These increases in lymph fluxes were comparable to those observed after pancreatitis and were also associated with decreases in concentrations of fibrinogen, platelets, and granulocytes. Pulmonary leukostasis was evident in this group upon histologic examination. In a third group, pretreatment with Trasylol prevented the increases in pulmonary lymph flow and transvascular protein clearance after pancreatitis, suggesting that the pancreatitis-induced pulmonary vascular injury is the result of the release of proteases. The results indicate a common pulmonary vascular response to acute pancreatitis and trypsin infusion. The release of proteases into the circulation after acute pancreatitis may be the initiating event mediating the pulmonary vascular injury. Images Figure 7 Figure 8 Figure 9 Figure 10 Figures 11 and 12

Tahamont, M. V.; Barie, P. S.; Blumenstock, F. A.; Hussain, M. H.; Malik, A. B.



Vascular permeability in a human tumour xenograft: molecular charge dependence  

PubMed Central

Molecular charge is one of the main determinants of transvascular transport. There are, however, no data available on the effect of molecular charge on microvascular permeability of macromolecules in solid tumours. To this end, we measured tumour microvascular permeability to different proteins having similar size but different charge. Measurements were performed in the human colon adenocarcinoma LS174T transplanted in transparent dorsal skinfold chambers in severe combined immunodeficient (SCID) mice. Bovine serum albumin (BSA) and IgG were fluorescently labelled and were either cationized by conjugation with hexamethylenediamine or anionized by succinylation. The molecules were injected i.v. and the fluorescence in tumour tissue was quantified by intravital fluorescence microscopy. The fluorescence intensity and pharmacokinetic data were used to calculate the microvascular permeability. We found that tumour vascular permeability of cationized BSA (pI-range: 8.6–9.1) and IgG (pI: 8.6–9.3) was more than two-fold higher (4.25 and 4.65 × 10?7cm s?1) than that of the anionized BSA (pI ? 2.0) and IgG (pI: 3.0–3.9; 1.11 and 1.93 × 10?7cm s?1, respectively). Our results indicate that positively charged molecules extravasate faster in solid tumours compared to the similar-sized compounds with neutral or negative charges. However, the plasma clearance of cationic molecules was ?2 × faster than that of anionic ones, indicating that the modification of proteins enhances drug delivery to normal organs as well. Therefore, caution should be exercised when such a strategy is used to improve drug and gene delivery to solid tumours. © 2000 Cancer Research Campaign

Dellian, M; Yuan, F; Trubetskoy, V S; Torchilin, V P; Jain, R K



Inhibition of vascular permeability changes in rats by captopril.  

PubMed Central

Systemic treatment of rats with captopril (50 mg/kg body wt per os), a specific competitive inhibitor of angiotensin l-converting enzyme, significantly inhibits vascular permeability changes induced by the intradermal injection of the vasoactive mediators histamine, bradykinin, serotonin, and compound 48/80. This effect of captopril is both dose- and time-dependent with approximately 60% inhibition of edema formation observed 7 h after captopril treatment (100 mg/kg body wt per os). The inhibitory effect of captopril on edema formation is temporally unrelated to the inhibition of serum angiotensin l-converting enzyme activity or serum prostaglandin E2 levels and is not inhibited by systemic treatment of rats with indomethacin. The data suggest that captopril may have potent antiinflammatory activity through as yet undefined mechanisms.

Fantone, J C; Schrier, D; Weingarten, B



Effect of leukotriene receptor antagonists on vascular permeability during endotoxic shock  

SciTech Connect

Evidence has accumulated that sulfidopeptide leukotrienes are significant pathogenic mediators of certain hematologic and hemodynamic sequelae of endotoxic shock. In the present study, the effects of a selective LTD4/E4 receptor antagonist, LY171883 (LY), or a selective LTD4 receptor antagonist, SKF-104353 (SKF), were assessed on splanchnic and pulmonary localization of 99mTechnetium-labeled human serum albumin (99mTc-HSA) in acute endotoxic shock in the rat. Dynamic gamma camera imaging of heart (H), midabdominal (GI), and lung regions of interest generated time activity curves for baseline and at 5-35 min after Salmonella enteritidis endotoxin (10 mg/kg, i.v.). Slopes of GI/H and lung/H activity (permeability index, GI/H or lung/H X 10(-3)/min) provided indices of intestinal and lung localization. Rats received LY (30 mg/kg, i.v.), LY vehicle (LY Veh), SKF (10 mg/kg), or SKF vehicle (SK Veh) 10 min prior to endotoxin or endotoxin vehicle. In rats receiving the LY Veh and endotoxin (n = 8) or SKF Veh and endotoxin (n = 12), the splanchnic permeability indices to 99mTc-HSA were increased 11.2-fold and 5.1-fold, respectively (P less than 0.05) compared to vehicle control groups not given endotoxin (n = 5). Pulmonary permeability index for 99mTc-HSA was increased (P less than 0.05) to a lesser extent (3.2-fold) by endotoxin compared to vehicle controls. Pretreatment with SKF reduced the mesenteric permeability index to control levels (P less than 0.05) during the 5-35 min time interval post-endotoxin. LY reduced the mesenteric permeability index by 70%. Pulmonary relative permeability to 99mTc-HSA was not affected by LY pretreatment. Both splanchnic and lung relative permeability to the isotope was transient; at 135-225 min post-endotoxin, splanchnic localization of 99mTc-HSA (n = 4) was not significantly different from vehicle controls in these vascular beds.

Cook, J.A.; Li, E.J.; Spicer, K.M.; Wise, W.C.; Halushka, P.V. (Medical Univ. of South Carolina, Charleston (USA))



Hypertonic saline increases vascular permeability in the rat trachea by producing neurogenic inflammation.  


In this study, we examined whether inhalation of hypertonic saline aerosols increases vascular permeability in the rat trachea, and we examined the role of neurogenic inflammation in this response. Stereological point counting was performed to measure the percent area occupied by Monastral blue-labeled blood vessels as a means of quantifying the increase in vascular permeability in tracheal whole mounts. Hypertonic saline aerosols (3.6-14.4% NaCl) increased vascular permeability in a dose-dependent fashion compared with 0.9% NaCl. Thus, the area density of Monastral blue-labeled vessels after inhalation of 3.6% NaCl was greater (21.2 +/- 3.5% mean +/- SEM, n = 5) than after 0.9% NaCl aerosol (3.3 +/- 0.9%, n = 5, P less than 0.5). The neutral endopeptidase inhibitor phosphoramidon (2.5 mg/kg, i.v.) significantly potentiated the increase of vascular permeability caused by 3.6% NaCl. Desensitization of sensory nerve endings by pretreatment with capsaicin markedly reduced the usual increase in vascular permeability caused by 3.6% NaCl, but the increase in vascular permeability induced by aerosolized substance P (10(-4) M) was unchanged. These findings suggest that hypertonic saline increases vascular permeability in the rat trachea by stimulating the release of neuropeptides from sensory nerves. PMID:1693378

Umeno, E; McDonald, D M; Nadel, J A



Hypertonic saline increases vascular permeability in the rat trachea by producing neurogenic inflammation.  

PubMed Central

In this study, we examined whether inhalation of hypertonic saline aerosols increases vascular permeability in the rat trachea, and we examined the role of neurogenic inflammation in this response. Stereological point counting was performed to measure the percent area occupied by Monastral blue-labeled blood vessels as a means of quantifying the increase in vascular permeability in tracheal whole mounts. Hypertonic saline aerosols (3.6-14.4% NaCl) increased vascular permeability in a dose-dependent fashion compared with 0.9% NaCl. Thus, the area density of Monastral blue-labeled vessels after inhalation of 3.6% NaCl was greater (21.2 +/- 3.5% mean +/- SEM, n = 5) than after 0.9% NaCl aerosol (3.3 +/- 0.9%, n = 5, P less than 0.5). The neutral endopeptidase inhibitor phosphoramidon (2.5 mg/kg, i.v.) significantly potentiated the increase of vascular permeability caused by 3.6% NaCl. Desensitization of sensory nerve endings by pretreatment with capsaicin markedly reduced the usual increase in vascular permeability caused by 3.6% NaCl, but the increase in vascular permeability induced by aerosolized substance P (10(-4) M) was unchanged. These findings suggest that hypertonic saline increases vascular permeability in the rat trachea by stimulating the release of neuropeptides from sensory nerves. Images

Umeno, E; McDonald, D M; Nadel, J A



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


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. PMID:23919323

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



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

SciTech Connect

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 in 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.

Li, E.J.; Cook, J.A.; Spicer, K.M.; Wise, W.C.; Rokach, J.; Halushka, P.V. (Medical Univ. of South Carolina, Charleston (USA))



Urokinase Plasminogen Activator Regulates Pulmonary Arterial Contractility and Vascular Permeability in Mice  

PubMed Central

The concentration of urokinase plasminogen activator (uPA) is elevated in pathological settings such as acute lung injury, where pulmonary arterial contractility and permeability are disrupted. uPA limits the accretion of fibrin after injury. Here we investigated whether uPA also regulates pulmonary arterial contractility and permeability. Contractility was measured using isolated pulmonary arterial rings. Pulmonary blood flow was measured in vivo by Doppler and pulmonary vascular permeability, according to the extravasation of Evans blue. Our data show that uPA regulates the in vitro pulmonary arterial contractility induced by phenylephrine in a dose-dependent manner through two receptor-dependent pathways, and regulates vascular contractility and permeability in vivo. Physiological concentrations of uPA (?1 nM) stimulate the contractility of pulmonary arterial rings induced by phenylephrine through the low-density lipoprotein receptor–related protein receptor. The procontractile effect of uPA is independent of its catalytic activity. At pathophysiological concentrations, uPA (20 nM) inhibits contractility and increases vascular permeability. The inhibition of vascular contractility and increase of vascular permeability is mediated through a two-step process that involves docking to N-methyl-d-aspartate receptor–1 (NMDA-R1) on pulmonary vascular smooth muscle cells, and requires catalytic activity. Peptides that specifically inhibit the docking of uPA to NMDA-R, or the uPA variant with a mutated receptor docking site, abolished both the effects of uPA on vascular contractility and permeability, without affecting its catalytic activity. These data show that uPA, at concentrations found under pathological conditions, reduces pulmonary arterial contractility and increases permeability though the activation of NMDA-R1. The selective inhibition of NMDAR-1 activation by uPA can be accomplished without a loss of fibrinolytic activity.

Nassar, Taher; Yarovoi, Serge; Fanne, Rami Abu; Waked, Otailah; Allen, Timothy C.; Idell, Steven; Cines, Douglas B.



Sorbinil prevents diabetes-induced increases in vascular permeability but does not alter collagen cross-linking.  


In recent studies we have demonstrated a marked increase in albumin permeation of new vessels formed by angiogenesis (in subcutaneous tissue) in the diabetic milieu. Likewise, lysyl oxidase-mediated collagen cross-linking is markedly increased in the scar tissue associated with angiogenesis. The present studies were undertaken to determine whether sorbinil, a chemical inhibitor of aldose reductase that has been shown to prevent and reverse diabetic cataracts and neuropathy, also could prevent the vascular permeability and collagen cross-linking changes in this model. Vascular permeation by 125I-BSA, collagen cross-linking, and tissue levels of sorbitol, myo-inositol, and scyllo-inositol were assessed in male Sprague-Dawley rats 3 wk after injection of streptozocin and induction of angiogenesis and collagen synthesis in polyester fabric implanted subcutaneously. Sorbinil (approximately 25 mg/kg/day) added to the diet of diabetic rats reduced the diabetes-induced increases in albumin permeation by 80%, completely prevented diabetes-induced changes in tissue levels of sorbitol and myo-inositol, and markedly reduced diabetes-induced changes in tissue levels of scyllo-inositol. In contrast, sorbinil had no effect on plasma glucose levels or collagen solubility (an index of collagen cross-linking). These observations indicate that increased vascular permeability associated with diabetes is linked to imbalances in sorbitol/inositol metabolism. These findings also indicate that diabetes-induced increases in vascular permeability and in collagen cross-linking are independent phenomena and diabetes-induced increases in vascular permeability are largely preventable by treatment with an aldose reductase inhibitor in the face of high plasma glucose levels. PMID:4007287

Williamson, J R; Chang, K; Rowold, E; Marvel, J; Tomlinson, M; Sherman, W R; Ackermann, K E; Kilo, C



Anatomic basis of ulnar index metacarpal reverse flow vascularized bone graft for index distal bone loss  

Microsoft Academic Search

Well-known advantages of vascularized bone grafts led us to determine the anatomical basis of a metacarpal vascularized bone\\u000a graft to find a solution for distal index bone loss. Seventeen adult human hands from fresh cadavers were dissected and analyzed.\\u000a For each hand, we studied the second dorsal metacarpal artery, the ulnar dorsal proper digital artery of index, and the ulnar

L. Ardouin; D. Le Nen; B. Geffard; N. Hanouz; C. Vielpeau; E. Salame



Pulmonary vascular permeability changes in an ovine model of methicillin-resistant Staphylococcus aureus sepsis  

PubMed Central

Introduction Endothelial dysfunction is a hallmark of sepsis, associated with lung transvascular fluid flux and pulmonary dysfunction in septic patients. We tested the hypothesis that methicillin-resistant Staphylococcus aureus (MRSA) sepsis following smoke inhalation increases pulmonary transvascular fluid flux via excessive nitric oxide (NO) production. Methods Ewes were chronically instrumented, and randomised into either a control or MRSA sepsis (MRSA and smoke inhalation) group. Results Pulmonary function remained stable in the control group, whereas the MRSA sepsis group developed impaired gas exchange and significantly increased lung lymph flow, permeability index and bloodless wet-to-dry weight-ratio (W/D ratio). The plasma nitrate/nitrite (NOx) levels, lung inducible nitric oxide synthases (iNOS) and endothelial nitric oxide synthases (eNOS), vascular endothelial growth factor (VEGF) protein expressions and poly-(ADP)-ribose (PAR) were significantly increased by MRSA challenge. Conclusions These results provide evidence that excessive NO production may mediate pulmonary vascular hyperpermeability in MRSA sepsis via up regulation of reactive radicals and VEGF.

Jonkam, Collette C; Bansal, Kamna; Traber, Daniel L; Hamahata, Atsumori; Maybauer, Marc O; Maybauer, Dirk M; Cox, Robert A; Lange, Matthias; Connelly, Rhykka L; Traber, Lillian D; Djukom, Clarisse D; Salsbury, John R; Herndon, David N; Enkhbaatar, Perenlei



Role of platelets in maintenance of pulmonary vascular permeability to protein  

SciTech Connect

The authors examined the role of platelets in maintenance of pulmonary vascular integrity by inducing thrombocytopenia in sheep using antiplatelet serum (APS). A causal relationship between thrombocytopenia and increase in pulmonary vascular permeability was established by platelet repletion using platelet-rich plasma (PRP). Sheep were chronically instrumented and lung lymph fistulas prepared to monitor pulmonary lymph flow (Q{sub lym}). A balloon catheter was positioned in the left atrium to assess pulmonary vascular permeability to protein after raising the left atrial pressure (P{sub la}). Thrombocytopenia was maintained for 3 days by daily intramuscular APS injections. In studies using cultured bovine pulmonary artery endothelial monolayers, transendothelia permeability of {sup 125}I-labeled albumin was reduced 50 and 95%, respectively, when 2.5 {times} 10{sup 7} or 5 {times} 10{sup 7} platelets were added onto endothelial monolayers. However, addition of 5 {times} 10{sup 6} platelets or 5 {times} 10{sup 7} red blood cells did not reduce endothelial monolayer albumin permeability. Results indicate that platelets are required for the maintenance of pulmonary vascular permeability. Reduction in permeability appears to involve an interaction of platelets with the endothelium.

Lo, S.K.; Burhop, K.E.; Kaplan, J.E.; Malik, A.B. (Albany Medical College of Union Univ., NY (USA))



Wogonin inhibits H2O2-induced vascular permeability through suppressing the phosphorylation of caveolin-1.  


Wogonin, a naturally occurring monoflavonoid extracted from the root of Scutellaria baicalensis Georgi, has been reported for its anti-oxidant activity. However, it is still unclear whether wogonin can inhibit oxidant-induced vascular permeability. In this study, we evaluated the effects of wogonin on H2O2-induced vascular permeability in human umbilical vein endothelial cells (HUVECs). We found that wogonin can suppress the H2O2-stimulated actin remodeling and albumin uptake of HUVECs, as well as transendothelial cell migration of the human breast carcinoma cell MDA-MB-231. The mechanism revealed that wogonin inhibited H2O2-induced phosphorylation of caveolin-1 (cav-1) associating with the suppression of stabilization of VE-cadherin and ?-catenin. Moreover, wogonin repressed anisomycin-induced phosphorylation of p38, cav-1 and vascular permeability. These results suggested that wogonin could inhibit H2O2-induced vascular permeability by downregulating the phosphorylation of cav-1, and that it might have a therapeutic potential for the diseases associated with the development of both oxidant and vascular permeability. PMID:23246481

Wang, Fei; Song, Xiuming; Zhou, Mi; Wei, Libin; Dai, Qinsheng; Li, Zhiyu; Lu, Na; Guo, Qinglong



Visualizing vascular permeability and lymphatic drainage using labeled serum albumin  

Microsoft Academic Search

During the early stages of angiogenesis, following stimulation of endothelial cells by vascular endothelial growth factor\\u000a (VEGF), the vascular wall is breached, allowing high molecular weight proteins to leak from the vessels to the interstitial\\u000a space. This hallmark of angiogenesis results in deposition of a provisional matrix, elevation of the interstitial pressure\\u000a and induction of interstitial convection. Albumin, the major

Katrien Vandoorne; Yoseph Addadi; Michal Neeman



Twist1 Controls Lung Vascular Permeability and Endotoxin-Induced Pulmonary Edema by Altering Tie2 Expression  

PubMed Central

Tight regulation of vascular permeability is necessary for normal development and deregulated vascular barrier function contributes to the pathogenesis of various diseases, including acute respiratory distress syndrome, cancer and inflammation. The angiopoietin (Ang)-Tie2 pathway is known to control vascular permeability. However, the mechanism by which the expression of Tie2 is regulated to control vascular permeability has not been fully elucidated. Here we show that transcription factor Twist1 modulates pulmonary vascular leakage by altering the expression of Tie2 in a context-dependent way. Twist1 knockdown in cultured human lung microvascular endothelial cells decreases Tie2 expression and phosphorylation and increases RhoA activity, which disrupts cell-cell junctional integrity and increases vascular permeability in vitro. In physiological conditions, where Ang1 is dominant, pulmonary vascular permeability is elevated in the Tie2-specific Twist1 knockout mice. However, depletion of Twist1 and resultant suppression of Tie2 expression prevent increase in vascular permeability in an endotoxin-induced lung injury model, where the balance of Angs shifts toward Ang2. These results suggest that Twist1-Tie2-Angs signaling is important for controlling vascular permeability and modulation of this mechanism may lead to the development of new therapeutic approaches for pulmonary edema and other diseases caused by abnormal vascular permeability.

Mammoto, Tadanori; Jiang, Elisabeth; Jiang, Amanda; Lu, Yongbo; Juan, Aimee M.; Chen, Jing; Mammoto, Akiko



Identifying tumor vascular permeability heterogeneity using reduced encoding techniques  

Microsoft Academic Search

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 = Kpt) which results in erroneous diagnostic information and we offer a potential solution using reduced encoding techniques to solve this problem. We compared the

Michael Aref



Real-Time Visualization and Quantitation of Vascular Permeability In Vivo: Implications for Drug Delivery  

PubMed Central

The leaky, heterogeneous vasculature of human tumors prevents the even distribution of systemic drugs within cancer tissues. However, techniques for studying vascular delivery systems in vivo often require complex mammalian models and time-consuming, surgical protocols. The developing chicken embryo is a well-established model for human cancer that is easily accessible for tumor imaging. To assess this model for the in vivo analysis of tumor permeability, human tumors were grown on the chorioallantoic membrane (CAM), a thin vascular membrane which overlays the growing chick embryo. The real-time movement of small fluorescent dextrans through the tumor vasculature and surrounding tissues were used to measure vascular leak within tumor xenografts. Dextran extravasation within tumor sites was selectively enhanced an interleukin-2 (IL-2) peptide fragment or vascular endothelial growth factor (VEGF). VEGF treatment increased vascular leak in the tumor core relative to surrounding normal tissue and increased doxorubicin uptake in human tumor xenografts. This new system easily visualizes vascular permeability changes in vivo and suggests that vascular permeability may be manipulated to improve chemotherapeutic targeting to tumors.

Pink, Desmond B. S.; Schulte, Wendy; Parseghian, Missag H.; Zijlstra, Andries; Lewis, John D.



Non-invasive optical modulation of local vascular permeability  

Microsoft Academic Search

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

Myunghwan Choi; Chulhee Choi



The induction of nitric oxide synthase and intestinal vascular permeability by endotoxin in the rat.  

PubMed Central

1. The effect of endotoxin (E. coli lipopolysaccharide) on the induction of nitric oxide synthase (NOS) and the changes in vascular permeability in the colon and jejunum over a 5 h period have been investigated in the rat. 2. Under resting conditions, a calcium-dependent constitutive NOS, determined by the conversion of radiolabelled L-arginine to citrulline, was detected in homogenates of both colonic and jejunal tissue. 3. Administration of endotoxin (3 mg kg-1, i.v.) led, after a 2 h lag period, to the appearance of calcium-independent NOS activity in the colon and jejunum ex vivo, characteristic of the inducible NOS enzyme. 4. Administration of endotoxin led to an increase in colonic and jejunal vascular permeability after a lag period of 3 h, determined by the leakage of radiolabelled albumin. 5. Pretreatment with dexamethasone (1 mg kg-1 s.c., 2 h prior to challenge) inhibited both the induction of NOS and the vascular leakage induced by endotoxin. 6. Administration of the NO synthase inhibitor NG-monomethyl-L-arginine (12.5-50 mg kg-1, s.c.) 3 h after endotoxin injection, dose-dependently reduced the subsequent increase in vascular permeability in jejunum and colon, an effect reversed by L-arginine (300 mg kg-1, s.c.). 7. These findings suggest that induction of NOS is associated with the vascular injury induced by endotoxin in the rat colon and jejunum.

Boughton-Smith, N. K.; Evans, S. M.; Laszlo, F.; Whittle, B. J.; Moncada, S.



Role of eicosanoids in PAF-induced increases of the vascular permeability in rat airways.  

PubMed Central

1. Platelet activating factor (PAF; 1.0 and 5.0 micrograms kg-1) injected in the tail vein of unanaesthetized rats dose-dependently increased the vascular permeability of the trachea, upper and lower bronchi (up to 400%) as measured by the extravasation of Evans blue dye. The permeability of the parenchyma was not affected by PAF treatment. 2. Pretreatment of the animals with an intravenous injection of the PAF antagonist BN-52021 (10 mg kg-1) abolished almost totally the vascular permeability changes elicited by PAF injection (5.0 micrograms kg-1). 3. Pretreatment of the animals with intravenous injections of inhibitors of thromboxane formation, indomethacin (10 mg kg-1) and compound OKY-046 (10 mg kg-1), and thromboxane antagonist, compound L-655,240 (5 mg kg-1), partially reduced PAF effects in the airways (from 28 to 69%). The thromboxane mimic U-44069 (5.0 micrograms kg-1) did not modify the vascular permeability of rat airways. The effect of a low dose of PAF (0.1 microgram kg-1) on the vascular permeability of the trachea and bronchi (but not of the parenchyma) was potentiated by compound U-44069 (5.0 micrograms kg-1) or noradrenaline (400 ng kg-1) whereas the effect of a high dose of PAF (5.0 micrograms kg-1) was not affected. 4. Neither the peptidoleukotriene antagonist MK-571 (10 mg kg-1) nor the 5-lipoxygenase inhibitor, L-663,536 (10 mg kg-1) given before the injection of PAF (5.0 micrograms kg-1) affected the protein extravasation in rat lung tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Sirois, M. G.; Plante, G. E.; Braquet, P.; Sirois, P.



Descriptive study of possible link between cardioankle vascular index and homocysteine in vascular-related diseases  

PubMed Central

Objectives Cardioankle vascular index (CAVI) is a new index of arterial stiffness independent of immediate blood pressure. Homocysteine (Hcy) is an independent risk factor for vascular diseases. The aim of this study was to investigate the relationship between Hcy and CAVI in the vascular-related diseases. Design Descriptive research. Participants 88 patients (M/F 46/42) with or without hypertension, coronary artery disease or arteriosclerosis obliterans were enrolled to our study. They were divided into two groups according to the level of Hcy. Methods CAVI, carotid-femoral pulse wave velocity (CF-PWV) and carotid-radial pulse wave velocity (CR-PWV) were measured by VS-1000 and Complior apparatus. Results There was significant correlation between Hcy and CF-PWV, CR-PWV, CAVI in the entire group (r=0.33, p=0.002; r=0.51, p<0.001; r=0.42, p<0.001, respectively). And there was significant correlation between Hcy and CF-PWV, CR-PWV, CAVI in the vascular-related disease group (r=0.23, p=0.048; r=0.51, p<0.001; r=0.392, p=0.001, respectively). The level of Hcy was significantly higher in patients with one or more vascular diseases than in patients without vascular diseases. The levels of CF-PWV, CR-PWV and CAVI were significantly higher in Hcy ?15??mol/l group than in Hcy <5??mol/l group (13.7±3.0 vs 10.8±2.5, p?index (BMI) and age were independent associating factors of CAVI in the entire study group (?=0.421, p=0.001; ?=?0.309, p=0.006; ?=0.297, p=0.012, respectively). And Hcy, BMI and age were independent influencing factors of CAVI in the vascular-related disease group (?=0.434, p=0.001; ?=?0.331, p=0.009; ?=0.288, p=0.022, respectively). Conclusions CAVI was positively correlated with Hcy in the vascular-related diseases.

Wang, Hongyu; Liu, Jinbo; Wang, Qi; Zhao, Hongwei; Shi, Hongyan; Yu, Xiaolan; Fu, Xiaobao



Identifying tumor vascular permeability heterogeneity using reduced encoding techniques  

NASA Astrophysics Data System (ADS)

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, ?educed-encoding I&barbelow;maging by G&barbelow;eneralized-series ?econstruction (RIGR), and ?wo-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. The top five Kp?t/VT "hot spots" and their corresponding ve can statistically differentiate invasive ductal carcinoma from non-invasive papillary carcinoma for the 469 mum and 938 mum resolution, p = 0.0017 and p = 0.0047, respectively, but not for 2500 mum resolution, p = 0.9008.

Aref, Michael


Expression of urocortin in rat lung and its effect on pulmonary vascular permeability  

Microsoft Academic Search

Urocortin (UCN), a newly identified, 40-amino-acid, corticotropin-releasing hormone (CRH) structurally related peptide, has been demonstrated to be expressed in the central nervous system and many peripheral tissues of rats and man. This study aimed to investigate the expres- sion profile of UCN in rat lung and the effect of UCN on lung vascular permeability. The expression of UCN mRNA was

Yuqing Wu; Yinyan Xu; Hong Zhou; Jin Tao; Shengnan Li



Vitronectin Increases Vascular Permeability by Promoting VE-Cadherin Internalization at Cell Junctions  

Microsoft Academic Search

BackgroundCross-talk between integrins and cadherins regulates cell function. We tested the hypothesis that vitronectin (VN), a multi-functional adhesion molecule present in the extracellular matrix and plasma, regulates vascular permeability via effects on VE-cadherin, a critical regulator of endothelial cell (EC) adhesion.Methodology\\/Principal FindingsAddition of multimeric VN (mult VN) significantly increased VE-cadherin internalization in human umbilical vein EC (HUVEC) monolayers. This effect

Rong Li; Meiping Ren; Ni Chen; Mao Luo; Zhuo Zhang; Jianbo Wu



Murine Model for Dengue Virus-Induced Lethal Disease with Increased Vascular Permeability  

Microsoft Academic Search

Lack of an appropriate animal model for dengue virus (DEN), which causes dengue fever and dengue hemorrhagic fever\\/dengue shock syndrome (DHF\\/DSS), has impeded characterization of the mechanisms underlying the disease pathogenesis. The cardinal feature of DHF\\/DSS, the severe form of DEN infection, is increased vascular permeability. To develop a murine model that is more relevant to DHF\\/DSS, a novel DEN

Sujan Shresta; Kristin L. Sharar; Daniil M. Prigozhin; P. Robert Beatty; Eva Harris



Suppression of vascular permeability and inflammation by targeting of the transcription factor c-Jun.  


Conventional anti-inflammatory strategies induce multiple side effects, highlighting the need for novel targeted therapies. Here we show that knockdown of the basic-region leucine zipper protein, c-Jun, by a catalytic DNA molecule, Dz13, suppresses vascular permeability and transendothelial emigration of leukocytes in murine models of vascular permeability, inflammation, acute inflammation and rheumatoid arthritis. Treatment with Dz13 reduced vascular permeability due to cutaneous anaphylactic challenge or VEGF administration in mice. Dz13 also abrogated monocyte-endothelial cell adhesion in vitro and abolished leukocyte rolling, adhesion and extravasation in a rat model of inflammation. Dz13 suppressed neutrophil infiltration in the lungs of mice challenged with endotoxin, a model of acute inflammation. Finally, Dz13 reduced joint swelling, inflammatory cell infiltration and bone erosion in a mouse model of rheumatoid arthritis. Mechanistic studies showed that Dz13 blocks cytokine-inducible endothelial c-Jun, E-selectin, ICAM-1, VCAM-1 and VE-cadherin expression but has no effect on JAM-1, PECAM-1, p-JNK-1 or c-Fos. These findings implicate c-Jun as a useful target for anti-inflammatory therapies. PMID:16823369

Fahmy, Roger G; Waldman, Alla; Zhang, Guishui; Mitchell, Ainslie; Tedla, Nicodemus; Cai, Hong; Geczy, Carolyn R; Chesterman, Colin N; Perry, Michael; Khachigian, Levon M



Intravital analysis of vascular permeability in mice using two-photon microscopy  

PubMed Central

Blood vessel endothelium forms a semi-permeable barrier and its permeability controls the traffics of plasma contents. Here we report an intravital evaluation system for vascular permeability in mice using two-photon microscopy. We used various sizes of fluorescein-conjugated dextran as a tracer and its efflux was quantified by measuring the changes of fluorescent intensity both on the blood vessel area and the interstitial space. Using this system, we demonstrated that skin blood vessels limited the passage of dextran larger than 70?kDa under homeostatic conditions. We evaluated the kinetics of vascular permeability in histamine- or IgE-induced type I allergic models and a hapten-induced type IV allergic model. In such inflammatory conditions, the hyperpermeability was selectively induced in the postcapillary venules and dextran as large as 2000-kDa leaked from the bloods. Taken together, our study provides a convenient method to characterize the skin blood vessels as a traffic barrier in physiological conditions.

Egawa, Gyohei; Nakamizo, Satoshi; Natsuaki, Yohei; Doi, Hiromi; Miyachi, Yoshiki; Kabashima, Kenji



Silver nanoparticles inhibit VEGF-and IL1?-induced vascular permeability via Src dependent pathway in porcine retinal endothelial cells  

Microsoft Academic Search

The aim of this study is to determine the effects of silver nanoparticles (Ag-NP) on vascular endothelial growth factor (VEGF)-and interleukin-1 beta (IL-1?)-induced vascular permeability, and to detect the underlying signaling mechanisms involved in endothelial cells. Porcine retinal endothelial cells (PRECs) were exposed to VEGF, IL-1? and Ag-NP at different combinations and endothelial cell permeability was analyzed by measuring the

Sardarpasha Sheikpranbabu; Kalimuthu Kalishwaralal; Deepak Venkataraman; Soo Hyun Eom; Sangiliyandi Gurunathan



Propofol-induced vascular permeability change is related to the nitric oxide signaling pathway and occludin phosphorylation  

Microsoft Academic Search

The present study was undertaken to elucidate the mechanism of intra-arterial propofol-induced vascular permeability change\\u000a resulting in tissue edema. The mechanism of propofol-induced hyperpermeability was examined in a rat femoral artery injection\\u000a model. Vascular permeability was determined by measuring the Evans blue content of the dorsal skin of the infused limb at\\u000a 15, 30, 45 and 60 min after propofol injection.

Yi-Shen Chen; Kuan-Hung Chen; Chien-Cheug Liu; Chien-Te Lee; Chien-Hui Yang; Kuan-Chih Chuang; Chung-Ren Lin



Role of nitric oxide, prostaglandins and tyrosine kinase in vascular endothelial growth factor-induced increase in vascular permeability in mouse skin  

Microsoft Academic Search

We investigated role of nitric oxide (NO), prostaglandins (PG) and tyrosine kinase in vascular endothelial growth factor\\u000a (VEGF)-induced increase in vascular permeability in mouse skin. Subcutaneous injection of VEGF (0.5–2.0 ng\\/site) induced dose-\\u000a and time-dependent increase in vascular permeability at the injection site determined by a leakage of Pontamine sky blue.\\u000a VEGF (1 ng\\/site)-induced dye leakage was partially inhibited by

E. Fujii; Kaoru Irie; Ken-ichi Ohba; Akira Ogawa; Toshimasa Yoshioka; Mitsunori Yamakawa; Takamura Muraki



Neurogenic inflammation, vascular permeability, and mast cells. Capsaicin desensitization fails to influence IgE-anti-DNP induced vascular permeability in rat airways.  


Mast cells and neuropeptide-containing nerves occur in close proximity throughout the mucosa. The vasodilation that characteristically occurs after mast cell mediator release in skin is dependent upon sensory nerve activation with neuropeptide release. It was therefore of interest to examine the relationship between antigen-induced mast cell activation, vascular permeability, and the influence of capsaicin-sensitive sensory nerves in the airways. To examine this question, capsaicin was administered systemically and the "desensitization" of the animals to topical capsaicin confirmed. Thereafer, capsaicin-desensitized animals were studied to see if mast cell mediator-induced vascular permeability was affected. Plasma protein extravasation (PPE) was induced in Sprague-Dawley rats by intratracheal infusion of capsaicin or by intratracheal infusion of mouse serum albumin-dinitrophenol (MSA-DNP) after passive sensitization with IgE-anti-DNP. Leaking vessels in the airways were localized by using Monastral blue B, a macromolecular tracer. In the trachea, leaking vessels were predominantly located in the anterior wall after capsaicin challenge and in the posterior wall after antigen challenge. PPE was quantified by preinjecting animals with 125I-labeled BSA and expressed as microliter of plasma deposited in the trachea, bronchi, lungs, and tracheobronchial lavage (TBL). Within one minute after challenge, concentrations of capsaicin greater than 10(-7) M significantly increased PPE in trachea and bronchial wall (+ 160% and + 175% above control, respectively, with 10(-5) M). PPE was also observed in the trachea and bronchi after antigen challenge in animals passively sensitized with IgE-anti-DNP (+ 200% and + 153%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2137314

Didier, A; Kowalski, M L; Jay, J; Kaliner, M A



Phosphorylation of VE-cadherin is modulated by haemodynamic forces and contributes to the regulation of vascular permeability in vivo  

PubMed Central

Endothelial adherens junctions maintain vascular integrity. Arteries and veins differ in their permeability but whether organization and strength of their adherens junctions vary has not been demonstrated in vivo. Here we report that vascular endothelial cadherin, an endothelial specific adhesion protein located at adherens junctions, is phosphorylated in Y658 and Y685 in vivo in veins but not in arteries under resting conditions. This difference is due to shear stress-induced junctional Src activation in veins. Phosphorylated vascular endothelial-cadherin is internalized and ubiquitinated in response to permeability-increasing agents such as bradykinin and histamine. Inhibition of Src blocks vascular endothelial cadherin phosphorylation and bradykinin-induced permeability. Point mutation of Y658F and Y685F prevents vascular endothelial cadherin internalization, ubiquitination and an increase in permeability by bradykinin in vitro. Thus, phosphorylation of vascular endothelial cadherin contributes to a dynamic state of adherens junctions, but is not sufficient to increase vascular permeability in the absence of inflammatory agents.

Orsenigo, Fabrizio; Giampietro, Costanza; Ferrari, Aldo; Corada, Monica; Galaup, Ariane; Sigismund, Sara; Ristagno, Giuseppe; Maddaluno, Luigi; Young Koh, Gou; Franco, Davide; Kurtcuoglu, Vartan; Poulikakos, Dimos; Baluk, Peter; McDonald, Donald; Grazia Lampugnani, Maria; Dejana, Elisabetta



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

PubMed Central

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 ?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.

Schnoor, Michael; Lai, Frank P.L.; Zarbock, Alexander; Klaver, Ruth; Polaschegg, Christian; Schulte, Dorte; Weich, Herbert A.; Oelkers, J. Margit; Rottner, Klemens



Increased pulmonary vascular permeability as a cause of re-expansion edema in rabbits  

SciTech Connect

In order to study the mechanism(s) underlying re-expansion edema, we measured the concentration of labeled albumin (RISA) in the extravascular, extracellular water (EVECW) of the lung as a measure of pulmonary vascular permeability. Re-expansion edema was first induced by rapid re-expansion of rabbit lungs that had been collapsed for 1 wk by pneumothorax. The RISA in EVECW was expressed as a fraction of its plasma concentration: (RISA)L/(RISA)PL. The volume of EVECW (ml/gm dry lung) was measured using a /sup 24/Na indicator. Results in re-expansion edema were compared with normal control lungs and with oleic acid edema as a model of permeability edema. In re-expanded lungs, EVECW (3.41 +/- SD 1.24 ml/g) and (RISA)L/(RISA)PL 0.84 +/- SD 0.15) were significantly increased when compared with normal control lungs (2.25 +/- 0.41 ml/g and 0.51 +/- 0.20, respectively). Results in oleic acid edema (5.66 +/- 2.23 ml/g and 0.84 +/- 0.23) were similar to re-expansion edema. This suggested that re-expansion edema is due to increased pulmonary vascular permeability caused by mechanical stresses applied to the lung during re-expansion.

Pavlin, D.J.; Nessly, M.L.; Cheney, F.W.



A Bayesian Image Analysis of Radiation Induced Changes in Tumor Vascular Permeability  

PubMed Central

Summary This work is motivated by a quantitative Magnetic Resonance Imaging study of the relative change in tumor vascular permeability during the course of radiation therapy. The differences in tumor and healthy brain tissue physiology and pathology constitute a notable feature of the image data—spatial heterogeneity with respect to its contrast uptake profile (a surrogate for permeability) and radiation induced changes in this profile. To account for these spatial aspects of the data, we employ a Gaussian hidden Markov random field (MRF) model. The model incorporates a latent set of discrete labels from the MRF governed by a spatial regularization parameter. We estimate the MRF regularization parameter and treat the number of MRF states as a random variable and estimate it via a reversible jump Markov chain Monte Carlo algorithm. We conduct simulation studies to examine the performance of the model and compare it with a recently proposed method using the Expectation-Maximization (EM) algorithm. Simulation results show that the Bayesian algorithm performs as well, if not slightly better than the EM based algorithm. Results on real data suggest that the tumor “core” vascular permeability increases relative to healthy tissue three weeks after starting radiotherapy, which may be an opportune time to initiate chemotherapy and warrants further investigation.

Zhang, Xiaoxi; Johnson, Timothy D.; Little, Roderick J. A.; Cao, Yue



Superconducting artificial materials with a negative permittivity, a negative permeability, or a negative index of refraction  

Microsoft Academic Search

Artificial materials are media made of inclusions such that the sizes and spacing of the inclusions is much smaller than the incident electromagnetic radiation. This allows a medium to act as an effective bulk medium to electromagnetic radiation. Artificial materials can be tailored to produce desired values of the permittivity, permeability, and index of refraction at specific frequencies. The applications

Michael Christopher Ricci



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

NASA Astrophysics Data System (ADS)

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.

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



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

PubMed Central

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.

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



Angiogenesis is regulated by angiopoietins during experimental autoimmune encephalomyelitis and is indirectly related to vascular permeability.  


The regulation of angiogenesis was studied over the course of the animal model of multiple sclerosis, acute experimental autoimmune encephalomyelitis (EAE) in mice using immunohistochemistry. During EAE, angiogenesis peaked 21 days after disease induction, with significant increases in gray matter and adjacent to the leptomeninges. Angiogenesis correlated with clinical and pathologic scores. Spinal cord expression of angiopoietin 1 (Ang-1) by neurons and glia was reduced at Day 14, but expression by inflammatory cells restored earlier levels at Day 21. Angiopoietin 2 expression increased markedly at Day 21 and was mostly associated with inflammatory cells. Levels of the angiopoietin receptor Tie-2 were reduced at Day 14, but recovered by day D21. Double labeling demonstrated Ang-1 expression on infiltrating CD3-positive T cells; Ang-2 was expressed by monocytes/macrophages. During EAE, the expression of vascular endothelial growth factor peaked at Day 14 and began to decrease by Day 21. Double labeling showed expression of Tie-2 and vascular endothelial growth factor receptor 2 but not Ang-2 in blood vessels at Day 21. Vascular permeability increased early in EAE, but was reduced by Day 21. Although individual values did not correlate with angiogenesis, the volume of permeable tissue showed a weak positive correlation with angiogenesis. These temporal changes in angiogenic factors suggest an integral role during EAE-related angiogenesis. PMID:22082662

Macmillan, Carolyn J; Starkey, Ryan J; Easton, Alexander S



Protein Kinase C? Phosphorylates Occludin Regulating Tight Junction Trafficking in Vascular Endothelial Growth Factor-Induced Permeability In Vivo  

PubMed Central

Vascular endothelial growth factor (VEGF)–induced breakdown of the blood-retinal barrier requires protein kinase C (PKC)? activation. However, the molecular mechanisms related to this process remain poorly understood. In this study, the role of occludin phosphorylation and ubiquitination downstream of PKC? activation in tight junction (TJ) trafficking and endothelial permeability was investigated. Treatment of bovine retinal endothelial cells and intravitreal injection of PKC? inhibitors as well as expression of dominant-negative kinase was used to determine the contribution of PKC? to endothelial permeability and occludin phosphorylation at Ser490 detected with a site-specific antibody. In vitro kinase assay was used to demonstrate direct occludin phosphorylation by PKC?. Ubiquitination was measured by immunoblotting after occludin immunoprecipitation. Confocal microscopy revealed organization of TJ proteins. The results reveal that inhibition of VEGF-induced PKC? activation blocks occludin Ser490 phosphorylation, ubiquitination, and TJ trafficking in retinal vascular endothelial cells both in vitro and in vivo and prevents VEGF-stimulated vascular permeability. Occludin Ser490 is a direct target of PKC?, and mutating Ser490 to Ala (S490A) blocks permeability downstream of PKC?. Therefore, PKC? activation phosphorylates occludin on Ser490, leading to ubiquitination required for VEGF-induced permeability. These data demonstrate a novel mechanism for PKC? targeted inhibitors in regulating vascular permeability.

Murakami, Tomoaki; Frey, Tiffany; Lin, Chengmao; Antonetti, David A.



Increased vascular permeability, angiogenesis and wound healing induced by the serum of natural latex of the rubber tree Hevea brasiliensis.  


Increases in vascular permeability and angiogenesis are crucial events to wound repair, tumoral growth and revascularization of tissues submitted to ischemia. An increased vascular permeability allows a variety of cytokines and growth factors to reach the damaged tissue. Nevertheless, the angiogenesis supply tissues with a wide variety of nutrients and is also important to metabolites clearance. It has been suggested that the natural latex from Hevea brasiliensis showed wound healing properties and angiogenic activity. Thus, the purpose of this work was to characterize its angiogenic activity and its effects on vascular permeability and wound healing. The serum fraction of the latex was separated from the rubber with reduction of the pH. The activity of the dialyzed serum fraction on the vascular permeability injected in subcutaneous tissue was assayed according Mile's method. The angiogenic activity was determined using a chick embryo chorioallantoic membrane assay and its effects on the wound-healing process was determined by the rabbit ear dermal ulcer model. The serum fraction showed evident angiogenic effect and it was effective in enhancing vascular permeability. In dermal ulcers, this material significantly accelerated wound healing. Moreover, the serum fraction boiled and treated with proteases lost these activities. These results are in accordance with the enhancement of wound healing observed in clinical trials carried out with a biomembrane prepared with the same natural latex. PMID:19943314

Mendonça, Ricardo José; Maurício, Vanessa Beatriz; Teixeira, Larissa de Bortolli; Lachat, João José; Coutinho-Netto, Joaquim



Extracellular carbonic anhydrase mediates hemorrhagic retinal and cerebral vascular permeability through prekallikrein activation.  


Excessive retinal vascular permeability contributes to the pathogenesis of proliferative diabetic retinopathy and diabetic macular edema, leading causes of vision loss in working-age adults. Using mass spectroscopy-based proteomics, we detected 117 proteins in human vitreous and elevated levels of extracellular carbonic anhydrase-I (CA-I) in vitreous from individuals with diabetic retinopathy, suggesting that retinal hemorrhage and erythrocyte lysis contribute to the diabetic vitreous proteome. Intravitreous injection of CA-I in rats increased retinal vessel leakage and caused intraretinal edema. CA-I-induced alkalinization of vitreous increased kallikrein activity and its generation of factor XIIa, revealing a new pathway for contact system activation. CA-I-induced retinal edema was decreased by complement 1 inhibitor, neutralizing antibody to prekallikrein and bradykinin receptor antagonism. Subdural infusion of CA-I in rats induced cerebral vascular permeability, suggesting that extracellular CA-I could have broad relevance to neurovascular edema. Inhibition of extracellular CA-I and kallikrein-mediated innate inflammation could provide new therapeutic opportunities for the treatment of hemorrhage-induced retinal and cerebral edema. PMID:17259996

Gao, Ben-Bo; Clermont, Allen; Rook, Susan; Fonda, Stephanie J; Srinivasan, Vivek J; Wojtkowski, Maciej; Fujimoto, James G; Avery, Robert L; Arrigg, Paul G; Bursell, Sven-Erik; Aiello, Lloyd Paul; Feener, Edward P



Synthesis, Storage, and Release of Vascular Endothelial Growth Factor\\/Vascular Permeability Factor (VEGF\\/VPF) by Human Mast Cells: Implications for the Biological Significance of VEGF206  

Microsoft Academic Search

Mast cells have been implicated in various diseases that are accompanied by neovascu- larization. The exact mechanisms by which mast cells might mediate an angiogenic response, however, are unclear and therefore, we have investigated the possible expres- sion of vascular endothelial growth factor\\/vascular permeability factor (VEGF\\/VPF) in the human mast cell line HMC-1 and in human skin mast cells. Reverse

Andreas Grutzkau; Sabine Kruger-Krasagakes; Hans Baumeister; Constanze Schwarz; Heidi Kogel; Pia Welker; Undine Lippert; Beate M. Henz; Annelie Moller


Role of Insulin Receptor Substrates and Protein Kinase C- in Vascular Permeability Factor\\/Vascular Endothelial Growth Factor Expression in Pancreatic Cancer Cells  

Microsoft Academic Search

Vascular permeability factor\\/vascular endothelial growth factor (VPF\\/VEGF), the critical molecule in tu- mor angiogenesis, is regulated by different stimuli, such as hypoxia and oncogenes, and also by growth factors. Previously we have shown that in AsPC-1 pancreatic adenocarcinoma cells, insulin-like growth factor recep- tor (IGF-IR) regulates VPF\\/VEGF expression. Insulin re- ceptor substrate-1 and -2 (IRS-1 and IRS-2), two major downstream

Matthias Neid; Kaustubh Datta; Susann Stephan; Ila Khanna; Soumitro Pal; Leslie Shaw; Morris White; Debabrata Mukhopadhyay



Gold nanoparticles inhibit vascular endothelial growth factor-induced angiogenesis and vascular permeability via Src dependent pathway in retinal endothelial cells  

Microsoft Academic Search

The purpose of this study was to investigate the effect of gold nanoparticles on the signaling cascade related to angiogenesis\\u000a and vascular permeability induced by Vascular Endothelial Growth Factor (VEGF) in Bovine retinal endothelial cells (BRECs).\\u000a The effect of VEGF and gold nanoparticles on cell viability, migration and tubule formation was assessed. PP2 (Src Tyrosine\\u000a Kinase inhibitor) was used as

Kalimuthu Kalishwaralal; Sardarpasha Sheikpranbabu; Selvaraj BarathManiKanth; Ravinarayanan Haribalaganesh; Sureshbabu Ramkumarpandian; Sangiliyandi Gurunathan



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

PubMed Central

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 ?g/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 ?g/stomach vs 1.175 ± 0.374 ?g/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.

Masri, Abeer A Al; Eter, Eman El



Vascular endothelial growth factor (VEGF), produced by feline infectious peritonitis (FIP) virus-infected monocytes and macrophages, induces vascular permeability and effusion in cats with FIP.  


Feline infectious peritonitis virus (FIPV) causes a fatal disease called FIP in Felidae. The effusion in body cavity is commonly associated with FIP. However, the exact mechanism of accumulation of effusion remains unclear. We investigated vascular endothelial growth factor (VEGF) to examine the relationship between VEGF levels and the amounts of effusion in cats with FIP. Furthermore, we examined VEGF production in FIPV-infected monocytes/macrophages, and we used feline vascular endothelial cells to examine vascular permeability induced by the culture supernatant of FIPV-infected macrophages. In cats with FIP, the production of effusion was related with increasing plasma VEGF levels. In FIPV-infected monocytes/macrophages, the production of VEGF was associated with proliferation of virus. Furthermore, the culture supernatant of FIPV-infected macrophages induced hyperpermeability of feline vascular endothelial cells. It was suggested that vascular permeability factors, including VEGF, produced by FIPV-infected monocytes/macrophages might increase the vascular permeability and the amounts of effusion in cats with FIP. PMID:21473893

Takano, Tomomi; Ohyama, Taku; Kokumoto, Aiko; Satoh, Ryoichi; Hohdatsu, Tsutomu



Effect of PAF on rat lung vascular permeability: role of platelets and polymorphonuclear leucocytes.  

PubMed Central

1. The objectives of the present experiments were to assess the contribution of polymorphonuclear leucocytes (PMNLs), platelets and their products such as thromboxane A2 (TxA2), histamine and 5-hydroxytryptamine to platelet activating factor (PAF)-mediated protein extravasation in rat lungs. 2. Intravenous injection of PAF (1.0 and 5.0 micrograms kg-1) increased dose-dependently (up to 7.5 fold) the vascular permeability of the trachea, upper and lower bronchi to Evans blue dye (EB), a marker of albumin extravasation. The permeability of the pulmonary parenchyma was not affected significantly by PAF. 3. Thrombocytopenia induced by administration of the IgG fraction of goat anti-rat platelet serum (APS; 15 mg 100 g-1, i.p., 16-18 h) reduced by 55, 58 and 40% the effects of the lower dose of PAF (1.0 microgram kg-1) and by 31, 23 and 15% the effects of the higher dose of PAF (5.0 micrograms kg-1) on the permeability of the trachea, upper and lower bronchi respectively to albumin. 4. PMNL depletion induced by administration of rabbit anti-rat polymorphonuclear serum (ANS; 2 mg kg-1, i.v., 24 h) did not reduce significantly the effects of the lower dose of PAF (1.0 microgram kg-1) on the airways, however the effects of the higher dose of PAF (5.0 micrograms kg-1) on the permeability of the trachea, upper and lower bronchi to albumin were reduced by 43, 25 and 23% respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Sirois, M. G.; de Lima, W. T.; de Brum Fernandes, A. J.; Johnson, R. J.; Plante, G. E.; Sirois, P.



Measurement of injectivity indexes in geothermal wells with two permeable zones  

SciTech Connect

Injectivity tests in wells with two permeable zones and internal flow is analyzed in order to include the usually severe thermal transient effects. A theoretical analysis is performed and a method devised to obtain information from the thermal transient, provided that temperature is measured simultaneously with pressure. The technique is illustrated with two real tests performed at Miravalles, Costa Rica. It allows to estimate total injectivity index as well as the injectivity index of each one of the two zones separately. Correct position of measuring tools and nature of spontaneous internal flow is also discussed.

Acuna, Jorge A.



Tumor metastasis but not tumor growth is dependent on Src-mediated vascular permeability.  


Vascular endothelial growth factor (VEGF)-induced vascular permeability (VP) is a hallmark of tumor growth and metastasis. Previous studies have shown a requirement for Src kinase in VEGF-mediated VP and signaling in blood vessels. In this study, we have examined the effect of Src-mediated reduced VP on tumor growth and metastasis. The growth and spontaneous metastasis of VEGF-expressing tumor cells were determined in Src-knockout (src(-/-)) or control mice (src(+/+) or src(+/-)). In comparison to control mice, src-null mice had a significant reduction in tumor-induced VP as well as a subsequent reduction in spontaneous metastasis. In contrast, primary tumor weight and vascular density were unchanged between src-null and control mice. Consistent with a role for Src in the extravasation of tumor cells from the circulation, direct intravenous injection of lung carcinoma cells resulted in a more than 2-fold reduction in lung tumor burden in src-null mice compared to control mice. The comparison of the results from the experimental metastasis and the spontaneous metastasis models suggests that there are defects in VP in the primary site of Src-deficient mice and that there may be an essential role for Src and Src-mediated VP in tumor metastasis to the lung. PMID:15486073

Criscuoli, Michele L; Nguyen, Mai; Eliceiri, Brian P



The diaphragms of fenestrated endothelia: gatekeepers of vascular permeability and blood composition.  


Fenestral and stomatal diaphragms are endothelial subcellular structures of unknown function that form on organelles implicated in vascular permeability: fenestrae, transendothelial channels, and caveolae. PV1 protein is required for diaphragm formation in vitro. Here, we report that deletion of the PV1-encoding Plvap gene in mice results in the absence of diaphragms and decreased survival. Loss of diaphragms did not affect the fenestrae and transendothelial channels formation but disrupted the barrier function of fenestrated capillaries, causing a major leak of plasma proteins. This disruption results in early death of animals due to severe noninflammatory protein-losing enteropathy. Deletion of PV1 in endothelium, but not in the hematopoietic compartment, recapitulates the phenotype of global PV1 deletion, whereas endothelial reconstitution of PV1 rescues the phenotype. Taken together, these data provide genetic evidence for the critical role of the diaphragms in fenestrated capillaries in the maintenance of blood composition. PMID:23237953

Stan, Radu V; Tse, Dan; Deharvengt, Sophie J; Smits, Nicole C; Xu, Yan; Luciano, Marcus R; McGarry, Caitlin L; Buitendijk, Maarten; Nemani, Krishnamurthy V; Elgueta, Raul; Kobayashi, Takashi; Shipman, Samantha L; Moodie, Karen L; Daghlian, Charles P; Ernst, Patricia A; Lee, Hong-Kee; Suriawinata, Arief A; Schned, Alan R; Longnecker, Daniel S; Fiering, Steven N; Noelle, Randolph J; Gimi, Barjor; Shworak, Nicholas W; Carrière, Catherine



Effect of forskolin on alterations of vascular permeability induced with bradykinin, prostaglandin E1, adenosine, histamine and carrageenin in rats.  


The effect of the diterpene forskolin on vascular permeability alone and in combination with bradykinin, prostaglandin E1, adenosine or histamine has been investigated in rats. Vascular permeability in rat skin was measured using [125I]-labelled bovine serum albumin ([125I]BSA) as a tracer. In addition, the effect of forskolin on footpad edema induced by the injection of a mixture of 2% carrageenin was determined. Forskolin caused a marked potentiation of the increase in vascular permeability in rat skin elicited by the intradermal injection of histamine or bradykinin. However, forskolin caused a significant suppression of the prostaglandin E1-induced vascular permeability response and at a low concentration suppressed the response to adenosine. Forskolin greatly potentiated the footpad edema induced with carrageenin in rats. Intravenous administration of the enzyme bromelain, which reduces plasma kininogen levels, inhibited the footpad edema induced with carrageenin or with a mixture of carrageenin and forskolin. Parenteral administration of a prostaglandin synthetase inhibitor, indomethacin, suppressed the footpad edema induced with carrageenin, but did not inhibit the footpad edema induced with a mixture of carrageenin and forskolin. An antihistamine, cyproheptadine, had no effect on carrageenin-induced footpad edema either in the presence or absence of forskolin. These results suggest that both bradykinin and prostaglandins are essential for the development of carrageenin-induced footpad edema and that bradykinin plays an important role in the potentiative effect of forskolin on footpad edema induced with carrageenin in rats. PMID:6683350

Sugio, K; Daly, J W



The application of fluorescein labeled serum proteins (FLSP) to the study of vascular permeability in the brain  

Microsoft Academic Search

1.Vascular permeability in normal and edematous brain tissue was studied by application of the fluorescein labeled serum proteins (FLSP) as well as by the use of free fluorescein isothiocyanate (FITC) marker.2.The electrophoretic studies demonstrated that the binding capacity of the FITC to albumin was of such degree that morphological observations made after injection of the free tracer can be considered

Igor Klatzo; Jaime Miquel; Richard Otenasek



Neurogenic inflammation in the rat trachea. II. Identity and distribution of nerves mediating the increase in vascular permeability  

Microsoft Academic Search

Summary This study addresses the question of whether increased vascular permeability, which is a prominent feature of neurogenic inflammation in the respiratory tract, is mediated by sensory axons that end near venules in the airway mucosa. In these experiments, neurogenic inflammation was produced in the tracheal and bronchial mucosa of atropine-treated Long-Evans rats by electrical stimulation of the left or

Donald M. McDonald; Robert A. Mitchell; Giorgio Gabella; Amy Haskell



Phosphoramidon blocks big-endothelin-1 but not endothelin-1 enhancement of vascular permeability in the rat.  

PubMed Central

1. Changes in vascular permeability following intravenous injections of human big-endothelin-1 (big-ET-1) and endothelin-1 (ET-1) were measured by extravasation of Evans blue dye (EB, 20 mg kg-1) in selected tissues. 2. A low dose of big-ET-1 (40 pmol kg-1) failed to alter vascular permeability but a dose of 400 pmol kg-1 increased EB extravasation in the trachea, upper and lower bronchi, and lung parenchyma by 55 to 69% (P < 0.05). Vascular permeability was also enhanced in the liver, spleen, kidney, heart, and diaphragm by 20, 14, 41, 25, and 67%, respectively (P < 0.05). 3. Upon injection of ET-1 (400 pmol kg-1), EB extravasation increased in the upper and lower bronchi, lung parenchyma, liver, pancreas, kidney, heart, and diaphragm. 4. Administration of ET-1 and big-ET-1 was not associated with significant systemic responses. 5. Pretreatment with phosphoramidon (PA) blocked the response to big-ET-1 in all tissues examined but this inhibitor failed to alter the response to ET-1. 6. We conclude from these results that the dose-dependent increase in vascular permeability induced by big-ET-1 in various tissues follows its conversion to ET-1 by the endothelin converting enzyme, a PA-sensitive process.

Lehoux, S.; Plante, G. E.; Sirois, M. G.; Sirois, P.; D'Orleans-Juste, P.



Increased vascular permeability in C1 inhibitor-deficient mice mediated by the bradykinin type 2 receptor  

PubMed Central

Heterozygosity for C1 inhibitor (C1INH) deficiency results in hereditary angioedema. Disruption of the C1INH gene by gene trapping enabled the generation of homozygous- and heterozygous-deficient mice. Mating of heterozygous-deficient mice resulted in the expected 1:2:1 ratio of wild-type, heterozygous, and homozygous-deficient offspring. C1INH-deficient mice showed no obvious phenotypic abnormality. However, following injection with Evans blue dye, both homozygous and heterozygous C1INH-deficient mice revealed increased vascular permeability in comparison with wild-type littermates. This increased vascular permeability was reversed by treatment with intravenous human C1INH, with a Kunitz domain plasma kallikrein inhibitor (DX88), and with a bradykinin type 2 receptor (Bk2R) antagonist (Hoe140). In addition, treatment of the C1INH-deficient mice with an angiotensin-converting enzyme inhibitor (captopril) increased the vascular permeability. Mice with deficiency of both C1INH and Bk2R demonstrated diminished vascular permeability in comparison with C1INH-deficient, Bk2R-sufficient mice. These data support the hypothesis that angioedema is mediated by bradykinin via Bk2R.

Han, Eun D.; MacFarlane, Ryan C.; Mulligan, Aideen N.; Scafidi, Jennifer; Davis, Alvin E.



Vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) in normal and atherosclerotic human arteries.  

PubMed Central

Vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) is an endothelial-cell-specific mitogen; as such, its role in angiogenesis has been studied extensively. VEGF/VPF may also serve as a local, endogenous regulator of large-vessel endothelial cell integrity. Surprisingly, however, VEGF/VPF expression in normal and/or atherosclerotic vessels has not been previously characterized. Accordingly, we studied normal human arteries and veins as well as atherosclerotic and restenotic human coronary arteries for evidence of VEGF/VPF expression. VEGF/VPF was detected immunohistochemically in sections of normal human aorta, mammary artery, and saphenous vein. Moreover, VEGF/ VPF expression was identified in 32 (97%) of 33 pathological coronary arterial specimens; the extent of VEGF/VPF staining was graded as moderate to strong in 21 of the 32 (66%) positive specimens. VEGF/VPF double immunostaining and in situ hybridization demonstrated that smooth muscle cells constitute the principal cellular source of VEGF/VPF. VEGF/VPF immunostaining among primary atherosclerotic lesions localized predominantly to the extracellular matrix. In restenotic specimens, VEGF/VPF immunostaining was more prominently cellular, particularly among proliferating smooth muscle cells. Although VEGF/VPF expression was observed in areas of macrophage infiltration, double immunostaining failed to localize VEGF/VPF to macrophages in these foci; instead, double immunostaining clearly identified CD45RO-positive cells as responsible for VEGF/VPF expression in such areas. No correlation could be demonstrated between VEGF/VPF immunostaining and extent of vasa vasorum. These findings thus establish that postnatal VEGF/VPF expression is a feature of normal human arteries and veins and is often extensively expressed in arteries narrowed by atherosclerotic plaque. VEGF/VPF expression in the wall and/or plaque of medium to large vessels suggests a role for VEGF/VPF other than promoting angiogenesis. This role may involve maintenance and repair of luminal endothelium. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7

Couffinhal, T.; Kearney, M.; Witzenbichler, B.; Chen, D.; Murohara, T.; Losordo, D. W.; Symes, J.; Isner, J. M.



A role for a CXCR2/phosphatidylinositol 3-kinase gamma signaling axis in acute and chronic vascular permeability.  


Most proangiogenic polypeptide growth factors and chemokines enhance vascular permeability, including vascular endothelial growth factor (VEGF), the main target for anti-angiogenic-based therapies, and interleukin-8 (IL-8), a potent proinflammatory mediator. Here, we show that in endothelial cells IL-8 initiates a signaling route that converges with that deployed by VEGF at the level of the small GTPase Rac1 and that both act through the p21-activated kinase to promote the phosphorylation and internalization of VE-cadherin. However, whereas VEGF activates Rac1 through Src-related kinases, IL-8 specifically signals to Rac1 through its cognate G protein-linked receptor, CXCR2, and the stimulation of the phosphatidylinositol 3-kinase gamma (PI3Kgamma) catalytic isoform, thereby providing a specific molecular targeted intervention in vascular permeability. These results prompted us to investigate the potential role of IL-8 signaling in a mouse model for retinal vascular hyperpermeability. Importantly, we observed that IL-8 is upregulated upon laser-induced retinal damage, which recapitulates enhanced vascularization, leakage, and inflammatory responses. Moreover, blockade of CXCR2 and PI3Kgamma was able to limit neovascularization and choroidal edema, as well as macrophage infiltration, therefore contributing to reduce retinal damage. These findings indicate that the CXCR2 and PI3Kgamma signaling pathway may represent a suitable target for the development of novel therapeutic strategies for human diseases characterized by vascular leakage. PMID:19255141

Gavard, Julie; Hou, Xu; Qu, Yi; Masedunskas, Andrius; Martin, Daniel; Weigert, Roberto; Li, Xuri; Gutkind, J Silvio



VEGFR2 induces c-Src signaling and vascular permeability in vivo via the adaptor protein TSAd  

PubMed Central

Regulation of vascular endothelial (VE) growth factor (VEGF)–induced permeability is critical in physiological and pathological processes. We show that tyrosine phosphorylation of VEGF receptor 2 (VEGFR2) at Y951 facilitates binding of VEGFR2 to the Rous sarcoma (Src) homology 2-domain of T cell–specific adaptor (TSAd), which in turn regulates VEGF-induced activation of the c-Src tyrosine kinase and vascular permeability. c-Src was activated in vivo and in vitro in a VEGF/TSAd-dependent manner, and was regulated via increased phosphorylation at pY418 and reduced phosphorylation at pY527. Tsad silencing blocked VEGF-induced c-Src activation, but did not affect pathways involving phospholipase C?, extracellular regulated kinase, and endothelial nitric oxide. VEGF-induced rearrangement of VE–cadherin–positive junctions in endothelial cells isolated from mouse lungs, or in mouse cremaster vessels, was dependent on TSAd expression, and TSAd formed a complex with VE-cadherin, VEGFR2, and c-Src at endothelial junctions. Vessels in tsad?/? mice showed undisturbed flow and pressure, but impaired VEGF-induced permeability, as measured by extravasation of Evans blue, dextran, and microspheres in the skin and the trachea. Histamine-induced extravasation was not affected by TSAd deficiency. We conclude that TSAd is required for VEGF-induced, c-Src-mediated regulation of endothelial cell junctions and for vascular permeability.

Sun, Zuyue; Li, Xiujuan; Massena, Sara; Kutschera, Simone; Padhan, Narendra; Gualandi, Laura; Sundvold-Gjerstad, Vibeke; Gustafsson, Karin; Choy, Wing Wen; Zang, Guangxiang; Quach, My; Jansson, Leif; Phillipson, Mia; Abid, Md Ruhul; Spurkland, Anne



Ultrastructural Localization of the Vascular Permeability Factor\\/Vascular Endothelial Growth Factor (VPF\\/VEGF) Receptor2 (FLK-1, KDR) in Normal Mouse Kidney and in the Hyperpermeable Vessels Induced by VPF\\/VEGF-expressing Tumors and Adenoviral Vectors  

Microsoft Academic Search

SUMMARY Vascular permeability factor\\/vascular endothelial growth factor (VPF\\/VEGF) interacts with two high-affinity tyrosine kinase receptors, VEGFR-1 and VEGFR-2, to in- crease microvascular permeability and induce angiogenesis. Both receptors are selectively expressed by vascular endothelial cells and are strikingly increased in tumor vessels. We used a specific antibody to localize VEGFR-2 (FLK-1, KDR) in microvascular endothelium of normal mouse kidneys and

Dian Feng; Janice A. Nagy; Rolf A. Brekken; Anna Pettersson; Eleanor J. Manseau; Kathryn Pyne; Richard Mulligan; Philip E. Thorpe; Harold F. Dvorak; Ann M. Dvorak


Preserved vascular integrity and enhanced survival following neuropilin-1 inhibition in a mouse model of CD8 T cell-initiated CNS vascular permeability  

PubMed Central

Background Altered permeability of the blood–brain barrier (BBB) is a feature of numerous neurological conditions including multiple sclerosis, cerebral malaria, viral hemorrhagic fevers and acute hemorrhagic leukoencephalitis. Our laboratory has developed a murine model of CD8 T cell-initiated central nervous system (CNS) vascular permeability in which vascular endothelial growth factor (VEGF) signaling plays a prominent role in BBB disruption. Findings In this study, we addressed the hypothesis that in vivo blockade of VEGF signal transduction through administration of peptide (ATWLPPR) to inhibit neuropilin-1 (NRP-1) would have a therapeutic effect following induction of CD8 T cell-initiated BBB disruption. We report that inhibition of NRP-1, a co-receptor that enhances VEGFR2 (flk-1) receptor activation, decreases vascular permeability, brain hemorrhage, and mortality in this model of CD8 T cell-initiated BBB disruption. We also examine the expression pattern of VEGFR2 (flk-1) and VEGFR1 (flt-1) mRNA expression during a time course of this condition. We find that viral infection of the brain leads to increased expression of flk-1 mRNA. In addition, flk-1 and flt-1 expression levels decrease in the striatum and hippocampus in later time points following induction of CD8 T cell-mediated BBB disruption. Conclusion This study demonstrates that NRP-1 is a potential therapeutic target in neuro-inflammatory diseases involving BBB disruption and brain hemorrhage. Additionally, the reduction in VEGF receptors subsequent to BBB disruption could be involved in compensatory negative feedback as an attempt to reduce vascular permeability.



Dissociation of cutaneous vascular permeability and the development of cutaneous late-phase allergic reactions  

SciTech Connect

Cutaneous late-phase allergic reactions (LPR) are characterized by an early, immediate hypersensitivity whealing reaction followed by persistent, localized induration that peaks 6 to 8 hours later. In this study we used rodents to examine the relationship between vascular permeability (VP) and induration during LPR. Efflux of macromolecular tracers from the vasculature into skin was measured with the use of radiolabeled albumin and neutral dextran tracers having large molecular radii. To induce LPR immunologically, we used either intradermal injections of antirat IgE or passive cutaneous sensitization with IgE antidinitrophenyl followed 24 hours later by intravenous injection of albumin-dinitrophenyl. (/sup 125/I)albumin and (/sup 3/H)dextran tracers were injected intravenously before and at various intervals after the induction of LPR. Although a marked increase in VP occurred within the first 30 minutes after induction of mast cell degranulation, analysis of radiolabeled tracer accumulation at 2, 4, 8, and 24 hours failed to demonstrate any further increase in VP. These findings indicate that the induration observed in rodent LPR is not associated with increased VP beyond the immediate hypersensitivity stage and suggest that impairment of lymphatic drainage, cellular infiltration, and/or fibrin deposition are contributing factors.

Keahey, T.M.; Indrisano, J.; Kaliner, M.A.



Dependence of vascular permeability enhancement on cysteine proteinases in vesicles of Porphyromonas gingivalis.  


Infection with Porphyromonas gingivalis is strongly associated with adult periodontitis, and proteinases are considered to be important virulent factors of the bacterium. In order to investigate the function of proteinases in disease development we examined vesicles, a biological carrier of these enzymes, for the generation of vascular permeability enhancement (VPE) activity, believed to correlate with the exudation of gingival crevicular fluid. The vesicles generated VPE activity from human plasma in a dose-dependent manner which could be inhibited 90% by antipain, a specific inhibitor of the Arg-specific cysteine proteinases (Arg-gingipains [RGPs] from P. gingivalis. Incubation of vesicles with high-molecular-weight-kininogen (HMWK)-deficient plasma did not result in VPE activity. On this basis, RGPs associated with vesicles were assumed to be responsible for most of the VPE activity generation via plasma prekallikrein activation and subsequent bradykinin production. The secondary pathway for VPE activity production was dependent on the direct release of bradykinin from HMWK by the concerted action of RGP and a Lys-specific cysteine proteinase (Lys-gingipain [KGP]), also associated with vesicles. These results indicate that RGP and KGP are biologically important VPE factors acting either via prekallikrein activation (RGP) and/or HMWK cleavage (RGP and KGP) to release BK and, thereby, contributing to the production of gingival crevicular fluid at periodontal sites infected with P. gingivalis. PMID:7729914

Imamura, T; Potempa, J; Pike, R N; Travis, J



Pharmaco-modulations of induced edema and vascular permeability changes by Vipera lebetina venom: inflammatory mechanisms.  


The inflammatory response induced by Vipera lebetina venom (VLV) in the mice hind paw was evaluated by paw edema value and vascular permeability changes. The edema was produced in a dose- and time-dependent manner. This response was maximal within 2 h and disappeared after 24 h The minimum edema-forming dose was estimated at 0.8 ?g/20 g body weight. Microscopic examination confirmed that VLV also induces skin structure alterations with collagen fiber dissociation and polynuclear infiltration, which is characteristic of edema formation. The induced edema with VLV (1 ?g/paw) could be due to the release of pharmacological active substances at the site of injection. Histamine, serotonine, and arachidonate metabolites may play important roles in the vasoactive and edematic effect of VLV since pretreatment of mice with cromoglycate, cyproheptadine, ibuprofen, loratidine, and indomethacin significantly reduced the edema formation (77, 63, 57, 45, and 43 %, respectively). The obtained results demonstrate that the induced edema and vasodilatation by this venom may be triggered and maintained by different pharmacological mechanisms, since cromoglycate and cyproheptadine were the most active inhibitors of the edema. The relationships between histamine and serotonin release from mast cells and arachidonate metabolites activation could be the main step in edema-forming and the induced vasodilatation by the venom. PMID:23108954

Sebia-Amrane, Fatima; Laraba-Djebari, Fatima



Vascular permeability and axonal regeneration in skin autotransplanted into the brain.  

PubMed Central

Pieces of skin were autotransplanted from the pinna of an ear into a cerebral hemisphere in 36 albino rats. The grafts were examined 2, 4 and 6 weeks later for signs of vascular permeability and for the presence of nerve fibres. An intravenously injected fluorescent protein exuded into the connective tissue of the dermis and into the spaces between epidermal cells. Extravascular leukocytes were also seen in the dermis. Nerve fibres, derived from the caudate nucleus, corpus callosum and neocortex, were seen in nearly all the grafts, entering both the dermis and epidermis. They were more numerous after the fourth and sixth than after the second post-operative week. A few of these axons were myelinated and a few contained acetylcholinesterase. It has thus been shown that central axons can regenerate into a region in which they are surrounded by proteins and cells derived from the blood, for at least 6 weeks. This observation does not support a recently advanced hypothesis invoking autoimmunity as the cause of the failure of most axons to regenerate following severance within the central nervous system. It is tentatively suggested that the presence of plasma proteins in the extracellular fluid around the tips of axons may be necessary for the occurrence of regeneration. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9

Heinicke, E A; Kiernan, J A



Dependence of vascular permeability enhancement on cysteine proteinases in vesicles of Porphyromonas gingivalis.  

PubMed Central

Infection with Porphyromonas gingivalis is strongly associated with adult periodontitis, and proteinases are considered to be important virulent factors of the bacterium. In order to investigate the function of proteinases in disease development we examined vesicles, a biological carrier of these enzymes, for the generation of vascular permeability enhancement (VPE) activity, believed to correlate with the exudation of gingival crevicular fluid. The vesicles generated VPE activity from human plasma in a dose-dependent manner which could be inhibited 90% by antipain, a specific inhibitor of the Arg-specific cysteine proteinases (Arg-gingipains [RGPs] from P. gingivalis. Incubation of vesicles with high-molecular-weight-kininogen (HMWK)-deficient plasma did not result in VPE activity. On this basis, RGPs associated with vesicles were assumed to be responsible for most of the VPE activity generation via plasma prekallikrein activation and subsequent bradykinin production. The secondary pathway for VPE activity production was dependent on the direct release of bradykinin from HMWK by the concerted action of RGP and a Lys-specific cysteine proteinase (Lys-gingipain [KGP]), also associated with vesicles. These results indicate that RGP and KGP are biologically important VPE factors acting either via prekallikrein activation (RGP) and/or HMWK cleavage (RGP and KGP) to release BK and, thereby, contributing to the production of gingival crevicular fluid at periodontal sites infected with P. gingivalis.

Imamura, T; Potempa, J; Pike, R N; Travis, J



Inhibitory effect of Lactobacillus gasseri TMC0356 and Lactobacillus GG on enhanced vascular permeability of nasal mucosa in experimental allergic rhinitis of rats.  


The nasal vascular permeability of ovablumin (OVA)-sensitized Brown Norway rats was evaluated by analyzing a brilliant blue concentration in perfusate from the nose after exposure of the nasal mucus to OVA. Oral administration of Lactobacillus GG and L. gasseri TMC0356 significantly inhibited the increase in nasal vascular permeability (P<0.01). The serum IgE of the tested rats also decreased, although the change was not statistically significant. These results indicate that Lactobacillus GG and L. gasseri TMC0356 might alleviate nasal allergic symptoms by suppressing the increase in nasal vascular permeability caused by local inflammation associated with allergic rhnititis. PMID:17151443

Kawase, Manabu; He, Fang; Kubota, Akira; Hata, Jun-Ya; Kobayakawa, Shin-Ichiro; Hiramatsu, Masaru



Design and Free-Space Measurements of Broadband, Low-Loss Negative-Permeability and Negative-Index Media  

Microsoft Academic Search

We present the design and measurement of broad- band, volumetric negative-permeability and negative-refrac- tive-index (NRI) media. Both of these media are fabricated using standard printed-circuit-board techniques and operate at X-band frequencies. The S-parameters of four-cell slabs of the negative-permeability and NRI media are measured, and the material parameters of the NRI lens are extracted. The four-cell-thick NRI lens exhibits a

Scott Michael Rudolph; Carl Pfeiffer; Anthony Grbic



Broadband, low-loss negative-permeability and negative-index media for free-space applications  

Microsoft Academic Search

We present broadband negative permeability and negative-refractive-index (NRI) media that operate in free space. Both of these media operate at X-band frequencies and are fabricated using standard printed-circuit-board techniques. The S-parameters of four-cell slabs of the negative permeability and NRI media are measured using a quasi-optical Gaussian beam measurement system. Using these data, the material parameters of the NRI lens

Scott M. Rudolph; Anthony Grbic



Sex steroid dependency of diabetes-induced changes in polyol metabolism, vascular permeability, and collagen cross-linking.  


The effects of castration on diabetes-induced increases in collagen cross-linking and vascular permeability and on polyol levels in new granulation tissue formed after induction of streptozocin (STZ) diabetes were examined in male Sprague-Dawley rats. New granulation tissue formation was induced by implanting sterile polyester fabric subcutaneously (s.c.) at the time of STZ injection 3 wk before assessment of vascular permeability and collagen cross-linking. Castration was performed 10 days before implanting the fabric. The characteristic increases in collagen cross-linking (manifested by decreased solubility in 0.5 M acetic acid) and in albumin permeation of the vasculature seen in intact diabetic rats were completely prevented by castration. Net collagen accumulation was not affected by diabetes or castration. Castration also markedly diminished diabetes-induced increases in tissue levels of sorbitol and completely prevented the decreases in tissue levels of myo-inositol and scyllo-inositol observed in intact diabetic rats, but had no effect on serum glucose levels, nonenzymatic glycosylation of plasma and granulation tissue proteins, or plasma somatomedin-C levels. The demonstration that castration prevents diabetes-induced increases in vascular permeability and collagen cross-linking as well as imbalances in tissue levels of sorbitol, myo-inositol, and scyllo-inositol in this model indicates that all of these changes are sex steroid-dependent phenomena. While the pathogenesis of these vascular permeability and collagen cross-linking changes is clearly multifactorial, these new findings: indicate that the role of sex steroids in the development of late complications of diabetes may be far more important than hitherto suspected, and suggest an explanation for the clinical observation that diabetic complications are uncommon in prepubertal diabetic subjects regardless of duration of diabetes. PMID:3940909

Williamson, J R; Rowold, E; Chang, K; Marvel, J; Tomlinson, M; Sherman, W R; Ackermann, K E; Berger, R A; Kilo, C



Local and systemic capsaicin pretreatment inhibits sneezing and the increase in nasal vascular permeability induced by certain chemical irritants  

Microsoft Academic Search

1.The effects of local exposure to chemical irritants and mechanical stimulation on sneezing reflexes have been studied in normal and capsaicin-pretreated, conscious guinea-pigs. The influence of local and systemic capsaicin pretreatment on vascular permeability to plasma proteins and the cardiovascular effects of local application of capsaicin to the nasal mucosa have also been studied in anaesthetized animals.2.Local application of capsaicin

Lars Lundblad; Jan M. Lundberg; Anders Änggård



Effects of endothelin-1 on vascular permeability in the conscious rat: interactions with platelet-activating factor.  

PubMed Central

1. The objectives of the present experiments were to assess the effects of endothelin-1 on the macrovascular permeability in selected vascular beds, to study the involvement of platelet-activating factor (PAF) in vascular responses to endothelin-1 and to examine the vascular effects of combined administration of endothelin-1 and PAF in conscious rats. 2. Intravenous bolus injection of endothelin-1 (0.1-2 nmol kg-1) resulted in a dose-dependent biphasic change in mean arterial blood pressure (MABP) with initial transient hypotension followed by a prolonged pressor action. These changes were accompanied by a dose-dependent increase in haematocrit values. 3. Endothelin-1 (0.1 and 1 nmol kg-1) increased dose-dependently the vascular permeability of the trachea, upper and lower bronchi, stomach, duodenum, spleen and kidney (up to 240%) as measured by the extravasation of Evans blue dye. The permeability of pulmonary parenchyma, liver and pancreas was not affected significantly by endothelin-1 treatment. 4. Pretreatment of animals with the specific PAF receptor antagonist, WEB 2086 (1 mg kg-1, i.v.) or BN 52021 (10 mg kg-1, i.v.) reduced the endothelin-1 (1 nmol kg-1)-induced rise in haematocrit by about 50 and 30%, respectively. Both antagonists were highly effective at inhibiting protein extravasation in the stomach, duodenum and kidney. On the other hand, BN 52021, but not WEB 2086, significantly attenuated the effect of endothelin-1 on permeability in the lower bronchi and spleen. Neither WEB 2086 nor BN 52021 modified the changes in MABP evoked by endothelin-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Filep, J. G.; Sirois, M. G.; Rousseau, A.; Fournier, A.; Sirois, P.



Tc-99m radioaerosol clearance as an index of pulmonary epithelial permeability  

SciTech Connect

This investigation examines radiopharmaceutical clearance as an index of alveolar-capillary membrane permeability and as an indicator of disease. Specific objectives include: evaluation of radiopharmaceutical chemical purity following aerosolization, investigation of a chemically related family of compounds to develop new radiopharmaceuticals with improved chemical properties, determination of reproducibility of the radiopharmaceutical clearance technique and the evaluation of the sensitivity of aerosolized solute clearance as an indicator of lung injury. The integrity of the radiopharmaceutical was examined prior to and following aerosol generation. The in vivo pharmacokinetics of a family of aerosolized solutes was evaluated in the beagle dog. The reproducibility of the biological response to radiopharmaceutical deposition was evaluated using dynamic functional imaging in humans and in the beagle. The sensitivity of the technique was evaluated using Tc-99m DTPA and an animal model for lung injury.

Waldman, D.L.



Prazosin treatment suppresses increased vascular permeability in both acute and passively transferred experimental autoimmune encephalomyelitis in the lewis rat  

SciTech Connect

Prazosin, an antagonist of the ..cap alpha../sub 1/-adrenoceptor, has been found to suppress the clinical and histologic expression of experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. This effect appears to be specific for the ..cap alpha../sub 1/-receptor. To determine the effect of this drug on vascular permeability to serum proteins and inflammatory cells, leakage of serum proteins into the central nervous system (CNS) was measured with (/sup 125/I)albumin, and quantitation of cellular inflammation was determined by an estimation of total DNA. The results show that in both actively induced and passively transferred models of the disease, treatment with prazosin significantly suppresses leakage of serum proteins into the CNS but does not significantly suppress the increase of DNA. The results of the (/sup 125/I)albumin studies additionally support the conclusion that the extent of vascular permeability to serum proteins in the spinal cord is a significant correlate of clinical disease. The results of the DNA estimation were at variance with the histologic evidence of cellular infiltration. The authors conclude that treatment with prazosin has a significant effect on the development of vascular edema in EAE. These results additionally validate a role for the adrenergic receptor in the development of EAE, and support the hypothesis that the primary site of action of prazosin is on the vascular ..cap alpha../sub 1/-adrenoceptor.

Goldmuntz, E.A.; Brosnan, C.F.; Norton, W.T.



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

PubMed Central

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-?B 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.

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.



The inhibition of advanced glycation end-products-induced retinal vascular permeability by silver nanoparticles  

Microsoft Academic Search

The increased permeability of the blood–retinal barrier is known to occur in patients with diabetes, and this defect contributes to retinal edema. This study aimed to determine the effects of silver nanoparticles (Ag-NPs) on advanced glycation end-products (AGEs)-induced endothelial cell permeability. Cultured porcine retinal endothelial cells (PRECs) were exposed to AGE-modified bovine serum albumin (AGE-BSA) and the endothelial cell permeability

Sardarpasha Sheikpranbabu; Kalimuthu Kalishwaralal; Kyung-jin Lee; Ramanathan Vaidyanathan; Soo Hyun Eom; Sangiliyandi Gurunathan



Vascular Permeability in a Human Tumor Xenograft: Molecular Size Dependence and Cutoff Size1  

Microsoft Academic Search

Molecular size is one of the key determinants of transvascular transport of therapeutic agents in tumors. However, there are no data in the literature on the molecular size dependence of microvascular permeability in tumors. Therefore, we measured microvascular permeability to various macromolecules in the human colon adenocarcinoma I SI74T trans planted in dorsal skin chambers in severe combined immunodeficient mice.

Fan Yuan; Marc Dellian; Dai Fukumura; Michael Leunig; David A. Berk; Vladimir P. Torchilin; Rakesh K. Jain



Elevated Augmentation Index Derived from Peripheral Arterial Tonometry is Associated with Abnormal Ventricular-Vascular Coupling  

PubMed Central

Background Although typically derived from the contour of arterial pressure waveform, augmentation index (AIx) may also be derived from the digital pulse volume waveform using finger plethysmography (peripheral arterial tonometry, PAT). Little is known regarding the physiologic correlates of AIx derived from PAT. In this study, we investigated the relation of PAT-AIx with measures of ventricular-vascular coupling. Methods Pulse volume waves were measured via PAT and used to derive AIx. Using 2-dimensional echocardiography, effective arterial elastance index (EaI) was estimated as end systolic pressure / stroke volume index. Left ventricular (LV) end-systolic elastance index (ELVI) was calculated as end systolic pressure / end systolic volume index. Ventricular-vascular coupling ratio was defined as EaI/ELVI. Results Given the bi-directional nature of ventricular-vascular uncoupling as measured by echocardiography, patients were separated into 3 groups: low EaI/ELVI (<0.6, n = 21), optimal EaI/ELVI (mean 0.6–1.2, n = 16) and high EaI/ELVI (>1.2, n = 10). Adjusting for potential confounders (age, mean arterial pressure, height, and heart rate) patients with optimal EaI/ELVI had lower AIx (1±4%, p<0.05) compared to those with low EaI/ELVI (13±4%) and high EaI/ELVI (19±5%). Conclusions Abnormal ventricular-vascular coupling, arising from either increased effective arterial elastance or increased ventricular elastance, is associated with increased AIx as measured by PAT. Additional research is needed to examine other vascular correlates of PAT-AIx.

Heffernan, Kevin S.; Patvardhan, Eshan A.; Hession, Michael; Ruan, Jenny; Karas, Richard H.; Kuvin, Jeffrey T.



Simvastatin Inhibits Leukocyte Accumulation and Vascular Permeability in the Retinas of Rats with Streptozotocin-Induced Diabetes  

PubMed Central

Leukocytes play important roles in the pathogenesis of diabetic retinopathy. Recently, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors have been reported to exert various effects in addition to their lipid-lowering ability. We investigated the effects of simvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, on leukocyte-induced diabetic changes in retinas. Diabetes was induced in Long-Evans rats with streptozotocin, and simvastatin administration was begun immediately after the induction of diabetes. Two weeks of treatment with simvastatin suppressed significantly the number of leukocytes adhering to retinal vessel endothelium and the number of leukocytes accumulated in the retinal tissue by 72.9% and 41.0%, respectively (P < 0.01). The expression of intercellular adhesion molecule-1 (ICAM-1) and the CD18 (the common ?-chain of ICAM-1 ligands) were both suppressed with simvastatin. The amount of vascular endothelial growth factor in the retina was attenuated in the simvastatin-treated group. To evaluate the effects of simvastatin on leukocyte-induced endothelial cell damage, vascular permeability in the retina was measured with fluorescein-labeled dextran. Treatment with simvastatin markedly reduced retinal permeability (P = 0.014). This suggests that simvastatin attenuates leukocyte-endothelial cell interactions and subsequent blood-retinal barrier breakdown via suppression of vascular endothelial growth factor-induced ICAM-1 expression in the diabetic retina. Simvastatin may thus be useful in the prevention of diabetic retinopathy.

Miyahara, Shinsuke; Kiryu, Junichi; Yamashiro, Kenji; Miyamoto, Kazuaki; Hirose, Fumitaka; Tamura, Hiroshi; Katsuta, Hideto; Nishijima, Kazuaki; Tsujikawa, Akitaka; Honda, Yoshihito



Model selection in magnetic resonance imaging measurements of vascular permeability: Gadomer in a 9L model of rat cerebral tumor.  


Vasculature in and around the cerebral tumor exhibits a wide range of permeabilities, from normal capillaries with essentially no blood-brain barrier (BBB) leakage to a tumor vasculature that freely passes even such large molecules as albumin. In measuring BBB permeability by magnetic resonance imaging (MRI), various contrast agents, sampling intervals, and contrast distribution models can be selected, each with its effect on the measurement's outcome. Using Gadomer, a large paramagnetic contrast agent, and MRI measures of T(1) over a 25-min period, BBB permeability was estimated in 15 Fischer rats with day-16 9L cerebral gliomas. Three vascular models were developed: (1) impermeable (normal BBB); (2) moderate influx (leakage without efflux); and (3) fast leakage with bidirectional exchange. For data analysis, these form nested models. Model 1 estimates only vascular plasma volume, v(D), Model 2 (the Patlak graphical approach) v(D) and the influx transfer constant K(i). Model 3 estimates v(D), K(i), and the reverse transfer constant, k(b), through which the extravascular distribution space, v(e), is calculated. For this contrast agent and experimental duration, Model 3 proved the best model, yielding the following central tumor means (+/-s.d.; n = 15): v(D) = 0.07 +/- 0.03 for K(i) = 0.0105 +/- 0.005 min(-1) and v(e) = 0.10 +/- 0.04. Model 2 K(i) estimates were approximately 30% of Model 3, but highly correlated (r = 0.80, P < 0.0003). Sizable inhomogeneity in v(D), K(i), and k(b) appeared within each tumor. We conclude that employing nested models enables accurate assessment of transfer constants among areas where BBB permeability, contrast agent distribution volumes, and signal-to-noise vary. PMID:16079791

Ewing, James R; Brown, Stephen L; Lu, Mei; Panda, Swayamprava; Ding, Guangliang; Knight, Robert A; Cao, Yue; Jiang, Quan; Nagaraja, Tavarekere N; Churchman, Jamie L; Fenstermacher, Joseph D



Duration of action of topical antiallergy drugs in a Guinea pig model of histamine-induced conjunctival vascular permeability.  


The topical application of 0.1% olopatadine has been shown to provide significant attenuation of histamine-induced conjunctival vascular permeability (CVP) within 5 min and for as long as 24 h following a topical administration. The duration of the action of olopatadine was compared to that of epinastine, azelastine, and ketotifen. Male Hartley outbred guinea pigs (weighing 250-300 g) were administered a drug or vehicle as single O.D. topical drops, at times ranging from 4 to 24 h prior to histamine challenge. One (1) h prior to histamine challenge, the animals were administered 1 mL of Evans blue dye (1 mg/mL) through the marginal ear vein. Histamine (300 ng) was administered by a subconjunctival injection, and the guinea pigs were sacrificed 30 min later. CVP was assessed as the area and color intensity stained with Evans blue dye. The potencies of each drug were determined by calculating a 50% effective dose (ED(50)) for the inhibition of vascular leakage, compared to vehicle treatment, at each time point. Olopatadine was the only compound tested that was significantly effective 16 h following a single topical application. The ED(50) for olopatadine at 16 h was 0.031%. Epinastine, azelastine, and ketotifen were only significantly effective for up to 4 h. Olopatadine exhibited the longest duration of action for inhibition of histamine-induced vascular permeability in guinea pigs of any topical antiallergic drug tested. Concentrations of olopatadine, which provided a greater than 50% inhibition of the histamine-induced vascular response, were consistently less than 0.1% over a 16-h pretreatment interval. PMID:17803429

Beauregard, Clay; Stephens, Donna; Roberts, Leighann; Gamache, Daniel; Yanni, John



Effect of Shear Stress on Permeability of Vascular Endothelial Monolayer Cocultured with Smooth Muscle Cells  

NASA Astrophysics Data System (ADS)

Effect of fluid shear stress on permeability of endothelial monolayer was investigated using an endothelial cell (EC)-smooth muscle cell (SMC) cocultured model (CM). Permeability of ECs to bovine serum albumin was measured after exposure to shear stress of 1.5Pa for 48 hours. Morphology and VE-cadherin expression of ECs in CM was almost same as of ECs cultured alone (monocultured model, MM). Under static condition, EC permeability was 5.1±3.0 × 10-6cm/sec (mean±SD) in MM and 6.5±3.4 × 10-6cm/sec in CM. After exposure to shear stress, EC permeability in CM (2.2±1.9 × 10-6cm/sec, p < 0.05) significantly decreased compared with the static model. However, EC permeability in MM (3.9±3.2 × 10-6cm/sec) did not significantly change compared with static cultured condition. These results suggested that cellular interactions between ECs and SMCs have important influences on EC permeability.

Sakamoto, Naoya; Ohashi, Toshiro; Sato, Masaaki


Diesel exhaust particles modulate vascular endothelial cell permeability: Implication of ZO-1 Expression  

PubMed Central

Exposure to air pollutants increases the incidence of cardiovascular disease. Recent toxicity studies revealed that ultra fine particles (UFP, dp<100–200 nm), the major portion of particulate matter (PM) by numbers in the atmosphere, induced atherosclerosis. In this study, we posited that variations in chemical composition in diesel exhausted particles (DEP) regulated endothelial cell permeability to a different extent. Human aortic endothelial cells (HAEC) were exposed to well-characterized DEP (dp<100 nm) emitted from a diesel engine in either idling mode (DEP1) or in urban dynamometer driving schedule (UDDS) (DEP2). Horse Radish Peroxidase-Streptavidin activity assay showed that DEP2 increased endothelial permeability to a greater extent than DEP1 (Control=0.077± 0.005, DEP1=0.175±0.003, DEP2=0.265±0.006, n=3, p<0.01). DEP2 also down-regulated tight junction protein, Zonular Occludin-1 (ZO-1), to a greater extent compared to DEP1. LDH and caspase-3 activities revealed that DEP-mediated increase in permeability was not due to direct cytotoxicity, and DEP-mediated ZO-1 down-regulation was not due to a decrease in ZO-1 mRNA. Hence, our findings suggest that DEP1 versus DEP2 differentially influenced the extent of endothelial permeability at the post-translational level. This increase in endothelium permeability is implicated in inflammatory cell transmigration into subendothelial layers with relevance to the initiation of atherosclerosis.

Li, Rongsong; Ning, Zhi; Cui, Jeffrey; Yu, Fei; Sioutas, Constantinos; Hsiai, Tzung



Diesel exhaust particles modulate vascular endothelial cell permeability: implication of ZO-1 expression.  


Exposure to air pollutants increases the incidence of cardiovascular disease. Recent toxicity studies revealed that ultra-fine particles (UFP, d(p)<100-200 nm), the major portion of particulate matter (PM) by numbers in the atmosphere, induced atherosclerosis. In this study, we posited that variations in chemical composition in diesel exhausted particles (DEP) regulated endothelial cell permeability to a different extent. Human aortic endothelial cells (HAEC) were exposed to well-characterized DEP (d(p)<100 nm) emitted from a diesel engine in either idling mode (DEP1) or in urban dynamometer driving schedule (UDDS) (DEP2). Horse Radish Peroxidase-Streptavidin activity assay showed that DEP2 increased endothelial permeability to a greater extent than DEP1 (control=0.077+/-0.005, DEP1=0.175+/-0.003, DEP2=0.265+/-0.006, n=3, p<0.01). DEP2 also down-regulated tight junction protein, Zonular Occludin-1 (ZO-1), to a greater extent compared to DEP1. LDH and caspase-3 activities revealed that DEP-mediated increase in permeability was not due to direct cytotoxicity, and DEP-mediated ZO-1 down-regulation was not due to a decrease in ZO-1 mRNA. Hence, our findings suggest that DEP1 vs. DEP2 differentially influenced the extent of endothelial permeability at the post-translational level. This increase in endothelium permeability is implicated in inflammatory cell transmigration into subendothelial layers with relevance to the initiation of atherosclerosis. PMID:20576493

Li, Rongsong; Ning, Zhi; Cui, Jeffrey; Yu, Fei; Sioutas, Constantinos; Hsiai, Tzung



Increased vascular permeability in the circumventricular organs of adult rat brain due to stimulation by extremely low frequency magnetic fields.  


It has been demonstrated that the exposure of biological systems to magnetic fields (MFs) can produce several beneficial effects: tissue recovery in chronic wounds, re-establishment of blood circulation after tissue ischemia or in necrotic tissues, improvement after epileptic episodes, angiogenesis, etc. In the current study, the effects of extremely low frequency (ELF) MF on the capillaries of some circumventricular organs (CVOs) are demonstrated; a vasodilator effect is reported as well as an increase in their permeability to non-liposoluble substances. For this study, 96 Wistar male rats (250 g body mass) were used and divided into three groups of 32 rats each: a control group (no treatment); a sham ELF-MF group; and an experimental group subjected to ELF-MF (120 Hz harmonic waves and 0.66 mT, root mean square) by the use of Helmholtz coils. All animals were administered colloidal carbon (CC) intravenously to study, through optical and transmission electron microscopy, the capillary permeability in CVOs and the blood-brain barrier (BBB) in brain areas. An increase in capillary permeability to CC was detected in the ELF-MF-exposed group as well as a significant increase in vascular area (capillary vasodilation); none of these effects were observed in individuals of the control and sham ELF-MF groups. It is important to investigate the mechanisms involved in the phenomena reported here in order to explain the effects of ELF-MF on brain vasculature. PMID:23060261

Gutiérrez-Mercado, Yanet K; Cañedo-Dorantes, Luis; Gómez-Pinedo, Ulises; Serrano-Luna, Gregorio; Bañuelos-Pineda, Jacinto; Feria-Velasco, Alfredo



Role of actin and myosin in the control of paracellular permeability in pig, rat and human vascular endothelium.  

PubMed Central

1. We have investigated the endothelial actomyosin system with particular emphasis on its possible role in actively opening a paracellular route for permeability. 2. Actin and myosin comprised 16% of total endothelial protein with a molar actin/myosin ratio of 16.2 which is close to the actin/myosin ratio of muscle (studies on freshly isolated pig pulmonary arterial endothelial cells, PAEC). 3. By immunocytochemistry at the light and electron microscope levels the bulk of actin and myosin was colocalized in close vicinity to the intercellular clefts of both micro- and macrovascular endothelial cells in situ and in vitro. 4. Calcium-ionophore-induced rise in permeability of human umbilical venous endothelial cells (HUVEC) and PAEC monolayers grown on filters in a two-chamber permeability system was caused by opening of intercellular gaps. Gap formation depended on the rise in intracellular Ca2+ and could be blocked by the calmodulin-binding drugs trifluperazine (TFP) and W7. 5. In skinned monolayers of cultured PAEC and in isolated sheets of HUVEC gap formation was shown to require ATP and occurred only when free myosin binding sites were available on endothelial actin filaments (experiments with myosin subfragment 1 modified by N-ethylmaleimide, S1-NEM). 6. These experiments suggest that actin and myosin in endothelial cells play a central role in regulating the width of the intercellular clefts, thereby controlling the paracellular pathway of vascular permeability. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15

Schnittler, H J; Wilke, A; Gress, T; Suttorp, N; Drenckhahn, D



Diesel exhaust particles modulate vascular endothelial cell permeability: Implication of ZO-1 expression  

Microsoft Academic Search

Exposure to air pollutants increases the incidence of cardiovascular disease. Recent toxicity studies revealed that ultra-fine particles (UFP, dp<100–200nm), the major portion of particulate matter (PM) by numbers in the atmosphere, induced atherosclerosis. In this study, we posited that variations in chemical composition in diesel exhausted particles (DEP) regulated endothelial cell permeability to a different extent. Human aortic endothelial cells

Rongsong Li; Zhi Ning; Jeffrey Cui; Fei Yu; Constantinos Sioutas; Tzung Hsiai



Hyperstimulation and a Gonadotropin-Releasing Hormone Agonist Modulate Ovarian Vascular Permeability by Altering Expression of the Tight Junction Protein Claudin-5  

Microsoft Academic Search

We investigated the mechanism by which a GnRH agonist (GnRHa) affects ovarian vascularity, vascular permeability, and expression of the tight junction protein claudin-5 in a rat model of ovarian hyperstimulation syndrome (OHSS). Hyper- stimulated rats received excessive doses of pregnant mare serum gonadotropin (PMSG; 50 IU\\/d) for 4 consecutive days, from d 25 to 28 of life, followed by 25

Yoshimitsu Kitajima; Toshiaki Endo; Kunihiko Nagasawa; Kengo Manase; Hiroyuki Honnma; Tsuyoshi Baba; Takuhiro Hayashi; Hideki Chiba; Norimasa Sawada; Tsuyoshi Saito



Real-Time Visualization and Quantitation of Vascular Permeability In Vivo: Implications for Drug Delivery  

Microsoft Academic Search

The leaky, heterogeneous vasculature of human tumors prevents the even distribution of systemic drugs within cancer tissues. However, techniques for studying vascular delivery systems in vivo often require complex mammalian models and time-consuming, surgical protocols. The developing chicken embryo is a well-established model for human cancer that is easily accessible for tumor imaging. To assess this model for the in

Desmond B. S. Pink; Wendy Schulte; Missag H. Parseghian; Andries Zijlstra; John D. Lewis



Association of the Cardioankle Vascular Index and Ankle-Brachial Index with Carotid Artery Intima Media Thickness in Hemodialysis Patients  

PubMed Central

The objectives of the present study are (1) to compare the cardioankle vascular index (CAVI), ankle-brachial index (ABI), and carotid artery intima-media thickness (CA-IMT) between HD patients with and without type 2 diabetes (T2D) or prevalence of cardiovascular (CV) disease and (2) also to evaluate the relationship of these indices with CA-IMT in these patients according to ABI levels. This study consisted of 132 HD patients with T2D and the same number of patients without T2D. The patients with diabetes or prevalence of CV disease had significantly higher CA-IMT and lower ABI values than those without diabetes or prevalence of CV disease, respectively. Although diabetic patients had higher CAVI than those without diabetes, CAVI did not differ between patients with or without prevalence of CV disease. In univariate analysis, CA-IMT was more strongly correlated with ABI than CAVI. However, the opposite was true in patients with an ABI value of more than 0.95. Both indices were significantly correlated with CA-IMT although ABI was a powerful determinant than CAVI. It appears that both indices are associated with CA-IMT in HD patients, especially with an ABI value of more than 0.95.

Gohda, Tomohito; Gotoh, Hiromichi; Gotoh, Yoshikazu; Yamaguchi, Saori; Tomino, Yasuhiko



Impact of Oncogenes in Tumor Angiogenesis: Mutant K-ras up-Regulation of Vascular Endothelial Growth Factor\\/Vascular Permeability Factor is Necessary, but not Sufficient for Tumorigenicity of Human Colorectal Carcinoma Cells  

Microsoft Academic Search

Targeted disruption of the single mutant K-ras allele in two human colorectal carcinoma cell lines (DLD-1 and HCT-116) leads to loss of tumorigenic competence in nude mice with retention of ability to grow indefinitely in monolayer culture. Because expression of the mutant K-ras oncogene in these cell lines is associated with marked up-regulation of vascular endothelial growth factor\\/vascular permeability factor

Futoshi Okada; Janusz W. Rak; Brad St. Croix; Blandine Lieubeau; Mitsunori Kaya; Luba Roncari; Senji Shirasawa; Takehiko Sasazuki; Robert S. Kerbel



Cardio-ankle vascular index (CAVI) as an indicator of arterial stiffness.  


Arterial stiffness has been identified as an independent predictor of prognostic outcomes for patients with cardiovascular disease. Although measurement of pulse wave velocity has been a widely accepted noninvasive approach to the assessment of arterial stiffness, its accuracy is hampered by changes in blood pressure. Taking the exponential relation between intravascular pressure and arterial diameter into consideration, a stiffness parameter can be obtained by plotting the natural logarithm of systolic-diastolic pressure ratio against the arterial wall extensibility. Cardio-ankle vascular index (CAVI), which is calculated based on the stiffness parameter thus obtained, is theoretically independent of changes in blood pressure. With this distinct advantage, CAVI has been widely applied clinically to assess arterial stiffness in subjects with known cardiovascular diseases including those with diagnosed atherosclerosis, coronary heart disease, and stroke as well as those at risk, including those with hypertension, diabetes, the elderly, and the obese. Because of its enhanced sensitivity, not only has the index been used to discern subtle changes in the disease process, it has also been utilized in studying normal individuals to assess their potential risks of developing cardiovascular diseases. The primary aims of assessing arterial stiffness using CAVI are not only to aid in early detection of arteriosclerosis to allow timely treatment and change in lifestyle, but also to quantitatively evaluate the progression of disease and the effectiveness of treatment. Despite its merit of being unaffected by blood pressure, discretion in data interpretation is suggested because an elevated CAVI represents not just vascular stiffness caused by pathological changes in the arterial wall, but can also be attributed to an increased vascular tone brought about by smooth muscle contraction. Moreover, certain patient populations, such as those with an ankle-brachial index < 0.9, may give falsely low CAVI and are suggested to be excluded from study. PMID:23667317

Sun, Cheuk-Kwan



MK2 plays an important role for the increased vascular permeability that follows thermal injury.  


We previously reported Rho kinase is involved in vessel hyper-permeability caused by burns. Here we further explore the Rho kinase downstream signaling, it is found that its specific inhibitor Y27632 significantly diminishes the activation of JNK and p38 MAPKs but not ERK that induced by serum from burned rats (burn-serum). JNK activation was found involved in the expression of HUVEC adhesion molecules following thermal injury, although not in the process of stress fiber formation. Inhibition of various MAPKs by specific inhibitors showed that SB203580 (inhibitor of p38), but neither SP600125 (inhibitor of JNK) nor PD98059 (inhibitor of ERK), abolish activation of the p38 downstream kinase MK2. Demonstration of stress fibers by fluorescent-labeled phalloidin showed that inhibition of MK2, either by its specific inhibitor or by dominant negative adeno-viral-carried constructs, significantly reduced burn-serum-induced HUVEC stress-fiber formation, while inhibition of another downstream p38 MAPK kinase, PRAK, had no such effects. Transfection of dominant negative adeno-viral MK2 (Ad-MK2(A)) significantly inhibited thermal injury-induced blood vessel hyper-permeability in rats and, moreover, prolonged the survival of burned rats beyond 72h following thermal injury. One of the mechanisms behind these phenomena is that Ad-MK2(A) causes a significant depression of burn-serum-induced HSP27-phosphorylation, while the adeno-viral transported dominant negative PRAK (Ad-PRAK(A)) does not block. Although the effect of blockade of MK2 through its adeno-viral approach requires further study and investigation of alternatives to know for sure, we may have found a new pathway behind thermal-injury-induced blood vessel hyper-permeability, namely: Rho kinase>p38>MK2>HSP27. PMID:23465795

Wu, Wei; Huang, Qiaobing; Miao, Jingxia; Xiao, Mingjia; Liu, Hongxia; Zhao, Kesen; Zhao, Ming



Further Studies on the Structural Requirements of Sugars as Antagonists of the Changes in Vascular Permeability Produced by Sugar Polymers in Rat Skin  

Microsoft Academic Search

Hexoses and pentoses, but not tetroses or trioses, are potent inhibitors of the increase in vascular permeability in rat skin produced by the polysaccharides – dextran, mannan and glucan. The most active sugars are those with a D-threo type of structure in their cyclic form. The alcohols corresponding to the active sugars are much less inhibitory in this test. The

G. B. West



Interleukin 10 and lnterleukin 13 Synergize to Inhibit Vascular Permeability Factor Release by Peripheral Blood Mononuclear Cells from Patients with Lipoid Nephrosis  

Microsoft Academic Search

It has been proposed that a vascular permeability factor (VPF) is involved in the pathogenesis of lipoid nephrosis (LN). There is now increasing evidence that interleukin 10 (IL-10) and interleukin 13 (IL-13) have regulatory effects on cytokine production by activated macrophages. These results prompted us to study the effects of recombinant human IL-10 and IL-13 on VPF secretion in LN.

Koichi Matsumoto; Hiroyuki Ohi; Katsuo Kanmatsuse



Mechanotransduction by GEF-H1 as a novel mechanism of ventilator-induced vascular endothelial permeability  

PubMed Central

Pathological lung overdistention associated with mechanical ventilation at high tidal volumes (ventilator-induced lung injury; VILI) compromises endothelial cell (EC) barrier leading to development of pulmonary edema and increased morbidity and mortality. We have previously shown involvement of microtubule (MT)-associated Rho-specific guanine nucleotide exchange factor GEF-H1 in the agonist-induced regulation of EC permeability. Using an in vitro model of human pulmonary EC exposed to VILI-relevant magnitude of cyclic stretch (18% CS) we tested a hypothesis that CS-induced alterations in MT dynamics contribute to the activation of Rho-dependent signaling via GEF-H1 and mediate early EC response to pathological mechanical stretch. Acute CS (30 min) induced disassembly of MT network, cell reorientation, and activation of Rho pathway, which was prevented by MT stabilizer taxol. siRNA-based GEF-H1 knockdown suppressed CS-induced disassembly of MT network, abolished Rho signaling, and attenuated CS-induced stress fiber formation and EC realignment compared with nonspecific RNA controls. Depletion of GEF-H1 in the murine two-hit model of VILI attenuated vascular leak induced by lung ventilation at high tidal volume and thrombin-derived peptide TRAP6. These data show for the first time the critical involvement of microtubules and microtubule-associated GEF-H1 in lung vascular endothelial barrier dysfunction induced by pathological mechanical strain.

Fu, Panfeng; Xing, Junjie; Yakubov, Bakhtiyor; Cokic, Ivan; Birukov, Konstantin G.



Quantitation and physiological characterization of angiogenic vessels in mice: effect of basic fibroblast growth factor, vascular endothelial growth factor/vascular permeability factor, and host microenvironment.  

PubMed Central

A prerequisite for the development of novel angiogenic and anti-angiogenic agents is the availability of routine in vivo assays that permit 1) repeated, long-term quantitation of angiogenesis and 2) physiological characterization of angiogenic vessels. We report here the development of such an assay in mice. Using this assay, we tested the hypothesis that the physiological properties of angiogenic vessels governed by the microenvironment and vessel origin rather than the initial angiogenic stimulus. Gels containing basic fibroblast growth factor (bFGF) or vascular endothelial growth (VEGF) were implanted in transparent windows in the dorsal skin or cranium of mice. Vessels could be continuously and non-invasively monitored and easily quantified for more than 5 weeks after gel implantation. Newly formed vessels were first visible on day 4 in the cranial window and day 10 in the dorsal skinfold chamber, respectively. The number of vessels was dependent on the dose of bFGF and VEGF. At 3000 ng/ml, bFGF- and VEGF-induced blood vessels had similar diameters, red blood cell velocities, and microvascular permeability to albumin. However, red blood cell velocities and microvascular permeability to albumin were higher in the cranial window than in the dorsal skinfold chamber. Leukocyte-endothelial interaction was nearly zero in both sites. Thus, newly grown microvessels resembled vessels of granulation and neoplastic tissue in many aspects. Their physiological properties were mainly determined by the microenvironment, whereas the initial angiogenic response was stimulated by growth factors. Images Figure 1 Figure 2 Figure 3 Figure 5

Dellian, M.; Witwer, B. P.; Salehi, H. A.; Yuan, F.; Jain, R. K.



The genesis of peritumoral vasogenic brain edema and tumor cysts: a hypothetical role for tumor-derived vascular permeability factor.  

PubMed Central

Cerebral edema and fluid-filled cysts are common accompaniments of brain tumors. They contribute to the mass effect imposed by the primary tumor and are often responsible for a patient's signs and symptoms. Cerebral edema significantly increases the morbidity associated with tumor biopsy, excision, radiation therapy, and chemotherapy. Both edema and cyst formation are thought to result from a deficiency in the blood-brain barrier, with consequent extravasation of water, electrolytes, and plasma proteins from altered tumor microvessels. The resultant expansion of the cerebral interstitial space contributes to the elevated intracranial pressure observed with brain tumors. Departure from the typical blood-brain barrier microvascular architecture may only partially explain the occurrence of edema and tumor cyst formation. Biochemical mediators have also been implicated in vascular extravasation. Vascular permeability factor or vascular endothelial growth factor (VPF/VEGF) is a protein that has recently been isolated from a variety of tumors including human brain tumors. VPFb is an extraordinarily potent inducer of both microvascular extravasation (edemagenesis) and the formation of new blood vessels (angiogenesis). Its role in tumor growth and progression would therefore appear pivotal. Herein, the author presents an updated account of the investigation of VPF. Historical and clinical perspectives of the study and treatment of tumor associated edema are provided. The efficacy of high-dose dexamethasone in the treatment of neoplastic brain edema is discussed. A hypothetical role for VPF in edemagenesis is presented and discussed. It is hoped that an expanded understanding of the mechanisms responsible for the genesis of edema will ultimately facilitate therapeutic intervention. Images Figure 1 Figure 2 Figure 3

Criscuolo, G. R.



Leukocyte-endothelial cell interactions are linked to vascular permeability via ICAM-1-mediated signaling.  


Two key characteristics of the inflammatory response are the recruitment of leukocytes to inflamed tissue as well as changes in vessel permeability. We explored the relationship between these two processes using intravital confocal microscopy in cremasters of anesthetized (65 mg/kg Nembutal ip) mice. We provide direct evidence that intercellular adhesion molecule-1 (ICAM-1) links leukocyte-endothelial cell interactions and changes in solute permeability (Ps). Importantly, we show that arterioles, not just venules, respond to proinflammatory stimuli, thus contributing to microvascular exchange. We identified two independent, ICAM-1-mediated pathways regulating Ps. Under control conditions in wild-type (WT) mice, there is a constitutive PKC-dependent pathway (Ps = 1.0 +/- 0.10 and 2.2 +/- 0.46 x 10(-6) cm/s in arterioles and venules, respectively), which was significantly reduced in ICAM-1 knockout (KO) mice (Ps = 0.54 +/- 0.07 and 0.77 +/- 0.11 x 10(-6) cm/s). The PKC inhibitor bisindolylmaleimid l (1 micromol/l in 0.01% DMSO) decreased P(s) in WT mice to levels similar to those in ICAM-1 KO mice. Likewise, a PKC activator (phorbol-12-myristate-acetate; 1 micromol/l in 0.01% DMSO) successfully restored Ps in ICAM-1 KO vessels to be not different from that of the WT controls. On the other hand, during TNF-alpha-induced inflammation, Ps in WT mice was significantly increased (2-fold in venules and 2.5-fold in arterioles) in a Src-dependent and PKC-independent manner. The blockade of Src (PP2; 2 micromol/l in 0.01% DMSO) but not PKC significantly reduced the TNF-alpha-dependent increase in Ps. We conclude that ICAM-1 plays an essential role in the regulation of Ps in microvessels and that there are two separate (constitutive and inducible) signaling pathways that regulate permeability under normal and inflamed conditions. PMID:18641276

Sumagin, Ronen; Lomakina, Elena; Sarelius, Ingrid H



Impact of Enzymatic Degradation of the Endothelial Glycocalyx on Vascular Permeability in an Awake Hamster Model  

PubMed Central

Background. The inside of the endothelium is covered by a glycocalyx layer, and enzymatic degradation of this layer induces vascular leakage ex vivo. We hypothesized that enzymatic degrading of the glycocalyx in an in vivo, whole body model, would induce plasma leakage and affect the microcirculation. Methods. Golden Syrian hamsters were divided into an enzyme (hyaluronidase) and a control group. Mean arterial pressure (MAP), heart rate (HR), hematocrit (Hct), base excess (BE), and plasma volume were obtained before, 45 and 120?min after enzyme/saline treatment. Plasma volume was evaluated by the distribution volume of indocyanine green and the microcirculation by functional capillary density (FCD). The enzymatic effect was determined by measuring plasma levels of hyaluronan (HA). Results. There were no differences in MAP, HR, Hct, and BE between the two groups. Enzyme treatment did not induce changes in plasma volume but reduced FCD. There was a 50–100-fold increase in plasma HA, but no relationship was found between HA levels and plasma volume or FCD. Conclusion. Vascular leakage was not confirmed in an in vivo, whole body model after degradation of the endothelial glycocalyx. The microcirculation was affected, but no relationship between plasma levels of HA and FCD was seen.

Landsverk, S. A.; Tsai, A. G.; Cabrales, P.; Intaglietta, M.



Radiation-induced changes in the profile of spinal cord serotonin, prostaglandin synthesis, and vascular permeability  

SciTech Connect

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 after 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 figs.

Siegal, T.; Pfeffer, M.R. [Hadassah Hebrew Univ. Hospital, Jerusalem (Israel)



Cross-talk between the complement and the kinin system in vascular permeability.  


The endothelium is a continuous physical barrier that regulates coagulation and selective passage of soluble molecules and circulating cells through the vessel wall into the tissue. Due to its anatomic localization, the endothelium may establish contact with components of the complement, the kinin and the coagulation systems which are the main, though not exclusive, inducers of vascular leakage. Although the complement and the kinin systems may act independently, increasing evidence suggest that there is a crosstalk that involve different components of both systems. Activation is required for the function of the two systems which are involved in pathological conditions such as hereditary and acquired angioedema (AE) and vasculitidis. The aim of this review is to discuss the contribution of complement and kinin systems to vascular leakage and the cross-talk between the two systems in the development of AE. This clinical condition is characterized by episodic and recurrent local edema of subcutaneous and submucosal tissues and is due to inherited or acquired C1-INH deficiency. Although the pathogenesis of the swelling in patients with AE was originally thought to be mediated by C2, ample evidence indicate bradykinin (BK) as the most effective mediator even though the possibility that both the complement and the kinin-forming systems may contribute to the edema has not been completely excluded. BK induces endothelial leakage interacting with B2 receptors but other molecules may be involved in the onset and maintenance of AE. In this review we shall discuss the role of B1 receptors and gC1qR/p33 in addition to that of B2 receptors in the onset of AE attacks and the importance of these receptors as new possible molecular targets for therapy. PMID:21762728

Bossi, Fleur; Peerschke, Ellinor I; Ghebrehiwet, Berhane; Tedesco, Francesco



Blood-brain barrier disruption and enhanced vascular permeability in the multiple sclerosis model EAE.  


Multiple sclerosis (MS) is a demyelinating disease characterized by the breakdown of the blood-brain barrier (BBB), and accumulation of inflammatory infiltrates in the central nervous system. Tight junctions are specialized cell-cell adhesion structures and critical components of the BBB that have previously been shown to be abnormally distributed in MS tissue. To evaluate whether experimental autoimmune encephalomyelitis (EAE) provides a suitable model for this aspect of MS disease, we examined the expression and distribution of ZO-1 over the course of disease in EAE. We observed a dramatic relocalization of ZO-1 which precedes overt clinical disease and correlates with the sites of inflammatory cell accumulation. Treatment of in vitro cultures of murine brain endothelial cells with components of EAE induction provided similar findings, with relocalization of ZO-1 and increased permeability of endothelial monolayers. BBB disruption in the EAE model appears to parallel disease progression in MS, with direct effects on the cerebrovascular endothelium, making it an ideal tool for future evaluation of tight junction breakdown and repair in MS-like pathology. PMID:20832870

Bennett, Jami; Basivireddy, Jayasree; Kollar, Anita; Biron, Kaan E; Reickmann, Peter; Jefferies, Wilfred A; McQuaid, Stephen



Measurement of canine gastric vascular permeability to plasma proteins in the normal and protein-losing states  

SciTech Connect

An isolated segment of the greater curvature of a dog's stomach was perfused at constant flow through a single cannulated artery with donor blood containing 131I-albumin, 125I-fibrinogen, and papaverine. Perfusion pressure was 30-50 mmHg, and venous pressure was set at 15 mmHg. Venous blood was collected in 1-min samples for 60 min. Filtration of fluid and loss of labeled proteins were calculated as the difference between measured arterial inflow and venous outflow. Permeability-surface area products (PS) were calculated for the proteins, and reflection coefficients (sigma) were calculated from solute flux and filtration. Intraarterial infusion of histamine (1.6-1.9 microgram . ml-1) increased filtration and PS and decreased sigma for albumin but not fibrinogen. When protein-losing was established by topical irrigation with 10 mM dithiothreitol in neutral solution, filtration and PS increased, and sigma for albumin but not fibrinogen decreased. Irrigation of the mucosa with 10 mM salicylic acid in 100 mN HCl caused bleeding that was quantitated by addition of 51Cr-erythrocytes to perfusing blood. Filtration and PS increased, and sigma for albumin but not fibrinogen decreased. Hematocrit of blood lost remained low during extensive mucosal damage. Effects of histamine infusion were attenuated or abolished by cimetidine (4 mg . kg-1 loading, 1.4 mg . kg-1 . h-1 continuous infusion) or by pyrilamine maleate (5 mg . kg-1 bolus injection at beginning of irrigation, repeated at 40-50 min). Pyrilamine attenuated or abolished effects of topical dithiothreitol or salicylic acid. We conclude that during protein loss caused by dithiothreitol or salicylic acid, histamine released within the mucosa causes increased vascular permeability for plasma proteins.

Wood, J.G.; Davenport, H.W.



Cyclosporine suppression of lymphocyte recruitment, regional blood flow, and vascular permeability at sites of allogeneic cellular interactions  

SciTech Connect

Although cyclosporine (CsA) has been thought to act primarily on the afferent phase of the immune response, we can demonstrate that it also acts at the efferent phase. The effect of CsA on lymphocyte recruitment (LR), regional blood flow (RBF), and vascular permeability (VP) was studied in paired, healed, subcutaneously placed urethane sponge grafts inoculated with specifically sensitized lymphocytes (SSLs) and allogeneic target cells. Intravenous injection of /sup 111/In-labelled unsensitized lymphocytes, /sup 86/RbCl and /sup 125/I-labelled albumin were used to assess LR, RBF, and VP, respectively. Suspensions of SSL and targets in CsA at 10 and 1 microgram/ml prior to graft inoculation markedly reduce the preferential increase in LR to the site of interaction between SSLs and targets bearing the sensitizing alloantigen (P less than 0.002 for both). Similarly, CsA blocks the preferential increase in RBF (P . 0.017) and VP (P less than 0.002) to the graft site. These effects persist for at least 24 hours. If SSLs and targets are washed after incubation with CsA, LR is still reduced. These results are consistent with the idea that cell-bound CsA blocks the elaboration of lymphokines which results from the interaction between SSLs and specific alloantigen in vivo. These lymphokines increase RBF and VP and are accompanied by an increase in LR. Inhibition of these vascular effects may prevent the recruitment of additional lymphocytes to the graft site. CsA may, therefore, prevent or interrupt allograft rejection by blocking amplification of the rejection mechanism at the graft site.

Hanto, D.W.; Harty, J.T.; Hoffman, R.; Simmons, R.L.



Isolation of a human placenta cDNA coding for a protein related to the vascular permeability factor.  

PubMed Central

A human cDNA coding for a protein related to the vascular permeability factor (VPF) was isolated from a term placenta cDNA library; we therefore named its product placenta growth factor (PlGF). PlGF is a 149-amino-acid-long protein and is highly homologous (53% identity) to the platelet-derived growth factor-like region of human VPF. Computer analyses reveal a putative signal peptide and two probable N-glycosylation sites in the PlGF protein, one of which is also conserved in human VPF. By using N-glycosidase F, tunicamycin, and specific antibodies produced in both chicken and rabbit, we demonstrate that PlGF, derived from transfected COS-1 cells, is actually N-glycosylated and secreted into the medium. In addition, PlGF, like VPF, proves to be a dimeric protein. Finally, a conditioned medium from COS-1 cells containing PlGF is capable of stimulating specifically the growth of CPA, a line of endothelial cells, in vitro. Images

Maglione, D; Guerriero, V; Viglietto, G; Delli-Bovi, P; Persico, M G



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

NASA Astrophysics Data System (ADS)

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.

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



Vascular permeability in cancer and infection as related to macromolecular drug delivery, with emphasis on the EPR effect for tumor-selective drug targeting  

PubMed Central

Tumor and inflammation have many common features. One hallmark of both is enhanced vascular permeability, which is mediated by various factors including bradykinin, nitric oxide (NO), peroxynitrite, prostaglandins etc. A unique characteristic of tumors, however, is defective vascular anatomy. The enhanced vascular permeability in tumors is also distinctive in that extravasated macromolecules are not readily cleared. We utilized the enhanced permeability and retention (EPR) effect of tumors for tumor selective delivery of macromolecular drugs. Consequently, such drugs, nanoparticles or lipid particles, when injected intravenously, selectively accumulate in tumor tissues and remain there for long periods. The EPR effect of tumor tissue is frequently inhomogeneous and the heterogeneity of the EPR effect may reduce the tumor delivery of macromolecular drugs. Therefore, we developed methods to augment the EPR effect without inducing adverse effects for instance raising the systemic blood pressure by infusing angiotensin II during arterial injection of SMANCS/Lipiodol. This method was validated in clinical setting. Further, benefits of utilization of NO-releasing agent such as nitroglycerin or angiotensin-converting enzyme (ACE) inhibitors were demonstrated. The EPR effect is thus now widely accepted as the most basic mechanism for tumor-selective targeting of macromolecular drugs, or so-called nanomedicine.

MAEDA, Hiroshi



Ozone-induced bronchial hyperresponsiveness in the rat is not accompanied by neutrophil influx or increased vascular permeability in the trachea  

SciTech Connect

We determined whether ozone-induced bronchial hyperresponsiveness in the rat is accompanied by neutrophil influx or increased vascular permeability in the trachea. Three groups of female Long-Evans rats were studied. One group was exposed to 4 ppm ozone for 2 h and studied immediately thereafter, another group was similarly exposed but was not studied until 24 h after the ozone exposure, and a third group consisted of control rats that breathed room air. Increases in total pulmonary resistance caused by acetylcholine aerosol were measured to assess bronchial responsiveness in these 3 groups. In parallel studies, neutrophil influx into the tracheal mucosa was quantified by counting cells within whole mounts of tracheas that were treated histochemically to stain the myeloperoxidase in neutrophils, and tracheal vascular permeability was quantified by measuring the amount of Evans blue dye extravasated into the trachea. In the rats studied immediately after the ozone exposure, the concentration of acetylcholine required to increase total pulmonary resistance to three-fold the baseline value was only 6% of that required in the controls. In the rats studied 24 h after the ozone exposure, this provocative acetylcholine concentration was not significantly different from that of the controls. Neither the number of neutrophils in the tracheal mucosa nor the amount of Evans blue dye extravasated into the trachea was significantly different from the corresponding control values at either time. We conclude that rats exposed to ozone develop bronchial hyperresponsiveness without detectable neutrophil influx or increased vascular permeability in the trachea.

Evans, T.W.; Brokaw, J.J.; Chung, K.F.; Nadel, J.A.; McDonald, D.M.



Upregulation of Tissue Factor by Activated Stat3 Contributes to Malignant Pleural Effusion Generation via Enhancing Tumor Metastasis and Vascular Permeability in Lung Adenocarcinoma  

PubMed Central

Malignant pleural effusion (MPE) is a poor prognostic sign for patients with lung cancer. Tissue factor (TF) is a coagulation factor that participates in angiogenesis and vascular permeability and is abundant in MPE. We previously demonstrated that autocrine IL-6-activated Stat3 contributes to tumor metastasis and upregulation of VEGF, resulting in the generation of MPE in lung adenocarcinoma. In this study, we found IL-6-triggered Stat3 activation also induces TF expression. By using pharmacologic inhibitors, it was shown that JAK2 kinase, but not Src kinase, contributed to autocrine IL-6-induced TF expression. Inhibition of Stat3 activation by dominant negative Stat3 (S3D) in lung adenocarcinoma suppressed TF-induced coagulation, anchorage-independent growth in vitro, and tumor growth in vivo. Consistently, knockdown of TF expression by siRNA resulted in a reduction of anchorage-independent growth of lung adenocarcinoma cells. Inhibition of TF expression also decreased the adhesion ability of cancer cells in normal lung tissues. In the nude mouse model, both lung metastasis and MPE generation were decreased when PC14PE6/AS2-siTF cells (TF expression was silenced) were intravenously injected. PC14PE6/AS2-siTF cells also produced less malignant ascites through inhibition of vascular permeability. In summary, we showed that TF expression plays a pivotal role in the pathogenesis of MPE generation via regulating of tumor metastasis and vascular permeability in lung adenocarcinoma bearing activated Stat3.

Yeh, Hsuan-Heng; Chang, Wen-Tsan; Lu, Kuang-Chu; Lai, Wu-Wei; Liu, Hsiao-Sheng; Su, Wu-Chou



Viral Vascular Endothelial Growth Factors Vary Extensively in Amino Acid Sequence, Receptor-binding Specificities, and the Ability to Induce Vascular Permeability yet Are Uniformly Active Mitogens  

Microsoft Academic Search

Infections of humans and ungulates by parapoxvi- ruses result in skin lesions characterized by extensive vascular changes that have been linked to viral-encoded homologues of vascular endothelial growth factor (VEGF). VEGF acts via a family of receptors (VEGFRs) to mediate endothelial cell proliferation, vascular perme- ability, and angiogenesis. The VEGF genes from inde- pendent parapoxvirus isolates show an extraordinary degree

Lyn M. Wise; Norihito Ueda; Nicola H. Dryden; Stephen B. Fleming; Carol Caesar; Sally Roufail; Marc G. Achen; Steven A. Stacker; Andrew A. Mercer



Transactivation of Vascular Endothelial Growth Factor Receptor-2 by Interleukin-8 (IL-8/CXCL8) Is Required for IL-8/CXCL8-induced Endothelial Permeability  

PubMed Central

Interleukin-8 (IL-8/CXCL8) is a chemokine that increases endothelial permeability during early stages of angiogenesis. However, the mechanisms involved in IL-8/CXCL8-induced permeability are poorly understood. Here, we show that permeability induced by this chemokine requires the activation of vascular endothelial growth factor receptor-2 (VEGFR2/fetal liver kinase 1/KDR). IL-8/CXCL8 stimulates VEGFR2 phosphorylation in a VEGF-independent manner, suggesting VEGFR2 transactivation. We investigated the possible contribution of physical interactions between VEGFR2 and the IL-8/CXCL8 receptors leading to VEGFR2 transactivation. Both IL-8 receptors interact with VEGFR2 after IL-8/CXCL8 treatment, and the time course of complex formation is comparable with that of VEGFR2 phosphorylation. Src kinases are involved upstream of receptor complex formation and VEGFR2 transactivation during IL-8/CXCL8-induced permeability. An inhibitor of Src kinases blocked IL-8/CXCL8-induced VEGFR2 phosphorylation, receptor complex formation, and endothelial permeability. Furthermore, inhibition of the VEGFR abolishes RhoA activation by IL-8/CXCL8, and gap formation, suggesting a mechanism whereby VEGFR2 transactivation mediates IL-8/CXCL8-induced permeability. This study points to VEGFR2 transactivation as an important signaling pathway used by chemokines such as IL-8/CXCL8, and it may lead to the development of new therapies that can be used in conditions involving increases in endothelial permeability or angiogenesis, particularly in pathological situations associated with both IL-8/CXCL8 and VEGF.

Petreaca, Melissa L.; Yao, Min; Liu, Yan; DeFea, Kathryn



Hypoxic retinal M?ller cells promote vascular permeability by HIF-1-dependent up-regulation of angiopoietin-like 4  

PubMed Central

Vision loss from ischemic retinopathies commonly results from the accumulation of fluid in the inner retina [macular edema (ME)]. Although the precise events that lead to the development of ME remain under debate, growing evidence supports a role for an ischemia-induced hyperpermeability state regulated, in part, by VEGF. Monthly treatment with anti-VEGF therapies is effective for the treatment of ME but results in a major improvement in vision in a minority of patients, underscoring the need to identify additional therapeutic targets. Using the oxygen-induced retinopathy mouse model for ischemic retinopathy, we provide evidence showing that hypoxic Müller cells promote vascular permeability by stabilizing hypoxia-inducible factor-1? (HIF-1?) and secreting angiogenic cytokines. Blocking HIF-1? translation with digoxin inhibits the promotion of endothelial cell permeability in vitro and retinal edema in vivo. Interestingly, Müller cells require HIF—but not VEGF—to promote vascular permeability, suggesting that other HIF-dependent factors may contribute to the development of ME. Using gene expression analysis, we identify angiopoietin-like 4 (ANGPTL4) as a cytokine up-regulated by HIF-1 in hypoxic Müller cells in vitro and the ischemic inner retina in vivo. ANGPTL4 is critical and sufficient to promote vessel permeability by hypoxic Müller cells. Immunohistochemical analysis of retinal tissue from patients with diabetic eye disease shows that HIF-1? and ANGPTL4 localize to ischemic Müller cells. Our results suggest that ANGPTL4 may play an important role in promoting vessel permeability in ischemic retinopathies and could be an important target for the treatment of ME.

Xin, Xiaoban; Rodrigues, Murilo; Umapathi, Mahaa; Kashiwabuchi, Fabiana; Ma, Tao; Babapoor-Farrokhran, Savalan; Wang, Shuang; Hu, Jiadi; Bhutto, Imran; Welsbie, Derek S.; Duh, Elia J.; Handa, James T.; Eberhart, Charles G.; Lutty, Gerard; Semenza, Gregg L.; Montaner, Silvia; Sodhi, Akrit



Relationship between Blood Stasis Syndrome Score and Cardioankle Vascular Index in Stroke Patients  

PubMed Central

Blood stasis syndrome (BSS) in traditional Asian medicine has been considered to correlate with the extent of atherosclerosis, which can be estimated using the cardioankle vascular index (CAVI). Here, the diagnostic utility of CAVI in predicting BSS was examined. The BSS scores and CAVI were measured in 140 stroke patients and evaluated with respect to stroke risk factors. Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic accuracy of CAVI for the diagnosis of BSS. The BSS scores correlated significantly with CAVI, age, and systolic blood pressure (SBP). Multiple logistic regression analysis showed that CAVI was a significant associate factor for BSS (OR 1.55, P = 0.032) after adjusting for the age and SBP. The ROC curve showed that CAVI and age provided moderate diagnostic accuracy for BSS (area under the ROC curve (AUC) for CAVI, 0.703, P < 0.001; AUC for age, 0.692, P = 0.001). The AUC of the “CAVI+Age,” which was calculated by combining CAVI with age, showed better accuracy (0.759, P < 0.0001) than those of CAVI or age. The present study suggests that the CAVI combined with age can clinically serve as an objective tool to diagnose BSS in stroke patients.

Cho, Ki-Ho; Kim, Kyoo-Pil; Woo, Byung-Cheol; Kim, Young-Jee; Park, Joo-Young; Cho, Seung-Yeon; Park, Seong-Uk; Jung, Woo-Sang; Park, Jung-Mi; Moon, Sang-Kwan



Effects of antihistamines on the lung vascular response to histamine in unanesthetized sheep. Diphenhydramine prevention of pulmonary edema and increased permeability.  

PubMed Central

To see whether antihistamines could prevent and reverse histamine-induced pulmonary edema and increased lung vascular permeability, we compared the effects of a 4-h intravenous infusion of 4 mug/kg per min histamine phosphate on pulmonary hemodynamics, lung lymph flow, lymph and plasma protein content, arterial blood gases, hematocrit, and lung water with the effects of an identical histamine infusion given during an infusion of diphenhydramine or metiamide on the same variables in unanesthetized sheep. Histamine caused lymph flow to increase from 6.0+/-0.5 to 27.0+/-5.5 (SEM) ml/h (P less than 0.05), lymph; plasma globulin concentration ratio to increase from 0.62+/-0.01 to 0.67+/-0.02 (P less than 0.05), left atrial pressure to fall from 1+/-1 to -3+/-1 cm H2O (P less than 0.05), and lung lymph clearance of eight protein fractions ranging from 36 to 96 A molecular radius to increase significantly. Histamine also caused increases in lung water, pulmonary vascular resistance, arterial PCO2, pH, and hematocrit, and decreases in cardiac output and arterial PO2. Diphenhydramine (3 mg/kg before histamine followed by 1.5 mg/kg per h intravenous infusion) completely prevented the histamine effect on hematocrit, lung lymph flow, lymph protein clearance, and lung water content, and reduced histamine effects on arterial blood gases and pH. 6 mg/kg diphenhydramine given at the peak histamine response caused lymph flow and lymph: plasma protein concentration ratios to fall. Metiamide (10 mg/kg per h) did not affect the histamine lymph response. We conclude that diphenhydramine can prevent histamine-induced pulmonary edema and can prevent and reverse increased lung vascular permeability caused by histamine, and that histamine effects on lung vascular permeability are H1 actions.

Brigham, K L; Bowers, R E; Owen, P J



Protective Effects of Fresh Frozen Plasma on Vascular Endothelial Permeability, Coagulation, and Resuscitation After Hemorrhagic Shock Are Time Dependent and Diminish Between Days 0 and 5 After Thaw  

PubMed Central

Background Clinical studies have shown that resuscitation with fresh frozen plasma (FFP) is associated with improved outcome after severe hemorrhagic shock (HS). We hypothesized that in addition to its effects on hemostasis, FFP has protective and stabilizing effects on the endothelium that translate into diminished endothelial cell (EC) permeability and improved resuscitation in vivo after HS. We further hypothesized that the beneficial effects of FFP would diminish over 5 days of routine storage at 4°C. Methods EC permeability was induced by hypoxia and assessed by the passage of 70-kDa Dextran between monolayers. Thrombin generation time and coagulation factor levels or activity were assessed in FFP. An in vivo rat model of HS and resuscitation was used to determine the effects of FFP on hemodynamic stability. Results Thawed FFP inhibits EC permeability in vitro by 10.2-fold. Protective effects diminish (to 2.5-fold) by day 5. Thrombin generation time is increased in plasma that has been stored between days 0 and 5. In vivo data show that day 0 FFP is superior to day 5 FFP in maintaining mean arterial pressure in rats undergoing HS with resuscitation. Conclusion Both in vitro and in vivo studies show that FFP has beneficial effects on endothelial permeability, vascular stability, and resuscitation in rats after HS. The benefits are independent of hemostasis and diminish between days 0 and 5 of storage.

Pati, Shibani; Matijevic, Nena; Doursout, Marie-Francoise; Ko, Tien; Cao, Yanna; Deng, Xiyun; Kozar, Rosemary A.; Hartwell, Elizabeth; Conyers, Jodie; Holcomb, John B.



Doppler resistive index to reflect regulation of renal vascular tone during sepsis and acute kidney injury.  


ABSTRACT: INTRODUCTION: Renal resistive index (RI), determined by Doppler ultrasonography, directly reveals and quantifies modifications in renal vascular resistance. The aim of this study was to evaluate if mean arterial pressure (MAP) is determinant of renal RI in septic, critically ill patients suffering or not from acute kidney injury (AKI). METHODS: This prospective observational study included 96 patients. AKI was defined according to RIFLE criteria and transient or persistent AKI according to renal recovery within 3 days. RESULTS: Median renal RIs were 0.72 (0.68-0.75) in patients without AKI and 0.76 (0.72-0.80) in patients with AKI (P=0.001). RIs were 0.75 (0.72-0.79) in transient AKI and 0.77 (0.70-0.80) in persistent AKI (P=0.84). RI did not differ in patients given norepinephrine infusion and was not correlated with norepinephrine dose. RI was correlated with MAP (?= -0.47; P=0.002), PaO2/FiO2 ratio (?= -0.33; P=0.04) and age (?=0.35; P=0.015) only in patients without AKI. CONCLUSIONS: A poor correlation between renal RI and MAP, age, or PaO2/FiO2 ratio was found in septic and critically ill patients without AKI compared to patients with AKI. These findings suggest that determinants of RI are multiple. Renal circulatory response to sepsis estimated by Doppler ultrasonography cannot reliably be predicted simply from changes in systemic hemodynamics. As many factors influence its value, the interest in a single RI measurement at ICU admission to determine optimal MAP remains uncertain. PMID:22971333

Dewitte, Antoine; Coquin, Julien; Meyssignac, Bertrand; Joannès-Boyau, Olivier; Fleureau, Catherine; Roze, Hadrien; Ripoche, Jean; Janvier, Gérard; Combe, Christian; Ouattara, Alexandre



Doppler resistive index to reflect regulation of renal vascular tone during sepsis and acute kidney injury  

PubMed Central

Introduction Renal resistive index (RI), determined by Doppler ultrasonography, directly reveals and quantifies modifications in renal vascular resistance. The aim of this study was to evaluate if mean arterial pressure (MAP) is determinant of renal RI in septic, critically ill patients suffering or not from acute kidney injury (AKI). Methods This prospective observational study included 96 patients. AKI was defined according to RIFLE criteria and transient or persistent AKI according to renal recovery within 3 days. Results Median renal RIs were 0.72 (0.68-0.75) in patients without AKI and 0.76 (0.72-0.80) in patients with AKI (P=0.001). RIs were 0.75 (0.72-0.79) in transient AKI and 0.77 (0.70-0.80) in persistent AKI (P=0.84). RI did not differ in patients given norepinephrine infusion and was not correlated with norepinephrine dose. RI was correlated with MAP (?= -0.47; P=0.002), PaO2/FiO2 ratio (?= -0.33; P=0.04) and age (?=0.35; P=0.015) only in patients without AKI. Conclusions A poor correlation between renal RI and MAP, age, or PaO2/FiO2 ratio was found in septic and critically ill patients without AKI compared to patients with AKI. These findings suggest that determinants of RI are multiple. Renal circulatory response to sepsis estimated by Doppler ultrasonography cannot reliably be predicted simply from changes in systemic hemodynamics. As many factors influence its value, the interest in a single RI measurement at ICU admission to determine optimal MAP remains uncertain.



Bevacizumab-Induced Alterations in Vascular Permeability and Drug Delivery: A Novel Approach to Augment Regional Chemotherapy for In-Transit Melanoma  

PubMed Central

Purpose To investigate whether the systemically administered anti-VEGF monoclonal antibody bevacizumab could improve regional chemotherapy treatment of advanced extremity melanoma by enhancing delivery and tumor uptake of regionally infused melphalan (LPAM). Experimental Design After treatment with systemic bevacizumab or saline, changes in vascular permeability were determined by spectrophotometric analysis of tumors infused with Evan’s blue dye. Changes in vascular structure and tumor hemoglobin-oxygen saturation HbO2 were determined by intravital microscopy and diffuse reflectance spectroscopy, respectively. Rats bearing the low-VEGF secreting DM738 and the high-VEGF secreting DM443 melanoma xenografts underwent isolated limb infusion (ILI) with melphalan (LPAM) or saline via the femoral vessels. The effect of bevacizumab on terminal drug delivery was determined by immunohistochemical analysis of LPAM-DNA adducts in tumor tissues. Results Single-dose bevacizumab given three days before ILI with LPAM significantly decreased vascular permeability (50.3% in DM443, P < 0.01 and 35% in DM738, P < 0.01) and interstitial fluid pressure (57% in DM443, P < 0.01 and 50% in DM738, P = 0.01). HbO2 decreased from baseline in mice following treatment with bevacizumab. Systemic bevacizumab significantly enhanced tumor response to ILI with LPAM in two melanoma xenografts, DM443 and DM738, increasing quadrupling time 37% and 113%, respectively (P = 0.03). Immunohistochemical analyses of tumor specimens showed that pretreatment with systemic bevacizumab markedly increased LPAM-DNA adduct formation. Conclusions Systemic treatment with bevacizumab before regional chemotherapy increases delivery of LPAM to tumor cells and represents a novel way to augment response to regional therapy for advanced extremity melanoma.

Turley, Ryan S.; Fontanella, Andrew N.; Padussis, James C.; Toshimitsu, Hiroaki; Tokuhisa, Yoshihiro; Cho, Eugenia H.; Hanna, Gabi; Beasley, Georgia M.; Augustine, Christina K.; Dewhirst, Mark W.; Tyler, Douglas S.



A new revised cardiac risk index incorporating fragmented QRS complex as a prognostic marker in patients undergoing noncardiac vascular surgery.  


The aim of this study was to investigate the value of a new Revised Cardiac Risk Index (RCRI) that includes consideration of QRS fragmentation (fQRS) as a predictor of cardiac events in patients undergoing noncardiac vascular surgery. Four hundred sixty-seven consecutive patients admitted for noncardiac vascular surgery were studied. Patients were allocated to RCRI 0, 1, 2, or ?3 groups according to the sum of diabetes, renal insufficiency, and histories of ischemic heart disease, congestive heart failure, and cerebrovascular disease. They were then reallocated to fragmented RCRI (fRCRI) 0, 1, 2, or ?3 groups after including a score of 1 or 0 corresponding to the presence or absence of fQRS. A major adverse cardiac event (MACE) was defined as a composite of death, myocardial infarction, congestive heart failure, and percutaneous coronary intervention before noncardiac vascular surgery. During index hospitalization, MACE developed in 38 patients (8.1%). fQRS was present in 169 (36.2%), and it was significantly greater in patients with MACE than in those without MACE (63.2% vs 34.3%, p <0.001). The proportions of RCRI 0, 1, 2, and ?3 were 46.9% (n = 219), 35.3% (n = 165), 12.4% (n = 58), and 5.4% (n = 25), respectively. When fRCRI data were included, 28 patients (48.3%) in RCRI 2 were reclassified as fRCRI ?3. By multivariate logistic regression analysis, fRCRI (odds ratio 1.529, 95% confidence interval 1.035 to 2.258, p = 0.033) and a left ventricular ejection fraction <50% independently predicted in-hospital MACE. In conclusion, fRCRI is an independent predictor of in-hospital MACE in patients undergoing noncardiac vascular surgery. PMID:23768543

Bae, Myung Hwan; Jang, Se Yong; Choi, Won Suk; Kim, Kyun Hee; Park, Sun Hee; Lee, Jang Hoon; Kim, Hyung Kee; Yang, Dong Heon; Huh, Seung; Park, Hun Sik; Cho, Yongkeun; Chae, Shung Chull



Association of cardio-ankle vascular index with physical fitness and cognitive symptoms in aging Finnish firefighters  

Microsoft Academic Search

Purpose  Monitoring cardiovascular risk factors is important in health promotion among firefighters. The assessment of arterial stiffness\\u000a (AS) may help to detect early signs of atherosclerosis. The aim of this study was to analyze associations between aerobic\\u000a fitness, cognitive symptoms and cardio-ankle vascular index (CAVI) as a measure for AS among Finnish firefighters.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  The data are one part of a large

H. Lindholm; A. Punakallio; S. Lusa; M. Sainio; E. Ponocny; R. Winker


Evaluation of Blood Pressure Control using a New Arterial Stiffness Parameter, Cardio-ankle Vascular Index (CAVI)  

PubMed Central

Arterial stiffness has been known to be a surrogate marker of arteriosclerosis, and also of vascular function. Pulse wave velocity (PWV) had been the most popular index and was known to be a predictor of cardiovascular events. But, it depends on blood pressure at measuring time. To overcome this problem, cardio-ankle vascular index (CAVI) is developed. CAVI is derived from stiffness parameter ? by Hayashi, and the equation of Bramwell-Hill, and is independent from blood pressure at a measuring time. Then, CAVI might reflect the proper change of arterial wall by antihypertensive agents. CAVI shows high value with aging and in many arteriosclerotic diseases and is also high in persons with main coronary risk factors. Furthermore, CAVI is decreased by an administration of ?1 blocker, doxazosin for 2-4 hours, Those results suggested that CAVI reflected the arterial stiffness composed of organic components and of smooth muscle cell contracture. Angiotensin II receptor blocker, olmesartan decreased CAVI much more than that of calcium channel antagonist, amlodipine, even though the rates of decreased blood pressure were almost same. CAVI might differentiate the blood pressure-lowering agents from the point of the effects on proper arterial stiffness. This paper reviewed the principle and rationale of CAVI, and the possibilities of clinical applications, especially in the studies of hypertension.

Shirai, Kohji; Utino, Junji; Saiki, Atsuhito; Endo, Kei; Ohira, Masahiro; Nagayama, Daiji; Tatsuno, Ichiro; Shimizu, Kazuhiro; Takahashi, Mao; Takahara, Akira



Reduced Retinal Neovascularization, Vascular Permeability, and Apoptosis in Ischemic Retinopathy in the Absence of Prolyl Hydroxylase-1 Due to the Prevention of Hyperoxia-Induced Vascular Obliteration  

PubMed Central

Purpose. Prolyl hydroxylases (PHDs) are oxygen sensors that stabilize hypoxia-inducible factors (HIFs) to induce proinflammatory, vasopermeability, and proapoptotic factors. These may be potential targets to reduce the complications of ischemic retinopathies. Methods. Oxygen-induced ischemic retinopathy (OIR) was generated as a model for retinopathy of prematurity (ROP) by placing 7-day-old mice in 75% oxygen for 5 days and returning them to the relative hypoxia of room air for 5 days. Neovascularization (NV) and avascular areas were assessed on retinal flat-mounts by image analysis. Blood-retinal barrier breakdown was assessed using 3H-mannitol as a tracer. Apoptosis was detected with TUNEL staining. HIF-1? and VEGF were quantified using Western blot analysis and ELISA. Results. PHD1-deficient mice demonstrated reduced hyperoxia-associated vascular obliteration during oxygen-induced ischemic retinopathy. This was associated with subsequent reduced avascularity, vascular leakage, and pathologic NV during the hypoxic phase, which could be accounted for by a reduced expression of HIF-1? and VEGF. Apoptosis in the retina was also reduced in PHD1-depleted mice after 2 days in hyperoxia. Conclusions. PHD1 deficiency is associated with a reduction of ischemia-induced retinal NV. The regulatory mechanism in this model appears to be: PHD1 depletion prevents HIF-1? degradation in hyperoxia, which induces VEGF, thus preventing hyperoxia-related vessel loss. Without a vessel deficiency, there would not be relative hypoxia when the mice are returned to room air and there would be no need to initiate angiogenesis signaling. Blocking PHD1 may be beneficial for ischemic retinopathies and inflammatory and neurodegenerative disorders.

Huang, Hu; Van de Veire, Sara; Dalal, Mansi; Parlier, Rachel; Semba, Richard D.; Carmeliet, Peter



Novel compliant and tissue-permeable microporous polyurethane vascular prosthesis fabricated using an excimer laser ablation technique.  


A small-diameter vascular prosthesis with a multiply pored structure could have great potential to elevate the patency rate, for the following two reasons: 1) increased flexibility of the graft may increase compliance matching, consequently minimizing intimal hyperplasia; and 2) enhanced transmural tissue ingrowth may accelerate endothelialization. In this study, we fabricated a polyurethane (PU)-based artificial graft with well-controlled micropores in terms of their diameter and distribution, which was achieved using a computer-aided excimer laser (KrF) ablation technique. Three types of microporous PU tubes (2 mm in internal diameter, 100 microns in wall thickness) were designed: pore size (100 microns) and longitudinal pore-to-pore distance (200 microns) were constant, and circumferential pore-to-pore intervals were 60 degrees (type 1), 30 degrees (type 2), and 15 degrees (type 3). The fabricated prostheses were coated with photoreactive gelatin, which was photogelled and chemically fixed on PU surfaces upon ultraviolet light irradiation. Scanning electron microscopy showed that pore size and arrangement were precisely controlled as designed, and that a gelatinous hydrogel layer was formed over the entire luminal surface. The stiffness parameter (beta), inversely related to compliance, was determined from the change in external diameter against intraluminal pressure. An increase in the number of pores around the circumference decreased the beta value. The type 3 graft, the stiffness parameter of which was very close to that of human coronary artery, was the most compliant among the three types. The combination of excimer laser-directed microporing and photochemical surface processing techniques enabled the development of a novel compliant small-caliber vascular prosthesis, which is expected to show enhanced transmural tissue in growth in vivo. PMID:8731146

Doi, K; Nakayama, Y; Matsuda, T



Novel Application of a Multiscale Entropy Index as a Sensitive Tool for Detecting Subtle Vascular Abnormalities in the Aged and Diabetic  

PubMed Central

Although previous studies have shown the successful use of pressure-induced reactive hyperemia as a tool for the assessment of endothelial function, its sensitivity remains questionable. This study aims to investigate the feasibility and sensitivity of a novel multiscale entropy index (MEI) in detecting subtle vascular abnormalities in healthy and diabetic subjects. Basic anthropometric and hemodynamic parameters, serum lipid profiles, and glycosylated hemoglobin levels were recorded. Arterial pulse wave signals were acquired from the wrist with an air pressure sensing system (APSS), followed by MEI and dilatation index (DI) analyses. MEI succeeded in detecting significant differences among the four groups of subjects: healthy young individuals, healthy middle-aged or elderly individuals, well-controlled diabetic individuals, and poorly controlled diabetic individuals. A reduction in multiscale entropy reflected age- and diabetes-related vascular changes and may serve as a more sensitive indicator of subtle vascular abnormalities compared with DI in the setting of diabetes.

Wu, Hsien-Tsai; Lo, Men-Tzung; Chen, Guan-Hong; Sun, Cheuk-Kwan; Chen, Jian-Jung



Blood pressure-independent effect of candesartan on cardio-ankle vascular index in hypertensive patients with metabolic syndrome  

PubMed Central

Angiotensin receptor blockers (ARBs) are known to reduce the cardiovascular risk in hypertensive patients. This study was designed to examine the effect of an ARB candesartan on subclinical atherosclerosis assessed by cardio-ankle vascular index (CAVI) in comparison with calcium channel blockers (CCBs) alone in hypertensive patients with metabolic syndrome (MetS). A total of 53 consecutive hypertensive patients with MetS were randomly assigned to the candesartan group, in which candesartan was added on, or the CCBs group, in which CCBs were added on. Clinical and biological parameters were obtained before and after the 12-month treatment period. The primary measure of efficacy was the %change in CAVI. When treated with candesartan, but not CCBs, CAVI significantly decreased from 8.7 to 7.7 by 11%. Blood pressure (BP) significantly decreased with both treatments, but the differences between groups were not significant. The changes in other parameters remained unchanged in both the groups. Analysis of covariance found that both the BP reduction and the therapy difference contributed to the decrease in CAVI, but the BP reduction was not involved in the decrease in CAVI caused by the difference in the therapy. Candesartan may be a better antihypertensive drug than CCBs to improve subclinical atherosclerosis of patients with MetS.

Bokuda, Kanako; Ichihara, Atsuhiro; Sakoda, Mariyo; Mito, Asako; Kinouchi, Kenichiro; Itoh, Hiroshi



Diabetes-induced increases in vascular permeability and changes in granulation tissue levels of sorbitol, myo-inositol, chiro-inositol, and scyllo-inositol are prevented by sorbinil.  


In a recently developed animal model, we investigated the pathogenesis of diabetic vascular disease and demonstrated that 125I-albumin permeation is markedly increased in new "granulation tissue" vessels formed in subcutaneous tissue after the onset of diabetes. The studies described in this report were undertaken to examine the effects of an aldose reductase inhibitor on diabetes-induced increases in vascular permeability in this animal model. 125I-albumin permeation was assessed 3 weeks after the subcutaneous implantation of sterile preweighed polyester fabric (to stimulate angiogenesis) in diabetic male Sprague-Dawley rats, in controls, and in diabetic rats given sorbinil approximately 12 or approximately 25 mg/kg/d mixed in ground rat chow. Sorbinil administration prevented the diabetes-induced increase in vascular permeability by approximately 60% at the lower dose and by approximately 80% at the higher dose without affecting body weight or plasma glucose levels. Diabetes-induced changes in tissue levels of sorbitol, myo-inositol, scyllo-inositol, and chiro-inositol were also prevented by the high dose of sorbinil (data were not obtained for the lower dose). These observations are consistent with evidence linking diabetic cataracts and neuropathy to imbalances in sorbitol/inositol metabolism and support the hypothesis that diabetic vascular disease as well as neuropathy and cataracts are mediated by excess metabolism of glucose through the polyol pathway. Furthermore, these observations suggest that increased vascular permeability associated with diabetic microangiopathy in humans may be prevented by inhibitors of aldose reductase without the need to normalize blood glucose levels. PMID:3959907

Williamson, J R; Chang, K; Rowold, E; Marvel, J; Tomlinson, M; Sherman, W R; Ackermann, K E; Kilo, C



Structure-Function Studies Using Deletion Mutants Identify Domains of gC1qR/p33 as Potential Therapeutic Targets for Vascular Permeability and Inflammation  

PubMed Central

The endothelial cell receptor complex for kininogen (HK) comprises gC1qR, cytokeratin 1, and urokinase-type plasminogen activator receptor and is essential for activation of the kinin system that leads to bradykinin (BK) generation. Of these, gC1qR/p33 constitutes a high affinity site for HK – the BK precursor – and is therefore critical for the assembly of the kinin-generating cascade. Previous studies have identified a putative HK site within the C-terminal domain (residues 204–218) of gC1qR recognized by mAb 74.5.2. In these studies, we used information from the crystal structure of gC1qR, to engineer several deletion (?) mutants and test their ability to bind and/or support BK generation. While deletion of residues 204–218 (gC1qR?204–218), showed significantly reduced binding to HK, BK generation was not affected when tested by a sensitive bradykinin immunoassay. In fact, all of the gC1qR deletion mutants supported BK generation with the exception of gC1qR?154–162 and a point mutation in which Trp 233 was substituted with Gly. Binding studies also identified the existence of two additional sites at residues 144–162 and 190–202. Moreover, binding of HK to a synthetic peptide 190–202 was inhibited by mAbs 48 and 83, but not by mAb 74.5.2. Since a single residue separates domains 190–202 and 204–218, they may be part of a highly stable HK binding pocket and therefore a potential target for drug design to prevent vascular permeability and inflammation.

Ghebrehiwet, Berhane; Jesty, Jolyon; Xu, Sulan; Vinayagasundaram, Rama; Vinayagasundaram, Uma; Ji, Yan; Valentino, Alisa; Hosszu, Kinga K.; Mathew, Sally; Joseph, Kusumam; Kaplan, Allen P.; Peerschke, Ellinor I. B.



Vascular complications and changes in body mass index in Japanese type 2 diabetic patients with abdominal obesity  

PubMed Central

Background Although many Asian type 2 diabetic patients have been considered to be not obese and have low capacity of insulin secretion, the proportion of obese patients with visceral fat accumulation has increased in recent years. We found previously considerable number of Japanese non-obese subjects (body mass index (BMI) vascular complications and changes in BMI. Methods We enrolled 88 Japanese hospitalized type 2 diabetic patients. Abdominal obesity represented waist circumference (WC) of ?85 cm for males and ?90 cm for females (corresponding to visceral fat area of 100 cm2). Subjects were divided into two groups; with or without abdominal obesity. Results Hypertension, dyslipidemia and cardiovascular diseases were significantly more in the patients with abdominal obesity. The prevalence of cardiovascular disease in the non-obese patients (BMI



Vascularity Index of Laryngeal Cancer Derived from 3-D Ultrasound: A Predicting Factor for the in vivo Assessment of Cervical Lymph Node Status  

Microsoft Academic Search

To demonstrate whether a calculated vascularity index (VI) can predict metastases of cervical lymph nodes, the VI values of the primary tumors were obtained by using 3-D sonography in 87 subjects with laryngeal cancer confirmed by laryngoscope and biopsy. N-staging of the subjects was determined by pathological nodal harvesting. The relationship between the VI and pathological N-staging was evaluated by

Jun Zhou; Shang-Yong Zhu; Ruo-Chuan Liu; Feng Luo; De-Xi Shu



Establishing baseline criteria of cardio-ankle vascular index as a new indicator of arteriosclerosis: a cross-sectional study  

PubMed Central

Background A cardio-ankle vascular index (CAVI) has been developed to represent the extent of arteriosclerosis throughout the aorta, femoral artery and tibial artery independent of blood pressure. To practically use CAVI as a diagnostic tool for determining the extent of arteriosclerosis, our study objectives were (1) to establish the baseline CAVI scores by age and gender among cardiovascular disease (CVD) risk-free persons, (2) to compare CAVI scores between genders to test the hypothesis that the extent of arteriosclerosis in men is greater than in women, and (3) to compare CAVI scores between the CVD risk-free group and the CVD high-risk group in order to test the hypothesis that the extent of arteriosclerosis in the CVD high-risk group is greater than in the CVD risk-free group. Methods Study subjects were 32,627 urban residents 20-74 years of age who participated in CVD screening in Japan during 2004-2006. A new device (model VaSera VS-1000) was used to measure CAVI scores. At the time of screening, CVD high-risk persons were defined as those having any clinical abnormalities of CVD, and CVD risk-free persons were defined as those without any clinical abnormalities of CVD. Age-specific average CAVI scores were compared between genders and between the CVD risk-free group and the CVD high-risk group. Student's t-test using two independent samples was applied to a comparison of means between two groups. Results Average age-specific baseline scores of CAVI in the CVD risk-free group linearly increased in both genders as their age increased. Average age-specific baseline scores of CAVI in the CVD risk-free group were significantly greater among men than among women. Average age-specific baseline scores of CAVI in the CVD risk-free group were significantly smaller than those in the CVD high-risk group in both genders after 40 years of age. Conclusions The baseline CAVI scores from the CVD risk-free group are useful for future studies as control values. The CAVI method is a useful tool to screen persons with moderate to advanced levels of arteriosclerosis.



Induction of Vascular Permeability: betaPIX and GIT1 Scaffold the Activation of Extracellular Signal-regulated Kinase by PAK  

Microsoft Academic Search

Increased permeability of blood vessels is an important component of inflammation, but in some circumstances it contributes to tissue injury and organ failure. Previous work showed that p21-activated kinase (PAK) is a critical regulator of endothelial cell- cell junctions through effects on myosin light chain phosphorylation and cell contractility. We now show that blocking PAK function inhibits fluid leak in

Rebecca Stockton; Jorg Reutershan; David Scott; John Sanders; Klaus Ley; Martin Alexander Schwartz



Recombinant Human Serum Albumin Dimer has High Blood Circulation Activity and Low Vascular Permeability in Comparison with Native Human Serum Albumin  

Microsoft Academic Search

\\u000a Purpose  Human serum albumin (HSA) is used clinically as an important plasma expander. Albumin infusion is not recommended for critically\\u000a ill patients with hypovolemia, burns, or hypoalbuminemia because of the increased leakage of albumin into the extravascular\\u000a spaces, thereby worsening edema. In the present study, we attempted to overcome this problem by producing a recombinant HSA\\u000a (rHSA) dimer with decreased vascular

Sadaharu Matsushita; Victor Tuan Giam Chuang; Masanori Kanazawa; Sumio Tanase; Keiichi Kawai; Toru Maruyama; Ayaka Suenaga; Masaki Otagiri



The Vesiculo-Vacuolar Organelle (VVO): A New Endothelial Cell Permeability Organelle  

Microsoft Academic Search

SUMMARY A newly defined endothelial cell permeability structure, termed the vesiculo- vacuolar organelle (VVO), has been identified in the microvasculature that accompanies tu- mors, in venules associated with allergic inflammation, and in the endothelia of normal venules. This organelle provides the major route of extravasation of macromolecules at sites of increased vascular permeability induced by vascular permeability factor\\/vascular en- dothelial

Ann M. Dvorak; Dian Feng



Changes of blood flow, oxygen tension, action potential and vascular permeability induced by arterial ischemia or venous congestion on the spinal cord in canine model.  


It is generally considered that the genesis of myelopathy associated with the degenerative conditions of the spine may result from both mechanical compression and circulatory disturbance. Many references about spinal cord tissue ischemic damage can be found in the literature, but not detailed studies about spinal cord microvasculature damage related to congestion or blood permeability. This study investigates the effect of ischemia and congestion on the spinal cord using an in vivo model. The aorta was clamped as an ischemia model of the spinal cord and the inferior vena cava was clamped as a congestion model at the 6th costal level for 30?min using forceps transpleurally. Measurements of blood flow, partial oxygen pressure, and conduction velocity in the spinal cord were repeated over a period of 1?h after release of clamping. Finally, we examined the status of blood-spinal cord barrier under fluorescence and transmission electron microscope. Immediately after clamping of the inferior vena cava, the central venous pressure increased by about four times. Blood flow, oxygen tension and action potential were more severely affected by the aorta clamping; but this ischemic model did not show any changes of blood permeability in the spinal cord. The intramedullar edema was more easily produced by venous congestion than by arterial ischemia. In conclusions, venous congestion may be a preceding and essential factor of circulatory disturbance in the compressed spinal cord inducing myelopathy. PMID:22912247

Kobayashi, Shigeru; Yoshizawa, Hidezo; Shimada, Seiichiro; Guerrero, Alexander Rodríguez; Miyachi, Masaya



Hyperemia-Related Changes in Arterial Stiffness: Comparison between Pulse Wave Velocity and Stiffness Index in the Vascular Reactivity Assessment.  


Carotid-to-radial pulse wave velocity (PWV(cr)) has been proposed to evaluate endothelial function. However, the measurement of PWV(cr) is not without limitations. A new simple approach could have wide application. Stiffness index (SI) is obtained by analysis of the peripheral pulse wave and gives reproducible information about stiffness of large arteries. This study assessed the effects of hyperemia on SI and compared it with PWV(cr) in 14 healthy subjects. Both were measured at rest and during 8 minutes after ischemia. SI temporal course was determined. At 1 minute, SI and PWV(cr) decreased (5.58 ± 0.24 to 5.34 ± 0.23?m/s, P < 0.05; 7.8 ± 1.0 to 7.2 ± 0.9?m/s; P < 0.05, resp.). SI was positively related to PWV(cr) in baseline (r = 0.62 , P < 0.05), at 1 minute (r = 0.79, P < 0.05), and during the whole experimental session (r = 0.52, P < 0.05). Conclusion. Hyperemia significantly decreases SI in healthy subjects. SI was related to PWV(cr) and could be used to facilitate the evaluation of hyperemia-related changes in arterial stiffness. PMID:22919496

Torrado, Juan; Bia, Daniel; Zócalo, Yanina; Farro, Ignacio; Farro, Federico; Armentano, Ricardo L



Hyperemia-Related Changes in Arterial Stiffness: Comparison between Pulse Wave Velocity and Stiffness Index in the Vascular Reactivity Assessment  

PubMed Central

Carotid-to-radial pulse wave velocity (PWVcr) has been proposed to evaluate endothelial function. However, the measurement of PWVcr is not without limitations. A new simple approach could have wide application. Stiffness index (SI) is obtained by analysis of the peripheral pulse wave and gives reproducible information about stiffness of large arteries. This study assessed the effects of hyperemia on SI and compared it with PWVcr in 14 healthy subjects. Both were measured at rest and during 8 minutes after ischemia. SI temporal course was determined. At 1 minute, SI and PWVcr decreased (5.58 ± 0.24 to 5.34 ± 0.23?m/s, P < 0.05; 7.8 ± 1.0 to 7.2 ± 0.9?m/s; P < 0.05, resp.). SI was positively related to PWVcr in baseline (r = 0.62 , P < 0.05), at 1 minute (r = 0.79, P < 0.05), and during the whole experimental session (r = 0.52, P < 0.05). Conclusion. Hyperemia significantly decreases SI in healthy subjects. SI was related to PWVcr and could be used to facilitate the evaluation of hyperemia-related changes in arterial stiffness.

Torrado, Juan; Bia, Daniel; Zocalo, Yanina; Farro, Ignacio; Farro, Federico; Armentano, Ricardo L.



Intestinal permeability.  

PubMed Central

Damage to the mucosal barrier may be assessed, non-invasively by use of sugar probes, which permeate through the transcellular or paracellular (tight junction) routes. A standardised test, with analysis of a five hour urine collection has proved useful in studying the sequelae of non-steroid anti-inflammatory drug (NSAID) administration, untreated coeliac disease, and enteric infections. Choice of probe molecule is crucial and lactulose/l-rhamnose seem to be satisfactory, in contrast with polyethylene glycol. Significant correlations have been seen between permeability and plasma IgA concentrates in nephropathy, and between permeability and the passage of neutrophil chemotactic agents. The increased permeability associated with NSAID treatment may relate to the adverse effects of NSAIDs on enterocyte mitochondrial morphology and metabolism. These two factors may predispose the mucosa to permeation of bacterial chemoattractant molecules that elaborate a local inflammatory response. A similar mechanism may operate in patients with untreated Crohn's disease, who show abnormally high permeability. Remission induced by treatment with elemental diets coincides with a reduction in permeability. The period to relapse correlated with the inability of patients to maintain low permeability to sugar probes. These results suggest a mechanism for the benefits of elemental enteral nutrients in the treatment of Crohn's disease.

Bjarnason, I



Diosmin Alleviates Retinal Edema by Protecting the Blood-Retinal Barrier and Reducing Retinal Vascular Permeability during Ischemia/Reperfusion Injury  

PubMed Central

Background and Purpose Retinal swelling, leading to irreversible visual impairment, is an important early complication in retinal ischemia/reperfusion (I/R) injury. Diosmin, a naturally occurring flavonoid glycoside, has been shown to have antioxidative and anti-inflammatory effects against I/R injury. The present study was performed to evaluate the retinal microvascular protective effect of diosmin in a model of I/R injury. Methods Unilateral retinal I/R was induced by increasing intraocular pressure to 110 mm Hg for 60 min followed by reperfusion. Diosmin (100 mg/kg) or vehicle solution was administered intragastrically 30 min before the onset of ischemia and then daily after I/R injury until the animals were sacrificed. Rats were evaluated for retinal functional injury by electroretinogram (ERG) just before sacrifice. Retinas were harvested for HE staining, immunohistochemistry assay, ELISA, and western blotting analysis. Evans blue (EB) extravasation was determined to assess blood–retinal barrier (BRB) disruption and the structure of tight junctions (TJ) was examined by transmission electron microscopy. Results Diosmin significantly ameliorated the reduction of b-wave, a-wave, and b/a ratio in ERG, alleviated retinal edema, protected the TJ structure, and reduced EB extravasation. All of these effects of diosmin were associated with increased zonular occluden-1 (ZO-1) and occludin protein expression and decreased VEGF/PEDF ratio. Conclusions Maintenance of TJ integrity and reduced permeability of capillaries as well as improvements in retinal edema were observed with diosmin treatment, which may contribute to preservation of retinal function. This protective effect of diosmin may be at least partly attributed to its ability to regulate the VEGF/PEDF ratio.

Tong, Nianting; Zhang, Zhenzhen; Zhang, Wei; Qiu, Yating; Gong, Yuanyuan; Yin, Lili; Qiu, Qinghua; Wu, Xingwei



Comparison of Two Methods for Calculating the Mean Vascularization Index of Ovarian Stroma on the Basis of Spatio-temporal Image Correlation High-Definition Flow Technology.  


The aim of our study was to determine the agreement between two different methods for calculating the mean vascularization index (VI) of ovarian stroma using spatio-temporal image correlation-high definition flow (STIC-HDF) technology. Stored 4-D STIC-HDF volume data for ovaries of 34 premenopausal women were assessed retrospectively. We calculated the mean VI from the VI values derived for each 3-D volume within the STIC sequence. Then, the examiner subjectively selected the two volumes with the highest and lowest color signals, respectively. We averaged these two values. Agreement between VI measurements was estimated by calculating intra-class correlation coefficients. The intra-class correlation coefficient for the VI was 0.999 (95% confidence interval: 0.999-1.000). The mean time needed to calculate the mean VI using the entire 4-D STIC sequence was significantly longer than the mean time needed to calculate the average value from the volumes with the highest and lowest color signals determined by the operator (p < 0001). We conclude that there is significant agreement between the two methods. Calculating the average VI from the highest and lowest values is less time consuming than calculating the mean VI from the complete STIC sequence. PMID:23969164

Kudla, Marek J; Kandzia, Tomasz; Alcázar, Juan Luis



Lipid uptake in expanded polytetrafluoroethylene vascular grafts  

Microsoft Academic Search

Purpose: The mechanisms of vascular prosthesis failure are reported to be associated, in part, with an atherosclerotic degenerative process that is related to an abnormal lipid infiltration. The lipid uptake in expanded polytetrafluoroethylene (ePTFE) vascular grafts was reproduced in vitro, and the effect of time on the permeability of these prostheses was studied. Methods: Water permeability tests were carried out

Patrick Vermette; Jules Thibault; Gaétan Laroche



Neutrophils, nitric oxide, and microvascular permeability in severe sepsis  

Technology Transfer Automated Retrieval System (TEKTRAN)

STUDY OBJECTIVES: Alterations in microvascular permeability are prevalent in patients with sepsis; a recent study reported that patients with septic shock had increased capillary filtration coefficient (Kf), a noninvasive index of microvascular permeability. We aimed to determine whether patients wi...


3'-Deoxy-3'-[(18)F]-fluorothymidine ([(18)F]-FLT) transport in newly diagnosed glioma: correlation with nucleoside transporter expression, vascularization, and blood-brain barrier permeability.  


3'-Deoxy-3'-[(18)F]-fluorothymidine ([(18)F]-FLT), a marker of cellular proliferation, has been used in positron emission tomography (PET) examination of gliomas. The aim of this study was to investigate whether the uptake of [(18)F]-FLT in glioma correlates with messenger RNA (mRNA) levels of the equilibrative nucleoside transporter 1 (ENT1), microvascular density (assessed by CD34 immunohistochemistry), and the blood-brain barrier (BBB) breakdown. A total of 21 patients with newly diagnosed glioma were examined with [(18)F]-FLT PET. Tumor lesions were identified as areas of focally increased [(18)F]-FLT uptake, exceeding that of surrounding normal tissue. Dynamic analysis of [(18)F]-FLT PET revealed correlations between the phosphorylation rate constant k (3) and ENT1 expression; however there was no correlation between the kinetic parameters and CD34 score. There was a good correlation between the gadolinium (Gd) enhancement score (evaluating BBB breakdown) and ENT1 expression, CD34 score, and Ki-67 index. This preliminary study suggests that ENT1 expression might not reflect accumulation of [(18)F]-FLT in vivo due to BBB permeability in glioma. PMID:23423309

Shinomiya, Aya; Miyake, Keisuke; Okada, Masaki; Nakamura, Takehiro; Kawai, Nobuyuki; Kushida, Yoshio; Haba, Reiji; Kudomi, Nobuyuki; Tokuda, Masaaki; Tamiya, Takashi



Vascular endothelial growth factors and angiogenesis in eye disease  

Microsoft Academic Search

The vascular endothelial growth factor (VEGF) family of growth factors controls pathological angiogenesis and increased vascular permeability in important eye diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). The purpose of this review is to develop new insights into the cell biology of VEGFs and vascular cells in angiogenesis and vascular leakage in general, and to provide

A. N. Witmer; G. F. J. M. Vrensen; C. J. F Van Noorden; R. O. Schlingemann



Significance of plasma D-dimer in relation to the severity of atherosclerosis among patients evaluated by non-invasive indices of cardio-ankle vascular index and carotid intima-media thickness  

Microsoft Academic Search

The aim of this study is to elucidate the usefulness of plasma D-dimer for the prediction of thrombotic events in highly atherosclerotic\\u000a patients. The severity of atherosclerosis was measured by non-invasive methods including cardio-ankle vascular index (CAVI)\\u000a and carotid intima-media thickness (IMT) in 100 patients with atherosclerosis aged 72.1 years on average. CAVI was significantly\\u000a correlated with the levels of D-dimer,

Shigeru Hayashi



MRI of Blood-Brain Barrier Permeability in Cerebral Ischemia  

PubMed Central

Quantitative measurement of blood–brain barrier (BBB) permeability using MRI and its application to cerebral ischemia are reviewed. Measurement of BBB permeability using MRI has been employed to evaluate ischemic damage during acute and subacute phases of stroke and to predict hemorrhagic transformation. There is also an emerging interest on the development and use of MRI to monitor vascular structural changes and angiogenesis during stroke recovery. In this review, we describe MRI BBB permeability and susceptibility-weighted MRI measurements and its applications to evaluate ischemic damage during the acute and subacute phases of stroke and vascular remodeling during stroke recovery.

Ewing, James R.; Chopp, Michael



Anisotropy of sandstone permeability  

Microsoft Academic Search

Small-scale probe permeability measurements on differently oriented faces of highly compacted and quartz-cemented Viking Formation sandstones yield detailed permeability distributions that appear to be diagnostic of the grain- and lamina-scale fabric of the samples. Permeability anisotropy of a single 'structureless'-appearing sample is low, reflected by a kV \\/ kH-ratio of 0.7; corresponding k-distributions are homogeneous. Permeability anisotropy of a strongly

Rudi Meyer


Corticosteroids inhibit the expression of the vascular endothelial growth factor gene in human vascular smooth muscle cells  

Microsoft Academic Search

The vascular endothelial growth factor (VEGF) is a specific mitogen for vascular endothelial cells and enhances vascular permeability and edemagenesis. VEGF is also a major regulator of angiogenesis and may be a key target for inhibiting angiogenesis in angiogenesis-associated diseases. Among the extensively studied angiostatic compounds are several corticosteroids when used alone or in combination with heparin. In this study

Markus Nauck; George Karakiulakis; André P Perruchoud; Eleni Papakonstantinou; Michael Roth



Spatial and Phenotypic Characterization of Vascular Remodeling in a Mouse Model of Asthma  

Microsoft Academic Search

Asthma is a chronic inflammatory disease characterized by airway wall remodeling in which vascular remodeling is thought to be a main contributor. Vascular endothelial growth factor (VEGF) is known as a major regulator of angiogenesis and enhancer of vascular permeability. Here, we define the spatial nature of vascular remodeling and the role of VEGF and its receptors (Flt-1 and Flk-1)

Xinming Su; Namiko Taniuchi; Enjing Jin; Masakazu Fujiwara; Lei Zhang; Mohammad Ghazizadeh; Hiroyuki Tashimo; Naomi Yamashita; Ken Ohta; Oichi Kawanami



Application of membrane permeability evaluated in in vitro analyses to estimate blood-retinal barrier permeability.  


The relationship between the in vitro membrane permeability and systemic blood-retinal barrier (BRB) permeability of drugs was investigated. To determine membrane permeability trend lines in this relationship, the apparent permeability (P(app)) and initial uptake rate (V) of 23 compounds were evaluated in a parallel artificial membrane permeability assay and the uptake study with a rat retinal endothelial cell line (TR-iBRB2 cells) for comparison with their retinal uptake index (RUI). The RUI values of compounds undergoing passive diffusion across the BRB were correlated with a log of the P(app) [RUI = 7.93 × 10 × exp (0.994 × log P(app)), r(2) = 0.660] and a log of the V [RUI = 26.5 × exp (1.55 × log V), r(2) = 0.581]. The RUI values of compounds undergoing carrier-mediated transport across the BRB were correlated with a log of the V [RUI = 26.5 × exp (0.887 × log V), r(2) = 0.559]. These results showed that the membrane permeability trend lines derived from the RUI and V values reflect the transport of drugs at the BRB, suggesting that an in vitro analysis-based estimation of the BRB permeability can be obtained using TR-iBRB2 cells and membrane permeability trend lines. PMID:22535532

Kubo, Yoshiyuki; Fukui, Eri; Akanuma, Shin-Ichi; Tachikawa, Masanori; Hosoya, Ken-Ichi



An in vivo assay to test blood vessel permeability.  


This method is based on the intravenous injection of Evans Blue in mice as the test animal model. Evans blue is a dye that binds albumin. Under physiologic conditions the endothelium is impermeable to albumin, so Evans blue bound albumin remains restricted within blood vessels. In pathologic conditions that promote increased vascular permeability endothelial cells partially lose their close contacts and the endothelium becomes permeable to small proteins such as albumin. This condition allows for extravasation of Evans Blue in tissues. A healthy endothelium prevents extravasation of the dye in the neighboring vascularized tissues. Organs with increased permeability will show significantly increased blue coloration compared to organs with intact endothelium. The level of vascular permeability can be assessed by simple visualization or by quantitative measurement of the dye incorporated per milligram of tissue of control versus experimental animal/tissue. Two powerful aspects of this assay are its simplicity and quantitative characteristics. Evans Blue dye can be extracted from tissues by incubating a specific amount of tissue in formamide. Evans Blue absorbance maximum is at 620 nm and absorbance minimum is at 740 nm. By using a standard curve for Evans Blue, optical density measurements can be converted into milligram dye captured per milligram of tissue. Statistical analysis should be used to assess significant differences in vascular permeability. PMID:23524912

Radu, Maria; Chernoff, Jonathan



Permeability and relative permeability in rocks  

SciTech Connect

Important features of the topology of the pore space of rocks can be usefully quantified by analyzing digitized images of rock cross sections. One approach computes statistical correlation functions using modern image processing techniques. These correlation functions contain information about porosity, specific surface area, tortuosity, formation factor, and elastic constants, as well as the fluid permeability and relative permeability. The physical basis of this approach is discussed and examples of the results for various sandstones are presented. The analysis shows that Kozeny-Carman relations and Archie's empirical laws must be modified to account for finite percolation thresholds in order to avoid unphysical behavior in the calculated relative permeabilities. 33 refs., 4 figs., 1 tab.

Blair, S.C.; Berryman, J.G.



Effect of hyperthermia on vascular functions of normal tissues and experimental tumors; brief communication.  


The effect of hyperthermia on vascular volume and vascular permeability of the Walker carcinoma 256, skin, and muscle of inbred SD male rats was investigated. Whereas heating at 43 degrees C for 1 hour induced a significant increase in the functional vascular volume and vascular permeability in the skin and muscle, it did not change these vascular functions in the tumors. The increased vascular volume in the normal tissues suggested an increased circulation, which may enhance the dissipation of heat and result in a differential effect of hyperthermia on normal tissues and tumors. PMID:625073

Song, C W



Vascular endothelial growth factor in the rat pituitary: differential distribution and regulation by estrogen  

Microsoft Academic Search

Vascular endothelial growth factor (VEGF), an endothelial cell mitogen and permeability factor, participates in tumor angiogenesis, but less is known about its regulation or function in normal vascular homeostasis. In the uterus, which undergoes cyclic changes in its vasculature, VEGF is induced by estrogen. Since the pituitary gland contains highly permeable capillaries and is estrogen-responsive, our objectives were to localize

A L Ochoa; N A Mitchner; C D Paynter; R E Morris; N Ben-Jonathan



Vascular growth factors in cerebral ischemia  

Microsoft Academic Search

During the past decade, there has been a surge of interest in growth factors (GFs) that act selectively on vascular endothelium\\u000a and perivascular cells. Studies employing mutant mice or the administration of recombinant proteins have suggested that these\\u000a factors not only mediate the proliferation of endothelial cells, but also regulate vascular differentiation, regression, and\\u000a permeability. During and after cerebral ischemia,

Susan D. Croll; Stanley J. Wiegand



Vascular lesions.  


Advances in laser and light-based technology have increased their potential applications, safety and efficacy for the management of vascular lesions in dermatology. Light devices for vascular lesions include the variable-pulse 532 nm potassium titanyl phosphate laser, 577 to 595 nm pulsed dye laser, intense pulsed light devices, and 800 to 940 nm diode, long-pulse 755 nm alexandrite and 1,064 nm Nd:YAG lasers. This review will discuss the various different laser and light-based devices, and provide a focused treatment approach for the management of common congenital and acquired vascular lesions. PMID:21865800

Ting, Patricia T; Rao, Jaggi



Inhibition of RHO-kinase depends on factors that modify endothelial permeability  

Microsoft Academic Search

The endothelium that lines the inner surface of all vessels plays the role of a barrier and regulates the permeability of\\u000a vascular walls that control the exchange between circulating blood and tissue fluids. The disturbance of normal functions\\u000a (endothelial dysfunction) can be caused both internal and external factors. Endothelial dysfunction is characterized by the\\u000a increasing permeability of the vascular wall,

K. M. Smurova; A. D. Verin; I. B. Alieva



Vascular Cures  


... Research Network . Innovating Results matter. We’re leaders in finding new ways to predict, treat and prevent vascular disease. Our newest program brings the power of genomics to find new ways to prevent death ...


Permeability Factor in Pollen Extracts Active in Non-sensitized Mice  

Microsoft Academic Search

MOST of the recent work on hypersensitivity to pollens has been concerned with the isolation and characterization of the pollen allergens. The presence of biologically active materials in pollens, other than allergens, has been overlooked. The results presented here, however, demonstrate that pollen extracts contain a factor which increases vascular permeability in normal non-sensitized mice. Permeability factor was first detected

Leon S. Kind; William Richards; Adrienne T. Smith; Phyllis Ellman



Toxicity of Kidney Bean (Phaseolus vulgaris) in Rats: Changes in Intestinal Permeability  

Microsoft Academic Search

Rats fed on diets containing kidney bean showed increased intestinal permeability to intravenously injected 125I-labelled rat serum proteins after an intragastric challenge with bean proteins. The enhanced accumulation of radioactive serum proteins in the lumen and walls of the small intestine indicated increased vascular permeability. It is suggested that dietary lectins may, at least in part, be responsible for this

Fiona Greer; Arpad Pusztai



ConcepTest: Permeability  

NSDL National Science Digital Library

Three similar containers were filled with flour, rice or Cheerios. If you were to pour water into each container, how would they rank in terms of permeability (from highest to lowest)? a. Flour, Rice, Cheerios b. ...


Prolactin and blood-brain barrier permeability.  


The blood-brain barrier (BBB) consists in part of a highly specialized set of cells which separates the brain from the vascular system. The BBB controls the entry and exit of substances from the brain tissue through tight junctions (TJs) between endothelial cells. It is known that the hormone prolactin (PRL) is able to regulate endothelial-dependent processes, like the balance between proliferation and apoptosis and the mammary epithelial permeability. However, the effects of PRL and the role it plays in the BBB permeability are still not well understood. A primary culture of bovine brain microvessel endothelial cells was used as in vitro model of BBB. Cells were treated with PRL (0.1, 1, 10 and 100 nM) for 24 hours. PRL significantly increased cellular proliferation at 10 and 100 nM, but did not modify basal apoptosis. These effects were dependent on the production of the mitogenic factor nitric oxide (NO). PRL significantly decreased the permeability and promoted an increase in trans-endothelial electrical resistance in a NO-independent way. PRL also increased the expression of the TJs proteins claudin-5 and occludin. The short form of the PRL receptor was detected in these cells but its expression was not modified by PRL. Together, these results suggest that PRL has the ability to increase cellular proliferation associated with a decrease on BBB permeability by increasing the expression of TJs proteins. PMID:23937200

Rosas-Hernandez, Hector; Cuevas, Elvis; Lantz, Susan M; Hamilton, W Ryan; Ramirez-Lee, Manuel A; Ali, Syed F; Gonzalez, Carmen



VEGFR-2-specific ligand VEGF-E induces non-edematous hyper-vascularization in mice  

Microsoft Academic Search

VEGF family members play important roles in angiogenesis and vascular permeability. VEGF-A-transgenic mice showed an increased vascularization with edema due to hyper-vascular permeability and subcutaneous hemorrhage as side effects. VEGF-A binds and activates two receptors, VEGFR-1 (Flt-1) and VEGFR-2 (KDR\\/Flk-1). To dissect the signals of these two receptors, we generated transgenic mice overexpressing either the VEGFR-2-specific ligand VEGF-ENZ-7 or VEGFR-1-specific

Atsushi Kiba; Hiroshi Sagara; Takeshi Hara; Masabumi Shibuya



The fms-Like Tyrosine Kinase, a Receptor for Vascular Endothelial Growth Factor  

Microsoft Academic Search

The fms-like tyrosine kinase (Flt) is a transmembrane receptor in the tyrosine kinase family. Expression of flt complementary DNA in COS cells conferred specific, high-affinity binding of vascular endothelial growth factor, also known as vascular permeability factor (VEGF-VPF), a factor that induces vascular permeability when injected in the guinea pig skin and stimulates endothelial cell proliferation. Expression of Flt in

Carlie de Vries; Jaime A. Escobedo; Hikaru Ueno; Keith Houck; Napoleone Ferrara; Lewis T. Williams



Integrin signaling in vascular function  

PubMed Central

Structured summary Purpose of review In the current review, we summarize recent progress on vasculature-specific function and regulation of integrins and integrin-associated proteins, including advances in our understanding of inside-out integrin activation. The studies on regulation of integrin activation received new impulse in 2009 with the identification of Kindlin protein family members as crucial mediators of integrin inside-out signaling. In the current review, we outline the recent findings on the role of Kindlins in the vascular system, as well as new studies that have begun shaping the mechanistic model of Kindlins’ function. Recent findings Several tissue-specific knockout models for integrins and genes associated with the integrin functions have been recently presented, including smooth muscle-specific ILK and endothelial-specific FAK and Talin-1 ablation. In the heterozygous animal knockout model, Kindlin-2 has been demonstrated as a crucial modulator of angiogenesis and vascular permeability. As a number of papers have advanced our understanding of Kindlin function, they are reviewed and discussed in further detail. New findings include an additional lipid binding site within the Kindlin molecule and preferential binding of non-phosphorylated form of ?-integrins. Summary The role of integrins in angiogenesis has been demonstrated to include, in addition to cell adhesion and mechanotransduction, specific signaling functions. The importance of integrin inside-out pathway in vascular physiology has been unequivocally proven, and endothelial permeability is directly regulated by this process. Inhibition of Kindlin-dependent steps in the inside-out pathway as an approach to block platelet aggregation should be paralog-specific, as it may have adverse effects on vascular permeability.

Malinin, Nikolay L.; Pluskota, Elzbieta; Byzova, Tatiana V.



Periodic layered waveguide with negative index of refraction  

Microsoft Academic Search

The authors demonstrate that a negative index of refraction can exist in a periodic layered waveguide composed of natural materials with either permittivity or permeability negative. They find that the negative index depends on component materials, their configurations, and working modes of the waveguide. In the long wave limit, the expressions of the effective permeability and permittivity of the waveguide

Rui-Xin Wu; Tianen Zhao; Ping Chen; Jie Xu; Xinyi Ji



Vascular Management in Rotationplasty  

PubMed Central

The Van Nes rotationplasty is a useful limb-preserving procedure for skeletally immature patients with distal femoral or proximal tibial malignancy. The vascular supply to the lower limb either must be maintained and rotated or transected and reanastomosed. We asked whether there would be any difference in the ankle brachial index or complication rate for the two methods of vascular management. Vessels were resected with the tumor in seven patients and preserved and rotated in nine patients. One amputation occurred in the group in which the vessels were preserved. Four patients died secondary to metastatic disease diagnosed preoperatively. The most recent ankle brachial indices were 0.96 and 0.82 for the posterior tibial and dorsalis pedis arteries, respectively, in the reconstructed group. The ankle brachial indices were 0.98 and 0.96 for the posterior tibial and dorsalis pedis arteries, respectively, in the rotated group. Outcomes appear similar using both methods of vascular management and one should not hesitate to perform an en bloc resection when there is a question of vascular involvement. Level of Evidence: Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence. Electronic supplementary material The online version of this article (doi:10.1007/s11999-008-0197-4) contains supplementary material, which is available to authorized users.

Hartman, Curtis W.; Simon, Pamela J.; Baxter, B. Timothy; Neff, James R.



Vascular management in rotationplasty.  


The Van Nes rotationplasty is a useful limb-preserving procedure for skeletally immature patients with distal femoral or proximal tibial malignancy. The vascular supply to the lower limb either must be maintained and rotated or transected and reanastomosed. We asked whether there would be any difference in the ankle brachial index or complication rate for the two methods of vascular management. Vessels were resected with the tumor in seven patients and preserved and rotated in nine patients. One amputation occurred in the group in which the vessels were preserved. Four patients died secondary to metastatic disease diagnosed preoperatively. The most recent ankle brachial indices were 0.96 and 0.82 for the posterior tibial and dorsalis pedis arteries, respectively, in the reconstructed group. The ankle brachial indices were 0.98 and 0.96 for the posterior tibial and dorsalis pedis arteries, respectively, in the rotated group. Outcomes appear similar using both methods of vascular management and one should not hesitate to perform an en bloc resection when there is a question of vascular involvement. PMID:18347891

Mahoney, Craig R; Hartman, Curtis W; Simon, Pamela J; Baxter, B Timothy; Neff, James R



Seismic waves increase permeability.  


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. PMID:16810253

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



Vascular Proliferation  

NSDL National Science Digital Library

This FlashTM animation depicts vascularization of the early germ disc. It is shown in the context of a transverse section through a trilaminar germ disc and yolk sac. Clicking shows the cardiogenic field developing into the heart tube, along with vasculogenesis of the major vessels. Clicking again shows angiogenesis of peripheral vessels throughout the developing embryo and yolk sac.

PhD Jack D Thatcher (West Virginia School of Osteopathic Medicine Structural Biology)



Vascular Caliber  

Microsoft Academic Search

Many aspects of vascular caliber can be accounted for on the basis of interactions between the frictional drag generated by the stream, and the sensitivity of the endothelial cells to this force. When the drag force on endothelial cells is at its critical set-point, these lining cells are at rest with respect to factors that affect caliber. An increase in

Simon Rodbard



Effect of polycaprolactone scaffold permeability on bone regeneration in vivo.  


Successful bone tissue engineering depends on the scaffold's ability to allow nutrient diffusion to and waste removal from the regeneration site, as well as provide an appropriate mechanical environment. Since bone is highly vascularized, scaffolds that provide greater mass transport may support increased bone regeneration. Permeability encompasses the salient features of three-dimensional porous scaffold architecture effects on scaffold mass transport. We hypothesized that higher permeability scaffolds will enhance bone regeneration for a given cell seeding density. We manufactured poly-?-caprolactone scaffolds, designed to have the same internal pore design and either a low permeability (0.688×10(-7)m(4)/N-s) or a high permeability (3.991×10(-7)m(4)/N-s), respectively. Scaffolds were seeded with bone morphogenic protein-7-transduced human gingival fibroblasts and implanted subcutaneously in immune-compromised mice for 4 and 8 weeks. Micro-CT evaluation showed better bone penetration into high permeability scaffolds, with blood vessel infiltration visible at 4 weeks. Compression testing showed that scaffold design had more influence on elastic modulus than time point did and that bone tissue infiltration increased the mechanical properties of the high permeability scaffolds at 8 weeks. These results suggest that for polycaprolactone, a more permeable scaffold with regular architecture is best for in vivo bone regeneration. This finding is an important step toward the end goal of optimizing a scaffold for bone tissue engineering. PMID:21395465

Mitsak, Anna G; Kemppainen, Jessica M; Harris, Matthew T; Hollister, Scott J



Quantification of tumor microvascular permeability in human glioma xenografts using dynamic T1 MRI with Gadomer-17  

NASA Astrophysics Data System (ADS)

Dynamic Magnetic Resonance Imaging (T1-mapping) using the Gadolinium complex Gadomer-17, was applied to characterize the vascular permeability of human glioma xenografts implanted in nude mice. We aimed at measuring permeability differences in two types of glioma xenograft lines with a known difference in perfusion status. The T1-data could be analyzed according to the Tofts-Kermode compartmental model for modeling tracer kinetics to vascular permeability. This vascular permeability was mapped as the permeability surface area product per unit of leakage volume (k). The two tumor types displayed different k-maps. For the fast growing E102 tumor, we observed a homogeneous distribution of the vascular permeability across the tumor with a mean k-value of (0.207 plus or minus 0.027) min-1. However, for the slowly growing E106 tumor, we could distinguish four different regions with different permeability characteristics: a well-perfused rim [k equals (0.30 plus or minus 0.09) min-1], regions at the inner side of the tumor with lower permeability [k equals (0.130 plus or minus 0.019) min-1], regions at the inner side of the tumor around necrotic regions demonstrating locally increased permeability [k equals (0.33 plus or minus 0.11) min-1], and necrotic regions.

Verhoye, Marleen; van der Sanden, Boudewijn P.; Rijken, P.; Peters, Hans; van der Kogel, A. J.; Pee, Gilke; Vanhoutte, Greet; Heerschap, Arend; van der Linden, Anne-Marie



Intestinal permeability: An overview  

Microsoft Academic Search

The noninvasive assessment of intestinal permeability in humans has a 20-year history. Because the tests are increasingly used in clinical practice and research and because there is much controversy, we reviewed the literature and outlined the potential and possible shortcomings of these procedures. Data was obtained from personal files and from a systemic search through MEDLINE and EMBASE. The principle

Ingvar Bjarnason; Andrew Macpherson; Daniel Hollander



The Ability of Permeability  

NSDL National Science Digital Library

In this activity (page 11 of the PDF), learners investigate how quickly water moves through various materials. They measure and compare the permeability of gravel, sand, and soil. Although this was created as a post-visit activity for a workshop about earth processes, it also makes an excellent stand alone activity.




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...


Vascular sarcomas.  


Vascular sarcomas are soft-tissue tumors that arise from the endothelium with a malignant potential. This review discusses the management of epithelioid hemangioendothelioma (EHE) and angiosarcoma. EHE is a vascular tumor of intermediate malignant potential with an indolent course. EHE arising from the liver, lung, or bone tends to be multifocal and the rate of progression is slow and often unpredictable. Treatment should be considered in patients with significant symptomatic deterioration and/or progressive disease on imaging studies. Various cytotoxic and targeted therapies are available for management, with disease stabilization as the most common outcome. Angiosarcoma is an aggressive vascular tumor with a high malignant potential. Multidisciplinary care is critical for the management of localized disease, and the best outcomes are often observed in patients when a combination of systemic and local therapy options is used. Metastatic angiosarcoma is treated primarily with systemic therapy, and several cytotoxic and targeted therapies are available, alone or in combination. The choice of therapy depends on several factors, such as cutaneous location of the tumor, performance status of the patient, toxicity of the treatment, and patient goals. PMID:23852636

Ravi, Vinod; Patel, Shreyaskumar



Inflammatory Cytokines in Vascular Dysfunction and Vascular Disease  

PubMed Central

The vascular inflammatory response involves complex interaction between inflammatory cells (neutrophils, lymphocytes, monocytes, macrophages), endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and extracellular matrix (ECM). Vascular injury is associated with increased expression of adhesion molecules by ECs and recruitment of inflammatory cells, growth factors, and cytokines, with consequent effects on ECs, VSMCs and ECM. Cytokines include tumor necrosis factors, interleukins, lymphokines, monokines, interferons, colony stimulating factors, and transforming growth factors. Cytokines are produced by macrophages, T cells and monocytes, as well as platelets, ECs and VSMCs. Circulating cytokines interact with specific receptors on various cell types and activate JAK-STAT, NF-?B, and Smad signaling pathways leading to an inflammatory response involving cell adhesion, permeability and apoptosis. Cytokines also interact with mitochondria to increasie the production of reactive oxygen species. Cytokine-induced activation of these pathways in ECs modifies the production/activity of vasodilatory mediators such as nitric oxide, prostacyclin, endothelium-derived hyperpolarizing factor, and bradykinin, as well as vasoconstrictive mediators such as endothelin and angiotensin II. Cytokines interact with VSMCs to activate Ca2+, protein kinase C, Rho-Kinase, and MAPK pathways, which promote cell growth and migration, and VSM reactivity. Cytokines also interact with integrins and matrix metalloproteinases (MMPs) and modify ECM composition. Persistent increases in cytokines are associated with vascular dysfunction and vascular disease such as atherosclerosis, abdominal aortic aneurysm, varicose veins and hypertension. Genetic and pharmacological tools to decrease the production of cytokines or to diminish their effects using cytokine antagonists could provide new approaches in the management of inflammatory vascular disease.

Sprague, Alexander H.; Khalil, Raouf A.



Anti-VEGF Agents for Ocular Angiogenesis and Vascular Permeability  

PubMed Central

We review articles describing intravitreal injection of anti-VEGF drug trials, while discussing the mechanisms of the action of anti-VEGF antibodies, and also evaluating their outcomes. Intraocular injections of anti-VEGF drug are considered to be an effective treatment for macular edema after retinal vein occlusion, however, recurrent/persistent edema is common. The recent reports may lead to a shift in treatment paradigm for DME, from laser photocoagulation, to newer approaches using anti-VEGF drugs. There have been several well-publicized prospective, randomized studies that demonstrated the efficacy of intravitreal injection of anti-VEGF drugs for patients with AMD. Adjuvant bevacizumab for neovascular glaucoma may prevent further PAS formation, and it is likely to open up a therapeutic window for a panretinal photocoagulation and trabeculectomy. Intravitreal injection of bevacizumab (IVB) results in a substantial decrease in bleeding from the retinal vessels or new vessels during a standard vitrectomy. IVB has also been reported to be effective for inducing the regression of new vessels in proliferative diabetic retinopathy. The use of bevacizumab in stage 4 or 5 retinopahty of permaturity (ROP) is to reduce the plus sign to help reduce hemorrhage during the subsequent vitrectomy. Some authors reported cases of resolution of stage 4?A ROP after bevacizumab injection.

Kimoto, Kenichi; Kubota, Toshiaki



Amifostine reduces lung vascular permeability via suppression of inflammatory signaling  

PubMed Central

Multiple events are involved in the development of acute inflammation and injury in the lungs. A progressive rise of oxidative stress due to altered reduction-oxidation (redox) homeostasis appears to be one of the hallmarks of lung pathologies such as injury, inflammation and ischemia/reperfusion. However, despite the growing evidence that alteration of the redox balance in the lungs, antioxidant therapy may attenuate acute lung injury and inflammation. We studied the effect of thiol antioxidant compound, amifostine, on acute lung dysfunction and pulmonary endothelial barrier compromise induced by gram-negative bacterial wall lypopolysacharide (LPS). In vitro, LPS as well as other producers of reactive oxygen spices (ROS), interleukin-6 (IL-6) and hydrogen peroxide (H2O2), induced significant reorganization of actin cytoskeleton accompanied by formation of stress fibers and paracellular gaps and associated with decreased transendothelial electrical resistance, a hallmark of endothelial barrier dysfunction. These disruptive effects were inhibited by pretreatment of endothelial monolayer with amifostine. Moreover, amifostine inhibited LPS-mediated ROS production and significantly suppressed LPS-, IL-6-, and H2O2-induced activation of redox sensitive signaling mechanisms including p38 and Erk1/2 MAP kinases, and NF?B pathway. In the murine model of LPS-induced acute lung injury, intraperitoneal administration of amifostine reduced LPS-induced oxidative stress and neutrophil recruitment to the lungs. These studies demonstrate for the first time that amifostine dramatically reduces endothelial cell barrier dysfunction and acute lung injury caused by bacterial products via inhibition of oxidative stress and redox-sensitive inflammatory pathways, and may therefore be considered for therapeutic treatment of lung inflammation.

Fu, Panfeng; Birukova, Anna A.; Sammani, Saad; Burdette, Dylan; Murley, Jeffrey S.; Garcia, Joe G.N.; Grdina, David J.; Birukov, Konstantin G.



Permeability evolution during dynamic stressing of dual permeability media  

NASA Astrophysics Data System (ADS)

Changes in permeability due to dynamic loading from earthquakes are observed commonly but the underlying mechanisms are poorly understood. This study reports fluid flow-through experiments on fractured rock that reproduce, at laboratory scale, transient changes in permeability that decay to background over extended periods of time. We explore this response as a particular form of poroelastic loading in dual-porosity and dual-permeability media subject to zero net strain but with incremented fracture fluid pressures. Initial augmentation of pore fluid pressure dilates the fracture and compacts the surrounding, low permeability matrix, resulting in a step-like (order of seconds), transient increase in the effective permeability of the rock mass. With time, fluid pressure diffusion into the low permeability matrix then resets the effective permeability to the background magnitude, with the rate controlled by a diffusive timescale. We show that for an increase in fracture pore fluid pressure, the magnitude of the transient increase in fracture permeability scales with the ratios of the pore pressure increase to the intact modulus and the fracture spacing to the initial fracture aperture, for a broad suite of experiments. The duration of the permeability transient, measured via the time to recover background permeability, scales inversely with matrix permeability and modulus of the intact matrix and directly with the square of the spacing between fractures.

Faoro, Igor; Elsworth, Derek; Marone, Chris



An emerging concept of vascular salt sensitivity  

PubMed Central

Excessive amounts of salt in food, as usually consumed worldwide, affect the vascular system, leading to high blood pressure and premature disabilities. Salt entering the vascular bed after a salty meal is transiently bound to the endothelial glycocalyx, a negatively charged biopolymer lining the inner surface of the blood vessels. This barrier protects the endothelium against salt overload. A poorly-developed glycocalyx increases the salt permeability of the vascular system and the amount of salt being deposited in the body, which affects organ function. A simple test system is now available that evaluates vascular salt sensitivity in humans and identifies individuals who are at risk of salt-induced hypertension. This short review aims to discuss how the underlying basic research can be translated into medical practice and, thus, meaningful health outcomes.

Kusche-Vihrog, Kristina



Liquid-permeable electrode  

SciTech Connect

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.

Folser, G.R.



[Venoruton and capillary permeability].  


A new system to evaluate capillary permeability, the vacuum suction chamber (VSC) device, was used to assess the effects of Venoruton in patients with venous hypertension. A temporary, superficial skin lesion (wheal) was produced with the VSC device by negative pressure (30 mmHg) applied for 10 minutes on the internal, perimalleolar region. Wheals disappear in less than 60 minutes in normals while in patients with venous hypertension the wheal is more persistent, requiring a significantly longer time to disappear. This new technique was used in association with laser-Doppler flowmetry to evaluate the efficacy of Venoruton (1000 mgs t.i.d.) administered for 2 weeks on venous hypertension. Results indicate a positive effect of Venoruton in reducing the abnormally increased capillary permeability in venous hypertension and are proportional to the changes observed in signs and symptoms after treatment. PMID:2779806

Cesarone, M R; Laurora, G; Gabini, M; Errichi, B M; Candiani, C; Belcaro, G



Induction of permeability across endothelial cell monolayers by tumor necrosis factor (TNF) occurs via a tissue factor-dependent mechanism: relationship between the procoagulant and permeability effects of TNF  

Microsoft Academic Search

Tumor necrosis factor (TNF) has marked effects on permeability and procoagulant activity on tumor-associated neovascula- ture when used in isolation perfusion, the latter effect primarily mediated via induction of cell surface expression of tissue factor (TF) on endothelial tissue. However, the cel- lular events that result in rapid alterations in endothelial cell (EC) permeability after intra- vascular TNF administration in

Josef Friedl; Markus Puhlmann; David L. Bartlett; Steven K. Libutti; Ewa N. Turner; Michael F. X. Gnant; H. Richard Alexander



Role of caveolin-1 in the regulation of pulmonary endothelial permeability.  


Endothelial permeability measurements of intact vascular beds and monolayer cultures are used to describe transport of small molecules (ions, water, and nutrients), macromolecules and plasma protein across the vascular endothelia. Disruption of the endothelial barrier leads to vascular hyper-permeability and protein-rich edema which is a key hallmark of inflammation. Transport of the most abundant plasma protein, albumin, occurs by means of transcellular and paracellular pathways. In healthy, noninflamed vessels, endothelial cell-cell contacts significantly restrict the paracellular permeability of albumin, whereas its transcellular transport from the blood to the abluminal perivascular interstitium occurs via caveolae. Thus, caveolae-mediated transport is a primary determinant of the basal endothelial permeability properties. Increased paracellular permeability induced during inflammation is thought to be due to the opening of interendothelial cell-cell junctions and disruption of endothelial cell-matrix contacts within the vasculature. We recently demonstrated that caveolae-mediated transendothelial transport (transcytosis) of macromolecules through the microvascular endothelial barrier is also an important mechanism responsible for inflammation-evoked pulmonary vascular hyperpermeability and protein-rich edema formation. Moreover, caveolin-1, a structural and scaffolding protein required for caveolae formation and transcellular transport, also plays an important role in oxidant-induced paracellular hyperpermeability. This review highlights the methods used to assess transcellular and paracellular permeability properties of the intact mouse lung and cultured endothelial cell monolayers. PMID:21874461

Sun, Yu; Minshall, Richard D; Hu, Guochang



Negative refractive index in chiral metamaterials.  


We experimentally demonstrate a chiral metamaterial exhibiting negative refractive index at terahertz frequencies. The presence of strong chirality in the terahertz metamaterial lifts the degeneracy for the two circularly polarized waves and allows for the achievement of negative refractive index without requiring simultaneously negative permittivity and negative permeability. The realization of terahertz chiral negative index metamaterials offers opportunities for investigation of their novel electromagnetic properties, such as negative refraction and negative reflection, as well as important terahertz device applications. PMID:19257274

Zhang, Shuang; Park, Yong-Shik; Li, Jensen; Lu, Xinchao; Zhang, Weili; Zhang, Xiang



Relative permeability through fractures  

SciTech Connect

The mechanism of two-phase flow through fractures is of importance in understanding many geologic processes. Currently, two-phase flow through fractures is still poorly understood. In this study, nitrogen-water experiments were done on both smooth and rough parallel plates to determine the governing flow mechanism for fractures and the appropriate methodology for data analysis. The experiments were done using a glass plate to allow visualization of flow. Digital video recording allowed instantaneous measurement of pressure, flow rate and saturation. Saturation was computed using image analysis techniques. The experiments showed that gas and liquid phases flow through fractures in nonuniform separate channels. The localized channels change with time as each phase path undergoes continues breaking and reforming due to invasion of the other phase. The stability of the phase paths is dependent on liquid and gas flow rate ratio. This mechanism holds true for over a range of saturation for both smooth and rough fractures. In imbibition for rough-walled fractures, another mechanism similar to wave-like flow in pipes was also observed. The data from the experiments were analyzed using Darcy's law and using the concept of friction factor and equivalent Reynold's number for two-phase flow. For both smooth- and rough-walled fractures a clear relationship between relative permeability and saturation was seen. The calculated relative permeability curves follow Corey-type behavior and can be modeled using Honarpour expressions. The sum of the relative permeabilities is not equal one, indicating phase interference. The equivalent homogeneous single-phase approach did not give satisfactory representation of flow through fractures. The graphs of experimentally derived friction factor with the modified Reynolds number do not reveal a distinctive linear relationship.

Diomampo, Gracel, P.



Wave propagation in media having negative permittivity and permeability  

Microsoft Academic Search

Wave propagation in a double negative (DNG) medium, i.e., a medium having negative permittivity and negative permeability, is studied both analytically and numerically. The choices of the square root that leads to the index of refraction and the wave impedance in a DNG medium are determined by imposing analyticity in the complex frequency domain, and the corresponding wave properties associated

Richard W. Ziolkowski; Ehud Heyman



Vascular Dementia  

PubMed Central

Cerebrovascular disease is the second leading cause of cognitive impairment in the elderly, either alone or in combination with Alzheimer's disease (AD). Vascular dementia (VaD) is heterogeneous in terms of both clinical phenotype and pathogenetic mechanisms. It may result from multiple cortical infarctions due to cerebral large vessel pathologies or to subcortical ischemic changes such as leukoaraiosis or lacunar infarction due to cerebral small artery disease. Clinical symptoms and signs vary depending on the location and size of the stroke lesion, and no single neuropsychological profile characteristic of VaD has been defined, although dysexecutive function is common. A slightly higher mortality rate and slower progression are reported in VaD compared with AD. VaD is potentially preventable by rigorous identification and treatment of cardiovascular disease risk factors, and modest symptomatic improvement with cholinesterase inhibitors has been reported.



Gas permeability of shocked chondrites  

NASA Astrophysics Data System (ADS)

The gas permeability of 11 ordinary chondrites was measured at various gas pressures (0.5-2.5 bars) under confining pressures up to 120 bars. The gas permeability ranges from less than a nanodarcy to a few millidarcies. There is a positive correlation between the permeability and the porosity. The permeabilithy decreased by as much as 50 percent when the confining pressure was increased from 10 to 100 bars, suggesting that the permeability of some chondrites is partly due to cracks. A linear relation between gas flow pressure dependence and confining pressure dependence of the gas permeability is observed, suggesting that on average, crack apertures are larger than pore spaces. The permeabilithy of heavily-shocked chondrites is less than of mildly shocked chondrites. Using the measured permeability data the size of a possible shocked-chondrite precursor body is estimated.

Matsui, T.; Sugiura, N.; Brar, N. S.



Porosity and Permeability  

NSDL National Science Digital Library

The students are exposed to a brief (approx. 5 minute) introduction/presentation on aquifers and groundwater including their geographical context, structure, and vocabulary. The students receive everyday materials with different properties: Styrofoam block, scrubbing pad, etc, and a dropper bottle filled with water. They are not initially told what to do, but instead asked what they are going to do. The idea is to use the dropper bottle to put water on the objects and notice if the water passes through or not? They are also encouraged to notice any physical features that may be responsible for these behaviors. Students typically won't talk to each other at first and won't know what to do. Asking them guided questions usually encourages conversation between the students. They can also be asked what other everyday objects could be used for this exercise. After they have explore everyday objects, they are introduced to a handsample of granite and a sandstone. Although they have not been exposed to rocks in lab, they can usually identify the granite right away, and the sandstone when about the size of the grains. They then will discuss the physical properties of the rocks and hypothesize what is more porous and permeable. They test this with the water dropper. Finally, as a class, we discuss that something that is porous and permeable like a sandstone makes a good aquifer, and where good aquifers are located.

Witherow, Rebecca


Effect of Vascular Endothelial Growth Factor on Cultured Endothelial Cell Monolayer Transport Properties  

Microsoft Academic Search

Vascular endothelial growth factor (VEGF) is a potent enhancer of microvascular permeability in vivo. To date, its effects on hydraulic conductivity (Lp) and diffusive albumin permeability (Pe) of endothelial monolayers have not been thoroughly assessed in vitro. We hypothesized that VEGF affects endothelial transport properties differently depending on vessel location and endothelial phenotype. Using three well-established endothelial cell culture models—human

Yong S. Chang; Lance L. Munn; Mechteld V. Hillsley; Randal O. Dull; Jin Yuan; Sunitha Lakshminarayanan; Thomas W. Gardner; Rakesh K. Jain; John M. Tarbell



Vascular holism: The epidemiology of vascular disease  

Microsoft Academic Search

This article reviews the distinguishing features of epidemiology and clinical medicine and their interdependence in clinical epidemiology as applied to vascular disease. Selected literature is reviewed to emphasize the principles of clinical epidemiology for five vascular disorders: abdominal aortic aneurysms, lower extremity peripheral arterial occlusive disease, cerebrovascular disease, deep vein thrombosis and pulmonary embolism, and varicose veins. These vascular disorders

Robert W. Barnes



Permeability correction factor for fractures with permeable walls  

NASA Astrophysics Data System (ADS)

Enhanced Geothermal Systems (EGS) are based on the premise that heat can be extracted from hot dry rocks located at significant depths by circulating fluid through fracture networks in the system. Heated fluid is recovered through production wells and the energy is extracted in a heat exchange chamber. There is much published research on flow through fractures, and many models have been developed to describe an effective permeability of a fracture or a fracture network. In these cases however, the walls of the fracture were modelled as being impermeable. In this paper, we have extended our previous work on fractures with permeable walls, and we introduce a correction factor to the equation that governs fracture permeability. The solution shows that the effective fracture permeability for fractures with permeable walls depends not only on the height of the channel, but also on the wall permeability and the wall Reynolds number of the fluid. We show that our solution reduces to the established solution when the fracture walls become impermeable. We also extend the discussion to cover the effective permeability of a system of fractures with permeable walls.

Mohais, R.; Xu, C.; Dowd, P. A.; Hand, M.



Vascular Endothelial Growth Factor (VEGF)-C Differentially Affects Tumor Vascular Function and Leukocyte Recruitment: Role of VEGF-Receptor 2 and Host VEGF-A1  

Microsoft Academic Search

Unlike vascular endothelial growth factor (VEGF)-A, the effect of VEGF-C on tumor angiogenesis, vascular permeability, and leukocyte recruitment is not known. To this end, we quantified in vivo growth and vascular function in tumors derived from two VEGF-C-overexpressing (VC1) and mock-transfected cell lines (T241 fibrosarcoma and VEGF- A2\\/2 embryonic stem cells) grown in murine dorsal skinfold chambers. VC1 tumors grew

Ananth Kadambi; Carla Mouta Carreira; Chae-ok Yun; Timothy P. Padera; Dennis E. J. G. J. Dolmans; Peter Carmeliet; Dai Fukumura; Rakesh K. Jain



Immigration Index  

NSDL National Science Digital Library

Striving to become the "immigration resource directory on the net," the Immigration Index is a newly launched Website dedicated to news and information about immigration worldwide. Along with breaking headlines from a variety of news sources about immigration-related issues such as asylum, migration, trafficking and women, and much more, the site contains a fully annotated collection of links to immigration materials all around the World Wide Web. Only a month old, some of the categories in the Index's hierarchy still need some filling in. In time, however, the Immigration Index promises to become an invaluable resource for interested parties.


Anthrax lethal toxin induces cell death-independent permeability in zebrafish vasculature  

PubMed Central

Vascular dysfunction has been reported in human cases of anthrax, in mammalian models of Bacillus anthracis, and in animals injected with anthrax toxin proteins. To examine anthrax lethal toxin effects on intact blood vessels, we developed a zebrafish model that permits in vivo imaging and evaluation of vasculature and cardiovascular function. Vascular defects monitored in hundreds of embryos enabled us to define four stages of phenotypic progression leading to circulatory dysfunction. We demonstrated increased endothelial permeability as an early consequence of toxin action by tracking the extravasation of fluorescent microspheres in toxin-injected embryos. Lethal toxin did not induce a significant amount of cell death in embryonic tissues or blood vessels, as shown by staining with acridine orange, and endothelial cells in lethal toxin-injected embryos continued to divide at the normal rate. Vascular permeability is strongly affected by the VEGF/vascular permeability factor (VPF) signaling pathway, and we were able to attenuate anthrax lethal toxin effects with chemical inhibitors of VEGFR function. Our study demonstrates the importance of vascular permeability in anthrax lethal toxin action and the need for further investigation of the cardiovascular component of human anthrax disease.

Bolcome, Robert E.; Sullivan, Sarah E.; Zeller, Rene; Barker, Adam P.; Collier, R. John; Chan, Joanne



Rocks of low permeability  

NASA Astrophysics Data System (ADS)

The 17th International Congress of the IAH (International Association of Hydrogeologists) will meet in Tucson, Ariz., January 7-10, 1985. The deadline for abstracts is March 1, 1984, and final papers are due October 15, 1984.The topic of the congress will be “Hydrogeology of Rocks of Low Permeability,” and speakers will include W. Back, J. F. Bredehoeft, G. de Marsily, J. E. Gale, P. Fritz, L. W. Gelhar, G. E. Grisak, C. W. Kreitler, M. R. Llamas, T. N. Narasimhan, I. Neretnieks, and E. P. Weeks. The congress will conclude with a panel discussion moderated by S. P. Neuman. Panelists include S. N. Davis, G. de Marsily, R. A. Freeze, P. A. Witherspoon, and I. Neretnieks.


Water permeability of plant cuticles  

Microsoft Academic Search

Using the system vapor\\/membrane\\/liquid, permeability coefficients of cuticular transpiration (Pct) were determined as functions of water activity in the vapor (awv). Enzymatically isolated cuticular membranes (CM) of Citrus aurantium L. and nonisolated CM of onion bulb scales and eggplant fruits were investigated. Pct of Citrus and eggplant CM decreased with decreasing awv, while permeability coefficients of CM of onion were

J. Schönherr; H. W. Schmidt



Permeability within basaltic oceanic crust  

Microsoft Academic Search

Water-rock interactions within the seafloor are responsible for significant energy and solute fluxes between basaltic oceanic crust and the overlying ocean. Permeability is the primary hydrologic property control- ling the form, intensity, and duration of seafloor fluid circulation, but after several decades of characterizing shallow oceanic basement, we are still learning how permeability is created and distributed and how it

Andrew T. Fisher



UK Index  

NSDL National Science Digital Library

The UK Index provides a searchable index of resources in or about the United Kingdom. The Quick Reference section offers links to News Resources in the UK such as the BBC, weather information, UK record charts, and UK related USENET newsgroups. The Foreign & Commonwealth Office provides good advice for travelers. The search engine allows the selection of categories such as arts or business to restrict the search to pages included in one category or a combination of categories.


Vascular endothelial growth factor gene and protein: strong expression in thyroiditis and thyroid carcinoma  

Microsoft Academic Search

Angiogenesis is implicated in several pathological con- ditions, such as inflammation and tumor growth. Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, is a potent stimulator of endothelial cell proliferation in vitro and in vivo. The present work aimed to compare VEGF expression in human normal thyroid glands, thyroiditis tissue and thyroid carcinomas using immunohistochemistry and in

M Klein; E Picard; J-M Vignaud; B Marie; L Bresler; B Toussaint; G Weryha; A Duprez; J Lecler



Expression of Vascular Endothelial Growth Factor and Its Receptors in Hematopoietic Malignancies1  

Microsoft Academic Search

Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis by acting as a potent inducer of vascular permeability as well as serving as a specific endothelial cell mitogen. The importance of angio- genic factors such as VEGF, although clearly established in solid tumors, has not been fully elucidated in human hematopoietic neoplasms. We examined the expression of mRNA

William T. Bellamy; Lynne Richter; Yvette Frutiger; Thomas M. Grogan



When Does Magma Become Permeable?  

NASA Astrophysics Data System (ADS)

It is commonly assumed that vesiculating magma will become permeable when its porosity reaches ~ 30%, the percolation threshold for spheres. However, porosity-permeability measurements of volcanic rocks suggests that the critical porosity for permeability development varies widely, from close to 0% in mafic lava flows and domes to >95% in basaltic reticulite. These differences can be explained by consideration of magma vesiculation and degassing histories. Rapid bubble nucleation and growth within volcanic conduits during pumice- and scoria-producing eruptions generates vesicularities of 60-70% before the bubble-bubble connectivity is sufficient for permeable gas flow. When syn-eruptive expansion is constrained by conduit walls, elongation of bubbles to form tube pumice increases permeability along the elongation direction, thus permitting efficient degassing. When syn-eruptive expansion is unconstrained (as in the case of basaltic fire fountains), magma vesicularities may exceed 95% before bubble-bubble connectivity is achieved, as seen in basaltic reticulite. When syn-eruptive expansion is slow, as in the case of breadcrust bombs, the porosity threshold for permeability approaches the theoretical value of ~30% as bubble coalescence rates approach rates of bubble growth. Maximum values of permeability in these samples vary as a function of the tortuosity of permeable pathways, as determined from measurements of electrical conductivity. Deformation and collapse of bubbles during emplacement of lava flows and domes further modifies the vesicle structure from connected spheres to disk-like cracks, as indicated by low measured electrical tortuosities. The effect on permeability is a hysteresis such that the magma maintains a high permeability to much lower vesicularities than under conditions of expansion. In low crystallinity melts, this hysteresis decreases the apparent percolation threshold from >60% to ~ 30%; in high crystallinity melts it appears that the crystals may aid the development of a crack-like bubble network such that percolation thresholds drop to < 10%. We conclude that both the percolation threshold and the maximum permeability, and thus the efficiency of degassing, depend on the decompression and deformation conditions. For this reason, consideration of controls on permeability development is critical for accurately modeling magma ascent and eruption. Furthermore, our data show that both the textures and permeabilities of clasts provide important insights into eruption dynamics.

Cashman, K. V.; Wright, H. M.; Rust, A. C.



[Update on vascular dementias].  


The concept of vascular dementia greatly evolved since Hachinski's description of multi-infarct dementia. Vascular dementias are reviewed with emphasis on current diagnostic criteria, elusive natural history, neuroradiological aspects, difficult epidemiological features and intriguing links with Alzheimer's disease. The recent proposed shift from vascular dementias to a broader definition of "vascular cognitive disorders", including non demented subjects with "vascular cognitive impairment", is described, followed by a brief review of current treatments. PMID:18342055

Auriacombe, S; Amarenco, P; Baron, J-C; Ceccaldi, M; Dartigues, J-F; Lehéricy, S; Hénon, H; Hinaut, P; Orgogozo, J-M



VE-Cadherin and Endothelial Adherens Junctions: Active Guardians of Vascular Integrity.  


VE-cadherin is a component of endothelial cell-to-cell adherens junctions, and it has a key role in the maintenance of vascular integrity. During embryo development, VE-cadherin is required for the organization of a stable vascular system, and in the adult it controls vascular permeability and inhibits unrestrained vascular growth. The mechanisms of action of VE-cadherin are complex and include reshaping and organization of the endothelial cell cytoskeleton and modulation of gene transcription. Here we review some of the most important pathways through which VE-cadherin modulates vascular homeostasis and discuss the emerging concepts in the overall biological role of this protein. PMID:24044891

Giannotta, Monica; Trani, Marianna; Dejana, Elisabetta



Permeability prediction from geologic models  

SciTech Connect

Permeability is a critical parameter for the petroleum geologist. By simulating the processes of compaction and cementation in a model porous medium, the authors have gained a new understanding of how permeability is controlled in reservoir sandstones. This understanding can be used predictively for simple sandstones. The geometry of the model pore system is completely defined, so permeability can be calculated directly directly using a network model for flow. The calculation is based on first principles and is physically rigorous. In contrast to many previous efforts to predict permeability, there are no adjustable parameters in the calculations (e.g., capillary pressure data or pore system data from thin sections) are required. The model-derived porosity-permeability trend for a compacted or quartz cemented sandstone, or a sandstone having a combination of these processes, closely matches measurements on Fontainebleau sandstone samples whose permeabilities span nearly five orders of magnitude. The model also correctly predicts mercury injection measurements of pore throat size distribution for the Fontainebleau sandstone. Pore-scale geometric features of the model are found to be spatially correlated, and this departure from randomness significantly affects macroscopic properties such as permeability. The agreement between predictions and measurements suggests that spatial correlation is inherent in granular porous media and consequently, uncorrelated (or arbitrarily correlated) models of transport in such media are unlikely to be physically representative. The authors also discuss extending the model to predict properties of more complicated rocks. 51 refs., 9 figs., 1 tab.

Bryant, S.; Cade, C.; Mellor, D.



Infrared magnetic and negative-index metamaterials  

Microsoft Academic Search

Negative-index materials have attracted much attention because of their many unconventional optical properties such as negative refractive angle, phase back propagation, reversed Doppler effect and reversed Cherenkov radiation. Recently, much progress has been made in this research area such as demonstrations of negative permeability \\

Shuang Zhang



The science of negative index materials  

Microsoft Academic Search

Metamaterials are designed to have structures that make available properties not found in Nature. Their unique properties (such as negative index of refraction, n) can be extended from GHz all the way to optical frequencies. We review the scaling properties of metamaterials that have been fabricated and give negative n and negative permeability, mu. It is found that most of

Costas M. Soukoulis; Jiangfeng Zhou; Thomas Koschny; Maria Kafesaki; Eleftherios N. Economou



Design and development of multilayer vascular graft  

NASA Astrophysics Data System (ADS)

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 strength, showed that the multilayer graft possessed properties mimicking those of native vessels. Achieving these FDA-required functional properties is essential because they play critical roles in graft performances in vivo such as thrombus formation, occlusion, healing, and bleeding. In addition, cell studies and animal studies have been performed on the multilayer graft. Our results show that the multilayer graft support mimetic vascular culture of cells and the acellular graft serves as an artery equivalent in vivo to sustain the physiological conditions and promote appropriate cellular activity. In conclusion, the newly-developed hybrid multilayer graft provides a proper balance of biomechanical and biochemical properties and demonstrates the potential for the use of vascular tissue engineering and regeneration.

Madhavan, Krishna


Functional Vascular Endothelium Derived from Human Induced Pluripotent Stem Cells  

PubMed Central

Summary Vascular endothelium is a dynamic cellular interface that displays a unique phenotypic plasticity. This plasticity is critical for vascular function and when dysregulated is pathogenic in several diseases. Human genotype-phenotype studies of endothelium are limited by the unavailability of patient-specific endothelial cells. To establish a cellular platform for studying endothelial biology, we have generated vascular endothelium from human induced pluripotent stem cells (iPSCs) exhibiting the rich functional phenotypic plasticity of mature primary vascular endothelium. These endothelial cells respond to diverse proinflammatory stimuli, adopting an activated phenotype including leukocyte adhesion molecule expression, cytokine production, and support for leukocyte transmigration. They maintain dynamic barrier properties responsive to multiple vascular permeability factors. Importantly, biomechanical or pharmacological stimuli can induce pathophysiologically relevant atheroprotective or atheroprone phenotypes. Our results demonstrate that iPSC-derived endothelium possesses a repertoire of functional phenotypic plasticity and is amenable to cell-based assays probing endothelial contributions to inflammatory and cardiovascular diseases.

Adams, William J.; Zhang, Yuzhi; Cloutier, Jennifer; Kuchimanchi, Pranati; Newton, Gail; Sehrawat, Seema; Aird, William C.; Mayadas, Tanya N.; Luscinskas, Francis W.; Garcia-Cardena, Guillermo



Endogenous endothelial cell signaling systems maintain vascular stability  

PubMed Central

The function of the endothelium is to provide a network to allow delivery of oxygen and nutrients to tissues throughout the body. This network is comprised of adjacent endothelial cells which utilize adherens junction proteins such as vascular endothelial cadherin (VE-cadherin) to maintain the appropriate level of vascular permeability. The disruption of VE-cadherin interactions during pathologic settings can lead to excessive vascular leak with adverse effects. Endogenous cell signaling systems have been defined that help to maintain the proper level of vascular stability. Perhaps the best described system is Angiopoietin-1 (Ang-1). Ang-1 acting through its receptor Tie2 generates a well described set of signaling events ultimately leading to enhanced vascular stability. In this review we will focus on what is known about additional endogenous cell signaling systems that stabilize the vasculature, and using Ang-1/Tie2 as a model, we will address where our understanding of these additional systems is lacking.

London, Nyall R.; Whitehead, Kevin J.; Li, Dean Y.





A device is presented for loading and unloading fuel elements containing material fissionable by neutrons of thermal energy. The device comprises a combination of mechanical features Including a base, a lever pivotally attached to the base, an Indexing plate on the base parallel to the plane of lever rotation and having a plurality of apertures, the apertures being disposed In rows, each aperture having a keyway, an Index pin movably disposed to the plane of lever rotation and having a plurality of apertures, the apertures being disposed in rows, each aperture having a keyway, an index pin movably disposed on the lever normal to the plane rotation, a key on the pin, a sleeve on the lever spaced from and parallel to the index pin, a pair of pulleys and a cable disposed between them, an open collar rotatably attached to the sleeve and linked to one of the pulleys, a pin extending from the collar, and a bearing movably mounted in the sleeve and having at least two longitudinal grooves in the outside surface.

Kock, L.J.



Diminished vascular response to noradrenaline in experimental chronic uremia  

Microsoft Academic Search

Diminished vascular response to noradrenaline in experimental chronic uremia. The vascular response to noradrenaline (NA) of the isolated perfused hind limb, an index of resistance vessels, was studied in an experimental model of chronic uremia (NX) in the rat. In this model of NX, only a slight and insignificant rise in arterial BP was observed. Plasma NA levels, but not

Wolfgang Rascher; Albert Schömig; Volker A Kreye; Eberhard Ritz




PubMed Central

Ionic lanthanum has been used to study transepithelial ion permeation in in vitro rabbit gallbladder and intestine (ileum) by adding 1 mM La3+ to only the mucosal bathing solution. Transepithelial fluid transport electrical potential differences (p.d.), and resistances were measured. During La3+ treatment the gallbladder's rate of active solute-coupled fluid transport remained constant, the resistance increased, and the 2:1 NaCl diffusion p.d. decreased. Mucosa-to-serosa fluxes of 140La3+ were measured and indicate a finite permeability of the gallbladder to La3+. La3+ also increased the transepithelial resistance and p d. of ileum. Electron microscopic examination of La3+-treated gallbladder showed: (a) good preservation of the fine structure, (b) electron-opaque lanthanum precipitates in almost every lateral intercellular space, most frequently near the apical end of the lateral spaces close to or within the junctional complex, (c) lanthanum among the subjacent muscle and connective tissue layers, and (d) lanthanum filling almost the entire length of so-called "tight" junctions. No observations were made which unequivocally showed the penetration of lanthanum into the gallbladder cells. Electron micrographs of similar La3+-treated ilea showed lanthanum deposits penetrating the junctional complexes. These results coupled with other physiological studies indicate that the low resistance pathway for transepithelial ion permeation in gallbladder and ileum is through the tight junctions A division of salt-transporting epithelia into two main groups, those with "leaky" junctional complexes and those with tight junctional complexes, has been proposed.

Machen, Terry E.; Erlij, David; Wooding, F. B. P.



Permeable conduits for disbursing fluids  

US Patent & Trademark Office Database

Integral conduits to disburse fluids along their length, fabricated out of two materials, and a method for manufacturing such structures with permeable wall parts; characterized by extruding a profile of thermoplastic material with a lengthwise extended slitted wall (10), and where this longitudinal slit is being outfitted with a permeable material consisting of one or more layers of fabric (12, 13, 13A, 13B, 14); the sides of the fabric strips being imbedded and sandwiched in the thermoplastic wall of the conduit, lengthwise along both sides of the slit; resulting in a hollow conduit with a lengthwise extended permeable wall section. Additionally, predetermined sections of the permeable fabric can be coated to block fluid emission from these selected sections (17, 19, 21). Fabrics of varying porosity are used to control emission of fluid. A longitudinal reinforcing element (23) may be captured within the structure (24) for securement purposes.



Vascular malformations in childhood.  


Vascular malformations are inborn errors of vascular embryogenesis present at birth that should be diagnosed in childhood and, when necessary, treated to prevent later complications. The current trend is to classify these lesions according to flow characteristics and the predominant type of vascular channel affected. Given the complexity, and in many cases, the rarity, of vascular malformations, they should be managed by multidisciplinary teams at vascular anomalies centers. Furthermore, because the association between vascular malformations and certain syndromes is becoming increasingly recognized, a better understanding of these lesions will help to improve overall patient management in this setting. PMID:22483320

Del Pozo, J; Gómez-Tellado, M; López-Gutiérrez, J C



Geothermal Permeability Enhancement - Final Report  

Microsoft Academic Search

The overall objective is to apply known permeability enhancement techniques to reduce the number of wells needed and demonstrate the applicability of the techniques to other undeveloped or under-developed fields.;\\u000a;\\u000aThe Enhanced Geothermal System (EGS) concept presented in this project enhances energy extraction from reduced permeability zones in the super-heated, vapor-dominated Aidlin Field of the The Geysers geothermal reservoir.;

Joe Beall; Mark Walters



Permeability of soils in Mississippi  

USGS Publications Warehouse

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.

O'Hara, Charles G.



1986 WIPP horizon permeability measurements  

SciTech Connect

A series of permeability measurements in the WIPP facility have been planned for fiscal year 1986. These measurements are to be made by S-Cubed and SNL and follow from and supplement previous measurements. These measurements are part of the overall WIPP horizon permeability testing and are justified and described in general terms in the previously published test plan; this paper discusses the technical motivation and test design concepts of these particular measurements.

Stormont, J.



VEGFR2 and Src kinase inhibitors suppress Andes virus-induced endothelial cell permeability.  


Hantaviruses predominantly infect human endothelial cells and, in the absence of cell lysis, cause two diseases resulting from increased vascular permeability. Andes virus (ANDV) causes a highly lethal acute pulmonary edema termed hantavirus pulmonary syndrome (HPS). ANDV infection enhances the permeability of endothelial cells in response to vascular endothelial growth factor (VEGF) by increasing signaling responses directed by the VEGFR2-Src-VE-cadherin pathway, which directs adherens junction (AJ) disassembly. Here we demonstrate that inhibiting pathway-specific VEGFR2 and Src family kinases (SFKs) blocks ANDV-induced endothelial cell permeability. Small interfering RNA (siRNA) knockdown of Src within ANDV-infected endothelial cells resulted in an ?70% decrease in endothelial cell permeability compared to that for siRNA controls. This finding suggested that existing FDA-approved small-molecule kinase inhibitors might similarly block ANDV-induced permeability. The VEGFR2 kinase inhibitor pazopanib as well as SFK inhibitors dasatinib, PP1, bosutinib, and Src inhibitor 1 dramatically inhibited ANDV-induced endothelial cell permeability. Consistent with their kinase-inhibitory concentrations, dasatinib, PP1, and pazopanib inhibited ANDV-induced permeability at 1, 10, and 100 nanomolar 50% inhibitory concentrations (IC(50)s), respectively. We further demonstrated that dasatinib and pazopanib blocked VE-cadherin dissociation from the AJs of ANDV-infected endothelial cells by >90%. These findings indicate that VEGFR2 and Src kinases are potential targets for therapeutically reducing ANDV-induced endothelial cell permeability and, as a result, capillary permeability during HPS. Since the functions of VEGFR2 and SFK inhibitors are already well defined and FDA approved for clinical use, these findings rationalize their therapeutic evaluation for efficacy in reducing HPS disease. Endothelial cell barrier functions are disrupted by a number of viruses that cause hemorrhagic, edematous, or neurologic disease, and as a result, our findings suggest that VEGFR2 and SFK inhibitors should be considered for regulating endothelial cell barrier functions altered by additional viral pathogens. PMID:21177802

Gorbunova, Elena E; Gavrilovskaya, Irina N; Pepini, Timothy; Mackow, Erich R



MARCKS protein mediates hydrogen peroxide regulation of endothelial permeability  

PubMed Central

Impairment of endothelial barrier function is implicated in many vascular and inflammatory disorders. One prevalent mechanism of endothelial dysfunction is an increase in reactive oxygen species under oxidative stress. Previous reports have demonstrated that hydrogen peroxide (H2O2), a highly stable reactive oxygen species that modulates physiological signaling pathways, also enhances endothelial permeability, but the mechanism of this effect is unknown. Here, we identify the actin-binding protein myristoylated alanine-rich C-kinase substrate (MARCKS) as a key mediator of the H2O2-induced permeability change in bovine aortic endothelial cells. MARCKS knockdown and H2O2 treatment alter the architecture of the actin cytoskeleton in endothelial cells, and H2O2 induces the phosphorylation and translocation of MARCKS from the cell membrane to the cytosol. Using pharmacological inhibitors and small interference RNA constructs directed against specific proteins, we uncover a signaling cascade from Rac1 to Abl1, phospholipase C?1, and PKC? that is triggered by H2O2 and leads to MARCKS phosphorylation. Our findings establish a distinct role for MARCKS in the regulation of H2O2-induced permeability change in endothelial cells, and suggest potential new therapeutic targets for the treatment of disorders involving oxidative stress and altered endothelial permeability.

Jin, Benjamin Y.; Lin, Alison J.; Golan, David E.; Michel, Thomas



Opening the flood-gates: how neutrophil-endothelial interactions regulate permeability  

PubMed Central

Many diseases have an inflammatory component, where neutrophil interactions with the vascular endothelium lead to barrier dysfunction and increased permeability. Neutrophils increase permeability through secreted products like the chemokines CXCL1, 2, 3 and 8, through adhesion-dependent processes like ?2 integrins interacting with endothelial ICAM-1, and combinations, where ?2 integrin engagement leads to degranulation and secretion of heparin-binding protein (HBP), which in turn increases permeability. Some neutrophil products like arachidonic acid or leukotriene (LT)A4 are further processed by endothelial enzymes through transcellular metabolism before the resulting products thromboxane A2, LTB4 or LTC4 can activate their cognate receptors. Neutrophils also generate reactive oxygen species that induce vascular leakage. This review focuses on the mechanisms of neutrophil-mediated leakage.

DiStasi, Matthew R.; Ley, Klaus



Vascular cognitive impairment  

Microsoft Academic Search

Opinion statement  Vascular cognitive impairment encompasses a spectrum of clinically defined syndromes ranging from vascular cognitive impairment-no\\u000a dementia, to vascular dementia. The underlying cerebrovascular pathology includes both overt infarction as well as rarefaction\\u000a of gray and white matter. Alzheimer’s pathology may coexist with vascular pathology. Diagnosis rests on identifying acquired\\u000a cognitive impairment in the setting of documented cerebrovascular disease, based on

Laura Pedelty; David L. Nyenhuis



Angiopoietin-2 is critical for cytokine-induced vascular leakage.  


Genetic experiments (loss-of-function and gain-of-function) have established the role of Angiopoietin/Tie ligand/receptor tyrosine kinase system as a regulator of vessel maturation and quiescence. Angiopoietin-2 (Ang-2) acts on Tie2-expressing resting endothelial cells as an antagonistic ligand to negatively interfere with the vessel stabilizing effects of constitutive Ang-1/Tie-2 signaling. Ang-2 thereby controls the vascular response to inflammation-inducing as well as angiogenesis-inducing cytokines. This study was aimed at assessing the role of Ang-2 as an autocrine (i.e. endothelial-derived) regulator of rapid vascular responses (within minutes) caused by permeability-inducing agents. Employing two independent in vivo assays to quantitatively assess vascular leakage (tracheal microsphere assay, 1-5 min and Miles assay, 20 min), the immediate vascular response to histamine, bradykinin and VEGF was analyzed in Ang-2-deficient (Ang-2(-/-)) mice. In comparison to the wild type control mice, the Ang2(-/-) mice demonstrated a significantly attenuated response. The Ang-2(-/-) phenotype was rescued by systemic administration (paracrine) of an adenovirus encoding Ang-2. Furthermore, cytokine-induced intracellular calcium influx was impaired in Ang-2(-/-) endothelioma cells, consistent with reduced phospholipase activation in vivo. Additionally, recombinant human Ang-2 (rhAng-2) alone was unable to induce vascular leakage. In summary, we report here in a definite genetic setting that Ang-2 is critical for multiple vascular permeability-inducing cytokines. PMID:23940579

Benest, Andrew V; Kruse, Karoline; Savant, Soniya; Thomas, Markus; Laib, Anna M; Loos, Elias K; Fiedler, Ulrike; Augustin, Hellmut G



Tetraspanins and vascular functions  

PubMed Central

Tetraspanins are multiple membrane-spanning proteins that likely function as the organizers of membrane microdomains. Tetraspanins associate with other membrane-bound molecules such as cell-adhesion proteins, growth factor receptors, and Ig superfamily members and regulate key cellular processes such as adhesion, migration, and fusion. Tetraspanins are widely expressed in vascular and haematopoietic cells and are involved in both physiological and pathological processes related to angiogenesis, vascular injury, thrombosis, and haemostasis. A wide body of evidence suggests that tetraspanins directly regulate the development and functions of the vascular system and the pathogenesis of vascular diseases. This article reviews current understanding of the roles of tetraspanins in vascular functions.

Zhang, Feng; Kotha, Jayaprakash; Jennings, Lisa K.; Zhang, Xin A.



Continuum percolation of permeable objects  

NASA Astrophysics Data System (ADS)

We study the extent to which excluded volume determines the percolation threshold for permeable elements in the continuum. An expansion due to Coniglio, De Angelis, Forlani, and Lauro exploits a similarity between the statistical mechanics of hard particles and statistics of percolation of permeable objects. This expansion shows that the expectation value of the excluded volume completely determines the threshold at lowest order in element density. Permeable rods in the continuum may be analyzed with the help of Onsager's treatment of virial coefficients for hard rods. Systems of rods provide cases in which higher-order terms will alter the proportionality of threshold to the inverse of the expected excluded volume and cases in which this proportionality remains exact.

Bug, A. L. R.; Safran, S. A.; Webman, I.



Wavelet Analysis of Permeability Anisotropy  

NASA Astrophysics Data System (ADS)

Since the permeability of porous media is anisotropic, an accurate representation of anisotropy is needed in order to reliably predict the movement of fluids and contaminants in the subsurface. We use wavelet analysis to identify principal axes of anisotropy in a porous medium and to identify the boundaries between regions with different principal axes. Wavelet analysis uses an integral transform that extracts local information at multiple scales and orientations. We have tested the technique on hypothetical two-dimensional permeability fields, and we have conducted a preliminary evaluation of the technique using laboratory-measured permeability data from a block of Massillon sandstone. We demonstrate the wavelet analysis technique for identifying principal axes of anisotropy, and we evaluate the effects of sparse data on the results.

Powell, K. L.; Neupauer, R. M.



Low-Dose Dopamine Agonist Administration Blocks Vascular Endothelial Growth Factor (VEGF)-Mediated Vascular Hyperpermeability without Altering VEGF Receptor 2Dependent Luteal Angiogenesis in a Rat Ovarian Hyperstimulation Model  

Microsoft Academic Search

No specific treatment is available for ovarian hyperstimula- tion syndrome (OHSS), the most important complication in infertile women treated with gonadotropins. OHSS is caused by increased vascular permeability (VP) through ovarian hy- persecretion of vascular endothelial growth factor (VEGF)- activating VEGF receptor 2 (VEGFR-2). We previously dem- onstrated in an OHSS rodent model that increased VP was prevented by inactivating

Raul Gomez; Miguel Gonzalez-Izquierdo; Ralf C. Zimmermann; Edurne Novella-Maestre; Isabel Alonso-Muriel; Jose Sanchez-Criado; Jose Remohi; Carlos Simon; Antonio Pellicer



Vascular cognitive impairment and vascular dementia  

Microsoft Academic Search

The criteria for vascular dementia (VaD) depend on first diagnosing dementia using Alzheimer-type criteria, upon which are superimposed vascular events, usually following a stroke model. This if often inappropriate, however, as memory loss is not always prominent in VaD. Alzheimer-type criteria will not detect these patients, and much brain injury can occur without resulting in classical features of stroke. VaD

Kenneth Rockwood



Can we predict blood brain barrier permeability of ligands using computational approaches?  


An ideal neurotherapeutics agent for central nervous system (CNS) molecular targets should cross Blood Brain Barrier (BBB) whereas peripherally acting agent should not cross BBB to avoid CNS related side effects. Hence prediction of BBB permeability index has been proved to be an efficient tool for drug discovery and development. Various experimental and computational approaches are being used in recent past for the prediction of BBB permeability and they have been successful up to some extent. However the accuracy and authenticity of these methods have been under question. The current review article attempts to answer a vital question that is, can we predict BBB permeability using computational approaches. PMID:23740390

Kumar, Rajnish; Sharma, Anju; Tiwari, Rajesh Kumar



AKAP12 regulates vascular integrity in zebrafish  

PubMed Central

The integrity of blood vessels controls vascular permeability and extravasation of blood cells, across the endothelium. Thus, the impairment of endothelial integrity leads to hemorrhage, edema, and inflammatory infiltration. However, the molecular mechanism underlying vascular integrity has not been fully understood. Here, we demonstrate an essential role for A-kinase anchoring protein 12 (AKAP12) in the maintenance of endothelial integrity during vascular development. Zebrafish embryos depleted of akap12 (akap12 morphants) exhibited severe hemorrhages. In vivo time-lapse analyses suggested that disorganized interendothelial cell-cell adhesions in akap12 morphants might be the cause of hemorrhage. To clarify the molecular mechanism by which the cell-cell adhesions are impaired, we examined the cell-cell adhesion molecules and their regulators using cultured endothelial cells. The expression of PAK2, an actin cytoskeletal regulator, and AF6, a connector of intercellular adhesion molecules and actin cytoskeleton, was reduced in AKAP12-depleted cells. Depletion of either PAK2 or AF6 phenocopied AKAP12-depleted cells, suggesting the reduction of PAK2 and AF6 results in the loosening of intercellular junctions. Consistent with this, overexpression of PAK2 and AF6 rescued the abnormal hemorrhage in akap12 morphants. We conclude that AKAP12 is essential for integrity of endothelium by maintaining the expression of PAK2 and AF6 during vascular development.

Kwon, Hyouk-Bum; Choi, Yoon Kyung; Lim, Jhong-Jae; Kwon, Seung-Hae; Her, Song; Kim, Hyun-Jin; Lim, Kyung-Joon; Ahn, Jong-Chan; Kim, Young-Myeong; Bae, Moon-Kyung; Park, Jeong Ae; Jeong, Chul-Ho; Mochizuki, Naoki



[The role of calcium for functioning of the vascular endothelium].  


The vascular endothelium plays many important functions and its mechanical failure or abnormal operation may have serious consequences to health and even life of the organism. It controls the contraction and relaxation of blood vessels, affects the inflammatory processes, immune response and blood clotting and regulation of the permeability and integrity of the vessel wall. Impaired secretion of nitric oxide and prostacyclin 2, whose secretion is calcium concentration dependent, indicates endothelial dysfunction. Calcium is very important in many processes typical for vascular endothelium and is essential for proper functioning. Oxidative stress, induction of pro-inflammatory response and, consequently, a significant increase in the production of reactive oxygen species are a cause of damage in the vascular endothelium. In this paper we will discuss selected issues concerning the functioning of the vascular endothelium in normal and pathological conditions, as well as their connection point at the regulation of calcium signaling in these cells. PMID:23662435

Drabarek, Beata; Dymkowska, Dorota



Complex vascular anomalies.  


The classification system for vascular anomalies now used by experts worldwide comprises two distinct disease entities that differ in their biologic and pathologic features: vascular tumors and vascular malformations. Vascular tumors include infantile and congenital hemangiomas, tufted angiomas, and kaposiform hemangioendotheliomas. Infantile hemangiomas, the most common vascular anomaly, generally have a predetermined life cycle (proliferation and subsequent involution). GLUT-1, a glucose transporter, is a marker for these specific lesions during all phases of development. Vascular malformations are classified according to their vascular tissue of origin and include capillary, venous, arteriovenous, lymphatic, and mixed malformations. Complex lymphatic malformations and complex mixed malformations, which may have most vascular components, are the most difficult vascular malformations to successfully treat. These lesions are present at birth and often expand or grow in response to trauma, infection, or hormonal changes. Imaging advancements have enabled more accurate assessments and improved management of vascular anomalies. In addition, many lesions are now being managed with targeted pharmacologic therapy. Propranolol and steroids are used for complex or disfiguring tumors, and new anti-angiogenesis inhibitors such as sirolimus are selectively used to treat lymphatic and venous lymphatic malformations that are poorly responsive to sclerotherapy, embolization, and surgical excision. Multimodal therapies are often essential for complex lesions and require the combined expertise of an interdisciplinary team. PMID:23989523

Azizkhan, Richard G



Measurement of braided preform permeability  

Microsoft Academic Search

Permeability is an important parameter in the simulation of resin transfer moulding (RTM) process. This is particularly so in the case of 3D braided preform reinforced composites, which have no distinct layers and consequently generally have higher levels of structural integrity than traditional laminated composites. Such braided preforms have the potential for widespread application in aerospace, marine, civil construction structures.

Xiaoqing Wu; Jialu Li; R. Ajit Shenoi



Wavelet Analysis of Permeability Anisotropy  

Microsoft Academic Search

Since the permeability of porous media is anisotropic, an accurate representation of anisotropy is needed in order to reliably predict the movement of fluids and contaminants in the subsurface. We use wavelet analysis to identify principal axes of anisotropy in a porous medium and to identify the boundaries between regions with different principal axes. Wavelet analysis uses an integral transform

K. L. Powell; R. M. Neupauer



Increasing permeability of subsurface formations  

Microsoft Academic Search

This is a method of increasing permeability of a fractured formation to fluid flow by depositing in the fractures a single layer or less of solid particle-form, propping agents of preselected size and strength. A large volume of nonpenetrating fluid which has been treated to control leakoff is injected to lenghten and seal the fracture walls. Conventional size sand is

W. J. Jr. McGuire; L. R. Kern



Sphingolipids in lung endothelial biology and regulation of vascular integrity.  


Of the multiple and diverse homeostatic events that involve the lung vascular endothelium, participation in preserving vascular integrity and therefore organ function is paramount. We were the first to show that the lipid growth factor and angiogenic factor, sphingosine-1-phosphate, is a critical agonist involved in regulation of human lung vascular barrier function (Garcia et al. J Clin Invest, 2011). Utilizing both in vitro models and preclinical murine, rat, and canine models of acute and chronic inflammatory lung injury, we have shown that S1Ps, as well as multiple S1P analogues such as FTY720 and ftysiponate, serve as protective agents limiting the disruption of the vascular EC monolayer in the pulmonary microcirculation and attenuate parenchymal accumulation of inflammatory cells and high protein containing extravasated fluid, thereby reducing interstitial and alveolar edema. The vasculo-protective mechanism of these therapeutic effects occurs via ligation of specific G-protein-coupled receptors and an intricate interplay of S1P with other factors (such as MAPKS, ROCKs, Rho, Rac1) with rearrangement of the endothelial cytoskeleton to form strong cortical actin rings in the cell periphery and enhanced cell-to-cell and cell-to-matrix tethering dynamics. This cascade leads to reinforcement of focal adhesions and paracellular junctional complexes via cadherin, paxillin, catenins, and zona occludens. S1P through its interaction with Rac and Rho influences the cytoskeletal rearrangement indicated in the later stages of angiogenesis as a stabilizing force, preventing excessive vascular permeability. These properties translate into a therapeutic potential for acute and chronic inflammatory lung injuries. S1P has potential for providing a paradigm shift in the approach to disruption of critical endothelial gatekeeper function, loss of lung vascular integrity, and increased vascular permeability, defining features of acute lung injury (ALI), and may prove to exhibit an intrinsically protective role in the pulmonary vasculature ameliorating agonist- or sepsis-induced pulmonary injury and vascular leakage. PMID:23563658

Abbasi, Taimur; Garcia, Joe G N



Simultaneous imaging of tumor oxygenation and microvascular permeability using Overhauser enhanced MRI  

PubMed Central

Architectural and functional abnormalities of blood vessels are a common feature in tumors. A consequence of increased vascular permeability and concomitant aberrant blood flow is poor delivery of oxygen and drugs, which is associated with treatment resistance. In the present study, we describe a strategy to simultaneously visualize tissue oxygen concentration and microvascular permeability by using a hyperpolarized 1H-MRI, known as Overhauser enhanced MRI (OMRI), and an oxygen-sensitive contrast agent OX63. Substantial MRI signal enhancement was induced by dynamic nuclear polarization (DNP). The DNP achieved up to a 7,000% increase in MRI signal at an OX63 concentration of 1.5 mM compared with that under thermal equilibrium state. The extent of hyperpolarization is influenced mainly by the local concentration of OX63 and inversely by the tissue oxygen level. By collecting dynamic OMRI images at different hyperpolarization levels, local oxygen concentration and microvascular permeability of OX63 can be simultaneously determined. Application of this modality to murine tumors revealed that tumor regions with high vascular permeability were spatio-temporally coincident with hypoxia. Quantitative analysis of image data from individual animals showed an inverse correlation between tumor vascular leakage and median oxygen concentration. Immunohistochemical analyses of tumor tissues obtained from the same animals after OMRI experiments demonstrated that lack of integrity in tumor blood vessels was associated with increased tumor microvascular permeability. This dual imaging technique may be useful for the longitudinal assessment of changes in tumor vascular function and oxygenation in response to chemotherapy, radiotherapy, or antiangiogenic treatment.

Matsumoto, Shingo; Yasui, Hironobu; Batra, Sonny; Kinoshita, Yuichi; Bernardo, Marcelino; Munasinghe, Jeeva P.; Utsumi, Hideo; Choudhuri, Rajani; Devasahayam, Nallathamby; Subramanian, Sankaran; Mitchell, James B.; Krishna, Murali C.



VEGF Is Involved in the Increase of Dermal Microvascular Permeability Induced by Tryptase  

PubMed Central

Tryptases are predominantly mast cell-specific serine proteases with pleiotropic biological activities and play a critical role in skin allergic reactions, which are manifested with rapid edema and increases of vascular permeability. The exact mechanisms of mast cell tryptase promoting vascular permeability, however, are unclear and, therefore, we investigated the effect and mechanism of tryptase or human mast cells (HMC-1) supernatant on the permeability of human dermal microvascular endothelial cells (HDMECs). Both tryptase and HMC-1 supernatant increased permeability of HDMECs significantly, which was resisted by tryptase inhibitor APC366 and partially reversed by anti-VEGF antibody and SU5614 (catalytic inhibitor of VEGFR). Furthermore, addition of tryptase to HDMECs caused a significant increase of mRNA and protein levels of VEGF and its receptors (Flt-1 and Flk-1) by Real-time RT-PCR and Western blot, respectively. These results strongly suggest an important role of VEGF on the permeability enhancement induced by tryptase, which may lead to novel means of controlling allergic reaction in skin.

Bai, Qianming; Li, Xiaobo; Wang, Xinhong; Xu, Yali; Wang, Li; Zhang, Qingyong; Yin, Lianhua



Slit2-Robo4 receptor responses inhibit ANDV directed permeability of human lung microvascular endothelial cells.  


Hantaviruses nonlytically infect human endothelial cells (ECs) and cause edematous and hemorrhagic diseases. Andes virus (ANDV) causes hantavirus pulmonary syndrome (HPS), and Hantaan virus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS). Hantaviruses enhance vascular endothelial growth factor directed EC permeability resulting in the disassembly of inter-endothelial cell adherens junctions (AJs). Recent studies demonstrate that Slit2 binding to Robo1/Robo4 receptors on ECs has opposing effects on AJ disassembly and vascular fluid barrier functions. Here we demonstrate that Slit2 inhibits ANDV and HTNV induced permeability and AJ disassembly of pulmonary microvascular ECs (PMECs) by interactions with Robo4. In contrast, Slit2 had no effect on the permeability of ANDV infected human umbilical vein ECs (HUVECs). Analysis of Robo1/Robo4 expression determined that PMECs express Robo4, but not Robo1, while HUVECs expressed both Robo4 and Robo1 receptors. SiRNA knockdown of Robo4 in PMECs prevented Slit2 inhibition of ANDV induced permeability demonstrating that Robo4 receptors determine PMEC responsiveness to Slit2. Collectively, this data demonstrates a selective role for Slit2/Robo4 responses within PMECs that inhibits ANDV induced permeability and AJ disassembly. These findings suggest Slit2s utility as a potential HPS therapeutic that stabilizes the pulmonary endothelium and antagonizes ANDV induced pulmonary edema. PMID:23702092

Gorbunova, Elena E; Gavrilovskaya, Irina N; Mackow, Erich R



Permeability in Damaged Porous Rocks  

NASA Astrophysics Data System (ADS)

A new damage model is proposed to assess permeability changes in deformable cracked porous rocks. It is assumed that cracks do not interact. The damage variable may thus be defined as the spectral decomposition of the second-order crack density tensor. Cracks do not intersect but they are connected to the natural porous network. Therefore, damage increases the intrinsic permeability of the porous medium at the scale of the Representative Elementary Volume (REV). A multi-scale approach is adopted to quantify the influence of anisotropic damage on the intrinsic permeability tensor. The thermodynamic framework encompasses both saturated and unsaturated porous media. In this latter case, three stress state variables are required to fully describe the material’s state. Assuming the solid phase to be incompressible makes it possible to resort to two stress state variables only. The stress/strain relationship is derived from Helmholtz free energy. The damage evolution function depends on tensile strains. The intrinsic permeability is split in a natural component and in a damaged component. This latter is first computed by assuming that the flow in cracks is laminar and oriented in the plane of the cracks. In a second stage, the permeability model is improved to account for flow occurring in the direction normal to the crack planes. Computations are presented for saturated rocks. Drained and undrained triaxial compression tests are simulated. Different materials are examined: granite, claystone and sandstone. The results are finally compared with the predictions of the THHMD model previously developed by the first author [1]. The models performance is discussed in the aim of assessing the Excavation Damaged Zone (EDZ).

Arson, C. F.; Pereira, J.



HABP2 is a Novel Regulator of Vascular Integrity  

PubMed Central

Objective We evaluated the role of the extracellular serine protease, Hyaluronic Acid Binding Protein 2 (HABP2), in vascular barrier regulation. Methods and Results Using immunoblot and immunohistochemical analysis, we observed that lipopolysaccharide (LPS)-induces HABP2 expression in murine lung endothelium in vivo and in human pulmonary microvascular endothelial cell (HPMVEC) in vitro. High molecular weight hyaluronan (HMW-HA, ~1 million Da) decreased HABP2 protein expression in HPMVEC and decreased purified HABP2 enzymatic activity whereas low MW HA (LMW-HA, ~2,500 Da) increased these activities. The effects of LMW-HA on HABP2 activity, but not HMW-HA, were inhibited with a peptide of the polyanion binding domain (PABD) of HABP2. Silencing (siRNA) HABP2 expression augmented HMW-HA-induced EC barrier enhancement and inhibited LPS and LMW-HA-mediated EC barrier disruption, results which were reversed with overexpression of HABP2. Silencing PAR receptors 1 and 3, RhoA or ROCK expression attenuated LPS, LMW-HA and HABP2-mediated EC barrier disruption. Utilizing murine models of acute lung injury, we observed that LPS- and ventilator-induced pulmonary vascular hyper-permeability were significantly reduced with vascular silencing (siRNA) of HABP2. Conclusions HABP2 negatively regulates vascular integrity via activation of PAR receptor/RhoA/ROCK signaling and represents a potentially useful therapeutic target for syndromes of increased vascular permeability.

Mambetsariev, N.; Mirzapoiazova, T.; Mambetsariev, B.; Sammani, S.; Lennon, F.E.; Garcia, J.G.N.; Singleton, P.A.



Infrared magnetic and negative-index metamaterials  

NASA Astrophysics Data System (ADS)

Negative-index materials have attracted much attention because of their many unconventional optical properties such as negative refractive angle, phase back propagation, reversed Doppler effect and reversed Cherenkov radiation. Recently, much progress has been made in this research area such as demonstrations of negative permeability "metamaterials" in the rf and microwave regimes, and the predictions and demonstrations (largely in the rf) of negative index materials (and predictions of diffraction-less "perfect" imaging in these materials). In this dissertation, fabrication and characterization of several novel metal-based metamaterial that show unconventional IR/optical properties are discussed. While metals provide a negative permittivity at frequencies below the plasma frequency, naturally occurring materials with negative permeability at optical frequencies are not available. Composite electromagnetic materials with resonant structures with sizes much less than the wavelength can act as an effective homogeneous media with a negative permeability. One widely used structure to achieve negative permeability in rf is the so called "split ring resonator" (SRR) proposed by Pendry. By using SRR, the highest resonant frequency that has been obtained is around 1 THz. The complexity of SRR makes it difficult to be further scaled down to reach magnetic resonance at infrared frequencies, even with electron beam lithography. As part of this dissertation, the fabrication, characterization and modeling of arrays of a new nanostructure design with resonances in the mid-IR region and properties that demonstrate strong magnetic activity indicative of negative permeability are described. This is the first experimental work on negative permeability reported in the mid-IR. In addition, interferometric lithography (IL) combined with self-aligned semiconductor processing techniques were used for the fabrication, leading to large area samples with good uniformity. By combining structures with magnetic response and electrical response, a negative refractive index metamaterial is designed and fabricated using IL. The refractive index of the fabricated structure is obtained uniquely from the experimental results by measuring both the amplitude and phase of the transmission and reflectance. This is the first demonstration of negative index metamaterials in the near-IR, about 4 orders of magnitude shorter than previously reported work. Furthermore, parametric studies and experimental results show that better design with very low loss can be achieved, which might lead to more useful applications.

Zhang, Shuang


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

PubMed Central

Purpose We apply positron emission tomography 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. Experimental Design Albumin and liposomes were labeled with 64Cu (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. Results 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 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 1–18% ID/cc compared with 1–9% 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. Conclusions 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.

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.



Drug permeability prediction using PMF method.  


Drug permeability determines the oral availability of drugs via cellular membranes. Poor permeability makes a drug unsuitable for further development. The permeability may be estimated as the free energy change that the drug should overcome through crossing membrane. In this paper the drug permeability was simulated using molecular dynamics method and the potential energy profile was calculated with potential of mean force (PMF) method. The membrane was simulated using DPPC bilayer and three drugs with different permeability were tested. PMF studies on these three drugs show that doxorubicin (low permeability) should pass higher free energy barrier from water to DPPC bilayer center while ibuprofen (high permeability) has a lower energy barrier. Our calculation indicates that the simulation model we built is suitable to predict drug permeability. PMID:23104229

Meng, Fancui; Xu, Weiren



Advances in Permeable Reactive Barrier Technologies.  

National Technical Information Service (NTIS)

Permeable reactive barriers (PRBs) are passive groundwater treatment systems that decontaminate groundwater as it flows through a permeable treatment medium under natural gradients. PRBs currently are being used to treat a wide variety of groundwater cont...



Evaluation of Permeable Reactive Barrier Performance.  

National Technical Information Service (NTIS)

Permeable reactive barriers (PRB) are developing into an entire new class of technologies for groundwater remediation. A permeable barrier is a porous 'barrier' that is placed in the path of a groundwater plume, in various configurations. The barrier, or ...



Regulation of paracellular permeability: factors and mechanisms.  


Epithelial permeability is composed of transcellular permeability and paracellular permeability. Paracellular permeability is controlled by tight junctions (TJs). Claudins and occludin are two major transmembrane proteins in TJs, which directly determine the paracellular permeability to different ions or large molecules. Intracellular signaling pathways including Rho/Rho-associated protein kinase, protein kinase Cs, and mitogen-activated protein kinase, modulate the TJ proteins to affect paracellular permeability in response for diverse stimuli. Cytokines, growth factors and hormones in organism can regulate the paracellular permeability via signaling pathway. The transcellular transporters such as Na-K-ATPase, Na(+)-coupled transporters and chloride channels, can interact with paracellular transport and regulate the TJs. In this review, we summarized the factors affecting paracellular permeability and new progressions of the related mechanism in recent studies, and pointed out further research areas. PMID:24062072

Hu, Yan-Jun; Wang, Yi-Dong; Tan, Fu-Qing; Yang, Wan-Xi



Mitochondrial Heat Shock Protein-90 Modulates Vascular Smooth Muscle Cell Survival and the Vascular Injury Response in Vivo  

PubMed Central

The healing response of blood vessels from the vascular injury induced by therapeutic interventions is characterized by increased cellularity and tissue remodeling. Frequently, this leads to intimal hyperplasia and lumen narrowing, with significant clinical sequelae. Vascular smooth muscle cells are the primary cell type involved in this process, wherein they express a dedifferentiated phenotype that transiently resembles neoplastic transformation. Recent studies have highlighted the role of mitochondrial proteins, such as the molecular chaperone heat shock protein-90 (Hsp90), in promoting cancer cell survival, which leads to new candidate chemotherapeutic agents for neoplastic disease. Herein, we identify mitochondrial Hsp90 as a key modulator of the vascular injury response. Hsp90 expression is up-regulated in injured arteries and colocalizes with the apoptosis inhibitor, survivin, in vascular smooth muscle cell in vitro and in vivo. By using a proteomic approach, we demonstrate that targeted disruption of mitochondrial Hsp90 chaperone function in vascular smooth muscle cell leads to loss of cytoprotective client proteins (survivin and Akt), induces mitochondrial permeability, and leads to apoptotic cell death. Hsp90 targeting using a cell-permeable peptidomimetic agent resulted in marked attenuation of neointimal lesions in a murine arterial injury model. These findings suggest that mitochondrial Hsp90 chaperone function is an important regulator of intimal hyperplasia and may have implications for molecular strategies that promote the long-term patency of cardiovascular interventions.

Hoel, Andrew W.; Yu, Peng; Nguyen, Khanh P.; Sui, Xinxin; Plescia, Janet; Altieri, Dario C.; Conte, Michael S.



Relationship between the Kramers-Kronig relations and negative index of refraction  

Microsoft Academic Search

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

Alkim Akyurtlu; Adil-Gerai Kussow



The permeability of liposomes to nonelectrolytes  

Microsoft Academic Search

Summary The effect of temperature on the permeability of nonelectrolytes across liposomal membranes above and below their transition temperature has been studied by using an osmotic method. Below their transition temperature, liposomes are osmotically insensitive structures but, on addition of gramicidin A, the water permeability so increased that the permeability of solutes could be studied. The measured activation energies for

B. Eleazar Cohen



Animal Cells Reversibly Permeable to Small Molecules  

Microsoft Academic Search

A cell preparation, useful for studying the regulation of metabolism, was developed by making monolayer baby hamster kidney cells permeable. Hypertonically treated cells were permeable to nucleotides, but retained their gross cellular morphology, intact organelles, 100% of their DNA, and 91% of their total protein. The permeable cell synthesized DNA, RNA, and protein rapidly when supplied with the appropriate substrates

John J. Castellot; Michael R. Miller; Arthur B. Pardee



Research on permeable concrete interface structure  

Microsoft Academic Search

A new method of designing pervious concrete is introduced. In order to achieve high performance permeable with excellent permeation coefficient and high compressive strength, permeable concrete interface structure was modified by introducing fly ash and mineral admixture. Influence of the addition of fly ash and silica fume on the permeation coefficient and compressive strength of permeable concrete was investigated. The

Aiju Zhang; Zicheng Li; Minjuan Zhou; Yaling Cao; Bo Jiang; Shuheng Qiu



Novel additives to retard permeable flow  

SciTech Connect

Low concentrations of surfactant and cosolute in water, can selectively retard permeable flow in high permeability rocks compared to low permeability ones. This represents a way forward for more efficient areal sweep efficiency when water flooding a reservoir during improved oil recovery. (author)

Golombok, Michael [Shell Exploration and Production, Kessler Park 1, 2288 GS Rijswijk (Netherlands); Department of Mechanical Engineering, Technische Universiteit Eindhoven, 5600 MB Eindhoven (Netherlands); Crane, Carel; Ineke, Erik; Welling, Marco [Shell Exploration and Production, Kessler Park 1, 2288 GS Rijswijk (Netherlands); Harris, Jon [Shell Exploration and Production, Kessler Park 1, 2288 GS Rijswijk (Netherlands); Shell UK Ltd., North Anderson Drive, Aberdeen, AB15 6BL (United Kingdom)



Review of hydrogen isotope permeability through materials  

SciTech Connect

This report is the first part of a comprehensive summary of the literature on hydrogen isotope permeability through materials that do not readily form hydrides. While we mainly focus on pure metals with low permeabilities because of their importance to tritium containment, we also give data on higher-permeability materials such as iron, nickel, steels, and glasses.

Steward, S.A.



Experimental Determination of Permeability-Stress Relationships  

Microsoft Academic Search

Large variations in permeability are probable in most soft ferromagnetic materials subjected to stress. The magnitude of these variations depends on the direction between the applied magnetizing force and the stress. In this paper techniques are described for measuring the ac permeability under two different stress conditions. ?∥ symbolizes the permeability when magnetizing force and induction are both parallel to

L. I. Mendelsohn; E. D. Orth; P. A. Robbins



Radiation Effects on the Cytoskeleton of Endothelial Cells and Endothelial Monolayer Permeability  

SciTech Connect

Purpose: To investigate the effects of radiation on the endothelial cytoskeleton and endothelial monolayer permeability and to evaluate associated signaling pathways, which could reveal potential mechanisms of known vascular effects of radiation. Methods and Materials: Cultured endothelial cells were X-ray irradiated, and actin filaments, microtubules, intermediate filaments, and vascular endothelial (VE)-cadherin junctions were examined by immunofluorescence. Permeability was determined by the passage of fluorescent dextran through cell monolayers. Signal transduction pathways were analyzed using RhoA, Rho kinase, and stress-activated protein kinase-p38 (SAPK2/p38) inhibitors by guanosine triphosphate-RhoA activation assay and transfection with RhoAT19N. The levels of junction protein expression and phosphorylation of myosin light chain and SAPK2/p38 were assessed by Western blotting. The radiation effects on cell death were verified by clonogenic assays. Results: Radiation induced rapid and persistent actin stress fiber formation and redistribution of VE-cadherin junctions in microvascular, but not umbilical vein endothelial cells, and microtubules and intermediate filaments remained unaffected. Radiation also caused a rapid and persistent increase in microvascular permeability. RhoA-guanosine triphosphatase and Rho kinase were activated by radiation and caused phosphorylation of downstream myosin light chain and the observed cytoskeletal and permeability changes. SAPK2/p38 was activated by radiation but did not influence either the cytoskeleton or permeability. Conclusion: This study is the first to show rapid activation of the RhoA/Rho kinase by radiation in endothelial cells and has demonstrated a link between this pathway and cytoskeletal remodeling and permeability. The results also suggest that the RhoA pathway might be a useful target for modulating the permeability and other effects of radiation for therapeutic gain.

Gabrys, Dorota [Department of Radiation Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice (Poland); Greco, Olga [Cancer Research UK Tumour Microcirculation Group, Academic Unit of Surgical Oncology, University of Sheffield, School of Medicine and Biomedical Sciences, Sheffield (United Kingdom); Patel, Gaurang; Prise, Kevin M. [Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, Northern Ireland (United Kingdom); Tozer, Gillian M. [Cancer Research UK Tumour Microcirculation Group, Academic Unit of Surgical Oncology, University of Sheffield, School of Medicine and Biomedical Sciences, Sheffield (United Kingdom); Kanthou, Chryso [Cancer Research UK Tumour Microcirculation Group, Academic Unit of Surgical Oncology, University of Sheffield, School of Medicine and Biomedical Sciences, Sheffield (United Kingdom)], E-mail:



Cyclic Stretch, Reactive Oxygen Species, and Vascular Remodeling  

PubMed Central

Abstract Blood vessels respond to changes in mechanical load from circulating blood in the form of shear stress and mechanical strain as the result of heart propulsions by changes in intracellular signaling leading to changes in vascular tone, production of vasoactive molecules, and changes in vascular permeability, gene regulation, and vascular remodeling. In addition to hemodynamic forces, microvasculature in the lung is also exposed to stretch resulting from respiratory cycles during autonomous breathing or mechanical ventilation. Among various cell signaling pathways induced by mechanical forces and reported to date, a role of reactive oxygen species (ROS) produced by vascular cells receives increasing attention. ROS play an essential role in signal transduction and physiologic regulation of vascular function. However, in the settings of chronic hypertension, inflammation, or acute injury, ROS may trigger signaling events that further exacerbate smooth muscle hypercontractility and vascular remodeling associated with hypertension and endothelial barrier dysfunction associated with acute lung injury and pulmonary edema. These conditions are also characterized by altered patterns of mechanical stimulation experienced by vasculature. This review will discuss signaling pathways regulated by ROS and mechanical stretch in the pulmonary and systemic vasculature and will summarize functional interactions between cyclic stretch- and ROS-induced signaling in mechanochemical regulation of vascular structure and function. Antioxid. Redox Signal. 11, 1651–1667.



Permeability relation for periodic structures  

Microsoft Academic Search

The permeability relation for periodic porous media is studied with respect to other petrophysical parameters such as formation factor, porosity, surface-to-volume ratio, and nuclear magnetic resonance (NMR) relaxation time. All these quantities were computed for periodic structures of simple, body-centered, and face-centered cubic arrays of touching and overlapping spheres. The formation factors were calculated by using a method which is

Keh-Jim Dunn; GeraldA LaTorraca; DavidJ Bergman



Refractive index in the viscous quark-gluon plasma  

NASA Astrophysics Data System (ADS)

Under the framework of the viscous chromohydrodynamics, the gluon self-energy is derived for the quark-gluon plasma with shear viscosity. The viscous chromoelectric permittivity and chromomagnetic permeability are evaluated from the gluon self-energy, through which the chromorefraction index is investigated. The numerical analysis indicates that the chromorefractive index becomes negative in some frequency range. The starting point for that frequency range is around the chromoelectric permittivity pole, and the chromomagnetic permeability pole determines the endpoint. As ?/s increases, the frequency range for the negative refraction becomes wider.

Jiang, Bing-feng; Hou, De-fu; Li, Jia-rong; Gao, Yan-jun



[Mechanism of vascular calcification].  


Vascular calcification is clinically important in the development of cardiovascular disease. It has been suggested that apoptosis and chondro/osteogenic differentiation of vascular smooth muscle cells (VSMC) play important roles in the initiation and progression of vascular calcification. During the process of vascular calcification, growth arrest-specific gene 6 (Gas6) mediated-survival pathway is downregulated in VSMC, leading to apoptosis. Chondro/osteogenic differentiation regulated by transcription factors such as core binding factor alpha1 (Cbfa1) or msh homeo box homolog 2 (Msx2), promotes VSMC calcification. It is clear that vascular calcification is an active process regulated by various factors including Gas6, Cbfa1, or Msx2. PMID:17339734

Son, Bo-Kyung; Akishita, Masahiro



Interleukin-8 Regulates Endothelial Permeability by Down-regulation of Tight Junction but not Dependent on Integrins Induced Focal Adhesions  

PubMed Central

Interleukin-8 (IL-8) is a common inflammatory factor, which involves in various non-specific pathological processes of inflammation. It has been found that increased endothelial permeability accompanied with high expression of IL-8 at site of injured endothelium and atherosclerotic plaque at early stages, suggesting that IL-8 participated in regulating endothelial permeability in the developing processes of vascular disease. The purpose of this study is to investigate the regulation effects of IL-8 on the vascular endothelial permeability, and the mRNA and protein expression of tight junction components (i.e., ZO-1, Claudin-5 and Occludin). Endothelial cells were stimulated by IL-8 with the dose of 50, 100 and 200 ng/mL, and duration of 2, 4, 6, 8h, respectively. The mRNA and protein expression level of tight junction components with IL-8 under different concentration and duration was examined by RT-PCR and Western blot, respectively. Meanwhile, the integrins induced focal adhesions event with IL-8 stimulation was also investigated. The results showed that IL-8 regulated the permeability of endothelium by down-regulation of tight junction in a dose- and time-dependence manner, but was not by integrins induced focal adhesions. This finding reveals the molecular mechanism in the increase of endothelial cell permeability induced by IL-8, which is expected to provide a new idea as a therapeutic target in vascular diseases.

Yu, Hongchi; Huang, Xianliang; Ma, Yunlong; Gao, Min; Wang, Ou; Gao, Ting; Shen, Yang; Liu, Xiaoheng



Factors affecting relative permeabilities during simultaneous flow of oil and polymer solution through porous media  

SciTech Connect

Buckley-Leverett theory has been modified for power-law fluids and modified fractional flow curves were obtained. The Johnson, Bossler, and Nauman method was modified to calculate individual relative permeabilities in multiphase systems from experimental data obtained for fired Berea sandstone cores using kerosene and polymer solutions. Two polyacrylamide polymers, having different molecular weights, were used to prepare polymer solutions at various concentrations (500-1500 ppm). Analytical results indicate that for a constant flow rate, the polymer solution fractional flow curve is an increasing function of power-law index (n). Fractional flow curves shift to the left as the flow rate increases for shear-thinning (n < 1) fluids and to the right for shear-thickening (n > 1) fluids. The experimental results show that, in relative permeability calculations, the use of a reference permeability that is decreased by the effect of adsorbed polymer leads to overestimating the non-wetting phase relative permeability. On the other hand, a reference permeability that neglects this adsorbed layer effect leads to underestimating the relative permeability of the wetting phase. The adsorbed layer has little or no effect on the relative permeability of the non-wetting phase. Comparison of relative permeabilities with and without polymer flow suggest that the presence of an adsorbed polymer layer increases the apparent water preferential wettability of the rock. The second drainage unsteady-state data showed that the relative permeability of the wetting phase was reduced, but no effect was observed on the non-wetting phase relative permeability.

Salman, M.J.



Studies on the Increase of Capillary Permeability in Rat Skin under the Action of Pyridoxal 5' Phosphate.  

National Technical Information Service (NTIS)

The activity of pyridoxal 5'-phosphate (PLP) is described on the vascular permeability response, measured in the abdominal wall of rats from the amount of extravased Evans blue labelled with radioactive iodine 125 or 131. The PLP effect is related to hist...

N. L. M. de Garcia Agudo



Effects of Flow Patterns on the Localization and Expression of VE-Cadherin at Vascular Endothelial Cell Junctions: In vivo and in vitro Investigations  

Microsoft Academic Search

Atherosclerosis occurs preferentially at vascular curvature and branch sites where the vessel walls are exposed to fluctuating shear stress and have high endothelial permeability. Endothelial permeability is modulated by intercellular adhesion molecules such as VE-cadherin. This study was designed to elucidate the effects of different flow patterns on the localization and expression of VE-cadherin in endothelial cells (ECs) both in

Hui Miao; Ying-Li Hu; Yan-Ting Shiu; Suli Yuan; Yihua Zhao; Roland Kaunas; Yingxiao Wang; Gang Jin; Shunichi Usami; Shu Chien



Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease  

Microsoft Academic Search

Aptamers are oligonucleotide ligands that are selected for high-affinity binding to molecular targets. Pegaptanib sodium (Macugen; Eyetech Pharmaceuticals\\/Pfizer) is an RNA aptamer directed against vascular endothelial growth factor (VEGF)-165, the VEGF isoform primarily responsible for pathological ocular neovascularization and vascular permeability. After nearly a decade of preclinical development to optimize and characterize its biological effects, pegaptanib was shown in clinical

Eugene W. M. Ng; David T. Shima; Perry Calias; Emmett T. Cunningham; David R. Guyer; Anthony P. Adamis



Hypoxic induction of human vascular endothelial growth factor expression through c-Src activation  

Microsoft Academic Search

ANGIOGENESIS, the formation of new microvasculature by capillary sprouting, is crucial for tumour development1. Hypoxic regions of solid tumours produce the powerful and directly acting angiogenic protein VEGF\\/VPF (vascular endothelial growth factor\\/vascular permeability factor)2-6. We now investigate the signal transduction pathway involved in hypoxic induction of VEGF expression. Hypoxia is known to induce a tyrosine kinase cascade that results in

Debabrata Mukhopadhyay; Leonidas Tsiokas; Xiao-Mai Zhou; David Foster; Joan S. Brugge; Vikas P. Sukhatme



Vascular Access in Children  

SciTech Connect

Establishment of stable vascular access is one of the essential and most challenging procedures in a pediatric hospital. Many clinical specialties provide vascular service in a pediatric hospital. At the top of the 'expert procedural pyramid' is the pediatric interventional radiologist, who is best suited and trained to deliver this service. Growing awareness regarding the safety and high success rate of vascular access using image guidance has led to increased demand from clinicians to provide around-the-clock vascular access service by pediatric interventional radiologists. Hence, the success of a vascular access program, with the pediatric interventional radiologist as the key provider, is challenging, and a coordinated multidisciplinary team effort is essential for success. However, there are few dedicated pediatric interventional radiologists across the globe, and also only a couple of training programs exist for pediatric interventions. This article gives an overview of the technical aspects of pediatric vascular access and provides useful tips for obtaining vascular access in children safely and successfully using image guidance.

Krishnamurthy, Ganesh, E-mail:; Keller, Marc S. [Children's Hospital of Philadelphia, Department of Radiology (United States)



The vascular contribution to Alzheimer's disease  

PubMed Central

AD (Alzheimer’s disease) is a progressive neurodegenerative disease of unknown origin. Despite questions as to the underlying cause(s) of this disease, shared risk factors for both AD and atherosclerotic cardiovascular disease indicate that vascular mechanisms may critically contribute to the development and progression of both AD and atherosclerosis. An increased risk of developing AD is linked to the presence of the apoE4 (apolipoprotein E4) allele, which is also strongly associated with increased risk of developing atherosclerotic cardiovascular disease. Recent studies also indicate that cardiovascular risk factors, including elevated blood cholesterol and triacylglycerol (triglyceride), increase the likelihood of AD and vascular dementia. Lipids and lipoproteins in the circulation interact intimately with the cerebrovasculature, and may have important effects on its constituent brain microvascular endothelial cells and the adjoining astrocytes, which are components of the neurovascular unit. The present review will examine the potential mechanisms for understanding the contributions of vascular factors, including lipids, lipoproteins and cerebrovascular A? (amyloid ?), to AD, and suggest therapeutic strategies for the attenuation of this devastating disease process. Specifically, we will focus on the actions of apoE, TGRLs (triacylglycerol-rich lipoproteins) and TGRL lipolysis products on injury of the neurovascular unit and increases in blood–brain barrier permeability.

Altman, Robin; Rutledge, John C.



Peroxynitrite: a mediator of increased microvascular permeability?  


1. Increased expression of inducible nitric oxide synthase (iNOS) and subsequent elevation of nitric oxide (NO) levels at inflammatory sites have led to the suggestion that peroxynitrite (the reaction product of superoxide and NO) is involved in pro-inflammatory processes. The present study has investigated the ability of peroxynitrite to induce oedema formation in the rat cutaneous microvasculature. 2. Peroxynitrite was synthesized from hydrogen peroxide and acidified nitrite. Spectrophotometry was used to measure the concentration and breakdown of peroxynitrite. It was also used to determine maximum amounts of hydrogen peroxide and sodium nitrite remaining after synthesis. 3. Oedema formation in response to intradermally (i.d.) injected peroxynitrite, hydrogen peroxide and sodium nitrite was measured by the extravascular accumulation of i.v. [125I]-albumin in the anaesthetized rat. 4. Peroxynitrite (40, 100 and 200 nmol/site) acted in a dose-dependent manner to cause a mean (+/- SEM) increase in plasma extravasation of 24 +/- 2, 55 +/- 5 and 69 +/- 6 microL, respectively (n = 4), with resulting inflammatory oedema. Peroxynitrite induced significantly larger plasma extravasation than equivalent vehicle controls at doses of 100 (P > 0.05) and 200 nmol (P > 0.001). This increased extravasation appears to be a direct microvascular response to peroxynitrite administration and not due to either a raised pH, necessary to stabilize the peroxynitrite, or contaminating concentrations of hydrogen peroxide or sodium nitrite from which peroxynitrite is formed. 5. These results suggest that peroxynitrite acts to increase microvascular permeability and oedema formation. Therefore, peroxynitrite may mediate vascular pro-inflammatory effects in addition to its direct cytotoxic activity. PMID:9363374

Greenacre, S; Ridger, V; Wilsoncroft, P; Brain, S D



Renal permeability alteration precedes hypertension and involves bradykinin in the spontaneously hypertensive rat.  

PubMed Central

Vascular permeability disorders have been described in experimental models, as well as in human hypertension. We recently described the fact that vascular permeability to albumin is heterogeneous in the normal rat. In the present study, we examine the contents of Evans blue dye (EB) bound to albumin in selected organs of unanesthetized Wistar Kyoto (WKY) and in spontaneously hypertensive rats (SHR) at various stages of development of hypertension. EB was injected in the caudal vein of paired 4, 8, 12, and 16-wk-old WKY and SHR. Rats were killed 10 min after EB injection and extraction of the marker was measured in selected tissues. In additional 4 and 16-wk-old animals, bradykinin B1 and B2 receptor antagonists (BKA) were also injected with EB. Renal contents of EB bound to albumin were higher in the SHR than in the WKY: 196 +/- 9, 202 +/- 10, 182 +/- 7, and 196 +/- 9, compared with 158 +/- 8, 155 +/- 7, 138 +/- 7, and 118 +/- 6 micrograms/g dry tissue, in the 4, 8, 12, and 16-wk-old rats, respectively. In the 4-wk-old SHR and WKY, blood pressure values were normal and comparable, yet the alteration in EB permeability was already present in the SHR. Both BKA failed to alter the renal EB extravasation in the WKY, but the B2-BKA restored the renal permeability to control levels in the SHR. We conclude that a selective defect in the renal vascular permeability to EB developed in the SHR. Since this finding precedes hypertension and is corrected by a selective B2-BKA, it is suggested that bradykinin is involved at an early stage of the disease in the SHR.

Plante, G E; Bissonnette, M; Sirois, M G; Regoli, D; Sirois, P



Vascular anomalies in children.  


Vascular anomalies are divided in two major categories: tumours (such as infantile hemangiomas) and malformations. Hemangiomas are common benign neoplasms that undergo a proliferative phase followed by stabilization and eventual spontaneous involution, whereas vascular malformations are rare structural anomalies representing morphogenetic errors of developing blood vessels and lymphatics. It is important to properly diagnose vascular anomalies early in childhood because of their distinct differences in morbidity, prognosis and need for a multidisciplinary management. We discuss a number of characteristic clinical features as clues for early diagnosis and identification of associated syndromes. PMID:22090176

Weibel, L



Src family kinases as mediators of endothelial permeability: effects on inflammation and metastasis  

Microsoft Academic Search

Src family kinases (SFKs) are signaling enzymes that have long been recognized to regulate critical cellular processes such\\u000a as proliferation, survival, migration, and metastasis. Recently, considerable work has elucidated mechanisms by which SFKs\\u000a regulate normal and pathologic processes in vascular biology, including endothelial cell proliferation and permeability. Further,\\u000a when inappropriately activated, SFKs promote pathologic inflammatory processes and tumor metastasis, in

M. P. Kim; S. I. Park; S. Kopetz; G. E. Gallick



Assessing vascular endothelial function using frequency and rank order statistics  

NASA Astrophysics Data System (ADS)

Using frequency and rank order statistics (FROS), this study analyzed the fluctuations in arterial waveform amplitudes recorded from an air pressure sensing system before and after reactive hyperemia (RH) induction by temporary blood flow occlusion to evaluate the vascular endothelial function of aged and diabetic subjects. The modified probability-weighted distance (PWD) calculated from the FROS was compared with the dilatation index (DI) to evaluate its validity and sensitivity in the assessment of vascular endothelial function. The results showed that the PWD can provide a quantitative determination of the structural changes in the arterial pressure signals associated with regulation of vascular tone and blood pressure by intact vascular endothelium after the application of occlusion stress. Our study suggests that the use of FROS is a reliable noninvasive approach to the assessment of vascular endothelial degeneration in aging and diabetes.

Wu, Hsien-Tsai; Hsu, Po-Chun; Sun, Cheuk-Kwan; Liu, An-Bang; Lin, Zong-Lin; Tang, Chieh-Ju; Lo, Men-Tzung



Vascular inflammation and endothelial dysfunction in fracture healing.  


Angiogenesis is an important step in bone fracture healing. In this article, we report on the healing of long bone fractures, and the involvement of the vascular and the inflammatory systems in the process. We conducted a prospective study of 20 healthy adults with traumatic long bone fracture. One week after fracture, and then 1 month later, we evaluated markers of inflammation: vascular responsiveness (brachial endothelial function and ankle brachial index) and inflammatory and cytokine levels osteopontin [OPN], E-selectin, and vascular endothelial growth factor [VEGF]). Long bone fractures caused intense vascular and inflammatory responses, represented by high levels of OPN, Eselectin, and VEGF. In vivo measurements demonstrated severe endothelial dysfunction, which could support the idea that the vascular system is recruited to build new blood vessels that support bone regeneration. PMID:22482094

Blum, Arnon; Zarqh, Oleg; Peleg, Aviva; Sirchan, Rizak; Blum, Nava; Salameh, Yosef; Ganaem, Maged



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

PubMed Central

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 diagnosis of brain microvascular pathology and potentially predict associated neurological sequelae. Finally, the algorithm could be implemented for intraoperative evaluation of micovascular integrity in other organs or during animal experiments.

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



tPA regulates pulmonary vascular activity through NMDA receptors  

PubMed Central

Tissue-type plasminogen activator (tPA) is a potent fibrinolytic enzyme used to treat acute coronary artery obstruction. However, tPA has shown limited utility in other disorders caused by thrombotic vascular occlusion, such as pulmonary embolism. We found that tPA caused dose-dependent effects on the contractility of pulmonary arterial rings that may affect its effectiveness as a thrombolytic agent. At low concentrations (1 nM), tPA stimulated pulmonary vascular contraction in response to phenylephrine, whereas at higher concentrations (20 nM) tPA inhibited pulmonary arterial contractility and promoted pulmonary vascular permeability through an interaction between its “docking site” and N-methyl d-aspartate receptor type 1 (NMDA-R1) expressed by pulmonary arteries. A hexapeptide derived from plasminogen activator inhibitor type 1 that blocked the docking site of tPA, but not its catalytic activity, inhibited its interaction with NMDA-R1, abolished inhibition of pulmonary artery contractility, attenuated vascular permeability, and facilitated fibrinolysis in a murine model of pulmonary embolism. Similar outcomes were seen using a tPA variant that lacks the docking site but retains catalytic activity. These data suggest that it is feasible to attenuate the deleterious extrafibrinolytic effects of tPA and improve its benefit:risk profile in the management of pulmonary embolism.

Nassar, Taher; Bdeir, Khalil; Yarovoi, Serge; Fanne, Rami Abu; Murciano, Juan-Carlos; Idell, Steven; Allen, Timothy Craig; Cines, Douglas B.



Women and Vascular Disease  


... People Are Talking: Know Your Treatment Options! Social Media Connect With ... as peripheral vascular disease (PVD), is a very common condition affecting 12–20 percent of Americans age 65 and ...


Society for Vascular Medicine  


... an initiative of the ABIM Foundation. SVM Seeks Journal Editor SVM is now seeking applicants for the ... Vascular Lab: Accreditation & More A program for lab technical and medical directors! Free to SVM Members! Everyone ...


Implications of Vascular Aging  

PubMed Central

Chronological age is a well established risk factor for the development of cardiovascular diseases. The changes that accumulate in the vasculature with age, though, are highly variable. It is now increasingly recognized that indices of vascular health are more reliable than age per se in predicting adverse cardiovascular outcomes. The variation in the accrual of these age-related vascular changes is a function of multiple genetic and environmental factors. In this review, we highlight some of the pathophysiological mechanisms that characterize the vascular aging phenotype. Furthermore, we provide an overview of the key outcome studies that address the value of these vascular health indices in general and discuss potential effects on perioperative cardiovascular outcomes.

Barodka, Viachaslau M.; Joshi, Brijen L.; Berkowitz, Dan E.; Hogue, Charles W.; Nyhan, Daniel



Understanding Pulmonary Vascular Disease  


... the major types of pulmonary vascular disease follows: Pulmonary Embolism A pulmonary embolism happens when the blood flow through the lung's ... pain, fainting and a rapid heart rate. A pulmonary embolism can damage the heart, and if not treated ...


Treatment of Vascular Injury.  

National Technical Information Service (NTIS)

The invention generally relates to the use of fibroblast growth factor ligands conjugated to cytotoxic agents in a manner to inhibit undesired cell proliferation, and more specifically, to the treatment of patients who have experienced vascular injury or ...

W. Casscells



Vascular Microenvironment in Gliomas  

Microsoft Academic Search

\\u000a Structural and functional abnormalities of the vascular microenvironment determine pathophysiological characteristics of gliomas,\\u000a such as loss of blood-brain barrier function, tumor cell invasiveness, or permselectivity for large molecules. Moreover, the\\u000a effectiveness of various therapeutic strategies critically depends upon the successful transvascular delivery of molecules.\\u000a In order to shed more light on the vascular microenvironment in gliomas, a variety of experimental

Peter Vajkoczy; Michael D. Menger


Permeability of a Cell Membrane Junction  

PubMed Central

The ion permeability of the membrane junctions between Chironomus salivary gland cells is strongly depressed by treatments that are generally known to inhibit energy metabolism. These treatments include prolonged cooling at 6°–8°C, and exposure to dinitrophenol, cyanide, oligomycin, and N-ethylmaleimide. Intracellular injection of ATP appears to prevent depression of junctional permeability by dinitrophenol or to reverse it. Ouabain, azide, p-chloromercuriphenylsulfonic acid, reserpine, and acetazolamide fail to depress junctional permeability. Thus the ion permeability of the junctional membranes appears to depend on energy provided by oxidative phosphorylation. Possible energy-linked processes for maintaining junctional permeability are discussed, including processes involving transport of permeability-modifying species such as Ca++.

Politoff, A. L.; Socolar, S. J.; Loewenstein, W. R.



Non-magnetic materials with negative refractive index  

NASA Astrophysics Data System (ADS)

We develop a new approach to materials with negative refraction index which can be implemented for optical and infrared frequencies. In contrast to conventional designs which require simultaneously negative dielectric permittivity and magnetic permeability, our system is intrinsically non-magnetic and makes use of an anisotropic dielectric constant to provide negative refractive index in waveguide geometry. The proposed approach is not limited to the proximity of a resonance and thus allows for low loss, critical for super-lensing applications.

Narimanov, Evgenii E.; Alekseyev, Leonid V.; Podolskiy, Viktor A.



Tumor-derived expression of vascular endothelial growth factor is a critical factor in tumor expansion and vascular function.  


There is considerable controversy concerning the importance of tumor-derived angiogenic factors to the neovascularization of solid tumors. Tumor, endothelial, and stromal expression of vascular endothelial growth factor (VEGF) have been hypothesized to be critical for tumor angiogenesis. To determine the relative contribution of tumor versus nontransformed tissue expression of VEGF to tumor growth, we used gene targeting and cre-loxP recombination to generate embryonic stem cell lines in which VEGF can be conditionally deleted. These lines were used to derive mouse embryonic fibroblast lines with null mutations in both alleles of VEGF. Upon immortalization and H-ras transformation, we used these VEGF null fibroblasts to make fibrosarcomas in immunocompromised mice. We report that tumorigenic VEGF expression is critical for ras-mediated tumorigenesis, and the loss of tumorigenic expression causes dramatic decreases in vascular density and vascular permeability and increases in tumor cell apoptosis. PMID:10197634

Grunstein, J; Roberts, W G; Mathieu-Costello, O; Hanahan, D; Johnson, R S



Vascular endothelial growth factor in the serum of patients with non-small cell lung cancer: correlation with platelet and leukocyte counts  

Microsoft Academic Search

Background: Vascular endothelial growth factor (VEGF) is a potent angiogenic peptide expressed in a wide variety of tumors, and it stimulates angiogenesis and increases vascular permeability. Increased expression of VEGF may be associated with advanced stage and poor prognosis in patients with non-small cell lung cancer (NSCLC). Methods: Using enzyme-linked immunosorbent assay, the levels of VEGF were determined in serum

Jin-Hyuk Choi; Hugh Chul Kim; Ho-Yeong Lim; Dong Ki Nam; Hyun Soo Kim; Jong Wook Yi; Mison Chun; Young Taek Oh; Seunghee Kang; Kwang Joo Park; Sung Chul Hwang; Yi Hyeong Lee; Myung Ho Hahn



Brain permeability of inhaled corticosteroids.  


The aim of this study was to evaluate if the permeability of inhaled corticosteroids entering the brain is reduced and if P-glycoprotein (P-gp) transporters are involved. Currently employed inhaled corticosteroids were given intravenously and intratracheally to rats at a dose of 100 microg kg-1. An ex-vivo receptor binding assay was used to monitor over 12 h the glucocorticoid receptor occupancy in the brain and a systemic reference organ (kidney). The involvement of P-gp in the brain permeability of triamcinolone acetonide was assessed in wild-type mice and mdr1a(-/-) knockout mice (mice lacking the gene for expressing P-gp). After both forms of administration, the average brain receptor occupancies were 20-56% of those of the reference organ, with the more lipophilic drugs showing a more pronounced receptor occupation. While the receptor occupancies in the liver of wild-type and mdr1a(-/-) mice were similar after administration of triamcinolone acetonide, brain receptor occupancies in mdr1a(-/-) mice were significantly greater (mdr1a(-/-): 47.6%, 40.2-55.0%, n=14; 2; wild-type: 11.5+/-33.0%, n=14; 3). Penetration into the brain for inhaled corticosteroids (especially those of lower lipophilicity) is reduced. Experiments in mdr1a(-/-) mice confirmed the involvement of P-gp transporters. Further studies are needed to assess whether potential drug interactions at the transporter level are of pharmacological significance. PMID:16105236

Arya, Vikram; Issar, Manish; Wang, Yaning; Talton, James D; Hochhaus, Guenther



Evaluation of vertical permeability anisotropy in fractured reservoirs  

SciTech Connect

In fractured reservoir flow simulations, the vertical permeability anisotropy ratio (Kv/Kh) is one of the most poorly defined input parameters. In the best cases, this ratio is obtained from well-test interpretation with partial penetration models. More generally, it is considered as a parameter that can be varied to allow matching of actual data in flow simulations. However it is obtained, extrapolation of the anisotropy ratio away from the well is difficult due to the lack of geological basis in its estimation. A more rigorous association with the fracture descriptions and structural controls is clearly required. This study presents a new approach based on stochastic fracture generation (Boolean technique) combined with upscaling techniques to calculate permeability tensors at different scales. Several geological cases are tested ([open quotes]homogeneous[close quotes] or layered reservoir) as well as the influence of many parameters: fracture form index, fracture width, and matrix permeability. For each case, the influence of fracture density is evaluated; typical curves, anisotropy ratios vs. density of fractures, are obtained, whose general form is the same, thereby allowing comparisons to be made.

Massonnat, G.J. (Elf Aquitaine, Pau (France)); Manisse, E. (Institut Physique du Globe, Strasbourg (France))



Inverse Conditional Simulation of Relative Permeabilities  

Microsoft Academic Search

The spatial variability of relative permeability curves has not attracted much attention yet. This paper addresses this issue,\\u000a and extends the self-calibration technique for the generation of absolute and relative permeabilities conditioned not only\\u000a to permeability data but also to saturation and pressure data.\\u000a \\u000a The paper starts with a sensitivity analysis presenting a synthetic example where the spatial variability of

Jame Gomez-Hernandez; Carolina Guardiola-Albert


Drug Permeability Studies in Regulatory Biowaiver Applications  

Microsoft Academic Search

The Biopharmaceutics Classification System is a drug development tool that estimates the contributions of solubility, dissolution,\\u000a and intestinal permeability affecting drug absorption from solid oral products. A regulatory guidance proposes human, animal,\\u000a and in vitro methods to determine the permeability class membership of a drug substance. Method suitability is a process to\\u000a establish and validate cellular or tissue permeability assays

Donna A. Volpe


Polysilicate esters for oil reservoir permeability control  

SciTech Connect

A method is described of recovering hydrocarbon oil from a subterranean oil-bearing formation comprising: injecting into the high permeability region or regions of the subterranean formation a permeability control agent comprising a liquid polysilicate ester, produced by the reaction of a hydroxyl group-containing organic compound with the product obtained by acidifying an alkali metal silicate, to plug the high permeability region or regions; subsequently injecting into the formation a flooding liquid; and recovering the oil from the formation.

Hoskin, D.H.; Rollman, L.D.



Predicting skin permeability from complex chemical mixtures  

SciTech Connect

Occupational and environmental exposure to topical chemicals is usually in the form of complex chemical mixtures, yet risk assessment is based on experimentally derived data from individual chemical exposures from a single, usually aqueous vehicle, or from computed physiochemical properties. We present an approach using hybrid quantitative structure permeation relationships (QSPeR) models where absorption through porcine skin flow-through diffusion cells is well predicted using a QSPeR model describing the individual penetrants, coupled with a mixture factor (MF) that accounts for physicochemical properties of the vehicle/mixture components. The baseline equation is log k {sub p} = c + mMF + a{sigma}{alpha} {sub 2} {sup H} + b{sigma}{beta} {sub 2} {sup H} + s{pi} {sub 2} {sup H} + rR {sub 2} + vV {sub x} where {sigma}{alpha} {sub 2} {sup H} is the hydrogen-bond donor acidity, {sigma}{beta} {sub 2} {sup H} is the hydrogen-bond acceptor basicity, {pi} {sub 2} {sup H} is the dipolarity/polarizability, R {sub 2} represents the excess molar refractivity, and V {sub x} is the McGowan volume of the penetrants of interest; c, m, a, b, s, r, and v are strength coefficients coupling these descriptors to skin permeability (k {sub p}) of 12 penetrants (atrazine, chlorpyrifos, ethylparathion, fenthion, methylparathion, nonylphenol, {rho}-nitrophenol, pentachlorophenol, phenol, propazine, simazine, and triazine) in 24 mixtures. Mixtures consisted of full factorial combinations of vehicles (water, ethanol, propylene glycol) and additives (sodium lauryl sulfate, methyl nicotinate). An additional set of 4 penetrants (DEET, SDS, permethrin, ricinoleic acid) in different mixtures were included to assess applicability of this approach. This resulted in a dataset of 16 compounds administered in 344 treatment combinations. Across all exposures with no MF, R{sup 2} for absorption was 0.62. With the MF, correlations increased up to 0.78. Parameters correlated to the MF include refractive index, polarizability and log (1/Henry's Law Constant) of the mixture components. These factors should not be considered final as the focus of these studies was solely to determine if knowledge of the physical properties of a mixture would improve predicting skin permeability. Inclusion of multiple mixture factors should further improve predictability. The importance of these findings is that there is an approach whereby the effects of a mixture on dermal absorption of a penetrant of interest can be quantitated in a standard QSPeR model if physicochemical properties of the mixture are also incorporated.

Riviere, Jim E. [Center for Chemical Toxicology Research and Pharmacokinetics, 4700 Hillsborough Street, North Carolina State University, Raleigh, NC 27606 (United States)]. E-mail:; Brooks, James D. [Center for Chemical Toxicology Research and Pharmacokinetics, 4700 Hillsborough Street, North Carolina State University, Raleigh, NC 27606 (United States)



Left handed metamaterials with negative index of refraction  

Microsoft Academic Search

Summary form only given. The author presents an introduction to the design and physical consequences of metamaterials with a frequency band with simultaneous negative permittivity and permeability. Negative index of refraction at microwave frequencies, and novel methods of construction are discussed.

S. Schultz



The Role of Multiferroics in the Negative Index of Refraction  

Microsoft Academic Search

We explore the possibility of realizing intrinsic far infrared negative index materials (NIM) in multiferroic crystals (crystals simultaneously possessing a ferroelectric and ferromagnetic phase) possessing electric and magnetic dipole resonances with nearby resonance frequencies, or overlapping regions of negative permittivity and permeability. We demonstrate the functionality of such a material using finite difference time domain simulations. In order to motivate

David W. Ward; Eric Statz; Kevin J. Webb; Keith A. Nelson



Index Funds Online  

NSDL National Science Digital Library

Matthew Roberts recently released Index Funds Online in response to the lack of index investment fund information on the Internet. Site features include the market performance newsletter Indexing Quarterly, background and definitional information on major US Indexes such as the S&P 500, and a library of new and interesting financial Websites, articles, and book reviews. Links to current index performance figures are also provided as well as a simple site search system and index fund discussion board.


EPA/ITRC-RTDF Permeable Reactive Barrier Short Course. Permeable Reactive Barriers: Application and Deployment.  

National Technical Information Service (NTIS)

Table of Contents: Permeable Reactive Barriers: Application and Deployment; Introduction to Permeable Reactive Barriers (PRBs) for Remediating and Managing Contaminated Groundwater in Situ; Collection and Interpretation of Design Data I: Site Characteriza...



The glycemic index and cardiovascular disease risk  

Microsoft Academic Search

Postprandial hyperglycemia is increasingly recognized as an independent risk factor for cardiovascular disease. Glycemic “spikes”\\u000a may adversely affect vascular structure and function via multiple mechanisms, including (acutely and\\/or chronically) oxidative\\u000a stress, inflammation, low-density lipoprotein oxidation, protein glycation, and procoagulant activity. Postprandial glycemia\\u000a can be reliably predicted by considering both the amount and type of carbohydrate. In particular, the glycemic index

Jennie Brand-Miller; Scott Dickinson; Alan Barclay; David Celermajer



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

PubMed Central

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.

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



Vascular cognitive impairment  

PubMed Central

The term vascular cognitive impairment (VCI) has been proposed to encompass all people with cognitive impairment of cerebrovascular origin. VCI is not a single condition, but has several clinical presentations, etiologies, and treatment. VCI forms a spectrum that includes vascular dementia, mixed Alzheimer’s disease with a vascular component, and VCI that does not meet dementia criteria. Multiple pathophysiological mechanisms contribute to VCI, accounting for its heterogeneity. Although main changes in the brain in VCI include cerebral infarcts, vascular cognitive impairment is thought to be due to factors beyond acute infarcts. Cerebral white matter lesions and silent brain infarcts are considered to be risk factors for VCI. The prevalence of VCI is high and this entity is poised to become the silent epidemic of the 21st century. Cognitive impairment due to cerebrovascular disease can to some extent be improved, and VCI prevented, if vascular risk factors are brought under control and strokes do not recur. Therefore, strategies that focus on the prevention and treatment of the cognitive impairment associated with cerebrovascular disease are high priority healthcare objectives.

Suvarna, Alladi



IFN-beta protects from vascular leakage via up-regulation of CD73.  


Changes in endothelial permeability are crucial in the pathogenesis of many diseases. Adenosine is one of the endogenous mediators controlling endothelial permeability under normal conditions, and an endothelial cell surface enzyme CD73 is a key regulator of adenosine production. Here we report that IFN-beta is a novel inducer of CD73. We found that pretreatment with IFN-beta dramatically improved the vascular barrier function in lungs after intestinal ischemia-reperfusion injury in wild-type animals in vivo. IFN-beta had absolutely no protective effects in CD73-deficient mice, which suffered from more severe lung damage than wild-type mice, showing that IFN-beta functions strictly in a CD73-dependent manner. Most importantly, IFN-beta treatment initiated after the ischemic period almost completely inhibited vascular leakage during the reperfusion. IFN-beta also induced the expression and activity of CD73 and concurrently decreased vascular permeability in cultured human pulmonary endothelial cells. These data show that induction of CD73 and improvement of vascular barrier are new mechanisms for the anti-inflammatory action of IFN-beta. Moreover, IFN-beta treatment may be useful in alleviating vascular leakage induced by ischemia-reperfusion injury. PMID:18034430

Kiss, Jan; Yegutkin, Gennady G; Koskinen, Kaisa; Savunen, Timo; Jalkanen, Sirpa; Salmi, Marko



Insulin increases glomerular filtration barrier permeability through dimerization of protein kinase G type I? subunits.  


The increase in the permeability of the glomerular barrier filtration to albumin is a well-known feature of diabetic microvasculature and a negative prognostic factor for vascular complications. However, the underlying mechanisms are incompletely understood. We demonstrated recently that superoxide anion generation increases dimerization of protein kinase G type I? (PKGI?) subunits, leading to podocyte dysfunction. Here we investigated whether high insulin concentration is involved in PKGI-dependent hyperpermeability of the diabetic glomerular filtration barrier. We assessed changes in insulin-induced glomerular permeability by measuring glomerular capillary permeability to albumin in isolated glomeruli from Wistar and obese and lean Zucker rats and transmembrane albumin flux in cultured rat podocytes. Expression of PKGI? and upstream proteins was confirmed in the podocytes using Western blotting and immunofluorescence. Insulin (300nM, 5min) increased NAD(P)H-dependent glomerular albumin permeability in Wistar rats and PKGI-dependent transmembrane albumin flux in cultured podocytes. Podocyte exposure to insulin in non-reducing conditions increased PKGI? interprotein disulfide bond formation, altered the phosphorylation of the PKG target proteins MYPT1 and MLC, and disrupted the actin cytoskeleton. The role of NADPH oxidase (NOX) in insulin-induced reactive oxygen species (ROS) generation and insulin-evoked increases in albumin permeability in podocytes was confirmed with NOX2 and NOX4 siRNA. Glomerular albumin permeability was increased in hyperinsulinemic Zucker obese rats with isolated glomeruli showing increased expression of PKGI? and NOX4. Taken together, these data demonstrate that insulin increases glomerular barrier albumin permeability via a PKGI-dependent mechanism involving NAD(P)H-dependent generation of superoxide anion. These findings reveal a role for insulin in the pathophysiology of diabetic glomerular nephropathy. PMID:23454089

Piwkowska, Agnieszka; Rogacka, Dorota; Kasztan, Ma?gorzata; Angielski, Stefan; Jankowski, Maciej



Cryopreservation of vascular tissues  

PubMed Central

Cryopreservation of human blood vessels may become an important tool in bypass surgery and peripheral vascular reconstruction. Ideally cryopreservation of a blood vessel should preserve functional characteristics comparable to those of fresh controls. The key advantage of cryopreservation is the fact that storage at deep subzero temperatures allows storage of structurally intact living vascular tissues for virtually infinite time. Originally developed for long-time storage of isolated cells, the techniques of cryopreservation of tissues are challenged by the fact that these are complex multicellular systems containing diverse types of cells with differing requirements for optimal preservation. Therefore, the post-thaw functional activity of vascular tissues is determined by the type of blood vessel and, in addition, by the cell packing effect. Moreover, evidence from pharmacological studies suggests that cryopreservation induces tissue specific changes in transmembrane signaling and the mechanisms coupling intracellular calcium release, sensitivity and calcium entry into the smooth muscle cells.



Observed Permeability Increases Generated by Seismic Waves  

Microsoft Academic Search

Earthquakes affect hydrological systems in a variety of ways: Water well levels, stream flows and spring discharge change at the time of earthquakes. Most of these hydrological observations can be explained by some form of permeability increase. However, to the best of our knowledge, direct measurements of permeability changes have never before been made for multiple earthquakes at a single,

J. E. Elkhoury; E. E. Brodsky; D. C. Agnew



Simulated fractal permeability for porous membranes  

Microsoft Academic Search

Fractal permeability model for bi-dispersed porous media is developed based on the fractal characteristics of pores in the membrane. The fractal permeability model is found to be a function of the tortuosity fractal dimension, pore area fractal dimension, sizes of particles and clusters, micro-porosity inside clusters, and the effective porosity of a medium. The pore area fractal dimension and the

M. R. Othman; Z. Helwani; Martunus



Theory of the BAT permeability test  

Microsoft Academic Search

The permeability test system arrangement for in situ measurement of the hydraulic conductivity (or permeability) is shown in figure 1. The measuring system comprises a test adapter that is equipped with a double-sided hypodermic needle and a gas\\/water container. The pressure in the container is measured with the aid of an electronic pressure transducer. The test can be carried out

A. J. G. Schellingerhout


Radionuclide assessment of pulmonary microvascular permeability  

Microsoft Academic Search

The literature has been reviewed to evaluate the technique and clinical value of radionuclide measurements of microvascular permeability and oedema formation in the lungs. Methodology, modelling and interpretation vary widely among studies. Nevertheless, most studies agree on the fact that the measurement of permeability via pulmonary radioactivity measurements of intravenously injected radiolabelled proteins versus that in the blood pool, the

A. B. Johan Groeneveld



Intestinal permeability and contractility in murine colitis.  

PubMed Central

We developed an in vitro organ bath method to measure permeability and contractility simultaneously in murine intestinal segments. To investigate whether permeability and contractility are correlated and influenced by mucosal damage owing to inflammation, BALB/c mice were exposed to a 10% dextran sulphate sodium (DSS) solution for 8 days to induce colitis. The effect of pharmacologically induced smooth muscle relaxation and contraction on permeability was tested in vitro. Regional permeability differences were observed in both control and 10% DSS-treated mice. Distal colon segments were less permeable to 3H-mannitol and 14C-PEG 400 molecules compared with proximal colon and ileum. Intestinal permeability in control vs. 10% DSS mice was not altered, although histologic inflammation score and IFN-gamma pro-inflammatory cytokine levels were significantly increased in proximal and distal colon. IL-1beta levels were enhanced in these proximal and distal segments, but not significantly different from controls. Any effect of pharmacologically induced contractility on intestinal permeability could not be observed. In conclusion, intestinal permeability and contractility are not correlated in this model of experimentally induced colitis in mice. Although simultaneous measurement in a physiological set-up is possible, this method has to be further validated.

van Meeteren, M E; van Bergeijk, J D; van Dijk, A P; Tak, C J; Meijssen, M A; Zijlstra, F J



Regulation of Water Permeability of Vacuolar Symplast  

Microsoft Academic Search

Effect of exogenous ABA and an inhibitor of energy metabolism NaN3 on water permeability of the desmotubules and tonoplast as the structural elements of vacuolar symplast ensuring water permeability of this transport system was investigated. The methodological approach based on the use of NMR with magnetic field pulse gradient is described in detail. It was shown that ABA affects water

G. A. Velikanov; L. P. Belova



Effect of Dead Algae on Soil Permeability  

SciTech Connect

Since existing basins support heavy growths of unicellular green algae which may be killed by temperature variation or by inadvertent pH changes in waste and then deposited on the basin floor, information on the effects of dead algae on soil permeability was needed. This study was designed to show the effects of successive algal kills on the permeability of laboratory soil columns.

Harvey, R.S.



A method of determination of permeability  

SciTech Connect

A method is proposed for determining permeability of coals under conditions of steady-state deformation and stationary filtration mode by employing a reference core made of gas-non-sorbing material with a known permeability. The approach has been developed to assess the time of transition to the stable filtration.

Kuznetsov, S.V.; Trofimov, V.A. [Russian Academy of Sciences, Moscow (Russian Federation)



Shedding light on the mitochondrial permeability transition.  


The mitochondrial permeability transition is an increase of permeability of the inner mitochondrial membrane to ions and solutes with an exclusion size of about 1500Da. It is generally accepted that the permeability transition is due to opening of a high-conductance channel, the permeability transition pore. Although the molecular nature of the permeability transition pore remains undefined, a great deal is known about its regulation and role in pathophysiology. This review specifically covers the characterization of the permeability transition pore by chemical modification of specific residues through photoirradiation of mitochondria after treatment with porphyrins. The review also illustrates the basic principles of the photodynamic effect and the mechanisms of phototoxicity and discusses the unique properties of singlet oxygen generated by specific porphyrins in discrete mitochondrial domains. These experiments provided remarkable information on the role, interactions and topology of His and Cys residues in permeability transition pore modulation and defined an important role for the outer membrane 18kDa translocator protein (formerly known as the peripheral benzodiazepine receptor) in regulation of the permeability transition. PMID:21377443

Ricchelli, Fernanda; Sileikyt?, Justina; Bernardi, Paolo



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


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

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



Nucleic acid indexing  


A restriction site indexing method for selectively amplifying any fragment generated by a Class II restriction enzyme includes adaptors specific to fragment ends containing adaptor indexing sequences complementary to fragment indexing sequences near the termini of fragments generated by Class II enzyme cleavage. A method for combinatorial indexing facilitates amplification of restriction fragments whose sequence is not known.

Guilfoyle, Richard A. (Madison, WI); Guo, Zhen (Bellevue, WA)



Nucleic acid indexing  


A restriction site indexing method for selectively amplifying any fragment generated by a Class II restriction enzyme includes adaptors specific to fragment ends containing adaptor indexing sequences complementary to fragment indexing sequences near the termini of fragments generated by Class II enzyme cleavage. A method for combinatorial indexing facilitates amplification of restriction fragments whose sequence is not known.

Guilfoyle, Richard A. (Madison, WI); Guo, Zhen (Bellevue, WA)



Novel role of stathmin in microtubule-dependent control of endothelial permeability  

PubMed Central

Microtubule (MT) dynamics in vascular endothelium are modulated by vasoactive mediators and are critically involved in the control of endothelial cell (EC) permeability via Rho GTPase-dependent crosstalk with the actin cytoskeleton. However, the role of regulators in MT stability in these mechanisms remains unclear. This study investigated the involvement of the MT-associated protein stathmin in the mediation of agonist-induced permeability in EC cultures and vascular leak in vivo. Thrombin treatment of human pulmonary ECs induced rapid dephosphorylation and activation of stathmin. Inhibition of stathmin activity by small interfering RNA-based knockdown or cAMP-mediated phosphorylation abrogated thrombin-induced F-actin remodeling and Rho-dependent EC hyperpermeability, while expression of a phosphorylation-deficient stathmin mutant exacerbated thrombin-induced EC barrier disruption. Stathmin suppression preserved the MT network against thrombin-induced MT disassembly and release of Rho-specific guanine nucleotide exchange factor, GEF-H1. The protective effects of stathmin knockdown were observed in vivo in the mouse 2-hit model of ventilator-induced lung injury and were linked to MT stabilization and down-regulation of Rho signaling in the lung. These results demonstrate the mechanism of stathmin-dependent control of MT dynamics, Rho signaling, and permeability and suggest novel potential pharmacological interventions in the prevention of increased vascular leak via modulation of stathmin activity.—Tian, X., Tian, Y., Sarich, N., Wu, T., Birukova, A. A. Novel role of stathmin in microtubule-dependent control of endothelial permeability.

Tian, Xinyong; Tian, Yufeng; Sarich, Nicolene; Wu, Tinghuai; Birukova, Anna A.



Composites with tuned effective magnetic permeability  

NASA Astrophysics Data System (ADS)

Pendry et al. [J. B. Pendry, A. J. Holden, D. J. Robbins, and W. J. Stewart, IEEE Trans. Microwave Theory Tech. 47, 2075 (1999)] and Smith et al. [D. R. Smith, W. J. Padilla, D. C. Vier, S. C. Nemat-Nasser, and S. Schultz, Phys. Rev. Lett. 84, 4184 (2000)] have shown that the effective magnetic permeability, ?, of free space can be rendered negative over a certain frequency range by a periodic arrangement of very thin conductors with suitable magnetic resonance properties, the so-called split-ring resonators. Because of its rather bulky architecture, this structure does not lend itself to a proper integration into a reasonably thin real composite structural panel. To remedy this fundamental barrier, we invented a new magnetic resonator consisting of very thin folded plates that are suitably nested within one another to form folded-doubled resonators (FDRs) that can be integrated into an actual composite panel. Measurements, using a focused beam electromagnetic characterization system combined with time-domain numerical simulations of the reflection and transmission coefficients of such a composite slab have revealed that indeed the composite has a negative ? over a frequency range of about 9.1-9.35 GHz [S. Nemat-Nasser, S. C. Nemat-Nasser, T. A. Plaisted, A. Starr, and A. Vakil Amirkhizi, in Biomimetics: Biologically Inspired Technologies, edited by Y. Bar Cohen (CRC Press, Boca Raton, FL, 2006)]. Thus, it has become possible to construct a structural composite panel with negative index of refraction by simultaneously creating negative effective ? and ? [V. G. Veselago, Sov. Phys. Usp. 10, 509 (1968); R. A. Shelby, D. R. Smith, and S. Schultz, Science 292, 77 (2001); A. F. Starr, P. M. Rye, D. R. Smith, and S. Nemat-Nasser, Phys. Rev. B 70, 113102 (2004)].

Amirkhizi, Alireza V.; Nemat-Nasser, Sia



Building Vascular Networks  

PubMed Central

Only a few engineered tissues—skin, cartilage, bladder—have achieved clinical success, and biomaterials designed to replace more complex organs are still far from commercial availability. This gap exists in part because biomaterials lack a vascular network to transfer the oxygen and nutrients necessary for survival and integration after transplantation. Thus, generation of a functional vasculature is essential to the clinical success of engineered tissue constructs and remains a key challenge for regenerative medicine. In this Perspective, we discuss recent advances in vascularization of biomaterials through the use of biochemical modification, exogenous cells, or microengineering technology.

Bae, Hojae; Puranik, Amey S.; Gauvin, Robert; Edalat, Faramarz; Carrillo-Conde, Brenda; Peppas, Nicholas A.; Khademhosseini, Ali



Brachial vascular reactivity in blacks.  


Endothelial function was studied ultrasonographically in a healthy subset of African Americans (blacks) because they have an increased risk of hypertension and vascular disease. Twenty-four healthy black and 28 well-matched white subjects were investigated. Ischemia was induced by inflating a cuff over the forearm to 40 mm Hg higher than systolic pressure for 5 minutes. Brachial artery diameter and blood flow velocity were measured at baseline and at 15, 45, and 60 seconds after deflation by use of an Acuson 128XP10 ultrasonograph with a 7.5 MHz transducer. Mean postischemic dilatation, an index of endothelial function, was 1.76+/-0.56% in blacks and 8.79+/-1.22% in whites (P<0.001). Median postischemic vasodilatation in black men [0% (0% to 2.86%)] was not significantly different to that in black women [0.82% (0% to 3.14%)], whereas white women [11.48% (8.70% to 14.29%)] dilated significantly more than white men [4.20% (2.13% to 5.56%)] (P<0.05). Both groups dilated significantly over baseline diameter to sublingual nitroglycerin administration 18.7+/-2.5% (blacks) and 20.2+/-3.2% (whites; P=NS). Mean hyperemic responses did not differ significantly between the 2 subject groups, nor did they differ between men and women of both ethnic groups. We conclude that endothelium-dependent vasodilatation is significantly impaired in healthy, young blacks compared with whites and that gender differences are not seen in blacks with regard to this phenomenon. An impairment in endothelium-dependent NO generation may be a contributing factor to future hypertension and vascular disease in healthy blacks. PMID:11082158

Perregaux, D; Chaudhuri, A; Rao, S; Airen, A; Wilson, M; Sung, B H; Dandona, P



Accuracy experimental study of the vascular interventional surgical robot propulsive mechanism  

Microsoft Academic Search

Accuracy is an important index of vascular interventional surgical robot system, and is influenced by the accuracies of image navigation and interventional robot, and random errors. Based on the vascular interventional surgical robot propulsive mechanism, a series of accuracy experiments are carried out, and the test results are analyzed, which validate that the propulsive mechanism satisfies the required design accuracy,

Liu Da; Dengling Liu



Taxol alleviates 2-methoxyestradiol-induced endothelial permeability.  


We have previously shown that the anti-cancer agent 2-methoxyestradiol (2ME) induces hyperpermeability across endothelial monolayers. Here, we show that both microtubule disruptor, 2ME, and microtubule stabilizer, paclitaxel (taxol), increase vascular lung permeability in vitro and in vivo. Simultaneous application of 2ME and taxol alleviates 2ME-induced endothelial barrier dysfunction, which is evident by the decreased Evans Blue Dye accumulation in lung tissue and increased transendothelial resistance across monolayers. 2ME significantly increases the level of p38 and MLC phosphorylation in both endothelial monolayers and murine lungs; this increase is suppressed in the presence of taxol. Taxol treatment leads to an immediate and sustained increase in tubulin acetylation in human pulmonary artery endothelial cells (HPAEC). Surprisingly, 2ME treatment also increases tubulin acetylation; however, the onset of this process is delayed and coincides with the stage of a partial barrier restoration in HPAEC monolayer. Inhibition of histone deacetylase 6 (HDAC6) with tubacin increases tubulin acetylation level, suppresses 2ME-induced HSP27 and MLC phosphorylation, and decreases 2ME-induced barrier dysfunction, suggesting barrier-protective and/or barrier-restorative role for tubulin acetylation in vascular endothelium. PMID:22074808

Gorshkov, Boris A; Zemskova, Marina A; Verin, Alexander D; Bogatcheva, Natalia V



Fibrinogen-induced increased pial venular permeability in mice  

PubMed Central

Elevated blood level of Fibrinogen (Fg) is commonly associated with vascular dysfunction. We tested the hypothesis that at pathologically high levels, Fg increases cerebrovascular permeability by activating matrix metalloproteinases (MMPs). Fibrinogen (4?mg/mL blood concentration) or equal volume of phosphate-buffered saline (PBS) was infused into male wild-type (WT; C57BL/6J) or MMP-9 gene knockout (MMP9?/?) mice. Pial venular leakage of fluorescein isothiocyanate-bovine serum albumin to Fg or PBS alone and to topically applied histamine (10?5?mol/L) were assessed. Intravital fluorescence microscopy and image analysis were used to assess cerebrovascular protein leakage. Pial venular macromolecular leakage increased more after Fg infusion than after infusion of PBS in both (WT and MMP9?/?) mice but was more pronounced in WT compared with MMP9?/? mice. Expression of vascular endothelial cadherin (VE-cadherin) was less and plasmalemmal vesicle-associated protein-1 (PV-1) was greater in Fg-infused than in PBS-infused both mice groups. However, in MMP9?/? mice, VE-cadherin expression was greater and PV-1 expression was less than in WT mice. These data indicate that at higher levels, Fg compromises microvascular integrity through activation of MMP-9 and downregulation of VE-cadherin and upregulation of PV-1. Our results suggest that elevated blood level of Fg could have a significant role in cerebrovascular dysfunction and remodeling.

Muradashvili, Nino; Qipshidze, Natia; Munjal, Charu; Givvimani, Srikanth; Benton, Richard L; Roberts, Andrew M; Tyagi, Suresh C; Lominadze, David



Group V phospholipase A2 increases pulmonary endothelial permeability through direct hydrolysis of the cell membrane  

PubMed Central

Acute lung injury (ALI) is characterized by inflammatory disruption of the alveolar–vascular barrier, resulting in severe respiratory compromise. Inhibition of the intercellular messenger protein, Group V phospholipase A2 (gVPLA2), blocks vascular permeability caused by LPS both in vivo and in vitro. In this investigation we studied the mechanism by which recombinant gVPLA2 increases permeability of cultured human pulmonary endothelial cells (EC). Exogenous gVPLA2 (500 nM), a highly hydrolytic enzyme, caused a significant increase in EC permeability that began within minutes and persisted for >10 hours. However, the major hydrolysis products of gVPLA2 (Lyso-PC, Lyso-PG, LPA, arachidonic acid) did not cause EC structural rearrangement or loss of barrier function at concentrations <10 ?M. Higher concentrations (? 30 ?M) of these membrane hydrolysis products caused some increased permeability but were associated with EC toxicity (measured by propidium iodide incorporation) that did not occur with barrier disruption by gVPLA2 (500 nM). Pharmacologic inhibition of multiple intracellular signaling pathways induced by gVPLA2 activity (ERK, p38, PI3K, cytosolic gIVPLA2) also did not prevent EC barrier disruption by gVPLA2. Finally, pretreatment with heparinase to prevent internalization of gVPLA2 did not inhibit EC barrier disruption by gVPLA2. Our data thus indicate that gVPLA2 increases pulmonary EC permeability directly through action as a membrane hydrolytic agent. Disruption of EC barrier function does not depend upon membrane hydrolysis products, gVPLA2 internalization, or upregulation of downstream intracellular signaling.

Munoz, Nilda M.; Desai, Anjali; Meliton, Lucille N.; Meliton, Angelo Y.; Zhou, Tingting; Leff, Alan R.; Dudek, Steven M.



Optical methods for measuring plasma membrane osmotic water permeability in cell layers  

NASA Astrophysics Data System (ADS)

Optical methods were developed to measure water permeability in cell layers and used to characterize water channel transfected cells and measure individual plasma membrane water permeabilities of epithelial cells. The general approach was to measure the rate of change of cell volume in response to osmotic gradients. Changes in solute concentration resulting from cell volume changes were used to generate optical signals. Because of the high data acquisition rates obtainable with optical instruments, very high water permeabilities found in cells containing water channels can be measured. Total internal reflection microfluorimetry was used to measure water permeability in cells grown on transparent, solid supports. The fluorescence measured from cells containing a cytosolic fluorophore was inversely proportional to cell volume. The method was applied to transfected cells which expressed water channels and to investigate a cell model of the vasopressin-regulated shuttling of AQP2. Interferometry was used to measure cell volume and water permeability in adherent or non-adherent epithelial cell layers. Volume changes were shown to alter the optical path length of light passing through a cell layer. An interferometer was used to convert the small changes in optical path length to measurable changes in intensity. Cell membrane osmotic water permeability was determined from the time course of interference signal in response to osmotic gradients. Individual plasma membrane water permeabilities of epithelial cells were measured. To overcome the difficulties associated with interferometry, a spatial filtering microscopy method was developed based on changes in transmitted light intensity in a phase contrast microscope occurring after volume changes induced by osmotic gradients. A theory based on the refractive index changes observed in cells by interferometry was developed to explain the dependence of transmitted light intensity on cell volume. The method was applied to measure water permeability in epithelial cells from human trachea and to study the vasopressin response in intact toad bladder. Together, these methods will allow the elucidation of the role of water channels in fluid transport.

Farinas, Javier Anibal


Low-loss single-layer metamaterial with negative index of refraction at visible wavelengths  

Microsoft Academic Search

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

C. García-Meca; R. Ortuño; R. Salvador; A. Martínez; J. Martí



Exact analytical treatment of the graded interfaces between positive and negative refractive index media  

Microsoft Academic Search

We investigated electrodynamics of structures incorporating composites with negative dielectric permittivity and magnetic permeability, the popular ¿left-handed metamaterials¿. We obtained the exact analytical solutions to the Helmholtz equation for gradient-index interfaces between the positive and negative index part in the special case of matched impedances of the two materials. We derived expressions for the field intensity and compared the analytical

P. Tassin; N. Dalarsson; M. Dalarsson; Z. Jaksic



Numerical study of electromagnetic waves interacting with negative index materials  

NASA Astrophysics Data System (ADS)

We study numerically the electromagnetic scattering properties of structures with negative indices of refraction. To perform this analysis, we utilize a commercial finite-element based electromagnetic solver (HFSS, Ansoft), in which a negative index material can be formed from mesh elements whose permittivity and permeability are both negative. In particular, we investigate the expected transmission characteristics of a finite beam incident on negative index prisms and lenses. We also confirm numerically the predicted superlens effect of an image formed by a planar slab with index n=-1, using two subwavelength (ë/20) slits as objects.

Kolinko, Pavel; Smith, David R.



Numerical study of electromagnetic waves interacting with negative index materials.  


We study numerically the electromagnetic scattering properties of structures with negative indices of refraction. To perform this analysis, we utilize a commercial finite-element based electromagnetic solver (HFSS, Ansoft), in which a negative index material can be formed from mesh elements whose permittivity and permeability are both negative. In particular, we investigate the expected transmission characteristics of a finite beam incident on negative index prisms and lenses. We also confirm numerically the predicted superlens effect of an image formed by a planar slab with index n=-1, using two subwavelength (ë/20) slits as objects. PMID:19461776

Kolinko, Pavel; Smith, David



[Clinical correlation of vascular parkinsonism].  


Vascular parkinsonism has not been well defined and the clinical correlation of vascular parkinsonism is still not clear. The aim of the study was to estimate prevalence of occurrence of vascular parkinsonism, analysis of risk factors leading to its development and to identify clinical features that suggest a vascular origin. 214 patients with Parkinson's disease were examined. Their ages ranged from 37 to 88 years (median 66.4 years). Evidence of vascular parkinsonism was assessed using a vascular rating scale previously described by Winikates and Jankovic. Statistical analysis was performed with Mann-Whitney U test, chi 2 Pearson test, chi 2 Yates test, Spearman rank correlation and Student's t test. Out of 214 patients 8 were proved to have developed Parkinson's disease due to vascular disease, what gave 3.74%. Out of risk factors for stroke 5 patients had hypertension, 3 had diabetes mellitus, 2 suffered from heart disease, 2 had infarctus myocardii, 1 had hyperlipidemia, 1 had atrial fibrillation. Additionally, those patients had neuroimaging (CT or MRI) evidence of vascular disease in one or more vascular territories. Patients with vascular parkinsonism were older, had shorter duration of disease, were more likely to present rigidity rather than tremor. Dementia and incontinence were more common in vascular group than in Parkinson's disease group. Patients with vascular parkinsonism were also significantly more likely to have corticospinal findings. Proving that Parkinson's disease had vascular etiology is extremely difficult. The test results are inconclusive. PMID:15098342

Honczarenko, Krystyna; Budzianowska, Anna



Relative permeabilities of plastic films to water and carbon dioxide.  


The permeabilities of several types of plastic films to water and to carbon dioxide were measured. No material was found to have a carbon dioxide permeability as great as its water permeability. PMID:16656548

Woolley, J T



Imaging chorioretinal vascular disease  

Microsoft Academic Search

Since its first description more than 40 years ago, fluorescein angiography had a crucial role in the diagnosis and management of chorioretinal vascular disorders such as neovascular age-related macular degeneration. Although fluorescein angiography permits visualization of the retinal microcirculation in exquisite detail, visualization of the choroidal circulation is more limited. Moreover, fluorescein angiography provides only minimal information regarding the functional

P A Keane; S R Sadda



Vascular air embolism.  


Vascular air embolism is a rare but potentially fatal event. It may occur in a variety of procedures and surgeries but is most often associated as an iatrogenic complication of central line catheter insertion. This article reviews the incidence, pathophysiology, diagnosis, treatment, and prevention of this phenomenon. PMID:23724390

Gordy, Stephanie; Rowell, Susan



EphB4 controls blood vascular morphogenesis during postnatal angiogenesis  

PubMed Central

Guidance molecules have attracted interest by demonstration that they regulate patterning of the blood vascular system during development. However, their significance during postnatal angiogenesis has remained unknown. Here, we demonstrate that endothelial cells of human malignant brain tumors also express guidance molecules, such as EphB4 and its ligand ephrinB2. To study their function, EphB4 variants were overexpressed in blood vessels of tumor xenografts. Our studies revealed that EphB4 acts as a negative regulator of blood vessel branching and vascular network formation, switching the vascularization program from sprouting angiogenesis to circumferential vessel growth. In parallel, EphB4 reduces the permeability of the tumor vascular system via activation of the angiopoietin-1/Tie2 system at the endothelium/pericyte interface. Furthermore, overexpression of EphB4 variants in blood vessels during (i) vascularization of non-neoplastic cell grafts and (ii) retinal vascularization revealed that these functions of EphB4 apply to postnatal, non-neoplastic angiogenesis in general. This implies that both neoplastic and non-neoplastic vascularization is driven not only by a vascular initiation program but also by a vascular patterning program mediated by guidance molecules.

Erber, Ralf; Eichelsbacher, Uta; Powajbo, Violetta; Korn, Tobias; Djonov, Valentin; Lin, Jihong; Hammes, Hans-Peter; Grobholz, Rainer; Ullrich, Axel; Vajkoczy, Peter



Coexistence of pheochromocytoma with uncommon vascular lesions  

PubMed Central

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.

Kota, Sunil Kumar; Kota, Siva Krishna; Meher, Lalit Kumar; Jammula, Sruti; Panda, Sandip; Modi, Kirtikumar D.



Fluid permeability of deformable fracture networks  

SciTech Connect

The authors consider the problem of defining the fracture permeability tensor for each grid lock in a rock mass from maps of natural fractures. For this purpose they implement a statistical model of cracked rock due to M. Oda [1985], where the permeability tensor is related to the crack geometry via a volume average of the contribution from each crack in the population. In this model tectonic stress is implicitly coupled to fluid flow through an assumed relationship between crack aperture and normal stress across the crack. The authors have included the following enhancements to the basic model: (1) a realistic model of crack closure under stress has been added along with the provision to apply tectonic stresses to the fracture system in any orientation, the application of stress results in fracture closure and consequently a reduction in permeability; (2) the fracture permeability can be superimposed onto an arbitrary anisotropic matrix permeability; (3) the fracture surfaces are allowed to slide under the application of shear stress, causing fractures to dilate and result in a permeability increase. Through an example, the authors demonstrate that significant changes in permeability magnitudes and orientations are possible when tectonic stress is applied to a fracture system.

Brown, S.R. [Sandia National Labs., Albuquerque, NM (United States). Geomechanics Dept.; Bruhn, R.L. [Univ. of Utah, Salt Lake City, UT (United States). Dept. of Geology and Geophysics



A Poroelastic Description of Permeability Evolution  

NASA Astrophysics Data System (ADS)

Pore pressure changes in a geothermal reservoir, as a result of injection and/or production of water, result in changes of stress acting on the reservoir rock and, consequently, changes in the mechanical and transport properties of the rock. Bulk modulus and permeability were measured at different pressures and temperatures. An outcropping equivalent of Rotliegend reservoir rock in the North German Basin (Flechtinger sandstone) was used to perform hydrostatic tests and steady state fluid flow tests. Permeability measurements were conducted while cycling confining pressure; the dependence of permeability on stress was determined at a constant downstream pressure of 1 MPa. Also, temperature was increased stepwise from 30 to 140 °C and crack porosity was calculated at different temperatures. Although changes in the volumes of cracks are not significant, the cracks control fluid flow pathways and, consequently, the permeability of the rock. A new model was derived which relates microstructure of porosity, the stress-strain curve, and permeability. Porosity change was described by the first derivative of the stress-strain curve. Permeability evolution was ascribed to crack closure and was related to the second derivative of the stress-strain curve. The porosity and permeability of Flechtinger sandstone were reduced by increasing the effective pressure and decreased after each pressure cycle.

Hassanzadegan, Alireza; Zimmermann, Günter



Pigment epithelium-derived factor and vascular endothelial growth factor in branch retinal vein occlusion with macular edema  

Microsoft Academic Search

Background  We investigated whether pigment epithelium-derived factor (PEDF) or vascular endothelial growth factor (VEGF) influence macular\\u000a edema in patients with branch retinal vein occlusion (BRVO). This investigation aimed to clarify the influence of PEDF in\\u000a the vitreous fluid on retinal vascular permeability in patients with macular edema secondary to BRVO. The findings were expected\\u000a to be useful for the treatment of

Hidetaka Noma; Hideharu Funatsu; Tatsuya Mimura; Seiyo Harino; Shuichiro Eguchi; Sadao Hori



Non-platelet-mediated vascular actions of 1-O-alkyl-2-acetyl- sn -3-glyceryl phosphorycholine (a synthetic PAF)  

Microsoft Academic Search

Rat platelets fully responsive to thrombin and collagen did not release3H-serotonin with up to 10 ?g\\/ml synthetic PAF. Therefore, an experimental approach using57Co and113Sn radiolabelled microspheres was developed to evaluate the effect of PAF on cardiac output (CO), peripheral vascular resistance (PVR) and redistribution of CO among organs. The effect on vascular permeability was studied by measuring the clearance of125I-HSA

M. Sánchez Crespo; F. Alonso; P. Iñarrea; J. Egido



Acute tumor vascular effects following fractionated radiotherapy in human lung cancer: In vivo whole tumor assessment using volumetric perfusion computed tomography  

SciTech Connect

Purpose: To quantitatively assess the in vivo acute vascular effects of fractionated radiotherapy for human non-small-cell lung cancer using volumetric perfusion computed tomography (CT). Methods and Materials: Sixteen patients with advanced non-small-cell lung cancer, undergoing palliative radiotherapy delivering 27 Gy in 6 fractions over 3 weeks, were scanned before treatment, and after the second (9 Gy), fourth (18 Gy), and sixth (27 Gy) radiation fraction. Using 16-detector CT, multiple sequential volumetric acquisitions were acquired after intravenous contrast agent injection. Measurements of vascular blood volume and permeability for the whole tumor volume were obtained. Vascular changes at the tumor periphery and center were also measured. Results: At baseline, lung tumor vascularity was spatially heterogeneous with the tumor rim showing a higher vascular blood volume and permeability than the center. After the second, fourth, and sixth fractions of radiotherapy, vascular blood volume increased by 31.6% (paired t test, p = 0.10), 49.3% (p = 0.034), and 44.6% (p = 0.0012) respectively at the tumor rim, and 16.4% (p = 0.29), 19.9% (p = 0.029), and 4.0% (p = 0.0050) respectively at the center of the tumor. After the second, fourth, and sixth fractions of radiotherapy, vessel permeability increased by 18.4% (p = 0.022), 44.8% (p = 0.0048), and 20.5% (p = 0.25) at the tumor rim. The increase in permeability at the tumor center was not significant after radiotherapy. Conclusion: Fractionated radiotherapy increases tumor vascular blood volume and permeability in human non-small-cell lung cancer. We have established the spatial distribution of vascular changes after radiotherapy; greater vascular changes were demonstrated at the tumor rim compared with the center.

Ng, Q.-S. [Marie Curie Research Wing, Mount Vernon Hospital, Northwood (United Kingdom); Goh, Vicky [Paul Strickland Scanner Centre, Mount Vernon Hospital, Northwood (United Kingdom); Milner, Jessica [Marie Curie Research Wing, Mount Vernon Hospital, Northwood (United Kingdom); Padhani, Anwar R. [Paul Strickland Scanner Centre, Mount Vernon Hospital, Northwood (United Kingdom); Saunders, Michele I. [Marie Curie Research Wing, Mount Vernon Hospital, Northwood (United Kingdom); Hoskin, Peter J. [Marie Curie Research Wing, Mount Vernon Hospital, Northwood (United Kingdom)]. E-mail:



Vascular continuity and auxin signals  

Microsoft Academic Search

Plant vascular tissues form systems of interconnected cell files throughout the plant body. Vascular tissues usually differentiate at predictable positions but the wide range of functional patterns generated in response to abnormal growth conditions or wounding reveals partially self-organizing patterning mechanisms. Signals ensuring aligned cell differentiation within vascular strands are crucial in self-organized vascular patterning, and the apical–basal flow of

Thomas Berleth; Jim Mattsson; Christian S Hardtke



Polysilicate esters for oil reservoir permeability control  

SciTech Connect

This patent describes a method of controlling the permeability of a subterranean, oil-bearing formation comprising the following steps: (i) acidifying an aqueous solution of an alkali metal silicate; (ii) reacting the product of step (i) with an organic, hydroxyl group-containing compound; (iii) injecting the polysilicate product of step (ii) into the high permeability region or regions of the formation to decrease the permeability thereof; (iv) injecting into the formation a flooding liquid or subjecting the formation to miscible displacement or thermal oil recovery processes; and (v) recovering the oil from the formation.

Hoskin, D.H.; Rollman, L.D.



Refractive Index of Light in the Quark-Gluon Plasma with the Hard-Thermal-Loop Perturbation Theory  

Microsoft Academic Search

The electric permittivity and magnetic permeability for the quark-gluon plasma (QGP) is calculated within the hard-thermal-loop (HTL) perturbation theory. The refractive indices in the magnetizable and non-magnetizable plasmas are calculated. In a magnetizable plasma, there is a frequency pole $\\\\omega_{mp}$ in the magnetic permeability and the refractive index. The refractive index becomes negative in the range $\\\\omega\\\\in[k,\\\\omega_{mp}]$, where $k$ is

Juan Liu; M. J. Luo; Qun Wang; Hao-jie Xu



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

NASA Astrophysics Data System (ADS)

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.

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



Glioblastoma Cell-Secreted Interleukin-8 Induces Brain Endothelial Cell Permeability via CXCR2  

PubMed Central

Glioblastoma constitutes the most aggressive and deadly of brain tumors. As yet, both conventional and molecular-based therapies have met with limited success in treatment of this cancer. Among other explanations, the heterogeneity of glioblastoma and the associated microenvironment contribute to its development, as well as resistance and recurrence in response to treatments. Increased vascularity suggests that tumor angiogenesis plays an important role in glioblastoma progression. However, the molecular crosstalk between endothelial and glioblastoma cells requires further investigation. To examine the effects of glioblastoma-derived signals on endothelial homeostasis, glioblastoma cell secretions were collected and used to treat brain endothelial cells. Here, we present evidence that the glioblastoma secretome provides pro-angiogenic signals sufficient to disrupt VE-cadherin-mediated cell-cell junctions and promote endothelial permeability in brain microvascular endothelial cells. An unbiased angiogenesis-specific antibody array screen identified the chemokine, interleukin-8, which was further demonstrated to function as a key factor involved in glioblastoma-induced permeability, mediated through its receptor CXCR2 on brain endothelia. This underappreciated interface between glioblastoma cells and associated endothelium may inspire the development of novel therapeutic strategies to induce tumor regression by preventing vascular permeability and inhibiting angiogenesis.

Dwyer, Julie; Hebda, Jagoda K.; Le Guelte, Armelle; Galan-Moya, Eva-Maria; Smith, Sherri S.; Azzi, Sandy; Bidere, Nicolas; Gavard, Julie



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

PubMed Central

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.

Reitan, Nina Kristine; Thuen, Marte; Goa, Pal Erik; de Lange Davies, Catharina



Radiation effects on the fibrinolytic system and their relation to hemorrhagic diathesis and increased endothelial permeability  

SciTech Connect

This study was designed to investigate the effects of wholebody X-irradiation on the fibrinolytic system, the causes of radiation-induced changes in plasmin (fibrinolytic) activity, and the contribution of increased plasmin activity to increased capillary (endothelial) permeability and hemorrhagic diathesis. The parameters evaluated using adult, male, Rochester ex-Wistar rats were: (1) plasmin, plasminogen, and plasminogen activator levels in plasma within one month after 425, 655, or 885 rad and at 3.5, 7 and 12 months after 425 rad, by a modified caseinolytic method; (2) tissue plasminogen activator activity (TPAA) in heart, kidneys, lungs, liver, pancreas and spleen, by a fibrin plate method (885 rad); (3) vascular permeability, by a radioisotopic method (885 rad); and (4) gross hemorrhagic response, scored for severity. The dose-dependent changes described in plasmin, plasminogen and plasminogen activator were multi-phasic. Epsilon-amino-caproic acid (0.3 gm/kg body weight) prevented the immediate and early radiation effects on these fibrinolytic components, and partially inhibited the later effects (within one month) whether administered only as a single injection before irradiation or maintained by daily water intake thereafter. The kidneys, spleen and pancreas were markedly susceptible to radiation-induced changes in TPAA. The lungs and liver showed significant changes in capillary permeability, which correlated positively with changes in vascular volume and blood plasmin and plasminogen activator levels. Increased plasmin (fibrinolytic) activity, superimposed on a hemostatic apparatus already impaired because of thrombocytopenia, contributed to hemorrhagic diathesis in acute radiation sickness.

Ballelos, E.E.



Cervico-Facial Vascular Malformations  

Microsoft Academic Search

\\u000a Craniofacial vascular lesions are best categorized into hemangiomas (i.e., showing proliferation and potential involution) and vascular malformations (i.e., not showing such behavior) [1]. While hemangiomas and PHACE syndrome will briefly be dealt with at the end of this chapter, vascular malformations are\\u000a the main focus of this paper.

Jeyaledchumy Mahadevan; Hortensia Alvarez; Pierre Lasjaunias


Vascular Dementia: A Radical Redefinition  

Microsoft Academic Search

Vascular dementia’ may be the leading cause of cognitive impairment in the world, yet there is little agreement as to what this concept encompasses or how it is defined. A critical review reaches the conclusion that the concept of ‘vascular dementia’ has become obsolete. ‘Vascular’ is too generic, and fails to identify specific etiologies which may be subject to current

Vladimir Hachinski



Correlation of soil radon and permeability with indoor radon potential in Ottawa.  


Soil gas radon and soil gas permeability measurements were conducted at 32 sites across the five most populated communities in the city of Ottawa where indoor radon measurements were available for 167 houses. A soil radon index (SRI) determined from the soil radon concentration and the soil gas permeability was used to characterise radon availability from soil to air. This study demonstrated that the average SRI in a community area correlates with the indoor radon potential (the percentage of homes above 200 Bq m(-3)) in that community. Soil gas radon concentrations together with soil gas permeability measurements can be a useful tool for the prediction of the indoor radon potential in the development of a Canadian radon risk map. PMID:19617242

Chen, Jing; Falcomer, Renato; Bergman, Lauren; Wierdsma, Jessica; Ly, Jim



The vascular depression hypothesis: mechanisms linking vascular disease with depression.  


The 'Vascular Depression' hypothesis posits that cerebrovascular disease may predispose, precipitate or perpetuate some geriatric depressive syndromes. This hypothesis stimulated much research that has improved our understanding of the complex relationships between late-life depression (LLD), vascular risk factors, and cognition. Succinctly, there are well-established relationships between LLD, vascular risk factors and cerebral hyperintensities, the radiological hallmark of vascular depression. Cognitive dysfunction is common in LLD, particularly executive dysfunction, a finding predictive of poor antidepressant response. Over time, progression of hyperintensities and cognitive deficits predicts a poor course of depression and may reflect underlying worsening of vascular disease. This work laid the foundation for examining the mechanisms by which vascular disease influences brain circuits and influences the development and course of depression. We review data testing the vascular depression hypothesis with a focus on identifying potential underlying vascular mechanisms. We propose a disconnection hypothesis, wherein focal vascular damage and white matter lesion location is a crucial factor, influencing neural connectivity that contributes to clinical symptomatology. We also propose inflammatory and hypoperfusion hypotheses, concepts that link underlying vascular processes with adverse effects on brain function that influence the development of depression. Testing such hypotheses will not only inform the relationship between vascular disease and depression, but also provide guidance on the potential repurposing of pharmacological agents that may improve LLD outcomes. PMID:23439482

Taylor, W D; Aizenstein, H J; Alexopoulos, G S



Indexed Bibliography on Tracking.  

National Technical Information Service (NTIS)

This document comprises a bibliography about tracking and related literature, with corresponding documentation in the form of indexed author and subject listings. Indexing was performed to enhance its utility as a reference. Topical subjects were distingu...

S. P. Schipani



Audio Indexing for Efficiency  

ERIC Educational Resources Information Center

This article describes Zimdex, an audio indexing system developed to solve the problem of indexing audio materials for individual instruction in the content area of the mathematics of life insurance. (Author)

Rahnlom, Harold F.; Pedrick, Lillian



Glycemic Index and Diabetes  


... food? Is the GI a better tool than carbohydrate counting? Glycemic index examples of foods. What is ... The glycemic index, or GI, measures how a carbohydrate-containing food raises blood glucose. Foods are ranked ...


Percolation model of relative permeability hysteresis  

NASA Astrophysics Data System (ADS)

A mathematical model of relative permeability hysteresis in drainage and imbibition is constructed on the basis of percolation theory. It is shown that the results are in qualitatively agreement with experimental data.

Kadet, V. V.; Galechyan, A. M.



Nitrogen Gas Permeability Tests at Avery Island.  

National Technical Information Service (NTIS)

Several nitrogen gas permeability tests have been performed at the Avery Island field site. These included a preliminary suite of tests performed at various locations around the site, tests performed in conjunction with the brine movement studies, and a s...

D. A. Blankenship R. G. Stickney



Quantitative Studies of Chloride Permeability of Concrete.  

National Technical Information Service (NTIS)

Studies were undertaken to develop a quantitative determination of chloride ion permeability in concrete based upon measuring the chloride ion migration in the concrete. The intent was to modify AASHTO standard method T-277 to measure the amount of chlori...

J. Walsh M. Sock J. Lima S. Quintin J. Fera



Abnormal intestinal permeability in Crohn's disease pathogenesis.  


Increased small intestinal permeability is a longstanding observation in both Crohn's disease patients and in their healthy, asymptomatic first-degree relatives. However, the significance of this compromised gut barrier function and its place in the pathogenesis of the disease remains poorly understood. The association between abnormal small intestinal permeability and a specific mutation in the NOD2 gene, which functions to modulate both innate and adaptive immune responses to intestinal bacteria, suggests a common, genetically determined pathway by which an abnormal gut barrier could result in chronic intestinal inflammation. Furthermore, rodent colitis models show that gut barrier defects precede the development of inflammatory changes. However, it remains possible that abnormal permeability is simply a consequence of mucosal inflammation. Further insight into whether abnormal barrier function is the cause or consequence of chronic intestinal inflammation will be crucial to understanding the role of intestinal permeability in the pathogenesis of Crohn's disease. PMID:22731729

Teshima, Christopher W; Dieleman, Levinus A; Meddings, Jon B



Turbulent friction in flows over permeable walls  

NASA Astrophysics Data System (ADS)

The experimental results of Nikuradse and the concept of hydraulically smooth, transitional, and rough flow regimes are commonly used as a benchmark for data interpretation and modeling of hydraulic resistance. However, Nikuradse's experiments were carried out in pipes with impermeable rough-walls whereas many geophysical flows occur over permeable walls and thus the permeability effects need to be quantified and accounted for. On the basis of our own experimental results, it is shown that wall permeability influences flow resistance dramatically and that the conventional ‘hydraulically-rough regime’, for which the friction factor depends only on the ratio of the roughness size to the flow thickness, does not apply to flows over permeable walls. Indeed, even at high Reynolds number (Re), the friction factor progressively increases with increasing Re. Possible mechanisms that explain this behavior, as well as the implications of these results for modeling of the friction factors and hyporheic exchange in porous-bed rivers are discussed.

Manes, C.; Pokrajac, D.; Nikora, V. I.; Ridolfi, L.; Poggi, D.



Microbial Characteristics of a Reactive Permeable Barrier.  

National Technical Information Service (NTIS)

Permeable reactive barriers for treatment of subsurface organic and inorganic contaminants is recent technology. Little research has been done to its potential problem areas and to measure long-term performance. Observed flow reductions and performance de...

K. A. Strevett M. S. Shaheed



Formation permeability damage induced by completion brines  

SciTech Connect

In a laboratory study to determine permeability changes induced by flooding large Berea and Casper sandstone cores with NaCl and KCl brine, the concentration of each brine was incrementally increased from 0 to 22 wt% and then decreased from 22 to 0 wt%. In both sandstones, the permeability to KCl brines increased noticeably with increases in KCl concentration up to 10 wt%. Permeability remained at the higher levels throughout the remainder of each flood until a critically low salinity level was reached, where dispersion of the interstitial fines took place. X-ray diffraction (XRD) analysis of the produced formation fines and scanning electron micrographs of the sandstone pore surfaces indicate that the improved permeability was primarily a result of alteration of illite in the clay minerals in the sandstones.

Azarl, M. (Halliburton Reservoir Services, Dallas, TX (US)); Leimkuhler, J.M. (Shell Offshore Inc., New Orleans, LA (US))



Mitochondria in vascular disease.  


Mitochondria are often regarded as the powerhouse of the cell by generating the ultimate energy transfer molecule, ATP, which is required for a multitude of cellular processes. However, the role of mitochondria goes beyond their capacity to create molecular fuel, to include the generation of reactive oxygen species, the regulation of calcium, and activation of cell death. Mitochondrial dysfunction is part of both normal and premature ageing, but can contribute to inflammation, cell senescence, and apoptosis. Cardiovascular disease, and in particular atherosclerosis, is characterized by DNA damage, inflammation, cell senescence, and apoptosis. Increasing evidence indicates that mitochondrial damage and dysfunction also occur in atherosclerosis and may contribute to the multiple pathological processes underlying the disease. This review summarizes the normal role of mitochondria, the causes and consequences of mitochondrial dysfunction, and the evidence for mitochondrial damage and dysfunction in vascular disease. Finally, we highlight areas of mitochondrial biology that may have therapeutic targets in vascular disease. PMID:22392270

Yu, Emma; Mercer, John; Bennett, Martin



Neurobiology of Vascular Dementia  

PubMed Central

Vascular dementia is, in its current conceptual form, a distinct type of dementia with a spectrum of specific clinical and pathophysiological features. However, in a very large majority of cases, these alterations occur in an already aged brain, characterized by a milieu of cellular and molecular events common for different neurodegenerative diseases. The cell signaling defects and molecular dyshomeostasis might lead to neuronal malfunction prior to the death of neurons and the alteration of neuronal networks. In the present paper, we explore some of the molecular mechanisms underlying brain malfunction triggered by cerebrovascular disease and risk factors. We suggest that, in the age of genetic investigation and molecular diagnosis, the concept of vascular dementia needs a new approach.

Enciu, Ana-Maria; Constantinescu, Stefan N.; Popescu, Laurentiu M.; Muresanu, Dafin F.; Popescu, Bogdan O.



[Vascular interventional radiology].  


Percutaneous transluminal recanalization of vessels (angioplasty) has been invented by radiologists. Their recent huge development may conceal 120 others endovascular interventional procedures performed by radiologists, surgeons, cardiologists, anesthetists. A variety of interventional endovascular instruments have been produced and used in a wide field of pathologies: balloons for proximal clamping, distal embolization by particles, arterial desobstruction by seeking devices, propping of vascular lumen by stenting, in situ infusion of drugs (fibrinolysis), filters, foreign body retrieval systems. Training in vascular interventional radiology must include experience with endovascular instruments, but also instruction in radiation effects and protection, practice in angiographic lab and perfect knowledge of clinical manifestations and natural history of the disease to be treated. PMID:1809485

Marache, P



Pathophysiology of vascular dementia  

PubMed Central

The concept of Vascular Dementia (VaD) has been recognized for over a century, but its definition and diagnostic criteria remain unclear. Conventional definitions identify the patients too late, miss subjects with cognitive impairment short of dementia, and emphasize consequences rather than causes, the true bases for treatment and prevention. We should throw out current diagnostic categories and describe cognitive impairment clinically and according to commonly agreed instruments that document the demographic data in a standardized manner and undertake a systematic effort to identify the underlying aetiology in each case. Increased effort should be targeted towards the concept of and criteria for Vascular Cognitive Impairment and Post-Stroke Dementia as well as for genetic factors involved, especially as these categories hold promise for early prevention and treatment.



Indexing of Feminist Periodicals  

Microsoft Academic Search

During the last twelve years there has been a phenomenal increase in the number of periodicals focusing on women's studies and feminism. Initially these titles were ignored by most indexing and abstracting services. The earliest indexing, by the Alternative Press Index and Women Studies Abstracts appeared in 1971 and 1972. Since 1975 there has been a marked increase in the

Mary Alice Sanguinetti



Dow Jones Internet Indexes  

NSDL National Science Digital Library

Dow Jones Indexes has created the Dow Jones Internet Index (DJII) to bring "an ordered perspective" to "the seeming chaos of Internet stocks." The new index includes companies that generate a minimum of 50 percent of their revenues from the Internet. Complete documentation of DJII components, data, historical values, and news are provided on-site.


Indexing multiversion databases  

Microsoft Academic Search

An ecient management of multiversion data with branched evolution is crucial for many applications. It requires databa- se designers aware of tradeos among index structures and policies. This paper defines a framework and an analysis method for understanding the behavior of dierent indexing policies. Given data and query characteristics the analysis allows determining the most suitable index structure. The analysis

Khaled Jouini; Geneviève Jomier



Generalized Partial Indexes  

Microsoft Academic Search

This paper demonstrates the use of generalized par- tial indexes for efficient query processing. We propose that partial indexes be built on those portions of the database that are statistically likely to be the most useful for query processing. We identify three classes of statistical infor- mation, and two levels at which it may be available. We describe indexing strategies

Praveen Seshadri; Arun N. Swami



Kaiser's Systematic Indexing.  

ERIC Educational Resources Information Center

|Describes a system of subject indexing developed by Julius Kaiser (1868-1927) which is based on "concretes" and "processes" to govern the form of subject headings and subdivisions. Elements of amplification, guides for the subject index, and criticism of Kaiser's systematic indexing are noted. Five sources are given. (EJS)|

Rodriguez, Robert D.



Neuroprotection in Vascular Dementia  

Microsoft Academic Search

Vascular dementia (VaD) is the second most common form of dementia after Alzheimer’s disease (AD), and one of the major causes of mental and physical disability in developed countries. As such, the identification and implementation of strategies which prevent the development of the condition or enable improvements in patients with VaD are healthcare objectives of the first order. VaD is

Eduardo Martínez-Vila; Manuel Murie-Fernández; Jaime Gállego Pérez-Larraya; Pablo Irimia



Epidemiology of Vascular Dementia  

Microsoft Academic Search

Vascular dementia (VaD) is the second commonest dementia after Alzheimer's disease (AD). Epidemiological studies of this condition suffer from many shortcomings related to definition of the disease, diagnostic criteria and assessment of subjects. The prevalence of VaD increases linearly with age and varies greatly from country to country, ranging from 1.2 to 4.2% of people over 65 years old, even

Réjean Hébert; Carol Brayne



Vascular Thoracic Outlet Syndrome  

Microsoft Academic Search

  Abstract\\u000a \\u000a The surgical treatment of 30 cases of vascular thoracic outlet syndrome (TOS) in 25 patients is presented. Patients included\\u000a 17 women and 8 men with average age of 26.1 years. The causes of compression were cervical rib (n = 16), soft tissue anomalies (n = 12), and scar tissue after clavicle fracture (n = 2). Ten subclavian artery aneurysms

Lazar B. Davidovic; Dusan M. Kostic; Nenad S. Jakovljevic; Ilija L. Kuzmanovic; Tijana M. Simic



Congenital Hepatic Vascular Malformations  

Microsoft Academic Search

\\u000a Congenital hepatic vascular malformations are rare entities that result in abnormal shunting of blood through the liver. Three\\u000a different types of shunting can occur: arteriovenous (hepatic artery to hepatic vein), arterioportal (hepatic artery to portal\\u000a vein) and portovenous (portal vein to hepatic vein). Malformations result from alterations in the formation of blood vessels\\u000a during fetal development and can occur as

Guadalupe Garcia-Tsao


Obesity and vascular compliance  

Microsoft Academic Search

Obesity has reached epidemic proportions in the United States and around the world, with an estimated prevalence of up to\\u000a 300 million persons, raising the specter of rising incidence rates of type 2 diabetes, coronary artery disease, strokes, and\\u000a other cardiovascular disorders. In recent years, measurements of vascular compliance (stiffening) and endothelial function\\u000a have been used as surrogates to predict

Sudha Ganne; Nathaniel Winer



Permeability of open-pore microcellular materials  

Microsoft Academic Search

A simple microstructure-based model is proposed for the permeability of open-pore microcellular materials. The permeability of aluminium open-pore foams produced using the replication process is measured using water or glycerine as the fluid, varying the average cell size (75 and 400 ?m) and the relative density from 12% to 32%. Data show the expected dependence on the square of the

Jean-François Despois; Andreas Mortensen



Magnetic levitation from negative permeability materials  

NASA Astrophysics Data System (ADS)

As left-handed materials and metamaterials are becoming more prevalent, we examine the effect of negative permeability upon levitation force. We first consider two half spaces of differing permeability and a point magnetic source, so that the method of images may be employed. We determine that the resulting force may be larger than for conventional magnetic materials. We then illustrate the inclusion of a finite sample thickness.

Coffey, Mark W.



Negative effective permeability in polaritonic photonic crystals  

Microsoft Academic Search

We find that a two-dimensional photonic crystal composed of polaritonic materials behaves as an effective medium with negative permeability in the micron wavelength range. The resonance in ?eff is due to the large values of &egr;(?) attained near the transverse phonon frequency ?T. The minimal wavelength for achieving an effective permeability less than ?1 in a LiTaO3 crystal, obtained by

Kerwyn Casey Huang; M. L. Povinelli; John D. Joannopoulos



Negative effective permeability in polaritonic photonic crystals  

Microsoft Academic Search

We find that a two-dimensional photonic crystal composed of polaritonic materials behaves as an effective medium with negative permeability in the micron wavelength range. The resonance in mueff is due to the large values of ?(omega) attained near the transverse phonon frequency omegaT. The minimal wavelength for achieving an effective permeability less than -1 in a LiTaO3 crystal, obtained by

Kerwyn Casey Huang; M. L. Povinelli; John D. Joannopoulos



Permeability of some fat products to moisture  

Microsoft Academic Search

Summary  Films of cocoa butter, highly hydrogenated cottonseed oil, mixtures of highly hydrogenated cottonseed oil and cottonseed oil,\\u000a chocolate liquor, and sweet milk chocolate were prepared; and their permeability to water vapor was determined by the cup\\u000a method. The permeability constant was calculated in terms of grams of water diffusing through a centimeter cube in one second\\u000a under a vapor pressure

Werner Landmann; N. V. Lovegren; R. O. Feuge



Ammonia and Urea Permeability of Mammalian Aquaporins  

Microsoft Academic Search

The humanaquaporins,AQP3,AQP7, AQP8,AQP9, and possibly AQP10, are permeable to ammonia, and AQP7, AQP9, and possibly AQP3,\\u000a are permeable to urea. In humans, these aquaporins supplement the ammonia transport of the Rhesus (Rh) proteins and the urea\\u000a transporters (UTs). The mechanism by which ammonium is transported by aquaporins is not fully resolved. A comparison of transport\\u000a equations, models, and experimental data

Thomas Litman; Rikke Søgaard; Thomas Zeuthen


Pulmonary vascular imaging  

SciTech Connect

A wide range of pulmonary vascular imaging techniques are available for the diagnostic evaluation of patients with suspected pulmonary vascular disease. The characteristics of any ideal technique would include high sensitivity and specificity, safety, simplicity, and sequential applicability. To date, no single technique meets these ideal characteristics. Conventional pulmonary angiography remains the gold standard for the diagnosis of acute thromboembolic disease despite the introduction of newer techniques such as digital subtraction angiography and magnetic resonance imaging. Improved noninvasive lower extremity venous testing methods, particularly impedance plethysmography, and ventilation-perfusion scanning can play significant roles in the noninvasive diagnosis of acute pulmonary emboli when properly applied. Ventilation-perfusion scanning may also be useful as a screening test to differentiate possible primary pulmonary hypertension from chronic thromboembolic pulmonary hypertension. And, finally, angioscopy may be a useful adjunctive technique to detect chronic thromboembolic disease and determine operability. Optimal clinical decision-making, however, will continue to require the proper interpretation of adjunctive information obtained from the less-invasive techniques, applied with an understanding of the natural history of the various forms of pulmonary vascular disease and with a knowledge of the capabilities and shortcomings of the individual techniques.

Fedullo, P.F.; Shure, D.



Vascular Lumen Formation  

PubMed Central

The vascular system developed early in evolution. It is required in large multicellular organisms for the transport of nutrients, oxygen, and waste products to and from tissues. The vascular system is composed of hollow tubes, which have a high level of complexity in vertebrates. Vasculogenesis describes the de novo formation of blood vessels, e.g., aorta formation in vertebrate embryogenesis. In contrast, angiogenesis is the formation of blood vessels from preexisting ones, e.g., sprouting of intersomitic blood vessels from the aorta. Importantly, the lumen of all blood vessels in vertebrates is lined and formed by endothelial cells. In both vasculogenesis and angiogenesis, lumen formation takes place in a cord of endothelial cells. It involves a complex molecular mechanism composed of endothelial cell repulsion at the cell–cell contacts within the endothelial cell cords, junctional rearrangement, and endothelial cell shape change. As the vascular system also participates in the course of many diseases, such as cancer, stroke, and myocardial infarction, it is important to understand and make use of the molecular mechanisms of blood vessel formation to better understand and manipulate the pathomechanisms involved.

Lammert, Eckhard; Axnick, Jennifer



Glycoconjugates and Related Molecules in Human Vascular Endothelial Cells  

PubMed Central

Vascular endothelial cells (ECs) form the inner lining of blood vessels. They are critically involved in many physiological functions, including control of vasomotor tone, blood cell trafficking, hemostatic balance, permeability, proliferation, survival, and immunity. It is considered that impairment of EC functions leads to the development of vascular diseases. The carbohydrate antigens carried by glycoconjugates (e.g., glycoproteins, glycosphingolipids, and proteoglycans) mainly present on the cell surface serve not only as marker molecules but also as functional molecules. Recent studies have revealed that the carbohydrate composition of the EC surface is critical for these cells to perform their physiological functions. In this paper, we consider the expression and functional roles of endogenous glycoconjugates and related molecules (galectins and glycan-degrading enzymes) in human ECs.

Toyoda, Masashi



Epithelial permeability reflects subclinical effects of contact lens wear  

PubMed Central

AIMS—Recently, it was reported by the authors that a single drop fluorophotometric technique for estimating corneal epithelial permeability (Pdc) to fluorescein is not sufficiently precise for monitoring permeability changes in individual patients, but may be useful for evaluating mean differences in Pdc in population based research. To determine whether this technique provides a more sensitive index of epithelial integrity compared with conventional clinical assessments, the effects of mild corneal trauma on Pdc, the slit lamp appearance of the cornea, and corneal thickness (CT) were assessed.?METHODS—After baseline slit lamp examinations (SLE) and CT measurements, one randomly chosen eye of each of 32 normal subjects underwent 1 hour of closed eye soft contact lens (CL) wear while the fellow eye served as a control (no CL). After removing the CL, the SLE and CT measurements were repeated. Then, Pdc to fluorescein was assessed using a single drop fluorophotometric method refined to enhance feasibility, precision, and accuracy.?RESULTS—The mean (95% confidence interval) difference in natural log (Pdc) between 32 pairs of eyes (CL minus no CL) was 0.341 (0.069, 0.613), p = 0.016. By contrast, none of the 32 subjects exhibited corneal epithelial disruption upon SLE with white light following the closed eye period. Also, no substantial differences were apparent in the corneal swelling response between paired eyes, mean ?CT (95% CI) = ?2.31(?7.53, 2.91) µm, p=0.37.?CONCLUSIONS—Pdc measurements, used in studies of modest sample size, appear capable of detecting average differences in corneal barrier function that remain undetectable by SLE or pachymetry.?? Keywords: contact lens; corneal epithelium; epithelial permeability; fluorophotometry; pachymetry

McNamara, N.; Fusaro, R.; Brand, R.; Polse, K.



Adrenal Androgen Dehydroepiandrosterone Sulfate Inhibits Vascular Remodeling Following Arterial Injury  

PubMed Central

Recent epidemiologic studies have suggested that serum dehydroepiandrosterone sulfate (DHEAS) levels have a significant inverse correlation with the incidence of cardiovascular diseases. However, direct evidence for the association with DHEAS and vascular disorders has not yet been explored. DHEAS significantly reduced neointima formation 28 days after surgery without altering other serum metabolite levels in a rabbit carotid balloon injury model. Immunohistochemical analyses revealed the reduction of proliferating cell nuclear antigen (PCNA) index and increase of TdT-mediated dUTP-biotin Nick End Labeling (TUNEL) index, expressing differentiated vascular smooth muscle cell (VSMC) markers in the media 7 days after surgery. In vitro, DHEAS exhibited inhibitory effects on VSMC proliferation and migration activities, inducing G1 cell cycle arrest with upregulation of one of the cyclin dependent kinase (CDK) inhibitors p16INK4a and apoptosis with activating peroxisome proliferator-activated receptor (PPAR)-? in VSMCs. DHEAS inhibits vascular remodeling reducing neointima formation after vascular injury via its effects on VSMC phenotypic modulation, functions and apoptosis upregulating p16INK4a/activating PPAR?. DHEAS may play a pathophysiological role for vascular remodeling in cardiovascular disease.

Ii, Masaaki; Hoshiga, Masaaki; Negoro, Nobuyuki; Fukui, Ryosuke; Nakakoji, Takahiro; Kohbayashi, Eiko; Shibata, Nobuhiko; Furutama, Daisuke; Ishihara, Tadashi; Hanafusa, Toshiaki; Losordo, Douglas W.; Ohsawa, Nakaaki



Increased microvascular permeability in canine endotoxic shock: protective effects of ibuprofen.  


The ability of sodium ibuprofen to prevent endotoxin-induced changes in vascular permeability was examined in an anesthetized canine model. Ibuprofen was administered i.v. (3.75 mg/kg) in two pretreatment doses before the administration of Escherichia coli endotoxin (0.5 mg/kg). Serum and left thoracic duct lymph samples were collected for measurement of total protein and separation by polyacrylamide gel electrophoresis. Four protein fractions with molecular weights (MW) ranging from 60,000 to 1,000,000 were consistently analyzed. Administration of endotoxin alone resulted in hypotension and was accompanied by an increase in microvascular permeability as evidenced by increases in lymph flow rate, protein flux, lymph/plasma protein ratio (L/P), and permeability-surface area product (PS). Pretreatment with ibuprofen attenuated the increase in permeability as reflected by significantly lower lymph flow rate, protein flux, L/P, and PS. Electrophoretic data illustrate partial to complete protection for all four MW fractions. These results suggest that endotoxin damages microvascular integrity and increases extravasation of macromolecules as great as 1,000,000 MW. This damage is attenuated significantly by pretreatment with ibuprofen. PMID:3197263

Hubbard, J D; Janssen, H F



Role of phosphodiesterases in the regulation of endothelial permeability in vitro.  

PubMed Central

Neutrophil-derived hydrogen peroxide (H2O2) is believed to play an important role in the pathogenesis of vascular injury and pulmonary edema. H2O2 time- and dose-dependently increased the hydraulic conductivity and decreased the selectivity of an endothelial cell monolayer derived from porcine pulmonary arteries. Effects of H2O2 on endothelial permeability were completely inhibited by adenylate cyclase activation with 10(-12) M cholera toxin or 0.1 microM forskolin. 10(-8) M Sp-cAMPS, a cAMP-dependent protein kinase A agonist, was similarly effective. The phosphodiesterase (PDE) inhibitors motapizone (10(-4) M), rolipram (10(-6) M), and zardaverine (10(-8) M), which specifically inhibit PDE-isoenzymes III, IV, and III/IV potently blocked H2O2-induced endothelial permeability when combined with 10(-6) M prostaglandin E1. Overall cellular cAMP content and inhibition of H2O2 effects on endothelial permeability were poorly correlated. H2O2 exposure resulted in a rapid and substantial decrease in endothelial cAMP content. The analysis of the PDE isoenzyme spectrum showed high activities of isoenzymes II, III, and IV in porcine pulmonary endothelial cells. The data suggest that adenylate cyclase activation/PDE inhibition is a powerful approach to block H2O2-induced increase in endothelial permeability. This concept appears especially valuable when endothelial PDE isoenzyme pattern and PDE inhibitor profile are matched optimally.

Suttorp, N; Weber, U; Welsch, T; Schudt, C



The Effect of a Cerebral Vasodilator, Vinpocetine, on Cerebral Vascular Resistance Evaluated by the Doppler Ultrasonic Technique in Patients with Cerebrovascular Diseases  

Microsoft Academic Search

Changes in cerebral vascular resistance were examined in patients with cerebral circulatory diseases by the Doppler ultrasonic technique after administration of a cerebral vasodilator, vinpocetine, for two months.Continuous index (CI) and pulsatility index (PI) of the blood flow pattern in the internal carotid artery were used as objective parameters for changes in cerebral vascular resistance.1. The CI and PI changed

Manabu Miyazaki



Effect of VEGF Treatment on the Blood-Spinal Cord Barrier Permeability in Experimental Spinal Cord Injury: Dynamic Contrast-Enhanced Magnetic Resonance Imaging  

PubMed Central

Abstract Compromised blood-spinal cord barrier (BSCB) is a factor in the outcome following traumatic spinal cord injury (SCI). Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis and vascular permeability. The role of VEGF in SCI is controversial. Relatively little is known about the spatial and temporal changes in the BSCB permeability following administration of VEGF in experimental SCI. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) studies were performed to noninvasively follow spatial and temporal changes in the BSCB permeability following acute administration of VEGF in experimental SCI over a post-injury period of 56 days. The DCE-MRI data was analyzed using a two-compartment pharmacokinetic model. Animals were assessed for open field locomotion using the Basso-Beattie-Bresnahan score. These studies demonstrate that the BSCB permeability was greater at all time points in the VEGF-treated animals compared to saline controls, most significantly in the epicenter region of injury. Although a significant temporal reduction in the BSCB permeability was observed in the VEGF-treated animals, BSCB permeability remained elevated even during the chronic phase. VEGF treatment resulted in earlier improvement in locomotor ability during the chronic phase of SCI. This study suggests a beneficial role of acutely administered VEGF in hastening neurobehavioral recovery after SCI.

Patel, Chirag B.; Cohen, David M.; Ahobila-Vajjula, Pallavi; Sundberg, Laura M.; Chacko, Tessy




PubMed Central

1. Erythrocyte ghosts from human blood w