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Sample records for vascular permeability index

  1. Vascular permeability in cerebral cavernous malformations.

    PubMed

    Mikati, Abdul G; Khanna, Omaditya; Zhang, Lingjiao; Girard, Romuald; Shenkar, Robert; Guo, Xiaodong; Shah, Akash; Larsson, Henrik B W; Tan, Huan; Li, Luying; Wishnoff, Matthew S; Shi, Changbin; Christoforidis, Gregory A; Awad, Issam A

    2015-10-01

    Patients with the familial form of cerebral cavernous malformations (CCMs) are haploinsufficient for the CCM1, CCM2, or CCM3 gene. Loss of corresponding CCM proteins increases RhoA kinase-mediated endothelial permeability in vitro, and in mouse brains in vivo. A prospective case-controlled observational study investigated whether the brains of human subjects with familial CCM show vascular hyperpermeability by dynamic contrast-enhanced quantitative perfusion magnetic resonance imaging, in comparison with CCM cases without familial disease, and whether lesional or brain vascular permeability correlates with CCM disease activity. Permeability in white matter far (WMF) from lesions was significantly greater in familial than in sporadic cases, but was similar in CCM lesions. Permeability in WMF increased with age in sporadic patients, but not in familial cases. Patients with more aggressive familial CCM disease had greater WMF permeability compared to those with milder disease phenotype, but similar lesion permeability. Subjects receiving statin medications for routine cardiovascular indications had a trend of lower WMF, but not lesion, permeability. This is the first demonstration of brain vascular hyperpermeability in humans with an autosomal dominant disease, as predicted mechanistically. Brain permeability, more than lesion permeability, may serve as a biomarker of CCM disease activity, and help calibrate potential drug therapy. PMID:25966944

  2. Control of vascular permeability by adhesion molecules

    PubMed Central

    Sarelius, Ingrid H; Glading, Angela J

    2014-01-01

    Vascular permeability is a vital function of the circulatory system that is regulated in large part by the limited flux of solutes, water, and cells through the endothelial cell layer. One major pathway through this barrier is via the inter-endothelial junction, which is driven by the regulation of cadherin-based adhesions. The endothelium also forms attachments with surrounding proteins and cells via 2 classes of adhesion molecules, the integrins and IgCAMs. Integrins and IgCAMs propagate activation of multiple downstream signals that potentially impact cadherin adhesion. Here we discuss the known contributions of integrin and IgCAM signaling to the regulation of cadherin adhesion stability, endothelial barrier function, and vascular permeability. Emphasis is placed on known and prospective crosstalk signaling mechanisms between integrins, the IgCAMs- ICAM-1 and PECAM-1, and inter-endothelial cadherin adhesions, as potential strategic signaling nodes for multipartite regulation of cadherin adhesion. PMID:25838987

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

    PubMed Central

    2012-01-01

    Introduction Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by features other than increased pulmonary vascular permeability. Pulmonary vascular permeability combined with increased extravascular lung water content has been considered a quantitative diagnostic criterion of ALI/ARDS. This prospective, multi-institutional, observational study aimed to clarify the clinical pathophysiological features of ALI/ARDS and establish its quantitative diagnostic criteria. Methods The extravascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI) were measured using the transpulmonary thermodilution method in 266 patients with PaO2/FiO2 ratio ? 300 mmHg and bilateral infiltration on chest radiography, in 23 ICUs of academic tertiary referral hospitals. Pulmonary edema was defined as EVLWI ? 10 ml/kg. Three experts retrospectively determined the pathophysiological features of respiratory insufficiency by considering the patients' history, clinical presentation, chest computed tomography and radiography, echocardiography, EVLWI and brain natriuretic peptide level, and the time course of all preceding findings under systemic and respiratory therapy. Results Patients were divided into the following three categories on the basis of the pathophysiological diagnostic differentiation of respiratory insufficiency: ALI/ARDS, cardiogenic edema, and pleural effusion with atelectasis, which were noted in 207 patients, 26 patients, and 33 patients, respectively. EVLWI was greater in ALI/ARDS and cardiogenic edema patients than in patients with pleural effusion with atelectasis (18.5 6.8, 14.4 4.0, and 8.3 2.1, respectively; P < 0.01). PVPI was higher in ALI/ARDS patients than in cardiogenic edema or pleural effusion with atelectasis patients (3.2 1.4, 2.0 0.8, and 1.6 0.5; P < 0.01). In ALI/ARDS patients, EVLWI increased with increasing pulmonary vascular permeability (r = 0.729, P < 0.01) and was weakly correlated with intrathoracic blood volume (r = 0.236, P < 0.01). EVLWI was weakly correlated with the PaO2/FiO2 ratio in the ALI/ARDS and cardiogenic edema patients. A PVPI value of 2.6 to 2.85 provided a definitive diagnosis of ALI/ARDS (specificity, 0.90 to 0.95), and a value < 1.7 ruled out an ALI/ARDS diagnosis (specificity, 0.95). Conclusion PVPI may be a useful quantitative diagnostic tool for ARDS in patients with hypoxemic respiratory failure and radiographic infiltrates. Trial registration UMIN-CTR ID UMIN000003627 PMID:23232188

  4. Endotoxin increases pulmonary vascular protein permeability in the dog

    SciTech Connect

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

    1986-10-01

    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.

  5. Atrial natriuretic factor increases vascular permeability

    NASA Technical Reports Server (NTRS)

    Lockette, Warren; Brennaman, Bruce

    1990-01-01

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

  6. Wogonin influences vascular permeability via Wnt/?-catenin pathway.

    PubMed

    Song, Xiuming; Zhou, Yuxin; Zhou, Mi; Huang, Yujie; Li, Zhiyu; You, Qidong; Lu, Na; Guo, Qinglong

    2015-07-01

    Wogonin, a flavone from the root of Scutellaria baicalensis Georgi, has shown various biological activities. In our previous study, it was confirmed that wogonin could decrease the expression of hypoxia-inducible factor-1? (HIF-1?) by affecting its stability under hypoxia. However, it is still unknown whether wogonin could influence Wnt/?-catenin pathway under hypoxia. In this study, we found that wogonin disrupted Wnt/?-catenin signaling and reduced the secretion of vascular endothelial growth factor (VEGF, also known as vascular permeability factor, VPF), which increased vascular permeability in certain diseases. It was found that wogonin suppressed HUVECs hyperactivity and actin remodeling induced by hypoxia, inhibited transendothelial cell migration of the human breast carcinoma cell MDA-MB-231 and the extravasated Evans in vivo Miles vascular permeability assay. Wogonin-treated cells showed a decrease in the expression of Wnt protein and its co-receptors, as well as a parallel increase in the expression of Axin and GSK-3? in degradation complex, leading to degradation of ?-catenin. In addition, wogonin promoted the binding between Axin and ?-catenin, increased ubiquitination of ?-catenin and promoted its degradation. Interestingly, wogonin decreased the expression of TCF-1, TCF-3, and LEF-1 and inhibited nuclear accumulation of ?-catenin as well as the binding of ?-catenin and TCF-1, TCF-3, or LEF-1. All of the above results showed that wogonin could inhibit the expression of VEGF, which is an important factor regulated by ?-catenin. Taken together, the results suggested that wogonin was a potent inhibitor of Wnt/?-catenin and influenced vascular permeability, and this might provide new therapeutics in certain diseases. PMID:24136474

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

    PubMed Central

    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.

    2011-01-01

    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 bloodbrain barrier permeability. Similar to the effect on in vitro cultures, this stabilizing effect on bloodbrain 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 MSCEC interaction. PMID:20446815

  8. Endothelial glycocalyx and coronary vascular permeability: the fringe benefit.

    PubMed

    Becker, Bernhard F; Chappell, Daniel; Jacob, Matthias

    2010-11-01

    Current concepts of vascular permeability are largely still based on the Starling principle of 1896. Starling's contribution to understanding vascular fluid homeostasis comes from realising that the transport of fluid to and from the interstitial space of peripheral tissues follows the balance between opposing oncotic and hydrostatic pressures. It is presumed that in peripheral tissues fluid is readily filtered from blood to tissues at the arterial/arteriolar side of the circulation and largely reabsorbed at the venular/venous aspect, excess fluid being removed from the tissue by the lymphatic system. This balance is determined particularly by the properties of the vascular barrier. Recent studies have shown that the endothelial glycocalyx, located with a thickness of at least 200 nm on the luminal side of healthy vasculature, plays a vital role in vascular permeability by constituting the vascular barrier together with the endothelial cells themselves. While water and electrolytes can freely pass through the glycocalyx, plasma proteins, especially albumin, interact strongly. Binding and intercalating plasma constituents with the structural elements of the glycocalyx creates the so-called endothelial surface layer. This is the actual interface between flowing blood and the endothelial cell membrane in vivo. The oncotic pressure difference pertinent to fluid homeostasis is not built up between the intravascular and the interstitial tissue spaces, but within a small protein-free zone beneath the glycocalyx surface layer. This explains why perturbation of the glycocalyx leads to a breakdown of both fluid and protein handling in the coronary vascular bed. Preventing damage to the glycocalyx seems to be a promising goal in cardioprotection in many clinical scenarios, including acute ischaemia, hypoxia and inflammation, and chronic vascular disease as in atherosclerosis, diabetes and hypertension. PMID:20859744

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

    NASA Astrophysics Data System (ADS)

    Roy Chaudhuri, Tista

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

  10. Guinea pig Hageman factor as a vascular permeability enhancement factor.

    PubMed Central

    Yamamoto, T.; Cochrane, C. G.

    1981-01-01

    Hageman factor was purified from guinea pig plasma by successive column chromatography. The guinea pig Hageman factor appeared homogeneous as a single-chain protein on polyacrylamide gels in the presence of sodium dodecyl sulfate (SDS) and beta-mercaptoethanol. The apparent molecular weight was 76,000 daltons by SDS--polyacrylamide gel electrophoresis and 105,000 daltons by gel filtration with a Sephadex G-150 column. Amino acid composition of the guinea pig Hageman factor was similar to that reported for human, bovine, and rabbit Hageman factors. The purified guinea pig Hageman factor, as well as guinea pig plasma, showed strong clotting time correction activity in Hageman-factor--deficient human plasma. The activity could be blocked by the IgG fraction of antiserums against guinea pig Hageman factor raised in rabbits or a goat. The concentration of Hageman factor in guinea pig plasma was determined to be 120 microgram/ml by quantitative radial immunodiffusion assay. The 28,000-dalton active form of Hageman factor (beta-HFa) was prepared from guinea pig Hageman factor by treatment with plasma kallikrein. beta-HFa caused an increase in vascular permeability when injected into guinea pig skin at concentrations as low as 3 x 10(-10) M (0.8 ng). Native, or zymogen Hageman factor did not cause an increase in permeability at concentrations of up to 2 x 10(-7) M. The increased permeability induced by beta-HFa was short lasting, with about a 50% decrease in activity apparent within 6 minutes after intradermal injection. The permeability enhancement activity of beta-HFa was inhibited by pretreatment of beta-HFa with diisopropylfluorophosphate. It may be concluded that active Hageman factor in the interstitial space of guinea pigs acts as a vascular permeability factor of far greater potency than bradykinin. Images Figure 3 Figure 4 Figure 6 Figure 7 PMID:6794374

  11. New sensitive fluorometric method for measurement of vascular permeability

    SciTech Connect

    Watanabe, K.; Nakagawa, H.; Tsurufuji, S.

    1984-06-01

    A sensitive fluorometric method has been developed for the measurement of vascular permeability in carrageenin air-pouch inflammation in rats. Fluorescein isothiocyanate-labeled bovine serum albumin (F-BSA) was used as a tracer. This fluorometric method is as simple and reliable as the method using radioiodine-labeled human serum albumin and has the advantages of low cost, no health hazard, and the fact that F-BSA can be stored over a long period. This fluorometric method is probably applicable to other inflammation models such as pleurisy and peritonitis in which inflammatory exudate can be collected.

  12. Increased lung vascular permeability after pancreatitis and trypsin infusion.

    PubMed Central

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

    1982-01-01

    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 PMID:6181692

  13. Pharmacologic modulation of pulmonary vascular permeability during air embolism.

    PubMed

    Huang, K L; Lin, Y C

    1997-01-01

    Pulmonary air embolism induces the generation of vasoactive and cytotoxic substances leading to lung injury. In the present study we investigated, in isolated and perfused rat lungs, the involvement of arachidonic acid metabolites in the alterations of vascular pressure, lung water content, and the filtration coefficient (Kf). We also tested the effects of a beta-agonist, a calcium channel blocker, and a cyclo-oxygenase inhibitor on the hemodynamic and the permeability changes following pulmonary air embolism. The artificially ventilated rat lungs were removed en bloc and suspended in a humidified chamber at 37 degrees C. The salt and buffered perfusate contained 4% Ficoll as albumin substitute for osmotic balance. We introduced air bubbles through the pulmonary artery. Air embolism increased pulmonary arterial resistance and caused pulmonary hypertension. Lungs receiving air infusion contained 88.6 +/- 0.6% water, which was significantly greater than the lung water content in the control groups (81.9 +/- 0.4%). Air embolism increased Kf by 145 +/- 19% from the baseline value. Pretreatment with indomethacin, isoproterenol, or nifedipine significantly reduced post-air-embolism lung water content to 85.8 +/- 0.5%, 84.1 +/- 0.4%, and 86.5 +/- 04%, respectively, and reduced the Kf increase to 17 +/- 8%, 1 +/- 9%, and 72 +/- 8%, respectively. These interventions did not alter the hemodynamic responses, except for the isoproterenol infusion, which shortened the half-time (T1/2) for pressure recovery after ending air infusion compared to the group with air embolism alone. Our results showed that indomethacin prevented vascular permeability increase and reduced pulmonary edema, suggesting that the cyclo-oxygenase products partially mediate the lung injury following air embolism. Furthermore, isoproterenol and nifedipine prevented or reduced the permeability increase, suggesting that alterations of the intracellular cAMP and cytosolic Ca2+ level play an important role in the pathophysiology of pulmonary air embolism. PMID:9444063

  14. Effect of leukotriene receptor antagonists on vascular permeability during endotoxic shock

    SciTech Connect

    Cook, J.A.; Li, E.J.; Spicer, K.M.; Wise, W.C.; Halushka, P.V. )

    1990-11-01

    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.

  15. Vascular endothelial growth factor regulates angiogenesis and vascular permeability in Kaposi's sarcoma.

    PubMed Central

    Cornali, E.; Zietz, C.; Benelli, R.; Weninger, W.; Masiello, L.; Breier, G.; Tschachler, E.; Albini, A.; Stürzl, M.

    1996-01-01

    Abundant vasculature with increased permeability is a prominent histological feature of Kaposi's sarcoma (KS), a multifocal, cytokine-regulated tumor. Here we report on the role of vascular endothelial growth factor (VEGF) in AIDS-KS angiogenesis and vascular permeability. We demonstrate that different cytokines, which were previously shown to be active in KS development, modulate VEGF expression in KS spindle cells and cooperate with VEGF on the functional level. Northern blot analysis as well as studies on single cells using in situ hybridization revealed that VEGF expression in cultivated AIDS-KS spindle cells is up-regulated by platelet-derived growth factor-B and interleukin-1 beta. Western blot and enzyme-linked immunosorbent assay analysis of cell culture supernatants demonstrated that the VEGF protein is secreted by stimulated AIDS-KS spindle cells in sufficiently high amounts to activate proliferation of human dermal microvascular endothelial cells. Basic fibroblast growth factor did not increase VEGF expression but acted synergistically with VEGF in the induction of angiogenic KS-like lesions in a mouse model in vivo. Angiogenesis and cellularity of KS-like lesions were clearly increased when both factors were injected simultaneously into the flanks of mice, compared with separate injection of each factor. A comparable angiogenic reaction as obtained by simultaneous injection of basic fibroblast growth factor and VEGF was observed when cell culture supernatants of AIDS-KS spindle cells were used for these experiments. Finally, analysis of primary human AIDS-KS lesions revealed that high amounts of VEGF mRNA and protein were present in KS spindle cells in vivo. These data provide evidence that VEGF, in concert with platelet-derived growth factor-B, interleukin-1 beta, and basic fibroblast growth factor, is a key mediator of angiogenesis and vascular permeability in KS lesions in vivo. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:8952523

  16. Predominant role of endothelial nitric oxide synthase in vascular endothelial growth factor-induced angiogenesis and vascular permeability

    PubMed Central

    Fukumura, Dai; Gohongi, Takeshi; Kadambi, Ananth; Izumi, Yotaro; Ang, Jennifer; Yun, Chae-Ok; Buerk, Donald G.; Huang, Paul L.; Jain, Rakesh K.

    2001-01-01

    Nitric oxide (NO) plays a critical role in vascular endothelial growth factor (VEGF)-induced angiogenesis and vascular hyperpermeability. However, the relative contribution of different NO synthase (NOS) isoforms to these processes is not known. Here, we evaluated the relative contributions of endothelial and inducible NOS (eNOS and iNOS, respectively) to angiogenesis and permeability of VEGF-induced angiogenic vessels. The contribution of eNOS was assessed by using an eNOS-deficient mouse, and iNOS contribution was assessed by using a selective inhibitor [l-N6-(1-iminoethyl) lysine, l-NIL] and an iNOS-deficient mouse. Angiogenesis was induced by VEGF in type I collagen gels placed in the mouse cranial window. Angiogenesis, vessel diameter, blood flow rate, and vascular permeability were proportional to NO levels measured with microelectrodes: Wild-type (WT) ? WT with l-NIL or iNOS?/? > eNOS?/? ? eNOS?/? with l-NIL. The role of NOS in VEGF-induced acute vascular permeability increase in quiescent vessels also was determined by using eNOS- and iNOS-deficient mice. VEGF superfusion significantly increased permeability in both WT and iNOS?/? mice but not in eNOS?/? mice. These findings suggest that eNOS plays a predominant role in VEGF-induced angiogenesis and vascular permeability. Thus, selective modulation of eNOS activity is a promising strategy for altering angiogenesis and vascular permeability in vivo. PMID:11226286

  17. Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization.

    PubMed Central

    Pierce, E A; Avery, R L; Foley, E D; Aiello, L P; Smith, L E

    1995-01-01

    Neovascular diseases of the retina are a major cause of blindness worldwide. Hypoxia is thought to be a common precursor to neovascularization in many retinal diseases, but the factors involved in the hypoxic neovascular response have not been fully identified. To investigate the role of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) in retinal neovascularization, the expression of VEGF/VPF mRNA and protein were studied in a mouse model of proliferative retinopathy. RNA (Northern) blot analysis revealed that retinal VEGF/VPF mRNA expression increased 3-fold between 6 and 12 hr of relative retinal hypoxia and remained elevated during the development of neovascularization. In situ hybridization localized VEGF/VPF mRNA to cells bodies in the inner nuclear layer of the retina. Immunohistochemical confocal microscopy demonstrated that VEGF/VPF protein levels increase with a time course similar to that of the mRNA. The cells in the inner nuclear layer of the retina that produce VEGF/VPF were identified morphologically as Mller cells. These data suggest that VEGF/VPF expression in the retina plays a central role in the development of retinal ischemia-induced ocular neovascularization. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:7846076

  18. Semaphorin3A elevates vascular permeability and contributes to cerebral ischemia-induced brain damage

    PubMed Central

    Hou, Sheng Tao; Nilchi, Ladan; Li, Xuesheng; Gangaraju, Sandhya; Jiang, Susan X.; Aylsworth, Amy; Monette, Robert; Slinn, Jacqueline

    2015-01-01

    Semaphorin 3A (Sema3A) increased significantly in mouse brain following cerebral ischemia. However, the role of Sema3A in stroke brain remains unknown. Our aim was to determine wether Sema3A functions as a vascular permeability factor and contributes to ischemic brain damage. Recombinant Sema3A injected intradermally to mouse skin, or stereotactically into the cerebral cortex, caused dose- and time-dependent increases in vascular permeability, with a degree comparable to that caused by injection of a known vascular permeability factor vascular endothelial growth factor receptors (VEGF). Application of Sema3A to cultured endothelial cells caused disorganization of F-actin stress fibre bundles and increased endothelial monolayer permeability, confirming Sema3A as a permeability factor. Sema3A-mediated F-actin changes in endothelial cells were through binding to the neuropilin2/VEGFR1 receptor complex, which in turn directly activates Mical2, a F-actin modulator. Down-regulation of Mical2, using specific siRNA, alleviated Sema3A-induced F-actin disorganization, cellular morphology changes and endothelial permeability. Importantly, ablation of Sema3A expression, cerebrovascular permeability and brain damage were significantly reduced in response to transient middle cerebral artery occlusion (tMCAO) and in a mouse model of cerebral ischemia/haemorrhagic transformation. Together, these studies demonstrated that Sema3A is a key mediator of cerebrovascular permeability and contributes to brain damage caused by cerebral ischemia. PMID:25601765

  19. Multiple roles of the PGE2-EP receptor signal in vascular permeability

    PubMed Central

    Omori, K; Kida, T; Hori, M; Ozaki, H; Murata, T

    2014-01-01

    Background and Purpose PGE2 is a major prostanoid that regulates inflammation by stimulating EP1–4 receptors. However, how PGE2 induces an initial inflammatory response to vascular hyper-permeability remains unknown. Here we investigated the role of the PGE2-EP receptor signal in modulating vascular permeability both in vivo and in vitro. Experimental Approach We used a modified Miles assay and intravital microscopy to examine vascular permeability in vivo. Endothelial barrier property was assessed by measuring transendothelial electrical resistance (TER) in vitro. Key Results Local administration of PGE2, an EP2 or EP4 receptor agonist into FVB/NJcl mouse ear skin caused vascular leakage, indicated by dye extravasation. Intravital microscopy and laser Doppler blood-flow imaging revealed that these treatments dilated peripheral vessels and increased local blood flow. Pretreatment with the vasoconstrictor phenylephrine inhibited the PGE2-induced blood flow increase and vascular leakage. In contrast to the EP2 and EP4 receptor agonists, administration of an EP3 receptor agonist suppressed vascular leakage without altering vascular diameter or blood flow. In isolated HUVECs, the EP3 receptor agonist elevated TER and blocked thrombin-induced dextran passage. Inhibiting PKA restored the hypo-permeability induced by the EP3 receptor agonist. Conclusions and Implications Activation of the PGE2-EP2 or -EP4 receptor signal induces vasodilatation in mural cells, resulting in increased local blood flow and hyper-permeability. In contrast, activation of the PGE2-EP3 receptor signal induces a cAMP-dependent enhancement of the endothelial barrier, leading to hypo-permeability. We provide the first evidence that endothelial cells and mural cells cooperate to modulate vascular permeability. PMID:24923772

  20. Recombinant tumor necrosis factor increases pulmonary vascular permeability independent of neutrophils.

    PubMed Central

    Horvath, C J; Ferro, T J; Jesmok, G; Malik, A B

    1988-01-01

    We studied the effects of intravenous infusion of recombinant human tumor necrosis factor type alpha (rTNF-alpha; 12 micrograms/kg) on lung fluid balance in sheep prepared with chronic lung lymph fistulas. The role of neutrophils was examined in sheep made neutropenic with hydroxyurea (200 mg/kg for 4 or 5 days) before receiving rTNF-alpha. Infusion of rTNF-alpha resulted in respiratory distress and 3-fold increases in pulmonary arterial pressure and pulmonary vascular resistance within 15 min, indicating intense pulmonary vasoconstriction. Pulmonary lymph flow (i.e., net transvascular fluid filtration rate) and transvascular protein clearance rate (a measure of vascular permeability to protein) increased 2-fold within 30 min. The increased permeability was associated with leukopenia and neutropenia. The pulmonary hypertension and vasoconstriction subsided but fluid filtration and vascular permeability continued to increase. Sheep made neutropenic had similar increases in pulmonary transvascular fluid filtration and vascular permeability. rTNF-alpha also produced concentration-dependent increases in permeability of 125I-labeled albumin across ovine endothelial cell monolayers in the absence of neutrophils or other inflammatory mediators. The results indicate that rTNF-alpha increases pulmonary vascular permeability to protein by an effect on the endothelium. PMID:3143114

  1. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis.

    PubMed Central

    Dvorak, H. F.; Brown, L. F.; Detmar, M.; Dvorak, A. M.

    1995-01-01

    VPF/VEGF is a multifunctional cytokine that contributes to angiogenesis by both direct and indirect mechanisms. On the one hand, VPF/VEGF stimulates the ECs lining nearby microvessels to proliferate, to migrate, and to alter their pattern of gene expression. On the other hand, VPF/VEGF renders these same microvascular ECs hyperpermeable so that they spill plasma proteins into the extravascular space, leading to the clotting of extravasated fibrinogen with deposition of a fibrin gel. Extravascular fibrin serves as a provisional matrix that favors and supports the ingrowth of new blood vessels and other mesenchymal cells that generate mature, vascularized stroma. These same principles apply in tumors, in several examples of non-neoplastic pathology, and in physiological processes that involve angiogenesis and new stroma generation. In all of these examples, microvascular hyperpermeability and the introduction of a provisional, plasma-derived matrix precede and accompany the onset of EC division and new blood vessel formation. It would seem, therefore, that tumors have "borrowed" fundamental mechanisms that developed in multicellular organisms for purposes of tissue defense, renewal, and repair. VPF/VEGF, therefore has taught us something new about angiogenesis; namely, that vascular hyperpermeability and consequent plasma protein extravasation are important, perhaps essential, elements in its generation. However, this finding raises a paradox. While VPF/VEGF induces vascular hyperpermeability, other potent angiogenic factors apparently do not, at least in subtoxic concentrations that are more than sufficient to induce angiogenesis. Nonetheless, wherever angiogenesis has been studied, the newly generated vessels have been found to be hyperpermeable. How, therefore, do angiogenic factors other than VPF/VEGF lead to the formation of new and leaky blood vessels? We do not as yet have a complete answer to this question. One possibility is that at least some angiogenic factors mediate their effect by inducing or stimulating the expression of VPF/VEGF. In fact, there is already one clear example of this. TGF-alpha is a potent angiogenic factor but does not itself increase microvascular permeability. However, TGF-alpha strikingly upregulates VPF/VEGF expression in cultured keratinocytes and is thought to be responsible, at least in part, for the overexpression of VPF/VEGF in psoriasis. Moreover, overexpression of TGF-alpha, along with that of the EGF receptor with which it interacts, is characteristic of many malignant tumors, raising the possibility that TGF-alpha acts to stimulate VPF/VEGF expression in other types of epithelial cells and in this manner induces angiogenesis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:7538264

  2. Phosphorylation and action of the immunomodulator FTY720 inhibits vascular endothelial cell growth factor-induced vascular permeability.

    PubMed

    Sanchez, Teresa; Estrada-Hernandez, Tatiana; Paik, Ji-Hye; Wu, Ming-Tao; Venkataraman, Krishnan; Brinkmann, Volker; Claffey, Kevin; Hla, Timothy

    2003-11-21

    FTY720, a potent immunosuppressive agent, is phosphorylated in vivo into FTY720-P, a high affinity agonist for sphingosine 1-phosphate (S1P) receptors. The effects of FTY720 on vascular cells, a major target of S1P action, have not been addressed. We now report the metabolic activation of FTY720 by sphingosine kinase-2 and potent activation of vascular endothelial cell functions in vitro and in vivo by phosphorylated FTY720 (FTY720-P). Incubation of endothelial cells with FTY720 resulted in phosphorylation by sphingosine kinase activity and formation of FTY720-P. Sphingosine kinase-2 effectively phosphorylated FTY720 in the human embryonic kidney 293T heterologous expression system. FTY720-P treatment of endothelial cells stimulated extracellular signal-activated kinase and Akt phosphorylation and adherens junction assembly and promoted cell survival. The effects of FTY720-P were inhibited by pertussis toxin, suggesting the requirement for Gi-coupled S1P receptors. Indeed, transmonolayer permeability induced by vascular endothelial cell growth factor was potently reversed by FTY720-P. Furthermore, oral FTY720 administration in mice potently blocked VEGF-induced vascular permeability in vivo. These findings suggest that FTY720 or its analogs may find utility in the therapeutic regulation of vascular permeability, an important process in angiogenesis, inflammation, and pathological conditions such as sepsis, hypoxia, and solid tumor growth. PMID:12954648

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

    PubMed Central

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

    2012-01-01

    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. PMID:22479438

  4. Twist1 controls lung vascular permeability and endotoxin-induced pulmonary edema by altering Tie2 expression.

    PubMed

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

    2013-01-01

    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. PMID:24023872

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

    PubMed Central

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

    2013-01-01

    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. PMID:24023872

  6. Wogonin inhibits LPS-induced vascular permeability via suppressing MLCK/MLC pathway.

    PubMed

    Huang, Yujie; Luo, Xuwei; Li, Xiaorui; Song, Xiuming; Wei, Libin; Li, Zhiyu; You, Qidong; Guo, Qinglong; Lu, Na

    2015-09-01

    Wogonin, a naturally occurring monoflavonoid extracted from the root of Scutellaria baicalensis Georgi, has been shown to have anti-inflammatory and anti-tumor activities and inhibits oxidant stress-induced vascular permeability. However, the influence of wogonin on vascular hyperpermeability induced by overabounded inflammatory factors often appears in inflammatory diseases and tumor is not well known. In this study, we evaluate the effects of wogonin on LPS induced vascular permeability in human umbilical vein endothelial cells (HUVECs) and investigate the underlying mechanisms. We find that wogonin suppresses the LPS-stimulated hyperactivity and cytoskeleton remodeling of HUVECs, promotes the expression of junctional proteins including VE-Cadherin, Claudin-5 and ZO-1, as well as inhibits the invasion of MDA-MB-231 across EC monolayer. Miles vascular permeability assay proves that wogonin can restrain the extravasated Evans in vivo. The mechanism studies reveal that the expressions of TLR4, p-PLC, p-MLCK and p-MLC are decreased by wogonin without changing the total steady state protein levels of PLC, MLCK and MLC. Moreover, wogonin can also inhibit KCl-activated MLCK/MLC pathway, and further affect vascular permeability. Significantly, compared with wortmannin, the inhibitor of MLCK/MLC pathway, wogonin exhibits similar inhibition effects on the expression of p-MLCK, p-MLC and LPS-induced vascular hyperpermeability. Taken together, wogonin can inhibit LPS-induced vascular permeability by suppressing the MLCK/MLC pathway, suggesting a therapeutic potential for the diseases associated with the development of both inflammatory and tumor. PMID:25956732

  7. Pulmonary vascular permeability to transferrin in the pulmonary oedema of renal failure.

    PubMed Central

    Rocker, G M; Morgan, A G; Pearson, D; Basran, G S; Shale, D J

    1987-01-01

    Thirteen patients with renal failure and pulmonary oedema were assessed for evidence of increased pulmonary vascular permeability to protein by a double isotope technique. Comparison was made with 10 patients with cardiogenic pulmonary oedema, 11 healthy volunteers, and 10 patients with the adult respiratory distress syndrome. There was no significant difference in the accumulation of a radiolabelled plasma protein (transferrin) in patients with renal or cardiogenic pulmonary oedema and normal volunteers. Patients with adult respiratory distress syndrome showed significantly greater protein permeability (p less than 0.001). In pulmonary oedema associated with renal failure managed by current regimens there was no evidence of increased permeability to transferrin. PMID:3660315

  8. Suppressions of Serotonin-Induced Increased Vascular Permeability and Leukocyte Infiltration by Bixa orellana Leaf Extract

    PubMed Central

    Sulaiman, NurShahira; Hakim, Muhammad Nazrul; Lian, Gwendoline Ee Cheng; Zakaria, Zainul Amirudin; Othman, Fauziah; Ahmad, Zuraini

    2013-01-01

    The aim of the present study was to evaluate the anti-inflammatory activities of aqueous extract of Bixa orellana (AEBO) leaves and its possible mechanisms in animal models. The anti-inflammatory activity of the extract was evaluated using serotonin-induced rat paw edema, increased peritoneal vascular permeability, and leukocyte infiltrations in an air-pouch model. Nitric oxide (NO), indicated by the sum of nitrites and nitrates, and vascular growth endothelial growth factor (VEGF) were measured in paw tissues of rats to determine their involvement in the regulation of increased permeability. Pretreatments with AEBO (50 and 150 mg kg−1) prior to serotonin inductions resulted in maximum inhibitions of 56.2% of paw volume, 45.7% of Evans blue dye leakage in the peritoneal vascular permeability model, and 83.9% of leukocyte infiltration in the air-pouch model. 57.2% maximum inhibition of NO and 27% of VEGF formations in rats' paws were observed with AEBO at the dose of 150 mg kg−1. Pharmacological screening of the extract showed significant (P < 0.05) anti-inflammatory activity, indicated by the suppressions of increased vascular permeability and leukocyte infiltration. The inhibitions of these inflammatory events are probably mediated via inhibition of NO and VEGF formation and release. PMID:24224164

  9. Suppressions of serotonin-induced increased vascular permeability and leukocyte infiltration by Bixa orellana leaf extract.

    PubMed

    Yong, Yoke Keong; Sulaiman, NurShahira; Hakim, Muhammad Nazrul; Lian, Gwendoline Ee Cheng; Zakaria, Zainul Amirudin; Othman, Fauziah; Ahmad, Zuraini

    2013-01-01

    The aim of the present study was to evaluate the anti-inflammatory activities of aqueous extract of Bixa orellana (AEBO) leaves and its possible mechanisms in animal models. The anti-inflammatory activity of the extract was evaluated using serotonin-induced rat paw edema, increased peritoneal vascular permeability, and leukocyte infiltrations in an air-pouch model. Nitric oxide (NO), indicated by the sum of nitrites and nitrates, and vascular growth endothelial growth factor (VEGF) were measured in paw tissues of rats to determine their involvement in the regulation of increased permeability. Pretreatments with AEBO (50 and 150?mg?kg?) prior to serotonin inductions resulted in maximum inhibitions of 56.2% of paw volume, 45.7% of Evans blue dye leakage in the peritoneal vascular permeability model, and 83.9% of leukocyte infiltration in the air-pouch model. 57.2% maximum inhibition of NO and 27% of VEGF formations in rats' paws were observed with AEBO at the dose of 150?mg?kg?. Pharmacological screening of the extract showed significant (P < 0.05) anti-inflammatory activity, indicated by the suppressions of increased vascular permeability and leukocyte infiltration. The inhibitions of these inflammatory events are probably mediated via inhibition of NO and VEGF formation and release. PMID:24224164

  10. Increased Vascular Permeability Evoked by Crush Injury in the Skin of the Rat

    PubMed Central

    Cummings, R.; Lykke, A. W. J.

    1970-01-01

    The vascular exudative response to cutaneous crush injury was studied in the rat by estimating the leakage of circulating Evans' blue as well as by labelling abnormally permeable vessels with circulating colloidal carbon. The time-course of increased vascular permeability evoked by moderate crush injury is characterized by a monophasic response which has a rapid onset and lasts no more than 4 hr. Increments in the intensity and/or duration of the stimulus are matched by increased intensity and duration of the monophasic response, but with strong crushing the initial phase is followed by a second or delayed response occurring 3-6 hr after injury. Labelling with circulating colloidal carbon indicates that in both phases of the permeability response, the effects are confined to venules. Antagonists of histamine and serotonin partially suppress exudation in the initial hr after injury, whereas antagonists of kinins and serotonin partially suppress the delayed phase of exudation. ImagesFig. 1 PMID:4392188

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

    PubMed Central

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

    1993-01-01

    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. PMID:7507778

  12. Different vascular permeability between the sensory and secretory circumventricular organs of adult mouse brain.

    PubMed

    Morita, Shoko; Miyata, Seiji

    2012-08-01

    The blood-brain barrier (BBB) prevents free access of circulating molecules to the brain and maintains a specialized brain environment to protect the brain from blood-derived bioactive and toxic molecules; however, the circumventricular organs (CVOs) have fenestrated vasculature. The fenestrated vasculature in the sensory CVOs, including the organum vasculosum of lamina terminalis (OVLT), subfornical organ (SFO) and area postrema (AP), allows neurons and astrocytes to sense a variety of plasma molecules and convey their information into other brain regions and the vasculature in the secretory CVOs, including median eminence (ME) and neurohypophysis (NH), permits neuronal terminals to secrete many peptides into the blood stream. The present study showed that vascular permeability of low-molecular-mass tracers such as fluorescein isothiocyanate (FITC) and Evans Blue was higher in the secretory CVOs and kidney as compared with that in the sensory CVOs. On the other hand, vascular permeability of high-molecular-mass tracers such as FITC-labeled bovine serum albumin and Dextran 70,000 was lower in the CVOs as compared with that in the kidney. Prominent vascular permeability of low- and high-molecular-mass tracers was also observed in the arcuate nucleus. These data demonstrate that vascular permeability for low-molecular-mass molecules is higher in the secretory CVOs as compared with that in the sensory CVOs, possibly for large secretion of peptides to the blood stream. Moreover, vascular permeability for high-molecular-mass tracers in the CVOs is smaller than that of the kidney, indicating that the CVOs are not totally without a BBB. PMID:22584508

  13. Inhibition of vascular endothelial growth factor (VEGF)-induced endothelial proliferation, arterial relaxation, vascular permeability and angiogenesis by dobesilate.

    PubMed

    Angulo, Javier; Peir, Concepcin; Romacho, Tania; Fernndez, Argentina; Cuevas, Begoa; Gonzlez-Corrochano, Roco; Gimnez-Gallego, Guillermo; de Tejada, Iigo Senz; Snchez-Ferrer, Carlos F; Cuevas, Pedro

    2011-09-30

    Vascular endothelial growth factor (VEGF) is a key factor in angiogenesis and vascular permeability which is associated with many pathological processes. 2,5-hydroxybenzene sulfonate (DHBS; dobesilate) is a small molecule with anti-angiogenic activity that has been described as an inhibitor of fibroblast growth factors (FGF). The aim of the present study was to evaluate the effects of DHBS on VEGF-induced actions. The effects of DHBS were evaluated on VEGF-induced proliferation in human umbilical vein endothelial cells (HUVEC) and rat aorta relaxation, as well as on in vivo VEGF-induced skin vascular permeability and neovascularization in rats. DHBS at 50 and 100 ?M concentration significantly inhibited the proliferation of HUVEC induced by VEGF (10 ng/ml), without significantly affecting HUVEC proliferation in the absence of VEGF. Rapid VEGF-induced activation of Akt in HUVEC was also prevented by DHBS (100 ?M). Additionally, DHBS (2 ?M) specifically inhibited the relaxation of rat aorta induced by VEGF (0.1 to 30 ng/ml), but not endothelium-dependent relaxation to acetylcholine (1 nM to 10 ?M). The in vivo enhancement of vascular permeability caused by VEGF injection (50 ?l at 10 ng/ml) in rat skin was also inhibited by DHBS co-administration (200 ?M) (74.83.8% inhibition of dye extravasation). Administration of DHBS (200 mg/kg/day; i.p.) also reduced VEGF-induced angiogenesis in vivo. DHBS inhibits main responses elicited in vitro and in vivo by VEGF. As a dual antagonist of VEGF and FGF activities, DHBS could be of therapeutic interest in the treatment of diseases related to VEGF/FGF overproduction and excessive angiogenesis. PMID:21703259

  14. Vascular stasis, intestinal hemorrhage, and heightened vascular permeability complicate acute portal hypertension in cd39-null mice.

    PubMed

    Sun, Xiaofeng; Crdenas, Andrs; Wu, Yan; Enjyoji, Keichi; Robson, Simon C

    2009-08-01

    Vasoactive factors that regulate splanchnic hemodynamics include nitric oxide, catecholamines, and possibly extracellular nucleosides/nucleotides (adenosine, ATP). CD39/ectonucleoside triphosphate diphosphohydrolase-1 (NTPDase1) is the major vascular ectonucleotidase that hydrolyzes extracellular nucleotides. CD39 activity may be modulated by vascular injury, inflammation, and altered oxygen tension. Altered Cd39 expression by the murine hepatosplanchnic vasculature may impact hemodynamics and portal hypertension (PHT) in vivo. We noted that basal portal pressures (PPs) were comparable in wild-type and Cd39-null mice (n = 9). ATP infusions resulted in increments in PP in wild-type mice, but, in contrast, this significantly decreased in Cd39-null mice (n = 9) post-ATP in a nitric oxide-dependent manner. We then studied Cd39/NTPDase1 deletion in the regulation of portal hemodynamics, vascular integrity, and intestinal permeability in a murine model of PHT. Partial portal vein ligation (PPVL) was performed in Cd39-null (n = 44) and wild-type (n = 23) mice. Sequential measurements obtained after PPVL were indicative of comparable levels of PHT (ranges 14-29 mmHg) in both groups. There was one death in the wild-type group and eight in the Cd39-null group from intestinal bleeding (P = 0.024). Circulatory stasis in the absence of overt portal vein thrombosis, portal congestion, intestinal hemorrhage, and increased permeability were evident in all surviving Cd39-null mice. Deletion of Cd39 results in deleterious outcomes post-PPVL that are associated with significant microcirculatory derangements and major intestinal congestion with hemorrhage mimicking acute mesenteric occlusion. Absent Cd39/NTPDase1 and decreased generation of adenosine in the splanchnic circulation cause heightened vascular permeability and gastrointestinal hemorrhage in PPVL. PMID:19520738

  15. Differential vascular permeability along the forebrain ventricular neurogenic niche in the adult murine brain.

    PubMed

    Coln-Casteln, Dannia; Ramrez-Santos, Jess; Gutirrez-Ospina, Gabriel

    2016-02-01

    Adult neurogenesis is influenced by blood-borne factors. In this context, greater or lesser vascular permeability along neurogenic niches would expose differentially neural stem cells (NSCs), transit amplifying cells (TACs), and neuroblasts to such factors. Here we evaluate endothelial cell morphology and vascular permeability along the forebrain neurogenic niche in the adult brain. Our results confirm that the subventricular zone (SVZ) contains highly permeable, discontinuous blood vessels, some of which allow the extravasation of molecules larger than those previously reported. In contrast, the rostral migratory stream (RMS) and the olfactory bulb core (OBc) display mostly impermeable, continuous blood vessels. These results imply that NSCs, TACs, and neuroblasts located within the SVZ are exposed more readily to blood-borne molecules, including those with very high molecular weights, than those positioned along the RMS and the OBc, subregions in which every stage of neurogenesis also takes place. These observations suggest that the existence of specialized vascular niches is not a precondition for neurogenesis to occur; specialized vascular beds might be essential for keeping high rates of proliferation and/or differential differentiation of neural precursors located at distinct domains. 2015 Wiley Periodicals, Inc. PMID:26492830

  16. The effect of ASK1 on vascular permeability and edema formation in cerebral ischemia.

    PubMed

    Song, Juhyun; Cheon, So Yeong; Lee, Won Taek; Park, Kyung Ah; Lee, Jong Eun

    2015-01-21

    Apoptosis signal-regulating kinase-1 (ASK1) is the mitogen-activated protein kinase kinase kinase (MAPKKK) and participates in the various central nervous system (CNS) signaling pathways. In cerebral ischemia, vascular permeability in the brain is an important issue because regulation failure of it results in edema formation and blood-brain barrier (BBB) disruption. To determine the role of ASK1 on vascular permeability and edema formation following cerebral ischemia, we first investigated ASK1-related gene expression using microarray analyses of ischemic brain tissue. We then measured protein levels of ASK1 and vascular endothelial growth factor (VEGF) in brain endothelial cells after hypoxia injury. We also examined protein expression of ASK1 and VEGF, edema formation, and morphological alteration through cresyl violet staining in ischemic brain tissue using ASK1-small interference RNA (ASK1-siRNA). Finally, immunohistochemistry was performed to examine VEGF and aquaporin-1 (AQP-1) expression in ischemic brain injury. Based on our findings, we propose that ASK1 is a regulating factor of vascular permeability and edema formation in cerebral ischemia. PMID:25446452

  17. Effect of complement activation with cobra venom factor on pulmonary vascular permeability.

    PubMed

    Johnson, A; Cooper, J A; Malik, A B

    1986-12-01

    We examined the effect of acute complement activation on lung vascular permeability to proteins in awake sheep prepared with lung lymph fistulas. Complement was activated by cobra venom factor (CVF) infusion (400 U/kg for 1 h iv). Studies were made in two groups of sheep: 1) infusion of CVF containing the endogenous phospholipase A2 (PLA2) (n = 6); and 2) infusion of CVF pretreated with bromophenacyl bromide to inhibit PLA2 activity (n = 5). Intravascular complement activation transiently increased mean pulmonary arterial pressure (Ppa) and pulmonary vascular resistance (PVR) in both groups. Pulmonary lymph flow (Qlym) and lymph protein clearance (Qlym X lymph-to-plasma protein concentration ratio) were also transiently increased in both groups. Pulmonary vascular permeability to proteins was assessed by raising left atrial pressure and determining the lymph-to-plasma protein concentration ratio (L/P) at maximal Qlym. In both groups the L/P at maximal Qlym was not different from normal. In a separate group (n = 4), CVF-induced complement activation was associated with 111In-oxine granulocyte sequestration in the lungs. In vitro plasma from CVF-treated animals aggregated neutrophils but did not stimulate neutrophils to produce superoxide anion generation. Therefore, CVF-induced complement activation results in pulmonary neutrophil sequestration and in increases in PVR and lymph protein clearance. The increase in lymph protein clearance is due to increased pulmonary microvascular pressure and not increased vascular permeability to proteins. PMID:3027023

  18. Intima modifier locus 2 controls endothelial cell activation and vascular permeability

    PubMed Central

    Smolock, Elaine M.; Burke, Ryan M.; Wang, Chenjing; Thomas, Tamlyn; Batchu, Sri N.; Qiu, Xing; Zettel, Martha; Fujiwara, Keigi; Berk, Bradford C.

    2014-01-01

    Carotid intima formation is a significant risk factor for cardiovascular disease. C3H/FeJ (C3H/F) and SJL/J (SJL) inbred mouse strains differ in susceptibility to immune and vascular traits. Using a congenic approach we demonstrated that the Intima modifier 2 (Im2) locus on chromosome 11 regulates leukocyte infiltration. We sought to determine whether inflammation was due to changes in circulating immune cells or activation of vascular wall cells in genetically pure Im2 (C3H/F.SJL.11.1) mice. Complete blood counts showed no differences in circulating monocytes between C3H/F and C3H/F.SJL.11.1 compared with SJL mice. Aortic vascular cell adhesion molecule-1 (VCAM-1) total protein levels were dramatically increased in SJL and C3H/F.SJL.11.1 compared with C3H/F mice. Immunostaining of aortic endothelial cells (EC) showed a significant increase in VCAM-1 expression in SJL and C3H/F.SJL.11.1 compared with C3H/F under steady flow conditions. Immunostaining of EC membranes revealed a significant decrease in EC size in SJL and C3H/F.SJL.11.1 vs. C3H/F in regions of disturbed flow. Vascular permeability was significantly higher in C3H/F.SJL.11.1 compared with C3H/F. Our results indicate that Im2 regulation of leukocyte infiltration is mediated by EC inflammation and permeability. RNA sequencing and pathway analyses comparing genes in the Im2 locus to C3H/F provide insight into candidate genes that regulate vascular wall inflammation and permeability highlighting important genetic mechanisms that control vascular intima in response to injury. PMID:24986958

  19. Inhibition of vascular permeability by antisense-mediated inhibition of plasma kallikrein and coagulation factor 12.

    PubMed

    Bhattacharjee, Gourab; Revenko, Alexey S; Crosby, Jeffrey R; May, Chris; Gao, Dacao; Zhao, Chenguang; Monia, Brett P; MacLeod, A Robert

    2013-06-01

    Hereditary angioedema (HAE) is a rare disorder characterized by recurrent, acute, and painful episodes of swelling involving multiple tissues. Deficiency or malfunction of the serine protease inhibitor C1 esterase inhibitor (C1-INH) results in HAE types 1 and 2, respectively, whereas mutations in coagulation factor 12 (f12) have been associated with HAE type 3. C1-INH is the primary inhibitor of multiple plasma cascade pathways known to be altered in HAE patients, including the complement, fibrinolytic, coagulation, and kinin-kallikrein pathways. We have selectively inhibited several components of both the kinin-kallikrein system and the coagulation cascades with potent and selective antisense oligonucleotides (ASOs) to investigate their relative contributions to vascular permeability. We have also developed ASO inhibitors of C1-INH and characterized their effects on vascular permeability in mice as an inducible model of HAE. Our studies demonstrate that ASO-mediated reduction in C1-INH plasma levels results in increased vascular permeability and that inhibition of proteases of the kinin-kallikrein system, either f12 or prekallikrein (PKK) reverse the effects of C1-INH depletion with similar effects on both basal and angiotensin converting enzyme (ACE) inhibitor-induced permeability. In contrast, inhibition of coagulation factors 11 (f11) or 7 (f7) had no effect. These results suggest that the vascular defects observed in C1-INH deficiency are dependent on the kinin-kallikrein system proteases f12 and PKK, and not mediated through the coagulation pathways. In addition, our results highlight a novel therapeutic modality that can potentially be employed prophylactically to prevent attacks in HAE patients. PMID:23582057

  20. A Neurodegenerative Vascular Burden Index and the Impact on Cognition

    PubMed Central

    Heinzel, Sebastian; Liepelt-Scarfone, Inga; Roeben, Benjamin; Nasi-Kordhishti, Isabella; Suenkel, Ulrike; Wurster, Isabel; Brockmann, Kathrin; Fritsche, Andreas; Niebler, Raphael; Metzger, Florian G.; Eschweiler, Gerhard W.; Fallgatter, Andreas J.; Maetzler, Walter; Berg, Daniela

    2014-01-01

    A wide range of vascular burden factors has been identified to impact vascular function and structure as indicated by carotid intimamedia thickness (IMT). On the basis of their impact on IMT, vascular factors may be selected and clustered in a vascular burden index (VBI). Since many vascular factors increase the risk of Alzheimers disease (AD), a multifactorial neurodegenerative VBI may be related to early pathological processes in AD and cognitive decline in its preclinical stages. We investigated an elderly cohort at risk for neurodegeneration (TREND study, n?=?1102) for the multifactorial influence of vascular burden factors on IMT measured by ultrasound. To create a VBI for this cohort, vascular factors and their definitions (considering medical history, medication, and/or blood marker data) were selected based on their statistical effects on IMT in multiple regressions including age and sex. The impact of the VBI on cognitive performance was assessed using the Trail-Making Test (TMT) and the consortium to establish a registry for Alzheimers disease (CERAD) neuropsychological battery. IMT was significantly predicted by age (standardized ??=?0.26), sex (0.09; males?>?females) and the factors included in the VBI: obesity (0.18), hypertension (0.14), smoking (0.08), diabetes (0.07), and atherosclerosis (0.05), whereas other cardiovascular diseases or hypercholesterolemia were not significant. Individuals with 2 or more VBI factors compared to individuals without had an odds ratio of 3.17 regarding overly increased IMT ( ??1.0?mm). The VBI showed an impact on executive control [log(TMT B?A), p?=?0.047] and a trend toward decreased global cognitive function (CERAD total score, p?=?0.057) independent of age, sex, and education. A VBI established on the basis of IMT may help to identify individuals with overly increased vascular burden linked to decreased cognitive function indicating neurodegenerative processes. The longitudinal study of this risk cohort will reveal the value of the VBI as prodromal marker for cognitive decline and AD. PMID:25071568

  1. Dynamics of neutrophil extravasation and vascular permeability are uncoupled during aseptic cutaneous wounding

    PubMed Central

    Kim, Min-Ho; Curry, Fitz-Roy E.; Simon, Scott I.

    2009-01-01

    Transport of macromolecules and transmigration of leukocytes across vascular endothelium are regulated by a tight molecular junction, but the mechanisms by which these two inflammatory events are differentially controlled in time and magnitude during aseptic cutaneous wounding remain elusive. A real-time fluorescence imaging technique was developed to simultaneously track influx of Alexa 680-labeled albumin and genetically tagged enhanced green fluorescent protein-neutrophils [polymorphonuclear neutrophils (PMN)] within the wound bed. Vascular permeability increased approximately threefold more rapidly than the rate of PMN influx, reaching a maximum at 12 h, on the order of ?0.15% per minute versus ?0.05% per minute for PMN influx, which peaked at 18 h. Systemic depletion of PMN with antibody blocked their extravasation to the wound but did not alter the increase in vascular permeability. In contrast, pretreatment with antiplatelet GPIb decreased permeability by 25% and PMN influx by 50%. Hyperpermeability stimulated by the endothelium-specific agonists VEGF or thrombin at 24 h postwounding was completely inhibited by blocking Rho-kinase-dependent signaling, whereas less inhibition was observed at 1 h and neutrophil influx was not perturbed. These data suggest that in aseptic wounds, the endothelium maintains a tight junctional barrier to protein leakage that is independent of neutrophil transmigration, partially dependent on circulating platelets, and associated with Rho-kinase-dependent signaling. PMID:19176758

  2. Oxidative stress and vascular permeability in steroid-induced osteonecrosis model.

    PubMed

    Ichiseki, Toru; Matsumoto, Tadami; Nishino, Mitsuru; Kaneuji, Ayumi; Katsuda, Shogo

    2004-01-01

    We focused on the role of oxidative stress in the pathogenesis of steroid-induced osteonecrosis (ON) and the possibility of preventing this condition by antioxidant administration. Methylprednisolone 4 mg/kg was injected only once into Japanese white rabbits. The involvement of oxidative stress and the presence/absence of bone circulatory impairment were investigated in groups of 10 rabbits killed at 3, 5, and 14 days each and in 10 rabbits administered the antioxidant glutathione. Reduced blood glutathione and lipid peroxide levels were determined biochemically, and the presence/absence of advanced glycation end-product expression was determined immunohistochemically. Vascular permeability in bone was confirmed by finding albumin leakage into the stroma. These blood biochemical and immunohistochemical studies clarified that the oxidative stress in this model developed 3-5 days after steroid administration. Elevated vascular permeability was observed in the 5- and 14-day groups. Hence, circulatory disturbance in bone was noted 5 days after steroid administration, coinciding with the onset of oxidative stress. The rate of ON development, which was 70% in the steroid-alone 14-day group, was significantly reduced to 0% in the steroid + antioxidant group. These results suggest the involvement of oxidative stress and vascular permeability in this steroid-induced ON model and the possibility of its prevention by suppression of oxidative stress. PMID:15449127

  3. Formation of a factor increasing vascular permeability during electrical stimulation of the saphenous nerve in rats

    PubMed Central

    Leme, J. Garcia; Hamamura, L.

    1974-01-01

    1 Increased vascular permeability following electric antidromic stimulation of the rat saphenous nerve was observed in the skin area supplied by the nerve, confirming previous results by other authors. 2 The phenomenon was not affected by pretreatment of the rats with diphenhydramine, burimamide or their combination; atropine, methysergide, methysergide plus diphenhydramine, carboxypeptidase B, acetylsalicylic acid, indomethacin or methiazinic acid. It was partially reduced by previous injection of cellulose-sulphate, a kininogen-depleting agent. 3 Perfusates from the subcutaneous tissue of the paw area supplied by the saphenous nerve contained permeability increasing activity as shown by intradermal tests in other rats. This activity was present in perfusates collected during nerve stimulation but not in those collected before stimulation. It was not destroyed by heating to 100 C, or by ?-chymotrypsin or trypsin. 4 Bradykinin-like activity may appear later in the perfusates, depending on the intensity of the stimuli. 5 It is concluded that following electrical antidromic stimulation of the saphenous nerve a permeability increasing factor is released, possibly from nerves. It is dialysable and can be distinguished from acetylcholine, histamine, 5-hydroxytryptamine, plasma kinins, substance P, prostaglandins and high molecular weight proteins. The increased vascular permeability induced by this factor leads to plasma exudation and activation of the kinin system. PMID:4141638

  4. Cadmium induces vascular permeability via activation of the p38 MAPK pathway

    SciTech Connect

    Dong, Fengyun; Guo, Fang; Li, Liqun; Guo, Ling; Hou, Yinglong; Hao, Enkui; Yan, Suhua; Allen, Thaddeus D.; Liu, Ju

    2014-07-18

    Highlights: • Low-dose cadmium (Cd) induces vascular hyper-permeability. • p38 MAPK mediates Cd-induced disruption of endothelial cell barrier function. • SB203850 inhibits Cd-induced membrane dissociation of VE-cadherin and β-catenin. • SB203850 reduces Cd-induced expression and secretion of TNF-α. - Abstract: The vasculature of various organs is a targeted by the environmental toxin, cadmium (Cd). However, mechanisms leading to pathological conditions are poorly understood. In the present study, we examined the effect of cadmium chloride (CdCl{sub 2}) on human umbilical vein endothelial cells (HUVECs). At 4 μM, CdCl{sub 2} induced a hyper-permeability defect in HUVECs, but not the inhibition of cell growth up to 24 h. This effect of CdCl{sub 2} was dependent on the activation of the p38 mitogen-activated protein kinase (MAPK) pathway. The p38 MAPK inhibitor SB203850 suppressed the CdCl{sub 2}-induced alteration in trans-endothelial electrical resistance in HUVEC monolayers, a model measurement of vascular endothelial barrier integrity. SB203850 also inhibited the Cd-induced membrane dissociation of vascular endothelial (VE) cadherin and β-catenin, the important components of the adherens junctional complex. In addition, SB203850 reduces the Cd-induced expression and secretion of tumor necrosis factor α (TNF-α). Taken together, our findings suggest that Cd induces vascular hyper-permeability and disruption of endothelial barrier integrity through stimulation of p38 MAPK signaling.

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

    PubMed Central

    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

    2012-01-01

    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. PMID:23169049

  6. Podocalyxin Regulates Murine Lung Vascular Permeability by Altering Endothelial Cell Adhesion

    PubMed Central

    Debruin, Erin J.; Hughes, Michael R.; Sina, Christina; Liu, Alex; Cait, Jessica; Jian, Zhiqi; Lopez, Martin; Lo, Bernard; Abraham, Thomas; McNagny, Kelly M.

    2014-01-01

    Despite the widespread use of CD34-family sialomucins (CD34, podocalyxin and endoglycan) as vascular endothelial cell markers, there is remarkably little known of their vascular function. Podocalyxin (gene name Podxl), in particular, has been difficult to study in adult vasculature as germ-line deletion of podocalyxin in mice leads to kidney malformations and perinatal death. We generated mice that conditionally delete podocalyxin in vascular endothelial cells (Podxl?EC mice) to study the homeostatic role of podocalyxin in adult mouse vessels. Although Podxl?EC adult mice are viable, their lungs display increased lung volume and changes to the matrix composition. Intriguingly, this was associated with increased basal and inflammation-induced pulmonary vascular permeability. To further investigate the etiology of these defects, we isolated mouse pulmonary endothelial cells. Podxl?EC endothelial cells display mildly enhanced static adhesion to fibronectin but spread normally when plated on fibronectin-coated transwells. In contrast, Podxl?EC endothelial cells exhibit a severely impaired ability to spread on laminin and, to a lesser extent, collagen I coated transwells. The data suggest that, in endothelial cells, podocalyxin plays a previously unrecognized role in maintaining vascular integrity, likely through orchestrating interactions with extracellular matrix components and basement membranes, and that this influences downstream epithelial architecture. PMID:25303643

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

    SciTech Connect

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

    1981-01-01

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2015-06-01

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

  9. Desert Hedgehog/Patch2 Axis Contributes to Vascular Permeability and Angiogenesis in Glioblastoma

    PubMed Central

    Azzi, Sandy; Treps, Lucas; Leclair, Hlose M.; Ngo, Hai-Mi; Harford-Wright, Elizabeth; Gavard, Julie

    2015-01-01

    Glioblastoma multiforme (GBM) constitutes the most common and the most aggressive type of human tumors affecting the central nervous system. Prognosis remains dark due to the inefficiency of current treatments and the rapid relapse. Paralleling other human tumors, GBM contains a fraction of tumor initiating cells with the capacity to self-renew, initiate and maintain the tumor mass. These cells were found in close proximity to brain vasculature, suggesting functional interactions between brain tumor-initiating cells (BTICs) and endothelial cells within the so-called vascular niche. However, the mechanisms by which these cells impact on the endothelium plasticity and function remain unclear. Using culture of BTICs isolated from a cohort of 14 GBM patients, we show that BTICs secretome promotes brain endothelial cell remodeling in a VEGF-independent manner. Gene array analysis unmasked that BTICs-released factors drove the expression of Ptch2 in endothelial cells. Interestingly, BTICs produce desert hedgehog (DHH) ligand, enabling a paracrine DHH/Ptch2 signaling cascade that conveys elevated permeability and angiogenesis. Finally, DHH silencing in BTICs dramatically reduced tumor growth, as well as vascularization and intra-tumor permeability. Collectively, our data unveil a role for DHH in exacerbated tumor angiogenesis and permeability, which may ultimately favor glioblastoma growth, and thus place the DHH/Ptch2 nexus as a molecular target for novel therapies. PMID:26635611

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

    PubMed Central

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

    2007-01-01

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

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

    PubMed

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

    2007-03-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2008-08-01

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

  13. Role of inflammatory mediators in lipid A analogue (ONO-4007)-induced vascular permeability change in mouse skin

    PubMed Central

    Ishida, Hiroyasu; Fujii, Emiko; Irie, Kaoru; Yoshioka, Toshimasa; Muraki, Takamura; Ogawa, Ryou

    2000-01-01

    Endotoxin shock is accompanied by an increase in peripheral vascular permeability. It has been postulated that most biological activities of LPS are derived from lipid A moiety. Here we examined the effect of lipid A analogue ONO-4007 in increasing vascular permeability and the possible mediators in mouse skin by a dye leakage method.Subcutaneous injection of ONO-4007 (12?mg?site?1) induced a dose-dependent increase in vascular permeability which was evident after 120?min.ONO-4007-induced dye leakage was significantly attenuated by pretreatments with anti-tumour necrosis factor-? (TNF-?) and anti-interleukin-1? (IL-1?) antibodies, but not with indomethacin (5?mg?kg?1) or diphenhydramine (10?mg?kg?1). ONO-4007-induced dye leakage was significantly inhibited by a pretreatment with NG-nitro-L-arginine methyl ester (L-NAME) (10?mg?kg?1) but not with aminoguanidine (50?mg?kg?1). In inducible nitric oxide synthase (iNOS)-deficient mice, ONO-4007 significantly increased the dye leakage, while ONO-4007 dilated rat thoracic aortic rings pre-contracted with phenylephrine, and the L-NAME pretreatment inhibited the dilation.Thus, TNF-?, IL-1? and constitutive NOSs-derived nitric oxide but not prostaglandins or histamine play a role in ONO-4007-induced increase in vascular permeability. Although ONO-4007 mimics LPS in increasing vascular permeability, mechanisms of permeability change elicited by ONO-4007 were not identical to those of LPS. PMID:10903960

  14. Vascular Endothelial Growth Factors Enhance the Permeability of the Mouse Blood-brain Barrier

    PubMed Central

    Jiang, Shize; Xia, Rui; Jiang, Yong; Wang, Lei; Gao, Fabao

    2014-01-01

    The blood-brain barrier (BBB) impedes entry of many drugs into the brain, limiting clinical efficacy. A safe and efficient method for reversibly increasing BBB permeability would greatly facilitate central nervous system (CNS) drug delivery and expand the range of possible therapeutics to include water soluble compounds, proteins, nucleotides, and other large molecules. We examined the effect of vascular endothelial growth factor (VEGF) on BBB permeability in Kunming (KM) mice. Human VEGF165 was administered to treatment groups at two concentrations (1.6 or 3.0 µg/mouse), while controls received equal-volume saline. Changes in BBB permeability were measured by parenchymal accumulation of the contrast agent Gd-DTPA as assessed by 7 T magnetic resonance imaging (MRI). Mice were then injected with Evans blue, sacrificed 0.5 h later, and perfused transcardially. Brains were removed, fixed, and sectioned for histological study. Both VEGF groups exhibited a significantly greater signal intensity from the cerebral cortex and basal ganglia than controls (P<0.001). Evans blue fluorescence intensity was higher in the parenchyma and lower in the cerebrovasculature of VEGF-treated animals compared to controls. No significant brain edema was observed by diffusion weighted MRI (DWI) or histological staining. Exogenous application of VEGF can increase the permeability of the BBB without causing brain edema. Pretreatment with VEGF may be a feasible method to facilitate drug delivery into the CNS. PMID:24551038

  15. Effect of Ultrasound on the Permeability of Vascular Wall to Nanoemulsion Droplets

    PubMed Central

    Thakkar, Dhaval; Gupta, Roohi; Monson, Kenneth; Rapoport, Natalya

    2013-01-01

    The effect of ultrasound on the permeability of blood vessels to nanoemulsion droplets was investigated using excised mouse carotid arteries as model blood vessels. Perfluorocarbon nanodroplets were formed by perfluoro-15-crown-5-ether (PFCE) and stabilized by poly(ethylene oxide)-co-poly(D,L-lactide) (PEG-PDLA) block copolymer shells. Nanodroplet fluorescence was imparted by interaction with FITC-dextran (molecular weight of 70,000 Da). The permeability of carotid arteries to nanodroplets was studied in the presence or absence of continuous wave (CW) or pulsed therapeutic 1-MHz ultrasound. The data showed that the application of ultrasound resulted in permeabilization of the vascular wall to nanodroplets. The effect of CW ultrasound was substantially stronger than that of pulsed ultrasound of the same total energy. No effect of blood vessel pre-treatment with ultrasound was observed. PMID:23849384

  16. Heterogeneous vascular permeability and alternative diffusion barrier in sensory circumventricular organs of adult mouse brain.

    PubMed

    Morita, Shoko; Furube, Eriko; Mannari, Tetsuya; Okuda, Hiroaki; Tatsumi, Kouko; Wanaka, Akio; Miyata, Seiji

    2016-02-01

    Fenestrated capillaries of the sensory circumventricular organs (CVOs), including the organum vasculosum of the lamina terminalis, the subfornical organ and the area postrema, lack completeness of the blood-brain barrier (BBB) to sense a variety of blood-derived molecules and to convey the information into other brain regions. We examine the vascular permeability of blood-derived molecules and the expression of tight-junction proteins in sensory CVOs. The present tracer assays revealed that blood-derived dextran 10 k (Dex10k) having a molecular weight (MW) of 10,000 remained in the perivascular space between the inner and outer basement membranes, but fluorescein isothiocyanate (FITC; MW: 389) and Dex3k (MW: 3000) diffused into the parenchyma. The vascular permeability of FITC was higher at central subdivisions than at distal subdivisions. Neither FITC nor Dex3k diffused beyond the dense network of glial fibrillar acidic protein (GFAP)-positive astrocytes/tanycytes. The expression of tight-junction proteins such as occludin, claudin-5 and zonula occludens-1 (ZO-1) was undetectable at the central subdivisions of the sensory CVOs but some was expressed at the distal subdivisions. Electron microscopic observation showed that capillaries were surrounded with numerous layers of astrocyte processes and dendrites. The expression of occludin and ZO-1 was also observed as puncta on GFAP-positive astrocytes/tanycytes of the sensory CVOs. Our study thus demonstrates the heterogeneity of vascular permeability and expression of tight-junction proteins and indicates that the outer basement membrane and dense astrocyte/tanycyte connection are possible alternative mechanisms for a diffusion barrier of blood-derived molecules, instead of the BBB. PMID:26048259

  17. EPHA4-FC TREATMENT REDUCES ISCHEMIA/REPERFUSION-INDUCED INTESTINAL INJURY BY INHIBITING VASCULAR PERMEABILITY.

    PubMed

    Woodruff, Trent M; Wu, Mike C-L; Morgan, Michael; Bain, Nathan T; Jeanes, Angela; Lipman, Jeffrey; Ting, Michael J; Boyd, Andrew W; Taylor, Stephen M; Coulthard, Mark G

    2016-02-01

    The inflammatory response is characterized by increased endothelial permeability, which permits the passage of fluid and inflammatory cells into interstitial spaces. The Eph/ephrin receptor ligand system plays a role in inflammation through a signaling cascade, which modifies Rho-GTPase activity. We hypothesized that blocking Eph/ephrin signaling using an EphA4-Fc would result in decreased inflammation and tissue injury in a model of ischemia/reperfusion (I/R) injury. Mice undergoing intestinal I/R pretreated with the EphA4-Fc had significantly reduced intestinal injury compared to mice injected with the control Fc. This reduction in I/R injury was accompanied by significantly reduced neutrophil infiltration, but did not affect intestinal inflammatory cytokine generation. Using microdialysis, we identified that intestinal I/R induced a marked increase in systemic vascular leakage, which was completely abrogated in EphA4-Fc-treated mice. Finally, we confirmed the direct role of Eph/ephrin signaling in endothelial leakage by demonstrating that EphA4-Fc inhibited tumor necrosis factor-?-induced vascular permeability in human umbilical vein endothelial cells. This study identifies that Eph/ephrin interaction induces proinflammatory signaling in vivo by inducing vascular leak and neutrophil infiltration, which results in tissue injury in intestinal I/R. Therefore, therapeutic targeting of Eph/ephrin interaction using inhibitors, such as EphA4-Fc, may be a novel method to prevent tissue injury in acute inflammation by influencing endothelial integrity and by controlling vascular leak. PMID:26771935

  18. PIV Measurements of Turbulent Flow Over a Permeable Wall using a Refractive-Index Matching Approach

    NASA Astrophysics Data System (ADS)

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

    2013-11-01

    Turbulent flows over permeable walls occur in a variety of natural environments and engineering applications. Unlike classical and widely-studied flows over impermeable walls, the peculiar dynamics of flow generated by permeable walls are poorly understood. Early studies suggest that the well-known higher energy dissipation induced by permeability (as compared to impermeable walls with similar roughness) can be explained by unveiling the flow interactions within the transition layer that forms at the interface between the overlying flow and the permeable wall. To overcome the challenges associated with quantifying the flow character both above and within a permeable wall, a Refractive-Index-Matching (RIM) approach was employed. Doing so facilitated optical access to the fluid flowing through the permeable wall, thus yielding direct PIV pore-space flow measurements within the transition layer. The permeable wall was formed by packing acrylic spheres in a cubic arrangement and was then immersed in an aqueous solution of sodium iodide at a concentration and temperature that ensured accurate refractive index match with the wall. Measurements were focused on the flow across the wall interface and the turbulent attributes of these surface-subsurface interactions were detailed.

  19. Functional Implication of Dp71 in Osmoregulation and Vascular Permeability of the Retina

    PubMed Central

    Sene, Abdoulaye; Tadayoni, Ramin; Pannicke, Thomas; Wurm, Antje; El Mathari, Brahim; Benard, Romain; Roux, Michel Joseph; Yaffe, David; Mornet, Dominique; Reichenbach, Andreas; Sahel, Jose-Alain; Rendon, Alvaro

    2009-01-01

    Functional alterations of Mller cells, the principal glia of the retina, are an early hallmark of most retina diseases and contribute to their further progression. The molecular mechanisms of these reactive Mller cell alterations, resulting in disturbed retinal homeostasis, remain largely unknown. Here we show that experimental detachment of mouse retina induces mislocation of the inwardly rectifying potassium channels (Kir4.1) and a downregulation of the water channel protein (AQP4) in Mller cells. These alterations are associated with a strong decrease of Dp71, a cytoskeleton protein responsible for the localization and the clustering of Kir4.1 and AQP4. Partial (in detached retinas) or total depletion of Dp71 in Mller cells (in Dp71-null mice) impairs the capability of volume regulation of Mller cells under osmotic stress. The abnormal swelling of Mller cells In Dp71-null mice involves the action of inflammatory mediators. Moreover, we investigated whether the alterations in Mller cells of Dp71-null mice may interfere with their regulatory effect on the blood-retina barrier. In the absence of Dp71, the retinal vascular permeability was increased as compared to the controls. Our results reveal that Dp71 is crucially implicated in the maintenance of potassium homeostasis, in transmembraneous water transport, and in the Mller cell-mediated regulation of retinal vascular permeability. Furthermore, our data provide novel insights into the mechanisms of retinal homeostasis provided by Mller cells under normal and pathological conditions. PMID:19809515

  20. Protein Kinase C? Phosphorylates Occludin Regulating Tight Junction Trafficking in Vascular Endothelial Growth FactorInduced Permeability In Vivo

    PubMed Central

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

    2012-01-01

    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. PMID:22438576

  1. Minocycline prevents retinal inflammation and vascular permeability following ischemia-reperfusion injury

    PubMed Central

    2013-01-01

    Background Many retinal diseases are associated with vascular dysfunction accompanied by neuroinflammation. We examined the ability of minocycline (Mino), a tetracycline derivative with anti-inflammatory and neuroprotective properties, to prevent vascular permeability and inflammation following retinal ischemia-reperfusion (IR) injury, a model of retinal neurodegeneration with breakdown of the blood-retinal barrier (BRB). Methods Male SpragueDawley rats were subjected to 45min of pressure-induced retinal ischemia, with the contralateral eye serving as control. Rats were treated with Mino prior to and following IR. At 48h after reperfusion, retinal gene expression, cellular inflammation, Evans blue dye leakage, tight junction protein organization, caspase-3 activation, and DNA fragmentation were measured. Cellular inflammation was quantified by flow-cytometric evaluation of retinal tissue using the myeloid marker CD11b and leukocyte common antigen CD45 to differentiate and quantify CD11b+/CD45low microglia, CD11b+/CD45hi myeloid leukocytes and CD11bneg/CD45hi lymphocytes. Major histocompatibility complex class II (MHCII) immunoreactivity was used to determine the inflammatory state of these cells. Results Mino treatment significantly inhibited IR-induced retinal vascular permeability and disruption of tight junction organization. Retinal IR injury significantly altered mRNA expression for 21 of 25 inflammation- and gliosis-related genes examined. Of these, Mino treatment effectively attenuated IR-induced expression of lipocalin 2 (LCN2), serpin peptidase inhibitor clade A member 3N (SERPINA3N), TNF receptor superfamily member 12A (TNFRSF12A), monocyte chemoattractant-1 (MCP-1, CCL2) and intercellular adhesion molecule-1 (ICAM-1). A marked increase in leukostasis of both myeloid leukocytes and lymphocytes was observed following IR. Mino treatment significantly reduced retinal leukocyte numbers following IR and was particularly effective in decreasing the appearance of MHCII+ inflammatory leukocytes. Surprisingly, Mino did not significantly inhibit retinal cell death in this model. Conclusions IR induces a retinal neuroinflammation within hours of reperfusion characterized by inflammatory gene expression, leukocyte adhesion and invasion, and vascular permeability. Despite Mino significantly inhibiting these responses, it failed to block neurodegeneration. PMID:24325836

  2. Pigment epithelium-derived factor inhibits vascular endothelial growth factor-and interleukin-1beta-induced vascular permeability and angiogenesis in retinal endothelial cells.

    PubMed

    Sheikpranbabu, Sardarpasha; Ravinarayanan, Haribalaganesh; Elayappan, Banumathi; Jongsun, Park; Gurunathan, Sangiliyandi

    2010-01-01

    Increased vascular permeability associated with retinal vascular leakage is known to occur in patients with diabetes, and contributes to endothelial barrier dysfunction. The purpose of this study was to examine the effect of pigment epithelium-derived factor (PEDF) on signaling cascade in porcine retinal endothelial cells (PREC) related to permeability and angiogenesis induced by vascular endothelial growth factor (VEGF)-and interleukin-1beta (IL-1beta). PREC were exposed to VEGF, IL-1beta and PEDF at different concentrations, and in vitro permeability was assessed by solute flux assay using 70-kDa RITC-dextran. Angiogenic assays such as proliferation, migration and tube formation were determined by MTT, wound-scratch method and on-gel assay system respectively. To explore the signaling pathways behind VEGF-and IL-1beta-induced PREC permeability, an inhibitor assay was carried out using PP2, a Src kinase inhibitor. Further, Src activity was assessed by transient transfection assay using constitutively active (CA) and dominant negative (DN) Src mutants. We report that VEGF-and IL-1beta-stimulates permeability, in a dose and time-dependent manner and PEDF inhibits the VEGF-and IL-1beta-induced PREC permeability. In addition, PEDF inhibits the VEGF-and IL-1beta-induced endothelial cell proliferation, migration and tube formation. In addition, overexpression of DN Src blocked both VEGF-and IL-1beta-stimulation of permeability, proliferation and migration, while overexpression of CA Src overpowers the inhibitory action of PEDF on permeability, proliferation and migration. These results demonstrate that PEDF may inhibit the VEGF-and IL-1beta-induced permeability and angiogenesis via Src-dependent pathway. PMID:20006737

  3. Activation of complement and neutrophils increases vascular permeability during air embolism.

    PubMed

    Huang, K L; Lin, Y C

    1997-04-01

    Pulmonary air embolism occurs in diving and aviation during acute pressure reductions and in clinical complications. Undoubtedly physical obstructions play a role, but bubbles in blood can produce a number of indirect effects leading to tissue injury. In the present study, we investigated the involvement of the complement system and polymorphonuclear leukocytes (PMN) in altering segmental vascular resistance, lung weight gain, and filtration coefficient (Kf), by using isolated and perfused rat lungs. After establishing ventilation with air and 5% CO2, the lung was removed en bloc and suspended in a humidified chamber at 37 degrees C. Lung weight and arterial and venous pressures were monitored continuously. The buffered salt perfusate contains 4% Ficoll for osmotic balance. We used four series of perfusates containing 20% of: a) normal plasma; b) decomplemented plasma (from donor rats pretreated with a cobra venom factor); c) normal plasma and PMN at 2 x 10(6).ml-1; and d) decomplemented plasma and PMN at 2 x 10(6).ml-1. Pulmonary air embolism, air bubbles introduced through the pulmonary artery, increased pulmonary arterial resistance and pulmonary arterial blood pressure. The lung weight and lung water content were greater than those in the control groups. Air embolism increased vascular permeability, which was shown by an elevated Kf after air infusion. After air embolism, Kf was 0.63 +/- 0.05 g.min-1.cm H2O-1.100 g-1 in lungs perfused with both PMN and plasma, which was significantly greater than those in lungs perfused with either plasma (0.49 +/- 0.04), decomplemented plasma (0.44 +/- 0.03), or PMN and decomplemented plasma (0.47 +/- 0.03). These results demonstrated that air embolism increases vascular permeability of the lung by pulmonary hypertension, activation of the complement, and activation of PMN. PMID:9096825

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

    PubMed Central

    Masri, Abeer A Al; Eter, Eman El

    2012-01-01

    AIM: To investigate the effect of administration of agmatine (AGM) on gastric protection against ischemia reperfusion (I/R) injury. METHODS: Three groups of rats (6/group); sham, gastric I/R injury, and gastric I/R + AGM (100 mg/kg, i.p. given 15 min prior to gastric ischemia) were recruited. Gastric injury was conducted by ligating celiac artery for 30 min and reperfusion for another 30 min. Gastric tissues were histologically studied and immunostained with angiopoietin 1 (Ang-1) and Ang-2. Vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein-1 (MCP-1) were measured in gastric tissue homogenate. To assess whether AKt/phosphatidyl inositol-3-kinase (PI3K) mediated the effect of AGM, an additional group was pretreated with Wortmannin (WM) (inhibitor of Akt/PI3K, 15 ?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 Evans blue dye. RESULTS: AGM markedly reduced Evans 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. PMID:22611311

  5. Placenta Growth Factor-1 Exerts Time-Dependent Stabilization of Adherens Junctions Following VEGF-Induced Vascular Permeability

    PubMed Central

    Cai, Jun; Wu, Lin; Qi, Xiaoping; Shaw, Lynn; Li Calzi, Sergio; Caballero, Sergio; Jiang, Wen G.; Vinores, Stanley A.; Antonetti, David; Ahmed, Asif; Grant, Maria B.; Boulton, Michael E.

    2011-01-01

    Increased vascular permeability is an early event characteristic of tissue ischemia and angiogenesis. Although VEGF family members are potent promoters of endothelial permeability the role of placental growth factor (PlGF) is hotly debated. Here we investigated PlGF isoforms 1 and 2 and present in vitro and in vivo evidence that PlGF-1, but not PlGF-2, can inhibit VEGF-induced permeability but only during a critical window post-VEGF exposure. PlGF-1 promotes VE-cadherin expression via the trans-activating Sp1 and Sp3 interaction with the VE-cadherin promoter and subsequently stabilizes transendothelial junctions, but only after activation of endothelial cells by VEGF. PlGF-1 regulates vascular permeability associated with the rapid localization of VE-cadherin to the plasma membrane and dephosphorylation of tyrosine residues that precedes changes observed in claudin 5 tyrosine phosphorylation and membrane localization. The critical window during which PlGF-1 exerts its effect on VEGF-induced permeability highlights the importance of the translational significance of this work in that PLGF-1 likely serves as an endogenous anti-permeability factor whose effectiveness is limited to a precise time point following vascular injury. Clinical approaches that would pattern nature's approach would thus limit treatments to precise intervals following injury and bring attention to use of agents only during therapeutic windows. PMID:21464949

  6. Interleukin-33 induces angiogenesis and vascular permeability through ST2/TRAF6-mediated endothelial nitric oxide production.

    PubMed

    Choi, Yeon-Sook; Choi, Hyun-Jung; Min, Jeong-Ki; Pyun, Bo-Jeong; Maeng, Yong-Sun; Park, Hongryeol; Kim, Jihye; Kim, Young-Myeong; Kwon, Young-Guen

    2009-10-01

    Interleukin-33 (IL-33), a member of the IL-1 cytokine family, is emerging as a new regulator of immune responses and inflammatory vascular diseases. Although IL-33 and its cognate receptor ST2 appear to be expressed in vascular cells, the precise role of IL-33 in the vasculature has not been determined. In this study, we report a novel role of IL-33 as a potent endothelial activator, promoting both angiogenesis and vascular permeability. IL-33 increased proliferation, migration, and morphologic differentiation of human endothelial cells, consistently with increased angiogenesis in vivo. IL-33 also increased endothelial permeability with reduced vascular endothelial-cadherin-facilitated cell-cell junctions in vitro and induced vascular leakage in mouse skin. These effects of IL-33 were blocked by knockdown of ST2. Ligation of IL-33 with ST2 rapidly increased endothelial nitric oxide (NO) production through TRAF6-mediated activation of phosphoinoside-3-kinase, Akt, and endothelial NO synthase. Moreover, pharmacologic or genetic blockage of endothelial NO generation resulted in the inhibition of angiogenesis and vascular hyperpermeability induced by IL-33. These data demonstrate that IL-33 promotes angiogenesis and vascular leakage by stimulating endothelial NO production via the ST2/TRAF6-Akt-eNOS signaling pathway. These findings open new perspectives for the role of IL-33 in the pathogenesis of angiogenesis-dependent and inflammatory vascular diseases. PMID:19661270

  7. Involvement of Protein Kinase C-? in Vascular Permeability in Acute Lung Injury

    PubMed Central

    Ahn, Jong J.; Jung, Jong P.; Park, Soon E.; Lee, Minhyun

    2015-01-01

    Pulmonary edema is a major cause of mortality due to acute lung injury (ALI). The involvement of protein kinase C-? (PKC-?) in ALI has been a controversial topic. Here we investigated PKC-? function in ALI using PKC-? knockout (KO) mice and PKC inhibitors. Our results indicated that although the ability to produce proinflammatory mediators in response to LPS injury in PKC-? KO mice was similar to that of control mice, they showed enhanced recruitment of neutrophils to the lung and more severe pulmonary edema. PKC-? inhibition promoted barrier dysfunction in an endothelial cell layer in vitro, and administration of a PKC-?-specific inhibitor significantly increased steady state vascular permeability. A neutrophil transmigration assay indicated that the PKC-? inhibition increased neutrophil transmigration through an endothelial monolayer. This suggests that PKC-? inhibition induces structural changes in endothelial cells, allowing extravasation of proteins and neutrophils. PMID:26330807

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

    PubMed Central

    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

    2012-01-01

    SUMMARY 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 non-inflammatory protein loosing enteropathy. Deletion of PV1 in endothelium, but not 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

  9. Enhanced vascular permeability in solid tumor involving peroxynitrite and matrix metalloproteinases.

    PubMed

    Wu, J; Akaike, T; Hayashida, K; Okamoto, T; Okuyama, A; Maeda, H

    2001-04-01

    Peroxynitrite (ONOO(-)), which is generated from nitric oxide (NO) and superoxide anion (O(2)(.-)) under pathological conditions, plays an important role in pathophysiological processes. Activation of matrix metalloproteinases (MMPs) contributes to tumor angiogenesis and metastasis. NO mediates the enhanced vascular permeability and retention (EPR) effect in solid tumors, and ONOO(-)activates proMMP to MMP in vitro. In this study, we examined the role of ONOO(-)in the EPR effect in solid tumors and normal tissues as related to MMP activation. Authentic ONOO(-), at 50 nmol or higher concentrations, induced the enhanced vascular permeability in normal dorsal skin of mice. ONOO(-)scavengers ebselen and uric acid significantly suppressed the EPR effect in mouse sarcoma 180 (S-180) tumors. Indirect evidence for formation of ONOO(-)in S-180 and mouse colon adenocarcinoma (C-38) tumors included strong immunostaining for nitrotyrosine in the tumor tissue, predominantly surrounding the tumor vessels. MMP inhibitor BE16627B (66.6 mg / kg i.v., given 2 times) or SI-27 (10 mg / kg i.p., given 2 times) significantly suppressed the ONOO(-)-induced EPR effect in S-180 tumors and in normal skin. Soybean trypsin inhibitor (Kunitz type), broad-spectrum proteinase inhibitor ovomacroglobulin, and bradykinin receptor antagonist HOE 140 also significantly suppressed the ONOO(-)-induced EPR effect in normal skin tissues. These data suggest that ONOO(-)may be involved in and promote the EPR effect in tumors, which could be mediated partly through activation of MMPs and a subsequent proteinase cascade to generate potent vasoactive mediators such as bradykinin. PMID:11346467

  10. Cardiopulmonary bypass increases pulmonary microvascular permeability through the Src kinase pathway: Involvement of caveolin-1 and vascular endothelial cadherin

    PubMed Central

    ZHANG, JUNWEN; JIANG, ZHAOLEI; BAO, CHUNRONG; MEI, JU; ZHU, JIAQUAN

    2016-01-01

    Changes in pulmonary microvascular permeability following cardiopulmonary bypass (CPB) and the underlying mechanisms have not yet been established. Therefore, the aim of the present study was to elucidate the alterations in pulmonary microvascular permeability following CPB and the underlying mechanism. The pulmonary microvascular permeability was measured using Evans Blue dye (EBD) exclusion, and the neutrophil infiltration and proinflammatory cytokine secretion was investigated. In addition, the activation of Src kinase and the phosphorylation of caveolin-1 and vascular endothelial cadherin (VE-cadherin) was examined. The results revealed that CPB increased pulmonary microvascular leakage, neutrophil count and proinflammatory cytokines in the bronchoalveolar lavage fluid, and activated Src kinase. The administration of PP2, an inhibitor of Src kinase, decreased the activation of Src kinase and attenuated the increase in pulmonary microvascular permeability observed following CPB. Two important proteins associated with vascular permeability, caveolin-1 and VE-cadherin, were significantly activated at 24 h in the lung tissues following CPB, which correlated with the alterations in pulmonary microvascular permeability and Src kinase. PP2 administration inhibited their activation, suggesting that they are downstream factors of Src kinase activation. The data indicated that the Src kinase pathway increased pulmonary microvascular permeability following CPB, and the activation of caveolin-1 and VE-cadherin may be involved. Inhibition of this pathway may provide a potential therapy for acute lung injury following cardiac surgery. PMID:26847917

  11. Differential permeability of uterine and liver vascular beds to estrogens and estrogen conjugates.

    PubMed

    Verheugen, C; Pardridge, W M; Judd, H L; Chaudhuri, G

    1984-12-01

    The role of capillary membrane permeability and the effect of plasma protein binding on the influx of unconjugated and conjugated estrogens into a target organ, the uterus, and a metabolic organ, the liver, were studied in anesthetized rats. In the absence of plasma proteins, estrone (E1) and estradiol (E2) were freely diffusible through the uterine capillaries, but influx was significantly reduced for estriol (E3) and estetrol. In the uterus, the influx of the conjugated estrogens was markedly restricted and approximated the influx of dextran, a vascular space marker. The polarity of the compound (based on the number of hydrogen bond-forming functional groups and the presence of charged groups) appeared to predict uterine endothelial membrane permeability better than the octanol/Ringer's partition coefficient. In contrast to the selective permeability properties of the uterine endothelial barrier, the limiting membrane lining the hepatic microcirculation, the hepatocyte cell membrane, was highly permeable to all unconjugated and conjugated estrogens. The addition of 4% albumin to the injection solution led to a significant inhibition of uterine influx of E2, but not E1 or E3. In the liver, only the influx of E1 sulfate was slightly diminished by 4% albumin. In all cases, the influx of estrogens greatly exceeded the rate that would be expected if only the fraction that was free (dialyzable) in vitro was diffusible in vivo. Human sera containing sex hormone-binding globulin and albumin caused inhibition of influx of E1 and E2 through the uterine capillary barriers, whereas in the liver, the influx of E2 sulfate, and E3 glucuronide were diminished. The results are compatible with a difference in permeability of the microvasculature of the two organs and a differential availability of protein-bound estrogen for influx into liver and uterus. With the exception of E1, which is nearly completely diffusible into both organs, the influx of estrogens and estrogen conjugates into liver is greatly amplified compared to that into a peripheral organ such as the uterus. PMID:6092408

  12. Baseflow index regionalization analysis in a mediterranean area and data scarcity context: Role of the catchment permeability index

    NASA Astrophysics Data System (ADS)

    Longobardi, Antonia; Villani, Paolo

    2008-06-01

    SummaryLow flow characteristics are affected by different physiographic factors such as climate, topography, geology and soils, and regional regression prediction models, to estimate low flow indexes at ungauged sites, mainly rely on these factors. The paper focuses on the baseflow index, one of the most important low flow characteristics for a catchment, and presents: (i) the analysis of baseflow separation algorithms for BFI evaluation and (ii) a regional approach to predict the BFI at ungauged sites in a Mediterranean region, for which only very poor data are available. The prediction of baseflow contribution to total streamflow is based on the introduction of a permeability index, at the catchment scale, and regional linear regression equations simply relate the latter to the BFI. For the studied area geological features have been found to be the major factor affecting baseflow and the permeability index estimation for a particular catchment, in an apparently over-simplified schematization, essentially reflects catchment lithology. As a matter of fact, an accurate catchment geology spatial variability description reduces the average long-term BFI index prediction error from 23% to 14% and above all increases the explained variance from 23% to 68%.

  13. Pirfenidone exhibits cardioprotective effects by regulating myocardial fibrosis and vascular permeability in pressure-overloaded hearts.

    PubMed

    Yamagami, Kiyoshi; Oka, Toru; Wang, Qi; Ishizu, Takamaru; Lee, Jong-Kook; Miwa, Keiko; Akazawa, Hiroshi; Naito, Atsuhiko T; Sakata, Yasushi; Komuro, Issei

    2015-08-01

    Although cardiac fibrosis causes heart failure, its molecular mechanisms remain elusive. In this study, we investigated the mechanisms of cardiac fibrosis and examined the effects of the antifibrotic drug pirfenidone (PFD) on chronic heart failure. To understand the responsible mechanisms, we generated an in vivo pressure-overloaded heart failure model via transverse aortic constriction (TAC) and examined the effects of PFD on chronic-phase cardiac fibrosis and function. In the vehicle group, contractile dysfunction and left ventricle fibrosis progressed further from 4 to 8 wk after TAC but were prevented by PFD treatment beginning 4 wk after TAC. We isolated cardiac fibroblasts and vascular endothelial cells from the left ventricles of adult male mice and investigated the cell-type-specific effects of PFD. Transforming growth factor-? induced upregulated collagen 1 expression via p38 phosphorylation and downregulated claudin 5 (Cldn5) expression in cardiac fibroblasts and endothelial cells, respectively; both processes were inhibited by PFD. Moreover, PFD inhibited changes in the collagen 1 and Cldn5 expression levels, resulting in reduced fibrosis and serum albumin leakage into the interstitial space during the chronic phase in TAC hearts. In conclusion, PFD inhibited cardiac fibrosis by suppressing both collagen expression and the increased vascular permeability induced by pressure overload. PMID:26055790

  14. Role of nitric oxide in tumor microcirculation. Blood flow, vascular permeability, and leukocyte-endothelial interactions.

    PubMed Central

    Fukumura, D.; Yuan, F.; Endo, M.; Jain, R. K.

    1997-01-01

    The present study was designed to define the role of nitric oxide (NO) in tumor microcirculation, through the direct intravital microcirculatory observations after administration of NO synthase (NOS) inhibitor and NO donor both regionally and systemically. More specifically, we tested the following hypotheses: 1) endogenous NO derived from tumor vascular endothelium and/or tumor cells increases and/or maintains tumor blood flow, decreases leukocyte-endothelial interactions, and increases vascular permeability, 2) exogenous NO can increase tumor blood flow via vessel dilatation and decrease leukocyte-endothelial interactions, and 3) NO production and tissue responses to NO are tumor dependent. To this end, a murine mammary adenocarcinoma (MCaIV) and a human colon adenocarcinoma (LS174T) were implanted in the dorsal skinfold chamber in C3H and severe combined immunodeficient mice, respectively, and observed by means of intravital fluorescence microscopy. Both regional and systemic inhibition of endogenous NO by N omega-nitro-L-arginine methyl ester (L-NAME; 100 mumol/L superfusion or 10 mg/kg intravenously) significantly decreased vessel diameter and local blood flow rate. The diameter change was dominant on the arteriolar side. Superfusion of NO donor (spermine NO, 100 mumol/L) increased tumor vessel diameter and flow rate, whereas systemic injection of spermine NO (2.62 mg/kg) had no significant effect on these parameters. Rolling and stable adhesion of leukocytes were significantly increased by intravenous injection of L-NAME. In untreated animals, both MCaIV and LS174T tumor vessels were leaky to albumin. Systemic NO inhibition significantly attenuated tumor vascular permeability of MCaIV but not of LS174T tumor. Immunohistochemical studies, using polyclonal antibodies to endothelial NOS and inducible NOS, revealed a diffuse pattern of positive labeling in both MCaIV and LS174T tumors. Nitrite and nitrate levels in tumor interstitial fluid of MCaIV but not of LS174T were significantly higher than that in normal subcutaneous interstitial fluid. These results support our hypotheses regarding the microcirculatory response to NO in tumors. Modulation of NO level in tumors is a potential strategy for altering tumor hemodynamics and thus improving oxygen, drug, gene vector, and effector cell delivery to solid tumors. Images Figure 5 PMID:9033284

  15. PEDF improves cardiac function in rats with acute myocardial infarction via inhibiting vascular permeability and cardiomyocyte apoptosis.

    PubMed

    Zhang, Hao; Wang, Zheng; Feng, Shou-Jie; Xu, Lei; Shi, He-Xian; Chen, Li-Li; Yuan, Guang-Da; Yan, Wei; Zhuang, Wei; Zhang, Yi-Qian; Zhang, Zhong-Ming; Dong, Hong-Yan

    2015-01-01

    Pigment epithelium-derived factor (PEDF) is a pleiotropic gene with anti-inflammatory, antioxidant and anti-angiogenic properties. However, recent reports about the effects of PEDF on cardiomyocytes are controversial, and it is not known whether and how PEDF acts to inhibit hypoxic or ischemic endothelial injury in the heart. In the present study, adult Sprague-Dawley rat models of acute myocardial infarction (AMI) were surgically established. PEDF-small interfering RNA (siRNA)-lentivirus (PEDF-RNAi-LV) or PEDF-LV was delivered into the myocardium along the infarct border to knockdown or overexpress PEDF, respectively. Vascular permeability, cardiomyocyte apoptosis, myocardial infarct size and animal cardiac function were analyzed. We also evaluated PEDF's effect on the suppression of the endothelial permeability and cardiomyocyte apoptosis under hypoxia in vitro. The results indicated that PEDF significantly suppressed the vascular permeability and inhibited hypoxia-induced endothelial permeability through PPARγ-dependent tight junction (TJ) production. PEDF protected cardiomyocytes against ischemia or hypoxia-induced cell apoptosis both in vivo and in vitro via preventing the activation of caspase-3. We also found that PEDF significantly reduced myocardial infarct size and enhanced cardiac function in rats with AMI. These data suggest that PEDF could protect cardiac function from ischemic injury, at least by means of reducing vascular permeability, cardiomyocyte apoptosis and myocardial infarct size. PMID:25768344

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

    PubMed

    Bao, Lingzhi; Shi, Honglian

    2010-11-15

    As a potent environmental oxidative stressor, arsenic exposure has been reported to exacerbate cardiovascular diseases and increase vascular endothelial cell monolayer permeability. However, the underlying mechanism of this effect is not well understood. In this paper, we test our hypothesis that reactive oxygen species (ROS)-induced vascular endothelial growth factor (VEGF) expression may play an important role in an arsenic-caused increase of endothelial cell monolayer permeability. The mouse brain vascular endothelial cell bEnd3 monolayer was exposed to arsenite for 1, 3, and 6 days. The monolayer permeability, VEGF protein release, and ROS generation were determined. In addition, VE-cadherin and zonula occludens-1 (ZO-1), two membrane structure proteins, were immunostained to elucidate the effects of arsenite on the cell-cell junction. The roles of ROS and VEGF in arsenite-induced permeability was determined by inhibiting ROS with antioxidants and immuno-depleting VEGF with a VEGF antibody. We observed that arsenite increased bEnd3 monolayer permeability, elevated the production of cellular ROS, and increased VEGF release. VE-cadherin and ZO-1 disruptions were also found in cells treated with arsenite. Furthermore, both antioxidant (N-acetyl cysteine and tempol) and the VEGF antibody treatments significantly lowered the arsenite-induced permeability of the bEnd3 monolayer as well as VEGF expression. VE-cadherin and ZO-1 disruptions were also diminished by N-acetyl cysteine and the VEGF antibody. Our data suggest that the increase in VEGF expression caused by ROS may play an important role in the arsenite-induced increase in endothelial cell permeability. PMID:20954712

  17. [Estimation of the Index Value of Dielectric Permeability inside the Membranes of Purple Bacteria].

    PubMed

    Borisov, A Y; Kozlovsky, V S

    2015-01-01

    The joint application of the precise X-ray data for isolated bacteriochlorophyll complexes of reaction centers and the fundamental formulae for the energy of interaction between two equal dipoles enabled us to suggest a new methodical approach for determination of the values of the index of dielectric permeability in the micro volume enclosing special pairs in Rhodobacter sphaeroides reaction centers. The most probable value for this parameter was thus determined within 1.66-1.76. This approach was generalized for the inner layer of the membranes of purple bacteria and yielded the index value about 1.70-1.85. It is argued that this range of dielectric permeability is adequate for bacterial and plant membranes as well. Low magnitude of this parameter contributes to higher efficiency of energy migration from vast light-harvesting chlorophyll "antenna" to the energy converting reaction centers and hence to higher efficiency of the whole photosynthesis. PMID:26394473

  18. A 3D porous media liver lobule model: the importance of vascular septa and anisotropic permeability for homogeneous perfusion.

    PubMed

    Debbaut, Charlotte; Vierendeels, Jan; Siggers, Jennifer H; Repetto, Rodolfo; Monbaliu, Diethard; Segers, Patrick

    2014-01-01

    The hepatic blood circulation is complex, particularly at the microcirculatory level. Previously, 2D liver lobule models using porous media and a 3D model using real sinusoidal geometries have been developed. We extended these models to investigate the role of vascular septa (VS) and anisotropic permeability. The lobule was modelled as a hexagonal prism (with or without VS) and the tissue was treated as a porous medium (isotropic or anisotropic permeability). Models were solved using computational fluid dynamics. VS inclusion resulted in more spatially homogeneous perfusion. Anisotropic permeability resulted in a larger axial velocity component than isotropic permeability. A parameter study revealed that results are most sensitive to the lobule size and radial pressure drop. Our model provides insight into hepatic microhaemodynamics, and suggests that inclusion of VS in the model leads to perfusion patterns that are likely to reflect physiological reality. The model has potential for applications to unphysiological and pathological conditions. PMID:23237543

  19. Quantitative and qualitative effects of experimental radioimmunotherapy on tumor vascular permeability.

    PubMed

    Blumenthal, R D; Kashi, R; Sharkey, R M; Goldenberg, D M

    1995-05-16

    Localization of radiolabeled antibodies in the perivascular space of tumors resulted in morphological changes in blood vessel structure and physiological changes in tumor vessel function. Vessel diameter decreased by day 14 and was associated with a significant decline in vascular volume (VV). Upon recovery of VV, the basement membrane surrounding the endothelium had thickened. Tumor vascular permeability (VP) decreased within 7 days of treatment and remained suppressed throughout the 42-day observation period of our study. The decline in VP, which could be visualized by fluorescent microscopy of FITC-dextran extravasation, was dose-related and could be quantified at doses as low as 800 cGy. The radioantibody-induced 50-80% decline in tumor VP was observed in 3 human colonic xenografts (GW-39, LSI74T and MOSER). Decreases in VP have been observed for proteins ranging in size from 20 to 150 kDa. Similar effects on VP were noted when low protein doses (10-30 micrograms), which resulted in heterogeneous antibody distribution, were used or with high protein doses (400-750 micrograms), which resulted in more uniform penetration of antibody. If 188Re or 90Y, radiometals with higher beta-energy and longer path lengths, were substituted for 131I, a similar decrease in VP was observed. The radioimmunotherapy (RAIT)-induced decrease in tumor VP resulted in a 90% decline in accretion of a second dose of radioantibody. The 10% of the second dose that was taken up by the tumor targeted many already non-viable tumor regions and some, but not all, viable tumor cell clusters. PMID:7759161

  20. Differentiation between vascular permeability factor and IL-2 in lymphocyte supernatants from patients with minimal-change nephrotic syndrome.

    PubMed Central

    Heslan, J M; Branellec, A I; Pilatte, Y; Lang, P; Lagrue, G

    1991-01-01

    Immunotherapy of cancers with recombinant IL-2 induces a vascular leak syndrome which is mainly due to an increase in vascular permeability. A lymphokine, the vascular permeability factor (VPF), which increases vascular permeability, has been characterized in minimal-change nephrotic syndrome (MCNS) and appeared very similar to IL-2. Here we have undertaken a further characterization of VPF in order to determine how closely related this factor was to human IL-2. Both the IL-2 bioassay and Western blot analysis of the MCNS lymphocyte concentrated supernatants with high VPF activity revealed the presence of low quantities of IL-2. Preparative isoelectrofocusing (IEF) of concentrated supernatants resolved each lymphokine in a separate peak, with apparent pIs of 5.2 for VPF and 7.5-10.1 for IL-2. Since a sensitive IL-2 ELISA failed to exhibit any significant antigenic presence of IL-2 in the IEF fractions with the highest VPF activity, we conclude that VPF activity of the concentrated supernatants is not related to IL-2 nor to a biologically inactive form of IL-2. When concentrated supernatants were subjected to preparative SDS-PAGE, VPF activity was recovered within low mol. wt material (1-12 kD). Immunoadsorption experiments gave definite proof since the complete removal of IL-2 from concentrated supernatants did not affect the VPF activity. Although high amounts of IL-2 increased vascular permeability, our experiments clearly demonstrate that VPF is a lymphokine distinct from IL-2. Images Fig. 1 Fig. 3 Fig. 4 PMID:1914229

  1. Simultaneous evaluation of vascular morphology, blood volume and transvascular permeability using SPION-based, dual-contrast MRI: imaging optimization and feasibility test.

    PubMed

    Kwon, Heon-Ju; Shim, Woo Hyun; Cho, Gyunggoo; Cho, Hyung Joon; Jung, Hoe Su; Lee, Chang Kyung; Lee, Yong Seok; Baek, Jin Hee; Kim, Eun Ju; Suh, Ji-Yeon; Sung, Yu Sub; Woo, Dong-Cheol; Kim, Young Ro; Kim, Jeong Kon

    2015-06-01

    Exploiting ultrashort-T(E) (UTE) MRI, T1-weighted positive contrast can be obtained from superparamagnetic iron oxide nanoparticles (SPIONs), which are widely used as a robust T2-weighted, negative contrast agent on conventional MR images. Our study was designed (a) to optimize the dual-contrast MRI method using SPIONs and (b) to validate the feasibility of simultaneously evaluating the vascular morphology, blood volume and transvascular permeability using the dual-contrast effect of SPIONs. All studies were conducted using 3?T MRI. According to numerical simulation, 0.15?mM was the optimal blood SPION concentration for visualizing the positive contrast effect using UTE MRI (T(E)?=?0.09?ms), and a flip angle of 40 could provide sufficient SPION-induced enhancement and acceptable measurement noise for UTE MR angiography. A pharmacokinetic study showed that this concentration can be steadily maintained from 30 to 360?min after the injection of 29?mg/kg of SPIONs. An in vivo study using these settings displayed image quality and CNR of SPION-enhanced UTE MR angiography (image quality score 3.5; CNR 146) comparable to those of the conventional, Gd-enhanced method (image quality score 3.8; CNR 148) (p?>?0.05). Using dual-contrast MR images obtained from SPION-enhanced UTE and conventional spin- and gradient-echo methods, the transvascular permeability (water exchange index 1.76-1.77), cerebral blood volume (2.58-2.60%) and vessel caliber index (3.06-3.10) could be consistently quantified (coefficient of variation less than 9.6%; Bland-Altman 95% limits of agreement 0.886-1.111) and were similar to the literature values. Therefore, using the optimized setting of combined SPION-based MRI techniques, the vascular morphology, blood volume and transvascular permeability can be comprehensively evaluated during a single session of MR examination. PMID:25865029

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

    PubMed

    Sebia-Amrane, Fatima; Laraba-Djebari, Fatima

    2013-04-01

    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 2h and disappeared after 24h The minimum edema-forming dose was estimated at 0.8?g/20g 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

  3. Neisseria meningitidis induces platelet inhibition and increases vascular endothelial permeability via nitric oxide regulated pathways.

    PubMed

    Kobsar, Anna; Siauw, Celine; Gambaryan, Stepan; Hebling, Sabrina; Speer, Christian; Schubert-Unkmeir, Alexandra; Eigenthaler, Martin

    2011-12-01

    Despite antibiotic therapy, infections with Neisseria meningitidis still demonstrate a high rate of morbidity and mortality even in developed countries. The fulminant septicaemic course, named Waterhouse-Friderichsen syndrome, with massive haemorrhage into the adrenal glands and widespread petechial bleeding suggest pathophysiological inhibition of platelet function. Our data show that N. meningitidis produces the important physiological platelet inhibitor and cardiovascular signalling molecule nitric oxide (NO), also known as endothelium-derived relaxing factor (EDRF). N. meningitidis -derived NO inhibited ADP-induced platelet aggregation through the activation of soluble guanylyl cyclase (sGC) followed by an increase in platelet cyclic nucleotide levels and subsequent activation of platelet cGMP- and cAMP- dependent protein kinases (PKG and PKA). Furthermore, direct measurement of horseradish peroxidase (HRP) passage through a vascular endothelial cell monolayer revealed that N. meningitidis significantly increased endothelial monolayer permeability. Immunfluorescence analysis demonstrated NO dependent disturbances in the structure of endothelial adherens junctions after co-incubation with N. meningitidis . In contrast to platelet inhibition, the NO effects on HBMEC were not mediated by cyclic nucleotides. Our study provides evidence that NO plays an essential role in the pathophysiology of septicaemic meningococcal infection. PMID:22072136

  4. Increased vascular permeability of solid tumors causes selectivity of 5-aminolevulinic acid (ALA) induced porphyrins

    NASA Astrophysics Data System (ADS)

    Abels, Christoph; Heil, Peter; Dellian, Marc; Kuhnle, Gerhard E.; Baumgartner, Reinhold; Goetz, Alwin E.

    1995-03-01

    To investigate pharmacokinetics of ALA-induced porphyrins the time course of fluorescence in neoplastic tissue and normal tissue following i.v. administration of ALA (100 mg kg-1, 500 mg kg-1 or 1000 mg kg-1 b.w.) was studied by means of intravital fluorescence microscopy. As a model the amelanotic melanoma (A-Mel- 3) growing in a transparent skin fold chamber preparation was used (n equals 18). Maximal fluorescence intensity was measured after 2.5 h in tumor and after 6 h in surrounding host tissue, highest tumor/host tissue ratio at 90 min (500 mg kg-1 b.w.). Heterogeneity of fluorescence intensity between different tumors ranged from 24% to 361% following injection of 500 mg/kg b.w. Twenty-four hours after systemic administration of ALA fluorescence intensity was decreased to baseline. Based upon these results a three- compartment model was calculated to simulate fluorescence kinetics in solid, well vascularized tumors assuming first-order kinetics. This compartment model supports the experimental findings, that the transient selectivity of ALA-induced fluorescence in tumors is caused by earlier uptake of ALA in tumors due to increased microvascular permeability and diffusion in neoplastic tissue. The heterogeneity might represent the different metabolic capacity of tumors to form porphyrins following exogenous administration of ALA.

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

    SciTech Connect

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

    1989-03-01

    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.

  6. Dengue virus NS1 triggers endothelial permeability and vascular leak that is prevented by NS1 vaccination.

    PubMed

    Beatty, P Robert; Puerta-Guardo, Henry; Killingbeck, Sarah S; Glasner, Dustin R; Hopkins, Kaycie; Harris, Eva

    2015-09-01

    The four dengue virus serotypes (DENV1 to DENV4) are mosquito-borne flaviviruses that cause up to ~100 million cases of dengue annually worldwide. Severe disease is thought to result from immunopathogenic processes involving serotype cross-reactive antibodies and T cells that together induce vasoactive cytokines, causing vascular leakage that leads to shock. However, no viral proteins have been directly implicated in triggering endothelial permeability, which results in vascular leakage. DENV nonstructural protein 1 (NS1) is secreted and circulates in patients' blood during acute infection; high levels of NS1 are associated with severe disease. We show that inoculation of mice with DENV NS1 alone induces both vascular leakage and production of key inflammatory cytokines. Furthermore, simultaneous administration of NS1 with a sublethal dose of DENV2 results in a lethal vascular leak syndrome. We also demonstrate that NS1 from DENV1, DENV2, DENV3, and DENV4 triggers endothelial barrier dysfunction, causing increased permeability of human endothelial cell monolayers in vitro. These pathogenic effects of physiologically relevant amounts of NS1 in vivo and in vitro were blocked by NS1-immune polyclonal mouse serum or monoclonal antibodies to NS1, and immunization of mice with NS1 from DENV1 to DENV4 protected against lethal DENV2 challenge. These findings add an important and previously overlooked component to the causes of dengue vascular leak, identify a new potential target for dengue therapeutics, and support inclusion of NS1 in dengue vaccines. PMID:26355030

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

    PubMed Central

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

    1991-01-01

    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) PMID:1667286

  8. Potent mast cell degranulation and vascular permeability triggered by urocortin through activation of corticotropin-releasing hormone receptors.

    PubMed

    Singh, L K; Boucher, W; Pang, X; Letourneau, R; Seretakis, D; Green, M; Theoharides, T C

    1999-03-01

    Urocortin (Ucn) is related to corticotropin-releasing hormone (CRH), and both are released in the brain under stress where they stimulate CRH 1 and 2 receptors (CRHR). Outside the brain, they may have proinflammatory actions through activation of mast cells, which are located perivascularly close to nerve endings and degranulate in response to acute psychological stress. Here, we report that a concentration of intradermal Ucn as low as 10 nM induced dose-dependent rat skin mast cell degranulation and increased vascular permeability. This effect appeared to be equipotent to that of calcitonin gene-related peptide and neurotensin. Ucn-induced skin vasodilation was inhibited by pretreatment with the mast cell stabilizer disodium cromoglycate (cromolyn) and was absent in the mast cell-deficient W/Wv mice. The selective nonpeptide CRH receptor 1 antagonist, antalarmin and the nonselective peptide antagonist astressin both reduced vascular permeability triggered by Ucn but not that by Substance P or histamine. In contrast, the peptide antagonist alpha-helical CRH-(9-41) reduced the effect of all three. The vasodilatory effect of Ucn was largely inhibited by pretreatment with H1 receptor antagonists, suggesting that histamine is the major mediator involved in vitro. Neuropeptide depletion of sensory neurons, treatment with the ganglionic blocker hexamethonium, or in situ skin infiltration with the local anesthetic lidocaine did not affect Ucn-induced vascular permeability, indicating that its in situ effect was not mediated through the peripheral nervous system. These results indicate that Ucn is one of the most potent triggers of rat mast cell degranulation and skin vascular permeability. This effect of Ucn may explain stress-induced disorders, such as atopic dermatitis or psoriasis, and may lead to new forms of treatment. PMID:10027877

  9. Expression of vascular permeability factor/vascular endothelial growth factor by human granulosa and theca lutein cells. Role in corpus luteum development.

    PubMed Central

    Kamat, B. R.; Brown, L. F.; Manseau, E. J.; Senger, D. R.; Dvorak, H. F.

    1995-01-01

    Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) is a cytokine that is overexpressed in many tumors, in healing wounds, and in rheumatoid arthritis. VPF/VEGF is thought to induce angiogenesis and accompanying connective tissue stroma in two ways: 1), by increasing microvascular permeability, thereby modifying the extracellular matrix and 2), as an endothelial cell mitogen. VPF/VEGF has been reported in animal corpora lutea and we investigated the possibility that it might be present in human ovaries and have a role in corpus luteum formation. We here report that VPF/VEGF mRNA and protein are expressed by human ovarian granulosa and theca cells late in follicle development and, subsequent to ovulation, by granulosa and theca lutein cells. Therefore, VPF/VEGF is ideally positioned to provoke the increased permeability of thecal blood vessels that occurs shortly before ovulation. VPF/VEGF likely also contributes to the angiogenesis and connective tissue stroma generation that accompany corpus luteum/corpus albicans formation. Finally, VPF/VEGF was overexpressed in the hyperthecotic ovarian stroma of Stein-Leventhal syndrome in which it may also have a pathophysiological role. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7531945

  10. Bactericidal/permeability-increasing protein protects vascular endothelial cells from lipopolysaccharide-induced activation and injury.

    PubMed

    Arditi, M; Zhou, J; Huang, S H; Luckett, P M; Marra, M N; Kim, K S

    1994-09-01

    Bactericidal/permeability-increasing protein (BPI), a human neutrophil granule protein, has been shown to bind lipopolysaccharide (LPS) and neutralize LPS-mediated cytokine production in adherent monocytes and the whole-blood system. In this study we investigated the ability of recombinant human BPI (rBPI) to inhibit LPS-induced vascular endothelial cell (EC) injury and activation. rBPI inhibited significantly both rough and smooth LPS-mediated injury for cultured bovine brain microvessel ECs, as measured by lactic dehydrogenase release, and blocked the LPS-induced interleukin-6 (IL-6) release from human umbilical vein ECs in a dose-dependent manner. BPI was able to inhibit LPS-mediated EC injury or activation whether it was added before or at the same time with LPS, but delaying the time of addition of rBPI resulted only in a partial inhibition. BPI also inhibited LPS-induced tumor necrosis factor alpha, IL-1 beta, and IL-6 release from human whole blood. This inhibition of tumor necrosis factor alpha, IL-1 beta, and IL-6 release from whole blood was maximal when BPI was premixed with LPS before addition to blood and was partial when BPI was added simultaneously with LPS, but no inhibition was observed when the addition of rBPI was delayed for 5 min. These findings suggest that rBPI is a potent inhibitor of LPS-mediated responses in ECs and whole blood and underscore the potential use of BPI in treatment or prevention of endotoxic shock. In contrast, the anti-lipid A monoclonal antibodies HA-1A and E5 were ineffective in inhibiting LPS-mediated EC injury and activation as well as LPS-induced cytokine release in whole blood. PMID:8063410

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

    PubMed

    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; Mehta, Dolly

    2012-10-22

    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 Ca(2+) entry, which is essential for increased endothelial permeability. Here, we addressed the role of Toll-like receptor 4 (TLR4) intersection with TRPC6-dependent Ca(2+) signaling in endothelial cells (ECs) in mediating lung vascular leakage and inflammation. We find that the endotoxin (lipopolysaccharide; LPS) induces Ca(2+) 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 Ca(2+) entry in ECs, which is secondary to the generation of diacylglycerol (DAG) induced by LPS. Ca(2+) 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 Ca(2+) entry into ECs, secondary to TLR4-induced DAG generation, participates in mediating both lung vascular barrier disruption and inflammation induced by endotoxin. PMID:23045603

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2014-01-01

    Purpose. Vascular endothelial growth factor (VEGF)-induced retinal vascular permeability contributes to diabetic macular edema (DME), a serious vision-threatening condition. Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) antagonist/reverse agonist, GSK0660, inhibits VEGF-induced human retinal microvascular endothelial cell (HRMEC) proliferation, tubulogenesis, and oxygen-induced retinal vasculopathy in newborn rats. These VEGF-induced HRMEC behaviors and VEGF-induced disruption of endothelial cell junctional complexes may well share molecular signaling events. Thus, we sought to examine the role of PPARβ/δ in VEGF-induced retinal hyperpermeability. Methods. Transendothelial electrical resistance (TEER) measurements were performed on HRMEC monolayers to assess permeability. Claudin-1/Claudin-5 localization in HRMEC monolayers was determined by immunocytochemistry. Extracellular signal-regulated protein kinases 1 and 2 (Erk 1/2) phosphorylation, VEGF receptor 1 (VEGFR1) and R2 were assayed by Western blot analysis. Expression of VEGFR1 and R2 was measured by quantitative RT-PCR. Last, retinal vascular permeability was assayed in vivo by Evans blue extravasation. Results. Human retinal microvascular endothelial cell monolayers treated with VEGF for 24 hours showed decreased TEER values that were completely reversed by the highest concentration of GSK0660 (10 μM) and PPARβ/δ-directed siRNA (20 μM). In HRMEC treated with VEGF, GSK0660 stabilized tight-junctions as evidenced by Claudin-1 staining, reduced phosphorylation of Erk1/2, and reduced VEGFR1/2 expression. Peroxisome proliferator-activated receptor β/δ siRNA had a similar effect on VEGFR expression and Claudin-1, supporting the specificity of GSK0660 in our experiments. Last, GSK0660 significantly inhibited VEGF-induced retinal vascular permeability and reduced retinal VEGFR1and R2 levels in C57BL/6 mice. Conclusions. These data suggest a protective effect for PPARβ/δ antagonism against VEGF-induced vascular permeability, possibly through reduced VEGFR expression. Therefore, antagonism/reverse agonism of PPARβ/δ siRNA may represent a novel therapeutic methodology against retinal hyperpermeability and is worthy of future investigation. PMID:25406289

  14. Inhibitory effects of aloe carboxypeptidase fraction on streptozotocin-induced enhancement of vascular permeability in the pancreatic islets.

    PubMed

    Beppu, H; Shimpo, K; Chihara, T; Tamai, I; Nomoto-Yamaji, S; Ozaki, S; Ito, S; Kuzuya, H

    2006-01-01

    The protective actions of components isolated from Aloe arborescens Miller var. natalensis Berger (Kidachi aloe in Japanese) on streptozotocin (Sz)-induced necrosis of B cells in the pancreatic islets of the mouse were investigated to clarify its action mechanism involved in anti-diabetic effects. In this experiment, phenol low molecular weight components of aloin and aloin A that were anti-oxidants and derived from the leaf skin or pulp extract, an aloe carboxypeptidase fraction that is a inhibitor of enhanced vascular permeability and a glycoprotein component that decreases blood glucose were tested with mice precedently administered with Sz which is known as a cytotoxin specific to B cells. The results showed that the treatment group receiving Sz followed by the aloe carboxypeptidase fraction increased the inhibition of dye leakage by 75.8% (p<0.001) in the extract of whole pancreas in comparison to the control group and the aloe carboxypeptidase fraction group also increased the inhibition effect by 68.4% (p<0.001) in the extract of pancreatic islets as compared to the control group. The carboxypeptidase is an aloe-derived protease known to inhibit the acetic acid-related enhancement of intraperitoneal vascular permeability in mice. Further, the elevation of blood glucose in Sz-induced diabetic mice intraperitoneally given the aloe carboxypeptitase fraction was significantly (p<0.01-0.001) restrained at 3, 7 and 14 days after the injection as compared to the control group given solvent only. The results of this experiment suggested that the inhibitory effect on the enhancement of vascular permeability related to the vascular acute inflammatory response at Sz-induced lesions of pancreatic islets was involved in the action mechanism of this enzyme. PMID:16360933

  15. Hypoxic retinal Muller cells promote vascular permeability by HIF-1-dependent up-regulation of angiopoietin-like 4.

    PubMed

    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

    2013-09-01

    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 Mller 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, Mller 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 Mller cells in vitro and the ischemic inner retina in vivo. ANGPTL4 is critical and sufficient to promote vessel permeability by hypoxic Mller cells. Immunohistochemical analysis of retinal tissue from patients with diabetic eye disease shows that HIF-1? and ANGPTL4 localize to ischemic Mller 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. PMID:23959876

  16. Sp1-mediated nonmuscle myosin light chain kinase expression and enhanced activity in vascular endothelial growth factorinduced vascular permeability

    PubMed Central

    2015-01-01

    Abstract Despite the important role played by the nonmuscle isoform of myosin light chain kinase (nmMLCK) in vascular barrier regulation and the implication of both nmMLCK and vascular endothelial growth factor (VEGF) in the pathogenesis of acute respiratory distress syndrome (ARDS), the role played by nmMLCK in VEGF-induced vascular permeability is poorly understood. In this study, the role played by nmMLCK in VEGF-induced vascular hyperpermeability was investigated. Human lung endothelial cell barrier integrity in response to VEGF is examined in both the absence and the presence of nmMLCK small interfering RNAs. Levels of nmMLCK messenger RNA (mRNA), protein, and promoter activity expression were monitored after VEGF stimulation in lung endothelial cells. nmMYLK promoter activity was assessed using nmMYLK promoter luciferase reporter constructs with a series of nested deletions. nmMYLK transcriptional regulation was further characterized by examination of a key transcriptional factor. nmMLCK plays an important role in VEGF-induced permeability. We found that activation of the VEGF signaling pathway in lung endothelial cells increases MYLK gene product at both mRNA and protein levels. Increased nmMLCK mRNA and protein expression is a result of increased nmMYLK promoter activity, regulated in part by binding of the Sp1 transcription factor on triggering by the VEGF signaling pathway. Taken together, these findings suggest that MYLK is an important ARDS candidate gene and a therapeutic target that is highly influenced by excessive VEGF concentrations in the inflamed lung. PMID:26697178

  17. Tumor-secreted vascular permeability factor increases cytosolic Ca2+ and von Willebrand factor release in human endothelial cells.

    PubMed Central

    Brock, T. A.; Dvorak, H. F.; Senger, D. R.

    1991-01-01

    Vascular permeability factor (VPF), a tumor-secreted heparin-binding protein (Mr approximately 38,000), is responsible for increased vessel permeability and fluid accumulation associated with tumor growth. Vascular permeability factor also promotes the growth of human umbilical vein endothelial cells (EC) and bovine pulmonary ECs in vitro. It is shown for the first time that guinea pig VPF (half-maximal and maximal dose approximately 0.4 and 22 pmol/l (picomolar), respectively), as well as human VPF, are potent stimuli for human ECs resulting in [Ca2+]i increases (maximal three- to fourfold) and inositol triphosphate (IP3) formation. Unlike the maximal responses to thrombin and histamine, the [Ca2+]i response to a maximal VPF dose was preceded by a characteristic 10- to 15-second delay. Guinea pig VPF also selectively increased [Ca2+]i in cultured aortic and pulmonary artery ECs, but not aortic smooth muscle cells, human fibroblasts, or neutrophils. Affinity-purified rabbit antibody (raised to a synthetic peptide representing VPF N-terminal amino acids 1 to 24) adsorbed all vessel permeability-increasing activity, EC growth-promoting activity, and specifically all activity responsible for increasing EC [Ca2+]i. Similar to other mediators that increase [Ca2+]i in cultured ECs, VPF also induced a 200% increase in von Willebrand factor release. Together these data indicate that VPF acts directly on ECs and that rapid cellular events in its in vivo/in vitro actions are likely to involve phospholipase C activation, [Ca2+]i increase, and von Willebrand factor release. PMID:1987767

  18. Stimulation of endothelial cell migration by vascular permeability factor/vascular endothelial growth factor through cooperative mechanisms involving the alphavbeta3 integrin, osteopontin, and thrombin.

    PubMed Central

    Senger, D. R.; Ledbetter, S. R.; Claffey, K. P.; Papadopoulos-Sergiou, A.; Peruzzi, C. A.; Detmar, M.

    1996-01-01

    We have identified several mechanisms by which the angiogenic cytokine vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) likely regulates endothelial cells (EC) migration. VPF/VEGF induced dermal microvascular EC expression of mRNAs encoding the alphav and beta3 integrin subunits resulting in increased levels of the alphavbeta3 heterodimer at the cell surface, and VPF/VEGF also induced mRNA encoding osteopontin (OPN), an alphavbeta3 ligand. OPN promoted EC migration in vitro; and VPF/VEGF induction of alphavbeta3 was accompanied by increased EC migration toward OPN. Because thrombin cleavage of OPN results in substantial enhancement of OPN's adhesive properties, and because VPF/VEGF promotes increased microvascular permeability leading to activation of the extrinsic coagulation pathway, we also investigated whether VPF/VEGF facilitates thrombin cleavage of OPN in vivo. Consistent with this hypothesis, co-injection of VPF/VEGF together with OPN resulted in rapid cleavage of OPN by endogenous thrombin. Furthermore, in comparison with native OPN, thrombin-cleaved OPN stimulated a greater rate of EC migration in vitro, which was additive to the increased migration associated with induction of alpha v beta 3. Thus, these data demonstrate cooperative mechanisms for VPF/VEGF regulation of EC migration involving the alphavbeta3 integrin, the alphavbeta3 ligand OPN, and thrombin cleavage of OPN. These findings also illustrate an operational link between VPF/VEGF induction of EC gene expression and VPF/VEGF enhancement of microvascular permeability, suggesting that these distinct biological activities may act accordingly to stimulate EC migration during angiogenesis. Images Figure 1 Figure 2 Figure 4 PMID:8686754

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

    SciTech Connect

    Waldman, D.L.

    1988-01-01

    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.

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

    PubMed

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

    2010-09-01

    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

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

    PubMed Central

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

    2010-01-01

    Exposure to air pollutants increases the incidence of cardiovascular disease. Recent toxicity studies revealed that ultra fine particles (UFP, dp<100200 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=0.1750.003, DEP2=0.2650.006, 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. PMID:20576493

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

    PubMed Central

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

    2015-01-01

    To examine the therapeutic effect of Src inhibitor on the VEGF mediating vascular hyperpermeability and bone destruction within steroid-associated osteonecrotic lesions in rabbits. Rabbits with high risk for progress to destructive repair in steroid-associated osteonecrosis were selected according to our published protocol. The selected rabbits were systemically administrated with either Anti-VEGF antibody (Anti-VEGF Group) or Src inhibitor (Src-Inhibition Group) or VEGF (VEGF-Supplement Group) or a combination of VEGF and Src inhibitor (Supplement & Inhibition Group) or control vehicle (Control Group) for 4 weeks. At 0, 2 and 4 weeks after administration, in vivo dynamic MRI, micro-CT based-angiography, histomorphometry and immunoblotting were employed to evaluate the vascular and skeletal events in different groups. The incidence of the destructive repair in the Anti-VEGF Group, Src-Inhibition Group and Supplement & Inhibition Group was all significantly lower than that in the Control Group. The angiogenesis was promoted in VEGF-Supplement Group, Src-Inhibition Group and Supplement & Inhibition Group, while the hyperpermeability was inhibited in Anti-VEGF Group, Src-Inhibition Group and Supplement & Inhibition Group. The trabecular structure was improved in Src-Inhibition Group and Supplement & Inhibition Group. Src inhibitor could reduce permeability without disturbing vascularization and prevent destructive repair in steroid-associated osteonecrosis. PMID:25748225

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

    PubMed

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

    2015-01-01

    To examine the therapeutic effect of Src inhibitor on the VEGF mediating vascular hyperpermeability and bone destruction within steroid-associated osteonecrotic lesions in rabbits. Rabbits with high risk for progress to destructive repair in steroid-associated osteonecrosis were selected according to our published protocol. The selected rabbits were systemically administrated with either Anti-VEGF antibody (Anti-VEGF Group) or Src inhibitor (Src-Inhibition Group) or VEGF (VEGF-Supplement Group) or a combination of VEGF and Src inhibitor (Supplement &Inhibition Group) or control vehicle (Control Group) for 4 weeks. At 0, 2 and 4 weeks after administration, in vivo dynamic MRI, micro-CT based-angiography, histomorphometry and immunoblotting were employed to evaluate the vascular and skeletal events in different groups. The incidence of the destructive repair in the Anti-VEGF Group, Src-Inhibition Group and Supplement &Inhibition Group was all significantly lower than that in the Control Group. The angiogenesis was promoted in VEGF-Supplement Group, Src-Inhibition Group and Supplement &Inhibition Group, while the hyperpermeability was inhibited in Anti-VEGF Group, Src-Inhibition Group and Supplement &Inhibition Group. The trabecular structure was improved in Src-Inhibition Group and Supplement &Inhibition Group. Src inhibitor could reduce permeability without disturbing vascularization and prevent destructive repair in steroid-associated osteonecrosis. PMID:25748225

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

    PubMed Central

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

    2013-01-01

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

  5. Vascular permeability changes in the central nervous system of rats with hyperacute experimental allergic encephalomyelitis induced with the aid of a substance from Bordetella pertussis.

    PubMed Central

    Bergman, R K; Munoz, J J; Portis, J L

    1978-01-01

    Development of hyperacute experimental allergic encephalomyelitis in Lewis rats after intraperitoneal administration of a mixture of guinea pig spinal cord emulsion and pertussigen from Bordetella pertussis was accompanied by an increase in vascular permeability in the central nervous system. The increased permeability was most striking in the spinal cord and seemed to be associated with the ascending development of paralysis. Rats that had completely recovered from paralysis did not have any increased permeability in the central nervous system. Rats which developed paralysis after inoculation with either guinea pig spinal cord emulsion alone or with complete Freund adjuvant had only a small degree, if any, of increased permeability in the vascular system of the central nervous system. Images PMID:211087

  6. Resolvin D1 Reverts Lipopolysaccharide-Induced TJ Proteins Disruption and the Increase of Cellular Permeability by Regulating I?B? Signaling in Human Vascular Endothelial Cells

    PubMed Central

    Zhang, Xingcai; Wang, Tingting; Gui, Ping; Yao, Chengye; Sun, Wei; Wang, Linlin; Wang, Huiqing; Xie, Wanli; Yao, Shanglong; Lin, Yun; Wu, Qingping

    2013-01-01

    Tight Junctions (TJ) are important components of paracellular pathways, and their destruction enhances vascular permeability. Resolvin D1 (RvD1) is a novel lipid mediator that has treatment effects on inflammatory diseases, but its effect on inflammation induced increase in vascular permeability is unclear. To understand whether RvD1 counteracts the lipopolysaccharide (LPS) induced increase in vascular cell permeability, we investigated the effects of RvD1 on endothelial barrier permeability and tight junction reorganization and expression in the presence or absence of LPS stimulation in cultured Human Vascular Endothelial Cells (HUVECs). Our results showed that RvD1 decreased LPS-induced increased in cellular permeability and inhibited the LPS-induced redistribution of zo-1, occludin, and F-actin in HUVECs. Moreover, RvD1 attenuated the expression of I?B? in LPS-induced HUVECs. The NF-?B inhibitor PDTC enhanced the protective effects of RvD1 on restoration of occludin rather than zo-1 expression in LPS-stimulated HUVECs. By contrast, the ERK1/2 inhibitor PD98059 had no effect on LPS-induced alterations in zo-1 and occludin protein expressions in HUVECs. Our data indicate that RvD1 protects against impairment of endothelial barrier function induced by LPS through upregulating the expression of TJ proteins in HUVECs, which involves the I?B? pathway but not the ERK1/2 signaling. PMID:24381712

  7. Improved survival and reduced vascular permeability by eliminating or blocking 12/15-lipoxygenase in mouse models of acute lung injury (ALI).5

    PubMed Central

    Zarbock, Alexander; DiStasi, Matthew R.; Smith, Emily; Sanders, John; Kronke, Gerhard; Harry, Brian; von Vietinghoff, Sibylle; Buscher, Konrad; Nadler, Jerry L.; Ley, Klaus

    2009-01-01

    Acute lung injury (ALI) is a prevalent disease associated with high mortality. 12/15 lipoxygenase (12/15-LO) is an enzyme producing 12-hydroxy-eicosatetraenoic acid (HETE) and 15-HETE from arachidonic acid. To test whether 12/15-LO is involved in increasing vascular permeability in the lung, we investigated the role of 12/15-LO in murine models of lipopolysaccharide (LPS)-induced pulmonary inflammation and clinically relevant acid-induced ALI. The vascular permeability increase upon LPS inhalation was abolished in Alox15?/? mice lacking 12/15-LO and in WT mice after pharmacological blockade of 12/15-LO. Alox15?/? mice also showed improved gas exchange, reduced permeability increase, and prolonged survival in the acid-induced ALI model. Bone marrow chimeras and reconstitution experiments revealed that 12-HETE produced by hematopoietic cells regulates vascular permeability through a CXCR2-dependent mechanism. Our findings suggest that 12/15-LO-derived 12-HETE is a key mediator of vascular permeability in acute lung injury. PMID:19752233

  8. Overexpression of vascular permeability factor (VPF/VEGF) and its endothelial cell receptors in delayed hypersensitivity skin reactions.

    PubMed

    Brown, L F; Olbricht, S M; Berse, B; Jackman, R W; Matsueda, G; Tognazzi, K A; Manseau, E J; Dvorak, H F; Van de Water, L

    1995-03-15

    Delayed hypersensitivity (DH) is a T cell-mediated form of immune response characterized by a predominantly perivascular, mononuclear cell infiltrate. The venules in DH reactions are hyperpermeable to plasma proteins, leading to extravasation of plasma fibrinogen and its extravascular clotting to form a fibrin gel that promotes induration and angiogenesis. The mechanisms responsible for microvascular hyperpermeability in DH are unknown. Recently, a cytokine named vascular permeability factor (VPF, also known as vascular endothelial growth factor or VEGF) has been implicated in the chronic vascular hyperpermeability and angiogenesis of solid and ascites tumors, healing wounds, rheumatoid arthritis, and psoriasis. These findings suggested that VPF/VEGF might also have a role in the pathogenesis of DH. Two model systems were studied: allergic contact dermatitis to poison ivy in human volunteers and classical tuberculin hypersensitivity in rats. In both, in situ hybridization revealed that the mRNAs encoding VPF/VEGF were strikingly overexpressed in keratinocytes of the epidermis; scattered mononuclear cells infiltrating the dermis also overexpressed VPF/VEGF mRNA, to a greater extent in rat tuberculin than in human contact reactions. In contact reactions, mRNAs for two VPF/VEGF vascular endothelial cell receptors, flt-1 and KDR, were also strikingly overexpressed. Abundant fibrin deposition in both models confirmed that dermal microvessels were indeed hyperpermeable to plasma fibrinogen. These results implicate VPF/VEGF as a potentially important mediator in the pathogenesis of cell-mediated immunity and provide further evidence that products of epithelial cells may regulate the inflammatory response. PMID:7876550

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

    PubMed Central

    Kumar, Ajay; Kumar, Ashok

    2015-01-01

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

  10. Differential effects of formaldehyde exposure on the cell influx and vascular permeability in a rat model of allergic lung inflammation.

    PubMed

    Lino-dos-Santos-Franco, Adriana; Domingos, Helori Vanni; de Oliveira, Ana Paula Ligeiro; Breithaupt-Faloppa, Ana Cristina; Peron, Jean Pierre Schatzmann; Bolonheis, Simone; Muscará, Marcelo Nicolas; Oliveira-Filho, Ricardo Martins; Vargaftig, B Boris; Tavares-de-Lima, Wothan

    2010-09-01

    Exposure to air pollutants such as formaldehyde (FA) leads to inflammation, oxidative stress and immune-modulation in the airways and is associated with airway inflammatory disorders such as asthma. The purpose of our study was to investigate the effects of exposure to FA on the allergic lung inflammation. The hypothesized link between reactive oxygen species and the effects of FA was also studied. To do so, male Wistar rats were exposed to FA inhalation (1%, 90 min daily) for 3 days, and subsequently sensitized with ovalbumin (OVA)-alum by subcutaneous route. One week later the rats received another OVA-alum injection by the same route (booster). Two weeks later the rats were challenged with aerosolized OVA. The OVA challenge of rats upon FA exposure induced an elevated release of LTB 4, TXB 2, IL-1 beta, IL-6 and VEGF in lung cells, increased phagocytosis and lung vascular permeability, whereas the cell recruitment into lung was reduced. FA inhalation induced the oxidative burst and the nitration of proteins in the lung. Vitamins C, E and apocynin reduced the levels of LTB 4 in BAL-cultured cells of the FA and FA/OVA groups, but increased the cell influx into the lung of the FA/OVA rats. In OVA-challenged rats, the exposure to FA was associated to a reduced lung endothelial cells expression of intercellular cell adhesion molecule 1 (ICAM-1). In conclusion, our findings suggest that FA down regulate the cellular migration into the lungs after an allergic challenge and increase the ability of resident lung cells likely macrophages to generate inflammatory mediators, explaining the increased lung vascular permeability. Our data are indicative that the actions of FA involve mechanisms related to endothelium-leukocyte interactions and oxidative stress, as far as the deleterious effects of this air pollutant on airways are concerned. PMID:20658762

  11. Negatively charged silver nanoparticles cause retinal vascular permeability by activating plasma contact system and disrupting adherens junction.

    PubMed

    Long, Yan-Min; Zhao, Xing-Chen; Clermont, Allen C; Zhou, Qun-Fang; Liu, Qian; Feener, Edward P; Yan, Bing; Jiang, Gui-Bin

    2016-05-01

    Silver nanoparticles (AgNPs) have been extensively used as antibacterial component in numerous healthcare, biomedical and consumer products. Therefore, their adverse effects to biological systems have become a major concern. AgNPs have been shown to be absorbed into circulation and redistributed into various organs. It is thus of great importance to understand how these nanoparticles affect vascular permeability and uncover the underlying molecular mechanisms. A negatively charged mecaptoundeonic acid-capped silver nanoparticle (MUA@AgNP) was investigated in this work. Ex vivo experiments in mouse plasma revealed that MUA@AgNPs caused plasma prekallikrein cleavage, while positively charged or neutral AgNPs, as well as Ag ions had no effect. In vitro tests revealed that MUA@AgNPs activated the plasma kallikrein-kinin system (KKS) by triggering Hageman factor autoactivation. By using specific inhibitors aprotinin and HOE 140, we demonstrated that KKS activation caused the release of bradykinin, which activated B2 receptors and induced the shedding of adherens junction protein, VE-cadherin. These biological perturbations eventually resulted in endothelial paracellular permeability in mouse retina after intravitreal injection of MUA@AgNPs. The findings from this work provided key insights for toxicity modulation and biomedical applications of AgNPs. PMID:26399585

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

    PubMed

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

    1996-01-01

    Our purpose was to compare baseline hemodynamic parameters of mild and severe preeclampsia. Patients admitted to the Medical University Labor and Delivery Unit with the diagnosis of preeclampsia who had not received prior antihypertensive or magnesium sulfate therapy were recruited for noninvasive hemodynamic monitoring with thoracic electrical bioimpedance. After stabilization in the lateral recumbent position, hemodynamic monitoring was begun. Baseline hemodynamic parameters, mean arterial pressure (MAP), heart rate (HR), systemic vascular resistance index (SVRI), cardiac index (CI), and stroke index (SI) were recorded. Stroke systemic vascular resistance index (SSVRI), the resistance imposed by vasculature on each beat of the heart, was calculated for each patient by multiplying SVRI by HR. For statistical analysis, unpaired Student's t-tests (two-tailed) were utilized (P < 0.01). Forty-one preeclamptic patients (20 mild, 21 severe) were enrolled. Mean gestational age of severe patients was 32.2 +/- 4.0 and of mild patients was 37.0 +/- 3.5. MAP, SBP, diastolic blood pressure, HR, and SSVRI were higher in the severe group. SVRI, CI, cardiac output, and SI did not differ significantly between groups. Severe preclampsia appears to be a more intensely vasoconstricted state than mild preeclampsia. Although CI is inversely proportional to SVRI, increased HR in severe preeclampsia prevents this expected decrease in cardiac output. PMID:8930798

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

    PubMed Central

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

    2010-01-01

    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. PMID:20348280

  14. Aminoguanidine effects on nerve blood flow, vascular permeability, electrophysiology, and oxygen free radicals

    SciTech Connect

    Kihara, Mikihiro; Schmelzer, J.D.; Poduslo, J.F.; Curran, G.L.; Nickander, K.K.; Low, P.A. )

    1991-07-15

    Since advanced glycosylation end products have been suggested to mediate hyperglycemia-induced microvascular atherogenesis and because aminoguanidine (AG) prevents their generation, the authors examined whether AG could prevent or ameliorate the physiologic and biochemical indices of streptozotocin (STZ)-induced experimental diabetic neuropathy. Four groups of adult Sprague-Dawley rats were studied: group I received STZ plus AG, group II received STZ plus AG, group III received STZ alone, and group IV was a control. They monitored conduction and action potential amplitudes serially in sciatic-tibial and caudal nerves, nerve blood flow, oxygen free radical activity (conjugated dienes and hydroperoxides), and the product of the permeability coefficient and surface area to {sup 125}I-labeled albumin. STZ-induced diabetes (group III) caused a 57% reduction in nerve blood flow and in abnormal nerve conduction and amplitudes and a 60% increase in conjugated dienes. Nerve blood flow was normalized by 8 weeks with AG (groups I and II) and conduction was significantly improved, in a dose-dependent manner, by 16 and 24 weeks in sciatic-tibial and caudal nerves, respectively. The permeability coefficient was not impaired, suggesting a normal blood-nerve barrier function for albumin, and the oxygen free-radical indices were not ameliorated by AG. They suggest that AG reverses nerve ischemia and more gradually improves their electrophysiology by an action on nerve microvessels. AG may have potential in the treatment of diabetic neuropathy.

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

    PubMed Central

    Criscuolo, G. R.

    1993-01-01

    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 PMID:7516104

  16. Host endothelial S1PR1 regulation of vascular permeability modulates tumor growth

    PubMed Central

    Sarkisyan, Gor; Gay, Laurie J.; Nguyen, Nhan; Felding, Brunhilde H.

    2014-01-01

    Understanding vascular growth and maturation in developing tumors has important implications for tumor progression, spread, and ultimately host survival. Modulating the signaling of endothelial G protein-coupled receptors (GPCRs) in blood and lymphatic vessels can enhance or limit tumor progression. Sphingosine 1-phosphate receptor 1 (S1PR1) is a GPCR for circulating lysophospholipid S1P that is highly expressed in blood and lymphatic vessels. Using the S1PR1- enhanced green fluorescent protein (eGFP) mouse model in combination with intravital imaging and pharmacologic modulation of S1PR1 signaling, we show that boundary conditions of high and low S1PR1 signaling retard tumor progression by enhancing or destabilizing neovasculature integrity, respectively. In contrast, midrange S1PR1 signaling, achieved by receptor antagonist titration, promotes abundant growth of small, organized vessels and thereby enhances tumor progression. Furthermore, in vivo S1PR1 antagonism supports lung colonization by circulating tumor cells. Regulation of endothelial S1PR1 dynamically controls vascular integrity and maturation and thus modulates angiogenesis, tumor growth, and hematogenous metastasis. PMID:24740542

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

    PubMed

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

    2015-07-01

    Sepsis is the leading cause of death in critically ill patients. In recent years, molecular hydrogen, as an effective free radical scavenger, has been shown a selective antioxidant and anti-inflammatory effect, and it is beneficial in the treatment of sepsis. Rho-associated coiled-coil protein kinase (ROCK) participates in junction between normal cells, and regulates vascular endothelial permeability. In this study, we used lipopolysaccharide to stimulate vascular endothelial cells and explored the effects of hydrogen-rich medium on the regulation of adhesion of monocytes to endothelial cells and vascular endothelial permeability. We found that hydrogen-rich medium could inhibit adhesion of monocytes to endothelial cells and decrease levels of adhesion molecules, whereas the levels of transepithelial/endothelial electrical resistance values and the expression of vascular endothelial cadherin were increased after hydrogen-rich medium treatment. Moreover, hydrogen-rich medium could lessen the expression of ROCK, as a similar effect of its inhibitor Y-27632. In addition, hydrogen-rich medium could also inhibit adhesion of polymorphonuclear neutrophils to endothelial cells. In conclusion, hydrogen-rich medium could regulate adhesion of monocytes/polymorphonuclear neutrophils to endothelial cells and vascular endothelial permeability, and this effect might be related to the decreased expression of ROCK protein. PMID:25895142

  18. Arterial stiffness evaluated by cardio-ankle vascular index (CAVI) in adolescent hypertension.

    PubMed

    Mestanik, Michal; Jurko, Alexander; Mestanikova, Andrea; Jurko, Tomas; Tonhajzerova, Ingrid

    2016-01-01

    Elevated blood pressure (BP) is a major risk factor for atherosclerosis. As the studies concerning vascular alterations in pediatric patients are rare, we aimed to study the relationship between hypertension and arterial stiffness in adolescence by novel method independent from BP during examination. Twenty nonobese adolescent boys (16.5 0.4 years) with newly diagnosed essential hypertension, 20 adolescent boys (16.7 0.4 years) with newly diagnosed white-coat hypertension, and 20 healthy controls matched to age and body mass index were examined. Cardio-ankle vascular index (CAVI), brachial-ankle pulse wave velocity (baPWV), pre-ejection period (PEP), and ejection time (ET) were evaluated. CAVI was significantly increased in essential hypertension patients compared with controls (p < 0.05) with no significant difference in white-coat hypertension patients. Significantly higher baPWV was found in essential and white-coat hypertension patients compared with controls (both p < 0.001). White-coat hypertension patients showed significantly shortened PEP and ET compared with controls (p < 0.01 and p < 0.001, respectively) and essential hypertension patients (both p < 0.05). For the first time, the arterial stiffness in adolescents with newly diagnosed essential and white-coat hypertension was studied using BP-independent index CAVI combined with conventional baPWV. Our study revealed significantly increased CAVI in adolescents with newly diagnosed essential hypertension compared with controls. Our findings could help to understand hypertension-atherosclerosis interaction. PMID:26588489

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

    SciTech Connect

    Siegal, T.; Pfeffer, M.R.

    1995-01-01

    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.

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

    SciTech Connect

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

    1982-04-01

    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.

  1. Effects of beta-hydroxybutyrate on brain vascular permeability in rats with traumatic brain injury.

    PubMed

    Orhan, Nurcan; Ugur Yilmaz, Canan; Ekizoglu, Oguzhan; Ahishali, Bulent; Kucuk, Mutlu; Arican, Nadir; Elmas, Imdat; Grses, Candan; Kaya, Mehmet

    2016-01-15

    This study investigates the effect of beta-hydroxybutyrate (BHB) on blood-brain barrier (BBB) integrity during traumatic brain injury (TBI) in rats. Evans blue (EB) and horseradish peroxidase (HRP) were used as determinants of BBB permeability. Glutathione (GSH) and malondialdehyde (MDA) levels were estimated in the right (injury side) cerebral cortex of animals. The gene expression levels for occludin, glucose transporter (Glut)-1, aquaporin4 (AQP4) and nuclear factor-kappaB (NF-?B) were performed, and Glut-1 and NF-?B activities were analyzed. BHB treatment decreased GSH and MDA levels in intact animals and in those exposed to TBI (P<0.05). Glut-1 protein levels decreased in sham, BHB and TBI plus BHB groups (P<0.05). NF-?B protein levels increased in animals treated with BHB and/or exposed to TBI (P<0.05). The expression levels of occludin and AQP4 did not significantly change among experimental groups. Glut-1 expression levels increased in BHB treated and untreated animals exposed to TBI (P<0.05). While NF-?B expression levels increased in animals in TBI (P<0.01), a decrease was noticed in these animals upon BHB treatment (P<0.01). In animals exposed to TBI, EB extravasation was observed in the ipsilateral cortex regardless of BHB treatment. Ultrastructurally, BHB attenuated but did not prevent the presence of HRP in brain capillary endothelial cells of animals with TBI; moreover, the drug also led to the observation of the tracer when used in intact rats (P<0.01). Altogether, these results showed that BHB not only failed to provide overall protective effects on BBB in TBI but also led to BBB disruption in healthy animals. PMID:26656066

  2. Decreased vascular permeability response to substance P in airways of genetically hypertensive rats

    PubMed Central

    Bakhle, Y S; Brogan, Juliet D; Bell, C

    1999-01-01

    The inbred genetically hypertensive strain (GH) of the Otago Wistar rat possesses more sensory neurons containing the neuropeptide substance P (SP) than does its genetically related control normotensive strain. As SP contributes to airway inflammation by increasing microvascular permeability, we assessed the extravasation of Evans Blue dye in trachea and main bronchus of anaesthetized GH and control rats, in the presence of endogenous (capsaicin-liberated) or exogenous SP. Following intravenous administration of either capsaicin (75??g?kg?1) or SP (3.3?nmol?kg?1), extravasation of Evans Blue in airways from GH rats was only about 60% of that in airways of control rats. This difference was not gender-specific and responses to capsaicin were abolished by pretreatment with a selective NK1 receptor antagonist SR 140333 (360?nmol?kg?1). By contrast, the extravasation of dye caused by intravenous 5-hydroxytryptamine (0.5??mol?kg?1) was similar in magnitude in both GH and control strains. Falls in systemic arterial blood pressure in response to exogenous SP (0.13?nmol?kg?1) or acetylcholine (0.22?nmol?kg?1) were also very similar between strains, but those in response to capsaicin (75??g?kg?1) in the GH rats were about double those in control rats. The hypotensive response to SP was abolished by SR 140333, but that to capsaicin was unaffected. Our results indicate that the increased peripheral innervation density by SP nerves in GH rats is accompanied by reduced inflammatory responses to SP. This does not involve decreased vasodilator potency of SP and is therefore probably related to altered endothelial responsiveness. PMID:10193773

  3. Cell Treatment for Stroke in Type Two Diabetic Rats Improves Vascular Permeability Measured by MRI

    PubMed Central

    Ding, Guangliang; Chen, Jieli; Chopp, Michael; Li, Lian; Yan, Tao; Li, Qingjiang; Cui, Chengcheng; Davarani, Siamak P. N.; Jiang, Quan

    2016-01-01

    Treatment of stroke with bone marrow stromal cells (BMSC) significantly enhances brain remodeling and improves neurological function in non-diabetic stroke rats. Diabetes is a major risk factor for stroke and induces neurovascular changes which may impact stroke therapy. Thus, it is necessary to test our hypothesis that the treatment of stroke with BMSC has therapeutic efficacy in the most common form of diabetes, type 2 diabetes mellitus (T2DM). T2DM was induced in adult male Wistar rats by administration of a high fat diet in combination with a single intraperitoneal injection (35mg/kg) of streptozotocin. These rats were then subjected to 2h of middle cerebral artery occlusion (MCAo). T2DM rats received BMSC (5x106, n = 8) or an equal volume of phosphate-buffered saline (PBS) (n = 8) via tail-vein injection at 3 days after MCAo. MRI was performed one day and then weekly for 5 weeks post MCAo for all rats. Compared with vehicle treated control T2DM rats, BMSC treatment of stroke in T2DM rats significantly (p<0.05) decreased blood-brain barrier disruption starting at 1 week post stroke measured using contrast enhanced T1-weighted imaging with gadopentetate, and reduced cerebral hemorrhagic spots starting at 3 weeks post stroke measured using susceptibility weighted imaging, although BMSC treatment did not reduce the ischemic lesion volumes as demarcated by T2 maps. These MRI measurements were consistent with histological data. Thus, BMSC treatment of stroke in T2DM rats initiated at 3 days after stroke significantly reduced ischemic vascular damage, although BMSC treatment did not change infarction volume in T2DM rats, measured by MRI. PMID:26900843

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

    PubMed

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

    2015-06-01

    The International Union for Conservation of Nature (IUCN) Red List Index (RLI) is used to measure trends in extinction risk of species over time. The development of 2 red lists for Spanish vascular flora during the past decade allowed us to apply the IUCN RLI to vascular plants in an area belonging to a global biodiversity hotspot. We used the Spanish Red Lists from 2000 and 2010 to assess changes in level of threat at a national scale and at the subnational scales of Canary Islands, Balearic Islands, and peninsular Spain. We assigned retrospective IUCN categories of threat to 98 species included in the Spanish Red List of 2010 but absent in the Spanish Red List of 2000. In addition, we tested the effect of different random and taxonomic and spatial Spanish samples on the overall RLI value. From 2000 to 2010, the IUCN categories of 768 species changed (10% of Spanish flora), mainly due to improved knowledge (63%), modifications in IUCN criteria (14%), and changes in threat status (12%). All measured national and subnational RLI values decreased during this period, indicating a general decline in the conservation status of the Spanish vascular flora. The Canarian RLI value (0.84) was the lowest, although the fastest deterioration in conservation status occurred on peninsular Spain (from 0.93 in 2000 to 0.92 in 2010). The RLI values based on subsamples of the Spanish Red List were not representative of RLI values for the entire country, which would discourage the use of small areas or small taxonomic samples to assess general trends in the endangerment of national biotas. The role of the RLI in monitoring of changes in biodiversity at the global and regional scales needs further reassessment because additional areas and taxa are necessary to determine whether the index is sufficiently sensitive for use in assessing temporal changes in species' risk of extinction. PMID:25580521

  5. Choroidal Vascularity Index (CVI) - A Novel Optical Coherence Tomography Parameter for Monitoring Patients with Panuveitis?

    PubMed Central

    Agrawal, Rupesh; Salman, Mohammed; Tan, Kara-Anne; Karampelas, Michael; Sim, Dawn A.; Keane, Pearse A.; Pavesio, Carlos

    2016-01-01

    Purpose To compute choroidal vascularity index (CVI) using an image binarization tool on enhanced depth imaging (EDI)-optical coherence tomography (OCT) scans as a non-invasive optical tool to monitor progression in panuveitis and to investigate the utility of volumetric data from EDI-OCT scans using custom image analysis software. Materials and Methods In this retrospective cohort study, segmented EDI-OCT scans of both eyes in 19 patients with panuveitis were taken at baseline and at 3-month follow-up and were compared with EDI-OCT scans of normal eyes. Subfoveal choroidal area was segmented into luminal (LA) and stromal interstitial area (SA). Choroidal vascularity index (CVI) was defined as the proportion of LA to the total circumscribed subfoveal choroidal area (TCA). Results The mean choroidal thickness was 265.5±100.1μm at baseline and 278.4±102.6μm at 3 months follow up (p = 0.06). There was no statistically significant difference in TCA between study and control eyes (p = 0.08). CVI in the control group was 66.9±1.5% at baseline and 66.4±1.5% at follow up. CVI was 74.1±4.7% at baseline and 69.4±4.8% at 3 months follow up for uveitic eyes (p<0.001). The % change in CVI was 6.2 ±3.8 (4.3 to 8.0) for uveitic eyes, which was significantly higher from % change in CVI for control eyes (0.7±1.1, 0.2 to 1.3, p<0.001). Conclusion The study reports composite OCT-derived parameters and CVI as a possible novel tool in monitoring progression in panuveitis. CVI may be further validated in larger studies as a novel optical tool to quantify choroidal vascular status. PMID:26751702

  6. Airway vascular damage in elite swimmers.

    PubMed

    Moreira, Andr; Palmares, Carmo; Lopes, Cristina; Delgado, Lus

    2011-11-01

    We postulated that high level swimming can promote airway inflammation and thus asthma by enhancing local vascular permeability. We aimed to test this hypothesis by a cross-sectional study comparing swimmers (n = 13, 17 3 years, competing 7 4 years, training 18 3 h per week), asthmatic-swimmers (n = 6, 17 2 years, competing 8 3 years, training 16 4 h per week), and asthmatics (n = 19, 14 3 years). Subjects performed induced sputum and had exhaled nitric oxide, lung volumes, and airway responsiveness determined. Airway vascular permeability index was defined as the ratio of albumin in sputum and serum. Results from the multiple linear regression showed each unit change in airway vascular permeability index was associated with an increase of 0.97% (95%CI: 0.02 to 1.92; p = 0.047) in sputum eosinophilis, and of 2.64% (95%CI:0.96 to 4.31; p = 0.006) in sputum neutrophils after adjustment for confounders. In a general linear model no significant differences between airway vascular permeability between index study groups existed, after controlling for sputum eosinophilis and neutrophils. In conclusion, competitive swimmers training in chlorine-rich pools have similar levels of airway vascular permeability than asthmatics. Although competitive swimming has been associated with asthma, airway inflammation and airway hyperesponsiveness do not seem to be dependent on increased airway vascular permeability. PMID:21669516

  7. [Study of mithochondrial permeability transition pore in the development of myocardial and vascular contractility disfunctions].

    PubMed

    Dmytriieva, A V; Sahach, V F; Bohuslavs'ky?, A Iu

    2005-01-01

    In experiments on the isolated myocardial and vascular preparations the role of the mithochondrial permiability transition pore (mPTP) in the development of reperfusion injury was investigated. Co-perfusion of the previously activated myocardial trabecula (MT) and arterial rings (AR) by solution collected during the first 5 min of isolated heart reperfusion, caused a sharp and significant decrease of tonic tension of both isolated preparations. Besides the significant inhibition of the MT and AR reactions after electrical stimulation, modulation of AR reaction by the influence of MT is also registered. The solution collected at first minutes of heart reperfusion, preserve a dilation property within 24 hours of storage at room temperature. Preliminary perfusion of MT and AR with methylen blue (MB, 10(-4) M/l) or the addition to the solution dithiothreitol (DTT, 2 x 10(-5) M/l) and diethyl maleate (DEM, 2 x 10(-5) M/l) resulted in an almost complete inhibition of this dilatation influence on the isolated preparations. The data received testify that the solution comprise a NO-containing substance, possible nitrosoglutation. Pre-incubation (2 min) MT in a solution with mPTP activator phenylarsine oxide (PAO, 10(-5) M/l) and subsequent reperfusion with a control solution resulted in deep and irreversible decrease of tonic tension and inhibition of contractility of both isolated preparations. The received data are qualitatively similar to results described above. Our data and results received in additional experiments on isolated mitochondria allow us to assert that solution flowing from the ischemized heart contains the stable mitochondrial factor (SMF) with a significant dilatation property. An addition of MB and DEM in the reperfusion solution abrogated its dilation influence. Co-perfusion (10 min) of the injured MT and AR by the solution with nitrosoglutation (10 (-5) M/l) restored normal contractility of the isolated preparations and modulation of the AR reaction by the influence of MT. It once again confirms the presence of an NO-containing substance in the SMF content. Thus, the mPTP activation plays the key role in the development ofmyocardial reperfusion injury and results in release of SMF, which can be the basic agent of paracrine regulation of myocardial contractility, coronary and peripheral vessels tone. PMID:16108221

  8. Enhanced vascular permeability facilitates entry of plasma HDL and promotes macrophage-reverse cholesterol transport from skin in mice

    PubMed Central

    Kareinen, Ilona; Ced, Ldia; Silvennoinen, Reija; Laurila, Pirkka-Pekka; Jauhiainen, Matti; Julve, Josep; Blanco-Vaca, Francisco; Escola-Gil, Joan Carles; Kovanen, Petri T.; Lee-Rueckert, Miriam

    2015-01-01

    Reverse cholesterol transport (RCT) pathway from macrophage foam cells initiates when HDL particles cross the endothelium, enter the interstitial fluid, and induce cholesterol efflux from these cells. We injected [3H]cholesterol-loaded J774 macrophages into the dorsal skin of mice and measured the transfer of macrophage-derived [3H]cholesterol to feces [macrophage-RCT (m-RCT)]. Injection of histamine to the macrophage injection site increased locally vascular permeability, enhanced influx of intravenously administered HDL, and stimulated m-RCT from the histamine-treated site. The stimulatory effect of histamine on m-RCT was abolished by prior administration of histamine H1 receptor (H1R) antagonist pyrilamine, indicating that the histamine effect was H1R-dependent. Subcutaneous administration of two other vasoactive mediators, serotonin or bradykinin, and activation of skin mast cells to secrete histamine and other vasoactive compounds also stimulated m-RCT. None of the studied vasoactive mediators affected serum HDL levels or the cholesterol-releasing ability of J774 macrophages in culture, indicating that acceleration of m-RCT was solely due to increased availability of cholesterol acceptors in skin. We conclude that disruption of the endothelial barrier by vasoactive compounds enhances the passage of HDL into interstitial fluid and increases the rate of RCT from peripheral macrophage foam cells, which reveals a novel tissue cholesterol-regulating function of these compounds. PMID:25473102

  9. Enhanced vascular permeability facilitates entry of plasma HDL and promotes macrophage-reverse cholesterol transport from skin in mice.

    PubMed

    Kareinen, Ilona; Ced, Ldia; Silvennoinen, Reija; Laurila, Pirkka-Pekka; Jauhiainen, Matti; Julve, Josep; Blanco-Vaca, Francisco; Escola-Gil, Joan Carles; Kovanen, Petri T; Lee-Rueckert, Miriam

    2015-02-01

    Reverse cholesterol transport (RCT) pathway from macrophage foam cells initiates when HDL particles cross the endothelium, enter the interstitial fluid, and induce cholesterol efflux from these cells. We injected [(3)H]cholesterol-loaded J774 macrophages into the dorsal skin of mice and measured the transfer of macrophage-derived [(3)H]cholesterol to feces [macrophage-RCT (m-RCT)]. Injection of histamine to the macrophage injection site increased locally vascular permeability, enhanced influx of intravenously administered HDL, and stimulated m-RCT from the histamine-treated site. The stimulatory effect of histamine on m-RCT was abolished by prior administration of histamine H1 receptor (H1R) antagonist pyrilamine, indicating that the histamine effect was H1R-dependent. Subcutaneous administration of two other vasoactive mediators, serotonin or bradykinin, and activation of skin mast cells to secrete histamine and other vasoactive compounds also stimulated m-RCT. None of the studied vasoactive mediators affected serum HDL levels or the cholesterol-releasing ability of J774 macrophages in culture, indicating that acceleration of m-RCT was solely due to increased availability of cholesterol acceptors in skin. We conclude that disruption of the endothelial barrier by vasoactive compounds enhances the passage of HDL into interstitial fluid and increases the rate of RCT from peripheral macrophage foam cells, which reveals a novel tissue cholesterol-regulating function of these compounds. PMID:25473102

  10. Monitoring Vascular Permeability and Remodeling After Endothelial Injury in a Murine Model Using a Magnetic Resonance Albumin-Binding Contrast Agent

    PubMed Central

    Phinikaridou, Alkystis; Lorrio, Silvia; Zaragoza, Carlos; Botnar, Ren M.

    2015-01-01

    Background Despite the beneficial effects of vascular interventions, these procedures may damage the endothelium leading to increased vascular permeability and remodeling. Re-endothelialization of the vessel wall, with functionally and structurally intact cells, is controlled by endothelial nitric oxide synthase (NOS3) and is crucial for attenuating adverse effects after injury. We investigated the applicability of the albumin-binding MR contrast agent, gadofosveset, to noninvasively monitor focal changes in vascular permeability and remodeling, after injury, in NOS3-knockout (NOS3?/?) and wild-type (WT) mice in vivo. Methods and Results WT and NOS3?/? mice were imaged at 7, 15, and 30 days after aortic denudation or sham-surgery. T1 mapping (R1=1/T1, s?1) and delayed-enhanced MRI were used as measurements of vascular permeability (R1) and remodeling (vessel wall enhancement, mm2) after gadofosveset injection, respectively. Denudation resulted in higher vascular permeability and vessel wall enhancement 7 days after injury in both strains compared with sham-operated animals. However, impaired re-endothelialization and increased neovascularization in NOS3?/? mice resulted in significantly higher R1 at 15 and 30 days post injury compared with WT mice that showed re-endothelialization and lack of neovascularization (R1 [s?1]=15 days: NOS3?/?4.02 [interquartile range, IQR, 3.774.41] versus WT2.39 [IQR, 2.352.92]; 30 days: NOS3?/?4.23 [IQR, 3.944.68] versus WT2.64 [IQR, 2.332.80]). Similarly, vessel wall enhancement was higher in NOS3?/? but recovered in WT mice (area [mm2]=15 days: NOS3?/?5.20 [IQR, 4.686.80] versus WT2.13 [IQR, 0.973.31]; 30 days: NOS3?/?7.35 [IQR, 5.668.61] versus WT1.60 [IQR, 1.403.18]). Ex vivo histological studies corroborated the MRI findings. Conclusions We demonstrate that increased vascular permeability and remodeling, after injury, can be assessed noninvasively using an albumin-binding MR contrast agent and may be used as surrogate markers for evaluating the healing response of the vessel wall after injury. PMID:25873720

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

    SciTech Connect

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

    1988-07-01

    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.

  12. Ankle brachial index screening for occult vascular disease is not useful in HIV-positive patients.

    PubMed

    Johns, Kevin; Saeedi, Ramesh; Mancini, G B John; Bondy, Greg

    2010-09-01

    Metabolic complications common to the HIV-positive population may increase the risk for cardiovascular disease. Asymptomatic peripheral arterial disease (PAD) is associated with increased cardiovascular risk. The ankle-brachial pressure index (ABI) is a screening tool commonly used for the detection of asymptomatic PAD. The prevalence of asymptomatic PAD based on ABI in HIV-positive patients is unknown. This study was cross-sectional in design and assessed PAD by measuring the systolic ABI as determined by a handheld 8-MHz Doppler probe with the patient at rest in a supine position. A brief medical history including pertinent risk factors was obtained. One hundred and sixty-seven HIV-positive patients were evaluated (97.6% male; mean age 52.0 years; 31.2% current smokers, 29.4% former smokers, 26.3% diabetes mellitus). Asymptomatic PAD (ABI < or = 0.9) was found in four patients (2.4%, 95% CI: 0.3-4.5%). Smoking was a significant predictor of PAD. Patients with a positive test for PAD had at least two major risk factors for the disease including smoking, a history of disease in another vascular bed, dyslipidemia, diabetes, and hypertension. All patients with a positive test for PAD had a high risk (>20%) for cardiovascular disease according to the Framingham risk score. Three of the four patients with positive tests had previously diagnosed vascular disease (CAD, stroke). Three patients presenting with PAD were evaluated and all had a positive ABI. The prevalence of PAD compared to previous studies on PAD in HIV was low and identified only those patients with high cardiovascular risk based on other features. ABI was not useful in detecting occult vascular disease in HIV-positive patients and offers no additional information to that derived from cardiovascular risk stratification. PMID:20718628

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

    PubMed Central

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

    1976-01-01

    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. PMID:956373

  14. Purification and biochemical characterization of a fibrin(ogen)olytic metalloprotease from Macrovipera mauritanica snake venom which induces vascular permeability.

    PubMed

    Lee, Eun Hee; Park, Jung Eun; Park, Jong Woo; Lee, Jung Sup

    2014-10-01

    In the present study, a novel fibrin(ogen)olytic metalloprotease from Macrovipera mauritanica snake venom was purified and characterized in terms of enzyme kinetics and substrate specificity. The purified enzyme [termed snake venom metalloprotease-Macrovipera mauritanica (SVMP?MM)] was composed of a single polypeptide with an apparent molecular weight of 27 kDa, as shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The N-terminus of the enzyme was composed of NH(2)-QRFAPRYIEL-COOH, as determined by N-terminal sequencing. The A?- and the B?-chains of fibrinogen were completely cleaved by SVMP-MM within 20 and 480 min, respectively. However, the ?-chain was much more resistant to digestion by the enzyme. The enzyme also exhibited proteolytic activity, cleaving the ?-? polymer of cross-linked fibrin, but did not effectively digest the ?-? polymer. To determine the kinetic parameters for SVMP-MM, a fluorescence-quenching peptide (termed o-aminobenzoic acid-HTEKLVTS-2,4-dinitrophenyl?NH(2)) containing a K-L sequence for SVMP-MM cleavage was designed and synthesized. The optimal pH and temperature for the enzyme activity were found to be 5.5 and 37?C, respectively, when the fluorogenic substrate was synthesized and used as a substrate. Among the various divalent cations tested, Ni(2+) and Cu(2+) showed strong inhibitory effects on enzyme activity, with an average of 69.6% inhibition. The enzyme activity was also inhibited by treatment with 1,10-phenanthroline, ethylenediaminetetraacetic acid and glycol-bis-(2?aminoethylether)-N,N,N',N'-tetra-acetic acid, but not with aprotinin, tosyl-lysine chloromethyl ketone and tosyl-phenylalanyl chloromethyl ketone, suggesting that SVMP-MM is a metalloprotease and not a serine protease. The enzymatic parameters, including the K(M), k(cat), and k(cat)/K(M) values were estimated to be 0.015 mM, 0.031 sec(-1), and 20.67 mM(-1)sec(-1), respectively. SVMP-MM induced vascular permeability by digesting type IV collagen. The results obtained in our study demonstrate that SVMP-MM is a fibrin(ogen)olytic P-I class metalloprotease, which can induce a hemorrhagic reaction in vivo. PMID:25069477

  15. Changes in pericytic expression of NG2 and PDGFRB and vascular permeability in the sensory circumventricular organs of adult mouse by osmotic stimulation.

    PubMed

    Morita, Shoko; Hourai, Atsushi; Miyata, Seiji

    2014-01-01

    The blood-brain barrier (BBB) is a barrier that prevents free access of blood-derived substances to the brain through the tight junctions and maintains a specialized brain environment. Circumventricular organs (CVOs) lack the typical BBB. The fenestrated vasculature of the sensory CVOs, including the organum vasculosum of the lamina terminalis (OVLT), subfornical organ (SFO) and area postrema (AP), allows parenchyma cells to sense a variety of blood-derived information, including osmotic ones. In the present study, we utilized immunohistochemistry to examine changes in the expression of NG2 and platelet-derived growth factor receptor beta (PDGFRB) in the OVLT, SFO and AP of adult mice during chronic osmotic stimulation. The expression of NG2 and PDGFRB was remarkably prominent in pericytes, although these angiogenesis-associated proteins are highly expressed at pericytes of developing immature vasculature. The chronic salt loading prominently increased the expression of NG2 in the OVLT and SFO and that of PDGFRB in the OVLT, SFO and AP. The vascular permeability of low-molecular-mass tracer fluorescein isothiocyanate was increased significantly by chronic salt loading in the OVLT and SFO but not AP. In conclusion, the present study demonstrates changes in pericyte expression of NG2 and PDGFRB and vascular permeability in the sensory CVOs by chronic osmotic stimulation, indicating active participation of the vascular system in osmotic homeostasis. PMID:23629811

  16. Correlation between cardio-ankle vascular index and biomarkers of oxidative stress.

    PubMed

    Chotimol, Phatiwat; Saehuan, Choedchai; Kumphune, Sarawut

    2016-04-01

    Arterial stiffness is a pathological event related to arteriosclerosis that is also closely related to oxidative stress. The cardio-ankle vascular index (CAVI) is a novel arteriosclerotic index that has been used to detect arterial stiffness. However, the association between CAVI and oxidative stress has not yet been elucidated, especially in patients with risk of metabolic disorders. The aim of this study was to investigate the correlation between arterial stiffness by CAVI and biomarkers of oxidative stress. A total of 83 participants were enrolled in this study. Venous blood samples were collected for measurement of plasma oxidative biomarkers. All participants were examined for CAVI score. The univariate analysis showed that age (p < 0.001), systolic blood pressure (SBP) (p = < 0.001), plasma triglyceride (p = 0.02), plasma glucose (p = 0.003) are related to CAVI value. However, the multivariate analysis showed that age was the only significant independent factor related to the CAVI value. In addition, the CAVI and plasma malondialdehyde (MDA) levels showed a positive correlation (r = 0.29, p < 0.01) while, the CAVI was negatively correlated with catalase (CAT) (r = -0.4, p < 0.001) and GPx (r = -0.60, p < 0.001). In conclusion, this study demonstrated that age is the most influential factor for assessing arterial stiffness by the CAVI method, which is possibly due to the increase in oxidative stress. PMID:26750574

  17. Recombinant tissue-type plasminogen activator transiently enhances blood-brain barrier permeability during cerebral ischemia through vascular endothelial growth factor-mediated endothelial endocytosis in mice.

    PubMed

    Suzuki, Yasuhiro; Nagai, Nobuo; Yamakawa, Kasumi; Muranaka, Yoshinori; Hokamura, Kazuya; Umemura, Kazuo

    2015-12-01

    Recombinant tissue-type plasminogen activator (rt-PA) modulates cerebrovascular permeability and exacerbates brain injury in ischemic stroke, but its mechanisms remain unclear. We studied the involvement of vascular endothelial growth factor (VEGF)-mediated endocytosis in the increase of blood-brain barrier (BBB) permeability potentiated by rt-PA after ischemic stroke. The rt-PA treatment at 4 hours after middle cerebral artery occlusion induced a transient increase in BBB permeability after ischemic stroke in mice, which was suppressed by antagonists of either low-density lipoprotein receptor families (LDLRs) or VEGF receptor-2 (VEGFR-2). In immortalized bEnd.3 endothelial cells, rt-PA treatment upregulated VEGF expression and VEGFR-2 phosphorylation under ischemic conditions in an LDLR-dependent manner. In addition, rt-PA treatment increased endocytosis and transcellular transport in bEnd.3 monolayers under ischemic conditions, which were suppressed by the inhibition of LDLRs, VEGF, or VEGFR-2. The rt-PA treatment also increased the endocytosis of endothelial cells in the ischemic brain region after stroke in mice. These findings indicate that rt-PA increased BBB permeability via induction of VEGF, which at least partially mediates subsequent increase in endothelial endocytosis. Therefore, inhibition of VEGF induction may have beneficial effects after thrombolytic therapy with rt-PA treatment after stroke. PMID:26219596

  18. Choroidal vascularity index as a measure of vascular status of the choroid: Measurements in healthy eyes from a population-based study

    NASA Astrophysics Data System (ADS)

    Agrawal, Rupesh; Gupta, Preeti; Tan, Kara-Anne; Cheung, Chui Ming Gemmy; Wong, Tien-Yin; Cheng, Ching-Yu

    2016-02-01

    The vascularity of the choroid has been implicated in the pathogenesis of various eye diseases. To date, no established quantifiable parameters to estimate vascular status of the choroid exists. Choroidal vascularity index (CVI) may potentially be used to assess vascular status of the choroid. We aimed to establish normative database for CVI and identify factors associated with CVI in healthy eyes. In this population-based study on 345 healthy eyes, choroidal enhanced depth imaging optical coherence tomography scans were segmented by modified image binarization technique. Total subfoveal choroidal area (TCA) was segmented into luminal (LA) and stromal (SA) area. CVI was calculated as the proportion of LA to TCA. Linear regression was used to identify ocular and systemic factors associated with CVI and subfoveal choroidal thickness (SFCT). Subfoveal CVI ranged from 60.07 to 71.27% with a mean value of 65.61 ± 2.33%. CVI was less variable than SFCT (coefficient of variation for CVI was 3.55 vs 40.30 for SFCT). Higher CVI was associated with thicker SFCT, but not associated with most physiological variables. CVI was elucidated as a significant determinant of SFCT. While SFCT was affected by many factors, CVI remained unaffected suggesting CVI to be a more robust marker of choroidal diseases.

  19. Choroidal vascularity index as a measure of vascular status of the choroid: Measurements in healthy eyes from a population-based study.

    PubMed

    Agrawal, Rupesh; Gupta, Preeti; Tan, Kara-Anne; Cheung, Chui Ming Gemmy; Wong, Tien-Yin; Cheng, Ching-Yu

    2016-01-01

    The vascularity of the choroid has been implicated in the pathogenesis of various eye diseases. To date, no established quantifiable parameters to estimate vascular status of the choroid exists. Choroidal vascularity index (CVI) may potentially be used to assess vascular status of the choroid. We aimed to establish normative database for CVI and identify factors associated with CVI in healthy eyes. In this population-based study on 345 healthy eyes, choroidal enhanced depth imaging optical coherence tomography scans were segmented by modified image binarization technique. Total subfoveal choroidal area (TCA) was segmented into luminal (LA) and stromal (SA) area. CVI was calculated as the proportion of LA to TCA. Linear regression was used to identify ocular and systemic factors associated with CVI and subfoveal choroidal thickness (SFCT). Subfoveal CVI ranged from 60.07 to 71.27% with a mean value of 65.61??2.33%. CVI was less variable than SFCT (coefficient of variation for CVI was 3.55 vs 40.30 for SFCT). Higher CVI was associated with thicker SFCT, but not associated with most physiological variables. CVI was elucidated as a significant determinant of SFCT. While SFCT was affected by many factors, CVI remained unaffected suggesting CVI to be a more robust marker of choroidal diseases. PMID:26868048

  20. Choroidal vascularity index as a measure of vascular status of the choroid: Measurements in healthy eyes from a population-based study

    PubMed Central

    Agrawal, Rupesh; Gupta, Preeti; Tan, Kara-Anne; Cheung, Chui Ming Gemmy; Wong, Tien-Yin; Cheng, Ching-Yu

    2016-01-01

    The vascularity of the choroid has been implicated in the pathogenesis of various eye diseases. To date, no established quantifiable parameters to estimate vascular status of the choroid exists. Choroidal vascularity index (CVI) may potentially be used to assess vascular status of the choroid. We aimed to establish normative database for CVI and identify factors associated with CVI in healthy eyes. In this population-based study on 345 healthy eyes, choroidal enhanced depth imaging optical coherence tomography scans were segmented by modified image binarization technique. Total subfoveal choroidal area (TCA) was segmented into luminal (LA) and stromal (SA) area. CVI was calculated as the proportion of LA to TCA. Linear regression was used to identify ocular and systemic factors associated with CVI and subfoveal choroidal thickness (SFCT). Subfoveal CVI ranged from 60.07 to 71.27% with a mean value of 65.61 ± 2.33%. CVI was less variable than SFCT (coefficient of variation for CVI was 3.55 vs 40.30 for SFCT). Higher CVI was associated with thicker SFCT, but not associated with most physiological variables. CVI was elucidated as a significant determinant of SFCT. While SFCT was affected by many factors, CVI remained unaffected suggesting CVI to be a more robust marker of choroidal diseases. PMID:26868048

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

    PubMed Central

    Nam, Su-Hyun; Kang, Sung-Goo; Lee, Yun-Ah; Song, Sang-Wook; Rho, Jun-Seung

    2015-01-01

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

  2. Characterization of cutaneous vascular permeability induced by platelet-activating factor in guinea pigs and rats and its inhibition by a platelet-activating factor receptor antagonist

    SciTech Connect

    Hwang, S.B.; Li, C.L.; Lam, M.H.; Shen, T.Y.

    1985-06-01

    Mechanisms of platelet-activating factor (PAF)-induced increases of cutaneous vascular permeability in guinea pigs and in rats were further explored. PAF so far is the most potent vasoactive mediator, being more than 1000-fold more potent than histamine and bradykinin in both species. In guinea pigs, there is a time delay of 5 to 10 minutes before PAF action, whereas, in the rat, the increased vasopermeability occurs immediately following the intradermal PAF injection. Relative vasoactive potencies of PAF and several structure-related analogues in both species correlate very well with their relative inhibition of the binding of /sup 3/H-PAF to specific receptor sites on isolated rabbit platelet plasma membranes and their aggregatory abilities of rabbit platelets. Furthermore, the PAF-induced cutaneous vascular permeability is inhibitable by a competitive specific PAF receptor antagonist, kadsurenone, suggesting that binding of PAF to its specific receptor site is the first step to initiate its action of increased cutaneous vascular permeability. Several pure cyclooxygenase inhibitors, including indomethacin, diflunisal, and flurbiprofen, and the dual cyclooxygenase/lipoxygenase inhibitor, BW755C, but not the histamine antagonists, inhibit the PAF-induced vasopermeability in guinea pigs. The inhibition by indomethacin or BW755C can be fully reversed by coinjection intradermally with PAF and prostaglandin E1 but not leukotriene B4. Also, prostaglandin E1 but not leukotriene B4 enhances the guinea pig in vivo response to PAF in this model. However, in rats, none of the cyclooxygenase inhibitors, histamine antagonists, or BW755C inhibit the PAF effect of cutaneous phenomena.

  3. Augmented EPR effect by photo-triggered tumor vascular treatment improved therapeutic efficacy of liposomal paclitaxel in mice bearing tumors with low permeable vasculature.

    PubMed

    Araki, Tomoya; Ogawara, Ken-ichi; Suzuki, Haruka; Kawai, Rie; Watanabe, Taka-ichi; Ono, Tsutomu; Higaki, Kazutaka

    2015-02-28

    The effects of photo-triggered tumor vascular treatment (PVT) on the structural and functional properties of tumor vasculature were assessed in Colon-26 (C26) and B16/BL6 (B16) tumor-bearing mice. Furthermore, anti-tumor efficacy of subsequently injected PEG liposomal paclitaxel (PL-PTX) was also evaluated. As a photosensitizer, a hydrophobic porphyrin derivative was used and formulated in polymeric nanoparticle composed of polyethylene glycol-block-polylactic acid to avoid its non-specific in vivo disposition. In the mice bearing C26 with high permeable vasculature, the prominent anti-tumor activity was confirmed by PVT alone, but the subsequently injected PL-PTX did not show any additive effect. PVT itself initially induced apoptotic cell death of tumor vascular endothelial cells and platelet aggregation, which would have subsequently induced apoptosis of C26 tumor cells surrounding the vasculature. On the other hand, in the mice bearing B16 with low permeable vasculature, PVT enhanced the anti-tumor activity of subsequently injected PL-PTX, which would be attributed to the tumor disposition amount and area of PEG liposomes enhanced by PVT. These results clearly indicated that the treatment would have made it possible to provide more efficient extravasation of PL-PTX, leading to its more potent anti-tumor effect. PMID:25553829

  4. Targeted gene disruption reveals the role of the cysteinyl leukotriene 2 receptor in increased vascular permeability and in bleomycin-induced pulmonary fibrosis in mice.

    PubMed

    Beller, Thomas C; Maekawa, Akiko; Friend, Daniel S; Austen, K Frank; Kanaoka, Yoshihide

    2004-10-29

    The cysteinyl leukotrienes (cys-LTs) mediate both acute and chronic inflammatory responses in mice, as demonstrated by the attenuation of the IgE/antigen-mediated increase in microvascular permeability and of bleomycin-induced pulmonary fibrosis, respectively, in a strain with targeted disruption of leukotriene C(4) synthase to prevent cys-LT synthesis. Our earlier finding that the acute, but not the chronic, injury was attenuated in a strain with targeted disruption of the cysteinyl leukotriene 1 (CysLT(1)) receptor suggested that the chronic injury might be mediated through the CysLT(2) receptor. Thus, we generated CysLT(2) receptor-deficient mice by targeted gene disruption. These mice developed normally and were fertile. The increased vascular permeability associated with IgE-dependent passive cutaneous anaphylaxis was significantly reduced in CysLT(2) receptor-null mice as compared with wild-type mice, whereas plasma protein extravasation in response to zymosan A-induced peritoneal inflammation was not altered. Alveolar septal thickening after intratracheal injection of bleomycin, characterized by interstitial infiltration with macrophages and fibroblasts and the accumulation of collagen fibers, was significantly reduced in CysLT(2) receptor-null mice as compared with the wild-type mice. The amounts of cys-LTs in bronchoalveolar lavage fluid after bleomycin injection were similar in the CysLT(2) receptor-null mice and the wild-type mice. Thus, in response to a particular pathobiologic event the CysLT(2) receptor can mediate an increase in vascular permeability in some tissues or promote chronic pulmonary inflammation with fibrosis. PMID:15328359

  5. The cytokine response of U937-derived macrophages infected through antibody-dependent enhancement of dengue virus disrupts cell apical-junction complexes and increases vascular permeability.

    PubMed

    Puerta-Guardo, Henry; Raya-Sandino, Arturo; González-Mariscal, Lorenza; Rosales, Victor H; Ayala-Dávila, José; Chávez-Mungía, Bibiana; Martínez-Fong, Daniel; Medina, Fernando; Ludert, Juan E; del Angel, Rosa María

    2013-07-01

    Severe dengue (SD) is a life-threatening complication of dengue that includes vascular permeability syndrome (VPS) and respiratory distress. Secondary infections are considered a risk factor for developing SD, presumably through a mechanism called antibody-dependent enhancement (ADE). Despite extensive studies, the molecular bases of how ADE contributes to SD and VPS are largely unknown. This work compares the cytokine responses of differentiated U937 human monocytic cells infected directly with dengue virus (DENV) or in the presence of enhancing concentrations of a humanized monoclonal antibody recognizing protein E (ADE-DENV infection). Using a cytometric bead assay, ADE-DENV-infected cells were found to produce significantly higher levels of the proinflammatory cytokines interleukin 6 (IL-6), IL-12p70, and tumor necrosis factor alpha (TNF-α), as well as prostaglandin E2 (PGE2), than cells directly infected. The capacity of conditioned supernatants (conditioned medium [CM]) to disrupt tight junctions (TJs) in MDCK cell cultures was evaluated. Exposure of MDCK cell monolayers to CM collected from ADE-DENV-infected cells (ADE-CM) but not from cells infected directly led to a rapid loss of transepithelial electrical resistance (TER) and to delocalization and degradation of apical-junction complex proteins. Depletion of either TNF-α, IL-6, or IL-12p70 from CM from ADE-DENV-infected cells fully reverted the disrupting effect on TJs. Remarkably, mice injected intraperitoneally with ADE-CM showed increased vascular permeability in sera and lungs, as indicated by an Evans blue quantification assay. These results indicate that the cytokine response of U937-derived macrophages to ADE-DENV infection shows an increased capacity to disturb TJs, while results obtained with the mouse model suggest that such a response may be related to the vascular plasma leakage characteristic of SD. PMID:23616663

  6. Correlation of oxygenation with vascular permeability-surface area but not with lung water in humans with acute respiratory failure and pulmonary edema.

    PubMed Central

    Brigham, K L; Kariman, K; Harris, T R; Snapper, J R; Bernard, G R; Young, S L

    1983-01-01

    We used a single-pass multiple tracer technique to measure cardiac output, extravascular lung water (EVLW) and lung vascular [14C]urea permeability-surface area (PSu) in 14 patients with acute respiratory failure and pulmonary edema. All patients had increased EVLW, but EVLW in the 10 surviving patients (0.26 +/- 0.06 SE ml/ml total lung capacity [TLC]) was not significantly different from that in the five patients who died (0.22 +/- 0.05). EVLW did not correlate with intravascular pressures or with alveolar-arterial oxygen pressure difference (A-aDO2). PSu was lower in surviving patients (0.50 +/- 0.16 SE ml/s X liter TLC) than in patients who died (3.44 +/- 0.36; P less than 0.05) and also lower than in previously reported data in patients with normal PSu. PSu correlated significantly with A-aDO2. Serial studies showed that PSu returned from a low value toward normal in a patient who survived but remained high in a patient who died. We conclude that the amount of edema in the lungs measured by indicator methods was not the principal determinant of either the magnitude of oxygenation defect or survival in the patients studied. We interpret the low PSu in surviving patients as decreased surface area and infer that the ability of the lung circulation to reduce perfusion of damaged and edematous areas was important in preserving oxygenation. A high PSu, presumably reflecting perfusion of areas with increased permeability, was a sign of especially poor prognosis. Multiple tracer techniques for measuring lung vascular PSu may help to define the pathogenesis and to evaluate therapies of acute lung injury in humans. Such measurements may be a more useful clinical tool than measurements of lung water in patients with acute respiratory failure and pulmonary edema. PMID:6874950

  7. Oxidative Stress and Modification of Renal Vascular Permeability Are Associated with Acute Kidney Injury during P. berghei ANKA Infection

    PubMed Central

    Elias, Rosa Maria; Correa-Costa, Matheus; Barreto, Claudiene Rodrigues; Silva, Reinaldo Correia; Hayashida, Caroline Y.; Castoldi, ngela; Gonalves, Giselle Martins; Braga, Tarcio Teodoro; Barboza, Renato; Rios, Francisco Jos; Keller, Alexandre Castro; Cenedeze, Marcos Antonio; Hyane, Meire Ioshie; D'Imprio-Lima, Maria Regina; Figueiredo-Neto, Antnio Martins; Reis, Marlene Antnia; Marinho, Cludio Romero Farias; Pacheco-Silva, Alvaro; Cmara, Niels Olsen Saraiva

    2012-01-01

    Malaria associated-acute kidney injury (AKI) is associated with 45% of mortality in adult patients hospitalized with severe form of the disease. However, the causes that lead to a framework of malaria-associated AKI are still poorly characterized. Some clinical studies speculate that oxidative stress products, a characteristic of Plasmodium infection, as well as proinflammatory response induced by the parasite are involved in its pathophysiology. Therefore, we aimed to investigate the development of malaria-associated AKI during infection by P. berghei ANKA, with special attention to the role played by the inflammatory response and the involvement of oxidative stress. For that, we took advantage of an experimental model of severe malaria that showed significant changes in the renal pathophysiology to investigate the role of malaria infection in the renal microvascular permeability and tissue injury. Therefore, BALB/c mice were infected with P. berghei ANKA. To assess renal function, creatinine, blood urea nitrogen, and ratio of proteinuria and creatininuria were evaluated. The products of oxidative stress, as well as cytokine profile were quantified in plasma and renal tissue. The change of renal microvascular permeability, tissue hypoxia and cellular apoptosis were also evaluated. Parasite infection resulted in renal dysfunction. Furthermore, we observed increased expression of adhesion molecule, proinflammatory cytokines and products of oxidative stress, associated with a decrease mRNA expression of HO-1 in kidney tissue of infected mice. The measurement of lipoprotein oxidizability also showed a significant increase in plasma of infected animals. Together, our findings support the idea that products of oxidative stress, as well as the immune response against the parasite are crucial to changes in kidney architecture and microvascular endothelial permeability of BALB/c mice infected with P. berghei ANKA. PMID:22952850

  8. Effects and mechanism analysis of vascular endothelial growth factor and salvianolic acid B on 125I-low density lipoprotein permeability of the rabbit aortary endothelial cells.

    PubMed

    Ba, Jianming; Peng, Hu; Chen, Yanqing; Gao, Yong

    2014-12-01

    Atherosclerosis is the common pathological basis of cardiovascular and cerebrovascular disease. This study aimed to investigate the effects of vascular endothelial growth factor (VEGF) and salvianolic acid B (SalB) on the permeability of the rabbit aortary endothelial cells (RAECs) and to figure out the possible underlying molecular mechanisms. The extravasation of (125)I-low density lipoprotein ((125)I-LDL) through the RAECs was significantly increased by VEGF and decreased by SalB. Meanwhile, the tight junction-associated proteins occludin and claudin-5 were found downregulated by VEGF and the caveolae structure proteins caveolin-1 and caveolin-2 upregulated, which were abolished by the infusion of SalB. In addition, a marked increase in levels of cGMP and protein kinase G-1 (PKG-1) as well as activation of nuclear factor-?B (NF-?B) p65 were found after VEGF infusion, which were attenuated by SalB. This study demonstrates that VEGF and SalB can alter the LDL permeability of the RAECs by a paracellular pathway (downregulation of occludin and claudin-5) and a transcellular pathway (upregulation of caveolin-1 and caveolin-2), in which the cGMP/PKG/NF-?B signal pathway is possibly involved. The experimental results provide a new method and basic knowledge of prevention and treatment for cardiovascular and cerebrovascular disease. PMID:25005771

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

    PubMed Central

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

    2015-01-01

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

  10. Simultaneous optical and mr imaging of tissue within implanted window chamber: System development and application in measuring vascular permeability

    NASA Astrophysics Data System (ADS)

    Shayegan Salek, Mir Farrokh

    Simultaneous optical imaging and MRI of a dorsal skin-fold window chamber mouse model is investigated as a novel methodology to study the tumor microenvironment. Simultaneous imaging with two modalities allows for cross-validation of results, integration of the capabilities of the two modalities in one study and mitigation of invasive factors, such as surgery and anesthesia, in an in-vivo experiment. To make this investigation possible, three optical imaging systems were developed that operated inside the MRI scanner. One of the developed systems was applied to estimate vascular kinetic parameters of tumors in a dorsal skin-fold window chamber mouse model with simultaneous optical and MRI imaging. The target of imaging was a molecular agent that was dual labeled with both optical and MRI contrast agents. The labeling of the molecular agent, characteristics of the developed optical systems, the methodologies of measuring vascular kinetic parameters using optical imaging and MRI data, and the obtained results are described and illustrated.

  11. Blood-ocular barrier breakdown in eyes with ocular melanoma. A potential role for vascular endothelial growth factor/vascular permeability factor.

    PubMed Central

    Vinores, S. A.; Kchle, M.; Mahlow, J.; Chiu, C.; Green, W. R.; Campochiaro, P. A.

    1995-01-01

    A series of 130 eyes with ocular melanomas, 19 normal eyes, and 18 eyes affected with other disorders leading to blood-ocular barrier (BOB) breakdown were immunohistochemically stained for albumin to localize sites of BOB failure within the retina, ciliary body, and iris. Thirty-nine of the eyes containing melanomas and all of the other eyes were also immunohistochemically stained for vascular endothelial growth factor (VEGF), to investigate its potential role as a mediator for BOB failure. Eyes with melanomas showed widespread leakage through the retinal pigment epithelium, and 58% demonstrated leakage from retinal vessels in the proximity of the tumor. BOB failure remote from the tumor also occurred in retina (50%), optic nerve head (77%), ciliary body (51%), and iris (51%), suggesting that a soluble mediator may be involved. VEGF was demonstrated intraretinally in the proximity of (46%) and remote from (24%) melanomas and in eyes affected by other disease processes, particularly those involving neoplasia or retinal detachments, usually within particular cell populations (ie, retinal vessel walls, ganglion cells, inner or outer nuclear layers, retinal pigment epithelium). VEGF localization in retina, ciliary body, and iris often coincided with sites of extravasated albumin. Preincubation of albumin or VEGF antibodies with normal serum or VEGF peptide, respectively, eliminated or markedly reduced all immunoreactivity. Only 1 of 14 normal postmortem eyes and 0 of 5 normal surgically removed eyes showed VEGF positivity in the retina, 5 of 19 normal eyes had weak positivity in the ciliary body, and VEGF was not demonstrated in the iris of normal eyes. VEGF cannot account for all of the BOB failure associated with ocular melanomas, but appears likely to play a contributing role in many cases. Images Figure 1 Figure 2 Figure 3 PMID:7485392

  12. Novel CCR3 Antagonists Are Effective Mono- and Combination Inhibitors of Choroidal Neovascular Growth and Vascular Permeability

    PubMed Central

    Nagai, Nori; Ju, Meihua; Izumi-Nagai, Kanako; Robbie, Scott J.; Bainbridge, James W.; Gale, David C.; Pierre, Esaie; Krauss, Achim H.P.; Adamson, Peter; Shima, David T.; Ng, Yin-Shan

    2016-01-01

    Choroidal neovascularization (CNV) is a defining feature of wet age-related macular degeneration. We examined the functional role of CCR3 in the development of CNV in mice and primates. CCR3 was associated with spontaneous CNV lesions in the newly described JR5558 mice, whereas CCR3 ligands localized to CNV-associated macrophages and the retinal pigment epithelium/choroid complex. Intravitreal injection of neutralizing antibodies against vascular endothelial growth factor receptor 2, CCR3, CC chemokine ligand 11/eotaxin-1, and CC chemokine ligand 24/eotaxin-2 all reduced CNV area and lesion number in these mice. Systemic administration of the CCR3 antagonists GW766994X and GW782415X reduced spontaneous CNV in JR5558 mice and laser-induced CNV in mouse and primate models in a dose-dependent fashion. Combination treatment with antivascular endothelial growth factor receptor 2 antibody and GW766994X yielded additive reductions in CNV area and hyperpermeability in mice. Interestingly, topical GW766994X and intravitreal anti-CCR3 antibody yielded strong systemic effects, reducing CNV in the untreated, contralateral eye. Contrarily, ocular administration of GW782415X in primates failed to substantially elevate plasma drug levels or to reduce the development of grade IV CNV lesions. These findings suggest that CCR3 signaling may be an attractive therapeutic target for CNV, utilizing a pathway that is at least partly distinct from that of vascular endothelial growth factor receptor. The findings also demonstrate that systemic exposure to CCR3 antagonists may be crucial for CNV-targeted activity. PMID:26188133

  13. Tumor Vascular Permeability Pattern Is Associated With Complete Response in Immunocompetent Patients With Newly Diagnosed Primary Central Nervous System Lymphoma

    PubMed Central

    Chung, Sae Rom; Choi, Young Jun; Kim, Ho Sung; Park, Ji Eun; Shim, Woo Hyun; Kim, Sang Joon

    2016-01-01

    Abstract A dynamic contrast-enhanced MR imaging (DCE-MRI) could provide the information about tumor drug delivery efficacy. We investigated the potential utility of the permeability pattern of DCE-MRI for predicting tumor response to high dose-methotrexate treatment and progression-free survival (PFS) in patients with primary CNS lymphoma (PCNSL). Clinical and conventional imaging parameters were assessed as potential predictors of tumor response in 48 immunocompetent PCNSL patients in a preliminary study. Fifty additional immunocompetent patients (27 men and 23 women; mean age, 60.6 years) with PCNSL underwent DCE-MRI before starting first-line treatment with high dose-methotrexate. The DCE-MRI pattern was categorized as diffuse or nondiffuse. After 4 courses of high dose methotrexate, patients underwent follow-up brain MR imaging to identify their complete response (CR). Predictors of CR and PFS were analyzed using clinical parameters, conventional MRI, and DCE-MRI. CR was noted in 20 (74.1%) of 27 patients with diffuse DCE-MRI pattern and in 4 (17.4%) of 23 patients with nondiffuse DCE-MRI pattern. The diffuse DCE-MRI pattern showed a significantly higher association with CR than the nondiffuse pattern (P < 0.001). Multivariate Cox proportional hazards model revealed that the DCE-MRI pattern (hazard ratio = 0.70; P = 0.045), age (hazard ratio = 1.47; P = 0.041), and adjuvant autologous stem-cell transplantation (hazard ratio = 6.97; P = 0.003) tended to be associated with a PFS. The pretreatment diffuse DCE-MRI pattern can be used as a potential imaging biomarker for predicting CR and a longer PFS in patients with newly diagnosed PCNSLs. PMID:26871782

  14. ICAM-2 regulates vascular permeability and N-cadherin localization through ezrin-radixin-moesin (ERM) proteins and Rac-1 signalling

    PubMed Central

    2014-01-01

    Background Endothelial junctions control functions such as permeability, angiogenesis and contact inhibition. VE-Cadherin (VECad) is essential for the maintenance of intercellular contacts. In confluent endothelial monolayers, N-Cadherin (NCad) is mostly expressed on the apical and basal membrane, but in the absence of VECad it localizes at junctions. Both cadherins are required for vascular development. The intercellular adhesion molecule (ICAM)-2, also localized at endothelial junctions, is involved in leukocyte recruitment and angiogenesis. Results In human umbilical vein endothelial cells (HUVEC), both VECad and NCad were found at nascent cell contacts of sub-confluent monolayers, but only VECad localized at the mature junctions of confluent monolayers. Inhibition of ICAM-2 expression by siRNA caused the appearance of small gaps at the junctions and a decrease in NCad junctional staining in sub-confluent monolayers. Endothelioma lines derived from WT or ICAM-2-deficient mice (IC2neg) lacked VECad and failed to form junctions, with loss of contact inhibition. Re-expression of full-length ICAM-2 (IC2 FL) in IC2neg cells restored contact inhibition through recruitment of NCad at the junctions. Mutant ICAM-2 lacking the binding site for ERM proteins (IC2 ?ERM) or the cytoplasmic tail (IC2 ?TAIL) failed to restore junctions. ICAM-2-dependent Rac-1 activation was also decreased in these mutant cell lines. Barrier function, measured in vitro via transendothelial electrical resistance, was decreased in IC2neg cells, both in resting conditions and after thrombin stimulation. This was dependent on ICAM-2 signalling to the small GTPase Rac-1, since transendothelial electrical resistance of IC2neg cells was restored by constitutively active Rac-1. In vivo, thrombin-induced extravasation of FITC-labeled albumin measured by intravital fluorescence microscopy in the mouse cremaster muscle showed that permeability was increased in ICAM-2-deficient mice compared to controls. Conclusions These results indicate that ICAM-2 regulates endothelial barrier function and permeability through a pathway involving N-Cadherin, ERMs and Rac-1. PMID:24593809

  15. The Role of Monitoring Arterial Stiffness with Cardio-Ankle Vascular Index in the Control of Lifestyle-Related Diseases.

    PubMed

    Shirai, Kohji; Saiki, Atsuhito; Nagayama, Daiji; Tatsuno, Ichiro; Shimizu, Kazuhiro; Takahashi, Mao

    2015-09-01

    Arteriosclerosis is a major contributor to cardiovascular diseases. One of the difficulties in controlling those diseases is the lack of a suitable indicator of arteriosclerosis or arterial injury in routine clinical practice. Arterial stiffness was supposed to be one of the monitoring indexes of arteriosclerosis. Cardio-ankle vascular index (CAVI) is reflecting the stiffness of the arterial tree from the origin of the aorta to the ankle, and one of the features of CAVI is independency from blood pressure at a measuring time. When doxazosin, an ?1-adrenergic blocker, was administered, CAVI decreased, indicating that arterial stiffness is composed of both organic stiffness and functional stiffness, which reflects the contraction of arterial smooth muscle. CAVI shows a high value with aging and in many arteriosclerotic diseases, and is also high in persons possessing main coronary risk factors such as diabetes mellitus, metabolic syndrome, hypertension and smoking. Furthermore, when the most of those risk factors were controlled by proper methods, CAVI improved. Furthermore, the co-relationship between CAVI and heart function was demonstrated during treatment of heart failure. This paper reviews the principle and rationale of CAVI, and discusses the meaning of monitoring CAVI in following up so-called lifestyle-related diseases and cardiac dysfunction in routine clinical practice. PMID:26587461

  16. The Role of Monitoring Arterial Stiffness with Cardio-Ankle Vascular Index in the Control of Lifestyle-Related Diseases

    PubMed Central

    Shirai, Kohji; Saiki, Atsuhito; Nagayama, Daiji; Tatsuno, Ichiro; Shimizu, Kazuhiro; Takahashi, Mao

    2015-01-01

    Arteriosclerosis is a major contributor to cardiovascular diseases. One of the difficulties in controlling those diseases is the lack of a suitable indicator of arteriosclerosis or arterial injury in routine clinical practice. Arterial stiffness was supposed to be one of the monitoring indexes of arteriosclerosis. Cardio-ankle vascular index (CAVI) is reflecting the stiffness of the arterial tree from the origin of the aorta to the ankle, and one of the features of CAVI is independency from blood pressure at a measuring time. When doxazosin, an ?1-adrenergic blocker, was administered, CAVI decreased, indicating that arterial stiffness is composed of both organic stiffness and functional stiffness, which reflects the contraction of arterial smooth muscle. CAVI shows a high value with aging and in many arteriosclerotic diseases, and is also high in persons possessing main coronary risk factors such as diabetes mellitus, metabolic syndrome, hypertension and smoking. Furthermore, when the most of those risk factors were controlled by proper methods, CAVI improved. Furthermore, the co-relationship between CAVI and heart function was demonstrated during treatment of heart failure. This paper reviews the principle and rationale of CAVI, and discusses the meaning of monitoring CAVI in following up so-called lifestyle-related diseases and cardiac dysfunction in routine clinical practice. PMID:26587461

  17. StructureFunction Studies Using Deletion Mutants Identify Domains of gC1qR/p33 as Potential Therapeutic Targets for Vascular Permeability and Inflammation

    PubMed Central

    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.

    2011-01-01

    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 204218) 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 204218 (gC1qR?204218), 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?154162 and a point mutation in which Trp 233 was substituted with Gly. Binding studies also identified the existence of two additional sites at residues 144162 and 190202. Moreover, binding of HK to a synthetic peptide 190202 was inhibited by mAbs 48 and 83, but not by mAb 74.5.2. Since a single residue separates domains 190202 and 204218, 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. PMID:22282702

  18. Nonalcoholic Fatty Liver Disease as a Risk Factor of Arterial Stiffness Measured by the Cardioankle Vascular Index

    PubMed Central

    Chung, Goh Eun; Choi, Su-Yeon; Kim, Donghee; Kwak, Min-Sun; Park, Hyo Eun; Kim, Min-Kyung; Yim, Jeong Yoon

    2015-01-01

    Abstract Nonalcoholic fatty liver disease (NAFLD) is associated with risk factors for cardiovascular disease. The cardioankle vascular index (CAVI), a new measure of arterial stiffness, was recently developed and is independent of blood pressure. We investigated whether NAFLD is associated with arterial stiffness as measured using the CAVI in an apparently healthy population. A total of 2954 subjects without any known liver diseases were enrolled. NAFLD was diagnosed via typical ultrasonography. The clinical characteristics examined included age, sex, body mass index (BMI), waist circumference (WC), and the levels of aspartate aminotransferase, alanine aminotransferase, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol triglycerides, and glucose. Arterial stiffness was defined using an age- and sex-specific threshold of the upper quartile of the CAVI. NAFLD was found in 1249 (42.3%) of the analyzed subjects. Using an age-, sex-, and BMI-adjusted model, NAFLD was associated with a 42% increase in the risk for arterial stiffness (highest quartile of the CAVI). The risk for arterial stiffness increased according to the severity of NAFLD (adjusted odds ratio [95% confidence interval], 1.27 [1.02???1.57] vs 1.78 [1.37???2.31], mild vs moderate-to-severe, respectively). When adjusted for other risk factors, including BMI, WC, smoking status, diabetes, and hypertension, these relationships remained statistically significant. Patients with NAFLD are at a high risk for arterial stiffness regardless of classical risk factors. The presence of cardiometabolic risk factors may attenuate the prediction of arterial stiffness by means of NAFLD presence. Thus, physicians should carefully assess subjects with NAFLD for atherosclerosis and associated comorbidities. PMID:25816034

  19. Physiological Cost Index and Comfort Walking Speed in Two Level Lower Limb Amputees Having No Vascular Disease

    PubMed Central

    Vllasolli, Teuta Osmani; Orovcanec, Nikola; Zafirova, Beti; Krasniqi, Blerim; Murtezani, Ardiana; Krasniqi, Valbona; Rama, Bukurije

    2015-01-01

    Background: The Physiological Cost Index (PCI) was introduced by MacGregor to estimate the energy cost in walking of healthy people, also it has been reported for persons with lower limb amputation, walking with prosthesis. Objective: To assess energy cost and walking speed in two level lower limb amputation: transfemoral and transtibial amputation and to determine if the age and prosthetic walking supported with walking aids have impact on energy cost and walking speed. Methods: A prospective cross sectional study was performed in two level lower limb amputees with no vascular disease who were rehabilitated at the Department of Prosthetics and Orthotics at the University Clinical Center of Kosovo. The Physiological Cost Index (PCI) was assessed by five minutes of continuous indoor walking at Comfort Walking Speed (CWS). Results: Eighty three lower limb amputees were recruited. It is shown relevant impact of level of amputation in PCI (t=6.8, p<0.001) and CWS (T=487, p<0.001). The great influence of using crutches during prosthetic walking in PCI (ANOVA F= 39.5 P < 0.001) and CWS (ANOVA F=32.01, P <0.001) has been shown by One Way ANOVA test. The correlation coefficient (R) showed a significant correlation of age with PCI and CWS in both groups of amputation. Conclusions: Walking with transfemoral prosthesis or using walking aids during prosthetic ambulation is matched with higher cost of energy and slower walking speed. Advanced age was shown with high impact on PCI and CWS in both groups of amputees. PMID:25870485

  20. Measurement of absolute cell volume, osmotic membrane water permeability, and refractive index of transmembrane water and solute flux by digital holographic microscopy

    NASA Astrophysics Data System (ADS)

    Boss, Daniel; Khn, Jonas; Jourdain, Pascal; Depeursinge, Christian; Magistretti, Pierre J.; Marquet, Pierre

    2013-03-01

    A dual-wavelength digital holographic microscope to measure absolute volume of living cells is proposed. The optical setup allows us to reconstruct two quantitative phase contrast images at two different wavelengths from a single hologram acquisition. When adding the absorbing dye fast green FCF as a dispersive agent to the extracellular medium, cellular thickness can be univocally determined in the full field of view. In addition to the absolute cell volume, the method can be applied to derive important biophysical parameters of living cells including osmotic membrane water permeability coefficient and the integral intracellular refractive index (RI). Further, the RI of transmembrane flux can be determined giving an indication about the nature of transported solutes. The proposed method is applied to cultured human embryonic kidney cells, Chinese hamster ovary cells, human red blood cells, mouse cortical astrocytes, and neurons.

  1. Measurement of absolute cell volume, osmotic membrane water permeability, and refractive index of transmembrane water and solute flux by digital holographic microscopy.

    PubMed

    Boss, Daniel; Khn, Jonas; Jourdain, Pascal; Depeursinge, Christian; Magistretti, Pierre J; Marquet, Pierre

    2013-03-01

    A dual-wavelength digital holographic microscope to measure absolute volume of living cells is proposed. The optical setup allows us to reconstruct two quantitative phase contrast images at two different wavelengths from a single hologram acquisition. When adding the absorbing dye fast green FCF as a dispersive agent to the extracellular medium, cellular thickness can be univocally determined in the full field of view. In addition to the absolute cell volume, the method can be applied to derive important biophysical parameters of living cells including osmotic membrane water permeability coefficient and the integral intracellular refractive index (RI). Further, the RI of transmembrane flux can be determined giving an indication about the nature of transported solutes. The proposed method is applied to cultured human embryonic kidney cells, Chinese hamster ovary cells, human red blood cells, mouse cortical astrocytes, and neurons. PMID:23487181

  2. Determination of permeability index using Stoneley slowness analysis, NMR models, and formation evaluations: a case study from a gas reservoir, south of Iran

    NASA Astrophysics Data System (ADS)

    Hosseini, Mirhasan; Javaherian, Abdolrahim; Movahed, Bahram

    2014-10-01

    In hydrocarbon reservoirs, permeability is one of the most critical parameters with a significant role in the production of hydrocarbon resources. Direct determination of permeability using Stoneley waves has always had some difficulties. In addition, some un-calibrated empirical models such as Nuclear Magnetic Resonance (NMR) models and petrophysical evaluation model (intrinsic permeability) do not provide reliable estimates of permeability in carbonate formations. Therefore, utilizing an appropriate numerical method for direct determination of permeability using Stoneley waves as well as an appropriate calibration method for the empirical models is necessary to have reliable results. This paper shows the application of a numerical method, called bisection method, in the direct determination of permeability from Stoneley wave slowness. In addition, a linear regression (least squares) method was used to calibrate the NMR models including Schlumberger Doll Research (SDR) and Timur-Coates models as well as the intrinsic permeability equation (permeability from petrophysical evaluations). The Express Pressure Tester (XPT) permeability was considered as an option for the reference permeability. Therefore, all permeability models were validated for the Stoneley permeability and calibrated for the empirical models with the XPT permeability. In order to have a quantitative assessment on the results and compare the results before and after the calibration, the Root Mean Squares Error (RMSE) was calculated for each of the used models. The results for the Stoneley permeability showed that, in many points there was not much difference between the Stoneley permeability calculated by the bisection method and the XPT permeability. Comparing the results showed that the calibration of the empirical models reduced their RMSE values. As a result of the calibration, the RMSE was decreased by about 39% for the SDR model, 18% for the Timur-Coates model, and 91% for the petrophysical evaluations model. Presented bisection method calculates permeability directly without of any inversion or external calibration.

  3. Capsaicin stimulation of the cochlea and electric stimulation of the trigeminal ganglion mediate vascular permeability in cochlear and vertebro-basilar arteries: a potential cause of inner ear dysfunction in headache.

    PubMed

    Vass, Z; Steyger, P S; Hordichok, A J; Trune, D R; Jancs, G; Nuttall, A L

    2001-01-01

    Trigeminal neurogenic inflammation is one explanation for the development of vascular migraine. The triggers for this inflammation and pain are not well understood, but are probably vasoactive components acting on the blood vessel wall. Migraine-related inner ear symptoms like phonophobia, tinnitus, fluctuation in hearing perception and increased noise sensitivity provide indirect evidence that cochlear blood vessels are also affected by basilar artery migraine. The purpose of this investigation was to determine if a functional connection exists between the cochlea and the basilar artery. Neuronally mediated permeability changes in the cochlea and basilar artery were measured by colloidal silver and Evans Blue extravasation, following orthodromic and antidromic stimulation of the trigeminal ganglion innervating the cochlea. Capsaicin and electrical stimulation induced both dose- and time-dependent plasma extravasation of colloidal silver and Evans Blue from the basilar artery and anterior inferior cerebellar artery. Both orthodromic and antidromic activation of trigeminal sensory fibers also induced cochlear vascular permeability changes and significant quantitative differences between the treated and control groups in spectrophotometric assays. These results characterize a vasoactive connection between the cochlea and vertebro-basilar system through the trigeminal sensory neurons. We propose that vertigo, tinnitus and hearing deficits associated with basilar migraine could arise by excitation of the trigeminal nerve fibers in the cochlea, resulting in local plasma extravasation. In addition, cochlear "dysfunction" may also trigger basilar and cluster headache by afferent input to the trigeminal system. PMID:11311800

  4. The Role of a Novel Arterial Stiffness Parameter, Cardio-Ankle Vascular Index (CAVI), as a Surrogate Marker for Cardiovascular Diseases.

    PubMed

    Saiki, Atsuhito; Sato, Yuta; Watanabe, Rena; Watanabe, Yasuhiro; Imamura, Haruki; Yamaguchi, Takashi; Ban, Noriko; Kawana, Hidetoshi; Nagumo, Ayako; Nagayama, Daiji; Ohira, Masahiro; Endo, Kei; Tatsuno, Ichiro

    2016-02-01

    Measurement of arterial stiffness in routine medical practice is important to assess the progression of arteriosclerosis. So far, many parameters have been proposed to quantitatively represent arterial stiffness. Among these, pulse wave velocity (PWV) has been most frequently applied to clinical medicine because those could be measured simply and non-invasively. PWV had established the usefulness of measuring arterial wall stiffness. However, PWV essentially depends on blood pressure at the time of measurement. Therefore, PWV is not appropriate as a parameter for the evaluation of arterial stiffness, particularly for the studies involving blood pressure changes.On the other hand, stiffness parameter ? is an index reflecting arterial stiffness without the influence of blood pressure. Recently, this parameter has been applied to develop a new arterial stiffness index called cardio-ankle vascular index (CAVI). Therefore, CAVI does not depend on blood pressure changes during the measurements; CAVI could represent the stiffness of the arterial tree from the origin of the aorta to the ankle.Many clinical studies obtained from CAVI are being accumulated. CAVI showed high value in arteriosclerotic diseases, such as coronary artery diseases, cerebral infarction, and chronic kidney diseases, and also in majority of people with various coronary risk factors. The improvement of those risk factors decreased CAVI. Furthermore, the role of CAVI as a predictor of cardio-vascular events was reported recently.We review the clinical studies on CAVI and discuss the clinical usefulness of CAVI as a candidate surrogate end-point marker for cardiovascular disease. PMID:26607350

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

    PubMed Central

    Jovanovski, Elena; Zurbau, Andreea

    2015-01-01

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

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

    PubMed

    Jovanovski, Elena; Zurbau, Andreea; Vuksan, Vladimir

    2015-04-01

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

  7. FECAL CALPROTECTIN AND GASTROINTESTINAL (GI) PERMEABILITY CORRELATE WITH DISEASE ACTIVITY INDEX, AND HISTOLOGIC, ENDOSCOPIC, AND RADIOLOGIC FINDINGS IN CHILDREN WITH CROHN DISEASE (CD)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fecal calprotectin and permeability are noninvasive measures of GI inflammation and damage, respectively. However, there are scant data as to the possible association between the tests and CD disease activity in children. We hypothesized that levels of fecal calprotectin and permeability would corre...

  8. Expansion Duroplasty Improves Intraspinal Pressure, Spinal Cord Perfusion Pressure, and Vascular Pressure Reactivity Index in Patients with Traumatic Spinal Cord Injury: Injured Spinal Cord Pressure Evaluation Study

    PubMed Central

    Phang, Isaac; Werndle, Melissa C.; Saadoun, Samira; Varsos, Georgios; Czosnyka, Marek; Zoumprouli, Argyro

    2015-01-01

    Abstract We recently showed that, after traumatic spinal cord injury (TSCI), laminectomy does not improve intraspinal pressure (ISP), spinal cord perfusion pressure (SCPP), or the vascular pressure reactivity index (sPRx) at the injury site sufficiently because of dural compression. This is an open label, prospective trial comparing combined bony and dural decompression versus laminectomy. Twenty-one patients with acute severe TSCI had re-alignment of the fracture and surgical fixation; 11 had laminectomy alone (laminectomy group) and 10 had laminectomy and duroplasty (laminectomy+duroplasty group). Primary outcomes were magnetic resonance imaging evidence of spinal cord decompression (increase in intradural space, cerebrospinal fluid around the injured cord) and spinal cord physiology (ISP, SCPP, sPRx). The laminectomy and laminectomy+duroplasty groups were well matched. Compared with the laminectomy group, the laminectomy+duroplasty group had greater increase in intradural space at the injury site and more effective decompression of the injured cord. In the laminectomy+duroplasty group, ISP was lower, SCPP higher, and sPRx lower, (i.e., improved vascular pressure reactivity), compared with the laminectomy group. Laminectomy+duroplasty caused cerebrospinal fluid leak that settled with lumbar drain in one patient and pseudomeningocele that resolved completely in five patients. We conclude that, after TSCI, laminectomy+duroplasty improves spinal cord radiological and physiological parameters more effectively than laminectomy alone. PMID:25705999

  9. The Ketogenic Diet Alters the Hypoxic Response and Affects Expression of Proteins Associated with Angiogenesis, Invasive Potential and Vascular Permeability in a Mouse Glioma Model

    PubMed Central

    Woolf, Eric C.; Curley, Kara L.; Liu, Qingwei; Turner, Gregory H.; Charlton, Julie A.; Preul, Mark C.; Scheck, Adrienne C.

    2015-01-01

    Background The successful treatment of malignant gliomas remains a challenge despite the current standard of care, which consists of surgery, radiation and temozolomide. Advances in the survival of brain cancer patients require the design of new therapeutic approaches that take advantage of common phenotypes such as the altered metabolism found in cancer cells. It has therefore been postulated that the high-fat, low-carbohydrate, adequate protein ketogenic diet (KD) may be useful in the treatment of brain tumors. We have demonstrated that the KD enhances survival and potentiates standard therapy in a mouse model of malignant glioma, yet the mechanisms are not fully understood. Methods To explore the effects of the KD on various aspects of tumor growth and progression, we used the immunocompetent, syngeneic GL261-Luc2 mouse model of malignant glioma. Results Tumors from animals maintained on KD showed reduced expression of the hypoxia marker carbonic anhydrase 9, hypoxia inducible factor 1-alpha, and decreased activation of nuclear factor kappa B. Additionally, tumors from animals maintained on KD had reduced tumor microvasculature and decreased expression of vascular endothelial growth factor receptor 2, matrix metalloproteinase-2 and vimentin. Peritumoral edema was significantly reduced in animals fed the KD and protein analyses showed altered expression of zona occludens-1 and aquaporin-4. Conclusions The KD directly or indirectly alters the expression of several proteins involved in malignant progression and may be a useful tool for the treatment of gliomas. PMID:26083629

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

    PubMed Central

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

    2013-01-01

    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. PMID:23637907

  11. A disorder of sympathomimetic amines leading to increased vascular permeability may be the etiologic factor in various treatment refractory health problems in women.

    PubMed

    Check, J H; Katsoff, D; Kaplan, H; Liss, J; Boimel, P

    2008-01-01

    There is an evidence that increased capillary permeability in the standing position is related to a deficit in the sympathetic nervous system. The leakage of this fluid leads to various clinical conditions which frequently puzzle the consulting physician because despite the frequency of this condition intelligent physicians and patients are unaware of the cause of their condition. One of the most common manifestations is the inability to lose weight despite proper dieting. A randomized study comparing the efficacy of a diuretic, a converting enzyme inhibitor, spironolactone and a sympathomimetic amine on weight loss in diet refractory women found that only the latter in the form of dextroamphetamine sulfate demonstrated significant weight reduction over a six month time span. In fact, the dextroamphetamine sulfate proved effective when given in the next 6 months to the three groups failing to respond for the first 6 months. The diagnosis of a deficit in sympathomimetic amines is established by demonstrating an abnormal clearance of a water load in the erect position and exclusion of other conditions that are associated with an abnormal free water clearance, e.g., hypothyroidism, renal or liver disease or congestive heart failure. The original definition of an abnormal water load test was excretion of <55% of a 1500 ml water load in 6h but we found that <75% defines a greater population who suffer from this problem. There are several conditions that have proven refractory to conventional theory that respond quickly and effectively to sympathomimetic amines. There have been many anecdotal reports of relieving interactable pain syndromes quickly and efficiently with sympathomimetic amine theory, despite failure with a multitude of other therapies. These include interstitial cystitis and pelvic pain that was attributed to endometriosis, gastrointestinal pain including esophagitis and gastroparesis, headaches, joint pain, fibromyalgia, and carpal tunnel syndrome. It is not clear if the improvement in pain is related to a decrease in fluid retention or a direct effect of the sympathomimetic amines on the sympathetic nervous system. Sympathomimetic amine theory has helped other conditions besides pain, e.g., chronic fatigue, vasomotor symptoms in young women not associated with decreased ovarian egg reserve, and chronic urticaria resistant to all other therapies. Thus, these studies strongly suggest that physicians be aware of this condition involving a deficit in the sympathetic nervous system when faced with various enigmatic complaints especially if standard therapy has not proven effective. PMID:17765403

  12. Crustal Permeability

    NASA Astrophysics Data System (ADS)

    Ingebritsen, S.; Gleeson, T.

    2014-12-01

    Existing data and models support a distinction between the hydrodynamics of the brittle upper crust, where topography, permeability contrasts, and magmatic heat sources dominate patterns of flow and externally derived (meteoric) fluids are common, and the ductile lower crust, dominated by devolatilization reactions and internally derived fluids. The permeability structure of the uppermost (~<1 km) crust is highly heterogeneous, and controls include primary lithology, porosity, rheology, geochemistry, and tectonic and time-temperature histories of the rocks. Systematic permeability differences among original lithologies persist to contact-metamorphic depths of 3-10 km, but are not evident at regional-metamorphic depths of 10-30+ km - presumably because, at such depths, metamorphic textures become largely independent of the original lithology. Permeability can vary in time as well as space, and its temporal evolution may be gradual or abrupt: streamflow responses to moderate to large earthquakes demonstrate that dynamic stresses can instantaneously change permeability by factors of up to 20 on a regional scale, whereas a 10-fold decrease in the permeability of a package of shale in a compacting basin may require 107years. Temporal variation is enhanced by strong chemical and thermal disequilibrium; thus lab experiments involving hydrothermal flow in crystalline rocks under pressure, temperature, and chemistry gradients often result in 10-fold permeability decreases over daily to sub-annual time scales. Recent research on enhanced geothermal reservoirs, ore-forming systems, and the hydrologic effects of earthquakes consistently shows that shear dislocation caused by tectonic forcing or fluid injection can increase near-to intermediate-field permeability by factors of 100 to 1000. Nonetheless, considering permeability as static parameter is often a reasonable assumption for low-temperature hydrogeologic investigations with time scales of days to decades.

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

    PubMed Central

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

    2012-01-01

    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. PMID:22919496

  14. Association Between Increased Vascular Nitric Oxide Bioavailability and Progression to Dengue Hemorrhagic Fever in Adults.

    PubMed

    Thein, Tun-Linn; Wong, Joshua; Leo, Yee-Sin; Ooi, Eng-Eong; Lye, David; Yeo, Tsin W

    2015-09-01

    In a prospective longitudinal adult study, vascular nitric oxide bioavailability measured as reactive hyperemia index was significantly higher at enrollment in patients who developed dengue hemorrhagic fever (DHF) (n = 11), compared with the non-DHF group (n = 63) and those with other febrile illnesses (n = 25) (P = .01). After adjustment for age, fever day, and body mass index, enrollment reactive hyperemia index was associated with a 4-fold increased risk for DHF, and predicted DHF with an area under the receiver operating curve of 0.86. Increased vascular nitric oxide in dengue is associated with increased vascular permeability and impaired homeostasis and may have utility as a predictor of DHF. PMID:25732810

  15. Negative associations between arterial stiffness parameter evaluated by cardio-ankle vascular index and serum low-density lipoprotein cholesterol concentration in early-stage atherosclerosis.

    PubMed

    Homma, Satoki; Kato, Kiyoe; Hayashi, Junichi; Yamamoto, Minoru

    2015-02-01

    The cardio-ankle vascular index (CAVI), calculated values from cardio-ankle pulse wave velocity and blood pressure, corresponds predominantly to the stiffness of the aorta and peripheral arteries of the lower limbs. However, the reported associations between CAVI and serum low-density lipoprotein cholesterol (LDL-C) levels remain inconsistent. A cross-sectional study of 1878 consecutive patients (mean age: 59.2 years) who underwent general health checkup showed a negative association between CAVI and serum LDL-C or non-high-density lipoprotein cholesterol (non-HDL-C) concentrations with age-adjusted correlation and multiple regression analysis. Using the similar analyses divided by the status of risk factors and degree of maximum carotid intima-media thickness (maxIMT), negative correlations between CAVI and LDL-C or non-HDL-C levels were observed only in nonrisk groups including nondiabetics patients or patients with maxIMT <1.0 mm, in those with expected low extent of advanced atherosclerotic lesions. In contrast, such a correlation was not found in each comparable risk-loaded group. PMID:24402322

  16. Vascular hyperpermeability and aging.

    PubMed

    Oakley, Ryan; Tharakan, Binu

    2014-04-01

    Vascular hyperpermeability, the excessive leakage of fluid and proteins from blood vessels to the interstitial space, commonly occurs in traumatic and ischemic injuries. This hyperpermeability causes tissue vasogenic edema, which often leads to multiple organ failure resulting in patient death. Vascular hyperpermeability occurs most readily in small blood vessels as their more delicate physical constitution makes them an easy target for barrier dysfunction. A single layer of endothelial cells, linked to one another by cell adhesion molecules, covers the interior surface of each blood vessel. The cell adhesion molecules play a key role in maintaining barrier functions like the regulation of permeability. Aging is a major risk factor for microvascular dysfunction and hyperpermeability. Apart from age-related remodeling of the vascular wall, endothelial barrier integrity and function declines with the advancement of age. Studies that address the physiological and molecular basis of vascular permeability regulation in aging are currently very limited. There have been many cellular and molecular mechanisms proposed to explain aging-related endothelial dysfunction but their true relationship to barrier dysfunction and hyperpermeability is not clearly known. Among the several mechanisms that promote vascular dysfunction and hyperpermeability, the following are considered major contributors: oxidative stress, inflammation, and the activation of apoptotic signaling pathways. In this review we highlighted (a) the physiological, cellular and molecular changes that occur in the vascular system as a product of aging; (b) the potential mechanisms by which aging leads to barrier dysfunction and vascular hyperpermeability in the peripheral and the blood-brain barrier; (c) the mechanisms by which the age-related increases in oxidative stress, inflammatory markers and apoptotic signaling etc. cause endothelial dysfunction and their relationship to hyperpermeability; and (d) the relationship between aging, vascular permeability and traumatic injuries. PMID:24729937

  17. Survey of ocular irritation predictive capacity using Chorioallantoic Membrane Vascular Assay (CAMVA) and Bovine Corneal Opacity and Permeability (BCOP) test historical data for 319 personal care products over fourteen years.

    PubMed

    Donahue, D A; Kaufman, L E; Avalos, J; Simion, F A; Cerven, D R

    2011-03-01

    The Chorioallantoic Membrane Vascular Assay (CAMVA) and Bovine Corneal Opacity and Permeability (BCOP) test are widely used to predict ocular irritation potential for consumer-use products. These in vitro assays do not require live animals, produce reliable predictive data for defined applicability domains compared to the Draize rabbit eye test, and are rapid and inexpensive. Data from 304 CAMVA and/or BCOP studies (319 formulations) were surveyed to determine the feasibility of predicting ocular irritation potential for various formulations. Hair shampoos, skin cleansers, and ethanol-based hair styling sprays were repeatedly predicted to be ocular irritants (accuracy rate=0.90-1.00), with skin cleanser and hair shampoo irritation largely dependent on surfactant species and concentration. Conversely, skin lotions/moisturizers and hair styling gels/lotions were repeatedly predicted to be non-irritants (accuracy rate=0.92 and 0.82, respectively). For hair shampoos, ethanol-based hair stylers, skin cleansers, and skin lotions/moisturizers, future ocular irritation testing (i.e., CAMVA/BCOP) can be nearly eliminated if new formulations are systematically compared to those previously tested using a defined decision tree. For other tested product categories, new formulations should continue to be evaluated in CAMVA/BCOP for ocular irritation potential because either the historical data exhibit significant variability (hair conditioners and mousses) or the historical sample size is too small to permit definitive conclusions (deodorants, make-up removers, massage oils, facial masks, body sprays, and other hair styling products). All decision tree conclusions should be made within a conservative weight-of-evidence context, considering the reported limitations of the BCOP test for alcohols, ketones, and solids. PMID:21147215

  18. 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.

    PubMed

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

    2013-10-01

    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

  19. 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...

  20. Respiratory mucosal permeability in asthma

    SciTech Connect

    Elwood, R.K.; Kennedy, S.; Belzberg, A.; Hogg, J.C.; Pare, P.D.

    1983-09-01

    The permeability of respiratory mucosa to technetium-labeled diethylenetriamine pentacetic acid (/sup 99m/Tc-DTPA) was measured in 10 clinically stable chronic asthmatics and the results were compared with those in 9 nonasthmatic control subjects. Nonspecific bronchial reactivity was measured using methacholine, and the PC20 was calculated. The intrapulmonary distribution and dose of the inhaled /sup 99m/Tc-DTPA was determined by a gamma camera and the half-life of the aerosolized label in the lung was calculated. The accumulation of radioactivity in the blood was monitored and a permeability index was calculated at 10, 25, and 60 min after aerosolization. Despite marked differences in airway reactivity, no differences in either parameter of permeability could be detected between the asthmatics and the control group. It is concluded that clinically stable asthmatics do not demonstrate increase mucosal permeability to small solutes when compared with normal subjects.

  1. Vascular Cures

    MedlinePLUS

    ... Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease Chronic Venous Insufficiency Congenital Vascular Malformation Critical Limb Ischemia (CLI) Deep Vein Thrombosis (DVT) Diabetes and Vascular Disease Fibromuscular Dysplasia High ...

  2. MRI of BloodBrain Barrier Permeability in Cerebral Ischemia

    PubMed Central

    Ewing, James R.; Chopp, Michael

    2013-01-01

    Quantitative measurement of bloodbrain 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. PMID:23997835

  3. Pressure sensitivity of low permeability sandstones

    USGS Publications Warehouse

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

    1987-01-01

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

  4. Diabetes and Retinal Vascular Dysfunction

    PubMed Central

    Shin, Eui Seok; Sorenson, Christine M.; Sheibani, Nader

    2014-01-01

    Diabetes predominantly affects the microvascular circulation of the retina resulting in a range of structural changes unique to this tissue. These changes ultimately lead to altered permeability, hyperproliferation of endothelial cells and edema, and abnormal vascularization of the retina with resulting loss of vision. Enhanced production of inflammatory mediators and oxidative stress are primary insults with significant contribution to the pathogenesis of diabetic retinopathy (DR). We have determined the identity of the retinal vascular cells affected by hyperglycemia, and have delineated the cell autonomous impact of high glucose on function of these cells. We discuss some of the high glucose specific changes in retinal vascular cells and their contribution to retinal vascular dysfunction. This knowledge provides novel insight into the molecular and cellular defects contributing to the development and progression of diabetic retinopathy, and will aid in the development of innovative, as well as target specific therapeutic approaches for prevention and treatment of DR. PMID:25667739

  5. Mast Cells Contribute to Radiation-Induced Vascular Hyperpermeability

    PubMed Central

    Park, Kyung Ran; Monsky, Wayne L.; Lee, Chang Geol; Song, Chang Ho; Kim, Dong Heui; Jain, Rakesh K.; Fukumura, Dai

    2016-01-01

    Induction of vascular hyperpermeability is one of the early vascular responses to radiation exposure and is considered to contribute to subsequent fibrosis and tissue injuries. However, the mechanism underlying radiation-induced hyperpermeability has not yet been clearly elucidated. Here, we provide experimental evidence indicating that mast cells contribute to the increase in vascular permeability for albumin in normal mouse skin after irradiation. Vascular permeability in the skin of C3H mice increased after 2, 15 and 50 Gy irradiation, peaked at 24 h after irradiation and gradually decreased thereafter to the baseline level within 3–10 days. Both the extent and duration of hyperpermeability were dose dependent. We found significant degranulation of mast cells in the skin after 15 Gy irradiation. To further investigate the role of mast cells in the radiation-induced increase in vascular permeability, we measured vascular permeability in the skin of mast cell-deficient mice (WWv) and their wild-type littermates at 24 h after irradiation. Vascular permeability in WWv mice did not change, whereas that in wild-type mice significantly increased after irradiation. There were no appreciable changes in the total tissue levels of vascular endothelial growth factor or endothelial nitric oxide synthase after 15 Gy irradiation and there was no detectable expression of inducible nitric oxide synthase. Collectively, these results show that exposure to radiation induces vascular hyperpermeability in a dose-dependent manner and that mast cells contribute to this process. PMID:26771172

  6. EPA Permeable Surface Research

    EPA Science Inventory

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

  7. Permeability of Clay Concretes

    NASA Astrophysics Data System (ADS)

    Solomon, F.; Ekolu, S. O.

    2015-11-01

    This paper presents an investigation on the effect of clay addition on water permeability and air permeability of concretes. Clay concrete mixes consisted of 0 to 40% clay content incorporated as cement replacement. Flow methods using triaxial cells and air permeameters were used for measuring the injected water and air flows under pressure. It was found that the higher the clay content in the mixture, the greater the permeability. At higher water-cement ratios (w/c), the paste matrix is less dense and easily allows water to ingress into concrete. But at high clay contents of 30 to 40% clay, the variation in permeability was significantly diminished among different concrete mixtures. It was confirmed that air permeability results were higher than the corresponding water permeability values when all permeability coefficients were converted to intrinsic permeability values.

  8. Ageing and vascular ageing.

    PubMed

    Jani, B; Rajkumar, C

    2006-06-01

    There is an age related decline in various physiological processes. Vascular ageing is associated with changes in the mechanical and the structural properties of the vascular wall, which leads to the loss of arterial elasticity and reduced arterial compliance. Arterial compliance can be measured by different parameters like pulse wave velocity, augmentation index, and systemic arterial compliance. There is evidence that arterial compliance is reduced in disease states such as hypertension, diabetes, and end stage renal failure. Changes in arterial compliance can be present before the clinical manifestation of cardiovascular disease. Pharmacological and non-pharmacological measures have been shown to improve arterial compliance. Arterial compliance may constitute an early cardiovascular risk marker and may be useful in assessing the effects of drugs on the cardiovascular system. Pharmacogenetics and genetics of arterial compliance in the future will improve our knowledge and understanding about vascular ageing. PMID:16754702

  9. Abnormal intestinal permeability and jejunal morphometry.

    PubMed Central

    Juby, L D; Dixon, M F; Axon, A T

    1987-01-01

    The cellobiose and mannitol differential sugar test is a non-invasive investigation of small bowel permeability, in which urinary recoveries of cellobiose and mannitol after a hyperosmolar oral load are expressed as a ratio to give a permeability index. Changes in the cellobiose:mannitol ratio often occur in coeliac disease, but some patients with abnormal permeability have normal jejunums by routine microscopy. Using computed morphometry the perimeter:lamina propria area index of jejunal biopsy samples was measured and compared with the cellobiose:mannitol ratio in three groups of patients: (i) those with coeliac disease with villous atrophy; (ii) those with normal jejunums and sugar test results: and (iii) those with normal jejunums but abnormal sugar test results. In addition to the expected difference in perimeter:lamina propria area index between patients with coeliac disease and those with normal findings (p less than 0.001), the index was also abnormal in patients with normal jejunums but abnormal sugar test results: (p less than 0.001 compared with group 1) and (0.01 greater than p greater than 0.001 compared with group 2). There was a significant overall correlation between the perimeter:lamina propria area index and cellobiose:mannitol ratio (p = 0.001). This study shows that computed jejunal morphometry can identify patients with subtle morphological changes that are related to abnormal intestinal permeability. Images Fig 1 PMID:3114327

  10. Vascular Tumors

    PubMed Central

    Sepulveda, Abel; Buchanan, Edward P.

    2014-01-01

    Vascular anomalies are divided into two main groups: tumors and malformations. Vascular tumors are a large and complex group of lesions, especially for clinicians with none or little experience in this field. In the past, these lesions caused a great deal of confusion because many appear analogous to the naked eye. Thankfully, recent advances in diagnostic techniques have helped the medical community to enhance our comprehension, accurately label, diagnose, and treat these lesions. In this article, we will review the most frequent vascular tumors and provide the reader with the tools to properly label, diagnose, and manage these complex lesions. PMID:25045329

  11. Endothelial permeability and VE-cadherin

    PubMed Central

    Gavard, Julie

    2014-01-01

    The endothelium forms a selective semi-permeable barrier controlling bidirectional transfer between blood vessel and irrigated tissues. This crucial function relies on the dynamic architecture of endothelial cellcell junctions, and in particular, VE-cadherin-mediated contacts. VE-cadherin indeed chiefly organizes the opening and closing of the endothelial barrier, and is central in permeability changes. In this review, the way VE-cadherin-based contacts are formed and maintained is first presented, including molecular traits of its expression, partners, and signaling. In a second part, the mechanisms by which VE-cadherin adhesion can be disrupted, leading to cellcell junction weakening and endothelial permeability increase, are described. Overall, the molecular basis for VE-cadherin control of the endothelial barrier function is of high interest for biomedical research, as vascular leakage is observed in many pathological conditions and human diseases. PMID:25422846

  12. Endothelial permeability and VE-cadherin

    PubMed Central

    Gavard, Julie

    2013-01-01

    The endothelium forms a selective semi-permeable barrier controlling bidirectional transfer between blood vessel and irrigated tissues. This crucial function relies on the dynamic architecture of endothelial cellcell junctions, and in particular, VE-cadherin-mediated contacts. VE-cadherin indeed chiefly organizes the opening and closing of the endothelial barrier, and is central in permeability changes. In this review, the way VE-cadherin-based contacts are formed and maintained is first presented, including molecular traits of its expression, partners, and signaling. In a second part, the mechanisms by which VE-cadherin adhesion can be disrupted, leading to cellcell junction weakening and endothelial permeability increase, are described. Overall, the molecular basis for VE-cadherin control of the endothelial barrier function is of high interest for biomedical research, as vascular leakage is observed in many pathological conditions and human diseases. PMID:24430214

  13. Vascular ring

    MedlinePLUS

    ... several curved pieces of tissue (arches). The body breaks down some of the remaining arches, while others form into arteries. Some arteries that should break down do not, which forms a vascular ring. With ...

  14. Vascular Diseases

    MedlinePLUS

    ... heart and blood vessels, such as diabetes or high cholesterol Smoking Obesity Losing weight, eating healthy foods, being active and not smoking can help vascular disease. Other treatments include medicines and surgery.

  15. Vascular permeability—the essentials

    PubMed Central

    2015-01-01

    The vasculature, composed of vessels of different morphology and function, distributes blood to all tissues and maintains physiological tissue homeostasis. In pathologies, the vasculature is often affected by, and engaged in, the disease process. This may result in excessive formation of new, unstable, and hyperpermeable vessels with poor blood flow, which further promotes hypoxia and disease propagation. Chronic vessel permeability may also facilitate metastatic spread of cancer. Thus, there is a strong incentive to learn more about an important aspect of vessel biology in health and disease: the regulation of vessel permeability. The current review aims to summarize current insights into different mechanisms of vascular permeability, its regulatory factors, and the consequences for disease. PMID:26220421

  16. Permeability and relative permeability in rocks

    SciTech Connect

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

    1990-10-01

    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.

  17. Vascular Calcification

    PubMed Central

    Demer, Linda L.; Tintut, Yin

    2009-01-01

    Summary Clinically, vascular calcification is now accepted as a valuable predictor of coronary heart disease.153 Achieving control over this process requires understanding mechanisms in the context of a tightly controlled regulatory network, with multiple, nested feedback loops and cross talk between organ systems, in the realm of control theory. Thus, treatments for osteoporosis such as calcitriol, estradiol, bisphosphonates, calcium supplements, and intermittent PTH are likely to affect vascular calcification, and, conversely, many treatments for cardiovascular disease such as statins, antioxidants, hormone replacement therapy, angiotensin-converting enzyme inhibitors, fish oils, and calcium channel blockers may affect bone health. As we develop and use treatments for cardiovascular and skeletal diseases, we must give serious consideration to the implications for the organ at the other end of the bone-vascular axis. PMID:11602487

  18. Effect of dengue virus-induced cytotoxin on capillary permeability.

    PubMed Central

    Dhawan, R.; Khanna, M.; Chaturvedi, U. C.; Mathur, A.

    1990-01-01

    Capillary permeability is increased in cases of dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) but its genesis is not known. Dengue type 2 virus (DV) induces production of a cytokine (CF2) by mouse macrophages. The present study was undertaken to investigate the effect of CF2 on capillary permeability. It was observed that intraperitoneal inoculation of CF2 in mice increased the capillary permeability in a dose-dependent manner, as shown by leakage of intravenously injected radioactive iodine (125I) or Evan's blue dye in the peritoneal cavity. Peak leakage occurred at 30 min and the vascular integrity was restored by 1-2 h. The increase in capillary permeability was abrogated by pretreatment of mice with avil (H1 receptor blocker) but not by ranitidine (H2 receptor blocker). The findings thus show that DV-induced CF2 increases the capillary permeability via release of histamine. PMID:2310617

  19. Metoclopramide and renal vascular resistance.

    PubMed

    Manara, A R; Bolsin, S; Monk, C R; Hartnell, G; Harris, R A

    1991-01-01

    We have studied the effect of i.v. metoclopramide on renal vascular resistance in nine healthy volunteers. Peak systolic and end-diastolic frequencies were measured using duplex Doppler ultrasound of a renal interlobar artery, before and after the administration of i.v. metoclopramide 10 mg, and the resistance index derived. There was no significant change in mean arterial pressure or resistance index following metoclopramide. PMID:1997046

  20. Permeability of porour rhyolite

    NASA Astrophysics Data System (ADS)

    Cashman, K.; Rust, A.; Wright, H.; Roberge, J.

    2003-04-01

    The development of permeability in bubble-bearing magmas determines the efficiency of volatile escape during their ascent through volcanic conduits, which, in turn, controls their explosive potential. As permeability requires bubble connectivity, relationships between permeability and porosity in silicic magmas must be controlled by the formation, growth, deformation and coalescence of their constituent bubbles. Although permeability data on porous volcanic pyroclasts are limited, the database can be greatly extended by including data for ceramic and metallic foams1. Several studies indicate that a single number does not adequately describe the permeability of a foam because inertial effects, which predominate at high flow rates, cause deviations from Darcy's law. These studies suggest that permeability is best modeled using the Forschheimer equation to determine both the Darcy permeability (k1) and the non-Darcian (k2) permeability. Importantly, at the high porosities of ceramic foams (75-95%), both k1 and k2 are strongly dependent on pore size and geometry, suggesting that measurement of these parameters provides important information on foam structure. We determined both the connected porosity (by He-pycnometry) and the permeability (k1 and k2) of rhyolitic samples having a wide range in porosity (22-85%) and vesicle textures. In general, these data support previous observations of a power law relationship between connected porosity and Darcy permeability2. In detail, variations in k1 increase at higher porosities. Similarly, k2 generally increases in both mean and standard deviation with increasing porosity. Measurements made on three mutually perpendicular cores from individual pumice clasts suggest that some of the variability can be explained by anisotropy in the vesicle structure. By comparison with ceramic foams, we suggest that the remaining variability results from differences either in average vesicle size or, more likely, in the size of apertures connecting individual vesicles. This interpretation is supported by the observation that clasts with high porosities but unusually low k1 and k2 also have high percentages of isolated pores (>10%), indicating extensive vesiculation but limited bubble coalescence; such clasts seem to be characteristic of ignimbrite deposits. 1Innocentini MDM, Salvini VR, Pandolfelli VC, Coury JC (1999) The permeability of ceramic foams. Amer Ceram Soc Bull 79:78-94. 2Klug C, Cashman KV (1996) Permeability development in vesiculating magmas - implications for fragmentation. Bull. Volcanol.58:87-100; Klug C, Cashman KV, Bacon C (2002) Structure and physical characteristics of pumice from the climactic eruption of Mt. Mazama (Crater Lake), Oregon. Bull Volcanol 64:486-501

  1. Increased endothelial cell permeability in endoglin-deficient cells.

    PubMed

    Jerkic, Mirjana; Letarte, Michelle

    2015-09-01

    Endoglin (ENG) is a TGF-? superfamily coreceptor essential for vascular endothelium integrity. ENG mutations lead to a vascular dysplasia associated with frequent hemorrhages in multiple organs, whereas ENG null mouse embryos die at midgestation with impaired heart development and leaky vasculature. ENG interacts with several proteins involved in cell adhesion, and we postulated that it regulates vascular permeability. The current study assessed the permeability of ENG homozygous null (Eng(-/-)), heterozygous (Eng(+/-)), and normal (Eng(+/+)) mouse embryonic endothelial cell (EC) lines. Permeability, measured by passage of fluorescent dextran through EC monolayers, was increased 2.9- and 1.7-fold for Eng(-/-) and Eng(+/-) ECs, respectively, compared to control ECs and was not increased by TGF-?1 or VEGF. Prolonged starvation increased Eng(-/-) EC permeability by 3.7-fold with no effect on control ECs; neutrophils transmigrated faster through Eng(-/-) than Eng(+/+) monolayers. Using a pull-down assay, we demonstrate that Ras homolog gene family (Rho) A is constitutively active in Eng(-/-) and Eng(+/-) ECs. We show that the endothelial barrier destabilizing factor thrombospondin-1 and its receptor-like protein tyrosine phosphatase are increased, whereas stabilizing factors VEGF receptor 2, vascular endothelial-cadherin, p21-activated kinase, and Ras-related C3 botulinum toxin substrate 2 are decreased in Eng(-/-) cells. Our findings indicate that ENG deficiency leads to EC hyperpermeability through constitutive activation of RhoA and destabilization of endothelial barrier function. PMID:25972355

  2. Mechanosensing at the Vascular Interface

    PubMed Central

    Tarbell, John M.; Simon, Scott I.; Curry, Fitz-Roy E.

    2015-01-01

    Mammals are endowed with a complex set of mechanisms that sense mechanical forces imparted by blood flow to endothelial cells (ECs), smooth muscle cells, and circulating blood cells to elicit biochemical responses through a process referred to as mechanotransduction. These biochemical responses are critical for a host of other responses, including regulation of blood pressure, control of vascular permeability for maintaining adequate perfusion of tissues, and control of leukocyte recruitment during immunosurveillance and inflammation. This review focuses on the role of the endothelial surface proteoglycan/glycoprotein layer—the glycocalyx (GCX)—that lines all blood vessel walls and is an agent in mechanotransduction and the modulation of blood cell interactions with the EC surface. We first discuss the biochemical composition and ultrastructure of the GCX, highlighting recent developments that reveal gaps in our understanding of the relationship between composition and spatial organization. We then consider the roles of the GCX in mechanotransduction and in vascular permeability control and review the prominent interaction of plasma borne sphingosine-1 phosphate (S1P), which has been shown to regulate both the composition of the GCX and the endothelial junctions. Finally, we consider the association of GCX degradation with inflammation and vascular disease and end with a final section on future research directions. PMID:24905872

  3. Mechanosensing at the vascular interface.

    PubMed

    Tarbell, John M; Simon, Scott I; Curry, Fitz-Roy E

    2014-07-11

    Mammals are endowed with a complex set of mechanisms that sense mechanical forces imparted by blood flow to endothelial cells (ECs), smooth muscle cells, and circulating blood cells to elicit biochemical responses through a process referred to as mechanotransduction. These biochemical responses are critical for a host of other responses, including regulation of blood pressure, control of vascular permeability for maintaining adequate perfusion of tissues, and control of leukocyte recruitment during immunosurveillance and inflammation. This review focuses on the role of the endothelial surface proteoglycan/glycoprotein layer-the glycocalyx (GCX)-that lines all blood vessel walls and is an agent in mechanotransduction and the modulation of blood cell interactions with the EC surface. We first discuss the biochemical composition and ultrastructure of the GCX, highlighting recent developments that reveal gaps in our understanding of the relationship between composition and spatial organization. We then consider the roles of the GCX in mechanotransduction and in vascular permeability control and review the prominent interaction of plasma-borne sphingosine-1 phosphate (S1P), which has been shown to regulate both the composition of the GCX and the endothelial junctions. Finally, we consider the association of GCX degradation with inflammation and vascular disease and end with a final section on future research directions. PMID:24905872

  4. Experimental Investigation on Sandstone Rock Permeability of Pakistan Gas Fields

    NASA Astrophysics Data System (ADS)

    Raza, Arshad; Bing, Chua Han; Nagarajan, Ramasamy; Hamid, Mohamed Ali

    2015-04-01

    Permeability is the ability of formation to produce hydrocarbon which is affected by compaction, pore size, sorting, cementation, layering and clay swelling. The effect of texture on permeability in term of grain size, sorting, sphericity, degree of cementing has been reported in literature. Also, the effect of permeability on capillary pressure, irreducible water saturation, displacement pressure and pore geometry constant has been studied separately. This preliminary study presents the experimental results of eight samples to understand the effect of similar factors of texture on permeability. With the knowledge of the results, it can be said that the effect of grain size, cementation, texture material, sphericity, and porosity can't be observed on permeability except sorting when less than ten samples are considered from different depositional environment. The results also show the impact of permeability on capillary pressure, irreducible water saturation, and displacement pressure and pore geometry index as similar as published in the literature.

  5. Pulmonary microvascular permeability in patients with severe mitral stenosis.

    PubMed Central

    Davies, S W; Wilkinson, P; Keegan, J; Bailey, J; Timmis, A D; Wedzicha, J A; Rudd, R M

    1991-01-01

    Patients with rheumatic mitral stenosis often have no pulmonary oedema despite considerably increased pulmonary venous pressure. Pulmonary microvascular permeability was measured non-invasively by a previously validated method of double isotope scintigraphy with indium-113m and technetium-99m. This permits calculation of an index reflecting transferrin efflux and thus, indirectly, the microvascular permeability. Fifteen patients with severe mitral stenosis (defined as valve area less than 1.0 cm2) were compared with a control group of 11 patients with mild coronary artery disease. The permeability index was significantly lower in patients with mitral stenosis than in the control group. Furthermore, the extent of reduction of the permeability index correlated with the severity of mitral stenosis as reflected by the Gorlin valve area. This finding may account for the relative resistance of these patients to pulmonary oedema despite chronic pulmonary venous hypertension. Images PMID:1867952

  6. Vascular parkinsonism.

    PubMed

    Sibon, Igor; Fenelon, Gilles; Quinn, Niall P; Tison, Franois

    2004-05-01

    The concept of vascular parkinsonism (VP) has been highly controversial since the initial paper by Critchley in 1929. This review tentatively delineates the extent of the spectrum of VP. Much confusion has arisen owing to the lack of clear definitions of parkinsonism, "atypical parkinsonism" and "pseudoparkinsonism", which we here attempt to define. Confusion has also arisen because incidental vascular lesions occurring in true idiopathic Parkinson's disease (IPD) are up to 10 times more common than parkinsonism due to cerebrovascular disease. VP is clinically heterogeneous. Most often VP is atypical and can be separated from IPD, on the basis of the presence of additional focal signs, and the absence of typical resting tremor in the upper limbs, of true akinesia (i. e.: with decrement and fatiguing of alternating movements), and of definite benefit from levodopa. Exceptionally, VP may mimic IPD or other degenerative diseases such as progressive supranuclear palsy or corticobasal degeneration. The lesions responsible for VP are mostly basal ganglia lacunes and/or subcortical white matter vasculopathy of the "Binswanger" type. Rarely, a single striatal infarct, striatal cribriform cavities or ischaemic changes in the substantia nigra have been described. Vascular "pseudo-parkinsonism" refers to isolated gait disorders called "lower body parkinsonism", "frontal-type gait disorders" or "gait ignition failure" that are reminiscent of, but distinct from, that found in IPD. The pathophysiology of VP is poorly understood. Why some patients develop parkinsonism and others do not, despite the same apparent lesion load, remains a mystery. PMID:15164182

  7. Tunable permeability of magnetic wires at microwaves

    NASA Astrophysics Data System (ADS)

    Panina, L. V.; Makhnovskiy, D. P.; Morchenko, A. T.; Kostishin, V. G.

    2015-06-01

    This paper presents the analysis into microwave magnetic properties of magnetic microwires and their composites in the context of applications in wireless sensors and tunable microwave materials. It is demonstrated that the intrinsic permeability of wires has a wide frequency dispersion with relatively large values in the GHz band. In the case of a specific magnetic anisotropy this results in a tunable microwave impedance which could be used for distributed wireless sensing networks in functional composites. The other range of applications is related with developing the artificial magnetic dielectrics with large and tunable permeability. The composites with magnetic wires with a circumferential anisotropy have the effective permeability which differs substantially from unity for a relatively low concentration (less than 10%). This can make it possible to design the wire media with a negative and tunable index of refraction utilising natural magnetic properties of wires.

  8. Effect of low shear stress on permeability and occludin expression in porcine artery endothelial cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    INTRODUCTION: Although both fluid shear stress and mass transport of atherogenic substances into the vascular wall are known to be important factors in atherogenesis, there has been little research on the effect of shear stress on vascular permeability. Therefore, the effects of shear stress on the ...

  9. Seismic waves increase permeability.

    PubMed

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

    2006-06-29

    Earthquakes have been observed to affect hydrological systems in a variety of ways--water well levels can change dramatically, streams can become fuller and spring discharges can increase at the time of earthquakes. Distant earthquakes may even increase the permeability in faults. Most of these hydrological observations can be explained by some form of permeability increase. Here we use the response of water well levels to solid Earth tides to measure permeability over a 20-year period. At the time of each of seven earthquakes in Southern California, we observe transient changes of up to 24 degrees in the phase of the water level response to the dilatational volumetric strain of the semidiurnal tidal components of wells at the Pion 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

  10. Vascular proteomics.

    PubMed

    Barderas, Maria G; Vivanco, Fernando; Alvarez-Llamas, Gloria

    2013-01-01

    Cardiovascular diseases constitute the largest of death in developed countries, being atherosclerosis the major contributor. Atherosclerosis is a process of chronic inflammation, characterized by the accumulation of lipids, cells, and fibrous elements in medium and large arteries. There is a continuum in atherosclerotic cardiovascular pathology that extends from the initial endothelial damage to diseases such as angina, myocardial infarction, and stroke. The extent of inflammation, proteolysis, calcification, and neovascularization influences the development of advanced lesions (atheroma plaques) on the arteries. Plaque rupture and the ensuing thrombosis cause the acute complications of atherosclerosis, i.e., myocardial infarction and cerebral ischemia. Thus, identification of early biomarkers of plaque unstability and susceptibility to rupture is of capital importance in preventing acute events. In recent years proteomics has been successfully applied to study proteins involved in these pathological processes. Thus, proteomic studies have been carried out focusing on different elements such as vascular tissues (arteries), artery layers, cells looking at proteomes and secretomes, plasma/serum, exosomes, lipoproteins, and metabolites. This chapter will provide an overview of latest advances in proteomic studies of atherosclerosis and related vascular diseases. PMID:23585080

  11. The Permeable Classroom.

    ERIC Educational Resources Information Center

    Sandy, Leo R.

    1998-01-01

    Discusses the concept of permeability as knowledge flow into and out of the classroom and applies it to three college courses taught by the author at Plymouth State College (New Hampshire). Experiential knowledge comes into the classroom through interviews, guest speakers, and panel presentations, and flows out through service-learning students

  12. Fractal Analysis of Stress Sensitivity of Permeability in Porous Media

    NASA Astrophysics Data System (ADS)

    Tan, Xiao-Hua; Li, Xiao-Ping; Liu, Jian-Yi; Zhang, Lie-Hui; Cai, Jianchao

    2015-12-01

    A permeability model for porous media considering the stress sensitivity is derived based on mechanics of materials and the fractal characteristics of solid cluster size distribution. The permeability of porous media considering the stress sensitivity is related to solid cluster fractal dimension, solid cluster fractal tortuosity dimension, solid cluster minimum diameter and solid cluster maximum diameter, Young's modulus, Poisson's ratio, as well as power index. Every parameter has clear physical meaning without the use of empirical constants. The model predictions of permeability show good agreement with those obtained by the available experimental expression. The proposed model may be conducible to a better understanding of the mechanism for flow in elastic porous media.

  13. Wood smoke inhalation increases pulmonary microvascular permeability

    SciTech Connect

    Nieman, G.F.; Clark, W.R. Jr.; Goyette, D.; Hart, A.K.; Bredenberg, C.E.

    1989-04-01

    The effect of wood smoke inhalation (SI) on pulmonary vascular permeability was studied in open-chested, anesthetized dogs. Animals were divided into two groups. A prenodal lymphatic vessel was cannulated in group I (n = 7), and baseline (BL) lung lymph flow (QL) and lymph (CL) and plasma (CP) protein concentrations were measured. The animals' lungs were then ventilated with wood smoke for 5 minutes. Left atrial pressure (Pla) was increased above baseline (mean 16.7 +/- 2.2 mm Hg), and the ratio of CL to CP was used to assess endothelial permeability at high lymph flows. There was little change in either QL (BL: 27 +/- 9; SI: 27 +/- 5 microliters/min) or CL/CP (BL: 0.76 +/- 0.03; SI: 0.74 +/- 0.02) after SI at normal Pla. Elevation of Pla caused a significant increase in QL (136 +/- 15 microliters/min), but CL/CP (0.67 +/- 0.02) failed to decrease significantly at high lymph flows. In group II (n = 15) total protein concentration of airway fluid was compared with that of plasma after smoke inhalation, intravenous alloxan, and increased Pla. The ratio of protein concentration in airway fluid to plasma after SI (0.70 +/- 0.07) was greater than that obtained with increased Pla (0.64 +/- 0.07) but less than that after alloxan (0.85 +/- 0.04). These data indicate that SI in the dog results in a moderate increase in pulmonary vascular permeability that is less severe than that induced by alloxan.

  14. Diabetes and Vascular Disease

    MedlinePLUS

    ... Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease Chronic Venous Insufficiency Congenital Vascular Malformation Critical Limb Ischemia (CLI) Deep Vein Thrombosis (DVT) Diabetes and Vascular Disease Fibromuscular Dysplasia High ...

  15. 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...

  16. Catalpol downregulates vascular endothelial?cadherin expression and induces vascular hyperpermeability.

    PubMed

    Zhang, Caiqing; Liu, Qingfa; Dong, Fengyun; Li, Liqun; Du, Juan; Xie, Qi; Hu, Hesheng; Yan, Suhua; Zhou, Xia; Li, Changsheng; Lobe, Corrinne G; Liu, Ju

    2016-01-01

    Catalpol, an iridiod glucoside isolated from Rehmannia glutinosa, has been reported to possess anti?inflammatory properties. However, the molecular mechanisms underlying this effect have not been fully elucidated. This study aimed to investigate the effects of catalpol on vascular permeability. Using Transwell permeability assays and measurements of trans?endothelial electrical resistance (TEER), it was demonstrated that 1mM catalpol induces a significant increase in the permeability of the monolayers of human umbilical vein endothelial cells (HUVECs). Western blotting and immunofluorescence demonstrated that catalpol inhibits the expression of vascular endothelial (VE)?cadherin, the key component of adherens junctions, but not occludin, the major constituent of tight junctions. In addition, catalpol inhibits the ETS transcription factor ERG, a positive regulator of VE?cadherin. Knockdown of ERG expression compromised the catalpol?induced reduction of TEER in HUVECs. The present study revealed a novel effect of catalpol on vascular permeability and gave insight into the multifaceted roles of catalpol in inflammation. PMID:26549479

  17. Liquid-permeable electrode

    DOEpatents

    Folser, George R. (Lower Burrell, PA)

    1980-01-01

    Electrodes for use in an electrolytic cell, which are liquid-permeable and have low electrical resistance and high internal surface area are provided of a rigid, porous, carbonaceous matrix having activated carbon uniformly embedded throughout. The activated carbon may be catalyzed with platinum for improved electron transfer between electrode and electrolyte. Activated carbon is mixed with a powdered thermosetting phenolic resin and compacted to the desired shape in a heated mold to melt the resin and form the green electrode. The compact is then heated to a pyrolyzing temperature to carbonize and volatilize the resin, forming a rigid, porous structure. The permeable structure and high internal surface area are useful in electrolytic cells where it is necessary to continuously remove the products of the electrochemical reaction.

  18. Intraocular Hemorrhage Causes Retinal Vascular Dysfunction via Plasma Kallikrein

    PubMed Central

    Liu, Jia; Clermont, Allen C.; Gao, Ben-Bo; Feener, Edward P.

    2013-01-01

    Purpose. Retinal hemorrhages occur in a variety of sight-threatening conditions including ocular trauma, high altitude retinopathy, and chronic diseases such as diabetic and hypertensive retinopathies. The goal of this study is to investigate the effects of blood in the vitreous on retinal vascular function in rats. Methods. Intravitreal injections of autologous blood, plasma kallikrein (PK), bradykinin, and collagenase were performed in Sprague-Dawley and Long-Evans rats. Retinal vascular permeability was measured using vitreous fluorophotometry and Evans blue dye permeation. Leukostasis was measured by fluorescein isothiocyanate–coupled concanavalin A lectin and acridine orange labeling. Retinal hemorrhage was examined on retinal flatmounts. Primary cultures of bovine retinal pericytes were cultured in the presence of 25 nM PK for 24 hours. The pericyte-conditioned medium was collected and the collagen proteome was analyzed by tandem mass spectrometry. Results. Intravitreal injection of autologous blood induced retinal vascular permeability and retinal leukostasis, and these responses were ameliorated by PK inhibition. Intravitreal injections of exogenous PK induced retinal vascular permeability, leukostasis, and retinal hemorrhage. Proteomic analyses showed that PK increased collagen degradation in pericyte-conditioned medium and purified type IV collagen. Intravitreal injection of collagenase mimicked PK's effect on retinal hemorrhage. Conclusions. Intraocular hemorrhage increases retinal vascular permeability and leukostasis, and these responses are mediated, in part, via PK. Intravitreal injections of either PK or collagenase, but not bradykinin, induce retinal hemorrhage in rats. PK exerts collagenase-like activity that may contribute to blood–retinal barrier dysfunction. PMID:23299478

  19. Permeability evolution during dynamic stressing of dual permeability media

    NASA Astrophysics Data System (ADS)

    Faoro, Igor; Elsworth, Derek; Marone, Chris

    2012-01-01

    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.

  20. Stainless Steel Permeability

    SciTech Connect

    Buchenauer, Dean A.; Karnesky, Richard A.

    2015-09-01

    An understanding of the behavior of hydrogen isotopes in materials is critical to predicting tritium transport in structural metals (at high pressure), estimating tritium losses during production (fission environment), and predicting in-vessel inventory for future fusion devices (plasma driven permeation). Current models often assume equilibrium diffusivity and solubility for a class of materials (e.g. stainless steels or aluminum alloys), neglecting trapping effects or, at best, considering a single population of trapping sites. Permeation and trapping studies of the particular castings and forgings enable greater confidence and reduced margins in the models. For FY15, we have continued our investigation of the role of ferrite in permeation for steels of interest to GTS, through measurements of the duplex steel 2507. We also initiated an investigation of the permeability in work hardened materials, to follow up on earlier observations of unusual permeability in a particular region of 304L forgings. Samples were prepared and characterized for ferrite content and coated with palladium to prevent oxidation. Issues with the poor reproducibility of measurements at low permeability were overcome, although the techniques in use are tedious. Funding through TPBAR and GTS were secured for a research grade quadrupole mass spectrometer (QMS) and replacement turbo pumps, which should improve the fidelity and throughput of measurements in FY16.

  1. Vascular Endothelium and Hypovolemic Shock.

    PubMed

    Gulati, Anil

    2016-01-01

    Endothelium is a site of metabolic activity and has a major reservoir of multipotent stem cells. It plays a vital role in the vascular physiological, pathophysiological and reparative processes. Endothelial functions are significantly altered following hypovolemic shock due to ischemia of the endothelial cells and by reperfusion due to resuscitation with fluids. Activation of endothelial cells leads to release of vasoactive substances (nitric oxide, endothelin, platelet activating factor, prostacyclin, mitochondrial N-formyl peptide), mediators of inflammation (tumor necrosis factor α, interleukins, interferons) and thrombosis. Endothelial cell apoptosis is induced following hypovolemic shock due to deprivation of oxygen required by endothelial cell mitochondria; this lack of oxygen initiates an increase in mitochondrial reactive oxygen species (ROS) and release of apoptogenic proteins. The glycocalyx structure of endothelium is compromised which causes an impairment of the protective endothelial barrier resulting in increased permeability and leakage of fluids in to the tissue causing edema. Growth factors such as angiopoetins and vascular endothelial growth factors also contribute towards pathophysiology of hypovolemic shock. Endothelium is extremely active with numerous functions, understanding these functions will provide novel targets to design therapeutic agents for the acute management of hypovolemic shock. Hypovolemic shock also occurs in conditions such as dengue shock syndrome and Ebola hemorrhagic fever, defining the role of endothelium in the pathophysiology of these conditions will provide greater insight regarding the functions of endothelial cells in vascular regulation. PMID:26638794

  2. Microvascular albumin permeability in isolated perfused lung: effects of EDTA

    SciTech Connect

    Kern, D.F.; Malik, A.B.

    1985-02-01

    The authors examined the effects of decreases in perfusate concentrations of calcium and magnesium on the pulmonary vascular permeability in the isolated perfused rabbit lung. The albumin permeability-surface area product (PS) and the albumin reflection coefficient (sigma) were determined in the same lung using /sup 125/I- and /sup 131/I-labeled albumin tracers. Decreases in vascular Ca/sup 2 +/ and Mg/sup 2 +/ concentrations were induced by adding ethylenediaminetetraacetic acid (EDTA) to the perfusate. Decreases in the concentration of these cations resulted in an increase in the PS from a control value of 1.18 +/- 0.13 X 10(-3) to 7.69 +/- 0. 75 X 10(-3) cm3 X min-1 X g wet lung wt-1 and a decrease in the sigma from 0.96 +/- 0.01 to 0.74 +/- 0.02. The decrease in sigma suggests an increase in the calculated equivalent pore radius from 44 to 63 A. The results indicate that Ca/sup 2 +/ and Mg/sup 2 +/ play a role in the maintenance of normal pulmonary vascular permeability to proteins.

  3. Fetal liver kinase 1 is a receptor for vascular endothelial growth factor and is selectively expressed in vascular endothelium.

    PubMed Central

    Quinn, T P; Peters, K G; De Vries, C; Ferrara, N; Williams, L T

    1993-01-01

    Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, induces endothelial proliferation in vitro and vascular permeability in vivo. The human transmembrane c-fms-like tyrosine kinase Flt-1 has recently been identified as a VEGF receptor. Flt-1 kinase has seven immunoglobulin-like extracellular domains and a kinase insert sequence, features shared by two other human gene-encoded proteins, kinase insert domain-containing receptor (KDR) and FLT-4. In this study we show that the mouse homologue of KDR, Flk-1, is a second functional VEGF receptor. Flk-1 binds VEGF with high affinity, undergoes autophosphorylation, and mediates VEGF-dependent Ca2+ efflux in Xenopus oocytes injected with Flk-1 mRNA. We also demonstrate by in situ hybridization that Flk-1 protein expression in the mouse embryo is restricted to the vascular endothelium and the umbilical cord stroma. VEGF and its receptors Flk-1/KDR and Flt-1 may play a role in vascular development and regulation of vascular permeability. Images Fig. 2 Fig. 4 PMID:8356051

  4. Endothelial permeability and VE-cadherin: a wacky comradeship.

    PubMed

    Gavard, Julie

    2014-01-01

    The endothelium forms a selective semi-permeable barrier controlling bidirectional transfer between blood vessel and irrigated tissues. This crucial function relies on the dynamic architecture of endothelial cell–cell junctions, and in particular, VE -cadherin-mediated contacts. VE -cadherin indeed chiefly organizes the opening and closing of the endothelial barrier, and is central in permeability changes. In this review, the way VE -cadherin-based contacts are formed and maintained is first presented, including molecular traits of its expression, partners, and signaling. In a second part, the mechanisms by which VE -cadherin adhesion can be disrupted, leading to cell–cell junction weakening and endothelial permeability increase, are described. Overall, the molecular basis for VE -cadherin control of the endothelial barrier function is of high interest for biomedical research, as vascular leakage is observed in many pathological conditions and human diseases. PMID:25422846

  5. Relative permeability through fractures

    SciTech Connect

    Diomampo, Gracel, P.

    2001-08-01

    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.

  6. Vascular malformations: localized defects in vascular morphogenesis.

    PubMed

    Brouillard, P; Vikkula, M

    2003-05-01

    Vascular anomalies are localized defects of the vasculature, and usually affect a limited number of vessels in a restricted area of the body. They are subdivided into vascular malformations and vascular tumours. Most are sporadic, but Mendelian inheritance is observed in some families. By genetic analysis, several causative genes have been identified during the last 10 years. This has shed light into the pathophysiological pathways involved. Interestingly, in most cases, the primary defect seems to affect the characteristics of endothelial cells. Only mutations in the glomulin gene, responsible for hereditary glomuvenous malformations, are thought to directly affect vascular smooth-muscle cells. PMID:12752563

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

    NASA Technical Reports Server (NTRS)

    Gorizontova, M. P.

    1980-01-01

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

  8. Preoperative dynamic contrast-enhanced MRI correlates with molecular markers of hypoxia and vascularity in specific areas of intratumoral microenvironment and is predictive of patient outcome

    PubMed Central

    Jensen, Randy L.; Mumert, Michael L.; Gillespie, David L.; Kinney, Anita Y.; Schabel, Matthias C.; Salzman, Karen L.

    2014-01-01

    Background Measures of tumor vascularity and hypoxia have been correlated with glioma grade and outcome. Dynamic contrast-enhanced (DCE) MRI can noninvasively map tumor blood flow, vascularity, and permeability. In this prospective observational cohort pilot study, preoperative imaging was correlated with molecular markers of hypoxia, vascularity, proliferation, and progression-free and overall patient survival. Methods Pharmacokinetic modeling methods were used to generate maps of tumor blood flow, extraction fraction, permeability-surface area product, transfer constant, washout rate, interstitial volume, blood volume, capillary transit time, and capillary heterogeneity from preoperative DCE-MRI data in human glioma patients. Tissue was obtained from areas of peritumoral edema, active tumor, hypoxic penumbra, and necrotic core and evaluated for vascularity, proliferation, and expression of hypoxia-regulated molecules. DCE-MRI parameter values were correlated with hypoxia-regulated protein expression at tissue sample sites. Results Patient survival correlated with DCE parameters in 2 cases: capillary heterogeneity in active tumor and interstitial volume in areas of peritumoral edema. Statistically significant correlations were observed between several DCE parameters and tissue markers. In addition, MIB-1 index was predictive of overall survival (P = .044) and correlated with vascular endothelial growth factor expression in hypoxic penumbra (r = 0.7933, P = .0071) and peritumoral edema (r = 0.4546). Increased microvessel density correlated with worse patient outcome (P = .026). Conclusions Our findings suggest that DCE-MRI may facilitate noninvasive preoperative predictions of areas of tumor with increased hypoxia and proliferation. Both imaging and hypoxia biomarkers are predictive of patient outcome. This has the potential to allow unprecedented prognostic decisions and to guide therapies to specific tumor areas. PMID:24305704

  9. Indexing Images.

    ERIC Educational Resources Information Center

    Rasmussen, Edie M.

    1997-01-01

    Focuses on access to digital image collections by means of manual and automatic indexing. Contains six sections: (1) Studies of Image Systems and their Use; (2) Approaches to Indexing Images; (3) Image Attributes; (4) Concept-Based Indexing; (5) Content-Based Indexing; and (6) Browsing in Image Retrieval. Contains 105 references. (AEF)

  10. [Research on permeability of landfill's body in primary compression].

    PubMed

    Liu, Hui; Huang, Tao; Zhang, Chi

    2009-12-01

    Refuse degradation and landfill leachate treatment are the main research directions of landfill technology at present, but permeability characteristics of landfill body are paid little attention on. According to this actuality, the study selected four kinds of landfill's bodies under different pressures as study objects and tested the permeability characteristics in the stage of main compression settlement. Through the laboratory physical simulation experiments, the results show that the data of determination and analysis on landfill's bodies under four difference pressures conform to Darcy's law. Because the change of COD is in the phase of acid producing, its impact on permeability can not be considered. Based on these conditions, the calculation results of permeability coefficient indicate that during the course of the main compression settlement, the change law of landfill permeability coefficient index is approximately agreed with nature exponential law, expect for the condition of landfill body without pressure. Meanwhile, the landfill permeability coefficient values under four difference pressures are in the range of 10(-4.5)-10(-5.3) m x s(-1), which are consistent with the typical representative values of garbage permeability coefficient. PMID:20187414

  11. Gas permeability of shocked chondrites

    NASA Astrophysics Data System (ADS)

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

    1986-03-01

    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.

  12. Design and development of multilayer vascular graft

    NASA Astrophysics Data System (ADS)

    Madhavan, Krishna

    2011-07-01

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

  13. Microcirculation-on-a-Chip: A Microfluidic Platform for Assaying Blood- and Lymphatic-Vessel Permeability

    PubMed Central

    Sato, Miwa; Sasaki, Naoki; Ato, Manabu; Hirakawa, Satoshi; Sato, Kiichi; Sato, Kae

    2015-01-01

    We developed a microfluidic model of microcirculation containing both blood and lymphatic vessels for examining vascular permeability. The designed microfluidic device harbors upper and lower channels that are partly aligned and are separated by a porous membrane, and on this membrane, blood vascular endothelial cells (BECs) and lymphatic endothelial cells (LECs) were cocultured back-to-back. At cell-cell junctions of both BECs and LECs, claudin-5 and VE-cadherin were detected. The permeability coefficient measured here was lower than the value reported for isolated mammalian venules. Moreover, our results showed that the flow culture established in the device promoted the formation of endothelial cell-cell junctions, and that treatment with histamine, an inflammation-promoting substance, induced changes in the localization of tight and adherens junction-associated proteins and an increase in vascular permeability in the microdevice. These findings indicated that both BECs and LECs appeared to retain their functions in the microfluidic coculture platform. Using this microcirculation device, the vascular damage induced by habu snake venom was successfully assayed, and the assay time was reduced from 24 h to 30 min. This is the first report of a microcirculation model in which BECs and LECs were cocultured. Because the micromodel includes lymphatic vessels in addition to blood vessels, the model can be used to evaluate both vascular permeability and lymphatic return rate. PMID:26332321

  14. Modeling of Microvascular Permeability Changes after Electroporation

    PubMed Central

    Corovic, Selma; Markelc, Bostjan; Dolinar, Mitja; Cemazar, Maja; Jarm, Tomaz

    2015-01-01

    Vascular endothelium selectively controls the transport of plasma contents across the blood vessel wall. The principal objective of our preliminary study was to quantify the electroporation-induced increase in permeability of blood vessel wall for macromolecules, which do not normally extravasate from blood into skin interstitium in homeostatic conditions. Our study combines mathematical modeling (by employing pharmacokinetic and finite element modeling approach) with in vivo measurements (by intravital fluorescence microscopy). Extravasation of fluorescently labeled dextran molecules of two different sizes (70 kDa and 2000 kDa) following the application of electroporation pulses was investigated in order to simulate extravasation of therapeutic macromolecules with molecular weights comparable to molecular weight of particles such as antibodies and plasmid DNA. The increase in blood vessel permeability due to electroporation and corresponding transvascular transport was quantified by calculating the apparent diffusion coefficients for skin microvessel wall (D [μm2/s]) for both molecular sizes. The calculated apparent diffusion coefficients were D = 0.0086 μm2/s and D = 0.0045 μm2/s for 70 kDa and 2000 kDa dextran molecules, respectively. The results of our preliminary study have important implications in development of realistic mathematical models for prediction of extravasation and delivery of large therapeutic molecules to target tissues by means of electroporation. PMID:25793292

  15. Society for Vascular Medicine

    MedlinePLUS

    ... SVM Fellows Course Patient Information Pages from Vascular Medicine April 2016 Lower extremity ulcers More info for ... 1, 2016 Archive Submit a Case New! Vascular Medicine Videos Geoff Barnes talks about the article, VTE: ...

  16. Vascular Disease Foundation

    MedlinePLUS

    ... collaboration. Learn more here . We are the only nonprofit organization representing the millions of patients with vascular ... here . @ 2015 Vascular Cures is a tax-exempt, nonprofit organization tax ID#: 94-2825216 as described in ...

  17. Tubedown regulation of retinal endothelial permeability signaling pathways

    PubMed Central

    Ho, Nhu; Gendron, Robert L.; Grozinger, Kindra; Whelan, Maria A.; Hicks, Emily Anne; Tennakoon, Bimal; Gardiner, Danielle; Good, William V.; Paradis, Hlne

    2015-01-01

    ABSTRACT Tubedown (Tbdn; Naa15), a subunit of the N-terminal acetyltransferase NatA, complexes with the c-Src substrate Cortactin and supports adult retinal homeostasis through regulation of vascular permeability. Here we investigate the role of Tbdn expression on signaling components of retinal endothelial permeability to understand how Tbdn regulates the vasculature and supports retinal homeostasis. Tbdn knockdown-induced hyperpermeability to Albumin in retinal endothelial cells was associated with an increase in the levels of activation of the Src family kinases (SFK) c-Src, Fyn and Lyn and phospho-Cortactin (Tyr421). The knockdown of Cortactin expression reduced Tbdn knockdown-induced permeability to Albumin and the levels of activated SFK. Inhibition of SFK in retinal endothelial cells decreased Tbdn knockdown-induced permeability to Albumin and phospho-Cortactin (Tyr421) levels. Retinal lesions of endothelial-specific Tbdn knockdown mice, with tissue thickening, fibrovascular growth, and hyperpermeable vessels displayed an increase in the levels of activated c-Src. Moreover, the retinal lesions of patients with proliferative diabetic retinopathy (PDR) associated with a loss of Tbdn expression and hyperpermeability to Albumin displayed increased levels of activated SFK in retinal blood vessels. Taken together, these results implicate Tbdn as an important regulator of retinal endothelial permeability and homeostasis by modulating a signaling pathway involving c-Src and Cortactin. PMID:26142315

  18. [Vascular anomalies: information documents].

    PubMed

    Philandrianos, C; Degardin, N; Casanova, D; Bardot, J; Petit, P; Bartoli, J-M; Magalon, G

    2011-06-01

    Vascular anomalies are a complex pathological group. They are composed of hemangiomas and other vascular tumors and congenital vascular malformations: venous, lymphatic, arteriovenous and capillary malformations. The management of these anomalies is difficult and must involve an interdisciplinary approach. To help patients to understand their pathology, we have made some information documents. PMID:20598795

  19. Sphingolipids affect fibrinogen-induced caveolar transcytosis and cerebrovascular permeability

    PubMed Central

    Muradashvili, Nino; Khundmiri, Syed Jalal; Tyagi, Reeta; Gartung, Allison; Dean, William L.; Lee, Menq-Jer

    2014-01-01

    Inflammation-induced vascular endothelial dysfunction can allow plasma proteins to cross the vascular wall, causing edema. Proteins may traverse the vascular wall through two main pathways, the paracellular and transcellular transport pathways. Paracellular transport involves changes in endothelial cell junction proteins, while transcellular transport involves caveolar transcytosis. Since both processes are associated with filamentous actin formation, the two pathways are interconnected. Therefore, it is difficult to differentiate the prevailing role of one or the other pathway during various pathologies causing an increase in vascular permeability. Using a newly developed dual-tracer probing method, we differentiated transcellular from paracellular transport during hyperfibrinogenemia (HFg), an increase in fibrinogen (Fg) content. Roles of cholesterol and sphingolipids in formation of functional caveolae were assessed using a cholesterol chelator, methyl-β-cyclodextrin, and the de novo sphingolipid synthesis inhibitor myriocin. Fg-induced formation of functional caveolae was defined by association and colocalization of Na+-K+-ATPase and plasmalemmal vesicle-associated protein-1 with use of Förster resonance energy transfer and total internal reflection fluorescence microscopy, respectively. HFg increased permeability of the endothelial cell layer mainly through the transcellular pathway. While MβCD blocked Fg-increased transcellular and paracellular transport, myriocin affected only transcellular transport. Less pial venular leakage of albumin was observed in myriocin-treated HFg mice. HFg induced greater formation of functional caveolae, as indicated by colocalization of Na+-K+-ATPase with plasmalemmal vesicle-associated protein-1 by Förster resonance energy transfer and total internal reflection fluorescence microscopy. Our results suggest that elevated blood levels of Fg alter cerebrovascular permeability mainly by affecting caveolae-mediated transcytosis through modulation of de novo sphingolipid synthesis. PMID:24829496

  20. Measurements on stress dependent permeability

    NASA Astrophysics Data System (ADS)

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

    2003-04-01

    Hydrostatic loading is the conventional test procedure to determine the stress dependence of permeability. However, hydrostatic tests do not truly reflect the deviatoric stress state that exists in most reservoirs. The main objective of the present project was to study permeability changes under deviatoric stresses, like encountered in standard triaxial tests. However in measuring permeability in a triaxial cell, end effects may be important. The friction between the axial steel pistons and the sample may cause stress concentrations and thereby a non-homogeneous strain pattern towards the sample ends. To overcome this problem, the cell was modified to have pressure outlets from the mid-section of the sample, with the pressure tubes connected to the outside of the cell for pressure recording. The cell was designed for 1.5 in plugs with plug lengths of about 80 mm. Tests have been performed on two types of high porosity outcrop chalk: Lige chalk with porosity around 40 percent and permeability 1-2 millidarcy, and Aalborg chalk with porosity around 45 percent and permeability in the range 3-5 millidarcy. Methanol was used as saturating fluid for the chalks. In addition some sandstone samples from core material were included. The porosity values were rather high, around 30 percent, and the permeability ranged from around 50 millidarcy to over one Darcy. Synthetic oil was used as saturating fluid for the sandstone samples, to avoid any reactions with clay minerals. The results so far can be summarized as follows:(1) In almost all the tests, the permeability calculated by the overall pressure drop is smaller than the mid-section permeability. The reduction could typically be around 20 percent. This means that end-effects play an important role.(2) The permeability generally decrease with increasing hydrostatic stresses. This is in agreement with observations from other sources.(3) During deviatoric phases the average stress level is increasing, but the changes in permeability are rather small, even if the tests are run beyond yield. The mid-section permeability seems to show a small increasing trend with increasing deviatoric stresses after yield. But the yield point does not seem to have any drastic effect on the permeability.(4) The overall permeability seems in general to show a decreasing trend under deviatoric stresses. The results indicate that permeability changes with pressure depletion under reservoir conditions may be much less than expected from hydrostatic tests or tests uncorrected for end-effects.

  1. Andes virus regulation of cellular microRNAs contributes to hantavirus-induced endothelial cell permeability.

    PubMed

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

    2010-11-01

    Hantaviruses infect human endothelial cells (ECs) and cause two diseases marked by vascular permeability defects, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Vascular permeability occurs in the absence of EC lysis, suggesting that hantaviruses alter normal EC fluid barrier functions. ECs infected by pathogenic hantaviruses are hyperresponsive to vascular endothelial growth factor (VEGF), and this alters the fluid barrier function of EC adherens junctions, resulting in enhanced paracellular permeability. Vascular permeability and VEGF-directed responses are determined by EC-specific microRNAs (miRNAs), which regulate cellular mRNA transcriptional responses. miRNAs mature within cytoplasmic processing bodies (P bodies), and the hantavirus nucleocapsid (N) protein binds RNA and localizes to P bodies, suggesting that hantaviruses may modify miRNA functions within infected ECs. Here we assessed changes in EC miRNAs following infection by the HPS-causing Andes hantavirus (ANDV). We analyzed 352 human miRNAs within ANDV-infected ECs using quantitative real-time (RT)-PCR arrays. Fourteen miRNAs, including six miRNAs that are associated with regulating vascular integrity, were upregulated >4-fold following infection by ANDV. Nine miRNAs were downregulated 3- to 3,400-fold following ANDV infection; these included miR-410, involved in regulating secretion, and miR-218, which is linked to the regulation of EC migration and vascular permeability. We further analyzed changes in miR-126, an EC-specific miRNA that regulates vascular integrity by suppressing SPRED1 and PIK3R2 mRNAs. While miR-126 levels were only slightly altered, we found that SPRED1 and PIK3R2 mRNA levels were increased 10- and 7-fold, respectively, in ANDV-infected ECs but were unaltered in ECs infected by the nonpathogenic Tula hantavirus (TULV). Consistent with increased SPRED1 expression, we found that the level of phospho-cofilin was decreased within ANDV-infected ECs. Moreover, small interfering RNA (siRNA) knockdown of SPRED1 dramatically decreased the permeability of ANDV-infected ECs in response to VEGF, suggesting that increased SPRED1 contributes to EC permeability following ANDV infection. These findings suggest that interference with normal miRNA functions contributes to the enhanced paracellular permeability of ANDV-infected ECs and that hantavirus regulation of miRNA functions is an additional determinant of hantavirus pathogenesis. PMID:20844033

  2. Vascular restoration therapy and bioresorbable vascular scaffold

    PubMed Central

    Wang, Yunbing; Zhang, Xingdong

    2014-01-01

    This article describes the evolution of minimally invasive intervention technologies for vascular restoration therapy from early-stage balloon angioplasty in 1970s, metallic bare metal stent and metallic drug-eluting stent technologies in 1990s and 2000s, to bioresorbable vascular scaffold (BVS) technology in large-scale development in recent years. The history, the current stage, the challenges and the future of BVS development are discussed in detail as the best available approach for vascular restoration therapy. The criteria of materials selection, design and processing principles of BVS, and the corresponding clinical trial results are also summarized in this article. PMID:26816624

  3. Soluble receptor for advanced glycation end products as an indicator of pulmonary vascular injury after cardiac surgery

    PubMed Central

    2013-01-01

    Background Cardiac surgery is frequently complicated by an acute vascular lung injury and this may be mediated, at least in part, by the (soluble) receptor for advanced glycation end products (sRAGE). Methods In two university hospital intensive care units, circulating sRAGE was measured together with the 68Gallium-transferrin pulmonary leak index (PLI), a measure of pulmonary vascular permeabiliy, in 60 consecutive cardiac surgery patients stratified by the amount of blood transfusion, within 3hours of admission to the intensive care. Results Cardiac surgery resulted in elevated plasma sRAGE levels compared to baseline (315??181 vs 110??55pg/ml, P?=?0.001). In 37 patients the PLI was elevated 50% above normal. The PLI correlated with sRAGE (r2?=?0.11, P?=?0.018). Plasma sRAGE discriminated well between those with an elevated PLI and those with a normal PLI (area under the operator curve 0.75; P?=?0.035; 95% CI 0.55-0.95), with 91% sensitivity but low specificity of 36% at a cutoff value of 200pg/mL. Blood transfusion did not influence sRAGE levels. Conclusions sRAGE is elevated in plasma after cardiac surgery and indicates increased pulmonary vascular permeability. The level of sRAGE is not affected by transfusion. PMID:24341821

  4. Retina vascular network recognition

    NASA Astrophysics Data System (ADS)

    Tascini, Guido; Passerini, Giorgio; Puliti, Paolo; Zingaretti, Primo

    1993-09-01

    The analysis of morphological and structural modifications of the retina vascular network is an interesting investigation method in the study of diabetes and hypertension. Normally this analysis is carried out by qualitative evaluations, according to standardized criteria, though medical research attaches great importance to quantitative analysis of vessel color, shape and dimensions. The paper describes a system which automatically segments and recognizes the ocular fundus circulation and micro circulation network, and extracts a set of features related to morphometric aspects of vessels. For this class of images the classical segmentation methods seem weak. We propose a computer vision system in which segmentation and recognition phases are strictly connected. The system is hierarchically organized in four modules. Firstly the Image Enhancement Module (IEM) operates a set of custom image enhancements to remove blur and to prepare data for subsequent segmentation and recognition processes. Secondly the Papilla Border Analysis Module (PBAM) automatically recognizes number, position and local diameter of blood vessels departing from optical papilla. Then the Vessel Tracking Module (VTM) analyses vessels comparing the results of body and edge tracking and detects branches and crossings. Finally the Feature Extraction Module evaluates PBAM and VTM output data and extracts some numerical indexes. Used algorithms appear to be robust and have been successfully tested on various ocular fundus images.

  5. Angiopoietin-2 Is Critical for Cytokine-Induced Vascular Leakage

    PubMed Central

    Thomas, Markus; Laib, Anna M.; Loos, Elias K.; Fiedler, Ulrike; Augustin, Hellmut G.

    2013-01-01

    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, 15 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

  6. Use of diagnostic modalities for assessing upper extremity vascular pathology.

    PubMed

    Grasu, Beatrice L; Jones, Christopher M; Murphy, Michael S

    2015-02-01

    Vascular pathology of the upper extremity requires consideration of constitutional, anatomic, and functional factors. The medical history and physical examination are essential. The Allen test can be performed alongside a handheld Doppler for arterial mapping. Useful studies include digital-brachial index measurements, digital plethysmography, laser Doppler, and color ultrasounds. Three-phase bone scintigraphy still plays a role in the evaluation of vascularity after of frostbite injury. Angiogram remains the gold standard radiographic instrument to evaluate vascular pathology of the upper extremity, but computed tomography and magnetic resonance scans have an increasing role in diagnosis of vascular pathology. PMID:25455352

  7. The M2 macrophages induce autophagic vascular disorder and promote mouse sensitivity to urethane-related lung carcinogenesis.

    PubMed

    Li, G-G; Guo, Z-Z; Ma, X-F; Cao, N; Geng, S-N; Zheng, Y-Q; Meng, M-J; Lin, H-H; Han, G; Du, G-J

    2016-06-01

    Tumor vessels are known to be abnormal, with typically aberrant, leaky and disordered vessels. Here, we investigated whether polarized macrophage phenotypes are involved in tumor abnormal angiogenesis and what is its mechanism. We found that there was no difference in chemotaxis of polarized M1 and M2 macrophages to lewis lung carcinoma (LLC) cells and that either M1 or M2 macrophage-conditioned media had no effect on LLC cell proliferation. Unexpectedly, the M2 but not M1 macrophage-conditioned media promoted the proliferation of human umbilical vein endothelial cells (HUVECs) and simultaneously increased endothelial cell permeability in vitro and angiogenic index in the chick embryo chorioallantoic membrane (CAM). The treatment with M2 but not M1 macrophage-conditioned media increased autophagosomes as well as microtubule-associated protein light chain 3B (LC3-B) expression (a robust marker of autophagosomes) but decreased p62 protein expression (a selective autophagy substrate) in HUVECs, the treatment with chloroquine that blocked autophagy abrogated the abnormal angiogenic efficacy of M2 macrophage-conditioned media. These results were confirmed in urethane-induced lung carcinogenic progression. Urethane-induced lung carcinogenesis led to more M2 macrophage phenotype and increased abnormal angiogenesis concomitant with the upregulation of LC3-B and the downregulation of p62. Clodronate liposome-induced macrophage depletion, chloroquine-induced autophagic prevention or salvianolic acid B-induced vascular protection decreased abnormal angiogenesis and lung carcinogenesis. In addition, we found that the tendency of age-related M2 macrophage polarization also promoted vascular permeability and carcinogenesis in urethane carcinogenic progression. These findings indicate that the M2 macrophages induce autophagic vascular disorder to promote lung cancer progression, and the autophagy improvement represents an efficacious strategy for abnormal angiogenesis and cancer prevention. PMID:26806760

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

    PubMed

    Jain, Swati; Sharma, Bhupesh

    2015-12-01

    Vascular risk factors are associated with a higher incidence of dementia. Diabetes mellitus is considered as a main risk factor for Alzheimer's disease and vascular dementia. Both forms of dementia are posing greater risk to the world population and are increasing at a faster rate. In the past we have reported the induction of vascular dementia by experimental diabetes. This study investigates the role of vildagliptin, a dipeptidyl peptidase-4 inhibitor in the pharmacological interdiction of pancreatectomy diabetes induced vascular endothelial dysfunction and subsequent vascular dementia in rats. Attentional set shifting and Morris water-maze test were used for assessment of learning and memory. Vascular endothelial function, blood brain barrier permeability, serum glucose, serum nitrite/nitrate, oxidative stress (viz. aortic superoxide anion, brain thiobarbituric acid reactive species and brain glutathione), brain calcium and inflammation (myeloperoxidase) were also estimated. Pancreatectomy diabetes rats have shown impairment of endothelial function, blood brain barrier permeability, learning and memory along with increase in brain inflammation, oxidative stress and calcium. Administration of vildagliptin has significantly attenuated pancreatectomy induced impairment of learning, memory, endothelial function, blood brain barrier permeability and biochemical parameters. It may be concluded that vildagliptin, a dipeptidyl peptidase-4 inhibitor may be considered as potential pharmacological agents for the management of pancreatectomy induced endothelial dysfunction and subsequent vascular dementia. The selective modulators of dipeptidyl peptidase-4 may further be explored for their possible benefits in vascular dementia. PMID:26382939

  9. Validation of biomarkers in subcortical ischaemic vascular disease of the Binswanger type: approach to targeted treatment trials

    PubMed Central

    Rosenberg, Gary A; Prestopnik, Jillian; Adair, John C; Huisa, Branko N; Knoefel, Janice; Caprihan, Arvind; Gasparovic, Charles; Thompson, Jeffrey; Erhardt, Erik B; Schrader, Ronald

    2015-01-01

    Objectives Vascular cognitive impairment (VCI) is a heterogeneous group of cerebrovascular diseases secondary to large and small vessel disease. We hypothesised that biomarkers obtained early in the disease could identify a homogeneous subpopulation with small vessel disease. Methods We obtained disease markers in 62 patients with VCI that included neurological findings, neuropsychological tests, multimodal MR and cerebrospinal fluid measurements of albumin ratio, matrix metalloproteinases (MMPs), amyloid-?142 and phosphorylated-?181. Proton MR spectroscopic imaging showed ischaemic white matter and permeability of the blood-brain barrier (BBB) was measured with dynamic contrast-enhanced MRI. We constructed a 10-point Binswanger disease score (BDS) with subjective and objective disease markers. In addition, an objective set of biomarkers was used for an exploratory factor analysis (EFA) to select patients with BD. Patients were followed for an average of 2 years to obtain clinical consensus diagnoses. Results An initial BDS of 6 or greater was significantly correlated with a final diagnosis of BD (p<0.05; area under the curve (AUC)=0.79). EFA reduced nine objective biomarkers to four factors. The most predictive of BD was the factor containing the inflammatory biomarkers of increased BBB permeability, elevated albumin index and reduced MMP-2 index (factor 2; AUC=0.78). Both measures independently predicted a diagnosis of BD, and combining them improved the diagnostic accuracy. Conclusions Biomarkers predicted the diagnosis of the BD type of subcortical ischaemic vascular disease. Using pathophysiological biomarkers to select homogeneous groups of patients needs to be tested in targeted treatment trials. PMID:25618903

  10. Geothermal Permeability Enhancement - Final Report

    SciTech Connect

    Joe Beall; Mark Walters

    2009-06-30

    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. The 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. Numerous geothermal reservoirs worldwide, over a wide temperature range, contain zones of low permeability which limit the development potential and the efficient recovery of heat from these reservoirs. Low permeability results from poorly connected fractures or the lack of fractures. The Enhanced Geothermal System concept presented here expands these technologies by applying and evaluating them in a systematic, integrated program.

  11. Imaging Pediatric Vascular Lesions

    PubMed Central

    Nguyen, Tuyet A.; Krakowski, Andrew C.; Naheedy, John H.; Kruk, Peter G.

    2015-01-01

    Vascular anomalies are commonly encountered in pediatric and dermatology practices. Most of these lesions are benign and easy to diagnose based on history and clinical exam alone. However, in some cases the diagnosis may not be clear. This may be of particular concern given that vascular anomalies may occasionally be associated with an underlying syndrome, congenital disease, or serious, life-threatening condition. Defining the type of vascular lesion early and correctly is particularly important to determine the optimal approach to management and treatment of each patient. The care of pediatric patients often requires collaboration from a multitude of specialties including pediatrics, dermatology, plastic surgery, radiology, ophthalmology, and neurology. Although early characterization of vascular lesions is important, consensus guidelines regarding the evaluation and imaging of vascular anomalies does not exist to date. Here, the authors provide an overview of pediatric vascular lesions, current classification systems for characterizing these lesions, the various imaging modalities available, and recommendations for appropriate imaging evaluation. PMID:26705446

  12. Update on Pharmacologic Retinal Vascular Toxicity.

    PubMed

    Schwartz, Stephen G; Grzybowski, Andrzej; Wasinska-Borowiec, Weronika; Flynn, Harry W; Mieler, William F

    2015-01-01

    Several medications are associated with retinal vascular toxicity. These include intraocular aminoglycosides, oral contraceptives, interferon alpha, several other agents, and talc, which occurs as a vehicle in some oral medications that may be abused intravenously. As a group, these entities represent a small but clinically relevant category of retinal toxicity from medications. Some of the manifestations (e.g., retinal vascular occlusion) are nonspecific, but others are more specific, including clinically visible talc emboli in retinal vessels. Toxicity may be asymptomatic or may cause irreversible visual loss. By maintaining a high index of suspicion, the correct diagnosis can usually be made. PMID:26350526

  13. Permeability of soils in Mississippi

    USGS Publications Warehouse

    O'Hara, Charles G.

    1994-01-01

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

  14. AKAP12 regulates vascular integrity in zebrafish

    PubMed Central

    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

    2012-01-01

    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. PMID:22192928

  15. Constraining Fault-Zone Permeability

    NASA Astrophysics Data System (ADS)

    Ge, S.; Ball, L. B.; Caine, J. S.; Revil, A.

    2011-12-01

    Faults are known to behave as hydrologic barriers, conduits, or combined barrier-conduits to fluid flow. On the basis of hydrological and geophysical data, this study presents a possible fault-zone permeability model for a buried reverse fault that juxtaposes Precambrian crystalline rocks against Tertiary sedimentary strata, the Elkhorn fault zone in South Park, Colorado. Permeameter tests and thin section analyses were performed on several samples taken from a 300-foot interval of core from the sedimentary footwall and yielded permeability values on the order of 10E-16 m^2. In-situ slug tests and single-well pumping tests conducted in both the footwall and hanging wall yielded larger permeability values, varying between 10E-14 to 10E-11 m^2, indicating a substantial change in permeability in the vicinity of the fault. Geophysical interpretations from electrical resistivity tomography and self-potential measurements suggest that these permeability estimates may be representative of a lithologically and hydrologically distinct fault zone. Permeability estimates, resistivity structure, and interpreted changes in groundwater flow direction near the fault are consistent with combined conduit-barrier behavior at the meter to tens-of-meters scale.

  16. Vascular tracers alter hemodynamics and airway pressure in anesthetized sheep

    SciTech Connect

    Albertine, K.H.; Staub, N.C.

    1986-11-01

    The technique of vascular labeling was developed to mark sites of increased microvascular permeability. We used the vascular labeling technique in anesthetized sheep and found that hemodynamics and airway pressure were adversely affected by intraarterial infusions of two vascular tracers. Monastral blue (nine sheep) immediately caused systemic arterial hypotension, pulmonary arterial hypertension, and bronchoconstriction. All three physiological responses were partially blocked by a cyclooxygenase inhibitor (indomethacin) but not by an H1-antihistamine (chlorpheniramine). Colloidal gold (nine sheep) caused immediate, but less dramatic, pulmonary arterial hypertension which was not attenuated by the blocking agents. We conclude that these two vascular tracers caused detrimental physiological side effects in sheep at the usual doses used to label injured microvessels in other species.

  17. Small intestinal permeability in older adults

    PubMed Central

    Valentini, Luzia; Ramminger, Sara; Haas, Verena; Postrach, Elisa; Werich, Martina; Fischer, Andr; Koller, Michael; Swidsinski, Alexander; Bereswill, Stefan; Lochs, Herbert; Schulzke, Jrg?Dieter

    2014-01-01

    Abstract It is not yet clear whether intestinal mucosal permeability changes with advancing age in humans. This question is of high importance for drug and nutrition approaches for older adults. Our main objective was to answer the question if small intestinal barrier integrity deteriorates with healthy aging. We conducted a cross?sectional study including the pooled data of 215 nonsmoking healthy adults (93 female/122 male), 84 of whom were aged between 60 and 82 years. After a 12?h fast, all participants ingested 10 g of lactulose and 5 g of mannitol. Urine was collected for 5 h afterwards and analyzed for test sugars. The permeability index (PI = lactulose/mannitol) was used to assess small intestinal permeability. Low?grade inflammation defined by high?sensitivity C?reactive protein ?1 mL/L and kidney function (estimated glomerular filtration rate) were determined in the older age group. The PI was similar in older compared to younger adults (P =0.887). However, the urinary recovery of lactulose and mannitol was lower in the older adults and this change was neither associated with urinary volume nor glomerular filtration rate. The PI was not significantly correlated with low?grade inflammation or presence of noninsulin?dependent type 2 diabetes. However, it significantly deteriorated in the copresence of both conditions compared to low?grade inflammation alone (P =0.043) or type 2 diabetes alone (P =0.015). Small intestinal mucosal barrier does not deteriorate with age per se. But low?grade inflammation coupled with minor disease challenges, such as type 2 diabetes, can compromise the small intestinal barrier. PMID:24771689

  18. Permeability extraction: A sonic log inversion

    SciTech Connect

    Akbar, N.; Kim, J.J.

    1994-12-31

    In this paper the authors provide the missing important link between permeability and acoustic velocities by generating a permeability-dependent synthetic sonic log in a carbonate reservoir. The computations are based on Akbar`s theory that relates wave velocity to frequency, rock properties (e.g., lithology, permeability, and porosity), and fluid saturation and properties (viscosity, density, and compressibility). An inverted analytical expression of the theory is used to extract permeability from sonic velocity. The synthetic sonic and the computed permeability are compared with the observed sonic log and with plug permeability, respectively. The results demonstrate, as predicted by theory, that permeability can be related directly to acoustic velocities.

  19. HABP2 is a Novel Regulator of Vascular Integrity

    PubMed Central

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

    2010-01-01

    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. PMID:20042707

  20. Vascular ring diagnosis following respiratory arrest.

    PubMed

    Robson, Evie Alexandra; Scott, Alison; Chetcuti, Philip; Crabbe, David

    2014-01-01

    Vascular rings can present with non-specific respiratory and/or oesophageal symptoms. Early diagnosis requires a high index of suspicion. This case report describes an uncommon acute presentation of a vascular ring. We report a thriving 14-month-old child with a long history of recurrent wheeze and 'noisy breathing'. He presented acutely with food bolus impaction in the oesophagus which led to a respiratory arrest. Oesophagoscopy and bronchoscopy suggested vascular ring anomaly. A contrast-enhanced CT scan demonstrated a right-sided aortic arch with left ligamentum arteriosum encircling the oesophagus and airway. The ligament was ligated and divided. At follow-up 6?months later, the infant had mild persistent stridor but was otherwise well. PMID:24895385

  1. [Vascular factors in glaucoma].

    PubMed

    Mottet, B; Aptel, F; Geiser, M; Romanet, J P; Chiquet, C

    2015-12-01

    The exact pathophysiology of glaucoma is not fully understood. Understanding of the vascular pathophysiology of glaucoma requires: knowing the techniques for measuring ocular blood flow and characterizing the topography of vascular disease and the mechanisms involved in this neuropathy. A decreased mean ocular perfusion pressure and a loss of vascular autoregulation are implicated in glaucomatous disease. Early decrease in ocular blood flow has been identified in primary open-angle glaucoma and normal pressure glaucoma, contributing to the progression of optic neuropathy. The vascular damage associated with glaucoma is present in various vascular territories within the eye (from the ophthalmic artery to the retina) and is characterized by a decrease in basal blood flow associated with a dysfunction of vasoregulation. PMID:26597554

  2. Pyrotechnic deflagration velocity and permeability

    SciTech Connect

    Begeal, D R; Stanton, P L

    1982-01-01

    Particle size, porosity, and permeability of the reactive material have long been considered to be important factors in propellant burning rates and the deflagration-to-detonation transition in explosives. It is reasonable to assume that these same parameters will also affect the deflagration velocity of pyrotechnics. This report describes an experimental program that addresses the permeability of porous solids (particulate beds), in terms of particle size and porosity, and the relationship between permeability and the behavior of pyrotechnics and explosives. The experimental techniques used to acquire permeability data and to characterize the pyrotechnic burning are discussed. Preliminary data have been obtained on the burning characteristics of titanium hydride/potassium perchlorate (THKP) and boron/calcium chromate (BCCR). With THKP, the velocity of a pressure wave (from hot product gases) in the unburned region shows unsteady behavior which is related to the initial porosity or permeability. Simultaneous measurements with pressure gauges and ion gauges reveal that the pressure wave precedes the burn front. Steady burning of BCCR was observed with pressure gauge diagnostics and with a microwave interferometry technique.

  3. Pulmonary vascular dysfunction in ARDS.

    PubMed

    Ryan, Donal; Frohlich, Stephen; McLoughlin, Paul

    2014-01-01

    Acute respiratory distress syndrome (ARDS) is characterised by diffuse alveolar damage and is frequently complicated by pulmonary hypertension (PH). Multiple factors may contribute to the development of PH in this setting. In this review, we report the results of a systematic search of the available peer-reviewed literature for papers that measured indices of pulmonary haemodynamics in patients with ARDS and reported on mortality in the period 1977 to 2010. There were marked differences between studies, with some reporting strong associations between elevated pulmonary arterial pressure or elevated pulmonary vascular resistance and mortality, whereas others found no such association. In order to discuss the potential reasons for these discrepancies, we review the physiological concepts underlying the measurement of pulmonary haemodynamics and highlight key differences between the concepts of resistance in the pulmonary and systemic circulations. We consider the factors that influence pulmonary arterial pressure, both in normal lungs and in the presence of ARDS, including the important effects of mechanical ventilation. Pulmonary arterial pressure, pulmonary vascular resistance and transpulmonary gradient (TPG) depend not alone on the intrinsic properties of the pulmonary vascular bed but are also strongly influenced by cardiac output, airway pressures and lung volumes. The great variability in management strategies within and between studies means that no unified analysis of these papers was possible. Uniquely, Bull et al. (Am J Respir Crit Care Med 182:1123-1128, 2010) have recently reported that elevated pulmonary vascular resistance (PVR) and TPG were independently associated with increased mortality in ARDS, in a large trial with protocol-defined management strategies and using lung-protective ventilation. We then considered the existing literature to determine whether the relationship between PVR/TPG and outcome might be causal. Although we could identify potential mechanisms for such a link, the existing evidence does not allow firm conclusions to be drawn. Nonetheless, abnormally elevated PVR/TPG may provide a useful index of disease severity and progression. Further studies are required to understand the role and importance of pulmonary vascular dysfunction in ARDS in the era of lung-protective ventilation. PMID:25593744

  4. VE-cadherin facilitates BMP-induced endothelial cell permeability and signaling.

    PubMed

    Benn, Andreas; Bredow, Clara; Casanova, Isabel; Vukičević, Slobodan; Knaus, Petra

    2016-01-01

    Several vascular disorders, such as aberrant angiogenesis, atherosclerosis and pulmonary hypertension, have been linked to dysfunctional BMP signaling. Vascular hyperpermeability via distortion of endothelial cell adherens junctions is a common feature of these diseases, but the role of BMPs in this process has not been investigated. BMP signaling is initiated by binding of ligand to, and activation of, BMP type I (BMPRI) and type II (BMPRII) receptors. Internalization of VE-cadherin as well as c-Src kinase-dependent phosphorylation have been implicated in the loosening of cell-cell contacts, thereby modulating vascular permeability. Here we demonstrate that BMP6 induces hyperpermeabilization of human endothelial cells by inducing internalization and c-Src-dependent phosphorylation of VE-cadherin. Furthermore, we show BMP-dependent physical interaction of VE-cadherin with the BMP receptor ALK2 (BMPRI) and BMPRII, resulting in stabilization of the BMP receptor complex and, thereby, the support of BMP6-Smad signaling. Our results provide first insights into the molecular mechanism of BMP-induced vascular permeability, a hallmark of various vascular diseases, and provide the basis for further investigations of BMPs as regulators of vascular integrity, both under physiological and pathophysiological conditions. PMID:26598555

  5. VE-cadherin facilitates BMP-induced endothelial cell permeability and signaling

    PubMed Central

    Benn, Andreas; Bredow, Clara; Casanova, Isabel; Vukičević, Slobodan; Knaus, Petra

    2016-01-01

    ABSTRACT Several vascular disorders, such as aberrant angiogenesis, atherosclerosis and pulmonary hypertension, have been linked to dysfunctional BMP signaling. Vascular hyperpermeability via distortion of endothelial cell adherens junctions is a common feature of these diseases, but the role of BMPs in this process has not been investigated. BMP signaling is initiated by binding of ligand to, and activation of, BMP type I (BMPRI) and type II (BMPRII) receptors. Internalization of VE-cadherin as well as c-Src kinase-dependent phosphorylation have been implicated in the loosening of cell–cell contacts, thereby modulating vascular permeability. Here we demonstrate that BMP6 induces hyperpermeabilization of human endothelial cells by inducing internalization and c-Src-dependent phosphorylation of VE-cadherin. Furthermore, we show BMP-dependent physical interaction of VE-cadherin with the BMP receptor ALK2 (BMPRI) and BMPRII, resulting in stabilization of the BMP receptor complex and, thereby, the support of BMP6-Smad signaling. Our results provide first insights into the molecular mechanism of BMP-induced vascular permeability, a hallmark of various vascular diseases, and provide the basis for further investigations of BMPs as regulators of vascular integrity, both under physiological and pathophysiological conditions. PMID:26598555

  6. Histamine Induces Vascular Hyperpermeability by Increasing Blood Flow and Endothelial Barrier Disruption In Vivo

    PubMed Central

    Ashina, Kohei; Tsubosaka, Yoshiki; Nakamura, Tatsuro; Omori, Keisuke; Kobayashi, Koji; Hori, Masatoshi; Ozaki, Hiroshi; Murata, Takahisa

    2015-01-01

    Histamine is a mediator of allergic inflammation released mainly from mast cells. Although histamine strongly increases vascular permeability, its precise mechanism under in vivo situation remains unknown. We here attempted to reveal how histamine induces vascular hyperpermeability focusing on the key regulators of vascular permeability, blood flow and endothelial barrier. Degranulation of mast cells by antigen-stimulation or histamine treatment induced vascular hyperpermeability and tissue swelling in mouse ears. These were abolished by histamine H1 receptor antagonism. Intravital imaging showed that histamine dilated vasculature, increased blood flow, while it induced hyperpermeability in venula. Whole-mount staining showed that histamine disrupted endothelial barrier formation of venula indicated by changes in vascular endothelial cadherin (VE-cadherin) localization at endothelial cell junction. Inhibition of nitric oxide synthesis (NOS) by L-NAME or vasoconstriction by phenylephrine strongly inhibited the histamine-induced blood flow increase and hyperpermeability without changing the VE-cadherin localization. In vitro, measurements of trans-endothelial electrical resistance of human dermal microvascular endothelial cells (HDMECs) showed that histamine disrupted endothelial barrier. Inhibition of protein kinase C (PKC) or Rho-associated protein kinase (ROCK), NOS attenuated the histamine-induced barrier disruption. These observations suggested that histamine increases vascular permeability mainly by nitric oxide (NO)-dependent vascular dilation and subsequent blood flow increase and maybe partially by PKC/ROCK/NO-dependent endothelial barrier disruption. PMID:26158531

  7. Vascular characteristics of patients with dementia.

    PubMed

    Morovi?, Sandra; Jurasi?, Miljenka-Jelena; Martini? Popovi?, Irena; Seri?, Vesna; Lisak, Marijana; Demarin, Vida

    2009-08-15

    Arterial beta stiffness index is a potential risk factor for increased stroke occurrence. Vascular component appears to be significant in both Alzheimer's disease (AD) and vascular dementia (VAD). We aimed to further explore vascular characteristics of patients with both types of cognitive decline using non-invasive neurosonological methods. There were 38 patients; 16 diagnosed with AD and 22 with VAD. Vascular risk factors were assessed and ultrasound measurements on common carotid artery (CCA) were performed using Aloka ProSound ALPHA 10 with 13 MHz linear probe. Among AD patients there were 5 with arterial hypertension (AH), 3 with atrial fibrillation (AF), 2 with diabetes mellitus (DM), 6 with hyper lipidemia and 1 smoker. Nineteen VAD patients had AH, 6 had AF, 12 had hyper lipidemia and one was diabetic. We found no statistically significant differences between groups regarding average body mass index (BMI), blood pressure, pulse pressure, intima-media thickness (IMT), CCA diameter or arterial beta stiffness indices. However, the trend of BMI increase, slight blood and pulse pressure decrease, CCA diameter increase and beta stiffness index increase was noted in VAD patients. Even though there was no significant difference found among two explored subgroups of patients with dementia, there was a tendency of greater systolic and diastolic diameters noted in VAD as well as greater stiffness, especially when measured in the right CCA. This indicates that VAD patients may have more prominent vascular changes that may help differentiate the type of dementia and further monitor these individuals. Further studies on a larger number of patients are needed support this evidence. PMID:19375085

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

    PubMed Central

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

    2013-01-01

    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. PMID:22841823

  9. Peripheral vascular disease: diagnosis and treatment.

    PubMed

    Sontheimer, Daniel L

    2006-06-01

    Peripheral vascular disease is a manifestation of systemic atherosclerosis that leads to significant narrowing of arteries distal to the arch of the aorta. The most common symptom of peripheral vascular disease is intermittent claudication. At other times, peripheral vascular disease leads to acute or critical limb ischemia. Intermittent claudication manifests as pain in the muscles of the legs with exercise; it is experienced by 2 percent of persons older than 65 years. Physical findings include abnormal pedal pulses, femoral artery bruit, delayed venous filling time, cool skin, and abnormal skin color. Most patients present with subtle findings and lack classic symptoms, which makes the diagnosis difficult. The standard office-based test to determine the presence of peripheral vascular disease is calculation of the ankle-brachial index. Magnetic resonance arteriography, duplex scanning, and hemodynamic localization are noninvasive methods for lesion localization and may be helpful when symptoms or findings do not correlate with the ankle-brachial index. Contrast arteriography is used for definitive localization before intervention. Treatment is divided into lifestyle, medical, and surgical therapies. Lifestyle therapies focus on exercise, smoking cessation, and dietary modification. Medical therapy is directed at reducing platelet aggregation. In addition, patients with contributing disorders such as hypertension, diabetes, and hyperlipidemia need to have these conditions managed as aggressively as possible. Surgical therapies include stents, arterectomies, angioplasty, and bypass surgery. PMID:16770929

  10. Thermal stress induces epithelial permeability.

    PubMed

    Moseley, P L; Gapen, C; Wallen, E S; Walter, M E; Peterson, M W

    1994-08-01

    The mechanisms by which heat injury results in multiorgan system failure are unknown, but the presence of endotoxemia and intestinal hemorrhage suggests that changes in gut epithelial permeability may be crucial to this process. To determine whether alterations in epithelial permeability occur at physiologically relevant temperatures, heat-induced changes on epithelial barrier integrity were studied using a high-resistance clone of Madin-Darby canine kidney epithelial cells. Transepithelial electrical conductance increased when monolayers were heated above 38.3 degrees C. Early changes in conductance were completely reversible with cooling. Increased conductance was due to increased paracellular permeability because heat also induced increased mannitol permeability across the monolayers. A conditioning heat stress (42 degrees C for 90 min) altered heat-induced permeability. When cell monolayers were exposed to this conditioning stress 48 h before measurement of conductance with increasing temperatures, the conductance increase did not occur until they were heated to 39.4 degrees C compared with 38.8 degrees C in naive control cells. This conditioning treatment also conferred thermotolerance as measured by cell survival after a lethal 45.0 degrees C heat stress. There was no difference in the temperature at which conductance increased between preheated and control cells 96 h after a preconditioning heat stress. The conditioning heat stress resulted in accumulation of heat-shock protein (HSP) 70 in cells at 48 h, but HSP 70 returned to control levels at 96 h. These studies demonstrate that small temperature elevations increase epithelial permeability and that prior heat stress which induces HSP 70 shifts the threshold temperature required to disrupt the epithelium. PMID:8074177

  11. Permeability enhancement by shock cooling

    NASA Astrophysics Data System (ADS)

    Griffiths, Luke; Heap, Michael; Reuschl, Thierry; Baud, Patrick; Schmittbuhl, Jean

    2015-04-01

    The permeability of an efficient reservoir, e.g. a geothermal reservoir, should be sufficient to permit the circulation of fluids. Generally speaking, permeability decreases over the life cycle of the geothermal system. As a result, is usually necessary to artificially maintain and enhance the natural permeability of these systems. One of the methods of enhancement -- studied here -- is thermal stimulation (injecting cold water at low pressure). This goal of this method is to encourage new thermal cracks within the reservoir host rocks, thereby increasing reservoir permeability. To investigate the development of thermal microcracking in the laboratory we selected two granites: a fine-grained (Garibaldi Grey granite, grain size = 0.5 mm) and a course-grained granite (Lanhelin granite, grain size = 2 mm). Both granites have an initial porosity of about 1%. Our samples were heated to a range of temperatures (100-1000 C) and were either cooled slowly (1 C/min) or shock cooled (100 C/s). A systematic microstructural (2D crack area density, using standard stereological techniques, and 3D BET specific surface area measurements) and rock physical property (porosity, P-wave velocity, uniaxial compressive strength, and permeability) analysis was undertaken to understand the influence of slow and shock cooling on our reservoir granites. Microstructurally, we observe that the 2D crack surface area per unit volume and the specific surface area increase as a result of thermal stressing, and, for the same maximum temperature, crack surface area is higher in the shock cooled samples. This observation is echoed by our rock physical property measurements: we see greater changes for the shock cooled samples. We can conclude that shock cooling is an extremely efficient method of generating thermal microcracks and modifying rock physical properties. Our study highlights that thermal treatments are likely to be an efficient method for the "matrix" permeability enhancement of granitic geothermal reservoirs.

  12. How to Prevent Vascular Disease

    MedlinePLUS

    ... Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease Chronic Venous Insufficiency Congenital Vascular Malformation Critical Limb Ischemia (CLI) Deep Vein Thrombosis (DVT) Diabetes and Vascular Disease Fibromuscular Dysplasia High ...

  13. PERMEABILITY OF BACTERIAL SPORES I.

    PubMed Central

    Black, S. H.; Gerhardt, Philipp

    1961-01-01

    Black, S. H. (The University of Michigan, Ann Arbor) and Philipp Gerhardt. Permeability of bacterial spores. I. Characterization of glucose uptake. J. Bacteriol. 82:743749. 1961.The total uptake of glucose by masses of clean, dormant spores was measured to assess their permeability. After correction for intercellular space, packed spores of Bacillus cereus strain terminalis were found in 87 determinations to be permeated by glucose to 40% of their weight. The glucose uptake was relatively independent of environmental variables, and thus was concluded to occur principally through a process of passive diffusion. PMID:13869665

  14. Vascular Access in Children

    SciTech Connect

    Krishnamurthy, Ganesh Keller, Marc S.

    2011-02-15

    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.

  15. Arginase and vascular aging

    PubMed Central

    Santhanam, Lakshmi; Christianson, David W.; Nyhan, Daniel; Berkowitz, Dan E.

    2008-01-01

    Vascular and associated ventricular stiffness is one of the hallmarks of the aging cardiovascular system. Both an increase in reactive oxygen species production and a decrease in nitric oxide (NO) bioavailability contribute to the endothelial dysfunction that underlies this vascular stiffness, independent of other age-related vascular pathologies such as atherosclerosis. The activation/upregulation of arginase appears to be an important contributor to age-related endothelial dysfunction by a mechanism that involves substrate (l-arginine) limitation for NO synthase (NOS) 3 and therefore NO synthesis. Not only does this lead to impaired NO production but also it contributes to the enhanced production of reactive oxygen species by NOS. Although arginase abundance is increased in vascular aging models, it appears that posttranslational modification by S-nitrosylation of the enzyme enhances its activity as well. The S-nitrosylation is mediated by the induction of NOS2 in the endothelium. Furthermore, arginase activation contributes to aging-related vascular changes by mechanisms that are not directly related to changes in NO signaling, including polyamine-dependent vascular smooth muscle proliferation and collagen synthesis. Taken together, arginase may represent an as yet elusive target for the modification of age-related vascular and ventricular stiffness contributing to cardiovascular morbidity and mortality. PMID:18719233

  16. The matrikine N-?-PGP couples extracellular matrix fragmentation to endothelial permeability

    PubMed Central

    Hahn, Cornelia S.; Scott, David W.; Xu, Xin; Roda, Mojtaba Abdul; Payne, Gregory A.; Wells, J. Michael; Viera, Liliana; Winstead, Colleen J.; Bratcher, Preston; Sparidans, Rolf W.; Redegeld, Frank A.; Jackson, Patricia L.; Folkerts, Gert; Blalock, J. Edwin; Patel, Rakesh P.; Gaggar, Amit

    2015-01-01

    The compartmentalization and transport of proteins and solutes across the endothelium is a critical biologic function altered during inflammation and disease, leading to pathology in multiple disorders. The impact of tissue damage and subsequent extracellular matrix (ECM) fragmentation in regulating this process is unknown. We demonstrate that the collagen-derived matrikine acetylated proline-glycine-proline (N-?-PGP) serves as a critical regulator of endothelial permeability. N-?-PGP activates human endothelial cells via CXC-chemokine receptor 2 (CXCR2), triggering monolayer permeability through a discrete intracellular signaling pathway. In vivo, N-?-PGP induces local vascular leak after subcutaneous administration and pulmonary vascular permeability after systemic administration. Furthermore, neutralization of N-?-PGP attenuates lipopolysaccharide-induced lung leak. Finally, we demonstrate that plasma from patients with acute respiratory distress syndrome (ARDS) induces VE-cadherin phosphorylation in human endothelial cells, and this activation is attenuated by N-?-PGP blockade with a concomitant improvement in endothelial monolayer impedance. These results identify N-?-PGP as a novel ECM-derived matrikine regulating paracellular permeability during inflammatory disease and demonstrate the potential to target this ligand in various disorders characterized by excessive matrix turnover and vascular leak such as ARDS. PMID:26229981

  17. Thromboxane A{sub 2} increases endothelial permeability through upregulation of interleukin-8

    SciTech Connect

    Kim, Su-Ryun; Medical Research Center for Ischemic Tissue Regeneration and School of Medicine, Pusan National University, Yangsan 626-870 ; Bae, Soo-Kyung; Park, Hyun-Joo; Kim, Mi-Kyoung; Kim, Koanhoi; Park, Shi-Young; Jang, Hye-Ock; Yun, Il; Kim, Yung-Jin; Yoo, Mi-Ae; Bae, Moon-Kyoung

    2010-07-02

    Thromboxane A{sub 2} (TXA{sub 2}), a major prostanoid formed from prostaglandin H{sub 2} by thromboxane synthase, is involved in the pathogenesis of a variety of vascular diseases. In this study, we report that TXA{sub 2} mimetic U46619 significantly increases the endothelial permeability both in vitro and in vivo. U46619 enhanced the expression and secretion of interleukin-8 (IL-8), a major inducer of vascular permeability, in endothelial cells. Promoter analysis showed that the U46619-induced expression of IL-8 was mainly regulated by nuclear factor-{kappa}B (NF-{kappa}B). U46619 induced the activation of NF-{kappa}B through I{kappa}B kinase (IKK) activation, I{kappa}B phosphorylation and NF-{kappa}B nuclear translocation. Furthermore, the inhibition of IL-8 or blockade of the IL-8 receptor attenuated the U46619-induced endothelial cell permeability by modulating the cell-cell junctions. Overall, these results suggest that U46619 promotes vascular permeability through the production of IL-8 via NF-{kappa}B activation in endothelial cells.

  18. Vascular pharmacotherapy and dementia.

    PubMed

    Piguet, Olivier; Garner, Brett

    2010-01-01

    The incidence of dementia is increasing dramatically with the ageing population. Increasing evidence indicates that vascular disease is associated with cognitive decline and with the most common form of dementia, Alzheimer's disease (AD). Cardiovascular risk factors such as hyperlipidaemia, hypertension and type 2 diabetes have attracted attention as potential targets in the prevention of dementia. The present review aims to provide a concise overview of the recent advances linking vascular disease with dementia (with a particular focus on AD) and to examine the evidence for efficacy, where possible, for utilising vascular pharmacotherapy as a treatment option for dementia. PMID:19485934

  19. Reinforcing endothelial junctions prevents microvessel permeability increase and tumor cell adhesion in microvessels in vivo

    NASA Astrophysics Data System (ADS)

    Fu, Bingmei M.; Yang, Jinlin; Cai, Bin; Fan, Jie; Zhang, Lin; Zeng, Min

    2015-10-01

    Tumor cell adhesion to the microvessel wall is a critical step during tumor metastasis. Vascular endothelial growth factor (VEGF), a secretion of tumor cells, can increase microvessel permeability and tumor cell adhesion in the microvessel. To test the hypothesis that inhibiting permeability increase can reduce tumor cell adhesion, we used in vivo fluorescence microscopy to measure both microvessel permeability and adhesion rates of human mammary carcinoma MDA-MB-231 cells in post-capillary venules of rat mesentery under the treatment of VEGF and a cAMP analog, 8-bromo-cAMP, which can decrease microvessel permeability. By immunostaining adherens junction proteins between endothelial cells forming the microvessel wall, we further investigated the structural mechanism by which cAMP abolishes VEGF-induced increase in microvessel permeability and tumor cell adhesion. Our results demonstrate that 1) Pretreatment of microvessels with cAMP can abolish VEGF-enhanced microvessel permeability and tumor cell adhesion; 2) Tumor cells prefer to adhere to the endothelial cell junctions instead of cell bodies; 3) VEGF increases microvessel permeability and tumor cell adhesion by compromising endothelial junctions while cAMP abolishes these effects of VEGF by reinforcing the junctions. These results suggest that strengthening the microvessel wall integrity can be a potential approach to inhibiting hematogenous tumor metastasis.

  20. Reinforcing endothelial junctions prevents microvessel permeability increase and tumor cell adhesion in microvessels in vivo

    PubMed Central

    Fu, Bingmei M.; Yang, Jinlin; Cai, Bin; Fan, Jie; Zhang, Lin; Zeng, Min

    2015-01-01

    Tumor cell adhesion to the microvessel wall is a critical step during tumor metastasis. Vascular endothelial growth factor (VEGF), a secretion of tumor cells, can increase microvessel permeability and tumor cell adhesion in the microvessel. To test the hypothesis that inhibiting permeability increase can reduce tumor cell adhesion, we used in vivo fluorescence microscopy to measure both microvessel permeability and adhesion rates of human mammary carcinoma MDA-MB-231 cells in post-capillary venules of rat mesentery under the treatment of VEGF and a cAMP analog, 8-bromo-cAMP, which can decrease microvessel permeability. By immunostaining adherens junction proteins between endothelial cells forming the microvessel wall, we further investigated the structural mechanism by which cAMP abolishes VEGF-induced increase in microvessel permeability and tumor cell adhesion. Our results demonstrate that 1) Pretreatment of microvessels with cAMP can abolish VEGF-enhanced microvessel permeability and tumor cell adhesion; 2) Tumor cells prefer to adhere to the endothelial cell junctions instead of cell bodies; 3) VEGF increases microvessel permeability and tumor cell adhesion by compromising endothelial junctions while cAMP abolishes these effects of VEGF by reinforcing the junctions. These results suggest that strengthening the microvessel wall integrity can be a potential approach to inhibiting hematogenous tumor metastasis. PMID:26507779

  1. Permeable Pavement Research Edison, NJ

    EPA Science Inventory

    This presentation gives the rationale behind NRMRLs decision to construct and test a permeable surface parking lot the Edison Environmental Center. It also describes the monitoring program and gives preliminary results. The presentation is being given at the request of the New...

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

    PubMed

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

    2011-01-01

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

  3. Role of connexin 43 in vascular hyperpermeability and relationship to Rock1-MLC20 pathway in septic rats.

    PubMed

    Zhang, Jie; Yang, Guang-Ming; Zhu, Yu; Peng, Xiao-Yong; Li, Tao; Liu, Liang-Ming

    2015-12-01

    Connexin (Cx)43 has been shown to participate in several cardiovascular diseases. Increased vascular permeability is a common and severe complication in sepsis or septic shock. Whether or not Cx43 takes part in the regulation of vascular permeability in severe sepsis is not known, and the underlying mechanism has not been described. With cecal ligation and puncture-induced sepsis in rats and lipopolysaccharide (LPS)-treated vascular endothelial cells (VECs) from pulmonary veins, the role of Cx43 in increased vascular permeability and its relationship to the RhoA/Rock1 pathway were studied. It was shown that vascular permeability in the lungs, kidneys, and mesentery in sepsis rats and LPS-stimulated monolayer pulmonary vein VECs was significantly increased and positively correlated with the increased expression of Cx43 and Rock1 in these organs and cultured pulmonary vein VECs. The connexin inhibitor carbenoxolone (10 mg/kg iv) and the Rock1 inhibitor Y-27632 (2 mg/kg iv) alleviated the vascular leakage of lung, mesentery, and kidney in sepsis rats. Overexpressed Cx43 increased the phosphorylation of 20-kDa myosin light chain (MLC20) and the expression of Rock1 and increased the vascular permeability and decreased the transendothelial electrical resistance of pulmonary vein VECs. Cx43 RNA interference decreased the phosphorylation of MLC20 and the expression of Rock1 and decreased LPS-stimulated hyperpermeability of cultured pulmonary vein VECs. The Rock1 inhibitor Y-27632 alleviated LPS- and overexpressed Cx43-induced hyperpermeability of monolayer pulmonary vein VECs. This report shows that Cx43 participates in the regulation of vascular permeability in sepsis and that the mechanism is related to the Rock1-MLC20 phosphorylation pathway. PMID:26342084

  4. What Is Vascular Disease?

    MedlinePLUS

    ... pulmonary embolism (blood clots), deep vein thrombosis (DVT), chronic venous insufficiency (CVI), and varicose veins. Everyone is at risk for vascular disease. With the increase in obesity and Type II diabetes in Americans and as the population ages, it ...

  5. Uterine Vascular Lesions

    PubMed Central

    Vijayakumar, Abhishek; Srinivas, Amruthashree; Chandrashekar, Babitha Moogali; Vijayakumar, Avinash

    2013-01-01

    Vascular lesions of the uterus are rare; most reported in the literature are arteriovenous malformations (AVMs). Uterine AVMs can be congenital or acquired. In recent years, there has been an increasing number of reports of acquired vascular lesions of the uterus following pregnancy, abortion, cesarean delivery, and curettage. It can be seen from these reports that there is confusion concerning the terminology of uterine vascular lesions. There is also a lack of diagnostic criteria and management guidelines, which has led to an increased number of unnecessary invasive procedures (eg, angiography, uterine artery embolization, hysterectomy for abnormal vaginal bleeding). This article familiarizes readers with various vascular lesions of the uterus and their management. PMID:24340126

  6. Vascular Health Activity Book

    MedlinePLUS

    ... Surgery Journal of Vascular Surgery IN THIS ISSUE AAA Anatomic Severity Grading Score Compliance of Post-EVAR Surveillance Frailty Predicts Outcomes of Ruptured AAA Access the Journal Venous and Lymphatic Disorders Venous ...

  7. Implications of Vascular Aging

    PubMed Central

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

    2011-01-01

    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. PMID:21474663

  8. Collagen vascular disease

    MedlinePLUS

    ... developed these disorders were previously said to have "connective tissue" or "collagen vascular" disease. We now have names ... be used. These include as undifferentiated systemic rheumatic (connective tissue) diseases or overlap syndromes.

  9. Assessing vascular endothelial function using frequency and rank order statistics

    NASA Astrophysics Data System (ADS)

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

    2013-08-01

    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.

  10. Iloprost attenuates the increased permeability in skeletal muscle after ischemia and reperfusion

    SciTech Connect

    Blebea, J.; Cambria, R.A.; DeFouw, D.; Feinberg, R.N.; Hobson, R.W. 2d.; Duran, W.N. )

    1990-12-01

    Increased vascular permeability is an early and sensitive indicator of ischemic muscle injury, occurring before significant histologic or radionuclide changes are evident. We investigated the effect of iloprost, a stable prostacyclin analog, on microvascular permeability in a rat striated muscle model. In six control and six experimental animals the cremaster muscle was dissected, placed in a closed-flow acrylic chamber, and suffused with a bicarbonate buffer solution. Dextran labeled with fluorescein was injected intravenously as a macromolecular tracer, and microvascular permeability was determined on the basis of clearance of the fluorescent tracer. Two hours of ischemia were followed by 2 hours of reperfusion. In the experimental group iloprost (0.5 microgram/kg/min) was given in a continuous intravenous infusion. Microvascular permeability increased significantly during reperfusion in both control and experimental animals (p less than 0.0001). Treatment with iloprost, however, significantly attenuated this response compared to the control group, 4.8 +/- 0.3 versus 7.3 +/- 0.5 microliters/gm/min, respectively (p less than 0.0001). Iloprost decreases the rise in vascular permeability after ischemia and reperfusion. Experimental clinical use of iloprost under controlled conditions in the treatment of patients with acute skeletal muscle ischemia appears justified.

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

    PubMed Central

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

    2010-01-01

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

  12. Vascular structures in dermoscopy*

    PubMed Central

    Ayhan, Erhan; Ucmak, Derya; Akkurt, ZeynepMeltem

    2015-01-01

    Dermoscopy is an aiding method in the visualization of the epidermis and dermis. It is usually used to diagnose melanocytic lesions. In recent years, dermoscopy has increasingly been used to diagnose non-melanocytic lesions. Certain vascular structures, their patterns of arrangement and additional criteria may demonstrate lesion-specific characteristics. In this review, vascular structures and their arrangements are discussed separately in the light of conflicting views and an overview of recent literature. PMID:26375224

  13. Permeability of compacting porous lavas

    NASA Astrophysics Data System (ADS)

    Ashwell, P. A.; Kendrick, J. E.; Lavallée, Y.; Kennedy, B. M.; Hess, K.-U.; Aulock, F. W.; Wadsworth, F. B.; Vasseur, J.; Dingwell, D. B.

    2015-03-01

    The highly transient nature of outgassing commonly observed at volcanoes is in part controlled by the permeability of lava domes and shallow conduits. Lava domes generally consist of a porous outer carapace surrounding a denser lava core with internal shear zones of variable porosity. Here we examine densification using uniaxial compression experiments on variably crystalline and porous rhyolitic dome lavas from the Taupo Volcanic Zone. Experiments were conducted at 900°C and an applied stress of 3 MPa to 60% strain, while monitoring acoustic emissions to track cracking. The evolution of the porous network was assessed via X-ray computed tomography, He-pycnometry, and relative gas permeability. High starting connected porosities led to low apparent viscosities and high strain rates, initially accompanied by abundant acoustic emissions. As compaction ensued, the lavas evolved; apparent viscosity increased and strain rate decreased due to strain hardening of the suspensions. Permeability fluctuations resulted from the interplay between viscous flow and brittle failure. Where phenocrysts were abundant, cracks had limited spatial extent, and pore closure decreased axial and radial permeability proportionally, maintaining the initial anisotropy. In crystal-poor lavas, axial cracks had a more profound effect, and permeability anisotropy switched to favor axial flow. Irrespective of porosity, both crystalline samples compacted to a threshold minimum porosity of 17-19%, whereas the crystal-poor sample did not achieve its compaction limit. This indicates that unconfined loading of porous dome lavas does not necessarily form an impermeable plug and may be hindered, in part by the presence of crystals.

  14. High membrane permeability for melatonin.

    PubMed

    Yu, Haijie; Dickson, Eamonn J; Jung, Seung-Ryoung; Koh, Duk-Su; Hille, Bertil

    2016-01-01

    The pineal gland, an endocrine organ in the brain, synthesizes and secretes the circulating night hormone melatonin throughout the night. The literature states that this hormone is secreted by simple diffusion across the pinealocyte plasma membrane, but a direct quantitative measurement of membrane permeability has not been made. Experiments were designed to compare the cell membrane permeability to three indoleamines: melatonin and its precursors N-acetylserotonin (NAS) and serotonin (5-HT). The three experimental approaches were (1) to measure the concentration of effluxing indoleamines amperometrically in the bath while cells were being dialyzed internally by a patch pipette, (2) to measure the rise of intracellular indoleamine fluorescence as the compound was perfused in the bath, and (3) to measure the rate of quenching of intracellular fura-2 dye fluorescence as indoleamines were perfused in the bath. These measures showed that permeabilities of melatonin and NAS are high (both are uncharged molecules), whereas that for 5-HT (mostly charged) is much lower. Comparisons were made with predictions of solubility-diffusion theory and compounds of known permeability, and a diffusion model was made to simulate all of the measurements. In short, extracellular melatonin equilibrates with the cytoplasm in 3.5 s, has a membrane permeability of ∼1.7 µm/s, and could not be retained in secretory vesicles. Thus, it and NAS will be "secreted" from pineal cells by membrane diffusion. Circumstances are suggested when 5-HT and possibly catecholamines may also appear in the extracellular space passively by membrane diffusion. PMID:26712850

  15. Vascular compression syndromes.

    PubMed

    Czihal, Michael; Banafsche, Ramin; Hoffmann, Ulrich; Koeppel, Thomas

    2015-11-01

    Dealing with vascular compression syndromes is one of the most challenging tasks in Vascular Medicine practice. This heterogeneous group of disorders is characterised by external compression of primarily healthy arteries and/or veins as well as accompanying nerval structures, carrying the risk of subsequent structural vessel wall and nerve damage. Vascular compression syndromes may severely impair health-related quality of life in affected individuals who are typically young and otherwise healthy. The diagnostic approach has not been standardised for any of the vascular compression syndromes. Moreover, some degree of positional external compression of blood vessels such as the subclavian and popliteal vessels or the celiac trunk can be found in a significant proportion of healthy individuals. This implies important difficulties in differentiating physiological from pathological findings of clinical examination and diagnostic imaging with provocative manoeuvres. The level of evidence on which treatment decisions regarding surgical decompression with or without revascularisation can be relied on is generally poor, mostly coming from retrospective single centre studies. Proper patient selection is critical in order to avoid overtreatment in patients without a clear association between vascular compression and clinical symptoms. With a focus on the thoracic outlet-syndrome, the median arcuate ligament syndrome and the popliteal entrapment syndrome, the present article gives a selective literature review on compression syndromes from an interdisciplinary vascular point of view. PMID:26515219

  16. Factors controlling permeability of the blood-brain barrier.

    PubMed

    Almutairi, Mohammed M A; Gong, Chen; Xu, Yuexian G; Chang, Yanzhong; Shi, Honglian

    2016-01-01

    As the primary protective barrier for neurons in the brain, the blood-brain barrier (BBB) exists between the blood microcirculation system and the brain parenchyma. The normal BBB integrity is essential in protecting the brain from systemic toxins and maintaining the necessary level of nutrients and ions for neuronal function. This integrity is mediated by structural BBB components, such as tight junction proteins, integrins, annexins, and agrin, of a multicellular system including endothelial cells, astrocytes, pericytes, etc. BBB dysfunction is a significant contributor to the pathogeneses of a variety of brain disorders. Many signaling factors have been identified to be able to control BBB permeability through regulating the structural components. Among those signaling factors are inflammatory mediators, free radicals, vascular endothelial growth factor, matrix metalloproteinases, microRNAs, etc. In this review, we provide a summary of recent progress regarding these structural components and signaling factors, relating to their roles in various brain disorders. Attention is also devoted to recent research regarding impact of pharmacological agents such as isoflurane on BBB permeability and how iron ion passes across BBB. Hopefully, a better understanding of the factors controlling BBB permeability helps develop novel pharmacological interventions of BBB hyperpermeability under pathological conditions. PMID:26403789

  17. Cytoskeletal mechanisms regulating vascular endothelial barrier function in response to acute lung injury

    PubMed Central

    Ksa, Anita; Csortos, Csilla; Verin, Alexander D

    2014-01-01

    Endothelial cells (EC) form a semi-permeable barrier between the interior space of blood vessels and the underlying tissues. In acute lung injury (ALI) the EC barrier is weakened leading to increased vascular permeability. It is widely accepted that EC barrier integrity is critically dependent upon intact cytoskeletal structure and cell junctions. Edemagenic agonists, like thrombin or endotoxin lipopolysaccharide (LPS), induced cytoskeletal rearrangement, and EC contractile responses leading to disruption of intercellular contacts and EC permeability increase. The highly clinically-relevant cytoskeletal mechanisms of EC barrier dysfunction are currently under intense investigation and will be described and discussed in the current review. PMID:25838980

  18. Permeable Pavement Research - Edison, New Jersey

    EPA Science Inventory

    This presentation provides the background and summary of results collected at the permeable pavement parking lot monitored at the EPA facility in Edison, NJ. This parking lot is surfaced with permeable interlocking concrete pavers (PICP), pervious concrete, and porous asphalt. ...

  19. Quantifying Evaporation in a Permeable Pavement System

    EPA Science Inventory

    Studies quantifying evaporation from permeable pavement systems are limited to a few laboratory studies and one field application. This research quantifies evaporation for a larger-scale field application by measuring the water balance from lined permeable pavement sections. Th...

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

    PubMed Central

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

    2013-01-01

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

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

    SciTech Connect

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

    2013-04-01

    Geochemical reactions may alter the permeability of leakage pathways in caprocks, which serve a critical role in confining CO{sub 2} in geologic carbon sequestration. A caprock specimen from a carbonate formation in the Michigan sedimentary Basin was fractured and studied in a high-pressure core flow experiment. Inflowing brine was saturated with CO{sub 2} at 40°C and 10 MPa, resulting in an initial pH of 4.6, and had a calcite saturation index of −0.8. Fracture permeability decreased during the experiment, but subsequent analyses did not reveal calcite precipitation. Instead, experimental observations indicate that calcite dissolution along the fracture pathway led to mobilization of less soluble mineral particles that clogged the flow path. Analyses of core sections via electron microscopy, synchrotron-based X-ray diffraction imaging, and the first application of microbeam Ca K-edge X-ray absorption near edge structure, provided evidence that these occlusions were fragments from the host rock rather than secondary precipitates. X-ray computed tomography showed a significant loss of rock mass within preferential flow paths, suggesting that dissolution also removed critical asperities and caused mechanical closure of the fracture. The decrease in fracture permeability despite a net removal of material along the fracture pathway demonstrates a nonintuitive, inverse relationship between dissolution and permeability evolution in a fractured carbonate caprock.

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

    SciTech Connect

    Gabrys, Dorota; Greco, Olga; Patel, Gaurang; Prise, Kevin M.; Tozer, Gillian M.; Kanthou, Chryso

    2007-12-01

    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.

  3. Review of hydrogen isotope permeability through materials

    SciTech Connect

    Steward, S.A.

    1983-08-15

    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.

  4. Novel additives to retard permeable flow

    SciTech Connect

    Golombok, Michael; Crane, Carel; Ineke, Erik; Welling, Marco; Harris, Jon

    2008-09-15

    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)

  5. Structure/Permeability Relationships Of Polyimide Membranes

    NASA Technical Reports Server (NTRS)

    St. Clair, A. K.; Yamamoto, H.; Mi, Y.; Stern, S. A.

    1995-01-01

    Report describes experimental study of permeabilities, by each of five gases, of membranes made of four different polyimides. Conducted to gain understanding of effects of molecular structures of membranes on permeabilities and to assess potential for exploitation of selective permeability in gas-separation processes. Gases used: H2, O2, N2, CO2, and CH4.

  6. Vapor-liquid phase separator permeability results

    NASA Technical Reports Server (NTRS)

    Yuan, S. W. K.; Frederking, T. H. K.

    1981-01-01

    Continued studies are described in the area of vapor-liquid phase separator work with emphasis on permeabilities of porous sintered plugs (stainless steel, nominal pore size 2 micrometer). The temperature dependence of the permeability has been evaluated in classical fluid using He-4 gas at atmospheric pressure and in He-2 on the basis of a modified, thermosmotic permeability of the normal fluid.

  7. Potassium permeability of Rickettsia prowazekii.

    PubMed Central

    Winkler, H H

    1984-01-01

    The potassium permeability of Rickettsia prowazekii was characterized by chemical measurement of the intracellular sodium and potassium pools and isotopic flux measurements with 86Rb+ as a tracer. R. prowazekii, in contrast to Escherichia coli, did not maintain a high potassium-to-sodium ratio in their cytoplasm except when the potassium-to-sodium ratio in the extracellular medium was high or when the extracellular concentrations of both cations were low (ca. 1 mM). Both influx and efflux assays with 86Rb+ demonstrated that the rickettsial membrane had limited permeability to potassium and that incorporation of valinomycin into these cells increased these fluxes at least 10-fold. The transport of potassium showed specificity and dependence on rickettsial metabolism. The increased flux of potassium which results from the incorporation of valinomycin into the rickettsial membrane was detrimental to both lysine transport and lysis of erythrocytes by the rickettsiae. PMID:6317650

  8. [Intestinal permeability disorders in children].

    PubMed

    Dupont, C; Barau, E; Molkhou, P

    1991-03-01

    The intestinal mucosa has a certain degree of "porosity", which allows some molecules and macromolecules that are not subject to active transport, to cross the intestinal wall and enter the blood circulation. This permeability of the intestinal mucosa, which depends mostly on the size of the molecule and the state of the mucosa, can be studied with the assistance of protein macromolecules in an allergy-immunological investigation, or with inert markers, so permitting evaluation of the state of integrity of the small intestine. The markers used are polyethylene glycols (PEG) of various molecular weights, Cr EDTA, the monosaccharide sugars mannitol or rhamnose and the disaccharide sugars lactulose or cellobiose. Study of the intestinal permeability to inert markers allows detection of coeliac or Crohn's disease. It can be repeated, especially at the time of food provocation tests needed in the diagnosis of food intolerances in pediatrics in the enteropathology to cows milk proteins, atopic dermatitis and irritable colon in children. PMID:2069683

  9. Permeability enhancement using explosive techniques

    SciTech Connect

    Adams, T.F.; Schmidt, S.C.; Carter, W.J.

    1980-01-01

    In situ recovery methods for many of our hydrocarbon and mineral resources depend on the ability to create or enhance permeability in the resource bed to allow uniform and predictable flow. To meet this need, a new branch of geomechanics devoted to computer prediction of explosive rock breakage and permeability enhancement has developed. The computer is used to solve the nonlinear equations of compressible flow, with the explosive behavior and constitutive properties of the medium providing the initial/boundary conditions and material response. Once the resulting computational tool has been verified and calibrated with appropriate large-scale field tests, it can be used to develop and optimize commercially useful explosive techniques for in situ resource recovery.

  10. Experimental Volcanology: Fragmentation and Permeability

    NASA Astrophysics Data System (ADS)

    Spieler, O.

    2005-12-01

    An increasing number of scientists design new experiments to analyse processes that control the dynamics of explosive eruptions. There research is mostly coupled to numerical models and aims toward its controlling parameters. The fragmentation process, its threshold and the speed of the fragmentation wave as well as the energy consumed by the fragmentation are some hot spots of the experimental volcanology. Analysing the fragmentation behaviour of volcaniclastics as close to the natural system as possible, we found a number of physical constrains. Identifying the porosity as determining factor of the threshold, we realised that neither threshold nor the speed of the fragmentation process are solely controlled by the rock density. The later results of the shock tube type apparatus lead to the analysis of the specific surface area and permeability as direct links to textural features. Permeability analysis performed in a modified shock tube type apparatus, show two clear, distinct trends for dome rock and pyroclastic samples. The specific surface determined by Argon sorbtion (BET) as well as textural features of pumices from Campi Flegrei, Montserrat and Krakatoa (1883) give in contrary evidence of a more complex story. Large spherical, or ellipsoidal bubbles around fractured crystals prove that the high permeability of the pumice has partially developed after the fixing of the bubble size distribution. This puts up the question, if permeability measurements on pyroclastic samples reveal relevant numbers! The surface tension controlled 'self sealing' behaviour of surfaces from foaming obsidian hinders in situ measurements. Close textural investigations will have to clarify how the 'post process' samples deviate from the syneruptive conduit filling.

  11. High Vascular PressureInduced Lung Injury Requires P450 EpoxygenaseDependent Activation of TRPV4

    PubMed Central

    Jian, Ming-Yuan; King, Judy A.; Al-Mehdi, Abu-Bakr; Liedtke, Wolfgang; Townsley, Mary I.

    2008-01-01

    High vascular pressure targets the lung septal network, causing acute lung injury. While calcium entry in septal endothelium has been implicated, the channel involved is not known. This study tested the hypothesis that the vanilloid transient receptor potential channel, TRPV4, is a critical participant in the permeability response to high vascular pressure. Isolated lungs from TRPV4+/+ or TRPV4?/? mice were studied at baseline or during high pressure challenge. Permeability was assessed via the filtration coefficient. Endothelial calcium transients were assessed using epifluorescence microscopy of the lung subpleural network. Light microscopy and point counting were used to determine the alveolar fluid volume fraction, a measure of alveolar flooding. Baseline permeability, calcium intensity, and alveolar flooding were no different in TRPV4+/+ versus TRPV4?/? lungs. In TRPV4+/+ lungs, the high pressureinduced permeability response was significantly attenuated by low calcium perfusate, the TRPV antagonist ruthenium red, the phospholipase A2 inhibitor methyl arachidonyl fluorophosphonate, or the P450 epoxygenase inhibitor propargyloxyphenyl hexanoic acid. Similarly, the high pressureinduced calcium transient in TRPV4+/+ lungs was attenuated with ruthenium red or the epoxygenase inhibitor. High vascular pressure increased the alveolar fluid volume fraction compared with control. In lungs from TRPV4?/? mice, permeability, calcium intensity, and alveolar fluid volume fraction were not increased. These data support a role for P450-derived epoxyeicosatrienoic aciddependent regulation of calcium entry via TRPV4 in the permeability response to high vascular pressure. PMID:17962608

  12. Vascular endothelial growth factor-dependent angiogenesis and dynamic vascular plasticity in the sensory circumventricular organs of adult mouse brain.

    PubMed

    Morita, Shoko; Furube, Eriko; Mannari, Tetsuya; Okuda, Hiroaki; Tatsumi, Kouko; Wanaka, Akio; Miyata, Seiji

    2015-03-01

    The sensory circumventricular organs (CVOs), which comprise the organum vasculosum of the lamina terminalis (OVLT), the subfornical organ (SFO) and the area postrema (AP), lack a typical blood-brain barrier (BBB) and monitor directly blood-derived information to regulate body fluid homeostasis, inflammation, feeding and vomiting. Until now, almost nothing has been documented about vascular features of the sensory CVOs except fenestration of vascular endothelial cells. We therefore examine whether continuous angiogenesis occurs in the sensory CVOs of adult mouse. The angiogenesis-inducing factor vascular endothelial growth factor-A (VEGF-A) and the VEGF-A-regulating transcription factor hypoxia-inducible factor-1α were highly expressed in neurons of the OVLT and SFO and in both neurons and astrocytes of the AP. Expression of the pericyte-regulating factor platelet-derived growth factor B was high in astrocytes of the sensory CVOs. Immunohistochemistry of bromodeoxyuridine and Ki-67, a nuclear protein that is associated with cellular proliferation, revealed active proliferation of endothelial cells. Moreover, immunohistochemistry of caspase-3 and the basement membrane marker laminin showed the presence of apoptosis and sprouting of endothelial cells, respectively. Treatment with the VEGF receptor-associated tyrosine kinase inhibitor AZD2171 significantly reduced proliferation and filopodia sprouting of endothelial cells, as well as the area and diameter of microvessels. The mitotic inhibitor cytosine-b-D-arabinofuranoside reduced proliferation of endothelial cells and the vascular permeability of blood-derived low-molecular-weight molecules without changing vascular area and microvessel diameter. Thus, our data indicate that continuous angiogenesis is dependent on VEGF signaling and responsible for the dynamic plasticity of vascular structure and permeability. PMID:25573819

  13. Advances in assessment of bone porosity, permeability and interstitial fluid flow.

    PubMed

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

    2013-01-18

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

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

    PubMed Central

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

    2012-01-01

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

  15. Endothelial Cell Permeability and Adherens Junction Disruption Induced by Junín Virus Infection

    PubMed Central

    Lander, Heather M.; Grant, Ashley M.; Albrecht, Thomas; Hill, Terence; Peters, Clarence J.

    2014-01-01

    Junín virus (JUNV) is endemic to the fertile Pampas of Argentina, maintained in nature by the rodent host Calomys musculinus, and the causative agent of Argentine hemorrhagic fever (AHF), which is characterized by vascular dysfunction and fluid distribution abnormalities. Clinical as well as experimental studies implicate involvement of the endothelium in the pathogenesis of AHF, although little is known of its role. JUNV has been shown to result in productive infection of endothelial cells (ECs) in vitro with no visible cytopathic effects. In this study, we show that direct JUNV infection of primary human ECs results in increased vascular permeability as measured by electric cell substrate impedance sensing and transwell permeability assays. We also show that EC adherens junctions are disrupted during virus infection, which may provide insight into the role of the endothelium in the pathogenesis of AHF and possibly, other viral hemorrhagic fevers. PMID:24710609

  16. Tumor vascular targeted liposomal-bortezomib minimizes side effects and increases therapeutic activity in human neuroblastoma.

    PubMed

    Zuccari, Guendalina; Milelli, Andrea; Pastorino, Fabio; Loi, Monica; Petretto, Andrea; Parise, Amelia; Marchetti, Chiara; Minarini, Anna; Cilli, Michele; Emionite, Laura; Di Paolo, Daniela; Brignole, Chiara; Piaggio, Francesca; Perri, Patrizia; Tumiatti, Vincenzo; Pistoia, Vito; Pagnan, Gabriella; Ponzoni, Mirco

    2015-08-10

    Neuroblastoma is a childhood cancer with poor long-term prognosis in advanced stages. A major aim in neuroblastoma therapy is to develop targeted drug delivery systems to ameliorate drug therapeutic index and efficacy. In this study, a novel bortezomib (BTZ) liposomal formulation was set-up and characterized. Since BTZ is freely permeable across the lipidic bilayer, an amino-lactose (LM) was synthesized as complexing agent to entrap BTZ inside the internal aqueous compartment of stealth liposomes. High encapsulation efficiency was achieved by a loading method based on the formation of boronic esters between the boronic acid moiety of BTZ and the hydroxyl groups of LM. Next, NGR peptides were linked to the liposome surface as a targeting-ligand for the tumor endothelial cell marker, aminopeptidase N. Liposomes were characterized for size, Z-potential, polydispersity index, drug content, and release. Lyophilization in the presence of cryoprotectants (trehalose, sucrose) was also examined in terms of particle size changes and drug leakage. BTZ was successfully loaded into non-targeted (SL[LM-BTZ]) and targeted (NGR-SL[LM-BTZ]) liposomes with an entrapment efficiency of about 68% and 57%, respectively. These nanoparticles were suitable for intravenous administration, presenting an average diameter of 170nm and narrow polydispersity. Therefore, orthotopic NB-bearing mice were treated with 1.0 or 1.5mg/kg of BTZ, either in free form or encapsulated into liposomes. BTZ loaded liposomes showed a significant reduction of drug systemic adverse effects with respect to free drug, even at the highest dose tested. Moreover, mice treated with 1.5mg/kg of NGR-SL[LM-BTZ] lived statistically longer than untreated mice (P=0.0018) and SL[LM-BTZ]-treated mice (P=0.0256). Our results demonstrate that the novel vascular targeted BTZ formulation is endowed with high therapeutic index and low toxicity, providing a new tool for future applications in neuroblastoma clinical studies. PMID:26031842

  17. Permeability of Soft Particles at Electrical Fields.

    PubMed

    Sierra-Martin, B; Maldonado-Valdivia, A; de Las Nieves, F J; Fernndez-Barbero, A

    2015-05-01

    The influence of the charge on the permeability of microgel particles is studied in the presence of electric fields. Electrophoresis experiments performed on pH-ionizable pNIPAM-AA microgels show that particles behave as permeable spheres when the network is ionized. However, they keep non-permeable in the absence of charge. The ionic nature of the network thus controls the permeability of the soft particles. A salt-dependent local viscosity explains these permeability changes. This is confirmed by NMR as alternative independent technique. Strongly hydrated counterions located around fixed charges on the network are considered responsible for the local viscosity variations. PMID:26504980

  18. Pulmonary vascular diseases.

    PubMed

    Cummings, Kristopher W; Bhalla, Sanjeev

    2015-06-01

    Pulmonary vascular diseases encompass a large and diverse group of underlying pathologies ranging from venous thromboembolism to congenital malformations to inflammatory vasculitides. As a result, patients can present either acutely with dyspnea and chest pain or chronically with dyspnea on exertion, hypoxia, and right heart failure. Imaging, particularly with multidetector CT, plays a key role in the evaluation and management of patients with suspected pulmonary vascular disease and, given the widespread routine use of high-quality CT pulmonary angiography, it is imperative that radiologists be familiar these pathologies. PMID:26024602

  19. Reducing permeability of highly permeable zones in subterranean formations

    SciTech Connect

    Allison, J.D.

    1988-08-30

    A process is described for reducing the permeability of a subterranean formation traversed by a well bore which comprises: (a) introducing into the formation via the well bore an aqueous solution of a water soluble polymer selected from the group consisting of polygalactomannan gums, hydroxyalkyl ethers of polygalactomannan gums, carboxyl alkyl ethers of polygalactomannan gums, their depolymerized counterparts, polyvinyl alcohol and mixtures thereof, the polymer being in the solution in an amount of from about 1% to 10% by weight of the solution; and (b) introducing into the formation via the well bore a slowly hydrolyzable alkoxy amine ester of boric acid.

  20. Regulation of endothelial permeability in the primate corpora lutea: implications for ovarian hyperstimulation syndrome.

    PubMed

    Herr, Daniel; Bekes, Inga; Wulff, Christine

    2015-02-01

    In a developing human corpus luteum, a closely regulated cellular communication system exists between the luteal steroidogenic cells and endothelial cells. This system guaranties the vascularization process during luteal formation. The process is combined with rapid release of large amounts of progesterone into the bloodstream. The regulation of endothelial proliferation and permeability by LH and human chorionic gonadotropin (hCG) is integral to this process. On the cellular level, endothelial permeability is regulated by intercellular junctions, such as adherens junctions (AJ) and tight junctions (TJ), which act as zipper-like structures between interacting endothelial cells. Several cell junctional proteins are localized to the corpus luteum, including Occludin, Nectin 2, Claudin 1, and Claudin 5, as well as, vascular endothelial (VE)-Cadherin. It has been assumed that regulation of AJ- and TJ-proteins is of particular importance for permeability, and accordingly, for the functionality of the corpus luteum in early pregnancy, because treatment with hCG induces downregulation of juntional proteins in the luteal vessels. The effect of hCG on the adhesive molecules is mediated by VE growth factor (VEGF). On a functional level, the hCG-dependent and VEGF-mediated decrease in junctional proteins causes a decrease in the density of cell-cell closure and, accordingly, an increase in endothelial permeability. In doing so, the different junctional proteins are not only directly influenced by VEGF but also interact among themselves and influence each other reciprocally. Disturbances in this strictly, regulated interactions may explain the development of pathologies with increased vascular permeability, such as the ovarian hyperstimulation syndrome. PMID:25301969

  1. Depressive behavior and vascular dysfunction: a link between clinical depression and vascular disease?

    PubMed

    d'Audiffret, Alexandre C; Frisbee, Stephanie J; Stapleton, Phoebe A; Goodwill, Adam G; Isingrini, Elsa; Frisbee, Jefferson C

    2010-05-01

    As chronic stress and depression have become recognized as significant risk factors for peripheral vascular disease in patients with no prior history of vasculopathy, we interrogated this relationship utilizing an established mouse model of chronic stress/depressive symptoms from behavioral research. Male mice were exposed to 8 wk of unpredictable chronic mild stress (UCMS; e.g., wet bedding, predator sound/smell, random disruption of light/dark cycle), with indexes of depressive behavior (coat status, grooming, and mobility) becoming exacerbated vs. controls. In vascular rings, constrictor (phenylephrine) and endothelium-independent dilator (sodium nitroprusside) responses were not different between groups, although endothelium-dependent dilation (methacholine) was attenuated with UCMS. Nitric oxide synthase (NOS) inhibition was without effect in UCMS but nearly abolished reactivity in controls, while cyclooxygenase inhibition blunted dilation in both. Combined blockade abolished reactivity in controls, although a significant dilation remained in UCMS that was abolished by catalase. Arterial NO production was attenuated by UCMS, although H2O2 production was increased. UCMS mice demonstrated an increased, although variable, insulin resistance and inflammation. However, while UCMS-induced vascular impairments were consistent, the predictive power of aggregate plasma levels of insulin, TNF-alpha, IL-1beta, and C-reactive peptide were limited. However, when separated into tertiles with regard to vascular outcomes, insulin resistance and hypertension were predictive of the most severe vascular impairments. Taken together, these data suggest that aggregate insulin resistance, inflammation, and hypertension in UCMS mice are not robust predictors of vascular dysfunction, suggesting that unidentified mechanisms may be superior predictors of poor vascular outcomes in this model. PMID:20167667

  2. Vicenin-2 and scolymoside inhibit high-glucose-induced vascular inflammation in vitro and in vivo.

    PubMed

    Ku, Sae-Kwang; Bae, Jong-Sup

    2016-03-01

    The vascular inflammatory process has been suggested to play a key role in the initiation and progression of atherosclerosis, a major complication of diabetes mellitus. Thus, in this study, we attempted to determine whether 2 structurally related flavonoids found in Cyclopia subternata, vicenin-2 and scolymoside, can suppress high-glucose (HG)-induced vascular inflammatory processes in human umbilical vein endothelial cells (HUVECs) and mice. The effects of vicenin-2 and scolymoside on HG-induced vascular inflammation were determined by measuring vascular permeability, leukocyte adhesion and migration, cell adhesion molecule (CAM) expression levels, and reactive oxygen species (ROS) formation. In addition, the anti-inflammation mechanism was investigated using immunofluorescence staining and Western blotting. The data showed that HG markedly increased vascular permeability, monocyte adhesion, expression of CAMs, formation of reactive oxygen species (ROS), and activation of nuclear factor (NF)-?B. Remarkably, pretreatment with vicenin-2 and scolymoside attenuated all of the above-mentioned vascular inflammatory effects of HG. HG-induced vascular inflammatory responses are critical events underlying the development of various diabetic complications; therefore, our results suggest that vicenin-2 and scolymoside have significant therapeutic benefits against diabetic complications and atherosclerosis. PMID:26766560

  3. Mechanisms of Microgravity Effect on Vascular Function

    NASA Technical Reports Server (NTRS)

    Purdy, Ralph E.

    1995-01-01

    The overall goal of the project is to characterize the effects of simulated microgravity on vascular function. Microgravity is simulated using the hindlimb unweighted (HU) rat, and the following vessels are removed from HU and paired control rats for in vitro analysis: abdominal aorta, carotid and femoral arteries, jugular and femoral veins. These vessels are cut into 3 mm long rings and mounted in tissue baths for the measurement of either isometric contraction, or relaxation of pre- contracted vessels. The isolated mesenteric vascular bed is perfused for the measurement of changes in perfusion pressure as an index of arteriolar constriction or dilation. This report presents, in addition to the statement of the overall goal of the project, a summary list of the specific hypotheses to be tested. These are followed by sections on results, conclusions, significance and plans for the next year.

  4. Pathogenesis of Vascular Anomalies

    PubMed Central

    Boon, Laurence M.; Ballieux, Fanny; Vikkula, Miikka

    2010-01-01

    Vascular anomalies are localized defects of vascular development. Most of them occur sporadically, i.e. there is no familial history of lesions, yet in a few cases clear inheritance is observed. These inherited forms are often characterized by multifocal lesions that are mainly small in size and increase in number with patients age. On the basis of these inherited forms, molecular genetic studies have unraveled a number of inherited mutations giving direct insight into the pathophysiological cause and the molecular pathways that are implicated. Genetic defects have been identified for hereditary haemorrhagic telangiectasia (HHT), inherited cutaneomucosal venous malformation (VMCM), glomuvenous malformation (GVM), capillary malformation - arteriovenous malformation (CM-AVM), cerebral cavernous malformation (CCM) and some isolated and syndromic forms of primary lymphedema. We focus on these disorders, the implicated mutated genes and the underlying pathogenic mechanisms. We also call attention to the concept of Knudsons double-hit mechanism to explain incomplete penetrance and the large clinical variation in expressivity of inherited vascular anomalies. This variability renders the making of correct diagnosis of the rare inherited forms difficult. Yet, the identification of the pathophysiological causes and pathways involved in them has had an unprecedented impact on our thinking of their etiopathogenesis, and has opened the doors towards a more refined classification of vascular anomalies. It has also made it possible to develop animal models that can be tested for specific molecular therapies, aimed at alleviating the dysfunctions caused by the aberrant genes and proteins. PMID:21095468

  5. Vascular air embolism

    PubMed Central

    Gordy, Stephanie; Rowell, Susan

    2013-01-01

    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

  6. Amputation in vascular disease.

    PubMed Central

    Robinson, K.

    1980-01-01

    The management of vascular amputees in the Roehampton Limb Surgery Unit since its opening in 1975 is outlined and the results in 167 cases presented. Of the 35 patients over the age of 80, 57% were walking independently at the time of their discharge from the unit. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:7377693

  7. Engineered Vascularized Muscle Flap.

    PubMed

    Egozi, Dana; Shandalov, Yulia; Freiman, Alina; Rosenfeld, Dekel; Ben-Shimol, David; Levenberg, Shulamit

    2016-01-01

    One of the main factors limiting the thickness of a tissue construct and its consequential viability and applicability in vivo, is the control of oxygen supply to the cell microenvironment, as passive diffusion is limited to a very thin layer. Although various materials have been described to restore the integrity of full-thickness defects of the abdominal wall, no material has yet proved to be optimal, due to low graft vascularization, tissue rejection, infection, or inadequate mechanical properties. This protocol describes a means of engineering a fully vascularized flap, with a thickness relevant for muscle tissue reconstruction. Cell-embedded poly L-lactic acid/poly lactic-co-glycolic acid constructs are implanted around the mouse femoral artery and vein and maintained in vivo for a period of one or two weeks. The vascularized graft is then transferred as a flap towards a full thickness defect made in the abdomen. This technique replaces the need for autologous tissue sacrifications and may enable the use of in vitro engineered vascularized flaps in many surgical applications. PMID:26779840

  8. Obesity and vascular dysfunction.

    PubMed

    Stapleton, Phoebe A; James, Milinda E; Goodwill, Adam G; Frisbee, Jefferson C

    2008-08-01

    One of the most profound challenges facing public health and public health policy in Western society is the increased incidence and prevalence of both overweight and obesity. While this condition can have significant consequences for patient mortality and quality of life, it can be further exacerbated as overweight/obesity can be a powerful stimulus for the development of additional risk factors for a negative cardiovascular outcome, including increased insulin resistance, dyslipidemia and hypertension. This manuscript will present the effects of systemic obesity on broad issues of vascular function in both afflicted human populations and in the most relevant animal models. Among the topics that will be covered are alterations to vascular reactivity (both dilator and constrictor responses), adaptations in microvascular network and vessel wall structure, and alterations to the patterns of tissue/organ perfusion as a result of the progression of the obese condition. Additionally, special attention will be paid to the contribution of chronic inflammation as a contributor to alterations in vascular function, as well as the role of perivascular adipose tissue in terms of impacting vessel behavior. When taken together, it is clearly apparent that the development of the obese condition can have profound, and frequently difficult to predict, impacts on integrated vascular function. Much of this complexity appears to have its basis in the extent to which other co-morbidities associated with obesity (e.g., insulin resistance) are present and exert contributing effects. PMID:18571908

  9. Vascular wall extracellular matrix proteins and vascular diseases

    PubMed Central

    Xu, Junyan; Shi, Guo-Ping

    2014-01-01

    Extracellular matrix proteins form the basic structure of blood vessels. Along with providing basic structural support to blood vessels, matrix proteins interact with different sets of vascular cells via cell surface integrin or non-integrin receptors. Such interactions induce vascular cell de novo synthesis of new matrix proteins during blood vessel development or remodeling. Under pathological conditions, vascular matrix proteins undergo proteolytic processing, yielding bioactive fragments to influence vascular wall matrix remodeling. Vascular cells also produce alternatively spliced variants that induce vascular cell production of different matrix proteins to interrupt matrix homeostasis, leading to increased blood vessel stiffness; vascular cell migration, proliferation, or death; or vascular wall leakage and rupture. Destruction of vascular matrix proteins leads to vascular cell or blood-borne leukocyte accumulation, proliferation, and neointima formation within the vascular wall; blood vessels prone to uncontrolled enlargement during blood flow diastole; tortuous vein development; and neovascularization from existing pathological tissue microvessels. Here we summarize discoveries related to blood vessel matrix proteins within the past decade from basic and clinical studies in humans and animals from expression to cross-linking, assembly, and degradation under physiological and vascular pathological conditions, including atherosclerosis, aortic aneurysms, varicose veins, and hypertension. PMID:25045854

  10. Baicalin, baicalein and wogonin inhibits high glucose-induced vascular inflammation in vitro and in vivo

    PubMed Central

    Ku, Sae-Kwang; Bae, Jong-Sup

    2015-01-01

    Vascular inflammatory process has been suggested to play a key role in initiation and progression of atherosclerosis, a major complication of diabetes mellitus. Thus, in this study, we attempted to determine whether three structurally related polyphenols found in the Chinese herb Huang Qui, namely baicalin, baicalein, and wogonin, can suppress vascular inflammatory processes induced by high glucose (HG) in human umbilical vein endothelial cells (HUVECs) and mice. Data showed that HG induced markedly increased vascular permeability, monocyte adhesion, expressions of cell adhesion molecules (CAMs), formation of reactive oxygen species (ROS) and activation of nuclear factor (NF)-?B. Remarkably, all of the above mentioned vascular inflammatory effects of HG were attenuated by pretreatment with baicalin, baicalein, and wogonin. Vascular inflammatory responses induced by HG are critical events underlying development of various diabetic complications, therefore, our results suggest that baicalin, baicalein, and wogonin may have significant therapeutic benefits against diabetic complications and atherosclerosis. [BMB Reports 2015; 48(9): 519-524] PMID:25739393

  11. Correlation of permeability with the structure of the endothelial layer of pulmonary artery intimal explants

    SciTech Connect

    Meyrick, B.; Perkett, E.A.; Harris, T.R.; Brigham, K.L.

    1987-06-01

    Changes in vascular permeability are associated with structural damage to endothelial cells. These functional and structural changes can be produced experimentally and examined by using intimal explants from bovine pulmonary artery. Correlation of functional with structural changes allows the authors to dissect the mechanisms responsible for endothelial damage. They have shown that incubation of intimal explants with histamine causes transient formation of interendothelial dilations and an increased rate of equilibration of tritiated water and (/sup 14/C)sucrose across the intimal explant. Exposure to endotoxin also causes interendothial dilations but the endothelial damage is more severe than that with histamine, and in vivo experiments show a more prolonged increase in pulmonary vascular permeability. Leukocyte migration has also been suggested to result in a decreased barrier function of the endothelial layer. Experiments with the endothelial layer of intimal explants and separated bovine leukocytes suggest that transendothelial migration may depend on the chemotactic stimulus. Migration toward lymphocyte-conditioned medium does result in increased equilibration of (/sup 14/C)sucrose. Finally, a theoretical model has been used to examine the permeability changes seen for the intimal explants exposed to histamine. The model consists of two compartments with radioactive tracers diffusing across a filter of known permeability. Such a model gives good agreement with data obtained in intact sheep, indicating that mathematical models allow quantitative estimates of barrier function in intimal explants that compare favorably with in vivo data.

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

    PubMed

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

    2015-09-01

    The angiopoietin (Ang) ligands are potential therapeutic targets for lymphatic related diseases, which include lymphedema and cancer. Ang-1 and Ang-2 functions are established, but those of Ang-4 are poorly understood. We used intravital fluorescence microscopy to characterize Ang-4 actions on T241 murine fibrosarcoma-associated vessels in mice. The diameters of lymphatic vessels draining Ang-4- or VEGF-C (positive control)-expressing tumors increased to 123 and 135 ?m, respectively, and parental, mock-transduced (negative controls) and tumors expressing Ang-1 or Ang-2 remained at baseline (?60 ?m). Ang-4 decreased human dermal lymphatic endothelial cell (LEC) monolayer permeability by 27% while increasing human dermal blood endothelial cell (BEC) monolayer permeability by 200%. In vivo, Ang-4 stimulated a 4.5-fold increase in tumor-associated blood vessel permeability compared with control when measured using intravital quantitative multiphoton microscopy. Ang-4 activated receptor signaling in both LECs and BECs, evidenced by tyrosine kinase with Ig and endothelial growth factor homology domains-2 (TIE2) receptor, protein kinase B, and Erk1,2 phosphorylation detectable by immunoblotting. These data suggest that Ang-4 actions are mediated through cell-type-specific networks and that lymphatic vessel dilation occurs secondarily to increased vascular leakage. Ang-4 also promoted survival of LECs. Thus, blocking Ang-4 may prune the draining lymphatic vasculature and decrease interstitial fluid pressure (IFP) by reducing vascular permeability. PMID:25977256

  13. Dammarenediol-II Prevents VEGF-Mediated Microvascular Permeability in Diabetic Mice.

    PubMed

    Kim, Su-Hyeon; Jung, Se-Hui; Lee, Yeon-Ju; Han, Jung Yeon; Choi, Yong-Eui; Hong, Hae-Deun; Jeon, Hye-Yoon; Hwang, JongYun; Na, SungHun; Kim, Young-Myeong; Ha, Kwon-Soo

    2015-12-01

    Diabetic retinopathy is a major diabetic complication predominantly caused by vascular endothelial growth factor (VEGF)-induced vascular permeability in the retina; however, treatments targeting glycemic control have not been successful. Here, we investigated the protective effect of dammarenediol-II, a precursor of triterpenoid saponin biosynthesis, on VEGF-induced vascular leakage using human umbilical vein endothelial cells (HUVECs) and diabetic mice. We overproduced the compound in transgenic tobacco expressing Panax ginseng dammarenediol-II synthase gene and purified using column chromatography. Analysis of the purified compound using a gas chromatography-mass spectrometry system revealed identical retention time and fragmentation pattern to those of authentic standard dammarenediol-II. Dammarenediol-II inhibited VEGF-induced intracellular reactive oxygen species generation, but it had no effect on the levels of intracellular Ca(2+) in HUVECs. We also found that dammarenediol-II inhibited VEGF-induced stress fiber formation and vascular endothelial-cadherin disruption, both of which play critical roles in modulating endothelial permeability. Notably, microvascular leakage in the retina of diabetic mice was successfully inhibited by intravitreal dammarenediol-II injection. Our results suggest that the natural drug dammarenediol-II may have the ability to prevent diabetic microvascular complications, including diabetic retinopathy. Copyright 2015 John Wiley & Sons, Ltd. PMID:26400610

  14. Vascular endothelial dysfunction and pharmacological treatment

    PubMed Central

    Su, Jin Bo

    2015-01-01

    The endothelium exerts multiple actions involving regulation of vascular permeability and tone, coagulation and fibrinolysis, inflammatory and immunological reactions and cell growth. Alterations of one or more such actions may cause vascular endothelial dysfunction. Different risk factors such as hypercholesterolemia, homocystinemia, hyperglycemia, hypertension, smoking, inflammation, and aging contribute to the development of endothelial dysfunction. Mechanisms underlying endothelial dysfunction are multiple, including impaired endothelium-derived vasodilators, enhanced endothelium-derived vasoconstrictors, over production of reactive oxygen species and reactive nitrogen species, activation of inflammatory and immune reactions, and imbalance of coagulation and fibrinolysis. Endothelial dysfunction occurs in many cardiovascular diseases, which involves different mechanisms, depending on specific risk factors affecting the disease. Among these mechanisms, a reduction in nitric oxide (NO) bioavailability plays a central role in the development of endothelial dysfunction because NO exerts diverse physiological actions, including vasodilation, anti-inflammation, antiplatelet, antiproliferation and antimigration. Experimental and clinical studies have demonstrated that a variety of currently used or investigational drugs, such as angiotensin-converting enzyme inhibitors, angiotensin AT1 receptors blockers, angiotensin-(1-7), antioxidants, beta-blockers, calcium channel blockers, endothelial NO synthase enhancers, phosphodiesterase 5 inhibitors, sphingosine-1-phosphate and statins, exert endothelial protective effects. Due to the difference in mechanisms of action, these drugs need to be used according to specific mechanisms underlying endothelial dysfunction of the disease. PMID:26635921

  15. The Vascular Depression Hypothesis: Mechanisms Linking Vascular Disease with Depression

    PubMed Central

    Taylor, Warren D.; Aizenstein, Howard J.; Alexopoulos, George S.

    2013-01-01

    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 late-life depression, vascular risk factors, and cerebral hyperintensities, the radiological hallmark of vascular depression. Cognitive dysfunction is common in late-life depression, 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 late-life depression outcomes. PMID:23439482

  16. Vascular neurobehcet disease: correlation with current disease activity forum and systemic vascular involvement.

    PubMed

    Mohammed, Reem H A; Nasef, Amr; Kewan, Hanady H; Al Shaar, Mohammed

    2012-07-01

    Behcet's syndrome (BS) is a chronic relapsing vascular inflammatory disease of unknown etiology with high morbidity and mortality. This research aims to study the clinical patterns of CNS disease in a group of patients with BS as well as the frequency and type of the associated radiographic findings suggestive of structural cerebral vascular disease. The findings were studied in relation to disease activity and features of systemic vascular involvement. Forty patients fulfilling the diagnostic criteria of the International Study Group for Behcet's Disease, mean age of 33.56 9.7 years, were enrolled. Patients were subjected to magnetic resonance imaging with conjugate survey of cerebral blood vessels' flow pattern abnormalities by transcranial Doppler study. Thirty healthy controls were included. Behcet's Disease Current Activity Form Score was used. Neuro-Behcet's syndrome (NBS) was diagnosed in 37.5% with headache being the most common (86.6% of cases), pyramidal affection (signs of upper motor neuron lesions/hemiplegia) was reported in 33.3%, attacks of disturbed conscious level in 26.6%, and cranial nerve affection in 6.5%. Of the patients, 66.6% with clinical features of NBS had statistically significant radiographic evidences of cerebrovascular disease (p = 0.01). Patients with NBS had significantly higher disease activity index score (r = 0.69, p = 0.0001). Radiographic findings and flow abnormalities were significantly less in patients on immune suppressants and antiplatelet drugs (p = 0.003, 0.04). BS patients with clinical neurologic disease were found to have radiographic findings suggestive of cerebral vascular disease with high disease activity index score. Drugs like immunosuppressants and oral antiplatelets might retard cerebral vascular disease progression and flow abnormalities, respectively. PMID:22415466

  17. Vortex rings impinging on permeable boundaries

    NASA Astrophysics Data System (ADS)

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

    2015-01-01

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

  18. Studies on the structure and permeability of the microvasculature in normal rat lymph nodes.

    PubMed Central

    Anderson, A. O.; Anderson, N. D.

    1975-01-01

    The structure and permeability of the microvasculature in normal rat lymph nodes was studied by regional perfusion techniques. The results indicated that characteristic vascular units supplied each cortical lobule of lymphatic tissue. Numerous arteriovenous communications and venous sphincters innervated by unmyelinated nerve fibers were found in this vascular bed. These specialized vascular structures permitted regional control of blood flow through high endothelial venules. Lymphocytes migrated across these venular walls by moving through intercellular spaces in the endothelium and between gaps in the laminated, reticular sheath. No direct anastomoses between blood vessels and lymphatics were seen, but tracer studies with horseradish peroxidase suggested that functional lymph node-venous communications were present in the walls of high endothelial venules. Images Figure 17 Figure 18 Figure 19 Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 Figure 16 PMID:1163637

  19. Predicting skin permeability from complex chemical mixtures.

    PubMed

    Riviere, Jim E; Brooks, James D

    2005-10-15

    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(p) = c + mMF + a sigma alpha2(H) + b sigma beta2(H) + s pi2(H) + rR2 + vV(x) where sigma alpha2(H) is the hydrogen-bond donor acidity, sigma beta2(H) is the hydrogen-bond acceptor basicity, pi2(H) is the dipolarity/polarizability, R2 represents the excess molar refractivity, and V(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(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, R2 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. PMID:16183383

  20. Predicting skin permeability from complex chemical mixtures

    SciTech Connect

    Riviere, Jim E. . E-mail: Jim_Riviere@ncsu.edu; Brooks, James D.

    2005-10-15

    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.

  1. Plant Vascular Biology 2010

    SciTech Connect

    Ding, Biao

    2014-11-17

    This grant supported the Second International Conference on Plant Vascular Biology (PVB 2010) held July 24-28, 2010 on the campus of Ohio State University, Columbus, Ohio. Biao Ding (Ohio State University; OSU) and David Hannapel (Iowa State University; ISU) served as co-chairs of this conference. Biao Ding served as the local organizer. PVB is defined broadly here to include studies on the biogenesis, structure and function of transport systems in plants, under conditions of normal plant growth and development as well as of plant interactions with pathogens. The transport systems cover broadly the xylem, phloem, plasmodesmata and vascular cell membranes. The PVB concept has emerged in recent years to emphasize the integrative nature of the transport systems and approaches to investigate them.

  2. Pathophysiology of vascular dementia

    PubMed Central

    2009-01-01

    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. PMID:19895675

  3. Pelvic Vascular Malformations

    PubMed Central

    Christenson, Brian M.; Gipson, Matthew G.; Smith, Mitchell T.

    2013-01-01

    Vascular malformations (VMs) comprise a wide spectrum of lesions that are classified by content and flow characteristics. These lesions, occurring in both focal and diffuse forms, can involve any organ and tissue plane and can cause significant morbidity in both children and adults. Since treatment strategy depends on the type of malformation, correct diagnosis and classification of a vascular lesion are crucial. Slow-flow VMs (venous and lymphatic malformations) are often treated by sclerotherapy, whereas fast-flow lesions (arteriovenous malformations) are generally managed with embolization. In addition, some cases of VMs are best treated surgically. This review will present an overview of VMs in the female pelvis as well as a discussion of endovascular therapeutic techniques. PMID:24436563

  4. Vascular health in space.

    PubMed

    Hughson, R L; Shoemaker, J K

    2004-07-01

    Space flight induces many changes within the cardiovascular system that have the potential during long-duration space missions on the International Space Station to result in structural and functional changes in the vascular system. In this paper, we will first briefly review the potential changes in reflex control of the vascular system as observed primarily in short-duration studies of humans. We will then show how the reflex responses might interact with other changes anticipated during long-duration missions based on evidence from animal and human experimentation. This evidence points to the potential for changes in blood vessel structure, metabolism and responses to vasodilator and constrictor substances that might have long-term health consequences paralleling the effects of aging on the cardiovascular system. PMID:16235421

  5. Neurobiology of Vascular Dementia

    PubMed Central

    Enciu, Ana-Maria; Constantinescu, Stefan N.; Popescu, Lauren?iu M.; Mure?anu, Dafin F.; Popescu, Bogdan O.

    2011-01-01

    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. PMID:21876809

  6. Vascular Cambium Development

    PubMed Central

    Nieminen, Kaisa; Blomster, Tiina; Helariutta, Ykä; Mähönen, Ari Pekka

    2015-01-01

    Secondary phloem and xylem tissues are produced through the activity of vascular cambium, the cylindrical secondary meristem which arises among the primary plant tissues. Most dicotyledonous species undergo secondary development, among them Arabidopsis. Despite its small size and herbaceous nature, Arabidopsis displays prominent secondary growth in several organs, including the root, hypocotyl and shoot. Together with the vast genetic resources and molecular research methods available for it, this has made Arabidopsis a versatile and accessible model organism for studying cambial development and wood formation. In this review, we discuss and compare the development and function of the vascular cambium in the Arabidopsis root, hypocotyl, and shoot. We describe the current understanding of the molecular regulation of vascular cambium and compare it to the function of primary meristems. We conclude with a look at the future prospects of cambium research, including opportunities provided by phenotyping and modelling approaches, complemented by studies of natural variation and comparative genetic studies in perennial and woody plant species. PMID:26078728

  7. Vascular Lumen Formation

    PubMed Central

    Lammert, Eckhard; Axnick, Jennifer

    2012-01-01

    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 cellcell 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. PMID:22474612

  8. [Vascular erectile dysfunction].

    PubMed

    Odriozola, Ander Astobieta; Quintanilla, Mikel Gamarra; Arias, Jos Gregorio Pereira; Tamayo, Asier Leibar; Gonzlez, Gaspar Ibarluzea

    2010-10-01

    Vascular etiology is present in up to 60% of the patients with erectile dysfunction (ED). Both small vessel disease, such as that in diabetes mellitus, and arteriosclerosis of bigger size arteries, as in hypertension, cause arterial insufficiency and erectile dysfunction. Tobacco smoking alters the arterial hemodynamics in the penis, causing erectile dysfunction in a high percentage of advanced age smokers: pelvic arteries fibrosis and stenosis accelerates the existing arteriosclerosis. Venous occlusive dysfunction may be due to the decrease of corpora cavernosa compliance or tunica albuginea inherent anomalies. Vascular endothelial growth factor may play a role in the modulation of vascularization of the normal penile architecture. Various events, all of them important, may cause erectile dysfunction. Moreover, no cause can participate independently. A cascade of situations (including psychological factors as well as organic) may lead to erectile dysfunction. A continuous understanding of organic causes of erectile dysfunction will allow physicians to discover treatments for their correction, as well as to give confidence to the patient. PMID:20978287

  9. Pulmonary vascular imaging

    SciTech Connect

    Fedullo, P.F.; Shure, D.

    1987-03-01

    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.

  10. The adaptation of the blood-brain barrier to vascular endothelial growth factor and placental growth factor during pregnancy

    PubMed Central

    Schreurs, Malou P. H.; Houston, Emily M.; May, Victor; Cipolla, Marilyn J.

    2012-01-01

    Vascular endothelial growth factor (VEGF) and placental growth factor (PLGF) are increased in the maternal circulation during pregnancy. These factors may increase blood-brain barrier (BBB) permeability, yet brain edema does not normally occur during pregnancy. We therefore hypothesized that in pregnancy, the BBB adapts to high levels of these permeability factors. We investigated the influence of pregnancy-related circulating factors on VEGF-induced BBB permeability by perfusing cerebral veins with plasma from nonpregnant (NP) or late-pregnant (LP) rats (n=6/group) and measuring permeability in response to VEGF. The effect of VEGF, PLGF, and VEGF-receptor (VEGFR) activation on BBB permeability was also determined. Results showed that VEGF significantly increased permeability (×107 μm3/min) from 9.7 ± 3.5 to 21.0 ± 1.5 (P<0.05) in NP veins exposed to NP plasma, that was prevented when LP veins were exposed to LP plasma; (9.7±3.8; P>0.05). Both LP plasma and soluble FMS-like tyrosine-kinase 1 (sFlt1) in NP plasma abolished VEGF-induced BBB permeability in NP veins (9.5±2.9 and 12±2.6; P>0.05). PLGF significantly increased BBB permeability in NP plasma (18±1.4; P<0.05), and required only VEGFR1 activation, whereas VEGF-induced BBB permeability required both VEGFR1 and VEGFR2. Our findings suggest that VEGF and PLGF enhance BBB permeability through different VEGFR pathways and that circulating sFlt1 prevents VEGF- and PLGF-induced BBB permeability during pregnancy. —Schreurs, M. P. H., Houston, E. M., May, V., Cipolla, M. J. The adaptation of the blood-brain barrier to vascular endothelial growth factor and placental growth factor during pregnancy. PMID:21911594

  11. Paracellular versus transcellular intestinal permeability to gliadin peptides in active celiac disease.

    PubMed

    Mnard, Sandrine; Lebreton, Corinne; Schumann, Michael; Matysiak-Budnik, Tamara; Dugave, Christophe; Bouhnik, Yoram; Malamut, Georgia; Cellier, Christophe; Allez, Matthieu; Crenn, Pascal; Schulzke, Joerg Dieter; Cerf-Bensussan, Nadine; Heyman, Martine

    2012-02-01

    The intestinal permeability of undegraded ?9-gliadin peptide 31-49 (p31-49) and 33-mer gliadin peptides is increased in active celiac disease. Two distinct transport pathways have been proposed: paracellular leakage through epithelial tight junctions and protected transcellular transport. To analyze the relative contribution of these pathways, we compared mucosa-to-serosa permeability of small and large permeability markers [ionic conductance (G), mannitol, 182 Da; horseradish peroxidase, 40 kDa] and gliadin peptides [33-mer (p56-88, 3900 Da), 19-mer (p31-49, 2245 Da; and p202-220, 2127 Da), and 12-mer (p57-68, 1453 Da)] in duodenal biopsy specimens mounted in Ussing chambers. The permeability of intact peptides was much higher for p31-49 or 33-mer than for horseradish peroxidase, p202-220, and p57-68. A positive correlation was observed between G, an index of paracellular diffusion of ions, and mannitol permeability. The absence of correlation between G and permeability to intact 33-mer or p31-49 did not favor paracellular diffusion of the peptides. Immunofluorescence studies indicated that 33-mer enters the early endosome antigen 1-positive compartment but escapes the lysosomal-associated protein 2-positive compartment. The results underline that mannitol and ionic conductance G cannot be considered markers of permeability to gliadin peptides. In active celiac disease, increases in transcellular permeability to intact gliadin peptides might be considered in treatment strategies aimed at controlling epithelial permeability to gluten. PMID:22119716

  12. Plasma From Patients With HELLP Syndrome Increases Blood–Brain Barrier Permeability

    PubMed Central

    Tremble, Sarah M.; Owens, Michelle Y.; Morris, Rachael; Cipolla, Marilyn J.

    2015-01-01

    Circulating inflammatory factors and endothelial dysfunction have been proposed to contribute to the pathophysiology of hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. To date, the occurrence of neurological complications in these women has been reported, but few studies have examined whether impairment in blood–brain barrier (BBB) permeability or cerebrovascular reactivity is present in women having HELLP syndrome. We hypothesized that plasma from women with HELLP syndrome causes increased BBB permeability and cerebrovascular dysfunction. Posterior cerebral arteries from female nonpregnant rats were perfused with 20% serum from women with normal pregnancies (n = 5) or women with HELLP syndrome (n = 5), and BBB permeability and vascular reactivity were compared. Plasma from women with HELLP syndrome increased BBB permeability while not changing myogenic tone and reactivity to pressure. Addition of the nitric oxide (NO) synthase inhibitor Nω-nitro-l-arginine methyl ester caused constriction of arteries that was not different with the different plasmas nor was dilation to the NO donor sodium nitroprusside different between the 2 groups. However, dilation to the small- and intermediate-conductance, calcium-activated potassium channel activator NS309 was decreased in vessels exposed to HELLP plasma. Thus, increased BBB permeability in response to HELLP plasma was associated with selective endothelial dysfunction. PMID:25194151

  13. Permeability Calculation in a Fracture Network - 12197

    SciTech Connect

    Lee, Cheo Kyung; Kim, Hyo Won; Yim, Sung Paal

    2012-07-01

    Laminar flow of a viscous fluid in the pore space of a saturated fractured rock medium is considered to calculate the effective permeability of the medium. The effective permeability is determined from the flow field which is calculated numerically by using the finite element method. The computation of permeability components is carried out with a few different discretizations for a number of fracture arrangements. Various features such as flow field in the fracture channels, the convergence of permeability, and the variation of permeability among different fracture networks are discussed. The longitudinal permeability in general appears greater than the transverse ones. The former shows minor variations with fracture arrangement whereas the latter appears to be more sensitive to the arrangement. From the calculations of the permeability in a rock medium with a fracture network (two parallel fractures aligned in the direction of 45-deg counterclockwise from the horizontal and two connecting fractures(narrowing, parallel and widening) the following conclusions are drawn. 1. The permeability of fractured medium not only depends on the primary orientation of the main fractures but also is noticeably influenced by the connecting fractures in the medium. 2. The transverse permeability (the permeability in the direction normal to the direction of the externally imposed macro-scale pressure gradient) is only a fraction of the longitudinal one, but is sensitive to the arrangement of the connecting fractures. 3. It is important to figure out the pattern of the fractures that connect (or cross) the main fractures for reliable calculation of the transverse permeability. (authors)

  14. [Preoperative cardiac risk evaluation of vascular surgery patients].

    PubMed

    Van Damme, H; Larbuisson, R; Limet, R

    2003-06-01

    Peripheral vascular surgery (carotid, infrainguinal or aortoiliacal) is characterised by an increased cardiac risk with an infarction rate of 1 to 4%. Sixty percent of the vascular patients present a concomitant coronary artery disease, often infraclinically. Preoperative cardiac risk stratification aims at reducing cardiac related morbidity and mortality. A clinical risk profile (patient's past history) and non-invasive cardiac tests allow subdividing the vascular patients into three categories: high risk, intermediate risk, and low risk. High-risk patients (unstable angina, recent infarction, overt congestive heart failure and critical aortic valve stenosis) require immediate intensive management of their underlying cardiac disease. This means delay or annulation of the planned vascular operation. For intermediate risk patients, a clinical cardiac risk index based on patient's past history (stable angina, previous infarction or episode of congestive heart failure, age of 70 years or more and diabetes) offers a rough orientation. These clinical markers lack specificity, since they are found in almost all vascular patients. The adjunction of a non-invasive cardiac testing allows to optimise the cardiac risk evaluation. Stress echocardiography with dobutamine has become a very popular test, with a negative predicting value exceeding 90%, but with a lack of specificity (many vascular patients have an uneventful postoperative outcome, despite a positive dobutamine test). These inconsistent results of cardiac risk evaluation render their routine use questionable. Nowadays, the management of patients requiring vascular surgery is based on the concept that every vascular patient should be considered as suffering from coronary artery disease. A certain degree of myocardial protection should be offered to every vascular surgery candidate. A preoperative treatment with betablockers provides myocardial protection against the operative stress and lowers myocardial oxygen requirement. There are arguments to continue or start aspirin treatment in the preoperative period, in order to lower the risk of sudden coronary thrombosis. PMID:12945241

  15. Role of sulfhydryls in mucosal injury caused by ethanol: relation to microvascular permeability, gastric motility and cytoprotection

    SciTech Connect

    Takeuchi, K.; Okada, M.; Niida, H.; Okabe, S.

    1989-02-01

    The relationship between gastric mucosal glutathione (GSH) levels, vascular permeability, gastric motility and mucosal injury caused by ethanol was investigated in rats. Oral administration of 50% ethanol (1 ml) produced elongated reddish bands of lesions in the mucosa with a significant reduction of GSH levels and increase of microvascular permeability. These lesions were significantly inhibited by pretreatment with s.c. administered diethylmaleate (DEM: 1 ml/kg), cysteamine (100 mg/kg) and 16, 16-dimethyl prostaglandin E2 (dmPGE2, 10 micrograms/kg) but worsened markedly by N-ethylmaleimide (NEM: 10 mg/kg). Irrespective of whether the animals were treated with 50% ethanol or not, the mucosal GSH levels were significantly decreased or increased, respectively, by DEM or cysteamine, and were not affected by both NEM and dmPGE2. NEM significantly enhanced the vascular permeability in the absence or presence of ethanol (greater than 10%), whereas other agents significantly inhibited only the increased vascular permeability caused by ethanol. On the other hand, gastric motility was potently and persistently inhibited by either DEM, cysteamine or dmPGE2 at the doses which prevented ethanol-induced mucosal injury, whereas NEM had no effect on the motility. These results suggest that 1) the mucosal GSH levels do not relate directly to either development or prevention of ethanol-induced gastric injury, 2) potentiation by NEM of the mucosal injury may be accounted for by its enhancement of the vascular permeability and 3) inhibition of gastric motility may be associated with prevention of mucosal lesions.

  16. Effect of Dead Algae on Soil Permeability

    SciTech Connect

    Harvey, R.S.

    2003-02-21

    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.

  17. SOIL-AIR PERMEABILITY METHOD EVALUATION

    EPA Science Inventory

    The feasibility of soil vapor extraction (SVE) is, in part, based on vadose zone soil-air permeability. ield, laboratory and empirical correlation methods for estimating soil-air permeability have been reviewed for their appropriateness in determining SVE feasibility, and the dev...

  18. Influence of fiber packing structure on permeability

    NASA Technical Reports Server (NTRS)

    Cai, Zhong; Berdichevsky, Alexander L.

    1993-01-01

    The study on the permeability of an aligned fiber bundle is the key building block in modeling the permeability of advanced woven and braided preforms. Available results on the permeability of fiber bundles in the literature show that a substantial difference exists between numerical and analytical calculations on idealized fiber packing structures, such as square and hexagonal packing, and experimental measurements on practical fiber bundles. The present study focuses on the variation of the permeability of a fiber bundle under practical process conditions. Fiber bundles are considered as containing openings and fiber clusters within the bundle. Numerical simulations on the influence of various openings on the permeability were conducted. Idealized packing structures are used, but with introduced openings distributed in different patterns. Both longitudinal and transverse flow are considered. The results show that openings within the fiber bundle have substantial effect on the permeability. In the longitudinal flow case, the openings become the dominant flow path. In the transverse flow case, the fiber clusters reduce the gap sizes among fibers. Therefore the permeability is greatly influenced by these openings and clusters, respectively. In addition to the porosity or fiber volume fraction, which is commonly used in the permeability expression, another fiber bundle status parameter, the ultimate fiber volume fraction, is introduced to capture the disturbance within a fiber bundle.

  19. A method of determination of permeability

    SciTech Connect

    Kuznetsov, S.V.; Trofimov, V.A.

    2007-11-15

    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.

  20. Permeability-porosity data sets for sandstones

    USGS Publications Warehouse

    Nelson, P.H.

    2004-01-01

    Due to the variable nature of permeability-porosity relations, core should be obtained and permeability (k) and porosity (??) should be determined on core plugs in the laboratory for the formation of interest. A catalog of k versus (??) data sets is now available on the Web. Examples from the catalog are considered to illustrate some aspects of k versus ?? dependencies in siliciclastic reservoirs.

  1. Low-level X-radiation effects on functional vascular changes in Syrian hamster cheek pouch epithelium during hydrocarbon carcinogenesis

    SciTech Connect

    Lurie, A.G.; Coghill, J.E.; Rippey, R.M.

    1985-07-01

    Effects of repeated low-level X radiation on functional microvascular changes in hamster cheek pouch epithelium during and following carcinogenesis by 7,12-dimethylbenz(a)anthracene (DMBA) were studied. Hamsters were treated with either radiation, DMBA, radiation + DMBA, or no treatment. Animals were sacrificed at 3-week intervals from 0 to 39 weeks after treatments began. Pouch vascular volume and permeability changes were studied by fractional distributions of radiotracers and were analyzed by a variety of statistical methods which explored the vascular parameters, treatment types, elapsed time, presence of the carcinogen, and histopathologic changes. All treatments resulted in significant changes in vascular volume with time, while only DMBA treatments alone resulted in significant changes in vascular permeability with time. As in prior studies, there were significant vascular volume differences between DMBA and DMBA + radiation groups of tumor-bearing cheek pouches. Radiation significantly affected DMBA-associated vascular volume and permeability changes during carcinogenesis. Several possible explanations for the relationship of these changes to the enhancement of DMBA carcinogenesis are discussed.

  2. Composites with tuned effective magnetic permeability

    NASA Astrophysics Data System (ADS)

    Amirkhizi, Alireza V.; Nemat-Nasser, Sia

    2007-07-01

    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)].

  3. Functional states of resident vascular stem cells and vascular remodeling

    PubMed Central

    Leach, Desiree F.; Nagarkatti, Mitzi; Nagarkatti, Prakash; Cui, Taixing

    2015-01-01

    Recent evidence indicates that different types of vascular stem cells (VSCs) reside within the mural layers of arteries and veins. The precise identities of these resident VSCs are still unclear; generally, postnatal vasculature contains multilineage stem cells and vascular cell lineage-specific progenitor/stem cells which may participate in both vascular repair and lesion formation. However, the underlying mechanism remains poorly understood. In this review, we summarize the potential molecular mechanisms, which may control the quiescence and activation of resident VSCs and highlight a notion that the differential states of resident VSCs are directly linked to vascular repair or lesion formation. PMID:26913049

  4. Targeting vascular and leukocyte communication in angiogenesis, inflammation and fibrosis.

    PubMed

    Kreuger, Johan; Phillipson, Mia

    2016-02-01

    Regulation of vascular permeability, recruitment of leukocytes from blood to tissue and angiogenesis are all processes that occur at the level of the microvasculature during both physiological and pathological conditions. The interplay between microvascular cells and leukocytes during inflammation, together with the emerging roles of leukocytes in the modulation of the angiogenic process, make leukocyte-vascular interactions prime targets for therapeutics to potentially treat a wide range of diseases, including pathological and dysfunctional vessel growth, chronic inflammation and fibrosis. In this Review, we discuss how the different cell types that are present in and around microvessels interact, cooperate and instruct each other, and in this context we highlight drug targets as well as emerging druggable processes that can be exploited to restore tissue homeostasis. PMID:26612664

  5. Vascular Endothelial growth factor signaling in hypoxia and Inflammation

    PubMed Central

    Ramakrishnan, S.; Anand, Vidhu; Roy, Sabita

    2014-01-01

    Infection, cancer and cardiovascular diseases are the major causes for morbidity and mortality in the United States according to the Center for Disease Control. The underlying etiology that contributes to the severity of these diseases is either hypoxia induced inflammation or inflammation resulting in hypoxia. Therefore, molecular mechanisms that regulate hypoxia-induced adaptive responses in cells are important areas of investigation. Oxygen availability is sensed by molecular switches which regulate synthesis and secretion of growth factors and inflammatory mediators. As a consequence, tissue microenvironment is altered by reprogramming metabolic pathways, angiogenesis, vascular permeability, pH homeostasis to facilitate tissue remodeling. Hypoxia inducible factor (HIF) is the central mediator of hypoxic response. HIF regulates several hundred genes and vascular endothelial growth factor (VEGF) is one of the primary target genes. Understanding the regulation of HIF and its influence on inflammatory response offers unique opportunities for drug development to modulate inflammation and ischemia in pathological conditions. PMID:24610033

  6. Vascular endothelial hyperpermeability induces the clinical symptoms of Clarkson disease (the systemic capillary leak syndrome)

    PubMed Central

    Xie, Zhihui; Ghosh, Chandra C.; Patel, Roshni; Iwaki, Shoko; Gaskins, Donna; Nelson, Celeste; Jones, Nina; Greipp, Philip R.

    2012-01-01

    The systemic capillary leak syndrome (SCLS) is a rare disorder characterized by transient episodes of hypotensive shock and anasarca thought to arise from reversible microvascular barrier dysfunction. Although the high prevalence of a monoclonal gammopathy of unknown significance in SCLS suggests a pathogenic contribution of endogenous immunoglobulins, the mechanisms of vascular hyperpermeability remain obscure. Herein, we report clinical and molecular findings on 23 patients, the largest SCLS case series to date. Application of episodic SCLS sera, but neither the purified immunoglobulin fraction nor sera obtained from patients during remission, to human microvascular endothelial cells caused vascular endothelial cadherin internalization, disruption of interendothelial junctions, actin stress fiber formation, and increased permeability in complementary functional assays without inducing endothelial apoptosis. Intravenous immunoglobulin, one promising therapy for SCLS, mitigated the permeability effects of episodic sera. Consistent with the presence of endogenous, nonimmunoglobulin, circulating permeability factor(s) constrained to SCLS episodes, we found that vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang2), were elevated in episodic SCLS sera but not in remission sera. Ab-based inhibition of Ang2 counteracted permeability induced by episodic SCLS sera. Comparable experiments with anti-VEGF Ab (bevacizumab) yielded less interpretable results, probably because of endothelial toxicity of VEGF withdrawal. Our results support a model of SCLS pathogenesis in which nonimmunoglobulin humoral factors such as VEGF and Ang2 contribute to transient endothelial contraction, suggesting a molecular mechanism for this highly lethal disorder. PMID:22411873

  7. Compact rock material gas permeability properties

    NASA Astrophysics Data System (ADS)

    Wang, Huanling; Xu, Weiya; Zuo, Jing

    2014-09-01

    Natural compact rocks, such as sandstone, granite, and rock salt, are the main materials and geological environment for storing underground oil, gas, CO2, shale gas, and radioactive waste because they have extremely low permeabilities and high mechanical strengths. Using the inert gas argon as the fluid medium, the stress-dependent permeability and porosity of monzonitic granite and granite gneiss from an underground oil storage depot were measured using a permeability and porosity measurement system. Based on the test results, models for describing the relationships among the permeability, porosity, and confining pressure of rock specimens were analyzed and are discussed. A power law is suggested to describe the relationship between the stress-dependent porosity and permeability; for the monzonitic granite and granite gneiss (for monzonitic granite (A-2), the initial porosity is approximately 4.05%, and the permeability is approximately 10-19 m2; for the granite gneiss (B-2), the initial porosity is approximately 7.09%, the permeability is approximately 10-17 m2; and the porosity-sensitivity exponents that link porosity and permeability are 0.98 and 3.11, respectively). Compared with moderate-porosity and high-porosity rocks, for which ? > 15%, low-porosity rock permeability has a relatively lower sensitivity to stress, but the porosity is more sensitive to stress, and different types of rocks show similar trends. From the test results, it can be inferred that the test rock specimens' permeability evolution is related to the relative particle movements and microcrack closure.

  8. Vascular effects of flavonoids.

    PubMed

    Almeida Rezende, Bruno; Pereira, Aline Carvalho; Cortes, Steyner F; Lemos, Virginia Soares

    2016-01-01

    Flavonoids are natural plant-derived polyphenolic compounds with various biological properties particularly in the cardiovascular system, including antiatherogenic, antioxidant, vasodilation, antihypertensive, and antiplatelet activities. These biological properties have been evaluated in several experimental and clinical studies. In addition, extensive reviews have discussed the antiatherogenic effect of these polyphenols. However, limited studies have investigated the potential therapeutic vascular effects of these compounds. This review brings together some recent studies, to establish the different signaling pathways involved in the molecular mechanisms that underlie the vasodilation induced by flavonoids. PMID:26555950

  9. The pathobiology of vascular dementia

    PubMed Central

    Iadecola, Costantino

    2013-01-01

    Vascular cognitive impairment defines alterations in cognition, ranging from subtle deficits to full-blown dementia, attributable to cerebrovascular causes. Often coexisting with Alzheimer’s disease, mixed vascular and neurodegenerative dementia has emerged as the leading cause of age-related cognitive impairment. Central to the disease mechanism is the crucial role that cerebral blood vessels play in brain health, not only for the delivery of oxygen and nutrients, but also for the trophic signaling that links inextricably the well being of neurons and glia to that of cerebrovascular cells. This review will examine how vascular damage disrupts these vital homeostatic interactions, focusing on the hemispheric white matter, a region at heightened risk for vascular damage, and on the interplay between vascular factors and Alzheimer’s disease. Finally, preventative and therapeutic prospects will be examined, highlighting the importance of midlife vascular risk factor control in the prevention of late-life dementia. PMID:24267647

  10. ROCK2 primes the endothelium for vascular hyperpermeability responses by raising baseline junctional tension

    PubMed Central

    Beckers, Cora M.L.; Knezevic, Nebojsa; Valent, Erik T.; Tauseef, Mohammad; Krishnan, Ramaswamy; Rajendran, Kavitha; Hardin, C. Corey; Aman, Jurjan; van Bezu, Jan; Sweetnam, Paul; van Hinsbergh, Victor W.M.; Mehta, Dolly; van Nieuw Amerongen, Geerten P.

    2015-01-01

    Rho kinase mediates the effects of inflammatory permeability factors by increasing actomyosin-generated traction forces on endothelial adherens junctions, resulting in disassembly of intercellular junctions and increased vascular leakage. In vitro, this is accompanied by the Rho kinase-driven formation of prominent radial F-actin fibers, but the in vivo relevance of those F-actin fibers has been debated, suggesting other Rho kinase-mediated events to occur in vascular leak. Here, we delineated the contributions of the highly homologous isoforms of Rho kinase (ROCK1 and ROCK2) to vascular hyperpermeability responses. We show that ROCK2, rather than ROCK1 is the critical Rho kinase for regulation of thrombin receptor-mediated vascular permeability. Novel traction force mapping in endothelial monolayers, however, shows that ROCK2 is not required for the thrombin-induced force enhancements. Rather, ROCK2 is pivotal to baseline junctional tension as a novel mechanism by which Rho kinase primes the endothelium for hyperpermeability responses, independent from subsequent ROCK1-mediated contractile stress-fiber formation during the late phase of the permeability response. PMID:25869521

  11. ROCK2 primes the endothelium for vascular hyperpermeability responses by raising baseline junctional tension.

    PubMed

    Beckers, Cora M L; Knezevic, Nebojsa; Valent, Erik T; Tauseef, Mohammad; Krishnan, Ramaswamy; Rajendran, Kavitha; Hardin, C Corey; Aman, Jurjan; van Bezu, Jan; Sweetnam, Paul; van Hinsbergh, Victor W M; Mehta, Dolly; van Nieuw Amerongen, Geerten P

    2015-07-01

    Rho kinase mediates the effects of inflammatory permeability factors by increasing actomyosin-generated traction forces on endothelial adherens junctions, resulting in disassembly of intercellular junctions and increased vascular leakage. In vitro, this is accompanied by the Rho kinase-driven formation of prominent radial F-actin fibers, but the in vivo relevance of those F-actin fibers has been debated, suggesting other Rho kinase-mediated events to occur in vascular leak. Here, we delineated the contributions of the highly homologous isoforms of Rho kinase (ROCK1 and ROCK2) to vascular hyperpermeability responses. We show that ROCK2, rather than ROCK1 is the critical Rho kinase for regulation of thrombin receptor-mediated vascular permeability. Novel traction force mapping in endothelial monolayers, however, shows that ROCK2 is not required for the thrombin-induced force enhancements. Rather, ROCK2 is pivotal to baseline junctional tension as a novel mechanism by which Rho kinase primes the endothelium for hyperpermeability responses, independent from subsequent ROCK1-mediated contractile stress-fiber formation during the late phase of the permeability response. PMID:25869521

  12. Phosphodiesterase 4 inhibition attenuates atrial natriuretic peptide-induced vascular hyperpermeability and loss of plasma volume.

    PubMed

    Lin, Yueh-Chen; Samardzic, Haris; Adamson, Roger H; Renkin, Eugene M; Clark, Joyce F; Reed, Rolf K; Curry, Fitz-Roy E

    2011-01-15

    Inhibition of phosphodiesterase 4 (PDE4) to increase endothelial cAMP and stabilize the endothelial barrier attenuates acute inflammatory increases in vascular permeability.We extended this approach to attenuate physiological increases in vascular permeability in response to atrial natriuretic peptide (ANP), which acts with the kidney to regulate plasma volume. We measured blood-to-tissue albumin clearance and changes in plasma volume in isoflurane-anaesthetized mice (C57BL/6J) pre-treated with rolipram (8 mg kg(-1) I.P., 30 min). Rolipram significantly reduced albumin permeability, measured using a dual-label fluorescence method, in skin and skeletal muscle compared with ANP alone (500 ng kg(-1) min(-1)). Skin and muscle tissue accounted for 70% of the reduction in whole body albumin clearance taking into account albumin clearance in gastrointestinal (GI) tissue, heart and kidney. The action of ANP and rolipram to modify albumin clearances in duodenum and jejunum could be accounted for by local increases in vascular perfusion to increase surface area for exchange. ANP increased haematocrit from 40.6% to 46.8%, corresponding to an average loss of 22% plasma fluid volume (227 ?l), and this was almost completely reversed with rolipram. Renal water excretion accounted for less than 30% of plasma fluid loss indicating that reduced albumin permeability and reduced filtration into vasodilated GI tissue were the predominant actions of PDE4 inhibition. Similar fluid retention was measured in mice with endothelial-restricted deletion of the guanylyl cyclase-A receptor for ANP. Stabilizing the endothelial barrier to offset ANP-induced increases in vascular permeability may be part of a strategy to maintain plasma volume. PMID:21098005

  13. Vascular endothelial growth factor from embryonic status to cardiovascular pathology

    PubMed Central

    Azimi-Nezhad, Mohsen

    2014-01-01

    Vascular endothelial growth factor (VEGF) is a multifunctional cytokine with distinct functions in angiogenesis, lymphangiogenesis, vascular permeability, and hematopoiesis. VEGF is a highly conserved, disulfide-bonded dimeric glycoprotein of 34 to 45 kDa produced by several cell types including fibroblasts, neutrophils, endothelial cells, and peripheral blood mononuclear cells, particularly T lymphocytes and macrophages. Six VEGF isoforms are generated as a result of alternative splicing from a single VEGF gene, consisting of 121, 145, 165, 183, 189, or 206 amino acids. VEGF121, VEGF145, and VEGF165 are secreted whereas VEGF183, VEGF189, and VEGF206 are cell membrane-bound. VEGF145 has a key role during the vascularization of the human ovarian follicle and corpus luteum, in the placentation and embryonic periods, and in bone and wound healing, while VEGF165 is the most abundant and biologically active isoform. VEGF has been linked with a number of vascular pathologies including cardiovascular diseases such ischemic heart disease, heart failure, stroke, and diabetes and its related complications. In this review we aimed to present some important roles of VEGF in a number of clinical issues and indicate its involvement in several phenomena from the initial steps of the embryonic period to cardiovascular diseases. PMID:26989723

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

    PubMed Central

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

    1985-01-01

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

  15. Diagnostically Challenging Epithelioid Vascular Tumors.

    PubMed

    Ko, Jennifer S; Billings, Steven D

    2015-09-01

    The diagnosis of vascular tumors is a challenging area in soft tissue pathology. Epithelioid vascular tumors pose a particular challenge. Due to the epithelioid morphology of the tumor cells, they can be misdiagnosed as a variety of other entities, including metastatic carcinoma or epithelioid sarcoma. Furthermore, it can be difficult to distinguish between different epithelioid vascular tumors. This review focuses on vascular tumors characterized by epithelioid endothelial cells, including epithelioid hemangioma, cutaneous epithelioid angiomatous nodule, epithelioid hemangioendothelioma, epithelioid sarcomalike hemangioendothelioma/pseudomyogenic hemangioendothelioma, and epithelioid angiosarcoma. PMID:26297060

  16. Vascular Distribution of Nanomaterials

    PubMed Central

    Stapleton, Phoebe A.; Nurkiewicz, Timothy R.

    2014-01-01

    Once considered primarily occupational, novel nanotechnology innovation and application has led to widespread domestic use and intentional biomedical exposures. With these exciting advances, the breadth and depth of toxicological considerations must also be expanded. The vascular system interacts with every tissue in the body, striving to homeostasis. Engineered nanomaterials (ENM) have been reported to distribute in many different organs and tissues. However, these observations have tended to use approaches requiring tissue homogenization and/or gross organ analyses. These techniques, while effective in establishing presence, preclude an exact determination of where ENM are deposited within a tissue. It is necessary to identify this exact distribution and deposition of ENM throughout the cardiovascular system, with respect to vascular hemodynamics and in vivo/ in vitro ENM modifications taken into account if nanotechnology is to achieve its full potential. Distinct levels of the vasculature will first be described as individual compartments. Then the vasculature will be considered as a whole. These unique compartments and biophysical conditions will be discussed in terms of their propensity to favor ENM deposition. Understanding levels of the vasculature will also be discussed. Ultimately, future studies must verify the mechanisms speculated on and presented herein. PMID:24777845

  17. [Classification of vascular neoplasms].

    PubMed

    Hundeiker, M

    1978-11-01

    Neoplasms of blood and lymph vessels differ from angiectatic and angiokeratotic nevi by real proliferating growth. According to their features of growth and their wall structures, they are classified into three main groups: angiomas, glomangiomas and malignant vascular tumors. Within the angiomas on the one hand, capillary angiomas are classified into: planotuberous and tuberonodous angiomas of childhood and Kasabach-Merritt syndrome, multilocular hemangiomatosis, progressive multiple angiomas, tardive ("senile") angiomas, eruptive angiomas (granulomata pediculata), papular angioplasia, gemmangioma, and benign juvenile hemangioendothelioma. On the other hand, cavernous angiomas, i.e. arterial and venous cavernomas, as well as blue rubberbleb nevus, Mafucci's syndrome, angioleiomyoma, benign juvenile hemangiopericytoma and cavernous lymphangioma, form thick walled structures without involution. Glomangiomas occur as solitary, multiple systematized, and multiple disseminated and familiar forms. Within the group of malignant vascular tumors--Kaposi sarcoma, lymphangiosarcoma in lymphedema, hemangioendothelioma and angioplastic reticulosarcoma, hemangio- or lymphangiosarcoma, angioendotheliomastosis proliferans, rarity and increasing loss of characteristic differentiated structures give rise to difficulties in nosologic classification. PMID:214413

  18. Tumoral and Choroidal Vascularization

    PubMed Central

    Jost, Maud; Maillard, Catherine; Lecomte, Julie; Lambert, Vincent; Tjwa, Marc; Blaise, Pierre; Alvarez Gonzalez, Maria-Luz; Bajou, Khalid; Blacher, Silvia; Motte, Patrick; Humblet, Chantal; Defresne, Marie Paule; Thiry, Marc; Frankenne, Francis; Gothot, Andr; Carmeliet, Peter; Rakic, Jean-Marie; Foidart, Jean-Michel; Nol, Agns

    2007-01-01

    An adequate balance between serine proteases and their plasminogen activator inhibitor-1 (PAI-1) is critical for pathological angiogenesis. PAI-1 deficiency in mice is associated with impaired choroidal neovascularization (CNV) and tumoral angiogenesis. In the present work, we demonstrate unexpected differences in the contribution of bone marrow (BM)-derived cells in these two processes regulated by PAI-1. PAI-1?/? mice grafted with BM-derived from wild-type mice were able to support laser-induced CNV formation but not skin carcinoma vascularization. Engraftment of irradiated wild-type mice with PAI-1?/? BM prevented CNV formation, demonstrating the crucial role of PAI-1 delivered by BM-derived cells. In contrast, the transient infiltration of tumor transplants by local PAI-1-producing host cells rather than by BM cells was sufficient to rescue tumor growth and angiogenesis in PAI-1-deficient mice. These data identify PAI-1 as a molecular determinant of a local permissive soil for tumor angiogenesis. Altogether, the present study demonstrates that different cellular mechanisms contribute to PAI-1-regulated tumoral and CNV. PAI-1 contributes to BM-dependent choroidal vascularization and to BM-independent tumor growth and angiogenesis. PMID:17717143

  19. Understanding vascular development

    PubMed Central

    Udan, Ryan S.; Culver, James C.; Dickinson, Mary E.

    2014-01-01

    The vasculature of an organism has the daunting task of connecting all the organ systems to nourish tissue and sustain life. This complex network of vessels and associated cells must maintain blood flow but constantly adapt to acute and chronic changes within tissues. While the vasculature has been studied for over a century, we are just beginning to understand the processes that regulate its formation and how genetic hierarchies are influenced by mechanical and metabolic cues to refine vessel structure and optimize efficiency. As we gain insights into the developmental mechanisms, it is clear that the processes that regulate blood vessel development can also enable the adult to adapt to changes in tissues that can be elicited by exercise, aging, injury, or pathology. Thus, research in vessel development has provided tremendous insights into therapies for vascular diseases and disorders, cancer interventions, wound repair and tissue engineering, and in turn, these models have clearly impacted our understanding of development. Here we provide an overview of the development of the vascular system, highlighting several areas of active investigation and key questions that remain to be answered. PMID:23799579

  20. Neurocutaneous vascular syndromes.

    PubMed

    Puttgen, Katherine B; Lin, Doris D M

    2010-10-01

    There have been significant recent advances in the past several years in the field of neurocutaneous vascular syndromes, including the development of more stringent diagnostic criteria for PHACE syndrome, the renaming of macrocephaly-cutis marmorata telangiectatica congenita to macrocephaly-capillary malformation to accurately reflect the true nature of the syndrome, and discovery of new genetic mutations such as RASA-1. There have also been advances in the understanding and management of Sturge-Weber syndrome.PHACE syndrome is a constellation of neurologic, arterial, cardiac, ophthalmologic, and sternal abnormalities associated with infantile hemangiomas. PHACE is an acronym for Posterior fossa malformation, Hemangioma, Arterial anomalies, Coarctation of the aorta, Eye abnormalities. Some authors include an "S" for PHACE(S) to denote the association of ventral defects including Sternal clefting and Supraumbilical raphe.The accurate diagnosis and work-up of these patients require coordination of care across multiple disciplines, including neuroradiology, radiology, dermatology, neurology, surgery, and interventional radiology, among others.This paper is meant to update clinicians and researchers about important advances in these rare, important vascular syndromes, to improve care, and lay the foundation for future directions for research. PMID:20582592

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

    NASA Astrophysics Data System (ADS)

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

    2010-05-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-06-01

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

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

    PubMed Central

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

    2015-01-01

    Vascular integrity is important in maintaining homeostasis of brain microenvironments. In various brain diseases including Alzheimers disease, stroke, and multiple sclerosis, increased paracellular permeability due to breakdown of blood-brain barrier is linked with initiation and progression of pathological conditions. We developed a capacitance sensor array to monitor dielectric responses of cerebral endothelial cell monolayer, which could be utilized to evaluate the integrity of brain microvasculature. Our system measured real-time capacitance values which demonstrated frequency- and time-dependent variations. With the measurement of capacitance at the frequency of 100?Hz, we could differentiate the effects of vascular endothelial growth factor (VEGF), a representative permeability-inducing factor, on endothelial cells and quantitatively analyse the normalized values. Interestingly, we showed differential capacitance values according to the status of endothelial cell monolayer, confluent or sparse, evidencing that the integrity of monolayer was associated with capacitance values. Another notable feature was that we could evaluate the expression of molecules in samples in our system with the reference of real-time capacitance values. We suggest that this dielectric spectroscopy system could be successfully implanted as a novel in vitro assay in the investigation of the roles of paracellular permeability in various brain diseases. PMID:26047027

  4. A Poroelastic Description of Permeability Evolution

    NASA Astrophysics Data System (ADS)

    Hassanzadegan, Alireza; Zimmermann, Gnter

    2014-07-01

    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.

  5. Permeability evolution during densification of magma

    NASA Astrophysics Data System (ADS)

    Wadsworth, Fabian B.; Scheu, Bettina; Heap, Michael; Schipper, C. Ian; Vasseur, Jeremie; Kennedy, Ben; von Aulock, Felix W.; Lavallee, Yan; Kendrick, Jackie E.; Dingwell, Donald B.

    2015-04-01

    Constraint of the gas permeability of magmas is of key importance to estimating outgassing timescales and the evolution of pore-space overpressure. Once magma develops a permeable pore phase over a sufficient lengthscale, densification will ensue. Densification can be driven by surface tension during the minimisation of internal surface area, by gravitational compaction or by anisotropic shear strain. In all cases, the evolution of permeability is not well constrained. We provide a suite of experiments using both natural and synthetic magmas with a wide range of initial pore volume fractions and geometries. In the first subset of experiments we bathe the magma in argon and measure the temporal evolution of the porosity during surface-tension driven densification. In the second subset, we apply an additional uniaxial load to the magma. In both scenarios we measure the gas permeability before and after experimentation. We find that there are unique trajectories of the porosity permeability relationship depending on the densification mechanism. This demonstrates the paucity of simple models for the description of porosity permeability relationships in magmas. We propose that densification should happen rapidly in volcanic conduits between eruptions and that permeable outgassing scenarios may be complicated by this process.

  6. Permeability profiles -- key to reservoir management

    SciTech Connect

    Georgi, D.; Kasap, E.; Tang, X.; Cheng, A.

    1998-06-01

    Three-dimensional seismic data being collected routinely today offer those responsible for reservoir management a detailed picture of the configuration of the subsurface. Often, the porosity of reservoir rocks can also be deduced. However, knowing porosity exists, i.e., that there is pore space and vugs for the storage of hydrocarbons, is important but valueless if hydrocarbons cannot be made to flow into wells. Permeability is the quantity that measures flow capability. Having a permeability profile is the key to reservoir management. Accurate values can be obtained from cores taken during drilling; however, cutting cores is expensive and cores taken to the surface may be damaged or not representative of the reservoir rock of interest. Rotary coring can provide limited permeability data but, generally, insufficient data are available to develop a permeability profile. Here, the authors are concerned with measuring permeability with instruments placed in a well or used for logging a well. They shall discuss permeability-measuring methods available from Western Atlas Logging Services (WALS). Together, they make it possible to obtain continuous permeability in any well without coring or extensive well testing.

  7. Using magnetic permeability bits to store information

    NASA Astrophysics Data System (ADS)

    Timmerwilke, John; Petrie, J. R.; Wieland, K. A.; Mencia, Raymond; Liou, Sy-Hwang; Cress, C. D.; Newburgh, G. A.; Edelstein, A. S.

    2015-10-01

    Steps are described in the development of a new magnetic memory technology, based on states with different magnetic permeability, with the capability to reliably store large amounts of information in a high-density form for decades. The advantages of using the permeability to store information include an insensitivity to accidental exposure to magnetic fields or temperature changes, both of which are known to corrupt memory approaches that rely on remanent magnetization. The high permeability media investigated consists of either films of Metglas 2826 MB (Fe40Ni38Mo4B18) or bilayers of permalloy (Ni78Fe22)/Cu. Regions of films of the high permeability media were converted thermally to low permeability regions by laser or ohmic heating. The permeability of the bits was read by detecting changes of an external 32 Oe probe field using a magnetic tunnel junction 10 ?m away from the media. Metglas bits were written with 100 ?s laser pulses and arrays of 300?nm diameter bits were read. The high and low permeability bits written using bilayers of permalloy/Cu are not affected by 10 Mrad(Si) of gamma radiation from a 60Co source. An economical route for writing and reading bits as small at 20?nm using a variation of heat assisted magnetic recording is discussed.

  8. Fluid permeability of deformable fracture networks

    SciTech Connect

    Brown, S.R.; Bruhn, R.L.

    1997-04-01

    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.

  9. Permeability and porosity of dental casting investments.

    PubMed

    Ballard, G T; Leinfelder, K F; Taylor, D F

    1975-08-01

    Permeability of various gypsum- and phosphate-bonded investments was measured during conventional burn-out procedures. Porosity determinations were made on specimens cooled to room temperature after burn-out. As a group, the gypsum-bonded investments were found to be more permeable than the phosphate-bonded investments. Two phosphate-bonded investments were determined to be relatively impermeable to gas flow, while another exhibited permeability comparable to that of the gypsum-bonded investments. In spite of differences in permeability, the porosity of each type of investment was nearly constant. The porosity of the phosphate-bonded investment was approximately three-fourths that of the gypsum investments. These investments were modified by the addition of varying amounts of acrylic polymer for the purpose of altering permeability. The addition of acrylic polymer increased porosity and permeability of all of the materials included in this investigation. The acrylic additives, however, had no effect on the permeability of relatively impermeable investments unless used in high concentration. The results of this investigation would tend to substantiate the need for special spruing and venting procedures. PMID:125332

  10. Changes in Permeability Produced By Distant Earthquakes

    NASA Astrophysics Data System (ADS)

    Manga, M.; Wang, C. Y.; Shi, Z.

    2014-12-01

    Oscillations in stress, such as those created by earthquakes, can increase permeability and fluid mobility in geologic media. In natural systems, strain amplitudes as small as 10-6 can increase discharge in streams and springs, change the water level of wells, and enhance production from petroleum reservoirs. Enhanced permeability typically recovers to pre-stimulated values over a period of months to years. This presentation will review some of the observations that indicate that dynamic stresses produced by seismic waves change permeability. We use the response of a set of wells distributed throughout China to multiple large earthquakes to probe the relationship between earthquake-generated stresses and water-level changes in wells. We find that dynamic stresses dominate the responses at distances more than 1 fault length from the earthquake and that permeability changes may explain the water level changes. Regions with high deformation rates are most sensitive to seismic waves. We also consider the response of a large alluvial fan in Taiwan to the 1999 M7.5 Chi-Chi earthquake where there were sustained changes in groundwater temperature after the earthquake. Using groundwater flow models, we infer that permeability increased by an order of magnitude over horizontal scales of tens of km, and vertical scales of several km. Permeability returned to the pre-earthquake value over many months. As much as half the total transport in the fan occurs during the short time periods with enhanced permeability.

  11. Permeable Gas Flow Influences Magma Fragmentation Speed.

    NASA Astrophysics Data System (ADS)

    Richard, D.; Scheu, B.; Spieler, O.; Dingwell, D.

    2008-12-01

    Highly viscous magmas undergo fragmentation in order to produce the pyroclastic deposits that we observe, but the mechanisms involved remain unclear. The overpressure required to initiate fragmentation depends on a number of physical parameters, such as the magma's vesicularity, permeability, tensile strength and textural properties. It is clear that these same parameters control also the speed at which a fragmentation front travels through magma when fragmentation occurs. Recent mathematical models of fragmentation processes consider most of these factors, but permeable gas flow has not yet been included in these models. However, it has been shown that permeable gas flow through a porous rock during a sudden decompression event increases the fragmentation threshold. Fragmentation experiments on natural samples from Bezymianny (Russia), Colima (Mexico), Krakatau (Indonesia) and Augustine (USA) volcanoes confirm these results and suggest in addition that high permeable flow rates may increase the speed of fragmentation. Permeability from the investigated samples ranges from as low as 5 x 10-14 to higher than 9 x 10- 12 m2 and open porosity ranges from 16 % to 48 %. Experiments were performed for each sample series at applied pressures up to 35 MPa. Our results indicate that the rate of increase of fragmentation speed is higher when the permeability is above 10-12 m2. We confirm that it is necessary to include the influence of permeable flow on fragmentation dynamics.

  12. Quantitative analysis of cytokine-induced vascular toxicity and vascular leak in the mouse brain.

    PubMed

    Irwan, Yetty Y; Feng, Yi; Gach, H Michael; Symanowski, James T; McGregor, John R; Veni, Gopalkrishna; Schabel, Matthias; Samlowski, Wolfram E

    2009-09-30

    A storm of inflammatory cytokines is released during treatment with pro-inflammatory cytokines, such as interleukin-2 (IL-2), closely approximating changes initially observed during sepsis. These signals induce profound changes in neurologic function and cognition. Little is known about the mechanisms involved. We evaluated a number of experimental methods to quantify changes in brain blood vessel integrity in a well-characterized IL-2 treatment mouse model. Measurement of wet versus dry weight and direct measurement of small molecule accumulation (e.g. [(3)H]-H(2)O, sodium fluorescein) were not sensitive or reliable enough to detect small changes in mouse brain vascular permeability. Estimation of brain water content using proton density magnetic resonance imaging (MRI) measurements using a 7T mouse MRI system was sensitive to 1-2% changes in brain water content, but was difficult to reproduce in replicate experiments. Successful techniques included use of immunohistochemistry using specific endothelial markers to identify vasodilation in carefully matched regions of brain parenchyma and dynamic contrast enhanced (DCE) MRI. Both techniques indicated that IL-2 treatment induced vasodilation of the brain blood vessels. DCE MRI further showed a 2-fold increase in the brain blood vessel permeability to gadolinium in IL-2 treated mice compared to controls. Both immunohistochemistry and DCE MRI data suggested that IL-2 induced toxicity in the brain results from vasodilation of the brain blood vessels and increased microvascular permeability, resulting in perivascular edema. These experimental techniques provide us with the tools to further characterize the mechanism responsible for cytokine-induced neuropsychiatric toxicity. PMID:19665029

  13. Permeability Barrier Generation in the Martian Lithosphere

    NASA Astrophysics Data System (ADS)

    Schools, Joe; Montési, Laurent

    2015-11-01

    Permeability barriers develop when a magma produced in the interior of a planet rises into the cooler lithosphere and crystallizes more rapidly than the lithosphere can deform (Sparks and Parmentier, 1991). Crystallization products may then clog the porous network in which melt is propagating, reducing the permeability to almost zero, i.e., forming a permeability barrier. Subsequent melts cannot cross the barrier. Permeability barriers have been useful to explain variations in crustal thickness at mid-ocean ridges on Earth (Magde et al., 1997; Hebert and Montési, 2011; Montési et al., 2011). We explore here under what conditions permeability barriers may form on Mars.We use the MELTS thermodynamic calculator (Ghiorso and Sack, 1995; Ghiorso et al., 2002; Asimow et al., 2004) in conjunction with estimated Martian mantle compositions (Morgan and Anders, 1979; Wänke and Dreibus, 1994; Lodders and Fegley, 1997; Sanloup et al., 1999; Taylor 2013) to model the formation of permeability barriers in the lithosphere of Mars. In order to represent potential past and present conditions of Mars, we vary the lithospheric thickness, mantle potential temperature (heat flux), oxygen fugacity, and water content.Our results show that permeability layers can develop in the thermal boundary layer of the simulated Martian lithosphere if the mantle potential temperature is higher than ~1500°C. The various Martian mantle compositions yield barriers in the same locations, under matching variable conditions. There is no significant difference in barrier location over the range of accepted Martian oxygen fugacity values. Water content is the most significant influence on barrier development as it reduces the temperature of crystallization, allowing melt to rise further into the lithosphere. Our lower temperature and thicker lithosphere model runs, which are likely the most similar to modern Mars, show no permeability barrier generation. Losing the possibility of having a permeability barrier likely changed the character of volcanism on Mars, maybe preventing the formation of new localized volcanic edifices in the Amazonian.

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

    NASA Astrophysics Data System (ADS)

    Farinas, Javier Anibal

    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.

  15. Gas Permeable Chemochromic Compositions for Hydrogen Sensing

    NASA Technical Reports Server (NTRS)

    Bokerman, Gary (Inventor); Mohajeri, Nahid (Inventor); Muradov, Nazim (Inventor); Tabatabaie-Raissi, Ali (Inventor)

    2013-01-01

    A (H2) sensor composition includes a gas permeable matrix material intermixed and encapsulating at least one chemochromic pigment. The chemochromic pigment produces a detectable change in color of the overall sensor composition in the presence of H2 gas. The matrix material provides high H2 permeability, which permits fast permeation of H2 gas. In one embodiment, the chemochromic pigment comprises PdO/TiO2. The sensor can be embodied as a two layer structure with the gas permeable matrix material intermixed with the chemochromic pigment in one layer and a second layer which provides a support or overcoat layer.

  16. Numerical study of a quasi-zero-index photonic metamaterial

    NASA Astrophysics Data System (ADS)

    Jia, Xiuli; Meng, Qingxin; Wang, Xiaoou; Zhou, Zhongxiang

    2016-04-01

    Nanostructures made of metallic cube are arranged in Kagome lattice. Transmitted and reflected electromagnetic fields of normally incident circular polarized plane waves are computed using a tri-dimensional (3D) finite-difference time domain (FDTD) algorithm. Equivalent refractive index, equivalent permittivity, equivalent permeability and normalized impedance are calculated using the modified S-parameter retrieval method. Around the 7.912×1014 Hz and 9.376×1014 Hz, the structure performance for quasi-zero-index frequency bands.

  17. Indexing Consistency and Quality.

    ERIC Educational Resources Information Center

    Zunde, Pranas; Dexter, Margaret E.

    A measure of indexing consistency is developed based on the concept of 'fuzzy sets'. It assigns a higher consistency value if indexers agree on the more important terms than if they agree on less important terms. Measures of the quality of an indexer's work and exhaustivity of indexing are also proposed. Experimental data on indexing consistency

  18. Isolated Vascular Vertigo

    PubMed Central

    2014-01-01

    Strokes in the distribution of the posterior circulation may present with vertigo, imbalance, and nystagmus. Although the vertigo due to a posterior circulation stroke is usually associated with other neurologic symptoms or signs, small infarcts involving the cerebellum or brainstem can develop vertigo without other localizing symptoms. Approximately 11% of the patients with an isolated cerebellar infarction present with isolated vertigo, nystagmus, and postural unsteadiness mimicking acute peripheral vestibular disorders. The head impulse test can differentiate acute isolated vertigo associated with cerebellar strokes (particularly within the territory of the posterior inferior cerebellar artery) from more benign disorders involving the inner ear. Acute audiovestibular loss may herald impending infarction in the territory of anterior inferior cerebellar artery. Appropriate bedside evaluation is superior to MRIs for detecting central vascular vertigo syndromes. This article reviews the keys to diagnosis of acute isolated vertigo syndrome due to posterior circulation strokes involving the brainstem and cerebellum. PMID:25328871

  19. FRACTAL VASCULAR GROWTH PATTERNS

    PubMed Central

    Bassingthwaighte, James B.

    2010-01-01

    Flow distributions in the heart and lung are heterogeneous but not at all random. The apparent degree of heterogeneity increases as one reduces the size of observable elements; the fact that the dispersion of flows shows a logarithmic relation to element size says that the system is statistically fractal. The fractal characterization is a statement that the system is nonrandom and that it shows correlation. The close near neighbor correlation has as the corollary of long tailing or falloff in correlation with distance, so called spatial persistence. Correlation can be expected because flow is delivered via a branching vascular system, and so it appears that the structure of the vasculature itself contributes. Since it is also practical and efficient for growth to occur via recursive rules, such as branch, grow, and repeat the branching and growing, it appears that fractals may be useful in understanding the ontological aspects of growth of tissues and organs, thereby minimizing the requirements for genetic material. PMID:25237211

  20. RhoA and ROCK mediate histamine-induced vascular leakage and anaphylactic shock

    PubMed Central

    Mikelis, Constantinos M.; Simaan, May; Ando, Koji; Fukuhara, Shigetomo; Sakurai, Atsuko; Amornphimoltham, Panomwat; Masedunskas, Andrius; Weigert, Roberto; Chavakis, Triantafyllos; Adams, Ralf; Offermanns, Stefan; Mochizuki, Naoki; Zheng, Yi; Gutkind, J. Silvio

    2015-01-01

    Histamine-induced vascular leakage is an integral component of many highly prevalent human diseases, including allergies, asthma, and anaphylaxis. Yet, how histamine induces the disruption of the endothelial barrier is not well defined. By using genetically modified animal models, pharmacologic inhibitors, and a synthetic biology approach, here we show that the small GTPase RhoA mediates histamine-induced vascular leakage. Histamine causes the rapid formation of focal adherens junctions, disrupting the endothelial barrier by acting on H1R G?q-coupled receptors, which is blunted in endothelial G?q/11 KO mice. Interfering with RhoA and ROCK function abolishes endothelial permeability, while phospholipase C? plays a limited role. Moreover, endothelial-specific RhoA gene deletion prevents vascular leakage and passive cutaneous anaphylaxis in vivo, and ROCK inhibitors protect from lethal systemic anaphylaxis. This study supports a key role for the RhoA signaling circuitry in vascular permeability, thereby identifying novel pharmacological targets for many human diseases characterized by aberrant vascular leakage. PMID:25857352

  1. Caffeine's Vascular Mechanisms of Action

    PubMed Central

    Echeverri, Daro; Montes, Flix R.; Cabrera, Mariana; Galn, Anglica; Prieto, Anglica

    2010-01-01

    Caffeine is the most widely consumed stimulating substance in the world. It is found in coffee, tea, soft drinks, chocolate, and many medications. Caffeine is a xanthine with various effects and mechanisms of action in vascular tissue. In endothelial cells, it increases intracellular calcium stimulating the production of nitric oxide through the expression of the endothelial nitric oxide synthase enzyme. Nitric oxide is diffused to the vascular smooth muscle cell to produce vasodilation. In vascular smooth muscle cells its effect is predominantly a competitive inhibition of phosphodiesterase, producing an accumulation of cAMP and vasodilation. In addition, it blocks the adenosine receptors present in the vascular tissue to produce vasoconstriction. In this paper the main mechanisms of action of caffeine on the vascular tissue are described, in which it is shown that caffeine has some cardiovascular properties and effects which could be considered beneficial. PMID:21188209

  2. Vascular Development in the Zebrafish

    PubMed Central

    Gore, Aniket V.; Monzo, Kathryn; Cha, Young R.; Pan, Weijun; Weinstein, Brant M.

    2012-01-01

    The zebrafish has emerged as an excellent vertebrate model system for studying blood and lymphatic vascular development. The small size, external and rapid development, and optical transparency of zebrafish embryos are some of the advantages the zebrafish model system offers. Multiple well-established techniques have been developed for imaging and functionally manipulating vascular tissues in zebrafish embryos, expanding on and amplifying these basic advantages and accelerating use of this model system for studying vascular development. In the past decade, studies performed using zebrafish as a model system have provided many novel insights into vascular development. In this article we discuss the amenability of this model system for studying blood vessel development and review contributions made by this system to our understanding of vascular development. PMID:22553495

  3. NASA In-step: Permeable Membrane Experiment

    NASA Technical Reports Server (NTRS)

    1992-01-01

    Viewgraphs on the Permeable Membrane Experiment are presented. An experiment overview is given. The Membrane Phase Separation Experiment, Membrane Diffusion Interference Experiment, and Membrane Wetting Experiment are described. Finally, summary and conclusions are discussed.

  4. Permeability After Impact Testing of Composite Laminates

    NASA Technical Reports Server (NTRS)

    Nettles, A.T.; Munafo, Paul (Technical Monitor)

    2002-01-01

    Since composite laminates are beginning to be identified for use in reusable launch vehicle propulsion systems, an understanding of their permeance is needed. A foreign object impact event can cause a localized area of permeability (leakage) in a polymer matrix composite and it is the aim of this study to assess a method of quantifying permeability-after-impact results. A simple test apparatus is presented and variables that could affect the measured values of permeability-after-impact were assessed. Once it was determined that valid numbers were being measured, a fiber/resin system was impacted at various impact levels and the resulting permeability measured, first with a leak check solution (qualitative) then using the new apparatus (quantitative). The results showed that as the impact level increased, so did the measured leakage. As the pressure to the specimen was increased, the leak rate was seen to increase in a non-linear fashion for almost all of the specimens tested.

  5. Permeability After Impact Testing of Composite Laminates

    NASA Technical Reports Server (NTRS)

    Nettles, Alan T.

    2003-01-01

    Since composite laminates are beginning to be identified for use in reusable launch vehicle propulsion systems, an understanding of their permeance is needed. A foreign object impact event can cause a localized area of permeability (leakage) in a polymer matrix composite and it is the aim of this study to assess a method of quantifying permeability-after-impact results. A simple test apparatus is presented and variables that could affect the measured values of permeability-after-impact were assessed. Once it was determined that valid numbers were being measured, a fiber/resin system was impacted at various impact levels and the resulting permeability measured, first with a leak check solution (qualitative) then using the new apparatus (quantitative). The results showed that as the impact level increased, so did the measured leakage. As the pressure to the specimen was increased, the leak rate was seen to increase in a non-linear fashion for almost all of the specimens tested.

  6. Abnormal intestinal permeability in Crohn's disease pathogenesis.

    PubMed

    Teshima, Christopher W; Dieleman, Levinus A; Meddings, Jon B

    2012-07-01

    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

  7. Permeable Reactive Zones for Groundwater Remediation

    EPA Science Inventory

    The presentation will cover aspects of the application of permeable reactive zones to treat contaminated ground water. Specific field studies will be discussed covering both granular iron-based and organic carbon-based reactive barriers. Specific contaminants addressed include:...

  8. Complex permeability measurements of microwave ferrites

    SciTech Connect

    Geyer, R.G.; Krupka, J.

    1996-12-31

    A rigorous and accurate method for the experimental determination of the complex permeability of demagnetized ferrites at microwave frequencies is presented. The measurement uses low-loss dielectric ring resonators, is nondestructive, and allows complex permeability characterization of a single ferrite sample to be performed at frequencies from 2 GHz to 25 GHz. A wide variety of ceramic microwave ferrites having various compositions and differing saturation magnetizations were measured in the demagnetized state. Generally, at any frequency greater than gyromagnetic resonance, the real part of the complex permeability increases as saturation magnetization increases. For the same frequency magnetic losses increases as saturation magnetization increases. The real permeability results are compared with magnetostatic theoretical predictions. Measurement data show excellent agreement with theoretical predictions, but only when 2{pi}{gamma}M{sub s}/{omega} < 0.75, where {gamma} is the gyromagnetic ratio, M{sub s} is saturation magnetization, and {omega} is the radian rf frequency.

  9. The Edison Environmental Center Permeable Pavement Site

    EPA Science Inventory

    This a presentation for a Community Outreach Event called "Chemistry Works and Celebration of International Year of Chemistry." It will review the permeable pavement research project at the Edison Environmental center.

  10. Flexible Sandwich Diaphragms Are Less Permeable

    NASA Technical Reports Server (NTRS)

    Michalovic, John G.; Vassallo, Franklin A.

    1993-01-01

    Diaphragms for use in refrigerator compressors made as laminates of commercially available elastomers and metals. Diaphragms flexible, but less permeable by chlorofluorocarbon refrigerant fluids than diaphragms made of homogeneous mixtures of materials.

  11. Permeability of gypsum samples dehydrated in air

    NASA Astrophysics Data System (ADS)

    Milsch, Harald; Priegnitz, Mike; Blcher, Guido

    2011-09-01

    We report on changes in rock permeability induced by devolatilization reactions using gypsum as a reference analog material. Cylindrical samples of natural alabaster were dehydrated in air (dry) for up to 800 h at ambient pressure and temperatures between 378 and 423 K. Subsequently, the reaction kinetics, so induced changes in porosity, and the concurrent evolution of sample permeability were constrained. Weighing the heated samples in predefined time intervals yielded the reaction progress where the stoichiometric mass balance indicated an ultimate and complete dehydration to anhydrite regardless of temperature. Porosity showed to continuously increase with reaction progress from approximately 2% to 30%, whilst the initial bulk volume remained unchanged. Within these limits permeability significantly increased with porosity by almost three orders of magnitude from approximately 7 10-19 m2 to 3 10-16 m2. We show that - when mechanical and hydraulic feedbacks can be excluded - permeability, reaction progress, and porosity are related unequivocally.

  12. PERMEABLE REACTIVE BARRIERS FOR GROUND WATER REMEDIATION

    EPA Science Inventory

    Permeable reactive barriers (PRB's) are an emerging, alternative in-situ approach for remediating groundwater contamination that combine subsurface fluid flow management with a passive chemical treatment zone. Removal of contaminants from the groundwater plume is achieved by alt...

  13. PERMEABLE REACTIVE BARRIERS FOR GROUNDWATER REMEDIATION

    EPA Science Inventory

    Permeable reactive barriers (PRB's) are an emerging, alternative in-situ approach for remediating groundwater contamination that combine subsurface fluid flow management with a passive chemical treatment zone. Removal of contaminants from the groundwater plume is achieved by alt...

  14. PERMEABILITY OF POLYMERIC MEMBRANE LINING MATERIALS

    EPA Science Inventory

    Permeabilities to three gases (carbon dioxide, methane, and nitrogen), water vapor, and five solvents (methanol, acetone, cyclohexane, xylene, and chloroform) are reported for a broad range of commercial polymeric membranes. Gas and water vapor transmission (WVT) data were determ...

  15. Lunar electrical conductivity and magnetic permeability

    NASA Technical Reports Server (NTRS)

    Dyal, P.; Parkin, C. W.; Daily, W. D.

    1975-01-01

    Improved analytical techniques are applied to a large Apollo magnetometer data set to yield values of electroconductivity, temperature, magnetic permeability, and iron abundance. Average bulk electroconductivity of the moon is calculated to be .0007 mho/m; a rapid increase with depth to about .003 mho/m within 250 km is indicated. The temperature profile, obtained from the electroconductivity profile for olivine, indicates high lunar temperatures at relatively shallow depths. Magnetic permeability of the moon relative to its environment is calculated to be 1.008 plus or minus .005; a permeability relative to free space of 1.012 plus 0.011, minus 0.008 is obtained. Lunar iron abundances corresponding to this permeability value are 2.5 plus 2.3, minus 1.7 wt% free iron and 5.0-13.5 wt% total iron for a moon composed of a combination of free iron, olivine, and orthopyroxene.

  16. Measuring Permeability of Composite Cryotank Laminants

    NASA Technical Reports Server (NTRS)

    Oliver, Stanley T.; Selvidge, Shawn; Watwood, Michael C.

    2004-01-01

    This paper describes a test method developed to identify whether certain materials and material systems are suitable candidates for large pressurized reusable cryogenic tanks intended for use in current and future manned launch systems. It provides a quick way to screen numerous candidate materials for permeability under anticipated loading environments consistent with flight conditions, as well as addressing reusability issues. cryogenic tank, where the major design issue was hydrogen permeability. It was successfully used to evaluate samples subjected to biaxial loading while maintaining test temperatures near liquid hydrogen. After each sample was thermally preconditioned, a cyclic pressure load was applied to simulate the in-plane strain. First permeability was measured while a sample was under load. Then the sample was unloaded and allowed to return to ambient temperature. The test was repeated to simulate reusability, in order to evaluate its effects on material permeability.

  17. Permeability of rayon based polymer composites

    NASA Technical Reports Server (NTRS)

    Stokes, E. H.

    1992-01-01

    Several types of anomalous rayon based phenolic behavior have been observed in post-fired nozzles and exit cones. Many of these events have been shown to be related to the development of internal gas pressure within the material. The development of internal gas pressure is a function of the amount of gas produced within the material and the rate at which that gas is allowed to escape. The latter property of the material is referred to as the material's permeability. The permeability of two dimensional carbonized rayon based phenolic composites is a function of material direction, temperature, and stress/strain state. Recently significant differences in the permeability of these materials has been uncovered which may explain their inconsistent performance. This paper summarizes what is known about the permeability of these materials to date and gives possible implications of these finding to the performance of these materials in an ablative environment.

  18. Quantifying glomerular permeability of fluorescent macromolecules using 2-photon microscopy in Munich Wistar rats.

    PubMed

    Sandoval, Ruben M; Molitoris, Bruce A

    2013-01-01

    Kidney diseases involving urinary loss of large essential macromolecules, such as serum albumin, have long been thought to be caused by alterations in the permeability barrier comprised of podocytes, vascular endothelial cells, and a basement membrane working in unison. Data from our laboratory using intravital 2-photon microscopy revealed a more permeable glomerular filtration barrier (GFB) than previously thought under physiologic conditions, with retrieval of filtered albumin occurring in an early subset of cells called proximal tubule cells (PTC)(1,2,3). Previous techniques used to study renal filtration and establishing the characteristic of the filtration barrier involved micropuncture of the lumen of these early tubular segments with sampling of the fluid content and analysis(4). These studies determined albumin concentration in the luminal fluid to be virtually non-existent; corresponding closely to what is normally detected in the urine. However, characterization of dextran polymers with defined sizes by this technique revealed those of a size similar to serum albumin had higher levels in the tubular lumen and urine; suggesting increased permeability(5). Herein is a detailed outline of the technique used to directly visualize and quantify glomerular fluorescent albumin permeability in vivo. This method allows for detection of filtered albumin across the filtration barrier into Bowman's space (the initial chamber of urinary filtration); and also allows quantification of albumin reabsorption by proximal tubules and visualization of subsequent albumin transcytosis(6). The absence of fluorescent albumin along later tubular segments en route to the bladder highlights the efficiency of the retrieval pathway in the earlier proximal tubule segments. Moreover, when this technique was applied to determine permeability of dextrans having a similar size to albumin virtually identical permeability values were reported(2). These observations directly support the need to expand the focus of many proteinuric renal diseases to included alterations in proximal tubule cell reclamation. PMID:23628966

  19. Serum Superoxide Dismutase Is Associated with Vascular Structure and Function in Hypertensive and Diabetic Patients

    PubMed Central

    Gómez-Marcos, Manuel A.; Blázquez-Medela, Ana M.; Gamella-Pozuelo, Luis; Recio-Rodriguez, José I.; García-Ortiz, Luis; Martínez-Salgado, Carlos

    2016-01-01

    Oxidative stress is associated with cardiac and vascular defects leading to hypertension and atherosclerosis, being superoxide dismutase (SOD) one of the main intracellular antioxidant defence mechanisms. Although several parameters of vascular function and structure have a predictive value for cardiovascular morbidity-mortality in hypertensive patients, there are no studies on the involvement of SOD serum levels with these vascular parameters. Thus, we assessed if SOD serum levels are correlated with parameters of vascular function and structure and with cardiovascular risk in hypertensive and type 2 diabetic patients. We enrolled 255 consecutive hypertensive and diabetic patients and 52 nondiabetic and nonhypertensive controls. SOD levels were measured with an enzyme-linked immunosorbent assay kit. Vascular function and structure were evaluated by pulse wave velocity, augmentation index, ambulatory arterial stiffness index, and carotid intima-media thickness. We detected negative correlations between SOD and pressure wave velocity, peripheral and central augmentation index and ambulatory arterial stiffness index, pulse pressure, and plasma HDL-cholesterol, as well as positive correlations between SOD and plasma uric acid and triglycerides. Our study shows that SOD is a marker of cardiovascular alterations in hypertensive and diabetic patients, since changes in its serum levels are correlated with alterations in vascular structure and function. PMID:26635913

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

    USGS Publications Warehouse

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

    2016-01-01

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

  1. Serum Superoxide Dismutase Is Associated with Vascular Structure and Function in Hypertensive and Diabetic Patients.

    PubMed

    Gmez-Marcos, Manuel A; Blzquez-Medela, Ana M; Gamella-Pozuelo, Luis; Recio-Rodriguez, Jos I; Garca-Ortiz, Luis; Martnez-Salgado, Carlos

    2016-01-01

    Oxidative stress is associated with cardiac and vascular defects leading to hypertension and atherosclerosis, being superoxide dismutase (SOD) one of the main intracellular antioxidant defence mechanisms. Although several parameters of vascular function and structure have a predictive value for cardiovascular morbidity-mortality in hypertensive patients, there are no studies on the involvement of SOD serum levels with these vascular parameters. Thus, we assessed if SOD serum levels are correlated with parameters of vascular function and structure and with cardiovascular risk in hypertensive and type 2 diabetic patients. We enrolled 255 consecutive hypertensive and diabetic patients and 52 nondiabetic and nonhypertensive controls. SOD levels were measured with an enzyme-linked immunosorbent assay kit. Vascular function and structure were evaluated by pulse wave velocity, augmentation index, ambulatory arterial stiffness index, and carotid intima-media thickness. We detected negative correlations between SOD and pressure wave velocity, peripheral and central augmentation index and ambulatory arterial stiffness index, pulse pressure, and plasma HDL-cholesterol, as well as positive correlations between SOD and plasma uric acid and triglycerides. Our study shows that SOD is a marker of cardiovascular alterations in hypertensive and diabetic patients, since changes in its serum levels are correlated with alterations in vascular structure and function. PMID:26635913

  2. Renal and Vascular Mechanisms of Thiazolidinedione-Induced Fluid Retention

    PubMed Central

    Yang, Tianxin; Soodvilai, Sunhapas

    2008-01-01

    Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor subtype γ (PPARγ) activators that are clinically used as an insulin sensitizer for glycemic control in patients with type 2 diabetes. Additionally, TZDs exhibit novel anti-inflammatory, antioxidant, and antiproliferative properties, indicating therapeutic potential for a wide variety of diseases associated with diabetes and other conditions. The clinical applications of TZDs are limited by the common major side effect of fluid retention. A better understanding of the molecular mechanism of TZD-induced fluid retention is essential for the development of novel therapies with improved safety profiles. An important breakthrough in the field is the finding that the renal collecting duct is a major site for increased fluid reabsorption in response to rosiglitazone or pioglitazone. New evidence also indicates that increased vascular permeability in adipose tissues may contribute to edema formation and body weight gain. Future research should therefore be directed at achieving a better understanding of the detailed mechanisms of TZD-induced increases in renal sodium transport and in vascular permeability. PMID:18784848

  3. Mineralocorticoid Receptors Modulate Vascular Endothelial Function in Human Obesity

    PubMed Central

    Hwang, Moon-Hyon; Yoo, Jeung-Ki; Luttrell, Meredith; Kim, Han-Kyul; Meade, Thomas H.; English, Mark; Segal, Mark S.; Christou, Demetra D.

    2015-01-01

    Obesity increases linearly with age and is associated with impaired vascular endothelial function and increased risk for cardiovascular disease. Mineralocorticoid receptors (MR) contribute to impaired vascular endothelial function in cardiovascular disease; however, their role in uncomplicated human obesity is unknown. Because plasma aldosterone levels are elevated in obesity and adipocytes may be a source of aldosterone, we hypothesized that MR modulate vascular endothelial function in older adults in an adiposity-dependent manner. To test this hypothesis, we administered MR blockade (Eplerenone; 100 mg/day) for 1 month in a balanced, randomized, double-blind, placebo-controlled, crossover study to 22 older adults (10 men, 5579 years) varying widely in adiposity (body mass index: 2045 kg/m2) but who were free from overt cardiovascular disease. We evaluated vascular endothelial function (brachial artery flow-mediated dilation [FMD] via ultrasonography) and oxidative stress (plasma F2-isoprostanes and vascular endothelial cell protein expression of nitrotyrosine and NADPH oxidase p47phox) during placebo and MR blockade. In the whole group, oxidative stress (P>0.05) and FMD did not change with MR blockade (6.390.67 vs. 6.230.73 %, P=0.7, placebo vs. Eplerenone). However, individual improvements in FMD in response to Eplerenone were associated with higher total body fat (body mass index: r=0.45, P=0.02 and DXA-derived % body fat: r=0.50, P=0.009) and abdominal fat (total: r=0.61, P=0.005, visceral: r=0.67, P=0.002 and subcutaneous: r=0.48, P=0.03). In addition, greater improvements in FMD with Eplerenone were related with higher baseline fasting glucose (r=0.53, P=0.01). MR influence vascular endothelial function in an adiposity-dependent manner in healthy older adults. PMID:23786536

  4. Fracture-permeability behavior of shale

    DOE PAGESBeta

    Carey, J. William; Lei, Zhou; Rougier, Esteban; Mori, Hiroko; Viswanathan, Hari

    2015-05-08

    The fracture-permeability behavior of Utica shale, an important play for shale gas and oil, was investigated using a triaxial coreflood device and X-ray tomography in combination with finite-discrete element modeling (FDEM). Fractures generated in both compression and in a direct-shear configuration allowed permeability to be measured across the faces of cylindrical core. Shale with bedding planes perpendicular to direct-shear loading developed complex fracture networks and peak permeability of 30 mD that fell to 5 mD under hydrostatic conditions. Shale with bedding planes parallel to shear loading developed simple fractures with peak permeability as high as 900 mD. In addition tomore » the large anisotropy in fracture permeability, the amount of deformation required to initiate fractures was greater for perpendicular layering (about 1% versus 0.4%), and in both cases activation of existing fractures are more likely sources of permeability in shale gas plays or damaged caprock in CO₂ sequestration because of the significant deformation required to form new fracture networks. FDEM numerical simulations were able to replicate the main features of the fracturing processes while showing the importance of fluid penetration into fractures as well as layering in determining fracture patterns.« less

  5. Fracture-permeability behavior of shale

    SciTech Connect

    Carey, J. William; Lei, Zhou; Rougier, Esteban; Mori, Hiroko; Viswanathan, Hari

    2015-05-08

    The fracture-permeability behavior of Utica shale, an important play for shale gas and oil, was investigated using a triaxial coreflood device and X-ray tomography in combination with finite-discrete element modeling (FDEM). Fractures generated in both compression and in a direct-shear configuration allowed permeability to be measured across the faces of cylindrical core. Shale with bedding planes perpendicular to direct-shear loading developed complex fracture networks and peak permeability of 30 mD that fell to 5 mD under hydrostatic conditions. Shale with bedding planes parallel to shear loading developed simple fractures with peak permeability as high as 900 mD. In addition to the large anisotropy in fracture permeability, the amount of deformation required to initiate fractures was greater for perpendicular layering (about 1% versus 0.4%), and in both cases activation of existing fractures are more likely sources of permeability in shale gas plays or damaged caprock in CO₂ sequestration because of the significant deformation required to form new fracture networks. FDEM numerical simulations were able to replicate the main features of the fracturing processes while showing the importance of fluid penetration into fractures as well as layering in determining fracture patterns.

  6. Vascular factors and epigenetic modifications in the pathogenesis of Alzheimer's disease.

    PubMed

    Leszek, Jerzy; Sochocka, Marta; Gąsiorowski, Kazimierz

    2012-12-15

    Alzheimer's disease (AD) is a debilitating illness with no known cure. Nowadays accumulating evidence suggested that the vascular endothelium and chronic hypoperfusion may play important role in pathobiology of AD. The vascular endothelium which regulates the passage of macromolecules and circulating cells from blood to tissue, is a major target of oxidative stress, playing a critical role in the pathophysiology of vascular diseases. Since the vascular endothelium, neurons and glia are all able to synthesize, store and release reactive oxygen species (ROS) and vascular active substances in response to certain stimuli, their contribution to the pathophysiology of AD can be very important. New evidence indicates that continuous formation of free ROS induces cellular damage and decreases antioxidant defenses. Specifically, oxidative stress increases vascular endothelial permeability and promotes leukocyte adhesion. We summarize the reports that sporadic, late-onset of AD results from vascular etiology. Recently an involvement of epigenetic alterations in the etiology of AD is also intensively investigated. Gaining a more complete understanding of the essential components and underlying mechanisms involved in epigenetic regulation could lead to novel treatments for a number of neurological and psychiatric conditions. PMID:23026534

  7. C-type natriuretic peptide modulates permeability of the blood–brain barrier

    PubMed Central

    Bohara, Manoj; Kambe, Yuki; Nagayama, Tetsuya; Tokimura, Hiroshi; Arita, Kazunori; Miyata, Atsuro

    2014-01-01

    C-type natriuretic peptide (CNP) is abundant in brain and is reported to exert autocrine function in vascular cells, but its effect on blood–brain barrier (BBB) permeability has not been clarified yet. Here, we examined this effect. Transendothelial electrical resistance (TEER) of in vitro BBB model, composed of bovine brain microvascular endothelial cells and astrocytes, was significantly dose dependently decreased by CNP (1, 10, and 100 nmol/L). C-type natriuretic peptide treatment reduced both the messenger RNA (mRNA) and protein expressions of tight junction (TJ) protein zonula occludens-1 (ZO-1). The effects on TEER, mRNA, and protein expressions of ZO-1 were mimicked by cyclic GMP (cGMP) analog 8-bromo-cGMP (1 μmol/L) and reversed by protein kinase G (PKG) inhibitor Rp-8-CPT-cGMPS (100 μmol/L), thus implying the role of PKG and cGMP signaling in BBB function. Transcription factor JunD knockdown by small interfering RNA resulted in no change of permeability by CNP. In vivo study of mouse brain by fluorimetric analysis with intravenous administration of sodium fluorescein (40 mg/kg) also showed a significant increase in BBB permeability by CNP (10 nmol/kg, intravenously). These findings suggest that CNP modulates the BBB permeability by altering ZO-1 expression. PMID:24398935

  8. Nanomedicine for drug targeting: strategies beyond the enhanced permeability and retention effect

    PubMed Central

    Nehoff, Hayley; Parayath, Neha N; Domanovitch, Laura; Taurin, Sebastien; Greish, Khaled

    2014-01-01

    The growing research interest in nanomedicine for the treatment of cancer and inflammatory-related pathologies is yielding encouraging results. Unfortunately, enthusiasm is tempered by the limited specificity of the enhanced permeability and retention effect. Factors such as lack of cellular specificity, low vascular density, and early release of active agents prior to reaching their target contribute to the limitations of the enhanced permeability and retention effect. However, improved nanomedicine designs are creating opportunities to overcome these problems. In this review, we present examples of the advances made in this field and endeavor to highlight the potential of these emerging technologies to improve targeting of nanomedicine to specific pathological cells and tissues. PMID:24904213

  9. The enhanced permeability retention effect: a new paradigm for drug targeting in infection.

    PubMed

    Azzopardi, Ernest A; Ferguson, Elaine L; Thomas, David W

    2013-02-01

    Multidrug-resistant, Gram-negative infection is a major global determinant of morbidity, mortality and cost of care. The advent of nanomedicine has enabled tailored engineering of macromolecular constructs, permitting increasingly selective targeting, alteration of volume of distribution and activity/toxicity. Macromolecules tend to passively and preferentially accumulate at sites of enhanced vascular permeability and are then retained. This enhanced permeability and retention (EPR) effect, whilst recognized as a major breakthrough in anti-tumoral targeting, has not yet been fully exploited in infection. Shared pathophysiological pathways in both cancer and infection are evident and a number of novel nanomedicines have shown promise in selective, passive, size-mediated targeting to infection. This review describes the similarities and parallels in pathophysiological pathways at molecular, cellular and circulatory levels between inflammation/infection and cancer therapy, where use of this principle has been established. PMID:23054997

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

    PubMed

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

    2013-03-30

    Fully permeable pavement is gradually gaining support as an alternative best management practice (BMP) for stormwater runoff management. As the use of these pavements increases, a definitive test method is needed to measure hydraulic performance and to evaluate clogging, both for performance studies and for assessment of permeability for construction quality assurance and maintenance needs assessment. Two of the most commonly used permeability measurement tests for porous asphalt and pervious concrete are the National Center for Asphalt Technology (NCAT) permeameter and ASTM C1701, respectively. This study was undertaken to compare measured values for both methods in the field on a variety of permeable pavements used in current practice. The field measurements were performed using six experimental section designs with different permeable pavement surface types including pervious concrete, porous asphalt and permeable interlocking concrete pavers. Multiple measurements were performed at five locations on each pavement test section. The results showed that: (i) silicone gel is a superior sealing material to prevent water leakage compared with conventional plumbing putty; (ii) both methods (NCAT and ASTM) can effectively be used to measure the permeability of all pavement types and the surface material type will not impact the measurement precision; (iii) the permeability values measured with the ASTM method were 50-90% (75% on average) lower than those measured with the NCAT method; (iv) the larger permeameter cylinder diameter used in the ASTM method improved the reliability and reduced the variability of the measured permeability. PMID:23434738

  11. Perfusion and vascular permeability: basic concepts and measurement in DCE-CT and DCE-MRI.

    PubMed

    Cuenod, C A; Balvay, D

    2013-12-01

    The microvascular network formed by the capillaries supplies the tissues and permits their function. It provides a considerable surface area for exchanges between blood and tissues. All pathological conditions cause changes in the microcirculation. These changes can be used as imaging biomarkers for the diagnosis of lesions and optimisation of treatment. Among the many imaging techniques developed to study the microcirculation, the analysis of the tissue kinetics of intravenously injected contrast agents is the most widely used, either as positive enhancement for CT, T1-weighted MRI and ultrasound - dynamic contrast-enhanced-imaging (DCE-imaging) - or negative enhancement in T2*-weighted brain MRI - dynamic susceptibility contrast-MRI (DSC-MRI) -. Acquisition involves an injection of contrast agent during the acquisition of a dynamic series of images on a zone of interest. These kinetics may be analyzed visually, to define qualitative criteria, or with software using mathematical modelling, to extract quantitative physiological parameters. The results depend on the acquisition conditions (type of imaging device, imaging mode, frequency and total duration of acquisition), the type of contrast agent, the data pre-processing (motion correction, conversion of the signal into concentration) and the data analysis method. Because of these multiple choices it is necessary to understand the physiological processes involved and understand the advantages and limits of each strategy. PMID:24211260

  12. The effects of heparin and related molecules on vascular permeability and neutrophil accumulation in rabbit skin.

    PubMed

    Jones, Helen; Paul, William; Page, Clive P

    2002-01-01

    Unfractionated heparin (UH) has been shown to possess a wide range of properties which are potentially anti-inflammatory. Many of these studies, including effects of heparin on adhesion of inflammatory cells to endothelium, have been carried out in vitro. In the present study, we have used radioisotopic techniques to study the effect of UH, and related molecules, on in vivo inflammatory responses (plasma exudation (PE) and PMN accumulation) in rabbit skin induced by cationic proteins, mediators and antigen. Intradermal (i.d.) pretreatment with UH dose-dependently inhibited poly-L-lysine (PLL)-induced responses. The same treatment had no effect on antigen (extract of Alternaria tenuis, AT)-, formyl-methionyl-leucyl-phenylalanine (fMLP)- or leukotriene (LT) B(4)-induced responses, although i.d. dextran sulphate (DS) significantly inhibited responses to all of these mediators. High dose (10,000 u kg(-1)) intravenous UH significantly decreased cutaneous responses to fMLP and LTB(4). By comparison, the selectin inhibitor, fucoidin, and DS, were very effective inhibitors of these responses, and of responses to AT and PLL. In contrast to the weak effect in the in vivo studies, UH significantly inhibited in vitro homotypic aggregation of rabbit PMNs, showing that it can modify PMN function. Our data with i.d. UH confirm the important ability of this molecule to interact with and neutralize polycationic peptides in vivo, suggesting that this is a prime role of endogenous heparin. The lack of effect of exogenous heparin on acute inflammatory responses induced by allergen, suggests that cationic proteins are unlikely to be primary mediators of the allergen-induced PE or PMN accumulation. PMID:11815383

  13. The effects of heparin and related molecules on vascular permeability and neutrophil accumulation in rabbit skin

    PubMed Central

    Jones, Helen; Paul, William; Page, Clive P

    2002-01-01

    Unfractionated heparin (UH) has been shown to possess a wide range of properties which are potentially anti-inflammatory. Many of these studies, including effects of heparin on adhesion of inflammatory cells to endothelium, have been carried out in vitro. In the present study, we have used radioisotopic techniques to study the effect of UH, and related molecules, on in vivo inflammatory responses (plasma exudation (PE) and PMN accumulation) in rabbit skin induced by cationic proteins, mediators and antigen. Intradermal (i.d.) pretreatment with UH dose-dependently inhibited poly-L-lysine (PLL)-induced responses. The same treatment had no effect on antigen (extract of Alternaria tenuis, AT)-, formyl-methionyl-leucyl-phenylalanine (fMLP)- or leukotriene (LT) B4-induced responses, although i.d. dextran sulphate (DS) significantly inhibited responses to all of these mediators. High dose (10,000 u kg−1) intravenous UH significantly decreased cutaneous responses to fMLP and LTB4. By comparison, the selectin inhibitor, fucoidin, and DS, were very effective inhibitors of these responses, and of responses to AT and PLL. In contrast to the weak effect in the in vivo studies, UH significantly inhibited in vitro homotypic aggregation of rabbit PMNs, showing that it can modify PMN function. Our data with i.d. UH confirm the important ability of this molecule to interact with and neutralize polycationic peptides in vivo, suggesting that this is a prime role of endogenous heparin. The lack of effect of exogenous heparin on acute inflammatory responses induced by allergen, suggests that cationic proteins are unlikely to be primary mediators of the allergen-induced PE or PMN accumulation. PMID:11815383

  14. General Surgery Resident Vascular Operative Experience in the Era of Endovascular Surgery and Vascular Fellowships.

    PubMed

    Yan, Huan; Maximus, Steven; Kim, Jerry J; Smith, Brian; Kim, Dennis; Koopmann, Matthew; DeVirgilio, Christian

    2015-10-01

    Advances in endovascular surgery have resulted in a decline in major open arterial reconstructions nationwide. Our objective is to investigate the effect of endovascular surgery on general surgery resident experience with open vascular surgery. Between 2004 and 2014, 112 residents graduated from two academic institutions in Southern California. Residents were separated into those who graduated in 2004 to 2008 (period 1) and in 2009 to 2014 (period 2). Case volumes of vascular procedures were compared using two-sample t test. A total of 43 residents were in period 1 and 59 residents were in period 2. In aggregate, there was no significant difference in open cases recorded between the two periods (84 vs 87, P = 0.194). Subgroup analysis showed period 2 recorded significantly fewer cases of open aneurysm repair (5 vs 3, P < 0.001), cerebrovascular (14 vs 10, P = 0.007), and peripheral obstructive procedures (16 vs 13, P = 0.017). Dialysis access procedures constituted the largest group of procedures and remained similar between the two periods (35 vs 42, P = 0.582). General surgery residents experienced a significant decline in several index open major arterial reconstruction cases. This decline was offset by maintenance of dialysis access procedures. If the trend continues, future general surgeons will not be proficient in open vascular procedures. PMID:26595111

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

    PubMed Central

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

    2013-01-01

    Hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) are diseases caused by hantavirus infections and are characterized by vascular leakage due to alterations of the endothelial barrier. Hantavirus-infected endothelial cells (EC) display no overt cytopathology; consequently, pathogenesis models have focused either on the influx of immune cells and release of cytokines or on increased degradation of the adherens junction protein, vascular endothelial (VE)-cadherin, due to hantavirus-mediated hypersensitization of EC to vascular endothelial growth factor (VEGF). To examine endothelial leakage in a relevant in vitro system, we co-cultured endothelial and vascular smooth muscle cells (vSMC) to generate capillary blood vessel-like structures. In contrast to results obtained in monolayers of cultured EC, we found that despite viral replication in both cell types as well as the presence of VEGF, infected in vitro vessels neither lost integrity nor displayed evidence of VE-cadherin degradation. Here, we present evidence for a novel mechanism of hantavirus-induced vascular leakage involving activation of the plasma kallikrein-kinin system (KKS). We show that incubation of factor XII (FXII), prekallikrein (PK), and high molecular weight kininogen (HK) plasma proteins with hantavirus-infected EC results in increased cleavage of HK, higher enzymatic activities of FXIIa/kallikrein (KAL) and increased liberation of bradykinin (BK). Measuring cell permeability in real-time using electric cell-substrate impedance sensing (ECIS), we identified dramatic increases in endothelial cell permeability after KKS activation and liberation of BK. Furthermore, the alterations in permeability could be prevented using inhibitors that directly block BK binding, the activity of FXIIa, or the activity of KAL. Lastly, FXII binding and autoactivation is increased on the surface of hantavirus-infected EC. These data are the first to demonstrate KKS activation during hantavirus infection and could have profound implications for treatment of hantavirus infections. PMID:23874198

  16. Endothelial cell permeability during hantavirus infection involves factor XII-dependent increased activation of the kallikrein-kinin system.

    PubMed

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

    2013-01-01

    Hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) are diseases caused by hantavirus infections and are characterized by vascular leakage due to alterations of the endothelial barrier. Hantavirus-infected endothelial cells (EC) display no overt cytopathology; consequently, pathogenesis models have focused either on the influx of immune cells and release of cytokines or on increased degradation of the adherens junction protein, vascular endothelial (VE)-cadherin, due to hantavirus-mediated hypersensitization of EC to vascular endothelial growth factor (VEGF). To examine endothelial leakage in a relevant in vitro system, we co-cultured endothelial and vascular smooth muscle cells (vSMC) to generate capillary blood vessel-like structures. In contrast to results obtained in monolayers of cultured EC, we found that despite viral replication in both cell types as well as the presence of VEGF, infected in vitro vessels neither lost integrity nor displayed evidence of VE-cadherin degradation. Here, we present evidence for a novel mechanism of hantavirus-induced vascular leakage involving activation of the plasma kallikrein-kinin system (KKS). We show that incubation of factor XII (FXII), prekallikrein (PK), and high molecular weight kininogen (HK) plasma proteins with hantavirus-infected EC results in increased cleavage of HK, higher enzymatic activities of FXIIa/kallikrein (KAL) and increased liberation of bradykinin (BK). Measuring cell permeability in real-time using electric cell-substrate impedance sensing (ECIS), we identified dramatic increases in endothelial cell permeability after KKS activation and liberation of BK. Furthermore, the alterations in permeability could be prevented using inhibitors that directly block BK binding, the activity of FXIIa, or the activity of KAL. Lastly, FXII binding and autoactivation is increased on the surface of hantavirus-infected EC. These data are the first to demonstrate KKS activation during hantavirus infection and could have profound implications for treatment of hantavirus infections. PMID:23874198

  17. NADPH Oxidases in Vascular Pathology

    PubMed Central

    Konior, Anna; Schramm, Agata; Czesnikiewicz-Guzik, Marta

    2014-01-01

    Abstract Significance: Reactive oxygen species (ROS) play a critical role in vascular disease. While there are many possible sources of ROS, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases play a central role. They are a source of “kindling radicals,” which affect other enzymes, such as nitric oxide synthase endothelial nitric oxide synthase or xanthine oxidase. This is important, as risk factors for atherosclerosis (hypertension, diabetes, hypercholesterolemia, and smoking) regulate the expression and activity of NADPH oxidases in the vessel wall. Recent Advances: There are seven isoforms in mammals: Nox1, Nox2, Nox3, Nox4, Nox5, Duox1 and Duox2. Nox1, Nox2, Nox4, and Nox5 are expressed in endothelium, vascular smooth muscle cells, fibroblasts, or perivascular adipocytes. Other homologues have not been found or are expressed at very low levels; their roles have not been established. Nox1/Nox2 promote the development of endothelial dysfunction, hypertension, and inflammation. Nox4 may have a role in protecting the vasculature during stress; however, when its activity is increased, it may be detrimental. Calcium-dependent Nox5 has been implicated in oxidative damage in human atherosclerosis. Critical Issues: NADPH oxidase-derived ROS play a role in vascular pathology as well as in the maintenance of normal physiological vascular function. We also discuss recently elucidated mechanisms such as the role of NADPH oxidases in vascular protection, vascular inflammation, pulmonary hypertension, tumor angiogenesis, and central nervous system regulation of vascular function and hypertension. Future Directions: Understanding the role of individual oxidases and interactions between homologues in vascular disease is critical for efficient pharmacological regulation of vascular NADPH oxidases in both the laboratory and clinical practice. Antioxid. Redox Signal. 20, 2794–2814. PMID:24180474

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

    PubMed Central

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

    2015-01-01

    Macrophage invasion is an important event during arteriogenesis, but the underlying mechanism is still only partially understood. The present study tested the hypothesis that nitric oxide (NO) and VE-cadherin, two key mediators for vascular permeability, contribute to this event in a rat ischemic hindlimb model. In addition, the effect of NO on expression of VE-caherin and endothelial permeability was also studied in cultured HUVECs. We found that: 1) in normal arteriolar vessels (NAV), eNOS was moderately expressed in endothelial cells (EC) and iNOS was rarely detected. In contrast, in collateral vessels (CVs) induced by simple femoral artery ligation, both eNOS and iNOS were significantly upregulated (P<0.05). Induced iNOS was found mainly in smooth muscle cells, but also in other vascular cells and macrophages; 2) in NAV VE-cadherin was strongly expressed in EC. In CVs, VE-cadherin was significantly downregulated, with a discontinuous and punctate pattern. Administration of nitric oxide donor DETA NONOate (NONOate) further reduced the amounts of Ve-cadherin in CVs, whereas NO synthase inhibitor L-NAME inhibited downregulation of VE-cadherin in CVs; 3) in normal rats Evans blue extravasation (EBE) was low in the musculus gracilis, FITC-dextron leakage was not detected in the vascular wall and few macrophages were observed in perivascular space. In contrast, EBE was significantly increased in femoral artery ligation rats, FITC-dextron leakage and increased amounts of macrophages were detected in CVs, which were further enhanced by administration of NONOate, but inhibited by L-NAME supplement; 4) in vitro experiments confirmed that an increase in NO production reduced VE-cadherin expression, correlated with increases in the permeability of HUVECs. In conclusion, our data for the first time reveal the expression profile of VE-cadherin and alterations of vascular permeability in CVs, suggesting that NO-mediated VE-cadherin pathway may be one important mechanism responsible, at least in part, for macrophage invasion during arteriogenesis. PMID:26133549

  19. NOVEL ATYPICAL PKC INHIBITORS PREVENT VASCULAR ENDOTHELIAL GROWTH FACTOR-INDUCED BLOOD-RETINAL BARRIER DYSFUNCTION

    PubMed Central

    Titchenell, Paul M.; Lin, Cheng-Mao; Keil, Jason M.; Sundstrom, Jeffrey M.; Smith, Charles D.; Antonetti, David A.

    2013-01-01

    SYNOPSIS Pro-inflammatory cytokines and growth factors such as vascular endothelial growth factor (VEGF) contribute to the loss of the blood-retinal barrier (BRB) and subsequent macular edema in various retinal pathologies. VEGF signaling requires conventional PKC (PKC?) activity; however, PKC? inhibition only partially prevents VEGF-induced endothelial permeability and does not affect pro-inflammatory cytokine-induced permeability suggesting the involvement of alternative signaling pathways. Here, we provide evidence for the involvement of atypical protein kinase C (aPKC) signaling in VEGF-induced endothelial permeability and identify a novel class of inhibitors of aPKC that prevent BRB breakdown in vivo. Genetic and pharmacological manipulations of aPKC isoforms were used to assess their contribution to endothelial permeability in culture. A chemical library was screened using an in vitro kinase assay to identify novel small molecule inhibitors and further medicinal chemistry was performed to delineate a novel pharmacophore. We demonstrate that aPKC isoforms are both sufficient and required for VEGF-induced endothelial permeability. Furthermore, these specific, potent, non-competitive, small molecule inhibitors prevented VEGF-induced tight junction internalization and retinal endothelial permeability in response to VEGF in both primary culture and in rodent retina. These data suggest that aPKC inhibition with 2-amino-4-phenyl-thiophene derivatives may be developed to preserve the BRB in retinal diseases such as diabetic retinopathy or uveitis and the blood-brain barrier (BBB) in the presence of brain tumors. PMID:22721706

  20. Heterogeneous Vascular Responses to Lifestyle Intervention in Obese Latino Adolescents

    PubMed Central

    Ryder, Justin R.; Vega-López, Sonia; Gaesser, Glenn A.; Buman, Matthew P.

    2014-01-01

    Abstarct Background/Objectives: Among adolescents, obesity may increase the risk for premature cardiovascular disease (CVD). Lifestyle interventions may prevent or delay the onset of CVD through improvements in vascular health. The purpose of this study was to examine the effects of a 12-week lifestyle intervention on markers of vascular health in obese Latino youth. Subjects/Methods: Fifteen obese Latino adolescents [body mass index (BMI) percentile=96.3±1.1%, 15.0±1.0 year, 8 females and 7 males] participated in a 12-week lifestyle intervention consisting of nutrition education and physical activity. Markers of vascular health included oxidized low-density lipoprotein (oxLDL), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble endothelial leukocyte adhesion molecule-1 (sE-Selectin). Results: Relative to baseline data, the intervention resulted in lower oxLDL (−21.8%, P=0.001) and sE-Selectin (−13.3%, P=0.008) concentrations; sICAM-1 and sVCAM-1 did not change significantly. When examining overall responsiveness to change for each marker, oxLDL was reduced in 93.3%, sE-Selectin was reduced in 78.6%, and sICAM-1 was reduced in 71.4% of participants, respectively, whereas sVCAM-1 was reduced in only 42.9% of participants following lifestyle. Using a composite change score (summed change in four markers) for each participant there was an improvement in at least three of four markers among 64% of participants; this was confirmed by principal component analysis. Conclusions: Therefore, although improvements in the vascular health of obese youth were observed, the vascular response to lifestyle intervention may be heterogeneous. Further investigation into the mechanisms mediating the heterogeneity in vascular response to lifestyle intervention is warranted. PMID:25162989

  1. Bacterial invasion of vascular cell types: vascular infectology and atherogenesis

    PubMed Central

    Kozarov, Emil

    2012-01-01

    To portray the chronic inflammation in atherosclerosis, leukocytic cell types involved in the immune response to invading pathogens are often the focus. However, atherogenesis is a complex pathological deterioration of the arterial walls, where vascular cell types are participants with regards to deterioration and disease. Since other recent reviews have detailed the role of both the innate and adaptive immune response in atherosclerosis, herein we will summarize the latest developments regarding the association of bacteria with vascular cell types: infections as a risk factor for atherosclerosis; bacterial invasion of vascular cell types; the atherogenic sequelae of bacterial presence such as endothelial activation and blood clotting; and the identification of the species that are able to colonize this niche. The evidence of a polybacterial infectious component of the atheromatous lesions opens the doors for exploration of the new field of vascular infectology and for the study of atherosclerosis microbiome. PMID:22185451

  2. Vascular Endothelial Growth Factor in Eye Disease

    PubMed Central

    Penn, J.S.; Madan, A.; Caldwell, R.B.; Bartoli, M.; Caldwell, R.W.; Hartnett, M.E.

    2012-01-01

    Collectively, angiogenic ocular conditions represent the leading cause of irreversible vision loss in developed countries. In the U.S., for example, retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration are the principal causes of blindness in the infant, working age and elderly populations, respectively. Evidence suggests that vascular endothelial growth factor (VEGF), a 40 kDa dimeric glycoprotein, promotes angiogenesis in each of these conditions, making it a highly significant therapeutic target. However, VEGF is pleiotropic, affecting a broad spectrum of endothelial, neuronal and glial behaviors, and confounding the validity of anti-VEGF strategies, particularly under chronic disease conditions. In fact, among other functions VEGF can influence cell proliferation, cell migration, proteolysis, cell survival and vessel permeability in a wide variety of biological contexts. This article will describe the roles played by VEGF in the pathogenesis of retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. The potential disadvantages of inhibiting VEGF will be discussed, as will the rationales for targeting other VEGF-related modulators of angiogenesis. PMID:18653375

  3. Permeability reduction in granite under hydrothermal conditions

    USGS Publications Warehouse

    Morrow, C.A.; Moore, Diane E.; Lockner, D.A.

    2001-01-01

    The formation of impermeable fault seals between earthquake events is a feature of many models of earthquake generation, suggesting that earthquake recurrence may depend in part on the rate of permeability reduction of fault zone materials under hydrothermal conditions. In this study, permeability measurements were conducted on intact, fractured, and gouge-bearing Westerly granite at an effective pressure of 50 MPa and at temperatures from 150?? to 500??C, simulating conditions in the earthquake-generating portions of fault zones. Pore fluids were cycled back and forth under a 2 MPa pressure differential for periods of up to 40 days. Permeability of the granite decreased with time t, following the exponential relation k = c(10-rt). For intact samples run between 250?? and 500??C the time constant for permeability decrease r was proportional to temperature and ranged between 0.001 and 0.1 days-1 (i.e., between 0.4 and 40 decades year-1 loss of permeability). Values of r for the lower-temperature experiments differed little from the 250??C runs. In contrast, prefractured samples showed higher rates of permeability decrease at a given temperature. The surfaces of the fractured samples showed evidence of dissolution and mineral growth that increased in abundance with both temperature and time. The experimentally grown mineral assemblages varied with temperature and were consistent with a rock-dominated hydrothermal system. As such mineral deposits progressively seal the fractured samples, their rates of permeability decrease approach the rates for intact rocks at the same temperature. These results place constraints on models of precipitation sealing and suggest that fault rocks may seal at a rate consistent with earthquake recurrence intervals of typical fault zones.

  4. Constructal vascularized structures

    NASA Astrophysics Data System (ADS)

    Cetkin, Erdal

    2015-06-01

    Smart features such as self-healing and selfcooling require bathing the entire volume with a coolant or/and healing agent. Bathing the entire volume is an example of point to area (or volume) flows. Point to area flows cover all the distributing and collecting kinds of flows, i.e. inhaling and exhaling, mining, river deltas, energy distribution, distribution of products on the landscape and so on. The flow resistances of a point to area flow can be decreased by changing the design with the guidance of the constructal law, which is the law of the design evolution in time. In this paper, how the flow resistances (heat, fluid and stress) can be decreased by using the constructal law is shown with examples. First, the validity of two assumptions is surveyed: using temperature independent Hess-Murray rule and using constant diameter ducts where the duct discharges fluid along its edge. Then, point to area types of flows are explained by illustrating the results of two examples: fluid networks and heating an area. Last, how the structures should be vascularized for cooling and mechanical strength is documented. This paper shows that flow resistances can be decreased by morphing the shape freely without any restrictions or generic algorithms.

  5. Vascular action of polyphenols.

    PubMed

    Ghosh, Dilip; Scheepens, Arjan

    2009-03-01

    Dietary patterns are widely recognised as contributors to cardiovascular and cerebrovascular disease. Endothelial function, the elastic properties of large arteries and the magnitude and timing of wave reflections are important determinants of cardiovascular performance. Several epidemiological studies suggest that the regular consumption of foods and beverages rich in flavonoids is associated with a reduction in the risk of several pathological conditions ranging from hypertension to coronary heart disease, stroke and dementia. The impairment of endothelial function is directly related to ageing and an association between decreased cerebral perfusion and dementia has been shown to exist. Cerebral blood flow (CBF) must be maintained to ensure a constant delivery of oxygen and glucose as well as the removal of waste products. Increasing blood flow is one potential way for improving brain function and the prospect for increasing CBF with dietary polyphenols is extremely promising. The major polyphenols shown to have some of these effects in humans are primarily from cocoa, wine, grape seed, berries, tea, tomatoes (polyphenolics and nonpolyphenolics), soy and pomegranate. There has been a significant paradigm shift in polyphenol research during the last decade. This review summarises our current knowledge in this area and points the way for the development of new types of functional foods targeted to brain health through improving vascular health. PMID:19051188

  6. Vascular imaging in diabetes.

    PubMed

    Levitt, K; Vivas, L; Courtney, B; Connelly, K A

    2014-04-01

    Diabetes is a global epidemic affecting individuals of all socioeconomic backgrounds. Despite intensive efforts, morbidity and mortality secondary to the micro- and macrovascular complications remain unacceptably high. As a result, the use of imaging modalities to determine the underlying pathophysiology, early onset of complications, and disease progression has become an integral component of the management of such individuals. Echocardiography, stress echocardiography, and nuclear imaging have been the mainstay of noninvasive cardiovascular imaging tools to detect myocardial ischemia, but newer modalities such as cardiac MRI, cardiac CT, and PET imaging provide incremental information not available with standard imaging. While vascular imaging to detect cerebrovascular and peripheral arterial disease non-invasively has traditionally used ultrasound, CT- and MRI-based techniques are increasingly being employed. In this review, we will provide an outline of recent studies utilizing non-invasive imaging techniques to assist in disease diagnosis as well as monitoring disease progression. In addition, we will review the evidence for newer modalities such as MR spectroscopy, 3D intravascular ultrasound, and optical coherence tomography that provide exquisite detail of metabolic function and coronary anatomy not available with standard imaging, but that have not yet become mainstream. PMID:24493479

  7. Site of Vascular Response to Thermal Injury in Skeletal Muscle

    PubMed Central

    Wells, F. R.

    1971-01-01

    The vascular response to mild thermal injury54 for 20 and 40 sec.was observed topographically in the cremaster muscle of the rat, in terms of exudation, labelling of damaged vessels by carbon particles in the circulation, and patency of the vascular plexus. It was confirmed that the permeability response is biphasic with an early, predominantly venular phase and a delayed predominantly capillary phase. The intensity and time-course of the responses are determined primarily by the degree of injury, but they may vary substantially, even to the extent of a triphasic response, according to the pretreatment of the rat's scrotum, the timing and degree of anaesthesia, the intravenous dosage of carbon and above all, on the period for which lesions are exposed to the circulating dye or carbon. After the more severe injury54 for 40 sec.the absence of an early response, and the interphase absence of exudation, are attributable to an initial vascular occlusion from which the heated muscle recovers within 1-3 hr. A second phase of occlusion follows, beginning after 6 hr and lasting more than 24 hr. With controlled pretreatment, standardized doses of carbon, an exposure period of 10 min., and heating at 54 for 40 sec., the delayed phase of permeability was associated almost exclusively with capillary labelling. Sodium salicylate in doses reported to suppress exudation and venular labelling, without affecting capillary labelling, was found to be too toxic for use as a reliable agent for establishing the necessary association of exudation with venular damage; moreover under the controlled conditions noted above they suppressed both venular and capillary labelling in parallel with exudation. Accordingly, the damaged capillary network must still be considered a major source of delayed exudation of plasma protein in thermally injured skeletal muscle, at least until the contribution of the post-capillary venules, indistinguishable from labelled capillaries proper except by the electron microscope, can be assessed. ImagesFigs. 1 and 4 PMID:5090686

  8. Vascular Endothelial Growth Factor Induces Endothelial Fenestrations In Vitro

    PubMed Central

    Esser, Sybille; Wolburg, Karen; Wolburg, Hartwig; Breier, Georg; Kurzchalia, Teymuras; Risau, Werner

    1998-01-01

    Abstract. Vascular endothelial growth factor (VEGF) is an important regulator of vasculogenesis, angiogenesis, and vascular permeability. In contrast to its transient expression during the formation of new blood vessels, VEGF and its receptors are continuously and highly expressed in some adult tissues, such as the kidney glomerulus and choroid plexus. This suggests that VEGF produced by the epithelial cells of these tissues might be involved in the induction or maintenance of fenestrations in adjacent endothelial cells expressing the VEGF receptors. Here we describe a defined in vitro culture system where fenestrae formation was induced in adrenal cortex capillary endothelial cells by VEGF, but not by fibroblast growth factor. A strong induction of endothelial fenestrations was observed in cocultures of endothelial cells with choroid plexus epithelial cells, or mammary epithelial cells stably transfected with cDNAs for VEGF 120 or 164, but not with untransfected cells. These results demonstrate that, in these cocultures, VEGF is sufficient to induce fenestrations in vitro. Identical results were achieved when the epithelial cells were replaced by an epithelial-derived basal lamina-type extracellular matrix, but not with collagen alone. In this defined system, VEGF-mediated induction of fenestrae was always accompanied by an increase in the number of fused diaphragmed caveolae-like vesicles. Caveolae, but not fenestrae, were labeled with a caveolin-1–specific antibody both in vivo and in vitro. VEGF stimulation led to VEGF receptor tyrosine phosphorylation, but no change in the distribution, phosphorylation, or protein level of caveolin-1 was observed. We conclude that VEGF in the presence of a basal lamina-type extracellular matrix specifically induces fenestrations in endothelial cells. This defined in vitro system will allow further study of the signaling mechanisms involved in fenestrae formation, modification of caveolae, and vascular permeability. PMID:9472045

  9. Nucleic acid indexing

    DOEpatents

    Guilfoyle, Richard A.; Guo, Zhen

    2001-01-01

    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.

  10. Nucleic acid indexing

    DOEpatents

    Guilfoyle, Richard A.; Guo, Zhen

    1999-01-01

    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.

  11. Indexing Consistency and Quality.

    ERIC Educational Resources Information Center

    Zunde, Pranas; Dexter, Margaret E.

    Proposed is a measure of indexing consistency based on the concept of "fuzzy sets." By this procedure a higher consistency value is assigned if indexers agree on the more important terms than if they agree on less important terms. Measures of the quality of an indexer's work and exhaustivity of indexing are also proposed. Experimental data on

  12. Lobby index in networks

    NASA Astrophysics Data System (ADS)

    Korn, A.; Schubert, A.; Telcs, A.

    2009-06-01

    We propose a new node centrality measure in networks, the lobby index, which is inspired by Hirschs h-index. It is shown that in scale-free networks with exponent ? the distribution of the l-index has power tail with exponent ?(?+1). Properties of the l-index and extensions are discussed.

  13. Digital image processing of vascular angiograms

    NASA Technical Reports Server (NTRS)

    Selzer, R. H.; Beckenbach, E. S.; Blankenhorn, D. H.; Crawford, D. W.; Brooks, S. H.

    1975-01-01

    The paper discusses the estimation of the degree of atherosclerosis in the human femoral artery through the use of a digital image processing system for vascular angiograms. The film digitizer uses an electronic image dissector camera to scan the angiogram and convert the recorded optical density information into a numerical format. Another processing step involves locating the vessel edges from the digital image. The computer has been programmed to estimate vessel abnormality through a series of measurements, some derived primarily from the vessel edge information and others from optical density variations within the lumen shadow. These measurements are combined into an atherosclerosis index, which is found in a post-mortem study to correlate well with both visual and chemical estimates of atherosclerotic disease.

  14. Vascular risk and Aβ interact to reduce cortical thickness in AD vulnerable brain regions

    PubMed Central

    Reed, Bruce R.; Madison, Cindee M.; Wirth, Miranka; Marchant, Natalie L.; Kriger, Stephen; Mack, Wendy J.; Sanossian, Nerses; DeCarli, Charles; Chui, Helena C.; Weiner, Michael W.; Jagust, William J.

    2014-01-01

    Objective: The objective of this study was to define whether vascular risk factors interact with β-amyloid (Aβ) in producing changes in brain structure that could underlie the increased risk of Alzheimer disease (AD). Methods: Sixty-six cognitively normal and mildly impaired older individuals with a wide range of vascular risk factors were included in this study. The presence of Aβ was assessed using [11C]Pittsburgh compound B–PET imaging, and cortical thickness was measured using 3-tesla MRI. Vascular risk was measured with the Framingham Coronary Risk Profile Index. Results: Individuals with high levels of vascular risk factors have thinner frontotemporal cortex independent of Aβ. These frontotemporal regions are also affected in individuals with Aβ deposition, but the latter show additional thinning in parietal cortices. Aβ and vascular risk were found to interact in posterior (especially in parietal) brain regions, where Aβ has its greatest effect. In this way, the negative effect of Aβ in posterior regions is increased by the presence of vascular risk. Conclusion: Aβ and vascular risk interact to enhance cortical thinning in posterior brain regions that are particularly vulnerable to AD. These findings give insight concerning the mechanisms whereby vascular risk increases the likelihood of developing AD and supports the therapeutic intervention of controlling vascular risk for the prevention of AD. PMID:24907234

  15. Quantitative Permeability Prediction for Anisotropic Porous Media

    NASA Astrophysics Data System (ADS)

    Sheng, Q.; Thompson, K. E.

    2012-12-01

    Pore-scale modeling as a predictive tool has become an integral to both research and commercial simulation in recent years. Permeability is one of the most important of the many properties that can be simulated. Traditionally, permeability is determined using Darcy's law, based on the assumption that the pressure gradient is aligned with the principal flow direction. However, a wide variety of porous media exhibit anisotropic permeability due to particle orientation or laminated structure. In these types of materials, the direction of fluid flow is not aligned with the pressure gradient (except along the principal directions). Thus, it is desirable to predict the full permeability tensor for anisotropic materials using a first-principles pore-scale approach. In this work, we present a fast method to determine the full permeability tensor and the principal directions using a novel network modeling algorithm. We also test the ability of network modeling (which is an approximate method) to detect anisotropy in various structures. Both computational fluid dynamics (CFD) methods and network modeling have emerged as effective techniques to predict rock properties. CFD models are more rigorous but computationally expensive. Network modeling involves significant approximations but can be orders-of-magnitude more efficient computationally, which is important for both speed and the ability to model larger scales. This work uses network modeling, with simulations performed on two types of anisotropic materials: laminated packings (with layers of different sized particles) and oriented packings (containing particles with preferential orientation). Pore network models are created from the porous media data, and a novel method is used to determine the permeability tensor and principal flow direction using pore network modeling. The method is verified by comparing the calculated principal directions with the known anisotropy and also by comparing permeability with values from CFD simulations. Results show that pore network modeling is able to detect anisotropic effects directly from fundamental descriptions of the pore geometry (such as microtomography images). This work is significant because it shows that pore-scale simulation can augment traditional core analysis in certain applications such as testing anisotropic materials since it is difficult to measure the permeability tensor experimentally. Using the fast network modeling algorithm, permeability can be measured in a pore-scale region with over one million pores while capturing anisotropy in a large span of length scales.

  16. Gastrointestinal permeability in patients with irritable bowel syndrome assessed using a four probe permeability solution

    PubMed Central

    Del Valle-Pinero, Arseima Y.; Van Deventer, Hendrick E.; Fourie, Nicolaas H.; Martino, Angela C.; Patel, Nayan S.; Remaley, Alan T.; Henderson, Wendy A.

    2013-01-01

    Background Abnormal gastrointestinal permeability has been linked to irritable bowel syndrome (IBS). The lactulose-to-mannitol ratio is traditionally used to assess small intestine permeability while sucralose and sucrose are used to assess colonic and gastric permeability respectively. We used a single 4-probe test solution to assess permeability throughout the gastrointestinal tract in IBS patients and healthy controls by measuring the recovery of the probes in urine after ingestion using a modified liquid chromatography mass spectrometry protocol. Methods Fasting participants (N = 59) drank a permeability test solution (100 ml: sucralose, sucrose, mannitol, and lactulose). Urine was collected over a 5-h period and kept frozen until analysis. Urinary sugar concentrations were measured using an liquid chromatography/triple quadruple mass spectrometer. Results Colonic permeability was significantly lower in IBS patients when compared to healthy controls (p = 0.011). Gastric and small intestinal permeability did not significantly differ between the groups. Conclusions The study demonstrates the clinical potential of this non-invasive method for assessing alterations in gastrointestinal permeability in patients with IBS. PMID:23328210

  17. Rk1, a ginsenoside, is a new blocker of vascular leakage acting through actin structure remodeling.

    PubMed

    Maeng, Yong-Sun; Maharjan, Sony; Kim, Jeong-Hun; Park, Jeong-Hill; Suk Yu, Young; Kim, Young-Myoung; Kwon, Young-Guen

    2013-01-01

    Endothelial barrier integrity is essential for vascular homeostasis and increased vascular permeability and has been implicated in many pathological processes, including diabetic retinopathy. Here, we investigated the effect of Rk1, a ginsenoside extracted from sun ginseng, on regulation of endothelial barrier function. In human retinal endothelial cells, Rk1 strongly inhibited permeability induced by VEGF, advanced glycation end-product, thrombin, or histamine. Furthermore, Rk1 significantly reduced the vessel leakiness of retina in a diabetic mouse model. This anti-permeability activity of Rk1 is correlated with enhanced stability and positioning of tight junction proteins at the boundary between cells. Signaling experiments revealed that Rk1 induces phosphorylation of myosin light chain and cortactin, which are critical regulators for the formation of the cortical actin ring structure and endothelial barrier. These findings raise the possibility that ginsenoside Rk1 could be exploited as a novel prototype compound for the prevention of human diseases that are characterized by vascular leakage. PMID:23894330

  18. Permeability evolution in sandstone: Digital rock approach

    NASA Astrophysics Data System (ADS)

    Kameda, Ayako

    Permeability is perhaps one of the most important yet elusive reservoir properties, since it poorly correlates with elastic properties, and as a result, cannot be mapped remotely. Physical permeability measurements may be augmented or even partially replaced by numerical experiments, provided that a numerical simulation accurately mimics the physical process. Numerical simulation of laboratory experiments on rocks, or digital rock physics, is an emerging field that may benefit the petroleum industry. For numerical experimentation to find its way into the mainstream, it has to be practical and easily repeatable, i.e., implemented on standard hardware and in real time. This condition reduces the feasible size of a digital sample to just a few grains across. Will the results be meaningful for a larger rock volume? The answer is that small fragments of medium- to high-porosity sandstone, such as cuttings, which are not statistically representative of a larger sample, cannot be used to numerically calculate the exact porosity and permeability of the sample. However, by using a significant number of such small fragments, it may be possible to establish a site-specific permeability-porosity trend, which can be used to estimate the absolute permeability from independent porosity data, obtained in the well or inferred from seismic measurements.

  19. Gas Permeability in Rubbery Polyphosphazene Membranes

    SciTech Connect

    Frederick F. Stewart; Christopher J. Orme; John R. Klaehn; Mason K. Harrup; Thomas A. Luther; Eric S. Peterson

    2006-09-01

    The synthesis, characterization, and gas permeability of ten new polyphosphazenes has been studied. Additionally, the first gas permeation data has been collected on hydrolytically unstable poly[bis-(chloro)phosphazene]. Gases used in this study include CO2, CH4, O2, N2, H2, and Ar. CO2 was the most permeable gas through any of the phosphazenes and a direct correlation between the Tg of the polymer and CO2 transport was noted with permeability increasing with decreasing polymer Tg. To a lesser degree, permeability of all the other gases studied also yielded increases with decreasing polymer Tg. The trend observed for these new polymers was further supported by published data for other phosphazenes. Furthermore, permeability data for all gases were found to correlate to the gas condensability and the gas critical pressures, except for hydrogen, suggesting that the nature of the gas is also a significant factor for permeation through rubbery phosphazene membranes. Ideal separation factors (á) for the CO2/H2 and CO2/CH4 gas pairs were calculated. For CO2/CH4, no increase in á was observed with decreasing Tg, however increases in á were noted for the CO2/H2 pair.

  20. Permeability of self-affine aperture fields.

    PubMed

    Talon, Laurent; Auradou, Harold; Hansen, Alex

    2010-10-01

    We introduce a model that allows for the prediction of the permeability of self-affine rough channels (one-dimensional fracture) and two-dimensional fractures over a wide range of apertures. In the lubrication approximation, the permeability shows three different scaling regimes. For fractures with a large mean aperture or an aperture small enough to the permeability being close to disappearing, the permeability scales as the cube of the aperture when the zero level of the aperture is set to coincide with the disappearance of the permeability. Between these two regimes, there is a third regime where the scaling is due to the self-affine roughness. For rough channels, the exponent is found to be 3-1/H, where H is the Hurst exponent. For two-dimensional fractures, it is necessary to introduce an equivalent aperture b(c) to make the scaling regime apparent. b(c) is defined as the hydraulic aperture of the most restrictive barrier crossing the fracture normal to the flow direction. This regime is characterized by an exponent higher than that for the one-dimensional case: it is 2.25 for H=0.8 and 2.16 for H=0.3. PMID:21230346

  1. Honeycomb Core Permeability Under Mechanical Loads

    NASA Technical Reports Server (NTRS)

    Glass, David E.; Raman, V. V.; Venkat, Venki S.; Sankaran, Sankara N.

    1997-01-01

    A method for characterizing the air permeability of sandwich core materials as a function of applied shear stress was developed. The core material for the test specimens was either Hexcel HRP-3/16-8.0 and or DuPont Korex-1/8-4.5 and was nominally one-half inch thick and six inches square. The facesheets where made of Hercules' AS4/8552 graphite/epoxy (Gr/Ep) composites and were nominally 0.059-in. thick. Cytec's Metalbond 1515-3M epoxy film adhesive was used for co-curing the facesheets to the core. The permeability of the specimens during both static (tension) and dynamic (reversed and non-reversed) shear loads were measured. The permeability was measured as the rate of air flow through the core from a circular 1-in2 area of the core exposed to an air pressure of 10.0 psig. In both the static and dynamic testing, the Korex core experienced sudden increases in core permeability corresponding to a core catastrophic failure, while the URP core experienced a gradual increase in the permeability prior to core failure. The Korex core failed at lower loads than the HRP core both in the transverse and ribbon directions.

  2. Permeability of Rigid Fibrous Refractory Insulations

    NASA Technical Reports Server (NTRS)

    Marschall, J.; Milos, F. S.; Rasky, Daniel J. (Technical Monitor)

    1996-01-01

    Rigid fibrous refractory insulations (TPS tiles) are integral components of many spacecraft thermal protection systems. These materials are composed of refractory fibers With diameters on the order of 1 to 15 micrometers. They are lightweight and have an open, highly porous microstructure. Typical densities are less than 500 kilograms per cubic meters, and porosities generally exceed 0.8. Because of their open porosity, these materials are permeable to gas glow. There are numerous instances in which internal gas transport in a thermal protection system could be important; examples include the penetration of hot boundary-layer gases into the insulation, the flow of decomposition (pyrolysis) products from the interior, the use of convective flows to mitigate ice formation caused by cryopumping, and the design of refractory vents for pressure equilibration during atmospheric entry. Computational analysis of gas flow through porous media requires values of permeability which have not previously been available for the rigid fibrous insulations used in thermal protection systems. This paper will document measurements of permeability for a variety of insulations from NASA's LI, FRCI, and AETB families of lightweight ceramic ablators. The directional anisotropy of permeability and its dependence on gas pressure and material density will be presented. It will be shown that rarified-flow effects are significant in the flow through such materials. Connections will be drawn between the insulation microstructure and permeability. The paper will also include representative computations of flow through rigid fibrous insulations.

  3. Social media in vascular surgery.

    PubMed

    Indes, Jeffrey E; Gates, Lindsay; Mitchell, Erica L; Muhs, Bart E

    2013-04-01

    There has been a tremendous growth in the use of social media to expand the visibility of various specialties in medicine. The purpose of this paper is to describe the latest updates on some current applications of social media in the practice of vascular surgery as well as existing limitations of use. This investigation demonstrates that the use of social networking sites appears to have a positive impact on vascular practice, as is evident through the incorporation of this technology at the Cleveland Clinic and by the Society for Vascular Surgery into their approach to patient care and physician communication. Overall, integration of social networking technology has current and future potential to be used to promote goals, patient awareness, recruitment for clinical trials, and professionalism within the specialty of vascular surgery. PMID:23321344

  4. Biomaterials for vascular tissue engineering

    PubMed Central

    Ravi, Swathi; Chaikof, Elliot L

    2010-01-01

    Cardiovascular disease is the leading cause of mortality in the USA. The limited availability of healthy autologous vessels for bypass grafting procedures has led to the fabrication of prosthetic vascular conduits. While synthetic polymers have been extensively studied as substitutes in vascular engineering, they fall short of meeting the biological challenges at the blood–material interface. Various tissue engineering strategies have emerged to address these flaws and increase long-term patency of vascular grafts. Vascular cell seeding of scaffolds and the design of bioactive polymers for in situ arterial regeneration have yielded promising results. This article describes the advances made in biomaterials design to generate suitable materials that not only match the mechanical properties of native vasculature, but also promote cell growth, facilitate extracellular matrix production and inhibit thrombogenicity. PMID:20017698

  5. Psoriasis and occlusive vascular disease.

    PubMed

    McDonald, C J; Calabresi, P

    1978-11-01

    To test the hypothesis that psoriasis is associated with an increased incidence of occlusive vascular disease (thrombophlebitis, myocardial infarction, pulmonary embolization, and cerebrovascular accident), the clinical records of 323 psoriatic and 325 non-psoriatic patients admitted to the dermatology service of the Roger Williams General Hospital were examined. The data obtained in this study suggest that (1) the occurrence rate of occlusive vascular disease is significantly greater in the psoriatic than in the non-psoriatic dermatological patient. This is particularly true in the male population; (2) psoriasis predisposes to occlusive vascular disease; and (3) the psoriatic patient with certain predisposing factors is at greater risk of experiencing an occlusive vascular episode than both the non-predisposed psoriatic and the non-psoriatic dermatological patient. PMID:708620

  6. Comparison of Steady State Method and Transient Methods for Water Permeability Measurement in Low Permeability Rocks

    NASA Astrophysics Data System (ADS)

    Boulin, P. F.; Bretonnier, P.; Gland, N.

    2010-12-01

    Very low permeability geomaterials (order of nanoDarcy (10-21 m2)), such as clays rocks, are studied for many industrial applications such as production from unconventional reserves of oil and gas, CO2 geological storage and deep geological disposal of high-level long-lived nuclear wastes. For these last two applications, clay efficiency as barrier relies mainly on their very low permeability. Laboratory measurement of low permeability to water (below 10-19 m2) remains a technical challenge. Some authors argue that steady state methods are irrelevant due to the time required to stabilize water fluxes in such low permeability media. Most of the authors measuring low permeabilities use a transient technique called pulse decay. This study aims to compare objectively these different types of permeability tests performed on a single clay sample. For the steady state method, a high precision pump was used to impose a pressure gradient and to measure the small resulting water flow rate at steady state. We show that with a suitable set-up, the steady state method enables to measure a very low permeability of 8 10-22 m2 in a period of three days. For a comparable duration, the pulse decay test, most commonly used for such low permeability measurements, provides only an average estimate of the permeability. Permeability measurements by pulse decay require to perform simulations to interpret the pressure relaxation signals. Many uncertainties remain such as the determination of the reservoirs storage factor, micro leakage effect, or the determination of the initial pulse pressure. All these uncertainties have a very significant impact on the determination of sample permeability and specific storage. Opposite to the wide-spread idea that transient techniques are required to measure very low permeability, we show that direct steady state measurement of water permeability with suitable equipments can be much faster and more accurate than measurement by pulse decay, especially in very low permeability porous media. In fact, low compressibilities of water and clay result in fast propagation of pressure wave and it cannot be argued that steady state conditions are not reachable in a reasonable amount of time.

  7. Piezo1 integration of vascular architecture with physiological force

    PubMed Central

    Tumova, Sarka; Muraki, Katsuhiko; Bruns, Alexander; Ludlow, Melanie J; Sedo, Alicia; Hyman, Adam J; McKeown, Lynn; Young, Richard S; Yuldasheva, Nadira Y; Majeed, Yasser; Wilson, Lesley A; Rode, Baptiste; Bailey, Marc A; Kim, Hyejeong R; Fu, Zhaojun; Carter, Deborah AL; Bilton, Jan; Imrie, Helen; Ajuh, Paul; Dear, T Neil; Cubbon, Richard M; Kearney, Mark T; Prasad, Raj K; Evans, Paul C; Ainscough, Justin FX; Beech, David J

    2014-01-01

    The mechanisms by which physical forces regulate endothelial cells to determine the complexities of vascular structure and function are enigmatic1-5. Studies of sensory neurons have suggested Piezo proteins as subunits of Ca2+-permeable non-selective cationic channels for detection of noxious mechanical impact6-8. Here we show Piezo1 (FAM38A) channels as sensors of frictional force (shear stress) and determinants of vascular structure in both development and adult physiology. Global or endothelial-specific disruption of mouse Piezo1 profoundly disturbed the developing vasculature and was embryonic lethal within days of the heart beating. Haploinsufficiency was not lethal but endothelial abnormality was detected in mature vessels. Importance of Piezo1 channels as sensors of blood flow was shown by Piezo1 dependence of shear stress-evoked ionic current and calcium influx in endothelial cells and the ability of exogenous Piezo1 to confer sensitivity to shear stress on otherwise resistant cells. Downstream of this calcium influx was protease activity and spatial organization of endothelial cells to the polarity of the applied force. The data suggest Piezo1 channels as pivotal integrators in vascular biology. PMID:25119035

  8. Vascular Reactivity is Impaired and Associated With Walking Ability in Patients With Intermittent Claudication.

    PubMed

    Silva, Rita de Cassia Gengo E; Wolosker, Nelson; Yugar-Toledo, Juan Carlos; Consolim-Colombo, Fernanda Marciano

    2015-08-01

    We verified whether vascular reactivity is impaired and whether there is any association between vascular reactivity, walking ability, and peripheral artery disease (PAD) severity in patients with intermittent claudication (IC). We studied 63 patients and 17 age- and sex-matched volunteers without PAD. Vascular reactivity was evaluated in the brachial artery during reactive hyperemia (flow-mediated dilation [FMD]) and after a sublingual single dose of nitroglycerin (nitroglycerin-induced vasodilation [NID]). Walking ability was verified by a 6-minute walk test. Vascular reactivity and walking ability were significantly worse in patients with IC compared with control participants. The ankle-brachial index correlated with FMD, NID, as well as total and pain-free distances. The NID and walking ability progressively decreased as PAD severity increased. Walking ability correlated with NID but not with FMD. In patients with IC, vascular reactivity is impaired and is related to the severity of PAD and to walking ability. PMID:25100750

  9. Tumor vascular permeabilization using localized mild hyperthermia to improve macromolecule transport.

    PubMed

    Kirui, Dickson K; Koay, Eugene J; Guo, Xiaojing; Cristini, Vittorio; Shen, Haifa; Ferrari, Mauro

    2014-10-01

    The abnormal tumor vasculature presents a major challenge to the adequate delivery of chemotherapeutics, often limiting efficacy. We developed a nanoparticle-based technique to deliver localized mild hyperthermia (MHT) used to transiently alter tumor vascular transport properties and enhance transport of macromolecules into tumor interstitium. The strategy involved administering and localizing accumulation of stealth gold nanorods (GNRs, 103 ?g of GNRs/g of tumor), and irradiating tumor with a low-photon laser flux (1 W/cm(2)) to generate MHT. The treatment increased vascular permeability within 24 h after treatment, allowing enhanced transport of macromolecules up to 54 nm in size. A mathematical model is used to describe changes in tumor mass transport properties where the rate of macromolecular exchange between interstitial and vascular region (R) and maximum dye enhancement (Ymax) of 23-nm dextran dye is analytically solved. During enhanced permeability, R increased by 200% while Ymax increased by 30% relative to untreated group in pancreatic CAPAN-1 tumors. MHT treatment also enhanced transport of larger dextran dye (54 nm) as assessed by intravital microscopy, without causing occlusive cellular damage. Enhanced vascular transport was prolonged for up to 24 h after treatment, but reversible with transport parameters returning to basal levels after 36 h. This study indicates that localized mild hyperthermia treatment opens a transient time-window with which to enable and augment macromolecule transport and potentially improve therapeutic efficacy. From the clinical editor: In this study, local intra-tumor mild hyperthermia is induced using a nanoparticle-based approach utilizing stealth gold nanorods and irradiating the tumor with low-photon laser flux, resulting in locally increased vascular permeability enabling enhanced delivery of therapeutics, including macromolecules up to 54 nm in size. Similar approaches would be very helpful in addressing treatment-resistant malignancies in clinical practice. PMID:24262998

  10. Dual energy micro-CT imaging of radiation-induced vascular changes in primary mouse sarcomas

    PubMed Central

    Moding, Everett J.; Clark, Darin P.; Qi, Yi; Li, Yifan; Ma, Yan; Ghaghada, Ketan; Johnson, G. Allan; Kirsch, David G.; Badea, Cristian T.

    2013-01-01

    Purpose To evaluate the effects of radiation therapy on primary tumor vasculature using dual energy (DE) micro-computed tomography (micro-CT). Methods and Materials The Cre-loxP system was used to generate primary sarcomas with mutant Kras and p53. Unirradiated tumors were compared to tumors irradiated with 20 Gy. A long-circulating PEGylated liposomal-iodinated contrast agent was administered one day after treatment, and mice were imaged immediately after injection (day 1) and three days later (day 4) using DE micro-CT. CT-derived tumor sizes were used to assess tumor growth. After DE decomposition, iodine maps were used to assess tumor fractional blood volume (FBV) at day 1 and tumor vascular permeability at day 4. For comparison, tumor vascularity and vascular permeability were also evaluated histologically using CD31 immunofluorescence and fluorescently-labeled dextrans. Results Radiation treatment significantly decreased tumor growth (P<0.05). There was a positive correlation between CT-measurement of tumor FBV and extravasated iodine with microvascular density (MVD) (R2=0.53) and dextran accumulation (R2=0.63), respectively. Despite no change in MVD measured by histology, tumor FBV significantly increased after irradiation as measured by DE micro-CT (0.070 vs. 0.091, P<0.05). Both dextran and liposomal-iodine accumulation in tumors increased significantly after irradiation with dextran fractional area increasing 4.2-fold and liposomal-iodine concentration increasing 3.0-fold. Conclusions DE micro-CT is an effective tool for non-invasive assessment of vascular changes in primary tumors. Tumor blood volume and vascular permeability increased after a single therapeutic dose of radiation treatment. PMID:23122984

  11. [Vascular tumors of the orbit].

    PubMed

    Cophignon, J; d'Hermies, F; Civit, T

    2010-01-01

    Vascular tumors of the orbit include capillary hemangioma, cavernous hemangioma, hemolymphangioma, hemangiopericytoma and a few rare tumors. Capillary hemangioma and hemol